WO1993010455A1 - Cuve centrifuge amelioree pour dosage immunologique automatique en phase solide - Google Patents

Cuve centrifuge amelioree pour dosage immunologique automatique en phase solide Download PDF

Info

Publication number
WO1993010455A1
WO1993010455A1 PCT/US1992/010247 US9210247W WO9310455A1 WO 1993010455 A1 WO1993010455 A1 WO 1993010455A1 US 9210247 W US9210247 W US 9210247W WO 9310455 A1 WO9310455 A1 WO 9310455A1
Authority
WO
WIPO (PCT)
Prior art keywords
tube
centrifuge vessel
biological sample
vertical axis
top end
Prior art date
Application number
PCT/US1992/010247
Other languages
English (en)
Inventor
Arthur L. Babson
Douglas R. Olson
Original Assignee
Cirrus Diagnostics, 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 Cirrus Diagnostics, Inc. filed Critical Cirrus Diagnostics, Inc.
Publication of WO1993010455A1 publication Critical patent/WO1993010455A1/fr

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366—Apparatus specially adapted for solid-phase testing
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/5302—Apparatus specially adapted for immunological test procedures
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/5302—Apparatus specially adapted for immunological test procedures
    • G01N33/5304—Reaction vessels, e.g. agglutination plates
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
    • G01N33/54326—Magnetic particles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5021—Test tubes specially adapted for centrifugation purposes

Definitions

  • the present invention is generally related to a centrifuge vessel which is rotated at high speed about its longitudinal axis and, more particularly, to a centrifuge vessel which can be used to separate an analyte from a biological solution in an automated fashion.
  • Centrifuges are well known commercial and laboratory tools that are used to separate materials of varying densities. Centrifuges are often used for clarifying liquids whereby suspended solids such as cells or proteins are sedimented from solution by high speed rotation of the centrifuge vessel. Two common types of centrifuges are the horizontal centrifuge and the fixed angle centrifuge.
  • sample containers of the solution to be centrifuged are placed in holders called "buckets". These buckets are subsequently attached to a vertical rotor in a balanced arrangement and swung to a horizontal plane under centrifugal force. While being rotated at high speeds in the horizontal position, the denser particles in the sample move along an unimpeded path toward the bottom of the buckets to form a smooth, even "pellet" of sedi ented material. The non-pelleted supernatant solution can be decanted from the bucket once centrifugation is halted.
  • a rotor holds a plurality of sample containers at fixed angles relative to the axis of rotation.
  • at least a pair of sample containers must be used in order to balance the rotor during high speed spinning.
  • the denser particles in the sample containers pellet along the side wall of the container. Pelleting on the side wall makes decanting of the supernatant more difficult because of the possible resuspension of the pellet; however, there are certain advantages in using the fixed angle centrifuge.
  • the rotor in both the horizontal and the fixed angle centrifuges, the rotor must be balanced accurately in order to prevent damage to the centrifuge.
  • the lab technician In order to properly balance the rotor, the lab technician must precisely weigh each centrifuge sample container using a balance and ⁇ then position two sample containers of dqual weight in the rotor on opposite sides. This balancing step is very tedious and often requires withdrawing 5 and adding back sample to the sample container until it reaches the desired weight.
  • a precipitating agent is first mixed with the biological specimen and given time to react with analyte therein. Then the
  • tube is rotated about its longitudinal axis at high speed. During high speed rotation, the contents of the tube is forced against the inner wall of the tube and moves upward towards the top of the tube " due to the tube's inclined inner surface.
  • the precipitate is deposited within V-shaped grooves on the tube's interior. After rotation is stopped, the precipitate is retained in the V-shaped grooves at the top of the tube while the liquid drops back to the bottom of
  • U.S. Patent No. 4,639,242 to Babson also discloses a procedure for using the tube whereby a radioactively labeled antibody is bound in the bottom of the tube.
  • the tube is rotated at high speed, thereby causing the fluid in the tube to rise to the top while the analyte remains bound to the antibody in the bottom of the tube.
  • the radioactivity in the bottom of the tube is counted while the tube is spinning.
  • the Babson tube disclosed in U.S. Patent No. 4,639,242 to Babson is more adaptable to an automated processing environment than conventional horizontal and fixed angle centrifuges because it does not require the batch step of balancing pairs of rotor tubes
  • the Babson tube is not suitable for some of today's processing environments. For example, in some environments it may not be desirable to have a precipitation step. Not only does precipitation require extra chemicals to be used and time for the precipitation reaction to take place, but in some environments precipitation may reduce yield or the precipitating agent itself may affect the measured results. In addition, it may be desirable to stop the tube from spinning and use other instrumentation to make radioactive, fluorescent, or other related readings.
  • centrifuge tube which includes a means for collecting biological fluid and wash liquid during rotation about its longitudinal axis and for storing that biological fluid and wash liquid separate from a bound analyte after the rotation of the centrifuge tube has ceased.
  • a centrifuge tube has been developed which is suitable for performing automated solid phase immunoassays.
  • immunoassays in the clinical laboratory have rapidly replaced other methods used to detect or quantitate substances in body fluids with important biologic or pharmacologic properties.
  • the high levels of sensitivity and specificity achieved with immunoassays result from the specific, high- affinity reversible binding of antigens to antibodies, and from the development of methods for attaching readily detected labels (radioactive isotopes, fluorescent or chemiluminescent molecules, enzymes and the like) to antigens or antibodies.
  • radioactive isotopes have been the most extensively used label, they are not preferred because of concerns with radioactivity. Because of these concerns,. the number of sensitive, specific immunoassays employing non-radioactive labels is rapidly expanding.
  • solid-phase immunoassaysn may be the interior of small test tubes (such as those available from Micromedic Systems, Inc. of Horsha , Pennsylvania) , microtiter trays (such as the 96 well trays available from Amersham International of Bucks, England) , macrobeads (such as those available from Abbott Laboratories of Abbott Park, Illinois) , or microparticles (such as those available from Pandex Laboratories, Inc. of Mundolein, Illinois) , or magnetic particles (such as those available from Corning Medical of
  • solid- phase immunoassay over liquid-phase immunoassay is that common reagents and serum constituents which can potentially interfere with the measurement of the label are removed in the washing step of the procedure. While a variety of immunoassay schemes involving a solid-phase reactant are possible, most schemes utilize a solid-phase antibody and are generally classified as competitive or noncpmpetitive.
  • antigen present in the sample or standard competes with a measured amount of labeled antigen for a limited number of binding sites on a solid-phase bound antibody. After removal of any unreacted antigen from the test system, and washing the solid support material, the bound label is quantitated by suitable means well known in the art.
  • the amount of labeled antigen bound to the solid-phase antibody is inversely related to the concentration of antigen (analyte) in the sample or standard.
  • an excess of labeled antibody binds to essentially all of the analyte present in the sample, and an excess of the solid-phase antibody also binds to additional sites on the analyte.
  • These two separate antigen-antibody reactions can be conducted either sequentially, by providing an intermediate washing step if the first reaction is with solid-phase antibody, or simultaneously. After the immunological reactions are allowed to reach equilibrium, the excess labeled antibody is removed, the solid phase is washed and the bound label quantitated by suitable means well known in the art.
  • This type of immunoassay is also called a "sandwich assay" because the antigen is sandwiched between the solid-phase and labeled antibodies.
  • immunometric assay it is also called an “immunometric assay” because the amount of label bound is usually a direct and linear function of the antigen concentration within the sample. It is also called a “two-site immunoassay” if the labeled and solid-phase antibodies are directed to distinct antigenic determinants on the analyte. This type of assay can only be used with large molecular weight analytes with multiple antibody binding sites.
  • the second antibody is unlabeled and the procedure is expanded to include an incubation of the sample with an excess of labeled third antibody specific for the IgG of the animal species from which the second antibody is elicited.
  • the immobilized and second antibodies are obtained from different animal species, in order to prevent the binding of labeled third antibody directly to the immobilized antibody.
  • washing coated tubes or microwells by alternately adding and aspirating water or wash solution, as is customarily done is inefficient since there is always some residual solution in the tube or well after each wash cycle.
  • four to six washes of about 4 ml are required to adequately wash the coated tubes conventionally used in present day immunoassay procedures.
  • provisions must be made to collect all the used wash solutions because they could possibly contain infectious agents from the sample specimens.
  • the centrifuge vessel offers a number of advantages over the present protocols and apparatus conventionally used in solid-phase immunoassay procedures.
  • the centrifuge vessel includes a central tube member and a peripheral waste chamber.
  • the analyte being tested for reacts with and is bound to a solid support positioned in the central tube and the excess sample fluid, reagents, and wash fluid are separated from the bound analyte by rotating the tube rapidly about its longitudinal axis. High speed rotation causes the fluids to move up the inclined wall of the central tube and droop into the peripheral waste chamber. Rotation continues until no fluid residue remains in the bottom of the tube. After rotation of the tube is halted, the excess sample fluid, reagents and wash fluid are safely stored in the waste chamber and do not re-mix with the bound analyte in the centrl tube.
  • a particular advantage of the present design is that multiple washings of the bound analyte can be performed in a sequential fashion as rapidly as the wash solution can be pipetted into the central tube of the vessel.
  • the ability to wash the bound analyte in the rapid fashion results from the excess fluids being transferred to the waste chamber almost instantaneously because of the high speed centrifugal forces acting on the centrifuge vessel. Because of the speed with which washing is accomplished, multiple vessels may be processed sequentially without impairing sample throughput.
  • the speed of processing the vessels allows for the precise control of the incubation times required by immunoassays, and allows for the normally labor- intensive immunoassay procedure to be automated.
  • the solid support is comprised of microparticles having a magnetizable core and a polymeric overcoating to which the biomaterial for binding the analyte in the biologic fluid is bound.
  • the microparticles have the advantage of providing a cummulatively large surface area for binding interactions and faster kinetics.
  • the biologic fluid is deposited in the centrifuge vessel and the microparticles present in the centrifuge tube become dispersed in the biologic fluid. After a sufficient reaction period, the biologic fluid is removed from the centrifuge tube by high speed rotation about its longitudinal axis and the microparticles are washed by pipetting water into the centrifuge tube and removing the water by high speed rotation.
  • the microparticles are held within the centrifuge tube by an external magnetic force exerted on the magnetizable cores of the microparticles.
  • the present invention greatly improves the utility of microparticles in automated immunoassay environments because it provides a device which will allow rapid and thorough washing. In the past, microparticles have been very difficult to wash because of trapped interstitial fluids between adjacent microparticles.
  • the high "G” forces imparted to the microparticle beads in the vertical direction which are developed during rotation about the central axis helps remove the trapped interstitial fluids.
  • Figure 1 is an isometric view of a centrifuge vessel
  • Figure 2 is a cross-sectional side view of the centrifuge vessel of Figure 1;
  • Figure 3 is a cross-sectional side view of a cap which fits on the centrifuge vessel
  • Figure 4 is a top view of the cap of Figure 3;
  • Figure 5 is a cross-sectional side view of a centrifuge vessel according to the present invention wherein microparticle beads are used as the solid support; and
  • Figure 6 is a cross-sectional side view of the centrifuge vessel of Figure 5 being rotated about its longitudinal axis at high speed where the microparticle beads are held in place by a magnetic force as fluid is expelled.
  • a generally cylindrical waste chamber 15 Integrally attached to tube 11 at a point between the upper and lower ends is a generally cylindrical waste chamber 15 having a circumferentially extending bottom portion 15a extending between tube 11 and the waste chamber's upwardly extending cylindrical side wall 15b.
  • the waste chamber 15 is open at its uppermost end 17 at a point above the top 16 of the tube 11.
  • the waste chamber is coaxial with the tube 11, and has an inner diameter greater than the outer diameter of the tube 11.
  • centrifuge vessel 10 may be manufactured from various materials, for ease of manufacture it is preferred that the vessel be molded from a plastic (polymeric) material which is compatible with its intended use.
  • the uppermost end 17 of waste chamber 15 may be sealed with a metal foil or polymeric membrane 19 to contain the liquid in the vessel as it is spun on its longitudinal axis or, it may, as will be discussed in conjunction with Figures 3-4, have a cap welded thereto. If a foil membrane 19 is used, the center of the membrane 19 is punctured to allow addition of the sample and reagents to tube 11. If a welded cap is used, a small foil cover over the central tube 11 is removed to allow the addition of the sample and the reagents.
  • Figures 3 and 4 show a hard cover cap 20 which may be used instead of the polymer or foil film 19 to cover the open end 17 of waste chamber 15.
  • the cap 20 has an outer flange 22 which fits inside and adjacent the inner diameter of sidewall 15b of waste chamber 15 and an outer welding region 24 which is welded to the top 17 of waste chamber 15. Welding can be accomplished using traditional heat staking or ultra-sonic technologies and the preferred welded joint is called a shear seal. It is anticipated that other suitable techniques, such as gluing, could be used for applying the cap 20 to the top 17 of waste chamber 15.
  • the cap 20 may include an inner flange 28, about the periphery of opening 30, that projects down into the top portion 13 of the center tube 11.
  • the diameter of the inner flange 28 is smaller than the diameter of the top portion 13 of the center tube 11 so that fluid can pass between the flange 28 and the center tube 11, then up over the top 16 of the center tube and into the waste chamber 15.
  • the advantages of welding a cap 20 to the centrifuge vessel 10 instead of applying a film 19 over the waste chamber 15 include allowing the centrifuge vessels 10 to be individually pressure tested for leaks prior to use and avoiding the additional processing step of trimming each foil or polymer film 19 to fit neatly on the centrifuge vessel 10. Pre- pressure testing the centrifuge vessels 10 is elieved to be important since the vessels 10 are subjected to intense pressure during the high speed spin.
  • the lower end 12 of the vessel 10 may be formed with a drive engagement means 14 that would allow a rotating axle member (not shown) to engage and spin the vessel 10 about its longitudinal axis.
  • a female socket 14 is adapted to fit in frictional engagement about a male rotor axle (not shown) to provide a union with the spinning rotor axle and thereby provide for the spinning of the vessel about its longitudinal axis.
  • centrifuge vessel 10 it is also possible to spin the centrifuge vessel 10 about its longitudinal axis using a set of three opposing rollers (see rollers 36 and 38 in Figure 6) which will engage the side wall of central tube 11 or the side wall 15b of waste chamber 15. If the three roller arrangement were used, the centrifuge vessel 10 would simply be placed between the rollers and at least one of the rollers would be driven at high speed. As the vessel is spun about its axis, any fluid within the central tube 11 will travel upward along the inner surface of the tube 11.
  • the inner surface of the tube 11 is preferably manufactured in such a manner so that the closed bottom 12 of the tube 11 has a slightly smaller inner diameter than the open top 16.
  • the outward flaring of the inner surface of the tube 11 provides an incline which aids in transporting fluid upward which is driven thereagainst under the centrifugal force.
  • the uppermost terminal end 16 of tube 11 is short of the cross- sectional plane passing through and defining the open uppermost end 17 of the chamber 15. This height differential provides a passage which allows fluid to pass from tube 11 into waste chamber 15.
  • Waste chamber 15 may also be manufactured with its inner diameter at the bottom portion 15a being slightly greater than its inner diameter at its uppermost end 17, thereby functioning to hold fluid at a position towards the base of waste chamber 15 as the centrifuge vessel 10 is being spun about its longitudinal axis.
  • the centrifuge vessel 10 does not need to be removed from the drive means to discard biological or wash fluid between washings since all of the wash fluid is transported to and held in waste chamber 15. Therefore, multiple washings are performed simply by repetitively pipetting wash fluid into the vessel 10 and discarding the waste wash fluid by rotating the centrifuge vessel 10 about its longitudinal axis at high speed.
  • the bottom inner portion of the tube 11 may be coated with an antigen or antibody protein (not shown) which binds to the inner surface of the tubell.
  • This coating preferably extends from the very bottom of the closed end 12 of the tube 11 upwards to a point anywhere less than about 25% of the overall length of tube 11 where the actual length of the coating is a matter of design of the coating process for manufacture of the coated tube.
  • a solid support 18 can be placed within the tube 11 where the solid support includes a binding surface, such as a bound antigen or antibody molecule, for selectively binding a specific analyte in the biological fluid under test.
  • Suitable solid supports 18 may include antigen or antibody coated spheres of organic polymers or inorganic polymers. Silica gels are a typical example of inorganic polymers used as binding spheres.
  • Suitable solid supports 18 are commercially available or can be easily manufactured and the choice of support 18 is dependent upon the binding characteristics of the appropriate antigen or antibody or the ligand used to bind the antigen or antibody to the support 18.
  • the present patent application is directed to an improvement, wherein microparticle beads 32 (see Figures 5 and 6) having a magnetizable core, a polymeric overcoat, and biomaterial bound to the polymeric overcoat for binding analyte in the biologic fluid are used in the centrifuge vessel.
  • microparticle beads 32 provide surface area and faster kinetics advantages in conducting mmunoassays.
  • a sample of fluid containing the analyte to be determined is added to the vessel's central tube 11, along with a solvent if required.
  • the microparticle beads 32 can be added to the vessel's central tube 11 as a suspension. If a competitive immunoassay is being performed, the labeled antigen is also added to the central tube 11. Addition of the sample, solvent, microparticle beads 32 and any other reagents can be achieved using a pipette probe or a hypodermic needle. It is contemplated that the additions can be made in an automated fashion using a machine which performs the pipetting. The tube 11 contents are then mixed by lateral agitation or by slowly rotating the vessel 10 about its longitudinal axis.
  • the analyte in the sample fluid binds to the antibody on the i microparticle beads 32 at the base 12 of the center tube 11.
  • the vessel 10 is rotated about its longitudinal axis at a speed sufficiently great to cause any fluid within the central tube 11 to be transferred into the waste chamber 15. Water or other wash fluids may be intermittently introduced
  • washing can be performed by stopping the tube 11, adding the water, and then starting the rotation of the tube 11 again, or by
  • the bound label in the lower portion of the central tube 11 may then be quantitated by suitable means well known in the • diagnostic arts.
  • FIGS 5 and 6 illustrate a particular embodiment of the invention wherein microparticle beads 32 are used as the solid support in the base 12 of center tube 11.
  • Microparticle beads 32 are available from a wide variety of sources including
  • the microparticle beads 32 have a magnetizable core, such as a ferrous material, and a polymeric overcoat, such as polystyrene or the like.
  • a magnetizable core such as a ferrous material
  • a polymeric overcoat such as polystyrene or the like.
  • microparticle beads 32 of Figure 5 have a diameter ranging from microns to a few millimeters, whereas macrobeads are typically on the order of a quarter of an inch in diameter.
  • the microparticle beads 32 have the advantage of providing a cummulatively large surface area for binding interactions and faster kinetics when conducting immunoassays.
  • Figure 6 shows that in operation, the biologic fluid 34, after a being intermingled for a sufficient reaction period with the microparticle beads 32 having the bound biomaterial for binding analyte in the fluid 34, is removed from the center tube 11 by high speed rotation about its longitudinal axis.
  • High speed rotation can be achieved using a drive roller 36 and free rollers 38 which contact the outside wall of the waste chamber 15 or by other means.
  • the microparticle beads 32 stay within the center tube 11 via an external magnetic force exerted on the magnetizable cores of the microparticle beads 32. It is contemplated that the external magnetic force could be supplied by fixed magnets or electromagnets 40 located at a spin station which exert a force through the bottom portion 12 of center tube 11.
  • the microparticle beads 32 are washed by pipetting water into the center tube 11 and removing the water by high speed rotatio .
  • Microparticle beads 32 are viewed as an important solid support medium since they provide enhanced reaction area per unit volume and faster reaction kinetics in conducting automated immunoassays. In the past, washing the bound biomaterial has been the most difficult step to automate. It is very difficult to thoroughly wash microparticle beads because biological fluid, which may contain free label, tends to become trapped in interstitial spaces.
  • the present invention greatly improves the utility of microparticle beads 32 in automated immunoassay environments because it provides a device which will allow rapid and thorough washing. During high speed rotation of the center tube 11, high "G" forces in the vertical direction are developed which cause fluid in the interstitial spaces of the microparticle beads 32 to be evacuated. Washing can be repeated rapidly simply by pipetting more water in the center tube 11 followed by high speed rotation.
  • the vessel 10 according to the present invention may be used in other procedures besides immunoassays.
  • affinity chromatography does not rely on general molecular properties such as size, electrical charge or density to carry out a separation. Instead, it involves a very specific interaction between two biomolecules, one of which is chemically attached (in solid phase separations) to a solid support phase, and the other of which is dissolved in solution. Such interactions are almost a universal feature of biomolecules.
  • the vessel of the present invention may be modified by chemically attaching an appropriate biomolecule to the microparticle beads 32, and utilizing the vessel 10 as an affinity chromatographic separation device. Once the interaction between the two biomaterials is completed, the vessel 11 may simply be spun rapidly about its longitudinal axis to remove the unbound biomaterial from the center of the tube 11 into the waste chamber 15.

Landscapes

  • Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Cell Biology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Microbiology (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Centrifugal Separators (AREA)

Abstract

Une cuve centrifuge (10) destinée à réaliser des dosages immunologiques automatiques comprend un tube central (11), une chambre d'évacuation externe (15), et une pluralité de grains de microparticules (32) placés dans le tube central (11). Les grains de microparticules (32) ont une partie centrale magnétisable sur laquelle agissent des sources magnétiques externes (40) lors des opérations de lavage.
PCT/US1992/010247 1991-11-21 1992-11-19 Cuve centrifuge amelioree pour dosage immunologique automatique en phase solide WO1993010455A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US79654091A 1991-11-21 1991-11-21
US796,540 1991-11-21

Publications (1)

Publication Number Publication Date
WO1993010455A1 true WO1993010455A1 (fr) 1993-05-27

Family

ID=25168432

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1992/010247 WO1993010455A1 (fr) 1991-11-21 1992-11-19 Cuve centrifuge amelioree pour dosage immunologique automatique en phase solide

Country Status (1)

Country Link
WO (1) WO1993010455A1 (fr)

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999025470A1 (fr) * 1997-11-19 1999-05-27 Trega Biosciences, Inc. Appareil et procede de separation des phases liquide et solide pour des syntheses organiques en phase solide
US6663832B2 (en) 1999-12-13 2003-12-16 Illumina, Inc. Oligonucleotide synthesizer
US6846460B1 (en) 1999-01-29 2005-01-25 Illumina, Inc. Apparatus and method for separation of liquid phases of different density and for fluorous phase organic syntheses
US7390459B2 (en) 1999-12-13 2008-06-24 Illumina, Inc. Oligonucleotide synthesizer
DE102008042971A1 (de) 2008-10-20 2010-04-22 Agilent Technologies Inc., Santa Clara Zentrifuge mit Magneteinrichtung
JP2010133952A (ja) * 2008-11-12 2010-06-17 F Hoffmann-La Roche Ag Ｍｗｐ蓋分離
WO2014150869A1 (fr) * 2013-03-15 2014-09-25 Inanovate, Inc. Dispositif de cartouche pour le traitement de tests résolus en temps
WO2014150853A1 (fr) * 2013-03-15 2014-09-25 Inanovate, Inc. Mesure d'analyte(s) à l'aide d'un dosage longitudinal
EP2835178A1 (fr) * 2013-08-06 2015-02-11 AusBio R&D Europe GmbH Centrifugeuse et procédé pour la centrifugation d'une unité de récipient de réaction
US8975087B2 (en) 2010-11-24 2015-03-10 Inanovate, Inc. Longitudinal assay
CN110586557A (zh) * 2019-09-11 2019-12-20 苏州长光华医生物医学工程有限公司 清洗分离装置

Citations (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3722790A (en) * 1969-07-30 1973-03-27 Rohe Scientific Corp Sequential centrifugal treatment of liquid samples
US3826622A (en) * 1969-07-30 1974-07-30 Rohe Scientific Corp Containers for use in an automated centrifuge
US3838809A (en) * 1973-04-16 1974-10-01 M Williams Automatic serum preparation station
US3985649A (en) * 1974-11-25 1976-10-12 Eddelman Roy T Ferromagnetic separation process and material
US4115534A (en) * 1976-08-19 1978-09-19 Minnesota Mining And Manufacturing Company In vitro diagnostic test
US4314968A (en) * 1979-10-26 1982-02-09 Jean Guigan Simultaneous analysis apparatus
US4458812A (en) * 1982-08-09 1984-07-10 Instrumentation Laboratory, Inc. Reagent storage vessel
US4470954A (en) * 1983-06-13 1984-09-11 Chiknas Steven G Rotor or carrier for centrifugal analyzer and bead washer
JPS60207058A (ja) * 1984-03-30 1985-10-18 Shimadzu Corp 抗体又は抗原不溶化担体
US4639242A (en) * 1985-02-04 1987-01-27 Babson Arthur L Vessel and procedure for automated assay
US4793973A (en) * 1985-07-08 1988-12-27 Serono Diagnostic Partners Container for adding antibodies or antigens to a biological liquid
EP0358948A2 (fr) * 1988-08-10 1990-03-21 E.I. Du Pont De Nemours And Company Méthode pour effectuer automatiquement des réactifs magnétiques en phase solide
US4933291A (en) * 1986-12-22 1990-06-12 Eastman Kodak Company Centrifugable pipette tip and pipette therefor
US5084240A (en) * 1988-07-25 1992-01-28 Cirrus Diagnostics Inc. Centrifuge vessel for automated solid-phase immunoassay

Patent Citations (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3722790A (en) * 1969-07-30 1973-03-27 Rohe Scientific Corp Sequential centrifugal treatment of liquid samples
US3826622A (en) * 1969-07-30 1974-07-30 Rohe Scientific Corp Containers for use in an automated centrifuge
US3838809A (en) * 1973-04-16 1974-10-01 M Williams Automatic serum preparation station
US3985649A (en) * 1974-11-25 1976-10-12 Eddelman Roy T Ferromagnetic separation process and material
US4115534A (en) * 1976-08-19 1978-09-19 Minnesota Mining And Manufacturing Company In vitro diagnostic test
US4314968A (en) * 1979-10-26 1982-02-09 Jean Guigan Simultaneous analysis apparatus
US4458812A (en) * 1982-08-09 1984-07-10 Instrumentation Laboratory, Inc. Reagent storage vessel
US4470954A (en) * 1983-06-13 1984-09-11 Chiknas Steven G Rotor or carrier for centrifugal analyzer and bead washer
JPS60207058A (ja) * 1984-03-30 1985-10-18 Shimadzu Corp 抗体又は抗原不溶化担体
US4639242A (en) * 1985-02-04 1987-01-27 Babson Arthur L Vessel and procedure for automated assay
US4793973A (en) * 1985-07-08 1988-12-27 Serono Diagnostic Partners Container for adding antibodies or antigens to a biological liquid
US4933291A (en) * 1986-12-22 1990-06-12 Eastman Kodak Company Centrifugable pipette tip and pipette therefor
US5084240A (en) * 1988-07-25 1992-01-28 Cirrus Diagnostics Inc. Centrifuge vessel for automated solid-phase immunoassay
EP0358948A2 (fr) * 1988-08-10 1990-03-21 E.I. Du Pont De Nemours And Company Méthode pour effectuer automatiquement des réactifs magnétiques en phase solide

Cited By (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6121054A (en) * 1997-11-19 2000-09-19 Trega Biosciences, Inc. Method for separation of liquid and solid phases for solid phase organic syntheses
WO1999025470A1 (fr) * 1997-11-19 1999-05-27 Trega Biosciences, Inc. Appareil et procede de separation des phases liquide et solide pour des syntheses organiques en phase solide
US7977456B2 (en) 1999-01-29 2011-07-12 Illumina, Inc. Apparatus and method for separation of liquid phases of different density and for fluorous phase organic syntheses
US6846460B1 (en) 1999-01-29 2005-01-25 Illumina, Inc. Apparatus and method for separation of liquid phases of different density and for fluorous phase organic syntheses
US8394923B2 (en) 1999-01-29 2013-03-12 Illumina, Inc. Apparatus and method for separation of liquid phases of different density and for fluorous phase organic syntheses
US8178652B2 (en) 1999-01-29 2012-05-15 Illumina, Inc. Apparatus and method for separation of liquid phases of different density and for fluorous phase organic syntheses
US7390459B2 (en) 1999-12-13 2008-06-24 Illumina, Inc. Oligonucleotide synthesizer
US8465694B2 (en) 1999-12-13 2013-06-18 Illumina, Inc. Oligonucleotide synthesizer
US6663832B2 (en) 1999-12-13 2003-12-16 Illumina, Inc. Oligonucleotide synthesizer
DE102008042971A1 (de) 2008-10-20 2010-04-22 Agilent Technologies Inc., Santa Clara Zentrifuge mit Magneteinrichtung
JP2010133952A (ja) * 2008-11-12 2010-06-17 F Hoffmann-La Roche Ag Ｍｗｐ蓋分離
US9316656B2 (en) 2008-11-12 2016-04-19 Roche Molecular Systems, Inc. Lid separation device and methods
JP2014178333A (ja) * 2008-11-12 2014-09-25 F Hoffmann-La Roche Ag Ｍｗｐ蓋分離
US10060919B2 (en) 2010-11-24 2018-08-28 Inanovate, Inc. Longitudinal assay
US9874559B2 (en) 2010-11-24 2018-01-23 Inanovate, Inc. Capacitive pumping and flow control
US8975087B2 (en) 2010-11-24 2015-03-10 Inanovate, Inc. Longitudinal assay
WO2014150869A1 (fr) * 2013-03-15 2014-09-25 Inanovate, Inc. Dispositif de cartouche pour le traitement de tests résolus en temps
WO2014150853A1 (fr) * 2013-03-15 2014-09-25 Inanovate, Inc. Mesure d'analyte(s) à l'aide d'un dosage longitudinal
JP2016534865A (ja) * 2013-08-06 2016-11-10 ヤンタイ・アウスビオ・ラボラトリーズ・カンパニー・リミテッド 遠心分離機、および反応容器ユニットに遠心力を作用させるための方法
JP2019013917A (ja) * 2013-08-06 2019-01-31 ヤンタイ・アウスビオ・ラボラトリーズ・カンパニー・リミテッド 遠心分離機、および反応容器ユニットに遠心力を作用させるための方法
WO2015018878A3 (fr) * 2013-08-06 2015-05-07 Yantai Ausbio Laboratories Co., Ltd. Centrifugeuse et procédé de centrifugation d'une unité de récipient de réaction
DE202014011068U1 (de) 2013-08-06 2017-08-16 Yantai Ausbio Laboratories Co., Ltd. Zentrifuge zum Zentrifugieren einer Reaktions-Gefässeinheit
DE202014011073U1 (de) 2013-08-06 2017-08-17 Yantai Ausbio Laboratories Co., Ltd. Zentrifuge zum Zentrifugieren einer Reaktions-Gefäßeinheit
DE202014011072U1 (de) 2013-08-06 2017-08-17 Yantai Ausbio Laboratories Co., Ltd. Zentrifuge zum Zentrifugieren einer Reaktions-Gefäßeinheit
DE202014011074U1 (de) 2013-08-06 2017-08-17 Yantai Ausbio Laboratories Co., Ltd. Zentrifuge zum Zentrifugieren einer Reaktions-Gefäßeinheit
DE202014011071U1 (de) 2013-08-06 2017-08-18 Yantai Ausbio Laboratories Co., Ltd. Zentrifuge zum Zentrifugieren einer Reaktions-Gefäßeinheit
DE202014011070U1 (de) 2013-08-06 2017-08-21 Yantai Ausbio Laboratories Co., Ltd. Zentrifuge zum Zentrifugieren einer Reaktions-Gefäßeinheit
WO2015018878A2 (fr) * 2013-08-06 2015-02-12 Yantai Ausbio Laboratories Co., Ltd. Centrifugeuse et procédé de centrifugation d'une unité de récipient de réaction
EP2835178A1 (fr) * 2013-08-06 2015-02-11 AusBio R&D Europe GmbH Centrifugeuse et procédé pour la centrifugation d'une unité de récipient de réaction
DE202014010544U1 (de) 2013-08-06 2015-11-26 Yantai Ausbio Laboratories Co., Ltd. Zentrifuge zum Zentrifugieren einer Reaktions-Gefäßeinheit
US10338063B2 (en) 2013-08-06 2019-07-02 Yantai Ausbio Laboratories Co., Ltd. Centrifuge and method for centrifuging a reaction vessel unit
US11885798B2 (en) 2013-08-06 2024-01-30 Yantai Ausbio Laboratories Co., Ltd. Centrifuge and method for loading and centrifuging a reaction vessel unit
US10928387B2 (en) 2013-08-06 2021-02-23 Yantai Ausbio Laboratories Co., Ltd. Centrifuge including a magnetic element and method for centrifuging a reaction vessel unit and using a magnetic element
US11885799B2 (en) 2013-08-06 2024-01-30 Yantai Ausbio Laboratories Co., Ltd. Centrifuge including a magnetic element and method for centrifuging a reaction vessel unit
DE202014011521U1 (de) 2013-08-06 2021-11-18 Yantai Ausbio Laboratories Co., Ltd. Zentrifuge und System zum Waschen von magnetischen Partikeln in einer Reaktions-Gefäßeinheit
DE202014011542U1 (de) 2013-08-06 2022-01-31 Yantai Ausbio Laboratories Co., Ltd. Zentrifuge zum Zentrifugieren einer Reaktions-Gefäßeinheit
DE202014011543U1 (de) 2013-08-06 2022-01-31 Yantai Ausbio Laboratories Co., Ltd. Zentrifuge zum Zentrifugieren einer Reaktions-Gefäßeinheit
DE202014011611U1 (de) 2013-08-06 2023-06-16 Yantai Ausbio Laboratories Co., Ltd. Zentrifuge zum Zentrifugieren einer Reaktions-Gefäßeinheit
DE202014011612U1 (de) 2013-08-06 2023-06-16 Yantai Ausbio Laboratories Co., Ltd. Zentrifuge zum Waschen einer Reaktions-Gefäßeinheit
DE202014011614U1 (de) 2013-08-06 2023-07-04 Yantai Ausbio Laboratories Co., Ltd. Zentrifuge zum Zentrifugieren einer Reaktions-Gefäßeinheit
CN110586557B (zh) * 2019-09-11 2021-08-20 苏州长光华医生物医学工程有限公司 清洗分离装置
CN110586557A (zh) * 2019-09-11 2019-12-20 苏州长光华医生物医学工程有限公司 清洗分离装置

Similar Documents

Publication Publication Date Title
US5084240A (en) Centrifuge vessel for automated solid-phase immunoassay
US8999729B2 (en) Device and analyzing system for conducting agglutination assays
JP2510932B2 (ja) 試料中における生物学的物質の存在を決定する方法及び装置
US4868130A (en) Methods for conducting specific binding assays
JP2854058B2 (ja) アッセイを実施するための方法及び装置
US4458020A (en) Integrated single tube plunger immunoassay system having plural reagent chambers
US5244635A (en) Centrifuge vessel with coaxial waste chamber having cap to prevent waste fluid transfer from the chamber into the vessel
US7713708B2 (en) Immunological assay system and method
US4639242A (en) Vessel and procedure for automated assay
US5318748A (en) Centrifuge vessel for automated solid-phase immunoassay having integral coaxial waste chamber
EP0595641A2 (fr) Essai immunologique simultané à une étape
US20040166551A1 (en) Detection of agglutination of assays
US10018645B2 (en) Immunodiagnostic test element having weakened foil layer
US5073341A (en) Devices for conducting specific binding assays
JPH087215B2 (ja) 抗原および／又は抗体の検出方法および検出用の試験キット
JPS596390B2 (ja) 実験分析装置
WO2006068935A1 (fr) Resuspension de particules magnetisables
WO1993010455A1 (fr) Cuve centrifuge amelioree pour dosage immunologique automatique en phase solide
US5098845A (en) Device and procedure for automated solid-phase immunoassay
JPH102900A (ja) サンプル液体中の分析物を検出する方法、試薬キット及び反応容器
US5258309A (en) Procedure for automated solid-phase immunoassay using a centrifuge tube
JP2007524831A (ja) 免疫学的アッセイシステムおよび方法

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): CA JP

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL SE

122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: CA