Plasma retention structure providing internal flow

• US 6,406,672 B1
• Filed: 01/28/2000
• Issued: 06/18/2002
• Est. Priority Date: 01/28/2000
• Status: Expired due to Term

• Current Assignee: Roche Diabetes Care Inc. (Roche Holding AG)
• Original Assignee: Roche Diagnostics Corporation (Roche Holding AG)
• Inventors: Cothrel, Andrew David, Bhullar, Raghbir Singh, Reiser, Wolfgang O. L.
• Primary Examiner(s): WALLENHORST, MAUREEN
• Application Number:
  US09/494,072
• Time in Patent Office: 872 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: 422/73
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0681 Filter
• 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 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 3/502753 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 blood plasma 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 capillary pathway having an inlet end coupled to the inlet port, the capillary pathway being dimensioned sufficiently small to assure transport of the blood sample including the plasma from the inlet end into the capillary pathway by capillary pressure, at least one partition fixed within the capillary pathway, each partition enclosing a hollow area and including at least one opening defined by confronting surfaces of the partition, each opening leading from the capillary pathway outside a partition to the hollow area within the partition, each opening having a dimension defined by the distance between the confronting surfaces of between about 0.1 and 15 μ

m.

2. The apparatus of claim 1 wherein the capillary pathway is defined in part by a first wall, a second wall confronting the first wall and separated therefrom by a distance sufficiently small to assure transport of the blood sample including the plasma between the first and second walls, and wherein the partitions project from the first wall toward the second wall.

3. The apparatus of claim 2 wherein the first wall includes a plurality of apertures through the first wall, each aperture being coincident with a hollow area enclosed by one of the partitions, the apparatus further comprising a backing member coupled to the first wall, the backing member and apertures defining a plurality of chambers coupled to each of the hollow areas.

4. The apparatus of claim 3 wherein the first wall includes at least one step surrounding each aperture defining a perimeter of each chamber, the apparatus further comprising a seal surrounding each of the chambers sealing the first wall to the backing member.

5. The apparatus of claim 4 wherein the first wall includes multiple steps surrounding each aperture defining a perimeter of each chamber.

6. The apparatus of claim 4 wherein the seal surrounding each of the chambers sealing the first wall to the backing member is fixed to the first wall.

7. The apparatus of claim 3 further comprising a plurality of pairs of electrodes fixed to the backing member, each pair of electrodes having a first end positioned within one of the chambers, and a second end situated adjacent an exposed edge of the backing member.

8. The apparatus of claim 7 wherein the second ends of all of the electrodes are located on a common exposed edge of the backing member.

9. The apparatus of claim 3 wherein the volume of each of the chambers is between about 0.1 and 100 nl.

10. The apparatus of claim 2 wherein the partitions projecting from the first wall toward the second wall include terminal ends contiguous to the second wall.

11. The apparatus of claim 1 wherein the average diameter of each hollow area is between about 40 and 300 μ

m.

12. The apparatus of claim 11 wherein each partition includes only a single opening.

13. An apparatus for separating blood plasma 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 capillary pathway having an inlet end coupled to the inlet port, the capillary pathway being defined in part by a first wall, a second wall confronting the first wall and separated therefrom by a distance sufficiently small to assure transport of the blood sample including the plasma between the first and second walls from the inlet end through the capillary pathway by capillary pressure, the capillary pathway including at least one partition projecting from the first wall toward the second wall, each partition enclosing a hollow area and including at least one opening defined by confronting surfaces of the partition, the opening leading from the capillary pathway outside the partition to the hollow area within the partition, the first wall including an aperture through the first wall coincident with the hollow area enclosed by each partition, the apparatus further comprising a backing member coupled to the first wall, the backing member and each aperture defining a chamber, each chamber being coupled to an adjacent hollow area.

14. The apparatus of claim 13 further comprising a plurality of pairs of electrodes fixed to the backing member, each pair of electrodes having a first end positioned within one of the chambers, and a second end situated adjacent an exposed edge of the backing member, the second ends of all of the electrodes being located on a common exposed edge of the backing member.

15. The apparatus of claim 13 wherein the inlet port has a volume of less than about 200 μ

l.

16. The apparatus of claim 15 wherein the capillary pathway has a volume of less than about 50 μ

l.

17. The apparatus of claim 15 wherein each hollow area has an average diameter of about 100 μ

m.

18. The apparatus of claim 15 wherein each of the chambers has a volume of about 5.0 nl.

19. The apparatus of claim 15 wherein each partition includes only a single opening.

20. The apparatus of claim 19 wherein the openings in each partition are arranged to face away from the inlet end of the capillary pathway.

21. The apparatus of claim 13 wherein the confronting surfaces defining each opening are spaced apart by between about 1.5 and 15 μ

m.