Biosensor

• US 9,034,264 B2
• Filed: 08/22/2014
• Issued: 05/19/2015
• Est. Priority Date: 12/28/2006
• Status: Active Grant

• Current Assignee: Highland Biosciences Limited
• Original Assignee: Highland Biosciences Limited
• Inventors: Day, Richard
• Primary Examiner(s): WHITE, DENNIS MICHAEL
• Application Number:
  US14/466,446
• Publication Number:
  US 20150000397A1
• Time in Patent Office: 270 Days
• Field of Search: 73 6441- 6442, 422/430, 422/68.1, 422/73, 422/82.01, 436/66, 436 69- 70, 435/13, 435/283.1, 435/287.1
• US Class Current: 422/82.01
• CPC Class Codes: G01N 11/16 by measuring damping effect upon oscillatory body
• CPC Class Codes: G01N 2291/014 Resonance or resonant frequency
• CPC Class Codes: G01N 2291/022 Liquids
• CPC Class Codes: G01N 2291/0255 (Bio)chemical reactions, e.g. on biosensors
• CPC Class Codes: G01N 2291/02818 Density, viscosity
• CPC Class Codes: G01N 2291/0427 Flexural waves, plate waves, e.g. Lamb waves, tuning fork, cantilever
• CPC Class Codes: G01N 2291/101 one transducer
• 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 29/222 Constructional or flow details for analysing fluids optoacoustic fluid cells G01N29/2425
• CPC Class Codes: G01N 29/245 Ceramic probes, e.g. lead zirconate titanate [PZT] probes
• CPC Class Codes: G01N 29/4427 with stored values, e.g. threshold values
• 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 33/4905 Determining clotting time of blood by chemical methods G01N33/86, C12Q1/54
• CPC Class Codes: G01N 9/002 using variation of the resonant frequency of an element vibrating in contact with the material submitted to analysis G01N9/34 takes precedence

Abstract

The present application provides apparatus and methods for determining the density of a fluid sample. In particular, it provides a sensor device which can be loaded with a fluid sample such as blood, and which further comprises at least one oscillating beam member or resonator. Exposure of the blood sample to clotting agents allows a clotting reaction to commence. The device allows the density of the sample fluid to be monitored with reference to the oscillation of the vibrating beam member, thus allowing the monitoring of the clotting of the fluid sample.

Claims

1. A resonant sensor assembly for monitoring density and/or viscosity of a fluid comprising:

a base substrate of fixed width and length;

at least three parallel resonating beam members patterned in and integral to the base substrate, wherein the at least three beam members comprise a central beam member and at least two outer beam members, and wherein a width of the central beam member is twice the width of the at least two outer beam members such that a third mode of oscillation of the at least three beam members is optimally excitable;

at least one vibration excitory element for use in providing a selective oscillation of at least one of the three beam members, wherein the at least one vibration excitory element is configured to cause at least one of the beam members to resonate in a transverse direction; and

at least one sensor element for use in determining a frequency of oscillation of at least one of the at least three beam members, whereby density and/or viscosity of a fluid can be monitored by monitoring oscillations of at least one beam member.

2. The resonant sensor assembly according to claim 1, wherein the base substrate further comprising one or two side beams patterned in and integral to the base substrate parallel and spaced from the resonating beam members.

3. The resonant beam assembly according to claim 1, wherein the at least one vibratory excitory element and the at least one sensor element are positioned on the central beam at the ends of the resonant modes.

4. The resonant beam assembly according to claim 1, wherein the at least one vibration excitory element and/or the at least one sensor element comprise thick film screen printed PZT.

5. The resonant beam assembly according to claim 4, wherein the at least one vibration excitory element and the at least one sensor element are insulated by a waterproof coating.

6. The resonant beam assembly according to claim 1 further comprising conductive tracks for connecting the at least one vibratory excitation element and/or at least one sensor element to an external control unit, wherein the tracks are insulated by a waterproof coating.

7. The resonant beam assembly according to claim 5 further comprising conductive tracks for connecting the at least one vibratory excitation element and/or sensor element to an external control unit, wherein the tracks are insulated by a waterproof coating.

8. The resonant beam assembly according to claim 4, wherein the resonant beam members are stainless steel.

9. The resonant beam assembly according to claim 5, wherein the resonant beam members are stainless steel.

10. The resonant beam assembly according to claim 1, wherein the base substrate is rectangular.

11. The resonant beam assembly according to claim 10, wherein the at least 3 beam members are orthogonal to the length of the base substrate.

12. The resonant beam assembly according to claim 1, wherein data obtained in relation to at least one parameter derived from the resonance of at least one resonating beam is communicated to an analysis apparatus which is located remotely from the resonant beam assembly to monitor density and/or viscosity of the fluid.

13. A sensor device comprising:

a resonant beam assembly including;

a base substrate of fixed width and length;

at least three parallel resonating beam members patterned in and integral to the base substrate, wherein the at least three beam members comprise a central beam member and at least two outer beam members, and wherein a width of the central beam member is twice the width of the at least two outer beam members such that a third mode of oscillation of the at least three beam members is optimally excitable;

at least one vibration excitory element for use in providing a selective oscillation of at least one of the three beam members, wherein the at least one vibration excitory element is configured to cause at least one of the beam members to resonate in a transverse direction; and

at least one sensor element for use in determining the frequency of oscillation of at least one of the at least three beam members, whereby density and/or viscosity of a fluid can be monitored by monitoring oscillations of at least one beam member; and

a reaction chamber.

14. The sensor device according to claim 13, wherein the reaction chamber has a volume less than about 100 ml.

15. A method using a resonant beam assembly for monitoring density and/or viscosity of a fluid sample, the method comprising:

using the resonant sensor assembly including;

a base substrate of fixed width and length; and

at least three parallel resonating beam members patterned in and integral to the base substrate, wherein the at least three beam members comprise a central beam member and at least two outer beam members, and wherein a width of the central beam member is twice the width of the at least two outer beam members such that a third mode of oscillation of the at least three beam members is optimally excitable;

providing a selective oscillation of at least one of three beam members via at least one vibration excitory element, wherein the at least one vibration excitory element is configured to cause at least one of the beam members to resonate in a transverse direction; and

determining a frequency of oscillation of at least one of the at least three beam members via at least one sensor element, whereby density and/or viscosity of a fluid can be monitored by monitoring oscillations of at least one beam member.

16. A method for monitoring density and/or viscosity of a fluid sample before and/or during and/or after a chemical reaction, the method comprising:

providing a sensor device comprising;

a plurality of layers, wherein one of the layers comprises a base substrate layer, and

at least three parallel resonating beam members which are fixed to the base substrate layer at each end of their length at a fixed position, wherein the at the three beam members comprise a central beam member and at least two outer beam members, wherein a width of the central beam member is twice a width of the at least two outer beam members;

providing, by at least one vibration excitory element, a selective oscillation of at least one of the at least three beam members, whereby a third mode of oscillation of the at least three beam members is optimally excitable;

determining, by at least one sensor element, the frequency of oscillation of at least one of the at least three beam members; and

receiving and retaining the fluid sample in a reaction chamber, wherein the reaction chamber accommodates the at least three beam members in a manner which allows the unimpeded oscillation of the at least three beam members whereby the density and/or viscosity of the fluid sample within the reaction chamber can be monitored by monitoring oscillations of at least one beam member within the reaction chamber.