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（BLMs）重要功能的机制尚不清楚，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，但由于准备和执行详细的实验研究的实质性瓶颈，发现受到限制。目的：本跨学科项目的目标是建立耦合微电子与生物界面的新技术和方法，从而实现膜蛋白的高通量表征。为了实现这一目标，我们提出设计一个CMOS实验室平台，该平台集成了包含1000个元件的微流控平面blm室阵列和嵌入式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：所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中，该模型仪器本身将为高通量生物膜表征提供突破性的新能力，从而在生物学、纳米材料和医学的许多领域取得重大进展。研究工作还将促进两个主要领域的科学和工程知识。更广泛的影响:将开发一种具有高通量生物膜表征新功能的模型仪器，使许多领域的重大后续进展能够改变知识前沿，推进我们对基本生物过程的基本理解，并有助于为传感器平台生成新的工程膜蛋白，高通量药物筛选，以及开发新的医学诊断和疾病治疗方法。这些都对社会有广泛的好处。多学科研究成果将通过研究生和本科生研究人员的直接参与，开发和交付大学预科STEM演示，以及参与基于新项目的多学科生物处理实验室课程，整合到教育中。此外，将为一名中学教育科学教师提供研究经验，他将把这些经验融入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、研究者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.