Lab-on-CMOS Electrochemical Microsystem for High Throughput Characterization of Membrane Proteins

膜蛋白是细胞的基本组成部分，将所有生物体与外界联系起来。各种膜蛋白赋予天然双层脂质膜（BLM）重要功能的机制知之甚少，特别是在分子和原子尺度上。尽管迫切需要了解新型膜蛋白的结构和功能，但发现受到准备和执行详细实验研究的实质性瓶颈的限制。目的：这个跨学科项目的目标是建立新的技术和方法耦合微电子与生物接口，使膜蛋白的高通量表征。为了实现这一目标，我们建议设计一个实验室上的CMOS平台，集成了1000个元素阵列的微流体平面BLM室与嵌入式CMOS电化学仪器电路。所提出的方法将克服重大的技术障碍，并为硅到蛋白质的通信途径提供新的机制，为未来的研究活动和商业产品提供新的方向。智力优势：提出的将微电子与生物界面耦合的方法将克服重大的技术障碍，并为硅到蛋白质的通信途径提供新的机制，为未来的研究活动和商业产品提供新的方向。这些方法将被纳入拟议的模型仪器本身将提供突破性的新能力，高通量生物膜表征，使生物学，纳米材料和医学的许多领域的重大后续进展。研究工作还将在两个主要领域推进科学和工程知识。将开发一种具有高通量生物膜表征新能力的模型仪器，从而在许多领域实现重大的后续进展，这些领域可以改变知识的前沿，推进我们对基本生物过程的基本理解，并有助于产生新的，用于传感器平台的工程化膜蛋白、高通量药物筛选以及新的医学诊断和疾病治疗的开发，所有这些都对社会产生了广泛的好处。多学科研究的结果将通过研究生和本科生研究人员的直接参与，开发和提供预college STEM演示文稿以及参与基于新项目的多学科生物加工实验室课程来整合到教育中。此外，将为中学教育科学教师提供研究经验，他们将把经验融入K-12课程的教学模块，包括针对代表性不足群体的学生的机会。该项目的结果将通过期刊出版物、会议报告和研究人员及其相关研究中心的网站进行传播。

Membrane proteins are the essential components of the cell that connect all living organisms to the outside world. The mechanisms by which various membrane proteins impart vital functions to natural bilayer lipid membranes (BLMs) are poorly understood, particularly at the molecular and atomic scales. Although there is a critical need to understand the structure and function of novel membrane proteins, discoveries are limited by the substantial bottleneck of preparing and executing detailed experimental studies. Objective: The goal of this interdisciplinary project is to establish new technologies and methodologies for coupling microelectronics with biological interfaces that will enable high throughput characterization of membrane proteins. To achieve this goal, we propose to design a lab-on-CMOS platform that integrates a 1000-element array of microfluidic planar-BLM chambers with embedded CMOS electrochemical instrumentation circuits. The proposed approaches will overcome significant technical barriers and contribute new mechanisms for silicon-to-protein communication pathways, enabling new directions for future research activities and commercial products. Intellectual Merit: The proposed approaches for coupling microelectronics with biological interfaces would overcome significant technical barriers and contribute new mechanisms for silicon-to-protein communication pathways, enabling a new direction for future research activities and commercial products. These approaches will be incorporated into the proposed model instrument which will itself provide ground-breaking new capabilities for high throughput biomembrane characterization enabling significant subsequent advances in many fields of biology, nanomaterials, and medicine. The research efforts would also advance scientific and engineering knowledge in two primary areas.Broader Impact: A model instrument will be developed with new capabilities for high throughput biomembrane characterization, enabling significant subsequent advances in many fields that could transform the frontiers of knowledge, advance our fundamental understanding of basic biological processes, and aid in the generation of new, engineered membrane proteins for sensor platforms, high throughput drug screening, and development of new medical diagnostics and disease treatments, all with wide-reaching benefits to society. Results of the multidisciplinary research will be integrated into education by direct involvement of graduate and undergraduate student researchers, development and delivery of a precollege STEM presentation, and participation in a novel project-based MultidisciplinaryBioprocessing Laboratory course. In addition, research experience will be provided for a secondary education science teacher who will integrate the experience into a teaching module for K-12 programs, including opportunities that target students from underrepresented groups. The results of this project will be disseminated through journal publications, conference presentations, and websites of the investigators and their associated research centers.