Diagnostic devices and apparatus for the controlled movement of reagents without membranes

• US 6,156,270 A
• Filed: 03/27/1997
• Issued: 12/05/2000
• Est. Priority Date: 05/21/1992
• Status: Expired due to Fees

• Current Assignee: BIOSITE INCORPORATED (Abbott Laboratories Incorporated)
• Original Assignee: Biosite Diagnostics Incorporated (Abbott Laboratories Incorporated)
• Inventors: Buechler, Kenneth Francis
• Primary Examiner(s): ALEXANDER, LYLE
• Application Number:
  US08/828,041
• Time in Patent Office: 1,349 Days
• Field of Search: 422/55, 422/56, 422/58, 422/72, 422/73, 422/82.05, 422/100, 422/102, 436/69, 436/180, 436/165, 436/170, 436/177, 436/518, 436/524, 436/531
• US Class Current: 422/417
• CPC Class Codes: B01D 15/3804 Affinity chromatography
• CPC Class Codes: B01J 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2200/0621 Control of the sequence of chambers filled or emptied
• CPC Class Codes: B01L 2200/0689 Sealing
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• 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 2300/0825 Test strips
• CPC Class Codes: B01L 2300/0851 Bottom walls
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2300/089 Virtual walls for guiding liquids
• CPC Class Codes: B01L 2300/165 Specific details about hydrophobic, oleophobic surfaces
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/086 using baffles or other fixed flow obstructions
• CPC Class Codes: B01L 2400/088 by specific surface properties
• 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: 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: B01L 3/502738 : characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/502746 : characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• CPC Class Codes: B29C 65/08 : using ultrasonic vibrations non-plastics element to plastics elements B29C65/645
• CPC Class Codes: B29C 65/7829 : said distance pieces being integral with at least one of the parts to be joined
• CPC Class Codes: B29C 65/8253 : by the use of waves or particle radiation, e.g. visual examination, scanning electron microscopy, or X-rays B29C65/8292 takes precedence
• CPC Class Codes: B29C 66/112 : Single lapped joints
• CPC Class Codes: B29C 66/1122 : Single lap to lap joints, i.e. overlap joints B29C66/45, B29C66/472, B29C66/52272 take precedence
• CPC Class Codes: B29C 66/114 : Single butt joints
• CPC Class Codes: B29C 66/30223 : said melt initiators being rib-like
• CPC Class Codes: B29C 66/53461 : joining substantially flat covers and/or substantially flat bottoms to open ends of container bodies
• CPC Class Codes: B29C 66/54 : Joining several hollow-preforms, e.g. half-shells, to form hollow articles, e.g. for making balls, containers; Joining several hollow-preforms, e.g. half-cylinders, to form tubular articles
• CPC Class Codes: B29C 66/61 : Joining from or joining on the inside for making tubes by bending sheets and joining from the inside B29C53/387
• CPC Class Codes: B29C 66/71 : characterised by the composition of the plastics material of the parts to be joined welding bar compositions B29C65/125
• CPC Class Codes: B29C 66/72321 : consisting of metals or their alloys
• CPC Class Codes: B29C 66/7234 : comprising a barrier layer
• CPC Class Codes: B29C 66/727 : being porous, e.g. foam
• CPC Class Codes: B29C 66/7392 : characterised by the material of at least one of the parts being a thermoplastic
• CPC Class Codes: B29C 66/73921 : characterised by the materials of both parts being thermoplastics
• CPC Class Codes: B29K 2001/00 : Use of cellulose, modified cellulose or cellulose derivatives, e.g. viscose, as moulding material
• CPC Class Codes: B29K 2023/00 : Use of polyalkenes or derivatives thereof as moulding material
• CPC Class Codes: B29K 2023/06 : PE, i.e. polyethylene
• CPC Class Codes: B29K 2023/12 : PP, i.e. polypropylene
• CPC Class Codes: B29K 2025/04 : Polymers of styrene
• CPC Class Codes: B29K 2025/06 : PS, i.e. polystyrene
• CPC Class Codes: B29K 2027/00 : Use of polyvinylhalogenides or derivatives thereof as moulding material
• CPC Class Codes: B29K 2027/12 : containing fluorine
• CPC Class Codes: B29K 2027/18 : PTFE, i.e. polytetrafluorethene , e.g. ePTFE, i.e. expanded polytetrafluorethene
• CPC Class Codes: B29K 2033/08 : Polymers of acrylic acid esters, e.g. PMA, i.e. polymethylacrylate
• CPC Class Codes: B29K 2033/12 : Polymers of methacrylic acid esters, e.g. PMMA, i.e. polymethylmethacrylate
• CPC Class Codes: B29K 2067/00 : Use of polyesters or derivatives thereof, as moulding material
• CPC Class Codes: B29K 2069/00 : Use of PC, i.e. polycarbonates or derivatives thereof, as moulding material
• CPC Class Codes: B29K 2075/00 : Use of PU, i.e. polyureas or polyurethanes or derivatives thereof, as moulding material
• CPC Class Codes: B29K 2077/00 : Use of PA, i.e. polyamides, e.g. polyesteramides or derivatives thereof, as moulding material
• CPC Class Codes: B29K 2079/08 : PI, i.e. polyimides or derivatives thereof
• CPC Class Codes: B29K 2081/00 : Use of polymers having sulfur, with or without nitrogen, oxygen or carbon only, in the main chain, as moulding material
• CPC Class Codes: B29K 2083/00 : Use of polymers having silicon, with or without sulfur, nitrogen, oxygen, or carbon only, in the main chain, as moulding material
• CPC Class Codes: B29L 2031/756 : Microarticles, nanoarticles
• CPC Class Codes: G01N 2035/00237 : Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 30/02 : Column chromatography
• CPC Class Codes: G01N 33/54366 : Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/558 : using diffusion or migration of antigen or antibody immunochromatographic test strips G01N33/54387
• CPC Class Codes: G01N 35/00 : Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
• CPC Class Codes: G01N 35/085 : Flow Injection Analysis
• CPC Class Codes: Y10T 436/25375 : Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]

Abstract

The assay devices, assay systems and device components of this invention comprise at least two opposing surfaces disposed a capillary distance apart, at least one of which is capable of immobilizing at least one target ligand or a conjugate in an amount related to the presence or amount of target ligand in the sample from a fluid sample in a zone for controlled fluid movement to, through or away the zone. The inventive device components may be incorporated into conventional assay devices with membranes or may be used in the inventive membrane-less devices herein described and claimed. These components include flow control elements, measurement elements, time gates, elements for the elimination of pipetting steps, and generally, elements for the controlled flow, timing, delivery, incubation, separation, washing and other steps of the assay process.

Claims

1. An analytical device for determining the presence or amount of a target ligand in a test sample, said device comprising:

one or more channels; and

an array of texture structures in fluid communication with at least one channel, each texture structure comprising a surface which comprises an immobilized ligand receptor covalently or non-covalently attached thereto, said immobilized ligand receptor capable of binding a target ligand,

whereby when test sample containing target ligand flows through said channel(s), said target ligand diffuses across the width of said channel(s) and binds to said ligand receptor immobilized on said texture structure.

2. The analytical device of claim 1 wherein said texture structures are made with copolymers, blends, laminates, metallized foils, metallized films or metals deposited on a material selected from the group consisting of

polyolefins, polyesters, styrene containing polymers, polycarbonate, acrylic polymers, chlorine containing polymers, acetal homopolymers and copolymers, cellulosics and their esters, cellulose nitrate, fluorine containing polymers, polyamides, polyimides, polymethylmcthacrylates, sulfur containing polymers, polyurethanes, silicon containing polymers, glass, silicone, and ceramic materials.

3. The device of claim 1 wherein the target ligand is an analyte, analyte conjugate, analyte-analog, analyte-analog conjugate, ancillary binding member, or labeled reagent.

4. The analytical device of claim 3 wherein said analyte is an antigen, nucleotide sequence, lectin, or avidin and said immobilized reagent is selected from the group consisting of antibody, complementary nucleotide sequence, carbohydrate or biotin.

5. The analytical device of claim 1 wherein said texture structures are made with plastics which are capable of being milled or injection molded or from surfaces of copper, silver and gold films upon which are adsorbed various long chain alkanethiols.

6. The analytical device of claim 5 wherein said structures comprise a plastic which is capable of being milled or injection molded.

7. The analytical device of claim 1 wherein said texture structures are similarly shaped, said shapes selected from the group consisting of diamonds, hexagons, octagons, rectangles, squares, circles, semi-circles, triangles and ellipses.

8. The analytical device of claim 7 wherein said array of texture structures are staggered relative to the direction of test sample flow.

9. The analytical device of claim 1 wherein said array of texture structures have one or more immobilized ligand receptors, each ligand receptor capable of binding a different target ligand, thereby permitting testing for two or more target ligands in said test sample.

10. The analytical device of claim 1 further comprising a reservoir for the addition of the test sample, said reservoir comprising a plurality of pathways each of which leads to an array of texture structures, said pathways capable of transporting the test sample from said reservoir to said array.

11. The analytical device of claim 1 wherein said texture structures are made with a plastic, elastomer, latex, silicon chip, or metal.

12. The analytical device of claim 11 wherein said texture structures are made with a material selected from the group consisting of fluoropolymer resin, polystyrene, polyacrylate, polycarbonate, polyethylene, polypropylene, silicon elastomers, polystyrene latex and hydrophobic polymers.

13. The analytical device of claim 12 wherein said texture structures are made with a hydrophobic polymer which comprises polypropylene, polyethylene, or polyester.

14. The analytical device of claim 1, comprising a zone, wherein said zone comprises:

a region capable of having a fluid placed thereon, and

a hydrophobic region adjacent to the region capable of containing a fluid placed thereon, whereby the hydrophobic region impedes the flow of fluid into that hydrophobic region.

15. The analytical device of claim 14, wherein said region capable of having a fluid placed thereon is a surface of a chamber,

wherein said chamber comprises at least one rectilinear angle when viewed along a cross section, and

wherein said hydrophobic region is comprised within the chamber adjacent the angle of the chamber.

16. The analytical device of claim 14, wherein said region capable of having a fluid placed thereon further comprises a post,

wherein said post is substantially perpendicular to a floor of this region;

and

wherein said post defines a rectilinear angle between a surface of the post and the floor.

17. The analytical device of claim 1, comprising a capillary space and a material configured to fit into said capillary space, wherein said material comprises a hydrophobic zone on a surface thereof.

18. The analytical device of claim 17, wherein said hydrophobic zone covers 1% to 90% of a surface of said material.

19. The analytical device of claim 17, wherein said material comprises a filter, membrane or mesh.

20. The analytical device of claim 17, wherein said material is capable of fitting into said capillary space,

wherein said capillary space comprises at least one rectilinear angle, and

wherein hydrophobic surface of said material is capable of being placed adjacent said angle of the capillary space.

21. The analytical device of claim 1, comprising a capillary space having a lumen,

wherein said lumen comprises at least one rectilinear angle when viewed in a cross section, and

wherein said capillary space comprises a hydrophobic zone on a lumenal surface.

22. The analytical device of claim 21, wherein said hydrophobic zone borders said rectilinear angle.

23. The analytical device of claim 21, wherein said hydrophobic zone substantially covers a surface adjacent said rectilinear angle.

24. The analytical device of claim 21, wherein said hydrophobic zone covers 1% to 90% of a surface adjacent said rectilinear angle.

25. The analytical device of claim 21, wherein said hydrophobic zone is adjacent to a hydrophilic surface.

26. An analytical device for determining a presence or amount of a ligand in a test sample, said device comprising:

an inlet port and a vent;

one or more channels;

an array of texture structures in fluid communication with at least one channel, each texture structure having a surface comprising an immobilized receptor covalently or non-covalently attached to said surface of said texture structure, said receptor capable of binding a ligand, whereby when said test sample containing a ligand flows through said channel(s), said ligand diffuses across the width of said channel(s) to bind said receptor immobilized on said texture structure; and

,

a labeled reagent comprising a specific binding member conjugated to a detectable label, said labeled reagent capable of producing a signal at said receptor immobilized on said texture structure to indicate the presence or amount of a ligand in a test sample.

27. The device of claim 26 wherein said ligand is an analyte, analyte conjugate, analyte-analog, analyte-analog conjugate, or ancillary binding member.

28. An assay device comprising:

a sample addition reservoir;

a sample reaction barrier fluidly connected to said sample addition reservoir;

a reaction chamber fluidly connected to said sample reaction barrier, said chamber having at least two fingers in walls thereof, wherein said barrier has a higher capillarity than said reaction chamber;

a time gate fluidly connected to the reaction chamber, said time gate capable of permitting fluid to pass therethrough at a desire d flow rate;

a diagnostic element fluidly connected to the time gate, said diagnostic element comprising an array of texture structures capable of immobilizing at least one conjugate in at least one zone; and

,

a used reagent reservoir fluidly connected to said diagnostic element, whereby fluid can flow in sequence from said sample addition reservoir, to said barrier, to said reaction chamber, to said time gate, to said diagnostic element then to said used reagent reservoir.

29. The device of claim 28 wherein the sample addition reservoir comprises a filter capable of separating particulate matter from a fluid sample.

30. The device of claim 28 wherein the sample reaction barrier comprises a plurality of texture structures on a surface thereof, wherein said texture structures have a texture height of 0.01 to 0.02 mm, a width of 0.10 to 0.20 mm, and a distance between adjacent texture structures is 0.08 to 0.10 mm.

31. The device of claim 28 wherein the reaction barrier comprises a capillary space having a height of about 0.03 to 0.07 mm.

32. The device of claim 28 wherein the reaction barrier comprises a corner, and comprises a hydrophobic zone at said corner.

33. The device of claim 28 wherein the reaction barrier comprises 10 vertical grooves, wherein each said groove is about 0.02 to 0.03 mm high, and each said groove is spaced about 0.5 to 1.5 mm apart.

34. The device of claim 28 wherein the reaction chamber comprises a capillary space about 0.03 to 1.0 mm high and a volume of about 0.2 to 6 μ

l.

35. The device of claim 28 wherein the reaction chamber comprises a plurality of texture structures, wherein each of said texture structures are posts about 0.015 to 0.03 mm high, with a diameter of about 0.05 to 0.1 mm, and wherein adjacent posts are spaced about 0.015 to 0.025 mm apart.

36. The device of claim 28 wherein the reaction chamber comprises a plurality of grooves oriented perpendicular to a predominant direction of fluid flow, wherein each of said grooves is about 0.03 to 0.07 mm high, and adjacent grooves are about 0.08 to 0.12 mm apart.

37. The device of claim 28 wherein the reaction chamber comprises an edge or corner, and comprises a hydrophobic zone at said edge or corner.

38. The device of claim 28 wherein the time gate comprises a height of about 0.02 to 0.12 mm, and a plurality of grooves oriented perpendicular to a predominant direction of fluid flow, wherein each of said grooves is about 0.03 to 0.07 mm high and adjacent grooves are about 0.08 to 0.12 mm apart.

39. The device of claim 28 wherein the diagnostic element comprises a height of about 0.01 to 0.05 mm, a volume of about 0.5 to 3 μ

l.

40. The device of claim 28 wherein each of said texture structures is about 0.01 to 0.02 mm high, a diameter of about 0.03 to 0.07 mm, and adjacent texture structures are about 0.04 to 0.09 mm apart.

41. The device of claim 28 wherein the diagnostic element comprises an edge or corner, and comprises a hydrophobic zone at said edge or corner.

42. The device of claim 28 wherein the used reagent reservoir comprises a height of about 0.01 to 0.05 mm, a volume of greater than about 1 μ

l.

43. The device of claim 28 wherein the used reagent reservoir comprises a plurality of texture structures, wherein each said texture structure comprises a height of 0.01 to 0.02 mm, a diameter of 0.03 to 0.07 mm, and wherein adjacent texture structures are about 0.04 to 0.09 mm apart.

44. The device of claim 28 further comprising a dead space region positioned between a surface of the diagnostic element and a surface of the used reagent reservoir.