Methods, devices, and systems for measuring physical properties of fluid

• US 9,518,905 B2
• Filed: 01/15/2013
• Issued: 12/13/2016
• Est. Priority Date: 01/16/2012
• Status: Active Grant

• Current Assignee: Abram Scientific, Inc.
• Original Assignee: Abram Scientific, Inc.
• Inventors: Abhishek, Ramkumar, Yoshimizu, Norimasa
• Primary Examiner(s): WILLIAMS, HEZRON
• Assistant Examiner(s): Eyassu, Marrit
• Application Number:
  US13/742,244
• Publication Number:
  US 20130192349A1
• Time in Patent Office: 1,428 Days
• Field of Search: 73/544.1, 73/617.9
• US Class Current: 1/1
• CPC Class Codes: G01N 11/16 by measuring damping effect upon oscillatory body
• CPC Class Codes: G01N 2291/02466 Biological material, e.g. blood
• CPC Class Codes: G01N 2291/02818 Density, viscosity
• CPC Class Codes: G01N 29/02 Analysing fluids using acoustic emission techniques G01N29/14 ; constructional or flow details for analysing fluids G01N29/222; optoacoustic fluid cells G01N29/2425
• CPC Class Codes: G01N 29/022 Fluid sensors based on microsensors, e.g. quartz crystal-microbalance [QCM], surface acoustic wave [SAW] devices, tuning forks, cantilevers, flexural plate wave [FPW] devices microdevices per se B81B
• CPC Class Codes: G01N 29/036 by measuring frequency or resonance of acoustic waves
• CPC Class Codes: G01N 33/48707 by electrical means G01N33/49, G01N33/493 take precedence
• CPC Class Codes: G01N 33/4905 Determining clotting time of blood by chemical methods G01N33/86, C12Q1/54

Abstract

Disclosed herein are devices for measuring, at one or more time points, one or more properties or changes in properties of a fluid sample. The devices may comprise a chamber defining an internal volume of the device suitable for receiving and retaining the fluid sample; a plurality of layers, the plurality comprising at least a first layer below the chamber, at least a second layer above the chamber, and a substrate layer between the first and second layers, wherein: the substrate layer is linked to at least one suspended element located within the chamber; the suspended element is linked to the substrate layer by at least two compliant structures located within the chamber; and the suspended element is configured to oscillate upon application of an actuating signal to at least one electrically conductive path, which runs across at least two of the compliant structures and the suspended element. Related methods and uses are also disclosed.

Claims

1. A device for measuring, at one or more time points, one or more properties or changes in properties of a fluid sample, the device comprising:

a chamber defining an internal volume of the device suitable for receiving and retaining the fluid sample;

a plurality of layers, the plurality comprising at least a first layer below the chamber, at least a second layer above the chamber, and a substrate layer between the first and second layers, wherein;

the substrate layer is linked to at least one suspended element located within the chamber;

the suspended element is comprised of an insulating material and at least one continuous patterned conductive layer providing at least one electrically conductive path which runs fully across the suspended element, said suspended element having a total metal content less than 50% by weight;

the suspended element is linked to the substrate layer by at least two compliant structures located within the chamber;

the suspended element and said at least two compliant structures are formed as part of the substrate layer;

and the suspended element is configured to oscillate upon application of an actuating signal to at least one said electrically conductive path, which runs fully across at least two of the said compliant structures and the suspended element, wherein the said actuating signal runs through only the said at least one continuous patterned conductive layer.

2. The device of claim 1, wherein the actuating signal runs fully across at least two of the compliant structures and the suspended element;

the suspended element and the at least two of the compliant structures are configured to have at least a first oscillation frequency and a second oscillation frequency;

oscillation at the first oscillation frequency induces a first acoustic field in the fluid sample with a first shear penetration depth smaller than a threshold value, wherein the threshold value ranges from 5 microns to 10 microns;

oscillation at the second oscillation frequency induces a second acoustic field in the fluid sample with a second shear penetration depth greater than the threshold value.

3. The device of claim 1, further comprising at least one magnetic field source configured to provide a magnetic field with field lines intersecting the suspended element and/or at least two of the compliant structures, such that the suspended element will oscillate when an electrical current flows through the electrically conductive path and at least one of the magnetic field and electrical current are time-varying.

4. The device of claim 1, further comprising at least one magnetic field source configured to provide a magnetic field with field lines intersecting the suspended element and/or at least two of the compliant structures, such that an oscillation of the suspended element induces a current or voltage across the electrically conductive path.

5. The device of claim 1, further comprising an actuator configured to cause the suspended element to oscillate by application of one or more excitation fields chosen from (i) piezoelectricity-based mechanical, (ii) capacitive, (iii) electromagnetic, and (iv) thermal excitation fields, wherein oscillation of the suspended element generates one or more signals chosen from (i) piezoelectricity-based electrical, (ii) capacitive, (iii) electromagnetic, (iv) thermal, and (v) optical detection signals.

6. The device of claim 1, wherein the device comprises at least two independent electrically conductive paths which run across a suspended element, such that one of the electrically conductive paths can be used to cause an oscillation of a suspended element and another of the electrically conductive paths can be used for detection of a current or voltage.

7. The device of claim 1, wherein the suspended element is separated from the layer below the chamber and/or the layer above the chamber by an adjustable distance.

8. The device of claim 1, wherein at least one of the substrate layer, the layer above the chamber, or the layer below the chamber comprise at least one electrically conductive path chosen from:

(i) an electrically conductive path including a heating element,

(ii) an electrically conductive path configured to perform electrochemical analysis,

(iii) an electrically conductive path configured to detect the presence of an analyte,

(iv) an electrically conductive path configured to detect the presence of he fluid in the chamber, and/or

(v) an electrically conductive path including a temperature sensing element.

9. The device of claim 1, wherein the device comprises at least one active agent chosen from:

(i) at least one clotting agent in an amount effective to induce clotting of a blood sample upon placement of the blood sample in the chamber and exposure of the blood sample to the clotting agent;

(ii) at least one anticoagulant;

(iii) at least one coagulation factor;

or

(iv) at least one agent that alters fluid viscosity in an amount sufficient to alter viscosity by at least 0.001 cP.

10. A method of measuring one or more properties or changes in properties of a fluid sample using a device according to claim 1, the method comprising:

placing the fluid sample in the chamber of the device;

oscillating at least one suspended element of the device, wherein the oscillation causes a current or voltage in at least one of the electrically conductive paths of the device;

measuring the current or voltage at one or more times; and

using one or more of the measurements of the current or voltage to calculate the one or more properties or changes in properties of the fluid sample.

11. The method of claim 10, wherein:

(i) at least one oscillation characteristic chosen from amplitude, a change in oscillation frequency, and quality factor is measured and used in the determination of one or more properties of the fluid sample, or

(ii) oscillation characteristics are measured at two or more of;

(a) a time point prior to a reaction in the fluid sample,

(b) a time point during the reaction in the fluid sample, and

(c) a time point after the reaction in the fluid sample, wherein the reaction changes one or more of the properties of the fluid sample being measured.

12. The method of claim 10, wherein the method comprises in-plane and out-of-plane oscillating steps and at least two properties of the fluid sample chosen from continuous phase viscosity, bulk viscosity, viscoelasticity, density, and concentration of an analyte in the fluid sample are determined.

13. The method of claim 10, wherein the fluid sample is a blood sample and at least one of blood clotting time, plasma viscosity, whole blood viscosity, blood viscoelasticity, blood density, and hematocrit is determined.

14. The device of claim 1, wherein the continuous patterned conductive layer is unitary.

15. A device for measuring, at one or more time points, one or more properties or changes in properties of a fluid sample, the device comprising:

a chamber defining an internal volume of the device suitable for receiving and retaining the fluid sample;

a plurality of layers, the plurality comprising at least a first layer below the chamber, at least a second layer above the chamber, and a substrate layer between the first and second layers, wherein;

the substrate layer is linked to at least one suspended element located within the chamber;

the suspended element is comprised of an insulating material and at least one continuous patterned conductive layer providing at least one electrically conductive path consisting of only the said at least one continuous patterned conductive layer and which runs fully across the suspended element, said suspended element having a total metal content less than 50% by weight;

the suspended element is linked to the substrate layer by at least two compliant structures located within the chamber;

the suspended element and said at least two compliant structures are formed as part of the substrate layer;

and the suspended element is configured to oscillate upon application of an actuating signal to at least one said electrically conductive path, which runs fully across at least two of the said compliant structures and the suspended element.

16. The device of claim 15, wherein the continuous patterned conductive layer is unitary.

17. A device for measuring, at one or more time points, one or more properties or changes in properties of a fluid sample, the device comprising:

a chamber defining an internal volume of the device suitable for receiving and retaining the fluid sample;

a plurality of layers, the plurality comprising at least a first layer below the chamber, at least a second layer above the chamber, and a substrate layer between the first and second layers, wherein;

the substrate layer is linked to at least one suspended element located within the chamber;

the suspended element is comprised of an insulating material and at least one continuous patterned conductive layer providing at least one electrically conductive path which runs fully across the suspended element, said suspended element having a total metal content less than 50% by weight;

the suspended element is linked to the substrate layer by at least two compliant structures located within the chamber;

the suspended element and said at least two compliant structures are formed as part of the substrate layer;

and the suspended element is configured to oscillate upon application of an actuating signal to at least one said electrically conductive path, which runs fully across at least two of the said compliant structures and the suspended element, wherein the said actuating signal does not energize an additional transducing element.

18. The device of claim 17, wherein the continuous patterned conductive layer is unitary.

19. The device of claim 17, wherein the additional transducing element is piezoelectric.

20. A device for measuring, at one or more time points, one or more properties or changes in properties of a fluid sample, the device comprising:

a chamber defining an internal volume of the device suitable for receiving and retaining the fluid sample;

a plurality of layers, the plurality comprising at least a first layer below the chamber, at least a second layer above the chamber, and a substrate layer between the first and second layers, wherein;

the substrate layer is linked to at least one suspended element located within the chamber;

the suspended element is comprised of an insulating material and at least one continuous patterned conductive layer providing at least one electrically conductive path that does not include an additional transducing element and which runs fully across the suspended element, said suspended element having a total metal content less than 50% by weight;

the suspended element is linked to the substrate layer by at least two compliant structures located within the chamber;

the suspended element and said at least two compliant structures are formed as part of the substrate layer;

and the suspended element is configured to oscillate upon application of an actuating signal to at least one said electrically conductive path, which runs fully across at least two of the said compliant structures and the suspended element.

21. The device of claim 20, wherein the continuous patterned conductive layer is unitary.

22. The device of claim 20, wherein the additional transducing element is piezoelectric.

23. A device for measuring, at one or more time points, one or more properties or changes in properties of a fluid sample, the device comprising:

a chamber defining an internal volume of the device suitable for receiving and retaining the fluid sample;

a plurality of layers, the plurality comprising at least a first layer below the chamber, at least a second layer above the chamber, and a substrate layer between the first and second layers, wherein;

the substrate layer is linked to at least one suspended element located within the chamber;

the suspended element consisting essentially of at least one insulating material and at least one continuous patterned conductive layer providing at least one electrically conductive path which runs fully across the suspended element, said suspended element having a total metal content less than 50% by weight;

the suspended element is linked to the substrate layer by at least two compliant structures located within the chamber;

the suspended element and said at least two compliant structures are formed as part of the substrate layer;

the suspended element is configured to oscillate upon application of an actuating signal to at least one said electrically conductive path, which runs fully across at least two of the said compliant structures and the suspended element; and

wherein the device comprises at least two independent electrically conductive paths which run across a suspended element, such that one of the electrically conductive paths can be used to cause an oscillation of a suspended element and another of the electrically conductive paths can be used for detection of a current or voltage.

24. The device of claim 23, wherein the continuous patterned conductive layer is unitary.