Cuvette-based apparatus for blood coagulation measurement and testing

• US 10,578,605 B2
• Filed: 12/05/2018
• Issued: 03/03/2020
• Est. Priority Date: 07/16/2008
• Status: Active Grant

• Current Assignee: Instrumentation Lab Co (Instrumentation Lab)
• Original Assignee: Instrumentation Lab Co (Instrumentation Lab)
• Inventors: Colella, Gregory M., Huang, Henry D., Kuklo, Jr., Anthony F., Shishkin, Dimitri, Figueroa, Maria, Mawhirt, James A.
• Primary Examiner(s): Kwak, Dean
• Application Number:
  US16/210,433
• Publication Number:
  US 20190107529A1
• Time in Patent Office: 454 Days
• Field of Search: 422 73, 422500-504, 422507
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2200/146 Employing pressure sensors
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/027 Digital display, e.g. LCD, LED
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• 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 2300/165 Specific details about hydrophobic, oleophobic surfaces
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/086 using baffles or other fixed flow obstructions
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502723 characterised by venting arrangements
• 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 3/502746 characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• CPC Class Codes: G01N 33/4905 Determining clotting time of blood by chemical methods G01N33/86, C12Q1/54
• CPC Class Codes: G01N 33/4915 using flow cells flow cytometry G01N15/14

Abstract

An apparatus for measuring blood clotting time includes a blood clot detection instrument and a cuvette for use with the blood clot detection instrument. The cuvette includes a blood sample receptor-inlet; a channel arrangement including at least one test channel for performing a blood clotting time measurement, a sampling channel having at least one surface portion that is hydrophilic, communicating with the blood sample receptor-inlet and the at least one test channel, and a waste channel having at least one surface portion that is hydrophilic, communicating with the sampling channel; and a vent opening communicating with the sampling channel. The sampling channel, the vent opening and the waste channel, coact to automatically draw a requisite volume of a blood sample deposited at the blood receptor-inlet, into the sampling channel. More specifically, air compressed within the blood clot detection instrument, the at least one test channel of the cuvette, and the section of the sampling channel extending beyond the vent opening of the cuvette, coacts with the waste channel to cause a leading edge of the blood sample drawn into the sampling channel from the blood receptor-inlet, to pull back within the sampling channel and uncover an optical sensor in of the blood clot detection instrument. The uncovering of the optical sensor activates a pump module of the blood clot detection instrument, which draws the requisite volume of the blood sample into the at least one test channel.

Claims

1. An apparatus for measuring blood clotting time, the apparatus comprising:

A) a blood clot detection instrument, the blood clot detection instrument comprising;

a pump module; and

at least one pressure sensor; and

B) a cuvette for use with the blood clot detection instrument, the cuvette comprising;

a main body including;

i) a blood sample receptor-inlet;

ii) a channel arrangement comprising;

a) at least one test channel for communicating with the pump module when the cuvette is operatively coupled to the clot detection instrument;

b) a sample channel fluidically coupled to the at least on test channel and to a sample deposit area at the blood sample receptor-inlet, at least a portion of the sample channel having a hydrophilic surface such that blood is automatically drawn from the sample-receptor inlet; and

c) a vent opening fluidically coupled to the sample channel, the vent opening configured to vent air from the sample channel as the sample channel fills with blood, a predetermined sample volume defined by a volume of the sample channel between the sample-receptor inlet and the vent opening;

d) a waste channel fluidically coupled to the sample channel between the blood sample receptor-inlet and the vent opening, a flow restriction at an intersection of the waste channel and the sample channel impeding blood from flowing into the waste channel until the sample channel is filled to the vent opening such that the sample channel automatically fills with the predetermined sample volume.

2. The apparatus of claim 1, wherein compressed air within the blood clot detection instrument, the at least one test channel, the sample channel, the vent opening and waste channel, is configured to automatically draw a requisite volume of a blood sample deposited at the blood receptor-inlet, into the sample channel, and

wherein the at least one test channel, the pump module and the at least one pressure sensor, coact to perform a blood clotting time measurement on the requisite volume of the blood sample.

3. The apparatus of claim 2, wherein the coaction between the sample channel and the vent opening includes a force generated by the at least one surface portion of the sample channel that is hydrophilic and which draws the blood from the blood sample deposited at the blood sample receptor-inlet into the sample channel and venting of air through the vent opening which is displaced from the sample channel by the incoming blood.

4. The apparatus of claim 1, wherein the channel arrangement further comprises a member associated with the waste channel for delaying the filling of the waste channel until the sample channel is filled.

5. The apparatus of claim 4 wherein the member associated with the waste channel comprises a jumper channel or a restriction.

6. The apparatus of claim 5, wherein the jumper channel or restriction has at least one surface portion, a coating, an insert or liner, and any combination thereof, that is hydrophilic.

7. The apparatus of claim 1, wherein the channel arrangement is formed in a surface of the main body.

8. The apparatus of claim 7, further comprising a substrate for closing and sealing at least a portion of the channel arrangement formed in the surface of the main body.

9. The apparatus of claim 8, wherein the substrate forms the at least one surface portion of the sample channel that is hydrophilic.

10. The apparatus of claim 8, wherein the substrate comprises a film with a hydrophilic surface, the hydrophilic surface of the substrate forming the at least one surface portion of the sample channel that is hydrophilic.

11. The apparatus of claim 8, wherein the substrate comprises a film and a layer of hydrophilic material disposed on the film, the hydrophilic material forming the at least one surface portion of the sample channel that is hydrophilic.

12. The apparatus of claim 11, wherein the hydrophilic material is an adhesive which attaches the substrate to the main body.

13. The apparatus of claim 1, further comprising a blood clotting reagent disposed in the at least one test channel.

14. The apparatus of claim 1, wherein the at least one test channel includes a section having at least one textured surface.

15. The apparatus of claim 1, therein the at least one test channel includes a restriction.

16. The apparatus of claim 1, wherein the main body is made of one of a hydrophobic material, a hydrophilic material, or a combination of a hydrophobic material and a hydrophilic material.

17. The apparatus of claim 1, wherein the waste channel has at least one surface portion, a coating, an insert or liner, and any combination thereof, that is hydrophilic.

18. The apparatus of claim 1, wherein the at least one test channel has at least one surface portion, a coating 1 an insert or liner and any combination thereof, that is hydrophilic or hydrophobic.

19. The apparatus of claim 1, wherein the channel arrangement further comprises a vent channel connecting the vent opening with the sample channel and wherein the vent channel has at least one surface portion, a coating, an insert or liner, and any combination thereof, that is hydrophilic.

20. The apparatus of claim 1;

wherein the channel arrangement further comprises a jumper channel connecting the waste channel with the sample channel, the jumper channel for delaying the filling of the waste channel until the sample channel is filled.

21. The apparatus of claim 1 wherein the blood clot detection instrument comprises:

a pump module for communicating with the test channel of the cuvette;

a pressure sensor; and

a central processing unit executing instructions for;

operating the pump module in a pressure alternating mode that causes a viscosity of the blood sample to increase over time;

the increase in viscosity of the blood causing a pumping pressure of the pump module to increase over time;

obtaining a baseline pumping pressure from the pressure sensor upon initial operation of the pump module in the pressure alternating mode;

obtaining additional pumping pressures over time from the pressure sensor;

determining a pumping pressure difference value between each additional pumping pressure and the baseline pumping pressure;

comparing the pumping pressure difference value to a predetermined threshold value; and

indicating the blood clotting time of the blood sample when the pumping pressure difference value equals or exceeds the predetermined threshold value, the indicated blood clotting time comprising a duration of time extending between the measurement of the additional pumping pressure used for determining the pumping pressure difference value that exceeded the predetermined threshold value and the measurement of the baseline pumping pressure.

22. The apparatus of claim 21, wherein the predetermined threshold may be fixed or dynamic.

23. The apparatus of claim 21, wherein the pump module, in the pressure alternating mode, creates positive and negative pressures in the test channel of the cuvette.

24. The apparatus of claim 21, wherein the pump module, in the pressure alternating mode, reciprocally moves the blood sample back and forth across a textured section or restricted area of the test channel, thereby mixing the blood sample with a reagent disposed in the test channel that triggers and accelerates clotting of the blood sample.

25. The apparatus of claim 1, wherein the at least one test channel comprises three test channels and further comprising a reagent in each of the test channels.

26. The apparatus of claim 25, wherein the reagents are all the same, different, or combinations thereof.

27. The apparatus of claim 1, wherein air compressed within the blood clot detection instrument, the at least one test channel of the cuvette, and the section of the sample channel extending beyond the vent opening of the cuvette, coacts with the waste channel to cause a leading edge of the blood sample draw-n into the sample channel from the blood receptor-inlet, to pull back within the sample channel and uncover an optical sensor of the blood dot detection instrument, the volume of the blood sample in the sample channel at the time when the blood sample is pulled back to uncover the optical sensor, equaling the requisite volume, the uncovering of the optical sensor activating the pump module of the blood clot detection instrument, which draws the requisite volume of the blood sample into the at least one test channel.

28. The apparatus of claim 1 further comprising;

a first substrate with hydrophilic properties for closing and sealing the sample channel and the waste channel; and

a second substrate with hydrophobic properties for closing and sealing the at least one test channel.

29. The apparatus of claim 28, wherein the sample channel and the waste channel are formed in a first surface of the cuvette and the first substrate is affixed to the first surface, and the at least one test channel is formed in second surface of the cuvette and the second substrate is affixed to the second surface.

30. The apparatus of claim 29, wherein the first and second surfaces are opposed to one another.

31. The apparatus of claim 28, wherein the channel arrangement further comprises:

a vent channel connecting the vent opening with sample channel; and

a jumper channel connecting the waste channel to the sample channel, for delaying the filling of the waste channel until the sample channel is filled,

wherein the first substrate closes and seals the vent channel and the jumper channel.