痕量检测用"电子ELISA"AlGaN/GaN HEMT 生化传感器研究

With the need for rapid detection of biomolecular analytes in the life sciences and medicine, the research community has made great progress in developing microscale and nanoscale sensors for many biological applications. Among a variety of sensors, field effect transistors (FETs) based devices are ideal biochemicalsensors that can directly convert interactions of biomarker to electrical signals for low cost, rapid, label free, and sensitive detection. Si-based MOSFETs have the great advantage of compatibility to the current microelectronic manufacturing processes, but suffer from current drift due to ion diffusion into the gate oxide layer, making them difficult to detect target analytes at low concentrations in physiological buffers or fluids with high ionic strengths. III-nitride semiconductors have attracted considerable interests for biosensor applications due to their unique properties, such as chemical inertness, non-toxicity, and thermal stability. Especially, III-nitrides FETs are ion-impermeable and highly stable in electrolytic solutions, making them ideal for detection at ultralow concentration in fluids with high ionic strengths. In this project, we developed an “Electronic ELISA” AlGaN/GaN HEMT biochemical sensor for trace detection. Our main work focus on investigation of sensing approaches to fabricate high performance portable sensors with high sensitivity and fast response. The sensor mechanism and technology was systematically researched. Factors influencing the capability of the “Electronic ELISA” AlGaN/GaN HEMT biochemical sensor were analyzed. The simulation of the response of the “Electronic ELISA” AlGaN/GaN HEMT will be discussed. The effect of molecular charge screening by dissolved solution counterions, Debye screening, on sensor response was demonstrated. This is a critical consideration for designing optimal protocols for label-free sensing using AlGaN/GaN HEMT biochemical sensor. A highly sensitive intensity interrogation scheme using “Linker molecule- gold nanoparticle (Au NP)” complexes was also proposed and demonstrated. Physics, Chemistry, Materials, and Microelectronics are involved and mainly deal with the devices people are most interested in. We expect that this unique “Electronic ELISA” AlGaN/GaN HEMT sensor would find its potential applications in various fields.

本项目以微/纳传感器在生物医学、环境监测等领域的痕量现场快速应用为研究背景，以提高传感器自身性能为研究目标，首次提出开展高灵敏度电子酶联免疫吸附测定（电子ELISA）技术的AlGaN/GaN HEMT生化传感器的研究，采用理论与实验相结合的方式探索生物分子膜、待测目标与器件电学量之间的转换机制，分析德拜长度对AlGaN/GaN HEMT传感器件的影响，研究降低或消除德拜长度影响的方法，探索采用“生物分子膜-纳米金”信号放大系统提高传感器灵敏度的方法，研究和解决“电子ELISA” AlGaN/GaN HEMT传感芯片的设计、加工、封装等共性关键技术。通过对该项目的研究，建立和完善AlGaN/GaN HEMT生化传感器的传感机理、制备与表征手段，促进微纳技术、生物技术、信息技术等以及有关交叉学科的发展。

从第一篇关于AlGaN/GaN HEMT结构的生化传感器至今，已有近十余年的研究历程，国内外的研究学者针对该结构的生化传感器开展了诸多研究，均取得了不错的进展。本项目以微/纳传感器在生物医学、环境监测等领域的痕量现场快速应用为研究背景，以提高GaN基传感器自身性能为研究目标，针对国内外对于AlGaN/GaN HEMT生化传感器从生化反应到器件电学信号获取之间转换机制不明确的问题，开展了对于传感区域表面特异性分子识别探针、目标检测物等对AlGaN/GaN异质结结构中2DEG影响的研究，探索了生物量与电学量之间的转换机制，构建了AlGaN/GaN HEMT生化传感器的传感机理模型。研究了“生物分子膜-纳米金”体系作为器件响应信号识别元件及信号放大工具的原理，实现了以金颗粒用巯基乙胺进行修饰的方法完成对TNT的高灵敏特异性识别，其检测极限可达到0.1ppt。研究了提高传感器信号稳定性的方法，提出了延伸栅式AlGaN/GaN HENT生化传感结构设计，该结构的传感器应用到前列腺特异性抗原（PSA）的检测中，实现了最低检测限位0.1 pg mL-1的检测。探索了在栅极区域修饰席夫碱提高表面修饰一致性的方法，实现了对痕量重金属离子锌离子（Zn2+）的检测。研究了基于差分式AlGaN/GaN HEMT的生化传感结构提高检测信号稳定性的方法，实现了对前列腺特异性抗原的极低浓度检测（100 fg/mL）。研究了基于AlGaN/GaN HEMT结构的“电子ELISA”检测方法，将传统ELISA方法中底物的显色反应以产生电学信号的电化学反应代替，本项目以磁珠作为ELISA生物链修饰平台，尿素-脲酶反应作为底物反应，使用AlGaN/GaN HEMT生化传感器检测底物反应所产生的氢离子，从而突破德拜半径屏蔽的影响，实现在生理溶液中对生物大分子的检测，实现在生理溶液中对PSA的检测，检测极限可达1 fg mL-1。该研究对理解AlGaN/GaN HEMT生物传感器的应用具有重要意义和价值。