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

• US 6,767,510 B1
• Filed: 03/13/2001
• Issued: 07/27/2004
• Est. Priority Date: 05/21/1992
• Status: Expired due to Fees

• Current Assignee: BIOSITE INCORPORATED (Abbott Laboratories Incorporated)
• Original Assignee: BIOSITE INCORPORATED (Abbott Laboratories Incorporated)
• Inventors: Buechler, Kenneth F.
• Primary Examiner(s): ALEXANDER, LYLE
• Application Number:
  US09/805,653
• Time in Patent Office: 1,232 Days
• Field of Search: 422/58, 422/61, 422/82.05, 422/77, 422/73, 436/69, 436/180, 436/165, 436/170, 436/177, 436/518, 436/524, 436/531, 436/164, 436/169
• US Class Current: 422/412
• CPC Class Codes: B01L 2200/0621 Control of the sequence of chambers filled or emptied
• CPC Class Codes: B01L 2200/0684 Venting, avoiding backpressure, avoid gas bubbles
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0825 Test strips
• CPC Class Codes: B01L 2300/089 Virtual walls for guiding liquids
• 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 2400/088 by specific surface properties
• 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: G01N 33/54387 Immunochromatographic test strips
• CPC Class Codes: G01N 33/558 using diffusion or migration of antigen or antibody immunochromatographic test strips G01N33/54387
• 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 for determining the presence or amount of a plurality of different target ligands in a sample, the device comprising:

a diagnostic element comprising a capillary space through which said sample flows, said capillary space comprising (i) a non-absorbent surface, and (ii) a plurality of discrete capture zones on said nonabsorbent surface, each discrete capture zone comprising a capture element that binds one target ligand in said plurality of different target ligands, wherein said nonabsorbent surface comprises a width dimension substantially perpendicular to the direction of fluid flow through the capillary space, and wherein each said discrete capture zone spans said width dimension.

2. The assay device of claim 1, comprising at least 50 said discrete capture zones, corresponding to at least 50 different target ligands.

3. The assay device of claim 1, wherein said capture element is selected from the group consisting of an antibody or binding fragment thereof, a nucleotide sequence, an enzyme, a chelator, and a biosensor.

4. The assay device of claim 1, wherein said device further comprises a chamber fluidly connected to said diagnostic element, and a time gate that delays fluid flow between said chamber and said diagnostic element until binding of a component from a fluid to a zone of said time gate renders said zone sufficiently hydrophilic to permit fluid flow over or through said time gate.

5. The assay device of claim 1, wherein said discrete capture zones comprise particles immobilized thereon, wherein said particles comprise said capture element immobilized thereon.

6. The device of claim 5 wherein the particles are latex.

7. The device of claim 5 wherein the particles are polystyrene.

8. The device of claim 5 wherein the particles are nanoparticles.

9. The device of claim 8 wherein the nanoparticles comprise silica, zirconia, alumina, titania, ceria, metal sols, or polystyrene.

10. The device of claim 8 wherein the nanoparticlcs have sizes in a range from about 1 nm to 100 nm.

11. The device of claim 8 wherein the nanoparticles are immobilized on said nonabsorbent surface through adsorption or covalent bonds.

12. The device of claim 5 wherein said particles are immobilized on said nonabsorbent surface by magnetic means, hydrophobic means, hydrogen bonding, electrostatic means, or entrapment.

13. The device of claim 5, wherein said particles have diameters ranging from about 0.1 mm to 10 mm.

14. The device of claim 5, wherein said receptor is immobilized on a surface of the particle.

15. A method for determining the presence or amount of a plurality of different target ligands in a sample, the method comprising:

contacting the diagnostic element of claim 1 with

(i) a sample, and

(ii) a labeled reagent that binds to said plurality of target ligands,

whereby said sample and said labeled reagent flow through said capillary space for capture of each said different target ligand at its corresponding capture zone; and

generating a plurality of detectable signals from label bound to each different target ligand at its corresponding capture zone, whereby said signals are related to the presence or amount of said plurality of different target ligands in said sample.

16. The method of claim 15, wherein said diagnostic element comprises at least 50 said discrete capture zones, corresponding to at least 50 different target ligands.

17. The method of claim 15, wherein said capture element is selected from the group consisting of an antibody or binding fragment thereof, a nucleotide sequence, an enzyme, a chelator, and a biosensor.

18. The method of claim 15, wherein said discrete capture zones comprise particles immobilized thereon, wherein said particles comprise said capture element immobilized thereon.

19. The method of claim 15, wherein said labeled reagent is a fluorescently labeled reagent.

20. A method for determining the presence or amount of a plurality of different target ligands in a sample, the method comprising:

contacting the diagnostic element of claim 1 with

(i) a sample, and

(ii) a plurality of ligand analogue conjugates, each ligand analogue conjugate corresponding to one of said plurality of different target ligands,

whereby said sample and said plurality of ligand analogue conjugates flow through said capillary space, whereby each different target ligand competes with its corresponding ligand analogue conjugate for capture at its corresponding capture zone; and

generating a plurality of detectable signals from ligand analogue conjugate bound at its corresponding capture zone, whereby said signals are related to the presence or amount of said plurality of different target ligands in said sample.

21. The method of claim 20, wherein said diagnostic element comprises at least 50 said discrete capture zones, corresponding to at least 50 different target ligands.

22. The method of claim 20, wherein said capture element is selected from the group consisting of an antibody or binding fragment thereof, a nucleotide sequence, an enzyme, a chelator, and a biosensor.

23. The method of claim 20, wherein said discrete capture zones comprise particles immobilized thereon, wherein said particles comprise said capture element immobilized thereon.

24. The method of claim 20, wherein said ligand analogue conjugate is a fluorescently labeled ligand analogue conjugate.

25. An assay device for determining the presence or amount of a plurality of different target ligands in a sample, the device comprising:

a diagnostic element comprising a capillary space through which said sample flows, said capillary space comprising (i) a non-absorbent hydrophilic surface region and (ii) a plurality of discrete capture zones on said nonabsorbent hydrophilic surface region, each discrete capture zone comprising a capture element that binds one target ligand in said plurality of different target ligands, wherein said nonabsorbent hydrophilic surface region comprises a width dimension substantially perpendicular to the direction of fluid flow through the capillary space, and wherein each said discrete capture zone spans said width dimension.

26. The assay device of claim 25, wherein said capture element is selected from the group consisting of an antibody or binding fragment thereof, a nucleotide sequence, an enzyme, a chelator, and a biosensor.

27. The assay device of claim 25, wherein said device further comprises a chamber fluidly connected to said diagnostic element, and a time gate that delays fluid flow between said chamber and said diagnostic element until binding of a component from a fluid to a zone of said time gate renders said zone sufficiently hydrophilic to permit fluid flow over or through said time gate.

28. The assay device of claim 25, wherein said discrete capture zones comprise particles immobilized thereon, wherein said particles comprise said capture element immobilized thereon.

29. The device of claim 28 wherein the particles are latex.

30. The device of claim 28 wherein the particles are polystyrene.

31. The device of claim 28 wherein the particles are nanoparticles.

32. The device of claim 31 wherein the nanoparticlcs comprise silica, zirconia, alumina, titania, ceria, metal sols, or polystyrene.

33. The device of claim 31 wherein the nanoparticles have sizes in a range from about 1 nm to 100 nn.

34. The device of claim 31 wherein the nanoparticles are immobilized on said nonabsorbent surface through adsorption or covalent bonds.

35. The device of claim 31 wherein said particles are immobilized on said nonabsorbent surface by magnetic means, hydrophobic means, hydrogen bonding, electrostatic means, or entrapment.

36. The device of claim 28, wherein said particles have diameters ranging from about 0.1 mm to 10 mm.

37. The device of claim 28, wherein said receptor is immobilized on a surface of the particle.