WO2022139819A1 - Lavage de microparticules de magnétisation dans une colonne de densité fluidique - Google Patents

Lavage de microparticules de magnétisation dans une colonne de densité fluidique Download PDF

Info

Publication number
WO2022139819A1
WO2022139819A1 PCT/US2020/066640 US2020066640W WO2022139819A1 WO 2022139819 A1 WO2022139819 A1 WO 2022139819A1 US 2020066640 W US2020066640 W US 2020066640W WO 2022139819 A1 WO2022139819 A1 WO 2022139819A1
Authority
WO
WIPO (PCT)
Prior art keywords
fluid density
magnetic
microparticles
magnetizing
density column
Prior art date
Application number
PCT/US2020/066640
Other languages
English (en)
Inventor
Keith William Joseph JARIABKA
Michelle Forshager ELLIS
Tod S. WOODFORD
Jody Lee CLAYBURN
Dawn M. Beachnau Hood
Sheldon A. BERNARD
Original Assignee
Hp Health Solutions Inc.
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 Hp Health Solutions Inc. filed Critical Hp Health Solutions Inc.
Priority to PCT/US2020/066640 priority Critical patent/WO2022139819A1/fr
Publication of WO2022139819A1 publication Critical patent/WO2022139819A1/fr

Links

Classifications

    • 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
    • G01N35/0098—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1003—Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor
    • C12N15/1006—Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor by means of a solid support carrier, e.g. particles, polymers
    • C12N15/1013—Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor by means of a solid support carrier, e.g. particles, polymers by using magnetic beads
    • 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
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
    • G01N33/54326—Magnetic particles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C1/00—Magnetic separation
    • B03C1/005—Pretreatment specially adapted for magnetic separation
    • B03C1/01—Pretreatment specially adapted for magnetic separation by addition of magnetic adjuvants
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C1/00—Magnetic separation
    • B03C1/02—Magnetic separation acting directly on the substance being separated
    • B03C1/28—Magnetic plugs and dipsticks
    • B03C1/288—Magnetic plugs and dipsticks disposed at the outer circumference of a recipient
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C2201/00—Details of magnetic or electrostatic separation
    • B03C2201/18—Magnetic separation whereby the particles are suspended in a liquid
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C2201/00—Details of magnetic or electrostatic separation
    • B03C2201/26—Details of magnetic or electrostatic separation for use in medical or biological applications
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M47/00—Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
    • C12M47/04—Cell isolation or sorting
    • 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
    • G01N1/34—Purifying; Cleaning
    • 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
    • G01N2035/00564—Handling or washing solid phase elements, e.g. beads

Definitions

  • Washing magnetizing microparticles in a fluid density column is important to remove contaminants.
  • Figure 1 is a block diagram of an example device to wash and/or move magnetizing microparticles in a fluid density column.
  • Figure 2A shows the example device of Figure 1 with a carriage holding a sample container that includes a fluid density column.
  • Figure 2B shows a perspective view of further details of the example device of Figure 1 with a carriage holding a cassette that includes a sample container, which includes a fluid density column.
  • Figure 3 is a perspective view of an example fluid density column showing example relative positions thereto of magnetic devices of the example device of Figure 1.
  • Figure 4 shows a top view of relative positions of the magnetic devices of the example device of Figure 1 to the fluid density column of Figure 3, with the fluid density column in cross-section through a plane parallel to the magnetic devices.
  • Figure 5 and Figure 6 show a sequence to wash and/or move magnetizing microparticles in a fluid density column.
  • Figure 7 show different path geometries for magnetizing microparticles that may be implemented in the example device of Figure 1 .
  • Figure 8A is a perspective view of an example sample preparation device that incorporates the device of Figure 1A.
  • Figure 8B is a block diagram of the device of Figure 8A.
  • Figure 8C is a block diagram of the device of Figure 8A with a carriage in a magnetizing microparticle washing position.
  • Figure 9 is a flow diagram of a method to wash and/or move magnetizing microparticles.
  • a biological component can be intermixed with other components in a biological sample that can interfere with subsequent analysis.
  • biological component can refer to materials of various types, including proteins, cells, cell nuclei, nucleic acids, bacteria, viruses, or the like, that can be present in a biological sample.
  • a “biological sample” can refer to a fluid or a dried or lyophilized material obtained for analysis from a living or deceased organism. Isolating the biological component from other components of the biological sample can permit subsequent analysis without interference and can increase an accuracy of the subsequent analysis.
  • Isolation can also be referred to as “purification”, whereby biological component may be separated from the rest of the biological sample after introduction to a sample preparation cartridge module interchangeably referred to hereafter as a sample container, a sample dispensing container, a cartridge module, and the like. It will be understood that the isolated biological component may be output in association with (e.g., bound to) particulate substrate and a reagent solution, or the like.
  • isolation or purification refers to the separation of the biological component from other components of the biological sample with which it was originally introduced in the cartridge module, but it does not mean that the biological component is completely isolated when it is dispensed.
  • isolation refers to the fact that the biological component is sufficiently separated or “purified” from other components of the original biological sample to facilitate further processing such as detection and/or amplification.
  • isolation techniques can include repeatedly dispersing and reaggregating samples.
  • the repeated dispersing and re-aggregating can result in a loss of a quantity of the biological component.
  • isolating a biological component with some of these techniques can be complex, time consuming, and labor intensive and can result in less than maximum yields of the isolated biological component.
  • Such Isolation techniques are done using specific devices.
  • Obtaining precise biological sample preparation devices can be challenging due to many moving parts present in the devices, for example to move a carriage holding a cartridge of sample dispensing containers relative to sample receiving wells.
  • the cartridge may hold a plurality of the sample dispensing containers or sample preparation devices or sample preparation cartridge modules which contain different respective biological samples.
  • sample dispensing containers or sample preparation devices or sample preparation cartridge modules may heat the samples to perform for example, lysis on cells in the biological samples to release biological component of interest, coming from the biological sample, may be a nucleic acid (such as DNA or RNA).
  • Resulting sample fluid may be drawn through a fluid density gradient in the sample dispensing containers and dispensed into sample receiving wells, which may be transferred to further analytical assay such as, for example, a Polymerase Chain Reaction (PCR).
  • PCR Polymerase Chain Reaction
  • initial quantities of the biological component of interest present in the biological sample may be small, precise dispensing of the component of interest from the sample dispensing containers into the sample receiving wells should occur so as to not lose any content and/or to prevent cross-contamination between samples.
  • a precise determination of a position of a shuttle and/or well carriage, that holds the sample receiving wells, relative to the carriage is important, and vice versa.
  • the device of the present disclosure is a device that can be used to prepare sample to be used in a process of preparing samples for a PCR (polymerase chain reaction) assay.
  • PCR assays are processes that can rapidly copy millions to billions of copies of a very small DNA or RNA sample.
  • PCR can be used for many different application, included sequencing genes, diagnosing viruses, identifying cancers, and others.
  • sequencing genes included in the PCR process, a small sample of DNA or RNA is combined with reactants that can form copies of the DNA or RNA.
  • the biological sample comprises a biological component.
  • the biological component of interest coming from the biological sample, may be a nucleic acid (such as DNA or RNA).
  • a particulate substrate can be configured to be associated with the biological component, to isolate the biological component from the biological sample.
  • the particulate substrate comprises paramagnetic beads and/or any magnetizing particle and/or magnetizing microparticles.
  • the biological component comprises nucleic acids such as DNA and/or RNA that may be extracted from the biological sample by lysing, bound to magnetic particulate substrate, and separated from the lysate and dragged towards an output by an externally generated (para)magnetic force.
  • Lysate may refer to the fluid containing the material resulting from the lysis of a biological sample. Such lysis may release the biological component that is contained therein. Lysing itself may include mixing and/or heating the biological sample, chemically lysing the biological sample, and/or a combination of the foregoing.
  • a biological component of interest, bonded to magnetizing microparticles may be dragged towards an output via a fluid density column to wash and/or move the magnetizing microparticles to isolate and/or purify a biological component of interest to remove contaminants.
  • a device that includes a carriage to hold a sample preparation cartridge module that includes a fluid density column with magnetizing microparticles therein, and magnetic devices that may be used to alternately apply respective magnetic fields at opposite sides of the fluid density column, after the carriage is moved to, and pauses at, given positions. Magnetic fields of the magnetic devices may then drag and/or move the magnetizing microparticles, with a biological component of interest bonded thereto in different path geometries, from side-to-side, through the fluid density column.
  • path geometries may include a zig-zag pattern which may be used to maximize a path of the magnetizing microparticles through the fluid density column.
  • a first aspect of the present specification provides a device comprising: a carriage to hold a sample container that includes a fluid density column and magnetizing microparticles therein; and magnetic devices to alternate applying magnetic fields at opposite sides of the fluid density column to move the magnetizing microparticles between the opposite sides of the fluid density column to move the magnetizing microparticles in the fluid density column, the magnetic devices being controllable to apply the magnetic fields independent of each other to control a path geometry of the magnetizing microparticles in the fluid density column.
  • the magnetic devices may be further to remove the magnetic fields the opposite sides of the fluid density column, and the carriage is further to move along a path, relative to the magnetic devices, while the magnetic fields are removed, to further control the path geometry of the magnetizing microparticles in the fluid density column into a zigzag pattern.
  • the magnetic devices may be further to pause applying the magnetic fields to the opposite sides of the fluid density column to further control the path geometry of the magnetizing microparticles in the fluid density column.
  • the magnetic devices may be further to pause applying the magnetic fields to the opposite sides of the fluid density column to further control the path geometry of the magnetizing microparticles in the fluid density column, and timing of the pause is controllable.
  • the carriage may be to move along a path, and a step size of the carriage along the path is controllable to further control the path geometry of the magnetizing microparticles in the fluid density column.
  • a second aspect of the present specification provides a device comprising: a carriage to hold a sample container that includes a fluid density column and magnetizing microparticles therein, the carriage to move along a path; and magnetic devices to move perpendicular to the path of the carriage, to alternate applying magnetic fields at opposite sides of the fluid density column to move the magnetizing microparticles between the opposite sides of the fluid density column to move the magnetizing microparticles in the fluid density column, positions of the magnetic devices being coordinated with a position of the carriage to control a path geometry of the magnetizing microparticles in the fluid density column into a zigzag pattern.
  • the magnetic devices may be further to pause when applying a magnetic field to one side of the fluid density column to shape the zigzag pattern of the path geometry.
  • the magnetic devices may be further to pause for different times, depending on a position of the carriage, when applying a magnetic field to one side of the fluid density column to shape the zigzag pattern of the path geometry.
  • a position of the carriage may be adjusted according to a step size or step sizes to shape the zigzag pattern of the path geometry.
  • a position of the carriage may be adjusted when the magnetic devices are removed from the opposite sides of the fluid density column to remove the magnetic fields therefrom.
  • a third aspect of the present specification provides a method comprising: controlling, at a sample preparation device, a carriage to move to, and pause at, a first position, the carriage holding a sample container that includes a fluid density column and magnetizing microparticles therein; controlling, at the sample preparation device, while the carriage is paused at the first position, a first magnetic device to apply a first magnetic field to a first side of the fluid density column for a first given time period to drag the magnetizing microparticles to the first side; controlling, at the sample preparation device, the first magnetic device to remove the first magnetic field from the first side of the fluid density column; controlling, at a sample preparation device, the carriage to move to, and pause at, a second position; controlling, at the sample preparation device, while the carriage is paused at the second position, a second magnetic device to apply a second magnetic field to a second side of the fluid density column for a second given time period, the second side opposite the first side, to drag the magnetizing microparticles to the second side
  • the method of the third aspect may further comprise, prior to moving the carriage to the first position: controlling both the first magnetic device and the second magnetic device to concurrently apply the first magnetic field and the second magnetic field to the first side and the second side of the fluid density column to drag the magnetizing microparticles to the first side and the second side.
  • the method of the third aspect may further comprise: continuing to control the first magnetic device and the second magnetic device to alternately apply the first magnetic field and the second magnetic field to the first side and the second side of the fluid density column as the carriage moves to, and pauses at, different positions.
  • the first position and the second position may be dependent on their relative positions to the first magnetic device and the second magnetic device to the fluid density column.
  • length of the first given time period and the second given time period may be controllable.
  • Figure 1 and Figure 2A are block diagrams of an example device 100 to wash and/or move magnetizing microparticles in a fluid density column.
  • Figure 2B shows a perspective view of details of a particular example device 100.
  • components of the device 100 may be components of a larger device used for sample preparation of biological samples. Such a sample preparation device is described below with respect to Figure 8A, Figure 8B and Figure 8C.
  • Figure 1 shows the device 100 without a sample preparation cartridge module
  • Figure 2A shows the device 100 with a sample preparation cartridge module 102 that includes a fluid density column 104 and magnetizing microparticles 106.
  • Figure 2B shows particular details of the device 100 with the sample preparation cartridge module 102 held in a cassette 107.
  • the device 100 comprises a carriage 108 to hold the sample preparation cartridge module 102, the carriage to move along a path 110, for example via a vertical carriage guide of the sample preparation device described below. While details of the carriage 108 are not depicted in Figure 1 and Figure 2A, it is understood that the carriage 108 and/or the device 100 may include any suitable combination of features to move the carriage 108 along the path 110 such as apertures for guiderails (e.g. of a vertical carriage guide described below with respect to Figure 8B), motors and the like. In general, the carriage 108 may be to move along the path 110 to different positions as described in further detail below.
  • the carriage 108 may include any suitable combination of features to receive and hold the sample preparation cartridge module 102 which, for example, may be provided in the cassette 107 (as best seen in Figure 2B) holding as few as one sample preparation cartridge module 102 (e.g. as depicted in Figure 2B) and/or a plurality of sample preparation cartridge modules holding respective samples, which may be processed concurrently in the sample preparation device described below.
  • the carriage 108 and/or the cassette 107 may hold a plurality of sample preparation cartridge modules 102, for example by receiving the cassette 107 of sample preparation cartridge modules 102 which hold the sample preparation cartridge modules 102 in a row, about parallel to one another.
  • apertures 112 in the carriage 108 through which dispensing tips 114 of the sample preparation cartridge modules 102 may extend to dispense samples therefrom.
  • apertures 112 may be in the cassette 107, and/or may correspond to one larger aperture 113 in the cassette 107 holding the sample preparation cartridge modules 102 rather than the carriage 108 itself (e.g. which, as depicted in Figure 2B, may include a larger aperture at a side through which the dispensing tips 114 of the sample preparation cartridge modules 102 may extend as held in the cassette 107).
  • FIG. 1 and Figure 2A there are eight apertures 112, indicating that the carriage 108 and/or the cassette 107 may hold as many as eight sample preparation cartridge modules 102, though the carriage 108 and/or the cassette 107, may hold as few as one sample preparation cartridge module 102 (e.g. as depicted) and/or a number of sample preparation cartridge modules 102 different from eight.
  • the device 100 may be adapted to process samples in any suitable number of sample preparation cartridge modules 102.
  • the device 100 further comprises magnetic devices 116-1 , 116-2 which are interchangeably referred to hereafter, collectively, as the magnetic devices 116 and, generically, as a magnetic device 116.
  • the magnetic devices 116 may move relative to the path 110 of the carriage 108, for example about perpendicular to the path 110 of the carriage 108, along respective paths 118-1 , 118-2 (e.g. paths 118 and/or a path 118).
  • the paths 118 are about parallel to one another, the magnetic devices 116 may move along any suitable paths to effect functionality as described herein.
  • the magnetic devices 116 may be mounted on robotic arms and/or actuators, and the like, which may be controlled to position the magnetic devices 116 as described herein.
  • the magnetic devices 116 are generally to alternate applying magnetic fields at opposite sides 120-1 , 120-2 (e.g. sides 120 and/or a side 120) of the fluid density column 104 to move the magnetizing microparticles 106 between the opposite sides of the fluid density column 104 to wash and/or move the magnetizing microparticles 106 in the fluid density column 104, the magnetic devices 116 being controllable to apply the magnetic fields independent of each other to control a path geometry (e.g. a wash path geometry) of the magnetizing microparticles 106 in the fluid density column 104, for example to wash the magnetizing microparticles 106 with a biological component of interest bonded thereto, as described below with respect to Figure 5, Figure 6 and Figure 7.
  • a path geometry e.g. a wash path geometry
  • the magnetic devices 116 may comprise electromagnetic magnetics which may be positioned at respective opposite sides 120 of the fluid density column 120 and turned on and/or turned off, independent of each other, to alternate applying magnetic to the opposite sides 120.
  • the magnetic devices 116 may comprise any suitable combination of magnets and/or permanent magnets, including, but not limited to, rare earth magnets, and the like, which may be used to apply magnetic fields to the magnetizing microparticles 106 in the fluid density column 104.
  • the magnetic devices 116 may have any suitable polarities, which may be the same, or different, relative to the sides 120.
  • the magnetic devices 116 may further comprise respective frames, and the like to hold a respective magnet at respective ends thereof (e.g. which extend towards the carriage 108) such that, when a magnetic device 116 is between adjacent fluid density columns 104, the magnets thereof are against backplanes thereof, for example as describe below with respect to Figure 4.
  • magnetic devices 116 While hereafter, functionality of the magnetic devices 116 is described with respect to moving the magnetic devices 116 along the paths 118 to alternate applying magnetic fields at the opposite sides 120, it is understood that such alternation of magnetic fields, and/or general control of the magnetic devices 116 to apply or remove magnetic fields at the opposite sides 120, alternately or currently may occur in any suitable manner.
  • the magnetic devices 116 are each depicted in two respective positions along the respective paths 118.
  • a first magnetic device 116-1 is depicted in Figure 1 and Figure 2A, in solid lines in a first position adjacent a first side 120-1 of the fluid density column 104 and in a second position in broken lines along the path 118- 1 , away from the sample preparation cartridge module 102.
  • a second magnetic device 116-2 is depicted in Figure 1 and Figure 2A, in broken lines in a respective first position adjacent a second side 120-2 of the fluid density column 104 and in a respective second position in solid lines along the path 118-2 away from the sample preparation cartridge module 102.
  • the first magnetic device 116-1 is shown at the first side 120-1 of the fluid density column 104, and the second magnetic device 116-2 is shown away from the second side 120-2 of the fluid density column 104, without showing the paths 118 and/or other positions of the magnetic devices 116
  • the paths 118 and/or other positions of the magnetic devices 116 are nonetheless understood to be similar to as depicted in Figure 1 and Figure 2A.
  • the magnetic devices 116 may hence include any suitable combination of actuators, motors, robotic arms, and the like, to move the magnetic devices 116 along the respective paths 118, for example independent from each other, towards the sample preparation cartridge module 102, and away from the sample preparation cartridge module 102, and/or to control the magnetic devices 116 to apply respective magnetic fields independent of each other.
  • the magnetic devices 116 comprise electromagnets
  • the device 100 is understood to include (and/or be powered by) any suitable combination of power supplies to independently control magnetic fields of the magnetic devices 116.
  • the carriage 108 may be moved independent of the magnetic devices 116 such that the carriage 108 and the magnetic devices 116 may be controlled to any suitable relative positions along the respective paths 110, 118.
  • the sides 120-1 , 120-2 (e.g. sides 120 and/or a side 120) of the fluid density column 104 are opposite one another, and hence the magnetic devices 116 are positioned along the paths 118 to move to the opposite sides 120 to respectively apply magnetic fields to the opposite sides 120, which may be used to control a path geometry (e.g. a wash path geometry) of the magnetizing microparticles 106 in the fluid density column 104.
  • a path geometry e.g. a wash path geometry
  • the magnetic devices 116 may be to alternate applying magnetic fields to the opposite sides 120 of the fluid density column 104 to move the magnetizing microparticles 106 between the opposite sides 120 of the fluid density column 104 to wash and/or move the magnetizing microparticles 106 in the fluid density column 104, the magnetic devices 116 being movable independent of each other and the carriage 108, to control a path geometry of the magnetizing microparticles 106 in the fluid density column 104.
  • an “XYZ” coordinate system 122 is also depicted in Figure 1 , Figure 2A, and Figure 2B, which will be used throughout the present specification to show relative positions of components of the device 100.
  • a “Z” direction may be along the path 110 of the carriage 108
  • a “Y” direction may be along the paths 118 of the magnetic devices 116 (e.g. when the paths 110, 118 are perpendicular to each other)
  • an X” direction may be perpendicular to the “Y” and “Y” directions and/or along a row of sample container positions (e.g. as indicated by the apertures 112) at the carriage 108.
  • the XYZ coordinate system 122 is provided on further figures herein to show relative orientations of the device 100, and the like, between the figures.
  • sample preparation cartridge module 102 may comprise a port for receiving a biological sample that includes a biological component of interest which may bond to the magnetizing microparticles 106.
  • the biological sample (hereafter referred to the sample) may be received into the sample preparation cartridge module 102 and heated in a region different from the fluid density column 104 to perform lysis on the sample to release a biological component of interest from cells in the sample.
  • the magnetizing microparticles 106 may initially be provided in the lysis region of the sample preparation cartridge module 102 so that the biological component of interest may bond to surfaces of the magnetizing microparticles 106.
  • the sample, with the magnetizing microparticles 106 may be moved into the fluid density column 104 for washing, and which may include introducing various chemicals into the fluid density column for example via actuation of reservoirs and/or blisters and/or pouches, and the like, at the sample preparation cartridge module 102 that include such chemicals.
  • the washing may result in isolation and/or purification of the biological component of interest bonded to the magnetizing microparticles 106.
  • the terms “wash” and/or “washing” may include, but is not limited to, a moving action of the magnetizing microparticles 106when dragged toward and/or through the fluid density column 104.
  • the terms “wash” and/or “washing” may refer to actions of elimination of components that are present in the biological sample that are not the biological component of interest (e.g. that are not bonded to the magnetizing microparticles 106).
  • sample preparation cartridge module 102 Further details of the sample preparation cartridge module 102, and associated sample processing, are described in further detail below with respect to Figure 8A, Figure 8B and Figure 8C.
  • the magnetizing microparticles 106 may be in the form of paramagnetic microparticles, superparamagnetic microparticles, diamagnetic microparticles, or a combination thereof, for example. In some examples, the magnetizing microparticles 106 are paramagnetic microparticles.
  • the term “magnetizing microparticles” or “magnetizing microparticle” is defined herein to include microparticles that may not be magnetic in nature unless and until a magnetic field is introduced at a strength and proximity to cause them to become magnetic. Their magnetic strength can be dependent on the magnetic field applied, for example by the magnetic devices 116, and may get stronger as the magnetic field is increased, or the magnetizing microparticles 106 get closer to a magnet applying the magnetic field.
  • paramagnetic microparticles have these properties, in that they have the ability to increase in magnetism when a magnetic field is present; however, paramagnetic microparticles are not magnetic when a magnetic field is not present. In some examples, the paramagnetic microparticles can exhibit no residual magnetism once the magnetic field is removed. A strength of magnetism of the paramagnetic microparticles can depend on the strength of the magnetic field, the distance between a source of the magnetic field and the paramagnetic microparticles, and a size of the paramagnetic microparticles.
  • “Superparamagnetic microparticles” can act similar to paramagnetic microparticles; however, they can exhibit magnetic susceptibility to a greater extent than paramagnetic microparticles in that the time it takes for them to become magnetized appears to be near zero seconds. “Diamagnetic microparticles,” on the other hand, can display magnetism due to a change in the orbital motion of electrons in the presence of a magnetic field.
  • the magnetizing microparticles 106 can be surface-activated to selectively bind with a biological component or can be bound to a biological component from a biological sample, for example the aforementioned viruses.
  • the device 100 may be used to process any suitable samples having any suitable biological component that may bind to the magnetizing microparticles 106.
  • an exterior of the magnetizing microparticles 106 can be surface-activated with interactive surface groups that can interact with a biological component of a biological sample or may include a covalently attached ligand.
  • the ligand can include proteins, antibodies, antigens, nucleic acid primers, nucleic acid probes, amino groups, carboxyl groups, epoxy groups, tosyl groups, sulphydryl groups, or the like.
  • the ligand can be a nucleic acid probe.
  • the ligand can be selected to correspond with and to bind with the biological component.
  • the ligand may vary based on the type of biological component targeted for isolation from the biological sample.
  • the ligand can include a nucleic acid probe when isolating a biological component that includes a nucleic acid sequence.
  • the ligand can include an antibody when isolating a biological component that includes antigen.
  • the magnetizing microparticles 106 can be surface-activated to bind to nucleic acids.
  • nucleic acid molecules DNA or RNA
  • Commercially available examples of magnetizing microparticles 106 that are surface-activated include those sold under the trade name DYNABEADS®, available from ThermoFischer Scientific (USA).
  • the magnetizing microparticles 106 can have an average particle size that can range from 10 nm to 50,000 nm. In yet other examples, the magnetizing microparticles 106 can have an average particle size that can range from 500 nm to 25,000 nm, from 10 nm to 1 ,000 nm, from 25,000 nm to 50,000 nm, or from 10 nm to 5,000 nm.
  • the term “average particle size” describes a diameter or average diameter, which may vary, depending upon the morphology of the individual particle.
  • a shape of the magnetizing microparticles 106 can be spherical, irregular spherical, rounded, semi-rounded, discoidal, angular, sub-angular, cubic, cylindrical, or any combination thereof.
  • the particles can include spherical particles, irregular spherical particles, or rounded particles.
  • the shape of the magnetizing microparticles 106 can be spherical and uniform, which can be defined herein as spherical or near- spherical, e.g., having a sphericity of >0.84. Thus, any individual particles having a sphericity of ⁇ 0.84 are considered non-spherical (irregularly shaped).
  • the particle size of the substantially spherical particle may be provided by its diameter, and the particle size of a non-spherical particle may be provided by its average diameter (e.g., the average of multiple dimensions across the particle) or by an effective diameter, e.g., the diameter of a sphere with the same mass and density as the non-spherical particle.
  • average diameter e.g., the average of multiple dimensions across the particle
  • an effective diameter e.g., the diameter of a sphere with the same mass and density as the non-spherical particle.
  • Figure 3 depicts a perspective view of a specific example fluid density column 104 of the sample preparation cartridge module 102 (e.g. similar to as depicted in Figure 2B) showing one set of example relative positions thereto of the magnetic devices 116 in one position of the carriage 108 and respective paths 118 thereof.
  • Figure 4 schematically depicts a top view of Figure 3, but with the fluid density column 104 (e.g. and a backplane thereof) depicted in cross-section through a plane parallel to the magnetic devices 116.
  • the example fluid density column 104 of Figure 3 is depicted without, for example, a lysis region or a port to receive a sample, but which are nonetheless understood to be present.
  • a sample that has undergone lysis may be introduced into the example fluid density column 104 from a lysis region, via an aperture 124 at an end of the example fluid density column 104 opposite the dispensing tip 114.
  • the fluid density column 104 becomes narrower the closer to the dispensing tip 114 (e.g. and/or the further from the aperture 124).
  • the example fluid density column 104 is understood to be held by a backplane 126, and the like, such that the sides 120 of the example fluid density column 104 extend from the backplane 126.
  • the backplane 126 and the fluid density column 104 may, for example, be provided as an integrated unit.
  • an associated sample preparation cartridge module 102 may be held by the carriage 108 such that the paths 118 of the magnetic devices 116 are on a same side of the carriage 108.
  • the sample preparation cartridge module 102 and/or the fluid density column 104, and the magnetic devices 116 may be adapted for other geometries, for example so that the magnetic devices 116 may provide the functionality as described herein, but from opposite sides of the carriage 108.
  • the magnetic devices 116, and the paths 118 are on a same side of the carriage 108
  • the first magnetic device 116-1 and the first path 118-1 may be on a first side of the carriage 108 (e.g. as depicted in Figure 1 and Figure 2A) and the second magnetic device 116-2 and the second path 118-2 may be on a second side of the carriage 108 opposite the first side.
  • the magnetic devices 116 may be longer along the paths 118 then as depicted in Figure 3 and Figure 4, but portions of the magnetic devices 116 that apply magnetic fields at the sides 120 may be smaller than an overall magnetic device 116; for example, the portions of the magnetic devices 116 depicted in Figure 3 and Figure 4 may comprise permanent magnets and/or electromagnets, with the remainder of the magnetic devices 116 comprising respective frames for holding the permanent magnets and/or the electromagnets, and attaching to an actuator, and the like.
  • the magnets of the magnetic devices 116 are positioned with opposite polarities facing each other across the fluid density column 104 therebetween; such a configuration may be more efficient for washing the magnetizing microparticles 106, as described below, and/or such a configuration may be for more efficient for collecting dispersed magnetizing microparticles 106 into clumps, as described below with respect to Figure 5.
  • the polarities may be arranged in any suitable manner. Put another way, the magnetic devices 116 may have opposing polarities across the fluid density column 104.
  • respective actuators, motors and the like, of the magnetic devices 116 may be to actuate the magnetic devices 116 to respective positions at the opposite sides 120 of the fluid density column 104, as depicted in Figure 1 , Figure 2A, Figure 2B, Figure 3 and/or Figure 4.
  • respective actuators, motors and the like, of the magnetic devices 116 may be to actuate the magnetic devices 116 towards the carriage 108 until respective motors thereof stall due the magnetic devices 116 encountering the backplane 126.
  • Figure 5 and Figure 6 depict a block diagram of the fluid density column 104 and the magnetic devices 116 to show a sequence of steps “A”, “B”, “C”, “D”, “E”, “F”, “G” to wash and/or move the magnetizing microparticles 106 in the fluid density column 104 to isolate and/or purify biological components of interest attached thereto; the sequence of steps “A”, “B”, “C”, “D”, “E”, “F”, “G” are understood to occur, one after the other, at the device 100.
  • the fluid density column 104 contains fluid for washing the magnetizing microparticles 106 which may be introduced via actuation of a reservoir at the sample preparation cartridge module 102 containing such a wash fluid, and the like.
  • the fluid density column 104 may, however, contain any suitable combination of fluids such that, initially, the magnetizing microparticles 106 are suspended in a fluid in the fluid density column 104 at an end opposite that of the tip 114, as in step “A”.
  • the magnetic devices 116 are depicted in either solid lines or broken lines.
  • a magnetic device 116 is depicted in solid lines, it is understood that the magnetic device 116 has been controlled to apply a respective magnetic field at a respective side 120 which may include, but is not limited to: a magnetic device 116 moving along a respective path 118 to be in a first position adjacent a respective side 120 of the fluid density column 104, for example, similar to the first magnetic device 116-1 in Figure 2A; and/or an electromagnet of a magnetic device 116 being turned on.
  • a magnetic device 116 when a magnetic device 116 is depicted in solid lines, it is understood that the magnetic device 116 has been controlled to remove a respective magnetic field from a respective side 120 which may include, but is not limited to: a magnetic device 116 moving along a respective path 118 (e.g. “out” of the page in Figure 5, Figure 6 and Figure 7) to be in a second position away from a respective side 120 of the fluid density column 104, for example, similar to the second position of the second magnetic device 116-2 in Figure 2A (e.g. the second position of the second magnetic device 116-2 depicted in solid lines in Figure 1 and Figure 2A); and/or an electromagnet of a magnetic device 116 being turned off.
  • the magnetic devices 116 are described as applying, or removing, magnetic fields via movement along the paths 118, it is understood that the same functionality may be achieved when the magnetic devices 116 include electromagnets by positioning both the magnetic devices 116 at the fluid density column 104 and turning the electromagnets on and off.
  • the carriage 108 may be controlled to move the fluid density column 104 to an initial position relative to the magnetic devices 116 so that both magnetic devices 116 may be controlled to move along the paths 118 to be adjacent opposite sides 120 of the fluid density column 104 at the end opposite that of the tip 114 and/or at an end adjacent a lysis region of the sample preparation cartridge module 102.
  • the magnetic devices 116 pause in these positions and exert a magnetic field on the magnetizing microparticles 106, which, as depicted in step “B” cause the magnetizing microparticles 106 to be dragged to both of the sides 120, adjacent respective magnetic devices 116 where they form respective clumps and/or groups.
  • some magnetizing microparticles 106 are dragged and/or pulled to the first side 120-1 , and other magnetizing microparticles 106 are dragged and/or pulled to the second side 120-2.
  • one of the magnetic devices 116 may be controlled to move away from a respective side 120; for example, as depicted, the first magnetic device 116-1 may be controlled to move away from the first side 120-1 removing a respective magnetic field from the magnetizing microparticles 106, such that the magnetizing microparticles 106 are dragged and/or pulled to the second side 120-2 by the second magnetic device 116-2, and may form a clump and/or a group at the second side 120-2.
  • steps “A”, “B” and “C” may be optional, such a process may assist with magnetizing the magnetizing microparticles 106, and the like.
  • the process of steps “A”, “B” and “C” may be used to collect the magnetizing microparticles 106, for example in a clump, at a respective side 120 of a fluid density column 104 to assist with the steps that are next described to wash and/or move the magnetizing microparticles 106.
  • both magnetic devices 116 are controlled to move away from their respective sides 120.
  • the carriage 108 is controlled to move the fluid density column 104 along the path 110 (for example as represented by the arrow 128) by a given distance 130 for example in the “Z” direction, which positions the magnetic devices 116 closer to the dispensing tip 114.
  • the fluid density column 104 has moved relative to the magnetic devices 116 in the “Z” direction while the magnetic devices 116 have not moved in the “Z” direction.
  • the position of the carriage 108 at step “D” (e.g.
  • the magnetizing microparticles 106 are offset from the magnetic devices 116 in the “Z” direction.
  • step “E” Attention is next directed to step “E”, depicted in Figure 6.
  • the first magnetic device 116-1 is controlled to move along the path 118-1 to be adjacent the first side 120-1 of the fluid density column 104 and the first magnetic device 116-1 is paused in this position for a first given time period.
  • a magnetic field of the first magnetic device 116-1 is applied to the magnetizing microparticles 106 to pull and/or drag the magnetizing microparticles 106 through the fluid of the fluid density column 104 to the first side 120-1 , adjacent the first magnetic device 116-1 , as represented by the arrow 132, and the magnetizing microparticles 106 depicted in broken lines about midway between the sides 120.
  • the magnetizing microparticles 106 again form a clump and/or group at the first side 120-1 .
  • the first given time period may be selected to ensure that the magnetic field of the first magnetic device 116-1 pulls and/or drags the magnetizing microparticles 106 to the first side 120-1 , though any suitable first given time period is within the scope of the present specification.
  • the magnetizing microparticles 106 may be washed, and a biological component bonded thereto may be isolated and/or purified, and furthermore the magnetizing microparticles 106 may disperse during such movement, for example as individual magnetizing microparticles 106 follow respective magnetic field lines of the magnetic field applied by the first magnetic device 116-1 .
  • Such dispersing is represented by the magnetizing microparticles 106 depicted in broken lines which are further apart than at the sides 120.
  • step “F” which is similar to step “D”
  • the first magnetic device 116-1 is controlled to move away from the side 120-1 and, when stopped, the carriage 108 is again controlled to move the fluid density column 104 along the path 110 (for example as represented by the arrow 134) by a given distance 136 for example in the “Z” direction, which may the same as, or (as depicted) different from, the given distance 130.
  • Such movement again positions the magnetic devices 116 closer to the dispensing tip 114 and the magnetizing microparticles 106 are again offset from the magnetic devices 116 in the “Z” direction.
  • the position of the carriage 108 at step “F” (e.g. as represented by the fluid density column 104 relative to the magnetic devices 116) may be referred to as a second position of the carriage 108.
  • step “G” is similar to step “E” but performed with the second magnetic device 120-1.
  • the second magnetic device 116-2 is controlled to move along the path 118-2 to be adjacent the second side 120-2 of the fluid density column 104 and the second magnetic device 116-2 is paused in this position for a second given time period which may be the same as, or different from the first given time period for which the first magnetic device 116-1 is paused in step “D”.
  • a magnetic field of the second magnetic device 116-2 is applied to the magnetizing microparticles 106 to again pull and/or drag the magnetizing microparticles 106 through the fluid of the fluid density column 104 to the second side 120-2, adjacent the second magnetic device 116-2, as represented by the arrow 138, and the magnetizing microparticles 106 depicted in broken lines about midway between the sides 120 (e.g. which are dispersed relative to at the sides 120).
  • the magnetizing microparticles 106 again form a clump and/or group at the second side 120-2.
  • the second given time period may be selected to ensure that the magnetic field of the second magnetic device 116-2 pulls and/or drags the magnetizing microparticles 106 to the second side 120-2, though any suitable second given time period is within the scope of the present specification.
  • the magnetizing microparticles 106 may be washed, and a biological component bonded thereto may be isolated and/or purified, and furthermore the magnetizing microparticles 106 may disperse during such movement, for example as individual magnetizing microparticles 106 follow respective magnetic field lines of the magnetic field applied by the second magnetic device 116-2.
  • step “D” to step “G” may be repeated any suitable number of times to move the magnetizing microparticles 106 towards the dispensing tip 114, for example to control a path geometry of the magnetizing microparticles 106, to wash and/or move the magnetizing microparticles 106, and isolate and/or purify a biological component bonded thereto.
  • the magnetic devices 116 may be controlled to alternate applying magnetic fields to the opposite sides 120 of the fluid density column 104 to move the magnetizing microparticles 106 between the opposite sides 120 of the fluid density column 104, the carriage 108 being moved along the path 110 between the magnetic devices 116 alternately applying magnetic fields to the opposite sides 120.
  • the arrows 132, 138 are understood to present a path of the magnetizing microparticles 106 through the fluid density column 104 which may be changed and/or controlled by controlling the given distances 130, 136, and/or subsequent given distances of movement of the carriage 108 as the process shown in step “D” to step “G” is repeated, as well as the first given time period and the second given time period (e.g. pause times) that the magnetic devices 116 respectively pause to drag and/or pull the magnetizing microparticles 106 through the fluid density column 104.
  • the first given time period and the second given time period e.g. pause times
  • the arrows 132, 138 represent a zig-zag pattern of a path geometry of the magnetizing microparticles 106 through the fluid density column 104, which may attempt balance a time to implement the washing, with maximizing the washing.
  • the given distances 130, 136 which may be referred to as “steps” (e.g. in this context a step of the carriage 108 may be distances through which the carriage 108 is moved and then paused), and the pause times of the magnetic devices 116 may be varied to control the path geometry.
  • steps e.g. in this context a step of the carriage 108 may be distances through which the carriage 108 is moved and then paused
  • the pause times of the magnetic devices 116 may be varied to control the path geometry.
  • a step size and/or a pause time may be varied according to a distance the magnetic devices 116 are from the dispensing tip 114, for example to take into account the narrowing of the fluid density column 104 from the aperture 124 to the dispensing tip 114.
  • pause times of the magnetic devices 116 may be controlled to be of a duration (e.g. which may be determined heuristically) to clump the magnetizing microparticles 106 at a side 120.
  • a pause time of a magnetic device 116 may be reduced (e.g.
  • a clump of the magnetizing microparticles 106 is pulled from an opposing side 120, but not given enough time to ‘re-clump’ and densely pack on a side 120 wall closest to a magnetic device 116 applying a magnetic field, for example to better position the magnetizing microparticles 106 away from the sides 120 to dispense out of the tip 114.
  • a magnetic field may assist with efficient dispensing of the magnetizing microparticles 106 with biological components of interest bonded thereto, for example to reduce a possibility of the magnetizing microparticles 106 being “stuck” at the sides 120 during dispensing.
  • Figure 7 shows different path geometries 702, 704, 706 showing different respective paths for the magnetizing microparticles 106 that may be implemented in the fluid density column 104 using the example device 100 of Figure 1 .
  • the path geometry 702 may be achieved to take into account the narrowing of the narrowing of the fluid density column 104 from the aperture 124 to the dispensing tip 114.
  • the step size of the carriage 108 may also be shortened or lengthened, the closer the magnetic devices 116 are to the dispensing tip 114, for example to decrease or increase an angle of movement of the magnetizing microparticles 106 between the sides 120.
  • a path geometry 704 includes diagonal regions from the second side 120-2 to the first side 120-1 , which are all of respective equal distances, and “horizontal" regions from the first side 120-1 to the second side 120-2 (e.g. movement between the sides 120 that is not diagonal) which are also all of respective equal distances.
  • Such a path geometry 704 may be achieved by moving the carriage 108 a same distance prior to applying a magnetic field to the first side 120-1 , and not moving the carriage 108 prior to applying a magnetic field to the second side 120-2.
  • the step “F” may be eliminated and/or a step size thereof (e.g. the distance 136) may be reduced to achieve such a path geometry 704.
  • the path geometry 704 illustrates that the pause times of the magnetic devices 116 may be controlled such that the magnetizing microparticles 106 may not be dragged and/or pulled all the way to the sides 120. While such a path geometry 704 may not be preferred, the path geometry 704 illustrates the many different path geometries that may be achieved using the device 100.
  • the path geometry 706 is provided to show that movement between the sides 120 and parallel to the sides 120, and the like, may be achieved using the device 100.
  • a path geometry 706 may be achieved by modifying the step “E” and/or the step “F” such that the carriage 108 moves the along the path 110 while a magnetic device 116 is adjacent a respective side 120 and/or by eliminating step “F” and/or reducing a step size thereof (e.g. the distance 136).
  • the path geometry 706 illustrates the many different path geometries that may be achieved using the device 100.
  • the magnetic devices 116 may be further to be removed from the opposite sides 120 of the fluid density column 104, and/or the magnetic devices 116 may be controlled to remove the magnetic fields from the opposite sides 120 of the fluid density column 104.
  • the carriage 108 may be further to move along the path 110 relative to the magnetic devices 116, while the magnetic devices 116 are removed from the opposite sides 120 of the fluid density column 104, and/or the magnetic devices 116 are controlled remove the magnetic fields from the opposite sides 120 of the fluid density column 104, to further control the path geometry of the magnetizing microparticles 106 in the fluid density column 104 into a zigzag pattern.
  • the magnetic devices 116 may be to further to pause applying magnetic fields to the opposite sides 120 of the fluid density column 104 to further control the path geometry of the magnetizing microparticles 106 in the fluid density column 104. Furthermore, a timing of the pause may be controllable (e.g. the first given time period and/or the second given time period may be controlled).
  • a step size of the carriage 108 along the path 110 may be controllable to further control the path geometry of the magnetizing microparticles 106 in the fluid density column 104.
  • the device 100 may be adapted to specifically control a path geometry of the magnetizing microparticles 106 into zig-zag pattern (e.g. the path geometry 702 and/or the path geometry 704).
  • the device 100 may comprise: the carriage 108 to hold the sample preparation cartridge module 102 that includes the fluid density column 104 and the magnetizing microparticles 106 therein, the carriage 108 to move along the path 110; and the magnetic devices 116 which may be to move perpendicular to the path 110 of the carriage 108, to alternate applying magnetic fields at opposite sides 120 of the fluid density column 104 to move the magnetizing microparticles 106 between the opposite sides 120 of the fluid density column 104 to wash and/or move the magnetizing microparticles 106 in the fluid density column 104, positions of the magnetic devices 116 being coordinated with a position of the carriage 108 to control a path geometry of the magnetizing microparticles 106 in the fluid density column 104 into a zigzag pattern.
  • the magnetic devices 116 may be to pause when applying a magnetic field to one side 120 of the fluid density column 104 to shape the zigzag pattern of the path geometry.
  • the magnetic devices 116 may be to pause for different times, depending on the position of the carriage 108, when applying a magnetic field to one side 120 of the fluid density column 104 to shape the zigzag pattern of the path geometry.
  • the position of the carriage 108 may be adjusted to adjust a relative position of the magnetic devices 116 relative to the fluid density column 104 and furthermore the position of the carriage 108 may be adjusted according to a step size or step sizes to shape the zigzag pattern of the path geometry.
  • the position of the carriage 108 may be adjusted when the magnetic devices 116 are removed from the opposite sides 120 of the fluid density column 104 to remove the magnetic fields therefrom, for example to move the fluid density column 104 relative to the magnetic devices 116 between alternation of the magnetic fields at the sides 120.
  • the device 100 may be adapted to include a plurality of the first magnetic devices 116-1 and a plurality of the second magnetic devices 116-2, which may be provided on plates, and the like, such that the first magnetic devices 116-1 move as a group and the second magnetic devices 116-2 as group, independent from the first magnetic devices 116-1.
  • Such groups of the magnetic devices 116 may be offset from each other along the “Z” axis so as to not interfere with each other, and furthermore the relative positions of the first magnetic devices 116-1 and adjacent second magnetic devices 116-2 may be staggered relative to each other along the “X” axis so that the first magnetic devices 116-1 may move to between sides 120 of two respective adjacent sample preparation cartridge modules 102, and, similarly, the second magnetic devices 116-2 may also move to between sides 120 of two respective adjacent sample preparation cartridge modules 102, but staggered (e.g. and/or alternating) with the first magnetic devices 116-1.
  • the magnetic devices 116 may be offset from each other along the “Z” axis, for example to accommodate respective actuators thereof.
  • Figure 8A and Figure 8B respectively depict a perspective view and a block diagram of an example sample preparation device 800 that incorporates aspects of the device 100 and of Figure 1.
  • the sample preparation device 800 (interchangeably referred to hereafter as the device 800) includes a chassis 802 that includes a cassette access door 804 for loading a cassette 107 that includes the sample preparation cartridge module 102 and/or sample preparation cartridge modules 102 therein, the sample preparation cartridge module 102 holding a sample for testing as described hereafter. While the sample preparation cartridge modules 102 are depicted herein as being in an elongate shape and/or in the form of a column, similar to Figure 2A and Figure 3, the sample preparation cartridge modules 102 may be any suitable shape.
  • the chassis 802 further includes a well access door 810 for loading a well holder 812 containing a well 814 and/or wells for receiving processed samples dispensed from the sample preparation cartridge module 102 after processing by the device 800. While only one sample preparation cartridge module 102 is depicted, and eight wells 814, it is understood that the cassette 107 may hold a same number of sample containers 108 as there are wells 814 at the well holder 812. For example, as depicted, similar to as described with respect to Figure 1 and Figure 2A, there may be eight sample preparation cartridge modules 102 and hence eight wells 814.
  • the components of the device 800 may cause the cassette 107 and the well holder 812 to be loaded into the device 800 in any suitable relative orientation including, but not limited to, about parallel to one another such that a line of the sample preparation cartridge module 102 is about aligned with a line of the wells 814.
  • the device 800 further comprises an input device 818, such as a touch screen display, and the like, which may be used to control the device 800 into a loading mode, which causes the cassette access door 804 and the well access door 810 to open such that the cassette 107 and the well holder 812, with the wells 814, may be manually loaded into the device 800.
  • a sample preparation cartridge module 102 is loaded with a sample 838 (e.g. such as a biological sample retrieved from a human by medical personnel), and the like, via the port 820.
  • the input device 818 may also be used to set given temperatures to which the sample preparation cartridge module 102 is to be heated and/or a heating cycle of the sample preparation cartridge module 102 and/or a heating/mixing cycle (e.g. setting mixing speeds of an actuator 844 of the device 800) and/or the input device 818 may be used to control step sizes of the carriage 108 and/or pause times of the magnetic devices 116 to control path geometry of the magnetizing microparticles 106.
  • the carriage 108 of the device 800 which may alternatively be referred to as the cassette carriage 108, is raised along a vertical carriage guide 826 to at least partially emerge from an opening that is normally covered by the cassette access door 804. The cassette 107 may then be manually loaded into the carriage 108.
  • the shuttle e.g. a well carriage
  • the planar surface e.g. a horizontal carriage guide
  • the well holder 812 is then manually loaded into a complementary shaped depression and/or holder 831 in the well carriage 108.
  • the terms vertical and horizontal are used herein with regards to a position of the device 800 (and the device 100) in a normal use mode, such terms are meant for ease of description only and/or to indicate relative positions of components of the device 800 (e.g. the guide 826 and the planar surface 830 may be about perpendicular to each other as one is vertical and the other horizontal, but may be in any suitable orientation).
  • the cassette carriage 108 moves the cassette 107 into the device 800 (e.g. closing the door 804), and then into different positions in the device 800, for example along the vertical carriage guide 826, to process the sample 838, for example at least by washing the magnetizing microparticles
  • the planar surface 830 moves inside the device 800 (e.g. closing the door 810) and the shuttle 828 is moved into a position to receive the sample 838 from the sample preparation cartridge module 102 into a corresponding well 814.
  • the shuttle 828 is moved into respective positions to receive respective samples 838 dispensed from respective sample preparation cartridge modules 102 into corresponding wells 814.
  • the shuttle 828 may be positioned at an angle relative to the cassette carriage 108 and/or the cassette
  • the device 800 is further understood to include motors and/or a servomotors, and the like, to move the planar surface 830 into and out of the device 800, and to linearly move the shuttle 828 along the planar surface 830.
  • the device 800 may further include respective components for opening and closing the doors 804, 810.
  • a sample preparation cartridge module 102 may be divided into a first region 832 and a second region 834 (e.g. that includes the fluid density column 104, for example as depicted in Figure 3), divided by a barrier 836.
  • a sample 838 is received into the sample preparation cartridge module 102 via the port 820, and may reside at a bottom of the first region 832, at the barrier 836; as depicted, the magnetizing microparticles 106 are initially located in the first region 832.
  • the sample preparation cartridge module 102 may further comprise an agitator 840 in the first region 832 which may be actuated via a mixer actuator 842 and an actuator 844, and the like of the device 800 as described below.
  • the mixer actuator 842 may include a servomotor and/or servomotors, and the like, to move/rotate the actuator 844 to mix the sample 838 via the agitator 840, while the sample 838 is heated, as described below.
  • the cassette 107 may be moved, along the vertical carriage guide 826, via the cassette carriage 108, into a heating position for heating by one or both of two heaters 846 (e.g. heaters 846-1 , 846-2) attached to respective mechanical devices 848 (e.g. mechanical devices 848-1 , 848-2).
  • two heaters 846 e.g. heaters 846-1 , 846-2
  • respective mechanical devices 848 e.g. mechanical devices 848-1 , 848-2).
  • the device 800 is understood to include respective temperature sensors at the heaters 846 and/or the mechanical devices 848 so that, in a heating position of the cassette carriage 108, the heaters 846 may be positioned adjacent the first region 832 of the sample preparation cartridge module 102 to heat the sample 838, while the agitator 840 is actuated by the actuator 844, to agitate and/or mix the sample 838 while it is being heated, for example to promote lysis in cells of the sample 838.
  • the actuator 844 itself is understood to be further moved by the mixer actuator 842 into a position to agitate and/or mix the sample 838, while it is being heated, and actuated by the mixer actuator 842 which may comprise any suitable combination of motors for moving and turning the actuator 844.
  • the actuator 844 may comprise a magnetic agitating device which agitates the sample 838 during lysis by applying a changing magnetic field to the first region 832 to move the magnetizing microparticles 106; in such examples, the agitator 840 may be omitted from the sample preparation cartridge module 102.
  • the agitator 840 is generally configured to mate with the actuator 844; for example, as depicted, the agitator 840 may be attached to a pressure source 850, such as a plunger, and the like, an outer surface of which may be used to both mate with the actuator 844, to actuate the agitator 840, and move the sample 838 to the second region 834, for example by applying pressure to the pressure source 850 via the mixer 844 to break the barrier 836.
  • a pressure source 850 such as a plunger, and the like
  • the second region 834 (e.g. the fluid density column 104) may further include a wash buffer which may be mixed with mixed with the biological components of interest (e.g. bonded to the magnetizing microparticles) (e.g. when plunged into the second region 834), by actuation of a suitable reservoir 852 of a plurality of reservoirs 852 that perform different functions for the sample preparation cartridge module 102.
  • the reservoirs 852 may alternatively be referred to as blisters and/or pouches, and the like.
  • one reservoir 852 may hold the wash buffer, another reservoir 852 may hold chemicals to stabilize the biological component of interest, another reservoir 852 may hold a grease barrier, and yet another reservoir 852 may be for dispensing the sample 838, including the magnetizing microparticles 106 with the biological component of interest bonded thereto, into a well 214, for example via the tip 114 of the sample preparation cartridge module 102.
  • the cassette 107 may hold a plurality of sample preparation cartridge modules 102 and hence the device 800 may be to actuate a plurality of corresponding reservoirs 852 (e.g. concurrently) on a plurality of sample preparation cartridge modules 102 for sample processing, and to actuate individual reservoirs 852 (e.g. independent of each other) on the sample preparation cartridge modules 102 for sample dispensing.
  • the device 800 may include a multiple reservoir actuator 856 including a plurality of reservoir tips 858 (though only one is depicted) which may be used to actuate (e.g.
  • the device 800 may include a plurality of single reservoir actuators 860 (though only one is depicted) including respective reservoir tips 862 (though, again, only one is depicted), for independently actuating respective reservoirs 852 at the plurality of sample preparation cartridge modules 102 to independently dispense samples 838 into respective wells 814 via respective tips 862.
  • the device 800 may comprise one single reservoir actuator 860 including one reservoir tip 862 that is movable within the device 800 between sample preparation cartridge modules 102.
  • the device 800 may include the magnetic devices 116, which may be actuated via a magnetic actuator and/or magnetic actuators 866 to move the magnetic devices 116 adjacent the sample preparation cartridge module 102, as described above, to attract the magnetizing microparticles 106 in the sample 838 to wash and/or move the magnetizing microparticles 106 to isolate and/or purify biological components of interest bonded thereto, and move the sample 838 towards the tip 114 and/or through the fluid density column 104 in the second region 834, as described with respect to Figure 5, Figure 6, and Figure 7, for example in combination with moving the sample preparation cartridge modules 102 via the carriage 108.
  • the device 800 further includes a cooler and/or air-intake port 868 and/or tube which may include a fan, and the like (not depicted) for drawing air into the device 800 via a filter 870, and an exhaust port 872 (which may also include a fan) for expelling air drawn into the device 800 via the cooler port 868 via a respective filter 874.
  • the ports 868, 872 may provide passive and/or active cooling at the device 800 to cool the sample 838 when heated.
  • the ports 868, 872 may be located in any respective suitable positions at the device 800.
  • the cassette carriage 108 may be moved into a sample dispensing position relative to the shuttle 828 and/or the wells 814 to dispense samples 838 into the wells 814 from the sample preparation cartridge modules 102; the shuttle 828 may be moved into sample receiving positions, relative to the carriage 108, to position the wells 814 relative to the sample preparation cartridge modules 102 to receive the samples 838 as dispensed via actuation of individual suitable reservoirs 852 by the single reservoir actuator 860.
  • the wells 814 may be moved back out of the device 800 via the planar surface 830 and the well access door 810 and transferred to, for example, a PCR assay device.
  • the device 800 further comprises a processor 890 and a memory 892.
  • the processor 890 may include a general-purpose processor and/or controller or special purpose logic, such as a microprocessor and/or microcontroller (e.g. a central processing unit (CPU) and/or a graphics processing unit (GPU) an integrated circuit or other circuitry), an application specific integrated circuit (ASIC), a Field Programmable Gate Array (FPGA), a programmable array logic (PAL), a programmable logic array (PLA), a programmable logic device (PLD), and the like.
  • a microprocessor and/or microcontroller e.g. a central processing unit (CPU) and/or a graphics processing unit (GPU) an integrated circuit or other circuitry
  • ASIC application specific integrated circuit
  • FPGA Field Programmable Gate Array
  • PAL programmable array logic
  • PLA programmable logic array
  • PLD programmable logic device
  • the processor 890 may be implemented as a hardware element with no software elements (e.g. such as an ASIC, an FPGA, a PAL, a PLA, a PLD etc.).
  • the memory 892 may comprise instructions 894 for controlling the processor 890 and/or a processor thereof to perform the various processes described herein and which may include the various positions at which the carriage 108 is to be located relative the magnetic devices 116 as described herein, among other possibilities.
  • a memory 892 may include, but is not limited to, any suitable combination of a volatile computer-readable medium (e.g., volatile RAM, a processor cache, a processor register, etc.), a non-volatile computer-readable medium (e.g., a magnetic storage device, an optical storage device (e.g. a Digital Versatile Disc (DVD), a paper storage device, flash memory, read-only memory, non-volatile RAM, etc.), and/or the like.
  • a volatile computer-readable medium e.g., volatile RAM, a processor cache, a processor register, etc.
  • a non-volatile computer-readable medium e.g., a magnetic storage device, an optical storage device (e.g. a Digital Versa
  • Figure 8C is substantially similar to Figure 8B with like components having like numbers.
  • the cassette 107 has been loaded into the cassette carriage 108, and the carriage access door 804 has been closed.
  • the wells 814 have been loaded into the shuttle 828 and the planar surface 830 (with the shuttle 828) has been moved into the device 800, and the well access door 810 has been closed.
  • the sample 838 has undergone lysis via heating by the heaters 846, and moved to the second region 834 of the sample preparation cartridge module 102 via the pressure source 850 being actuated (e.g.
  • reservoirs 852 containing the wash buffer have been concurrently actuated by the multiple reservoir actuator 856 and the tips 858. As such, the reservoirs 852 associated with the wash buffer are no longer seen at the sample preparation cartridge module 102.
  • the sample 838 including the magnetizing microparticles 106 with the biological component of interest bonded thereto is located at a “top” of the fluid density column 104 (e.g. an end opposite the tip 114).
  • the carriage 108 has been moved to a magnetizing microparticle washing position, similar to that of step “A, “B” and/or “C” and the magnetic actuator 866 has moved the magnet devices 116 at opposite sides 120 of the fluid density column 104 to begin washing of the magnetizing microparticles 106 to purify and/or isolate a biological component of interest attached thereto.
  • method 900 may be performed with the device 800 (e.g. via the processor 890 implementing the instructions 894 stored at the memory 892).
  • the method 900 may be one way in which the device 800 may be configured.
  • the following discussion of method 900 may lead to a further understanding of the device 800, and their various components.
  • method 900 may not be performed in the exact sequence as shown, and various blocks may be performed in parallel rather than in sequence, or in a different sequence altogether.
  • the method 900 may be performed by the device 100.
  • the processor 890 and/or the device 800 controls the carriage 108 to move to, and pause at, a first position (e.g. as seen in step “D” of Figure 5), the carriage 108 holding the sample preparation cartridge module 102 that includes the fluid density column 104 and the magnetizing microparticles 106 therein.
  • the processor 890 and/or the device 800 controls, while the carriage 108 is paused at the first position, a first magnetic device 116-1 to apply a first magnetic field to a first side 120-1 of the fluid density column 104 for a first given time period to drag the magnetizing microparticles 106 to the first side 120-1 (e.g. as seen in step “E” of Figure 6).
  • the processor 890 and/or the device 800 controls the first magnetic device 116-1 to remove the first magnetic field from the first side 120-1 of the fluid density column 104 (e.g. as seen in step “F” of Figure 6).
  • the processor 890 and/or the device 800 controls the carriage 108 to move to, and pause at, a second position (e.g. as also seen in step “F” of Figure 6).
  • the processor 890 and/or the device 800 while the carriage 108 is paused at the second position, controls a second magnetic device 116-2 to apply a second magnetic field to a second side 120-2 of the fluid density column 104 (e.g. as seen in step “G” of Figure 6) for a second given time period, the second side 120-2 opposite the first side 120-1 , to drag the magnetizing microparticles 106 to the second side 120-2. and
  • the processor 890 and/or the device 800 controls the second magnetic device 116-2 to remove the second magnetic field to the second side 120-2 of the fluid density column 104 (e.g. similar to as in step “C” of Figure 6).
  • the method 900 may further comprise, prior to moving the carriage 108 to the first position at the block 902, the processor 890 and/or the device 800 controlling both the first magnetic device 116-1 and the second magnetic device 116-2 to concurrently apply the first magnetic field and the second magnetic field to the first side 120-1 and the second side 120-2 of the fluid density column 104 to drag the magnetizing microparticles 106 to the first side 120-1 and the second side 120-2 (e.g. as seen in step “B” of Figure 5).
  • the method 900 may further comprise, the processor 890 and/or the device 800 continuing to control the first magnetic device 116-1 and the second magnetic device 116-2 to alternately apply the first magnetic field and the second magnetic field to the first side 120-1 and the second side 120-2 of the fluid density column 104 as the carriage 108 moves to, and pauses at, different positions (e.g. the steps “D”, “E”, “F”, and “G” of Figure 5 and Figure 6 may be repeated any suitable number of times to wash and/or move the magnetizing microparticles 106 and move the magnetizing microparticles 106 towards the tip 114 of the sample preparation cartridge module 102, for example to control a path geometry of the magnetizing microparticles 106).
  • the steps “D”, “E”, “F”, and “G” of Figure 5 and Figure 6 may be repeated any suitable number of times to wash and/or move the magnetizing microparticles 106 and move the magnetizing microparticles 106 towards the tip 114 of the sample preparation cartridge module 102, for example to control a path
  • the first position (e.g. described at the block 902) and the second position (e.g. described at the block 908) of the carriage 108 may be dependent on their relative positions to the first magnetic device 116-1 and the second magnetic device 116-2 to the fluid density column 104 (e.g. to control the path geometry of the magnetizing microparticles 106 and/or which may be due to the narrowing of the fluid density column 104).
  • respective lengths of the first given time period (e.g. for which the first magnetic device 116-1 pauses at the block 904) and the second given time period (e.g. for which the second magnetic device 116-2 pauses at the block 910) may be controllable (e.g. to control the path geometry of the magnetizing microparticles 106).

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Biomedical Technology (AREA)
  • Genetics & Genomics (AREA)
  • Physics & Mathematics (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Analytical Chemistry (AREA)
  • Hematology (AREA)
  • General Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Urology & Nephrology (AREA)
  • Microbiology (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Cell Biology (AREA)
  • Plant Pathology (AREA)
  • Medicinal Chemistry (AREA)
  • Biophysics (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

Un dispositif donné à titre d'exemple comprend : un chariot destiné à contenir un récipient d'échantillon à l'intérieur duquel se trouvent une colonne de densité fluidique et des microparticules de magnétisation, le chariot se déplaçant le long d'une trajectoire. Le dispositif donné à titre d'exemple comprend en outre : des dispositifs magnétiques destinés à se déplacer par rapport à la trajectoire du chariot, pour appliquer en alternance des champs magnétiques sur les côtés opposés de la colonne de densité fluidique afin de déplacer les microparticules de magnétisation entre les côtés opposés de la colonne de densité fluidique de façon à déplacer les microparticules de magnétisation dans la colonne de densité fluidique, les dispositifs magnétiques étant mobiles indépendamment les uns des autres et du chariot pour réguler la forme de la trajectoire des microparticules de magnétisation dans la colonne de densité fluidique.
PCT/US2020/066640 2020-12-22 2020-12-22 Lavage de microparticules de magnétisation dans une colonne de densité fluidique WO2022139819A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/US2020/066640 WO2022139819A1 (fr) 2020-12-22 2020-12-22 Lavage de microparticules de magnétisation dans une colonne de densité fluidique

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US2020/066640 WO2022139819A1 (fr) 2020-12-22 2020-12-22 Lavage de microparticules de magnétisation dans une colonne de densité fluidique

Publications (1)

Publication Number Publication Date
WO2022139819A1 true WO2022139819A1 (fr) 2022-06-30

Family

ID=82158294

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2020/066640 WO2022139819A1 (fr) 2020-12-22 2020-12-22 Lavage de microparticules de magnétisation dans une colonne de densité fluidique

Country Status (1)

Country Link
WO (1) WO2022139819A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060094051A1 (en) * 2004-11-03 2006-05-04 Jeong-Gun Lee Apparatus and method for purification of nucleic acids by phase separation using laser and beads
US20110207229A1 (en) * 2008-10-16 2011-08-25 Koninklijke Philips Electronics N.V. Method and device for determining the amount of magnetically labeled target components
RU2484139C1 (ru) * 2012-05-17 2013-06-10 Общество с ограниченной ответственностью "Научно-Производственное Объединение ДНК-Технология" Устройство для выделения нуклеиновых кислот

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060094051A1 (en) * 2004-11-03 2006-05-04 Jeong-Gun Lee Apparatus and method for purification of nucleic acids by phase separation using laser and beads
US20110207229A1 (en) * 2008-10-16 2011-08-25 Koninklijke Philips Electronics N.V. Method and device for determining the amount of magnetically labeled target components
RU2484139C1 (ru) * 2012-05-17 2013-06-10 Общество с ограниченной ответственностью "Научно-Производственное Объединение ДНК-Технология" Устройство для выделения нуклеиновых кислот

Similar Documents

Publication Publication Date Title
JP4856831B2 (ja) 磁性粒子を流体と混合するための装置および方法
JP6030197B2 (ja) 液体媒体中で磁性粒子を操作及び混合するためのデバイス及び方法
JP5752042B2 (ja) 磁性試薬、磁性試薬キット、磁性担体処理方法およびその処理装置
EP2309278B1 (fr) Dispositif et procede de separation, de melange et de concentration des particules magnetiques avec liquides et leurs utilisations dans des methodes de purification
US20090035746A1 (en) Device and Method for Preparing a Sample for an Analysis and Device and Method for Analyzing a Sample
US20150093750A1 (en) Magnetically assisted processing of a medium
JP7155258B2 (ja) 磁気粒子を用いて生物学的試料をプロセシングするための方法
JP5336495B2 (ja) 磁性粒子を用いて液体を処理する装置及び方法
US5835329A (en) Apparatus for agitation separation of magnetic particles
WO2022139819A1 (fr) Lavage de microparticules de magnétisation dans une colonne de densité fluidique
WO2022139820A1 (fr) Dispositifs pour commander des microparticules de magnétisation dans des colonnes de densité de fluide
US20110028703A1 (en) Method and apparatus for suspending magnetic microparticles
WO2022125070A1 (fr) Préparation d'échantillon avec chambres de plongée et de mélange
JP5979838B2 (ja) 生物学的材料の単離のための結合粒子のための懸濁容器
WO2022139809A1 (fr) Dispositifs de retenue d'une cassette contenant un module de cartouche de préparation d'échantillon
WO2022139822A1 (fr) Dispositifs et procédés d'actionnement de réservoir
WO2022139813A1 (fr) Dispositifs et procédés d'établissement de points de référence pour la distribution d'échantillon
AU2020385010A1 (en) Microfluidic device for and methods of using surface-attached posts and capture beads in a microfluidic chamber

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: 20967187

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 20967187

Country of ref document: EP

Kind code of ref document: A1