WO2014150290A1 - Devices, systems and methods for sample preparation - Google Patents
Devices, systems and methods for sample preparation Download PDFInfo
- Publication number
- WO2014150290A1 WO2014150290A1 PCT/US2014/022847 US2014022847W WO2014150290A1 WO 2014150290 A1 WO2014150290 A1 WO 2014150290A1 US 2014022847 W US2014022847 W US 2014022847W WO 2014150290 A1 WO2014150290 A1 WO 2014150290A1
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- WIPO (PCT)
- Prior art keywords
- vessel
- sample
- sonicator
- pathogen
- assay
- Prior art date
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Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
- B01L3/5082—Test tubes per se
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F31/00—Mixers with shaking, oscillating, or vibrating mechanisms
- B01F31/80—Mixing by means of high-frequency vibrations above one kHz, e.g. ultrasonic vibrations
- B01F31/86—Mixing by means of high-frequency vibrations above one kHz, e.g. ultrasonic vibrations with vibration of the receptacle or part of it
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
- C12Q1/04—Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/38—Diluting, dispersing or mixing samples
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/487—Physical analysis of biological material of liquid biological material
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/025—Align devices or objects to ensure defined positions relative to each other
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0848—Specific forms of parts of containers
- B01L2300/0858—Side walls
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/286—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q involving mechanical work, e.g. chopping, disintegrating, compacting, homogenising
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/40—Concentrating samples
- G01N1/4077—Concentrating samples by other techniques involving separation of suspended solids
- G01N2001/4094—Concentrating samples by other techniques involving separation of suspended solids using ultrasound
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N2035/00465—Separating and mixing arrangements
- G01N2035/00524—Mixing by agitating sample carrier
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N2035/00465—Separating and mixing arrangements
- G01N2035/00534—Mixing by a special element, e.g. stirrer
- G01N2035/00554—Mixing by a special element, e.g. stirrer using ultrasound
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/00584—Control arrangements for automatic analysers
- G01N35/00722—Communications; Identification
- G01N35/00871—Communications between instruments or with remote terminals
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
Definitions
- detection and identification of pathogens in a biological sample may be important in the diagnosis and treatment of patients exposed to, or suspected of suffering, from infectious diseases.
- present methods for detecting or identifying pathogens are often inaccurate, difficult, expensive, and time-consuming. Accordingly, rapid, accurate and straightforward methods for the detection and identification of pathogens from small samples are desired.
- a sonicator may be used for aerosolization of a liquid, e.g., aerosolization of a liquid sample, or of a solution comprising a sample.
- a sonicator may be used to heat a solution, such as a sample, or a solution comprising a sample.
- a sonicator may be used for dispersing a sample, or a sample in a solution, or other material, such as, e.g., dispersing a solid or semi-solid sample in a solution.
- a sonicator may be used to disintegrate a material, such as a sample, e.g., a solid or semi-solid sample may be exposed to sonication for disintegration, which may aid in its subsequent mixing into a reagent such as a diluent.
- a sonicator may be used to de-gas a liquid, such as a fluid sample; in embodiments, gas released in this way may become better available for assay.
- a sonicator may be used to disrupt a cell, such as a pathogen cell in a sample. Disruption of a cell will typically expose cellular contents (intracellular material, including, e.g., nuclear material from within a cell or organelle) to testing, and to provide more accessible proteins and protein/membrane complexes for assay
- Devices, systems and methods for disrupting pathogens in a biological sample comprise a sonicator; the sonicator may be configured to provide ultrasonic energy to a sample solution containing a pathogen effective to disrupt the pathogen, e.g., to disrupt a membrane of the pathogen. Such disruption may be effective to release pathogen-identifying material from the pathogen, aiding in the detection, identification, or measurement of the pathogen.
- multipurpose devices are provided which include a sonicator configured to disrupt pathogen cells in a biological sample, exposing pathogen-identifying material for assay. Multipurpose devices are provided DEVICES, SYSTEMS AND METHODS FOR SAMPLE PREPARATION
- a biological sample may comprise blood, urine, sputum, tears, material obtained from a nasal swab, throat swab, cheek swab, or other sample obtained from a subject.
- a device as disclosed herein may be suitable for detection, identification, or measurement of pathogen-identifying material in a biological sample.
- a device for assaying a sample for the presence of pathogen-identifying material in a sample may comprise a sonicator, wherein said sonicator comprises means for contacting a wall of a vessel containing at least a portion of a biological sample.
- a device for assaying a sample for the presence of pathogen-identifying material in a sample may comprise: a sonicator; an sample handling system for transporting at least a portion of a biological sample; a vessel holder effective to hold a vessel having a wall; and a detector DEVICES, SYSTEMS AND METHODS FOR SAMPLE PREPARATION
- a sonicator may comprise a tip; in embodiments, a sonicator tip may be effective to contact said vessel wall and to transfer ultrasonic energy to said vessel wall from said sonicator.
- a sonicator may comprise a sonicator horn, which horn may have a tip, and said horn and tip may be effective to contact said vessel wall and to transfer ultrasonic energy to said vessel wall from said sonicator.
- a device may further comprise a communication assembly, which may comprise a display element or a communication element effective to report the results of said detection and/or measurement.
- a communication assembly such as a display element and/or
- a sonicator of such an automated assay device has a sonicator tip configured to contact the external face of the vessel wall effective to transfer ultrasonic energy from the sonicator to the vessel wall upon operation of the sonicator.
- a detector of such an automated assay device includes an optical detector.
- the device is configured to apply force to a vessel while applying a sonicator tip to a wall of a vessel.
- the assay for pathogen-identifying material of such an automated assay device may be or include an assay selected from an assay for the detection of pathogen-identifying material in a sample; an assay for the identification of pathogen-identifying material in a sample; and an assay for the measurement of the amount of pathogen-identifying material in a sample.
- the assay for pathogen-identifying material comprises an isothermal assay. DEVICES, SYSTEMS AND METHODS FOR SAMPLE PREPARATION
- the detector means comprises optical detection means.
- an assay of such an automated assay device comprises an assay selected from an assay for detection pathogen-identifying material in a sample; an assay for identification of pathogen-identifying material in a sample; and an assay for measurement of an amount of pathogen-identifying material in a sample.
- the assay for pathogen-identifying material comprises an isothermal assay.
- Biological samples suitable for use in the devices disclosed herein, and suitable for assay by an automated assay device as disclosed herein, include samples selected from blood, urine, sputum, tears, material from a nasal swab, material from a throat swab, material from a cheek swab, and another bodily fluid, excretion, secretion, and tissue obtained from a subject.
- Applicants disclose a method of detecting the presence of pathogen-identifying material in a biological sample, comprising:
- the contacting step may comprise:
- the detecting in such methods may comprise optical detection.
- a method of detecting the presence of pathogen-identifying material as disclosed herein comprises performing an isothermal assay for the detection of the presence of pathogen-identifying material.
- a further method of identifying pathogen-identifying material in a biological sample comprises:
- the vessel transporting at least a portion of the biological sample to a vessel, the vessel having an interior portion and a vessel wall having an external face, effective to place the portion of the biological sample into the interior portion of the vessel;
- identifying comprises optical detection.
- the identification of pathogen-identifying material comprises performing an isothermal assay for the identification of pathogen-identifying material.
- Applicants further disclose a method of disrupting a pathogen in a biological sample, comprising:
- a vessel transporting at least a portion of a biological sample to a vessel, the vessel having an interior portion and a vessel wall having an external face, effective to place the portion of the biological sample into the interior portion of the vessel;
- a yet further method of detecting the presence of pathogen-identifying material in a biological sample comprises:
- the vessel transporting at least a portion of a biological sample to a vessel, the vessel having a mating socket, an interior portion, and an exterior wall, effective to place the portion of the biological sample into the interior portion of the vessel;
- the detecting the presence of pathogen-identifying material in such a method comprises performing an isothermal assay. In embodiments, the detecting the presence of pathogen-identifying material in such a method comprises optical detection.
- Another method of measuring an amount of a pathogen-identifying material in a biological sample comprising:
- Measuring an amount of a pathogen-identifying material in the sample Measuring an amount of a pathogen-identifying material in the sample.
- the contacting step of such a method comprises:
- the vessel transporting at least a portion of the biological sample to a vessel, the vessel having an interior portion and a vessel wall having an external face, effective to place the portion of the biological sample into the interior portion of the vessel;
- the measuring step comprises optical detection.
- Another method of measuring an amount of a pathogen-identifying material in a biological sample comprises:
- Applicants also disclose systems comprising an automated assay device as disclosed herein.
- a system comprises an automated assay device as disclosed herein, wherein the automated assay device comprises a sonicator having a sonicator tip; and a vessel, wherein the vessel comprises a vessel wall having an external face, the external face comprising a sonicator-contacting portion, wherein the sonicator- contacting portion comprises a flat area complementary to a flat portion of the sonicator tip.
- the flat area of the vessel comprises a flat area of a side wall of the vessel in embodiments of such a system.
- the flat area of a vessel comprises a flat area of a bottom wall of the vessel.
- the vessel comprises a plurality of flat areas; in embodiments, at least one of the flat areas of the vessel comprises a flat area of a side wall of the vessel; or at least one of the flat areas of the vessel comprises a flat area of a bottom wall of the vessel; orat least one of the flat areas of the vessel comprises a flat area of a side wall of the vessel, and at least one of the flat areas of the vessel comprises a flat area of a bottom wall of the vessel.
- vessels herein such vessels comprising an internal portion for holding a sample, a side wall, a bottom wall, and a mating socket configured to mate with a sample handling system, wherein at least one of the vessel walls comprises a flat area configured to make contact with a sonicator tip effective that ultrasonic energy from a sonicator in contact with the vessel is transferred to a sample held in the internal portion during operation of the sonicator.
- the flat area of the vessel comprises a flat area of a side wall of the vessel; or the flat area of the vessel comprises a flat area of a bottom wall of the vessel; or the vessel comprises a plurality of flat areas; or at least one of the flat areas of the vessel comprises a flat area of a side wall of the vessel; or at least one of the flat areas of the vessel comprises a flat area of a bottom wall of the vessel; or at least one of the flat areas of the vessel comprises a flat area of a side wall of the vessel, and at least one of the flat areas of the vessel comprises a flat area of a bottom wall of the vessel; and combinations and multiples thereof.
- a device for assaying a sample for the presence of pathogen-identifying material in a sample may comprise a sonicator, wherein said sonicator comprises means for contacting a wall of a vessel containing at least a portion of a biological sample.
- a device for assaying a sample for the presence of pathogen-identifying DEVICES, SYSTEMS AND METHODS FOR SAMPLE PREPARATION may comprise a sonicator, wherein said sonicator comprises means for contacting a wall of a vessel containing at least a portion of a biological sample.
- material in a sample may comprise: a sonicator; sample handling system means for transporting at least a portion of a biological sample; means for holding a vessel having a wall; means for contacting said vessel wall with at least a portion of said sonicator; and means for detecting, identifying, or measuring pathogen-identifying material (e.g., means for detecting an optical signal, and/or measuring an optical property of the combined
- Applicants further disclose systems comprising a device as disclosed herein.
- a system as disclosed herein may be used to detect the presence of, identify, or measure the amount of, pathogen-identifying material in a sample.
- a system for detecting the presence of pathogen-identifying material in a sample may comprise a device as disclosed herein, and a means for communicating information from said device to a computer, a computer network, a telephone, a telephone network, or a device configured to display information communicated from said device.
- Applicants disclose herein systems for identifying pathogen-identifying material in a biological sample, e.g., a sample of blood, urine, sputum, tears, material from a nasal swab, throat swab, cheek swab, or other sample obtained from a subject.
- a biological sample e.g., a sample of blood, urine, sputum, tears, material from a nasal swab, throat swab, cheek swab, or other sample obtained from a subject.
- a system for identifying pathogen-identifying material in a sample may comprise a device as disclosed herein, and a means for communicating information from said device to a computer, a computer network, a wide-area network, a local-area network, a virtual private network, a fiber-optical network, a telephone, a telephone network (which may DEVICES, SYSTEMS AND METHODS FOR SAMPLE PREPARATION
- Applicants disclose herein systems for measuring the amount of pathogen-identifying material in a biological sample e.g. a sample of blood, urine, sputum, tears, material from a nasal swab, throat swab, cheek swab, or other sample obtained from a subject.
- a system for measuring the amount of pathogen-identifying material in a sample may comprise a device as disclosed herein, and a means for communicating information from said device to a computer, a computer network, a telephone, a telephone network, or a device configured to display information communicated from said device.
- a means for communicating information may include means for one-way communication and may include means for two-way communication, and may include means for communication with multiple locations or entities.
- a system for detecting the presence of pathogen-identifying material in a sample, a system for identifying pathogen-identifying material in a sample, and a system for measuring the amount of pathogen-identifying material in a sample may comprise a device as disclosed herein, and a communication assembly, which may comprise a channel for communicating information from said device to a computer, said wherein said channel is selected from a computer network, a telephone network, a metal communication link, an optical communication link, and a wireless communication link.
- a communication assembly e.g., comprising a channel for communicating information, may comprise a one-way communication channel and may be a two-way communication channel, and may comprise channels for communication with multiple locations or entities.
- the methods disclosed herein may be performed on a device, or on a system, for processing a sample as disclosed herein.
- the methods disclosed herein can be readily incorporated into and used in an automated assay device, and in an automated assay system, as disclosed herein.
- systems as disclosed herein may include a communication assembly for transmitting or receiving a protocol based on the analyte to be detected (e.g., pathogen-identifying material) or based on other analytes to be detected by the device or system.
- an assay protocol may be changed based on optimal scheduling of a plurality of assays to be performed by a device, or may be changed based on results previously obtained from a sample from a subject, or based on results previously obtained from a different sample from the subject.
- a communication assembly may comprise a channel for communicating information from said device to a computer, said DEVICES, SYSTEMS AND METHODS FOR SAMPLE PREPARATION
- systems as disclosed herein may transmit signals to a central location, or to an end user, and may include a communication assembly for transmitting such signals.
- Systems as disclosed herein may be configured for updating a protocol as needed or on a regular basis.
- Applicants disclose devices configured to detect, identify, or measure pathogen-identifying material in a biological sample, e.g., of blood, urine, sputum, material obtained from a nasal swab, a throat swab, a cheek swab, or other sample. Such detection, identification, or measurements may be made according to a method disclosed herein.
- a biological sample e.g., of blood, urine, sputum, material obtained from a nasal swab, a throat swab, a cheek swab, or other sample.
- Devices configured to detect, identify, or measure pathogen-identifying material in a biological sample, e.g., of blood, urine, sputum, material obtained from a nasal swab, a throat swab, a cheek swab, or other sample, according to a method disclosed herein may be configured to determine pathogen-identifying material from a biological sample that comprises no more than about 1000 ⁇ ⁇ of a biological sample, or no more than about 500 ⁇ ⁇ of a biological sample, or no more than about 250 ⁇ a biological sample, or no more than about 150 ⁇ ⁇ of a biological sample, or no more than about 100 ⁇ ⁇ of a biological sample, or no more than about 50 ⁇ ⁇ of a biological sample, or, in embodiments, wherein said sample of blood comprises no more than about 25 ⁇ ⁇ of a biological sample, or wherein said sample of blood comprises no more than about 10 ⁇ ⁇ of a biological sample, or wherein said sample of blood comprises less than about 10
- Such devices may be configured to detect, identify, or measure pathogen-identifying material in a biological sample, e.g., of blood, urine, sputum, material obtained from a nasal swab, a throat swab, a cheek swab, or other sample, in less than about one hour, or, in embodiments, in less than about 40 minutes, or in less than about 30 minutes, or in less than about 20 minutes, or less than about 10 minutes, or less than about 5 minutes, or less.
- a biological sample e.g., of blood, urine, sputum, material obtained from a nasal swab, a throat swab, a cheek swab, or other sample, in less than about one hour, or, in embodiments, in less than about 40 minutes, or in less than about 30 minutes, or in less than about 20 minutes, or less than about 10 minutes, or less than about 5 minutes, or less.
- Devices disclosed herein may be configured to perform an assay for the detection, identification, or measurement of pathogen-identifying material, and also to perform an assay for the measurement of another analyte in the biological sample, e.g., of blood, urine, sputum, material obtained from a nasal swab, a throat swab, a cheek swab, or other sample.
- another analyte in the biological sample e.g., of blood, urine, sputum, material obtained from a nasal swab, a throat swab, a cheek swab, or other sample.
- Fig. 4 shows an example of an embodiment of a sonicator having a collet for holding a vessel.
- the collet may be cinched around a vessel contained within the collet to provide a tight fit between the collet and vessel; such a tight fit may aid in the efficient transfer of ultrasonic energy between the transducer of the sonicator (via the collet) and the vessel.
- Devices, systems, and methods disclosed herein may comprise, and may be used with, devices, systems, and methods as disclosed in, for example, U.S. Patent 8,088,593; U.S. Patent 8,380,541 ; U.S. Pat. App. Ser. No. 61/799,533, filed March 15, 2013; U.S. Pat. App. Ser. No. 13/769,798, filed February 18, 2013; U.S. Pat. App. Ser. No. 13/769,779, filed February 18, 2013; U.S. Pat. App. Ser. No. 13/244,947 filed Sept. 26, 201 1;
- test refers to tests, measurements, observations, and other experimental procedures which may be applied to a DEVICES, SYSTEMS AND METHODS FOR SAMPLE PREPARATION
- the term "ultrasound” refers to vibrations at frequencies beyond those capable of being detected by a human subject, i.e., frequencies greater than about 20,000 cycles per second (20 kiloHerz (kHz)).
- the term "sonicator” refers to a device effective to provide ultrasonic energy, e.g., by providing mechanical energy, typically in the form of vibrations, at ultrasonic frequencies.
- a sonicator may include a driving element which provides high- frequency vibrations; for example, many sonicators utilize piezoelectric materials to produce high-frequency vibrations.
- Piezoelectric ultrasound generators typically require high voltages (e.g., provided by a time -varying electrical input having peak voltages of about 200 volts (V) to about 400 V, e.g., about 50 root-mean-square volts (VRMS) to about 300 VRMS) to provide the needed alternating current drive to operate such generators.
- V volts
- VRMS root-mean-square volts
- horn and “sonicator horn” refer to a portion of a sonicator configured to focus ultrasonic energy, or to provide a pathway for the direction of ultrasonic energy, to a destination.
- a horn may be designed and configured to transfer or transmit ultrasonic energy in an efficient manner, and may, for example, be configured to resonate at particular frequencies which may be tuned or adapted to particular frequencies of choice of a driving element of a sonicator.
- a horn may have a tip, or tip portion; a horn tip or DEVICES, SYSTEMS AND METHODS FOR SAMPLE PREPARATION
- PMMA polymethylmethacrylate
- poly(4-methylbutene) other acrylic
- the terms "measure”, “measurement”, “measuring”, and grammatical equivalents refer to a determination of the amounts of a target analyte found in a sample. Thus, measurement provides quantitative information which may not be provided by detection or identification, or which may be more precise that information provided by detection or identification.
- nucleic acid refers to nucleotides and nucleosides which make up, for example, deoxyribonucleic acid (DNA) macromolecules and ribonucleic acid (RNA) macromolecules. Nucleic acids may be identified by the base attached to the sugar (e.g., deoxyribose or ribose); nucleic acid sequences may be used to identify an organism from which the nucleic acid sequence was obtained.
- DNA deoxyribonucleic acid
- RNA ribonucleic acid
- polypeptide and protein may be used interchangeably to refer to molecules comprised of amino acids linked by peptide bonds. Individual amino acids may be termed “residues” of a polypeptide or protein. Unique amino acid sequences of polypeptides may be used to identify the organisms from which the polypeptides were obtained.
- antibody fragments include Fab, Fab', Fab'-SH, F(ab')2, Fd, Fc, Fv, diabodies, and any other "Non-single-chain antigen-binding unit" as described, e.g., in U.S. Pat. No. 7429652.
- pathogen refers to an agent that may cause a disease, such as an infectious disease, in a subject.
- Pathogens include, for example, Gram- negative bacteria, Gram-positive bacteria, other bacteria, RNA viruses, DNA viruses, prions, yeast, fungi, protozoans, helminths, nematodes, and any other pathogenic agent which may sicken a subject or, if transmitted from a subject who may not suffer disease, could cause disease in a further subject to which the pathogen is transmitted.
- the proteins, and the nuclear material of such organisms is indicative of the particular type of organism, and may be used to detect the presence of such an organism, and to identify it.
- Quantitative measurements of pathogen-identifying material provide measurements of the amounts of such organisms in a biological sample, and may be used to determine the severity of an infection, or to track the progress of a disease, and to track the course and success of its treatment.
- probe refers to a material which is useful to identify a target compound or cell; a probe may be, e.g., a nucleic acid probe, a protein probe, or other probe.
- a target compound may be produced by, or found in or on, a prion, a virus, a bacterium, a yeast, a fungus, a protozoan, or other pathogen.
- a probe, as used herein, may comprise RNA or DNA, or analogs of RNA or DNA, effective that the probe may recognize and bind (e.g., hybridize) to a target nucleic acid.
- a target nucleic acid may be, e.g., a viral, bacterial, yeast, fungal, protozoan, helminth, nematode, or other nucleic acid sequence (which may be a portion of a longer nucleic acid sequence).
- a probe as used herein, may comprise a polypeptide or protein, such as an antibody or antibody fragment, which may recognize and bind to a target compound or portion of a compound (e.g., an epitope of a protein that is indicative of a target pathogen).
- a marker or label may be linked (non-covalently or covalently) to a nucleic acid probe, an antibody or antibody fragment, or other probe.
- a label may alter its detectability (e.g., become detectable, or increase, or decrease its detectability) upon contact with its target.
- a label may detach from its probe upon contact between the probe and its target, and thus may alter its detectability. Such alterations in detectability are useful in assays for detecting, identifying, or measuring analytes in a sample.
- a label may be, for example, a dye, an epitope tag, a fluorescent moiety, a luminescent moiety, a chemiluminescent moiety, an enzymatic label, a magnetic label, a paramagnetic label, a contrast agent, a nanoparticle, a radioisotope, biotin, streptavidin, and a quencher.
- a nanoparticle may be a particle of an element, such as a gold nanoparticle, or of an alloy or compound, such as a quantum dot (a particle of a semiconductor material), or other particle having a size typically in a range between about 1 nm to about 100 nm.
- a device may be part of a system, a component of which may be a sample processing device.
- a device may be a sample processing device.
- a sample processing device DEVICES, SYSTEMS AND METHODS FOR SAMPLE PREPARATION
- a sample processing device may be configured to facilitate collection of a sample, prepare a sample for a clinical test, or effect a chemical reaction with one or more reagents or other chemical or physical processing, as disclosed herein.
- a sample processing device may be configured to obtain data from a sample.
- a sample processing device may be configured to transmit data obtained from a sample.
- a sample processing device may be configured to analyze data from a sample.
- a sample processing device may be configured to communicate with another device, or a laboratory, or an individual affiliated with a laboratory, to analyze data obtained from a sample.
- a sample processing device may be configured to be placed in or on a subject.
- a sample processing device may be configured to accept a sample from a subject, either directly or indirectly.
- a sample may be, for example, a biological sample, e.g., of blood, urine, sputum, material obtained from a nasal swab, a throat swab, a cheek swab, or other sample, (e.g., a sample obtained from a fingerstick, or from venipuncture, or an arterial biological sample, e.g., of blood, urine, sputum, material obtained from a nasal swab, a throat swab, a cheek swab, or other sample,), a urine sample, a biopsy sample, a tissue slice, stool sample, or other biological sample; a water sample, a soil sample, a food sample, an air sample; or other sample.
- a biological sample e.g., of blood, urine, sputum
- a biological sample e.g., of blood, urine, sputum, material obtained from a nasal swab, a throat swab, a cheek swab, or other sample, may comprise, e.g., whole blood, plasma, or serum.
- a sample processing device may receive a sample from the subject through a housing of the device. The sample collection may occur at a sample collection site, or elsewhere. The sample may be provided to the device at a sample collection site.
- a sample processing device may be configured to accept or hold a cartridge.
- a sample processing device may comprise a cartridge.
- the cartridge may be removable from the sample processing device.
- a sample may be provided to the cartridge of the sample processing device.
- a sample may be provided to another portion of a sample processing device.
- the cartridge and/or device may comprise a sample collection unit that may be configured to accept a sample.
- a cartridge may include a sample, and may include reagents for use in processing or testing a sample, disposables for use in processing or testing a sample, or other materials. Following placement of a cartridge on, or insertion of a cartridge into, a sample processing device, one or more components of the cartridge may be brought into fluid communication with other components of the sample processing device. For example, if a DEVICES, SYSTEMS AND METHODS FOR SAMPLE PREPARATION
- sample is collected at a cartridge, the sample may be transferred to other portions of the sample processing device.
- the reagents may be transferred to other portions of the sample processing device, or other components of the sample processing device may be brought to the reagents.
- the reagents or components of a cartridge may remain on-board the cartridge.
- no fluidics are included that require tubing or that require maintenance (e.g., manual or automated maintenance).
- a sample or reagent may be transferred to a device, such as a sample processing device.
- a sample or reagent may be transferred within a device. Such transfer of sample or reagent may be accomplished without providing a continuous fluid pathway from cartridge to device. Such transfer of sample or reagent may be accomplished without providing a continuous fluid pathway within a device.
- such transfer of sample or reagent may be accomplished by a sample handling system (e.g., a pipette); for example, a sample, reagent, or aliquot thereof may be aspirated into an open-tipped transfer component, such as a pipette tip, which may be operably connected to a sample handling system which transfers the tip, with the sample, reagent, or aliquot thereof contained within the tip, to a location on or within the sample processing device.
- the sample, reagent, or aliquot thereof can be deposited at a location on or within the sample processing device.
- Sample and reagent, or multiple reagents may be mixed using a sample handling system in a similar manner.
- One or more components of the cartridge may be transferred in an automated fashion to other portions of the sample processing device, and vice versa.
- a device such as a sample processing device, may have a sample handling system (also termed herein a fluid handling system).
- a sample handling system may perform, or may aid in performing, transport, dilution, extraction, aliquotting, mixing, and other actions with a fluid, such as a sample.
- a sample handling system may be contained within a device housing.
- a sample handling system may permit the collection, delivery, processing and/or transport of a fluid, dissolution of dry reagents, mixing of liquid and/or dry reagents with a liquid, as well as collection, delivery, processing and/or transport of non-fluidic components, samples, or materials.
- the handling system may dispense or aspirate a fluid.
- the sample may include one or more particulate or solid matter floating within a fluid.
- a sample handling system may comprise a pipette, pipette tip, syringe, capillary, or other component.
- the sample handling system may have portion with an interior surface and an exterior surface and an open end.
- the sample handling system may comprise a pipette, which may include a pipette body and a pipette nozzle, and may comprise a pipette tip.
- a pipette tip may or may not be removable from a pipette nozzle.
- a sample handling system may use a pipette mated with a pipette tip; a pipette tip may be disposable. A tip may form a fluid-tight seal when mated with a pipette. A pipette tip may be used once, twice, or more times.
- a sample handling system may use a pipette or similar device, with or without a pipette tip, to aspirate, dispense, mix, transport, or otherwise handle the fluid.
- the fluid may be dispensed from the sample handling system when desired.
- the fluid may be contained within a pipette tip prior to being dispensed, e.g., from an orifice in the pipette tip.
- a sample handling system may include one or more fluidically isolated or hydraulically independent units.
- the sample handling system may include one, two, or more pipette tips.
- the pipette tips may be configured to accept and confine a fluid.
- the tips may be fluidically isolated from or hydraulically independent of one another.
- the fluid contained within each tip may be fluidically isolated or hydraulically independent from one fluids in other tips and from other fluids within the device.
- the fluidically isolated or hydraulically independent units may be movable relative to other portions of the device and/or one another.
- the fluidically isolated or hydraulically independent units may be individually movable.
- a sample handling system may comprise one or more base or support.
- a base or support may support one or more pipette or pipette units.
- a base or support may connect one or more pipettes of the sample handling system to one another.
- sample preparation action or step may include one or more of the following: centrifugation, separation, filtration, dilution, enriching, purification, precipitation, incubation, pipetting, transport, chromatography, cell lysis, cytometry, pulverization, grinding, activation, ultrasonication, micro column processing, processing with magnetic beads, processing with nanoparticles, or other sample preparation action or steps.
- sample preparation may include one or more step to separate blood into serum and/or particulate fractions, or to separate any other sample into various components.
- Sample preparation may include one or more step to dilute and/or concentrate a sample, such as a biological sample, e.g., of blood, urine, sputum, material obtained from a nasal swab, a throat swab, a cheek swab, or other sample, or other biological samples.
- Sample preparation may include adding an anti-coagulant or other ingredients to a sample.
- Sample preparation may also include purification of a sample.
- all sample processing, preparation, or assay actions or steps are performed by a single device. In embodiments, all sample processing, preparation, or assay actions or steps are performed within a housing of a single device.
- sample processing, preparation, or assay actions or steps are performed by a single device, and may be performed within a housing of a single device. In embodiments, many sample processing, preparation, or assay actions or steps are performed by a single device, and may be performed within a housing of a single device. In embodiments, sample processing, preparation, or assay actions or steps may be performed by more than one device.
- a sample processing device may be configured to run one or more assay on a sample, and to obtain data from the sample.
- An assay may include one or more physical or chemical treatments, and may include running one or more chemical or physical reactions.
- a sample processing device may be configured to perform one, two or more assays on a small sample of bodily fluid.
- One or more chemical reaction may take place on a sample having a volume, as described elsewhere herein. For example one or more chemical reaction may take place in a pill having less than femtoliter volumes.
- the volume of a sample may be a small volume, where a small volume may be a volume that is less than about 1000 ⁇ L, or less than about 500 ⁇ ,, or less than about 250 ⁇ ,, or less than about 150 ⁇ ,, or less than about 100 ⁇ ,, or less than about 75 ⁇ ,, or less than about 50 ⁇ ,, or less than about 40 ⁇ ,, or less than about 20 xL, or less than about 10 ⁇ L, or other small volume.
- all sample assay actions or steps are performed on a single sample. In embodiments, all sample assay actions or steps are performed by a single device.
- all sample assay actions or steps are performed within a housing of a single device. In embodiments, most sample assay actions or steps are performed by a single device, and may be performed within a housing of a single device. In embodiments, many sample assay actions or steps are performed by a single device, and may be performed within a housing of a single device. In embodiments, sample processing, preparation, or assay actions or steps may be performed by more than one device.
- a sample processing device may be configured to perform a plurality of assays on a sample.
- a sample processing device may be configured to detect, or to identify, or to measure pathogen-identifying material in a sample.
- a sample processing device may be configured to perform a plurality of assays on a single sample.
- a sample processing device may be configured to perform a plurality of assays on a single biological sample, where the biological sample is a small sample.
- a small sample may have a sample volume that is a small volume of less than about 1000 ⁇ ,, or less than about 500 ⁇ ,, or less than about 250 ⁇ ,, or less than about 150 ⁇ ,, or less than about 100 ⁇ ,, or less than about 75 ⁇ ,, or less than about 50 ⁇ ,, or less than about 40 ⁇ ,, or less than about 20 ⁇ ,, or less than about 10 ⁇ ,, or other small volume.
- a sample processing device may be capable of performing multiplexed assays on a single sample. A plurality of assays may be run simultaneously; may be run sequentially; or some assays may be run simultaneously while others are run sequentially.
- control assays and/or calibrators can also be incorporated into the device; control assays and assay on calibrators may be performed simultaneously with assays performed on a sample, or may be performed before or after assays performed on a sample, or any combination thereof.
- all sample assay actions or steps are performed by a single device.
- all of a plurality of assay actions or steps are performed within a housing of a DEVICES, SYSTEMS AND METHODS FOR SAMPLE PREPARATION
- sample assay actions or steps, of a plurality of assays are performed by a single device, and may be performed within a housing of a single device. In embodiments, many sample assay actions or steps, of a plurality of assays, are performed by a single device, and may be performed within a housing of a single device.
- sample processing, preparation, or assay actions or steps may be performed by more than one device.
- all of a plurality of assays may be performed in a short time period.
- a short time period comprises less than about three hours, or less than about two hours, or less than about one hour, or less than about 40 minutes, or less than about 30 minutes, or less than about 25 minutes, or less than about 20 minutes, or less than about 15 minutes, or less than about 10 minutes, or less than about 5 minutes, or less than about 4 minutes, or less than about 3 minutes, or less than about 2 minutes, or less than about 1 minute, or other short time period.
- a sample processing device may be configured to detect one or more signals relating to the sample.
- a sample processing device may be configured to identify one or more properties of the sample. For instance, the sample processing device may be configured to detect the presence or concentration of one analyte or a plurality of analytes or a disease condition in the sample (e.g., in or through a bodily fluid, secretion, tissue, or other sample).
- the sample processing device may be configured to detect a signal or signals that may be analyzed to detect the presence or concentration of one or more analytes (which may be indicative of a disease condition) or a disease condition in the sample.
- the signals may be analyzed on board the device, or at another location. Running a clinical test may or may not include any analysis or comparison of data collected.
- a chemical reaction or other processing step may be performed, with or without the sample.
- steps, tests, or assays that may be prepared or run by the device may include, but are not limited to immunoassay, nucleic acid assay, receptor-based assay, cytometric assay, colorimetric assay, enzymatic assay, electrophoretic assay, electrochemical assay, spectroscopic assay, chromatographic assay, microscopic assay, topographic assay, calorimetric assay, turbidmetric assay, agglutination assay, radioisotope assay, viscometric assay, coagulation assay, clotting time assay, protein synthesis assay, histological assay, culture assay, osmolarity assay, and/or other types of assays,
- Steps, tests, or assays that may be prepared or run by the device may include imaging, including microscopy, cytometry, and other techniques preparing or utilizing images. Steps, tests, or assays that may be prepared or run by the device may further include an assessment of histology, morphology, kinematics, dynamics, and/or state of a sample, which may include such assessment for cells.
- a device may be capable of performing all on-board steps (e.g., steps or actions performed by a single device) in a short amount of time.
- a device may be capable of performing all on-board steps on a single sample in a short amount of time. For example, from sample collection from a subject to transmitting data and/or to analysis may take about 3 hours or less, 2 hours or less, 1 hour or less, 50 minutes or less, 45 minutes or less, 40 minutes or less, 30 minutes or less, 20 minutes or less, 15 minutes or less, 10 minutes or less, 5 minutes or less, 4 minutes or less, 3 minutes or less, 2 minutes or less, or 1 minute or less.
- the amount of time from accepting a sample within the device to transmitting data and/or to analysis from the device regarding such a sample may depend on the type or number of steps, tests, or assays performed on the sample.
- the amount of time from accepting a sample within the device to transmitting data and/or to analysis from the device regarding such a sample may take about 3 hours or less, 2 hours or less, 1 hour or less, 50 minutes or less, 45 minutes or less, 40 minutes or less, 30 minutes or less, 20 minutes or less, 15 minutes or less, 10 minutes or less, 5 minutes or less, 4 minutes or less, 3 minutes or less, 2 minutes or less, or 1 minute or less.
- a device may be configured to prepare a sample for disposal, or to dispose of a sample, such as a biological sample, following processing or assaying of a sample.
- a sample processing device may be configured to transmit data obtained from a sample.
- a sample processing device may be configured to communicate over a network.
- a sample processing device may include a communication assembly that may interface with the network.
- a sample processing device may be connected to the network via a wired connection or wirelessly.
- the network may be a local area network (LAN) or a wide area network (WAN) such as the Internet.
- the network may be a personal area network.
- the network may be a virtual private network (VPN).
- the network may include the cloud.
- the sample processing device may be connected to the network by wire, cable, fiber optical, microwave, infrared, acoustic, or other connections or connection means.
- the sample processing device may be connected to the network without requiring an intermediary device, or an intermediary device may be DEVICES, SYSTEMS AND METHODS FOR SAMPLE PREPARATION
- a sample processing device may communicate over a network with another device, which may be any type of networked device, including but not limited to a personal computer, server computer, or laptop computer; personal digital assistants (PDAs) such as a Windows CE device; phones such as cellular phones, smartphones (e.g., iPhone, Android, Blackberry, etc.), or location-aware portable phones (such as GPS); a roaming device, such as a network-connected roaming device; a wireless device such as a wireless email device or other device capable of communicating wireless with a computer network; or any other type of network device that may communicate possibly over a network and handle electronic transactions.
- PDAs personal digital assistants
- Such communication may include providing data to a cloud computing infrastructure or any other type of data storage infrastructure which may be accessed by other devices.
- a sample processing device may provide data regarding a sample to, e.g., a health care professional, a health care professional location, such as a laboratory, or an affiliate thereof.
- a laboratory, health care professional, or subject may have a network device able to receive or access data provided by the sample processing device.
- a sample processing device may be configured to provide data regarding a sample to a database.
- a sample processing device may be configured to provide data regarding a sample to an electronic medical records system, to a laboratory information system, to a laboratory automation system, or other system or software.
- a sample processing device may provide data in the form of a report.
- a laboratory, device, or other entity or software may perform analysis on data regarding a sample in real-time.
- a software system may perform chemical analysis and/or pathological analysis, or these could be distributed amongst combinations of lab, clinical, and specialty or expert personnel.
- Analysis may include qualitative and/or quantitative evaluation of a sample.
- Data analysis may include a subsequent qualitative and/or quantitative evaluation of a sample.
- a report may be generated based on raw data, pre- processed data, or analyzed data. Such a report may be prepared so as to maintain confidentiality of the data obtained from the sample, the identity and other information regarding the subject from whom a sample was obtained, analysis of the data, and other confidential information.
- the report and/or the data may be transmitted to a health care professional.
- Data obtained by a sample processing device, or analysis of such data, or reports, may be provided to a database, an electronic medical records system, to a laboratory information system, to a laboratory automation system, or other system or software.
- DEVICES, SYSTEMS AND METHODS FOR SAMPLE PREPARATION may be provided to a database, an electronic medical records system, to a laboratory information system, to a laboratory automation system, or other system or software.
- the following examples disclose devices comprising a sonicator effective to disrupt pathogens in a biological sample.
- Embodiments of systems disclosed herein include devices which have a sonicator configured to apply ultrasonic energy to a sample solution.
- Application of ultrasonic energy to a sample solution containing a pathogen may be effective to disrupt the pathogen and to release pathogen-identifying material into the solution, where it can be detected and the pathogen identified.
- the amounts of pathogens present in the sample solution may be quantified following application of ultrasonic energy effective to disrupt the pathogen and to release pathogen-identifying material into the solution.
- a schematic illustration representing elements of an embodiment of a system comprising devices having a sonicator is shown in Fig. 1
- a tip portion of a sonicator of a device of a system as disclosed herein be configured to improve the transfer of ultrasonic energy to a sample solution, or to provide better contact between the sonicator and a vessel containing a sample solution, or both.
- a sonicator of a device of a system as disclosed herein may have a sonicator horn; such a sonicator horn may have a tip portion, which may be configured to improve the transfer of ultrasonic energy to a sample solution, or to provide better contact between a sonicator and a vessel containing a sample solution, or both.
- FIG. 1 provides an illustration of several components of an examplary system as disclosed herein.
- a system 10 may include a controller 12; a power supply 16; a sonicator 18 (having a sonicator horn 20, with a tip portion 21); a sample handling system 14; a vessel DEVICES, SYSTEMS AND METHODS FOR SAMPLE PREPARATION
- a communication assembly 32 may be in communication with external devices, or with a user, or with a laboratory, or with a network (e.g., a computer network, such as a local area network, a wide area network, the cloud, etc.), or other communication destination.
- a network e.g., a computer network, such as a local area network, a wide area network, the cloud, etc.
- a device of a system 10 as disclosed herein may comprise a sample handling system 14 configured to place a sample within a vessel 22, by, for example, delivering at least a portion of a sample to a vessel 22 and depositing the at least a portion into a chamber of the vessel 22.
- a sample handling system 14 may also be configured to place a reagent, or other agent or material, within a vessel 22, by, for example, delivering the reagent, other agent, or material, to a vessel and depositing it into a chamber of the vessel.
- a device of a system 10 as disclosed herein may comprise a detector 30 for detecting pathogen-identifying material from a sample.
- a detector 30 may be any detector effective to detect the presence of pathogen-identifying material in a sample. Such detection may be aided by use of a label or other readily detectable agent, which may be used in conjunction with a reagent that specifically binds to, or reacts with, a pathogen-identifying material.
- a system 10 as disclosed herein may comprise a controller 12 to operate the components of the system.
- a device of a system 10 as disclosed herein may comprise a controller 12 to operate components of the device.
- a controller 12 may comprise a processor, or other component, device, or element effective to oversee and control the operation of a device.
- a controller may further comprise communication components, devices, or elements effective to provide communication with and between the controller 12 and other components and elements of the device or system. Such internal communication linkages are illustrated in Fig. 1 by dotted lines.
- these internal communication linkages include a quick release connection 28, allowing easy and rapid connection and disconnection of these linkages; for example, such a linkage (e.g., a quick release connection 28) may be useful in quickly adding, or quickly removing, a sonicator 18 from a device, or for quickly swapping one sonicator 18 for another sonicator 18 in a device.
- a linkage e.g., a quick release connection 28
- such a quick release connection may be useful in "hot swapping" of a sonicator 18 (connecting a sonicator, removing a sonicator, or replacing one sonicator by another sonicator during use of the sonicator or of other components, or without requirement that the remainder of the device or system be shut down for such DEVICES, SYSTEMS AND METHODS FOR SAMPLE PREPARATION
- linkages may be direct connections lacking a quick release connection 28, or may have other, less-readily disconnected, linkages. It will be understood that, in embodiments of the present devices and systems, other communication linkages may also be provided.
- a system 10 as disclosed herein may comprise a
- a device of a system 10 as disclosed herein may comprise a communication assembly 32, which may comprise one or more communications link(s).
- a device of a system 10 as disclosed herein may comprise a communication assembly 32, which may comprise one or more communications link(s).
- communication assembly may comprise a display, for receiving instructions and information, and for providing information and data to a user, or to other components or equipment (illustrated by the element numbered 34, which may represent one or more of, e.g., a user, another device, a laboratory, a network, the cloud, or other communication destination).
- such a communication assembly 32 may comprise a one-way communication link (e.g., from the device or system to an element 34, which may comprise a user, another device, a laboratory, a network, the cloud, or other communication destination; or to the device or system from an element 34 which may comprise a user, another device, a laboratory, a network, the cloud, or other communication source) and, in embodiments, may include a two-way (or multiple-way) communication link(s), e.g., between the device or system and a user, another device, a laboratory, a network, the cloud, or other communication targets., as represented by element 34.
- Such communication links with communication destinations or sources are indicated by the dotted arrows in the figure.
- a device or system 10 as disclosed herein may comprise a power supply 16 to enable the operation of the components.
- Power connections are illustrated in Fig. 1 by solid lines. It will be understood that, in embodiments of the present devices and systems, other power connections may also be provided.
- the power connection to the sonicator 18 includes a quick release connection 28, allowing easy and rapid connection and disconnection of that connection.
- a quick release connection 28 may be useful in quickly adding, or quickly removing, a sonicator 18 from a device, or for quickly replacing a sonicator 18 in a device.
- Fig. 2 may provide an illustration of an embodiment in which a distal portion of the sonicator 40 (e.g., the tip 44 of the sonicator horn 42, shown within vessel 46), termed in this example the "tip" 44, contacts a sample solution in a vessel 46.
- the tip 44 contacts the sample solution.
- Direct contact with the sample solution provides for direct transfer of energy from the sonicator 40 to the sample solution.
- such direct contact requires that the tip 44 touch or enter into the sample solution, providing a possible source of contamination of the sample (and subsequent samples) and requiring cleaning steps and/or coating of the tip 44 to reduce such
- Fig. 2 may also provide an illustration of an embodiment in which the tip 44 is separated from the sample solution by a compliant barrier (such a compliant barrier conforms, to a greater or lesser degree, to the outline of the tip 44 as the tip 44 is pressed into DEVICES, SYSTEMS AND METHODS FOR SAMPLE PREPARATION
- FIG. 3 An alternative embodiment is shown in Fig. 3, showing a sonicator 50 having a sonicator horn 52 and sonicator tip 54 in contact with a vessel 56 having a flat face 58 on a wall of the vessel 56.
- Fig. 3 shows an example in which a distal portion of the sonicator 50 contacts a flat face 58 of the vessel 56 holding a sample solution; flat face 58 is configured to be complementary to sonicator tip 54 for efficient energy transfer between the sonicator and the vessel and its contents.
- no portion of the sonicator 50 contacts the sample solution, preventing contamination of the sample and of the sonicator 50, so that there is no requirement to clean or condition the sonicator tip 54 before its re-use.
- a wall 58 of a vessel which may be more rigid, and less compliant than a compliant barrier, may be more efficient at transferring ultrasonic energy from a tip 54 to a solution than a compliant barrier; for example, a rigid wall may absorb less energy than would be absorbed by a compliant barrier.
- sonicator 50 Although the contact between sonicator 50 and sample solution is indirect in embodiments comprising the configuration illustrated in Fig. 3, ample ultrasonic energy is transferred via the wall of a vessel 56 into a sample solution contained therein, and cells, including pathogen cells, may be, and have been, disrupted in this way. Ultrasonic energy transfer from sonicator 50 to sample solution is improved in this configuration by providing a flat surface 58 on a wall of the vessel 56, as disclosed herein, which is complementary to a flat surface on the sonicator tip 54. Transmission of ultrasonic energy in the configuration illustrated in Fig. 3 is improved by tight contact between a sonicator tip 54 and a wall of a vessel 56. Application of force between a wall of a vessel 56 (particularly a flat face 58 of a vessel 56) and the sonicator tip 54 is also helpful to provide effective ultrasonic energy transfer from sonicator 50 to sample solution.
- a contact force of between about 2 N to about 10 N, or between about 2 N to 6 N, or between about 3 N to about 5 N, or about 4 N is useful for providing effective transfer of ultrasonic energy for disruption of pathogens by contacting a wall of a vessel containing a sample solution.
- preferred vessel materials for ultrasonic energy transfer through a vessel wall include polystyrene, polycarbonate, and polyethylene.
- Polystyrene was found to be a better material than polycarbonate and polyethylene; polycarbonate was found to be a better material than polyethylene.
- Ultrasonic disruption of pathogens may be performed with varying frequencies of ultrasonic energy. Higher frequencies allow for shorter sonicator horns;
- ultrasonic frequencies suitable for use in devices, systems and methods disclosed herein include ultrasonic frequencies of from about 20 kHz to about 60 kHz, or from about 20 kHz to about 50 kHz, or from about 20 kHz to about 40 kHz.
- suitable ultrasonic frequencies include frequencies of about 20 kHz, about 25 kHz, about 28 kHz, about 30 kHz, about 35 kHz, about 40 kHz, about 45 kHz, about 50 kHz, about 55 kHz, and about 60 kHz.
- a sonicator may include or have attached to it multiple elements.
- Fig. 4 shows an example of an embodiment of a sonicator 60 having a transducer 62, a motor 64, a drawbar 66, a horn 68, and a collet 70.
- a motor 64 may be effective to move (e.g., rotate) a drawbar 66 connected to a collet 70 at the tip of the sonicator 60.
- a motor 64 may be effective to move (e.g., rotate) a drawbar 66 connected to a collet 70 at the tip of the sonicator 60.
- such a sonicator 60 may have a hollow sonicator horn 68; in the embodiment shown, the hollow sonicator horn 68 encloses, and allows passage of, a drawbar 66 which provides functional connection between a collet 70 at the distal end of the sonicator 60 and transducer 62 (and thus with the sonicator body as well).
- a drawbar 66 such as the drawbar 66 shown in DEVICES, SYSTEMS AND METHODS FOR SAMPLE PREPARATION
- a sonicator 60 having such a horn 68 and drawbar 66 may be configured to transfer ultrasonic energy from its proximal end (shown here adjacent the motor 64, near the transducer 62) to its distal end (adjacent the collet 70).
- a collet 70 such as the collet 70 shown in the figure may be configured to mate with and hold a vessel effective to provide ultrasonic energy to a sample within a vessel.
- a sonicator 60 having such components at its tip may be configured to transfer ultrasonic energy to a sample solution, and in embodiments, may be configured to transfer ultrasonic energy to a sample solution via a vessel wall.
- a vessel When a vessel is in place within the vessel holder 112, activation of the solenoid 120 and the resulting movement presses the tip of the sonicator horn 104 into contact with a side wall of the vessel.
- the action of the solenoid 120 generates a force at the area of contact between the tip of the sonicator horn 104 and the vessel wall.
- a force may be, for example, between about 2 N and about 10 N, or between about 2 N and about 6 N, or preferably between about 3 N and about 5 N, or, in embodiments, about 4 N of force.
- a vessel holder 1 12 may have a further aperture 1 16 in a vessel holder wall 1 18, allowing access to another portion of the vessel, and including optical access without possible interference by the vessel holder 1 12.
- a vessel holder 112 may have walls 1 18 without apertures; such walls 118 may be configured for optical access as well, by construction using suitable materials; by providing a wall of proper flatness, orientation, or thickness of the wall; by proper preparation or construction of the wall surface, or by other means.
- a power connection 1 10 to a sonicator 102 may also serve as a control connection (or one of the control connections) that controls the frequency, cycling, or other aspects of sonicator operation. Note also that a DEVICES, SYSTEMS AND METHODS FOR SAMPLE PREPARATION
- control/power connection 1 10 to the sonicator 102 may include a quick release connection 108 (as illustrated in Fig. 5), allowing easy and rapid connection and disconnection of that connection; for example, such a quick release connection 108 may be useful in adding, removing, or replacing a sonicator 102. In embodiments, such a quick release connection may be useful in "hot swapping" of a sonicator 102. In embodiments, such a control/power connection 110 may be a direct connection lacking a quick release, or may have other, less- readily disconnected, linkages.
- FIG. 6 provides further illustration of a sonicator assembly 100, and the design and operation of a movable sonicator 102 operably connected to a solenoid 120 for moving a sonicator horn 104 and its tip into functional contact with a wall of a vessel containing a sample solution.
- Figs. 6A and 6B present a side view of an embodiment of a sonicator 102 mounted and operably connected with a solenoid 120 that is configured to move the sonicator horn 104 in a transverse direction. In Fig. 6A, the solenoid is not activated.
- Fig. 6 the solenoid is not activated.
- FIG. 6A shows a side view of an embodiment of a sonicator 102 mounted with a solenoid 120 configured to move the sonicator horn 104 in a transverse direction (e.g., leftwardly or rightwardly as shown in the figure).
- the oval encloses an area of interest, in which the tip of the sonicator horn 104 moves to and contacts a vessel wall when a vessel is in place within the vessel holder.
- a spring 126 is provided to urge the sonicator 102 away from the vessel holder 1 12 upon release of solenoid force drawing the sonicator 102 towards the vessel holder 1 12.
- the sonicator horn 104 is disposed so as to approach a vessel held within the vessel holder 1 12 when the sonicator 102 is moved to the right in the figure. At rest (with the solenoid 126 off), as shown in Fig. 6A, the sonicator horn 104 does not contact a vessel held within the vessel holder 1 12, and the spring 126 is in an extended conformation.
- the solenoid 120 is activated in Fig. 6B, the sonicator horn 104 is in contact with an outer wall of a vessel held within the vessel holder 1 12, and the spring 126 is in a compressed conformation. Operation of the sonicator 102 in this configuration, in which the sonicator horn 104 is in contact with a wall of a vessel held within the vessel holder 112, is effective to provide ultrasonic energy to a sample solution within the vessel.
- Transfer of ultrasonic energy is improved by providing a firm contact between the tip of the sonicator horn 104 and the vessel wall; as discussed above, ultrasonic energy transfer is improved by providing transverse force (towards the vessel wall) of between about 2 N and about 10 N, or between about 2 N and about 6 N, or about 3N to about 5N, or about 4 N of force.
- transverse force towards the vessel wall
- Providing sufficient ultrasonic energy for a sufficient amount of time is effective to disrupt cells within the sample solution; in particular, pathogen cells within the sample solution may be DEVICES, SYSTEMS AND METHODS FOR SAMPLE PREPARATION
- Fig. 7 provides a further, more detailed illustration of contact between the tip of sonicator horn 104 and a vessel wall. Also shown are sonicator mount 106, spring 126, base 125 with attachment mechanism 122, and a clamp 128 for securing a sonicator 102 to a sonicator mount 106.
- the vessel 130 is held in the vessel holder 112; in this example, the vessel 130 has a vessel cap 132.
- a vessel 130 may be filled with a sample solution prior to placement of the vessel cap 132.
- a vessel 130 may be filled with sample solution through a vessel cap 132, e.g., by a conduit through the vessel cap 132.
- Such a conduit may be temporary (e.g., may be provided by a hollow needle piercing the cap 132, where the path of the needle may reseal following removal of the needle from the cap 132).
- Such a conduit may be permanent, e.g., may be a channel or tube that is a permanent feature of the vessel cap 132.
- such a conduit may itself be capped.
- the vessel 130 may be filled by the sample handling system.
- the cap 132 may be placed on the vessel 130 by the sample handling system following filling of the vessel 130.
- the cap 132 may be removed by the sample handling system; for example, in embodiments, the cap 132 may be removed by the sample handling system prior to filling the vessel 130 with sample solution.
- a cap 132 as shown in Fig. 7 may be effective to prevent loss of sample fluid during sonication, and to prevent spread of sample contents (by spillage, aerosolization, or other means) outside the vessel.
- a vessel 130 is shown held in a vessel holder 112, and a sonicator horn 104 is shown in contact with a side wall of the vessel 130.
- Such a configuration is an operative configuration effective to disrupt cells within the sample solution, such as pathogen cells within the sample solution.
- FIG. 8 A schematic illustration of a device 200 (enclosed by a device housing 202) having a sonicator 204 and other features as disclosed herein is provided in Fig. 8.
- the device illustrated by the figure has a sonicator 204 with a sonicator horn 208, which can be made to contact a wall of a vessel 212 (e.g., by motion of a movable sonicator mount 206, as indicated in Figs. 6A, 6B, and 7).
- the vessel 212 can contain a sample solution, and is configured to be held by a vessel holder 210.
- the vessel 212 shown in Fig. 8 has a vessel cap 214.
- the amount of energy provided by a sonicator 204 may depend on the ultrasonic frequency of the ultrasonic energy applied.
- the amount of energy provided by a sonicator 204 may depend on the amplitude of the displacement produced by the ultrasonic energy.
- the amount of energy provided by a sonicator 204 may depend on the duration of the application of the ultrasonic energy.
- the amount of energy provided may depend on the contact force applied by the sonicator 204 to the vessel 212.
- the amount of energy provided by a sonicator 204 may depend on the area of contact between a sonicator 204 and a vessel 212.
- the duration of power applied to a solution may differ depending on the use of the sonicator; for example, the duration of application of ultrasonic power used to heat a solution will depend on the initial temperature of the solution, and the desired final temperature.
- the shape of the control signal sent to an ultrasonic transducer affects the power applied to a solution, and some shapes may be more effective than others depending on the use of the sonicator.
- the operation of the multiplexer 304 selection may be according to a set pattern or frequency, or may be controlled, for example, by a controller as shown in Fig. 1, or may be controlled by other means.
- 2, 3, 4, 5, 6, 7, 8, 9, 10, or more sonicators may be configured in this way, and may be controlled in this way.
- a single sonicator may contact a plurality of vessels.
- the vessels may be disposed in an array of vessels.
- An array of vessels may be a linear array, in which a sonicator may move along the array and contact vessels sequentially.
- An array of vessels may be circular, or semicircular array, in which a sonicator rotates around an axis effective to position the sonicator tip for contact with vessels disposed in such a circular or semicircular array.
- An array of vessels may comprise a combination of linear and curved arrays, may have an irregular shape, or vessesl may be disposed in any shaped array suitable for contact with a sonicator tip.
- multiple sonicators may contact a plurality of vessels, e.g., with a first sonicator contacting a first vessel, a second sonicator contacting a second vessel, and so forth.
- the vessels may be disposed in an array of vessels.
- the sonicators may be disposed in an array of sonicators.
- An array of sonicators, an array of vessels, and both arrays may be a linear array, may be a curved array, may be a combination of such arrays, may be an irregular array, and may be any shaped array suitable for contact between a sonicator tip and a vessel.
- FIG. 10 An embodiment of a vessel suitable for containing a sample solution for sonication is shown in several views in Fig. 10.
- a side view of a vessel 502 having mating sockets 504, with a flat wall surface 510 facing outward, a flat bottom 506, and an opening 508 (for filling the vessel) shown at the top is provided in Fig. 10A.
- a side view with a flat wall surface 510 facing rightward is shown in Fig. 10B while Fig. IOC shows an angled view of the vessel 502.
- Fig. 10D shows a cross-sectional view of a vessel 502.
- the vessel 502 of this embodiment has a flat side wall 510 and a flat bottom 506; both the flat side wall 510 and the flat bottom 506 are configured to make effective contact with a tip portion of a sonicator, such as a tip of a sonicator horn to provide for transfer of ultrasonic energy from the sonicator to a sample solution within the vessel.
- a sonicator such as a tip of a sonicator horn
- the wider portion at the top of the vessel includes surfaces and mating sockets 504.
- the mating sockets 504 comprise recesses configured for engagement of a transport and/or force-providing member (e.g., a nozzle of a sample handling system) which a) allows transport of the vessel 502 and b) provides a surface for provision of downward force to oppose upward force of a sonicator horn placed on a flat bottom surface 506 of the vessel. Openings of the mating sockets 504 are visible in this view, as is an inner ridge 514 within the internal chamber 512 of the vessel.
- a transport and/or force-providing member e.g., a nozzle of a sample handling system
- mating sockets 504 may be configured to mate with a mechanical component configured to transport a vessel, or to apply force to a vessel, or both.
- a mechanical component may be, or may comprise, a sample handling system.
- such a mechanical component may comprise a pipette, a nozzle, or other mechanical component.
- Fig. 1 1 provides further embodiments of vessels suitable for containing a sample solution for sonication.
- Embodiments of vessels 602 with caps 604 shown in Fig. 1 1 have rounded bottoms 606, which are believed to be more suitable for mixing, re-suspension, and other applications in which a sonicator is applied to a wall of a vessel.
- Figs. 1 1A, 11C, and 1 ID show embodiments of tubular vessels with rounded bottoms 606.
- Fig. 1 IB shows an embodiment of a conical vessel 602 with a rounded bottom 606.
- Fig. 1 1C an embodiment of an elongated tubular vessel 602 with a rounded bottom 606.
- FIG. 12C shows an embodiment of an elongated tubular vessel 602 with a rounded bottom 606 and a protruding flat surface 608 configured to engage with a sonicator tip. It will be understood that, in embodiments, an elongated tubular vessel 602 with a rounded bottom 606 may have two, three, or more protruding flat surfaces 608 configured to engage with a sonicator tip. DEVICES, SYSTEMS AND METHODS FOR SAMPLE PREPARATION
- Fig. 12D shows an embodiment of a wide tubular vessel 602 with a rounded bottom 606 having a cap 604 connected to the vessel via cap linkage 612.
- a cap 604 may be removable, yet remain linked to the remainder of the vessel 602.
- a cap linkage 612 may comprise a hinge, a tab, a thread, a perforated tab, or any element effective to connect the cap 604 with the body of the vessel 602 and allow the opening and closing of the vessel 602 by movement of the cap 604.
- a vessel 816 having a flat bottom 824 may be contacted as illustrated by a tip 822 of a sonicator 802. Such contact is effective to transfer ultrasonic energy to the wall (i.e., flat bottom 824) of the vessel 816 and thereby to a sample solution contained within the vessel 816, effective to disrupt cells in the sample solution.
- a sonicator tip 822 may contact a wall of a vessel 816, such as a lower wall 824 as illustrated in Fig. 13, while the vessel 816 is held in a vessel holder.
- a vessel 816 held in a vessel holder may be in contact with no other components that provide restraint or retaining forces.
- force 820 urging contact between a sonicator tip 822 and a wall of a vessel 816 may be provided by one or more of a solenoid, a spring, a sample handling system, or other means.
- a power/control connection 808 to a sonicator 802 may serve both as a power connection and as a control connection (or one of the control connections) that control the frequency, cycling, or other aspects of sonicator 802 operation.
- a control/power connection 808 to the sonicator 802 may include a quick release connection 810.
- such a control/power connection 808 may be a direct connection lacking a quick release, or may have other, less- readily disconnected, linkages.
- Detection Limit indicates the lower limit for detection of pathogen nucleic acids.
- the cycle number at which a trace passes this threshold is the "cycle threshold” or "Ct" number; a target is considered detected when the results pass the threshold.
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- Investigating Or Analysing Biological Materials (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Sampling And Sample Adjustment (AREA)
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Abstract
Description
Claims
Priority Applications (15)
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EP14768967.3A EP2972310A4 (en) | 2013-03-15 | 2014-03-10 | Devices, systems and methods for sample preparation |
CN201480027228.8A CN105229465A (en) | 2013-03-15 | 2014-03-10 | For device, the system and method for sample preparation |
EP21181603.8A EP3974842A1 (en) | 2013-03-15 | 2014-03-10 | Devices, systems and methods for sample preparation |
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MX2015011773A MX348826B (en) | 2013-03-15 | 2014-03-10 | Devices, systems and methods for sample preparation. |
BR112015022167A BR112015022167A2 (en) | 2013-03-15 | 2014-03-10 | sample preparation devices, systems and methods |
SG11201507322UA SG11201507322UA (en) | 2013-03-15 | 2014-03-10 | Devices, systems and methods for sample preparation |
CA2906484A CA2906484A1 (en) | 2013-03-15 | 2014-03-10 | Devices, systems and methods for sample preparation |
KR1020157027838A KR20150130387A (en) | 2013-03-15 | 2014-03-10 | Devices, systems and methods for sample preparation |
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IL241429A IL241429A (en) | 2013-03-15 | 2015-09-10 | Devices, systems and methods for sample preparation |
HK16107548.4A HK1219535A1 (en) | 2013-03-15 | 2016-06-28 | Devices, systems and methods for sample preparation |
US15/865,004 US20180224472A1 (en) | 2013-03-15 | 2018-01-08 | Devices, systems and methods for sample preparation |
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US10316346B2 (en) | 2014-09-26 | 2019-06-11 | TB Healthcare Co., Ltd. | Method and apparatus for dispersion of microbes in a liquid suspension |
WO2016189259A1 (en) * | 2015-05-28 | 2016-12-01 | bioMérieux | Device for the preparation of biological samples and use thereof |
FR3036799A1 (en) * | 2015-05-28 | 2016-12-02 | Biomerieux Sa | DEVICE FOR THE PREPARATION OF BIOLOGICAL SAMPLES |
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MX2015011773A (en) | 2016-07-20 |
KR20150130387A (en) | 2015-11-23 |
IL241429A0 (en) | 2015-11-30 |
HK1219535A1 (en) | 2017-04-07 |
JP2019095457A (en) | 2019-06-20 |
EP2972310A4 (en) | 2016-12-07 |
BR112015022167A2 (en) | 2017-07-18 |
US20160069916A1 (en) | 2016-03-10 |
CN105229465A (en) | 2016-01-06 |
EP3974842A1 (en) | 2022-03-30 |
SG11201507322UA (en) | 2015-10-29 |
JP2021073445A (en) | 2021-05-13 |
US20180224472A1 (en) | 2018-08-09 |
MX348826B (en) | 2017-06-30 |
CA2906484A1 (en) | 2014-09-25 |
AU2014237362A1 (en) | 2015-09-17 |
US9885729B2 (en) | 2018-02-06 |
IL241429A (en) | 2017-02-28 |
EP2972310A1 (en) | 2016-01-20 |
JP2016517516A (en) | 2016-06-16 |
MX368673B (en) | 2019-10-10 |
CN111366434A (en) | 2020-07-03 |
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