WO2021056208A1 - 生化物质分析***、方法及装置 - Google Patents

生化物质分析***、方法及装置 Download PDF

Info

Publication number
WO2021056208A1
WO2021056208A1 PCT/CN2019/107593 CN2019107593W WO2021056208A1 WO 2021056208 A1 WO2021056208 A1 WO 2021056208A1 CN 2019107593 W CN2019107593 W CN 2019107593W WO 2021056208 A1 WO2021056208 A1 WO 2021056208A1
Authority
WO
WIPO (PCT)
Prior art keywords
signal
flow cell
fluid
module
component
Prior art date
Application number
PCT/CN2019/107593
Other languages
English (en)
French (fr)
Inventor
姜鹤鸣
邢楚填
梁埈模
隋相坤
刘健
奇里塔拉兹万
王忠海
亚当斯西蒙·罗伯特
王乐
森科马克·弗雷德里克
乌里奇克雷格·爱德华
文思成
高斌
牟峰
Original Assignee
深圳华大智造科技有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 深圳华大智造科技有限公司 filed Critical 深圳华大智造科技有限公司
Priority to KR1020227013709A priority Critical patent/KR20220066162A/ko
Priority to JP2022518312A priority patent/JP7457798B2/ja
Priority to CN201980100118.2A priority patent/CN114341618B/zh
Priority to EP19946668.1A priority patent/EP4036554A4/en
Priority to US17/763,295 priority patent/US20220341848A1/en
Priority to PCT/CN2019/107593 priority patent/WO2021056208A1/zh
Priority to AU2019467369A priority patent/AU2019467369B2/en
Priority to CA3151328A priority patent/CA3151328A1/en
Publication of WO2021056208A1 publication Critical patent/WO2021056208A1/zh
Priority to AU2023266236A priority patent/AU2023266236A1/en

Links

Images

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03—Cuvette constructions
    • G01N21/0332—Cuvette constructions with temperature control
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/13—Moving of cuvettes or solid samples to or from the investigating station
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/84—Systems specially adapted for particular applications
    • G01N21/85—Investigating moving fluids or granular solids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N2021/0193—Arrangements or apparatus for facilitating the optical investigation the sample being taken from a stream or flow to the measurement cell
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03—Cuvette constructions
    • G01N2021/0325—Cells for testing reactions, e.g. containing reagents
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/636—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited using an arrangement of pump beam and probe beam; using the measurement of optical non-linear properties
    • G01N2021/637—Lasing effect used for analysis
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N2021/6482—Sample cells, cuvettes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03—Cuvette constructions
    • G01N21/05—Flow-through cuvettes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters

Definitions

  • the invention relates to the field of biochemical substance analysis, in particular to a biochemical substance analysis system, method and device.
  • the flow cell is the area where the test sample reacts with the test fluid (such as reagent); the test system is used to apply the test excitation and record the response signal of the test reaction; the fluid system is responsible for inputting the test fluid participating in the test reaction and discharging the test response after the test reaction. scrap.
  • test fluid such as reagent
  • the test system is used to apply the test excitation and record the response signal of the test reaction
  • the fluid system is responsible for inputting the test fluid participating in the test reaction and discharging the test response after the test reaction. scrap.
  • the flow cell (that is, the sample carrier) is an area for loading samples of biochemical substances and performing detection and analysis reactions, and it usually contains a cavity for accommodating samples and fluids.
  • the flow cell In the field of sequencing, the flow cell is the area where the samples for gene sequencing are loaded and the sequencing reaction occurs. It usually contains a cavity for holding samples and fluids. It is also generally referred to as flow cell, reaction cell, chip, sequencing chip, gene Common English names for sequencing chips or cartridges are FlowCell, Flowcell, Chip, ChipKit, Cartridge, etc. Due to the non-repeatability of sample loading and the avoidance of cross-contamination between different samples, sequencing chips are usually designed for one-time use, repeated installation and disassembly, and a fully enclosed style.
  • the sequencing chip can have one or more independent channels, each channel has an inlet and an outlet, which are used to detect the fluid input and output of the reaction.
  • the upper surface of the sequencing chip is usually a light-permeable material, which can transmit the excitation light signal and the excited light signal, and can pass through the surface for optical signal detection; the lower surface of the sequencing chip is usually the substrate, and the tested gene sample can pass through some Kind of biological or chemical reaction is fixed on its surface.
  • the signal detection system can send out excitation signals and receive feedback signals.
  • Second-generation sequencing technology The commonly used detection method is laser-induced fluorescence, that is, using a laser to excite the sample to make it emit fluorescence signal feedback, and then use an area scan camera to take pictures and record the excited optical signal. Therefore, the detection system is essentially an optical imaging system, which is mainly composed of lasers, objective lenses, filters, tube lenses, cameras, and workpiece tables. Among them, the laser is used to excite the fluorescent signal feedback of the tested sample in the sequencing reaction, and the module composed of the objective lens, filter, tube lens, camera and other components is responsible for collecting the fluorescent signal emitted by the tested sample.
  • the sequencing chip Since the area taken by the area scan camera is usually much smaller than the design detection area of the sequencing chip, when the detection system is working, the sequencing chip needs to move with the workpiece stage, gradually traverse all the reaction areas, and use the camera for real-time exposure. Receive the fluorescent signal from each detection area in the sequencing chip one by one.
  • the fluid that participates in the detection reaction is the sequencing fluid.
  • the fluid system is responsible for inputting the sequencing fluid to be reacted into the sequencing chip, and at the same time discharging the reacted sequencing fluid out of the sequencing chip, usually by the sequencing fluid box , Sampling needle, pipeline, liquid pump and other components.
  • the sequencing fluid box is a container for loading the sequencing fluid;
  • the pipe is a closed channel that connects the components of the fluid system and allows the sequencing fluid to pass through;
  • the liquid pump is the power source that drives the sequencing fluid to move in the fluid system.
  • Common fluid systems are usually designed in series.
  • the sequencing fluid box In order to avoid cross-contamination caused by the use of liquid pumps, the sequencing fluid box is generally placed upstream, and the fluid needle is used as the inlet of the fluid system, and the sequencing chip and the liquid pump are connected downstream through a pipeline.
  • the pipe connected to the sequencing chip and the liquid pump is usually called the main pipe, and this pipe is the necessary route for the input and output of the sequencing fluid to the fluid system.
  • insert the fluid needle into the sequencing fluid box and turn on the fluid pump so that the sequencing fluid flows along the fluid needle and into the sequencing chip through the pipeline, and the existing sequencing fluid in the sequencing chip will be discharged along the pipeline of the liquid pump.
  • the physical essence of this design method is to use a liquid pump to establish a negative pressure, so that the pressure of the entire fluid system is lower than the outside atmospheric pressure, and use the outside atmospheric pressure to press the sequencing fluid into the fluid system.
  • a biochemical substance analysis system is provided.
  • the biochemical substance analysis system is used to complete the detection of the biological characteristics of the sample in the flow cell, including a detection system, a scheduling system, a biochemical reaction system, and a control system, wherein the scheduling The system is used to schedule the flow cell at different positions, the positions including the position in the detection system and the position in the biochemical reaction system, and the biochemical reaction system is used to make the sample in the flow cell generate
  • the detection system is used to perform signal detection on a sample that has reacted to obtain a signal representing the biological characteristics of the sample
  • the control system is used to control the coordinated operation of the detection system, the scheduling system, and the biochemical reaction system .
  • a biochemical substance analysis method including:
  • Signal detection is performed on the sample in the flow cell in the detection system to obtain a signal reflecting the biological characteristics of the sample.
  • a biochemical substance analysis device includes the above-mentioned biochemical substance analysis system; or, the biochemical substance analysis device applies the above-mentioned biochemical substance analysis method to obtain the biological characteristics of the sample in the reaction flow cell.
  • the user only needs to place the detection fluid, cleaning fluid, and sample-loaded flow cell required for sequencing into the gene sequencer through the interface on the gene sequencer.
  • the gene sequencer and the gene sequencing system can automatically complete gene sequencing. Improved the degree of automation of gene sequencing.
  • Fig. 1 is a three-dimensional schematic diagram of the gene sequencer in the first embodiment of the present invention.
  • Figure 2 is a schematic diagram of the gene sequencing system of the gene sequencer of the present invention.
  • Fig. 3 is a schematic diagram of each module of the signal detection system in the system shown in Fig. 2.
  • Fig. 4 is a schematic diagram of various components of the fluid transport module in the system shown in Fig. 2.
  • Fig. 5 is a schematic diagram of various components of the detection reaction module in the system shown in Fig. 2.
  • Fig. 6 is a schematic diagram of various modules of the waste processing system in the system shown in Fig. 2.
  • FIG. 7 is a schematic diagram of the operation logic of the transfer system in the system shown in FIG. 2.
  • Fig. 8 is a schematic diagram of various modules of the signal processing system in the system shown in Fig. 2.
  • FIG. 9 is a schematic block diagram of the biochemical substance analysis system provided by the second embodiment of the present invention.
  • FIG. 10 is a flowchart of the biochemical substance analysis method provided in the third embodiment of the present invention.
  • FIG. 11 is a schematic diagram of a biochemical substance analysis device provided by the fourth embodiment of the present invention.
  • FIG. 12 is a schematic diagram of a biochemical substance analysis device provided by Embodiment 5 of the present invention.
  • M, N and X refer to an indefinite number or order everywhere, and they are not used as a reference to a specific number or order. In other words, the same M, N, and X may refer to different numbers or orders in different places.
  • FIG. 1 is a schematic diagram of a gene sequencer in an embodiment of the present invention.
  • the gene sequencer 1 includes a housing 2 and a gene sequencing system 3 placed in the housing 2 and interacting with the outside through the housing 2.
  • the housing 2 is provided with a plurality of input and output interfaces.
  • the input and output interfaces include information input and output interfaces, such as a display interface 201, a keyboard and mouse 207, etc.
  • the keyboard and mouse 207 is It is hidden in the housing 2 and can be withdrawn from the housing 2 when needed.
  • the input and output interfaces also include material input and output interfaces, such as the flow cell insertion interface 203, the fluid cartridge replacement interface 205, and the like. The user can set the necessary parameters/commands through the information input interface, and connect the flow cell loaded with the sample (i.e. sample carrier), the fluid box (such as the sample carrier) containing the required sequencing fluid (such as the reagent) and the cleaning fluid (such as the cleaning solution).
  • the “flow cell” referred to in the present invention is an area used for loading samples of biochemical substances and detecting and analyzing reactions. It usually contains a cavity for accommodating samples and fluids, which should be understood as a sample carrier in a broad sense. That is to say, in addition to the sequencing chip in the case of sequencing, it can also be understood as other sample carriers in other cases.
  • the gene sequencing system 3 includes a signal detection system 31, a signal processing system 32, a fluid system 33, a waste processing system 34, a transfer system 35, a control system 36, and a user interaction system 37 and other subsystems.
  • a signal detection system 31 After one or more flow cells 38 are placed in the gene sequencer 1, each flow cell 38 is shifted by the transfer system 35 in various related subsystems, so that the sample in the flow cell 38 completes the detection reaction and performs a signal. Detection.
  • the signal detection system 31 is used to perform signal detection on the samples in the flow cell 38, including applying excitation signals, receiving and recording feedback signals from the samples, and so on.
  • the signal detection system 31 further includes an excitation signal transmission module 301, a signal channel module 303, a feedback signal receiving module 305, a received signal correction module 306, a detection fixed component 308 and a mobile component 310. It should be noted that in this embodiment, only one signal detection system 31 is shown to detect the sample in the flow cell 38. In fact, there can be multiple signal detection systems 31 as required, for example, as required.
  • M is a natural number greater than 1
  • signal detection systems 31 are set in the gene sequencer 1, and each signal detection system 31 performs at least one detection on a sample in a flow cell 38 according to the control of the control system 36 to complete the detection. The signal of at least one base of the sample in the flow cell 38 is detected.
  • the gene sequencer 1 can perform signal detection on the samples in the multiple flow cells 38 at the same time.
  • the excitation signal transmitting module 301 is used to apply an excitation signal to the sample in the flow cell 38 to detect whether a feedback signal can be obtained.
  • the composition of the sample can be judged by the feedback signal.
  • the excitation signal can be an optical signal or an electrical signal. If the excitation signal is an optical signal, the excitation signal emission module 301 can be a light source such as a laser or LED; if the excitation signal is an electrical signal, the excitation signal emission module 301 can be power supply.
  • the signal channel module 303 is used to make the excitation signal emitted by the excitation signal transmitting module 301 reach the flow cell 38 according to a preset path, and make the feedback signal start from the flow cell 38 and reach the feedback signal receiving module 305 according to the preset path.
  • the excitation signal is an optical signal
  • the signal channel module 303 may be a set of optical modules composed of one or more optical components such as an objective lens, a tube lens, a lens, and a filter;
  • the excitation signal is an electrical signal, the The signal channel module 303 may be a group of electrical modules composed of one or more electrical components such as conductive cables, resistors, capacitors, rectifiers, and filters.
  • the feedback signal receiving module 305 is used to receive the feedback signal sent out after the sample is excited by the excitation signal. If the excitation signal is an optical signal, the feedback signal receiving module 305 can be various area scan cameras, line scan cameras, or other optical signal receivers such as photodiodes, photomultiplier tubes, etc.; if the excitation signal is an electrical signal, Then the feedback signal receiving module 305 may be an electrical signal receiving component such as a signal acquisition card.
  • the received signal correction module 306 is used to adjust the transmission path of the excitation signal and the reception path of the feedback signal, so that the transmitted excitation signal and the received feedback signal are adapted and have the best effect.
  • the excitation signal is an optical signal
  • the received signal correction module 306 may be various types of auto-focus components and combinations thereof; if the excitation signal is an electrical signal, the received signal correction module 306 may be various types of autofocus components. Class rectifier components and their combinations.
  • the detection fixing assembly 308 is used to detachably install and fix the flow cell 38, so that the flow cell 38 and the detection fixing assembly 308 remain relatively stationary during signal detection.
  • the moving component 310 is connected to the detecting and fixing component 308, and is used to drive the detecting and fixing component 310 to move within a certain range, so that all areas of the flow cell 38 that need to be detected can perform signal detection.
  • the mobile component 310 may be a mobile control device such as an XY mobile platform.
  • the signal processing system 32 is used to process and analyze the feedback signal received by the signal detection system 31 to obtain sequencing data and generate a report.
  • the signal processing system 32 includes a signal transmission module 312, a signal processing module 314, and a data storage module 316. The sub-modules of the signal processing system 32 will be described in detail below.
  • the signal transmission module 312 is configured to receive the feedback signal transmitted by the signal detection system 31, buffer the feedback signal, and wait for subsequent processing and analysis.
  • the gene sequencer 1 can be equipped with multiple signal detection systems 31 according to needs. When multiple signal detection systems 31 are set up, the feedback signal received by each signal detection system 31 can be sent to the signal transmission module 312 for buffering, waiting for subsequent processing and analysis.
  • the signal transmission module 312 may be various types of non-volatile signal buffer devices.
  • the signal processing module 314 is used to obtain the buffered feedback signal from the signal transmission module 312, convert it into data for analysis through an algorithm, further analyze the data to generate a sequencing report, and output the sequencing report to the user interaction System 37.
  • the data storage module 316 is used to compress the processed data and sequencing reports, and store them in a storage medium as a backup, so that the user can call and view them at any time.
  • the fluid system 33 is used to store test fluids such as test reagents to be used during the sample test, input the test fluids into the flow cell 38 to perform a test reaction, and discharge all waste materials after the test reaction is completed to the waste processing system 34.
  • the fluid system 33 includes a detection reaction module 318, a reaction temperature control component 320, a fluid transportation module 322, a non-temperature control storage component 324, a temperature control storage component 326, and a storage temperature control component 328 and other sub-modules. Or components. It should be noted that only one fluid system 33 is shown in this embodiment. In fact, there can be multiple fluid systems 33 as required.
  • N can be set in the gene sequencer 1 as required (N is A natural number greater than 1) fluid systems 33, each fluid system 33 is used to load a flow cell 38 and input a specific fluid to the flow cell 38 according to the sequencing requirements, so that the sample in the flow cell 38 undergoes a detection reaction , Each detection site of the flow cell 38 forms a specific substance or structure that can be detected by the signal detection system 31.
  • the gene sequencer 1 can load multiple flow cells 38 at the same time, and input specific fluids for each flow cell 38 according to the sequencing requirements, so that the sample in each flow cell 38 Complete the detection reaction.
  • the sub-modules and components of the fluid system 33 will be described in detail below.
  • the detection reaction module 318 is used to detachably install the flow cell 38 for detection reaction, so that the flow cell 38 can be repeatedly fixed to the detection reaction module 318 through physical connections.
  • the flow cell 38 and the detection reaction module 318 After being installed on the detection reaction module 318, the flow cell 38 and the detection reaction module 318 remain relatively static, and the contact surface of the flow cell 38 and the detection reaction module 318 is kept in full contact, The heat exchange efficiency is ensured, and the inlet for fluid entry and the outlet for fluid discharge of the flow cell 38 are hermetically connected with other modules of the fluid system 33.
  • the detection reaction module 318 is an interaction module of the fluid system 33 and the flow cell 38.
  • the flow channel part inside the detection reaction module 318 can also determine the flow mode of the fluid entering the flow cell 38 and exiting the flow cell 38.
  • the reaction temperature control component 320 is used to control the temperature of the detection reaction module 318 and the flow cell 38 to meet the temperature conditions required by the flow cell 38 during the detection reaction.
  • the reaction temperature control component 320 may be a TEC or other temperature-controlling components or a collection thereof.
  • the fluid transport module 322 is used to take the fluid participating in the detection reaction from the storage module (ie, the non-temperature-controlled storage component 324 and/or the temperature-controlled storage component 326), and transport it into the flow cell 38 through the inlet of the flow cell 38, so that The sample in the flow cell 38 undergoes a detection reaction, and the waste after the detection reaction is discharged to the waste treatment system 34 through the outlet of the flow cell 38.
  • the fluid transport module 322 may be composed of pumps, valves, pipes, and the like.
  • the non-temperature-controlled storage component 324 is used to store the detection fluid that participates in the detection reaction and does not require storage temperature.
  • the non-temperature-controlled storage component 324 is a container that contains one or more sub-containers inside, and each sub-container is provided with a sampling needle (not shown) connected to the fluid transport module 322 as a detection The fluid enters the inlet of the fluid transport module 322.
  • the temperature-controlled storage component 326 is used to store the detection fluids that are required to be stored at a storage temperature (for example, need to be in a fixed temperature or temperature range) that participate in the detection reaction.
  • the temperature control storage component 326 is further used to periodically discharge waste materials such as condensate generated by temperature control to the waste treatment system 34.
  • the temperature-controlled storage component 326 is a temperature-controlled container, and the inside of the temperature-controlled container can contain one or more sub-containers. Each sub-container is provided with a sampling needle connected to the fluid transport module 322 as a detection fluid entering the fluid transport module 322. Entrance.
  • the storage temperature control component 328 is used to control the temperature of the temperature control storage component 326 to meet the storage conditions of the detection fluid that requires storage temperature.
  • the storage temperature control component 328 may be a TEC or other temperature control components or a collection thereof.
  • the waste material processing system 34 is used to store the waste material discharged from the fluid system 33.
  • the waste material may be discharged waste liquid.
  • the waste processing system 34 is further connected to a waste storage device 4 provided outside the gene sequencer 1 for discharging waste into the waste storage device 4.
  • the waste includes, but is not limited to, the waste generated by the detection reaction.
  • the waste processing system 34 includes a waste collection module 330 and a waste transportation module 332 and other sub-modules.
  • the waste collection module 330 is used to collect and store all wastes discharged from the fluid system 33, including wastes from detection reactions, and other wastes generated by the fluid system 33 during operation.
  • the waste collection module 330 includes a power component, and the power component is used to drive the waste into the waste collection module 330 when certain waste materials lack power.
  • the power component may be a liquid pump.
  • the waste collection module 330 is provided with a device or container capable of holding waste materials.
  • the waste transportation module 332 is used for discharging the waste stored in the waste collection module 330 to the waste storage device 4 outside the gene sequencer 1.
  • the waste transportation module 332 may be a module composed of fluid components such as pumps, valves, and pipes.
  • the waste storage device 4 is used to centrally store waste materials from the detection reaction and other waste materials, and is placed outside the gene sequencer 1 to facilitate centralized storage and processing of waste materials.
  • the waste storage device 4 may be a customized waste bucket, or a special waste collection and processing device customized for users.
  • the transfer system 35 is used to move the flow cell 38 to different positions in the gene sequencer 1 as needed. For example, the flow cell 38 needs to be transferred between the fluid system 33 and the signal detection system 31.
  • the transfer system 35 removes the flow cell 38 from the detection fixing module 308 of the signal detection system 31 and installs it to the detection reaction module of the fluid system 33 318; when the detection reaction is completed and signal detection is required, the transfer system 35 removes the flow cell 38 from the detection reaction module 318 and installs it on the detection fixed module 308 of the signal detection system 31.
  • the transfer system 35 may be a robot, or a mechanical arm, or may also be a mechanical device for the purpose of automated transfer, such as a conveyor belt.
  • the control system 36 is used to control the cooperative work of various components in the signal detection system 31, the fluid system 33, the waste disposal system 34 and the transfer system 35.
  • the control system 36 includes sub-modules such as a detection control module 334, a temperature control module 336, a fluid control module 338, a waste control module 340, a transfer control module 342, and a system control module 344.
  • the detection control module 334 is used to control the operation of the components of the signal detection system 31, and convert the instructions issued by the user through the system control module 344 into signals executable by the components of the signal detection system 31. Further, in this embodiment mode, the detection control module 334 also controls the power supply of the signal detection system 31.
  • the detection control module 334 may be an electronic control board composed of electronic components, boards, cables, etc., or a collection of other electronic control components with specific purposes. It should be noted that when multiple signal detection systems 31 are designed in the gene sequencer 1 as required, the detection control module 334 may also be multiple, and each signal detection system 31 is performed by a corresponding detection control module 334. Control, each detection control module 334 can control only one signal detection system 31 to ensure that each signal detection system 31 has independence during operation and does not interfere with each other.
  • the temperature control module 336 is used to control the operation of the reaction temperature control component 320 and the storage temperature control component 328 in the fluid system 33, and convert the temperature control instructions issued by the user through the system control module 344 into signals executable by the components of the above modules . Further, in this embodiment mode, the temperature control module 336 also controls the power supply of the above-mentioned modules.
  • the detection control module 334 may be an electronic control board composed of electronic components, boards, cables, etc., or a collection of other electronic control components with specific purposes.
  • the fluid control module 338 is used to control the operation of each component of the fluid system 33, and convert the instructions issued by the user through the system control module 344 into executable signals for each component of the fluid system 33. Furthermore, in this embodiment, the fluid control module 338 also controls the power supply of the fluid system 33.
  • the fluid control module 338 may be an electronic control board composed of electronic components, boards, cables, etc., or a collection of other electronic control components with specific purposes. It should be noted that when multiple fluid systems 33 are designed in the gene sequencer 1 as required, each fluid system 33 is controlled by a corresponding fluid control module 338, and each fluid control module 338 can only control one fluid. System 33 to ensure that each fluid system 33 is independent when working and will not interfere with each other.
  • the waste control module 340 is used to control the operation of each component of the waste processing system 34, and convert the instructions issued by the user through the system control module 344 into executable signals for each component of the waste processing system 34. Further, in this embodiment, the waste control module 340 also controls the power supply of the waste processing system 34.
  • the waste control module 340 may be an electronic control board composed of electronic components, boards, cables, etc., or a collection of other electronic control components with specific purposes.
  • the transfer control module 342 is used to control the operation of the components of the transfer system 35, and convert the instructions issued by the user through the system control module 344 into signals executable by the components of the transfer system 35. Furthermore, in this embodiment mode, the transfer control module 342 also controls the power supply of the transfer system 35.
  • the transfer control module 342 may be an electronic control board composed of electronic components, boards, cables, etc., or a collection of other electronic control components with specific purposes.
  • the system control module 344 is configured to issue user instructions to the aforementioned control modules, and transmit the feedback of the aforementioned control modules to the user interaction system 37.
  • the system control module 344 may be an electronic control board composed of electronic components, boards, cables, etc., or a collection of other electronic control components with specific purposes.
  • the user interaction system 37 is used for human-computer interaction, so that the gene sequencing system 3 can receive the user's instructions and give feedback to the user's instructions.
  • the gene sequencing system 3 receives user instructions and feedback to the user mainly involves two aspects.
  • the first aspect is the whole machine running software developed to interact with the system control module 344, so that the user can Input the relevant parameters to run the detection reaction process of the whole machine; the second aspect comes from the signal processing system 32, the signal processing system 3 provides the processed detection data, so that the user can intuitively see the detection result.
  • the user interaction system 37 is composed of sub-modules such as a visual interaction module 346 and an input module 348.
  • the user interaction system 37 includes an information input and output interface arranged on the housing 2.
  • the visual interaction module 346 includes a display interface 201
  • the input module 348 includes a keyboard and mouse arranged on the housing.
  • the visual interaction module 346 is used to visually display human-computer interaction content to facilitate human-computer interaction.
  • the visual interaction module 346 may be various types of displays, or various types of touch screen displays, and other devices for visual output.
  • the input module 348 is used to input various instructions of the user to the whole machine.
  • the input module 348 may be various input and output devices, including various types of keyboards, mice, and other input devices.
  • the transfer system 35 is connected to the signal detection system 31 and the fluid system 33 with a long dashed line, which means that the flow cell 38 needs to be transferred between the signal detection system 31 and the fluid system 33, and needs to be fixed separately after the transfer is completed.
  • the control of the flow cell 38 by the signal detection system 31 and the fluid system 33 is a short-term control behavior.
  • the flow cell 38 is acquired by the transfer system 35, the flow cell is completely separated from the control of the signal detection system 31 or the fluid system 33. It is only controlled by the transfer system 35 and finally transferred to the designated location.
  • the solid line is used to connect the signal detection system 31 and the signal processing system 32, which represents the signal/data transmission between the signal detection system 31 and the signal processing system 32; the solid line is used to connect the fluid system 33 and the waste processing system 34 Connected to the waste storage device 4 in turn, representing the material transfer between the fluid system 33 and the waste processing system 34 and the waste storage device 4; use a solid line to connect the detection reaction module 318 and the reaction temperature control component 320, and to control the temperature
  • the storage component 326 and the storage temperature control component 328 are connected, which means that the reaction temperature control component 320 needs to control the temperature of the detection reaction module 318 on demand, and the storage temperature control component 328 needs to control the temperature of the temperature control storage component 326 on demand. Therefore, in this embodiment, the solid-line connection modules/components in FIG. 2 represent the data or substance transmission process.
  • control system 36 is connected to the signal detection system 31, the fluid system 33, the waste disposal system 34, and the user interaction system 37 respectively using dotted and dashed lines, which represents that the control system 36 respectively connects the signal detection system 31 and the fluid system 33.
  • the flow cell 38 is placed in the signal detection system 31 and the fluid system 33 and is represented by a long dashed box, which means that the flow cell 38 is not always installed at the two positions, but according to the progress of the sequencing.
  • the transfer system 35 transfers and fixes at one of the two positions as needed.
  • the flow cell 38 can also be placed at the above two positions at the same time. Only after the flow cell 38 is installed in the signal detection system 31 or the fluid system 33 can the signal detection system 31 or the fluid system 33 start to work.
  • the excitation signal transmission module 301 includes an excitation signal transmission component 3011, an excitation signal arrangement component 3012, a general excitation signal distribution component 3013 and other components.
  • the feedback signal receiving module 305 includes a feedback signal receiving component 3051, a feedback signal sorting component 3052, a general feedback signal distribution component 3053 and other components.
  • the signal channel module 303 includes components such as a general signal distribution component 3031 and a general signal transceiver component 3032.
  • the received signal correction module 306 includes a correction signal transmission component 3061, a correction signal distribution component 3062, a signal correction component 3063 and other components. The detailed description of each of the above components is as follows.
  • the excitation signal emitting component 3011 is used to emit an excitation signal to the sample in the flow cell 38.
  • the excitation signal can excite the feedback signal of the sample.
  • the excitation signal emitting component 3011 can be a voltage, current, or charge trigger device;
  • the excitation signal emitting component 3011 can It is a light source device such as lasers and LED lights.
  • the excitation signal sorting component 3012 is used to sort the transmitted excitation signals to meet the requirements of receiving samples.
  • this component can be a circuit module with functions such as shaping and filtering;
  • the excitation signal sorting component 3012 can be a lens, a reflection Optical equipment such as mirrors and filters.
  • the general excitation signal distribution component 3013 is used for grouping and summarizing the transmitted excitation signals, so as to simplify the transmission requirements of the excitation signals, and can also realize the sorting requirements of the excitation signals at the same time.
  • the general excitation signal distribution component 3013 may be a circuit module with functions such as shaping and filtering; corresponding to signal detection that uses optical methods to stimulate feedback signals, the general excitation signal distribution
  • the component 3013 may be an optical device such as a lens, a mirror, a filter, or a combination thereof.
  • the excitation signal transmission module 301 includes A general excitation signal distribution components 3013, A ⁇ M excitation signal transmission components 3011, and A ⁇ M excitation signal sorting components 3012. Therefore, every M excitation signal
  • the signal transmitting component 3011 and every M excitation signal sorting components 3012 correspond to a general excitation signal distribution component 3013.
  • the feedback signal receiving component 3051 is used to receive the feedback signal emitted from the sample, the feedback signal is excited by the excitation signal, and by detecting the feedback signal, it can be analyzed whether the sample contains a certain substance or component to be detected.
  • the feedback signal receiving component 3051 can be a voltage, current, or charge recording device;
  • the feedback signal receiving component 3051 can It is a photosensitive recording device such as area scan camera (such as CCD), line scan camera (such as TDI), and CMOS.
  • the feedback signal sorting component 3052 is used to sort the received feedback signals to meet the recording requirements of the feedback signals.
  • the feedback signal processing component 3052 can be a circuit module with functions such as shaping and filtering; corresponding to signal detection that uses optical methods to stimulate feedback signals, the feedback signal processing component 3052 It can be an optical device such as a lens, a mirror, a filter, or a combination thereof.
  • the general feedback signal distribution component 3053 is used for grouping and summarizing the received feedback signals, so as to simplify the recording requirements of the feedback signals, and can also realize the requirements for sorting the feedback signals at the same time.
  • the general feedback signal distribution component 3053 can be a circuit module with functions such as shaping and filtering; corresponding to signal detection that uses optical methods to stimulate feedback signals, the general feedback signal distribution
  • the component 3053 may be an optical device such as a lens, a mirror, a filter, or a combination thereof.
  • the feedback signal receiving module 305 includes B general feedback signal distribution components 3053, B ⁇ N feedback signal receiving components 3051, and B ⁇ N feedback signal sorting components 3052. Therefore, every N feedback signal receiving components 3051 and every N feedback signal sorting components 3052 correspond to a general feedback signal distribution component 3053.
  • the general signal distribution component 3031 is used for grouping the excitation signal and the feedback signal to simplify the transmission requirement of the excitation signal and the recording requirement of the feedback signal, and can also realize the requirement of sorting the excitation signal and the feedback signal at the same time.
  • the general signal distribution component 3031 may be a circuit module with functions such as shaping and filtering; corresponding to signal detection that uses optical methods to stimulate feedback signals, the general signal distribution component 3031 It can be an optical device such as a lens, a mirror, a filter, or a combination thereof.
  • the universal signal transceiver component 3032 is used to implement the transition of the excitation signal from the signal channel module 303 to the sample, and the transition of the feedback signal from the sample to the signal channel module 303.
  • the general signal transceiving component 3032 can be controlled by the signal correction component 3063 to perform fine adjustments to achieve the best transceiving effect of the excitation signal and the feedback signal.
  • the universal signal transceiving component 3032 can be an electronic release device such as probes and wires; corresponding to signal detection that uses optical methods to stimulate feedback signals, the universal signal transceiving component 3032 can It is an optical device such as an objective lens, a mirror, a filter, or a combination thereof.
  • the correction signal transmitting component 3061 is used to transmit a correction signal to the sample.
  • the correction signal does not stimulate the feedback signal of the sample, but can be used to detect the working state of the signal channel module 303 to determine whether the detection signal channel module 303 is in the best working condition. status.
  • the correction signal emitting component 3061 can be a voltage, current or charge trigger device; corresponding to optical signal detection, the correction signal emitting component 3061 can be a light source device such as a laser or an LED.
  • the correction signal distribution component 3062 is used to transmit the correction signal emitted by the correction signal transmission component 3061 to the general signal distribution component 3031, or receive the correction signal fed back from the general signal distribution component 3031, so as to feed back the feedback correction signal to
  • the signal correction component 3063 determines whether the general signal transceiver component 3032 needs to be fine-tuned by the signal correction component 3063.
  • the correction signal distribution component 3062 can be a circuit module with functions such as shaping and filtering; corresponding to optical signal detection, the correction signal distribution component 3062 can be a lens, a mirror, a filter, etc.
  • Optical equipment such as optical sheets or combinations thereof.
  • the signal correction component 3063 is used to control the general signal transceiving component 3032 to perform fine-tuning, so as to optimize the transceiving effect of the excitation signal and the feedback signal.
  • the signal correction component 3063 can be a circuit module with functions such as shaping and filtering; corresponding to optical signal detection, the signal correction component 3063 can be an optical device with auto-focusing function.
  • the solid line represents the channel through which the excitation signal or feedback signal is transmitted between the components.
  • the first transmission channel is the excitation signal from the excitation signal transmitting component 3011, which passes through the excitation signal in turn.
  • the second transmission channel is the feedback signal from the flow cell Start at 38, go through the general signal transceiving component 3032, general signal distribution component 3031, general feedback signal distribution component 3053, feedback signal sorting component 3052, and finally arrive at the feedback signal receiving component 3051, and receive the feedback signal sent by the sample being excited.
  • the third transmission channel is the correction signal from the correction signal transmission component 3061, through the correction signal distribution component 3062, the general signal distribution component 3031, the general signal transceiving component 3032, arrives at the flow cell 38 and returns, the returned correction signal passes through the general signal transceiving component 3032.
  • the dotted line represents the feedback of the signal correction component 3063 to the universal signal transceiving component 3032, which means that the signal correction component 3063 adjusts the state of the universal signal transceiving component 3032 according to the returned correction signal.
  • the adjustment of the universal signal transceiver component 3032 can be to adjust the position of the electronic probe or other electronic equipment relative to the sample, or to adjust the electronic indicators such as voltage and current released by the universal signal transceiver component 3032 to the sample ;
  • the adjustment of the universal signal transceiver component 3032 can be auto focus or fine adjustment of the material position of the objective lens.
  • FIG. 4 is a further detailed schematic diagram of the fluid transport module 322 in this embodiment.
  • the fluid transport module 322 includes components such as a power component 3220, a protection component 3221, a detection component 3222, a sample storage component 3223, a distribution component 3224, and a total distribution component 3225.
  • the detailed description of each of the above components is as follows.
  • the power assembly 3220 is used to create a pressure gradient (pressure difference) in the fluid system 33 so as to drive the detection fluid to move in the fluid system 33.
  • the power component 3220 can be various types of pumps used to drive liquid movement, for example, injection pumps, plunger pumps, diaphragm pumps, gear pumps, peristaltic pumps and other common types of pumps, or high-pressure air and other gas pressures. source.
  • the protection component 3221 is used to protect the safe operation of the fluid system 33. When the fluid system 33 is abnormal, the protection mechanism is activated to avoid damage to other components in the fluid system 33.
  • the protection component 3221 may be various types of valves, for example, solenoid valves, one-way valves, pressure relief valves, etc., and may also be components that control the opening and closing of pipelines, such as manual switches.
  • the detection component 3222 is used to detect the preset index of the fluid system 33 to find whether the preset index of the fluid system 33 is abnormal.
  • the detection component 3222 may be various types of sensors, for example, a pressure sensor, a flow sensor, a speed sensor, an air bubble sensor, and so on.
  • the sample storage component 3223 is used to temporarily store the test fluid.
  • the sample storage component 3223 may be a container with a specific shape, or it may be just a section of pipe.
  • the distribution assembly 3224 is used to connect different pipes and components of the fluid system 33 as needed.
  • the distribution assembly 3224 can be various types of solenoid valves, for example, a multi-port direct-acting solenoid valve, a multi-port pilot solenoid valve, etc., or a rotary valve of various models, or a combination of multiple solenoid valves.
  • the fluid transport module 322 includes M fluid transport working groups 3226, and each fluid transport working group 3226 includes at least one power component, one protection component 3221, one detection component 3222, and one A sample storage component 3223 and a distribution component 3224 are used to extract part of the testing fluid from the temperature-controlled storage component 326 and/or non-temperature-controlled storage component 324 for temporary storage in the sample storage component 3223, and set the sample storage component 3223 for temporary storage and testing
  • the beneficial effect of the fluid is that when one of the fluid transport working groups 3226 injects the detection fluid into the detection reaction module 318 and the flow cell 38 through the total distribution assembly 3225, the remaining fluid transport working groups 3226 can use this time gap to absorb
  • the test fluid is prepared to save the preparation time before the test fluid is injected.
  • the fluid transport module 322 has a total of M protection components 3221, M detection components 3222, M sample storage components 3223, and M distribution components 3224. All the fluid transportation working groups 3226 are connected to the total distribution assembly 3225 so as to uniformly allocate which fluid transportation working group 3226 is connected to the detection reaction module 318.
  • the positions of the protection component 3221, the detection component 3222, and the sample storage component 3223 can be interchanged, and the above functions can still be realized.
  • the total distribution assembly 3225 has a similar function to the distribution assembly 3224, and is used to connect different pipes and components in the fluid system 33 as needed.
  • the total distribution assembly 3225 can be various types of solenoid valves, for example, multi-port direct-acting solenoid valves, multi-port pilot solenoid valves, etc., or various types of rotary valves, or it can be composed of multiple A collection of solenoid valves and/or rotary valves.
  • the dotted line with arrows represents the direction of liquid movement of a fluid transport working group 3226 of the fluid transport module 322 when preparing to detect the fluid, using the pressure gradient produced by the power component 3220, the temperature control storage component 326 or non-temperature control
  • the detection fluid in the storage component 324 is temporarily stored in the sample storage component 3223 through the distribution component 3224.
  • the solid line with an arrow represents the direction of liquid movement when a fluid transport working group 3226 of the fluid transport module 322 outputs the detection fluid to the detection reaction module 318 and the flow cell 38.
  • the pressure gradient produced by the power assembly is used temporarily.
  • the detection fluid stored in the sample storage component 3223 flows out from the sample storage component 3223, passes through the distribution component 3224 and the total distribution component 3225, and is output to the flow channel in the detection reaction module 318.
  • the solid arrow connecting the non-temperature-controlled storage component 324 to the power component 3220 indicates that the detection fluid in the non-temperature-controlled storage component 324 may need to be used for fluid flow when the power component 3220 continues to produce pressure gradients.
  • the fluid can be a certain liquid or high-pressure gas stored in the non-temperature-controlled storage component 324.
  • the power component 3220 is not connected to the non-temperature-controlled storage component 324, but is further connected to a storage device that stores fluid, the fluid being a liquid or a high-pressure gas, and the power
  • the component 3220 continuously creates a pressure gradient to inject the fluid stored in the sample storage component 3223 into the flow cell, the fluid in the storage device supplements the power component 3220 with fluid.
  • a long dashed line with an arrow connects the protection component 3221 and the waste treatment system 34, as well as the temperature control storage component 326 and the waste treatment system 34, respectively.
  • the connection of the protection component 3221 and the waste disposal system 34 means that when a problem occurs in the fluid transportation working group 3226, the protection component 3221 starts to work, and some excess fluid may be discharged from the protection component 3221 to the waste disposal system 34.
  • the connection of the temperature-controlled storage component 326 and the waste processing system 34 represents that there is a temperature difference between the temperature of the temperature-controlled storage component 326 and the outside temperature. When the temperature of the temperature-controlled storage component 326 is lower than the outside temperature, condensate will be generated. The liquid is collected in the waste disposal system 34.
  • FIG. 5 is a detailed schematic diagram of the detection reaction module 318 in this embodiment.
  • the detection reaction module 318 includes components such as an inlet switch component 3181, an outlet switch component 3182, a bypass switch component 3183, and a main switch component 3184.
  • the detailed description of each component of the detection reaction module 318 is as follows.
  • the inlet switch assembly 3181 is used to control the opening or closing of the pipe at the inlet of the flow cell 38.
  • the inlet switch assembly 3181 may be various types of solenoid valves, for example, a multi-port direct-acting solenoid valve, a multi-port pilot solenoid valve or a rotary valve of various types, or it may be composed of multiple solenoid valves. And/or a collection of rotary valves.
  • each inlet of the flow cell 38 corresponds to an inlet switch assembly 3181 to ensure that each inlet of the flow cell 38 has an inlet switch assembly 3181 for control, and each inlet The switch assembly 3181 can be independently controlled.
  • the outlet switch assembly 3182 is used to control the opening or closing of the pipe at the outlet of the flow cell 38.
  • the outlet switch assembly 3182 may be various types of solenoid valves, for example, a multi-port direct-acting solenoid valve, a multi-port pilot solenoid valve, or a rotary valve of various types, or it may be composed of multiple solenoid valves. And/or a collection of rotary valves.
  • each outlet of the flow cell 38 corresponds to an outlet switch assembly 3182 to ensure that each outlet of the flow cell 38 has an outlet switch assembly 3182 for control, and each outlet The switch assembly 3182 can be independently controlled.
  • the bypass switch assembly 3183 is used to control the opening or closing of the pipeline at the inlet of the flow cell 38.
  • the bypass switch assembly 3183 may be various types of solenoid valves, for example, a multi-port direct-acting solenoid valve, a multi-port pilot solenoid valve, or a rotary valve of various types, and it may also be composed of multiple solenoid valves. A collection of valves and/or rotary valves.
  • the main switch assembly 3184 is used to control the opening or closing of the pipeline of the main outlet of the detection reaction module 318.
  • the master switch assembly 3184 may be various types of solenoid valves, for example, a multi-port direct-acting solenoid valve, a multi-port pilot solenoid valve, or a rotary valve of various types, or it may be composed of multiple solenoid valves. And/or a collection of rotary valves.
  • the detection reaction module 318 can be provided with M inlet switch assemblies 3181, N outlet switch assemblies 3182, and X bypass switch assemblies 3183 at the same time.
  • Each inlet switch assembly 3181 and each bypass switch assembly 3183 independently control a channel connected from the fluid transport module 322, and all outlet switch assemblies 3182 are collectively connected to the master switch assembly 3184.
  • the solid line with an arrow starts from the fluid transport module 322, connects the bypass switch assembly 3183, the main switch assembly 3184, and finally reaches the waste disposal system 34.
  • This process represents when the fluid transport module 322 moves to the detection response
  • some of the fluid injected by the module 318 cannot be input into the flow cell 38 for a detection reaction, it needs to be directly discharged to the path that the waste treatment system 34 needs to pass.
  • These fluids include, but are not limited to, fluids used to clean the sample storage assembly 3223 or other pipes in the fluid transport module 322, fluids that have a risk of cross-contamination and need to be eliminated, or the remaining detection fluids after certain detection reaction steps.
  • the dotted line with arrows starts from the fluid transport module 322, connects the inlet switch assembly 3181, the flow cell inlet 381, the flow cell outlet 382, the outlet switch assembly 3182, the master switch assembly 3184, and finally arrives at the waste disposal system 34.
  • This process represents the path through which the detection fluid enters the flow cell 38 from the flow cell inlet 381 and exits the flow cell 38 from the flow cell outlet 382 when the fluid transport module 322 injects the detection fluid into the detection reaction module 318 to participate in the detection reaction.
  • These fluids are mainly fluids that need to be injected into the flow cell 38 such as detection fluids.
  • the long dashed line with arrows has two paths.
  • the first path starts from the fluid transport module 322, connects the inlet switch assembly 3181, the flow cell inlet 381 in turn, and passes through the shaded peripheral area at the flow cell inlet 381 Y, finally arrives at the waste disposal system 34.
  • the second path starts from the fluid transport module 322, connects the bypass switch assembly 3183, the outlet switch assembly 3182, and the flow cell outlet 382 in sequence, passes through the shaded peripheral zone Z at the flow cell outlet 382, and finally reaches the waste disposal system 34. It should be noted that when the second path is executed, the main switch assembly 3184 needs to be turned off.
  • the shaded area at the flow cell inlet 381 and the flow cell outlet 382 represents the sealed area between the detection reaction module 318 and the flow cell inlet 381 and the flow cell outlet 382. Since the detection of the flow cell 38 needs to be transferred regularly, this sealed area It needs to be cleaned in time to prevent the detection of fluid residue. According to the above analysis, these two processes respectively represent when the fluid transport module 322 injects some fluid into the detection reaction module 318 to clean the sealing areas Y and Z between the detection reaction module 318 and the flow cell inlet 381 and flow cell outlet 382, the cleaning fluid They are discharged to the path required by the waste disposal system 34 respectively.
  • the above two processes can only be performed after the flow cell 38 is transferred away, so as not to contaminate the sample inside the flow cell 38 by the cleaning fluid. If the areas Y and Z are in an open state, the waste treatment system 34 is required to provide power components for transferring the cleaning fluid overflowing from the flow cell inlet 381 and the flow cell outlet 382; if the areas Y and Z are in a sealed state, there is no need The waste disposal system 34 provides power components, but requires additional tools to seal the above-mentioned areas Y and Z and retain the passage of liquid in and out.
  • FIG. 6 is a detailed schematic diagram of the waste collection module 330 and the waste transportation module 332 of this embodiment.
  • the waste collection module 330 includes a waste collection power component 3301, a waste storage component 3302, a waste detection component 3303 and other components.
  • the waste transportation module 332 includes a waste discharge power assembly 3321 and a waste transfer assembly 3322 and other components.
  • the waste collection power assembly 3301 is used to provide power for certain waste materials that lack power driving.
  • the waste collection power assembly 3301 can be various types of pumps used to drive liquid movement, for example, injection pumps, plunger pumps, diaphragm pumps, gear pumps, peristaltic pumps and other common types of pumps, or high-pressure air, etc. Gas pressure source.
  • the waste storage component 3302 is used to store waste materials of the detection reaction, and the waste storage component 3302 can temporarily store waste materials of all the fluid systems 33 in the genetic testing device 1.
  • the waste storage component 3302 may be a container with a specific shape.
  • the waste detection component 3303 is used to detect the amount of waste stored in the waste storage component 3302, so that when the amount of waste in the waste storage component 3302 reaches a preset amount, the waste transportation module 332 is used to discharge the waste to the waste storage device 4 for storage.
  • the waste detection component 3303 can be a gravity detection device, which judges the amount of waste collected by gravity, or a volume detection device, which judges the amount of waste collected by volume, or a height detection device, which judges the amount of waste collected by the liquid level. The amount of waste collected.
  • the waste discharge power assembly 3321 is used to provide power for transporting waste from the waste storage assembly 3302 to the waste storage device 4.
  • the waste discharge power assembly 3321 can be various types of pumps used to drive liquid movement, such as injection pumps, plunger pumps, diaphragm pumps, gear pumps, peristaltic pumps and other common types of pumps, or high-pressure air, etc. Gas pressure source.
  • the waste transfer component 3322 is arranged on the housing 2 of the gene sequencer 1 and is a component that transfers the internal pipeline and the external pipeline.
  • the waste transfer component 3322 may be various types of connectors, such as through-board connectors.
  • the dotted and dashed lines with arrows start from the fluid system 33, connect the waste collection power assembly 3301 in turn, and finally reach the waste storage assembly 3302.
  • the waste collection power assembly 3301 connected to the waste collection module 330 provides power for the waste to flow into the waste storage assembly 3302 through a path for temporary storage.
  • the waste includes, but is not limited to, the condensate generated by the temperature control storage module 326 because the temperature is lower than the outside, and the cleaning fluid pushed by the detection reaction module 318 to clean the sealed peripheral area Y, Z to the area Y, Z.
  • the long dashed line with arrows starts from the fluid system 33 and directly reaches the waste storage assembly 3302.
  • This process represents the path required to push the waste directly into the waste storage assembly 3302 when the fluid system 33 can provide power.
  • the power for this process is provided by the power assembly 3220 of the fluid transportation module 322 in the fluid system 33, so it can be directly discharged into the waste storage assembly 3302.
  • the waste includes, but is not limited to, the waste generated by the detection reaction of the flow cell 38, and the waste discharged by the fluid system 33 cleaning the sample storage assembly 3223 or other pipes.
  • the solid line with an arrow starts from the waste storage component 3302, passes through the waste transfer component 3322, and reaches the waste storage device 4.
  • This process represents when the waste contained in the waste storage component 3302 exceeds the set threshold, The path required to transport waste from the waste storage assembly 3302 to the waste storage device 4.
  • the waste is all waste generated by all the fluid systems 33 of the whole machine working within a certain period of time.
  • the dotted line represents the measurement of the amount of waste in the waste storage component 3302 by the waste detection component 3303.
  • the control system 36 controls the waste transportation module 332
  • the waste discharging power assembly 3321 starts to work, and transports the waste in the waste storage assembly 3302 to the waste storage device 4 for storage.
  • FIG. 7 shows the operation logic of the transfer system 35 in this embodiment.
  • the object transferred by the transfer system 35 is the flow cell 38, and the flow cell 38 is a container for loading a sample to perform a detection reaction.
  • the flow cell 38 can be a closed sequencing chip or an open substrate for loading samples.
  • the main transfer destinations of the flow cell 38 are: the flow cell starting position O, the Nth fluid system 33, the Mth signal detection system 31, the flow cell temporary storage position T, and the flow cell disposal position D , Where M and N respectively represent the arbitrary numbers of the fluid system 33 and the signal detection system 31 when there are multiple fluid systems 33 and signal detection systems 31 in the gene sequencer 1 at the same time.
  • the starting position O of the flow cell is the starting position for starting sample detection in the flow cell 38.
  • the starting position O of the flow cell is the flow cell insertion interface 203. The user places the sample-loaded flow cell 38 at the start position O of the flow cell, and after confirmation by the user interaction system 37, the transfer system 35 transfers it to the machine for detection reaction.
  • the position of the flow cell 38 in the Nth fluid system 33 is located on the detection reaction module 318 of the Nth fluid system 33, when the flow cell 38 is installed at the position, the control system 36 controls to input the detection fluid
  • the flow cell 38 performs a detection reaction.
  • the position of the flow cell 38 in the M-th signal detection system 31 the position is located on the detection fixing assembly 308 of the M-th signal detection system 31.
  • the control system 36 controls the M-th signal detection system 31.
  • Each signal detection system 31 applies an excitation signal to the sample, and then collects the feedback signal of the sample.
  • Temporary flow cell storage position T The position is set on a fixed position in the gene sequencer 1 for temporarily placing the flow cell 38.
  • Flow cell disposal position D The position is the position where the flow cell 38 is discarded after the detection reaction is completed or interrupted and abandoned.
  • the transfer system 35 places the discarded flow cell 38 in this position, and then the user collects and disposes of it. .
  • the solid line with an arrow starts from the starting position O of the flow cell, and is connected to the Nth fluid system 33, the Mth signal detection system 31, and the flow cell discarding position D, respectively.
  • the flow cell starting position O, the Nth fluid system 33, and the Mth signal detection system 31 are respectively bidirectionally connected, but the Nth fluid system 33, the Mth signal detection system 31 and the flow cell disposal position There is a one-way connection between D.
  • This path represents that the user places the prepared flow cell 38 at the starting position O of the flow cell, and then the whole machine controls the flow cell 38 to perform detection reactions between the Nth fluid system 33 and the Mth signal detection system 31. And the flow of signal detection, but once the flow cell 38 is discarded, it cannot be returned to the transfer system 35 for continued use.
  • the specific execution path in the detection reaction can be customized according to the different principles of the detection reaction.
  • the dotted line with arrows starts from the flow cell starting position O, and connects the flow cell temporary storage position T and the flow cell discarding position D.
  • the flow cell starting position O, the flow cell temporary storage position T and The Nth fluid systems 33 are connected in two directions respectively, but the temporary storage position T of the flow cell and the discard position D of the flow cell are connected in one direction.
  • This path represents the process in which the flow cell 38 moves from the flow cell starting position O or the Nth fluid system 33 to the flow cell temporary storage position T for temporary storage, or some tools used by the user move from the flow cell starting position O
  • the specific execution path can be customized according to different needs.
  • FIG. 8 is a detailed schematic diagram of the signal transmission module 312, the signal processing module 314, and the data storage module 316 in this embodiment.
  • the signal transmission module 312 includes components such as a signal transmission component 3121 and a signal buffer component 3122.
  • the signal processing module 314 includes a data analysis component 3141.
  • the data storage module 316 includes components such as a data compression component 3161 and a data storage component 3162.
  • the signal transmission component 3121 is used to collect and transmit the feedback signal obtained by the signal detection system 31.
  • the signal transmission component 3121 may be a device that collects electronic signals such as voltage and current at regular intervals, such as a data acquisition card.
  • the signal buffer component 3122 is used to buffer the feedback signal before the feedback signal is processed. After the feedback signal is opened in the buffer, it can wait to be called and processed.
  • the signal cache component 3122 may be a computer's memory or other levels of cache.
  • the data analysis component 3141 is used to extract the feedback signal temporarily written in the signal buffer component 3122, perform operations such as conversion and filtering, so that the feedback signal becomes data that can be analyzed and a sequencing report is generated.
  • the data analysis component 3141 may be hardware used by a computer for processing, for example, hardware such as memory, CPU, GPU, etc., which cooperates with processing and analysis programs to perform operation processing.
  • the data compression component 3161 is used to compress the processed data before storage to reduce storage space and time for writing storage.
  • the data compression component 3161 may be hardware used by a computer for processing, for example, hardware such as memory, CPU, GPU, etc., which cooperates with processing and analysis programs for running processing.
  • the data storage component 3162 is used to store the compressed data and the generated sequencing report, so as to save and back up the analyzed test results.
  • the data storage component 3162 may be various computer storage media, for example, hard disk, flash disk, magnetic disk and other hardware.
  • the solid line with arrows starts from the signal detection system 31, connects the signal transmission component 3121, the signal buffer component 3122, the data analysis component 3141, and the data compression component 3161 in sequence, and finally reaches the data storage component 3162.
  • This process represents Starting from the signal detection system 31 receiving the feedback signal of the sample, the feedback signal is gradually converted into data that can be used for analysis, the analysis is performed to obtain the detection result, and the path required for storage is performed.
  • electrical signal detection electrical signals such as voltage and current are gradually converted into digital data that can be read and written and analyzed; corresponding to optical signal detection, digital photos and other data are gradually converted The digital data can be read and written and stored.
  • the long dashed line with arrows starts from the data analysis component 3141 and directly reaches the user interaction system 37.
  • This process represents the real-time feedback of the signal processing system 32 to the user when the data is obtained and processed.
  • the signal processing system 32 may only include the signal transmission component 3121, and the signal transmission component 3121 collects the feedback signal obtained by the signal detection system 31 and transmits the feedback signal to the gene sequencer 1 External data processing device.
  • the signal processing system 32 may not include the signal buffer component 3122 and the data analysis component 3141, and the signal transmission component 3121 collects the feedback signal obtained by the signal detection system 31, and then transmits the feedback signal to the data compression
  • the component 3161 is compressed by the data compression component 3161 and stored in the data storage component 3162. After that, the data storage component 3162 can be removed from the gene sequencer 1 and accessed by a data processing device set outside the gene sequencer 1 To generate a sequencing report.
  • the signal processing system 32 may not include the signal buffer component 3122, the data analysis component 3141, and the data storage component 3162.
  • the signal transmission component 3121 collects the feedback signal obtained by the signal detection system 31, The feedback signal is transmitted to the data compression component 3161, compressed by the data compression component 3161, and then transmitted to a data processing device arranged outside the gene sequencer 1.
  • FIG. 9 is a schematic diagram of the biochemical substance analysis system provided in the second embodiment of the present invention.
  • the biochemical substance analysis system 5 is used to receive the flow cell and complete the detection of the biological characteristics of the sample in the flow cell.
  • the biological characteristics may be the gene sequence of the sample.
  • the biochemical substance analysis system includes: a detection system 51 and a scheduling system 53 , The biochemical reaction system 55 and the control system 57, the scheduling system 53 is used to schedule the flow cell at different positions, the positions including the position in the detection system 51 and the position in the biochemical reaction system 55 Site, the biochemical reaction system 55 is used for reacting the sample in the flow cell, for example, for injecting a reactant into the flow cell to cause the sample in the flow cell to react, and the detection system 51 is used for Signal detection is performed on the sample that has reacted to obtain a signal representing the biological characteristics of the sample.
  • the control system 57 is used to control the coordinated operation of the detection system 51, the scheduling system 53 and the biochemical reaction system 55.
  • the detection system 51 may include the signal detection system 31 in the first embodiment or both the signal detection system 31 and the signal processing system 32 in the first embodiment, and the signal representing the biological characteristics of the sample may be The feedback signal obtained by the signal detection system 31 or the analyzable data obtained after the feedback signal is processed by the signal processing system 32.
  • the scheduling system 53 may include the transfer system 35 in the first embodiment, and the biochemical reaction system 55 may include the fluid system 33 in the first embodiment or both the fluid system 33 and the waste treatment system 34 in the first embodiment.
  • the control system 57 may include the control system 36 of the first embodiment.
  • FIG. 10 is a flowchart of the biochemical substance analysis method provided in the third embodiment of the present invention.
  • the biochemical substance analysis method includes:
  • Step S1001 receiving a flow cell, and transferring the received flow cell to the biochemical reaction system;
  • Step S1003 inputting reactants into the flow cell in the biochemical reaction system to cause the sample in the flow cell to undergo a biochemical reaction;
  • Step S1005 Transfer the flow cell where the sample has completed the biochemical reaction to the detection system
  • Step S1007 Perform signal detection on the sample in the flow cell in the detection system to obtain a signal reflecting the biological characteristics of the sample.
  • the biochemical substance analysis method may further include: judging whether the site where the flow cell is loaded in the biochemical reaction system is free, and Or when multiple sites are free, load the flow cell onto one of the free sites, and when none of the sites are free, place the flow cell in a flow cell temporary storage position.
  • the biochemical substance analysis method may further include: judging whether the site where the flow cell is loaded in the detection system is free, one or more The flow cell is loaded on one of the free sites when the individual sites are free, and the flow cell is placed in a flow cell temporary storage position when the sites are not free.
  • the biochemical substance analysis method before receiving the flow cell, further includes: detecting whether there is a flow cell at the site of the receiving flow cell, and when there is a flow cell at the site of the receiving flow cell Receiving the flow cell.
  • the biochemical substance analysis method further includes: re-transferring the flow cell that has completed the detection to the biochemical reaction system and repeating the whole process of reaction-transfer-detection.
  • the biochemical substance analysis method further includes: transferring the flow cell that has completed the detection to a flow cell discarding position that receives the discarded flow cell.
  • the step S1003 further includes: sucking fluid from the fluid storage module and temporarily storing it in the sample storage component, and pushing the fluid temporarily stored in the sample storage component into the storage module.
  • the flow cell is used to make the sample in the flow cell react.
  • the step S1003 further includes: after the fluid is temporarily stored in the sample storage assembly, judging whether the passage for the fluid to enter the flow cell is occupied, if the passage is Occupied, the fluid continues to be temporarily stored in the sample storage assembly, and if the channel is not occupied, the temporarily stored fluid is pushed into the flow cell through the channel.
  • the step of reacting further includes: while pushing the first fluid from the sample storage assembly temporarily storing the first fluid into the flow cell, pushing the second fluid into the flow cell.
  • the fluid is drawn from the storage module for storing the second fluid and temporarily stored in the sample storage assembly for temporarily storing the second fluid.
  • the detection step may further include: processing the signal to obtain analyzable data or a detection report.
  • FIG. 11 is a schematic diagram of a biochemical substance analysis device using a biochemical substance analysis system according to the fourth embodiment of the present invention.
  • the biochemical substance analysis device 6 includes at least a biochemical substance analysis system 61, and the biochemical substance analysis system 61 may be the biochemical substance analysis system 5 provided in the second embodiment.
  • FIG. 12 is a schematic diagram of a biochemical substance analysis device using a biochemical substance analysis method according to the fifth embodiment of the present invention.
  • the biochemical substance analysis device 7 runs the biochemical substance analysis method provided in the third embodiment to obtain the biological characteristic signal, analyzable data or detection report of the sample in the reaction flow cell.
  • the user only needs to add the detection fluid, cleaning fluid, and sample loaded for sequencing.
  • the flow cell is placed in the gene sequencer through the interface on the gene sequencer, and the relevant parameters are set through the user interaction system, and the gene sequencer and the gene sequencing system can automatically complete the gene sequencing.
  • the gene sequencer and gene sequencing system provided by the embodiments of the present invention can also realize simultaneous detection of multiple flow cells by providing multiple signal detection systems and/or multiple fluid systems, which improves the gene sequencer and gene sequencing system.
  • the detection throughput can be provided.
  • the gene sequencer and gene sequencing system provided by the embodiments of the present invention can also be configured by multiple fluid transport working groups, each fluid transport working group includes a sample storage component, and one of the fluid transport working groups is directed to the detection reaction module and the flow
  • each fluid transport working group includes a sample storage component
  • one of the fluid transport working groups is directed to the detection reaction module and the flow
  • other fluid transport teams can use this time gap to absorb fluid for preparation, thereby saving the preparation time before fluid is injected into the flow cell, and also improving the detection throughput of the gene sequencer and the gene sequencing system.

Landscapes

  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

一种生化物质分析***（3），用于对流动池（38）内样品的生物特征的检测，包括检测***（31）、调度***、生化反应***及控制***（36）。调度***用于将流动池（38）在不同位点进行调度，位点包括位于检测***（31）的位点与位于生化反应***的位点，生化反应***用于使流动池（38）内的样品发生反应，检测***（31）用于对已发生反应的样品执行信号检测以获得代表样品的生物特征的信号，控制***（36）用于控制检测***（31）、调度***与生化反应***的协同作业。该***提高了生化物质分析的自动化程度和通量。

Description

生化物质分析***、方法及装置 技术领域
本发明涉及生化物质分析领域，尤其涉及一种生化物质分析***、方法及装置。
背景技术
常见的用于样品检测的仪器至少需要包括流动池、检测***、流体***等部分。流动池是被测样品与检测流体(如试剂)发生检测反应的区域；检测***用于施加检测激励并记录检测反应的响应信号；流体***负责输入参加检测反应的检测流体以及排出检测反应之后的废料。以常见的基于第二代测序技术设计制造的基因测序仪为例，其整机***主要由流动池、信号检测***及流体***组成。
流动池(即样品载体)是用于加载生化物质的样品并发生检测分析反应的区域，其通常含有容纳样品和流体的腔体。在测序领域，流动池是用于加载基因测序的样品并发生测序反应的区域，其通常含有容纳样品和流体的腔体，一般也会被称为流动槽、反应池、芯片、测序芯片、基因测序芯片或者卡盒等，常见的英文名称有Flow Cell、Flowcell、Chip、Chip Kit和Cartridge等。由于样品加载的不可重复性，以及避免不同样品间的交叉污染等要求，测序芯片通常被设计为一次性使用、可反复安装拆卸，以及全封闭的样式。测序芯片可以拥有一个或多个独立通道，每个通道拥有一个入口和一个出口，用于检测反应的流体输入和输出。测序芯片的上表面通常为可透光材料，可透过激发光信号和被激发的光信号，可透过该表面进行光学信号检测；测序芯片的下表面通常为基底，被测基因样品可通过某种生物或化学反应固定在其表面。
信号检测***，可发出激励信号和接收反馈信号。第二代测序技术 常用的检测方法是激光诱导荧光，即使用激光器激发样品，使其发出荧光信号反馈，然后使用面阵相机拍照记录被激发出的光学信号。因此，该检测***本质上为光学成像***，主要由激光器、物镜、滤光片、筒镜、相机、工件台等部件组成。其中，激光器用于激发测序反应中被检测样品的荧光信号反馈，而物镜、滤光片、筒镜、相机等部件组成的模块负责采集被检测样品发出的荧光信号。由于通常面阵相机拍照的区域要远小于测序芯片的设计检测区域，因此在检测***工作时，需要测序芯片随着工件台进行移动，逐渐遍历所有的反应区域，同时使用相机进行实时曝光，才能逐个接收测序芯片中各检测区域发出的荧光信号。
流体***，在基因测序仪中，参加检测反应的流体就是测序流体，流体***是负责将待反应的测序流体输入测序芯片，同时将反应后的测序流体排出测序芯片的***，一般由测序流体盒、取样针、管道、液泵等部件组成。其中，测序流体盒是用于装载测序流体的容器；管道是连接流体***各部件并使测序流体通过的封闭通道；液泵是驱动测序流体在流体***中运动的动力源。常见的流体***通常设计为串联形式，为避免使用液泵产生交叉污染，一般将测序流体盒放在上游，使用流体针作为流体***的入口，通过管道将其下游依次连接测序芯片和液泵。连接到测序芯片和液泵的管道通常称为主管道，该管道是测序流体输入和输出流体***的必经途径。流体***在工作时，将流体针***测序流体盒中并开启液泵，使测序流体沿着流体针，通过管道流入测序芯片，同时测序芯片中的已有测序流体将沿着液泵的管道排出。这种设计方式的物理本质是使用液泵建立负压，使整个流体***的压力低于外界大气压力，利用外界大气压力将测序流体压入流体***。
然现有的检测仪器还是具有自动化程度不高及通量较低的问题。
发明内容
为了解决现有技术的上述部分或全部问题以及其他潜在问题，有必要提出一种生化物质分析***、方法及装置。
第一方面，提供一种生化物质分析***，所述生化物质分析***用于完成对流动池内样品的生物特征的检测，包括检测***、调度***、生化反应***及控制***，其中，所述调度***用于将所述流动池在不同位点进行调度，所述位点包括位于检测***的位点与位于生化反应***的位点，所述生化反应***用于使所述流动池内的样品发生反应，所述检测***用于对已发生反应的样品执行信号检测以获得代表所述样品的生物特征的信号，所述控制***用于控制所述检测***、调度***与生化反应***的协同作业。
第二方面，提供一种生化物质分析方法，包括：
接收流动池，并将接收的所述流动池转移至生化反应***；
在生化反应***内使所述流动池内的样品发生反应；
将样品已完成生化反应的流动池转移至检测***；及
在检测***内对所述流动池内的样品执行信号检测以获得反应所述样品的生物特征的信号。
第三方面，提供一种生化物质分析装置，所述生化物质分析装置包括上述的生化物质分析***；或者，所述生化物质分析装置应用上述的生化物质分析方法以获得反应流动池内样品的生物特征的信号、可分析数据或检测报告。
本发明的实施方式提供的生化物质分析***、方法及装置，用户仅需要将测序所需的检测流体、清洗流体及装载了样品的流动池通过基因测序仪上的接口置入基因测序仪内，通过用户交互***设置相关参数，基因测序仪及基因测序***便可自动完成基因测序。提高了基因测序的自动化程度。
附图说明
为了更清楚地说明本发明实施例的技术方案，下面将对本发明实施例中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图 仅仅是本发明的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图获得其他的附图。
图1是本发明实施方式一中的基因测序仪的立体示意图。
图2是本发明基因测序仪的基因测序***示意图。
图3是图2所示***中的信号检测***各模块示意图。
图4是图2所示***中的流体运输模块的各组件示意图。
图5是图2所示***中的检测反应模块各组件示意图。
图6是图2所示***中的废料处理***各模块示意图。
图7是图2所示***中的转移***的运行逻辑示意图。
图8是图2所示***中的信号处理***各模块示意图。
图9是本发明实施方式二提供的生化物质分析***的方框示意图。
图10使本发明实施方式三提供的生化物质分析方法的流程图。
图11是本发明实施方式四提供的生化物质分析装置的示意图。
图12是本发明实施方式五提供的生化物质分析装置的示意图。
如下具体实施方式将结合上述附图进一步说明本发明。
主要元件符号说明
Figure PCTCN2019107593-appb-000001
Figure PCTCN2019107593-appb-000002
Figure PCTCN2019107593-appb-000003
具体实施方式
以下将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
需要说明的是，当组件被称为“固定于”、“安装于”另一个组件，它可以直接在另一个组件上或者也可以存在居中的组件。当一个组件被认为是“设置于”另一个组件，它可以是直接设置在另一个组件上或者可能同时存在居中组件。本文所使用的术语“及/或”包括一个或多个相关的所列项目的所有的和任意的组合。
文中M、N和X等数量代词在各处均指代不定数量或顺序，其不作为对特定数量或顺序的指代。也就是说，同样的M、N和X在不同地方可能指代不同的数量或顺序。
请参阅图1所示，为本发明一实施方式中的基因测序仪的示意图。所述基因测序仪1包括壳体2及置于壳体2内并通过壳体2与外界交互 的基因测序***3。
在本实施方式中，所述壳体2上设置有多个输入输出接口，所述输入输出接口包括信息输入输出接口，如显示界面201、键盘鼠标207等，本实施方式中，键盘鼠标207被隐藏于壳体2中，在需要使用时可从壳体2中抽出。所述输入输出接口还包括物质输入输出接口，如流动池置入接口203、流体盒置换接口205等。用户可通过信息输入接口设置必要的参数/指令，并将加载了样品的流动池(即样品载体)、盛放需要的测序流体(如试剂)与清洗流体(如清洗液)的流体盒(如试剂盒)通过相应的物质输入输出接口置入基因测序仪1中后，启动基因测序仪1，基因测序仪1根据设定参数/指令自动完成对流动池内样品的检测，并将结果信息通过信息输入输出接口输出给用户。
其中，本发明所称的“流动池”是用于加载生化物质的样品并发生检测分析反应的区域，其通常含有容纳样品和流体的腔体，应当将其理解为广义上的样品载体。亦即是说，除在测序情况下可以理解为测序芯片外，在其它情况下还可以理解为其它样品载体。
请参阅图2所示，在本实施例中，所述基因测序***3包括信号检测***31、信号处理***32、流体***33、废料处理***34、转移***35、控制***36和用户交互***37等子***。在一或多个流动池38被置入基因测序仪1中后，每一流动池38被转移***35在各个相关子***中进行位置转换，以使流动池38内样品完成检测反应并进行信号检测。
以下对各子***进行详细说明。
所述信号检测***31用于对流动池38内的样品执行信号检测，包括施加激励信号，接收和记录来自样品的反馈信号等。在本实施方式中，所述信号检测***31进一步包括激励信号发射模块301、信号通道模块303、反馈信号接收模块305、接收信号校正模块306、检测固定组件308及移动组件310。需要注意的是，本实施例中仅示出了一个信号 检测***31对流动池38内的样品进行检测，实际上，根据需要，所述信号检测***31可以为多个，例如，可以根据需要在基因测序仪1中设置M(M为大于1的自然数)个信号检测***31，每一信号检测***31根据控制***36的控制对一流动池38内的样品执行至少一次检测，以完成对该流动池38中样品的至少一个碱基的信号检测。当基因测序仪1中设置了多个信号检测***31时，基因测序仪1可同时对多个流动池38中的样品进行信号检测。
以下对所述信号检测***31的各子模块进行详细说明。
所述激励信号发射模块301用于对流动池38中的样品施加激励信号，以检测是否可以获得反馈信号。通过反馈信号则可判断样品的成分。激励信号可以是光信号或电信号，如果激励信号是光信号，则所述激励信号发射模块301可以是激光器、LED等光源；如果激励信号是电信号，则所述激励信号发射模块301可以是电源。
所述信号通道模块303用于使激励信号发射模块301发射的激励信号按照预设的路径抵达流动池38，并使反馈信号从流动池38出发按照预设的路径抵达反馈信号接收模块305。如果激励信号是光信号，则所述信号通道模块303可以是一组由物镜、筒镜、镜片、滤光片等一或多个光学部件组成的光学模块；如果激励信号是电信号，则所述信号通道模块303可以是一组由导电线缆、电阻、电容、整流器、滤波器等一或多个电学部件组成的电学模块。
所述反馈信号接收模块305用于接收样品被激励信号激发后发出的反馈信号。如果激励信号是光信号，则所述反馈信号接收模块305可以是各类面阵相机、线扫描相机、或是其它例如光电二极管、光电倍增管等光信号接收器；如果激励信号是电信号，则所述反馈信号接收模块305可以是信号采集卡等电信号接收部件。
所述接收信号校正模块306用于对激励信号的发射路径和反馈信号的接收路径进行调校，使发射的激励信号和接收的反馈信号相适配且 效果最佳。在本实施例中，如果激励信号是光信号，则所述接收信号校正模块306可以是各类自动对焦组件及其组合；如果激励信号是电信号，则所述接收信号校正模块306可以是各类整流部件及其组合。
所述检测固定组件308用于可卸式安装和固定流动池38，使流动池38在进行信号检测时与所述检测固定组件308保持相对静止。
所述移动组件310与所述检测固定组件308相连接，用于驱使所述检测固定组件310在一定范围内移动，以使流动池38的所有需检测的区域都能进行信号检测。在本实施例中，所述移动组件310可以是XY移动平台等移动控制设备。
所述信号处理***32用于对所述信号检测***31接收的反馈信号进行处理和分析，得到测序数据并生成报告。在本实施例中，所述信号处理***32包括信号传输模块312、信号处理模块314和数据存储模块316。以下对所述信号处理***32的各子模块进行详细说明。
所述信号传输模块312用于接收信号检测***31传输过来的反馈信号，将反馈信号进行缓存，等待后续的处理分析。如前所述，根据需要，所述基因测序仪1可以设置多个信号检测***31。在设置了等多个信号检测***31时，每一信号检测***31所接收的反馈信号都可送至所述信号传输模块312进行缓存，等待后续处理分析。所述信号传输模块312可以是各类非易失性信号缓存装置。
所述信号处理模块314用于从所述信号传输模块312中获取缓存的反馈信号，通过算法转化为可供分析的数据，进一步分析所述数据以生成测序报告，并将测序报告输出到用户交互***37。
所述数据存储模块316用于将处理完成的数据及测序报告进行压缩，存储在存储介质中以作为备份，以使用户可以随时调用和查看。
所述流体***33用于在样品检测期间存储待用的检测流体如检测试剂，将检测流体输入流动池38进行检测反应，并将完成检测反应后的所有废料排出至废料处理***34。在本实施例中，所述流体***33 包括检测反应模块318、反应温控组件320、流体运输模块322、非控温存储组件324、控温存储组件326和存储温控组件328等多个子模块或组件。需要注意的是，本实施例中仅示出了一个流体***33，实际上，根据需要，所述流体***33可以为多个，例如，可以根据需要在基因测序仪1中设置N(N为大于1的自然数)个流体***33，每一流体***33用于加载一流动池38并对所述流动池38依照测序所需输入特定的流体，以便所述流动池38中的样品发生检测反应，在所述流动池38的各检测位点形成可被所述信号检测***31检测到的特定物质或结构。当基因测序仪1中设置多个流体***33时，基因测序仪1可以同时加载多个流动池38，对每一流动池38依照测序所需输入特定流体，以便每一流动池38中的样品完成检测反应。以下对所述流体***33的各子模块、组件进行详细说明。
所述检测反应模块318用于可卸式安装进行检测反应的流动池38，使流动池38可以通过物理连接的方式多次重复固定至所述检测反应模块318上，在本实施方式中，在被安装至所述检测反应模块318上后，所述流动池38与所述检测反应模块318之间保持相对静止，且所述流动池38与所述检测反应模块318的接触面保持充分接触，确保热交换效率，以及将流动池38的用于流体进入的入口与用于流体排出的出口与流体***33的其它模块密封连接。所述检测反应模块318是流体***33与流动池38的交互模块。所述检测反应模块318内部的流道部分还可以决定流体输入流动池38和排出流动池38的流动方式。
所述反应温控组件320用于控制检测反应模块318与流动池38的温度，以满足流动池38在进行检测反应时所需要的温度条件。在本是是方式中，所述反应温控组件320可以是TEC或是其它可以控制温度的组件或其集合。
所述流体运输模块322用于将参加检测反应的流体从存储模块(即非控温存储组件324及/或控温存储组件326)中取出，通过流动池38的 入口运输进流动池38，使流动池38内样品进行检测反应，并使检测反应后的废料通过流动池38的出口排出至废料处理***34。所述流体运输模块322可以由泵、阀、管道等构成。
所述非控温存储组件324用于存储参加检测反应的对存储温度没有要求的检测流体。在本实施方式中，所述非控温存储组件324为一容器，所述容器内部容纳一个或多个子容器，每个子容器设置一个采样针(图未示)连接到流体运输模块322，作为检测流体进入流体运输模块322的入口。
所述控温存储组件326用于存储参加检测反应的对存储温度有要求(例如需在固定的温度或温度范围下)存放的检测流体。所述控温存储组件326还进一步用于定期将由于控温产生的冷凝液等废料排放至废料处理***34。所述控温存储组件326为一控温容器，所述控温容器内部可以容纳一个或多个子容器，每个子容器设置一个采样针连接到流体运输模块322，作为检测流体进入流体运输模块322的入口。
所述存储温控组件328用于控制控温存储组件326的温度，以满足对存储温度有要求的检测流体的存储条件。所述存储温控组件328可以是TEC或是其它可以控制温度的组件或其集合。
所述废料处理***34用于存储从流体***33排出的废料，在本实施方式中，所述废料可以是排出的废液。在本实施方式中，所述废料处理***34还进一步与一设置于基因测序仪1外的废料存储装置4相连，用于将废料排放到所述废料存储装置4中。所述废料包括但不限于由检测反应产生的废料。所述废料处理***34包括废料收集模块330和废料运输模块332等子模块。
其中，所述废料收集模块330用于收集并存储从所述流体***33排出的所有废料，包括检测反应的废料，以及由流体***33在工作时产生的其它废料。在本实施方式中，所述废料收集模块330包括动力组件，所述动力组件用于在某些废料缺乏动力时能驱动所述废料进入废料 收集模块330内。所述动力组件可以是液泵。所述废料收集模块330内设有可以盛放废料的装置或容器。
所述废料运输模块332用于将存储在所述废料收集模块330中的废料排放到基因测序仪1外的废料存储装置4中。所述废料运输模块332可以是一个由泵、阀、管道等流体部件组成的模块。
所述废料存储装置4用于集中存放检测反应的废料及其他废料，置于基因测序仪1外，方便废料的集中存储和处理。所述废料存储装置4可以是定制的废料桶，也可以是为用户定制的特殊的废料收集和处理装置。
所述转移***35用于使流动池38按需移动到所述基因测序仪1内的不同位置，例如，流动池38需要在流体***33和信号检测***31之间转移。当完成信号检测的一流动池38需进行下一步的检测反应时，所述转移***35将流动池38从信号检测***31的检测固定模块308上取下，安装到流体***33的检测反应模块318上；当完成检测反应，需做信号检测时，所述转移***35将检测反应模块318上的流动池38取下，安装到信号检测***31的检测固定模块308上。所述转移***35可以是一个机器人，或者是一个机械臂，或者也可以是传送带等以自动化转移为目的的机械装置。
所述控制***36用于控制信号检测***31、流体***33、废料处理***34和转移***35中各部件的协同工作。在本实施方式中，所述控制***36包括检测控制模块334、温度控制模块336、流体控制模块338、废料控制模块340、转移控制模块342和***控制模块344等子模块。
其中，所述检测控制模块334用于控制信号检测***31各部件的运行，将用户通过***控制模块344下发的指令转化成信号检测***31各部件可执行的信号。进一步地，在本实施例方式中，所述检测控制模块334还控制信号检测***31的供电。所述检测控制模块334可 以是由电子元件、板卡、线缆等组成的电子控制板卡，或是其它的有特定用途的电子控制组件的集合。需要注意的是，当根据需要在基因测序仪1中设计了多个信号检测***31时，所述检测控制模块334也可以为多个，每个信号检测***31由一对应检测控制模块334进行控制，每一检测控制模块334可以仅控制一个信号检测***31，以确保每个信号检测***31在工作时具有独立性，不至于互相干扰。
所述温度控制模块336用于控制流体***33中反应温控组件320和存储温控组件328的运行，将用户通过***控制模块344下发的温度控制指令转化成上述模块各部件可执行的信号。进一步地，在本实施例方式中，所述温度控制模块336还控制上述模块的供电。所述检测控制模块334可以是由电子元件、板卡、线缆等组成的电子控制板卡，或是其它的有特定用途的电子控制组件的集合。
所述流体控制模块338用于控制流体***33各部件的运行，将用户通过***控制模块344下发的指令转化为流体***33各部件可执行的信号。进一步地，在本实施例方式中，所述流体控制模块338还控制流体***33的供电。所述流体控制模块338可以是由电子元件、板卡、线缆等组成的电子控制板卡，或是其它的有特定用途的电子控制组件的集合。需要注意的是，当根据需要在基因测序仪1中设计了多个流体***33时，每个流体***33由一对应的流体控制模块338进行控制，每一流体控制模块338可仅控制一个流体***33，以确保每个流体***33在工作时具有独立性，不至于互相干扰。
所述废料控制模块340用于控制废料处理***34各部件的运行，将用户通过***控制模块344下发的指令转化为废料处理***34各部件可执行的信号。进一步地，在本实施例方式中，所述废料控制模块340还控制废料处理***34的供电。所述废料控制模块340可以是由电子元件、板卡、线缆等组成的电子控制板卡，或是其它的有特定用途的电子控制组件的集合。
所述转移控制模块342用于控制转移***35各部件的运行，将用户通过***控制模块344下发的指令转化为转移***35各部件可执行的信号。进一步地，在本实施例方式中，所述转移控制模块342还控制转移***35的供电。所述转移控制模块342可以是由电子元件、板卡、线缆等组成的电子控制板卡，或是其它的有特定用途的电子控制组件的集合。
所述***控制模块344用于将用户的指令下发给上述各控制模块，并将上述各控制模块的反馈传输到用户交互***37。所述***控制模块344可以是由电子元件、板卡、线缆等组成的电子控制板卡，或是其它的有特定用途的电子控制组件的集合。
所述用户交互***37用于人机交互，使基因测序***3可以接收用户的指令，以及对用户的指令进行反馈。在本实施方式中，所述基因测序***3接收用户指令与对用户的反馈主要涉及两个方面，第一个方面是为了与***控制模块344进行交互而开发的整机运行软件，使用户可以输入相关的参数运行整机的检测反应流程；第二个方面来自信号处理***32，信号处理***3提供了经过处理后的检测数据，使用户可以直观的看到检测结果。在本实施方式中，所述用户交互***37由视觉交互模块346、输入模块348等子模块组成。所述用户交互***37包括设置于所述壳体2上的信息输入输出接口，如，视觉交互模块346包括显示界面201，而输入模块348包括设置于壳体上的键盘鼠标等。
所述视觉交互模块346用于从视觉上显示人机交互内容，以便于进行人机互动。所述视觉交互模块346可以是各种型号的显示器，或各种型号的触摸屏显示器，以及其它用于视觉输出的设备。
所述输入模块348用于输入用户对整机的各种指令。所述输入模块348可以是各种输入输出设备，包括各种型号的键盘，鼠标，以及其它可以用于输入的设备。
图2中，使用长虚线将转移***35分别与信号检测***31以及流 体***33连接起来，代表流动池38需在信号检测***31以及流体***33之间进行转移，当转移完成后需要分别固定在两个***上完成特定的检测/反应步骤。信号检测***31以及流体***33对流动池38的控制为一种短期的控制行为，当流动池38被转移***35获得时，流动池即完全脱离了信号检测***31或流体***33的控制，只由转移***35进行控制并最终转移到指定位置。
图2中，使用实线将信号检测***31与信号处理***32连接起来，代表信号检测***31与信号处理***32之间的信号/数据传输；使用实线将流体***33、废料处理***34和废料存储装置4依次连接起来，代表流体***33与废料处理***34和废料存储装置4之间的物质传输；使用实线将检测反应模块318和反应温控组件320连接起来，以及将控温存储组件326和存储温控组件328连接起来，代表反应温控组件320需按需对检测反应模块318进行控温，以及存储温控组件328需按需对控温存储组件326进行控温。因此本实施例中，图2中的实线连接模块/组件代表了数据或物质的传输过程。
图2中，使用点虚线将控制***36分别与信号检测***31、流体***33、废料处理***34、及用户交互***37分别连接起来，代表了控制***36分别对信号检测***31、流体***33、废料处理***34及用户交互***37的控制及信息交换。因此本实施例中，图2中的点虚线代表了一种可持续或非持续的控制信号传递过程。
此外，图2中，流动池38置于信号检测***31与流体***33中并用长虚线框表示，代表了该流动池38并不是一直安装在该两个位置，而是根据测序的进度，由转移***35按需转移并固定在该两个位置的其一。作为另一种实施方式，上述两个位置也可以同时都放置流动池38。而只有流动池38安装至信号检测***31或流体***33后，信号检测***31或流体***33中才能开始工作。
请参阅图3所示，为本实施方式中信号检测***31中各模块的进 一步细化示意图。其中，激励信号发射模块301包括激励信号发射组件3011、激励信号整理组件3012、通用激励信号分配组件3013等组件。反馈信号接收模块305包括反馈信号接收组件3051、反馈信号整理组件3052及通用反馈信号分配组件3053等组件。信号通道模块303包括通用信号分配组件3031及通用信号收发组件3032等组件。接收信号校正模块306包括校正信号发射组件3061、校正信号分配组件3062及信号校正组件3063等组件。上述各组件的详细说明如下。
所述激励信号发射组件3011用于对流动池38内的样品发射激励信号，所述激励信号可激发样品的反馈信号，通过检测样品的反馈信号，可分析样品是否含有某种被检测的组分。对应于采用电学方式激发反馈信号的信号检测，所述激励信号发射组件3011可以是电压、电流或电荷的触发装置；对应于采用光学方式激发反馈信号的信号检测，所述激励信号发射组件3011可以是激光器、LED灯等光源装置。
所述激励信号整理组件3012用于对发射的激励信号进行整理，以适应样品的接收要求。对应于采用电学方式激发反馈信号的信号检测，该组件可以是有整形、滤波等功能的电路模块；对应于采用光学方式激发反馈信号的信号检测，所述激励信号整理组件3012可以是透镜、反射镜、滤光片等光学设备。
所述通用激励信号分配组件3013用于对发射的激励信号进行分组并汇总，以简化激励信号的发射要求，也可以同时实现对激励信号的整理要求。对应于采用电学方式激发反馈信号的信号检测，所述通用激励信号分配组件3013可以是有整形、滤波等功能的电路模块；对应于采用光学方式激发反馈信号的信号检测，所述通用激励信号分配组件3013可以是透镜、反射镜、滤光片或其组合等光学设备。
图3所示实施方式中，激励信号发射模块301共包括A个通用激励信号分配组件3013、A×M个激励信号发射组件3011与A×M个激励信号整理组件3012，因此，每M个激励信号发射组件3011与每M个 激励信号整理组件3012对应一个通用激励信号分配组件3013。
所述反馈信号接收组件3051用于接收从样品发射的反馈信号，该反馈信号被激励信号激发，通过检测该反馈信号，可分析该样品是否含有某种被检测的物质或组分。对应于采用电学方式激发反馈信号的信号检测，所述反馈信号接收组件3051可以是电压、电流或电荷的记录装置；对应于采用光学方式激发反馈信号的信号检测，所述反馈信号接收组件3051可以是面阵相机(如CCD)、线扫描相机(如TDI)、CMOS等感光记录装置。
所述反馈信号整理组件3052用于对接收的反馈信号进行整理，以适应反馈信号的记录要求。对应于采用电学方式激发反馈信号的信号检测，所述反馈信号整理组件3052可以是有整形、滤波等功能的电路模块；对应于采用光学方式激发反馈信号的信号检测，所述反馈信号整理组件3052可以是透镜、反射镜、滤光片或其组合等光学设备。
所述通用反馈信号分配组件3053用于对接收的反馈信号进行分组并汇总，以简化反馈信号的记录要求，也可以同时实现对反馈信号的整理要求。对应于采用电学方式激发反馈信号的信号检测，所述通用反馈信号分配组件3053可以是有整形、滤波等功能的电路模块；对应于采用光学方式激发反馈信号的信号检测，所述通用反馈信号分配组件3053可以是透镜、反射镜、滤光片或其组合等光学设备。
图3所示实施方式中，反馈信号接收模块305包括B个通用反馈信号分配组件3053、B×N个反馈信号接收组件3051与B×N个反馈信号整理组件3052。因此，每N个反馈信号接收组件3051与每N个反馈信号整理组件3052对应一个通用反馈信号分配组件3053。
所述通用信号分配组件3031用于对激励信号和反馈信号进行分组，以简化激励信号的发射要求与反馈信号的记录要求，也可以同时实现对激励信号与反馈信号的整理要求。对应于采用电学方式激发反馈信号的信号检测，所述通用信号分配组件3031可以是有整形、滤波等功 能的电路模块；对应于采用光学方式激发反馈信号的信号检测，所述通用信号分配组件3031可以是透镜、反射镜、滤光片或其组合等光学设备。
所述通用信号收发组件3032用于实现激励信号从信号通道模块303到样品的过渡、以及反馈信号从样品到信号通道模块303的过渡。所述通用信号收发组件3032可以受控于信号校正组件3063进行微调，以实现激励信号和反馈信号的最佳收发效果。对应于采用电学方式激发反馈信号的信号检测，所述通用信号收发组件3032可以是探针、导线等电子释放设备；对应于采用光学方式激发反馈信号的信号检测，所述通用信号收发组件3032可以是物镜、反射镜、滤光片或其组合等光学设备。
所述校正信号发射组件3061用于对样品发射校正信号，该校正信号不激发样品的反馈信号，但可用于检测信号通道模块303的工作状态，以判断检测信号通道模块303是否处于最佳的工作状态。对应于电学方式的信号检测，所述校正信号发射组件3061可以是电压、电流或电荷的触发装置；对应于光学方式的信号检测，所述校正信号发射组件3061可以是激光器、LED等光源装置。
所述校正信号分配组件3062用于将校正信号发射组件3061发射的校正信号传递给通用信号分配组件3031，或者接收从通用信号分配组件3031反馈回的校正信号，以便将反馈回的校正信号反馈给信号校正组件3063，由信号校正组件3063判断是否需对通用信号收发组件3032进行微调。对应于电学方式的信号检测，所述校正信号分配组件3062可以是有整形、滤波等功能的电路模块；对应于光学方式的信号检测，所述校正信号分配组件3062可以是透镜、反射镜、滤光片或其组合等光学设备。
所述信号校正组件3063用于控制通用信号收发组件3032进行微调，以便将激励信号和反馈信号的收发效果最优化。对应于电学方式的 信号检测，所述信号校正组件3063可以是有整形、滤波等功能的电路模块；对应于光学方式的信号检测，所述信号校正组件3063可以是具有自动对焦功能的光学设备。
图3中，实线代表激励信号或反馈信号在各组件之间传输的通道，本实施方式中有三个重要的传递通道，第一个传递通道是激励信号从激励信号发射组件3011，依次经过激励信号整理组件3012、通用激励信号分配组件3013、通用信号分配组件3031、通用信号收发组件3032，最终抵达流动池38，实现激励信号对待测样品的激励；第二个传递通道是反馈信号从流动池38出发，依次经过通用信号收发组件3032、通用信号分配组件3031、通用反馈信号分配组件3053、反馈信号整理组件3052，最终抵达反馈信号接收组件3051，接收到样品被激励所发出的反馈信号。第三个传递通道是校正信号从校正信号发射组件3061，经过校正信号分配组件3062、通用信号分配组件3031、通用信号收发组件3032、抵达流动池38并返回，返回的校正信号经过通用信号收发组件3032、通用信号分配组件3031、校正信号分配组件3062，抵达信号校正组件3063，实现校正信号对信号通道模块303的工作状态的检测和评估；
图3中，虚线代表信号校正组件3063对通用信号收发组件3032的反馈，意味着信号校正组件3063根据返回的校正信号，对通用信号收发组件3032的状态进行调整。对应于电学方式的信号检测，对通用信号收发组件3032的调整可以是调整电子探针或其它电子设备相对样品的位置，或者是调整通用信号收发组件3032对样品所释放的电压、电流等电子指标；对应于光学方式的信号检测，对通用信号收发组件3032的调整可以是自动对焦或对物镜的物料位置进行微调等。
请参阅图4所示，为本实施方式中流体运输模块322的进一步细化示意图。所述流体运输模块322包括动力组件3220、保护组件3221、检测组件3222、样品存储组件3223、分配组件3224及总分配组件3225 等组件。上述各各组件的详细说明如下。
所述动力组件3220用于在流体***33中制造压力梯度(压力差)，从而驱动检测流体在流体***33中运动。所述动力组件3220可以是各种型号的用于驱动液体运动的泵，例如，注射泵、柱塞泵、隔膜泵、齿轮泵、蠕动泵等常见种类的泵，也可以是高压空气等气体压力源。
所述保护组件3221用于保护流体***33安全运行，当流体***33发生异常时启动保护机制，以避免损害流体***33内的其它组件。所述保护组件3221可以是各种型号的阀门，例如，电磁阀、单向阀、泄压阀等，也可以是手动开关等控制管道开闭的部件。
所述检测组件3222用于检测流体***33的预设指标，以发现流体***33的预设指标是否异常。所述检测组件3222可以是各种型号的传感器，例如，压力传感器、流量传感器、速度传感器、气泡传感器等。
所述样品存储组件3223用于暂时存储检测流体。所述样品存储组件3223可以是一个有特定形状的容器，也可以仅是一段管道。
所述分配组件3224用于按需连通流体***33不同的管道和部件。所述分配组件3224可以是各种型号的电磁阀，例如，多通的直动式电磁阀、多通的先导式电磁阀等，或者是各种型号的旋转阀，还可以是由多个电磁阀及/或旋转阀组成的集合。
图4所示实施方式中，该流体运输模块322包括M个流体运输工作组3226，每个流体运输工作组3226至少包含1个动力组件、1个保护组件3221、1个检测组件3222、1个样品存储组件3223和1个分配组件3224，以实现从控温存储组件326及/或非控温存储组件324中吸取部分检测流体临时存放于样品存储组件3223中，设置样品存储组件3223临时存放检测流体的有益效果在于：可以实现在其中1个流体运输工作组3226通过总分配组件3225向检测反应模块318以及流动池38中注入检测流体时，其余的流体运输工作组3226可以利用这个时间间隙吸取检测流体进行准备，以节约检测流体注入前的准备时间。因此， 本实施方式中，流体运输模块322共有M个保护组件3221，M个检测组件3222，M个样品存储组件3223和M个分配组件3224。所有的流体运输工作组3226均连接到总分配组件3225，以便于统一分配哪个流体运输工作组3226与检测反应模块318连接。此外，在其他实施方式中，保护组件3221，检测组件3222，样品存储组件3223的位置可以互换，仍然可以实现上述功能。
所述总分配组件3225与分配组件3224功能相似，用于按需连通流体***33内不同的的管道和部件。所述总分配组件3225可以是各种型号的电磁阀，例如，多通的直动式电磁阀、多通的先导式电磁阀等，或者是各种型号的旋转阀，还可以是由多个电磁阀及/或旋转阀组成的集合。
图4中，带有箭头的点虚线代表流体运输模块322的一个流体运输工作组3226在准备检测流体时的液体运动方向，利用动力组件3220制造的压力梯度，控温存储组件326或非控温存储组件324中的检测流体经过分配组件3224临时存储在样品存储组件3223中。
图4中，带有箭头的实线代表流体运输模块322的一个流体运输工作组3226在向检测反应模块318和流动池38输出检测流体时的液体运动方向，利用动力组件制造的压力梯度，临时存储在样品存储组件3223中的检测流体从样品存储组件3223中流出，经过分配组件3224和总分配组件3225输出到检测反应模块318中的流道中。需注意的是，从非控温存储组件324连接到动力组件3220的实线箭头，该箭头代表动力组件3220在持续制造压力梯度时，可能需要使用非控温存储组件324中的检测流体进行流体的补充，该流体可以为存放在非控温存储组件324中的某种液体或高压气体。
在其他实施方式中，所述动力组件3220不是连接至非温控存储组件324中，而是另连接至一存储装置，所述存储装置存放流体，所述流体为液体或高压气体，所述动力组件3220在持续制造压力梯度使存储 于样品存储组件3223中的流体注入流动池时，所述存储装置内的流体对动力组件3220进行流体补充。
图4中，带有箭头的长虚线分别连接了保护组件3221和废料处理***34、以及控温存储组件326和废料处理***34。保护组件3221和废料处理***34的连接代表了当流体运输工作组3226出现问题时，保护组件3221开始工作，将可能从保护组件3221中排出一些多余的流体到废料处理***34。控温存储组件326和废料处理***34的连接代表了由于控温存储组件326的温度与外界温度会存在温度差，当控温存储组件326的温度低于外界时会产生冷凝液，所述冷凝液被收集至废料处理***34中。
请参阅图5所示，为本实施方式中的检测反应模块318的细化示意图。所述检测反应模块318包括入口开关组件3181、出口开关组件3182、旁路开关组件3183、及总开关组件3184等组件。所述检测反应模块318的各组件的详细说明如下。
所述入口开关组件3181用于控制流动池38入口的管道打开或关闭。所述入口开关组件3181可以是各种型号的电磁阀，例如，多通的直动式电磁阀、多通的先导式电磁阀或者是各种型号的旋转阀，还可以是由多个电磁阀及/或旋转阀组成的集合。当流动池38的入口数为多个时，流动池38的每一入口对应一入口开关组件3181，以保证流动池38的每个入口都有一个入口开关组件3181用于控制，且每个入口开关组件3181均可被独立控制。
所述出口开关组件3182用于控制流动池38出口的管道打开或关闭。所述出口开关组件3182可以是各种型号的电磁阀，例如，多通的直动式电磁阀、多通的先导式电磁阀或者是各种型号的旋转阀，还可以是由多个电磁阀及/.或旋转阀组成的集合。当流动池38的出口数为多个时，流动池38的每一出口对应一出口开关组件3182，以保证流动池38的每个出口都有一个出口开关组件3182用于控制，且每个出口开关 组件3182均可被独立控制。
所述旁路开关组件3183用于控制流动池38入口的管道打开或关闭。所述旁路开关组件3183可以是各种型号的电磁阀，例如，多通的直动式电磁阀、多通的先导式电磁阀或者是各种型号的旋转阀，还可以是由多个电磁阀及/或旋转阀组成的集合。
所述总开关组件3184用于控制检测反应模块318的总出口的管道打开或关闭。所述总开关组件3184可以是各种型号的电磁阀，例如，多通的直动式电磁阀、多通的先导式电磁阀或者是各种型号的旋转阀，还可以是由多个电磁阀及/或旋转阀组成的集合。
图5中，所述检测反应模块318可同时设置M个入口开关组件3181，N个出口开关组件3182和X个旁路开关组件3183。每个入口开关组件3181和每个旁路开关组件3183都独立控制1条从流体运输模块322中连接过来的通道，所有出口开关组件3182均汇总连接到总开关组件3184。
图5中，带有箭头的实线从流体运输模块322开始，依次连接了旁路开关组件3183、总开关组件3184，最终抵达废料处理***34，这个过程代表了当流体运输模块322向检测反应模块318注入的某些流体不能输入流动池38做检测反应时，需要直接排出到废料处理***34所需要经过的路径。这些流体包括且不限于用于清洗流体运输模块322中的样品存储组件3223或其它管道的流体、有交叉污染风险需要排除的流体、或者某些检测反应步骤后残余的检测流体。
图5中，带有箭头的点虚线从流体运输模块322开始，依次连接了入口开关组件3181，流动池入口381，流动池出口382、出口开关组件3182、总开关组件3184，最终抵达废料处理***34，这个过程代表了当流体运输模块322向检测反应模块318注入检测流体参加检测反应时，检测流体由流动池入口381进入流动池38并由流动池出口382流出流动池38所需要经过的路径。这些流体主要是检测流体等需要注入 流动池38的流体。
带有箭头的实线和带有箭头的点虚线所代表的过程都要经过总开关组件3184才能进入废料处理***34，其动力来源于流体运输模块322的动力组件3220。
图5中，带有箭头的长虚线有两条路径，第一条路径从流体运输模块322开始，依次连接了入口开关组件3181、流动池入口381，经过流动池入口381处阴影标示的***区域Y，最终抵达废料处理***34。第二个路径从流体运输模块322开始，依次连接了旁路开关组件3183、出口开关组件3182，流动池出口382，经过流动池出口382处阴影标示的***区域Z，最终抵达废料处理***34。需说明的是，第二个路径在执行的时候，需关闭总开关组件3184。流动池入口381和流动池出口382处的阴影区域代表了检测反应模块318与流动池入口381和流动池出口382之间的密封区域，由于流动池38的检测需要做定期转移，因此这个密封区域需要及时清洗，防止检测流体的残留。根据以上分析，这两个过程分别代表了当流体运输模块322向检测反应模块318注入某些流体清洗检测反应模块318与流动池入口381和流动池出口382的密封区域Y、Z时，清洗流体分别排出到废料处理***34所需经过的路径。需要注意的是，上述两个过程只能在流动池38转移走之后才能执行，以免清洗流体污染流动池38内部的样品。如果该区域Y、Z处于开放状态，则需要废料处理***34提供动力组件用于转移从流动池入口381和流动池出口382溢出的清洗流体；如果该区域Y、Z处于密封状态，则不需要废料处理***34提供动力组件，而是需要额外的工具使上述区域Y、Z密封并保留进出液的通路。
请参阅图6所示，为本实施方式的废料收集模块330和废料运输模块332的细化示意图。所述废料收集模块330包括废料收集动力组件3301、废料存储组件3302和废料检测组件3303等组件。所述废料运输模块332包括废料排放动力组件3321和废料转接组件3322等组件。
所述废料收集动力组件3301用于为某些缺乏动力驱动的废料提供动力。所述废料收集动力组件3301可以是各种型号的用于驱动液体运动的泵，例如，注射泵、柱塞泵、隔膜泵、齿轮泵、蠕动泵等常见种类的泵，也可以是高压空气等气体压力源。
所述废料存储组件3302用于存储检测反应的废料，所述废料存储组件3302可以临时存储基因测试装置1内所有流体***33的废料。所述废料存储组件3302可以是一个有特定形状的容器。
所述废料检测组件3303用于检测废料存储组件3302中存放的废料量，以便废料存储组件3302中的废料量达到预设量时使用废料运输模块332将废料排出至废料存储装置4中存放。所述废料检测组件3303可以是重力检测装置，通过重力判断已经收集的废料量，也可以是体积检测装置，通过体积判断已经收集的废料量，还可以是高度检测装置，通过液面高度判断已经收集的废料量。
所述废料排放动力组件3321用于提供将废料从废料存储组件3302运输至废料存储装置4的动力。所述废料排放动力组件3321可以是各种型号的用于驱动液体运动的泵，例如，注射泵、柱塞泵、隔膜泵、齿轮泵、蠕动泵等常见种类的泵，也可以是高压空气等气体压力源。
所述废料转接组件3322设置在基因测序仪1的壳体2上，为将机内管道与机外管道转接的组件。所述废料转接组件3322可以是各种型号的接头，例如穿板接头等。
图6中，带有箭头的点虚线从流体***33开始，依次连接了废料收集动力组件3301，最终抵达废料存储组件3302，这个过程代表了当流体***33的某些废料缺乏动力驱动时，需要连接到废料收集模块330的废料收集动力组件3301为该废料提供动力，使其流入废料存储组件3302暂时存储所需要经过的路径。该废料包括且不限于控温存储模块326由于温度低于外界所产生的冷凝液、检测反应模块318清洗密封的***区域Y、Z所推至该区域Y、Z的清洗流体。
图6中，带有箭头的长虚线从流体***33开始，直接抵达废料存储组件3302，这个过程代表了当流体***33可以提供动力时，将废料直接推入废料存储组件3302所需要经过的路径。这个过程的动力由流体***33中流体运输模块322的动力组件3220提供，因此可以直接排放到废料存储组件3302中。该废料包括且不限于流动池38做检测反应产生的废料，流体***33清洗样品存储组件3223或其它管道而排放的废料。
图6中，带有箭头的实线从废料存储组件3302开始，经过废料转接组件3322，抵达废料存储装置4，这个过程代表了当废料存储组件3302内容纳的废料超过设定的阈值时，将废料从废料存储组件3302运输至废料存储装置4所需要经过的路径。该废料为整机所有流体***33在一定时间段内工作产生的所有废料。
图6中，点虚线代表废料检测组件3303对废料存储组件3302内废料量的测量，当废料检测组件3303检测到废料存储组件的废料量超过设定的阈值时，控制***36控制废料运输模块332的废料排放动力组件3321开始工作，将废料存储组件3302内的废料运输至废料存储装置4存储。
请参阅图7所示，示出了本实施方式中的转移***35的运行逻辑。转移***35转移的对象是流动池38，流动池38是加载样品进行检测反应的容器。流动池38可以是一个封闭的测序芯片，也可以是一个开放性的用于加载样品的基底。在本实施方式中，流动池38主要的转移目的地有：流动池起始位置O，第N个流体***33，第M个信号检测***31，流动池暂存位置T和流动池废弃位置D，其中，M，N分别代表当基因测序仪1内同时有多个流体***33和信号检测***31时，流体***33和信号检测***31的任意编号。
所述流动池起始位置O是启动流动池38内样品检测的起始位置，在本实施例中，所述流动池起始位置O为流动池置入接口203。用户将 加载好样品的流动池38放在流动池起始位置O，经过用户交互***37确认后，由转移***35转移到机内进行检测反应。
流动池38在第N个流体***33中的位置，所述位置位于第N个流体***33的检测反应模块318上，当流动池38安装到所述位置后，控制***36控制将检测流体输入流动池38进行检测反应。
流动池38在第M个信号检测***31中的位置：所述位置位于第M个信号检测***31的检测固定组件308上，当流动池38安装到所述位置后，控制***36控制第M个信号检测***31对样品施加激励信号，之后收集样品的反馈信号。
流动池暂存位置T：所述位置设置于基因测序仪1内的一固定位置上，用于临时放置流动池38。
流动池废弃位置D：所述位置是检测反应全部结束或中断放弃后，流动池38被废弃后放置的位置，转移***35将废弃的流动池38放置到该位置，之后由用户进行收集和处理。
图7中，带有箭头的实线从流动池起始位置O开始，分别连接了第N个流体***33，第M个信号检测***31，以及流动池废弃位置D。其中，流动池起始位置O、第N个流体***33和第M个信号检测***31之间分别是双向连接，但第N个流体***33、第M个信号检测***31与流动池废弃位置D之间是单向连接。这个路径代表了用户将制备好的流动池38放在流动池起始位置O，然后由整机控制流动池38在第N个流体***33和第M个信号检测***31之间分别作检测反应和信号检测的流程，但一旦流动池38被废弃就不能返回转移***35继续使用。检测反应中具体的执行路径可以根据检测反应的不同原理而定制。
图7中，带有箭头的点虚线从流动池起始位置O开始，连接了流动池暂存位置T和流动池废弃位置D，其中，流动池起始位置O，流动池暂存位置T和第N个流体***33之间分别是双向连接，但流动池暂存位置T与流动池废弃位置D之间是单向连接。这个路径代表了流动 池38从流动池起始位置O或者第N个流体***33移动到流动池暂存位置T做暂时存放的过程，或者是用户使用的某些工具从流动池起始位置O开始进入转移***35，用于清洗第N个流体***33的检测反应模块318与流动池38的密封区域Y、Z的流程，但一旦流动池38或该些工具被废弃，其不能返回转移***35继续使用。具体的执行路径可以根据不同需求而定制。
请参阅图8所示，为本实施方式中信号传输模块312、信号处理模块314和数据存储模块316的细化示意图。所述信号传输模块312包括信号传输组件3121与信号缓存组件3122等组件。所述信号处理模块314包括数据分析组件3141。所述数据存储模块316包括数据压缩组件3161和数据存储组件3162等组件。
所述信号传输组件3121用于收集和传输信号检测***31获得的反馈信号。所述信号传输组件3121可以是数据采集卡等定时采集电压电流等电子信号的设备。
所述信号缓存组件3122用于在反馈信号被处理前将反馈信号缓存的组件，反馈信号在缓存中打开之后就可以等待调用和处理。所述信号缓存组件3122可以是计算机的内存或其它各级缓存。
所述数据分析组件3141用于将临时写在信号缓存组件3122中的反馈信号进行提取，执行转化和过滤等操作，使反馈信号成为可以进行分析的数据及生成测序报告。所述数据分析组件3141可以是计算机用于处理的硬件，例如，内存、CPU、GPU等硬件，配合处理和分析的程序进行运行处理。
所述数据压缩组件3161用于将处理后的数据进行存储前的压缩，减小存储空间和写存储的时间。所述数据压缩组件3161可以是计算机用于处理的硬件，例如，内存、CPU、GPU等硬件，配合处理和分析的程序进行运行处理。
所述数据存储组件3162用于存储经过压缩后的数据和生成的测序 报告，以将分析后的检测结果进行保存和备份。所述数据存储组件3162可以是各种计算机存储介质，例如，硬盘、闪盘、磁盘等硬件。
图8中，带有箭头的实线从信号检测***31开始，依次连接了信号传输组件3121、信号缓存组件3122、数据分析组件3141及数据压缩组件3161，最终抵达数据存储组件3162，这个过程代表了从信号检测***31接收到样品的反馈信号开始，将反馈信号逐步转化为可以用来分析的数据，进行分析得到检测结果并进行存储所需要经过的路径。在这个过程中，对应于电学方式的信号检测，电压、电流等电信号被逐步转化为可读写分析的数字数据并存储；对应于光学方式的信号检测，则是将数码照片等数据逐步转化为可读写分析的数字数据并存储。
图8中，带有箭头的长虚线从数据分析组件3141开始，直接抵达用户交互***37，这个过程代表了信号处理***32在获得数据并处理时对用户的实时反馈。
可以理解，在其他实施方式中，所述信号处理***32可以只包括信号传输组件3121，通过信号传输组件3121收集信号检测***31获得的反馈信号及将反馈信号传输至设置于基因测序仪1之外的数据处理装置。
可以理解，在其他实施方式中，所述信号处理***32可以不包括信号缓存组件3122及数据分析组件3141，信号传输组件3121收集信号检测***31获得的反馈信号后，将反馈信号传输至数据压缩组件3161，通过数据压缩组件3161压缩后存储于数据存储组件3162中，之后，数据存储组件3162可从所述基因测序仪1上取下并被设置于基因测序仪1之外的数据处理装置访问，以生成测序报告。
可以理解，在其他实施方式中，所述信号处理***32还可以不包括信号缓存组件3122、数据分析组件3141及数据存储组件3162，通过信号传输组件3121收集信号检测***31获得的反馈信号后，将反馈信号传输至数据压缩组件3161，通过数据压缩组件3161压缩后传输给设 置于基因测序仪1之外的数据处理装置。
请参阅图9，为本发明实施例二提供的生化物质分析***的示意图。所述生化物质分析***5用于接收流动池并完成对流动池内样品的生物特征的检测，所述生物特征可以是样品的基因序列，所述生化物质分析***包括：检测***51、调度***53、生化反应***55及控制***57，所述调度***53用于将所述流动池在不同位点进行调度，所述位点包括位于检测***51内的位点与位于生化反应***55内的位点，所述生化反应***55用于使所述流动池内的样品发生反应，例如用于注入反应物质至所述流动池以使所述流动池内的样品发生反应，所述检测***51用于对已发生反应的样品执行信号检测以获得代表所述样品的生物特征的信号，所述控制***57用于控制所述检测***51、调度***53与生化反应***55的协同作业。具体地，所述检测***51可以包括实施方式一中的信号检测***31或者同时包括实施方式一中的信号检测***31与信号处理***32，所述代表所述样品的生物特征的信号可以是信号检测***31获得的反馈信号或者是所述反馈信号经由信号处理***32处理后获得的可分析数据。所述调度***53可以包括实施方式一中的转移***35，所述生化反应***55可以包括实施方式一中的流体***33或者同时包括实施方式一中的流体***33与废料处理***34。所述控制***57可以包括实施方式一种的控制***36
请参阅图10，为本发明实施例三提供的生化物质分析方法的流程图，所述生化物质分析方法包括：
步骤S1001，接收流动池，并将接收的所述流动池转移至生化反应***；
步骤S1003，在生化反应***内输入反应物质至所述流动池以使所述流动池内的样品发生生化反应；
步骤S1005，将样品已完成生化反应的流动池转移至检测***；
步骤S1007，在检测***内对所述流动池内的样品执行信号检测以 获得反应所述样品的生物特征的信号。
进一步地，在其他实施方式中，在将所述流动池转移至所述生化反应***前，所述生化物质分析方法还可以包括：判断生化反应***中加载流动池的位点是否空闲，在一或多个位点空闲的情况下将所述流动池加载至其中一个空闲的位点上，及在位点均不空闲的情况下将所述流动池置于一流动池暂存位置。
进一步地，在其他实施方式中，在将所述流动池转移至所述检测***前，所述生化物质分析方法还可以包括：判断检测***中加载流动池的位点是否空闲，在一或多个位点空闲的情况下将所述流动池加载至其中一个空闲的位点上，及在位点均不空闲的情况下将所述流动池置于一流动池暂存位置。
进一步地，在其他实施方式中，接收流动池前，所述生化物质分析方法还包括：侦测接收流动池的位点是否存在流动池，及在所述接收流动池的位点存在流动池时接收所述流动池。
进一步地，在其他实施方式中，在完成检测后，所述生化物质分析方法还包括：将完成检测的所述流动池重新转移至生化反应***并重复反应-转移-检测整个过程。
进一步地，在其他实施方式中，在完成检测后，所述生化物质分析方法还包括：将完成检测的所述流动池转移至接收废弃流动池的流动池废弃位置。
进一步地，在其他实施方式中，所述步骤S1003进一步包括：从存储流体的存储模块中吸取流体并暂存于样品存储组件中，及将暂存于所述样品存储组件中的流体推入所述流动池，以使所述流动池内的样品发生反应。
进一步地，在其他实施方式中，所述步骤S1003进一步包括：在将流体暂存于所述样品存储组件中后，判断所述流体进入所述流动池的通道是否被占用，若所述通道被占用，将所述流体继续暂存于所述样品存 储组件，若所述通道未被占用，将所述暂存的流体通过所述通道推入所述流动池。
进一步地，在其他实施方式中，所述发生反应的步骤进一步包括：在将第一种流体从暂存所述第一种流体的样品存储组件推入所述流动池的同时，将第二种流体从存储所述第二种流体的存储模块中吸取并暂存于用于暂存所述第二种流体的样品存储组件中。
进一步地，在其他实施方式中，所述检测步骤进一步可包括：对所述信号进行处理以获得可分析数据或者检测报告。
请参阅图11所示，为本发明实施方式四提供的应用生化物质分析***的生化物质分析装置的示意图。所述生化物质分析装置6包括至少一生化物质分析***61，所述生化物质分析***61可以是实施方式二中提供的生化物质分析***5。
请参阅图12所示，为本发明实施方式五提供的应用生化物质分析方法的生化物质分析装置的示意图。所述生化物质分析装置7运行实施方式三提供的生化物质分析方法以获得反应流动池内样品的生物特征的信号、可分析数据或检测报告。
综上所述，本发明实施方式提供的基因测序***、生化物质分析***、方法及应用生化物质分析***或方法的装置，用户仅需要将测序所需的检测流体、清洗流体及装载了样品的流动池通过基因测序仪上的接口置入基因测序仪内，通过用户交互***设置相关参数，基因测序仪及基因测序***便可自动完成基因测序。
本发明实施方式提供的基因测序仪及基因测序***，还通过设置多个信号检测***及/或多个流体***，可实现同时对多个流动池进行检测，提高了基因测序仪及基因测序***的检测通量。
本发明实施方式提供的基因测序仪及基因测序***，还可通过设置多个流体运输工作组，每一流体运输工作组包括一样品存储组件，在其中一个流体运输工作组向检测反应模块及流动池注入流体时，其他流体 运输工作组可以利用这个时间间隙吸取流体进行准备，从而节约了流体注入流动池前的准备时间，同样提高了基因测序仪与基因测序***的检测通量。
最后应说明的是，以上实施例仅用以说明本发明的技术方案而非限制，尽管参照较佳实施例对本发明进行了详细说明，本领域的普通技术人员应当理解，可以对本发明的技术方案进行修改或等同替换，而不脱离本发明技术方案的精神和范围。

Claims (39)

  1. 一种生化物质分析***，其特征在于，所述生化物质分析***用于对流动池内样品的生物特征的检测，包括检测***、调度***、生化反应***及控制***，其中，所述调度***用于将所述流动池在不同位点进行调度，所述位点包括位于检测***的位点与位于生化反应***的位点，所述生化反应***用于使所述流动池内的样品发生反应，所述检测***用于对已发生反应的样品执行信号检测以获得代表所述样品的生物特征的信号，所述控制***用于控制所述检测***、调度***与生化反应***的协同作业。
  2. 如权利要求1所述的生化物质分析***，其特征在于，所述调度***包括转移***，所述转移***用于移动所述流动池至不同位点。
  3. 如权利要求1或2所述的生化物质分析***，其特征在于，所述生化反应***包括流体***，所述流体***用于输入反应物质至所述流动池以使所述流动池内的样品发生反应；或者，所述生化反应***包括流体***与废料处理***，所述流体***用于输入反应物质至所述流动池以使所述流动池内的样品发生反应，所述废料处理***用于收集所述流体***排出的废料。
  4. 如权利要求1至3任一项所述的生化物质分析***，其特征在于，所述检测***包括信号检测***，所述信号检测***用于对已发生检测反应的所述样品执行信号检测以获得来自所述样品的反馈信号，所述反馈信号即为代表所述样品的生物特征的信号；或者，所述检测***包括信号检测***与信号处理***，所述信号处理***用于收集所述反馈信号以便所述反馈信号可被用于生成测序报告。
  5. 如权利要求1所述的生化物质分析***，其特征在于，所述生化物质分析***置于一基因测序仪内，并通过设置于基因测序仪上的流动池置入接口接收加载了待检测的样品的流动池。
  6. 如权利要求3所述的生化物质分析***，其特征在于，所述流体***为一或多个，及/或，所述信号检测***为一或多个。
  7. 如权利要求3、4或6任一项所述的生化物质分析***，其特征在于，所述流体***包括检测反应模块、流体运输模块及用于存储流体的存储模块，所述检测反应模块用于可卸式安装所述流动池，所述流体运输模块用于将存储于所述存储模块的流体注入至所述流动池。
  8. 如权利要求7所述的生化物质分析***，其特征在于，流体运输模块还用于将所述流体***的废料排出至所述废料处理***。
  9. 如权利要求7或8所述的生化物质分析***，其特征在于，所述流体运输模块包括流体运输工作组，所述流体运输工作组包括动力组件、样品存储组件及分配组件，所述动力组件用于提供压力梯度以从所述存储模块中吸取流体，所述流体通过所述分配组件后暂存于所述样品存储组件中，所述动力组件还用于提供压力梯度以将存储于所述样品存储组件中的流体通过分配组件注入至所述流动池。
  10. 如权利要求9所述的生化物质分析***，其特征在于，所述分配组件分别连接至所述流动池、所述存储模块及所述样品存储组件，所述样品存储组件置于所述分配组件与所述动力组件之间。
  11. 如权利要求10所述的生化物质分析***，其特征在于，所述动力组件还连接至所述存储模块或另一存储装置，所述存储模块或另一存储装置为所述动力组件在制造压力梯度使存储于 所述样品存储组件中的流体注入所述流动池时，提供流体补充。
  12. 如权利要求9所述的生化物质分析***，其特征在于，所述流体运输工作组还包括检测组件与保护组件，所述检测组件用于检测所述流体***的预设指标，以发现所述流体***的预设指标是否异常，所述保护组件用于在所述流体***发生异常时启动保护机制，以避免损害所述流体***。
  13. 如权利要求9所述的生化物质分析***，其特征在于，所述流体运输工作组的数量为多个，所述流体***还包括总分配组件，所述多个流体运输工作组均连接至所述总分配组件，由所述总分配组件按需连通不同的所述流体运输工作组与所述流动池。
  14. 如权利要求13所述的生化物质分析***，其特征在于，在其中一个所述流体运输工作组通过所述总分配组件向所述流动池注入流体时，其中另一个或多个所述流体运输工作组从所述存储模块中吸取流体存入所述样品存储组件中。
  15. 如权利要求4所述的生化物质分析***，其特征在于，所述信号检测***包括激励信号发射模块、信号通道模块、反馈信号接收模块、检测固定组件，所述检测固定组件用于可卸式安装和固定所述流动池，所述激励信号发射模块用于对所述流动池中的样品施加激励信号，所述反馈信号接收模块用于接收样品被激励信号激发后发出的反馈信号，所述信号通道模块用于使所述激励信号发射模块发射的激励信号按照预设的路径抵达所述流动池，并使反馈信号从所述流动池出发按照预设的路径抵达所述反馈信号接收模块。
  16. 如权利要求15所述的生化物质分析***，其特征在于，所述信号检测***还包括移动组件，用于驱使所述检测固定组件在 一定范围内移动，以使所述流动池不同位置的样品进行信号检测。
  17. 如权利要求15所述的生化物质分析***，其特征在于，所述信号检测***还包括接收信号校正模块，用于对所述信号通道模块进行调校，使所述反馈信号接收模块接收的反馈信号和所述激励信号发射模块发射的激励信号相适配。
  18. 如权利要求17所述的生化物质分析***，其特征在于，所述信号通道模块包括通用信号分配组件及通用信号收发组件，所述接收信号校正模块包括校正信号发射组件、校正信号分配组件及信号校正组件，所述通用信号分配组件用于对激励信号和反馈信号进行分组，所述通用信号收发组件用于实现激励信号从所述信号通道模块到样品的过渡、以及反馈信号从样品到所述信号通道模块的过渡，所述校正信号发射组件用于对样品发射校正信号，该校正信号不激发样品的反馈信号，所述校正信号分配组件用于将校正信号传递给所述通用信号分配组件，或者接收从所述通用信号分配组件反馈回的校正信号，以便将反馈回的校正信号反馈给所述信号校正组件，所述信号校正组件用于根据反馈回的校正信号控制所述通用信号收发组件进行微调，以优化激励信号和反馈信号的收发效果。
  19. 如权利要求7所述的生化物质分析***，其特征在于，所述检测反应模块包括入口开关组件、出口开关组件、旁路开关组件、及总开关组件，所述入口开关组件连接于所述流体运输模块与所述流动池的流动池入口之间，所述出口开关组件连接于所述旁路开关组件、所述总开关组件及所述流动池的流动池出口之间，所述总开关组件连接所述废料处理***。
  20. 如权利要求19所述的生化物质分析***，其特征在于，所述流体运输模块向所述检测反应模块注入参加检测反应的流体 时，所述流体经所述入口开关组件与所述流动池入口进入所述流动池并由所述流动池出口、所述出口开关组件及所述总开关组件流入所述废料处理***；所述流体运输模块向所述检测反应模块注入不能输入所述流动池做检测反应的流体时，所述流体经由所述旁路开关组件与所述总开关组件流入所述废料处理***；所述流体运输模块向所述检测反应模块注入清洗所述检测反应模块与所述流动池入口之间的密封区域的流体时，所述流体经由所述入口开关组件、所述密封区域进入所述废料处理***；及/或，所述流体运输模块向所述检测反应模块注入清洗所述检测反应模块与所述流动池出口之间的密封区域的流体时，所述流体经由旁路开关组件、所述出口开关组件、所述密封区域进入所述废料处理***。
  21. 如权利要求3所述的生化物质分析***，其特征在于，所述废料处理***包括废料收集模块用于收集所述流体***的废料，所述废料收集模块包括废料收集动力组件及废料存储组件，所述废料收集动力组件用于为缺乏动力驱动的废料提供动力，所述废料存储组件用于存储收集的废料。
  22. 如权利要求21所述的生化物质分析***，其特征在于，所述废料处理***包括废料运输模块，所述废料运输模块用于即将存储在所述废料收集模块中的废料排放出去。
  23. 如权利要求22所述的生化物质分析***，其特征在于，所述废料运输模块包括废料排放动力组件和废料转接组件，所述废料转接组件为管道转接组件用于转接至所述基因测序***外的管道，所述废料排放动力组件用于提供将废料从所述废料存储组件排出的动力。
  24. 如权利要求23所述的生化物质分析***，其特征在于，所述废料收集模块还包括废料检测组件，所述废料检测组件用于检 测所述废料存储组件中存放的废料量。
  25. 如权利要求24所述的生化物质分析***，其特征在于，当所述废料检测组件检测到所述废料存储组件的废料量超过设定的阈值时，所述控制***控制所述废料排放动力组件排放所述废料。
  26. 如权利要求4所述的生化物质分析***，其特征在于，所述信号处理***包括信号传输模块，所述信号传输模块用于收集所述信号检测***的反馈信号，及将所述反馈信号进行缓存。
  27. 如权利要求26所述的生化物质分析***，其特征在于，所述信号处理***还包括信号处理模块，所述信号处理模块用于从所述信号传输模块中获取缓存的反馈信号，将所述反馈信号转化为可分析的数据，并进一步分析所述数据以生成测序报告。
  28. 如权利要求27所述的生化物质分析***，其特征在于，所述信号处理***还包括数据存储模块，用于将所述信号处理模块处理完成的数据及测序报告进行压缩存储。
  29. 如权利要求27所述的生化物质分析***，其特征在于，还包括用户交互***，所述用户交互***包括视觉交互模块，所述信号处理模块还用于将所述测序报告输出给所述视觉交互模块以呈现给用户。
  30. 一种生化物质分析方法，其特征在于，包括：
    接收流动池，并将接收的所述流动池转移至生化反应***；
    在生化反应***内使所述流动池内的样品发生反应；
    将样品已完成生化反应的流动池转移至检测***；及
    在检测***内对所述流动池内的样品执行信号检测以获得反应所述样品的生物特征的信号。
  31. 如权利要求30所述的方法，其特征在于，在将所述流动池转移至所述生化反应***前，所述方法还包括：判断生化反应系 统中加载流动池的位点是否空闲，在一或多个位点空闲的情况下将所述流动池加载至其中一个空闲的位点上，及在位点均不空闲的情况下将所述流动池置于一流动池暂存位置。
  32. 如权利要求30所述的方法，其特征在于，在将所述流动池转移至所述检测***前，所述还包括：判断检测***中加载流动池的位点是否空闲，在一或多个位点空闲的情况下将所述流动池加载至其中一个空闲的位点上，及在位点均不空闲的情况下将所述流动池置于一流动池暂存位置。
  33. 如权利要求30所述的方法，其特征在于，接收流动池前，所述方法还包括：侦测接收流动池的位点是否存在流动池，及在所述接收流动池的位点存在流动池时接收所述流动池。
  34. 如权利要求30所述的方法，其特征在于，在完成检测后，所述方法还包括：将完成检测的所述流动池重新转移至生化反应***并重复所述反应-转移-检测的整个过程；或者，将完成检测的所述流动池转移至接收废弃流动池的流动池废弃位置。
  35. 如权利要求30所述的方法，其特征在于，所述反应步骤进一步包括：从存储流体的存储模块中吸取流体并暂存于样品存储组件中，及将暂存于所述样品存储组件中的流体推入所述流动池，以使所述流动池内的样品发生反应。
  36. 如权利要求35所述的方法，其特征在于，所述反应步骤进一步包括：在将流体暂存于所述样品存储组件中后，判断所述流体进入所述流动池的通道是否被占用，若所述通道被占用，将所述流体继续暂存于所述样品存储组件，若所述通道未被占用，将所述暂存的流体通过所述通道推入所述流动池。
  37. 如权利要求35所述的方法，其特征在于，所述反应步骤进一步包括：在将第一种流体从暂存所述第一种流体的样品存储组件推入所述流动池的同时，将第二种流体从存储所述第二种流 体的存储模块中吸出并暂存于用于暂存所述第二种流体的样品存储组件中。
  38. 如权利要求30所述的方法，其特征在于，所述检测步骤进一步包括：对所述信号进行处理以获得可分析数据或者检测报告。
  39. 一种生化物质分析装置，其特征在于，所述生化物质分析装置包括如权利要求1至29任一项所述的生化物质分析***；或者所述生化物质分析装置应用如权利要求30至38任一项所述的生化物质分析方法以获得反应流动池内样品的生物特征的信号、可分析数据或检测报告。
PCT/CN2019/107593 2019-09-24 2019-09-24 生化物质分析***、方法及装置 WO2021056208A1 (zh)

Priority Applications (9)

Application Number Priority Date Filing Date Title
KR1020227013709A KR20220066162A (ko) 2019-09-24 2019-09-24 생화학 물질 분석 시스템, 방법 및 장치
JP2022518312A JP7457798B2 (ja) 2019-09-24 2019-09-24 生化学物質分析システム、方法及び装置
CN201980100118.2A CN114341618B (zh) 2019-09-24 2019-09-24 生化物质分析***、方法及装置
EP19946668.1A EP4036554A4 (en) 2019-09-24 2019-09-24 SYSTEM, METHOD AND DEVICE FOR BIOCHEMICAL SUBSTANCE ANALYSIS
US17/763,295 US20220341848A1 (en) 2019-09-24 2019-09-24 Biochemical substance analysis system, method, and device
PCT/CN2019/107593 WO2021056208A1 (zh) 2019-09-24 2019-09-24 生化物质分析***、方法及装置
AU2019467369A AU2019467369B2 (en) 2019-09-24 2019-09-24 Biochemical substance analysis system, method, and device
CA3151328A CA3151328A1 (en) 2019-09-24 2019-09-24 Biochemical substance analysis system, method, and device
AU2023266236A AU2023266236A1 (en) 2019-09-24 2023-11-13 Biochemical substance analysis system, method, and device

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2019/107593 WO2021056208A1 (zh) 2019-09-24 2019-09-24 生化物质分析***、方法及装置

Publications (1)

Publication Number Publication Date
WO2021056208A1 true WO2021056208A1 (zh) 2021-04-01

Family

ID=75164833

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2019/107593 WO2021056208A1 (zh) 2019-09-24 2019-09-24 生化物质分析***、方法及装置

Country Status (8)

Country Link
US (1) US20220341848A1 (zh)
EP (1) EP4036554A4 (zh)
JP (1) JP7457798B2 (zh)
KR (1) KR20220066162A (zh)
CN (1) CN114341618B (zh)
AU (2) AU2019467369B2 (zh)
CA (1) CA3151328A1 (zh)
WO (1) WO2021056208A1 (zh)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114391037A (zh) * 2019-09-27 2022-04-22 深圳华大智造科技股份有限公司 流动池及应用所述流动池的生化物质反应装置

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050032072A1 (en) * 2003-08-08 2005-02-10 Perlegen Sciences, Inc. Fragmentation and labelling with a programmable temperature control module
CN101004423A (zh) * 2006-01-19 2007-07-25 博奥生物有限公司 流体样品分析用卡盒***
CN102703312A (zh) * 2012-05-24 2012-10-03 中国科学院北京基因组研究所 一种dna测序仪
CN103336130A (zh) * 2013-06-21 2013-10-02 嘉善加斯戴克医疗器械有限公司 一种全血免疫分析装置及使用此装置的血液分析仪
CN106967600A (zh) * 2016-01-13 2017-07-21 深圳华大基因研究院 芯片座、芯片固定构件及样品加载仪
CN107828641A (zh) * 2017-08-23 2018-03-23 苏州思维医疗科技有限公司 一种基因测序仪
CN208857264U (zh) * 2018-08-16 2019-05-14 深圳华大智造科技有限公司 加载装置及基因测序***
CN110161003A (zh) * 2019-05-17 2019-08-23 深圳市刚竹医疗科技有限公司 光学检测装置及实时荧光定量核酸扩增检测***

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6814933B2 (en) * 2000-09-19 2004-11-09 Aurora Biosciences Corporation Multiwell scanner and scanning method
JP2006038881A (ja) * 2005-10-20 2006-02-09 Hitachi Ltd 生体サンプルの自動分析システム
CN101460953B (zh) * 2006-03-31 2012-05-30 索雷克萨公司 用于合成分析的序列的***和装置
US20170022558A1 (en) * 2007-10-30 2017-01-26 Complete Genomics, Inc. Integrated system for nucleic acid sequence and analysis
CN204832037U (zh) * 2012-04-03 2015-12-02 伊鲁米那股份有限公司 检测设备
JP5978147B2 (ja) * 2013-02-12 2016-08-24 株式会社日立ハイテクノロジーズ 生体物質分析装置
JP6681329B2 (ja) * 2013-08-08 2020-04-15 イラミーナ インコーポレーテッド フローセルへ試薬を送達するための流体システム
CN104569462B (zh) * 2013-10-15 2017-12-08 深圳迈瑞生物医疗电子股份有限公司 一种样本容器的搬送装置及方法

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050032072A1 (en) * 2003-08-08 2005-02-10 Perlegen Sciences, Inc. Fragmentation and labelling with a programmable temperature control module
CN101004423A (zh) * 2006-01-19 2007-07-25 博奥生物有限公司 流体样品分析用卡盒***
CN102703312A (zh) * 2012-05-24 2012-10-03 中国科学院北京基因组研究所 一种dna测序仪
CN103336130A (zh) * 2013-06-21 2013-10-02 嘉善加斯戴克医疗器械有限公司 一种全血免疫分析装置及使用此装置的血液分析仪
CN106967600A (zh) * 2016-01-13 2017-07-21 深圳华大基因研究院 芯片座、芯片固定构件及样品加载仪
CN107828641A (zh) * 2017-08-23 2018-03-23 苏州思维医疗科技有限公司 一种基因测序仪
CN208857264U (zh) * 2018-08-16 2019-05-14 深圳华大智造科技有限公司 加载装置及基因测序***
CN110161003A (zh) * 2019-05-17 2019-08-23 深圳市刚竹医疗科技有限公司 光学检测装置及实时荧光定量核酸扩增检测***

Also Published As

Publication number Publication date
CA3151328A1 (en) 2021-04-01
CN114341618A (zh) 2022-04-12
KR20220066162A (ko) 2022-05-23
AU2023266236A1 (en) 2023-12-07
EP4036554A1 (en) 2022-08-03
JP2022550706A (ja) 2022-12-05
JP7457798B2 (ja) 2024-03-28
EP4036554A4 (en) 2023-05-24
AU2019467369A1 (en) 2022-04-21
AU2019467369B2 (en) 2023-10-19
US20220341848A1 (en) 2022-10-27
CN114341618B (zh) 2024-05-14

Similar Documents

Publication Publication Date Title
US10054605B2 (en) Sample analyzer
CN1739071B (zh) 多层次控制器***
EP2299281B1 (en) Rack collecting unit and sample processing apparatus
EP1460431A2 (en) Automatic analyzer
US9103807B2 (en) Rack collecting unit and sample processing apparatus
JP2016050934A (ja) 検査システムおよび検査方法
JP2008039554A (ja) 自動分析装置
AU2023266236A1 (en) Biochemical substance analysis system, method, and device
JP2007309675A (ja) サンプルラック供給回収装置
CN104483469A (zh) 样本分析装置、样本分析***及其的管理方法
JPWO2016017442A1 (ja) 自動分析装置
JP2012058132A (ja) 検体処理装置および検体処理方法
CN111650168A (zh) 全自动微流控分析仪
JPWO2007132631A1 (ja) 洗浄装置および自動分析装置
JP2004028931A (ja) 自動分析システム
WO2011122606A1 (ja) 検体分析装置
WO2020018725A1 (en) Automatized, programmable, high-throughput culture and analysis systems and methods
JP3626032B2 (ja) 自動分析方法および自動分析装置
CN109283351B (zh) 全自动凝血分析仪
JP2024075643A (ja) 生化学物質分析システム、方法及び装置
CN202257125U (zh) 样本有形成分分析仪自动检测控制装置
US11480565B2 (en) Automated immunoassay
CN212622232U (zh) 全自动微流控分析仪
US9664675B2 (en) Automated analyzer
US20230194558A1 (en) End effector assemblies, systems, and methods of use

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 19946668

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 3151328

Country of ref document: CA

ENP Entry into the national phase

Ref document number: 2022518312

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2019467369

Country of ref document: AU

Date of ref document: 20190924

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 20227013709

Country of ref document: KR

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 2019946668

Country of ref document: EP

Effective date: 20220425