Cartridge device with fluidic junctions for coagulation assays in fluid samples

• US 10,048,282 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 Incorporated)
• Original Assignee: Abbott Point Of Care Incorporated (Abbott Laboratories Incorporated)
• Inventors: Di Tullio, Katrina Petronilla, Taylor, Jay Kendall, Lee-Yow, Niko Daniel, Ball, Sheila Diane, Campbell, John Lewis Emerson
• Primary Examiner(s): Kwak, Dean
• Application Number:
  US14/866,432
• Publication Number:
  US 20160091510A1
• 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 2400/0672 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 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• 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: G01N 2333/974 Thrombin
• CPC Class Codes: G01N 27/4166 measuring a particular property of an electrolyte
• CPC Class Codes: G01N 33/4905 Determining clotting time of blood by chemical methods G01N33/86, C12Q1/54
• 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 fluidic junctions and methods for assaying coagulation in a fluid sample received within the fluidic junctions. For example, the present invention may be directed to a 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 second reagent, a second sensor region, and a second fluidic lock valve. The sample analysis cartridge further includes a pump configured to push the first segment over the first sensor region to the first fluidic lock valve, and push the second segment over the second sensor region to the second fluidic lock valve.

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

wherein the second conduit further comprises a flow restrictor downstream of the first junction and upstream of the second sensor region, configured to cause the biological sample to preferential enter the first conduit and form the first segment of the biological sample; 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 push the first segment of the biological sample over the first sensor region to the first fluidic lock valve, such that the first segment of the biological sample is locked within the first conduit; and

to push the second segment of the biological sample over the second sensor region to the second fluidic lock valve, such that the second segment of the biological sample is locked within the second conduit;

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 sensor region comprises the first reagent; and

the second sensor region comprises the second reagent.

3. The sample analysis cartridge of claim 2, wherein:

the first reagent is disposed in a first layer formed on the first sensor; and

the second reagent is disposed in a second layer formed on the second sensor.

4. The sample analysis cartridge of claim 2, wherein:

the first reagent is dissolvable into the first segment of the biological sample; and

the second reagent is dissolvable into the second segment of the biological sample.

5. The sample analysis cartridge of claim 1, wherein the first and second sensors are electrochemical sensors.

6. The sample analysis cartridge of claim 1, wherein the flow restrictor is a capillary burst valve, a fluidic constriction, a fluidic resistance, or any combination thereof.

7. The sample analysis cartridge of claim 1, wherein the first segment of the biological sample has a larger volume than the second segment of the biological sample.

8. The sample analysis cartridge of claim 1, wherein the first fluidic lock valve provides a first pressure resistance such that the second segment of the biological sample pushes past the flow restrictor and allows for the second segment of the biological sample to be locked in the second conduit independent of the first segment of the biological sample in the first conduit.

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

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

11. The sample analysis of claim 10, wherein any residual pressure or movement of the biological sample after the pushing the first and second segments of the biological sample over the first and second sensor regions, respectively, proceeds into the overflow conduit.

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

the second conduit further comprises a first flow restrictor downstream of the first junction and upstream of the second sensor region, configured to cause the biological sample to preferential enter the first conduit and form the first segment of the biological sample;

the analysis cartridge further comprises an overflow conduit fluidically connected to the conduit at a second junction; and

the overflow conduit comprises a second flow restrictor configured to divert flow of the biological sample to the first junction.

13. The sample analysis cartridge of claim 12, wherein the first fluidic lock valve provides a first pressure resistance and the second fluidic lock valve provides a second pressure resistance.

14. The sample analysis cartridge of claim 13, 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.

15. The sample analysis cartridge of claim 14, wherein the second flow restrictor region comprises a lower pressure resistance than that of the first and second pressure resistances.

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

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