Capillary hematocrit separation structure and method

• US 6,319,719 B1
• Filed: 10/28/1999
• Issued: 11/20/2001
• Est. Priority Date: 10/28/1999
• Status: Expired due to Fees

• Current Assignee: Roche Diabetes Care Inc. (Roche Holding AG)
• Original Assignee: Roche Diagnostics Corporation (Roche Holding AG)
• Inventors: Bhullar, Raghbir S., Wilsey, Christopher D., Shelton, Jeffrey N.
• Primary Examiner(s): WALLENHORST, MAUREEN
• Application Number:
  US09/428,691
• Time in Patent Office: 754 Days
• Field of Search: 436/70, 436/164, 436/165, 436/175, 436/177, 422/55, 422/58, 422/73, 422/101, 422/102
• US Class Current: 436/70
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0825 Test strips
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/086 using baffles or other fixed flow obstructions
• 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: B01L 3/502753 characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• CPC Class Codes: G01N 33/491 by separating the blood components G01N15/05 takes precedence
• CPC Class Codes: Y10T 436/25125 Digestion or removing interfering materials
• CPC Class Codes: Y10T 436/25375 Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]

Abstract

A capillary hematocrit separation structure is included within a housing having a fluid inlet port, a reaction region, and a capillary pathway connecting the inlet port and the reaction region. The capillary pathway is dimensioned so that the driving force for the movement of liquid through the capillary pathway arises from capillary pressure. A plurality of obstructions are fixed in the capillary pathway, each obstruction having a concave portion facing toward the vented reaction region on the down stream side of the obstructions as viewed with reference to a liquid flowing from the inlet port to the reaction region. The capillary pathway in a hematocrit separation structure for a single drop sample size includes about 10⁵ obstructions, each obstruction including a concave portion having a volume of between about 10⁻⁴ to 10⁻⁵ μl for selectively receiving hematocrit.

Claims

1. An apparatus for separating hematocrit from a whole blood sample having a selected total volume, the sample including a partial volume of blood plasma and a partial volume of hematocrit, the apparatus comprising:

a body having an inlet port for receiving a whole blood sample, a reaction region spaced from the inlet port, and at least one capillary pathway having an inlet end coupled to the inlet port and an outlet end coupled to the reaction region, each capillary pathway being dimensioned sufficiently small to assure transport of a portion of the blood sample from the inlet end to the outlet end by capillary pressure, each capillary pathway including a plurality of obstructions, the obstructions having a concave portion facing toward the outlet end of the pathway for separating hematocrit from the portion of the blood sample transported through the capillary pathway to deliver a reaction volume of plasma to the reaction region.

2. The apparatus of claim 1 wherein the concave portions of all the obstructions have a total volume at least equal to the reaction volume times the ratio of said partial volume of the hematocrit to said total volume of the sample.

3. The apparatus of claim 1 wherein each capillary pathway volume is less than the sum of said partial volumes of the blood plasma and hematocrit.

4. The apparatus of claim 1 wherein the obstructions, in cross-section, have a crescent moon shape.

5. The apparatus of claim 1 wherein the obstructions, in cross section, have a bullet shape.

6. The apparatus of claim 1 wherein the obstructions are separated from each other, on a nearest neighbor basis, by about 10⁻

5 meters.

7. The apparatus of claim 1 wherein the inlet port has a volume that is less than about 50 μ

l.

8. The apparatus of claim 7 wherein the sum of the inlet port volume and the capillary pathway volume is less than about 20 μ

l.

9. The apparatus of claim 1 wherein the reaction region contains a dry reagent selected to detect an analyte in the blood plasma.

10. The apparatus of claim 1 wherein the reaction region includes an optical window permitting optical detection of an analyte in the blood plasma.

11. The apparatus of claim 1 wherein the reaction region includes electrochemical apparatus for detection of an analyte in the blood plasma.

12. In a clinical diagnostic device comprising a housing having a fluid inlet port, a vented reaction region, and at least one capillary pathway connecting the inlet port and the reaction region and in which the driving force for the movement of liquid through the at least one capillary pathway arises from capillary pressure, an improvement comprising:

a plurality of obstructions fixed in the at least one capillary pathway, each obstruction having a concave portion facing toward the vented reaction region.

13. The clinical diagnostic device of claim 12 wherein the obstructions, in cross-section, have a crescent moon shape.

14. The clinical diagnostic device of claim 12 wherein the obstructions, in cross-section, have a bullet shape.

15. The clinical diagnostic device of any of claims 12-14 wherein the obstructions are separated from each other, on a nearest neighbor basis, by about 10⁻

5 meters.

16. The clinical diagnostic device of claim 15 wherein the inlet port has a volume that is less than about 50 μ

l.

17. The clinical diagnostic device of claim 16 wherein a sum of the inlet port volume and the volume of the at least one capillary pathway is less than about 20 μ

l.

18. The clinical diagnostic device of claim 15 wherein the reaction region contains a dry reagent selected to detect an analyte in a liquid applied to the device.

19. The clinical diagnostic device of claim 15 wherein the reaction region includes an optical window permitting optical detection of an analyte in a liquid applied to the device.

20. The clinical diagnostic device of claim 15 wherein the reaction region includes electrochemical apparatus for detection of an analyte in a liquid applied to the device.

21. The clinical diagnostic device of any of claims 12-14 wherein the inlet port has a volume that is less than about 50 μ

l.

22. The clinical diagnostic device of any of claims 12-14 wherein a sum of the volume of the inlet port and the at least one capillary pathway is less than about 20 μ

l.

23. The clinical diagnostic device of any of claims 12-14 wherein the reaction region contains a dry reagent selected to detect an analyte in a liquid applied to the device.

24. The clinical diagnostic device of any of claims 12-14 wherein the reaction region includes an optical window permitting optical detection of an analyte in a liquid applied to the device.

25. The clinical diagnostic device of any of claims 12-14 wherein the reaction region includes electrochemical apparatus for detection of an analyte in a liquid applied to the device.

26. A method for detecting an analyte in blood plasma comprising the steps of:

providing a reagent in a reaction region of a clinical diagnostic device,

separating a specimen amount of blood plasma from a whole blood sample by;

introducing a whole blood sample containing a partial volume of blood plasma into an inlet end of a capillary pathway leading to the reaction region, the capillary pathway containing a plurality of obstructions fixed in the capillary pathway, each obstruction having a concave portion facing away from the inlet end in the direction of flow of the blood sample from the inlet end to the reaction region,

allowing sufficient time for the specimen amount of blood plasma to flow through the length of the capillary pathway to the reaction region, and observing the reaction between the blood plasma and the reagent in the reaction region of the device to detect said analyte.

27. The method of claim 26 further comprising the step of hydrophilizing the capillary pathway and reaction region prior to the introducing step.