Method for measuring binding kinetics with a resonating sensor

Abstract

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.

What is claimed is: 
     
         1 . A method 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 method comprising:
 prior to exposing the one or more resonating devices to the fluid sample, 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;   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;   in response to the detecting of the introduction of the fluid sample, initiating automated measurement of the binding kinetics of the analyte material to the at least one resonating sensor having the binding sites.   
     
     
         2 . The method of  claim 1 , wherein the automatically detecting of the introduction of the fluid sample to the one or more resonating devices includes detecting a change in viscosity of a fluid in physical contact with a surface of the one or more resonating devices. 
     
     
         3 . The method of  claim 1 , wherein initiating the automated measurement of the binding kinetics includes monitoring of 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. 
     
     
         4 . The method of  claim 1 , wherein the detection of the characteristic change in the one or more resonator output signals includes detection of 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. 
     
     
         5 . The method of  claim 1 , wherein initiating operation of the one or more resonating devices includes operating the one or more resonating devices in ambient air, and wherein the fluid sample is a liquid. 
     
     
         6 . The method of  claim 1 , wherein the fluid sample is an unrefined biological sample. 
     
     
         7 . The method of  claim 1 , wherein initiating automated measurement of the binding kinetics includes 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. 
     
     
         8 . The method of  claim 7 , wherein initiating automated measurement of the binding kinetics includes measuring 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. 
     
     
         9 . The method of  claim 7 , wherein initiating automated measurement of the binding kinetics includes measuring a rate of change of the one or more resonator output signals within 0.05 second of the detecting of the introduction of the fluid sample. 
     
     
         10 . The method of  claim 1 , wherein initiating automated measurement of the binding kinetics includes measuring 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. 
     
     
         11 . The method of  claim 1 , wherein the one or more resonating devices includes at least one reference resonator that lacks any binding sites for the analyte material, and wherein initiating measurement of the binding kinetics includes measuring a difference between at least one sensor output signal of the at least one sensing resonator and at least one reference output signal of the at least one reference resonator. 
     
     
         12 . The method of  claim 11 , further comprising operating each of the at least one sensing resonator and the at least one reference resonator at their corresponding resonant frequencies, which are potentially different from one another. 
     
     
         13 . The method of  claim 1 , further comprising:
 based on the binding kinetics, determining a measure of concentration of the analyte in the fluid sample.   
     
     
         14 . The method of  claim 1 , wherein automatically detecting introduction of a fluid sample to the one or more resonating devices includes 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.