WO1992008972A1 - Dispositif de reaction d'agglutination ameliore dote de chambres geometriquement modifiees - Google Patents

Dispositif de reaction d'agglutination ameliore dote de chambres geometriquement modifiees Download PDF

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Publication number
WO1992008972A1
WO1992008972A1 PCT/US1991/008549 US9108549W WO9208972A1 WO 1992008972 A1 WO1992008972 A1 WO 1992008972A1 US 9108549 W US9108549 W US 9108549W WO 9208972 A1 WO9208972 A1 WO 9208972A1
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WO
WIPO (PCT)
Prior art keywords
layer
chamber
path
slot
defining
Prior art date
Application number
PCT/US1991/008549
Other languages
English (en)
Inventor
Robert G. Parsons
Bob O. Basore
Michael B. O'connell
Kevin J. Forney
Paul J. Ropella
Andrew J. Muetterties
Original Assignee
Abbott Laboratories
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 Abbott Laboratories filed Critical Abbott Laboratories
Publication of WO1992008972A1 publication Critical patent/WO1992008972A1/fr

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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
    • G01N33/5302—Apparatus specially adapted for immunological test procedures
    • G01N33/5304—Reaction vessels, e.g. agglutination plates
    • 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
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/069—Absorbents; Gels to retain a fluid
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0803—Disc shape
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0825—Test strips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0864—Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0887—Laminated structure
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces

Definitions

  • the present invention is directed to an improved device for performing an agglutination reaction of immunochemical particles.
  • the agglutination reaction device is designed to provide a convenient means for performing and reading the results of an agglutination reaction.
  • a particular improvement involves varying the geometry, namely the width and/or depth, of a portion of the path along which liquid in the device flows by capillary action.
  • a typical agglutination reaction consists of the clumping together (or aggregation) in suspension of antigen- or antibody-bearing cells, microorganisms, or particles in the presence of specific analytes. This clumping or agglutination of particles is then monitored to determine the absence or presence of an analyte sought to be detected.
  • U.S. Patent 4,596,695 discloses an agglutination reaction chamber for reacting immunochemical particle reagents.
  • the chamber includes a first transparent panel having a first surface and a second panel having a second surface spaced apart from the first
  • S UBSTITUTE SHEET surface to define a chamber inbetween.
  • the chamber intrinsically causes immunochemical particle reagents to flow by capillary action without an external motion imparted to the chamber during which flow the immunochemical particle reagents can react.
  • An object of the present invention is to provide a device that can be easily adapted for use in the automated diagnosis of a plurality of samples. Another object of the present invention is to provide a device capable of performing multiple, highly sensitive, diagnostic tests simultaneously on a single sample in a single device.
  • the present invention is directed to a device in which the agglutination reaction can be rapidly performed and monitored with a minimum of sample material.
  • the present invention is directed to a device having multiple channels radiating from a central well where multiple reactions on a single sample can be rapidly performed and monitored with a minimum of sample material with the results of such reactions being easily, visibly observable.
  • the present invention is directed to devices for performing agglutination reactions having enhanced performance properties through utilization of a means for controlling the flow of liquid through the reaction chamber of the device, namely, through modification of the geometric configuration of the agglutination reaction chamber or the internal shape of the chamber so as to provide a non-random patterned array of aggregated agglutinates which non-random pattern is more easily observable than agglutinates aggregated in a random array.
  • the present invention provides a device for performing agglutination reactions comprising: in adherent
  • SUBSTITUTE SHEET relationship a first wettable layer, a second liquid- occlusive layer parallel to and overlying the first layer, and a third layer parallel to and overlying the second layer and having a window for observing particles.
  • the second layer is interposed between, and is in adherent relationship to, the first and third layers.
  • the second layer has at least one general slot therein defining a channel for directing liquid conducted by capillary action through a chamber defined by the slot in conjunction with the first and third layers. Agglutination reactions can be performed in the chamber.
  • the chamber has a proximate zone and a distal zone.
  • the aforesaid slot in the second layer defines at least approximately parallel walls in the proximate zone thereby defining a first path of approximately constant width.
  • the aforesaid slot in the second layer also defines walls in the distal zone which are spaced to define a second path of increased width compared to the first path.
  • the present invention also provides in particular for such a device for performing agglutination reactions in which the second layer has at least one general slot therein defining a channel for directing liquid conducted by capillary action through a chamber defined by the slot and by the first and third layers and within which chamber agglutination reactions can be performed.
  • the chamber has a proximate zone and a distal zone.
  • the slot in the second layer defines walls in the proximate zone which with the first and third layers define a first path of approximately
  • the slot in the second layer also defines walls in the distal zone which with the first and third layers define a second path of increasing depth compared to the first path whereby agglutination reactions in the chamber result in the formation of a non-random pattern of aggregated particles in the distal zone of the chamber which non-random pattern is more readily observable through the window of the third layer than if a random pattern of aggregated particles occurred instead.
  • the present invention provides a device for performing simultaneously a plurality of agglutination reactions.
  • the device comprises: in adherent relationship, a first wettable layer, a second liquid- occlusive layer parallel to and overlying the first layer, and a third layer parallel to and overlying the second layer and having windows for observing particles.
  • the second layer is interposed between and is in adherent relationship to the first and third layers.
  • the general slot of the second layer has a plurality of slotted arms (also slots) in radial spatial relationship to each other. These radiating slots respectively define channels for directing liquid conducted by capillary action through chambers respectively defined by the slots in conjunction with the first and third layers. Agglutination reactions can be performed simultaneously in these chambers.
  • Each of the chambers has a proximate zone and a distal zone, and each of the slots defines at least approximately parallel walls in the corresponding proximate zone thereby defining a corresponding first path of approximately constant width and defines walls in the corresponding distal zone which are spaced to define a corresponding second path of increased width compared to the first path.
  • Agglutination reactions performed in the corresponding chambers can result in the formation of a non-random pattern of aggregated particles in the distal zone of each chamber
  • SUBSTITUTE SHEET which non-random pattern is more readily observable through the window of the third layer than if a random pattern of aggregated particles occurred instead.
  • An agglutination reaction device of the present invention additionally can include a sample receiving well contiguous with the ingress of the agglutination chamber.
  • the reagent in an agglutination reaction chamber of the present invention, can be present in dried spots or strips. It is also possible to suspend the reagent in a water-soluble polymer.
  • a copending United States Patent Application, Serial Number 07/138,253, filed on December 23, 1987, entitled "Agglutination Reaction Device” (the disclosure of which is hereby specifically incorporated herein by reference), teaches an agglutination reaction chamber which is constructed to be very small in size to accommodate automated and efficient use of sample and reagents.
  • the length of such a chamber is from about 10 to about 75 millimeters (mm)
  • the channels are from about 0.01 to about 5.0 mm in depth and from about 0.1 to about 10.0 mm in width.
  • a typical overall size for such an agglutination reaction device having four chambers and a sample receiving well is about 37.5 mm x 12.5 mm x 1.5 mm (1 x w x h) .
  • the aforesaid copending United States Patent Application also generally discloses a means for controlling the flow of fluid in an agglutination reaction chamber involving the configuration of the channel or geometric formations within the channel such as ridges, particularly ridges formed in the channel which extend across the entire width of the channel and for at least a portion of the length of the channel.
  • the aforesaid copending United States Patent Application also discloses another means for controlling the flow of fluid in the
  • SUBSTITUTE SHEET chamber namely utilization of a water-soluble material, such as a water-soluble polymer, (e.g., polyvinylpyrrolidone, polyvinylalcohol, gelatin, or bovine serum albumin) dried in portions of the channel.
  • a water-soluble material such as a water-soluble polymer, (e.g., polyvinylpyrrolidone, polyvinylalcohol, gelatin, or bovine serum albumin) dried in portions of the channel.
  • the present invention is directed to devices for performing agglutination reactions having improved properties including improved means for controlling the rate of liquid flow per unit area through the agglutination chamber so as to produce a non-random pattern of aggregated agglutinated particles.
  • the present invention also is directed to such devices constructed in the form of convenient, disposable structures, such as disposable, laminated cards, optionally mounted in disposable rigid containers.
  • SUBSTITUTE SHEET Figure 1 is an exploded, top perspective view of an embodiment showing a three layer structure comprising a first or base layer, a second layer showing a cutout for a round receiving well and an agglutination chamber having a flared portion at its distal end, a strip of porous absorbent material, and a third or top layer.
  • Figure 2 is an exploded, top perspective view of another embodiment showing a three layer structure comprising a first or base layer, a second layer showing a cutout for a round receiving well and an agglutination chamber having a flared portion at its distal end with an integral porous absorbent strip in the second layer at the distal end of the chamber, and a third or top layer.
  • Figure 3 is a top plan view of another embodiment showing the parts of a laminated structure comprising a base layer, a second layer having a cutout for a round receiving well and multiple radiating agglutination chambers having flared distal zones, an annular structure (ring) having alternating liquid absorbent regions (4) and liquid-occlusive regions (26), and another round layer which in cooperation with the annular structure forms the top layer.
  • a laminated structure comprising a base layer, a second layer having a cutout for a round receiving well and multiple radiating agglutination chambers having flared distal zones, an annular structure (ring) having alternating liquid absorbent regions (4) and liquid-occlusive regions (26), and another round layer which in cooperation with the annular structure forms the top layer.
  • Figure 4 is a schematic diagram illustrating regions of different flow rate per unit area outward from the receiving well for an agglutination chamber having a flared distal end, and illustrating a band of agglutinated particles in the flared distal end.
  • Figure 5 is a schematic diagram illustrating regions of different flow rate per unit area outward from the receiving well for an agglutination chamber having a semicircular, or bowl-shaped, distal end, and illustrating a band of agglutinated particles in the semicircular end.
  • Figure 6 is a schematic diagram illustrating regions of different flow rate per unit area outward from
  • the present invention is directed to improved devices suitable for performing agglutination reactions. Surprisingly, it has been found that the devices of the present invention, for performing agglutination reactions, provide enhanced properties over prior art devices.
  • the devices of the present invention utilize a means for controlling the rate of flow per unit area of liquid through the reaction chamber of the device. In particular these means consist of modifying the geometric configuration of the chamber or the internal shape of the chamber as illustrated in Figures 1, 2, 3, 4, 5 and 6.
  • Figure 1 represents an embodiment of a device for performing agglutination reactions according to the invention.
  • This embodiment has, in adherent relationship, a first wettable, but liquid-occlusive, layer (1), a second liquid-occlusive layer (2) parallel to and overlying the first layer (1), and a third liquid-occlusive, preferably non-wettable, layer (3) parallel to and overlying the second layer (2) and having a window, or viewing area, for observing particles.
  • the first layer (1) is made of a liquid-occlusive material having a water-wettable surface.
  • the third layer (3) is made from a clear, liquid-occlusive, non-wettable, film, such as a clear polycarbonate film, and therefore also serves as a window, or viewing area, for observing particles in the agglutination chamber.
  • the second layer (2) is interposed between, and is adhered to, the first layer (1) and third layer (3), for example by means of an adhesive on each side of layer (2) facing the topside of the first layer (1) and
  • the second layer (2) has a general slot (25) cut through its thickness defining a channel for directing liquid for conduction by capillary action through the chamber defined by the slot (25) in conjunction with the first layer (1) and third layer (3) respectively.
  • each of the first and third layers serve respectively as the floor and roof of the agglutination chamber with part of the walls of the slot (25) of the second layer (2) defining the walls (9) of the chamber.
  • the agglutination reaction chamber has a proximate zone (6) and a distal zone (7) , which proximate zone (6) is represented by the generally rectangular portion of the slot (25) of the second layer (2) with the distal zone (7) being represented by the deltoid or flared portion of the slot (25) of the second layer (2).
  • the embodiment illustrated by Figure 1 has a well-defining slot (8) in the third layer (3) and a corresponding second well-defining slot (5) in the second layer (2) of the same size and configuration as the well- defining slot (8) in the third layer (3).
  • the well- defining slot (5) in the second layer (2) is positioned directly below the well-defining slot (8) in the third layer (3) such that when all three layers are laminated together, the second well-defining slot (5) in conjunction with the well-defining slot (8) along with the corresponding portion of the first layer define a well for receiving liquid, the well being in liquid communication with the proximate zone (6) of the chamber.
  • the bottom of the well is formed from a corresponding circular portion of the first layer (1) which portion can be considered to be the projection of the outline of slots (5) and (8) onto the surface of layer (1).
  • SUBSTITUTE SHEET overall rate of liquid flow through the agglutination chamber is controlled by means of a strip of porous absorbent material (4), preferably filter paper, in liquid communication with the chamber and positioned adjacent to the distal end of the chamber, and preferably extending partially into the distal end of the chamber, when the structures of Figure 1 are laminated respectively together.
  • the absorbent porous material for example paper, is to be distinguished from water-soluble materials such as dried coatings of water- soluble polymers such as polyvinylpyrrolidone, polyvinylalcohol, gelatin, or bovine serum albumin.
  • the porous absorbent material utilized in present invention is itself generally not water-soluble.
  • layer (3) as shown in Figure 1 has a slot (28), of slightly larger dimensions as the strip of porous paper (4) , such that when the respective layers are adhered together, the strip of porous absorbent material (4) lies partially within the slot (28), more particularly so that a front minor portion of the strip (4) lies within the distal zone (7) of the slot (25) with the remaining major portion of the strip lying within slot (28), so as to prevent disadvantageous formation of microcapillary channels at the sides of and along the length of the strip (4).
  • the resulting laminated structure can be thought of as being in the form of a thin, disposable card with the paper strip (4) being in liquid communication with the distal zone (7) of the agglutination chamber.
  • the solution when a solution of cells is introduced into the receiving well of a device of the invention, which well is in liquid communication with the proximate end of the reaction chamber; and the chamber contains antibodies directed against antigens on the cells and which antigens are dried onto the floor of the chamber, the solution will migrate through the chamber by capillary
  • SUBSTITUTE SHEET action mix with the antisera, and the cells will aggregate. This will all occur without any centrifugation or mixing steps. Control of the overall rate of flow of the liquid through the channel is necessary because the agglutination reaction occurs preferably during the period of liquid flow. Sufficient incubation time is built into the period of liquid flow to achieve optimum reaction of the reagents.
  • the general slot (25) in layer (2) defines at least approximately parallel walls (9) in the proximate zone (6) of the chamber thereby defining a first path of approximately constant width.
  • the general slot (2) defines walls in the distal zone (7) which are spaced to define a second path of increased width compared to the first path of the proximate zone (6).
  • FIG. 4 shows a schematic representation of an approximately semicircular band (27) of agglutinated particles in the zone of increasing chamber width, namely in the flared (here approximately deltoid-shaped) "second path" of the chamber in the distal zone (7) of the chamber.
  • the side walls in the second path can be formed to be convex giving an approximately semicircular or bowl-shaped configuration to the second path as illustrated in Figure 5.
  • the side walls of the second path can be formed to provide a second path with an approximately rectangular shape as illustrated in Figure 6.
  • Figure 2 represents another embodiment of a device, in the form of a laminated card when the layers shown in Figure 2 are adhered together, for performing agglutination reactions.
  • This embodiment has, in adherent relationship, a first wettable, but liquid-occlusive, layer (1), a second layer (2) parallel to and overlying the first layer (1), and a third liquid-occlusive, preferably non- wettable, layer (3) parallel to and overlying the second layer (2) and having a window, or viewing area, for observing particles.
  • the first layer (1) is made of a liquid-occlusive material having a water-wettable surface.
  • this embodiment also utilizes a third layer (3) made from a clear, liquid-occlusive, preferably non-wettable film, such as a clear polycarbonate film or a non-wettable cellophane tape, which therefore also serves as a window for observing particles in the agglutination chamber.
  • the second layer (2) is interposed between, and is adhered to, the first layer (1) and third layer (3) , for example by means of an adhesive on each side of layer (2) facing the topside of the first layer (1) and the underside of the third layer
  • the second layer (2) has a general slot (25) cut through its thickness defining a channel for directing liquid for conduction by capillary action through the chamber defined by the slot (25) in conjunction with the first (1) and third (3) layers respectively.
  • each of the first and third layers serve respectively as the floor and roof of the agglutination chamber with part of the walls of the slot (25) of the second layer (2) defining the walls (9) of the chamber, the other part of the walls of slot (25) defining the walls of the circular receiving well (5).
  • the agglutination reaction chamber has a proximate zone (6) and a distal zone (7), which proximate zone (6) is represented by the generally rectangular portion of the slot (25) of the second layer (2) with the distal zone (7) being represented by the deltoid or flared portion of the slot (25) of the second layer (2).
  • Each of the embodiments illustrated by Figures 1 and 2 has a well-defining slot (8) in the third layer (3) and a corresponding second well-defining slot (5) in the second layer (2) of the same size and configuration as the well-defining slot (8) in the third layer (3).
  • the well- defining slot (5) in the second layer (2) is positioned directly below the well-defining slot (8) in the third layer (3) such that when all three layers are laminated together, the second well-defining slot (5) in conjunction with the well-defining slot (8) along with the corresponding portion of the first layer define a circular well for receiving liquid, the well being in liquid communication with the proximate zone (6) of the chamber.
  • the bottom of the well is formed from a corresponding circular portion of the first layer (1).
  • S UBSTITUTE SHEET layer (2) is made of a liquid absorbent material, such as absorbent paper, selectively impregnated through its thickness with a substance, such as a water-repellent ink, to form an impregnated region (26) and a non-impregnated region (4).
  • the non-impregnated region (4) is liquid absorbent and the impregnated region (26) is liquid- occlusive.
  • the non-impregnated region (4) which is in liquid communication with the distal zone (7) of the chamber serves as means for controlling the overall rate of liquid flow through the agglutination chamber.
  • the second layer (2) also has a slot (25) in the impregnated region (26) defining a channel for directing liquid conducted by capillary action through a chamber defined by the slot (25) in conjunction with the first layer (1) and third layer (3).
  • This chamber also has a proximate zone (6) and a distal zone (7). It is within this chamber that agglutination reactions can be performed.
  • the non-impregnated region (4) is located adjacent to the distal end of the agglutination chamber and is in liquid communication with the chamber.
  • Figure 3 illustrates an exploded, plan view of a preferred embodiment of the invention. This embodiment provides for performing a plurality of agglutination reactions utilizing a minimal amount of liquid sample.
  • the device in assembled form can be thought of a relatively thin, laminated, disposable card having in this particular illustration six agglutination chambers radiating from a common liquid receiving well.
  • the device of Figure 3 comprises, in adherent relationship, an approximately circular first wettable but liquid-occlusive layer (1), an approximately circular second liquid-occlusive layer (2) parallel to and overlying the first layer (1), and a third liquid-occlusive layer (3) parallel to and overlying the second layer (2) .
  • These respective layers can be bonded together, for example, by means of an adhesive between the
  • the third layer (3) is made of a circular clear plastic film, such as a polycarbonate film, thereby providing windows, or viewing areas, for observing particles in the six radiating agglutination chambers.
  • the second layer (2) interposed between and in adherent relationship to the first and third layers has a slot (25) in the form of a central, circular portion (5) having six radial, slotted arms extending outward therefrom. These radial arms of the slot (25) define six channels for directing liquid conducted by capillary action through chambers respectively defined by the radial, slotted arms in conjunction with the first layer (1) and the third layer (3) .
  • agglutination reactions can be performed simultaneously.
  • Each of the six chambers has a generally rectangular proximate zone (6) and a generally flared or deltoid shaped distal zone (7) .
  • the overall rate of liquid flow through each agglutination chamber in this embodiment is controlled by means of a strip of porous absorbent material (4), preferably filter paper, projecting from a generally annular ring (27) of such porous material, into the distal zone (7) of each of the channels defined by the radial, slotted arms.
  • the annular ring (27) is selectively impregnated through its thickness with a substance to provide alternating non-impregnated liquid absorbent regions (4) and impregnated liquid-occlusive regions (26).
  • non-impregnated strips (4) of paper projecting from the annular ring (27) are in liquid communication with the chambers and are positioned adjacent to the distal ends of the chambers, preferably positioned partially in the distal ends, when the structures of Figure 3 are laminated respectively together.
  • the third layer (3) of the device represented by Figure 3 has a circular well-defining slot (8), and the second layer has a corresponding circular second well-
  • SUBSTITUTE SHEET defining slot (5) of the same size and configuration as the well-defining slot (8) in the third layer (3).
  • the well- defining slot (5) of the second layer (2) is positioned directly below the well-defining slot in the third layer (3) in the assembled configuration.
  • the second well- defining slot (5) in conjunction with the well-defining slot (8) in the third layer (3) and the respective circular portion of the first layer (1) define a well for receiving liquid, the well being in liquid communication with the proximate zone (6) of each of the chambers.
  • the resulting, generally circular laminated structure can be thought of as being in the form of a relatively thin, disposable card with the fluid-absorbent paper strip (4) being in liquid communication with the distal zone (7) of the agglutination chamber.
  • the flow rate per unit area in the distal zone of the reaction chamber of an embodiment of the invention can be gradually decreased along the general direction of flow by gradually increasing the space between the floor and the roof of the chamber along the direction of liquid flow, for example by gradually bowing the roof of the chamber in the distal zone upward and/or by gradually bowing the floor of the chamber in the distal zone downward. It has been found that such modification of the space between the floor and the roof of the chamber in the distal zone of the chamber can also contribute to the formation of regular patterns of agglutinated particles being formed in the distal zone of the chamber.
  • the space between the floor and the roof of the chamber can be gradually increased by stamping a spherical dome-shaped or cylindrical dome-shaped configuration in an area of the third layer (3) in such manner that when the third layer is adhered to the second layer (2) the dome in the third layer overlies the distal zone of the reaction chamber.
  • a spherical dome-shaped or cylindrical dome-shaped configuration in an area of the third layer (3) in such manner that when the third layer is adhered to the second layer (2) the dome in the third layer overlies the distal zone of the reaction chamber.
  • SUBSTITUTE SHEET increasing space between the floor and the roof of the distal zone of the reaction chamber is to stamp a spherical bowl-shaped or cylindrical bowl-shaped depression in the base or first layer (1) in such manner that when the first layer (1) is adhered to the second layer (2) the bowl- shaped depression occurs in the floor of the distal zone of the reaction chamber.
  • a soluble reagent can be dried as spots or strips in the reaction chamber, for example, in blood typing.
  • a particulate reagent such as a latex reagent, can be dried in the chamber.
  • a reagent can be dispersed in a solution which is placed in the chamber.
  • One preferred reagent solution is microparticulates in a solution of dextran and sucrose.
  • the microparticulate reagent is mixed in a solution of about 2.5 to about 5.0 percent by weight dextran and from about 15 to about 20 percent by weight sucrose.
  • FICOLL a trademark by Sigma Chemical Co., St. Louis, MO for a nonionic synthetic polymer of sucrose
  • the flow of the liquid through the chamber can be controlled as described above to accommodate any necessary incubation times and assay sequences.
  • a particularly advantageous feature of the present invention is that it provides for the ability to simultaneously perform multiple assays while utilizing a very small amount of sample material, for instance, a single drop. Also, the agglutination assay is essentially self-performing once the drop has been added to the agglutination reaction device. It is important to note
  • a device of the invention is suitable for use in an automated fashion where the agglutination reaction can be monitored by an optical scanner.
  • the construction of the agglutination reaction device enables one to use an image analysis system available from Olympus (CUE-2, Lake Success, N.Y.) to determine the quantity and concentration of agglutinated material.
  • the agglutination reaction device is illuminated, such that transmitted or reflected light can be read by the reader.
  • the image is then computer analyzed to determine the quantity of agglutination which has occurred and to enhance the image for very accurate and sensitive determinations.
  • the uniformity of the reacted sample and reagents achieved by the agglutination reaction device provides an excellent imaging format for a reader or other imaging devices. Besides being able to read the transmission of light through the bottom of the agglutination reaction device, it is also possible to read reflected light because the sample and reacted reagents are confined to capillary chambers formed by the agglutination reaction device.
  • S UBSTITUTE SHEET bottom surface, of an agglutination chamber of the present invention be hydrophilic or wettable such that capillary flow is induced when a sample is placed in contact with the ingress of the proximate zone of the chamber.
  • This can be accomplished by using a hydrophilic or water-wettable material for the surface.
  • Suitable materials for preparing a wettable layer for various embodiments of the invention include, for example, cellulose acetate butyrate, a wettable nylon material, or a layer coated with an acrylic latex emulsion to render the surface water-wettable.
  • the "roof" of an agglutination chamber of the invention may be either wettable or non-wettable.
  • the small size of the reaction devices of the invention allows for the rapid and convenient handling of a plurality of devices and therefore samples. A device can then be loaded into an automated apparatus which indexes and scans the individual channels for the assay result and records this information for future access.
  • the small dimensions of the agglutination reaction device also provide for efficient use of sample and reagents.
  • Laminate disposable cards were prepared by assembling together a wettable base layer, a die cut adhesive core layer, paper strip assemblies, and a clear
  • Steel rule dies were prepared to cut the channel shapes as shown in Figure 1 from a second sheet of two-sided adhesive (3.1 mil, Specialty Tapes, Division of RSW Inc., Racine, WI) which has release liner on both adhesive surfaces.
  • One piece of release liner was removed from the die-cut part and this adhesive layer was placed onto the nylon surface of the base subassembly.
  • Pieces of filter paper 2.5X19 millimeter, 1CHR, Whatman, Clifton, New Jersey
  • ARCare 7597 Adhesive Research, Glen Rock, PA
  • Laminate disposable cards were prepared using a 3"X6" piece of paperboard coated with a wettable acrylic latex emulsion coat (Part 150HT(26-1), Daubert Coated Products, Dixon, IL) in place of the nylon base subassemblies described in Example 1. Die-cut core layers
  • SUBSTITUTE SHEET were prepared using 3.1 mil two-sided adhesive (ARCare 7580, Adhesive Research, Glen Rock, PA). All other steps in card assembly were identical to those of Example 1.
  • erythrocytes (Duracytes TM, Abbott Laboratories, North Chicago, IL) were coated with affinity purified goat antibodies directed against Hepatitis B surface antigen (HBsAg) at a final concentration of 100 ug/ml (micrograms/milliliter) in the presence of 0.05% (weight/volume) chromic chloride in 0.1 M (Molar) acetate buffer at a pH of 4.0. These cells were overcoated with 1% (weight/volume; w/v) human serum albumin (Sigma Chemical Co., St.
  • Laminate disposable cards were prepared as described in Example 2 with a flared channel design as shown in Figure 1.
  • Duracytes coated with anti-HBsAg (Example 3) were mixed with sera containing various concentrations of HBsAg and were introduced into the laminate disposable cards having flared channels. After 5 minutes, aggregated particles appeared and formed into an easily visible band of agglutinates which stretched across the flared portion of the channel as shown in Figure 4. In channels where there was not any HBsAg present, the Duracytes did not aggregate and no band of cells was visible.

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Abstract

Dispositif permettant d'obtenir des réactions d'agglutination et comprenant: dans une relation d'adhérence, une première couche mouillable (1), une seconde arrêtant le liquide (2) parallèle à la première couche (1) qu'elle recouvre, ainsi qu'une troisième couche (3) parallèle à la seconde couche (2) qu'elle recouvre et dotée d'une fenêtre permettant l'observation de particules. La seconde couche est interposée entre les première et troisième couches avec lesquelles elle est en relation d'adhérence. La seconde couche (2) présente au moins une fente générale (25) définissant un canal permettant d'orienter du liquide conduit par capillarité à travers une chambre définie par la fente conjointement avec les première (1) et troisième (3) couches. La chambre présente une zone proximale ainsi qu'une zone distale. La géométrie de ladite chambre est modifiée afin de ménager des chemins d'écoulement ayant différents débits par zone unitaire le long desdits chemins. Cet agencement desdits chemins différents permet d'obtenir des réactions d'agglutination dans ladite chambre avec comme résultat la formation d'une configuration non aléatoire de particules agrégées dans la zone distale de ladite chambre. Ladite configuration non aléatoire est plus facilement observable qu'une configuration aléatoire de particules agrégées.
PCT/US1991/008549 1990-11-16 1991-11-15 Dispositif de reaction d'agglutination ameliore dote de chambres geometriquement modifiees WO1992008972A1 (fr)

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US61481790A 1990-11-16 1990-11-16
US614,817 1990-11-16

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AU (1) AU9064391A (fr)
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Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995017966A1 (fr) * 1993-12-29 1995-07-06 Abbott Laboratories Procedes et dispositifs d'immunodiagnostic a evacuation automatique des gaz pour la realisation d'immunodosages
WO1995017965A1 (fr) * 1993-12-28 1995-07-06 Abbott Laboratories Dispositifs a ecoulement de sous-surface et leur utilisation pour effectuer des titrages
WO1995019845A2 (fr) * 1994-01-22 1995-07-27 Bio-Diagnostics Limited Dispositif de diagnostic
GB2301666A (en) * 1994-01-22 1996-12-11 Bio Diagnostics Ltd Diagnostic device
EP1003038A1 (fr) * 1997-07-28 2000-05-24 Dainabot Co., Ltd. Appareil de dosage immunologique
WO2001002093A2 (fr) * 1999-07-07 2001-01-11 3M Innovative Properties Company Article de detection comprenant une couche mince de commande d'ecoulement de fluide
US6375871B1 (en) 1998-06-18 2002-04-23 3M Innovative Properties Company Methods of manufacturing microfluidic articles
SG91262A1 (en) * 1999-03-19 2002-09-17 Roche Diagnostics Gmbh Multilayered analytical device
US7223364B1 (en) 1999-07-07 2007-05-29 3M Innovative Properties Company Detection article having fluid control film
EP4067907A4 (fr) * 2019-11-22 2023-10-11 BOE Technology Group Co., Ltd. Puce et système de détection

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4906439A (en) * 1986-03-25 1990-03-06 Pb Diagnostic Systems, Inc. Biological diagnostic device and method of use

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3889885T2 (de) * 1987-12-23 1994-12-15 Abbott Lab Vorrichtung zur Agglutinierungsreaktion.

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4906439A (en) * 1986-03-25 1990-03-06 Pb Diagnostic Systems, Inc. Biological diagnostic device and method of use

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP0557433A4 *

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995017965A1 (fr) * 1993-12-28 1995-07-06 Abbott Laboratories Dispositifs a ecoulement de sous-surface et leur utilisation pour effectuer des titrages
WO1995017966A1 (fr) * 1993-12-29 1995-07-06 Abbott Laboratories Procedes et dispositifs d'immunodiagnostic a evacuation automatique des gaz pour la realisation d'immunodosages
US5478751A (en) * 1993-12-29 1995-12-26 Abbott Laboratories Self-venting immunodiagnositic devices and methods of performing assays
WO1995019845A2 (fr) * 1994-01-22 1995-07-27 Bio-Diagnostics Limited Dispositif de diagnostic
WO1995019845A3 (fr) * 1994-01-22 1995-09-08 Bio Diagnostics Ltd Dispositif de diagnostic
GB2301666A (en) * 1994-01-22 1996-12-11 Bio Diagnostics Ltd Diagnostic device
GB2301666B (en) * 1994-01-22 1998-03-11 Bio Diagnostics Ltd Diagnostic device
US5772961A (en) * 1994-01-22 1998-06-30 Bio-Diagnostics Limited Device for use in diagnosis
EP1003038A1 (fr) * 1997-07-28 2000-05-24 Dainabot Co., Ltd. Appareil de dosage immunologique
EP1003038A4 (fr) * 1997-07-28 2002-09-04 Dainabot Co Ltd Appareil de dosage immunologique
US6537828B1 (en) 1997-07-28 2003-03-25 Dainabot Co., Ltd. Immunoassay apparatus
US6375871B1 (en) 1998-06-18 2002-04-23 3M Innovative Properties Company Methods of manufacturing microfluidic articles
SG91262A1 (en) * 1999-03-19 2002-09-17 Roche Diagnostics Gmbh Multilayered analytical device
US6881378B1 (en) 1999-03-19 2005-04-19 Roche Diagnostics Gmbh Multilayered analytical device
WO2001002093A2 (fr) * 1999-07-07 2001-01-11 3M Innovative Properties Company Article de detection comprenant une couche mince de commande d'ecoulement de fluide
WO2001002093A3 (fr) * 1999-07-07 2001-07-26 3M Innovative Properties Co Article de detection comprenant une couche mince de commande d'ecoulement de fluide
US7223364B1 (en) 1999-07-07 2007-05-29 3M Innovative Properties Company Detection article having fluid control film
EP1196243B2 (fr) † 1999-07-07 2009-12-16 3M Innovative Properties Company Produit de detection comprenant une couche mince de commande d'ecoulement de fluide
EP4067907A4 (fr) * 2019-11-22 2023-10-11 BOE Technology Group Co., Ltd. Puce et système de détection

Also Published As

Publication number Publication date
CA2100365A1 (fr) 1992-05-17
EP0557433A4 (en) 1994-06-01
EP0557433A1 (fr) 1993-09-01
AU9064391A (en) 1992-06-11
TW201823B (fr) 1993-03-11

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