WO2023213793A1 - Methods and systems for histological sample preparation - Google Patents

Methods and systems for histological sample preparation Download PDF

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Publication number
WO2023213793A1
WO2023213793A1 PCT/EP2023/061508 EP2023061508W WO2023213793A1 WO 2023213793 A1 WO2023213793 A1 WO 2023213793A1 EP 2023061508 W EP2023061508 W EP 2023061508W WO 2023213793 A1 WO2023213793 A1 WO 2023213793A1
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sample
hsp
specimen
data
specimen data
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PCT/EP2023/061508
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French (fr)
Inventor
Maria SIEVERT
Dominik SIEVERT
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Inveox Gmbh
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Publication of WO2023213793A1 publication Critical patent/WO2023213793A1/en

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    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16HHEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H10/00ICT specially adapted for the handling or processing of patient-related medical or healthcare data
    • G16H10/40ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis

Definitions

  • the current invention generally relates to methods and systems for handling specimens, such as biopsy specimens.
  • tissue samples are known in the art.
  • microscopic anatomy is the branch of biology that studies the microscopic anatomy of biological tissue, organs and cells - commonly referred to as histology.
  • Histopathology is the branch of histology (hereinafter used as an inclusive term for microscopic anatomy techniques) that includes the examination and microscopic identification and study of diseased tissue.
  • the specimens are usually transferred from an originating body, for example, during surgical pathology or autopsy, to a specialised centre, such as a histology laboratory, where different analyses, such as microscopic examination, are possible not only for the size and the quality of the instruments, but also for the qualification and experience of the analysing specialists (e.g., histotechnicians, histotechnologists).
  • a specialised centre such as a histology laboratory
  • analyses such as microscopic examination
  • biopsy samples taken from human tissue are extracted and placed into a cavity filled with a fixative, such as formalin, during a histology process often referred as fixation. This is generally done to maintain the morphological structure of the sample specimen.
  • fixation such as formalin
  • Specimens received for histological examination may come from a number of different sources. They range from very large specimens or whole organs to tiny fragments of specimens. For example, the following are some of the specimen types commonly received in a histopathology lab. Excision specimens also called surgical biopsies, where whole organs or affected areas are removed.
  • incisional biopsy specimens are to be analysed, where specimen is removed for diagnosis from within an affected area, punch biopsies, where punches are used to remove a small piece of suspicious specimen for examination, shave biopsies, where small fragments of specimen are "shaved" from a surface (usually skin), curetting, where specimen is removed in small pieces from the lining of the uterus or cervix by a curette.
  • punch biopsies where punches are used to remove a small piece of suspicious specimen for examination
  • shave biopsies where small fragments of specimen are "shaved" from a surface (usually skin), curetting, where specimen is removed in small pieces from the lining of the uterus or cervix by a curette.
  • This is a surgical instrument for removing dead specimen, growths, etc., from the walls of certain body cavities, core biopsies, where a small specimen sample is percutaneously removed using a special needle sometimes through the skin.
  • Specimens are usually received immersed in a fixative or preservative but sometimes arrive untreated and must be immediately fixed. Fixation of the sample at the beginning of the process can be a step in preparing specimens for microscopic examination. It's objective is to prevent decay and preserve cells and specimens in an analysable state. It does this by preventing autolysis. The sooner fixation is initiated following separation of a specimen from its blood supply the better the result can be.
  • the most popular fixing agent is formaldehyde, usually in the form of a phosphate-buffered solution, in general referred to as formalin. Ideally specimens should be fixed by immersion in formalin for six to twelve hours before they are processed.
  • specimens may require further dissection to produce representative pieces from appropriate areas. For example, multiple samples may be taken from the excision margins of a tumour to ensure that the tumour has been completely removed.
  • the entire specimen may be processed.
  • the specimens selected for processing will be placed in cassettes in the form of small and perforated baskets and batches will be attached onto a specimen processor for embedding.
  • the tissue sample is embedded in a harder medium, such as paraffin wax, epoxy, acrylic, agar, gelatine, celloidin and other types of waxes.
  • a water-based embedding medium can be used, e.g., a water-based glycol.
  • tissue Once the tissue has been embedded into the wax, it will be cut into sections, in a process called sectioning, often achieved using a machinery called microtome.
  • sectioning often achieved using a machinery called microtome.
  • the slices with the microtome wrinkles may be introduced into the cut section, which can be removed by floating the sections into warm water for de-wrinkling. After that, the slices are attached on a microscope slide.
  • the wax can be removed (i.e., deparaffinization), such that the sliced tissue sections can be stained.
  • Staining such as, with Haematoxylin (H) and Eosin (E), make the cellular and nuclear structures of the tissue more visible under the microscope.
  • the tissue between the microscopic slides can then be observed using a microscope by skilled persons, such as, histologists.
  • histotechniques or histological sample preparation (HSP), with the individual stages referred to as histological sample preparation steps.
  • the histotechniques or histological sample preparation aim at preparing specimens, such as, biopsy or forensic samples, for examination under microscope.
  • An important step of histotechniques is the recording of newly received specimens in the histology laboratory, referred to as specimen accessioning. Before specimens are accepted by a laboratory, the identification or labelling and accompanying documentation will be carefully checked, all details recorded and specimen tracking commenced.
  • patient information and history medical data (e.g., medication), other relevant information (e.g., pictures during patient treatment), along with a description of the site of origin is obtained.
  • the specimen containers are associated with documents, such as, a laboratory order, comprising such information.
  • the received specimens are assigned with a unique identifier that will identify each specimen for each patient. It is vital that patient or research specimens are properly identified and the risk of wrong results, e.g., mix-ups, minimized.
  • a further important step of specimen handling is gross-examination, also referred to as grossing, which involves a careful examination and description of the specimen that will include the appearance, the number of pieces and their dimensions. Grossing also includes removing the specimen from the container and placing them in small cassettes which hold the tissue samples for further processing.
  • specimen accessioning and gross examination will be conducted by a specialised person, such as, a pathologist, pathology assistant or pathology resident, generally referred to as a practitioner. That is, the skilled person would receive the specimen, usually contained in a specimen container, read the information comprised in the accompanied documents, read the labels assigned to the container, examine the specimens, implement a description of the specimen. Further the pathologist, pathology assistant, or pathology resident, can open the containers, drain the fixation liquid inside the containers during a draining process, pick the tissue samples, place them in cassettes and label the cassettes accordingly to be able to at least identify the samples placed therein. This process requires careful handling from the practitioner, as the fixation liquid and/or the tissue sample may be dangerous to the health of the practitioner.
  • the practitioner may be required to determine what strainers to use, how long to apply the stain, how long to let the samples dehydrate, what solutions or temperature to use during dehydration, chose colour and number of biopsy cassettes to label, acquire the information to provide in the labels, etc.
  • a non-optimal synchronization of the histological sample preparation (e.g., FCFS) steps may lead to the increase of waiting times before a sample is processed in a respective step.
  • samples A and B may require the same processing steps.
  • Sample C may require different and longer processing steps compared to A and B.
  • it can be more efficient to process A and B before C.
  • C is very fragile and cannot tolerate long waiting times, then the processing of C before A and B can be more optimal.
  • decisions are currently generally taken by the practitioner, or not taken at all as the samples may be treated in a first-come-first-served or random manner.
  • tissue samples are generally processed in the same manner which can lead to suboptimal and/or inferior results.
  • limited customization to the histological sample preparation steps are done - however, they generally require a practitioner to examine or identify the sample and/or handle the laboratory order and/or other documents related to the sample and extract required information from therein and then correspondingly either manually carry out the process or configure a machinery for carrying the process.
  • the present invention solves or at least alleviates the above discussed disadvantages of current techniques, at least by providing devices, system and methods that deal with specimen data aggregation and flow within the different stages of the histological sample preparation.
  • the present invention discloses a specimen data aggregating system (referred in the following as “the system” or “HSP system”) configured to aggregate specimen data during a histological sample preparation (referred in the following for the sake of brevity by the abbreviation HSP) of at least one sample (interchangeably referred to as specimen or tissue), which can be a histological, pathological, forensic pathology, medical, biological, veterinary, surgical, anatomical, agricultural tissue and/or biopsy sample.
  • the system comprises at least one aggregating component configured to acquire specimen data related to the at least one sample, at least one memory device configured to receive and store the acquired specimen data and at least one processing unit configured to process the acquired specimen data to generate at least one adjustment for adjusting the HSP of the at least one sample.
  • the acquired specimen data can relate to specimen features, such as, visual, physical, chemical and/or medical property of a sample.
  • the generated adjustment can relate to guidance, instructions, parameters, configurations and the like for performing the HSP or a part of the HSP.
  • a generated adjustment can be "Dehydrate sample ⁇ X> using a ⁇ 90%> concentrated alcohol solution for ⁇ 45> minutes. Next dehydrate sample ⁇ X> using ⁇ absolute alcohol> for ⁇ 60> minutes. Next clear the sample using ⁇ Xylene> for ⁇ 60> minutes", wherein the parameters indicated between " ⁇ >” can be parameters calculated by the processing unit during the generation of the adjustments.
  • Generating adjustments based on specimen data can be particularly advantageous as it allows the customization (i.e., adjustment) of HSP to each specimen or group of specimens.
  • the dehydration and clearing step is customized according to the properties of sample(s) ⁇ X>.
  • the present invention allows for the acquisition of specimen data and customization of the HSP of a sample according to the properties of the sample.
  • the at least one processing unit can be configured to process the acquired specimen data and generate a sequence of samples to undergo HSP.
  • the at least one processing unit can output a sequence of unique IDs assigned to each sample (or group of samples). Said sequence can be configured to indicate on which order to process the samples.
  • the sequence of samples can comprise a prioritization of samples and/or an order of samples to undergo HSP.
  • the at least one processing unit can be configured to calculate the throughput of a sequence of samples and to generate the sequence with the highest throughput. That is, different samples may require different times on different HSP stages or steps. This and the order of processing the samples can affect the total time for performing the HSP.
  • the processing unit can be configured determine which sequence results in the lowest total time for performing the HSP of the samples in the sequence.
  • the at least one processing unit can be configured to calculate at least one waiting time for each of the at least one samples and the at least one processing unit can be configured to generate the sequence based on the at least one calculated waiting time. That is, due to overloading one or more samples may have to wait before undergoing HSP or a particular HSP step. Waiting times can increase the age of the samples which can cause sample degradation. As such, it can be advantageous to minimize the waiting times for a sample and/or the average waiting time for a plurality of samples and/or the longest waiting time among a plurality of waiting times.
  • the at least pone processing unit can thus be configured to generate a sequence that can minimize the waiting times for a sample and/or the average waiting time for a plurality of samples and/or the longest waiting time among a plurality of waiting times.
  • the generation of the sequence of sample to undergo HSP may involve an optimization problem.
  • the optimization problem may have one or more parameters to optimize, such as, throughput, waiting time, etc.
  • the optimization problem may have one or more constraints, such as, a minimum throughput to be reached, a maximum tolerable (total) waiting time for one or more or each sample, etc.
  • the at least one processing unit can generate a sequence which provides an optimal (or nearly optimal) order for processing the samples.
  • the at least one generated adjustment comprises the generated sequence.
  • Configuring the at least one processing unit to generate the sequence can be advantageous as it can allow for an efficient synchronization of HSP of multiple samples. That is, the processing of multiple samples over multiple HSP stages can be efficiently synchronized. This can increase the throughput of sample preparation and/or increase time efficiency and/or decrease sample waiting times.
  • the at least one processing unit may generate a deadline for the at least one sample to undergo HSP.
  • the said deadline can indicate the maximum waiting time for a sample (before undergoing HSP or a particular HSP step).
  • the said deadline can also indicate the latest time that the sample can undergo HSP (or a particular HSP step) after which the sample is expected to fully degrade and become undiagnosable.
  • the deadline can be generated as part of the adjustments.
  • the HSP comprises a plurality of steps (as it is typical for the current histotechniques) and the at least one processing unit can configured to process the acquired specimen data to generate a selection of the plurality of steps for the at least one sample to undergo.
  • the at least one processing unit generates a "plan" that indicates which steps of the HSP will a sample undergo. The selection of the plurality of steps can be generated as part of the adjustments.
  • the at least one processing unit can be configured to process the acquired specimen data to generate a timetable comprising at least one entry, wherein each entry can indicate for at least one specimen, an HSP step and a time for the at least one specimen to undergo the HSP step.
  • the timetable can be considered as a generalized version of the sequence of samples discussed above and as such it can be generated in a similar manner as discussed for the sequence of samples. The timetable can be generated as part of the adjustments.
  • the at least one processing unit can be configured to calculate at least one HSP parameter.
  • the HSP parameter can be configured to receive a plurality of values and based on the values it receives the HSP of the at least one sample can be correspondingly adjusted.
  • At least one HSP parameter can relate to a particular HSP step.
  • each HSP step can comprise one or more customizable HSP parameters.
  • the dehydration step may comprise ⁇ duration>, ⁇ type and amount of dehydrating solution> as HSP parameters. Based on the values that the HSP parameters of a HSP step receive, the HSP step can be correspondingly be performed or customized.
  • a first dehydration step can comprise the parameters ⁇ 30 min>, ⁇ alcohol solution>, ⁇ 80% concentrations ⁇ sample X>, ⁇ order I> and a second dehydration step can comprise the parameters ⁇ 45 min>, ⁇ alcohol solutions ⁇ 100% concentration >, ⁇ sample X>, ⁇ order Ils
  • the dehydration step of sample X is performed by first immersing it for 30 minutes in an 80% alcohol solution, and then for 45 minutes in a ⁇ 100% alcohol solution.
  • the HSP parameters can relate to or comprise a duration parameter that can indicate a duration of performing an action during the HSP of the sample.
  • the duration parameter can be a duration of dehydration step, a duration of letting the at least one sample immersed in a solution, e.g., alcohol solution, a duration of heating the at least one sample, a duration of freezing the at least one sample, a duration of letting the at least one sample immersed in a stain, e.g., Haematoxylin and Eosin, a duration of letting the at least one sample immersed in warm water, e.g., for de- wrinkling.
  • a duration of dehydration step e.g., alcohol solution
  • a duration of heating the at least one sample e.g., a duration of freezing the at least one sample
  • a duration of letting the at least one sample immersed in a stain e.g., Haematoxylin and Eosin
  • the HSP parameter can relate to or comprise a selection among different options, such as, a selection of different available processes, methods, compounds (e.g., solutions), devices, and/or machines that can be utilized during the HSP of the at least one sample.
  • Some non-limiting examples can be a selection of at least one fixation liquid, e.g., formalin, a selection of at least one sample dehydration method, a selection of at least one dehydrating agent, e.g., alcohol solution, a selection of at least one clearing agent, e.g., xylene, a selection of at least one embedding material, e.g., wax, a selection of at least one sectioning device, e.g., a type of knife, a selection of at least one sectioning method, e.g., angle of cutting, force of cutting, direction of cutting, number of "waste" cuttings, slice thickness, number of cuts or slices, a selection of staining agents, e.g., Haematoxyl
  • the HSP parameter can relate to or comprise an/a amount/number of a compound or components or parts or devices or processes or machines that can be utilized during the HSP of the at least one sample.
  • Some non-limiting examples can be a number of samples, an amount of fixation liquid, a number of sample containers, a number of biopsy cassettes, an amount of dehydrating agent, an amount of clearing agent, an amount of embedding material, an amount of stain, a number of slices, a number of microscope slides. It will be understood that the above list is not meant as an exhaustive or limiting list of amount/number parameters, but instead it is an illustrative one for increasing clarity.
  • the HSP parameter can relate to or comprise a position and/or orientation (i.e., pose) parameter that can indicate a position and/or orientation of at least one sample.
  • a position and/or orientation i.e., pose
  • Some non-limiting examples can be a position and/or orientation of at least one sample in a sample container, a position and/or orientation of at least one sample in a biopsy cassette, a position and/or orientation of at least one sample in an embedding medium, a position and/or orientation of at least one slice of sample in a sample, a position and/or orientation of at least one slice of a sample in a microscope slide.
  • the calculation (i.e., generation) of the at least one HSP parameter can be advantageous as they can allow adjusting the HSP process. More particularly, they can allow tailored or particular adjustments to the HSP step. For example, by calculating a duration HSP parameter of the dehydration step that particular step can be adjusted. In other words, the HSP parameters allow for more granular adjustments to the HSP step. As such, the degree (or detailedness) of adjusting the HSP based on the sample properties can be increased.
  • the at least one aggregating component can be configured to acquire specimen data related to the at least one sample during a first HSP step. A first HSP step. Furthermore, the aggregating component can be configured to communicate (i.e., transmit) the acquired specimen data. Further still, the system can be configured to provide the specimen data acquired at the first HSP step to a second HSP step. The at least one processing unit can further be configured to process the specimen data acquired at a first HSP step to generate at least one adjustment for adjusting a second HSP step. It will be noted that herein first and second are used to differentiate a first HSP step from a second HSP step and not the order of the said HSP steps.
  • the system can be configured to facilitate information flow, more particularly the flow of specimen data, among different stages of the HSP.
  • This can be advantageous as data acquired during a first HSP step can be used at a second HSP step. As such, a higher utilization of the specimen data can be achieved.
  • some or all the specimen data acquired in earlier HSP steps can be used at later HSP steps and/or to calculate adjustments related to the later HSP steps.
  • some HSP steps may cause changes to the sample and such may cause information loss.
  • the dehydration step may change the colour of the sample and thus the original colour information can be lost.
  • Specimen data acquired in earlier steps can be beneficial in such cases.
  • colour information acquired before the dehydration step can be used to retrieve original colour information at a later stage (e.g., during diagnosis the original colour may be needed by the pathologist).
  • the HSP of at least one sample can comprise one or more HSP steps.
  • HSP steps can be a sample fixation step, a specimen accessioning step, a fixation liquid disposal step, a specimen gross-examination step, a specimen dehydration step, a specimen clearing step, a specimen embedding step, a specimen de-paraffinization step, a specimen sectioning step, a specimen de-wrinkling step, a specimen sliding step, a specimen staining step, a specimen cover-slipping step, a specimen diagnosis step, a specimen molecular analysis step.
  • the HSP step can refer to any of the histotechniques and generally relate to steps, processes and/or techniques that prepare a sample for histological examination (e.g., under microscope).
  • the at least one aggregating component can be configured to acquire specimen data that relate to a physical and/or chemical property of the at least one sample. That is, different properties or features of the sample can be extracted from or comprised in the specimen data.
  • the at least one aggregating component can be configured to acquire specimen data related to the at least one sample during a HSP step and wherein the acquired specimen data facilitate the HSP step and/or an adjustment of the HSP step. That is, the at least one generated adjustment can facilitate adjusting a step of the HSP of the at least one sample.
  • the at least one aggregating component can comprise at least one sensor device that can be configured to acquire sensor data related to the sample.
  • the sensor data can indicate the specimen data. That is, specimen data can be extracted from the sensor data.
  • a sensor processing unit can be configured to process the sensor data to extract specimen data. That is, the aggregating component can be configured to acquire specimen data by comprising a sensor device that collects sensor data and wherein the sensor data can be processed to extract the specimen data.
  • the sensor processing unit can be integrated to the sensor device.
  • the at least one processing unit can comprise the sensor processing unit. That is, the processing of the sensor data to extract specimen data can be performed by a sensor processing unit integrated to the sensor device or alternatively/additionally by the at least one processing unit.
  • the sensor device can be configured to measure a physical and/or chemical property of the at least one sample.
  • the sensor device can allow assessing or extracting features of the sample.
  • the at least one sensor device may comprise at least one visual camera, at least one stereo camera, at least one depth sensor, e.g., a time-of- flight (ToF) sensor, at least one laser sensor, e.g., a light detection and ranging (LIDAR) sensor, at least one ultrasound scanner, at least one projectional radiography scanner, at least one computed tomography scanner, at least one fluoroscope, at least one thermometer, at least one pH meter, at least one pressure meter, at least one device configured to measure a thickness and/or size and/or area and/or volume and/or stiffness and/or acidity and/or temperature of the at least one sample and/or any combination thereof.
  • the above list is not meant as an exhaustive or limiting list of sensor devices, but instead it is an illustrative one for increasing clarity.
  • the aggregator component can comprise at least one communication component configured to transmit and/or receive data, preferably, the acquired specimen data and/or the at least one generated adjustment.
  • the communication component is particularly advantageous as it can facilitate specimen data sharing (i.e., flow) between different HSP steps or devices.
  • the system may comprise a plurality of aggregating components that can be provided at different stages of the HSP (i.e., at different HSP steps).
  • the aggregating components can comprise at least one corresponding communication component and can be interconnected with each other, e.g., through a mesh network.
  • One or more of the aggregating components can be configured to acquire specimen data through a sensor device. The acquired specimen data can then be communicated to the other aggregating components in the network. In other words, a complete information flow or sharing between the different aggregating components (at different HSP steps) of the system can be achieved.
  • the system further comprises at least one HSP device that can be configured to facilitate the HSP of the at least one sample.
  • the HSP device can facilitate one HSP step, e.g., a staining device facilitating the staining step of the HSP.
  • the HSP device can facilitate multiple HSP steps, generally, multiple consecutive HSP steps, e.g., a sample processing device configured to perform sample accessioning, fixation liquid disposal and insertion of samples into biopsy cassettes.
  • the HSP device may fully automate the at least one HSP step. However, in some embodiments, the HSP device may assist on performing at least one HSP step.
  • the HSP device can comprise the aggregator component.
  • the HSP device can comprise the features and advantages of the aggregator component, as discussed above. That is, the HSP device can be configured not only for facilitating the HSP process, but in addition it can be configured to aggregate specimen data.
  • the HSP device can comprise a device and/or machine that is configured to carry out or facilitate at least one HSP step. That is, the HSP device can comprise at least one hardware component configured to handle at least one sample, at least one software component comprising instructions for performing the HSP or an HSP step of at least one sample and/or at least one input/output component configured to facilitate the HSP device receiving and outputting at least one sample. Said components are particularly advantageous to configured the HSP device for performing or facilitating at least one HSP step.
  • the aggregator component can be configured as a dongle or attachment device.
  • the HSP device can be configured as a modular device.
  • the aggregator component can be attached to a one device or machine that is configured to carry out or facilitate at least one HSP step.
  • the features of the said device or machine can be extended to include the specimen data aggregating feature.
  • This can be advantageous, as the same aggregator component can be shared among different HSP steps or devices. For example, after sectioning step and during dewrinkling, sliding and staining step, the sample is sliced. The same aggerating component can thus be used on the above steps, e.g., for scanning the slices of the sample.
  • a first HSP device can be configured to acquire specimen data and transmit the acquired specimen data.
  • the first HSP device can comprise at least one aggregator component and wherein the said aggregator component can comprise at least one sensor device configured to acquire specimen data and at least one communication component configured to transmit the acquired specimen data.
  • a second HSP device can be configured to receive the specimen data transmitted by the first HSP device.
  • the second HSP device can comprise an aggregator component and wherein the aggregator component comprises at least one communication component configured to receive specimen data.
  • specimen data acquired by the first HSP device are shared with and re-used by the second HSP device.
  • the second HSP device can be configured to transmit specimen data.
  • the second HSP device can comprise an aggregating component that can comprise a communication component configured to transmit data.
  • a third HSP device can be configured to receive the specimen data transmitted by the second HSP device and/or the first HSP device.
  • the specimen data can be communicated over one or more hops among the HSP devices.
  • the system may comprise a plurality of HSP devices that can be interconnected with each other, e.g., through a mesh network.
  • One or more of the HSP devices can be configured to acquire specimen data through a sensor device. The acquired specimen data can then be communicated to the other HSP devices in the network. In other words, a complete information flow or sharing between the different HSP device can be achieved.
  • HSP devices can be at least one accessioning device, at least one draining device, at least one dehydration device, at least one embedding device, at least one sectioning device, at least one de-wrinkling and sliding device, at least one staining device, at least one diagnosis device, at least one postdiagnosis device. It will be understood that the above list is not meant as an exhaustive or limiting list of HSP devices, but instead it is an illustrative one for increasing clarity.
  • the HSP devices can be adjusted or customized according to one of the generated adjustments.
  • the HSP device can process at least one sample according to one or more customized or adjusted HSP steps.
  • the adjustment of a HSP device may comprise an adjustment of a hardware component of the HSP device (e.g., changing a cutting knife for use during sectioning, preparation of an alcohol solution for use during dehydration, etc.), an adjustment of the software component of the HSP device (e.g., the setting of a duration parameter) and/or an adjustment of the input/output component of the HSP device.
  • Such adjustments can be performed automatically or manually.
  • the HSP device can be configured to receive pre-generated adjustments.
  • the adjustments can be generated by the at least one processing unit external to the HSP device.
  • the HSP device can be configured to receive specimen data, or raw specimen data.
  • the HSP device can comprise a data processing device that can be configured to process specimen data and generate at least one adjustment.
  • the data processing device can for example be at least one of the processing unit that is comprised internally by the HSP device.
  • the software component of the HSP device can comprise machine-readable instructions and the data processing device can be configured to execute a routine according to the machine-readable instructions for controlling the hardware components of the HSP device.
  • the system can comprise a central engine.
  • the central engine can comprise a database, wherein the database can be configured to store specimen data.
  • the database can comprise the at least one memory device.
  • the central engine can comprise at least one computing unit.
  • the computing unit may comprise the at least one processing unit configured to process the acquired specimen data to generate at least one adjustment for adjusting the HSP of the at least one sample. That is, in some embodiments, the processing of the specimen data can be centralized. In such embodiments, it can further be advantageous to provide a data connection between the central engine and the at least one aggregating component.
  • the central engine can comprise at least one communication component configured to communicate with the at least one aggregating component. That is, the central engine can receive specimen data.
  • the central engine can transmit the central data.
  • the central engine can transmit the generated adjustments based on the specimen data (e.g., to a HSP device or output device).
  • the calculation of adjustments can be done in a distributed or centralized manner.
  • a data processing device may process specimen data and generate adjustments at different HSP steps.
  • Said data processing device mat be integrated with the at least one aggregating component and/or with at least one HSP device.
  • the processing of the specimen data and the generation of adjustments may be carried out by the central engine.
  • the at least one processing unit can be further configured to generate at least one instruction for performing the at least one adjustment.
  • the instructions can comprise text, image(s), video(s), audio, diagram(s), flowchart(s), indication(s), haptic feedback, or any combination thereof. That is, the instructions can comprise guidance information on how to perform at least one adjustment of the HSP.
  • the system can further comprise at least one output device configured to output textual, graphical, visual, haptic data or any combination thereof.
  • the output device can be configured to output specimen data and/or the at least one generated adjustment and/or instructions for performing the at least one generated adjustment.
  • the output device can be configured to output data with a predefined layout, in a graphical form or any combination thereof.
  • the output device can be configured to communicate with at least one aggregating component, processing unit, HSP device, aggregating device, consumer device, central engine or any combination thereof.
  • the output device can comprise at least one display, at least one mobile display, at least one wearable device, at least one mobile phone, at least one smartphone, at least one tablet, at least one smart watch, at least one workstation, at least one mobile workstation, at least one computer, at least one mobile computer, at least one headphone or any combination thereof. It will be understood that the above list is not meant as an exhaustive or limiting list of output devices, but instead it is an illustrative one for increasing clarity.
  • the at least one processing unit can be configured to process external specimen data to generate the at least one adjustment. That is, the at least one processing unit may be configured to consider external specimen data, in addition to specimen data.
  • the external specimen data can generally comprise data related to a sample that were generated externally to the system, such as, an external facility, e.g., the sample originating facility, and/or data related to a sample that can be stored in an external database (e.g., a database of the sample originating facility).
  • the external specimen data can comprise medical, clinical or history data (or any combination thereof). Said data may relate to a sample, patient, disease or sample originating facility or any combination thereof. Considering the external specimen data can provide a more complete description of the sample to the system and thus, a better adjustment of the of the HSP of the sample can be performed.
  • the external specimen data can be acquired by any of the at least one aggregating component, central engine or communication component. This can be achieved by establishing a wired and/or wireless connection (which can be local or remote) with an external database that comprises the external specimen data. The transmission of the external specimen data can be facilitated by configuring an application programming interface (API) between the at least one aggregating component, central engine or communication component and the external database.
  • API application programming interface
  • the external specimen data are stored in the at least one memory device.
  • the external specimen data can be provided to a laboratory order that can correspond to one or more samples.
  • the laboratory order can comprise the external specimen data in a standard format or layout, such as, in a tabular format.
  • the laboratory order may comprise a physical sheet comprising textual information and/or electronic data that can be transmitted, such as, though a wired (e.g., USB) or wireless (e.g., NFC) connection.
  • a practitioner may input the external specimen data.
  • the practitioner may input the external specimen data using an input device (e.g., keyboard and mouse) causing the external specimen data to be stored at the at least one memory device.
  • the system can further be configured to consider external specimen data.
  • the external specimen data can be combined with the specimen data and can be treated in a similar manner as discussed in relation to the specimen data.
  • At least one processing unit can be configured to generates for at least one specimen or group of specimens a corresponding case profile. That is, a case profile can correspond to one specimen. However, in some instances a case profile may also correspond to a group of specimens.
  • a data processing device of an HSP device such as, of a specimen accessioning device, can be configured to generate for at least one specimen or group of specimens a corresponding case profile.
  • the case profile can comprise specimen data. That is, the case profile may facilitate aggregating (i.e., accumulating) specimen data, as the acquired specimen data can be accumulated in a case profile.
  • the case profile may also comprise external specimen data.
  • the case profile can comprise an HSP template that can indicate a standard HSP wherein one or more HSP parameters can be adjusted. That is, for one or a group of specimens initially a standard HSP procedure can be selected. This selection can be done automatically or manually, e.g., during specimen accessioning step, and can be based on specimen data and/or external specimen data.
  • the HSP template or the standard HSP procedure can comprise one or more HSP parameters.
  • the HSP template can be modified (i.e., adjusted). One manner of doing this is by setting or adjusting at least one HSP parameter.
  • the case profile may comprise the at least one generated adjustment.
  • the case profile can accumulate a detailed information related to the sample and the HSP steps performed on the sample.
  • the system can be configured to output the acquired specimen data, external specimen data and/or the at least one generated adjustment to a practitioner during the diagnosis step. This can assist the pathologist with the diagnosis of the sample.
  • the system can comprise an output device configured to data to a practitioner during the diagnosis step.
  • the diagnosis of a first sample can be feedback to the at least one processing unit and the at least one processing device can be configured to process said feedback and generate at least one adjustment for the HSP of a second sample.
  • the at least one adjustment generated based on the diagnosis of the first sample can comprise a cleaning of at least one HSP device. This can particularly be advantageous, when a sample is diagnosed with a dangerous and contiguous disease.
  • the at least one sensor device can comprise at least one visual camera.
  • the at least one sensor device can comprise at least one depth sensor.
  • the at least one sensor device can comprise at least one thermometer.
  • the at least one sensor device can comprise at least one pH meter.
  • the at least one sensor device can comprise at least one three-dimensional scanner.
  • the at least one sensor device can comprise at least one projectional radiography scanner. [0091] In some embodiments, the at least one sensor device can comprise at least one computed tomography scanner.
  • the at least one sensor device can comprise at least one fluoroscope.
  • the at least one sensor device can be configured to measure at least on of: a thickness, size, area, volume, stiffness, acidity and temperature of the at least one sample.
  • the at least one sensor device can comprise at least one DNA sequencer.
  • DNA refers to the deoxyribonucleic acid.
  • the at least one sensor device can comprise at least one immunostaining device.
  • an immunostaining device is a device that uses an antibody-based method to detect a particular protein or another antibody in a sample.
  • the at least one sensor device can comprise at least one immunohistochemistry staining device.
  • immunohistochemistry is used in histology to detect the presence of specific protein markers that can assist with diagnosis.
  • IHC can involve the process of selectively identifying proteins in a sample by exploiting the principle of antibodies binding specifically to antigens or another antibody in biological tissues.
  • a detective marker e.g., horseradish peroxidase (HRP) or fluorescent substance
  • HRP horseradish peroxidase
  • fluorescent substance can be used to label a primary antibody which can then bind to particular proteins in the sample. This is generally referred to as a direct immunohistochemistry method.
  • an unlabeled primary antibody which can also be referred to as a first antibody, may bind to a target protein in the sample.
  • a second labeled antibody may be used which can react with the primary antibody.
  • the at least one sensor device can comprise at least one mass spectrometry analyzer.
  • the present invention discloses a corresponding specimen data aggregating method comprising any of the features discussed above in correspondence to any of the system embodiment.
  • a detailed discussion as provided in the above and below for the system embodiments, is omitted. Numbered Embodiments
  • a specimen data aggregating system configured to aggregate specimen data during a histological sample preparation (HSP) of at least one sample, comprising: at least one aggregating component configured to acquire specimen data related to the at least one sample; at least one memory device configured to receive and store the acquired specimen data; at least one processing unit configured to process the acquired specimen data to generate at least one adjustment for adjusting the HSP of the at least one sample.
  • HSP histological sample preparation
  • specimen data and sample data are used interchangeably.
  • the at least one processing unit is configured to process the acquired specimen data to generate a sequence of samples to undergo HSP.
  • sequence of samples comprises a prioritization of at least one sample and/or an ordering of at least two samples to undergo HSP.
  • the at least one processing unit is configured to calculate a throughput (i.e., number of samples that undergo the HSP per unit time) of a sequence of samples and the processing unit is configured to generate the sequence of samples with the highest throughput.
  • a throughput i.e., number of samples that undergo the HSP per unit time
  • A5. The system according to any of the 3 preceding embodiments, wherein the at least one processing unit is configured to calculate at least one waiting time for at least one sample and the at least one processing unit is configured to generate the sequence of samples based on the at least one calculated waiting time.
  • A6 The system according to any of the 4 preceding embodiments, wherein the at least one generated adjustment comprises the generated sequence of samples.
  • the at least one processing unit is configured to process the acquired specimen data to generate a deadline for at least one sample to undergo HSP.
  • the at least one generated adjustment comprises the generated deadline.
  • the HSP comprises a plurality of steps and the at least one processing unit is configured to process the acquired specimen data to generate a selection of the plurality of HSP steps for at least one sample to undergo.
  • the at least one processing unit is configured to process the acquired specimen data to generate a timetable comprising at least one entry, wherein each entry indicates for at least one specimen, an HSP step and a time for the at least one specimen to undergo the HSP step.
  • A13 The system according to any of the preceding embodiments, wherein the at least one processing unit is configured to calculate at least one HSP parameter.
  • an HSP parameter is configured to receive a plurality of values and based on the values it receives the HSP of the at least one sample is correspondingly adjusted.
  • At least one HSP parameter is related to at least one HSP step and wherein the HSP parameter is configured to receive a plurality of values and based on the values it receives the HSP step is correspondingly adjusted.
  • an HSP parameter relates to a duration of performing an action, such as, at least one of: a duration of dehydration step, a duration of letting the at least one sample immersed in a solution, e.g., alcohol solution, a duration of heating the at least one sample, a duration of freezing the at least one sample, a duration of letting the at least one sample immersed in a stain, e.g., Haematoxylin and Eosin, a duration of letting the at least one sample immersed in warm water, e.g., for dewrinkling.
  • a duration of dehydration step such as, at least one of: a duration of dehydration step, a duration of letting the at least one sample immersed in a solution, e.g., alcohol solution, a duration of heating the at least one sample, a duration of freezing the at least one sample, a duration of letting the at least one sample immersed in a stain, e.g., Haematoxylin
  • an HSP parameter relates to a selection of a process/compound/device that is utilized during the HSP of the at least one sample, such as, at least one of: a selection of at least one fixation liquid, e.g., formalin, a selection of at least one sample dehydration method, a selection of at least one dehydrating agent, e.g., alcohol solution, a selection of at least one clearing agent, e.g., xylene, a selection of at least one embedding material, e.g., wax, a selection of at least one sectioning device, e.g., a type of knife, a selection of at least one sectioning method, e.g., angle of cutting, force of cutting, direction of cutting, number of "waste" cuttings, slice thickness, number of cuts or slices, a selection of staining agents, e.g., Haematoxylin and Eosin.
  • a selection of at least one fixation liquid e.g., formalin
  • an HSP parameter relates to an amount/number of a compound/component/part that is utilized during the HSP of the at least one sample, such as, at least one of: a number of samples, an amount of fixation liquid, a number of sample containers, a number of biopsy cassettes, an amount of dehydrating agent, an amount of clearing agent, an amount of embedding material, an amount of stain, a number of slices, a number of microscope slides.
  • an HSP parameter relates to a position and/or orientation of at least one sample, such as, at least one of: a position and/or orientation of at least one sample in a sample container, a position and/or orientation of at least one sample in a biopsy cassette, a position and/or orientation of at least one sample in an embedding medium, a position and/or orientation of at least one slice of sample in a sample, a position and/or orientation of at least one slice of a sample in a microscope slide.
  • A20 The system according to any of the preceding embodiments, wherein the at least one aggregating component is configured to acquire specimen data related to the at least one sample during a first HSP step.
  • A21 The system according to any of the preceding embodiments, wherein the at least one aggregating component is configured to communicate the acquired specimen data.
  • A22 The system according to any of the preceding embodiments, wherein the system is configured to provide the specimen data acquired at a first HSP step to a second HSP step.
  • the at least one processing unit is configured to process the specimen data acquired at a first HSP step to generate at least one adjustment for adjusting a second HSP step.
  • A24 configured to aggregate specimen data during a histological sample preparation (HSP) of at least one sample, wherein the HSP comprises at least one step.
  • HSP histological sample preparation
  • a step of the HSP (i.e., HSP step) of at least one sample comprises at least one of the: a sample fixation step, a specimen accessioning step, a fixation liquid disposal step, a specimen gross-examination step, a specimen dehydration step, a specimen clearing step, a specimen embedding step, a specimen de-paraffinization step, a specimen sectioning step, a specimen de-wrinkling step, a specimen sliding step, a specimen staining step, a specimen cover-slipping step, a specimen diagnosis step, a specimen molecular diagnosis step.
  • A26 The system according to any of the preceding embodiments, wherein the at least aggregating component is configured to acquire specimen data that relate to a physical and/or chemical property of at least one sample.
  • the at least one aggregating component is configured to acquire specimen data related to at least one sample during a step of the HSP of the at least one sample.
  • the at least aggregating component is configured to acquire specimen data related to at least one sample that facilitate a step of the HSP of the at least one sample.
  • A29 The system according to any of the preceding embodiments, wherein the at least one aggregating component is configured to acquire specimen data related to the at least one sample that facilitate the adjustment of a step of the HSP of the at least one sample.
  • A30 The system according to any of the preceding embodiments, wherein the at least one generated adjustment facilitates adjusting a step of the HSP of the at least one sample.
  • the at least one aggregating component comprises at least one sensor device (310).
  • A32 The system according to the preceding embodiment, wherein the at least one sensor device (310) is configured to acquire sensor data related to the sample.
  • A33 The system according to the preceding embodiment, wherein a sensor processing unit is configured to process the sensor data to extract specimen data.
  • A34 The system according to any of the 3 preceding embodiments, wherein a sensor processing unit is integrated to the sensor device (310).
  • A35 The system according to any of the 2 preceding embodiments, wherein the at least one processing unit comprises the sensor processing unit.
  • A36 The system according to any of the 5 preceding embodiments, wherein the at least one sensor device (310) is configured to measure a physical and/or chemical property of the at least one sample.
  • the at least one sensor device (310) comprises at least one of the: at least one visual camera, at least one stereo camera, at least one depth sensor, e.g., a time-of-flight (ToF) sensor, at least one laser sensor, e.g., a light detection and ranging (LIDAR) sensor, at least one ultrasound scanner, at least one projectional radiography scanner, at least one computed tomography scanner, at least one fluoroscope, at least one thermometer, at least one pH meter, at least one pressure meter, at least one device configured to measure a thickness and/or size and/or area and/or volume and/or stiffness and/or acidity and/or temperature of the at least one sample.
  • the at least one sensor device comprises at least one of the: at least one visual camera, at least one stereo camera, at least one depth sensor, e.g., a time-of-flight (ToF) sensor, at least one laser sensor, e.g., a light detection and ranging (LIDAR) sensor,
  • the aggregating component comprises at least one communication component (106, 306) configured to transmit and/or receive data, preferably, the acquired specimen data and/or the at least one generated adjustment.
  • A39 The system according to any of the preceding embodiment, further comprising at least one HSP device (40) configured to facilitate the HSP of at least one sample, such as, at least one HSP step of at least one sample.
  • HSP device configured to facilitate the HSP of at least one sample, such as, at least one HSP step of at least one sample.
  • A40 The system according to the preceding embodiment, wherein the HSP device (40) comprises at least one aggregating component.
  • the HSP device comprises a device and/or machine that is configured to carry out or facilitate at least one HSP step of at least one sample, said device and/or machine comprising at least one of at least one hardware component (102, 302) configured to handle at least one sample, at least one software component (104, 304) comprising instructions for performing the HSP or an HSP step of at least one sample, at least one input/output component (108, 308) configured to facilitate the HSP device (40) receiving and outputting at least one sample.
  • the HSP device comprises a device and/or machine that is configured to carry out or facilitate at least one HSP step of at least one sample, said device and/or machine comprising at least one of at least one hardware component (102, 302) configured to handle at least one sample, at least one software component (104, 304) comprising instructions for performing the HSP or an HSP step of at least one sample, at least one input/output component (108, 308) configured to facilitate the HSP device (40) receiving and outputting at least one sample.
  • At least one aggregating component is configured as an attachment or dongle that is configured to be attached or interfaced with at least one device or machine that is configured to carry out or facilitate at least one HSP step.
  • A43 The system according to any of the 4 preceding embodiments, wherein a first HSP device (40-1) is configured to acquire the specimen data and transmit the acquired specimen data.
  • the first HSP device (40-1) comprises at least one aggregating component and wherein the said aggregating component comprises at least one sensor device (310) configured to acquire specimen data and at least one communication component (306) configured to transmit the acquired specimen data.
  • a second HSP device (40-11) is configured to receive the specimen data transmitted by the first HSP device (40-1).
  • the second HSP device (40-11) comprises an aggregating component and wherein the aggregating component comprises at least one communication component (106, 306) configured to receive specimen data.
  • A47 The system according to any of the 2 preceding embodiments, wherein the second HSP device (40-11) is configured to transmit specimen data.
  • A48 The system according to the preceding embodiment, wherein a third HSP device (40-III) is configured to receive the specimen data transmitted by the second HSP device (40-11) and/or the first HSP device.
  • the at least one HSP device (40) comprises at least one of at least one accessioning device (40A), at least one draining device (40G), at least one dehydration device (40B), at least one embedding device (40C), at least one sectioning device (40D), at least one de-wrinkling and sliding device (40H), at least one staining device (40E), at least one diagnosis device, at least one post-diagnosis device.
  • A50 The system according to any of the preceding embodiments, wherein the HSP device (40) can be configured to be adjusted according to one of the generated adjustments.
  • A52 The system according to any of the 13 preceding embodiments, wherein the at least one HSP device (40) comprises a data processing device.
  • A53 The system according to the preceding embodiment and with the features of embodiment A41, wherein the software component (104, 304) comprises machine- readable instructions and the data processing device is configured to execute a routine according to the machine-readable instructions for controlling the hardware components (102, 302).
  • A54 The system according to any of the 2 preceding embodiments, wherein the data processing device the HSP device (40) is configured to process specimen data to generate at least one adjustment for adjusting the HSP of the at least one sample.
  • A55 The system according to any of the 3 preceding embodiments, wherein the at least one processing unit comprises the data processing device.
  • A56 The system according to any of the preceding embodiments, wherein at least one HSP device (40) is configured as an aggregator device (30).
  • an aggregator device (30) comprises at least one hardware component (302) configured to handle the at least one sample.
  • an aggregator device (30) comprises at least one software component (304) comprising instructions for controlling the hardware component (302).
  • an aggregator device (30) comprises at least one input/output component (308) configured to facilitate the aggregator device (30) receiving and outputting at least one sample.
  • an aggregator device (30) comprises at least one aggregating component.
  • A61 The system according to the preceding embodiment, wherein the at least one aggregating component comprised by the aggregator device (30) comprises a sensor device (310).
  • A62 The system according to any of the 2 preceding embodiments, wherein the at least one aggregating component comprised by the aggregator device (30) comprises a communication component (306).
  • A63 The system according to any of the preceding embodiments and with the features of embodiment A43 and A56, wherein the first HSP device (40-1) is configured as an aggregator device (30).
  • A64 The system according to any of the preceding embodiments, wherein at least one HSP device (40) is configured as a consumer device (10).
  • a consumer device comprises at least one hardware component (102) configured to handle the at least one sample.
  • a consumer device comprises at least one software component (104) comprising instructions for controlling a hardware component (102).
  • a consumer device (10) comprises at least one input/output component (108) configured to facilitate the consumer device (10) receiving and outputting at least one sample.
  • A68 The system according to any of the preceding embodiments, wherein a consumer device (10) comprises the at least one aggregating component.
  • A69 The system according to any of the 2 preceding embodiments, wherein the at least one aggregating component comprised by the consumer device (10) comprises a communication component (106).
  • the central engine (20) comprises a database (201) configured to store specimen data.
  • A74 The system according to the preceding embodiment, wherein the database (201) comprises the at least one memory component.
  • A75 The system according to any of the 3 preceding embodiments, wherein the central engine (20) comprises at least one computing unit (203).
  • A76 The system according to the preceding embodiment, wherein the computing unit (203) comprises the at least one processing unit.
  • A77 The system according to any of the preceding embodiment, wherein the central engine (20) comprises at least one communication component (206).
  • A78 The system according to any of the preceding embodiments, wherein the communication component (206) is configured to communicate with at least one aggregating component.
  • A79 The system according to any of the preceding embodiments, wherein the at least one processing unit generates instructions for performing the at least one adjustment.
  • A80 The system according to the preceding embodiment, wherein the instructions comprise text, image(s), video(s), audio, diagram(s), flowchart(s), indication(s), haptic feedback, or any combination thereof.
  • system further comprises at least one output device (50) configured to output textual, graphical, visual, haptic data or any combination thereof.
  • A82 The system according to the preceding embodiment, wherein the output device (50) is configured to output specimen data.
  • A84 The system according to any of the 2 preceding embodiments, wherein the output device (50) is configured to output the at least one generated adjustment.
  • A85 The system according to any of the 3 preceding embodiments, wherein the output device (50) is configured to output at least one instruction for performing the at least one adjustment.
  • A86 The system according to any of the preceding embodiments, wherein the output device (50) is configured to communicate with at least one aggregating component, processing unit, HSP device (40), aggregating device (30), consumer device (10), central engine (20) or any combination thereof.
  • the output device comprises at least one of: at least one display, at least one mobile display, at least one wearable device, at least one mobile phone, at least one smartphone, at least one tablet, at least one smart watch, at least one workstation, at least one mobile workstation, at least one computer, at least one mobile computer, at least one headphone.
  • the at least one processing unit is configured to process external specimen data to generate the at least one adjustment and wherein the external specimen data comprise medical, clinical and/or history data that relate to a sample, patient, a disease, sample originating facility or any combination thereof.
  • A91 The system according to any of the 3 preceding embodiments, wherein the at least one aggregating component is configured to receive the external specimen data.
  • A92 The system according to any of the 4 preceding embodiments, wherein a central engine (20) is configured to receive the external specimen data.
  • A93 The system according to any of the 5 preceding embodiments, wherein a communication component (106, 206, 306) is configured to receive the external specimen data.
  • A94 The system according to any of the 6 preceding embodiments, wherein the at least one memory component stores the external specimen data.
  • At least one processing unit is configured to generate for at least one specimen or group of specimens a corresponding case profile.
  • A97 The system according to any of the preceding embodiments, wherein a data processing device of a HSP device (40), such as, of a specimen accessioning device, is configured to generate for at least one specimen or group of specimens a corresponding case profile.
  • a data processing device of a HSP device 40
  • the case profile comprises specimen data.
  • case profile comprises external specimen data.
  • case profile comprises a HSP template that indicates a standard HSP wherein one or more HSP parameters can be adjusted.
  • A101 The system according to any of the 5 preceding embodiments, wherein the case profile comprises the at least one generated adjustment.
  • A102 The system according to any of the preceding embodiment, wherein the system is configured to output the acquired specimen data to a practitioner during the diagnosis step.
  • A103 The system according to any of the preceding embodiments, wherein the system is configured to output external specimen data to a practitioner during the diagnosis step.
  • A104 The system according to any of the preceding embodiment, wherein the system is configured to output the at least one generated adjustment to a practitioner during the diagnosis step.
  • A105 The system according to any of the 3 preceding embodiments, wherein the system comprises an output device (50) configured to data to a practitioner during the diagnosis step.
  • diagnosis of a first sample is feedback to the at least one processing unit and the at least one processing device is configured to process said feedback and generate at least one adjustment for the HSP of a second sample.
  • A107 The system according to the preceding embodiment, wherein the at least one adjustment generated based on the diagnosis of the first sample, comprises a cleaning of at least one HSP device.
  • A108 The system according to any of the preceding embodiments, wherein the at least one sensor device (310) comprises at least one visual camera.
  • the at least one sensor device (310) comprises at least one depth sensor.
  • the at least one sensor device (310) comprises at least one thermometer.
  • the at least one sensor device (310) comprises at least one pH meter.
  • At least one sensor device (310) comprises at least one projectional radiography scanner.
  • At least one sensor device (310) comprises at least one computed tomography scanner.
  • Al 15 The system according to any of the preceding embodiments, wherein the at least one sensor device (310) comprises at least one fluoroscope.
  • Al 16 The system according to any of the preceding embodiments, wherein the at least one sensor device (310) is configured to measure at least on of: a thickness, size, area, volume, stiffness, acidity and temperature of the at least one sample.
  • At least one sensor device (310) comprises at least one DNA sequencer.
  • DNA refers to the deoxyribonucleic acid.
  • At least one sensor device (310) comprises at least one immunostaining device.
  • an immunostaining device is a device that uses an antibody-based method to detect a particular protein or another antibody in a sample.
  • At least one sensor device (310) comprises at least one immunohistochemistry staining device.
  • IHC immunohistochemistry
  • a detective marker e.g., horseradish peroxidase (HRP) or fluorescent substance
  • HRP horseradish peroxidase
  • a primary antibody which can then bind to particular proteins in the sample.
  • HRP horseradish peroxidase
  • a direct immunohistochemistry method an unlabeled primary antibody, which can also be referred to as a first antibody, may bind to a target protein in the sample.
  • a second labeled antibody may be used which can react with the primary antibody.
  • the at least one sensor device (310) comprises at least one mass spectrometry analyzer.
  • a specimen data aggregating method configured to aggregate specimen during a histological sample preparation (HSP) of at least one sample, the method comprising: at least one aggregating component acquiring specimen data related to the at least one sample; at least one memory device receiving and storing the acquired specimen data; at least one processing unit processing the acquired specimen data and generating at least one adjustment for adjusting the HSP of the at least one sample based on the acquired specimen data.
  • HSP histological sample preparation
  • A121 The system according to the preceding embodiment, wherein the system is configured to carry out the method according to any of the preceding method embodiments.
  • Figure 1 depicts a typical procedure for producing and diagnosing microscope slides from histological samples according to prior art
  • Figure 2 illustrates a first histological sample preparation system embodiment configured for collecting specimen data and processing the specimen based on customized techniques
  • Figures 3a to 3c illustrate methods of histological sample preparation according to different embodiments of the present invention
  • Figures 4a to 4h illustrate a plurality of histological sample preparation steps according to an aspect of the present invention
  • Figure 5a and 5b illustrate a plurality of histological sample preparation steps according to another aspect of the present invention
  • Figure 6 illustrates a second histological sample preparation system embodiment configured for collecting specimen data and handling the specimen based on customized techniques
  • Figure 7 illustrates a third histological sample preparation system embodiment comprising an output device.
  • specimen, sample and tissue are used interchangeably and generally refer to biological and/or histological samples that can be treated with histotechniques.
  • histology is used to generally refer to microscopic anatomy, i.e., the branch of biology that studies the microscopic anatomy of biological tissue, organs and cells.
  • histological sample preparation involves the treatment of a sample using at least one of the histotechniques.
  • HSP is used to refer to histological sample preparation.
  • Fig. 1 illustrates a typical existing method for HSP.
  • HSP histotechniques
  • the specimens are received in a clinical, histology or forensic laboratory, typically immersed in a sample container with formalin (or any fixation liquid).
  • a practitioner handles the sample container (or a rack, bucket or bag of sample containers), checks for completeness (i.e., check if an indicated number of samples or sample containers has been received) and registers it (or them) by recording data related to the specimen(s).
  • This data may include information related to the specimen(s), such as number of sample container(s), respective origin of sample container(s), number of specimens in each sample container, type of specimen(s), possible diseases infecting the specimen(s), an indication of completeness of the samples and/or sample containers, etc.
  • the practitioner may record the samples with a unique ID which can be used internally (in the lab) or externally for identifying samples and/or linking them with the originating procedure or patient.
  • the practitioner extracts the specimen data from a laboratory order that comes with the sample container(s) and/or by examining the samples contained therein.
  • the practitioner can record the specimen data in a laboratory information system (LIS) - typically used by clinical laboratories for storing and managing their data.
  • LIS laboratory information system
  • the practitioner may handle the specimens to the dehydration phase.
  • excessive liquid is removed from the specimens. This is typically done by the practitioner diving the specimens in alcohol solutions.
  • the sample is immersed in solutions with increasing alcohol concentration.
  • the practitioner applies his/her knowledge and judgment to determine the alcohol concentration of each solution and the duration of letting the samples immersed in each alcohol solution.
  • the same dehydration procedure is used for multiple or all samples.
  • the practitioners may be discouraged to individualize the dehydration step for each sample. This may be the case particularly during work overload.
  • non-individualized dehydration process may lead to improper dehydration causing tissue damage and/or shrinkage.
  • An example of an improper dehydration can be dehydrating a delicate sample too fast by immersing it directly in a strong alcohol solution. Tissue damage can then lead to inferior results during the diagnosis step, making the overall HSP less accurate and less efficient. Or, if otherwise the practitioner individualizes the dehydration step to each sample this may lead to delays in HSP. These delays may cause the sample to degrade as it ages, which can then cause inferior results during the diagnosis step.
  • the sample may undergo a clearing process.
  • the clearing step is particularly necessary when the dehydration step is performed by immersing the samples in alcohol solutions.
  • the alcohol in the sample is replaced with a wax miscible compound, such as, xylene. This is done by treating the dehydrated sample with the paraffin miscible compound.
  • the clearing step facilitates the following step wherein the sample is embedded in a harder medium and the harder medium is paraffin.
  • the practitioner may embed the samples in a harder medium, typically paraffin wax.
  • a harder medium typically paraffin wax.
  • extra effort is required from the practitioner to identify the type and size of the samples and then apply his/her knowledge and judgment to embed the sample properly in the harder medium, such as paraffin.
  • This includes determining the type and amount of embedding material, position of the sample in the biopsy cassette wherein it will be embedded (e.g., at the bottom of the cassette) and, more importantly, the orientation of the sample, to ensure that the slices created after cutting the specimens will expose the required or necessary features.
  • the practitioner typically handles the embedded sample in a machinery for cutting or slicing, such as, a microtome.
  • a machinery for cutting or slicing such as, a microtome.
  • the microtome is a device that is able to cut thin slices from the embedded sample.
  • different cuts may be performed depending on the required slice thickness and type of knife used.
  • the practitioner is required to apply his/her knowledge and judgment to determine the type of slicing, which may be a time-consuming and non-ergonomic process leading to inefficiency and inferior diagnosis results.
  • the slices may comprise wrinkles caused by the knife during cutting.
  • the practitioner may typically submerge the slices into warm water. Based on the type of sample, slice thickness and size (or area) of the slices, the practitioner may determine a temperature of the water and duration of submergence of the sample into it for de-wrinkling. Again, the practitioner is required to apply his/her knowledge and judgment to examine the slices and determine the duration and temperature for de-wrinkling, which may be a time-consuming and non-ergonomic process leading to inefficiency and inferior diagnosis results. Otherwise, the practitioner may use the same de-wrinkling process, wherein the same water temperature and duration is used for every slice.
  • some samples may be damaged (e.g., very thin slices that may require a lower-than-average temperature) or wrinkles may not be removed (e.g., thick slices that may require a higher- than-average temperature).
  • the practitioner attaches the slices on microscope slide and may handle the slide with the sample into the staining phase.
  • one or more particular stains are applied on the sample to make cell structures more visible.
  • this step is performed the same irrespective of the sample.
  • excessive stain is used to ensure that the whole sample is stained.
  • it may be inefficient as the excessive stain can be wasted. This is particularly the case if the stain is poured over the microscope slide or if the specimen can contaminate the stain and make it unusable for future staining of slides.
  • the use of excessive stain may have a negative impact on the visibility of the microscopic structures of the sample and/or may cause artefacts to be created therein. As such, excessive use of stain may lead to inferior diagnosis results.
  • the use of less than required stain may not contribute on increasing the visibility of the microscopic structures of the samples.
  • the use of the right amount and type of stain, depending on slice thickness, size and type and other factors can be advantageous, in that it can increase the accuracy of the diagnosis results.
  • the amount of stain the same is true for the time of letting the slices in contact with the stain (particularly when the slices are immersed in the stain).
  • the practitioner may prepare the slides for observation under microscope. Generally, the practitioner covers the sample attached on a microscope slide with a second microscope slide or plastic/glass film. Then, a pathologist observes the slides under microscope for the diagnosis.
  • the practitioner may misjudge and wrongly preform a step, e.g., mislabel or misidentify a sample, mix-ups, use a wrong slice thickness during sectioning, apply excessive stain, etc.
  • the practitioner particularly during a work flux, may be discouraged to individualize or customize the techniques on a sample per sample base (or on a sample group base) - but rather performs a standard technique for all of them.
  • Fig. 2 depicts a histological sample preparation (HSP) system 1 according to one aspect of the present invention.
  • the HSP system 1 can be configured to facilitate histological sample preparation. More particularly, the HSP system 1 can be configured to at least facilitate obtaining specimen data, utilize the specimen data for performing the HSP, allow the flow of specimen data between the different HSP steps and devices, adjust HSP steps according to specimen data, synchronize the HSP for multiple samples, or any combination thereof. This can lead to a more accurate, time-efficient, ergonomic and safe specimen processing or preparation in a clinical, histological, surgical, anatomical pathology and/or forensics laboratory.
  • the HSP system 1 can comprise at least one aggregator device 30 and optionally at least one consumer device 10 and further optionally at least one central engine 20.
  • the HSP system 1 in a first configuration can comprise a plurality of aggregator devices 30.
  • the HSP system 1 in a second configuration can comprise a plurality of aggregator devices 30 and a central engine 20.
  • it can comprise one or more aggregator devices 30 and one or more consumer devices 10.
  • a fourth configuration it can comprise one or more aggregator devices 30 and one or more consumer devices 10 and a central engine 20.
  • the aggregator device 30 can be configured to acquire specimen data.
  • the aggregator device 30 can be equipped with at least one sensor device 310, for sake of brevity also referred to as sensor 310, which can be configured for sensing and obtaining specimen data.
  • the at least one sensor 310 can be configured to obtain sensor data related to the at least one specimen, which sensor data can be used to extract specimen data. That is, while sensor data can generally comprise numerical data (as output by the sensor), the specimen data can relate to features of the specimen (e.g., size, colour, shape, pressure, temperature, acidity, pH (the scale used to measure acidity), etc.) which can be extracted partially or fully based on the sensor data.
  • features of the specimen e.g., size, colour, shape, pressure, temperature, acidity, pH (the scale used to measure acidity), etc.
  • the sensor device 310 can comprise at least one visual camera, at least one stereo camera, at least one ToF sensor, at least one LIDAR, at least one ultrasound scanner, at least one thermometer, at least one pH meter, at least one pressure meter, at least one device configured to measure the thickness and/or size and/or area and/or volume and/or stiffness and/or acidity and/or temperature of a sample, and/or any combination thereof.
  • the sensor device 310 can comprise any sensor or meter device configured to measure and/or assess and/or indicate a physical and/or chemical property, preferably of (and not limited to) at least one specimen and/or slice of a specimen.
  • the said chemical and/or physical property can comprise (but not limited to) a size, area, volume, thickness, shape, stiffness, temperature, acidity (e.g., pH), etc.
  • the sensor device 310 can be configured to facilitate a corresponding HSP step wherein the aggregator device 30 comprising the sensor device 310 is utilized. That is, at different HSP steps different measures may be required and the sensor device 310 can be configured correspondingly to measure, asses and/or indicate the respective measures.
  • the aggregator device 30 can comprise a specimen input and output component 308.
  • the specimen input component 308 can be configured to facilitate the provisioning or input or insertion of at least one specimen on the aggregator device 308.
  • the input component 308 may be configured to receive at least one sample container, at least one rack of sample containers, at least one bag of sample containers, at least one biopsy cassette containing a specimen (which can be closed or opened - i.e., with or without a lid), at least one embedded specimen, at least one specimen slice or at least one microscope slide (e.g., glass slide) wherein a specimen slice is attached.
  • the input component 308 can be configured to receive any form of the sample depending on the respective HSP step.
  • the specimen output component 308 can correspondingly be configured to facilitate outputting at least one specimen from the aggregator device 308.
  • the specimen input and output component 308 can comprise one component configured to facilitate both the insertion and output of specimens from the aggregator device.
  • the specimen input and output component 308 can be separate components.
  • the aggregator device 30 can further be configured to communicate or transmit or output the aggregated or obtained specimen data and/or sensor data.
  • the aggregator device 30 can thus be equipped with at least one communication component 306.
  • the communication component 306 can be a communication cable connector 306 allowing at least one wired connection to be connected therein.
  • the communication component 306 can comprise a USB port/ cable, ethernet port/cable, optical data interface and/or the like.
  • the communication component 306 can be configured for wireless communication.
  • the communication component 306 can comprise at least one radio-frequency (RF) antenna, that can be configured to wirelessly transmit the specimen data.
  • the communication component 306 may utilize cellular technology (e.g., GSM, 3G, 4G, 5G), WIFI, Bluetooth, IEEE802.15.4 and/or other wireless technologies and any combinations thereof.
  • the aggregator device 30 may be configured to carry out or facilitate at least one HSP step (i.e., at least one of the histotechniques).
  • the aggregator device 30 can be referred to as a HSP device 40 (see Figs. 4a to 5b).
  • the aggregator device 30 may not only serve the purpose of acquiring specimen data, but may also be configured to facilitate or carry out the processing of the specimens - i.e., carry out or facilitate at least one of the histotechniques for preparing the sample for diagnosis.
  • the aggregator device 30 can comprise at least one hardware component 302 and at least one software component 304.
  • the hardware component 302 can be configured for handling the tissue during processing.
  • the software component 304 may comprise a computer implemented method 304 that can comprise instructions for controlling the hardware component for carrying out or facilitating the sample processing.
  • the software component 304 may thus comprise machine readable instructions which can be provided to the hardware components 302 causing them to perform actions for handling and processing the samples.
  • the software component 304 can be implemented by a skilled person and uploaded to a memory component (not shown) of the aggregator device 30. Alternatively, or additionally, said machine readable instructions can also be provided and/or indicated on a label (e.g., a machine-readable code) associated to a sample.
  • a label associated with at least one specimen or specimen container, or specimen cassette
  • instructions on how to process the sample can be directly or indirectly inferred.
  • One particular way of achieving this is configuring the said label associated with at least one specimen to provide information related to the sample.
  • one or more instructions for handling the specimen can be inferred.
  • the said label may directly and readily comprise the instruction(s). This provides an efficient manner of customizing the HSP steps to a specimen (or a plurality of specimens).
  • the specimen data aggregating features i.e., the sensor 310 and/or the communication component 306
  • the aggregating components can be configured to be attached to the said device or machine and the said device or machine can be configured to receive or allow/facilitate the attachment of the aggregating components to the said device or machine.
  • said device or machine can comprise the hardware component 302 and/or the software component 304 and/or the specimen input and output component 308 - as such, configured to carry out or facilitate at least one HSP step.
  • the aggregating components can comprise the sensor device 310 and the communication component 306 - as such, configured to acquire and communicate sensor data and/or specimen data.
  • the aggregating components can be provided and/or attached to the device or machine that is configured to carry out or facilitate at least one HSP step - thus forming the aggregator device 30.
  • the aggregator components can be configured as a dongle that can be attached, provided and/or interfaced with at least one device or machine that is configured to carry out or facilitate at least one HSP step, thus providing additional functionality (e.g., specimen data aggregation) to the at least one device or machine that is configured to carry out or facilitate at least one HSP step.
  • the software component 304 and/or the hardware component 302 can be adjusted or configured or customized based on the specimen data which can be collected by the sensor device 310 and/or received by the communication component 306. This can allow the HSP steps to be adjusted or configured or individualized according to the specimen data.
  • an adjustment of the HSP step may comprise both the adjustment of software component 304 and hardware component 302 of the aggregator device 30.
  • an adjustment of the HSP step may comprise the adjustment of software component 304 or hardware component 302. That is, based on the required adjustments and/or on the HSP step, the software component 304 and/or the hardware component 302 may be configured to allow adjusting or individualizing the HSP step. This is discussed in more detail with respects to Figs. 4a to 5b, wherein particular HSP devices 40 (which can be a consumer device 10 or an aggregator device 30 configured to facilitate or carry out a particular HSP step) are discussed.
  • the adjustment of the HSP step can be performed either automatically, manually or a combination thereof. That is, the aggregator device 30 can be configured to automatically adjust the HSP step based on the received or acquired specimen data. Additionally or alternatively, the aggregator device 30 can be configured to allow a manual adjustment of the HSP step.
  • a skilled person can adjust the aggregator device 30, more particularly the software component 304 and/or the hardware component 302, to perform the HSP step according to the specimen data.
  • the specimen data may be provided or displayed to the skilled person by the aggregator device 30.
  • the aggregator device 30 may comprise or be connected to a display (see Fig. 7) wherein the specimen data can be displayed to facilitate the skilled person to adjust the aggregator device 30 accordingly.
  • a list of adjustments and/or instructions of adjustments can be provided or displayed to the skilled person. That is, the aggregator device 30 can be configured to generate at least one adjustment and/or instructions for performing the adjustments based on the specimen data. The generated adjustments and/or instructions may then be output to the skilled person for guiding the skilled person to manually carry out the adjustments.
  • the software component 304 can be automatically adjusted based on the specimen data.
  • the HSP system 1 can be configured to obtain specimen data and calculate or generate processing or HSP parameters based on specimen data, that can be used to customize the processing of the specimen.
  • instruction(s) of how to perform the individualization or adjustment of the processing of the specimens may be generated. Said processing parameters and instructions for adjusting the HSP may be displayed to a practitioner for assisting or guiding the practitioner.
  • the generation of said adjustments and/or instructions to perform the adjustments can be performed by a data processing device comprised by the aggregator device 30 (e.g., see Figs. 4a to 4h) and/or by a processing device external to the aggregator device, such as, but not limited to, the central engine 20 (e.g., see Figs. 5a and 5b).
  • a data processing device comprised by the aggregator device 30 (e.g., see Figs. 4a to 4h) and/or by a processing device external to the aggregator device, such as, but not limited to, the central engine 20 (e.g., see Figs. 5a and 5b).
  • the consumer device 10 and the aggregator device 30 share similar or corresponding features.
  • the similar features with the aggregator device 30 will be only briefly introduced, while the differentiating or unique features of the consumer device 10 will be described in more detail.
  • the consumer device 10 can comprise a specimen input and output component 108.
  • the specimen input and output component 108 similar to the specimen input and output component 308 of the aggregator device 30, can be configured to facilitate inputting and outputting at least one specimen in/from the consumer device 10.
  • the consumer device 10 comprises at least one hardware component 102 and at least one software component 104.
  • the hardware component 102 and/or the software component 104 can be adjusted to carry out or facilitate a HSP step according to specimen data.
  • the hardware component 102 and the software component 104 can be adjusted to allow customization of a HSP step - as discussed for the aggregator device 30.
  • the consumer device 10 can further comprise at least one communication component 106.
  • the consumer device 10 can be formed by attaching or providing or interfacing the communication component 106 (that can be configured as a dongle) to a machine or device configured to carry out or facilitate an HSP step (similar to the aggregator device 30).
  • the communication component 306 of the aggregator device 30 can be configured for at least transmitting specimen data
  • the communication component 106 of the consumer device 10 can be configured for at least receiving specimen data.
  • the aggregator device 30 can be configured to acquire and/or aggregate and/or communicate specimen data (which the aggregator device 30 can acquire through the at least one sensor 310) and the consumer device 10 can be configured to receive specimen data.
  • This feature indicates the main difference between the aggregator device 30 and the consumer device 10. That is, in terms of specimen data acquisition the aggregator device 30 can be configured to actively obtain specimen data by utilizing at least one sensor 310, while the consumer device 10 can be configured to passively obtain specimen data through the communication component 106.
  • the aggregator device 30 can be configured to obtain specimen data using the at least one sensor device 310 and optionally to receive further specimen data through the communication component 306.
  • the consumer device 10 can be configured to receive specimen data only through the communication component 106 (as it does not comprise a sensor 310).
  • specimen data can be aggregated by the aggregator devices 30.
  • the aggregated specimen data can be shared with the other consumer devices 30 and optionally with the other aggregator devices 10.
  • the aggregator devices 30 can be configured to carry out or facilitate at least one HSP step based on the specimen data acquired by the respective sensor 310 and/or received by the communication component 306.
  • the consumer device 10 can be configured to carry out or facilitate at least one HSP step based on the specimen data received by the communication component 106.
  • the consumer device 10 more particularly a data processing device (not shown) that can be comprised by the consumer device 10 can be configured to generate at least one adjustment and/or instruction(s) of how to perform the at least one adjustment of the processing of the specimens based on the specimen data received by the communication component 106.
  • said adjustments and/or instructions can be generated externally to the consumer device 10 (e.g., by the central engine 20) and can be received by the consumer device 10 through the communication component 106.
  • the consumer device 10 can be further configured to carry out or facilitate at least one HSP step based on the received adjustments.
  • the consumer device 10 can also be configured to output said adjustments and/or instructions, e.g., to a practitioner, for guiding the practitioner.
  • the HSP system 1 can further comprise a central engine 20.
  • the central engine 20 can comprise a communication component 206.
  • the communication component 206 can be configured to at least send data to the consumer device 10 (more particularly to the communication component 106) and to at least receive data from the aggregator device 30 (more particularly from the communication component 306).
  • the central engine 20 can receive specimen data that is acquired by the at least one sensor 310 of the at least one aggregator device 30 and can provide specimen data to the at least one consumer device 10.
  • the central engine 20 can be configured to facilitate the sharing of the specimen data between the different devices of the HSP system 1.
  • the central engine 20 may be configured to receive specimen data from external sources.
  • external sources may include, an external database that can be accessed through an Internet, remote or local connection, a human operator uploading specimen data to the central engine 20 (e.g., typing the data in a keyboard), etc.
  • an application programming interface API can be configured between the central engine 20 (or in general HSP system 1) and an external and possibly remote repository (not shown), e.g., the database of the hospital wherein a specimen originates).
  • the central engine 20 can further comprise a database 201, or repository 201 or memory component 201.
  • the database 201 can be configured to store specimen data.
  • the database 201 may also comprise further information related to the HSP system 1, the clinical laboratory, accounting, sample sender facilities (i.e., originating sites) and/or the employees therein.
  • the database 201 may comprise a laboratory information database.
  • the central engine 20 can further comprise a computing unit 203.
  • the computing unit 203 can be configured to control the operations of the central engine 20 and/or calculate HSP parameters based on specimen data.
  • the central engine 20 can be partially or fully cloud-based. In such embodiments, a remote and preferably secure connection can be established between the central engine 20 and the aggregator/consumer devices 30/10.
  • the aggregator device 30 and/or the consumer device 10 can comprise a (respective) data processing unit.
  • the data processing unit can for example be configured to process data, such as, sensor or specimen data to extract specimen features, determine process parameters, customize process parameters, synchronize sample preparation among multiple samples, generate at least one adjustment, generate at least one instruction for performing the adjustment and the like.
  • Fig. 3a illustrates an exemplary configuration of the HSP system 1 configured to process at least one specimen for preparation for diagnosis, for example, in a histological or forensics laboratory. That is, the HSP system 1 is configured to perform a plurality of histotechniques to prepare microscope slides from histology samples.
  • the HSP system 1 can comprise a first aggregator device 30A, configured to carry out or facilitate the specimen accessioning step of HSP and a second aggregator device 30F configured to carry out or facilitate the diagnosis of the specimen.
  • the HSP system 1 can further comprise consumer devices 10B, 10C, 10D and 10E, configured to carry out or facilitate the dehydration, embedding, sectioning and staining step respectively.
  • the aggregator device 30A can acquire specimen data and can communicate the acquired specimen data to the central engine 20.
  • the central engine 20 can receive the specimen data, may store the specimen data and can share the specimen data with the other consumer and/or aggregator devices 10B, 10C, 10D, 10E and 30F of the HSP system 1.
  • specimen data e.g., regarding a diagnosis of the sample
  • Fig. 3b illustrates another exemplary configuration of the HSP system 1 configured to process at least one specimen for preparation for diagnosis, for example, in a histological or forensics laboratory.
  • the HSP system 1 can comprise only aggregator devices 30. More particularly, the HSP system 1 can comprise an aggregator device 30A configured to carry out or facilitate specimen accessioning, another aggregator device 30B configured to carry out or facilitate specimen dehydration, another aggregator device 30C configured to carry out or facilitate embedding step, another aggregator device 30D configured to carry out or facilitate specimen sectioning, another aggregator device 30E configured to carry out specimen slice staining and another aggregator device 30F configured to carry out or facilitate the diagnosis step 30F.
  • Specimen data can thus be collected through all the HSP steps and can be communicated to the central engine 20.
  • the central engine 20 can share the specimen data among the different aggregator devices. Thus, at any specimen processing step specimen data collected by previous step can be utilized.
  • Fig. 3c illustrates an embodiment of the HSP system 1 which generalizes the preceding embodiments of the HSP system 1. That is, in general, the HSP system 1 can comprise a plurality of devices configured for carrying out or facilitating at least one HSP step. Each of the said devices can be configured whether as an aggregator device 30 or as a consumer device 10. Furthermore, said devices can be connected to the central engine 20 such that they can receive and/or transmit data to/from the central engine 20.
  • the devices of the HSP system can be configured to communicate directly with each other, for example, through a mesh network.
  • This can be particularly advantageous as it can allow the flow or sharing of information between the different devices and between the different stages of HSP.
  • the information obtained during accessioning e.g., size of a sample
  • the dehydration step wherein it can be used to determined how to perform the dehydration for the sample.
  • Fig. 2 introduces a HSP system 1 according to one embodiment of the present invention.
  • the HSP steps can be carried out or facilitated by at least one aggregator device 30 and further optionally by at least one consumer device 10 and further optionally by at least one central engine 20.
  • Figs. 3a - 3c particular embodiments or arrangements or configurations of the HSP system 1 are illustrated.
  • the HSP system 1 can comprise a plurality of HSP devices wherein each HSP device can be configured for carrying out or facilitating a respective HSP step.
  • the HSP devices of the HSP system 1 can be configured either as aggregator devices 30 or as consumer devices 10.
  • At least one of the HSP devices can be configured as an aggregator device 30, preferably the sample accessioning device 30A can be configured as an aggregator device 30. In some other embodiments of the HSP system 1, all the HSP embodiments can be configured as aggregator devices 30, such as the embodiment depicted in Fig. 3b. In general, the HSP devices of the HSP system can be configured either as an aggregator device 30 or as a consumer device 10, as illustrated in Fig. 3c.
  • Fig. 4a depicts an embodiment of a generalized HSP device 40.
  • the HSP device 40 can be configured either as a consumer device 10 or as an aggregator device 30 (see Fig. 2).
  • the HSP device 40 can comprise a specimen input and output component 108, a hardware component 102, a software component 104 and a communication component 106. That is, the HSP device 40 if configured as a consumer device 10 can comprise any of the features of the consumer device 10 as discussed with reference to Fig. 2.
  • the HSP device 40 can comprise a specimen input and output component 308, a hardware component 302, a software component 304 and a communication component 306. That is, the HSP device 40 if configured as an aggregator device 30 can comprise any of the features of the aggregator device 30 as discussed with reference to Fig. 2.
  • the HSP device 40 can be configured to process, handle, prepare and/or treat or at least facilitate the processing, handling, preparation and/or treatment of at least one specimen. That is, the HSP device 40 can be configured to carry out or facilitate at least one HSP step.
  • at least one input sample 43 can be provided or input to the HSP device 40.
  • the at least one input sample 43 can be provided in a sample container, in a sample container in a rack or bag of sample containers, in a biopsy cassette, embedded in a harder medium, as a slice, as a slice attached to a microscope slide, etc. This depends on the HSP step that the HSP device 40 can be configured to carry out or facilitate.
  • the HSP device 40 can output the at least one sample.
  • the output sample 47 can represent a modified or processed version of the input sample 43, depending on the process that the HSP device 40 is configured to carry out or facilitate.
  • the HSP device 40 can be configured to receive raw specimen data 42. That is, the HSP device 40 can utilize the communication component 108/308 (see Fig. 2) to receive the raw specimen data 42. This is particularly advantageous when the HSP device 40 is configured as a consumer device 10. Nevertheless, in some embodiments it can be advantageous to configure the aggregator devices 30 to receive specimen data 42 (in addition to the specimen data it can extract using the sensor device 310).
  • the raw specimen data 42 refer to data directly related to specimens, that comprise or indicate at least one physical or chemical property of the specimens, such as, type of sample, number of samples, size of samples.
  • the raw specimen data 42 provided to an HSP device 40 can comprise data based on which physical and/or chemical properties of a specimen can be extracted or inferred and the respective HSP step can be performed or customized.
  • the raw specimen data 42 can comprise sensor data.
  • the raw specimen data can also comprise external data provided by other facilities (e.g., the site of origin of the sample), other procedures (e.g., surgery, biopsy, radiology), etc.
  • the raw specimen data can also comprise data indicating a history of the specimen, such as, an originating patient, procedure, facility, a disease associated with the specimen, etc. This will be further clarified with the examples discussed in Figs. 4b to 4h.
  • Raw specimen data 42 are to be distinguished from pre-processed specimen data 42' or processing parameters 42' discussed in Figs. 5a and 5b.
  • the HSP device 40 can further be configured to calculate HSP parameters (which can also be referred to as processing parameters).
  • the HSP parameters can comprise a set of parameters that can receive different values and based on the values they can receive the HSP can be correspondingly adjusted. In other words, the HSP parameters can be calculated based on the raw specimen data 42 and this can allow the HSP to be adjusted or customized according to specimen features.
  • the HSP device 40 can comprise a data processing device (not shown) that can be configured to calculate the HSP parameters based on the raw specimen data 42.
  • Such embodiments of the HSP device 40 are to be distinguished from HSP device embodiments 40' which are generally not configured or do not comprise a data processing device configured to calculate the HSP parameters, but instead they can readily receive such parameters (see Figs. 5a and 5b).
  • the HSP device 40 can further comprise a sensor device 310 configured to acquire specimen data (see Fig. 2). More particularly, the HSP device 40 can comprise at least one sensor device 310 configured to measure sensor data, at least one computing unit (not shown) configured to process the sensor data for extracting specimen data. Alternatively, the HSP device 40 may only obtain sensor data and the processing of the sensor data for extracting specimen data may be performed externally (e.g., in a cloud workstation and/or central engine 20).
  • the HSP device 40 can be configured to output data. Outputting the output data 44 can be facilitated by a communication component 108, 308 (see Fig. 2) that can be comprised by the HSP device 40.
  • the output data 44 may comprise log data, which can comprise data that record the progress of the respective HSP step.
  • the log data may comprise a process start/complete time, a process successful/fail indicator, data regarding the consumption or usage of certain materials during HSP, etc.
  • the output data 44 can comprise sensor data and/or data that can be obtained by a sensor device 310.
  • the output data 44 may also comprise the calculated HSP parameters.
  • the output data 44 can comprise a sequence of samples (e.g., their respective IDs) that were processed by the respective HSP device 40 and/or to be processed by the following HSP devices 40. The later can facilitate synchronizing the sample treatment.
  • the HSP device 40 can output the output data 44 not only when configured as an aggregator device 30, but also when configured as a consumer device 10. While the aggregator devices 10 can acquire sensor data and/or specimen data and output them, the consumer devices 10 cannot acquire sensor data. However, consumer devices 10 may output specimen data that they can receive through the communication component 108. Alternatively, the consumer devices 10 may receive sensor data through the communication component 108, process them to extract specimen data and output the extracted specimen data as output data 44.
  • Fig. 4b depicts a sample accessioning device 40A.
  • the sample accessioning device 40A is an example of the HSP device 40 discussed in Fig. 4a.
  • the sample accessioning device 40A can comprise the features discussed with respect to the HSP device 40.
  • the other examples of the HSP device 40 discussed with respect to Figs. 4c to 4h.
  • elements in the figures sharing the same number as a reference sign comprise similar features. A character is added after each number on the reference sign to distinguish among different examples or embodiments of the same component.
  • the sample accessioning device 40A can be configured to carry out or facilitate sample accessioning, for example, in a laboratory, such as histology or forensic laboratory. More particularly, sample accessioning device 40A can comprise a hardware component 102, 302 and a software component 104, 304 that can be configured to carry out or facilitate sample accessioning (see Fig. 2). As such, the sample accessioning device 40A can be configured to receive at least one specimen 43A. The reception of the at least one specimen 43A can be facilitated by the specimen input component 108, 308 (see Fig. 2). The at least one specimen can generally be provided to the sample accessioning device 40A immersed in a sample container 43A. In some embodiments, a plurality of sample containers 43A can be provided to the sample accessioning device 40A, such as a rack or bag of sample containers 43A.
  • the sample accessioning device 40A can be configured to receive raw specimen data 42A.
  • the reception of the raw specimen data 42A can be facilitated by the communication component 106, 306.
  • the raw specimen data 42A can comprise a laboratory order 42A.
  • the laboratory order can comprise a form (e.g., a standard form) that can comprise information related to the facility that the sample(s) originate, number of samples, a type of sample, a description of sample, the originating patient, type of testing or examinations requested and/or the like. From therein, information regarding the specimen 43A and/or the sample container 43A and/or the rack of specimen containers 43A can be extracted.
  • the laboratory order 42A can be provided to the sample accessioning device 40A electronically (e.g., through an application programming interface with the facility wherein the specimens originated).
  • the laboratory order 42A can be provided to the sample accessioning device 40A in a paper format, with corresponding coding, formatting and/or layout, which the sample accessioning device 40A can be configured to scan and extract information from therein.
  • the sample accessioning device 40A may comprise input devices (e.g., keyboard, touchscreen, mouse, microphone configured to facilitate reception of voice commands or the like) which can facilitate a human operator provide the laboratory order 42A to the sample accessioning device 40A.
  • the laboratory order can comprise a standardized form wherein the fields of the form comprise information regarding the input sample 43A.
  • specimen data regarding the input sample 43A may be provided in an identification label 42A attached in the sample container 43A wherein the specimen is immersed in.
  • the identification label 42A may comprise an optical label 42A.
  • the identification label 42A may comprise any machine-readable code, such as (but not limited to), a barcode, a QR code, a standardized font set like OCR and/or a human readable information.
  • the identification label 42A may additionally or alternatively comprise an RFID tag or any device, apparatus or assembly of devices configured for near field communication.
  • the identification label 42A may comprise a unique registration number of the sample container 10 which can later be correlated to a specimen.
  • the identification label can comprise information regarding the number of specimens in the sample container 10, the size of specimens in the sample specimen container 43A, a time when the samples were obtained, a duration the samples have been put in the fixation liquid, a temperature of the sample, or a combination thereof.
  • the identification label 42A may comprise information about the type of specimen and/or of a reference for billing and/or identification purposes.
  • the sample accessioning device 40A can be configured as an aggregator device 30 (see Fig. 2).
  • the sample accessioning device 40A can be equipped with at least one sensor 310 (see Fig. 2).
  • the at least one sensor 310 can comprise at least one identification label reader 310, such as, a barcode reader, QR code reader, RFID reader.
  • the sample accessioning device 40A can be configured to automatically detect the identification label 42A and extract specimen data.
  • the senor 310 can comprise at least one visual camera, stereo camera, ToF sensor, LIDAR, ultrasound sensor, at least one thermometer, at least one pH meter, at least one pressure meter, at least one device configured to measure the thickness and/or size and/or area and/or volume and/or stiffness and/or acidity and/or temperature of a sample or any combination thereof.
  • the at least one sensor 310 can be configured to capture images or scan or collect sensor data from the input sample 43A from one or more angles.
  • the collected sensor data can be processed to detect at least one sample that can be immersed in a sample container. This can allow the sample accessioning device 40A to automatically obtain specimen data, such as, a type of specimen(s), a number of specimens, a size of specimen(s) and a shape of specimen(s).
  • the sample accessioning device 40A can be configured to obtain specimen data related to the at least one input sample 43A.
  • the sample accessioning device 40A can passively obtain the specimen data.
  • the sample accessioning device 40A can receive the specimen data through the communication component 108, 308 and/or through an input device configured to facilitate a human operator input the specimen data to the sample accessioning device 40A.
  • the sample accessioning device 40A can be configured as a consumer device 10 (see Fig. 2).
  • the sample accessioning device 40A can be configured to actively extract specimen data.
  • the sample accessioning device 40A can be equipped with at least one sensor 310 (see Fig. 2).
  • the sample accessioning device 40A can be configured as an aggregator device 30.
  • the sample accessioning device 40A can utilize the at least one sensor 310 to extract specimen data from the laboratory order 42A and/or identification label 42A and/or by capturing sensor data of the input sample 43A.
  • the sample accessioning device 40A can be configured to register the at least one input sample 43A.
  • the sample accessioning device 40A can register the received input sample 43A to a laboratory information system (LIS).
  • the sample accessioning device 40A can generate a specimen case profile 44A, which can also be referred to as specimen profile 44A, based on the information that can be extracted from the laboratory order 42A and based on the sensor and/or specimen data that can be acquired by the sensor 310 and/or through the communication component 106, 306.
  • the specimen profile 44A can comprise specimen data. Said specimen data can relate to specimen features, e.g., physical and/or chemical properties of the specimen.
  • the specimen profile can comprise a routine that specifies how the specimen is to be processed (e.g., comprises HSP parameters).
  • Said HSP parameter can comprise and not limited to, a number, colour, size, type of cassettes to use, type and amount of staining, type of dehydration, etc.
  • the routine for processing the specimens may be extended or adjusted during the aggregation of specimen data.
  • a template routine for processing the corresponding sample(s) can be selected.
  • the selection of the template routine can be based on the specimen data and HSP parameters, such as, but not limited to type and number of specimens. As generally, this information can be known during the accessioning phase, the selection of the template routine can be performed automatically. For example, the selection can be performed by the data processing unit comprised by the accessioning device 40A and/or by the central engine 20.
  • the template routine may be a routine with empty process parameters that can be completed.
  • the template routine may also be a standard (or typical) routine which can be adjusted or individualized, automatically and/or manually, according to the specimen data.
  • the specimen profile 44A can be identified through a unique case number that can be assigned to it when the specimen profile 44A is generated.
  • the specimen profile 44A can comprise specimen data that were extracted during the specimen accessioning step, such as, type of samples, number of samples, size of samples, number of cassettes (see Fig. 4c) etc.
  • the specimen profile 44A can be generated for each specimen 43A or for each sample container 43A or for each rack of sample containers 43A or for a plurality of specimens or specimen containers.
  • the specimen profile 44A is created for specimens with the same origin (e.g., from the same patient, same surgical procedure, etc.).
  • a specimen profile 44A can be linked to an originating patient, medical procedure, medical facility, doctor, etc., however said information may or may not be comprised in the specimen profile 44A (for privacy reasons).
  • identification IDs are used to make the link between a specimen profile and a patient and the link may be stored in a secured database that may or may not be managed by the facility that processes the specimens. Identification IDs can also be provided on stickers or labels (i.e., identification labels) that can be attached to the containers, cassettes and/or laboratory orders.
  • Fig. 4c depicts a draining device 40G.
  • the draining device 40G can be configured to separate or at least facilitate the separation of the at least one specimen from the fixation liquid contained in an input sample container 43G.
  • the input sample container 43G to the draining device 40G can correspond to the output sample 47A of the sample accessioning device 40A. That is, a sample container can be transported from the sample accessioning device 40A to the draining device 40G.
  • the transportation can be done automatically, e.g., using robotic arms, transmission belts, actuator systems, or can be manually handled by a human operator.
  • the reception of the at least one specimen 43G can be facilitated by the specimen input component 108, 308 (see Fig. 2).
  • the output of the at least one specimen 47G can be facilitated by the specimen output component 108, 308 (see Fig. 2).
  • the specimen accessioning device 40A and the draining device 40G can be individual devices or can be partially or fully integrated in one device. This is in general valid also for the other HSP devices 40 discussed in the following, which can either be individual devices or all or some of them can be integrated in one device.
  • the separation of the at least one specimen from the fixation liquid can be performed by draining the liquid out of the sample container 43G.
  • the sample container can be enclosed on one of its sides (e.g., the top) with a container lid configured to releasably connect to a filter. Both the container lid and the filter can be releasably connected to the sample container.
  • the container lid can block both the liquid and the specimens from escaping from the sample container.
  • the filter can be configured to block only the specimens from escaping the sample container.
  • Such a sample container, container lid and filter are launched by Inveox GmbH and disclosed in the European patent application EP 17176690.0 "Pathology Assembly", which is hereby incorporated by reference.
  • the draining device 40G can be configured to open the container lid from the sample container. Such an opening may comprise a decapping, an unthreading, an unlatching process or similar. It can further be configured to rotate the sample container (after or prior the container lid removal) such that the fixation liquid can be disposed of the sample container and the sample(s) can rest on the filter.
  • the filter can further be configured to receive a cassette. More particularly, an enclosing body (generally smaller than the sample container and easier to handle, can be releasably attached to the filter forming a cassette 47G comprising the sample within. Thus, the at least one sample can be enclosed between the filter and the enclosing body of the cassette 47G.
  • the draining device 40G can be configured to receive raw specimen data 42G regarding the input sample 43G, that can comprise a case number, type of samples, number of samples size of samples, number of required cassettes or any combination thereof.
  • the case number 42G can be used by the draining device 40G to keep track of the respective specimen it is handling, such as, e.g., to confirm the successful transfer of the sample(s) into the biopsy cassette 47G.
  • the case number 42G can also be used by the draining device 40G for labelling the cassettes 47G.
  • the draining device 40G can be configured to label the cassettes 47G, wherein at least one specimen can be inserted, with the case number of the specimen(s). This can be advantageous as it can alleviate or remove the issue of mixing specimens from different patients which can lead to a misdiagnosis.
  • the draining device can further be configured to output verification or log data.
  • the verification or log data indicate a state of the draining process, e.g., whether it was performed successfully.
  • the draining device 40G can be configured as a consumer device 10 (see Fig. 2).
  • the draining device can be configured to carry out or facilitate the processing of the input sample 43G, comprising liquid disposal, cassette labelling and sample insertion into cassettes. The above processes may be handled automatically by the draining device or a human operator may assist in some tasks (e.g., sample insertion into cassettes).
  • the draining device 40G configured as a consumer device 10 can be configured to receive the raw specimen data 42G.
  • said raw specimen data 42G can correspond to the output data 44A that were output by the specimen accessioning device 40A. Said data can be transferred from the specimen accessioning device 40A to the draining device 40G either indirectly via the central engine 20 (see Fig. 2) or directly (see Fig. 6).
  • the draining device 40G can be configured as an aggregator device 30 (see Fig. 2).
  • the draining device 40G can comprise at least one sensor device 310.
  • the sensor device can be configured to collect sensor data before, during and/or after the liquid disposal from the sample container and sample insertion into cassettes. Said sensor data can be processed to obtain specimen data, such as, type of sample(s), number of samples, size of samples. Said specimen data can be output by the draining device 40 as output data 44G.
  • the output data 44G can comprise log data that can indicate the progress of the draining process.
  • the output data 44G can comprise a sequence of samples (e.g., their respective IDs) that were processed by the draining device 44G and/or to be processed by the following HSP devices.
  • Inveox GmbH has launched and disclosed a sample processing system for automatically processing a histological, pathological, medical, biological, veterinary and/or agricultural sample positioned in a sample container that is configured to be opened.
  • Said sample processing system can be particularly advantageous for handling the specimen during the specimen accessioning and liquid draining steps.
  • Said sample processing system is disclosed in the European patent application EP 18162231.7 "Sample processing system and method for automatically processing histological samples", which is hereby incorporated by reference.
  • the sample processing system and methods disclosed therein are particularly advantageous to be incorporated in the present invention, as it can significantly increase the automation of specimen accessioning, liquid disposal and transfer of specimens into cassettes.
  • the sample processing system as disclosed in EP 18162231.7 can be further configured as a HSP device 40A/G for carrying out the specimen accessioning and draining steps.
  • Fig. 4d depicts a specimen dehydration device 40B.
  • the specimen dehydration device 40B can be configured to receive an input sample 43B.
  • the reception of the at least one specimen 43B can be facilitated by the specimen input component 108, 308 (see Fig. 2).
  • the input sample 43B can generally be contained in a cassette 47G as prepared by the draining device 40G. That is, the input sample 43B to the specimen dehydration device 40B can correspond to the output sample 47G of the draining device 40G. That is, a sample can be transported from the draining device 40G to the dehydration device 40B.
  • the transportation can be done automatically, e.g., using robotic arms, transmission belts, actuator systems, or can be manually handled by a human operator.
  • the specimen dehydration device 40B can be configured to dehydrate or at least facilitate the dehydration of the received input sample 43B and output the dehydrated sample 47B.
  • the dehydrated samples 47B can be contained in cassettes 47B.
  • the output of the dehydrated sample 47B can be facilitated by the output component 108, 308 (see Fig. 2).
  • the specimen dehydration device can also be configured to perform the clearing of the specimens during which step the alcohol in the specimen (which is not miscible with wax) is replaced with a wax miscible component, such as, xylene.
  • a wax miscible component such as, xylene.
  • other method of dehydration and/or clearing can be used, while the purpose of such methods is generally dehydrating the sample and preparing it for embedding in a harder medium, such as, wax.
  • the specimen dehydration device 40B can be configured to receive raw specimen data 42B, such as a type of sample, size of sample or the like.
  • the received raw specimen data 42B can correspond to aggregated specimen data that can be output by HSP devices of preceding steps.
  • the raw specimen data 42B received by the specimen dehydration device can correspond to output data 44 that is output by the specimen accessioning device 40A and/or draining device 40G. Said data can be transferred from the preceding HSP devices 40 to the sample dehydration device 40B either indirectly via the central engine 20 (see Fig. 2) or directly (see Fig. 6).
  • the specimen dehydration device 40B can be configured to calculate specific dehydration process parameters, such as, number of required dehydrating solutions (typically alcohol solutions), concentration of each solution (e.g., concentration of alcohol), duration of immersing the specimen in each solution and/or temperature (if specimens are dehydrated through heating, e.g., with a microwave).
  • the dehydration process parameters that can be calculated by the dehydration device 40B based on specimen data 42B, depend on the dehydration method that is/will be used. This can allow the adaptation of the dehydration process to the specimen features. This is particularly advantageous when individual dehydration processes are needed, e.g., for bone marrow samples. For example, a soft tissue may require to be slowly dehydrated to avoid damage of the tissue, while harder specimens may be immersed to more concentrated dehydrating solutions and be dehydrated faster.
  • the specimen dehydration device 40B can be configured to output the output data 44B.
  • the output data 44B may comprise the calculated dehydration process parameters, such as, a type of dehydration liquid used, a concentration of the used dehydration liquid(s), a duration that the specimen(s) were immersed in each solution, the dehydrating method used (e.g., dehydration using alcohol solutions, heating, microwave, etc.), used temperature for dehydration, used pressure, etc.
  • other log data regarding the progress of the dehydration process can be output as output data 44B by the dehydration device 40B. This data can be used for qualitative analysis of the corresponding processes.
  • the output data 44B can comprise a sequence of samples (e.g., their respective IDs) that were processed by the dehydration device 40B and/or to be processed by the following HSP devices 40.
  • the dehydration device 40 can be configured to automatically handle the at least one input sample 43B during the dehydration process. That is, the dehydration device can comprise in separate containers solvents and solutes that can be combined to create dehydration solutions. A pumping system can transport the different solvents and solutes to a container wherein they can be mixed according to ratios calculated during the calculation of dehydration process parameters.
  • the dehydration device 40B can further comprise a conveyor system (e.g., a robotic arm, conveyor belt) which can transport the input sample 43B from the input component 108, 308 (see Fig. 2) to the different containers comprising the dehydration solutions.
  • the conveyor system can be configured to immerse the sample(s) in the dehydration solutions.
  • the dehydration device 40B can comprise a timer which can be used to let the samples immersed in the dehydration solutions according to the calculated durations based on the raw specimen data 42B.
  • the dehydration step may require immersing the specimen in multiple dehydration solutions with different concentrations of the dehydrant in the solution.
  • the specimen may be immersed in alcohol solutions with 75%, 85% and 95% alcohol concentration.
  • multiple solutions with respective concentrations can be mixed in separate containers.
  • the sample can be immersed in each of them.
  • one container with the dehydration solution with can be used wherein the concentration of the dehydrant(s) can be re-adjusted by adding dehydrant or solute. This can be repeated as many times as calculated during the calculation of the dehydration process parameters and can be adjusted for optimal outcomes.
  • the dehydration device 40B can be configured to drain the dehydration solutions directly on the cassette wherein the specimen is contained, wherein the cassette is configured to maintain (or to be filled by) a liquid such as the dehydration solution.
  • the cassette can be provided in a compartment wherein the dehydration solution(s) is/are flushed over the cassettes. If multiple dehydration solutions are required, the dehydration solution in the container with cassettes can be changed or alternatively the concentration of the solution can be adjusted (by adding solvent or solute).
  • the dehydration device 40B can comprise a dehydration solution concentration measurement device (e.g., alcohol concentration measurement device) that can facilitate mixing and/or regulating the dehydration solution.
  • a dehydration solution concentration measurement device e.g., alcohol concentration measurement device
  • the dehydration device 40B can be configured to dehydrate the specimens through heating, e.g., using a microwave device.
  • the dehydration device 40B can further comprise a temperature measurement device (i.e., a thermometer) that can facilitate heating the specimens at a particular temperature for optimal dehydration.
  • the dehydration step or a portion of it can be manually performed.
  • the dehydration device can be configured to facilitate the dehydration step.
  • the dehydration device can be configured to provide or display the dehydration process parameters to the practitioner.
  • the practitioner may directly create the solutions and/or immerse the samples in the respective solutions and/or prepare an oven or microwave for the upcoming dehydration process and/or preset an oven or microwave at a calculated temperature - without having to examine the specimens (as is typically done in current practices, see Fig. 1).
  • timers of the dehydration device 40B can alarm the practitioner when the specimen is ready for the next handling.
  • Fig. 4e depicts a specimen embedding device 40C.
  • the specimen embedding device 40C can be configured to receive an input sample 43C.
  • the input sample 43C can generally be contained in a cassette.
  • the input sample 43C can be dehydrated.
  • the input sample 43C can correspond to the output sample 47B of the dehydration device 40B. That is, the sample can be transported from the dehydration device 40B to the embedding device 40C for further processing.
  • the transportation can be done automatically, e.g., using robotic arms, transmission belts, actuator systems, or can be manually handled by a human operator.
  • the reception of the input sample 43C by the specimen embedding device 40C can be facilitated by the specimen input component 108, 308 (see Fig. 2).
  • the specimen embedding device 40C can be configured to carry out or facilitate the embedding step of HSP. That is, the specimen embedding device 40C can be configured to carry out or facilitate inserting specimens in an embedding medium, such as, paraffin wax. Thus, after processing the embedded specimen 47C can be output.
  • an embedding medium such as, paraffin wax
  • the specimen embedding device 40C can be configured to receive raw specimen data 42C, such as, type, size, shape and orientation of sample (before embedding).
  • the received raw specimen data 42C can correspond to aggregated specimen data that can be output by HSP devices 40 of preceding steps.
  • the raw specimen data 42C received by the specimen embedding device 40C can correspond to output data 44 that is output by the specimen accessioning device 40A and/or draining device 40G and/or specimen dehydration device 40B.
  • Said data can be transferred from the preceding HSP devices 40 to the sample embedding device 40C either indirectly via the central engine 20 (see Fig. 2) or directly (see Fig. 6).
  • the embedding device 40C may calculate the type and/or amount of embedding material that might be needed.
  • the specimen embedding device 40C can be further configured to calculate an advantageous sample orientation. It can do this by considering the received raw specimen data 42C. Depending on the raw specimen data, particularly on the type of the sample, some orientations of the sample in the embedding medium may be more advantageous than others. This is because the sample needs to oriented in such a way that particular features of the sample are visible on the slices after the sample is cut. For example, for a skin sample it may be advantageous that the sample is oriented in such a way that the skin layers are visible on the slices after cutting. Thus, based on the raw specimen data 42C the embedding device can calculate an advantageous orientation of the sample.
  • the embedding device 40C may determine the amount of movements on each of the robotic arm's degrees of freedom by calculating the required motion to position the sample from the initial orientation of the sample to the calculated advantageous orientation.
  • the initial orientation of the sample can either be extracted from received raw specimen data 42C, or by collecting sensor data. In the latter case, the embedding device 40C can be configured as an aggregating device 30 comprising at least one sensor 310.
  • the embedding device 40B can provide improved ergonomics, guidance and instructions for carrying out the embedding step.
  • the embedding device may output with the output data 44C the used type/amount of embedding material that was used during embedding. This information may be output with other log data that indicate the progress of the embedding step.
  • the embedding device 40C may output the calculated advantageous orientation of the sample in the embedding medium.
  • the output data 44C can comprise a sequence of samples (e.g., their respective IDs) that were processed by the embedding device 40C and/or to be processed by the following HSP devices 40.
  • the embedding device 40C may be configured as a consumer device 10.
  • the embedding device can be configured to receive specimen data, calculate an advantageous orientation of the specimen to be embedded, and facilitate or carry out the actual embedding of the specimen in the embedding medium.
  • the embedding device 40C may be configured as an aggregator device 30.
  • the embedding device 40C can further comprise a sensor 310 that can be configured collect sensor data of the sample before, during or after embedding it in the embedding medium. The collected sensor data may be used to extract the specimen orientation at the different stages of embedding. This can be used to verify that the specimen is embedded correctly.
  • Fig. 4f depicts a sectioning device 40D.
  • the sectioning device 40D can be configured to receive an embedded sample 43D and cut it into thin slices 47D.
  • the embedded sample 43D can be received after it is output by the sample embedding device 40C. That is, the input sample 43D to the sectioning device 40D can correspond to the output sample 47C from the embedding device 40C.
  • the transportation of the sample from the embedding device 40C to the sectioning device 40D can be done automatically, e.g., using robotic arms, transmission belts, actuator systems, or can be manually handled by a human operator.
  • the sectioning device 40D can comprise a microtome.
  • the sectioning device 40D can comprise one or more knives and can be configured to cut the embedded sample 43D into slices 47D of different thickness.
  • the sectioning device 40D can also be configured to cut the embedded sample 43D into slices using laser cutting techniques.
  • the type of knife (or laser) used and/or the slice thickness can depend on the type and size of the sample.
  • the sectioning device 40D can be configured to cut the embedded sample 43D according to different axis. The cutting axis or orientation of cutting or direction of cutting can depend on the orientation of the sample in the embedding medium.
  • the sectioning device 40D can be configured to receive raw specimen data 42D.
  • the received raw specimen data 42D can correspond to aggregated specimen data that can be output by HSP devices 40 of preceding steps.
  • the raw specimen data 42D received by the specimen dehydration device can correspond to output data 44 that is output by the specimen accessioning device 40A and/or draining device 40G and/or dehydration device 40B and/or embedding device 40C.
  • Said data can be transferred from the preceding HSP devices 40 to the sectioning device 40D either indirectly via the central engine 20 (see Fig. 2) or directly (see Fig. 6).
  • the raw specimen data 42D can comprise the type of sample, size of sample and orientation or position of sample in the embedding medium. Processing the raw specimen data 42D the sectioning device 40D can calculate a type of knife, a slice thickness, a speed, an angle, a force to use during sectioning of the embedded sample, how many cuts to make, how much embedding material to cut before reaching to the sample (based on the position of the sample in the embedding material), where/how to cut to obtain a preferable slice with all features required (e.g., a slice with a maximum surface) and/or any combination thereof. Said calculated data can be output by the sectioning device as output data 44D. In addition, log data indicating the progress of the sectioning process can be output by the sectioning device. Furthermore, the output data 44C can comprise a sequence of samples (e.g., their respective IDs) that were processed by the sectioning device 40D and/or to be processed by the following HSP devices 40.
  • the sectioning device can be configured to automatically perform the sectioning step. That is, the embedded sample 43D can be provided to the sectioning device (for example, in the input component 108, 308, see Fig. 2) as well as the raw specimen data 42D.
  • the sectioning device 40D can than automatically or manually be triggered to calculate sectioning parameters to use during cutting (as discussed above).
  • the sectioning device 40D can further be automatically or manually triggered to automatically be configured with the calculated parameters and perform the slicing of the embedded sample.
  • some tasks of the sectioning step may be manually performed.
  • the sectioning device 40D calculates the sectioning parameters (as discussed above), it can display such parameters to a practitioner. The practitioner can then configure the sectioning device according to the parameters (e.g., mount the required knife and set the thickness). After that, the slicing can be performed. Alternatively, the calculated sectioning parameters can be output to the practitioner for guiding the practitioner to perform the sectioning step.
  • the sectioning device can generally be configured as a consumer device 10. However, in some embodiments it can be advantageous to configured the sectioning device 40D as an aggregator device. For example, the sectioning device 40D may collect sensor data of the embedded sample 43D to determine and/or verify the orientation of the sample in the embedded medium. Alternatively or additionally, the sectioning device 40D configured as an aggregator device may collect sensor data of the slices 47D to determine the shape and/or size of each slice. The extracted information may then be output as output data 44D.
  • Fig. 4g depicts a de-wrinkling and sliding device 40H.
  • the de-wrinkling and sliding device 40H can be configured to receive slices 43H and de-wrinkle them.
  • the input slices 43H can correspond to the output slices 47D from the sectioning device 40D. That is, during the sectioning step, the slices may be wrinkled. The wrinkles can be removed by immersing the slices into warm water.
  • the de-wrinkling and sliding device 40H can be configured to carry out or facilitate immersing the slices 43H into warm water.
  • the de- wrinkling and sliding device 40H may comprise a container with warm water.
  • the de-wrinkling and sliding device 40H may comprise a conveyor system may transport the slices 43H into a container with warm water.
  • a human operator may handle the slices 43H into the container with warm water.
  • the de-wrinkling and sliding device 40H can comprise a processing unit configured to calculate a duration of immersing the samples in the warm water for de-wrinkling and/or a temperature of the water.
  • the parameters for the de- wrinkling process (e.g., duration and temperature) generally depend on the input sample 43H, such as the type of sample, size (or area) of sample, thickness of the slices and other similar features of the input sample 43H.
  • the de-wrinkling and sliding device 40H can be configured to receive raw specimen data 42H, which can comprise the type of sample, size of sample, thickness of slice and other similar features of the input sample 43H. Based on the raw specimen data the de-wrinkling and sliding device 40H can calculate at least one parameter for the de-wrinkling process, such as, the duration of the process, the temperature of the water, the amount of water.
  • the de-wrinkling and sliding device 40H can additionally comprise a heating element and or a temperature sensor.
  • the de-wrinkling and sliding device 40H can be configured to utilize said device to automatically set the temperature of the water used for de-wrinkling.
  • the de-wrinkling and sliding device 40H can be configured to calculate a number of slides required. That is, after de-wrinkling the slices may be attached to a respective microscope slide 47H. Generally, a specimen can be cut into multiple slices. Some or all of them may be required for diagnosis. Thus, some or all of them need to be attached to a microscope slide to be prepared for diagnosis.
  • the de-wrinkling and sliding device 40H can be configured to calculate a required number of slides based on the raw specimen data 42H, such as, the number of slices 43H received by the de-wrinkling and sliding device 40H.
  • the amount of slides can be determined during the specimen accessioning step, when the specimen profile is generated, and this information can be extracted from the raw specimen data 42H.
  • the calculated or extracted number of slides can be displayed or provided to a practitioner, such that the practitioner can know ahead of the sliding process the number of slides that is required for the process. This alleviates the need of the practitioner to count the number of slices in order to determine the number of slides require. Present technology makes said information available to the practitioner. Additionally, this facilitates the automation of such a step.
  • the de-wrinkling and sliding device 40H can be configured to calculate an advantageous orientation of orienting the slices in the slide. This is particularly advantageous when multiple slices can be loaded in a slide.
  • the calculated advantageous orientation can be output by the de-wrinkling and sliding device 40H, preferably to instruct a practitioner during slide loading.
  • the de-wrinkling and sliding device 40H can output the output data 44H, which can comprise log data indicating the progress of the de-wrinkling and sliding process, such as, number of used slides, temperature of water, duration of de-wrinkling.
  • the de-wrinkling and sliding device 40H may be configured as a consumer device 10.
  • the de-wrinkling and sliding device 40H can comprise the features discussed above.
  • the de-wrinkling and sliding device 40H can be configured as an aggregator device 30.
  • the de-wrinkling and sliding device 40H can comprise the above features and in addition it can comprise a sensor device 310.
  • the sensor device 310 can be configured to capture sensor data of the input sample 43H and/or slides 47H and/or sensor data during the de-wrinkling and/or sliding process. The captured sensor data can be used to detect certain errors during the processing the input samples 43H.
  • the captured sensor data of the input sample 43H can be used to extract raw specimen data, such as, the area of the slices 43H (which can be used to calculate de-wrinkling parameter), number of slices 43H (which can be used to calculate number of required slides).
  • the captured sensor data of the slides 47H (with the slices attached therein) can be used to determine the size of the slices in each slide, the position of the slices in the respective slices, etc.
  • the information extracted from sensor data can be output by the de-wrinkling and sliding device 40H.
  • the de-wrinkling and sliding device 40H can be further configured to label the slides 47H.
  • the slides 47H can comprise a slide labelling section 471 which can be configured to receive at least one label.
  • the slide labelling section 471 can receive the at least one label by sticking and/or writing (e.g., via a laser) and/or printing a label therein.
  • the label can comprise human and/or machine-readable information. It can comprise identification information (e.g., specimen case number) and/or other specimen data that can preferably assist the next processing steps (e.g., staining and diagnosis).
  • the label may comprise and/or indicate the case number, slide number, barcode for staining, an area and/or thickness of a slice in the slides 47H and/or a position of the slice in the slide 47H - which information can assist the staining process.
  • Fig. 4h depicts a staining device 40E.
  • the staining device 40E can be configured to receive slides 43E (which can be the output slides 47H from the de-wrinkling and sliding device 40H) and facilitate or carry out staining the slices comprised in the input slides 43E.
  • Staining the slices can make structures of the specimen (or cells of specimens) more visible, hence easier to diagnose particularly under microscope. More particularly, different specimen origins need different staining, e.g., bones compared to skin samples.
  • the staining device 40E can be configured to carry out or facilitate staining the slides 43E.
  • the staining device 40E can be configured to automatically carry out or facilitate the staining step.
  • the staining device 40E may comprise one or more stain pouring components that can be positioned on top of each input slide 43E to apply stain or a spray of stain and/or solvent on an area of interest, preferably comprising a part or all the slice.
  • the staining device 40E can be configured to comprise for each type of stain a respective stain pouring component.
  • the staining may be applied by submerging the slides into a container with the respective stain.
  • the staining device may comprise a conveyor or pick- and-place (e.g., robotic arm) system configured to handle the slides 43E and submerge them into one or more containers with stain.
  • the staining may be performed manually.
  • it can be advantageous to know the type and amount of stain and solvent required to stain a respective slide 43E and/or the timing used for staining, i.e., how long the stain and solvent is applied to the slides.
  • using the proper type and amount of stain(s) can be advantageous as it may make structures of the specimen more visible, avoid creation of artefacts and lead to more accurate diagnosis results. Overall, it can contribute on make the process more accurate and efficient.
  • the staining device 40E can comprise a processing unit that can be configured to calculate staining process parameters, such as, a type of stain, amount of stain, duration of staining and/or the like.
  • the staining parameters can depend on the features of the respective slide to be stained.
  • the staining device can be configured to receive raw specimen data 42E, such as the type of sample, size (or area) of slice, position of the slice on the slide.
  • the received raw specimen data 42E may be processed for calculating staining process parameters.
  • a practitioner profile may be considered during the calculation of the staining process parameters.
  • the slides 43E can be stained according to the practitioner's preferences - hence leading to better diagnosis results.
  • the staining device 40E can output the output data 44E, which can comprise log data indicating the progress of staining process, such as, staining process parameters.
  • the staining device 40E may be configured as a consumer device 10. In such embodiments, the staining device 40E can comprise the features discussed above. Alternatively, the staining device 40E can be configured as an aggregator device 30. In such embodiments, the staining device 40E can comprise the above features and in addition it can comprise a sensor device 310.
  • the sensor device 310 can be configured to capture sensor data of the input sample 43E and/or of the stained slides 47E and/or sensor data during the staining process. Alternatively or additionally, the sensor device 310 can be configured to read a label of the slides 43E. The captured sensor data can be used to detect certain errors during the staining of the slides 43E.
  • the captured sensor data of the input sample 43E can be used to extract raw specimen data, such as, the area, number, type and/or thickness of the slices in the slides 43E (which can be used to calculate the type and/or amount of stain needed).
  • the captured sensor data of the input slides 43E can be used to determine the position of the slices in the respective slides 43E.
  • the staining device can be configured to apply the stain in the particular position wherein the slice is positioned within the slide 43E. It will be noted, that even when the staining device 40E, is configured as a consumer device 10, it can still be advantageous to further configure it to apply the stain at a particular position with the slide.
  • the staining device 40E configured as a consumer device 10 can obtain the position of the slice within the slide by receiving it from raw specimen data 42E.
  • the de-wrinkling and sliding device 40H may be configured to obtain said position and communicate it to the staining device 40E.
  • the specimens can be treated by other devices or processes related to histology, such as, immunostaining devices, sequencing devices or other molecular diagnostic devices, which devices and processes can be used to treat the sample or slices of the sample before or after the initial diagnosis based on the clinical background information of a patient.
  • devices or processes related to histology such as, immunostaining devices, sequencing devices or other molecular diagnostic devices, which devices and processes can be used to treat the sample or slices of the sample before or after the initial diagnosis based on the clinical background information of a patient.
  • FIG. 5a depicts a schematic of an alternative embodiment of an HSP device 40'.
  • HSP device 40' depicts a schematic of an alternative embodiment of an HSP device 40'.
  • the HSP device 40' can be configured to directly receive pre-processed sample data and/or process parameters. As such, the HSP device 40' may not be configured to calculate process parameters. Instead, the process parameters may already be calculated externally to the HSP device 40' (e.g., in the central engine 20, see Fig. 2) and be provided to the HSP device 40'. Thus, the HSP device 40' can be configured to facilitate or carry out the adjustment of the process (or of its hardware and/or software components) according to the process parameters, and to facilitate or carry out the processing of the sample according to the received process parameters.
  • FIG. 5b This is further illustrated in Fig. 5b, with the example of a sectioning device 40D'.
  • the sectioning device 40D' depicted in Fig. 5b directly received process parameters, such as, type of knife, slice thickness, number of slices and/or direction of cut.
  • Fig. 6 illustrates an alternative embodiment of the HSP system 1 depicted in Fig. 2.
  • the aggregator device 30 and consumer device 10 can be configured to communicate directly with each other.
  • the other features of the HSP system 1 discussed with respect to Fig. 2 can also be comprised by the HSP system 1' and are omitted herein for the sake of brevity.
  • Fig. 7 illustrates an alternative embodiment of the HSP system 1, further comprising an output device 50.
  • the output device 50 can be configured to output data.
  • the output device 50 may comprise a display 50 configured to output visual data, such as, text, images and/or video.
  • the output device may comprise a speaker 50 configured to output audio data.
  • the output device 50 may also be configured to output or indicate data/information/indications through haptic feedback.
  • the output device 50 can be configured to output any of specimen data, raw specimen data, pre-processed specimen data, HSP parameters, HSP log data, specimen case profile, specimen processing routine, HSP adjustments, instructions/illustrations for adjusting a HSP device and/or a HSP step, pictures of the specimen/slides or consumables and the like.
  • the output device 50 may receive said data to output from the central engine 20, aggregator device 30 and/or consumer device 10.
  • the output device 50 can be particularly advantageous as it can be configured to output data to a practitioner.
  • specimen data may readily be available for the practitioner on the output device 50. This alleviates the disadvantages of the current practices, as partially discussed with reference to Fig. 1, and can lead to a more accurate, time-efficient, ergonomic and safe specimen processing in a clinical, histological and/or forensics laboratory.
  • the output device 50 may comprise a user device 50 (or user token 50) that can be handled by the practitioner.
  • the mobile device 50 can be a smartphone, laptop, tablet, personal computer, workstation, wearable device, and/or similar devices. It can also be a customized device 50 configured with the features of the output device 50.
  • the output device 50 can alternatively or additionally be distributed among the different aggregator devices 30 and/or consumer device 10 and/or central engine 20.
  • the output device 50 attached to a respective device 30, 10, 20 can output specimen data (and/or other data) tailored to the respective device.
  • the output device 50 can be attached to a sectioning device 40D and can output sectioning parameters, such as a type of knife and slice thickness for sectioning a particular sample.
  • said output device attached to the sectioning device 40D can output instructions on how to configure the sectioning device 40D for slicing a particular sample.
  • the output device may comprise a touchscreen 50 (or more generally may integrate an input device to allow the practitioner to input commands therein). This can allow the practitioner to select what to output on the output display 50.
  • the output device 50 can be particularly advantageous when one or more HSP steps are performed manually by a practitioner.
  • the output device 50 e.g., a mobile display, a wearable
  • the output device 50 can readily provide instructions and/or HSP parameters to the practitioner.

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Abstract

A specimen data aggregating system and method configured to aggregate specimen data during a histological sample preparation (HSP) of at least one sample, comprising at least one aggregating component configured to acquire specimen data related to the at least one sample, at least one memory device configured to receive and store the acquired specimen data, and at least one processing unit configured to process the acquired specimen data to generate at least one adjustment for adjusting the HSP of the at least one sample.

Description

Methods and systems for histological sample preparation
Field of invention
[0001] The current invention generally relates to methods and systems for handling specimens, such as biopsy specimens.
Introduction
[0002] Many medical procedures require tissue samples to be analysed for various reasons. Several steps for handling and analysing such specimens (or tissue samples) are known in the art. For example, microscopic anatomy is the branch of biology that studies the microscopic anatomy of biological tissue, organs and cells - commonly referred to as histology. Histopathology is the branch of histology (hereinafter used as an inclusive term for microscopic anatomy techniques) that includes the examination and microscopic identification and study of diseased tissue.
[0003] The specimens are usually transferred from an originating body, for example, during surgical pathology or autopsy, to a specialised centre, such as a histology laboratory, where different analyses, such as microscopic examination, are possible not only for the size and the quality of the instruments, but also for the qualification and experience of the analysing specialists (e.g., histotechnicians, histotechnologists).
[0004] Nowadays, biopsy samples taken from human tissue are extracted and placed into a cavity filled with a fixative, such as formalin, during a histology process often referred as fixation. This is generally done to maintain the morphological structure of the sample specimen. The sample can then be placed into a prepared envelope and shipped to the histological laboratory for further processing.
[0005] Specimens received for histological examination may come from a number of different sources. They range from very large specimens or whole organs to tiny fragments of specimens. For example, the following are some of the specimen types commonly received in a histopathology lab. Excision specimens also called surgical biopsies, where whole organs or affected areas are removed. Furthermore, incisional biopsy specimens are to be analysed, where specimen is removed for diagnosis from within an affected area, punch biopsies, where punches are used to remove a small piece of suspicious specimen for examination, shave biopsies, where small fragments of specimen are "shaved" from a surface (usually skin), curetting, where specimen is removed in small pieces from the lining of the uterus or cervix by a curette. This is a surgical instrument for removing dead specimen, growths, etc., from the walls of certain body cavities, core biopsies, where a small specimen sample is percutaneously removed using a special needle sometimes through the skin.
[0006] Specimens are usually received immersed in a fixative or preservative but sometimes arrive untreated and must be immediately fixed. Fixation of the sample at the beginning of the process can be a step in preparing specimens for microscopic examination. It's objective is to prevent decay and preserve cells and specimens in an analysable state. It does this by preventing autolysis. The sooner fixation is initiated following separation of a specimen from its blood supply the better the result can be. The most popular fixing agent is formaldehyde, usually in the form of a phosphate-buffered solution, in general referred to as formalin. Ideally specimens should be fixed by immersion in formalin for six to twelve hours before they are processed.
[0007] Larger specimens may require further dissection to produce representative pieces from appropriate areas. For example, multiple samples may be taken from the excision margins of a tumour to ensure that the tumour has been completely removed. In the case of small specimens, the entire specimen may be processed. The specimens selected for processing will be placed in cassettes in the form of small and perforated baskets and batches will be attached onto a specimen processor for embedding. During the embedding process the tissue sample is embedded in a harder medium, such as paraffin wax, epoxy, acrylic, agar, gelatine, celloidin and other types of waxes. In case of pre-frozen specimens, a water-based embedding medium can be used, e.g., a water-based glycol.
[0008] Once the tissue has been embedded into the wax, it will be cut into sections, in a process called sectioning, often achieved using a machinery called microtome. During the process of cutting the slices with the microtome wrinkles may be introduced into the cut section, which can be removed by floating the sections into warm water for de-wrinkling. After that, the slices are attached on a microscope slide.
[0009] Further, the wax can be removed (i.e., deparaffinization), such that the sliced tissue sections can be stained. Staining, such as, with Haematoxylin (H) and Eosin (E), make the cellular and nuclear structures of the tissue more visible under the microscope. The tissue between the microscopic slides can then be observed using a microscope by skilled persons, such as, histologists.
[0010] The above-described processes can be referred to as histotechniques or histological sample preparation (HSP), with the individual stages referred to as histological sample preparation steps. In simple words, the histotechniques or histological sample preparation aim at preparing specimens, such as, biopsy or forensic samples, for examination under microscope. An important step of histotechniques is the recording of newly received specimens in the histology laboratory, referred to as specimen accessioning. Before specimens are accepted by a laboratory, the identification or labelling and accompanying documentation will be carefully checked, all details recorded and specimen tracking commenced. During this step, patient information and history, medical data (e.g., medication), other relevant information (e.g., pictures during patient treatment), along with a description of the site of origin is obtained. Usually, the specimen containers are associated with documents, such as, a laboratory order, comprising such information. The received specimens are assigned with a unique identifier that will identify each specimen for each patient. It is vital that patient or research specimens are properly identified and the risk of wrong results, e.g., mix-ups, minimized.
[0011] A further important step of specimen handling is gross-examination, also referred to as grossing, which involves a careful examination and description of the specimen that will include the appearance, the number of pieces and their dimensions. Grossing also includes removing the specimen from the container and placing them in small cassettes which hold the tissue samples for further processing.
[0012] Normally, specimen accessioning and gross examination will be conducted by a specialised person, such as, a pathologist, pathology assistant or pathology resident, generally referred to as a practitioner. That is, the skilled person would receive the specimen, usually contained in a specimen container, read the information comprised in the accompanied documents, read the labels assigned to the container, examine the specimens, implement a description of the specimen. Further the pathologist, pathology assistant, or pathology resident, can open the containers, drain the fixation liquid inside the containers during a draining process, pick the tissue samples, place them in cassettes and label the cassettes accordingly to be able to at least identify the samples placed therein. This process requires careful handling from the practitioner, as the fixation liquid and/or the tissue sample may be dangerous to the health of the practitioner.
[0013] While the procedure may be satisfactory to some extent, it has certain drawbacks and limitations. As an initial matter, such a process may be prone to errors or mistakes. The practitioner may mislabel the cassettes or mix the containers and/or the accompanied documents which can cause wrong results, e.g., due to mix-ups. Further, having a pathologist, pathology assistant or pathology resident performing such tasks can be time inefficient. Further still, it will be understood that the described processes may require a skilled person become in contact with dangerous substances, such as the fixation liquid, and pathologic samples which can be a hazard to the health of the skilled person.
[0014] In this regard, advancements in technology are continuously contributing in automating histological tissue preparation in a histology lab. For example, Inveox GmbH has disclosed and launched a machine for automatically processing multiple sample containers. Such a machine is disclosed in the application EP 18162231.7. [0015] Although, part of the histological sample preparation in a histology laboratory is handled by machines, still a practitioner is required to synchronize the process, decide on what histotechniques to carry out, decide on how or what parameters to use for carrying out the histotechniques, manually extract and/or register information related to the specimens and manually carry out the information flow between the different HSP steps. For example, the practitioner may be required to determine what strainers to use, how long to apply the stain, how long to let the samples dehydrate, what solutions or temperature to use during dehydration, chose colour and number of biopsy cassettes to label, acquire the information to provide in the labels, etc.
[0016] Thus, current practices, though satisfactory to some extent, are associated with certain disadvantages.
[0017] As an initial matter, current practices generally miss synchronizing the flow of the histological sample preparation (i.e., in what order to treat samples), wherein samples arriving in a laboratory are generally handled in a first-come-first-served (FCFS) manner (or even randomly handled). Sometimes, a practitioner may synchronize the flow of the histological sample preparation. However, this may be time consuming, error prone, and ineffective. Firstly, due to the large number of steps required to process the samples it may not be possible for the practitioner to optimally synchronize the histological sample preparation steps, e.g., determine a sequence of specimens to process. A non-optimal synchronization of the histological sample preparation (e.g., FCFS) steps may lead to the increase of waiting times before a sample is processed in a respective step. For example, samples A and B may require the same processing steps. Sample C may require different and longer processing steps compared to A and B. Thus, it can be more efficient to process A and B before C. Alternatively, if C is very fragile and cannot tolerate long waiting times, then the processing of C before A and B can be more optimal. Such decisions are currently generally taken by the practitioner, or not taken at all as the samples may be treated in a first-come-first-served or random manner.
[0018] In addition, current practices require the practitioner to deal with the specimen data (i.e., information flow). That is, during HSP information related to a sample from preceding steps may be required in following steps. For example, the type of the sample - said information generally acquired at accessioning phase - may be required during dehydration phase to determine how to perform the dehydration. In current practices, the carry or flow of said information in the given example from the accessioning phase to the dehydration phase is typically carried out by the practitioner - e.g., handling the laboratory order and/or other documents related to the sample and extracting required information from therein at each stage. However, this may be error prone (the practitioner may obtain the wrong documents or may misidentify the information in the document) and time consuming (the practitioner needs to read and identify in the documents the required information or alternatively examine the sample directly). As such, the time from tissue accessioning in the lab to tissue diagnosis is increased. As the sample ages, artefacts may be developed in the specimen and this may decrease accuracy of the diagnosis and may even render the specimen un-diagnosable.
[0019] Additionally still, depending on the type, size, age or other features of the specimen it can be advantageous or even necessary that they are treated according to a corresponding process. For example, a sample may arrive non fixated and thus may require immediate fixation while another sample may arrive in the lab already fixated and does not required fixation. A large sample may require more time for dehydration compared to a small sample. A skin sample may require a different sectioning technique compared to a blood vessel sample. Currently, the tissue samples are generally processed in the same manner which can lead to suboptimal and/or inferior results. In some instances, limited customization to the histological sample preparation steps are done - however, they generally require a practitioner to examine or identify the sample and/or handle the laboratory order and/or other documents related to the sample and extract required information from therein and then correspondingly either manually carry out the process or configure a machinery for carrying the process.
[0020] All in all, present techniques although satisfactory to some extent, have certain drawbacks and limitations - particularly regarding the synchronization of histological sample preparation steps, flow of information related to the samples and customization of said steps depending on specimen features and especially for molecular analysis, where information gets lost and/or destructed through the current processes. As discussed, current techniques are time inefficient, which translates to aging of specimens and the introduction of artefacts in the specimen. This will increase the likelihood of a misdiagnosis or can even render the specimen undiagnosable. As further discussed, current techniques either uniformly treat samples, which may not be advantageous for the diagnosis, or inefficiently require a practitioner to extract sample features (e.g., by examination of the sample) and correspondingly customize the process. Thus, further solutions in this regard can contribute on increasing efficiency and accuracy of specimen processing.
Summary
[0021] The present invention solves or at least alleviates the above discussed disadvantages of current techniques, at least by providing devices, system and methods that deal with specimen data aggregation and flow within the different stages of the histological sample preparation. [0022] In a first embodiment, the present invention discloses a specimen data aggregating system (referred in the following as "the system" or "HSP system") configured to aggregate specimen data during a histological sample preparation (referred in the following for the sake of brevity by the abbreviation HSP) of at least one sample (interchangeably referred to as specimen or tissue), which can be a histological, pathological, forensic pathology, medical, biological, veterinary, surgical, anatomical, agricultural tissue and/or biopsy sample.
[0023] The system comprises at least one aggregating component configured to acquire specimen data related to the at least one sample, at least one memory device configured to receive and store the acquired specimen data and at least one processing unit configured to process the acquired specimen data to generate at least one adjustment for adjusting the HSP of the at least one sample. The acquired specimen data can relate to specimen features, such as, visual, physical, chemical and/or medical property of a sample. The generated adjustment can relate to guidance, instructions, parameters, configurations and the like for performing the HSP or a part of the HSP.
[0024] For example, a generated adjustment can be "Dehydrate sample <X> using a <90%> concentrated alcohol solution for <45> minutes. Next dehydrate sample <X> using <absolute alcohol> for <60> minutes. Next clear the sample using <Xylene> for <60> minutes", wherein the parameters indicated between "<>" can be parameters calculated by the processing unit during the generation of the adjustments.
[0025] Generating adjustments based on specimen data can be particularly advantageous as it allows the customization (i.e., adjustment) of HSP to each specimen or group of specimens. As illustrated by the above example, the dehydration and clearing step is customized according to the properties of sample(s) <X>.
[0026] As thus, instead of having a practitioner examine a sample and then utilize his/her knowledge and experience to determine on certain parameters for performing the HSP of said sample, or instead of having all the samples undergo a standard HSP, the present invention allows for the acquisition of specimen data and customization of the HSP of a sample according to the properties of the sample.
[0027] In some embodiments, the at least one processing unit can be configured to process the acquired specimen data and generate a sequence of samples to undergo HSP. For example, the at least one processing unit can output a sequence of unique IDs assigned to each sample (or group of samples). Said sequence can be configured to indicate on which order to process the samples. Thus, the sequence of samples can comprise a prioritization of samples and/or an order of samples to undergo HSP. [0028] In some embodiments, the at least one processing unit can be configured to calculate the throughput of a sequence of samples and to generate the sequence with the highest throughput. That is, different samples may require different times on different HSP stages or steps. This and the order of processing the samples can affect the total time for performing the HSP. As such, the processing unit can be configured determine which sequence results in the lowest total time for performing the HSP of the samples in the sequence.
[0029] Additionally or alternatively, the at least one processing unit can be configured to calculate at least one waiting time for each of the at least one samples and the at least one processing unit can be configured to generate the sequence based on the at least one calculated waiting time. That is, due to overloading one or more samples may have to wait before undergoing HSP or a particular HSP step. Waiting times can increase the age of the samples which can cause sample degradation. As such, it can be advantageous to minimize the waiting times for a sample and/or the average waiting time for a plurality of samples and/or the longest waiting time among a plurality of waiting times. The at least pone processing unit can thus be configured to generate a sequence that can minimize the waiting times for a sample and/or the average waiting time for a plurality of samples and/or the longest waiting time among a plurality of waiting times.
[0030] In general, the generation of the sequence of sample to undergo HSP may involve an optimization problem. The optimization problem may have one or more parameters to optimize, such as, throughput, waiting time, etc. In addition, the optimization problem may have one or more constraints, such as, a minimum throughput to be reached, a maximum tolerable (total) waiting time for one or more or each sample, etc. By solving the optimization problem, the at least one processing unit can generate a sequence which provides an optimal (or nearly optimal) order for processing the samples.
[0031] In some embodiments, the at least one generated adjustment comprises the generated sequence.
[0032] Configuring the at least one processing unit to generate the sequence, as discussed, can be advantageous as it can allow for an efficient synchronization of HSP of multiple samples. That is, the processing of multiple samples over multiple HSP stages can be efficiently synchronized. This can increase the throughput of sample preparation and/or increase time efficiency and/or decrease sample waiting times.
[0033] Alternatively or additionally, the at least one processing unit may generate a deadline for the at least one sample to undergo HSP. The said deadline can indicate the maximum waiting time for a sample (before undergoing HSP or a particular HSP step). The said deadline can also indicate the latest time that the sample can undergo HSP (or a particular HSP step) after which the sample is expected to fully degrade and become undiagnosable. The deadline can be generated as part of the adjustments.
[0034] In some embodiments, the HSP comprises a plurality of steps (as it is typical for the current histotechniques) and the at least one processing unit can configured to process the acquired specimen data to generate a selection of the plurality of steps for the at least one sample to undergo. In other words, the at least one processing unit generates a "plan" that indicates which steps of the HSP will a sample undergo. The selection of the plurality of steps can be generated as part of the adjustments.
[0035] In some embodiments, the at least one processing unit can be configured to process the acquired specimen data to generate a timetable comprising at least one entry, wherein each entry can indicate for at least one specimen, an HSP step and a time for the at least one specimen to undergo the HSP step. The timetable can be considered as a generalized version of the sequence of samples discussed above and as such it can be generated in a similar manner as discussed for the sequence of samples. The timetable can be generated as part of the adjustments.
[0036] In some embodiments, the at least one processing unit can be configured to calculate at least one HSP parameter. The HSP parameter can be configured to receive a plurality of values and based on the values it receives the HSP of the at least one sample can be correspondingly adjusted. At least one HSP parameter can relate to a particular HSP step. For example, each HSP step can comprise one or more customizable HSP parameters. For example, the dehydration step may comprise <duration>, <type and amount of dehydrating solution> as HSP parameters. Based on the values that the HSP parameters of a HSP step receive, the HSP step can be correspondingly be performed or customized. For example, a first dehydration step can comprise the parameters <30 min>, <alcohol solution>, <80% concentrations <sample X>, <order I> and a second dehydration step can comprise the parameters <45 min>, <alcohol solutions <~100% concentration >, <sample X>, <order Ils Based on the above HSP parameters that can be generated by the at least one processing unit based on specimen data (of sample X), the dehydration step of sample X is performed by first immersing it for 30 minutes in an 80% alcohol solution, and then for 45 minutes in a ~100% alcohol solution.
[0037] The HSP parameters can relate to or comprise a duration parameter that can indicate a duration of performing an action during the HSP of the sample. Some nonlimiting examples of the duration parameter can be a duration of dehydration step, a duration of letting the at least one sample immersed in a solution, e.g., alcohol solution, a duration of heating the at least one sample, a duration of freezing the at least one sample, a duration of letting the at least one sample immersed in a stain, e.g., Haematoxylin and Eosin, a duration of letting the at least one sample immersed in warm water, e.g., for de- wrinkling. It will be understood that the above list is not meant as an exhaustive or limiting list of duration HSP parameters, but instead it is an illustrative one for increasing clarity.
[0038] The HSP parameter can relate to or comprise a selection among different options, such as, a selection of different available processes, methods, compounds (e.g., solutions), devices, and/or machines that can be utilized during the HSP of the at least one sample. Some non-limiting examples can be a selection of at least one fixation liquid, e.g., formalin, a selection of at least one sample dehydration method, a selection of at least one dehydrating agent, e.g., alcohol solution, a selection of at least one clearing agent, e.g., xylene, a selection of at least one embedding material, e.g., wax, a selection of at least one sectioning device, e.g., a type of knife, a selection of at least one sectioning method, e.g., angle of cutting, force of cutting, direction of cutting, number of "waste" cuttings, slice thickness, number of cuts or slices, a selection of staining agents, e.g., Haematoxylin and Eosin. It will be understood that the above list is not meant as an exhaustive or limiting list of selections, but instead it is an illustrative one for increasing clarity.
[0039] In some embodiments, the HSP parameter can relate to or comprise an/a amount/number of a compound or components or parts or devices or processes or machines that can be utilized during the HSP of the at least one sample. Some non-limiting examples can be a number of samples, an amount of fixation liquid, a number of sample containers, a number of biopsy cassettes, an amount of dehydrating agent, an amount of clearing agent, an amount of embedding material, an amount of stain, a number of slices, a number of microscope slides. It will be understood that the above list is not meant as an exhaustive or limiting list of amount/number parameters, but instead it is an illustrative one for increasing clarity.
[0040] In some embodiments, the HSP parameter can relate to or comprise a position and/or orientation (i.e., pose) parameter that can indicate a position and/or orientation of at least one sample. Some non-limiting examples can be a position and/or orientation of at least one sample in a sample container, a position and/or orientation of at least one sample in a biopsy cassette, a position and/or orientation of at least one sample in an embedding medium, a position and/or orientation of at least one slice of sample in a sample, a position and/or orientation of at least one slice of a sample in a microscope slide. It will be understood that the above list is not meant as an exhaustive or limiting list of position and/or orientation parameters, but instead it is an illustrative one for increasing clarity.
[0041] The calculation (i.e., generation) of the at least one HSP parameter can be advantageous as they can allow adjusting the HSP process. More particularly, they can allow tailored or particular adjustments to the HSP step. For example, by calculating a duration HSP parameter of the dehydration step that particular step can be adjusted. In other words, the HSP parameters allow for more granular adjustments to the HSP step. As such, the degree (or detailedness) of adjusting the HSP based on the sample properties can be increased.
[0042] In some embodiments, the at least one aggregating component can be configured to acquire specimen data related to the at least one sample during a first HSP step. A first HSP step. Furthermore, the aggregating component can be configured to communicate (i.e., transmit) the acquired specimen data. Further still, the system can be configured to provide the specimen data acquired at the first HSP step to a second HSP step. The at least one processing unit can further be configured to process the specimen data acquired at a first HSP step to generate at least one adjustment for adjusting a second HSP step. It will be noted that herein first and second are used to differentiate a first HSP step from a second HSP step and not the order of the said HSP steps.
[0043] As such, the system can be configured to facilitate information flow, more particularly the flow of specimen data, among different stages of the HSP. This can be advantageous as data acquired during a first HSP step can be used at a second HSP step. As such, a higher utilization of the specimen data can be achieved. Instead of acquiring the specimen data at each HSP step, some or all the specimen data acquired in earlier HSP steps can be used at later HSP steps and/or to calculate adjustments related to the later HSP steps. Furthermore, some HSP steps may cause changes to the sample and such may cause information loss. For example, the dehydration step may change the colour of the sample and thus the original colour information can be lost. Specimen data acquired in earlier steps can be beneficial in such cases. For example, colour information acquired before the dehydration step can be used to retrieve original colour information at a later stage (e.g., during diagnosis the original colour may be needed by the pathologist).
[0044] In some embodiments, the HSP of at least one sample can comprise one or more HSP steps. Some non-limiting examples of HSP steps can be a sample fixation step, a specimen accessioning step, a fixation liquid disposal step, a specimen gross-examination step, a specimen dehydration step, a specimen clearing step, a specimen embedding step, a specimen de-paraffinization step, a specimen sectioning step, a specimen de-wrinkling step, a specimen sliding step, a specimen staining step, a specimen cover-slipping step, a specimen diagnosis step, a specimen molecular analysis step. It will be understood that the above list is not meant as an exhaustive or limiting list of HSP steps, but instead it is an illustrative one for increasing clarity. In general, the HSP step can refer to any of the histotechniques and generally relate to steps, processes and/or techniques that prepare a sample for histological examination (e.g., under microscope).
[0045] In some embodiment, the at least one aggregating component can be configured to acquire specimen data that relate to a physical and/or chemical property of the at least one sample. That is, different properties or features of the sample can be extracted from or comprised in the specimen data. In some embodiments, the at least one aggregating component can be configured to acquire specimen data related to the at least one sample during a HSP step and wherein the acquired specimen data facilitate the HSP step and/or an adjustment of the HSP step. That is, the at least one generated adjustment can facilitate adjusting a step of the HSP of the at least one sample.
[0046] In some embodiments, the at least one aggregating component can comprise at least one sensor device that can be configured to acquire sensor data related to the sample. The sensor data can indicate the specimen data. That is, specimen data can be extracted from the sensor data. Furthermore, a sensor processing unit can be configured to process the sensor data to extract specimen data. That is, the aggregating component can be configured to acquire specimen data by comprising a sensor device that collects sensor data and wherein the sensor data can be processed to extract the specimen data. In some embodiments, the sensor processing unit can be integrated to the sensor device. Alternatively or additionally, the at least one processing unit can comprise the sensor processing unit. That is, the processing of the sensor data to extract specimen data can be performed by a sensor processing unit integrated to the sensor device or alternatively/additionally by the at least one processing unit.
[0047] The sensor device can be configured to measure a physical and/or chemical property of the at least one sample. Thus, the sensor device can allow assessing or extracting features of the sample. The at least one sensor device may comprise at least one visual camera, at least one stereo camera, at least one depth sensor, e.g., a time-of- flight (ToF) sensor, at least one laser sensor, e.g., a light detection and ranging (LIDAR) sensor, at least one ultrasound scanner, at least one projectional radiography scanner, at least one computed tomography scanner, at least one fluoroscope, at least one thermometer, at least one pH meter, at least one pressure meter, at least one device configured to measure a thickness and/or size and/or area and/or volume and/or stiffness and/or acidity and/or temperature of the at least one sample and/or any combination thereof. It will be understood that the above list is not meant as an exhaustive or limiting list of sensor devices, but instead it is an illustrative one for increasing clarity.
[0048] In some embodiments, the aggregator component can comprise at least one communication component configured to transmit and/or receive data, preferably, the acquired specimen data and/or the at least one generated adjustment. The communication component is particularly advantageous as it can facilitate specimen data sharing (i.e., flow) between different HSP steps or devices.
[0049] In some embodiments, the system may comprise a plurality of aggregating components that can be provided at different stages of the HSP (i.e., at different HSP steps). The aggregating components can comprise at least one corresponding communication component and can be interconnected with each other, e.g., through a mesh network. One or more of the aggregating components can be configured to acquire specimen data through a sensor device. The acquired specimen data can then be communicated to the other aggregating components in the network. In other words, a complete information flow or sharing between the different aggregating components (at different HSP steps) of the system can be achieved.
[0050] In some embodiments, the system further comprises at least one HSP device that can be configured to facilitate the HSP of the at least one sample. In some embodiments, the HSP device can facilitate one HSP step, e.g., a staining device facilitating the staining step of the HSP. In some embodiments, the HSP device can facilitate multiple HSP steps, generally, multiple consecutive HSP steps, e.g., a sample processing device configured to perform sample accessioning, fixation liquid disposal and insertion of samples into biopsy cassettes. In some further embodiments, the HSP device may fully automate the at least one HSP step. However, in some embodiments, the HSP device may assist on performing at least one HSP step.
[0051] The HSP device can comprise the aggregator component. As such, the HSP device can comprise the features and advantages of the aggregator component, as discussed above. That is, the HSP device can be configured not only for facilitating the HSP process, but in addition it can be configured to aggregate specimen data.
[0052] The HSP device can comprise a device and/or machine that is configured to carry out or facilitate at least one HSP step. That is, the HSP device can comprise at least one hardware component configured to handle at least one sample, at least one software component comprising instructions for performing the HSP or an HSP step of at least one sample and/or at least one input/output component configured to facilitate the HSP device receiving and outputting at least one sample. Said components are particularly advantageous to configured the HSP device for performing or facilitating at least one HSP step.
[0053] In some embodiments, the aggregator component can be configured as a dongle or attachment device. In such devices, the HSP device can be configured as a modular device. For example, the aggregator component can be attached to a one device or machine that is configured to carry out or facilitate at least one HSP step. Thus, the features of the said device or machine can be extended to include the specimen data aggregating feature. This can be advantageous, as the same aggregator component can be shared among different HSP steps or devices. For example, after sectioning step and during dewrinkling, sliding and staining step, the sample is sliced. The same aggerating component can thus be used on the above steps, e.g., for scanning the slices of the sample. [0054] In some embodiments, a first HSP device can be configured to acquire specimen data and transmit the acquired specimen data. For example, the first HSP device can comprise at least one aggregator component and wherein the said aggregator component can comprise at least one sensor device configured to acquire specimen data and at least one communication component configured to transmit the acquired specimen data.
[0055] Furthermore, a second HSP device can be configured to receive the specimen data transmitted by the first HSP device. For example, the second HSP device can comprise an aggregator component and wherein the aggregator component comprises at least one communication component configured to receive specimen data. Thus, specimen data acquired by the first HSP device are shared with and re-used by the second HSP device.
[0056] Further still, the second HSP device can be configured to transmit specimen data. For example, the second HSP device can comprise an aggregating component that can comprise a communication component configured to transmit data. A third HSP device can be configured to receive the specimen data transmitted by the second HSP device and/or the first HSP device. Thus, the specimen data can be communicated over one or more hops among the HSP devices.
[0057] Thus, as illustrated by the above embodiments, the system may comprise a plurality of HSP devices that can be interconnected with each other, e.g., through a mesh network. One or more of the HSP devices can be configured to acquire specimen data through a sensor device. The acquired specimen data can then be communicated to the other HSP devices in the network. In other words, a complete information flow or sharing between the different HSP device can be achieved.
[0058] Some non-limiting examples of the HSP devices can be at least one accessioning device, at least one draining device, at least one dehydration device, at least one embedding device, at least one sectioning device, at least one de-wrinkling and sliding device, at least one staining device, at least one diagnosis device, at least one postdiagnosis device. It will be understood that the above list is not meant as an exhaustive or limiting list of HSP devices, but instead it is an illustrative one for increasing clarity.
[0059] In some embodiments, the HSP devices can be adjusted or customized according to one of the generated adjustments. Thus, the HSP device can process at least one sample according to one or more customized or adjusted HSP steps. The adjustment of a HSP device may comprise an adjustment of a hardware component of the HSP device (e.g., changing a cutting knife for use during sectioning, preparation of an alcohol solution for use during dehydration, etc.), an adjustment of the software component of the HSP device (e.g., the setting of a duration parameter) and/or an adjustment of the input/output component of the HSP device. Such adjustments can be performed automatically or manually.
[0060] In some embodiments, the HSP device can be configured to receive pre-generated adjustments. For example, the adjustments can be generated by the at least one processing unit external to the HSP device.
[0061] Alternatively, the HSP device can be configured to receive specimen data, or raw specimen data. The HSP device can comprise a data processing device that can be configured to process specimen data and generate at least one adjustment. The data processing device can for example be at least one of the processing unit that is comprised internally by the HSP device.
[0062] In some embodiments, the software component of the HSP device can comprise machine-readable instructions and the data processing device can be configured to execute a routine according to the machine-readable instructions for controlling the hardware components of the HSP device.
[0063] In some embodiments, the system can comprise a central engine. The central engine can comprise a database, wherein the database can be configured to store specimen data. For example, the database can comprise the at least one memory device. Furthermore, the central engine can comprise at least one computing unit. The computing unit may comprise the at least one processing unit configured to process the acquired specimen data to generate at least one adjustment for adjusting the HSP of the at least one sample. That is, in some embodiments, the processing of the specimen data can be centralized. In such embodiments, it can further be advantageous to provide a data connection between the central engine and the at least one aggregating component. Thus, the central engine can comprise at least one communication component configured to communicate with the at least one aggregating component. That is, the central engine can receive specimen data. Furthermore, the central engine can transmit the central data. In addition, the central engine can transmit the generated adjustments based on the specimen data (e.g., to a HSP device or output device).
[0064] In other words, the calculation of adjustments can be done in a distributed or centralized manner. When performed in a distributed manner, a data processing device may process specimen data and generate adjustments at different HSP steps. Said data processing device mat be integrated with the at least one aggregating component and/or with at least one HSP device. Alternatively, when performed in a centralized manner the processing of the specimen data and the generation of adjustments may be carried out by the central engine. [0065] In some embodiments, the at least one processing unit can be further configured to generate at least one instruction for performing the at least one adjustment. The instructions can comprise text, image(s), video(s), audio, diagram(s), flowchart(s), indication(s), haptic feedback, or any combination thereof. That is, the instructions can comprise guidance information on how to perform at least one adjustment of the HSP.
[0066] In some embodiments, the system can further comprise at least one output device configured to output textual, graphical, visual, haptic data or any combination thereof.
[0067] In some embodiments, the output device can be configured to output specimen data and/or the at least one generated adjustment and/or instructions for performing the at least one generated adjustment. Preferably, the output device can be configured to output data with a predefined layout, in a graphical form or any combination thereof.
[0068] In some embodiments, the output device can be configured to communicate with at least one aggregating component, processing unit, HSP device, aggregating device, consumer device, central engine or any combination thereof.
[0069] In some embodiments, the output device can comprise at least one display, at least one mobile display, at least one wearable device, at least one mobile phone, at least one smartphone, at least one tablet, at least one smart watch, at least one workstation, at least one mobile workstation, at least one computer, at least one mobile computer, at least one headphone or any combination thereof. It will be understood that the above list is not meant as an exhaustive or limiting list of output devices, but instead it is an illustrative one for increasing clarity.
[0070] In some embodiments, the at least one processing unit can be configured to process external specimen data to generate the at least one adjustment. That is, the at least one processing unit may be configured to consider external specimen data, in addition to specimen data. The external specimen data can generally comprise data related to a sample that were generated externally to the system, such as, an external facility, e.g., the sample originating facility, and/or data related to a sample that can be stored in an external database (e.g., a database of the sample originating facility). For example, the external specimen data can comprise medical, clinical or history data (or any combination thereof). Said data may relate to a sample, patient, disease or sample originating facility or any combination thereof. Considering the external specimen data can provide a more complete description of the sample to the system and thus, a better adjustment of the of the HSP of the sample can be performed.
[0071] The external specimen data can be acquired by any of the at least one aggregating component, central engine or communication component. This can be achieved by establishing a wired and/or wireless connection (which can be local or remote) with an external database that comprises the external specimen data. The transmission of the external specimen data can be facilitated by configuring an application programming interface (API) between the at least one aggregating component, central engine or communication component and the external database.
[0072] In some embodiments, the external specimen data are stored in the at least one memory device.
[0073] In some embodiments, the external specimen data can be provided to a laboratory order that can correspond to one or more samples. The laboratory order can comprise the external specimen data in a standard format or layout, such as, in a tabular format. The laboratory order may comprise a physical sheet comprising textual information and/or electronic data that can be transmitted, such as, though a wired (e.g., USB) or wireless (e.g., NFC) connection. In some embodiments, a practitioner may input the external specimen data. For example, the practitioner may input the external specimen data using an input device (e.g., keyboard and mouse) causing the external specimen data to be stored at the at least one memory device.
[0074] That is, in some embodiments, the system can further be configured to consider external specimen data. The external specimen data can be combined with the specimen data and can be treated in a similar manner as discussed in relation to the specimen data.
[0075] In some embodiments, at least one processing unit can be configured to generates for at least one specimen or group of specimens a corresponding case profile. That is, a case profile can correspond to one specimen. However, in some instances a case profile may also correspond to a group of specimens.
[0076] In some embodiments, a data processing device of an HSP device, such as, of a specimen accessioning device, can be configured to generate for at least one specimen or group of specimens a corresponding case profile.
[0077] The case profile can comprise specimen data. That is, the case profile may facilitate aggregating (i.e., accumulating) specimen data, as the acquired specimen data can be accumulated in a case profile.
[0078] The case profile may also comprise external specimen data.
[0079] In some embodiments, the case profile can comprise an HSP template that can indicate a standard HSP wherein one or more HSP parameters can be adjusted. That is, for one or a group of specimens initially a standard HSP procedure can be selected. This selection can be done automatically or manually, e.g., during specimen accessioning step, and can be based on specimen data and/or external specimen data. The HSP template or the standard HSP procedure can comprise one or more HSP parameters. In general, the HSP template can be modified (i.e., adjusted). One manner of doing this is by setting or adjusting at least one HSP parameter.
[0080] The case profile may comprise the at least one generated adjustment. As such, the case profile can accumulate a detailed information related to the sample and the HSP steps performed on the sample.
[0081] In some embodiments, the system can be configured to output the acquired specimen data, external specimen data and/or the at least one generated adjustment to a practitioner during the diagnosis step. This can assist the pathologist with the diagnosis of the sample.
[0082] In some embodiments, the system can comprise an output device configured to data to a practitioner during the diagnosis step.
[0083] In some embodiments, the diagnosis of a first sample can be feedback to the at least one processing unit and the at least one processing device can be configured to process said feedback and generate at least one adjustment for the HSP of a second sample.
[0084] In some embodiments, the at least one adjustment generated based on the diagnosis of the first sample, can comprise a cleaning of at least one HSP device. This can particularly be advantageous, when a sample is diagnosed with a dangerous and contiguous disease.
[0085] In some embodiments, the at least one sensor device can comprise at least one visual camera.
[0086] In some embodiments, the at least one sensor device can comprise at least one depth sensor.
[0087] In some embodiments, the at least one sensor device can comprise at least one thermometer.
[0088] In some embodiments, the at least one sensor device can comprise at least one pH meter.
[0089] In some embodiments, the at least one sensor device can comprise at least one three-dimensional scanner.
[0090] In some embodiments, the at least one sensor device can comprise at least one projectional radiography scanner. [0091] In some embodiments, the at least one sensor device can comprise at least one computed tomography scanner.
[0092] In some embodiments, the at least one sensor device can comprise at least one fluoroscope.
[0093] In some embodiments, the at least one sensor device can be configured to measure at least on of: a thickness, size, area, volume, stiffness, acidity and temperature of the at least one sample.
[0094] In some embodiments, the at least one sensor device can comprise at least one DNA sequencer. The skilled person will appreciate that DNA refers to the deoxyribonucleic acid.
[0095] In some embodiments, the at least one sensor device can comprise at least one immunostaining device. The skilled person will appreciate that an immunostaining device is a device that uses an antibody-based method to detect a particular protein or another antibody in a sample.
[0096] In some embodiments, the at least one sensor device can comprise at least one immunohistochemistry staining device. The skilled person will appreciate that immunohistochemistry, abbreviated as IHC, is used in histology to detect the presence of specific protein markers that can assist with diagnosis. IHC can involve the process of selectively identifying proteins in a sample by exploiting the principle of antibodies binding specifically to antigens or another antibody in biological tissues. For example, a detective marker (e.g., horseradish peroxidase (HRP) or fluorescent substance) can be used to label a primary antibody which can then bind to particular proteins in the sample. This is generally referred to as a direct immunohistochemistry method. In another example, an unlabeled primary antibody, which can also be referred to as a first antibody, may bind to a target protein in the sample. In such implementations, a second labeled antibody may be used which can react with the primary antibody.
[0097] In some embodiments, the at least one sensor device can comprise at least one mass spectrometry analyzer.
[0098] In a second embodiment, the present invention discloses a corresponding specimen data aggregating method comprising any of the features discussed above in correspondence to any of the system embodiment. For the sake of brevity, a detailed discussion, as provided in the above and below for the system embodiments, is omitted. Numbered Embodiments
Below, system embodiments will be discussed. These embodiments are abbreviated by the letter "A" followed by a number. Whenever reference is herein made to system embodiments, these embodiments are meant.
Al. A specimen data aggregating system configured to aggregate specimen data during a histological sample preparation (HSP) of at least one sample, comprising: at least one aggregating component configured to acquire specimen data related to the at least one sample; at least one memory device configured to receive and store the acquired specimen data; at least one processing unit configured to process the acquired specimen data to generate at least one adjustment for adjusting the HSP of the at least one sample.
It will be noted that the terms, specimen data and sample data are used interchangeably.
A2. The system according to any of the preceding embodiments, wherein the at least one processing unit is configured to process the acquired specimen data to generate a sequence of samples to undergo HSP.
A3. The system according to the preceding embodiment, wherein the sequence of samples comprises a prioritization of at least one sample and/or an ordering of at least two samples to undergo HSP.
A4. The system according to any of the 2 preceding embodiments, wherein the at least one processing unit is configured to calculate a throughput (i.e., number of samples that undergo the HSP per unit time) of a sequence of samples and the processing unit is configured to generate the sequence of samples with the highest throughput.
A5. The system according to any of the 3 preceding embodiments, wherein the at least one processing unit is configured to calculate at least one waiting time for at least one sample and the at least one processing unit is configured to generate the sequence of samples based on the at least one calculated waiting time.
A6. The system according to any of the 4 preceding embodiments, wherein the at least one generated adjustment comprises the generated sequence of samples.
A7. The system according to any of the preceding embodiments, wherein the at least one processing unit is configured to process the acquired specimen data to generate a deadline for at least one sample to undergo HSP. A8. The system according to the preceding embodiment, wherein the at least one generated adjustment comprises the generated deadline.
A9. The system according to any of the preceding embodiment, wherein the HSP comprises a plurality of steps and the at least one processing unit is configured to process the acquired specimen data to generate a selection of the plurality of HSP steps for at least one sample to undergo.
A10. The system according to the preceding embodiment, wherein the generated adjustment comprises the selection of the plurality of HSP steps.
All. The system according to any of the preceding embodiments, wherein the at least one processing unit is configured to process the acquired specimen data to generate a timetable comprising at least one entry, wherein each entry indicates for at least one specimen, an HSP step and a time for the at least one specimen to undergo the HSP step.
A12. The system according to the preceding embodiment, wherein the at least one generated adjustment comprises the generated timetable.
A13. The system according to any of the preceding embodiments, wherein the at least one processing unit is configured to calculate at least one HSP parameter.
A14. The system according to any of the preceding embodiment, wherein an HSP parameter is configured to receive a plurality of values and based on the values it receives the HSP of the at least one sample is correspondingly adjusted.
A15. The system according to any of the preceding embodiments, wherein at least one HSP parameter is related to at least one HSP step and wherein the HSP parameter is configured to receive a plurality of values and based on the values it receives the HSP step is correspondingly adjusted.
A16. The system according to any of the preceding embodiments, wherein an HSP parameter relates to a duration of performing an action, such as, at least one of: a duration of dehydration step, a duration of letting the at least one sample immersed in a solution, e.g., alcohol solution, a duration of heating the at least one sample, a duration of freezing the at least one sample, a duration of letting the at least one sample immersed in a stain, e.g., Haematoxylin and Eosin, a duration of letting the at least one sample immersed in warm water, e.g., for dewrinkling.
A17. The system according to any of the preceding embodiments, wherein an HSP parameter relates to a selection of a process/compound/device that is utilized during the HSP of the at least one sample, such as, at least one of: a selection of at least one fixation liquid, e.g., formalin, a selection of at least one sample dehydration method, a selection of at least one dehydrating agent, e.g., alcohol solution, a selection of at least one clearing agent, e.g., xylene, a selection of at least one embedding material, e.g., wax, a selection of at least one sectioning device, e.g., a type of knife, a selection of at least one sectioning method, e.g., angle of cutting, force of cutting, direction of cutting, number of "waste" cuttings, slice thickness, number of cuts or slices, a selection of staining agents, e.g., Haematoxylin and Eosin.
A18. The system according to any of the preceding embodiments, wherein an HSP parameter relates to an amount/number of a compound/component/part that is utilized during the HSP of the at least one sample, such as, at least one of: a number of samples, an amount of fixation liquid, a number of sample containers, a number of biopsy cassettes, an amount of dehydrating agent, an amount of clearing agent, an amount of embedding material, an amount of stain, a number of slices, a number of microscope slides.
A19. The system according to any of the preceding embodiments, wherein an HSP parameter relates to a position and/or orientation of at least one sample, such as, at least one of: a position and/or orientation of at least one sample in a sample container, a position and/or orientation of at least one sample in a biopsy cassette, a position and/or orientation of at least one sample in an embedding medium, a position and/or orientation of at least one slice of sample in a sample, a position and/or orientation of at least one slice of a sample in a microscope slide.
A20. The system according to any of the preceding embodiments, wherein the at least one aggregating component is configured to acquire specimen data related to the at least one sample during a first HSP step.
A21. The system according to any of the preceding embodiments, wherein the at least one aggregating component is configured to communicate the acquired specimen data.
A22. The system according to any of the preceding embodiments, wherein the system is configured to provide the specimen data acquired at a first HSP step to a second HSP step.
A23. The system according to any of the preceding embodiments, wherein the at least one processing unit is configured to process the specimen data acquired at a first HSP step to generate at least one adjustment for adjusting a second HSP step.
A24. The system according to any of the preceding embodiments, configured to aggregate specimen data during a histological sample preparation (HSP) of at least one sample, wherein the HSP comprises at least one step.
A25. The system according to the preceding embodiment, wherein a step of the HSP (i.e., HSP step) of at least one sample comprises at least one of the: a sample fixation step, a specimen accessioning step, a fixation liquid disposal step, a specimen gross-examination step, a specimen dehydration step, a specimen clearing step, a specimen embedding step, a specimen de-paraffinization step, a specimen sectioning step, a specimen de-wrinkling step, a specimen sliding step, a specimen staining step, a specimen cover-slipping step, a specimen diagnosis step, a specimen molecular diagnosis step.
A26. The system according to any of the preceding embodiments, wherein the at least aggregating component is configured to acquire specimen data that relate to a physical and/or chemical property of at least one sample.
A27. The system according to any of the preceding embodiments, wherein the at least one aggregating component is configured to acquire specimen data related to at least one sample during a step of the HSP of the at least one sample.
A28. The system according to any of the preceding embodiments, wherein the at least aggregating component is configured to acquire specimen data related to at least one sample that facilitate a step of the HSP of the at least one sample. A29. The system according to any of the preceding embodiments, wherein the at least one aggregating component is configured to acquire specimen data related to the at least one sample that facilitate the adjustment of a step of the HSP of the at least one sample.
A30. The system according to any of the preceding embodiments, wherein the at least one generated adjustment facilitates adjusting a step of the HSP of the at least one sample.
A31. The system according to any the preceding embodiments, wherein the at least one aggregating component comprises at least one sensor device (310).
A32. The system according to the preceding embodiment, wherein the at least one sensor device (310) is configured to acquire sensor data related to the sample.
A33. The system according to the preceding embodiment, wherein a sensor processing unit is configured to process the sensor data to extract specimen data.
A34. The system according to any of the 3 preceding embodiments, wherein a sensor processing unit is integrated to the sensor device (310).
A35. The system according to any of the 2 preceding embodiments, wherein the at least one processing unit comprises the sensor processing unit.
A36. The system according to any of the 5 preceding embodiments, wherein the at least one sensor device (310) is configured to measure a physical and/or chemical property of the at least one sample.
A37. The system according to any of the 6 preceding embodiments, wherein the at least one sensor device (310) comprises at least one of the: at least one visual camera, at least one stereo camera, at least one depth sensor, e.g., a time-of-flight (ToF) sensor, at least one laser sensor, e.g., a light detection and ranging (LIDAR) sensor, at least one ultrasound scanner, at least one projectional radiography scanner, at least one computed tomography scanner, at least one fluoroscope, at least one thermometer, at least one pH meter, at least one pressure meter, at least one device configured to measure a thickness and/or size and/or area and/or volume and/or stiffness and/or acidity and/or temperature of the at least one sample.
A38. The system according to any of the preceding embodiments, wherein the aggregating component comprises at least one communication component (106, 306) configured to transmit and/or receive data, preferably, the acquired specimen data and/or the at least one generated adjustment.
A39. The system according to any of the preceding embodiment, further comprising at least one HSP device (40) configured to facilitate the HSP of at least one sample, such as, at least one HSP step of at least one sample.
A40. The system according to the preceding embodiment, wherein the HSP device (40) comprises at least one aggregating component.
A41. The system according to any of the 2 preceding embodiments, wherein the HSP device comprises a device and/or machine that is configured to carry out or facilitate at least one HSP step of at least one sample, said device and/or machine comprising at least one of at least one hardware component (102, 302) configured to handle at least one sample, at least one software component (104, 304) comprising instructions for performing the HSP or an HSP step of at least one sample, at least one input/output component (108, 308) configured to facilitate the HSP device (40) receiving and outputting at least one sample.
A42. The system according to any of the preceding embodiments, wherein at least one aggregating component is configured as an attachment or dongle that is configured to be attached or interfaced with at least one device or machine that is configured to carry out or facilitate at least one HSP step.
A43. The system according to any of the 4 preceding embodiments, wherein a first HSP device (40-1) is configured to acquire the specimen data and transmit the acquired specimen data.
A44. The system according to the preceding embodiment, wherein the first HSP device (40-1) comprises at least one aggregating component and wherein the said aggregating component comprises at least one sensor device (310) configured to acquire specimen data and at least one communication component (306) configured to transmit the acquired specimen data. A45. The system according to any of the 2 preceding embodiments, wherein a second HSP device (40-11) is configured to receive the specimen data transmitted by the first HSP device (40-1).
A46. The system according to the preceding embodiment, wherein the second HSP device (40-11) comprises an aggregating component and wherein the aggregating component comprises at least one communication component (106, 306) configured to receive specimen data.
A47. The system according to any of the 2 preceding embodiments, wherein the second HSP device (40-11) is configured to transmit specimen data.
A48. The system according to the preceding embodiment, wherein a third HSP device (40-III) is configured to receive the specimen data transmitted by the second HSP device (40-11) and/or the first HSP device.
A49. The system according to any of the preceding embodiments, wherein the at least one HSP device (40) comprises at least one of at least one accessioning device (40A), at least one draining device (40G), at least one dehydration device (40B), at least one embedding device (40C), at least one sectioning device (40D), at least one de-wrinkling and sliding device (40H), at least one staining device (40E), at least one diagnosis device, at least one post-diagnosis device.
A50. The system according to any of the preceding embodiments, wherein the HSP device (40) can be configured to be adjusted according to one of the generated adjustments.
A51. The system according to any of the preceding embodiments and with the features of embodiment A41, wherein at least one hardware component (102, 302) and/or at least one software component (104, 304) and/or at least one input/output component (108, 308) of the HSP device (40) can be adjusted according to one of the generated adjustments.
A52. The system according to any of the 13 preceding embodiments, wherein the at least one HSP device (40) comprises a data processing device. A53. The system according to the preceding embodiment and with the features of embodiment A41, wherein the software component (104, 304) comprises machine- readable instructions and the data processing device is configured to execute a routine according to the machine-readable instructions for controlling the hardware components (102, 302).
A54. The system according to any of the 2 preceding embodiments, wherein the data processing device the HSP device (40) is configured to process specimen data to generate at least one adjustment for adjusting the HSP of the at least one sample.
A55. The system according to any of the 3 preceding embodiments, wherein the at least one processing unit comprises the data processing device.
A56. The system according to any of the preceding embodiments, wherein at least one HSP device (40) is configured as an aggregator device (30).
A57. The system according to any of the preceding embodiments, wherein an aggregator device (30) comprises at least one hardware component (302) configured to handle the at least one sample.
A58. The system according to any of the preceding embodiments, wherein an aggregator device (30) comprises at least one software component (304) comprising instructions for controlling the hardware component (302).
A59. The system according to any of the preceding embodiments, wherein an aggregator device (30) comprises at least one input/output component (308) configured to facilitate the aggregator device (30) receiving and outputting at least one sample.
A60. The system according to any of the preceding embodiments, wherein an aggregator device (30) comprises at least one aggregating component.
A61. The system according to the preceding embodiment, wherein the at least one aggregating component comprised by the aggregator device (30) comprises a sensor device (310).
A62. The system according to any of the 2 preceding embodiments, wherein the at least one aggregating component comprised by the aggregator device (30) comprises a communication component (306).
A63. The system according to any of the preceding embodiments and with the features of embodiment A43 and A56, wherein the first HSP device (40-1) is configured as an aggregator device (30). A64. The system according to any of the preceding embodiments, wherein at least one HSP device (40) is configured as a consumer device (10).
A65. The system according to any of the preceding embodiments, wherein a consumer device (10) comprises at least one hardware component (102) configured to handle the at least one sample.
A66. The system according to any of the preceding embodiments, wherein a consumer device (10) comprises at least one software component (104) comprising instructions for controlling a hardware component (102).
A67. The system according to any of the preceding embodiments, wherein a consumer device (10) comprises at least one input/output component (108) configured to facilitate the consumer device (10) receiving and outputting at least one sample.
A68. The system according to any of the preceding embodiments, wherein a consumer device (10) comprises the at least one aggregating component.
A69. The system according to any of the 2 preceding embodiments, wherein the at least one aggregating component comprised by the consumer device (10) comprises a communication component (106).
A70. The system according to any of the preceding embodiments and with the features of embodiments A45 and A64, wherein the second HSP device (40-11) is configured as a consumer device (10) or as an aggregator device (30).
A71. The system according to any of the preceding embodiments and with the features of embodiment A48 and A56/A64, wherein the third HSP device (40-III) is configured as an aggregator device (30) or as a consumer device (10).
A72. The system according to any of the preceding embodiments, wherein the system further comprises a central engine (20).
A73. The system according to the preceding embodiment, wherein the central engine (20) comprises a database (201) configured to store specimen data.
A74. The system according to the preceding embodiment, wherein the database (201) comprises the at least one memory component.
A75. The system according to any of the 3 preceding embodiments, wherein the central engine (20) comprises at least one computing unit (203). A76. The system according to the preceding embodiment, wherein the computing unit (203) comprises the at least one processing unit.
A77. The system according to any of the preceding embodiment, wherein the central engine (20) comprises at least one communication component (206).
A78. The system according to any of the preceding embodiments, wherein the communication component (206) is configured to communicate with at least one aggregating component.
A79. The system according to any of the preceding embodiments, wherein the at least one processing unit generates instructions for performing the at least one adjustment.
A80. The system according to the preceding embodiment, wherein the instructions comprise text, image(s), video(s), audio, diagram(s), flowchart(s), indication(s), haptic feedback, or any combination thereof.
A81. The system according to any of the preceding embodiments, wherein the system further comprises at least one output device (50) configured to output textual, graphical, visual, haptic data or any combination thereof.
A82. The system according to the preceding embodiment, wherein the output device (50) is configured to output specimen data.
A83. The system according to any of the two preceding embodiments, wherein the output device (50) is configured to output specimen data with a predefined layout, in a graphical form or any combination thereof.
A84. The system according to any of the 2 preceding embodiments, wherein the output device (50) is configured to output the at least one generated adjustment.
A85. The system according to any of the 3 preceding embodiments, wherein the output device (50) is configured to output at least one instruction for performing the at least one adjustment.
A86. The system according to any of the preceding embodiments, wherein the output device (50) is configured to communicate with at least one aggregating component, processing unit, HSP device (40), aggregating device (30), consumer device (10), central engine (20) or any combination thereof.
A87. The system according to any of the preceding embodiment wherein the output device comprises at least one of: at least one display, at least one mobile display, at least one wearable device, at least one mobile phone, at least one smartphone, at least one tablet, at least one smart watch, at least one workstation, at least one mobile workstation, at least one computer, at least one mobile computer, at least one headphone.
A88. The system according to any of the preceding embodiments, wherein the at least one processing unit is configured to process external specimen data to generate the at least one adjustment and wherein the external specimen data comprise medical, clinical and/or history data that relate to a sample, patient, a disease, sample originating facility or any combination thereof.
A89. The system according to the preceding embodiments, wherein the external specimen data are generated externally to the system, such as, by an external facility, for example, the originating facility wherein the sample(s) is/are obtained.
A90. The system according to any of the 2 preceding embodiments, wherein the external specimen data are stored in an external database.
A91. The system according to any of the 3 preceding embodiments, wherein the at least one aggregating component is configured to receive the external specimen data.
A92. The system according to any of the 4 preceding embodiments, wherein a central engine (20) is configured to receive the external specimen data.
A93. The system according to any of the 5 preceding embodiments, wherein a communication component (106, 206, 306) is configured to receive the external specimen data.
A94. The system according to any of the 6 preceding embodiments, wherein the at least one memory component stores the external specimen data.
A95. The system according to any of the 7 preceding embodiments, wherein the external specimen data are provided in a laboratory order of at least one sample.
A96. The system according to any of the preceding embodiments, wherein at least one processing unit is configured to generate for at least one specimen or group of specimens a corresponding case profile.
A97. The system according to any of the preceding embodiments, wherein a data processing device of a HSP device (40), such as, of a specimen accessioning device, is configured to generate for at least one specimen or group of specimens a corresponding case profile. A98. The system according to any of the 2 preceding embodiments, wherein the case profile comprises specimen data.
A99. The system according to any of the 3 preceding embodiments, wherein the case profile comprises external specimen data.
A100. The system according to any of the 4 preceding embodiments, wherein the case profile comprises a HSP template that indicates a standard HSP wherein one or more HSP parameters can be adjusted.
A101. The system according to any of the 5 preceding embodiments, wherein the case profile comprises the at least one generated adjustment.
A102. The system according to any of the preceding embodiment, wherein the system is configured to output the acquired specimen data to a practitioner during the diagnosis step.
A103. The system according to any of the preceding embodiments, wherein the system is configured to output external specimen data to a practitioner during the diagnosis step.
A104. The system according to any of the preceding embodiment, wherein the system is configured to output the at least one generated adjustment to a practitioner during the diagnosis step.
A105. The system according to any of the 3 preceding embodiments, wherein the system comprises an output device (50) configured to data to a practitioner during the diagnosis step.
A106. The system according to any of the preceding embodiments, wherein the diagnosis of a first sample is feedback to the at least one processing unit and the at least one processing device is configured to process said feedback and generate at least one adjustment for the HSP of a second sample.
A107. The system according to the preceding embodiment, wherein the at least one adjustment generated based on the diagnosis of the first sample, comprises a cleaning of at least one HSP device.
A108. The system according to any of the preceding embodiments, wherein the at least one sensor device (310) comprises at least one visual camera.
A109. The system according to any of the preceding embodiments, wherein the at least one sensor device (310) comprises at least one depth sensor. A110. The system according to any of the preceding embodiments, wherein the at least one sensor device (310) comprises at least one thermometer.
Alli. The system according to any of the preceding embodiments, wherein the at least one sensor device (310) comprises at least one pH meter.
Al 12. The system according to any of the preceding embodiments, wherein the at least one sensor device (310) comprises at least one three-dimensional scanner.
Al 13. The system according to any of the preceding embodiments, wherein the at least one sensor device (310) comprises at least one projectional radiography scanner.
Al 14. The system according to any of the preceding embodiments, wherein the at least one sensor device (310) comprises at least one computed tomography scanner.
Al 15. The system according to any of the preceding embodiments, wherein the at least one sensor device (310) comprises at least one fluoroscope.
Al 16. The system according to any of the preceding embodiments, wherein the at least one sensor device (310) is configured to measure at least on of: a thickness, size, area, volume, stiffness, acidity and temperature of the at least one sample.
Al 17. The system according to any of the preceding embodiments, wherein the at least one sensor device (310) comprises at least one DNA sequencer.
The skilled person will appreciate that DNA refers to the deoxyribonucleic acid.
Al 18. The system according to any of the preceding embodiments, wherein the at least one sensor device (310) comprises at least one immunostaining device.
The skilled person will appreciate that an immunostaining device is a device that uses an antibody-based method to detect a particular protein or another antibody in a sample.
Al 19. The system according to any of the preceding embodiments, wherein the at least one sensor device (310) comprises at least one immunohistochemistry staining device.
The skilled person will appreciate that immunohistochemistry, abbreviated as IHC, is used in histology to detect the presence of specific protein markers that can assist with diagnosis. IHC can involve the process of selectively identifying proteins in a sample by exploiting the principle of antibodies binding specifically to antigens or another antibody in biological tissues. For example, a detective marker (e.g., horseradish peroxidase (HRP) or fluorescent substance) can be used to label a primary antibody which can then bind to particular proteins in the sample. This is generally referred to as a direct immunohistochemistry method. In another example, an unlabeled primary antibody, which can also be referred to as a first antibody, may bind to a target protein in the sample. In such implementations, a second labeled antibody may be used which can react with the primary antibody.
A120. The system according to any of the preceding embodiments, wherein the at least one sensor device (310) comprises at least one mass spectrometry analyzer.
Below, method embodiments will be discussed. These embodiments are abbreviated by the letter "M" followed by a number. Whenever reference is herein made to method embodiments, these embodiments are meant.
Ml. A specimen data aggregating method configured to aggregate specimen during a histological sample preparation (HSP) of at least one sample, the method comprising: at least one aggregating component acquiring specimen data related to the at least one sample; at least one memory device receiving and storing the acquired specimen data; at least one processing unit processing the acquired specimen data and generating at least one adjustment for adjusting the HSP of the at least one sample based on the acquired specimen data.
M2. The method according to the preceding embodiment, comprising corresponding features to the system features according to any of the system embodiments.
A121. The system according to the preceding embodiment, wherein the system is configured to carry out the method according to any of the preceding method embodiments.
Brief description of drawings
Figure 1 depicts a typical procedure for producing and diagnosing microscope slides from histological samples according to prior art;
Figure 2 illustrates a first histological sample preparation system embodiment configured for collecting specimen data and processing the specimen based on customized techniques;
Figures 3a to 3c illustrate methods of histological sample preparation according to different embodiments of the present invention; Figures 4a to 4h illustrate a plurality of histological sample preparation steps according to an aspect of the present invention;
Figure 5a and 5b illustrate a plurality of histological sample preparation steps according to another aspect of the present invention;
Figure 6 illustrates a second histological sample preparation system embodiment configured for collecting specimen data and handling the specimen based on customized techniques;
Figure 7 illustrates a third histological sample preparation system embodiment comprising an output device.
Detailed description of drawings
[0099] In the following, exemplary embodiments of the invention will be described, referring to the figures. These examples are provided to give further understanding of the invention, without limiting its scope.
[0100] In the following description, a series of features and/or steps are described. The skilled person will appreciate that unless required by the context, the order of features and steps is not critical for the resulting configuration and its effect. Further, it will be apparent to the skilled person that irrespective of the order of features and steps, the presence or absence of time delay between steps can be present between some or all of the described steps.
[0101] In the following and in general throughout this document, the terms specimen, sample and tissue are used interchangeably and generally refer to biological and/or histological samples that can be treated with histotechniques. In addition, the term histology is used to generally refer to microscopic anatomy, i.e., the branch of biology that studies the microscopic anatomy of biological tissue, organs and cells. In addition, histological sample preparation involves the treatment of a sample using at least one of the histotechniques. For the sake of brevity, the abbreviation HSP is used to refer to histological sample preparation.
[0102] Fig. 1 illustrates a typical existing method for HSP. According to current practices, the specimen is treated through different processes, generally referred to as histotechniques (i.e., HSP). They typically initiate with specimen accessioning and conclude with diagnosis. During sample accessioning, the specimens are received in a clinical, histology or forensic laboratory, typically immersed in a sample container with formalin (or any fixation liquid). At this step, a practitioner handles the sample container (or a rack, bucket or bag of sample containers), checks for completeness (i.e., check if an indicated number of samples or sample containers has been received) and registers it (or them) by recording data related to the specimen(s). This data may include information related to the specimen(s), such as number of sample container(s), respective origin of sample container(s), number of specimens in each sample container, type of specimen(s), possible diseases infecting the specimen(s), an indication of completeness of the samples and/or sample containers, etc. Furthermore, the practitioner may record the samples with a unique ID which can be used internally (in the lab) or externally for identifying samples and/or linking them with the originating procedure or patient. Typically, the practitioner extracts the specimen data from a laboratory order that comes with the sample container(s) and/or by examining the samples contained therein. The practitioner can record the specimen data in a laboratory information system (LIS) - typically used by clinical laboratories for storing and managing their data.
[0103] At a next step, the practitioner may handle the specimens to the dehydration phase. During this step, excessive liquid is removed from the specimens. This is typically done by the practitioner diving the specimens in alcohol solutions. Generally, to avoid tissue damage, the sample is immersed in solutions with increasing alcohol concentration. The practitioner applies his/her knowledge and judgment to determine the alcohol concentration of each solution and the duration of letting the samples immersed in each alcohol solution. In many existing practices, the same dehydration procedure is used for multiple or all samples. In general, due to the time and effort consuming process of examining the samples, determining a corresponding dehydration procedure for each sample and preparing the respective alcohol solutions, the practitioners may be discouraged to individualize the dehydration step for each sample. This may be the case particularly during work overload. As a result, non-individualized dehydration process may lead to improper dehydration causing tissue damage and/or shrinkage. An example of an improper dehydration can be dehydrating a delicate sample too fast by immersing it directly in a strong alcohol solution. Tissue damage can then lead to inferior results during the diagnosis step, making the overall HSP less accurate and less efficient. Or, if otherwise the practitioner individualizes the dehydration step to each sample this may lead to delays in HSP. These delays may cause the sample to degrade as it ages, which can then cause inferior results during the diagnosis step.
[0104] At a next step, the sample may undergo a clearing process. The clearing step is particularly necessary when the dehydration step is performed by immersing the samples in alcohol solutions. During the clearing process, the alcohol in the sample is replaced with a wax miscible compound, such as, xylene. This is done by treating the dehydrated sample with the paraffin miscible compound. The clearing step facilitates the following step wherein the sample is embedded in a harder medium and the harder medium is paraffin. [0105] It will be noted, that the above dehydrating and clearing steps illustrate only one of the ways that such processes can be done. Alternatively, the dehydration of samples can be done or assisted by a microwave.
[0106] At a next step, the practitioner may embed the samples in a harder medium, typically paraffin wax. During this step, extra effort is required from the practitioner to identify the type and size of the samples and then apply his/her knowledge and judgment to embed the sample properly in the harder medium, such as paraffin. This includes determining the type and amount of embedding material, position of the sample in the biopsy cassette wherein it will be embedded (e.g., at the bottom of the cassette) and, more importantly, the orientation of the sample, to ensure that the slices created after cutting the specimens will expose the required or necessary features.
[0107] At a next step, the practitioner typically handles the embedded sample in a machinery for cutting or slicing, such as, a microtome. The microtome is a device that is able to cut thin slices from the embedded sample. Generally, at this step different cuts may be performed depending on the required slice thickness and type of knife used. Again, the practitioner is required to apply his/her knowledge and judgment to determine the type of slicing, which may be a time-consuming and non-ergonomic process leading to inefficiency and inferior diagnosis results.
[0108] During the sectioning process, the slices may comprise wrinkles caused by the knife during cutting. To remove the wrinkles, the practitioner may typically submerge the slices into warm water. Based on the type of sample, slice thickness and size (or area) of the slices, the practitioner may determine a temperature of the water and duration of submergence of the sample into it for de-wrinkling. Again, the practitioner is required to apply his/her knowledge and judgment to examine the slices and determine the duration and temperature for de-wrinkling, which may be a time-consuming and non-ergonomic process leading to inefficiency and inferior diagnosis results. Otherwise, the practitioner may use the same de-wrinkling process, wherein the same water temperature and duration is used for every slice. However, as the same water temperature and duration is used some samples may be damaged (e.g., very thin slices that may require a lower-than-average temperature) or wrinkles may not be removed (e.g., thick slices that may require a higher- than-average temperature).
[0109] At a next stage, the practitioner attaches the slices on microscope slide and may handle the slide with the sample into the staining phase. At this step, one or more particular stains are applied on the sample to make cell structures more visible. Typically, this step is performed the same irrespective of the sample. Generally, excessive stain is used to ensure that the whole sample is stained. However, this is not advantageous. Firstly, it may be inefficient as the excessive stain can be wasted. This is particularly the case if the stain is poured over the microscope slide or if the specimen can contaminate the stain and make it unusable for future staining of slides. Secondly, the use of excessive stain may have a negative impact on the visibility of the microscopic structures of the sample and/or may cause artefacts to be created therein. As such, excessive use of stain may lead to inferior diagnosis results. On the other hand, the use of less than required stain may not contribute on increasing the visibility of the microscopic structures of the samples. In other words, at this stage the use of the right amount and type of stain, depending on slice thickness, size and type and other factors can be advantageous, in that it can increase the accuracy of the diagnosis results. As for the amount of stain, the same is true for the time of letting the slices in contact with the stain (particularly when the slices are immersed in the stain).
[0110] After staining, the practitioner may prepare the slides for observation under microscope. Generally, the practitioner covers the sample attached on a microscope slide with a second microscope slide or plastic/glass film. Then, a pathologist observes the slides under microscope for the diagnosis.
[0111] As it can be observed, typical current practices in HSP require manual labour at almost each step. Furthermore, the manual labour is required not only for handling or preparing or processing the tissue, but also for determining certain parameters for performing each technique. In one aspect, this is time inefficient, non-ergonomic and inconvenient - as the practitioner has to judge at each stage on how to perform the respective HSP step. This may lead to delays and thus tissue aging and degradation. In another aspect, this may make the process more error prone and lead to inferior diagnosis results. The practitioner (due to tiring or simple human mistake) may misjudge and wrongly preform a step, e.g., mislabel or misidentify a sample, mix-ups, use a wrong slice thickness during sectioning, apply excessive stain, etc. The practitioner, particularly during a work flux, may be discouraged to individualize or customize the techniques on a sample per sample base (or on a sample group base) - but rather performs a standard technique for all of them.
[0112] Fig. 2 depicts a histological sample preparation (HSP) system 1 according to one aspect of the present invention. The HSP system 1 can be configured to facilitate histological sample preparation. More particularly, the HSP system 1 can be configured to at least facilitate obtaining specimen data, utilize the specimen data for performing the HSP, allow the flow of specimen data between the different HSP steps and devices, adjust HSP steps according to specimen data, synchronize the HSP for multiple samples, or any combination thereof. This can lead to a more accurate, time-efficient, ergonomic and safe specimen processing or preparation in a clinical, histological, surgical, anatomical pathology and/or forensics laboratory. [0113] According to an embodiment, the HSP system 1 can comprise at least one aggregator device 30 and optionally at least one consumer device 10 and further optionally at least one central engine 20. For example, in a first configuration the HSP system 1 can comprise a plurality of aggregator devices 30. In a second configuration the HSP system 1 can comprise a plurality of aggregator devices 30 and a central engine 20. In a third configuration it can comprise one or more aggregator devices 30 and one or more consumer devices 10. In a fourth configuration it can comprise one or more aggregator devices 30 and one or more consumer devices 10 and a central engine 20.
[0114] The aggregator device 30 can be configured to acquire specimen data. Thus, the aggregator device 30 can be equipped with at least one sensor device 310, for sake of brevity also referred to as sensor 310, which can be configured for sensing and obtaining specimen data. More particularly, the at least one sensor 310 can be configured to obtain sensor data related to the at least one specimen, which sensor data can be used to extract specimen data. That is, while sensor data can generally comprise numerical data (as output by the sensor), the specimen data can relate to features of the specimen (e.g., size, colour, shape, pressure, temperature, acidity, pH (the scale used to measure acidity), etc.) which can be extracted partially or fully based on the sensor data. The sensor device 310 can comprise at least one visual camera, at least one stereo camera, at least one ToF sensor, at least one LIDAR, at least one ultrasound scanner, at least one thermometer, at least one pH meter, at least one pressure meter, at least one device configured to measure the thickness and/or size and/or area and/or volume and/or stiffness and/or acidity and/or temperature of a sample, and/or any combination thereof. In other words, the sensor device 310 can comprise any sensor or meter device configured to measure and/or assess and/or indicate a physical and/or chemical property, preferably of (and not limited to) at least one specimen and/or slice of a specimen. The said chemical and/or physical property can comprise (but not limited to) a size, area, volume, thickness, shape, stiffness, temperature, acidity (e.g., pH), etc. In some embodiments, the sensor device 310 can be configured to facilitate a corresponding HSP step wherein the aggregator device 30 comprising the sensor device 310 is utilized. That is, at different HSP steps different measures may be required and the sensor device 310 can be configured correspondingly to measure, asses and/or indicate the respective measures.
[0115] In addition, the aggregator device 30 can comprise a specimen input and output component 308. The specimen input component 308 can be configured to facilitate the provisioning or input or insertion of at least one specimen on the aggregator device 308. Depending on the respective HSP device, the input component 308 may be configured to receive at least one sample container, at least one rack of sample containers, at least one bag of sample containers, at least one biopsy cassette containing a specimen (which can be closed or opened - i.e., with or without a lid), at least one embedded specimen, at least one specimen slice or at least one microscope slide (e.g., glass slide) wherein a specimen slice is attached. It will be understood that the input component 308 can be configured to receive any form of the sample depending on the respective HSP step. The specimen output component 308 can correspondingly be configured to facilitate outputting at least one specimen from the aggregator device 308. In some embodiments, the specimen input and output component 308 can comprise one component configured to facilitate both the insertion and output of specimens from the aggregator device. Alternatively, the specimen input and output component 308 can be separate components.
[0116] The aggregator device 30 can further be configured to communicate or transmit or output the aggregated or obtained specimen data and/or sensor data. The aggregator device 30 can thus be equipped with at least one communication component 306. The communication component 306 can be a communication cable connector 306 allowing at least one wired connection to be connected therein. For example, the communication component 306 can comprise a USB port/ cable, ethernet port/cable, optical data interface and/or the like. Additionally or alternatively, the communication component 306 can be configured for wireless communication. Thus, the communication component 306 can comprise at least one radio-frequency (RF) antenna, that can be configured to wirelessly transmit the specimen data. For example, the communication component 306 may utilize cellular technology (e.g., GSM, 3G, 4G, 5G), WIFI, Bluetooth, IEEE802.15.4 and/or other wireless technologies and any combinations thereof.
[0117] In addition, the aggregator device 30 may be configured to carry out or facilitate at least one HSP step (i.e., at least one of the histotechniques). In such embodiments, the aggregator device 30 can be referred to as a HSP device 40 (see Figs. 4a to 5b). This is advantageous, as the aggregator device 30 may not only serve the purpose of acquiring specimen data, but may also be configured to facilitate or carry out the processing of the specimens - i.e., carry out or facilitate at least one of the histotechniques for preparing the sample for diagnosis. Thus, the aggregator device 30 can comprise at least one hardware component 302 and at least one software component 304. The hardware component 302 can be configured for handling the tissue during processing. The software component 304 may comprise a computer implemented method 304 that can comprise instructions for controlling the hardware component for carrying out or facilitating the sample processing. The software component 304 may thus comprise machine readable instructions which can be provided to the hardware components 302 causing them to perform actions for handling and processing the samples. The software component 304 can be implemented by a skilled person and uploaded to a memory component (not shown) of the aggregator device 30. Alternatively, or additionally, said machine readable instructions can also be provided and/or indicated on a label (e.g., a machine-readable code) associated to a sample. That is, by reading, scanning, deciphering and/or decoding a label associated with at least one specimen (or specimen container, or specimen cassette) instructions on how to process the sample can be directly or indirectly inferred. One particular way of achieving this, is configuring the said label associated with at least one specimen to provide information related to the sample. Thus, one or more instructions for handling the specimen can be inferred. Alternatively, the said label may directly and readily comprise the instruction(s). This provides an efficient manner of customizing the HSP steps to a specimen (or a plurality of specimens).
[0118] Alternatively, the specimen data aggregating features (i.e., the sensor 310 and/or the communication component 306), which in the following can be referred to as aggregating components, can be configured as an attachment to a device or machine that is configured to carry out or facilitate at least one HSP step. In such embodiments, the aggregating components can be configured to be attached to the said device or machine and the said device or machine can be configured to receive or allow/facilitate the attachment of the aggregating components to the said device or machine. For example, said device or machine can comprise the hardware component 302 and/or the software component 304 and/or the specimen input and output component 308 - as such, configured to carry out or facilitate at least one HSP step. The aggregating components can comprise the sensor device 310 and the communication component 306 - as such, configured to acquire and communicate sensor data and/or specimen data. The aggregating components can be provided and/or attached to the device or machine that is configured to carry out or facilitate at least one HSP step - thus forming the aggregator device 30. In simple words, the aggregator components can be configured as a dongle that can be attached, provided and/or interfaced with at least one device or machine that is configured to carry out or facilitate at least one HSP step, thus providing additional functionality (e.g., specimen data aggregation) to the at least one device or machine that is configured to carry out or facilitate at least one HSP step.
[0119] In some embodiment the software component 304 and/or the hardware component 302 can be adjusted or configured or customized based on the specimen data which can be collected by the sensor device 310 and/or received by the communication component 306. This can allow the HSP steps to be adjusted or configured or individualized according to the specimen data.
[0120] It will be noted that an adjustment of the HSP step may comprise both the adjustment of software component 304 and hardware component 302 of the aggregator device 30. Alternatively, an adjustment of the HSP step may comprise the adjustment of software component 304 or hardware component 302. That is, based on the required adjustments and/or on the HSP step, the software component 304 and/or the hardware component 302 may be configured to allow adjusting or individualizing the HSP step. This is discussed in more detail with respects to Figs. 4a to 5b, wherein particular HSP devices 40 (which can be a consumer device 10 or an aggregator device 30 configured to facilitate or carry out a particular HSP step) are discussed.
[0121] The adjustment of the HSP step, can be performed either automatically, manually or a combination thereof. That is, the aggregator device 30 can be configured to automatically adjust the HSP step based on the received or acquired specimen data. Additionally or alternatively, the aggregator device 30 can be configured to allow a manual adjustment of the HSP step. Thus, a skilled person can adjust the aggregator device 30, more particularly the software component 304 and/or the hardware component 302, to perform the HSP step according to the specimen data. The specimen data may be provided or displayed to the skilled person by the aggregator device 30. For example, the aggregator device 30 may comprise or be connected to a display (see Fig. 7) wherein the specimen data can be displayed to facilitate the skilled person to adjust the aggregator device 30 accordingly. Furthermore, a list of adjustments and/or instructions of adjustments can be provided or displayed to the skilled person. That is, the aggregator device 30 can be configured to generate at least one adjustment and/or instructions for performing the adjustments based on the specimen data. The generated adjustments and/or instructions may then be output to the skilled person for guiding the skilled person to manually carry out the adjustments. In a preferred embodiment, the software component 304 can be automatically adjusted based on the specimen data.
[0122] Thus, instead of having a skilled person acquire specimen data (e.g., by examining the sample) and determine how to individualize the processing or preparation or treatment of said sample or, as it is typical, having all the sample processed in the same manner, the present invention alleviates these drawbacks. Instead, the HSP system 1 can be configured to obtain specimen data and calculate or generate processing or HSP parameters based on specimen data, that can be used to customize the processing of the specimen. In addition, instruction(s) of how to perform the individualization or adjustment of the processing of the specimens may be generated. Said processing parameters and instructions for adjusting the HSP may be displayed to a practitioner for assisting or guiding the practitioner. The generation of said adjustments and/or instructions to perform the adjustments can be performed by a data processing device comprised by the aggregator device 30 (e.g., see Figs. 4a to 4h) and/or by a processing device external to the aggregator device, such as, but not limited to, the central engine 20 (e.g., see Figs. 5a and 5b).
[0123] The consumer device 10 and the aggregator device 30 share similar or corresponding features. Thus, for the sake of brevity, in the following description of the consumer device 10 the similar features with the aggregator device 30 will be only briefly introduced, while the differentiating or unique features of the consumer device 10 will be described in more detail.
[0124] The consumer device 10 can comprise a specimen input and output component 108. The specimen input and output component 108, similar to the specimen input and output component 308 of the aggregator device 30, can be configured to facilitate inputting and outputting at least one specimen in/from the consumer device 10. Similar to the aggregator device 30, the consumer device 10 comprises at least one hardware component 102 and at least one software component 104. The hardware component 102 and/or the software component 104 can be adjusted to carry out or facilitate a HSP step according to specimen data. Furthermore, the hardware component 102 and the software component 104 can be adjusted to allow customization of a HSP step - as discussed for the aggregator device 30. Similarly, still to the aggregator device 30, the consumer device 10 can further comprise at least one communication component 106. In some embodiments, the consumer device 10 can be formed by attaching or providing or interfacing the communication component 106 (that can be configured as a dongle) to a machine or device configured to carry out or facilitate an HSP step (similar to the aggregator device 30).
[0125] While the communication component 306 of the aggregator device 30 can be configured for at least transmitting specimen data, the communication component 106 of the consumer device 10 can be configured for at least receiving specimen data. In other words, the aggregator device 30 can be configured to acquire and/or aggregate and/or communicate specimen data (which the aggregator device 30 can acquire through the at least one sensor 310) and the consumer device 10 can be configured to receive specimen data. This feature indicates the main difference between the aggregator device 30 and the consumer device 10. That is, in terms of specimen data acquisition the aggregator device 30 can be configured to actively obtain specimen data by utilizing at least one sensor 310, while the consumer device 10 can be configured to passively obtain specimen data through the communication component 106. More generally, the aggregator device 30 can be configured to obtain specimen data using the at least one sensor device 310 and optionally to receive further specimen data through the communication component 306. The consumer device 10 can be configured to receive specimen data only through the communication component 106 (as it does not comprise a sensor 310).
[0126] Thus, in a system with multiple aggregator devices 30 and consumer devices 10, specimen data can be aggregated by the aggregator devices 30. The aggregated specimen data can be shared with the other consumer devices 30 and optionally with the other aggregator devices 10. The aggregator devices 30 can be configured to carry out or facilitate at least one HSP step based on the specimen data acquired by the respective sensor 310 and/or received by the communication component 306. The consumer device 10 can be configured to carry out or facilitate at least one HSP step based on the specimen data received by the communication component 106.
[0127] In addition, the consumer device 10, more particularly a data processing device (not shown) that can be comprised by the consumer device 10 can be configured to generate at least one adjustment and/or instruction(s) of how to perform the at least one adjustment of the processing of the specimens based on the specimen data received by the communication component 106. Alternatively, said adjustments and/or instructions can be generated externally to the consumer device 10 (e.g., by the central engine 20) and can be received by the consumer device 10 through the communication component 106. The consumer device 10 can be further configured to carry out or facilitate at least one HSP step based on the received adjustments. The consumer device 10 can also be configured to output said adjustments and/or instructions, e.g., to a practitioner, for guiding the practitioner.
[0128] Furthermore, to facilitate the aggregation or the flow of the specimen data for each specimen and/or the sharing of the specimen data between the aggregator device(s) 30 and consumer device(s) 10, the HSP system 1 can further comprise a central engine 20. The central engine 20 can comprise a communication component 206. The communication component 206 can be configured to at least send data to the consumer device 10 (more particularly to the communication component 106) and to at least receive data from the aggregator device 30 (more particularly from the communication component 306). Thus, through the communication component 206 the central engine 20 can receive specimen data that is acquired by the at least one sensor 310 of the at least one aggregator device 30 and can provide specimen data to the at least one consumer device 10. Thus, the central engine 20 can be configured to facilitate the sharing of the specimen data between the different devices of the HSP system 1.
[0129] In addition, the central engine 20 may be configured to receive specimen data from external sources. Such external sources may include, an external database that can be accessed through an Internet, remote or local connection, a human operator uploading specimen data to the central engine 20 (e.g., typing the data in a keyboard), etc. For example, an application programming interface (API) can be configured between the central engine 20 (or in general HSP system 1) and an external and possibly remote repository (not shown), e.g., the database of the hospital wherein a specimen originates).
[0130] The central engine 20 can further comprise a database 201, or repository 201 or memory component 201. The database 201 can be configured to store specimen data. The database 201 may also comprise further information related to the HSP system 1, the clinical laboratory, accounting, sample sender facilities (i.e., originating sites) and/or the employees therein. The database 201 may comprise a laboratory information database. [0131] The central engine 20 can further comprise a computing unit 203. The computing unit 203 can be configured to control the operations of the central engine 20 and/or calculate HSP parameters based on specimen data. The central engine 20 can be partially or fully cloud-based. In such embodiments, a remote and preferably secure connection can be established between the central engine 20 and the aggregator/consumer devices 30/10. However, some computations can also be done on the aggregator devices 30 and/or consumer device 10 (see, Fig. 4a). In such embodiments, the aggregator device 30 and/or the consumer device 10 can comprise a (respective) data processing unit. The data processing unit can for example be configured to process data, such as, sensor or specimen data to extract specimen features, determine process parameters, customize process parameters, synchronize sample preparation among multiple samples, generate at least one adjustment, generate at least one instruction for performing the adjustment and the like.
[0132] Fig. 3a, illustrates an exemplary configuration of the HSP system 1 configured to process at least one specimen for preparation for diagnosis, for example, in a histological or forensics laboratory. That is, the HSP system 1 is configured to perform a plurality of histotechniques to prepare microscope slides from histology samples. The HSP system 1 can comprise a first aggregator device 30A, configured to carry out or facilitate the specimen accessioning step of HSP and a second aggregator device 30F configured to carry out or facilitate the diagnosis of the specimen. In addition, the HSP system 1 can further comprise consumer devices 10B, 10C, 10D and 10E, configured to carry out or facilitate the dehydration, embedding, sectioning and staining step respectively.
[0133] During the specimen accessioning the aggregator device 30A can acquire specimen data and can communicate the acquired specimen data to the central engine 20. The central engine 20 can receive the specimen data, may store the specimen data and can share the specimen data with the other consumer and/or aggregator devices 10B, 10C, 10D, 10E and 30F of the HSP system 1. Furthermore, during the diagnosis step 30F specimen data (e.g., regarding a diagnosis of the sample) can be acquired by the aggregator device 30F and can be communicated to the central engine 20.
[0134] Thus, information regarding the specimen is acquired by the aggregator device 30A and is provided to the other stages and devices 10B to 10E and 30F. The flow of information is facilitated by the engine 20, which communicates the information to the devices of the HSP system.
[0135] Fig. 3b, illustrates another exemplary configuration of the HSP system 1 configured to process at least one specimen for preparation for diagnosis, for example, in a histological or forensics laboratory. According to the embodiment illustrated in Fig. 3b, the HSP system 1 can comprise only aggregator devices 30. More particularly, the HSP system 1 can comprise an aggregator device 30A configured to carry out or facilitate specimen accessioning, another aggregator device 30B configured to carry out or facilitate specimen dehydration, another aggregator device 30C configured to carry out or facilitate embedding step, another aggregator device 30D configured to carry out or facilitate specimen sectioning, another aggregator device 30E configured to carry out specimen slice staining and another aggregator device 30F configured to carry out or facilitate the diagnosis step 30F. Specimen data can thus be collected through all the HSP steps and can be communicated to the central engine 20. The central engine 20 can share the specimen data among the different aggregator devices. Thus, at any specimen processing step specimen data collected by previous step can be utilized.
[0136] Fig. 3c, illustrates an embodiment of the HSP system 1 which generalizes the preceding embodiments of the HSP system 1. That is, in general, the HSP system 1 can comprise a plurality of devices configured for carrying out or facilitating at least one HSP step. Each of the said devices can be configured whether as an aggregator device 30 or as a consumer device 10. Furthermore, said devices can be connected to the central engine 20 such that they can receive and/or transmit data to/from the central engine 20.
[0137] In some embodiments, the devices of the HSP system 1, such as, the aggregator devices 30 and/or the consumer devices 10 and/or the central engine 20, can be configured to communicate directly with each other, for example, through a mesh network. This can be particularly advantageous as it can allow the flow or sharing of information between the different devices and between the different stages of HSP. For example, the information obtained during accessioning (e.g., size of a sample) can be shared or provided to the dehydration step wherein it can be used to determined how to perform the dehydration for the sample.
[0138] Generally and simply speaking, Fig. 2 introduces a HSP system 1 according to one embodiment of the present invention. The HSP steps can be carried out or facilitated by at least one aggregator device 30 and further optionally by at least one consumer device 10 and further optionally by at least one central engine 20. Then with reference to Figs. 3a - 3c, particular embodiments or arrangements or configurations of the HSP system 1 are illustrated. As depicted by Figs. 3a to 3c, the HSP system 1 can comprise a plurality of HSP devices wherein each HSP device can be configured for carrying out or facilitating a respective HSP step. The HSP devices of the HSP system 1 can be configured either as aggregator devices 30 or as consumer devices 10. In some embodiments of the HSP system 1, such as the one depicted in Fig. 3a, at least one of the HSP devices can be configured as an aggregator device 30, preferably the sample accessioning device 30A can be configured as an aggregator device 30. In some other embodiments of the HSP system 1, all the HSP embodiments can be configured as aggregator devices 30, such as the embodiment depicted in Fig. 3b. In general, the HSP devices of the HSP system can be configured either as an aggregator device 30 or as a consumer device 10, as illustrated in Fig. 3c.
[0139] In the above, embodiments of the present invention were discussed from a system perspective. In the following and particularly with reference to Figs. 4a to 4h and Figs. 5a to 5b, embodiments of the present invention will be discussed in more detail from a device perspective. With reference to Fig. 4a and Fig. 5a general HSP device embodiments will be discussed. With reference to Figs. 4b to 4h and Fig. 5b, some particular examples of HSP devices for carrying out or facilitating particular HSP steps (i.e., histotechniques) will be discussed. It will be noted that the provided examples of the HSP steps are arbitrarily chosen and are not to be interpreted as an exhaustive list of HSP steps wherein embodiments of the present technology may be utilized. It will be understood from the teachings of this document that embodiments of the present invention can be applied to other HSP steps which for the sake of brevity may not have been explicitly mentioned or discussed in this document. This statement is true in general for all the embodiments of the present invention.
[0140] Fig. 4a depicts an embodiment of a generalized HSP device 40. The HSP device 40 can be configured either as a consumer device 10 or as an aggregator device 30 (see Fig. 2). As a consumer device 10, the HSP device 40 can comprise a specimen input and output component 108, a hardware component 102, a software component 104 and a communication component 106. That is, the HSP device 40 if configured as a consumer device 10 can comprise any of the features of the consumer device 10 as discussed with reference to Fig. 2. On the other hand, as an aggregator device 30, the HSP device 40 can comprise a specimen input and output component 308, a hardware component 302, a software component 304 and a communication component 306. That is, the HSP device 40 if configured as an aggregator device 30 can comprise any of the features of the aggregator device 30 as discussed with reference to Fig. 2.
[0141] The HSP device 40 can be configured to process, handle, prepare and/or treat or at least facilitate the processing, handling, preparation and/or treatment of at least one specimen. That is, the HSP device 40 can be configured to carry out or facilitate at least one HSP step. Thus, at least one input sample 43 can be provided or input to the HSP device 40. The at least one input sample 43 can be provided in a sample container, in a sample container in a rack or bag of sample containers, in a biopsy cassette, embedded in a harder medium, as a slice, as a slice attached to a microscope slide, etc. This depends on the HSP step that the HSP device 40 can be configured to carry out or facilitate. After processing, preparing or treating the at least one input sample 43, the HSP device 40 can output the at least one sample. The output sample 47 can represent a modified or processed version of the input sample 43, depending on the process that the HSP device 40 is configured to carry out or facilitate.
[0142] Further, the HSP device 40 can be configured to receive raw specimen data 42. That is, the HSP device 40 can utilize the communication component 108/308 (see Fig. 2) to receive the raw specimen data 42. This is particularly advantageous when the HSP device 40 is configured as a consumer device 10. Nevertheless, in some embodiments it can be advantageous to configure the aggregator devices 30 to receive specimen data 42 (in addition to the specimen data it can extract using the sensor device 310). Generally speaking, the raw specimen data 42 refer to data directly related to specimens, that comprise or indicate at least one physical or chemical property of the specimens, such as, type of sample, number of samples, size of samples. The raw specimen data 42 provided to an HSP device 40 can comprise data based on which physical and/or chemical properties of a specimen can be extracted or inferred and the respective HSP step can be performed or customized. In some embodiments, the raw specimen data 42 can comprise sensor data. The raw specimen data can also comprise external data provided by other facilities (e.g., the site of origin of the sample), other procedures (e.g., surgery, biopsy, radiology), etc. The raw specimen data can also comprise data indicating a history of the specimen, such as, an originating patient, procedure, facility, a disease associated with the specimen, etc. This will be further clarified with the examples discussed in Figs. 4b to 4h. Raw specimen data 42 are to be distinguished from pre-processed specimen data 42' or processing parameters 42' discussed in Figs. 5a and 5b.
[0143] The HSP device 40 can further be configured to calculate HSP parameters (which can also be referred to as processing parameters). The HSP parameters can comprise a set of parameters that can receive different values and based on the values they can receive the HSP can be correspondingly adjusted. In other words, the HSP parameters can be calculated based on the raw specimen data 42 and this can allow the HSP to be adjusted or customized according to specimen features. The HSP device 40 can comprise a data processing device (not shown) that can be configured to calculate the HSP parameters based on the raw specimen data 42. Such embodiments of the HSP device 40 are to be distinguished from HSP device embodiments 40' which are generally not configured or do not comprise a data processing device configured to calculate the HSP parameters, but instead they can readily receive such parameters (see Figs. 5a and 5b).
[0144] If configured as an aggregator device 30, the HSP device 40 can further comprise a sensor device 310 configured to acquire specimen data (see Fig. 2). More particularly, the HSP device 40 can comprise at least one sensor device 310 configured to measure sensor data, at least one computing unit (not shown) configured to process the sensor data for extracting specimen data. Alternatively, the HSP device 40 may only obtain sensor data and the processing of the sensor data for extracting specimen data may be performed externally (e.g., in a cloud workstation and/or central engine 20).
[0145] Furthermore, the HSP device 40 can be configured to output data. Outputting the output data 44 can be facilitated by a communication component 108, 308 (see Fig. 2) that can be comprised by the HSP device 40. The output data 44 may comprise log data, which can comprise data that record the progress of the respective HSP step. The log data may comprise a process start/complete time, a process successful/fail indicator, data regarding the consumption or usage of certain materials during HSP, etc. The output data 44 can comprise sensor data and/or data that can be obtained by a sensor device 310. The output data 44 may also comprise the calculated HSP parameters. Furthermore, the output data 44 can comprise a sequence of samples (e.g., their respective IDs) that were processed by the respective HSP device 40 and/or to be processed by the following HSP devices 40. The later can facilitate synchronizing the sample treatment.
[0146] It will be noted, that the HSP device 40 can output the output data 44 not only when configured as an aggregator device 30, but also when configured as a consumer device 10. While the aggregator devices 10 can acquire sensor data and/or specimen data and output them, the consumer devices 10 cannot acquire sensor data. However, consumer devices 10 may output specimen data that they can receive through the communication component 108. Alternatively, the consumer devices 10 may receive sensor data through the communication component 108, process them to extract specimen data and output the extracted specimen data as output data 44.
[0147] Fig. 4b depicts a sample accessioning device 40A. The sample accessioning device 40A is an example of the HSP device 40 discussed in Fig. 4a. Thus, the sample accessioning device 40A can comprise the features discussed with respect to the HSP device 40. The same is true for the other examples of the HSP device 40, discussed with respect to Figs. 4c to 4h. In fact, elements in the figures sharing the same number as a reference sign comprise similar features. A character is added after each number on the reference sign to distinguish among different examples or embodiments of the same component.
[0148] The sample accessioning device 40A can be configured to carry out or facilitate sample accessioning, for example, in a laboratory, such as histology or forensic laboratory. More particularly, sample accessioning device 40A can comprise a hardware component 102, 302 and a software component 104, 304 that can be configured to carry out or facilitate sample accessioning (see Fig. 2). As such, the sample accessioning device 40A can be configured to receive at least one specimen 43A. The reception of the at least one specimen 43A can be facilitated by the specimen input component 108, 308 (see Fig. 2). The at least one specimen can generally be provided to the sample accessioning device 40A immersed in a sample container 43A. In some embodiments, a plurality of sample containers 43A can be provided to the sample accessioning device 40A, such as a rack or bag of sample containers 43A.
[0149] The sample accessioning device 40A can be configured to receive raw specimen data 42A. The reception of the raw specimen data 42A can be facilitated by the communication component 106, 306. The raw specimen data 42A can comprise a laboratory order 42A. The laboratory order can comprise a form (e.g., a standard form) that can comprise information related to the facility that the sample(s) originate, number of samples, a type of sample, a description of sample, the originating patient, type of testing or examinations requested and/or the like. From therein, information regarding the specimen 43A and/or the sample container 43A and/or the rack of specimen containers 43A can be extracted. The laboratory order 42A can be provided to the sample accessioning device 40A electronically (e.g., through an application programming interface with the facility wherein the specimens originated). Alternatively or additionally, the laboratory order 42A can be provided to the sample accessioning device 40A in a paper format, with corresponding coding, formatting and/or layout, which the sample accessioning device 40A can be configured to scan and extract information from therein. Alternatively or additionally, the sample accessioning device 40A may comprise input devices (e.g., keyboard, touchscreen, mouse, microphone configured to facilitate reception of voice commands or the like) which can facilitate a human operator provide the laboratory order 42A to the sample accessioning device 40A. To further facilitate the provisioning of the laboratory order 42A to the sample accessioning device 40A, the laboratory order can comprise a standardized form wherein the fields of the form comprise information regarding the input sample 43A.
[0150] Alternatively or additionally, specimen data regarding the input sample 43A may be provided in an identification label 42A attached in the sample container 43A wherein the specimen is immersed in. The identification label 42A may comprise an optical label 42A. The identification label 42A may comprise any machine-readable code, such as (but not limited to), a barcode, a QR code, a standardized font set like OCR and/or a human readable information. The identification label 42A may additionally or alternatively comprise an RFID tag or any device, apparatus or assembly of devices configured for near field communication. The identification label 42A may comprise a unique registration number of the sample container 10 which can later be correlated to a specimen. Alternatively or additionally, the identification label can comprise information regarding the number of specimens in the sample container 10, the size of specimens in the sample specimen container 43A, a time when the samples were obtained, a duration the samples have been put in the fixation liquid, a temperature of the sample, or a combination thereof. Further, the identification label 42A may comprise information about the type of specimen and/or of a reference for billing and/or identification purposes. [0151] The sample accessioning device 40A can be configured as an aggregator device 30 (see Fig. 2). Thus, the sample accessioning device 40A can be equipped with at least one sensor 310 (see Fig. 2). The at least one sensor 310 can comprise at least one identification label reader 310, such as, a barcode reader, QR code reader, RFID reader. Thus, the sample accessioning device 40A can be configured to automatically detect the identification label 42A and extract specimen data.
[0152] In addition, the sensor 310 can comprise at least one visual camera, stereo camera, ToF sensor, LIDAR, ultrasound sensor, at least one thermometer, at least one pH meter, at least one pressure meter, at least one device configured to measure the thickness and/or size and/or area and/or volume and/or stiffness and/or acidity and/or temperature of a sample or any combination thereof. The at least one sensor 310 can be configured to capture images or scan or collect sensor data from the input sample 43A from one or more angles. The collected sensor data can be processed to detect at least one sample that can be immersed in a sample container. This can allow the sample accessioning device 40A to automatically obtain specimen data, such as, a type of specimen(s), a number of specimens, a size of specimen(s) and a shape of specimen(s).
[0153] Generally and simply speaking, the sample accessioning device 40A can be configured to obtain specimen data related to the at least one input sample 43A. The sample accessioning device 40A can passively obtain the specimen data. For example, the sample accessioning device 40A can receive the specimen data through the communication component 108, 308 and/or through an input device configured to facilitate a human operator input the specimen data to the sample accessioning device 40A. In such embodiments, the sample accessioning device 40A can be configured as a consumer device 10 (see Fig. 2). Alternatively, the sample accessioning device 40A can be configured to actively extract specimen data. In such embodiments, the sample accessioning device 40A can be equipped with at least one sensor 310 (see Fig. 2). That is, the sample accessioning device 40A can be configured as an aggregator device 30. In such embodiments, the sample accessioning device 40A can utilize the at least one sensor 310 to extract specimen data from the laboratory order 42A and/or identification label 42A and/or by capturing sensor data of the input sample 43A.
[0154] The sample accessioning device 40A can be configured to register the at least one input sample 43A. For example, the sample accessioning device 40A can register the received input sample 43A to a laboratory information system (LIS). The sample accessioning device 40A can generate a specimen case profile 44A, which can also be referred to as specimen profile 44A, based on the information that can be extracted from the laboratory order 42A and based on the sensor and/or specimen data that can be acquired by the sensor 310 and/or through the communication component 106, 306. The specimen profile 44A can comprise specimen data. Said specimen data can relate to specimen features, e.g., physical and/or chemical properties of the specimen. In addition, the specimen profile can comprise a routine that specifies how the specimen is to be processed (e.g., comprises HSP parameters). Said HSP parameter can comprise and not limited to, a number, colour, size, type of cassettes to use, type and amount of staining, type of dehydration, etc.
[0155] At this stage, not all the HSP parameters may be filled. That is, the routine for processing the specimens may be extended or adjusted during the aggregation of specimen data. For example, when the case profile 44A is generated a template routine for processing the corresponding sample(s) can be selected. The selection of the template routine can be based on the specimen data and HSP parameters, such as, but not limited to type and number of specimens. As generally, this information can be known during the accessioning phase, the selection of the template routine can be performed automatically. For example, the selection can be performed by the data processing unit comprised by the accessioning device 40A and/or by the central engine 20. The template routine may be a routine with empty process parameters that can be completed. The template routine may also be a standard (or typical) routine which can be adjusted or individualized, automatically and/or manually, according to the specimen data.
[0156] The specimen profile 44A can be identified through a unique case number that can be assigned to it when the specimen profile 44A is generated. The specimen profile 44A can comprise specimen data that were extracted during the specimen accessioning step, such as, type of samples, number of samples, size of samples, number of cassettes (see Fig. 4c) etc. The specimen profile 44A can be generated for each specimen 43A or for each sample container 43A or for each rack of sample containers 43A or for a plurality of specimens or specimen containers. Preferably, the specimen profile 44A is created for specimens with the same origin (e.g., from the same patient, same surgical procedure, etc.). In other words, a specimen profile 44A can be linked to an originating patient, medical procedure, medical facility, doctor, etc., however said information may or may not be comprised in the specimen profile 44A (for privacy reasons). Generally, identification IDs are used to make the link between a specimen profile and a patient and the link may be stored in a secured database that may or may not be managed by the facility that processes the specimens. Identification IDs can also be provided on stickers or labels (i.e., identification labels) that can be attached to the containers, cassettes and/or laboratory orders.
[0157] Fig. 4c, depicts a draining device 40G. The draining device 40G can be configured to separate or at least facilitate the separation of the at least one specimen from the fixation liquid contained in an input sample container 43G. The input sample container 43G to the draining device 40G can correspond to the output sample 47A of the sample accessioning device 40A. That is, a sample container can be transported from the sample accessioning device 40A to the draining device 40G. The transportation can be done automatically, e.g., using robotic arms, transmission belts, actuator systems, or can be manually handled by a human operator. The reception of the at least one specimen 43G can be facilitated by the specimen input component 108, 308 (see Fig. 2). The output of the at least one specimen 47G can be facilitated by the specimen output component 108, 308 (see Fig. 2).
[0158] The specimen accessioning device 40A and the draining device 40G can be individual devices or can be partially or fully integrated in one device. This is in general valid also for the other HSP devices 40 discussed in the following, which can either be individual devices or all or some of them can be integrated in one device.
[0159] The separation of the at least one specimen from the fixation liquid can be performed by draining the liquid out of the sample container 43G. In some embodiments, the sample container can be enclosed on one of its sides (e.g., the top) with a container lid configured to releasably connect to a filter. Both the container lid and the filter can be releasably connected to the sample container. The container lid can block both the liquid and the specimens from escaping from the sample container. The filter can be configured to block only the specimens from escaping the sample container. Thus, by removing only the container lid the fixation liquid can be drained out of the container. Such a sample container, container lid and filter are launched by Inveox GmbH and disclosed in the European patent application EP 17176690.0 "Pathology Assembly", which is hereby incorporated by reference.
[0160] The draining device 40G can be configured to open the container lid from the sample container. Such an opening may comprise a decapping, an unthreading, an unlatching process or similar. It can further be configured to rotate the sample container (after or prior the container lid removal) such that the fixation liquid can be disposed of the sample container and the sample(s) can rest on the filter. The filter can further be configured to receive a cassette. More particularly, an enclosing body (generally smaller than the sample container and easier to handle, can be releasably attached to the filter forming a cassette 47G comprising the sample within. Thus, the at least one sample can be enclosed between the filter and the enclosing body of the cassette 47G.
[0161] It will be noted that the description above relates to an example of how the draining device 40G can be configured to separate the specimens from the fixation liquids and to further transfer the specimens into biopsy cassettes. [0162] The draining device 40G can be configured to receive raw specimen data 42G regarding the input sample 43G, that can comprise a case number, type of samples, number of samples size of samples, number of required cassettes or any combination thereof. The case number 42G can be used by the draining device 40G to keep track of the respective specimen it is handling, such as, e.g., to confirm the successful transfer of the sample(s) into the biopsy cassette 47G. The case number 42G can also be used by the draining device 40G for labelling the cassettes 47G. That is, the draining device 40G can be configured to label the cassettes 47G, wherein at least one specimen can be inserted, with the case number of the specimen(s). This can be advantageous as it can alleviate or remove the issue of mixing specimens from different patients which can lead to a misdiagnosis.
[0163] The draining device can further be configured to output verification or log data. The verification or log data indicate a state of the draining process, e.g., whether it was performed successfully.
[0164] The draining device 40G can be configured as a consumer device 10 (see Fig. 2). In such embodiments, the draining device can be configured to carry out or facilitate the processing of the input sample 43G, comprising liquid disposal, cassette labelling and sample insertion into cassettes. The above processes may be handled automatically by the draining device or a human operator may assist in some tasks (e.g., sample insertion into cassettes). In addition, the draining device 40G configured as a consumer device 10 can be configured to receive the raw specimen data 42G. In some embodiments, said raw specimen data 42G can correspond to the output data 44A that were output by the specimen accessioning device 40A. Said data can be transferred from the specimen accessioning device 40A to the draining device 40G either indirectly via the central engine 20 (see Fig. 2) or directly (see Fig. 6).
[0165] Alternatively, the draining device 40G can be configured as an aggregator device 30 (see Fig. 2). Thus, the draining device 40G can comprise at least one sensor device 310. The sensor device can be configured to collect sensor data before, during and/or after the liquid disposal from the sample container and sample insertion into cassettes. Said sensor data can be processed to obtain specimen data, such as, type of sample(s), number of samples, size of samples. Said specimen data can be output by the draining device 40 as output data 44G. In addition, the output data 44G can comprise log data that can indicate the progress of the draining process. Furthermore, the output data 44G can comprise a sequence of samples (e.g., their respective IDs) that were processed by the draining device 44G and/or to be processed by the following HSP devices.
[0166] Inveox GmbH has launched and disclosed a sample processing system for automatically processing a histological, pathological, medical, biological, veterinary and/or agricultural sample positioned in a sample container that is configured to be opened. Said sample processing system can be particularly advantageous for handling the specimen during the specimen accessioning and liquid draining steps. Said sample processing system is disclosed in the European patent application EP 18162231.7 "Sample processing system and method for automatically processing histological samples", which is hereby incorporated by reference. The sample processing system and methods disclosed therein are particularly advantageous to be incorporated in the present invention, as it can significantly increase the automation of specimen accessioning, liquid disposal and transfer of specimens into cassettes. In other words, the sample processing system as disclosed in EP 18162231.7 can be further configured as a HSP device 40A/G for carrying out the specimen accessioning and draining steps.
[0167] Fig. 4d, depicts a specimen dehydration device 40B. The specimen dehydration device 40B can be configured to receive an input sample 43B. The reception of the at least one specimen 43B can be facilitated by the specimen input component 108, 308 (see Fig. 2). The input sample 43B can generally be contained in a cassette 47G as prepared by the draining device 40G. That is, the input sample 43B to the specimen dehydration device 40B can correspond to the output sample 47G of the draining device 40G. That is, a sample can be transported from the draining device 40G to the dehydration device 40B. The transportation can be done automatically, e.g., using robotic arms, transmission belts, actuator systems, or can be manually handled by a human operator.
[0168] The specimen dehydration device 40B can be configured to dehydrate or at least facilitate the dehydration of the received input sample 43B and output the dehydrated sample 47B. The dehydrated samples 47B can be contained in cassettes 47B. The output of the dehydrated sample 47B can be facilitated by the output component 108, 308 (see Fig. 2).
[0169] The specimen dehydration device can also be configured to perform the clearing of the specimens during which step the alcohol in the specimen (which is not miscible with wax) is replaced with a wax miscible component, such as, xylene. However, also other method of dehydration and/or clearing can be used, while the purpose of such methods is generally dehydrating the sample and preparing it for embedding in a harder medium, such as, wax.
[0170] The specimen dehydration device 40B can be configured to receive raw specimen data 42B, such as a type of sample, size of sample or the like. The received raw specimen data 42B can correspond to aggregated specimen data that can be output by HSP devices of preceding steps. For example, the raw specimen data 42B received by the specimen dehydration device can correspond to output data 44 that is output by the specimen accessioning device 40A and/or draining device 40G. Said data can be transferred from the preceding HSP devices 40 to the sample dehydration device 40B either indirectly via the central engine 20 (see Fig. 2) or directly (see Fig. 6).
[0171] Based on the raw specimen data 42B the specimen dehydration device 40B can be configured to calculate specific dehydration process parameters, such as, number of required dehydrating solutions (typically alcohol solutions), concentration of each solution (e.g., concentration of alcohol), duration of immersing the specimen in each solution and/or temperature (if specimens are dehydrated through heating, e.g., with a microwave). In general, the dehydration process parameters that can be calculated by the dehydration device 40B based on specimen data 42B, depend on the dehydration method that is/will be used. This can allow the adaptation of the dehydration process to the specimen features. This is particularly advantageous when individual dehydration processes are needed, e.g., for bone marrow samples. For example, a soft tissue may require to be slowly dehydrated to avoid damage of the tissue, while harder specimens may be immersed to more concentrated dehydrating solutions and be dehydrated faster.
[0172] The specimen dehydration device 40B can be configured to output the output data 44B. The output data 44B may comprise the calculated dehydration process parameters, such as, a type of dehydration liquid used, a concentration of the used dehydration liquid(s), a duration that the specimen(s) were immersed in each solution, the dehydrating method used (e.g., dehydration using alcohol solutions, heating, microwave, etc.), used temperature for dehydration, used pressure, etc. In addition, other log data regarding the progress of the dehydration process can be output as output data 44B by the dehydration device 40B. This data can be used for qualitative analysis of the corresponding processes. Furthermore, the output data 44B can comprise a sequence of samples (e.g., their respective IDs) that were processed by the dehydration device 40B and/or to be processed by the following HSP devices 40.
[0173] The dehydration device 40 can be configured to automatically handle the at least one input sample 43B during the dehydration process. That is, the dehydration device can comprise in separate containers solvents and solutes that can be combined to create dehydration solutions. A pumping system can transport the different solvents and solutes to a container wherein they can be mixed according to ratios calculated during the calculation of dehydration process parameters. The dehydration device 40B can further comprise a conveyor system (e.g., a robotic arm, conveyor belt) which can transport the input sample 43B from the input component 108, 308 (see Fig. 2) to the different containers comprising the dehydration solutions. The conveyor system can be configured to immerse the sample(s) in the dehydration solutions. The dehydration device 40B can comprise a timer which can be used to let the samples immersed in the dehydration solutions according to the calculated durations based on the raw specimen data 42B. [0174] Generally, the dehydration step may require immersing the specimen in multiple dehydration solutions with different concentrations of the dehydrant in the solution. For example, the specimen may be immersed in alcohol solutions with 75%, 85% and 95% alcohol concentration. In some embodiments, multiple solutions with respective concentrations can be mixed in separate containers. During dehydration the sample can be immersed in each of them. Alternatively, one container with the dehydration solution with can be used wherein the concentration of the dehydrant(s) can be re-adjusted by adding dehydrant or solute. This can be repeated as many times as calculated during the calculation of the dehydration process parameters and can be adjusted for optimal outcomes.
[0175] In an alternative embodiment, the dehydration device 40B can be configured to drain the dehydration solutions directly on the cassette wherein the specimen is contained, wherein the cassette is configured to maintain (or to be filled by) a liquid such as the dehydration solution. For example, one or more cassettes can be provided in a compartment wherein the dehydration solution(s) is/are flushed over the cassettes. If multiple dehydration solutions are required, the dehydration solution in the container with cassettes can be changed or alternatively the concentration of the solution can be adjusted (by adding solvent or solute).
[0176] The dehydration device 40B can comprise a dehydration solution concentration measurement device (e.g., alcohol concentration measurement device) that can facilitate mixing and/or regulating the dehydration solution.
[0177] In a yet alternative embodiment, the dehydration device 40B can be configured to dehydrate the specimens through heating, e.g., using a microwave device. The dehydration device 40B can further comprise a temperature measurement device (i.e., a thermometer) that can facilitate heating the specimens at a particular temperature for optimal dehydration.
[0178] In some embodiments, the dehydration step or a portion of it can be manually performed. In such embodiments, the dehydration device can be configured to facilitate the dehydration step. The dehydration device can be configured to provide or display the dehydration process parameters to the practitioner. As such, for example, the practitioner may directly create the solutions and/or immerse the samples in the respective solutions and/or prepare an oven or microwave for the upcoming dehydration process and/or preset an oven or microwave at a calculated temperature - without having to examine the specimens (as is typically done in current practices, see Fig. 1). Furthermore, timers of the dehydration device 40B can alarm the practitioner when the specimen is ready for the next handling. Thus, even if the dehydration step is manually performed, the dehydration device 40B can provide improved ergonomics for carrying out the dehydration step. [0179] Fig. 4e, depicts a specimen embedding device 40C. The specimen embedding device 40C can be configured to receive an input sample 43C. The input sample 43C can generally be contained in a cassette. The input sample 43C can be dehydrated. For example, the input sample 43C can correspond to the output sample 47B of the dehydration device 40B. That is, the sample can be transported from the dehydration device 40B to the embedding device 40C for further processing. The transportation can be done automatically, e.g., using robotic arms, transmission belts, actuator systems, or can be manually handled by a human operator. The reception of the input sample 43C by the specimen embedding device 40C can be facilitated by the specimen input component 108, 308 (see Fig. 2).
[0180] The specimen embedding device 40C can be configured to carry out or facilitate the embedding step of HSP. That is, the specimen embedding device 40C can be configured to carry out or facilitate inserting specimens in an embedding medium, such as, paraffin wax. Thus, after processing the embedded specimen 47C can be output.
[0181] The specimen embedding device 40C can be configured to receive raw specimen data 42C, such as, type, size, shape and orientation of sample (before embedding). The received raw specimen data 42C can correspond to aggregated specimen data that can be output by HSP devices 40 of preceding steps. For example, the raw specimen data 42C received by the specimen embedding device 40C can correspond to output data 44 that is output by the specimen accessioning device 40A and/or draining device 40G and/or specimen dehydration device 40B. Said data can be transferred from the preceding HSP devices 40 to the sample embedding device 40C either indirectly via the central engine 20 (see Fig. 2) or directly (see Fig. 6).
[0182] Based on the received raw specimen data 42C the embedding device 40C may calculate the type and/or amount of embedding material that might be needed. The specimen embedding device 40C can be further configured to calculate an advantageous sample orientation. It can do this by considering the received raw specimen data 42C. Depending on the raw specimen data, particularly on the type of the sample, some orientations of the sample in the embedding medium may be more advantageous than others. This is because the sample needs to oriented in such a way that particular features of the sample are visible on the slices after the sample is cut. For example, for a skin sample it may be advantageous that the sample is oriented in such a way that the skin layers are visible on the slices after cutting. Thus, based on the raw specimen data 42C the embedding device can calculate an advantageous orientation of the sample.
[0183] It can further be advantageous to configure the embedding device to automatically position the specimen in the embedding medium in the calculated orientation. For example, a robotic arm may pick the sample and position it according to the calculated orientation in the embedding medium. The embedding device 40C may determine the amount of movements on each of the robotic arm's degrees of freedom by calculating the required motion to position the sample from the initial orientation of the sample to the calculated advantageous orientation. The initial orientation of the sample can either be extracted from received raw specimen data 42C, or by collecting sensor data. In the latter case, the embedding device 40C can be configured as an aggregating device 30 comprising at least one sensor 310.
[0184] As the process of handling the specimens in the embedding medium may be challenging, a practitioner may check whether the sample is properly oriented and/or a practitioner may correct the orientation of the sample. Alternatively, the practitioner may handle the specimen him-/her- self in the embedding medium according to the calculated orientation. In such embodiments, the embedding device can be configured to provide the calculated advantageous orientation to the practitioner. Thus, even if the embedding step is manually performed, the embedding device 40B can provide improved ergonomics, guidance and instructions for carrying out the embedding step.
[0185] The embedding device may output with the output data 44C the used type/amount of embedding material that was used during embedding. This information may be output with other log data that indicate the progress of the embedding step. In addition, the embedding device 40C may output the calculated advantageous orientation of the sample in the embedding medium. Furthermore, the output data 44C can comprise a sequence of samples (e.g., their respective IDs) that were processed by the embedding device 40C and/or to be processed by the following HSP devices 40.
[0186] The embedding device 40C may be configured as a consumer device 10. In such embodiments, the embedding device can be configured to receive specimen data, calculate an advantageous orientation of the specimen to be embedded, and facilitate or carry out the actual embedding of the specimen in the embedding medium.
[0187] Alternatively, the embedding device 40C may be configured as an aggregator device 30. In such embodiments, the embedding device 40C can further comprise a sensor 310 that can be configured collect sensor data of the sample before, during or after embedding it in the embedding medium. The collected sensor data may be used to extract the specimen orientation at the different stages of embedding. This can be used to verify that the specimen is embedded correctly.
[0188] Fig. 4f depicts a sectioning device 40D. The sectioning device 40D can be configured to receive an embedded sample 43D and cut it into thin slices 47D. The embedded sample 43D can be received after it is output by the sample embedding device 40C. That is, the input sample 43D to the sectioning device 40D can correspond to the output sample 47C from the embedding device 40C. The transportation of the sample from the embedding device 40C to the sectioning device 40D can be done automatically, e.g., using robotic arms, transmission belts, actuator systems, or can be manually handled by a human operator.
[0189] Generally, the sectioning device 40D can comprise a microtome. The sectioning device 40D can comprise one or more knives and can be configured to cut the embedded sample 43D into slices 47D of different thickness. The sectioning device 40D can also be configured to cut the embedded sample 43D into slices using laser cutting techniques. The type of knife (or laser) used and/or the slice thickness can depend on the type and size of the sample. In addition, the sectioning device 40D can be configured to cut the embedded sample 43D according to different axis. The cutting axis or orientation of cutting or direction of cutting can depend on the orientation of the sample in the embedding medium.
[0190] The sectioning device 40D can be configured to receive raw specimen data 42D. The received raw specimen data 42D can correspond to aggregated specimen data that can be output by HSP devices 40 of preceding steps. For example, the raw specimen data 42D received by the specimen dehydration device can correspond to output data 44 that is output by the specimen accessioning device 40A and/or draining device 40G and/or dehydration device 40B and/or embedding device 40C. Said data can be transferred from the preceding HSP devices 40 to the sectioning device 40D either indirectly via the central engine 20 (see Fig. 2) or directly (see Fig. 6).
[0191] The raw specimen data 42D can comprise the type of sample, size of sample and orientation or position of sample in the embedding medium. Processing the raw specimen data 42D the sectioning device 40D can calculate a type of knife, a slice thickness, a speed, an angle, a force to use during sectioning of the embedded sample, how many cuts to make, how much embedding material to cut before reaching to the sample (based on the position of the sample in the embedding material), where/how to cut to obtain a preferable slice with all features required (e.g., a slice with a maximum surface) and/or any combination thereof. Said calculated data can be output by the sectioning device as output data 44D. In addition, log data indicating the progress of the sectioning process can be output by the sectioning device. Furthermore, the output data 44C can comprise a sequence of samples (e.g., their respective IDs) that were processed by the sectioning device 40D and/or to be processed by the following HSP devices 40.
[0192] In some embodiments, the sectioning device can be configured to automatically perform the sectioning step. That is, the embedded sample 43D can be provided to the sectioning device (for example, in the input component 108, 308, see Fig. 2) as well as the raw specimen data 42D. The sectioning device 40D can than automatically or manually be triggered to calculate sectioning parameters to use during cutting (as discussed above). The sectioning device 40D can further be automatically or manually triggered to automatically be configured with the calculated parameters and perform the slicing of the embedded sample.
[0193] Alternatively, some tasks of the sectioning step may be manually performed. For example, after the sectioning device 40D calculates the sectioning parameters (as discussed above), it can display such parameters to a practitioner. The practitioner can then configure the sectioning device according to the parameters (e.g., mount the required knife and set the thickness). After that, the slicing can be performed. Alternatively, the calculated sectioning parameters can be output to the practitioner for guiding the practitioner to perform the sectioning step.
[0194] The sectioning device can generally be configured as a consumer device 10. However, in some embodiments it can be advantageous to configured the sectioning device 40D as an aggregator device. For example, the sectioning device 40D may collect sensor data of the embedded sample 43D to determine and/or verify the orientation of the sample in the embedded medium. Alternatively or additionally, the sectioning device 40D configured as an aggregator device may collect sensor data of the slices 47D to determine the shape and/or size of each slice. The extracted information may then be output as output data 44D.
[0195] Fig. 4g, depicts a de-wrinkling and sliding device 40H. The de-wrinkling and sliding device 40H can be configured to receive slices 43H and de-wrinkle them. The input slices 43H can correspond to the output slices 47D from the sectioning device 40D. That is, during the sectioning step, the slices may be wrinkled. The wrinkles can be removed by immersing the slices into warm water. Thus, the de-wrinkling and sliding device 40H can be configured to carry out or facilitate immersing the slices 43H into warm water. For example, the de- wrinkling and sliding device 40H may comprise a container with warm water. In addition, the de-wrinkling and sliding device 40H may comprise a conveyor system may transport the slices 43H into a container with warm water. Alternatively, a human operator may handle the slices 43H into the container with warm water.
[0196] Additionally still, the de-wrinkling and sliding device 40H can comprise a processing unit configured to calculate a duration of immersing the samples in the warm water for de-wrinkling and/or a temperature of the water. The parameters for the de- wrinkling process (e.g., duration and temperature) generally depend on the input sample 43H, such as the type of sample, size (or area) of sample, thickness of the slices and other similar features of the input sample 43H. Thus, the de-wrinkling and sliding device 40H can be configured to receive raw specimen data 42H, which can comprise the type of sample, size of sample, thickness of slice and other similar features of the input sample 43H. Based on the raw specimen data the de-wrinkling and sliding device 40H can calculate at least one parameter for the de-wrinkling process, such as, the duration of the process, the temperature of the water, the amount of water.
[0197] The de-wrinkling and sliding device 40H can additionally comprise a heating element and or a temperature sensor. The de-wrinkling and sliding device 40H can be configured to utilize said device to automatically set the temperature of the water used for de-wrinkling.
[0198] In addition, the de-wrinkling and sliding device 40H can be configured to calculate a number of slides required. That is, after de-wrinkling the slices may be attached to a respective microscope slide 47H. Generally, a specimen can be cut into multiple slices. Some or all of them may be required for diagnosis. Thus, some or all of them need to be attached to a microscope slide to be prepared for diagnosis. The de-wrinkling and sliding device 40H can be configured to calculate a required number of slides based on the raw specimen data 42H, such as, the number of slices 43H received by the de-wrinkling and sliding device 40H. Alternatively, the amount of slides can be determined during the specimen accessioning step, when the specimen profile is generated, and this information can be extracted from the raw specimen data 42H. The calculated or extracted number of slides can be displayed or provided to a practitioner, such that the practitioner can know ahead of the sliding process the number of slides that is required for the process. This alleviates the need of the practitioner to count the number of slices in order to determine the number of slides require. Present technology makes said information available to the practitioner. Additionally, this facilitates the automation of such a step.
[0199] The de-wrinkling and sliding device 40H can be configured to calculate an advantageous orientation of orienting the slices in the slide. This is particularly advantageous when multiple slices can be loaded in a slide. The calculated advantageous orientation can be output by the de-wrinkling and sliding device 40H, preferably to instruct a practitioner during slide loading.
[0200] The de-wrinkling and sliding device 40H can output the output data 44H, which can comprise log data indicating the progress of the de-wrinkling and sliding process, such as, number of used slides, temperature of water, duration of de-wrinkling.
[0201] The de-wrinkling and sliding device 40H may be configured as a consumer device 10. In such embodiments, the de-wrinkling and sliding device 40H can comprise the features discussed above. Alternatively, the de-wrinkling and sliding device 40H can be configured as an aggregator device 30. In such embodiments, the de-wrinkling and sliding device 40H can comprise the above features and in addition it can comprise a sensor device 310. The sensor device 310 can be configured to capture sensor data of the input sample 43H and/or slides 47H and/or sensor data during the de-wrinkling and/or sliding process. The captured sensor data can be used to detect certain errors during the processing the input samples 43H. The captured sensor data of the input sample 43H can be used to extract raw specimen data, such as, the area of the slices 43H (which can be used to calculate de-wrinkling parameter), number of slices 43H (which can be used to calculate number of required slides). The captured sensor data of the slides 47H (with the slices attached therein) can be used to determine the size of the slices in each slide, the position of the slices in the respective slices, etc. The information extracted from sensor data can be output by the de-wrinkling and sliding device 40H.
[0202] The de-wrinkling and sliding device 40H can be further configured to label the slides 47H. The slides 47H can comprise a slide labelling section 471 which can be configured to receive at least one label. The slide labelling section 471 can receive the at least one label by sticking and/or writing (e.g., via a laser) and/or printing a label therein. The label can comprise human and/or machine-readable information. It can comprise identification information (e.g., specimen case number) and/or other specimen data that can preferably assist the next processing steps (e.g., staining and diagnosis). For example, the label may comprise and/or indicate the case number, slide number, barcode for staining, an area and/or thickness of a slice in the slides 47H and/or a position of the slice in the slide 47H - which information can assist the staining process.
[0203] Fig. 4h, depicts a staining device 40E. The staining device 40E can be configured to receive slides 43E (which can be the output slides 47H from the de-wrinkling and sliding device 40H) and facilitate or carry out staining the slices comprised in the input slides 43E. Staining the slices (with particular stains, such as, Haematoxylin and Eosin stain) can make structures of the specimen (or cells of specimens) more visible, hence easier to diagnose particularly under microscope. More particularly, different specimen origins need different staining, e.g., bones compared to skin samples. Thus, the staining device 40E can be configured to carry out or facilitate staining the slides 43E.
[0204] The staining device 40E can be configured to automatically carry out or facilitate the staining step. For example, the staining device 40E may comprise one or more stain pouring components that can be positioned on top of each input slide 43E to apply stain or a spray of stain and/or solvent on an area of interest, preferably comprising a part or all the slice. As multiple stains can be applied to the slides, the staining device 40E can be configured to comprise for each type of stain a respective stain pouring component. Alternatively, the staining may be applied by submerging the slides into a container with the respective stain. For example, the staining device may comprise a conveyor or pick- and-place (e.g., robotic arm) system configured to handle the slides 43E and submerge them into one or more containers with stain. Alternatively, the staining may be performed manually. [0205] In any case, it can be advantageous to know the type and amount of stain and solvent required to stain a respective slide 43E and/or the timing used for staining, i.e., how long the stain and solvent is applied to the slides. As discussed, using the proper type and amount of stain(s) can be advantageous as it may make structures of the specimen more visible, avoid creation of artefacts and lead to more accurate diagnosis results. Overall, it can contribute on make the process more accurate and efficient. The staining device 40E can comprise a processing unit that can be configured to calculate staining process parameters, such as, a type of stain, amount of stain, duration of staining and/or the like. The staining parameters can depend on the features of the respective slide to be stained. Thus, the staining device can be configured to receive raw specimen data 42E, such as the type of sample, size (or area) of slice, position of the slice on the slide. The received raw specimen data 42E may be processed for calculating staining process parameters. In addition, a practitioner profile may be considered during the calculation of the staining process parameters. Thus, the slides 43E can be stained according to the practitioner's preferences - hence leading to better diagnosis results.
[0206] The staining device 40E can output the output data 44E, which can comprise log data indicating the progress of staining process, such as, staining process parameters.
[0207] The staining device 40E may be configured as a consumer device 10. In such embodiments, the staining device 40E can comprise the features discussed above. Alternatively, the staining device 40E can be configured as an aggregator device 30. In such embodiments, the staining device 40E can comprise the above features and in addition it can comprise a sensor device 310. The sensor device 310 can be configured to capture sensor data of the input sample 43E and/or of the stained slides 47E and/or sensor data during the staining process. Alternatively or additionally, the sensor device 310 can be configured to read a label of the slides 43E. The captured sensor data can be used to detect certain errors during the staining of the slides 43E. The captured sensor data of the input sample 43E can be used to extract raw specimen data, such as, the area, number, type and/or thickness of the slices in the slides 43E (which can be used to calculate the type and/or amount of stain needed). The captured sensor data of the input slides 43E can be used to determine the position of the slices in the respective slides 43E. Thus, the staining device can be configured to apply the stain in the particular position wherein the slice is positioned within the slide 43E. It will be noted, that even when the staining device 40E, is configured as a consumer device 10, it can still be advantageous to further configure it to apply the stain at a particular position with the slide. This can allow the staining device 40E to apply the stain only (or mostly) to the slice within the slide 43E, rather than wasting the stain. In such embodiments, the staining device 40E configured as a consumer device 10 can obtain the position of the slice within the slide by receiving it from raw specimen data 42E. For example, the de-wrinkling and sliding device 40H may be configured to obtain said position and communicate it to the staining device 40E.
[0208] Alternatively or additionally, the specimens can be treated by other devices or processes related to histology, such as, immunostaining devices, sequencing devices or other molecular diagnostic devices, which devices and processes can be used to treat the sample or slices of the sample before or after the initial diagnosis based on the clinical background information of a patient.
[0209] Fig. 5a, depicts a schematic of an alternative embodiment of an HSP device 40'. For the sake of brevity, in the following only unique or differentiation features of the HSP device 40' with respect to the HSP device 40 discussed with respect to Fig. 4a, will be discussed.
[0210] The HSP device 40' according to the embodiment of Fig. 5a, different from the HSP device 40 of Fig. 4a, can be configured to directly receive pre-processed sample data and/or process parameters. As such, the HSP device 40' may not be configured to calculate process parameters. Instead, the process parameters may already be calculated externally to the HSP device 40' (e.g., in the central engine 20, see Fig. 2) and be provided to the HSP device 40'. Thus, the HSP device 40' can be configured to facilitate or carry out the adjustment of the process (or of its hardware and/or software components) according to the process parameters, and to facilitate or carry out the processing of the sample according to the received process parameters.
[0211] This is further illustrated in Fig. 5b, with the example of a sectioning device 40D'. Thus, instead of receiving raw specimen data 42 and calculating the sectioning process parameters (such as, type of knife, slice thickness, etc) as discussed for the embodiment illustrated in Fig. 4f, the sectioning device 40D' depicted in Fig. 5b directly received process parameters, such as, type of knife, slice thickness, number of slices and/or direction of cut.
[0212] Fig. 6, illustrates an alternative embodiment of the HSP system 1 depicted in Fig. 2. According to the embodiment of Fig. 6, in the HSP system 1', the aggregator device 30 and consumer device 10 can be configured to communicate directly with each other. The other features of the HSP system 1 discussed with respect to Fig. 2, can also be comprised by the HSP system 1' and are omitted herein for the sake of brevity.
[0213] Fig. 7, illustrates an alternative embodiment of the HSP system 1, further comprising an output device 50. The output device 50 can be configured to output data. The output device 50 may comprise a display 50 configured to output visual data, such as, text, images and/or video. The output device may comprise a speaker 50 configured to output audio data. The output device 50 may also be configured to output or indicate data/information/indications through haptic feedback.
[0214] The output device 50 can be configured to output any of specimen data, raw specimen data, pre-processed specimen data, HSP parameters, HSP log data, specimen case profile, specimen processing routine, HSP adjustments, instructions/illustrations for adjusting a HSP device and/or a HSP step, pictures of the specimen/slides or consumables and the like. The output device 50 may receive said data to output from the central engine 20, aggregator device 30 and/or consumer device 10.
[0215] The output device 50 can be particularly advantageous as it can be configured to output data to a practitioner. Thus, specimen data may readily be available for the practitioner on the output device 50. This alleviates the disadvantages of the current practices, as partially discussed with reference to Fig. 1, and can lead to a more accurate, time-efficient, ergonomic and safe specimen processing in a clinical, histological and/or forensics laboratory.
[0216] The output device 50 may comprise a user device 50 (or user token 50) that can be handled by the practitioner. The mobile device 50 can be a smartphone, laptop, tablet, personal computer, workstation, wearable device, and/or similar devices. It can also be a customized device 50 configured with the features of the output device 50.
[0217] The output device 50 can alternatively or additionally be distributed among the different aggregator devices 30 and/or consumer device 10 and/or central engine 20. In such embodiments, the output device 50 attached to a respective device 30, 10, 20 can output specimen data (and/or other data) tailored to the respective device. For example, the output device 50 can be attached to a sectioning device 40D and can output sectioning parameters, such as a type of knife and slice thickness for sectioning a particular sample. In addition, said output device attached to the sectioning device 40D can output instructions on how to configure the sectioning device 40D for slicing a particular sample.
[0218] In a preferred embodiment, the output device may comprise a touchscreen 50 (or more generally may integrate an input device to allow the practitioner to input commands therein). This can allow the practitioner to select what to output on the output display 50.
[0219] The output device 50 can be particularly advantageous when one or more HSP steps are performed manually by a practitioner. In such embodiments, the output device 50 (e.g., a mobile display, a wearable) can readily provide instructions and/or HSP parameters to the practitioner.

Claims

Claims
1. A specimen data aggregating system configured to aggregate specimen data during a histological sample preparation (HSP) of at least one sample, comprising: at least one aggregating component configured to acquire specimen data related to the at least one sample; at least one memory device configured to receive and store the acquired specimen data; at least one processing unit configured to process the acquired specimen data to generate at least one adjustment for adjusting the HSP of the at least one sample.
2. The system according to the preceding claim, wherein the at least one processing unit is configured to process the acquired specimen data to generate a sequence of samples to undergo HSP, and wherein the sequence of samples comprises a prioritization of at least one sample and/or an ordering of at least two samples to undergo HSP, and wherein the at least one processing unit is configured to generate the sequence of samples that maximizes a sample preparation throughput and/or sample waiting time.
3. The system according to any of the preceding claims, wherein the at least one processing unit is configured to calculate at least one HSP parameter, and wherein an HSP parameter is configured to receive a plurality of values and based on the values it receives the HSP, such as, an HSP step, of at least one sample is correspondingly adjusted, and wherein an HSP parameter comprises a duration of performing an action during HSP of a sample, a selection of a process to be utilized during the HSP of a sample, a selection of a compound to be utilized during the HSP of a sample, a selection of a device to be utilized during the HSP of a sample, an amount of a compound to be utilized during the HSP of a sample, a number of a component to be utilized during the HSP of a sample, a number of a part to be utilized during the HSP of a sample, a position of a sample, an orientation of a sample or any combination thereof.
4. The system according to any of the preceding claims, wherein the at least one aggregating component is configured to communicate the acquired specimen data and wherein the aggregating component comprises at least one communication component (106, 306) configured to transmit and/or receive data, preferably, the acquired specimen data and/or the at least one generated adjustment.
5. The system according to any of the preceding claims, wherein the aggregating component comprises at least one sensor device (310) configured to measure a visual, physical, chemical and/or medical property of a sample.
6. The system according to any of the preceding claims, wherein at least one aggregating component is configured as an attachment or dongle that is configured to be attached or interfaced with at least one device or machine that is configured to carry out or facilitate at least one HSP step.
7. The system, according to any of the preceding claims, further comprising at least one HSP device (40) configured to facilitate the HSP of at least one sample, such as, at least one HSP step of at least one sample.
8. The system according to any the preceding claim, wherein a first HSP device (40-1) is configured to acquire sample data and transmit the acquired sample data, and wherein a second HSP device (40-11) is configured to receive the sample data transmitted by the first HSP device (40-1).
9. The system according to any of the 2 preceding claims, wherein the HSP device (40) can be configured to be adjusted according to one of the generated adjustments and wherein at least one hardware component (102, 302) and/or at least one software component (104, 304) and/or at least one input/output component (108, 308) of the HSP device (40) can be adjusted according to one of the generated adjustments.
10. The system according to any of the preceding claims, wherein the system further comprises a central engine (20), wherein the central engine (20) comprises at least one of: a database (201) configured to store specimen data, wherein the database (201) comprises the at least one memory component, and at least one computing unit (203), wherein the computing unit (203) comprises the at least one processing unit, and at least one communication component (206), wherein the communication component (206) is configured to communicate with at least one aggregating component.
11. The system according to any of the preceding claims, wherein the at least one processing unit generates instructions for performing the at least one adjustment and wherein the instructions comprise text, image(s), video(s), audio, diagram(s), flowchart(s), indication(s), haptic feedback, or any combination thereof.
12. The system according to any of the preceding claims, wherein the system further comprises at least one output device (50) configured to output textual, graphical, visual, haptic data or any combination thereof and the output device (50) is configured to output at least one of specimen data, and the at least one generated adjustment, and at least one instruction for performing the at least one adjustment.
13. The system according to any of the preceding claims, wherein the at least one processing unit is configured to process external sample data to generate the at least one adjustment and wherein the external sample data comprise medical, clinical and/or history data that relate to a sample, patient, a disease, sample originating facility or any combination thereof.
14. The system according to any of the preceding claims, wherein the system is configured to output the acquired specimen data, external specimen data, the at least one generated adjustment or any combination thereof to a practitioner during the diagnosis step.
15. A specimen data aggregating method configured to aggregate specimen during a histological sample preparation (HSP) of at least one sample, the method comprising: at least one aggregating component acquiring specimen data related to the at least one sample; at least one memory device receiving and storing the acquired specimen data; at least one processing unit processing the acquired specimen data and generating at least one adjustment for adjusting the HSP of the at least one sample based on the acquired specimen data.
PCT/EP2023/061508 2022-05-02 2023-05-02 Methods and systems for histological sample preparation WO2023213793A1 (en)

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US20080031094A1 (en) * 2006-08-01 2008-02-07 Covaris, Inc. Methods and apparatus for treating samples with acoustic energy
JP2011242154A (en) * 2010-05-14 2011-12-01 Hitachi High-Technologies Corp Automatic analysis system and device management server
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