APPARATUS AND METHOD FOR PLATELET FUNCTION AND DRUG REPSONSE TESTING BASED ON MICROFLUIDIC CHIP

• US 20150338424A1
• Filed: 12/26/2013
• Published: 11/26/2015
• Est. Priority Date: 12/27/2012
• Status: Active Grant

• Current Assignee: Korea University Research and Business Foundation (Korea University)
• Original Assignee: Korea University Research and Business Foundation (Korea University)
• Inventors: SHIN, Se Hyun, LIM, Chae Seung
• Granted Patent: US 9,983,220 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• 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 for testing a function and a drug response of a platelet based on a microfluidic chip comprising:

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.

2. The apparatus for testing the function and the drug response of the platelet based on the microfluidic chip according to claim 1, wherein the measuring device comprises:

a sample container containing the blood sample therein;

a micro channel connected to the sample container and guiding the shear flow of the blood sample;

a measuring chamber connected to the micro channel, wherein the aggregation and the adhesion of the platelet is generated in the measuring chamber; and

a sensing part measuring the aggregation and the adhesion of the platelet generated in the measuring chamber.

3. The apparatus for testing the function and the drug response of the platelet based on the microfluidic chip according to claim 1, wherein the fluid driving device comprises:

a linear actuator;

a piston linearly reciprocating which is driven by the linear actuator; and

a cylinder in which the piston is installed such that the piston linearly reciprocates therein.

4. The apparatus for testing the function and the drug response of the platelet based on the microfluidic chip according to claim 1, wherein a valve is installed between the measuring device and the fluid driving device and controls supply and cut-off of a driving pressure.

5. The apparatus for testing the function and the drug response of the platelet based on the microfluidic chip according to claim 4, wherein the valve generates a pulsatile flow through periodic open and close.

6. The apparatus for testing the function and the drug response of the platelet based on the microfluidic chip according to claim 2, wherein the plurality of the micro channel is arranged in parallel.

7. The apparatus for testing the function and the drug response of the platelet based on the microfluidic chip according to claim 6, wherein reagents which are different from each other are supplied in the measuring chamber connected to the micro channel arranged in parallel.

8. The apparatus for testing the function and the drug response of the platelet based on the microfluidic chip according to claim 2, wherein the sensing part comprises at least one of an electrode sensor measuring electrical impedance, an optical sensor measuring turbidity, a pressure sensor measuring a fluctuation pressure, and an image sensor measuring a oscillating flow distance of the blood sample.

9. The apparatus for testing the function and the drug response of the platelet based on the microfluidic chip according to claim 8, wherein the electrode sensor has two electrodes which are installed at both side in the measuring chamber and measures the change of the electrical impedance which is changed by the aggregation and adhesion of the platelet in the measuring chamber.

10. The apparatus for testing the function and the drug response of the platelet based on the microfluidic chip according to claim 8, wherein the optical sensor is disposed opposite to a light source outside of the measuring chamber and measure the change of the optical turbidity which is changed by the aggregation and adhesion of the platelet in the measuring chamber.

11. The apparatus for testing the function and the drug response of the platelet based on the microfluidic chip according to claim 8, wherein the pressure sensor is disposed at the valve connecting the measuring device with the fluid driving device or in the sample container, and measures the change of the fluctuation pressure which is changed by the aggregation and adhesion of the platelet in the measuring chamber.

12. The apparatus for testing the function and the drug response of the platelet based on the microfluidic chip according to claim 8, wherein the image sensor comprises:

a light source; and

an optical measuring sensor receiving a light which transmits through the blood sample in the micro channel and converting the received light to an electrical signal, such that measuring the oscillating flow distance of the blood sample.

13. The apparatus for testing the function and the drug response of the platelet based on the microfluidic chip according to claim 8, wherein the light source comprises a light emitting diode (LED), and wherein the optical measuring sensor comprises a charge coupled device (CCD) sensor array.

14. The apparatus for testing the function and the drug response of the platelet based on the microfluidic chip according to claim 2,

wherein the measuring chamber is positioned at the central part of the micro channel, and

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

15. The apparatus for testing the function and the drug response of the platelet based on the microfluidic chip according to claim 2, wherein a plurality of micro-pillars are installed in the measuring chamber and induces the decrease of the flow of the blood sample by promoting the aggregation and the adhesion of the platelet.

16. The apparatus for testing the function and the drug response of the platelet based on the microfluidic chip according to claim 2, wherein the measuring chamber is equipped with a plurality of beads therein.

17. The apparatus for testing the function and the drug response of the platelet based on the microfluidic chip according to claim 2, wherein one or more type of the reagents which is selected among Fibrinogen, Arachidonic acid, Collagen, Epinephrine, Adenosine diphosphate (ADP), Prostaglandin E1 (PGE1), Thrombin receptor activating peptide (TRAP), P2Y1 receptor antagonist, and P2Y12 receptor antagonist supplied in the measuring chamber.

18. The apparatus for testing the function and the drug response of the platelet based on the microfluidic chip according to claim 17,

wherein the P2Y1 receptor antagonist comprises one of more type of the drug which is selected among MRS 2179, MRS 2279, MRS 2500, A2P5P, A3P5P, and A3P5PS,

wherein the P2Y12 receptor antagonist comprises one or more type of the drug which is selected among Clopidogrel, Ticlopidine, Prasugrel, AR-C67085MX, Cangrelor, C1330-7, MRS 2395, and 2-methylthioadenosine-5′

-monophosphate, and

wherein the drug is supplied through at least one method of a surface coating and a liquid injection.

19. The apparatus for testing the function and the drug response of the platelet based on the microfluidic chip according to claim 1,

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

1; and

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

20. A method for a platelet function and drug response test based on a microfluidic chip comprising:

injecting a blood sample into sample containers which are disposed both sides;

generating a oscillating shear flow of the blood sample through a micro channel connected to the sample container;

supplying a drug in a measuring chamber which is positioned at the central part of the micro channel, the drug reacts the platelet; and

measuring a change which is caused by an aggregation and adhesion of a platelet in the measuring chamber.