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WO2018031232A1 - Concentration et mélange sans contact de matériau magnétique dans un liquide - Google Patents

Concentration et mélange sans contact de matériau magnétique dans un liquide Download PDF

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Publication number
WO2018031232A1
WO2018031232A1 PCT/US2017/043810 US2017043810W WO2018031232A1 WO 2018031232 A1 WO2018031232 A1 WO 2018031232A1 US 2017043810 W US2017043810 W US 2017043810W WO 2018031232 A1 WO2018031232 A1 WO 2018031232A1
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WO
WIPO (PCT)
Prior art keywords
liquid
sample
magnetic material
magnets
wells
Prior art date
Application number
PCT/US2017/043810
Other languages
English (en)
Inventor
Kyle Lapham
Original Assignee
Counsyl, 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 Counsyl, Inc. filed Critical Counsyl, Inc.
Publication of WO2018031232A1 publication Critical patent/WO2018031232A1/fr

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Classifications

    • 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
    • B03C1/025—High gradient magnetic separators
    • B03C1/031—Component parts; Auxiliary operations
    • B03C1/033—Component parts; Auxiliary operations characterised by the magnetic circuit
    • B03C1/0332—Component parts; Auxiliary operations characterised by the magnetic circuit using permanent magnets
    • 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

Definitions

  • the invention relates to methods for concentrating magnetic material in liquid and/or dispersing magnetic material in liquid to effect mixing of the liquid.
  • Magnetic affinity beads are used for a number of applications, such as isolation of biomolecules or diagnostic assays. Placing magnets underneath sample tubes or wells of a multiwell plate is a common way to concentrate the beads at the bottom of the tube or well to facilitate removal of excess fluid and washing of the beads. Since magnetic field strength is limited by distance, the closer the magnet is to the beads, the better it works. The problem with this is that in larger or tall sample tubes or wells, pulling magnetic material down to the bottom is less efficient, and positioning the magnet at the top results in the beads collecting at the top of the sample liquid rather than the bottom of the tube or well. An improved method for concentrating magnetic material such as magnetic beads in liquid samples is needed.
  • Mixing of liquid in sample tubes or wells of a multiwell plate may be performed by a number of methods, including pipetting up and down, shaking, agitating, or inverting. Pipetting contacts the liquid, which may introduce contamination, uses consumables (pipet tips), and may remove small amounts of liquid, reducing the liquid volume and potentially removing sample substances. Shaking, inverting, or other mechanical mixing methods may result in splashing and/or cross-contamination between adjacent or nearby sample tubes or wells. An improved method for mixing liquid in sample tubes or wells of a multiwell plate is needed.
  • a method for concentrating magnetic material in liquid in a well of a sample processing plate that includes a plurality of wells or in a sample tube in a tube rack that includes a plurality of sample tubes, wherein the sample processing plate or tube rack includes a top and a bottom, wherein the plate or tube rack includes open spaces between the wells on the bottom of the plate or between the sample tubes on the bottom of the tube rack.
  • the method includes moving magnets up and down from beneath and within the spaces between wells or sample tubes, wherein the magnetic material in the liquid is attracted to the magnets when they are in proximity of the magnetic material, thereby concentrating the magnetic material in the liquid.
  • the magnets are in the form of the magnetic rods or pins.
  • the magnetic material is in the form of magnetic affinity beads.
  • the sample processing plate or tube rack is configured above a platform that includes a plurality of the magnets configured to fit between the wells of the sample processing plate or between the sample tubes in the tube rack.
  • movement of the magnets is controlled by a control system that controls the magnets to concentrate the magnetic material in the wells or sample tubes.
  • the liquid in the well or sample tube includes one or more of biomolecules, nucleic acids, proteins, peptides, antibodies, antibody fragments, antibody-small molecule conjugates, enzymes, metabolites, structural proteins, tissues, seeds, cells, organelles, membranes, blood, plasma, saliva, urine, semen, oocytes, skin, hair, feces, cheek swabs, pap smear lysate, organic molecules, pharmaceutical compounds, bacteria, viruses, and nanoparticles.
  • the magnetic material is in the form of magnetic affinity beads that include an affinity ligand or moiety that binds to a component or compound in the liquid, and the method further includes aspirating liquid from the well or sample tube, thereby separating the bound component or compound from other components in the liquid.
  • the magnets include neodymium iron boron, samarium cobalt, alnico, ceramic, and/or ferrite.
  • the magnetic material in the liquid includes a ferromagnetic material selected from iron, cobalt, nickel, a rare earth metal, or an alloy thereof.
  • a method for mixing liquid in a well of a sample processing plate that includes a plurality of wells or in a sample tube in a tube rack that includes a plurality of sample tubes, wherein the sample processing plate or tube rack Includes a top and a bottom, wherein the plate or tube rack includes open spaces between the wells on the bottom of the plate or between the sample tubes on the bottom of the tube rack.
  • the method includes moving magnets up and down from beneath and within the spaces between wells or sample tubes, wherein the magnetic material in liquid is attracted to the magnets when they are in proximity of the magnetic material, thereby dispersing the magnetic material and mixing the liquid.
  • the magnets are in the form of the magnetic rods or pins.
  • the magnetic material is in the form of magnetic affinity beads.
  • the sample processing plate or tube rack is configured above a platform that includes a plurality of the magnets configured to fit between the wells of the sample processing plate or between the sample tubes in the tube rack.
  • movement of the magnets is controlled by a control system that controls the magnets to disperse the magnetic material, thereby mixing the liquid in the wells or sample tubes.
  • the liquid in the well or sample tube includes one or more of biomolecules, nucleic acids, proteins, peptides, antibodies, antibody fragments, antibody-small molecule conjugates, enzymes, metabolites, structural proteins, tissues, seeds, cells, organelles, membranes, blood, plasma, saliva, urine, semen, oocytes, skin, hair, feces, cheek swabs, pap smear lysate, organic molecules, pharmaceutical compounds, bacteria, viruses, and nanoparticles.
  • the magnets include neodymium iron boron, samarium cobalt, alnico, ceramic, and/or ferrite.
  • the magnetic material in the liquid includes a ferromagnetic material selected from iron, cobalt, nickel, a rare earth metal, or an alloy thereof.
  • Figures 1A and 1 B show two embodiments of magnet arrays for concentration of magnetic material in liquid and/or mixing of liquid in wells of a multiwell sample processing plate or in sample tubes in a tube rack.
  • Figure 2 shows an embodiment of a multiwell sample processing plate configured with a magnet array underneath the plate and configured such that the magnets fit and are movable within the interwell spaces of the plate, concentrating magnetic material in the wells of a multiwell sample processing plate.
  • Figures 3A, 3B, and 3C show an embodiment in which a magnet is moved up and gradually moved down alongside a well of a multiwell sample processing plate or a sample tube to concentrate and pull down magnetic material in liquid in the well or tube.
  • Figure 4 shows an embodiment in which a magnet is moved up and down alongside a well of a multiwell sample processing plate or a sample tube to disperse magnetic material in liquid in the well, thereby mixing the liquid in the well or tube.
  • the magnetic material is in the form of magnetic beads, e.g., magnetic affinity beads.
  • the magnets may be used to concentrate magnetic material, e.g., magnetic beads, at a specific location within the container, e.g., well or sample tube, facilitating removal of excess fluid and washing of the magnetic material. Further, since magnetic field strength is limited by distance, the closer the magnet is to the magnetic material, the better the attraction.
  • the magnetic field may be adjusted inside the container, e.g., well or sample tube, in real time by dynamically moving the magnets in relation to the top and bottom of the container, thereby mixing the magnetic material, e.g., magnetic beads, and consequently the liquid within the container, e.g., well or tube.
  • This may be used as an alternative to shaking or inverting, for example the container or, for example a multiwell sample processing plate or sample tube rack, which can result in splashing and cross-contamination between wells or tubes, or pipetting liquid up and down, which contacts the liquid, potentially resulting in contamination, and uses consumables (pipet tips).
  • Mixing of the liquid by movement of magnets up and down alongside the container, e.g., between wells of a multiwell plate or between sample tubes in a tube rack, as described herein, is a contactless mixing method that involves movement of the magnetic material in the container, e.g., wells or tubes, rather than the liquid.
  • magnetic material in liquid in a sample container may be concentrated by movement of one or more magnet alongside the container, such as between adjacent wells of a multiwell plate (e.g., from beneath the plate and up and down in the interwell space between adjacent wells) or between adjacent sample tubes in a tube rack (e.g., from beneath the tube rack and up and down between adjacent sample tubes), thereby concentrating the magnetic material in the liquid by attraction to the external magnet(s).
  • liquid containing magnetic material therein in a sample container such as, but not limited to, a well of a multiwell plate or a sample tube
  • a sample container such as, but not limited to, a well of a multiwell plate or a sample tube
  • liquid containing magnetic material therein in a sample container may be mixed by movement of one or more magnet alongside the container, such as between adjacent wells of a multiwell plate (e.g., from beneath the plate and up and down in the interwell space between adjacent wells) or between adjacent sample tubes in a tube rack (e.g., from beneath the tube rack and up and down between adjacent sample tubes), thereby dispersing the magnetic material in the liquid by attraction to the external magnet(s) and mixing the liquid.
  • Magnetics e.g, rods or pins that fit alongside a container for liquid, such as within interwell spaces of sample plates or between sample tubes in a tube rack
  • Suitable materials for this purpose include, but are not limited to, Neodymium Iron Boron, Samarium Cobalt, Alnico (e.g., iron alloys, which in addition to iron are composed primarily of aluminum, nickel, and cobalt, and also including copper and sometimes titanium), Ceramic or Ferrite magnets.
  • Magnetic material in liquid in a container may be moved by attraction to the magnets, for example magnets that fit within the interwell spaces of a multiwell sample processing plate or between sample tubes in a tube rack, may be, for example, in the form of magnetic beads, optionally coupled to functional groups, affinity ligands, antibodies or fragments thereof, or other reagents for binding or reaction with one or more compound(s) or component(s) in a liquid sample.
  • Suitable materials for this purpose include, but are not limited to, ferromagnetic materials such as iron, cobalt, nickel, some rare earth metals and various alloys of these materials.
  • magnetic affinity beads can bind to a target molecule within a liquid sample, i.e., the liquid contains a target molecule to which an affinity moiety on the magnetic beads binds.
  • Magnetic affinity beads may be added to the container, for example, wells or a multiwell sample processing plate or sample tubes, prior to, simultaneously with, or after addition of samples for analysis.
  • the affinity beads may be coated in antibodies, streptavidin, or cationic or anionic moieties.
  • the magnetic affinity beads are capable of separating one or more molecule(s) or component(s) of a sample from other components of the sample.
  • the magnetic material e.g. , magnetic beads
  • the magnetic material may contain an affinity reagent, ligand, or substance that may bind to or immobilize one or more components or moieties in a sample.
  • Magnetic material e.g., magnetic affinity beads, may contain one or more affinity moiety that is capable of binding to a target molecule when present in a liquid sample.
  • a plurality of liquid samples is analyzed or one or more target molecule(s) extracted from each liquid sample.
  • the plurality of samples includes blood or saliva.
  • method includes extraction of DNA from the plurality of samples using magnetic beads.
  • a sample input may include, but is not limited to, biomolecules, nucleic acids (including DNA or RNA), proteins, peptides, antibodies, antibody fragments, antibody-small molecule conjugates, enzymes, metabolites, structural proteins, tissues, seeds, cells, organelles, membranes, blood, plasma, saliva, urine, semen, oocytes, skin, hair, feces, cheek swabs, pap smear lysate, organic molecules, pharmaceutical compounds, bacteria, viruses, or nanoparticles.
  • nucleic acids including DNA or RNA
  • proteins proteins, peptides, antibodies, antibody fragments, antibody-small molecule conjugates
  • enzymes metabolites, structural proteins, tissues, seeds, cells, organelles, membranes, blood, plasma, saliva, urine, semen, oocytes, skin, hair, feces, cheek swabs, pap smear lysate, organic molecules, pharmaceutical compounds, bacteria, viruses, or nanoparticles.
  • magnetic material may be concentrated in any liquid sample container that has accessible space for a magnet, e.g., a magnetic rod or pin, along at least one side or surface on the outside of the container.
  • magnetic material may be concentrated in wells of a multiwell sample processing plate or in sample tubes in a tube rack.
  • a sample processing plate or sample tube rack is configured such that there is open space between the bottoms and at least a portion of the sides of adjacent wells of the plate, i.e., interwell spaces that are accessible from the bottom of the plate, or between adjacent sample tubes.
  • Magnets are configured to move up and down in the spaces between adjacent wells or tubes from beneath the plate or tube rack, thereby concentrating magnetic material in liquid in the wells or tubes by attraction to the external magnets.
  • a platform underneath a sample processing plate 240 is configured such that the magnets 230 may be moved up and down in the interwell spaces 244, thereby moving magnetic material 243, e.g., magnetic affinity beads, within the liquid 242 in the wells 241 and concentrating the magnetic material by attraction to the magnets.
  • the platform includes a plurality of magnets that are configured to fit into the open spaces between sample tubes in a tube rack, and the platform underneath the tube rack is configured such that the magnets may be moved up and down between the sample tubes, moving magnetic material, e.g., magnetic affinity beads, within the liquid in the sample tubes and concentrating the magnetic material by attraction to the magnets.
  • the magnets are used to concentrate magnetic material at a specific location within a container such as a well or sample tube, shown schematically in Figs. 3A-3C.
  • the magnets 230 may be moved slowly up and down alongside the container, for example, in the interwell space of a sample processing plate or between sample tubes, and then moved slowly down to concentrate the magnetic material 243, e.g., beads, in liquid 242, for example, at or near the bottom of the container, by attraction to magnet(s) on the outside of the container, e.g., well or sample tube. Movement of the magnets may be controlled by a control system.
  • liquid may be mixed in any liquid sample container that has accessible space for a magnet, e.g., a magnetic rod or pin, along at least one side or surface on the outside of the container.
  • Liquid containing magnetic material therein may be mixed by using one or more magnet(s) to disperse the magnetic material, thereby mixing the liquid.
  • magnetic material may be dispersed, mixing liquid in wells of a multiwell sample processing plate or in sample tubes in a tube rack.
  • a sample processing plate or sample tube rack is configured such that there is open space between the bottoms and at least a portion of the sides of adjacent wells of the plate, i.e., interwell spaces that are accessible from the bottom of the plate, or between adjacent sample tubes.
  • Magnets are configured to move up and down in the spaces between adjacent wells or tubes from beneath the plate or tube rack, thereby dispersing magnetic material in liquid in the wells or tubes that is attracted to the external magnets, thereby mixing liquid in the wells or tubes.
  • magnets are used to disperse magnetic material within a container such as a well or sample tube.
  • magnets 230 may be moved slowly to the top of the wells or sample tubes and then rapidly moved down to create a dispersion of the magnetic material 243 in the liquid 242.
  • Quick movement may be used to break the magnetic field and disperse the magnetic material 243, e.g., magnetic affinity beads.
  • the rate of movement of the magnet(s) may be adjusted depending on the amount of magnetic material and viscosity of liquid in the well or sample tube, thereby creating a uniform or substantially uniform dispersion of the magnetic material in the well or sample tube and facilitating contactless mixing of the liquid. Movement of the magnets may be controlled by a control system.
  • a multiwell sample processing plate or a sample tube rack is supported on or suspended above a platform that includes a plurality of magnets, e.g., magnetic pins or rods, 230 that are configured to fit into the open spaces between the wells or the sample tubes.
  • a platform that includes a plurality of magnets, e.g., magnetic pins or rods, 230 that are configured to fit into the open spaces between the wells or the sample tubes.
  • the platform includes a plurality of magnets each configured underneath a well of a sample processing plate or a sample tube when the plate or sample tube rack is supported on the platform.
  • the platform includes a plurality of magnets configured to move between in the interwell space from below a sample processing plate or configured to move between sample tubes from below a sample tube rack when the sample processing plate or sample tube rack is supported on the platform.
  • the magnets may be movable relative to the plate or tube rack.
  • the plate or tube rack may be movable relative to the magnets.
  • the plate or tube rack is stationary and the magnets are individually movable (e.g., in a vertical ("z") direction relative to a horizontal configuration of the sample processing plate or tube rack) or magnets covering sections of a plate may be movable together as a group, for example, half plate, quadrants, rows, columns, or other subsections of a plate or tube rack.
  • the plate or tube rack is configured on a support base that fits beneath the plate rack or tube and contains an array of magnets (e.g., pins or rods) that are configured to move within the interwell spaces of the plate or between sample tubes in the tube.
  • a cushioning material for example, rubber, may be provided between the outer edges of the sample processing plate or tube rack and the corresponding edges of the support base that the plate or tube rack fits within, to absorb vibration from movement of the magnets.
  • the magnets are fixedly mounted to a base plate which is configured to be moved relative to the sample processing plate or sample tube rack, to move the magnets between wells of the plate or between sample tubes.
  • the magnets are fixedly mounted to a base plate and the sample processing plate or sample tube rack is configured to be moved relative to the base plate, to move the magnets between wells of the plate or between sample tubes.
  • magnets may be movable via mechanical devices (e.g., springs) or via actuators (e.g., hydraulic, pneumatic, electrical, thermal, mechanical).
  • actuators e.g., hydraulic, pneumatic, electrical, thermal, mechanical.
  • the magnets are movable via an electronically controlled actuator mechanism.
  • an actuator is coupled to a spring for quick release in one direction.
  • a magnet array may be configured such that one magnet is used per well or sample tube to move magnetic material within liquid in the well or sample tube, or the array may be configured such that the well or sample tube is surrounded to two or more magnets.
  • a well or sample tube may be surrounded by two magnets that are 180 ° apart.
  • a well or sample tube is surrounded by four magnets that are 90 ° apart.
  • the platform that contains the magnet array or a platform that supports a platform that contains the magnet array may be configured to perform one or more function(s) with regard to a sample processing plate or sample tube rack supported thereon, such as, but not limited to, shaking, heating, and/or cooling.
  • the platform includes tip-tilt mechanism.
  • the methods described herein are applied to concentration of magnetic material (e.g., pulling magnetic material to the bottom or near the bottom of wells) and/or mixing of liquid in wells of multiwell sample processing plates.
  • sample processing plates e.g., plates that include a plurality of wells, may be used, including, but not limited to, a 6-well plate, a 12-well plate, a 24-well plate, a 48-well plate, a 96-well plate, a 192-well plate, a 384-well plate, a 1536-well plate, or a multi-well plate capable of holding any number of separated samples.
  • maximum well volume of the sample processing plate may be about 18 microliters, about 250 microliters, about 1.1 milliliters, about 2.2 milliliters, about 5 milliliters, or about 10 milliliters.
  • the sample processing plate is configured such that there is open space between the bottoms and at least a portion of the sides of adjacent wells of the plate, i.e., having interwell space that is accessible from the bottom of the plate.
  • magnetic material e.g., magnetic affinity beads
  • magnetic material is pre-loaded into the sample processing plate prior to transferring of a liquid sample into the sample processing plate.
  • magnetic material e.g., magnetic affinity beads
  • the methods described herein are applied to concentration of magnetic material (e.g., pulling magnetic mate ial to the bottom or near the bottom of sample tubes) and/or mixing of liquid in sample tubes in a tube rack.
  • sample tubes may be used that are capable of holding any number of separated samples.
  • the sample tubes are conical.
  • the sample tubes are Vacutainer ® or similar tubes (i.e., sterile glass or plastic tubes, e.g., round bottom tubes, with a closure, such as a rubber stopper, such that the tubes may be evacuated to create a vacuum inside the tube, thereby facilitating the draw of a predetermined amount of liquid, such as a biological sample).
  • the sample tubes may be configured to contain 5 ml, 15 ml, or 50 ml liquid volumes.
  • the tube rack is configured such that there is open space between the bottoms and sides of adjacent sample tubes, i.e., having space between tubes that is accessible from the bottom of the tube rack.
  • magnetic material e.g., magnetic affinity beads
  • magnetic mate ial e.g., magnetic affinity beads
  • magnetic affinity beads is not pre-loaded into the sample tubes, but is added simultaneously with or after transferring a liquid sample into the sample tubes. Separation of magnetic material from liquid
  • concentration of the magnetic material using magnets as described herein may be used for separation of the magnetic material from the liquid in the container, e.g. , well or sample tube.
  • the magnetic base forces the magnetic affinity beads to a desired location within the container, e.g., well or sample tube, such as the bottom or near the bottom of the sample wells or tubes.
  • the magnetic force holding the magnetic material may avoid or reduce the suction force of aspiration, e.g., aspiration with liquid aspiration nozzles.
  • the magnets as described herein may be used to concentrate and immobilize magnetic affinity beads prior to aspiration of the liquid from the wells or sample tubes.
  • each well of the sample processing plate or each tube in a tube rack includes magnetic affinity beads that can bind to a target molecule within a liquid sample.
  • the magnetic affinity beads may be added to the wells or tubes prior to, simultaneously with, or after addition of liquid samples for analysis.
  • the magnetic affinity beads may be coated in antibodies or fragments thereof, streptavidin, or cationic or anionic moieties.
  • the magnetic affinity beads are pre-loaded into wells of the sample processing plate prior into sample tubes prior to transferring of the liquid sample into wells of the sample processing plate or into the sample tubes.
  • the magnetic affinity beads are not pre-loaded into wells of the sample processing plate or into sample tubes, but are added after transferring of the liquid sample into wells of the sample processing plate or into the sample tubes, for example, via a liquid dispensing apparatus.
  • one or more affinity reagent(s) may be used that bind to target molecule(s) when present in a liquid sample.
  • Affinity reagent(s) may include, but are not limited to, antibodies, peptides, nucleic acids, or other small molecules that specifically bind to a target molecule or substance.
  • An affinity reagent may produce a detectable signal when bound to a target molecule or substance, or a secondary reagent may be added that produces a signal when bound to or when interacting with the affinity reagent that is bound to the target or that produces a signal when bound to or interacting with the target when separated from other components of a sample.
  • one or more affinity reagent(s) may be attached to the magnetic beads, which may be separated from other components of the sample using magnets to concentrate the magnetic beads, as described herein.
  • a further liquid reagent may be dispensed that contains a molecule or substance that produces a signal when in contact with a target molecule if bound to the affinity reagent(s).
  • Nonlimiting examples of reagents that may be used for signal detection include ROX (carboxy-X-rhodamine) for volume measurement, and pico green or broad range dyes for DNA quantification.
  • a system for concentrating magnetic material in liquid and/or mixing liquid, for example, in wells of a multiwell sample processing plate or in sample tubes in a tube rack, may be integrated with a system for liquid handling in which any of a number of other operations on liquid are performed, for example, but not limited to, dispensing liquid, aspirating liquid, detecting a signal in liquid or in a container that previously contained liquid, and/or sensing a parameter such as liquid level and/or temperature, .
  • a system e.g., a system with magnets or a magnet array as described herein
  • a system for concentrating magnetic material in liquid and/or mixing liquid for example, in wells of a multiwell sample processing plate or in sample tubes in a tube rack
  • a system for liquid handling in which any of a number of other operations on liquid are performed, for example, but not limited to, dispensing liquid, aspirating liquid, detecting a signal in liquid or in a container that previously contained liquid, and/or sensing a parameter such as liquid
  • the system includes at least one device that dispenses liquid and at least one device that aspirates liquid.
  • the system includes at least one device that dispenses liquid, at least one device that aspirates liquid, and at least one device that senses a parameter in wells of a sample processing plate or in sample tubes. In some embodiments, the system includes at least one device that dispenses liquid, at least one device that aspirates liquid, and at least one device that detects a signal in wells of a sample processing plate or in sample tubes. In some embodiments, the system includes at least one device that dispenses liquid, at least one device that aspirates liquid, at least one device that senses a parameter in wells of a sample processing plate or in sample tubes, and at least one device that detects a signal in wells of the sample processing plate or in sample tubes.
  • a liquid handling system includes at least one device that is configured to dispense magnetic affinity beads in liquid into wells of a sample processing plate or into sample tubes.
  • the affinity beads may include, for example, one or more affinity moiety that is capable of binding to a target molecule when present in a sample.
  • the affinity beads are capable of separating one or more molecule(s) or component(s) of a sample from other components of the sample.

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Abstract

La présente invention concerne des procédés de concentration de matériau magnétique, tel que des billes d'affinité magnétique, dans des échantillons liquides dans des récipients d'échantillon tels que des puits de plaques de traitement d'échantillon multipuits ou de tubes d'échantillon. L'invention concerne en outre des procédés de dispersion d'un matériau magnétique dans des échantillons liquides pour effectuer le mélange du liquide. Les procédés de l'invention comprennent le déplacement d'aimants, tels que des tiges ou des broches magnétiques, pour concentrer ou disperser un matériau magnétique, tel que le déplacement d'aimants dans des espaces inter-puits d'une plaque multipuits ou dans des espaces entre des tubes à échantillons dans un portoir de tubes.
PCT/US2017/043810 2016-08-06 2017-07-25 Concentration et mélange sans contact de matériau magnétique dans un liquide WO2018031232A1 (fr)

Applications Claiming Priority (2)

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US201662371752P 2016-08-06 2016-08-06
US62/371,752 2016-08-06

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WO2018031232A1 true WO2018031232A1 (fr) 2018-02-15

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CN113218740A (zh) * 2021-06-04 2021-08-06 苏州四正柏生物科技有限公司 多因子检测样本前处理装置
WO2021203005A1 (fr) * 2020-04-03 2021-10-07 Beckman Coulter, Inc. Ensembles électromagnétiques pour traiter des fluides
WO2024163768A3 (fr) * 2023-02-03 2024-09-12 Somalogic Operating Co., Inc. Systèmes et procédés de séparation magnétique de mélanges

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Publication number Priority date Publication date Assignee Title
WO2021203005A1 (fr) * 2020-04-03 2021-10-07 Beckman Coulter, Inc. Ensembles électromagnétiques pour traiter des fluides
CN115551641A (zh) * 2020-04-03 2022-12-30 贝克曼库尔特有限公司 用于处理流体的电磁组件
CN113218740A (zh) * 2021-06-04 2021-08-06 苏州四正柏生物科技有限公司 多因子检测样本前处理装置
WO2024163768A3 (fr) * 2023-02-03 2024-09-12 Somalogic Operating Co., Inc. Systèmes et procédés de séparation magnétique de mélanges

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