Optical Blood-Coagulation Sensor

• US 20150305681A1
• Filed: 12/19/2013
• Published: 10/29/2015
• Est. Priority Date: 12/19/2012
• Status: Active Grant

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Nadkarni, Seemantini K.
• Granted Patent: US 11,172,888 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61B 2560/0425 Ergonomically shaped housings A61B2560/0418 takes precedence
• CPC Class Codes: A61B 5/02028 Determining haemodynamic parameters not otherwise provided for, e.g. cardiac contractility or left ventricular ejection fraction
• CPC Class Codes: A61B 5/15 Devices for taking samples of blood hypodermic syringes A61M5/178
• CPC Class Codes: A61B 5/6898 Portable consumer electronic devices, e.g. music players, telephones, tablet computers
• CPC Class Codes: A61B 5/7214 using signal cancellation, e.g. based on input of two identical physiological sensors spaced apart, or based on two signals derived from the same sensor, for different optical wavelengths
• CPC Class Codes: A61B 5/7246 using correlation, e.g. template matching or determination of similarity
• CPC Class Codes: G01N 2021/479 Speckle
• CPC Class Codes: G01N 21/4788 Diffraction for sizing particles G01N15/0205
• CPC Class Codes: G01N 21/51 inside a container, e.g. in an ampoule G01N21/53 takes precedence
• CPC Class Codes: G01N 2201/0221 Portable; cableless; compact; hand-held
• CPC Class Codes: G01N 33/4905 Determining clotting time of blood by chemical methods G01N33/86, C12Q1/54

Abstract

Hand-held optical thromboelastographic sensor and method of using the same for simultaneous assessment of multiple parameters of blood coagulation at a point-of-care. The sensor includes an optical system registering laser speckle intensity associated with a stationary blood sample and data-processing circuitry programmed to derive the multiple parameters from speckle intensity. The circuitry may be part of a mobile device configured to operate without communication with a central server and/or data storage.

Claims

1. A hand-held optical thromboelastographer operable at a point-of-case without access to a central server, comprising:

an assembly including a housing unit that contains

a base substrate defining a void therein and having a first surface with an aperture providing access to said void, the base substrate being removably reinsertable into the housing unit;

a superstrate juxtaposed with the first surface over the aperture to form a closed chamber including the void such as to prevent access to said chamber through the aperture; and

a detector disposed to acquire light scattered, by a medium within the chamber through the superstrate and to provide a data output representing a cross-polarized speckle pattern generated by the medium;

and

a hand-held data-processing unit that includes electronic circuitry that is in operable communication with the detector and that is programmed

to measure, based on the data output, a time-averaged total reflectance parameter characterizing the medium;

to calculate, based on the total reflectance parameter, a mean square displacement associated with optical scatterers of the medium; and

to produce an output representing a time-dependent product of a time-dependent effective radius of an optical scatterer of the medium and a viscoelastic modulus of the medium.

2. An optical thromboelastographer according to claim 1,

wherein the medium includes a stationary sample of blood in the amount not exceeding 100 μ

L,

wherein the electronic circuitry is programmed to produce the output representing the time-dependent product at a single frequency defined to maximize a correlation between a blood-coagulation parameter derived from said time-dependent product and a reference coagulation parameter obtained with the use of a mechanical thromboelastographer, and

wherein the assembly is removably attachable to the hand-held data-processing unit to perform testing of viscoelasticity of the stationary sample of blood at a point-of-care.

3. An optical thromboelastographer according to claim 1, wherein the electronic circuitry is further programmed to compute, based at least on said ratio, at least first and second time-dependent characteristics of the medium.

4. An optical thromboelastographer according to claim 3,

wherein the medium includes a stationary sample of blood and the at least first and second parameters include a clotting time, a rate of clot formation, a clot strength, a fibrinolysis function, and a platelet aggregation function,

the optical thromboelastographer further comprising an output device operably cooperated with the electronic circuitry to display a visually-perceivable representation of the at least first and second parameters.

5. An optical thromboelastographer according to claim 1, wherein the electronic circuitry is further programmed to determine a viscoelastic modulus of the medium corrected for changes of at least one of optical absorption and optical scattering of the medium.

6. An optical thromboelastographer according to claim 1, further comprising a vibration-isolating platform operable to compensate for a relative movement between the base substrate and the housing unit.

7. A hand-held optical thromboelastographer operable at a point-of-case without access to a central cerver, comprising:

an assembly including a housing unit that contains

a sample cartridge having a chamber in a plane-parallel substrate, said chamber being optically accessible through a superstate sealingly overlaying the chamber, said chamber being fluidly accessible through a channel, said cartridge being removably reinsertable into the housing unit;

an optical train transmitting light that has traversed said chamber, the optical train devoid of optical power and including an array of optical apertures; and

a detector disposed to acquire light scattered by a medium within the chamber through the array of optical apertures and to provide a data output representing a cross-polarized speckle pattern generated by the medium;

a hand-held data-processing unit that includes electronic circuitry that is in operable communication with the detector and that is programmed

to measure, based on the data output, an optical thickness of the medium within the chamber;

to calculate, on said optical thickness and an autocorrelation function of the cross-polarized speckle pattern, a mean square displacement associated with optical scatterers of the medium; and

to produce an output representing, when the medium includes a stationary sample of blood, a platelet aggregation function and at least first and second parameters including a clotting time, a rate of clot formation, a clot strength, and a fibrinolysis function;

and

an output device operably cooperated with the electronic circuitry to display a visually-perceivable representation of the output, said assembly being removably attached to the output device during operation of the optical thromboelastographer.

a time-dependent product of a time-dependent effective radius of an optical scatterer of the medium and a viscoelastic modulus of the medium.

8. An optical thromboelastographer according to claim 7, wherein the medium includes a stationary sample of blood in the amount not exceeding 100 microliters, wherein the electronic circuitry is further programmed to produce the output representing the time-dependent product at a single frequency defined to maximize a correlation between a blood-coagulation parameter derived from said time-dependent product and a reference coagulation parameter obtained with the use of a mechanical thromboelastographer.

9. An optical thromboelastographer according to claim 8, wherein the electronic circuitry is further programmed to determine at least one of (i) a viscoelastic modulus of the medium corrected for changes of at least one of optical absorption and optical scattering of the medium and (ii) a time-dependent product of a time-dependent effective radius of an optical scatterer of the medium and a viscoelastic modulus of the medium.

10. A method for determining a descriptor of coagulation of a stationary blood sample at a point-of-care with an optical thromboelastographer, the method comprising:

with an optical detector, disposed in a housing removably attachable to a hand-held data-processing unit, acquiring light scattered by the stationary blood sample,

said blood sample positioned in a chamber formed by a void in a base substrate and an optically-transparent superstrate layered over a surface of the base substrate such as to prevent access to said void through an aperture defined by the void in the surface;

producing data output representing a cross-polarized speckle pattern produced by the stationary blood sample; and

calculating, with a data-processing electronic circuitry, a plurality of time-dependent parameters associated with the coagulation of the stationary blood sample based on a time-dependent parameter representing a product of a viscoelastic parameter of the stationary blood sample and a time-dependent radius of an optical scatterer of said blood sample,

the plurality of time-dependent parameters including a clotting time, a clot rate, a clot strength, a fibrinogen function, a fibrinolysis function, and a platelet aggregation function.

11. A method according to claim 10, further comprising determining, based on the data output, a time-averaged total reflectance parameter characterizing the stationary blood sample.

12. A method according to claim 11, further comprising calculating, based on the total reflectance parameter, a mean square displacement of optical scatterers of the stationary blood sample.

13. A method according to claim 10, wherein the calculating includes calculating a product of a time-dependent effective radius of an optical scatterer of the stationary blood sample and a viscoelastic parameter of said blood sample, the viscoelastic parameter of said blood sample having been determined at a single frequency chosen to maximize a correlation between a blood-coagulation parameter derived from said product and a reference coagulation parameter obtained with the use of a mechanical thromboelastographer

14. A method according to claim 10, wherein the producing includes producing data output representing a cross-polarized speckle pattern that is compensated for mechanical vibrations associated with the optical thromboelastographer.