A Digital and Open-Source Amplifier for Oocyte Ion Channel Measurements

Ion channels and transporters are critical components of the nervous system, and their electrophysiological characterization plays an essential part in understanding many neurological diseases. Voltage clamp techniques characterize ion channel electrical behavior by controlling membrane voltage while measuring membrane current. Cut-Open Vaseline Gap (COVG) is a specific voltage clamp technique that provides a unique combination of high-speed/low-noise needed to resolve fast protein dynamics and the rare ability to control both intra- and extra- cellular solutions. However, the COVG technique is regarded as challenging in part because the only commercial amplifier is manually operated and requires considerable experience and skill. Further, this commercial amplifier is no longer supported. The COVG user community needs an easy-to-use, high-performance replacement that also makes the technique accessible to more laboratories. In this proposal, we will design, build, and test a new COVG amplifier that leverages modern digital electronics. This digital amplifier will use an innovative approach to automate experiment setup and to continuously adapt setup parameters during the experiment. These approaches will decrease the time required for experiments and maintain optimal feedback as system parameters evolve. The amplifier will have multiple inputs and outputs that are controlled and read digitally. These multiple signals will be used in digital signal processing and control systems algorithms to improve the speed of the ion channel voltage control and allow the experimenter to resolve faster dynamics. The modular amplifier design will create general-use circuit building blocks with digital control systems for feed- back. These components can be leveraged by the electrophysiology community to extend this development to applications beyond COVG. This project will challenge students with instrumentation development that uses and develops skills in:

  1. Circuit design and simulations
  2. On the bench testing,
  3. FPGA coding and simulations
  4. PCB layout
  5. Control system implementation within an FPGA
  6. Python programming for instrument and FPGA control

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