Adaptive voltage clamp
Adaptive voltage clamp…or ‘online Vx estimation’ allows voltage protocols individually optimized for each cell’s electrical properties. The system will automatically perform Boltzmann fits online for each cell to estimate the cell-specific voltage needed to activate half of the receptor population or the voltage that keeps half of the cells in an inactivated state.
Adaptive Voltage Protocols give a lot tighter screening data, as demonstrated in this application report and this poster by Charles River Laboratories.
Individually estimated Vhalf is attractive to increase the precision of pharmacological data. Vhalf is located on the steepest part of the activation curve. Even slight cell-to-cell variance will significantly impact the elicited current and, thus, the pharmacologically relevant response.
Example of online Vhalf estimation and subsequent use of Vhalf.
Fig. 6 from the Application Report “Vhalf adaptive protocols on Qube” authored by Juha Kammonen from Charles River Laboratories.
An adaptive protocol first includes an activation or inactivation protocol from which the specific parameters can be estimated. Immediately after that, the estimated values can be used in the voltage protocol, adapting the experimental protocol to the cell’s electrical properties.
If an unstable cell gives rise to a low-quality fit, a backup mechanism will take over and clamp the cell to a predefined value, so there will be no data loss.
- Automated cell-specific Boltzmann fit
- Clamping to the cell-specific Vhalf
- Activation and inactivation protocols
- Online parameter quality control
- No data loss if Boltzmann fit is poor
Read more in this application report (Qube) and this poster (QPatchII)
Adaptive protocols are available for all APC systems.