A fast, scalable acoustic resonator-based biosensor array system for simultaneous detection of multiple biomarkers
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This thesis is about the design of a biosensor system for detection of multiple cancer biomarkers. Accurate diagnosis and prognosis of cancer requires early detection. Equally important, though, is the measurement of biomarker-velocity and detection of multiple biomarkers. Early detection requires highly sensitive biosensors capable of detection at very low concentrations of target molecules. Biomarker-velocity can be measured by monitoring concentration of target molecule over a period of time. This requires a system which is very easy to use, fast, flexible, inexpensive and portable, thus enabling its ubiquitous presence at the point of care. For detection of multiplexed biomarkers, biosensors which easily lend to array configuration are required. Conventional techniques do not fulfill either all or some aspects of the requirements listed above. In this work, we present the design of a biosensor system, keeping in view the desired features described above, to achieve the ultimate goal of enabling ubiquitous presence of biosensor at the point of care. We focus on acoustic transducer based biosensors. The two fundamental components of design in an acoustic biosensor are the design of an acoustic transducer and the design of a novel electrical interface for the transducer. For transducer design, we introduce and present the design of a single structure, GHz range, multi-mode acoustic resonator. We present this as a suitable transducer for liquid phase biosensors, which is the preferred medium for sensing of cancer biomarkers. We explore the underlying physics and do experimental and theoretical characterization of this device. The transducer needs to be functionalized with a chemically sensitive layer which performs the molecular recognition of cancer biomarkers. We present the experimental exploration of a reversible and oriented immobilization based Histidine-Ni(2+) interaction which used NTA as the chelator for anchoring onto the device. Then we discuss the microfluidic design to enable liquid phase operation. We used SU-8 polymer barriers for liquid containment and addressed the challenges of making it compatible with ZnO based devices. An electrical interface is needed to excite and extract the sensor response. We have presented here a novel method to measure and track a resonator's response and extract its characteristic parameters. This method measures the wideband frequency response of the resonator with a much simpler setup as compared to conventional methods. We have proposed and demonstrated the use of a white noise signal as a viable signal for broadband excitation of resonator-based sensing platforms. We have also established, shown through simulation and prototype measurements, the feasibility of the proposed method. The accuracy and speed of the system can be further greatly improved by FFT-based digital implementation of the spectral analysis system. We have presented an example hardware implementation of FFT-based signal analyzer, and have discussed the hardware resources required for actual implementation in a chip form. Lastly we discuss the measurement protocol and sensor results for head and neck cancer and prostate cancer biomarkers. These results demonstrate the usability of the proposed sensor system for detection of cancer biomarkers.