Development Of A Novel Patch-Clamp Amplifier

Researches on biological membranes would be helpful for exploring the mechanisms of life. The Patch clamp technique is one of the most popular methods for studying electrophysiological properties of membranes and brings a great advancement in the cellular and molecular biology.As a key equipment in this technique, patch-clamp amplifier acts as a high-gain current-to-voltage converter to detect the ultra-weak signals (picoampere order) in cell membranes. Different to the conventional amplifier, the novel one has been constructed as a virtual instrument to achieve hardware controls by buttons or sliders in the soft-panel. Another advantage is its full automatic accomplishment for parameter adjustments and compensations, which could provide simplification for experimental procedures. This thesis has been organized into five sections:1. A parameter setting system by employing a programmable logic device and USB-controller to implement the digital control of analog signal pathway in the amplifier. The method is based on serial communication that is reliable, low-cost and easy to update.2. Design of a resistor-feedback headstage made up by integrated chips, which could be easily fabricated without distinct difference. The headstage's dynamic and noise characteristic has also been modeled and measured to evaluate the performance. The tests results show it could gratify the need for both whole-cell and single-channel recoding.3. Design of a signal conditioning system for the headstage. The conditioning system is used to reconstruct the channel currents and mainly includes frequency compensation to extend bandwidth, programmable gain to scale the signals and output filter to minimize noise. 4. Design of several automatic compensation modules. Based on the theoretical basis of parameter models, a series of adjustment circuits and algorithms are adopted to remove the electrode offset and to cancel the transient currents caused by pipette capacitance (C-fast) and membrane capacitance (C-slow). Design of series resistance compensation and its influence to the stability of the amplifier is also discussed.5. Design of calibration and test modules. Calibration can collect and correct parameters in the equipment to improve the system precision. Test can scan the hardware to help developers and users for troubleshooting.