Diagnostic flow cell device

• US 5,520,787 A
• Filed: 03/03/1995
• Issued: 05/28/1996
• Est. Priority Date: 02/09/1994
• Status: Expired due to Fees

• Current Assignee: Abbott Laboratories Incorporated
• Original Assignee: Abbott Laboratories Incorporated
• Inventors: Marciniec, Edmund T., Safford, Lance K., Ford, Jay R., Norlie, John D. Jr., Johnson, Kenneth S., Schultz, Steven G., Hanagan, Ted J.
• Primary Examiner(s): Bell, Bruce F.
• Application Number:
  US08/400,412
• Time in Patent Office: 452 Days
• Field of Search: 204/403, 204/409, 204/412, 204/153.12, 204/415, 204/418, 422/82.06, 422/82.07, 422/82.08, 422/82.09, 422/82.01, 422/82.02, 422/68.1, 435/817, 435/288, 435/291
• US Class Current: 204/403.14
• CPC Class Codes: B01L 2200/0689 Sealing
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0406 capillary forces
• 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 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: C12Q 1/001 Enzyme electrodes
• CPC Class Codes: Y10S 435/817 Enzyme or microbe electrode

Abstract

The present invention provides a diagnostic flow cell for determining the presence or amount of an analyte which may be contained in a test sample. The flow cell comprises a spacing layer having a longitudinal void disposed between a pair of opposed substrates. The spacing layer and the opposed substrates define a flow channel wherein reagent means can be immobilized. When the immobilized reagent means is contacted with an analyte, the reagent means can produce an electrically, optically, or electrically and optically detectable response to the analyte. Hence, the reagent means that is immobilized within the flow channel can comprise (i) a counter electrode, a reference electrode and a working electrode, (ii) an optically sensitive dye or (iii) a counter electrode, a reference electrode and a working electrode and an optically sensitive dye. The flow cell can be interfaced with means for introducing a test sample into and out of the flow cell'"'"'s flow channel and detection means for detecting a signal generated by the immobilized reagent means.

The present invention also provides methods for detecting the presence or amount of an analyte which may be contained in a test sample.

Claims

1. A multi flat-layered diagnostic flow cell for determining the presence or amount of an analyte in a test sample, said flow cell being reusable for a plurality of test samples, and comprising:

i) a hydrophobic spacing layer disposed between a first and a second opposed substrate, said first and second substrates being chemically inert and non-conductive, and wherein said spacing layer has a longitudinal void and wherein said spacing layer and said opposed substrates define a flow channel;

ii) fastening means for coupling said spacing layer and said opposed substrates;

iii) inlet means for permitting said sample to enter said flow channel;

iv) outlet means for permitting said sample to exit said flow channel; and

v) means for producing a detectable signal, wherein said means is at least partially contained within said flow channel;

said means comprising a working electrode containing an immobilized bioreagent enzyme dispersed within a latex resin binding reagent.

2. The flow cell of claim 1 wherein said first opposed substrate comprises a material selected from the group consisting of glass, silicon, polyester, polycarbonate, polystyrene, molded plastics and film plastics.

3. The flow cell of claim 1 wherein said second opposed substrate comprises a material selected from the group consisting of glass, silicon, polyester, polycarbonate, polystyrene, molded plastics and film plastics.

4. The flow cell of claim 1 wherein said spacing layer comprises a material selected from the group consisting of printing inks, latexes, urethanes, vinyls, polyesters, and combinations of one or more printing inks, latexes, urethanes, vinyls and polyesters.

5. The flow cell of claim 1 further comprising a hydrophobic mask layer disposed between said substrates.

6. The flow cell of claim 5 wherein said mask layer comprises a material selected from the group consisting of printing inks, latexes, urethanes, vinyls, polyesters and combinations of one or more printing inks, latexes, urethanes, vinyls and polyesters.

7. The flow cell of claim 1 wherein said fastening means is selected from the group consisting of a rivet, a nut and a bolt, a sonic weld and an adhesive.

8. The flow cell of claim 7 wherein said adhesive is selected from the group consisting of an ultraviolet cured pressure sensitive adhesive, a heat cured pressure sensitive adhesive and a pressure activated adhesive.

9. The flow cell of claim 1 wherein said fastening means is a polyurethane ultraviolet cured pressure sensitive adhesive.

10. The flow cell of claim 1 wherein said means for producing a detectable signal further comprises a reference electrode, and a counter electrode.

11. The flow cell of claim 10 wherein said reference electrode comprises a redox couple and a first conductive trace.

12. The flow cell of claim 11 wherein said redox couple is selected from the group consisting of silver/silver chloride/graphite, mercury/mercurous chloride, silver/silver iodide and silver/silver chloride.

13. The flow cell of claim 11 wherein said redox couple comprises silver/silver chloride.

14. The flow cell of claim 11 wherein said conductive trace comprises a material selected from the group consisting of carbon, gold, nickel, silver, palladium, ruthenium, rhodium, tin oxide, indium tin oxide and combinations of one or more of carbon, gold, nickel, silver, palladium, ruthenium, rhodium, tin oxide and indium tin oxide.

15. The flow cell of claim 11 wherein said conductive trace comprises graphite and screen printed ink.

16. The flow cell of claim 11 wherein said conductive trace is a flat layer.

17. The flow cell of claim 10 wherein said counter electrode comprises a material selected from the group consisting of carbon, gold, nickel, silver, palladium, ruthenium, rhodium, tin oxide, indium tin oxide and combinations of one or more of carbon, gold, nickel, silver, palladium, ruthenium, rhodium, tin oxide and indium tin oxide.

18. The flow cell of claim 10 wherein said counter electrode comprises graphite and screen printed ink.

19. The flow cell of claim 10 wherein said reagent means further comprises an optically active dye.

20. The flow cell of claim 19 wherein said dye is selected from the group consisting of a pH sensitive dye, an oxygen sensitive dye and an ion sensitive dye.

21. The flow cell of claim 19 wherein said dye comprises platinum tetra(pentafluorophenyl)porphyrin.

22. The flow cell of claim 10 wherein said working electrode comprises a second conductive trace.

23. The flow cell of claim 22 wherein said conductive trace comprises a material selected from the group consisting of carbon, gold, nickel, silver, palladium, ruthenium, rhodium, tin oxide, indium tin oxide and combinations of one or more of carbon, gold, nickel, silver, palladium, ruthenium, rhodium, tin oxide and indium tin oxide.

24. The flow cell of claim 22 wherein said conductive trace comprises graphite and screen printed ink.

25. The flow cell of claim 22, wherein said enzyme is immobilized to a solid phase material and is further immobilized to said conductive trace.

26. The flow cell of claim 25, wherein said enzyme is selected from the group consisting of glucose oxidase, glutamate oxidase, lactate oxidase, glycerol phosphate oxidase, cholesterol oxidase, cholesterol esterase, lipase, glycerol kinase, glutamate dehydrogenase, creatine deaminase, and uricase.

27. The flow cell of claim 26, wherein said latex resin is selected from the group consisting of acrylic latex, styrene acrylic latexes, vinyl acetate latex and polyurethane latex.

28. The flow cell of claim 27, wherein said solid phase material is selected from the group consisting of agarose and derivatives thereof, polyacrylamide and derivatives thereof, silicas, aluminosilicates, aluminum oxides, carbon or graphite particles, and platinum group metal oxides.

29. The flow cell of claim 22 wherein said conductive trace is a flat layer.

30. The flow cell of claim 1 wherein said reagent means comprises an optically active dye.

31. The flow cell of claim 30 wherein said dye is selected from the group consisting of a pH sensitive dye, an oxygen sensitive dye and an ion sensitive dye.

32. The flow cell of claim 30 wherein said dye comprises platinum tetra(pentafluorophenyl)prophyrin.

33. The flow cell of claim 1 wherein said flow cell further comprises flow means for introducing said test sample into said flow channel wherein said flow means is interfaced with said inlet and outlet means;

and detection means for detecting a detactable signal wherein said detection means is interfaced with said immobilized reagent means.

34. The flow cell of claim 1, wherein said inlet means and said outlet means comprises a pair of apertures within said second substrate.

35. The flow cell of claim 34, wherein said apertures are aligned within said second substrate at opposite ends of said flow channel.

36. The flow cell of claim 1, wherein said enzyme is selected from the group consisting of glucose oxidase, glutamate oxidase, lactate oxidase, glycerol phosphate oxidase, cholesterol oxidase, cholesterol esterase, lipase, glycerol kinase, glutamate dehydrogenase, creatine deaminase, and uricase.

37. The flow cell of claim 36, wherein said latex resin is selected from the group consisting of acrylic latex, styrene acrylic latexes, vinyl acetate latex and polyurethane latex.

38. A multiflat-layered diagnostic flow cell for determining the presence or amount of one or more analytes in a test sample, said flow cell being reusable for a plurality of test samples, and comprising:

i) a hydrophobic spacing layer disposed between a first and second opposed substrate, said first and second substrates being chemically inert and non-conductive, and wherein said spacing layer has a longitudinal void and wherein said spacing layer and said opposed substrates define a flow channel;

ii) fastening means for coupling said spacing layer and said opposed substrates;

iii) inlet means for permitting said sample to enter said flow channel;

iv) outlet means for permitting said sample to exit said flow channel; and

v) means for producing a detectable signal, wherein said means is at least partially contained within said flow channel;

said means comprising a working electrode containing at least one immobilized bioreagent dispersed within a latex resin binding reagent.

39. The flow cell of claim 38 wherein working electrode comprises a conductive trace which is a flat layer.