Method and apparatus for precise transfer and manipulation of fluids by centrifugal and/or capillary forces

• US 7,459,127 B2
• Filed: 02/26/2002
• Issued: 12/02/2008
• Est. Priority Date: 02/26/2002
• Status: Expired due to Term

• Current Assignee: Siemens Healthcare Diagnostics Incorporated (Siemens AG)
• Original Assignee: Siemens Healthcare Diagnostics Incorporated (Siemens AG)
• Inventors: Bartos, Holger, Blankenstein, Gert, Peters, Ralf-Peter, Pugia, Michael J.
• Primary Examiner(s): SIEFKE, SAMUEL P
• Application Number:
  US10/082,415
• Publication Number:
  US 20030166265A1
• Time in Patent Office: 2,471 Days
• Field of Search: 42/681, 42/72, 42/81, 42/99, 421/00
• US Class Current: 422/502
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/165 Specific details about hydrophobic, oleophobic surfaces
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/06 Valves, specific forms thereof
• CPC Class Codes: B01L 2400/0688 surface tension valves, capillary stop, capillary break
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• 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 3/502723 characterised by venting arrangements
• 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: F04B 19/006 Micropumps F04B43/043 and F04B43/095 take precedence
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

A micro-liter liquid sample, particularly a biological sample, is analyzed in a device employing centrifugal and capillary forces. The sample is moved through one or more sample wells arrayed within a small flat chip via interconnecting capillary passageways. The passageways may be either hydrophobic or hydrophilic and may include hydrophobic or hydrophilic capillary stops.

Claims

1. A microfluidic device for dispensing and analyzing a uniform volume of a liquid sample comprising:

(a) a sample well for receiving and transferring a portion of said liquid sample;

(b) a hydrophilic capillary passageway in liquid communication with said sample well of (a) for receiving a portion of said sample from said sample well of (a), a segment of said hydrophilic capillary passageway disposed between two vents from said hydrophilic capillary passageway to the atmosphere, said segment defining said uniform volume of said liquid sample;

(c) a transfer hydrophilic capillary passageway in liquid communication between said segment of said hydrophilic capillary passageway of (b) and a reagent well, said transfer hydrophilic capillary passageway entering said segment between said two vents to atmosphere, whereby when said uniform volume of said segment is transferred to said reagent well air enters said segment from said two vents and displaces said uniform of liquid sample,

(d) a hydrophilic capillary stop disposed within said transfer hydrophilic capillary passageway of (c) between the entrance to said segment and said reagent well, said capillary stop for preventing transfer of said uniform sample volume until the resistance of said capillary stop is overcome by a means for applying force using pressure, vacuum, or electroosmosis.

2. A device of claim 1 further comprising at least one second reagent well in liquid communication through a hydrophilic capillary passageway with said first reagent well.

3. A device of claim 2 further comprising at least one third reagent well in liquid communication through a hydrophilic capillary passageway with at least one of said second reagent wells of claim 2.

4. A device of claim 1 wherein said first reagent well contains a reagent adapted to react with a component contained in said uniform liquid sample.

5. A device of claim 4 wherein said first reagent well contains a reagent adapted to react with a component contained in said uniform liquid sample and thereby produce a response indicating the amount of said component in said liquid sample.

6. A device of claim 4 wherein said first reagent well contains a reagent adapted to react with a component contained in said uniform liquid sample and thereby reduce interference of said component with a second component to be detected.

7. A device of claim 4 wherein said first reagent well contains a reagent adapted to pretreat said liquid sample.

8. A device of claim 5 wherein said first reagent well contains a reagent adapted to react with a component in said liquid sample and thereby produce a reacted component.

9. A device of claim 8 wherein said reacted component is further reacted in a second reagent well to produce a response indicating the amount of said component in said liquid sample.

10. A device of claim 1 wherein the walls of said hydrophilic capillary passageway of (b) have a hydrophilic surface adjusted to provide substantially complete removal of said liquid sample.

11. A device of claim 1 further comprising electrodes disposed in said first reagent well for measuring properties of said sample fluid.

12. A device of claim 2 further comprising electrodes disposed in at least one of said second reagent wells for measuring properties of said sample fluid.

13. A device of claim 3 further comprising electrodes disposed in at least one of said third reagent wells for measuring properties of said sample fluid.

14. A microfluidic device for dispensing and analyzing a uniform volume of a liquid sample comprising:

(a) a sample well for receiving and transferring a portion of said liquid sample;

(b) a hydrophilic capillary passageway in liquid communication with said sample well of (a) for receiving a portion of said sample from said sample well of (a), a segment of said hydrophilic capillary passageway disposed between two vents from said hydrophilic capillary passageway to the atmosphere, said segment defining said uniform volume of said liquid sample;

(c) a transfer hydrophilic capillary passageway in liquid communication between said segment of said hydrophilic capillary passageway of (b) and a reagent well, said transfer hydrophilic capillary passageway entering said segment between said two vents to atmosphere, whereby when said uniform volume of said segment is transferred to said reagent well air enters said segment from said two vents and displaces said uniform of liquid sample,

(d) a hydrophobic capillary stop disposed within said transfer hydrophilic capillary passageway of (c) between the entrance to said segment and said reagent well, said capillary stop for preventing transfer of said uniform sample volume until the resistance of said capillary stop is overcome by a means for applying force using pressure, vacuum, or electroosmosis.

15. A device of claim 14 further comprising at least one second reagent well in liquid communication through a hydrophilic capillary passageway with said first reagent well.

16. A device of claim 15 further comprising at least one third reagent well in liquid communication through a hydrophilic capillary passageway with at least one of said second reagent wells of claim 15.

17. A device of claim 14 wherein said first reagent well contains a reagent adapted to react with a component contained in said uniform liquid sample.

18. A device of claim 17 wherein said first reagent well contains a reagent adapted to react with a component contained in said uniform liquid sample and thereby produce a response indicating the amount of said component in said liquid sample.

19. A device of claim 17 wherein said first reagent well contains a reagent adapted to react with a component contained in said uniform liquid sample and thereby reduce interference of said component with a second component to be detected.

20. A device of claim 17 wherein said first reagent well contains a reagent adapted to pretreat said liquid sample.

21. A device of claim 18 wherein said first reagent well contains a reagent adapted to react with a component in said liquid sample and thereby produce a reacted component.

22. A device of claim 21 wherein said reacted component is further reacted in a second reagent well to produce a response indicating the amount of said component in said liquid sample.

23. A device of claim 14 wherein the walls of said hydrophilic capillary passageway of (b) have a hydrophilic surface adjusted to provide substantially complete removal of said liquid sample.

24. A device of claim 14 further comprising electrodes disposed in said first reagent well for measuring properties of said sample fluid.

25. A device of claim 15 further comprising electrodes disposed in at least one of said second reagent wells for measuring properties of said sample fluid.

26. A device of claim 16 further comprising electrodes disposed in at least one of said third reagent wells for measuring properties of said sample fluid.