Devices and method for performing blood coagulation assays by piezoelectric sensing

• US 6,200,532 B1
• Filed: 11/20/1998
• Issued: 03/13/2001
• Est. Priority Date: 11/20/1998
• Status: Expired due to Fees

• Current Assignee: TRINITY BIOTECH MANUFACTURING LIMITED AND TRINITY BIOTECH, PLC
• Original Assignee: Akzo Nobel N.V. (Nouryon BV)
• Inventors: Moreno, Mario, Wu, Jogin R.
• Primary Examiner(s): Redding, David A.
• Application Number:
  US09/197,481
• Time in Patent Office: 844 Days
• Field of Search: 436/69, 422/73, 73/644.1, 73/644.2, 73/644.3
• US Class Current: 422/73
• CPC Class Codes: G01N 2291/0256 Adsorption, desorption, surface mass change, e.g. on biosensors
• CPC Class Codes: G01N 29/036 by measuring frequency or resonance of acoustic waves
• CPC Class Codes: G01N 33/4905 Determining clotting time of blood by chemical methods G01N33/86, C12Q1/54

Abstract

A device and method for performing blood coagulation assays, particularly prothrombin times and activated partial thromboplastin times and other clotting parameters are disclosed. The device comprises a disposable strip (containing a sample inlet for sample delivery, a capillary channel for driving force, and a reaction chamber with an appropriate dry reagent for a specific assay) and a piezoelectric sensor. The device could also include a heating element for temperature control, and a magnetic bender. The magnetic bender is driven by an electromagnetic field generator and is attached onto a piezoelectric film in contact with the blood sample. Electric signal generated at the piezo film is characterized by its frequency and amplitude due to the movement of the attached metal film. The signal collected at the site of the piezo film represents the process of a biochemical reaction in the reaction chamber, while blood sample proceeds to the point at which clot formation starts and is amplified by an amplifier and rectified into a Dc voltage and is sent to a recording unit and/or display unit.

Claims

1. A device for measuring at least one blood coagulation parameter, comprising;

a housing;

a sample inlet for the addition of a blood sample to the device;

a reaction chamber within the housing for the flow or holding of sample within the device;

an electromagnetic wave generator proximate to said reaction chamber for passing electromagnetic waves through the sample in the reaction chamber; and

a piezoelectric device for monitoring changes to said electromagnetic waves after passing through said sample so as to detect a changing coagulation parameter of the blood sample.

2. The device of claim 1, further comprising a coagulation reagent for causing coagulation of said blood sample within said reaction chamber.

3. The device of claim 1, further comprising a filter for causing a separation of a first part of the blood sample from a second part of the blood sample.

4. The device of claim 3, wherein said filter comprises an asymmetric membrane.

5. The device of claim 4, wherein said filter further comprises a capillary channel for drawing the blood sample through said asymmetric membrane.

6. The device of claim 4, wherein said asymmetric membrane is a single layer membrane disposed in the proximity of said sample inlet.

7. The device of claim 6, wherein said asymmetric membrane has a thickness of from about 30 to 500 μ

m.

8. The device of claim 7, wherein said asymmetric membrane has a thickness of from about 50 to 200 μ

m.

9. The device of claim 4, wherein said asymmetric membrane comprises polysulfonate.

10. The device of claim 1, further comprising a heater for maintaining a predetermined temperature of the device when in use.

11. The device of claim 2, further comprising a control chamber.

12. The device of claim 11, wherein said reaction chamber comprises said coagulation reagent, and said control chamber does not.

13. The device of claim 12, wherein said reaction chamber and said control chamber have substantially the same geometry and dimensions.

14. The device of claim 12, further comprising an air reservoir in communication with both said reaction and control chambers.

15. The device of claim 1, wherein said reaction chamber comprises an elongated channel.

16. The device of claim 12, further comprising a first air reservoir in communication with said control chamber.

17. The device of claim 1, wherein said reaction and control chambers are in a concentric spiral formation.

18. The device of claim 17, wherein a piezoelectric device is within or adjacent each chamber, said piezoelectric devices detecting a distance of flow within each chamber.

19. The device of claim 18, further comprising a circuit for comparing signals from said reaction and control chambers.

20. The device of claim 1, further comprising a bender for vibrating within said reaction chamber, said piezoelectric device generating electric signal corresponding to the frequency and amplitude from the bender vibration after passing through the blood sample.

21. The device of claim 20, wherein a changing amplitude is detected at the piezoelectric device during clot formation.

22. The device of claim 20, wherein said bender is a magnetic bender and said electromagnetic wave generator is capable of causing said bender to vibrate.

23. The device of claim 22, wherein said electromagnetic wave generator comprises an AC excitation generator coil and an electromagnet.

24. The device of claim 22, wherein said piezoelectric device is attached at at least one end thereof to an internal wall of said reaction chamber, and said bender is attached to said piezoelectric device.

25. The device of claim 22, further comprising an electronic circuit connected to said piezoelectric device for signal amplification and/or filtering.

26. The device of claim 12, wherein said coagulation reagent is a PT or APTT reagent.

27. The device of claim 1, wherein the piezoelectric device comprises one or more of lead-zirconate-titanate, BaTiO₃, lead-magnesium-niobate, or polyvinylidene fluoride.

28. The device of claim 1, wherein said electromagnetic wave generator is an infrared light source, where piezoelectric signal is generated from energy transfer mechanism changes upon formation of a clot.

29. The device of claim 28, further comprising a focusing lens and mirror between said reaction chamber and said infrared light source.

30. The device of claim 28, wherein at least a part of a wall of said housing is substantially transparent for the passage of said infrared energy.

31. The device of claim 1, further comprising a reflective layer proximate to said piezoelectric device.

32. The device of claim 31, wherein said electromagnetic wave generator is a light source whereby part of the incident light for said light source is reflected by said reflective layer to a signal detector, whereby another part of said incident light reflects from said solid liquid boundary of the piezoelectric film and blood sample back to said signal detector to form two beams of light interfered coherently.

33. The device of claim 32, wherein variations of the piezoelectric device are translated into a change in the intensity of the interferometric modulated light.