Method for uniform application of fluid into a reactive reagent area

• US 20040265171A1
• Filed: 06/27/2003
• Published: 12/30/2004
• Est. Priority Date: 06/27/2003
• Status: Abandoned Application

• Current Assignee: Siemens Healthcare Diagnostics Incorporated (Siemens AG)
• Original Assignee: Siemens Healthcare Diagnostics Incorporated (Siemens AG)
• Inventors: Blankenstein, Gert, Peters, Ralf-Peter, Pugia, Michael J., Profitt, James A., Kuo, Hai-Hang, Schulman, Lloyd S.
• Application Number:
  US10/608,400
• Publication Number:
  US 20040265171A1
• Time in Patent Office: Days
• US Class Current: 422/400
• 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 2300/0816 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 2400/0409 centrifugal forces
• CPC Class Codes: B01L 2400/0418 electro-osmotic flow [EOF]
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• 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 3/502723 characterised by venting arrangements
• 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: Y10T 436/2575 Volumetric liquid transfer

Abstract

Analytical results obtained with microfluidic devices are improved by providing structural features in areas containing dry supported reagents, the structural features directing the flow of a sample over the area in a predetermined uniform manner and facilitating the purging of air.

Claims

1. A microfluidic device for assaying a liquid biological sample of 10 μ

L or less, said device including at least one space in which a reagent or conditioning agent is immobilized on a substrate, the improvement comprising a microstructure disposed in said space for directing said sample over said substrate containing said reagent in a predetermined uniform manner and purging air from said space.

2. A microfluidic device of claim 1 wherein said microstructure is a uniform array of posts having more than one column of posts disposed at a right angle to the flow of said sample.

3. A microfluidic device of claim 2 wherein said microstructure has a second column of posts adjacent to a first column of posts, said posts of said second column positioned between the posts of said first column, thereby preventing said sample liquid from flowing in a straight line through said space.

4. A microfluidic device of claim 2 wherein said posts have at least one wedge-shaped cutout aligned vertically to said substrate for facilitating movement of the sample liquid onto said substrate.

5. A microfluidic device of claim 1 wherein said microstructure is positioned above said substrate.

6. A microfluidic device of claim 1 wherein said microstructure contacts said substrate.

7. A microfluidic device of claim 1 wherein said microstructure is a ramp for directing flow upward or downward to a substrate disposed on a plateau.

8. A microfluidic device of claim 1 wherein said microstructure is a groove or weir disposed perpendicularly to the direction of sample flow.

9. A method of distributing a liquid sample of 10 μ

L or less uniformly over a reagent or conditioning agent immobilized on a substrate in a well of a microfluidic device comprising passing said sample through a microstructure, said microstructure facilitating movement of said sample in a predetermined uniform manner onto said substrate and purging air from said well.

10. A method of claim 9 wherein said microstructure is a uniform array of posts disposed at a right angle to sample flow.

11. A method of claim 10 wherein said microstructure has a second column of posts adjacent to a first column of posts, said posts of said second column positioned between the posts of said first column, thereby preventing said liquid sample from flowing in a straight line over said substrate.

12. A method of claim 10 wherein said posts have at least one wedge-shaped cutout aligned vertically to said substrate for facilitating movement of said liquid onto said substrate.

13. A method of claim 9 wherein said microstructure is positioned above said substrate.

14. A method of claim 9 wherein said microstructure contacts said substrate.

15. A method of claim 9 wherein said microstructure is a ramp for directing flow upward to a substrate disposed on a plateau.

16. A method of claim 9 wherein said microstructure is a groove or weir disposed perpendicularly to the direction of sample flow.

17. A microfluidic device for assaying a liquid biological sample of 10 μ

L or less comprising

(a) an inlet port for receiving said sample;

(b) a capillary passageway in fluid communication with said inlet port;

(c) a metering capillary or metering well in fluid communication with the capillary passageway of (b), thereby permitting said sample to flow into said metering capillary or metering well;

(d) at least one conditioning well containing a reagent for conditioning said sample;

(e) at least one capillary passageway in fluid communication with said conditioning well of (d) and said metering capillary or metering well of (c);

(f) at least one reagent well for contacting said sample after conditioning with a reagent for assaying the amount of an analyte in said sample, said reagent well containing a reagent disposed on a substrate and microstructures for passing said sample over said substrate in a predetermined uniform manner and purging air from said well.

18. A microfluidic device of claim 17 wherein said microstructure is a uniform array of posts disposed at a right angle to the flow of said sample.

19. A microfluidic device of claim 17 wherein said microstructure is a ramp containing at least one groove for directing flow upward to the substrate, and substrate being disposed on a plateau.

20. A microfluidic device of claim 17 wherein said microstructure is a groove or weir disposed perpendicularly to sample flow.

21. A microfluidic device for assaying a biological sample comprising an absorbent substrate strip having an inlet end and an outlet end and containing a sequence of reagents on said for reaction with said sample, wherein said sample is in contact with said inlet end of said strip and said outlet end of said strip is in contact with an absorbent material for removing liquid from said outlet end.

22. A microfluidic device of claim 21 wherein said inlet end of said strip extends into a pre-chamber for holding said sample.

23. A microfluidic device of claim 21 wherein said inlet end of said strip is on a plateau above a pre-chamber for holding said sample and a wall containing at least one groove extends from said sample in said pre-chamber to said plateau.

24. A microfluidic device for assaying the amount of glucose in a sample of blood comprising

(a) an entry port for receiving said sample;

(b) an inlet passageway containing ridges or grooves disposed perpendicularly to the sample flow to create a uniform liquid front, said passageway widening into a reagent chamber;

(c) said reagent chamber of (b) containing microstructures and a chromagenic glucose reagent disposed on a porous substrate; and

(d) a vent passageway in communication with said reagent chamber for venting air displaced from said reagent chamber.

25. A microfluidic device of claim 24 wherein said microstructures of (c) are a uniform array of posts having more than one column of posts disposed at a right angle to the flow of said sample.

26. A microfluidic device of claim 25 wherein said posts have at least one wedge-shaped cutout aligned vertically to said substrate for facilitating movement of said sample toward said substrate.