An Integrated BiChip for Ion-Channel Studies

这项研究的目的是开发一种二维平面膜片钳生物芯片，以研究捕获在纳米孔中的生物细胞上的离子通道。离子通道是神经系统、心脏和骨骼肌中兴奋性的分子元素。该方法结合了生物技术、微电子学、MEMS、硅微流体、先进的信号处理和软件开发来检测离子通道的快速打开和关闭。低噪声、相关双采样(CDS)信号读出与开关电容和前置放大器相结合，全部采用1.5微米CMOS工艺，对于1-10 kHz的离子通道开关频率，跨阻增益为1V/pA。智力价值：体外研究离子通道和细胞功能是生物学研究和其他领域的基础，如临床诊断、治疗、药物筛选和环境监测。生物芯片将使离子通道模型的实验验证成为可能，并在药物实验中提取离子通道的时间和频率响应。固态模拟工具提供了新的技术来模拟和表征离子通道中的电势、电场和离子浓度，例如KCSA离子通道。这些模拟为离子通道中的离子传输提供了新的见解--这对于了解心血管和中枢神经系统的疾病和过程非常重要。广泛影响这项研究涉及工程学与物理和生命科学的整合。此外，该计划通过将纳米技术应用于离子通道研究的最新发展引入课堂，将研究和教育结合在一起。该方案通过采用新的分析和测量技术，如生物电子学/生物光子学实验室，对离子通道特性进行实验，从而加强了物质基础设施。促进伙伴关系将在大学内部-跨部门和学院-以及与制药行业。NSF Reus和LeHigh的暑期奖学金之间将引入一项合作努力，因为每年将把本科生，特别是未被充分代表的少数族裔介绍到离子通道研究的跨学科研究和教育领域。

The object of this research is to develop a 2-D planar, patch-clamp biochip to study ion-channels on biological cells trapped in nanopores located in nanowells. Ion-channels are the molecular elements of excitability in the nervous system, heart and skeletal muscles.The approach combines biotechnology, microelectronics, MEMS, silicon microfluidics, advanced signal processing, and software development to sense the rapid openings and closings of the ion-channels. A low noise, correlated-double-sampling (CDS) signal readout combines with a switched-capacitor, 'head-stage' preamplifier, all in 1.5 micronCMOS technology, for a transimpedance gain of 1V/pA for 1-10 kHz ion-channel switching frequencies.Intellectual Merit:The study of ion-channels and cellular functions in vitro is fundamental to biological research and other fields, such as clinical diagnostics, therapy, pharmacological drug screening, and environmental monitoring. A biochip will enable experimental verification of ion-channel models as well as to extract ion-channel time and frequency response in pharmacological drug experiments. Solid-state simulation tools provide new techniques to model and characterize potential, electric field and ion concentration in ion-channels, such as the KcsA ion-channel. These simulations offer new insight into ion transport in ion-channels -important to understand diseases and processes in cardiovascular and central nervous systems.Broader ImpactThis research involves the integration of engineering together with the physical and life sciences. In addition, the program integrates research and education through the introduction into the classroom of the latest developments in nanotechnology as applied to the study of ion-channels. The program enhances the physical infrastructure with the incorporation of new analytical and measurement techniques, such as a bioelectronics/biophotonics laboratory to conduct experiments on ion-channel characterization. Promotion of partnerships will be within the university - across departments and colleges - as well as with the pharmaceutical industry. A cooperative effort will be introduced between NSF REUs and Lehigh's summer scholarships, as each year, undergraduates, particularly underrepresented minorities, will be introduced intointerdisciplinary research and educational in the study of ion-channels.