Abstract
This research discusses the design, fabrication and characterization of electrical double layer gated, high field modulated AlGaN/GaN high electron mobility transistor (HEMT) based biosensor for cellular and sub-cellular diagnostics. GaN HEMT chips are assembled into a sensor array on a thermo-curable polymer substrate in a simple and robust packaging process. The biosensor array is used to capture, detect and count cells such as circulating tumor cells (CTCs) and cancer stem cells (CSCs). The sensor array is highly sensitive with up to single cell resolution. The present method can detect cells in their native electrolyte composition, in a very short time (5 mins) with extremely low cost compared to the conventional whole cell assays. The effect of cellular binding in different test environments is studied and reported. GaN HEMT biosensor can dynamically monitor bioelectric signals such as membrane potential of cancer cells which can be used to study ion channel gating. The enhanced sensitivity in high ionic strength solution is investigated and the physical interactions at the microenvironment of the cell and substrate interface is studied. It is demonstrated that using the high field modulated FET sensing mechanism we can detect biomolecules one order in magnitude beyond the Debye length in high ionic strength solution. A quantitative model is proposed for the characterization of FET based sensor. This sensor array has the potential to be used as a point of care diagnostic tool in various applications such as detection of rare cells, pathogens and studying the dynamics of cellular interactions. The sensing structure is re-designed to detect and enumerate extracellular vesicles (EVs), exosomes in particular, which are sub-cellular components used for cellular communication. CD-63 Antibody functionalized GaN HEMT sensor is used to enumerate EVs in high ionic strength solution, without requiring additional sample pre-treatments. The dynamic range of EV detection is 107-1010 EV/mL which is comparable with nanoparticle tracking analysis which is the existing gold standard. The surface markers on EV can be characterized using our HEMT biosensor based on the EV-secondary antibody binding induced change in sensor response. The sensor characteristics under external stimulation of EV is also studied and reported. This research focuses on developing a rapid EV quantification methodology which has diagnostic and prognostic potentials.