Resonant acoustic profiling for biological detection and diagnostics

Abstract

We have employed bulk acoustic wave and surface acoustic wave devices for the sensitive and specific detection of biological agents in complex liquid media. We have produced a robotic liquid delivery system coupled to a multi-layer microfluidic manifold that delivers liquids in a controlled manner to pairs of resonant acoustic sensors in a dasiaUSBpsila type docking station. These resonators were fabricated on a single wafer of piezoelectric material, and a rapid switching process between active areas employed to eliminate cross talk and interference. System performance was enhanced using a proprietary FPGA-based network analyzer with internal digital synthesizer, RF switches and calibration elements. Before the signal was sent to the sensor interface, the impedance of the signal path was transferred to match the sensor interface impedance. The sensors are coated with proprietary planar surface chemistries and polymeric interfaces optimised for biological compatibility, shear modulus and penetration depth to maximise acoustic coupling of a binding signal to the sensor. An optimised elastomeric mounting was developed to minimise the impact of thermal and motional stress on the piezoelectric material, whilst simultaneously providing a sub-microlitre microfluidic dead volume above the sensor. Herein we demonstrate the utility of the system using analytes at each end of the molecular weight range: small molecular weight drug candidates binding to a protein receptor and high molecular weight bacteria binding to an antibody.