Portable coagulation monitoring device and method of assessing coagulation response

• US 8,450,078 B2
• Filed: 12/17/2010
• Issued: 05/28/2013
• Est. Priority Date: 12/18/2009
• Status: Active Grant

• Current Assignee: Entegrion, Inc.
• Original Assignee: Entegrion, Inc.
• Inventors: Dennis, Robert Glenn, Fischer, Thomas H., DaCorta, Joseph Anthony
• Primary Examiner(s): Shen, Bin
• Application Number:
  US12/971,013
• Publication Number:
  US 20110151491A1
• Time in Patent Office: 893 Days
• Field of Search: 435/4, 435/13
• US Class Current: 435/13
• CPC Class Codes: G01N 2011/008 optical properties
• CPC Class Codes: G01N 21/17 Systems in which incident light is modified in accordance with the properties of the material investigated where the material investigated is optically excited causing a change in wavelength of the incident light G01N21/63
• 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

A device, system and method is disclosed in which small volume blood samples are subjected to shear forces and shear stresses between two parallel planar surfaces to which linear motion trajectories are imparted. The formation of clots or coagulation of the sample is measured from dynamic mechanical coupling which occurs between the two parallel planar surfaces. Detection of the coagulation response can be achieved through optical probing or by measurement of physical effects of the blood sample binding to the planar surfaces, and restricting movement thereof.

Claims

1. A method of measuring coagulation response in a blood sample, comprising:

placing a sample droplet of whole blood between and in contact with first and second facing surfaces of two oppositely disposed parallel glass plates;

moving at least one plate linearly with respect to the other plate at a predetermined speed sufficient to activate platelets through exposure to shear forces; and

optically detecting, via measurement of mechanical displacement, the interaction between the first and second surfaces resulting from changes in the viscosity of the sample fluid and binding to the plate surfaces in order to measure coagulation response of the droplet of blood.

2. The method of claim 1, further comprising moving at least one plate at a first speed and optically detecting adherence of the sample droplet of blood to the surfaces of the plates to determine platelet response during coagulation.

3. The method of claim 2, further comprising subsequently moving at least one plate at a second speed slower than the first speed, and optically detecting the level of coagulation of the blood sample as indicative of Fibrin polymerization response.

4. The method of claim 1, wherein the relative motions between the two plates is controlled to generate arbitrarily selected waveforms to induce desired fluid shear rates at selected amplitudes, frequency, duration, and sequence such that the device is enabled to emulate fluid shear as desired over a very broad range, from DC (zero shear) to shear rates that would cause fluid cavitation and subsequent destruction of the cellular components of the sample, and continuously including all points in the shear rate spectrum between these two points.

5. The method of claim 4, wherein the shear rate is controlled in a sequence of values to generate specific protocols or plate motion paradigms for targeted diagnostic or analytic objectives, the targeted diagnostic or analytic objectives comprising one or more of rapid initiation of primary coagulation, destructive or non-destructive viscoelastic evaluation of early, mid-phase, or late-phase clotting, emulation of clinically-accepted or otherwise recognized shear rate protocols for comparison with other commercial or experimental devices, or validation testing against known standards.

6. The method of claim 1, wherein said plates are part of a cassette insertable in a device for measuring coagulation, and wherein said plates are transparent.

7. The method of claim 6, wherein the cassette further comprises memory, and further comprising storing thereon information about coagulation response resulting from said optical detection.

8. The method of claim 1, further comprising a step of sample optical detection by transmitting electromagnetic waves into the sample droplet, and detecting at least one of transmission, absorption, reflection and refraction of the electromagnetic waves through the sample droplet at respective light detectors, to generate analog signals representative of coagulation properties of the blood in the sample droplet for primary and secondary coagulation mechanisms.

9. The method of claim 8, further comprising converting said signals to digital signals, storing the digital signals and analyzing the stored digital signals in a predetermined manner to obtain selected information about the coagulation response of the blood in the sample droplet.

10. The method of claim 1, further comprising at least one voice coil actuator motor connectable to at least one plate for moving said at least one plate, and moving said at least one plate with said motor.

11. The method of claim 10, further comprising a processor connected to said motor and controlling operation thereof with said processor in a predetermined manner.

12. The method of claim 1, further comprising:

moving one plate relative to the other plate in a manner causing the other plate to move due to visco-elastic coupling between the blood and the other plate; and

determining the visco-elastic properties of the blood from the movement of the other plate.

13. The method of claim 1, further comprising:

detecting strain rates caused by movement of the one plate and the other plate caused by visco-elastic coupling between the one plate and the other plate caused by the blood sample; and

determining the coagulation state of the blood by inference analysis based on visco-elasticity of the blood sample determined from mechanical coupling between the two plates and the resulting said strain rates.

14. The method of claim 1, further comprising continually measuring the visco-elasticity of the blood over time to monitor changes over time of the coagulation response of the blood.

15. A method of measuring coagulation response in a blood sample comprising:

placing a sample droplet of whole blood between and in contact with first and second facing surfaces of two oppositely disposed glass plates;

moving at least one plate linearly with respect to the other plate at a first speed sufficient to activate platelets through exposure to shear forces;

optically detecting, via measurement of mechanical displacement, the interaction between the first and second surfaces in order to measure a first coagulation response of the blood indicative of platelet response;

moving at least one plate linearly with respect to the other plate at a second speed; and

optically detecting, via measurement of mechanical displacement and coupling, the interaction between the movement of the first and second surfaces in order to measure the terminal coagulation response of the blood indicative of rate and completeness of fibrin polymerization.

16. The method of claim 15, further comprising continually measuring the visco-elasticity of the blood sample over time to monitor changes over time of the coagulation response of the blood.