Measurement of binding kinetics with a resonating sensor

• US 8,409,875 B2
• Filed: 10/20/2011
• Issued: 04/02/2013
• Est. Priority Date: 10/20/2010
• Status: Active Grant

• Current Assignee: Zomedica Biotechnologies LLC
• Original Assignee: Rapid Diagnostek, Inc. (Qorvo, Inc.)
• Inventors: Johal, Gaganbir Singh, Harmon, Ian Robert, Van Deusen, Richard Allen
• Primary Examiner(s): Yang, N. C.
• Application Number:
  US13/278,032
• Publication Number:
  US 20120100636A1
• Time in Patent Office: 530 Days
• Field of Search: None
• US Class Current: 436/501
• CPC Class Codes: G01N 2291/0255 (Bio)chemical reactions, e.g. on biosensors
• CPC Class Codes: G01N 2291/0256 Adsorption, desorption, surface mass change, e.g. on biosensors
• CPC Class Codes: G01N 2291/0426 Bulk waves, e.g. quartz crystal microbalance, torsional waves
• CPC Class Codes: G01N 24/00 Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects
• 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 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/557 using kinetic measurement, i.e. time rate of progress of an antigen-antibody interaction

Abstract

A subject material in a fluid sample is detected using a resonating sensor immersible in the fluid sample. Binding kinetics of an interaction of an analyte material present in the fluid sample are measured with the resonating sensor, which has binding sites for the analyte material. Prior to exposing the resonating sensor to the fluid sample, operation of the resonating sensor is initiated, producing a sensor output signal representing a resonance characteristic of the resonating sensor. Optionally, a reference resonator that lacks binding sites for the analyte is used to produce a reference output signal. Introduction of a fluid sample to the resonating sensor is automatically detected based on a characteristic change in the sensor output signal or a reference output signal. In response to the detecting of the introduction of the fluid sample, automated measurement of the binding kinetics are measured.

Claims

1. Apparatus for measuring binding kinetics of an interaction of an analyte material present in a fluid sample comprising:

a resonator interface adapted to be operatively coupled with one or more resonating devices, at least one of which is a sensing resonator having binding sites for the analyte material, wherein the one or more resonating devices are adapted to be driven into an oscillating motion by actuation circuitry;

measurement circuitry arranged to be coupled to the one or more resonating devices via the resonator interface, and wherein the measurement circuitry is configured to measure one or more resonator output signals representing a resonance characteristic of the oscillating motion of the one or more resonating devices; and

a controller operatively coupled with the actuation and measurement circuitry, the controller being interfaced with data storage containing instructions executable by the controller that, when executed, cause the controller to;

detect introduction of the fluid sample into contact with the one or more resonating devices based on detection, via the measurement circuitry, of a characteristic change in the one or more resonator output signals caused by the introduction of the fluid sample; and

in response to the detection of the introduction of the fluid sample, initiate measurement, via the measurement circuitry, of the binding kinetics of the analyte material to the at least one sensing resonator;

wherein the characteristic change in the one or more resonator output signals caused by the introduction of the fluid sample causes a change to a new resonance point in the oscillating motion of the one or more resonating devices, and wherein the one or more resonating devices are driven at the new resonance point in response to the characteristic change in the one or more resonator output signals.

2. The apparatus of claim 1, wherein each of the one or more resonating devices is a bulk acoustic wave device having a resonant frequency in the range of several hundred megahertz to several gigahertz.

3. The apparatus of claim 1, wherein the resonator interface is further adapted to be operatively coupled with a reference resonator that lacks any binding sites for the analyte material, and wherein the reference resonator is adapted to be driven by the actuation circuitry having provisions for driving the at least one sensing resonator and the at least one reference resonator at different resonant frequencies.

4. The apparatus of claim 1, wherein the controller is further configured to monitor the one or more resonator output signals from a time reference based on the time of occurrence of the characteristic change in the one or more resonator output signals.

5. The apparatus of claim 1, wherein the controller is further configured to detect a step change in a resonant characteristic of the one or more resonating devices selected from the group consisting of:

a frequency, a phase angle, or any combination thereof.

6. The apparatus of claim 1, wherein the controller is further configured to initiate measurement of the binding kinetics of the analyte material by initiating measurement of a rate of change of the one or more resonator output signals within one second of the detecting of the introduction of the fluid sample.

7. The apparatus of claim 1, wherein the controller is further configured to initiate measurement of the binding kinetics of the analyte material by initiating measurement of a rate of change of the one or more resonator output signals within 0.1 second of the detecting of the introduction of the fluid sample.

8. The apparatus of claim 1, wherein the controller is further configured to initiate measurement of the binding kinetics of the analyte material by initiating measurement of a total amount of change of the one or more resonator output signals time-referenced from the detection of the characteristic change in the one or more resonator output signals.

9. The apparatus of claim 1, wherein the controller is further configured to determine a measure of concentration of the analyte in the fluid sample based on the binding kinetics.

10. The apparatus of claim 1, wherein the controller is further configured to detect introduction of the fluid sample into contact with the one or more resonating devices by comparing a degree of the characteristic change in the one or more resonator output signals against a threshold value or target range of values such that false detections are suppressed.

12. The apparatus of claim 1, wherein the actuation circuitry is part of the resonator interface.

13. The apparatus of claim 1, wherein the actuation circuitry is configured to drive the one or more resonating devices at the new resonance point in response to the characteristic change in the one or more resonator output signals prior to the initiation of the measurement.

14. The apparatus of claim 1, wherein the instructions executable by the controller, when executed, further cause the controller to cause the actuation circuitry is to drive the one or more resonating devices at the new resonance point.

11. A system for measuring binding kinetics of an interaction of an analyte material present in a fluid sample with one or more resonating devices, at least one of which is a sensing resonator having binding sites for the analyte material, the system comprising:

means for initiating operation of the one or more resonating devices that produces one or more resonator output signals representing a resonance characteristic of each of the one or more of the resonating sensors;

means for automatically detecting introduction of a fluid sample to the one or more resonating devices based on detection of a characteristic change in the one or more resonator output signals caused by the introduction of the fluid sample; and

means for initiating automated measurement of the binding kinetics of the analyte material to the at least one resonating sensor having the binding sites in response to the detecting of the introduction of the fluid sample;

wherein the characteristic change in the one or more resonator output signals caused by the introduction of the fluid sample causes a change to a new resonance point in the oscillating motion of the one or more resonating devices and wherein the one or more resonating devices are driven at the new resonance point in response to the characteristic change in the one or more resonator output signals.