Apparatus and method for detecting small changes in attached mass of piezoelectric devices used as sensors

• US 4,905,701 A
• Filed: 06/15/1988
• Issued: 03/06/1990
• Est. Priority Date: 06/15/1988
• Status: Expired due to Fees

• Current Assignee: National Research Development Corporation
• Original Assignee: National Research Development Corporation
• Inventors: Cornelius, George
• Primary Examiner(s): JAWORSKI, FRANCIS J
• Application Number:
  US07/206,768
• Time in Patent Office: 629 Days
• Field of Search: 73/19, 73/24, 73/32 A, 73/53-54, 73/59, 128/631, 128/738, 128/632, 128/660.01, 374/117, 310/313 R, 310/313 B, 333/150-152, 324/71.1, 436/806, 422/68
• US Class Current: 600/437
• CPC Class Codes: G01N 2291/011 Velocity or travel time
• CPC Class Codes: G01N 2291/012 Phase angle
• CPC Class Codes: G01N 2291/014 Resonance or resonant frequency
• CPC Class Codes: G01N 2291/0256 Adsorption, desorption, surface mass change, e.g. on biosensors
• CPC Class Codes: G01N 2291/0422 Shear waves, transverse waves, horizontally polarised waves
• CPC Class Codes: G01N 2291/0423 Surface waves, e.g. Rayleigh waves, Love waves
• CPC Class Codes: G01N 2291/0426 Bulk waves, e.g. quartz crystal microbalance, torsional waves
• 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: Y10S 436/806 Electrical property or magnetic property

Abstract

In analysis, particularly for medical diagnostics, material can be selectively bound to the surface of a piezoelectric crystal by a reagent. The amount of material so bound affects the speed of propagation of an acoustic wave launched and received on the crystal surface by respective electrode pairs. Previously the crystal was used as a resonant element in an oscillator controlling the frequency of oscillation and so indicating the amount of bound material. However, the oscillator was either unstable or the range of bound masses too small to be of practical use. In the present invention delay between launch and reception of the acoustic wave provides a control signal for a voltage controlled oscillator. A much more stable system can therefore be constructed with a wide working range and high stability since the crystal is no longer the resonant element. Much greater sensitivity is also possible since the oscillator frequency may be greatly increased. A control signal representative of delay may be produced by a phase comparator comparing the phase of two input signals: one direct from the oscillator, and one from the reception of an acoustic wave on the crystal surface launched using a signal from the oscillator. The signal to the crystal may be modulated using a low frequency oscillator before it reaches the crystal to aid the oscillator in following frequency changes due to changing crystal surface conditions and the resulting signal may be summed with the output of a resonance oscillator before application to the crystal to aid the oscillator in initially settling to a stable frequency.

Claims

1. Apparatus for obtaining an indication of an amount of an analyte bound to a piezoelectric device, comprising

an electrical oscillator having a control terminal, the frequency of an output signal of the said oscillator being variable over a range in dependence upon the value of a control signal applied to the said control terminal,

a piezoelectric device carrying a reagent for selectively binding an analyte to a surface of the device,

launching and reception means coupled to the said device and to the said oscillator for use in launching acoustic waves at the output frequency of the said oscillator across the said device and for use in receiving acoustic waves propagating across the said device, and

measurement means, with input coupled to the said launching and reception means and output coupled to the said control terminal, for deriving a signal representative of the time required for an acoustic wave to travel across the said device between launch and reception by the said launch and reception means, whereby the output frequency of the said oscillator depends on the speed of propagation of acoustic waves across the said device and therefore on the amount of analyte bound to said surface.

2. Apparatus according to claim 1 wherein the launching and reception means comprises

means for making contact with first and second electrode means mounted on the said device in contact with the surface thereof, the first electrode means being for launching surface acoustic waves across the surface of the said device, and

second electrode means for receiving the said acoustic waves and deriving an electrical signal representative thereof.

3. Apparatus according to claim 2 wherein the measurement means comprises

phase-comparator means, having first and second inputs and an output, for generating an output signal having a value representative of any phase difference in signals applied to the first and second inputs, the first said input being coupled to the output of the said oscillator, the second input being coupled to the said second electrode means, and the said output being coupled to the said control terminal of the said oscillator.

4. Apparatus according to claim 3 wherein the said oscillator is a voltage-controlled oscillator, and the apparatus includes

a low-frequency square-wave electrical oscillator having a repetition frequency at least an order of magnitude below the lowest frequency of the said voltage-controlled oscillator when the apparatus is in operation, and

a modulator, having first and second inputs and an output, for generating an amplitude modulated signal at the said modulator output from signals applied at the first and second said modulator input terminals,

the said voltage-controlled oscillator being coupled to the said means for making contact with the said first electrode means through the said modulator by way of the first said input and the said output of the said modulator, and

the said second modulator input being coupled to the said low-frequency oscillator.

5. Apparatus according to claim 4 including means for introducing a 90°

phase shift between the output of the said voltage-controlled oscillator and the first said input of the said modulator.

6. Apparatus according to claim 3 wherein the said oscillator is a voltage-controlled oscillator, and the apparatus includes

a low-frequency rectangular-wave electrical oscillator having a repetition frequency at least an order of magnitude below the lowest frequency of the said voltage-controlled oscillator when the apparatus is in operation,

a reference oscillator having an output frequency within the said range of the voltage-controlled oscillator,

a modulator, having first and second inputs and an output, for generating an amplitude modulated signal at the said modulator output from signals applied at the first and second said modulator input terminals from the said low-frequency oscillator and the said reference oscillator, respectively,

summing means having first and second inputs and an output providing an output signal which is representative of the sum (taking account of sign) of the instantaneous magnitudes of signals applied at the said first and second summing means inputs,

the said voltage-controlled oscillator being coupled to the said means for making contact with the said first electrode means through the said summing means by way of the first said summing means input and the said output of the said summing means, and

the said modulator being connected to the said second summing means input.

7. Apparatus according to claim 1 wherein the said launching and reception means comprise

first and second interdigitated electrodes for launching acoustic waves on the surface of the device,

third and fourth interdigitated electrodes for receiving said acoustic waves,

a first connection used in coupling said first electrode to the said oscillator, the second electrode having no low conductivity connection to the said oscillator,

a second connection used in coupling the said third electrode to the said measurement means, and

a third connection used in coupling the said fourth electrode to a ground connection between the said oscillator and the said measurement means.

8. Apparatus for indicating the amount of material bound to the surface of a piezoelectric device, comprising

a piezoelectric device carrying a reagent for selectively binding an analyte to a surface of the device, the device having first and second electrocde means mounted on the surface thereof for launching and receiving, respectively, acoustic waves on the said surface,

first and second contact means for making electrical contact with the first and second electrode means, respectively,

a voltage-controlled oscillator having a control terminal, the frequency of the said oscillator being variable over a range in dependence on the magnitude of a d.c. control signal applied to the said control terminal,

phase-comparator means, having first and second inputs and an output, for generating a d.c. output signal of magnitude representaive of any phase difference in signals applied to the said first and second phase-comparator inputs, the first input being coupled to the said oscillator and the second input being coupled to the second contact means, and the said phase comparator output being coupled to the said control terminal.

9. Apparatus according to claim 8 including

first and second electrode means mounted on the piezoelectric device for launching and receiving, respectively, acoustic waves on the said surface.

10. Apparatus according to claim 9 including

a low-frequency electrical oscillator having an output frequency at least an order of magnitude below the lowest frequency of the said voltage controlled oscillator when the apparatus is in operation, and

a modulator, having first and second inputs and an output, for generating an amplitude modulated signal at the said modulator output from signals applied at the first and second said modulator input terminals,

the said voltage-controlled oscillator being coupled to the said first electrode means through the said modulator by way of the first said input and the said output of the said modulator, and

the said second modulator input being coupled to the said low-frequency oscillator.

11. Apparatus according to claim 9 including

a low-frequency rectangular-wave electrical oscillator having a repetition frequency at least an order of magnitude below the lowest frequency of the said voltage controlled oscillator when the apparatus is in operation,

a reference oscillator having an output frequency within the said range of the voltage-controlled oscillator,

a modulator, having first and second inputs and an output, for generating an amplitude modulated signal at the said modulator output from signals applied at the first and second said modulator input terminals from said low-frequency oscillator and the said reference oscillator, respectively,

summing means having first and second inputs and an output providing an output signal which is representative of the sum (taking account of sign) of the instantaneous magnitudes of signals applied at the said first and second summing means inputs,

the said voltage-controlled oscillator being coupled to the said first electrode means through the said summing means by way of the firsat said input summing means and the said output of the said summing means, and

the said modulator being connected to the said second summing means input.

12. A method of obtaining an indication of the amount of analyte bound to a piezoelectric device, comprising the steps of

applying a reagent to the device which selectively binds an analyte to said surface,

obtaining an output signal from an electrical oscillator having a frequency which is variable over a range in dependence upon the value of a control signal applied to the said oscillator,

using the said oscillator output signal to generate a launch signal to launch an acoustic wave across the device,

receiving the said acoustic wave,

deriving, from the said oscillator output and the received acoustic wave, a delay signal representative of the time required by an acoustic wave to travel across the said device between launch and reception, and

deriving the said control signal for the said oscillator from the said delay signal,

whereby the frequency of the said oscillator provides an indication of the said speed of propagation and therefore the amount of analyte bound to said surface.

13. A method as in claim 12 wherein the acoustic wave launched across the device is a surface wave.

14. A method according to claim 13 wherein deriving the said delay signal includes

deriving an electrical signal from the said received acoustic wave, and

deriving the said delay signal as representative of the relative phase of the said launch signal and the said electrical signal derived from the said received acoustic wave.

15. A method according to claim 14 including

using a rectangular-wave modulating signal, having a repetition frequency at least an order of magnitude below the frequency of the said oscillator output signal, to modulate the said oscillator output signal in deriving the said launch signal.

16. A method according to claim 15, including

summing the modulated oscillator output signal with the output signal of a reference oscillator having a frequency with the said range in deriving the said launch signal.

17. A method according to claim 12 of obtaining an indication of changes in amount of material bound to the said device including

observing changes in the frequency of oscillation of the said oscillator over an interval in which the said change in amount may occur.

18. A piezoelectric device carrying a reagent for selectively binding an analyte to the surface of the said device,

the said device having

first and second electrodes in close proximity for launching acoustic waves on the surface of the crystal,

third and fourth electrodes in close proximity but spaced from the said first and second electrodes for receiving acoustic waves on the said surface,

a first connection for use in coupling said first electrode to an oscillator, the second electrode having no low conductivity connection for coupling the said second electrode to the said oscillator,

a second connection for use in coupling the said third electrode to phase comparison means, and

a third connection for coupling the said fourth electrode to a ground connection between the said oscillator and the said measurement means.

19. A method according to claim 18 including

using a rectangular-wave modulating signal, having a repetition frequency at least an order of magnitude below the frequency of the said oscillator output signal, to modulate a reference signal having a frequency within the said range, and

summing the modulated reference signal with the said oscillator output signal in deriving the said launch signal.