The Patch-clamp amplifier is the "gold standard" to measure currents flowing through ion channels, the structures responsible for cell membrane conductivity. Ion channels are widely targeted by drugs used in therapy and hence the automated, high-throughput screening of drugs that affects the function of specific ion channels is of great interest. In this thesis, we present the design, fabrication, and test results from a fully integrated, dual-channel, patch-clamp amplifier system that occupies an area of only 3 x 3mm 2.;The system was fabricated in Silicon-on-Sapphire (SOS) technology and has series resistance and parasitic capacitive compensation capability. The system was designed to compensate for the distributed series resistance present in a population patch-clamp system and to achieve 100% series resistance compensation. Furthermore, the system was designed with the ability to compensate for leak currents that result from inadequate sealing between the cell membrane and the electrode. An anti-aliasing filter and an input-reconstruction filter was integrated to the system to minimize the number of external components necessary for integration into larger systems. The circuit employs selectable feedback resistors to enable the recording of currents of varying magnitude. All operational amplifiers in the design were implemented using a constant-transconductance, rail-to-rail operational amplifier. A supply-independent biasing circuit was designed to bias the operational amplifiers. A serial digital interface was integrated to the design to facilitate the control of the patch-clamp system with a personal computer.;We have demonstrated the circuit's usefulness by recording ion channel currents from live cells. The system can be used as is to substitute a rack-mounted commercial patch-clamp system that is a million times larger in volume. More importantly, it is ready to be integrated into a larger high-throughput system. The hope is that the integrated patch-clamp system would facilitate the fabrication of massively parallel high-throughput systems that would make the functional analysis of ion channels and genes and also the screening of drugs a much more efficient and failsafe process.
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机译：膜片钳放大器是“金标准”，用于测量流过离子通道的电流，离子通道是负责细胞膜电导的结构。离子通道已广泛用于治疗中的药物，因此，对影响特定离子通道功能的药物进行自动，高通量筛选非常令人关注。在本文中，我们介绍了一个完全集成的，双通道，膜片钳放大器系统的设计，制造和测试结果，该系统仅占3 x 3mm 2的面积；该系统采用蓝宝石硅制造（SOS）技术并具有串联电阻和寄生电容补偿功能。设计该系统是为了补偿总体膜片钳系统中存在的分布式串联电阻，并实现100％串联电阻补偿。此外，该系统被设计为具有补偿由于细胞膜和电极之间的密封不足而引起的泄漏电流的能力。系统中集成了抗混叠滤波器和输入重建滤波器，以最大程度地减少集成到较大系统中所需的外部组件数量。该电路采用可选择的反馈电阻器来记录变化幅度的电流。设计中的所有运算放大器均使用恒定跨导，轨到轨运算放大器实现。设计了独立于电源的偏置电路来偏置运算放大器。串行数字接口已集成到设计中，以方便用个人计算机控制膜片钳系统。;我们已经通过记录活细胞的离子通道电流证明了该电路的有用性。该系统可以按原样使用，取代体积大一百万倍的机架式商用膜片钳系统。更重要的是，它已准备好集成到更大的高通量系统中。希望是，集成的膜片钳系统将有助于大规模并行的高通量系统的制造，这将使离子通道和基因的功能分析以及药物筛选成为一个更加有效和故障安全的过程。
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