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

• US 6,019,944 A
• Filed: 05/23/1995
• Issued: 02/01/2000
• Est. Priority Date: 05/21/1992
• Status: Expired due to Term

• Current Assignee: BIOSITE INCORPORATED (Abbott Laboratories Incorporated)
• Original Assignee: Biosite Diagnostics Incorporated (Abbott Laboratories Incorporated)
• Inventors: Buechler, Kenneth F.
• Primary Examiner(s): ALEXANDER, LYLE
• Application Number:
  US08/447,895
• Time in Patent Office: 1,715 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: 422/412
• 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: B01J 2219/00828 Silicon wafers or plates
• CPC Class Codes: B01J 2219/00833 Plastic
• CPC Class Codes: B01J 2219/00844 Comprising porous material
• CPC Class Codes: B01J 2219/00889 Mixing micromixers B01F33/30
• CPC Class Codes: B01J 2219/00932 Sonic or ultrasonic vibrations
• CPC Class Codes: B01J 2219/00952 Sensing operations
• 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 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/069 Absorbents; Gels to retain a fluid
• CPC Class Codes: B01L 2300/0825 Test strips
• 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 2400/0688 surface tension valves, capillary stop, capillary break
• CPC Class Codes: B01L 2400/086 using baffles or other fixed flow obstructions
• 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 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 66/727 : being porous, e.g. foam
• CPC Class Codes: B29K 2025/06 : PS, i.e. polystyrene
• 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 2069/00 : Use of PC, i.e. polycarbonates or derivatives thereof, as moulding material
• CPC Class Codes: B29L 2031/756 : Microarticles, nanoarticles
• CPC Class Codes: G01N 2333/59 : Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g. HCG; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
• CPC Class Codes: G01N 30/02 : Column chromatography
• CPC Class Codes: G01N 33/54366 : Apparatus specially adapted for solid-phase testing
• CPC Class Codes: Y10S 977/775 : Nanosized powder or flake, e.g. nanosized catalyst
• 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 assay device comprising:

i. a sample addition reservoir positioned so that one side of said sample addition reservoir is adjacent to a sample reaction barrier (ii);

ii. a sample reaction barrier between said sample addition reservoir and said reaction chamber, said barrier having a capillarity greater than the capillarity of said reaction chamber, whereby absent an externally applied force, fluid flows from the sample reaction barrier to the reaction chamber pursuant to capillary force;

iii. a reaction chamber adapted for receiving fluid from said sample reaction barrier, said chamber comprising a wall which comprises at least two fingers;

iv. a time gate positioned immediately adjacent to the reaction chamber to receive fluid into said diagnostic element;

v. a diagnostic element capable of immobilizing at least one conjugate in at least one zone; and

.

vi. a used reagent reservoir disposed a capillary space away from said diagnostic element, so that fluid flow is directed into said capillary space.

2. Device of claim 1 wherein said diagnostic element further comprises fingers positioned downstream from said zone or zones to prevent fluid from flowing backwards over said zone(s).

3. Device of claim 1 wherein said diagnostic element is comprised of a non-porous surface.

4. An assay device comprising:

i. a sample addition reservoir;

ii. a reaction chamber;

iii. a sample reaction barrier between said sample addition reservoir and said reaction chamber, said sample reaction barrier having a greater capillarity than said reaction chamber, wherein said reaction chamber is adapted to receive fluid flow from said sample reaction barrier;

iv. a wall perpendicular or substantially perpendicular to fluid flow in said sample reaction barrier, said wall located at the interface between said sample reaction barrier and said reaction chamber, said wall comprising grooves perpendicular or substantially perpendicular to fluid flow in said sample reaction barrier, said grooves having widths of between 0.5 mm to 2 mm wide and 0.1 mm to 1.5 mm in depth, whereby absent an externally applied force, fluid flows from the sample reaction barrier to the reaction chamber pursuant to capillary force;

iv. a time gate for delaying fluid flow from said reaction chamber to a separation element (v), said time gate located between said reaction chamber and said separation element, said time gate comprising at least one hydrophobic surface which is capable of binding at least one component present in said fluid; and

whereby the delay of fluid flow is related to the rate of binding of the component to said hydrophobic surface whereby binding of the component to said hydrophobic surface changes said hydrophobic surface into a hydrophilic surface whereby fluid can flow into said separation element;

v. a separation element capable of entrapping, or removing by binding at least one component from said fluid;

vi. a time gate for delaying fluid flow from said separation element to a diagnostic element (vii) so as to maximize desired binding interactions in said diagnostic element, said time gate located between said separation element and said diagnostic element, said time gate comprising at least one hydrophobic surface which is capable of binding at least one component present in said fluid; and

whereby the delay of fluid flow is related to the rate of binding the component to said hydrophobic surface whereby binding of the component to said hydrophobic surface changes said hydrophobic surface into a hydrophilic surface whereby fluid can flow into said diagnostic element (vii);

vii. a diagnostic element capable of immobilizing at least one conjugate in at least one zone; and

,

viii. a used reagent reservoir.

5. Device of claim 4 wherein said means (vi) is a nonporous or porous surface.

6. Device of claim 4 wherein said diagnostic element (viii) is a nonporous or porous surface.

7. Diagnostic assay device comprising:

i. a sample addition reservoir;

ii. a sample reaction barrier between said sample addition reservoir and a reaction chamber (iii), said sample reaction barrier comprising a first capillary;

iii. the reaction chamber, said reaction chamber comprising a second capillary, said second capillary adapted to receive fluid flow from said first capillary, said first capillary having a greater capillarity than said second capillary;

iv. a wall perpendicular or substantially perpendicular to fluid flow in said first capillary, said wall located at the interface between said first capillary and said second capillary, said wall comprising grooves substantially perpendicular to fluid flow in said first capillary, said grooves having widths of between 0.5 mm to 2 mm wide and 0.1 mm to 1.5 mm in depth, whereby absent an externally applied force, fluid flows from the sample reaction barrier to a reaction chamber pursuant to capillary force;

v. a membrane comprising a time gate, said time gate for delaying fluid flow from said membrane to a diagnostic element (vi), said time gate immobilized in said membrane, with said time gate located next to, or a capillary distance from, said diagnostic element, said time gate comprising at least one hydrophobic surface which is capable of binding at least one component present in said fluid; and

whereby the delay of fluid flow is related to the rate of binding the component to said hydrophobic surface whereby binding of the component to said hydrophobic surface changes said hydrophobic surface into a hydrophilic surface whereby fluid can flow into said diagnostic element;

vi. a diagnostic element capable of immobilizing at least one conjugate in at least one zone; and

,

vii. a used reagent reservoir.

8. An assay device comprising:

i. a sample addition reservoir;

ii. a reaction chamber;

iii. a sample reaction barrier between said sample addition reservoir and said reaction chamber, said sample reaction barrier having a greater capillarity than said reaction chamber, wherein said reaction chamber is adapted to receive fluid flow from said sample reaction barrier;

iv. a wall perpendicular or substantially perpendicular to a fluid flow direction in said sample reaction barrier, said wall located at the interface between said sample reaction barrier and said reaction chamber, said wall comprising grooves perpendicular or substantially perpendicular to the fluid flow direction in said sample reaction barrier, said grooves having widths of between 0.5 mm to 2 mm wide and 0.1 mm to 1.5 mm in depth, whereby absent an externally applied force, fluid flows from the sample reaction barrier to a reaction chamber pursuant to capillary force; and

.

v. a diagnostic element capable of immobilizing at least one conjugate in at least one zone, said diagnostic element fluidly connected to said reaction chamber.

9. The device of claim 8 further comprising a used reagent reservoir, fluidly connected to said diagnostic element.

10. The device of claim 8 wherein the sample addition reservoir comprises a filter element capable of removing particulate matter from a sample.

11. The device of claim 8 further comprising a means for entrapping, or removing by binding, at least one component from a fluid.

12. The device of claim 8 wherein said diagnostic element is a nonporous surface or a porous surface.

13. The device of claim 8 further comprising a time gate that can delay flow of a fluid.

14. The device of claim 13 wherein the time gate is located on a hydrophilic surface between said reaction chamber and said diagnostic element, or on a hydrophobic surface between said reaction chamber and said diagnostic element.

15. The device of claim 13 wherein the time gate is adapted to allow fluid flow from said reaction chamber to said diagnostic element through said time gate by capillary action, surface tension, hydrostatic pressure or a combination thereof.

16. The device of claim 13 wherein the time gate is positioned between said reaction chamber and said diagnostic element, wherein the time gate delays fluid flow from said reaction chamber to the diagnostic element, said time gate comprising at least one hydrophobic surface which is capable of binding at least one component present in said fluid;

and whereby the delay of fluid flow is related to the rate of binding the component to said hydrophobic surface, whereby binding of the component to the hydrophobic surface changes said hydrophobic surface into a hydrophilic surface whereby fluid can advance.

17. An assay device for detecting at least one target ligand in a fluid sample, the device comprising:

a first capillary region and a second capillary region, said first capillary region having a greater capillarity than said second capillary region; and

,

a wall perpendicular or substantially perpendicular to a fluid flow direction in said first capillary region, said wall located at an interface between said first capillary region and said second capillary region, said wall comprising grooves perpendicular or substantially perpendicular to the fluid flow direction in said first capillary region, wherein said grooves are between 0.5 mm to 2 mm wide and 0.1 mm to 1.5 mm deep, whereby absent an externally applied force, fluid flows from the first capillary region to the second capillary region pursuant to capillary force.

18. An assay device for detecting at least one target ligand in a fluid sample, said assay device comprising:

a. a sample addition reservoir;

b. a time gate for delaying fluid flow;

c. a diagnostic element;

wherein said assay device is configured and arranged such that said fluid sample flows from said sample addition reservoir to said time gate to said diagnostic element.

19. The assay device of claim 18, wherein said time gate comprises at least one hydrophobic surface.

20. The assay device of claim 18, wherein said time gate comprises hydrophobic poly-electrolytes.

21. The assay device of claim 18, wherein said time gate is V-shaped.

22. The assay device of claim 18, wherein said diagnostic element is clear.

23. The assay device of claim 18, wherein said diagnostic element immobilizes said target ligand for detection.

24. The assay device of claim 18, comprising a used reagent reservoir configured and arranged after said diagnostic element.

25. The assay device of claim 18, wherein said diagnostic element comprises latex particles.

26. The assay device of claim 25, wherein said latex particles have a diameter between 0.01 μ

m and 10 μ

m.

27. The assay device of claim 18, wherein said time gate comprises latex particles.

28. The assay device of claim 27, wherein said latex particles have a diameter between 0.01 μ

m and 10 μ

m.

29. The assay device of claim 27, wherein said protrusion is 1 nm to 0.5 mm.

30. The assay device of claim 18, wherein said time gate comprises at least one groove.

31. The assay device of claim 30, wherein said groove is parallel to the direction of flow of said fluid sample.

32. The assay device of claim 30, wherein said groove is perpendicular to the direction of flow of said fluid sample.

33. The assay device of claim 18, comprising a reaction chamber configured and arranged between said time gate and said diagnostic element.

34. The assay device of claim 33, wherein said reaction chamber is 0.05 mm to 10 mm deep.

35. The assay device of claim 33, wherein said reaction chamber comprises a ramp.

36. The assay device of claim 35, wherein said ramp is at an angle between 25 degrees and 45 degrees relative to the floor of said reaction chamber.

37. The assay device of claim 18, comprising a sample-reaction barrier configured and arranged between said sample reservoir and said time gate.

38. The assay device of claim 37, wherein said sample-reaction barrier comprises more than one groove between 10 and 500 grooves per centimeter.

39. The assay device of claim 37, wherein said sample-reaction barrier comprises at least one groove.

40. The assay device of claim 39, wherein said groove is perpendicular to the direction of flow of said fluid sample.

41. The assay device of claim 39, wherein said groove is parallel to the direction of flow of said fluid sample.

42. The assay device of claim 39, wherein said groove is 0.01 mm to 0.5 mm deep.

43. The assay device of claim 39, wherein said groove is 0.5 mm to 2 mm wide.

44. The assay device of claim 18, wherein said diagnostic element comprises at least one groove.

45. The assay device of claim 44, wherein said groove is parallel to the direction of flow of said fluid sample.

46. The assay device of claim 44, wherein said groove is perpendicular to the direction of flow of said fluid sample.

47. The assay device of claim 44, wherein said groove is a protrusion.

48. The assay device of claim 44, wherein said groove is spaced between 1 nm and 0.5 mm apart from another groove.

49. The assay device of claim 44, wherein said groove is a depression.

50. The assay device of claim 49, wherein said depression is 1 nm to 0.5 mm.