Blood Based Biomarker Detection Using FET Biosensor: Towards Self-Health Management
Authors: Sarangadharan Indu , Hsu Chen-Pin , Chu Chia-Ho , Regmi Abiral , Chen Yen Wen , Wang Yu-Lin 
Published: February 2020

Diseases that are the leading causes of mortality worldwide such as cardiovascular diseases (CVD), cancer and infectious diseases can be better managed and cured with early and prompt diagnosis and prognosis. Molecular biomarkers in whole blood (blood serum proteins) have predictive, diagnostic and prognostic capacity and semiconductor based electronic biosensors can be used to deliver reliable and affordable point-of-care disease monitoring. GaN High Electron Mobility Transistor (HEMT) based sensors have previously been used in a variety of applications such as ion, gas and biomolecule sensing. However, the limitations of FET biosensors set by the charge screening effect in high ionic strength solutions required additional sample processing steps, making them practically unusable in terms of point-of-care testing. With a novel biosensing technique enabling direct detection of target proteins in high salt concentration medium using GaN HEMT and innovative biosensor packaging methodology, a portable biosensor system has been designed and fabricated which can provide quantitative blood biomarker analysis in 5 minutes with less than 5 µl sample. Antibody or aptamer functionalized reference gate electrode and transistor channel form an electrical double layer (EDL) FET structure that can detect binding of target proteins with very high sensitivity. The sensing and packaging techniques have been specifically optimized to meet the requirements and convenience of a mobile diagnostic system that can be used by anyone, at all times.

HEMT chip is fabricated in a 4-5 mask process: mesa isolation, ohmic metal deposition and annealing, interconnect metal deposition and device passivation. A simple and robust two step epoxy based planar HEMT chip packaging allows for easy integration with commercially available reader sockets, much like the micro-SD card. A single step surface functionalization strategy is followed for immobilizing receptors which allows for high sensitivity with a wide dynamic range of detection. Pulsed gate voltage modulates the channel conductivity which behaves as a function of the charge distribution within the EDL structure. Thus, without complex sample pre-treatments and extremely low sampling requirements, quantitative detection of protein biomarkers can be achieved.

The structural design of EDL FET brings the potential to investigate the binding events that were previously undetectable in traditional FET based biosensors. Results from testing purified proteins and clinical serum samples elucidate the potential of the sensing technique to overcome the charge screening effect and offer sensing beyond Debye length in physiological salt environment, with high sensitivity and ultra-low detection limit. This diagnostic technique can be applied to all types of FET based sensors that uses immunological reactions to detect the target. Owing to standard semiconductor fabrication processes and minimal or no sampling requirements, the portable sensing system can be affordable and accessible to all. Enabled with cloud management, this diagnostic system houses the potential to be a pioneering IoT biosensor.

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