Self contained immunoassay element

• US 4,918,025 A
• Filed: 03/03/1987
• Issued: 04/17/1990
• Est. Priority Date: 03/03/1987
• Status: Expired due to Term

• Current Assignee: Behringwerke Aktiengesellschaft (Sanofi )
• Original Assignee: PB Diagnostic Systems, Inc. (Sanofi )
• Inventors: Grenner, Gerd
• Primary Examiner(s): Nucker, Christine M.
• Assistant Examiner(s): WARDEN, JILL ALICE
• Application Number:
  US07/021,136
• Time in Patent Office: 1,141 Days
• Field of Search: 422/56, 422/58, 422/102, 422/68, 422/101, 436/807, 436/165, 435/4, 435/7
• US Class Current: 435/7.94
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/069 Absorbents; Gels to retain a fluid
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 3/5027 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 B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: G01N 33/528 Atypical element structures, e.g. gloves, rods, tampons, toilet paper
• CPC Class Codes: G01N 33/5302 Apparatus specially adapted for immunological test procedures
• CPC Class Codes: Y10S 436/807 Apparatus included in process claim, e.g. physical support structures

Abstract

An element for analysis of a liquid sample including a capillary containing a fixed reagent in fluid communication with reagent reservoirs and a waste liquid reservoir. A sample introducing means is provided which permits analyte in a sample to interact with the fixed reagent. A labelled reagent is provided which interacts with either the fixed reagent or the analyte in a manner which permits detection of the concentration of analyte in the sample. The capillary, reagent reservoirs, waste liquid reservoir and the sample introducing means are arranged within a common housing so that reagent waste liquid need not be removed from the element.

Claims

1. A self-contained element for analysis of a liquid sample containing a component to be determined which comprises:

a housing containing a capillary tube having opposed interior top and bottom surfaces, a portion of at least one of said top and bottom surfaces having bound thereto a first reagent consisting of either said component to be determined or the binding partner of said component to be determined, said bound first reagent defining a reaction zone and interactive with said component to be determined to form a first nondiffusible species, and at least one of said top and bottom surfaces including a transparent area to permit measurement of radiation from at least a portion of said reaction zone;

a labelled second reagent, said second reagent consisting of said component to be determined or the binding partner of said component to be determined and being interactive with said first nondiffusible species or said first reagent to form a second labelled species;

means for introducing at least a portion of said sample and said labelled second reagent into said capillary tube by capillary forces;

at least one reactant reservoir containing a wash solution or a third reagent which is interactive with said second labelled species, said at least one reactant reservoir being in fluid communication with said capillary tube;

a waste reservoir in fluid communication with said capillary tube adapted to receive waste fluid from said capillary tube;

and said means for introducing said sample and said labelled second reagent, said at least one reactant reservoir and said waste reservoir being housed within said housing.

2. The element of claim 1 wherein said means for introducing said sample into said capillary comprises an inlet and a porous membrane in fluid communication with said capillary.

3. The element of claim 2 including a filter element contiguous with said membrane.

4. The element of claim 1 wherein said means for introducing said sample includes said labelled reagent adapted to be introduced into said capillary with said sample.

5. The element of claim 4 wherein said labelled reagent is a labelled antibody.

6. The element of claim 4 wherein the label of said labelled reagent is an enzyme.

7. The element of any one of claims 2 or 3 wherein said porous membrane contains said labelled reagent adapted to be introduced into said capillary with said sample.

8. The element of any one of claims 2 or 3 wherein said porous membrane contains a labelled antibody.

9. The element of any one of claims 2 or 3 wherein the label of said labelled reagent is an enzyme.

10. The element of any one of claims 1, 2, 3 or 4 having one reactant reservoir.

11. The element of any one of claims 1, 2, 3 or 4 having two reactant reservoirs.

12. The element of any one of claims 1, 2, 3, or 4 having three reactant reservoirs.

13. The element of any one of claims 1, 2, 3 or 4 wherein said waste reservoir contains a liquid absorbing material.

14. A process for analyzing for an analyte in a liquid sample within the confines of a self-contained element housing which comprises:

introducing a liquid sample into a porous layer within said element, said porous layer containing a labelled reagent which is interactive with said analyte;

passing said analyte and said labelled reagent by capillary force into a capillary having opposed top and bottom surfaces and a first reagent bound to at least one of said top and bottom surfaces, said first reagent being interactive with said analyte and said labelled reagent to form a first nondiffusible species comprising said labelled reagent, said analyte and said first reagent;

washing the interior of said capillary with a liquid composition positioned in a reservoir within said element and in fluid communication with said capillary to pass the portion of the sample noninteracted with said first reagent into a wastereservoir located within said element, and rendering said labelled reagent detectable.

15. The process of claim 14 wherein said labelled reagent is rendered detectable after said analyte interacts with said first reagent and said labelled reagent.

16. The process of claim 14 wherein said labelled reagent is rendered detectable by washing said capillary with a sufficient amount of a liquid composition to remove noninteracted sample from said capillary and to form a detectable species with substantially all of the labelled reagent interacted with said analyte in said capillary.

17. The process of claim 14 wherein said labelled reagent is rendered detectable by washing said capillary with a wash solution to remove noninteracted sample from said capillary and replacing said wash solution in said capillary with a second liquid reagent.

18. The process of any one of claims 14, 15, 16 or 17 wherein said labelled reagent is labelled with an enzyme.

19. A process for analyzing for an analyte in a liquid sample within the confines of a self-contained element housing which comprises:

introducing by capillary forces a liquid sample into a capillary having opposed top and bottom surfaces and a first reagent bound to at least one of said surfaces, said first reagent being interactive with said analyte to form a first nondiffusible species comprising said analyte and said first reagent;

washing said capillary with a liquid wash composition positioned in a reservoir within said element, said reservoir being in fluid communication with said capillary to pass the portion of the sample noninteracted with said first reagent into a waste reservoir located within said element;

passing a labelled reagent interactive with said analyte from a reservoir within said element into said capillary and directing the liquid wash composition from said capillary into said waste reservoir;

incubating said labelled reagent and said first nondiffusible species to effect interaction between said analyte and said first reagent to form a second nondiffusible species;

and rendering said second nondiffusible species detectable.

20. The process of claim 19 wherein said labelled reagent is rendered detectable by washing said capillary with a sufficient amount of a liquid composition to remove noninteracted sample from said capillary and to form a detectable species with substantially all of the labelled reagent interacted with said analyte in said capillary.

21. A process for analyzing for an analyte in a liquid sample within the confines of a self-contained element housing which comprises:

introducing a liquid sample containing an analyte into a porous layer within said element, said porous layer containing a labelled reagent;

introducing by capillary forces the labelled reagent and said analyte into a capillary having an inner surface and a first reagent bound to said inner surface, said first reagent being interactive with said analyte to form a first nondiffusible species comprising said analyte and said first reagent and a second nondiffusible species comprising said first reagent and said labelled reagent;

washing said capillary with a liquid composition positioned in a reservoir within said element and in fluid communication with said capillary to pass the portion of the sample and labelled reagent noninteracted with said first reagent into a waste reservoir located with in said element

and rendering said labelled reagent detectable.

22. The process of claim 21 wherein said labelled reagent is rendered detectable after said labelled reagent interacts with said first reagent.

23. The process of claim 21 wherein said labelled reagent is rendered detectable by washing said capillary with a sufficient amount of liquid composition to remove noninteracted sample from said capillary and to form a detectable species with substantially all of the labelled reagent interacted with said first reagent in said capillary.

24. The process of claim 21 wherein said labelled reagent is rendered detectable by washing said capillary with a wash solution to remove noninteracted sample from said capillary and replacing said wash solution in said capillary with a second liquid reagent.