Cartridge device with segmented fluidics for assaying coagulation in fluid samples

• US 10,048,281 B2
• Filed: 09/25/2015
• Issued: 08/14/2018
• Est. Priority Date: 09/26/2014
• Status: Active Grant

• Current Assignee: Abbott Point Of Care Incorporated (Abbott Laboratories)
• Original Assignee: Abbott Point Of Care Incorporated (Abbott Laboratories)
• Inventors: Di Tullio, Katrina Petronilla, Taylor, Jay Kendall, Campbell, John Lewis Emerson, Elbuken, Caglar, Ball, Shelia Diane, Lightstone, Noam Saul
• Primary Examiner(s): Kwak, Dean
• Application Number:
  US14/866,402
• Publication Number:
  US 20160091509A1
• Time in Patent Office: 1,054 Days
• Field of Search: 422 73, 422500-505
• 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 2300/0663 Whole sensors
• 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 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0633 with moving parts
• CPC Class Codes: B01L 2400/0672 Swellable plugs
• CPC Class Codes: B01L 2400/0688 surface tension valves, capillary stop, capillary break
• CPC Class Codes: B01L 2400/0694 vents used to stop and induce flow, backpressure valves
• 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 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: G01N 2333/745 Assays involving non-enzymic blood coagulation factors
• CPC Class Codes: G01N 2333/974 Thrombin
• CPC Class Codes: G01N 33/86 involving blood coagulating time or factors, or their receptors

Abstract

The present invention relates to analytical testing devices comprising segmented fluidics and methods for assaying coagulation in a fluid sample received within the segmented fluidics. For example, the present invention may be directed to sample analysis cartridge including an inlet chamber, a first conduit comprising a first junction configured to split a biological sample into at least first and second segments, a second conduit comprising a first reagent, a first sensor region, and a first fluidic lock valve, and a third conduit comprising a first flow restrictor region, a second reagent, and a second sensor region. The sample analysis cartridge further includes a pump configured to independently mix the first segment in the second conduit and the second segment in the third conduit, and independently position the first segment over the first sensor region and position the second segment over the second sensor region.

Claims

1. A sample analysis cartridge comprising:

an inlet chamber configured to receive a biological sample;

a conduit fluidically connected to the inlet chamber and configured to receive the biological sample from the inlet chamber, the conduit splitting at a first junction into a first conduit and a second conduit configured to split the biological sample into at least first and second segments;

the first conduit fluidically connected to the conduit at the first junction and configured to receive the first segment of the biological sample, the first conduit comprising a first reagent, a first sensor region comprising a first sensor, and a first fluidic lock valve downstream of the first sensor region;

the second conduit fluidically connected to the conduit at the first junction and configured to receive the second segment of the biological sample, the second conduit comprising a second sensor region comprising a second sensor,

a first flow restrictor downstream of the first junction and upstream of the second sensor region and a second reagent; and

an air bladder connected to the inlet chamber and forming a part of a pump configured during operation;

to displace fluids within conduits of the sample analysis cartridge;

to independently mix the first segment of the biological sample in the first conduit to dissolve the first reagent into the first segment of the biological sample and mix the second segment of the biological sample in the second conduit to dissolve the second reagent into the second segment of the biological sample; and

to independently position the first segment of the biological sample over the first sensor region and position the second segment of the biological sample over the second sensor region;

wherein the first sensor region comprises at least one prothrombin time sensor, and the second sensor region comprises at least one activated partial thromboplastin time sensor;

wherein the first reagent comprises a first thrombin-cleavable peptide with a detectable moiety, and the second reagent comprises a second thrombin-cleavable peptide with a detectable moiety; and

wherein the first reagent is different from the second reagent.

2. The sample analysis cartridge of claim 1, wherein the first junction is a T-junction.

3. The sample analysis cartridge of claim 2, wherein the first and second sensors are electrochemical sensors.

4. The sample analysis cartridge of claim 1, wherein the first flow restrictor is configured to cause the biological sample to preferentially enter the first conduit and form the first segment of the biological sample.

5. The sample analysis cartridge of claim 4, wherein the first flow restrictor is a capillary burst valve, a fluidic constriction, a fluidic resistance, or any combination thereof.

6. The sample analysis cartridge of claim 4, wherein the first segment of the biological sample has a larger volume than the second segment of the biological sample.

7. The sample analysis cartridge of claim 4, wherein the first fluidic lock valve is configured to lock the first segment of the biological sample within the first conduit.

8. The sample analysis cartridge of claim 7, wherein the first fluidic lock valve is a membrane sponge valve, a microchannel capillary, or a micro-array valve.

9. The sample analysis cartridge of claim 7, wherein the first fluidic lock valve provides a first pressure resistance such that the second segment of the biological sample pushes past the first flow restrictor and allows for the second segment of the biological sample to be mixed in the second conduit independent of the first segment of the biological sample in the first conduit.

10. The sample analysis cartridge of claim 1, wherein:

the second conduit further comprises a second fluidic lock valve; and

the pump is further configured to independently lock the first segment of the biological sample in the first conduit using the first fluidic lock valve and lock the second segment of the biological sample in the second conduit using the second fluidic lock valve.

11. The sample analysis cartridge of claim 10, wherein the first fluidic lock valve is a membrane sponge valve, a microchannel capillary, or a micro-array valve and the second fluidic lock valve is a membrane sponge valve, a microchannel capillary, or a micro-array valve.

12. The sample analysis cartridge of claim 1, further comprising an overflow conduit fluidically connected to the conduit at a second junction, the overflow conduit comprises a second flow restrictor configured to divert flow of the biological sample to the first junction.

13. The sample analysis of claim 12, wherein any residual pressure or movement of the biological sample after the positioning the first and second segments of the biological sample over the first and second sensor regions, respectively, proceeds into the overflow conduit.

14. The sample analysis cartridge of claim 12, wherein:

the second conduit further comprises a second fluidic lock valve; and

the pump is further configured to independently lock the first segment of the biological sample in the first conduit using the first fluidic lock valve and lock the second segment of the biological sample in the second conduit using the second fluidic lock valve.

15. The sample analysis cartridge of claim 14, wherein the first fluidic lock valve provides a first pressure resistance and the second fluidic lock valve provides a second pressure resistance.

16. The sample analysis cartridge of claim 15, wherein any residual pressure or movement of the biological sample after the locking the first and second segments of the biological sample proceeds into the overflow conduit.

17. The sample analysis cartridge of claim 16, wherein the second flow restrictor provides a lower pressure resistance than that of the first and second pressure resistances.

18. The sample analysis cartridge of claim 1, wherein the first thrombin-cleavable peptide is different from the second thrombin-cleavable peptide.

19. The sample analysis cartridge of claim 1, wherein the first sensor region comprises the first reagent for analysis of an extrinsic pathway of coagulation in the first segment of the biological sample, and the second sensor region comprises the second reagent for analysis of an intrinsic pathway of coagulation in the second segment of the biological sample.