該研究討論了用於細胞和亞細胞診斷的電雙層門控，高場調製AlGaN / GaN高電子遷移率晶體管（HEMT）生物傳感器的設計，製造和表徵。 GaN HEMT芯片通過簡單而堅固的封裝工藝組裝到熱固性聚合物基板上的傳感器陣列中。生物傳感器陣列用於捕獲，檢測和計數細胞，例如循環腫瘤細胞（CTC）和癌症幹細胞（CSC）。傳感器陣列具有高達單細胞分辨率的高靈敏度。與常規全細胞測定相比，本方法可以在非常短的時間（5分鐘）內以極低的成本檢測其天然電解質組合物中的細胞。研究並報導了細胞結合在不同測試環境中的作用。 GaN HEMT生物傳感器可以動態監測生物電信號，例如癌細胞的膜電位，可用於研究離子通道門控。研究了高離子強度溶液中增強的靈敏度，並研究了細胞和基質界面微環境的物理相互作用。已經證明，使用高場調製FET傳感機制，我們可以在高離子強度溶液中檢測超過德拜長度一個數量級的生物分子。提出了一種用於表徵基於FET的傳感器的定量模型。該傳感器陣列有可能用作各種應用中的臨床診斷工具，例如檢測稀有細胞，病原體和研究細胞相互作用的動態。重新設計傳感結構以檢測和計數細胞外囊泡（EV），特別是外來體，作為亞細胞間質負責與細胞間的聯繫。 CD-63抗體功能化GaN HEMT傳感器用於在高離子強度溶液中計數EV，無需額外的樣品預處理。 EV檢測的動態範圍為107-1010 EV / mL，這與現有的金標準納米粒子跟踪分析相當。可以使用我們的HEMT生物傳感器基於EV-二抗結合誘導的傳感器響應變化來表徵EV上的表面標誌物。還研究和報告了EV外部刺激下的傳感器特性。該研究的重點是開發具有診斷和預後潛力的快速EV量化方法。

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.

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