A Digital and Open-Source Amplifier for Oocyte Ion Channel Measurements - Project Summary / Abstract
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 proposed 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. Examples include Two-Electrode Voltage-Clamp (TEVC) and dynamic clamp.
A critical contribution of this proposal is the training of undergraduate electrical and computer engineers and
neuroscience students, which will be facilitated by an open-source ethos. The design, build, and test of this
electrical instrument includes a variety of sub-projects each with a separate focus that augments our under-
graduate curricula. These sub-projects will be easily accessible to undergraduate students through hosting in a
publicly accessible repository (e.g. using GitHub) following best practices of open-source software. The ampli-
fier will be evaluated for repeatability and reproducibility using oocytes by a set of beta-testing labs. Following
biological validation, the hardware, software, and ordering information will be publicly available to encourage elec-
trophysiology experimenters to contribute improvements and modify the instrument to enable novel experiments.
Experimenters may utilize components of this design to develop new electrical instrumentation based on digital
feedback for techniques other than COVG.
