Method and apparatus for splitting of specimens into multiple channels of a microfluidic device

• US 20040121450A1
• Filed: 12/19/2002
• Published: 06/24/2004
• Est. Priority Date: 12/19/2002
• Status: Active Grant

• Current Assignee: Siemens Healthcare Diagnostics Incorporated (Siemens AG)
• Original Assignee: Bayer Corporation (Bayer AG)
• Inventors: Blankenstein, Gert, Peters, Ralf-Peter, Pugia, Michael J., Profitt, James A.
• Granted Patent: US 7,125,711 B2
• Time in Patent Office: Days
• US Class Current: 435/287.1
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2200/0684 Venting, avoiding backpressure, avoid gas bubbles
• CPC Class Codes: B01L 2300/0803 Disc shape
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• 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 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: G01N 2035/00158 Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 2035/00237 Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 2035/1034 Transferring microquantities of liquid
• CPC Class Codes: G01N 35/00069 whereby the sample substrate is of the bio-disk type, i.e. having the format of an optical disk

Abstract

A microliter liquid sample, particularly a biological sample, is analyzed in a device employing centrifugal and capillary forces. The sample is moved by capillary forces into one or more metering wells which define the amount of said sample to be analyzed in subsequent steps. The defined amount of the sample is transferred from the metering wells to one or more conditioning and reagent wells for measuring the amount of an analyte contained in each metered amount of the sample.

Claims

1. A multi-purpose microfluidic device for analyzing a biological fluid sample comprising:

(a) at least one sample well for receiving said sample;

(b) at least two metering wells for defining the amount of said sample to be analyzed;

(c) a capillary passageway communicating with said at least one sample well of (a) for transferring said sample from said sample well to said at least two metering wells of (b) by capillary action;

(d) at least one reagent well communicating with each of said at least two metering wells through a capillary passageway;

(e) a capillary stop disposed within each of said capillary passageways of (d) for preventing transfer of said sample from each of said at least two metering wells to said at least one reagent well;

(f) optionally at least one conditioning well in fluid communication through a capillary passageway with said at least one reagent well or with at least one of said at least two metering wells;

(g) optionally at least one waste well for receiving portions of said sample of (a) from said at least one reagent well;

(h) sufficient vent channels for venting air to atmosphere from said metering wells of (b), said reagent well(s) of (d), and said conditioning well(s) of (f);

and wherein said sample well of (a), said metering wells of (b), and said reagent wells of (d) and the conditioning wells of (f), said vent channels, and said capillary stop of (e) are positioned on a flat disc and capillary passageways are formed in said disc connecting said wells to each other and said wells to said vent channels, thereby providing a device for analyzing said biological fluid sample.

2. A multi-purpose device of claim 1, wherein said capillary stop of (e) is a hydrophilic stop.

3. A multi-purpose device of claim 1, wherein said capillary stop of (e) is a hydrophobic stop.

4. A multi-purpose device of claim 1, wherein said capillary passageway of (c) includes a capillary stop.

5. A multi-purpose device of claim 1, wherein said capillary passageways have a width of about 10-500 μ

m and a depth of at least 5 μ

m.

6. A multi-purpose device of claim 1, wherein said sample has a volume of about 0.3 to 2.0 μ

L.

7. A multi-purpose device of claim 1, wherein said sample is a member of the group consisting of blood, urine, water, saliva, spinal fluid, intestinal fluid, food, and blood plasma.

8. A multi-purpose device of claim 1, wherein said sample is assayed for a protein, a cell, a small organic molecule, or a metal.

9. A multi-purpose device of claim 8 wherein said protein is selected from the group consisting of albumin, HbAlc, protease, protease inhibitor, CRP, esterase, and BNP.

10. A multi-purpose device of claim 8 wherein said cell is selected from the group consisting of E. Coli, pseudomonas, white blood cells, red blood cells, h. pylori, strep a, chlamdia, and mononucleosis.

11. A multi-purpose device of claim 8 wherein said metal is selected from the group consisting of iron, manganese, sodium, potassium, lithium, calcium and magnesium.

12. A multi-purpose device of claim 1 further comprising at least one conditioning or reagent well disposed between said sample well and at least one of said metering wells for preconditioning or reacting said sample.