Apparatus and method for platelet function and drug response testing based on microfluidic chip

• US 9,983,220 B2
• Filed: 12/26/2013
• Issued: 05/29/2018
• Est. Priority Date: 12/27/2012
• Status: Active Grant

• Current Assignee: Korea University Research and Business Foundation
• Original Assignee: Korea University Research and Business Foundation
• Inventors: Shin, Se Hyun, Lim, Chae Seung
• Primary Examiner(s): Wecker, Jennifer
• Application Number:
  US14/655,437
• Publication Number:
  US 20150338424A1
• Time in Patent Office: 1,615 Days
• 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 2300/0627 Sensor or part of a sensor is integrated
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0663 Whole sensors
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0478 pistons
• CPC Class Codes: B01L 2400/06 Valves, specific forms thereof
• 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: G01N 15/0612 Optical scan of the deposits G01N15/0625 takes precedence
• CPC Class Codes: G01N 15/1433 using image recognition
• CPC Class Codes: G01N 15/1484 microstructural devices
• CPC Class Codes: G01N 2015/0092 Monitoring flocculation or agglomeration
• CPC Class Codes: G01N 33/49 Blood chemical methods for determining blood cell populations G01N33/5094; chemical analysis of blood groups or blood types G01N33/80
• CPC Class Codes: G01N 33/86 involving blood coagulating time or factors, or their receptors

Abstract

The present invention relates to an apparatus and a method for testing a function and a drug response of a platelet based on a microfluidic chip. The apparatus for test comprises a measuring device containing a blood sample and measuring aggregation and adhesion of a platelet generated by flow of the blood sample; and a fluid driving device which is connected to the measuring device and generates a oscillating shear flow of the blood sample. Therefore, activation of factors such as a platelet and von Willebrand factor (vWF) etc. can be activated uniformly and completely, and a repeatability of the platelet aggregation can be increased.

Claims

1. An apparatus to test a function and a drug response of a platelet based on a microfluidic chip, the apparatus comprising:

a measuring device comprising sample containers containing a blood sample, a micro channel connecting the sample containers and configured to guide a shear flow of the blood sample, a measuring chamber connected to the micro channel at a center of the micro channel, and a sensor configured to measure aggregation and adhesion of a platelet generated in the measuring chamber; and

a fluid driving device connected to the measuring device and configured to generate a linearly reciprocating flow of the blood sample which is in the micro channel,

wherein the aggregation and the adhesion of the platelet is generated in the measuring chamber while the blood sample reciprocately flows along the micro channel,

wherein the micro channel is arranged in parallel with other micro channels, and

wherein reagents which are different from each other are supplied in the measuring chamber.

2. The apparatus according to claim 1, wherein the fluid driving device comprises

a linear actuator,

a piston driven by the linear actuator and configured to linearly reciprocate, and

a cylinder housing the piston and configured to enable the piston linearly to reciprocate in the cylinder.

3. The apparatus according to claim 1, further comprising a valve installed between the measuring device and the fluid driving device and configured to control supply and cut-off of a driving pressure.

4. The apparatus according to claim 3, wherein the valve is configured to generate a pulsatile flow through periodic opening and closing of the value.

5. The apparatus according to claim 1, wherein the sensor comprises any one or any combination of any two or more of an electrode sensor configured to measure electrical impedance, an optical sensor configured to measure turbidity, a pressure sensor configured to measure a fluctuation pressure, and an image sensor configured to measure a oscillating flow distance of the blood sample.

6. The apparatus according to claim 5, wherein the electrode sensor comprises two electrodes installed in the measuring chamber and configured to measure a change of the electrical impedance caused by the aggregation and adhesion of the platelet in the measuring chamber.

7. The apparatus according to claim 5, wherein the optical sensor is disposed opposite to a light source outside of the measuring chamber and configured to measure a change of the optical turbidity which caused by the aggregation and adhesion of the platelet in the measuring chamber.

8. The apparatus according to claim 5, wherein the pressure sensor is disposed at the valve connecting the measuring device with the fluid driving device or in the sample container, and is configured to measure a change of the fluctuation pressure caused by the aggregation and adhesion of the platelet in the measuring chamber.

9. The apparatus according to claim 5, wherein the image sensor comprises

a light source, and

an optical measuring sensor configured to receive a light which is transmitted through the blood sample which is in the micro channel, and convert the received light to an electrical signal to measure the oscillating flow distance of the blood sample.

10. The according to claim 9, wherein the light source comprises a light emitting diode (LED), and wherein the optical measuring sensor comprises a charge coupled device (CCD) sensor array.

11. The apparatus according to claim 1,

wherein a rapidly channel-expanding part is formed in the measuring chamber to decrease a flow velocity of the blood sample.

12. The apparatus according to claim 1, wherein micro-pillars are installed in the measuring chamber and to induce a decrease of the flow of the blood sample by promoting the aggregation and the adhesion of the platelet.

13. The apparatus according to claim 1, wherein the measuring chamber contains.

14. The apparatus according to claim 1, wherein the reagents comprise any one or any combination of any two or more of Fibrinogen, Arachidonic acid, Collagen, Epinephrine, Adenosine diphosphate (ADP), Prostaglandin E1 (PGE1), Thrombin receptor activating peptide (TRAP), P2Y1 receptor antagonist, and P2Y12 receptor antagonist.

15. The apparatus according to claim 14,

wherein the P2Y1 receptor antagonist comprises any one of any combination of any two or more of MRS 2179, MRS 2279, MRS 2500, A2P5P, A3P5P, and A3P5PS,

wherein the P2Y12 receptor antagonist comprises any one or any combination of any two or more of Clopidogrel, Ticlopidine, Prasugrel, AR-C67085MX, Cangrelor, C1330-7, MRS 2395, and 2-methylthioadenosine-5′

-monophosphate, and

wherein the drug is supplied by either one of both of a surface coating and a liquid injection.

16. The apparatus according to claim 1,

wherein a minimum shear rate of the shear flow which is generated by the fluid driving device is at least 5000 s⁻

1; and

wherein a minimum shear stress of the shear flow which is generated by the fluid driving device is at least 8 Pa.