An Integrated BiChip for Ion-Channel Studies

本研究的目的是开发一种二维平面膜片钳生物芯片，用于研究被困在纳米孔中的生物细胞的离子通道。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、MEMS、硅微流体、先进的信号处理和软件开发来感知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，“头级”前置放大器相结合，全部采用1.5微cmos技术，在1-10 kHz离子通道开关频率下可获得1V/pA的跨阻增益。智力优势：离子通道和细胞功能的体外研究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以及提取药理学药物实验中的离子通道时间和频率响应成为可能。固态模拟工具为离子通道（如KcsA离子通道）中的电位、电场和离子浓度建模和表征提供了新技术。这些模拟为离子通道中的离子运输提供了新的见解，这对理解心血管和中枢神经系统的疾病和过程非常重要。更广泛的影响这项研究涉及工程、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，将研究和教育结合起来。该计划通过结合新的分析和测量技术来增强物理基础设施，例如生物电子学/生物光子学实验室进行离子通道表征实验。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。每年，NSF REUs和里海大学的夏季奖学金将会进行合作，因为本科生，特别是少数族裔，将会被引入到离子通道的跨学科研究和教育中。

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.