Apparatus and method for measuring binding kinetics with a resonating sensor

Abstract

Apparatus and method for detecting a presence of a subject material in a fluid sample using at least one 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, which produces a sensor output signal representing a resonance characteristic of the resonating sensor. Optionally, a reference resonator is used that produces a reference output signal. The reference resonator lacks binding sites for the analyte. Introduction of a fluid sample to the resonating sensor is automatically detected based on detection of a characteristic change in the sensor output signal or a reference output signal, or both. In response to the detecting of the introduction of the fluid sample, automated measurement of the binding kinetics of the analyte material to the resonating sensor are measured.

1 - 25 . (canceled) 
     
     
         26 . An apparatus for measuring binding kinetics of an interaction of an analyte material present in a fluid sample, comprising:
 a sensing resonator comprising binding sites for the analyte material;   actuation circuitry configured to drive the sensing resonator into an oscillating motion;   measurement circuitry arranged to be coupled to the sensing resonator and configured to measure one or more resonator output signals representing resonance characteristics of the oscillating motion of the sensing resonator;   a controller operatively coupled with the actuation and measurement circuitry, the controller being interfaced with data storage containing instructions that, when executed, cause the controller to:
 adjust the frequency at which the actuation circuitry drives the sensing resonator to maintain a resonance point of the sensing resonator. 
   
     
     
         27 . The apparatus of  claim 26 , wherein the frequency at which the actuation circuitry drives the sensing resonator is a frequency of maximum group delay. 
     
     
         28 . The apparatus of  claim 26 , wherein the data storage containing the instructions that, when executed, cause the controller to:
 process data from the measurement circuitry to determine the frequency at which the actuation circuitry drives the sensing resonator.   
     
     
         29 . The apparatus of  claim 28 , wherein the data storage containing the instructions that, when executed, cause the controller to:
 process data from the measurement circuitry to determine a frequency of maximum group delay and wherein the frequency at which the actuation circuitry drives the sensing resonator is the frequency of maximum group delay.   
     
     
         30 . The apparatus of  claim 26 , further comprising a reference resonator free of binding sites for the analyte material, wherein the reference resonator is operably coupled to the actuation circuitry and the measurement circuitry. 
     
     
         31 . The apparatus of  claim 30 , wherein the actuation circuitry is configured to independently drive the reference resonator and the sensing resonator into oscillating motion. 
     
     
         32 . The apparatus of  claim 26 , wherein the sensing resonator is a bulk acoustic wave resonator having a resonant frequency in the range of several hundred megahertz to several gigahertz. 
     
     
         33 . A method carried out by an apparatus for measuring binding kinetics of an interaction of an analyte material present in a fluid sample, the method comprising:
 contacting a sensing resonator with the fluid sample, wherein the sensing resonator comprises binding sites for the analyte material;   actuating the sensing resonator into an oscillating motion;   measuring one or more resonator output signals representing resonance characteristics of the oscillating motion of the sensing resonator; and   adjusting the actuation frequency of the sensing resonator to maintain a resonance point of the sensing resonator.   
     
     
         34 . The method of  claim 33 , wherein adjusting the actuation frequency of the sensing resonator to maintain a resonance point of the sensing resonator comprises adjusting the frequency to a frequency of maximum group delay. 
     
     
         35 . The method of  claim 33 , wherein the frequency at which the sensing resonator is actuated is based on data obtained from measuring the one or more resonator output signals. 
     
     
         36 . The method of  claim 35 , further comprising determining a frequency of maximum group delay based on data obtained from measuring the one or more resonator output signals, and wherein adjusting the actuation frequency of the sensing resonator to maintain a resonance point of the sensing resonator comprises adjusting the frequency to a frequency of maximum group delay. 
     
     
         37 . The method of  claim 33 , further comprising:
 contacting a reference resonator with the fluid sample, wherein the reference resonator is free of binding sites for the analyte material   actuating the reference resonator into an oscillating motion;   measuring one or more resonator output signals representing resonance characteristics of the oscillating motion of the reference resonator; and   adjusting the actuation frequency of the reference resonator to maintain a resonance point of the reference resonator.   
     
     
         38 . The method of  claim 37 , further comprising comparing the one or more resonator output signals representing resonance characteristics of the oscillating motion of the sensing resonator to the one or more resonator output signals representing resonance characteristics of the oscillating motion of the reference resonator. 
     
     
         39 . The method of  claim 33 , wherein the sensing resonator is a bulk acoustic wave resonator having a resonant frequency in the range of several hundred megahertz to several gigahertz.