WO2003086637A1 - Immunoassay probe - Google Patents
Immunoassay probe Download PDFInfo
- Publication number
- WO2003086637A1 WO2003086637A1 PCT/US2003/011157 US0311157W WO03086637A1 WO 2003086637 A1 WO2003086637 A1 WO 2003086637A1 US 0311157 W US0311157 W US 0311157W WO 03086637 A1 WO03086637 A1 WO 03086637A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- probe
- magnet
- magnetizable
- particles
- magnetic field
- Prior art date
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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
- B03C1/02—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
- B03C2201/26—Details of magnetic or electrostatic separation for use in medical applications
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S436/00—Chemistry: analytical and immunological testing
- Y10S436/807—Apparatus included in process claim, e.g. physical support structures
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/11—Automated chemical analysis
- Y10T436/113332—Automated chemical analysis with conveyance of sample along a test line in a container or rack
Definitions
- This invention relates to clinical diagnostic assays, in particular, immunoassays utilizing magnetizable particles and methods thereof.
- Immunoassays such as chemiluminescent immunoassays, generally require two antibody preparations, a first antibody used to capture and immobilize a target antigen molecule, and a second antibody used to attach a detection label to the antigen.
- Immobilization of the antigen to be detected in an immunoassay may be accomplished using magnetizable beads, and detection may be accomplished by using a suitable visualant such as isoluminol chemiluminescence.
- the assay involves the following major steps. For example, a sample containing the antigen is mixed with a first antibody to the antigen which is coupled to magnetizable latex beads, and the mixture is allowed to react. A second antibody, typically to a different epitope on the antigen, coupled to isoluminol, is added to the sample in step 1 and the mixture is allowed to react. A magnetic field is applied to retain the magnetizable beads (with antigen bound, labeled antibody) against the inside wall of the container.
- a wash fluid is introduced to remove the unbound labeled antibody. Washing the magnetizable beads typically occurs by immobilizing the beads in the magnetic field, introducing a wash fluid, removing the magnetic field, and repeatedly expelling beads into and aspirating the beads from a container to recover all of the beads and to homogeneously mix and resuspend the beads in the wash fluid.
- the magnetizable beads with antigen bound, labeled antibody are resuspended in a suitable optical cuvette.
- An activating reagent such as hydrogen peroxide which activates isoluminol is added with the beads in the cuvette and light is emitted in a chemiluminescent reaction. The light emitted from the chemiluminescent reaction is detected using a suitable photodetector. For some applications, additional steps of reagent addition and/or washing may be necessary.
- the invention described herein features an analytical instrument including a probe with a reservoir, a dilutor assembly for introducing fluid containing magnetizable particles into the probe reservoir, and a plurality of magnetic devices for applying a magnetic field gradient to the particles in the probe reservoir.
- the analytical instrument has a magnetic washing station and a sampling station.
- the probe containing magnetic particles in the probe reservoir is moved into the magnetic washing station, that includes the magnets.
- the magnets include, for example, at least a first magnet and a second magnet, the second magnet having a magnetic field of different magnitude than the first magnet.
- Other magnetic devices are contemplated by the invention, such as one or more solenoid coils, and are not limited to the magnetic devices decried herein.
- the invention includes a device for manipulating a magnetizable particle in a fluid medium.
- the device may be used in an analytical instrument for determining the presence or measuring the quantity of an analyte in body fluids.
- the device includes a probe for holding and transporting the magnetizable particles and the probe is transportable to a plurality of positions.
- the device further includes a first magnet for generating a first magnetic field, and a second magnet for generating a second magnetic field.
- the probe is moveable in a plurality of probe positions between the first and second magnets. At least one of the probe positions immobilizes the magnetic particles in the fluid medium and at least another position resuspends the particles in a fluid medium.
- the magnetizable beads are immobilized against an inner wall of the probe.
- the inner wall of the probe may be curved or flat.
- the magnitude of the first magnetic field is different than the magnitude of the second magnetic field.
- the first magnet is in the range of about 1 to 5 times the strength of the second magnet.
- the first magnet is in the range of about 1 to 2 times the strength of the second magnet.
- the first magnet is separated from the second magnet by a gap in the range of about 1/16 inch to 40 inches, preferably, 1.5 to 2.5 inches, more preferably 1.95 inches.
- the device has a transport stage for moving the probe between the plurality of probe positions.
- the transport stage may also move the probe between a sample station and a magnetic washing station.
- the probe has a thermal control element, and/or a liquid sensing element.
- the device has a dilutor assembly for introducing a fluid from a fluid reservoir into the probe reservoir through the top end of the probe.
- the top end of the probe is opposite to an end of the probe used for receiving a sample.
- the dilutor assembly introduces fluid to the sample end of the probe.
- the invention is a method for washing a magnetizable particle including the steps of aspirating a fluid sample comprising magnetizable particles into a probe.
- the probe has a top end that is opposite to an end of said probe for receiving a sample.
- the probe is transported by the transport stage to a magnetic washing station.
- the magnetic washing station has a first magnet for generating a first magnetic field and a second magnet for generating a second magnetic field.
- the probe is moved in the magnetic washing station to a capture position, and then to a resuspend position.
- the magnetizable particles are expelled from the probe.
- the resuspend position is closer to the second magnet than the neutral position.
- the lumen of the probe is flushed in the capture position with a diluent from a diluter assembly.
- the diluent for flushing may be introduced at a second end of the probe and expelled at a first end of the probe.
- the magnetizable particles are expelled into a container which may be a microtiter well.
- the magnetizable particles are incubated with a body fluid and/or an immunoassay is performed.
- FIG. 1 illustrates an embodiment of the device according to the invention.
- FIGS. 2A-2D illustrates in cross-section, various embodiments of the probe according to the invention.
- FIG. 3 illustrates one embodiment of the relative positioning of a first magnet to a second magnet in the magnetic washing station according to the invention.
- FIGS. 4A-4D illustrate various positions of the probe as the probe is moved by the transport stage.
- FIG. 5 is a graphic illustration of the relative force on a magnetizable bead as a function of the position of the bead between two magnets.
- FIGS. 6A-6B illustrate the steps according to one embodiment of the invention for aspirating a sample with magnetizable beads into the probe.
- FIG. 7 A illustrates one embodiment of the transport stage joined to the probe positioned in the sampling station.
- FIG. 7B illustrates the transport stage joined to the probe positioned over the magnetic washing station.
- FIG. 7C illustrates one embodiment of the probe in the neutral position of the magnetic washing station.
- FIG. 7D illustrates one embodiment of the probe in the capture position of the magnetic washing station.
- FIG. 7E illustrates one embodiment of the probe in the resuspend position of the magnetic washing station.
- FIG. 7F illustrates one embodiment for dispensing the magnetizable particles from the probe reservoir through the probe sample end into a container.
- FIG. 8 A illustrates the distribution of the magnetizable particles in the probe reservoir when the probe is in the neutral position in the magnetic washing station as viewed from the top of the magnetic washing station.
- FIG. 8B illustrates the distribution of magnetizable particles when the probe is in the capture position in the magnetic washing station as viewed from the top of the magnetic washing station.
- FIG. 8C illustrates the distribution of magnetizable particles when the probe is in the resuspend position in the magnetic washing station, as viewed from the top of the magnetic washing station.
- FIG. 9 illustrates one embodiment of the probe according to the invention.
- FIG. 10A illustrates one embodiment of a cross-section of the probe and the distribution of magnetizable particles in the probe reservoir when the probe is moved from the neutral position to the capture position in the magnetic washing station.
- FIG. 10B illustrates the probe and the position of the magnetizable particles following a short dwell time in the capture position in the magnetic washing station.
- FIG. 10C illustrates the probe and the position of the magnetizable particles when the dwell time of the probe in the capture position is longer than the dwell time of the probe in the capture position illustrated in FIG. 10B.
- FIG. 11 A illustrates another embodiment of a cross-section of the probe and the distribution of the magnetizable particles in the probe reservoir when the probe is moved from the neutral position to the capture position in the magnetic washing probe.
- FIG. 1 IB illustrates the probe and the position of the magnetizable particles following a short dwell time in the capture position in the magnetic washing station.
- FIG. 11C illustrates the probe and the position of the magnetizable particles when the dwell time of the probe in the capture position is longer than the dwell time of the probe in the capture position illustrated in FIG. 1 IB.
- the invention is a device, such as a clinical analytical instrument, including a washing probe for use in analyzing fluids, such as blood, in assays using magnetizable particles.
- a transportable probe that has a reservoir for holding a fluid medium containing a plurality of magnetizable particles, at least two magnets, and a probe transport stage.
- the probe is moveable by the transport stage in a plurality of positions with respect to at least one magnet.
- the plurality of probe positions with respect to at least one magnet repositions the magnetizable particles in the probe reservoir between at least a capture position and a resuspend position.
- the invention is a device having a probe that serves as a reservoir for washing, rinsing, or otherwise manipulating magnetizable particles, such as beads, in a fluid medium such as a suspension or a solution.
- the device 6 includes a probe assembly 30, a sampling station 20 and a magnetic washing station 40.
- the probe assembly 30 has a probe 10 in combination with a dilutor assembly 15, flexible tubing 25, and transport stage 35.
- the probe 10, illustrated in FIG. 1 is generally a hollow tube having a top end 12, a sample end 14 opposite to the top end 12, a reservoir 16 extending along at least a portion of the length of the probe 10 from the top end 12 to the sample end 14, and at least one probe wall 18.
- the probe 10 is substantially straight, rigid and has a round cross-section.
- a cross-section of the probe 10 is polygonal and at least one wall of the probe 10 is flat.
- a cross-section of the probe 10 is round, oval, or D-shaped.
- the sample end 14 of the probe may terminate in a nozzle 17, illustrated in FIG. 1, having a cross-sectional diameter that is smaller than the reservoir 16 of the probe 10.
- the nozzle 17 increases the velocity of the fluid expelled from the sample end 14 of the probe 10.
- the shape of the probe 10 is not limited to those illustrated and may include other shapes.
- the probe 10 may be manufactured from non-magnetic materials such as glass, plastic, ceramics, composite materials, metals, metal alloys, or other materials known to one skilled in the art.
- the probe 10 may be manufactured from one material and clad in another material or may be made from multiple layers of the same material.
- the dilutor assembly 15 is operatively joined to the top end 12 of the probe 10 by tubing 25, such as flexible tubing.
- the dilutor assembly 15, for example, is a syringe pump with a rotary directional valve.
- the dilutor assembly 15 pumps fluid such as a diluent or a wash fluid from a container (not shown) into the tubing 25, through the top end 12 of the probe 10, into the reservoir 16 of the probe 10, and dispenses the fluid out of the probe 10 through the sample end 14.
- the syringe pump may be optionally ported via the flexible tubing 25 to the probe 10, or to a container of fluid (not shown) upstream from the probe 10.
- the dilutor assembly 15 may also be an aspirator for aspirating fluid, for example, sample fluid such as body fluids, through the sample end 14 of the probe 10 into the reservoir 16 of the probe 10.
- the tubing 25 connecting the dilutor assembly 15 to the probe 10 is manufactured from polytetrafiuoroethylene, rubber, polyvinylchloride, polyethylene, or other materials known in the art.
- the probe assembly 30 further includes a transport stage 35 to which the probe 10 is joined.
- the three axis transport stage 35 moves the probe 10 in a plurality of directions including at least bi-directional horizontal and bi-directional vertical movement.
- the transport stage 35 may have a vertical motion that moves the probe 10 vertically, a horizontal motion that moves the probe 10 horizontally and/or a rotary motion that swings the probe 10 in an arc.
- the magnetic washing station 40 has a plurality of magnets fixed in position relative to each other.
- the magnetic washing station 40 has two permanent rectangular magnets 50, 51, i.e., a first magnet 50 generating a first magnetic field, and a second magnet 51 generating a second magnetic field.
- the first magnet 50 and the second magnet 51 have different strengths and generate magnetic fields of unequal magnitude.
- the first magnet 50 is stronger than the second magnet 51, i.e., the magnetic field generated by the first magnet 50 is greater in magnitude than the magnetic field generated by the second magnet 51.
- the first magnet 50 may be 1 -5 times as strong as the second magnet 51, preferably 1-2 times as strong.
- the magnets 50, 51 are mounted vertically and parallel to each other, with like poles of the magnets 50, 51 facing each other and separated by an air gap 53.
- the gap 53 separating the first " magnet 50 from the second magnet 51 is in the range of one-sixteenth inch to 40 inches, in particular, 1.5 to 2.5 inches. In another embodiment, the gap 53 is determined to be 2.5 times to 1000 times the diameter of the probe 10.
- the magnets 50, 51 are NeFeB magnets with magnetic faces 2.8 inches high and 0.5 inches wide.
- the air gap indicated by arrow 53 between the face of the strong magnet 50 and the face of the weak magnet 51 is 1.95 inches.
- the resultant flux density at any point on the central axis between the magnets is calculated as the algebraic sum of the flux densities from each individual magnet.
- the transport stage 35 moves the probe 10 from a sample station (not shown) to a position above the magnetic washing station 40.
- the probe 10 is lowered by the transport stage 35 to a neutral position 80 between the first magnet 50 and the second magnet 51.
- the neutral position 80 is a position along a line drawn perpendicular to the face of the first magnet 50 and the face of the second magnet 51 where the resultant magnetic force on a magnetizable particle 100 is zero in the resultant magnetic field B generated by the first magnet 50 and the second magnet 51.
- the neutral position 80 is a position of the probe 10 in the magnetic washing station where the probe 10 is closer to the weaker magnet 51, i.e., the magnet generating a weaker magnetic field, for example as shown in FIG. 4B, than to the stronger first magnet 50.
- the transport stage 35 moves the probe 10 from the neutral position 80 to a capture position 60.
- the capture position 60 is adjacent the stronger magnet 50 where the strength of the magnetic field of the first magnet 50 relative to the second magnet 51 is greatest.
- the transport stage 35 moves the probe 10 from the capture position 60 to a resuspend position 70.
- the probe 10 in the resuspend position 70 is closer to the second magnet 51 than is the probe 10 in the capture position 60 or the neutral position 80.
- the force of the magnetic field generated by the second magnet 51 is greater than the force of the magnetic field on a magnetizable particle 100 in the probe 10 generated by the first magnet 50.
- the overall force of the magnetic field is closer to zero in the resuspend position 70 than in the capture position 60.
- the capture position 60 is 4.2 mm from the first magnet 50
- the neutral position 80 is 22 mm from the second magnet 51
- the resuspend position 70 is 14 mm from the second magnet 51.
- the invention is a method for immobilizing and washing magnetizable beads 100 in, for example, an automated instrument for performing an immunoassay.
- the probe 10 is positioned at the sampling station 20, illustrated in FIG. 6A, at a position external to the magnetic washing station 40, and the sample end 14 of the probe 10 is lowered into a container such as a well in a microtiter plate until the sample end 14 of the probe 10 meets a fluid sample containing magnetizable particles 100.
- negative pressure generated by the dilutor assembly 15 causes an aliquot of fluid containing magnetizable particles 100 to be aspirated through the sample end 14 of the probe 10 and into the reservoir 16 of the probe 10.
- the magnetizable particles 100 are made from a material that may be attracted to a magnet. Such materials include, for example, iron, iron oxide and other such materials known to the skilled person.
- the particle 100 is a magnetizable latex particle having an iron oxide core surrounded by a polystyrene shell that is coated with a polymer bearing functional groups to which an antibody, or variants thereof, can be attached, for example, 280 nanometer DynabeadsTM M-280 Sheep anti Mouse IgG, (DYNAL, Inc., Lake Successful, New York).
- the magnetizable particles 100 may be paramagnetic particles, typically 1-20 ⁇ m in size having a composition including ion oxides and various other materials, e.g., agarose or cellulose which may also have functional group, e.g., aminosilanes, for antibody attachment (Advanced Magnetics, Inc., Cambridge, Massachusetts).
- the fluid in which the magnetizable particle 100 is suspended may be a body fluid, such as blood, containing an analyte of interest, a wash fluid a diluent, or a fluid containing a visualant such as fluorescein, rhodamine, gold particles, horseradish peroxidase, isoluminol, a labelled molecule such as a labelled antibody, an unlabelled antibody, variants thereof, or other compounds directed to the analyte of interest.
- a body fluid such as blood, containing an analyte of interest, a wash fluid a diluent, or a fluid containing a visualant such as fluorescein, rhodamine, gold particles, horseradish peroxidase, isoluminol, a labelled molecule such as a labelled antibody, an unlabelled antibody, variants thereof, or other compounds directed to the analyte of interest.
- the probe 10 holding the magnetizable particles 100 and the sample fluid in the probe reservoir 16 is moved by the transport stage 35 from the sampling station 20 , as indicated by arrow (a), to a position above the magnetic washing station 40, illustrated in FIG. 7B.
- the transport stage 35 moves the probe 10 as indicated by the arrow (a) into the neutral position 80 of the magnetic washing station 40, illustrated in FIG. 7C, such that the probe reservoir 16 is positioned in the area between the first magnet 50 and the second magnet 51 and the sample end 14 of the probe 10 is substantially outside of the magnetic field generated by the first magnet 50 and the second magnet 51.
- the calculated relative force on a magnetizable particle in a magnetic field B between magnet 50 and magnet 51 is proportional to BdelB, the product of the field strength times the field gradient.
- BdelB the calculated relative force on a magnetizable particle 100 is graphically illustrated as a function of the neutral position 80 of the probe 10 in the magnetic washing station 40.
- the relative force BdelB on a magnetizable particle 100 in the neutral position 80 is zero, i.e., the relative force of the resultant magnetic fields generated by the first magnet 50 and the second magnet 51 in the neutral position 80 does not favor movement of the magnetizable particle 100 toward the first magnet 50 or the second magnet 51.
- the capture position 60 is adjacent the first magnet 50 when the magnetizable particles 100 are in the capture position 60, they are positioned in the magnetic field of greatest magnitude generated by the first magnet 50.
- the calculated relative force on a magnetizable particle 100 is a function of the capture position 60 of the probe 10 in the magnetic washing station 40.
- the relative force BdelB generated by the first magnet 50 and the second magnet 51 on a magnetizable particle in a position between the neutral position 80 and the capture position 60 favors movement of the magnetizable particle 100 in the direction of the first magnet 50.
- FIG. 5 illustrates that the relative force BdelB in the (positive) direction of the first magnet 50 is maximal in the capture position 60.
- the transport stage 35 joined to the probe 10 holding the magnetizable particles 100 in the probe reservoir 16 moves the probe 10 in a horizontal plane from the capture position 80 into the resuspend position 70.
- the resuspend position 70 is closer to the second magnet 51 than the neutral position 80 or the capture position 60.
- the calculated relative force on a magnetizable particle 100 is graphically illustrated as a function of the resuspend position 70 of the probe 10 in the magnetic washing station 40.
- the relative force BdelB generated by the first magnet 50 and the second magnet 51 on a magnetizable particle 100 in a position between the neutral position 80 and the second magnet 51 favors movement of the magnetizable particle 100 in the direction of the second magnet 51.
- FIG. 7E illustrates the resuspend position 70 is any position between the neutral position 80 and the second magnet 51 where the relative force BdelB is in the direction of the second magnet 51.
- the dilutor assembly 15 expels the magnetizable particles 100 from the probe reservoir 16 through the sample end 14 of the probe 10 into a container.
- FIGS. 8A-8C illustrate the distribution of the magnetizable particles 100 in the probe reservoir 16 when the probe 10 is in the probe neutral position 80, the probe capture position 60, and the probe resuspend position 70. Illustrated in FIG. 8 A, as viewed from the top of the probe 10, in the neutral position 80 the magnetizable particles 100 are distributed randomly in the fluid medium of the probe reservoir 16. Referring now to FIG. 8B, in the capture position 60, the magnetizable particles 100 move from their free random distribution in the probe neutral position, to an immobilized position on the inside of the wall 18 on the side of the probe 10 that is closest to the first magnet 50. Referring now to FIG.
- the magnetizable particles 100 move away from their immobilized position on the side of the probe 10.
- the magnetizable particles 100 move away from the wall 18 where the particles 100 were immobilized in the capture position 60, and become suspended and dispersed in the fluid medium of the probe reservoir 16.
- the dwell time is brief enough to prevent the particles from being captured on the opposite side of the probe wall 18.
- the invention described herein has several advantages over known devices that resort to steps that repeatedly expel and aspirate the magnetizable particle mixture in and out of the probe 10 through the probe sample end 14 in order to mix and resuspend the magnetizable particles 100 in the fluid medium.
- the invention described herein minimizes the volume of fluid required to wash the magnetizable particles 100 because the particles 100 are resuspended in the wash fluid without requiring the step-by-step addition of successive volumes of wash fluid in order to flush the particles 100 from the probe lumen.
- the washing step described herein is faster than washing steps that repeatedly expel and aspirate the magnetizable particle mixture in and out of the probe. Aerosolizing the wash fluid is also minimized according to the method of the invention because it is not necessary to forcefully expel the particles in the wash fluid from the probe in order to resuspend the particles. Minimizing aerosol is particularly important when body fluids which may harbor pathogens are sampled by the probe.
- immobilization of the magnetizable particles 100 held within the probe reservoir 16 is accomplished by a tandem capture method.
- the length of the reservoir 16 in probe 10, illustrated in FIG. 9, is the sum of the length of the first portion 11 of the probe reservoir 16 which corresponds to the height h of the first magnet 50, plus the length of the second portion 9 of the probe reservoir 16 which corresponds to the length of the probe reservoir 16 in excess of the length of the first portion 11.
- magnetizable beads 100 are aspirated into and fill the length of the probe reservoir 16.
- the probe reservoir is moved adjacent the first magnet 50 into the capture position 60.
- the magnetizable beads 100 in the first portion 11 are in the magnetic field of the first magnet 50.
- the magnetizable beads 100 in the first portion 11 of the probe reservoir 16 are immobilized by the magnetic field of the first magnet 50 on the inner wall of the first portion 11 of the probe reservoir 16.
- the magnetizable beads 100 in the second portion 9 of the probe reservoir 16 are introduced by the dilutor assembly 15 from the second portion 9 into the first portion 11. Once the beads 100 from the second portion 9 are in the magnetic field of the first magnet 50, the beads 100 are immobilized on the im er wall 18 of the first portion 11 of the probe reservoir 16.
- the shape of the probe 10 in cross-section may vary from round to polygonal.
- the probe 10 has a round cross section as shown in FIGS. 10A- 10C.
- the magnetizable particles 100 are randomly distributed in the probe reservoir 16 when the round probe 10 is in the neutral position 80, illustrated in FIG. 10A.
- the magnetizable particles 100 tend to move toward the rectangular magnet 50 as indicated by the arrows shown in FIG. 10 A.
- the magnetizable particles 100 accumulate on the portion of the inside circumference of the wall 18 that is closest to the first magnet 50, illustrated in FIG. 10B.
- the magnetizable particles 100 tend to migrate to and aggregate at a point on the inside wall 18 of the probe 10 closest to the first magnet 50, as illustrated in FIG. IOC.
- the probe 10 has a "D" shape cross-section as shown in FIGS. 11A-1 lC.
- the wall 18 of the probe reservoir 16 closest to the rectangular magnet 50 is substantially flat, i.e., a cross section through the probe reservoir 16 is "D" shaped with the flat side of the "D" nearest the first magnet 50.
- the magnetizable particles 100 are randomly distributed in the probe reservoir 16 when the probe 10 is in the neutral position 80, illustrated in FIG. 10A.
- the magnetizable particles 100 tend to distribute uniformly across the inside flat surface of the wall 18 of the probe, illustrated in FIG. 1 IB. With increasing dwell time in the capture position 60, the magnetizable particles 100 tend to remain distributed relatively uniformly, as described above, on the inside wall 18 of the probe 10 closest to the rectangular magnet 50, illustrated in FIG. 1 lC.
- the invention is a method for washing a magnetizable particle 100 used in an assay for detecting an analyte, such as in an immunoassay.
- an antibody directed to the analyte of interest is bound to a magnetizable particle 100, such as a magnetizable bead, and mixed with an aliquot of a sample, such as blood.
- the sample and magnetizable beads 100 are aspirated through the ⁇ sample end 14 of the probe 10 into the probe reservoir 16.
- the probe 10 holding the sample and the magnetizable beads 100 is raised by the transport stage 35 and moved to the magnetic washing station 40 over the two magnets 50, 51.
- the probe 10 is lowered by the transport stage 50 between the two magnets 50, 51 into the neutral position 80.
- the probe 10 is then moved horizontally by the transport stage 35 into the capture position 60.
- the magnetizable beads 100 bound to the antibody directed to the analyte of interest in the blood sample are immobilized in the probe reservoir 16 by the magnetic field of the first magnet 50.
- a wash fluid is introduced by the dilutor assembly 15 through the tubing 25 and into the top 12 of the probe 10 and expelled through the sample end 14.
- the probe is moved horizontally to the resuspend position 70 where the magnetizable beads 100 are resuspended and mixed in the fluid before the mixture containing the magnetizable particles 100 is expelled through the sample end 14 of the probe 100.
- the probe 100 is moved by the transport stage 35 back to the sample station 20 to pick up another sample.
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
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JP2003583638A JP2005522679A (en) | 2002-04-12 | 2003-04-10 | Immunoassay probe |
CA002481545A CA2481545A1 (en) | 2002-04-12 | 2003-04-10 | Immunoassay probe |
AU2003226075A AU2003226075B2 (en) | 2002-04-12 | 2003-04-10 | Immunoassay probe |
EP03746724A EP1494814A1 (en) | 2002-04-12 | 2003-04-10 | Immunoassay probe |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US37233102P | 2002-04-12 | 2002-04-12 | |
US60/372,331 | 2002-04-12 |
Publications (1)
Publication Number | Publication Date |
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WO2003086637A1 true WO2003086637A1 (en) | 2003-10-23 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/US2003/011157 WO2003086637A1 (en) | 2002-04-12 | 2003-04-10 | Immunoassay probe |
Country Status (6)
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US (1) | US7514270B2 (en) |
EP (1) | EP1494814A1 (en) |
JP (1) | JP2005522679A (en) |
AU (1) | AU2003226075B2 (en) |
CA (1) | CA2481545A1 (en) |
WO (1) | WO2003086637A1 (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2008075287A2 (en) * | 2006-12-20 | 2008-06-26 | Philips Intellectual Property & Standards Gmbh | Method and arrangement for separating magnetic particles, magnetic particles and use magnetic particles |
US7731899B2 (en) | 2007-02-08 | 2010-06-08 | Biokit, S.A. | Apparatus and methods for dispensing sample holders |
EP2208531A1 (en) | 2008-12-30 | 2010-07-21 | Atonomics A/S | Distribution of particles in capillary channel by application of magnetic field |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070207272A1 (en) * | 2006-03-03 | 2007-09-06 | Puri Ishwar K | Method and apparatus for magnetic mixing in micron size droplets |
US20080188176A1 (en) * | 2007-02-07 | 2008-08-07 | Hunt John W | Roof vent shield |
DE102007039899B3 (en) * | 2007-08-23 | 2009-04-09 | Siemens Ag | Sensor for enabling the detection of a substance in the body of a living being |
JP5319672B2 (en) * | 2008-06-12 | 2013-10-16 | 株式会社日立ハイテクノロジーズ | Analyzer using magnetic particles |
US10416046B2 (en) * | 2013-04-11 | 2019-09-17 | Rarecyte, Inc. | Device, system, and method for selecting a target analyte |
US10072927B2 (en) | 2016-01-07 | 2018-09-11 | Rarecyte, Inc. | Detecting a substrate |
US11054346B2 (en) * | 2013-04-11 | 2021-07-06 | Rarecyte, Inc. | Detecting a substrate |
US11209425B2 (en) * | 2015-03-10 | 2021-12-28 | Siemens Healthcare Diagnostic Inc. | Quantitation of functional groups on solid supports |
CN113376370A (en) * | 2020-03-09 | 2021-09-10 | 陈琪 | Method and device for separating magnetic particles |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5681478A (en) * | 1989-12-07 | 1997-10-28 | Diatec Instruments A/S | Method and apparatus for magnetically separating and resuspending super-paramagnetic particles in a solution |
US6143578A (en) * | 1996-05-10 | 2000-11-07 | Bayer Corporation | Method and apparatus for wash, resuspension, recollection and localization of magnetizable particles in assays using magnetic separation technology |
US20010007312A1 (en) * | 1995-02-21 | 2001-07-12 | Siddiqi Iqbal W. | Apparatus and method for mixing and separation employing magnetic particles |
Family Cites Families (157)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3952599A (en) | 1972-05-18 | 1976-04-27 | Ayres Waldemar A | Fractional-fill capillary pipette and method |
FI55093C (en) | 1974-07-05 | 1979-05-10 | Osmo Antero Suovaniemi | FOERFARANDE FOER EXAKT MAETNING AV ABSORPTION AV SMAO VAETSKEMAENGDER SAMT ANORDNING FOER DESS GENOMFOERANDE |
SE380099B (en) | 1974-02-07 | 1975-10-27 | Monega Anstalt | |
DE2422260B2 (en) | 1974-05-08 | 1979-04-12 | Compur-Electronic Gmbh, 8000 Muenchen | Device for the production of a measuring liquid to be optically examined |
SE381577B (en) | 1974-06-24 | 1975-12-15 | Mediplast Ab | DEVICE FOR TRANSFERRING A LIQUID, AS BLOOD FROM A CYLINDRICAL CONTAINER TO A PIPETTE |
US3939834A (en) | 1974-09-24 | 1976-02-24 | Mcmahon Patrick J | Metal coated articles |
US3985649A (en) | 1974-11-25 | 1976-10-12 | Eddelman Roy T | Ferromagnetic separation process and material |
SE389972B (en) | 1975-03-27 | 1976-11-29 | Autochem Instrument Ab | DEVICE FOR DOSING A LIQUID INTO A PROVER AND FOR AGITATING THE CONTENTS OF THE PROVER |
US4067776A (en) | 1975-11-25 | 1978-01-10 | Research Foundation Of Children's Hospital | Method for differential diagnosis of meningitis with a limulus lysate test |
US4022577A (en) | 1976-03-12 | 1977-05-10 | The University Of Virginia | Automated radioimmunoassay |
GB1575805A (en) | 1976-03-12 | 1980-10-01 | Technicon Instr | Automatic diagnostic apparatus |
US4292920A (en) | 1976-04-26 | 1981-10-06 | Smith Kendall O | Magnetic attraction transfer devices for use in solid phase radioimmunoassays and in other assay methods |
GB1581541A (en) | 1976-06-18 | 1980-12-17 | Unilever Ltd | Cheese |
US4066407A (en) | 1976-12-16 | 1978-01-03 | Vincent Lupica | Body fluid testing system and process |
US4275591A (en) | 1977-07-25 | 1981-06-30 | Becton, Dickinson And Company | Protective shield for capillary pipette |
US4195526A (en) | 1978-02-09 | 1980-04-01 | Corning Glass Works | Hand-held pipetter |
US4783250A (en) | 1979-08-21 | 1988-11-08 | Pons B Stanley | Immobilized electrochemical cell devices and methods of manufacture |
DE2937476A1 (en) | 1979-09-17 | 1981-04-02 | Agfa-Gevaert Ag, 5090 Leverkusen | DEVICE FOR MEASURING THE SURFACE TENSION |
US4483825A (en) | 1982-07-09 | 1984-11-20 | Fatches Keith R | Pipette and filter combination |
EP0105834A3 (en) | 1982-09-07 | 1984-10-10 | Greiner Instruments AG | Method and apparatus for transferring a fluid sample to microlitre and millilitre aggregates |
IT1153640B (en) | 1982-11-05 | 1987-01-14 | Italiana L P Spa | APPARATUS FOR THE MEASUREMENT OF THE SPEED OF ERITROSEDIMENTATION OF THE BLOOD |
US5175086A (en) | 1983-01-24 | 1992-12-29 | Olympus Optical Co., Ltd. | Method for effecting heterogeneous immunological analysis |
US4567149A (en) | 1983-03-17 | 1986-01-28 | Mast Immunosystems, Ltd. | Binding assay system and method of making and using same |
US4701418A (en) | 1984-03-30 | 1987-10-20 | Dianon Systems, Inc. | Method for determining lipid bound sialic acid in whole blood |
US4748128A (en) | 1984-03-30 | 1988-05-31 | Dianon Systems, Inc. | Method for determining lipid bound sialic acid in plasma |
US4677067A (en) | 1984-06-22 | 1987-06-30 | Bio-Magnetech Corporation | Magnetotactic bacteria in clinical assay, immunoassay, and cell separation procedures and the like |
US5009847A (en) | 1984-06-22 | 1991-04-23 | Solomons Clive C | Kit for determining blood platelet stress |
GB8418828D0 (en) | 1984-07-24 | 1984-08-30 | Lab Ltd Ab Ag | Calf screening |
DE3586892T2 (en) | 1984-09-18 | 1993-05-06 | Sumitomo Electric Industries | DEVICE FOR SEPARATING CELLS. |
DE3522610A1 (en) | 1985-06-12 | 1986-12-18 | Kernforschungsanlage Jülich GmbH, 5170 Jülich | CHAMBER FOR THE TREATMENT OF CELLS IN THE ELECTRIC FIELD |
SE448031B (en) | 1985-06-18 | 1987-01-12 | Scomas Ab | PROCEDURE AND APPARATUS FOR INDICATING THE DETECTION OF PIPETTE POSITIONS AT A TEST PLATE |
CH663476A5 (en) | 1985-07-08 | 1987-12-15 | Serono Diagnostics Ltd | ENCLOSURE FOR THE DETERMINATION OF ANTIBODIES OR ANTIGENS IN A BIOLOGICAL LIQUID. |
US4710472A (en) * | 1985-09-25 | 1987-12-01 | The United States Of America As Represented By The Secretary Of The Navy | Magnetic separation device |
US4795698A (en) | 1985-10-04 | 1989-01-03 | Immunicon Corporation | Magnetic-polymer particles |
US5597531A (en) * | 1985-10-04 | 1997-01-28 | Immunivest Corporation | Resuspendable coated magnetic particles and stable magnetic particle suspensions |
CH671526A5 (en) | 1985-12-17 | 1989-09-15 | Hamilton Bonaduz Ag | |
US4798705A (en) | 1985-12-24 | 1989-01-17 | Eastman Kodak Company | Compact analyzer |
US5104621A (en) | 1986-03-26 | 1992-04-14 | Beckman Instruments, Inc. | Automated multi-purpose analytical chemistry processing center and laboratory work station |
US4873875A (en) | 1986-06-27 | 1989-10-17 | Prism Technology, Inc. | System for optically interrogating liquid samples and for withdrawing selected sample portions |
US4721680A (en) | 1986-08-11 | 1988-01-26 | Multi-Technology, Inc. | Methods of using micro pipette tips |
FR2607407B1 (en) | 1986-11-27 | 1991-08-02 | Marteau D Autry Eric | METHOD AND DEVICE FOR CALIBRATING A PIPETTE FOR SAMPLING AND DOSING |
US4933291A (en) | 1986-12-22 | 1990-06-12 | Eastman Kodak Company | Centrifugable pipette tip and pipette therefor |
US5110727A (en) | 1987-04-03 | 1992-05-05 | Cardiovascular Diagnostics, Inc. | Method for performing coagulation assays accurately, rapidly and simply, using dry chemical reagents and paramagnetic particles |
CA1321940C (en) | 1987-05-02 | 1993-09-07 | Teruaki Itoh | Apparatus for distributing sample liquid |
IT210344Z2 (en) | 1987-05-25 | 1988-12-06 | Sta Te Spa | EQUIPMENT FOR THE MEASUREMENT OF THE SPEED OF ERITROSEDIMENTATION OF BLOOD THROUGH PIPETTES. |
US4988618A (en) | 1987-11-16 | 1991-01-29 | Gene-Trak Systems | Magnetic separation device and methods for use in heterogeneous assays |
FR2624757B1 (en) | 1987-12-17 | 1990-05-25 | Roussel Uclaf | DEVICE FOR THE EXTRACTION OF A SEPARATE PHASE |
US4895650A (en) | 1988-02-25 | 1990-01-23 | Gen-Probe Incorporated | Magnetic separation rack for diagnostic assays |
US4962044A (en) | 1988-04-25 | 1990-10-09 | Hoffmann-La Roche Inc. | Test tube filter/dispenser apparatus and method |
EP0339980B1 (en) | 1988-04-26 | 1994-07-20 | Nippon Telegraph And Telephone Corporation | Magnetic micro-particles, method and apparatus for collecting specimens for use in labelling immune reactions, and method and device for preparing specimens |
US5354663A (en) | 1988-05-04 | 1994-10-11 | Charm Sciences, Inc. | Microbial inhibition test kit and method |
GB8816982D0 (en) | 1988-07-16 | 1988-08-17 | Probus Biomedical Ltd | Bio-fluid assay apparatus |
US5147529A (en) | 1988-08-10 | 1992-09-15 | E. I. Du Pont De Nemours And Company | Method for automatically processing magnetic solid phase reagents |
US5045453A (en) | 1988-08-26 | 1991-09-03 | Dianon Systems, Inc. | Method for determining sialic acid in plasma |
US5068089A (en) | 1988-09-09 | 1991-11-26 | Androscore Corporation | Kit for testing human males for fertility |
US5536475A (en) | 1988-10-11 | 1996-07-16 | Baxter International Inc. | Apparatus for magnetic cell separation |
US6020210A (en) * | 1988-12-28 | 2000-02-01 | Miltenvi Biotech Gmbh | Methods and materials for high gradient magnetic separation of biological materials |
ATE114507T1 (en) | 1988-12-28 | 1994-12-15 | Stefan Miltenyi | METHODS AND MATERIALS FOR HIGH GRADUATION MAGNETIC SEPARATION OF BIOLOGICAL MATERIALS. |
US4931257A (en) | 1989-01-05 | 1990-06-05 | Eastman Kodak Company | Positively engaged pipette and pipette support |
US5437979A (en) | 1989-07-24 | 1995-08-01 | Beckman Instruments, Inc. | Solid phase system for sequential reactions |
FI84764C (en) | 1989-09-25 | 1992-01-10 | Labsystems Oy | SPOLNINGSANORDNING. |
US4970892A (en) | 1989-11-15 | 1990-11-20 | Enhorning Goran E | Method and apparatus for determining surface tension or if a surfactant will keep a narrow passageway open |
US5250262A (en) | 1989-11-22 | 1993-10-05 | Vettest S.A. | Chemical analyzer |
US5183638A (en) | 1989-12-04 | 1993-02-02 | Kabushiki Kaisha Nittec | Automatic immunity analysis apparatus with magnetic particle separation |
GB9020352D0 (en) | 1990-09-18 | 1990-10-31 | Anagen Ltd | Assay or reaction apparatus |
US5010930A (en) | 1989-12-22 | 1991-04-30 | Eastman Kodak Company | Pipette and liquid transfer apparatus for dispensing liquid for analysis |
US5411072A (en) | 1990-01-10 | 1995-05-02 | Panelfold, Inc. | Foldable partition |
US5026526A (en) | 1990-02-09 | 1991-06-25 | Eastman Kodak Company | Automated capping means for analyzer pipette |
JP2626738B2 (en) | 1990-03-13 | 1997-07-02 | 三共株式会社 | Chemiluminescence detector |
US5084041A (en) | 1990-04-13 | 1992-01-28 | T Systems, Inc. | Multicompartment biological fluid specimen collection bag |
US5160329A (en) | 1990-04-13 | 1992-11-03 | T Systems Inc. | Biological fluid specimen collection bag |
US5141871A (en) | 1990-05-10 | 1992-08-25 | Pb Diagnostic Systems, Inc. | Fluid dispensing system with optical locator |
US5200151A (en) | 1990-05-21 | 1993-04-06 | P B Diagnostic Systems, Inc. | Fluid dispensing system having a pipette assembly with preset tip locator |
US5156948A (en) | 1990-07-20 | 1992-10-20 | Christensen Dale A | Method and kit for diagnosis of diseases |
WO1992005440A1 (en) | 1990-09-26 | 1992-04-02 | Akers Research Corporation | Improved ligand assay |
US5541072A (en) | 1994-04-18 | 1996-07-30 | Immunivest Corporation | Method for magnetic separation featuring magnetic particles in a multi-phase system |
US5622831A (en) * | 1990-09-26 | 1997-04-22 | Immunivest Corporation | Methods and devices for manipulation of magnetically collected material |
US5200084A (en) | 1990-09-26 | 1993-04-06 | Immunicon Corporation | Apparatus and methods for magnetic separation |
CA2046713A1 (en) | 1990-10-16 | 1992-04-17 | Richard M. Martinelli | Amplification of midivariant dna templates |
US5334538A (en) | 1990-11-26 | 1994-08-02 | V-Tech, Inc. | Gold sol immunoassay system and device |
US5128103A (en) | 1990-12-14 | 1992-07-07 | E. I. Du Pont De Nemours And Company | Apparatus for automatically processing magnetic solid phase reagents |
JPH04248447A (en) | 1991-02-01 | 1992-09-03 | Sanyo Electric Co Ltd | Blood analyzer |
US5137352A (en) | 1991-02-05 | 1992-08-11 | Tantec, Inc. | Method and apparatus for determining the contact angle of liquid droplets on curved substrate surfaces |
US5138868A (en) | 1991-02-13 | 1992-08-18 | Pb Diagnostic Systems, Inc. | Calibration method for automated assay instrument |
CA2384514C (en) * | 1991-03-04 | 2006-07-25 | Bayer Corporation | Automated analyzer |
US5242833A (en) * | 1991-03-20 | 1993-09-07 | Reference Diagnostics, Inc. | Lipid fractionation |
US5186827A (en) | 1991-03-25 | 1993-02-16 | Immunicon Corporation | Apparatus for magnetic separation featuring external magnetic means |
US5466574A (en) | 1991-03-25 | 1995-11-14 | Immunivest Corporation | Apparatus and methods for magnetic separation featuring external magnetic means |
US5262325A (en) | 1991-04-04 | 1993-11-16 | Ibex Technologies, Inc. | Method for the enzymatic neutralization of heparin |
US5171537A (en) | 1991-05-06 | 1992-12-15 | Richard E. MacDonald | Activated immunodiagnostic pipette tips |
US5289385A (en) | 1991-06-03 | 1994-02-22 | Abbott Laboratories | Adaptive scheduling system and method for operating a biological sample analyzer with variable rinsing |
FR2677453B1 (en) | 1991-06-10 | 1993-10-08 | Aegys Technology Sa | METHOD AND APPARATUS FOR SPECTROPHOTOMETRIC DOSING OF AQUEOUS LIQUIDS. |
US5232665A (en) | 1991-07-26 | 1993-08-03 | E. I. Du Pont De Nemours And Company | Multi-linear automatic apparatus for processing immunoassays |
US5670113A (en) * | 1991-12-20 | 1997-09-23 | Sibia Neurosciences, Inc. | Automated analysis equipment and assay method for detecting cell surface protein and/or cytoplasmic receptor function using same |
US5268147A (en) | 1992-02-26 | 1993-12-07 | Miles, Inc. | Reversible direction capsule chemistry sample liquid analysis system and method |
US5399497A (en) | 1992-02-26 | 1995-03-21 | Miles, Inc. | Capsule chemistry sample liquid analysis system and method |
US5376313A (en) | 1992-03-27 | 1994-12-27 | Abbott Laboratories | Injection molding a plastic assay cuvette having low birefringence |
IT1274578B (en) | 1992-05-13 | 1997-07-17 | Francesco Leopardi | SAFETY CLOSURE DEVICE FOR CONTAINERS FOR ORGANIC LIQUIDS |
US5270210A (en) | 1992-07-16 | 1993-12-14 | Schiapparelli Biosystems, Inc. | Capacitive sensing system and wash/alignment station for a chemical analyzer |
US5897783A (en) * | 1992-09-24 | 1999-04-27 | Amersham International Plc | Magnetic separation method |
DE69329135T2 (en) | 1992-09-24 | 2001-01-11 | Amersham Pharm Biotech Uk Ltd | Magnetic deposition method and apparatus |
US5344610A (en) | 1993-02-03 | 1994-09-06 | Eastman Kodak Company | Aspirator probe with long pivot arm to minimize tip flick |
FI932866A0 (en) * | 1993-06-21 | 1993-06-21 | Labsystems Oy | Separeringsfoerfarande |
WO1994018565A1 (en) * | 1993-02-01 | 1994-08-18 | Labsystems Oy | Method and means for magnetic particle specific binding assay |
AU6357394A (en) | 1993-03-04 | 1994-09-26 | Sapidyne, Inc. | Assay flow apparatus and method |
US5607766A (en) * | 1993-03-30 | 1997-03-04 | American Filtrona Corporation | Polyethylene terephthalate sheath/thermoplastic polymer core bicomponent fibers, method of making same and products formed therefrom |
US5403707A (en) | 1993-05-14 | 1995-04-04 | Eastman Kodak Company | Diagnostic compositions, elements, methods and test kits for amplification and detection of retroviral DNA using primers having matched melting temperatures |
US6174668B1 (en) * | 1993-05-14 | 2001-01-16 | Johnson & Johnson Clinical Diagnostics, Inc. | Diagnostic compositions, elements, methods and test kits for amplification and detection of two or more target DNA's using primers having matched melting temperatures |
US5578269A (en) * | 1993-06-11 | 1996-11-26 | Ortho Diagnostic Systems Inc. | Automated blood analysis system with an integral centrifuge |
EP0644426B1 (en) | 1993-09-17 | 2004-05-06 | F. Hoffmann-La Roche Ag | Analyser with a device for suspending particles, and suspension method therefor |
ES2170083T3 (en) * | 1993-09-17 | 2002-08-01 | Hoffmann La Roche | ANALYZER WITH A DEVICE FOR SEPARATION OF MAGNETIC MICROPARTICLES. |
JP3115501B2 (en) * | 1994-06-15 | 2000-12-11 | プレシジョン・システム・サイエンス株式会社 | Method for controlling desorption of magnetic material using dispenser and various devices processed by this method |
DE4423878A1 (en) * | 1994-07-07 | 1996-01-11 | Boehringer Mannheim Gmbh | Device and method for separating magnetic microparticles |
FI944940A0 (en) * | 1994-10-20 | 1994-10-20 | Labsystems Oy | Tvaofasigt separeringsfoerfarande |
FI944939A0 (en) * | 1994-10-20 | 1994-10-20 | Labsystems Oy | Foerfarande Foer separering av partiklar |
CA2203886C (en) * | 1994-10-28 | 2003-09-02 | Soren-Peter Olesen | Patch clamp apparatus and technique having high throughput and low fluid volume requirements |
US5599501A (en) * | 1994-11-10 | 1997-02-04 | Ciba Corning Diagnostics Corp. | Incubation chamber |
JP3130222B2 (en) * | 1995-02-14 | 2001-01-31 | 三菱電機株式会社 | Method for analyzing minute foreign matter, analyzer, and method for producing semiconductor element or liquid crystal display element using the same |
US6884357B2 (en) * | 1995-02-21 | 2005-04-26 | Iqbal Waheed Siddiqi | Apparatus and method for processing magnetic particles |
EP0763739B1 (en) * | 1995-03-20 | 2005-06-01 | Precision System Science Co., Ltd. | Method and apparatus for liquid treatment utilizing dispenser |
US5578270A (en) | 1995-03-24 | 1996-11-26 | Becton Dickinson And Company | System for nucleic acid based diagnostic assay |
JP3985872B2 (en) * | 1995-07-31 | 2007-10-03 | プレシジョン・システム・サイエンス株式会社 | container |
US6232124B1 (en) * | 1996-05-06 | 2001-05-15 | Verification Technologies, Inc. | Automated fingerprint methods and chemistry for product authentication and monitoring |
US5888835A (en) * | 1996-05-10 | 1999-03-30 | Chiron Diagnostics Corporation | Method and apparatus for wash, resuspension, recollection and localization of magnetizable particles in assays using magnetic separation technology |
US6509193B1 (en) * | 1996-05-20 | 2003-01-21 | Precision System Science Co., Ltd. | Method and apparatus for controlling magnetic particles by pipetting machine |
EP0920627B1 (en) * | 1996-06-07 | 2004-05-12 | Immunivest Corporation | Magnetic separation employing external and internal gradients |
US6790366B2 (en) * | 1996-06-07 | 2004-09-14 | Immunivest Corporation | Magnetic separation apparatus and methods |
US5885529A (en) * | 1996-06-28 | 1999-03-23 | Dpc Cirrus, Inc. | Automated immunoassay analyzer |
AU726719B2 (en) * | 1996-09-16 | 2000-11-16 | Stomp, Inc. | Optical disc adhesive label applicator |
US6066297A (en) * | 1997-01-03 | 2000-05-23 | Matrix Technologies Corporation | Small sample volume displacement pipette tips |
US5888758A (en) * | 1997-03-19 | 1999-03-30 | Integrated Biomedical Technology, Inc. | Broad range total available chlorine test strip |
CA2287962C (en) * | 1997-05-02 | 2007-01-02 | Gen-Probe Incorporated | Reaction receptacle apparatus |
US5985214A (en) * | 1997-05-16 | 1999-11-16 | Aurora Biosciences Corporation | Systems and methods for rapidly identifying useful chemicals in liquid samples |
JP4104704B2 (en) * | 1997-10-01 | 2008-06-18 | シスメックス株式会社 | Cleaning agent for automatic analyzer |
US6537505B1 (en) * | 1998-02-20 | 2003-03-25 | Bio Dot, Inc. | Reagent dispensing valve |
ATE363339T1 (en) * | 1998-05-01 | 2007-06-15 | Gen Probe Inc | STIRRING DEVICE FOR THE FLUID CONTENTS OF A CONTAINER |
US20040047765A1 (en) * | 1998-10-16 | 2004-03-11 | Gordon Steven J. | Automated robotic workstation and methods of operation thereof |
US20030012699A1 (en) * | 1998-11-18 | 2003-01-16 | Thomas Moore | Simultaneous handling of magnetic beads in a two-dimensional arrangement |
US6723237B1 (en) * | 1999-01-18 | 2004-04-20 | Precision Systems Science Co., Ltd. | Concentration device using magnetic particles and method therefor |
JP3330929B2 (en) * | 1999-01-25 | 2002-10-07 | 浜松ホトニクス株式会社 | Pipette adapter, pipette for absorbance measurement, tip, absorbance measurement device and absorbance measurement method |
AR022333A1 (en) * | 1999-01-26 | 2002-09-04 | Anitua Aldecoa Eduardo | OSEO FABRIC REGENERATOR |
US6225128B1 (en) * | 1999-02-19 | 2001-05-01 | Wrs And Associates | Color test card package for testing for the presence of lead |
US6225126B1 (en) * | 1999-02-22 | 2001-05-01 | Haemoscope Corporation | Method and apparatus for measuring hemostasis |
US6193892B1 (en) * | 1999-03-03 | 2001-02-27 | Promega Corporation | Magnetic separation assembly and method |
US6225061B1 (en) * | 1999-03-10 | 2001-05-01 | Sequenom, Inc. | Systems and methods for performing reactions in an unsealed environment |
US6368872B1 (en) * | 1999-10-22 | 2002-04-09 | Tecan Trading Ag | Apparatus and method for chemical processing |
JP4141608B2 (en) * | 2000-01-17 | 2008-08-27 | プレシジョン・システム・サイエンス株式会社 | Container transfer processing system |
US6370942B1 (en) * | 2000-05-15 | 2002-04-16 | Dade Behring Inc. | Method for verifying the integrity of a fluid transfer |
ATE419919T1 (en) * | 2000-05-19 | 2009-01-15 | Becton Dickinson Co | SYSTEM AND METHOD FOR TREATING MAGNETIC PARTICLES IN TEST LIQUIDS FOR COLLECTING DNA AND RNA |
US6672458B2 (en) * | 2000-05-19 | 2004-01-06 | Becton, Dickinson And Company | System and method for manipulating magnetically responsive particles fluid samples to collect DNA or RNA from a sample |
TWI295688B (en) * | 2000-06-07 | 2008-04-11 | A method for inhibition of enterovirus and/or influenza virus reproduction by allophycocyanin in vitro | |
US20020048821A1 (en) * | 2000-08-24 | 2002-04-25 | David Storek | Sample preparing arrangement and a method relating to such an arrangement |
DE10057396C1 (en) * | 2000-11-18 | 2002-04-04 | Karlsruhe Forschzent | Separation of e.g. biomolecules from dispersion or solution, employs magnetic particles onto which substance is sorbed, and electromagnet for their extraction |
JP5193408B2 (en) * | 2001-09-13 | 2013-05-08 | ベックマン コールター, インコーポレイテッド | Automatic analyzer |
DE10156790A1 (en) * | 2001-11-19 | 2003-06-18 | Chemagen Biopolymer Technologi | Device and method for treating magnetic particles |
US8409528B2 (en) * | 2003-06-19 | 2013-04-02 | Abbott Laboratories | Apparatus and method for handling fluids for analysis |
US7488451B2 (en) * | 2003-09-15 | 2009-02-10 | Millipore Corporation | Systems for particle manipulation |
-
2003
- 2003-04-10 AU AU2003226075A patent/AU2003226075B2/en not_active Expired - Fee Related
- 2003-04-10 US US10/411,441 patent/US7514270B2/en not_active Expired - Fee Related
- 2003-04-10 JP JP2003583638A patent/JP2005522679A/en active Pending
- 2003-04-10 CA CA002481545A patent/CA2481545A1/en not_active Abandoned
- 2003-04-10 WO PCT/US2003/011157 patent/WO2003086637A1/en active Application Filing
- 2003-04-10 EP EP03746724A patent/EP1494814A1/en not_active Withdrawn
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5681478A (en) * | 1989-12-07 | 1997-10-28 | Diatec Instruments A/S | Method and apparatus for magnetically separating and resuspending super-paramagnetic particles in a solution |
US20010007312A1 (en) * | 1995-02-21 | 2001-07-12 | Siddiqi Iqbal W. | Apparatus and method for mixing and separation employing magnetic particles |
US6143578A (en) * | 1996-05-10 | 2000-11-07 | Bayer Corporation | Method and apparatus for wash, resuspension, recollection and localization of magnetizable particles in assays using magnetic separation technology |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008075287A2 (en) * | 2006-12-20 | 2008-06-26 | Philips Intellectual Property & Standards Gmbh | Method and arrangement for separating magnetic particles, magnetic particles and use magnetic particles |
WO2008075287A3 (en) * | 2006-12-20 | 2008-08-14 | Philips Intellectual Property | Method and arrangement for separating magnetic particles, magnetic particles and use magnetic particles |
US7731899B2 (en) | 2007-02-08 | 2010-06-08 | Biokit, S.A. | Apparatus and methods for dispensing sample holders |
US8480954B2 (en) | 2007-02-08 | 2013-07-09 | Biokit, S.A. | Apparatus and methods for dispensing sample holders |
US9523699B2 (en) | 2007-02-08 | 2016-12-20 | Biokit, S.A. | Apparatus and methods for dispensing sample holders |
EP2208531A1 (en) | 2008-12-30 | 2010-07-21 | Atonomics A/S | Distribution of particles in capillary channel by application of magnetic field |
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Publication number | Publication date |
---|---|
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US7514270B2 (en) | 2009-04-07 |
CA2481545A1 (en) | 2003-10-23 |
AU2003226075B2 (en) | 2008-09-25 |
US20030194799A1 (en) | 2003-10-16 |
EP1494814A1 (en) | 2005-01-12 |
AU2003226075A1 (en) | 2003-10-27 |
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