Integrated Sensing: An Integrated Biosensor System for Cellular Studies

集成传感：用于细胞研究的集成生物传感器系统

• 批准号: 0225436
• 负责人: Marvin White
• 金额: $ 15万
• 依托单位: Lehigh University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-15 至 2006-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0225436&HistoricalAwards=false
• 关键词: Integrated; Sensing; Biosensor; System; Cellular

In biological research, the study of cellular functions in vitro is basic to other fields, such as clinical diagnostics, therapy, pharmacological drug screening, and environmental monitoring. In our proposal, biotechnology, silicon micromachining, microelectronics sensor and signal processing technology are used to realize a multi-purpose biological sensor with integrated lownoise signal processing. We research program to for culture, characterization and manipulation of biological cells in silicon chips. In particular, the proposed integrated biosensor system structure can be used as a planar patch-clamp setup for the experimental testing and evaluation of the effect of drugs on prepared ion channels. The proposed device can also act as a miniaturized platform for cell culture and characterization of a cell population together with counting and sizing within the culture chamber. The basic biosensor is a 2D planar 'patch-clamp', which can be employed for sensing the ion-transport through ion channels, the count and size of biological particles, and culturing or sorting cells. We believe the proposed biosensor will enable eventually electronic DNA sequencing through the measurement of ionic current changes as a sequence single-stranded DNA bases pass through a nanoscale pore, which is fabricated and sized to electrically control the single-stranded DNA. A major objective of our proposal is to develop a bio-electronic interface that integrates biological ion channels into a 'nanowell' with associated integrated electronics. The biosensor combines control electronics into a low noise, correlated-double-sampling (CDS)sensitive signal readout with a switched capacitor 'headstage' preamplifier. On-chip electronics will reduce the recording impedance levels, minimize the output leads, prevent crosstalk, and amplify the low-level ion-channel signals. In addition, the biosensor system will enable rapid, computer-aided, automated testing and characterization of ion-channels and their interaction with drugs. The biosensor will also enable experimental verification of ion channel models as well as provide data, which can be analyzed with various algorithms to extract information regarding time and frequency response of the ion channels and their relationship to pharmacological drug investigations. This effort will also explore the use of 'on-chip' adaptive signal processing to electrically model biological cells in real-time with voltage-clamp stimuli applied to the cells.

在生物学研究中，体外细胞功能的研究是其他领域的基础，如临床诊断，治疗，药理学药物筛选和环境监测。 本研究将生物技术、硅微加工技术、微电子传感器技术和信号处理技术相结合，实现了一种集成低噪声信号处理的多功能生物传感器。我们的研究项目是在硅芯片上培养、表征和操纵生物细胞。特别是，所提出的集成生物传感器系统结构可以用作平面膜片钳设置的实验测试和评价药物对制备的离子通道的影响。所提出的装置还可以充当用于细胞培养和细胞群体表征以及培养室内的计数和尺寸确定的小型化平台。基本的生物传感器是一个二维平面的“膜片钳”，它可以用于感测通过离子通道的离子传输，生物颗粒的计数和大小，以及培养或分选细胞。我们相信，所提出的生物传感器将最终使电子DNA测序通过测量离子电流的变化作为一个序列的单链DNA碱基通过纳米级孔，这是制造和大小的电控制的单链DNA。我们的建议的一个主要目标是开发一个生物电子接口，将生物离子通道集成到一个“细胞”与相关的集成电子。该生物传感器将控制电子器件与低噪声、相关双采样（CDS）敏感信号读出器结合在一起，并带有开关电容器“头台”放大器。片上电子器件将降低记录阻抗水平，最大限度地减少输出引线，防止串扰，并放大低水平离子通道信号。此外，生物传感器系统将能够快速，计算机辅助，自动化测试和表征离子通道及其与药物的相互作用。该生物传感器还将能够对离子通道模型进行实验验证，并提供数据，这些数据可以用各种算法进行分析，以提取关于离子通道的时间和频率响应及其与药理学药物研究的关系的信息。这项工作还将探索使用“片上”自适应信号处理，以实时电模拟生物细胞与电压钳刺激施加到细胞。