Microfluidic chip for coagulation sensing

• US 10,725,019 B2
• Filed: 01/30/2015
• Issued: 07/28/2020
• Est. Priority Date: 01/30/2015
• Status: Active Grant

• Current Assignee: Hewlett-Packard Development Company, L.P. (HP Inc.)
• Original Assignee: Hewlett-Packard Development Company, L.P. (HP Inc.)
• Inventors: Valencia, Melinda M, Domingue, Chantelle E, Sells, Jeremy, Giri, Manish, Bengali, Sadiq
• Primary Examiner(s): Sines, Brian J.
• Application Number:
  US15/522,831
• Publication Number:
  US 20170328882A1
• Time in Patent Office: 2,006 Days
• Field of Search: 422 681, 422502, 422503, 422504, 436 43, 436 63, 436178, 436180
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2400/0442 thermal energy, e.g. vaporisation, bubble jet
• 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 3/502715 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: B81B 1/00 Devices without movable or flexible elements, e.g. microcapillary devices
• CPC Class Codes: G01N 27/02 by investigating impedance
• CPC Class Codes: G01N 33/4905 Determining clotting time of blood by chemical methods G01N33/86, C12Q1/54

Abstract

Example implementations relate to coagulation sensing. For example, a microfluidic chip for coagulation sensing may include a microfluidic channel, an outlet at an end of the microfluidic channel having an air interface, and an impedance sensor located within the microfluidic channel and within a particular proximity to the air interface, the impedance sensor to determine a stage of a coagulation cascade of a blood sample flowing through the microfluidic channel to the impedance sensor.

Claims

1. A microfluidic chip, comprising:

a microfluidic chip;

an outlet at an end of the microfluidic channel having an air interface; and

an impedance sensor located within the microfluidic channel at the outlet having the air interface, the impedance sensor configured to determine a stage of a coagulation cascade of a blood sample flowing through the microfluidic channel to the impedance sensor.

2. The microfluidic chip of claim 1, further comprising a resistor pump in the microfluidic channel to accelerate a flow of the blood sample through the microfluidic channel and eject the blood sample from a nozzle at the end of the microfluidic channel.

3. The microfluidic chip of claim 1, further comprising a plurality of microfluidic channels, each channel ending in a nozzle with an air interface and an impedance sensor to detect a change in impedance in response to detection of aggregated platelets in the blood sample, the nozzles arranged to simulate flow of blood to a wound without introduction of any reagent to the blood sample.

4. The microfluidic chip of claim 1, further comprising a resistive element inside the microfluidic channel to provide controlled heating of the blood sample to with a temperature feedback provided by a Thermal Sense Resistor.

5. The microfluidic chip of claim 1, further comprising a filter located at an inlet of the microfluidic channel, the microfluidic channel having a narrowing portion by which the microfluidic channel narrows to a smaller diameter in a direction away from the inlet.

6. The microfluidic chip of claim 1, further comprising the impedance sensor to detect a change in impedance in response to detection of a full hemostatic plug in the blood sample.

7. The microfluidic chip of claim 1, further comprising:

a plurality of microfluidic channels to direct a flow of a blood sample, wherein each of the plurality of microfluidic channels includes a nozzle at the outlet having an air interface, the nozzle being a fluid outlet for fluid to exit the microfluidic channel;

each of the microfluidic channels having a respective impedance sensor, each impedance sensor including an input high-side electrode and an input low-side electrode, the input high-side electrode proximal to the air interface relative to the input low-side electrode, each impedance sensor to detect a stage of coagulation of the blood sample during a period of time, based on a change of impedance detected by each impedance sensor; and

an electrical output to output an electrical signal representing sensed data from the multiple impedance sensors.

8. The microfluidic chip of claim 7, wherein the nozzle has a diameter of less than 100 micrometers.

9. The microfluidic chip of claim 7, wherein the input high-side electrode and the input low-side electrode are separated by a distance of less than 50 micrometers.

10. The microfluidic chip of claim 8, wherein each of the input high-side electrode and the input low-side electrode have a thickness of less than 5000 Angstroms.

11. The microfluidic chip of claim 1, further comprising:

an input for connection to a cassette that includes a fluid reservoir, the input to receive a blood sample from the cassette;

the microfluidic channel to direct a flow of the blood sample to a nozzle at the outlet at an end of the microfluidic channel, the nozzle having the air interface to accumulate the blood sample; and

the sensor having an input electrode proximal to the nozzle and an electric ground located distal to the nozzle.

12. The microfluidic chip of claim 1, further comprising a nozzle, wherein the nozzle is located within a narrowing portion of the microfluidic channel.

13. The microfluidic chip of claim 11, further comprising the impedance sensor to detect a primary hemostasis stage of coagulation in the blood sample in response to detecting an impedance value between 0.4×

10⁴ Ohms and 1.0×

10⁴ Ohms.

14. The microfluidic chip of claim 11, further comprising the impedance sensor to detect a secondary hemostasis stage of coagulation in the blood sample in response to detecting an impedance value between 1.6×

10⁴ Ohms and 1.8×

10⁴ Ohms.

15. The microfluidic chip of claim 11, further comprising the impedance sensor to detect a full hemostatic plug in response to detecting an impedance value of at least 1.8×

10⁴ Ohms.

16. A microfluidic chip, comprising:

a microfluidic channel;

an outlet at an end of the microfluidic channel having an air interface; and

an impedance sensor located within the microfluidic channel, the impedance sensor to determine a stage of a coagulation cascade of a blood sample flowing through the microfluidic channel to the impedance sensor;

wherein the sensor is located less than 100 micrometers (μ

m) from the outlet having the air interface.

17. The microfluidic chip of claim 16, wherein the sensor and the outlet are located a same distance away from an inlet of the microfluidic channel.