Semiconductor sensor arrays for electrophysiology and cellular analysis

该计划旨在开发与生物细胞接口的半导体芯片，以提高筛选新药化合物的速度。与商用技术相比，新平台将能够更快速地筛选离子通道和G蛋白偶联受体（GPCR）药物发现中的目标化合物。计划中的工作将利用现有的互补金属氧化物半导体（CMOS）制造技术来制造低成本的一次性硅集成电路传感器，这些传感器直接在芯片上与生物细胞连接。CMOS是高通量细胞分析的首选技术，因为与传统药物筛选中使用的被动孔板相比，它能够更密集地集成传感器。该技术还允许通过在每个片上感测位置集成数据采集和处理电路来进行并行细胞记录。此外，CMOS允许传感器和传感器电子器件非常接近地存在在一起，允许高带宽，低干扰接口，用于准确记录细胞电流。此外，几乎所有商品微电子设计中使用的CMOS技术成本非常低，因为它利用了与半导体制造业相关的巨大规模经济。目的之一是设计CMOS传感器阵列，用于基于平面膜片钳电生理的高通量药物筛选。另一个目标是开发用于细胞阻抗分析的CMOS传感器阵列，以观察细胞毒性、受体-配体相互作用以及细胞粘附和扩散。这些新的筛选技术将使加拿大制药业受益，使其能够在更短的时间内对潜在的药物毒性进行更彻底的分析，从而使新药能够更快地以更低的成本推向市场。拟议的计划还将培养CMOS微系统开发方面的高素质人才，他们将为加拿大生物技术和半导体研究以及工业部门的发展做出贡献。

The proposed program seeks to develop semiconductor chips that interface with biological cells to increase the rate at which new drug compounds are screened. New platforms will enable more rapid screening of target compounds in ion channel and G-protein coupled receptor (GPCR) drug discovery compared to commercially-available technologies. The planned effort will leverage established complementary metal-oxide-semiconductor (CMOS) manufacturing to fabricate low-cost, disposable silicon integrated-circuit sensors that interface with biological cells directly on chip. CMOS is the technology of choice for high-throughput cellular analysis because it enables denser integration of sensors compared to passive well plates used in conventional drug screening. This technology also permits parallel cellular recording through integration of data-acquisition and processing circuits at each on-chip sensing location. In addition, CMOS allows transducers and sensor electronics to exist together in very close proximity, permitting a high-bandwidth, low-interference interface for accurately recording cell currents. Furthermore, CMOS technology, which is used in the design of virtually all commodity microelectronics, is very low cost because it leverages the tremendous economies of scale associated with the semiconductor manufacturing industry. One objective is to design CMOS sensor arrays for high-throughput drug-screening based on planar patch-clamp electrophysiology. Another objective is to develop CMOS sensor arrays for cellular impedance analysis to observe cytotoxicity, receptor-ligand interactions, and cellular adhesion and spreading. These new screening technologies will benefit the Canadian pharmaceutical industry by enabling more thorough analysis of potential drug toxicity in less time, allowing new drugs to be brought to market more quickly and at a lower cost. The proposed program will also train highly qualified personnel in CMOS microsystem development who will contribute to the growth of Canada's biotechnology and semiconductor research and industrial sectors.