This project develops a new hardware module that drastically improves the temporal resolution of current patch-clamp from the microsecond domain to the picosecond domain. The hardware module can be attached to a commercially available AFM (atomic force microscopy) platform, as well as a commercially available microwave generator. The new module has both scientific impact to the ion-channel and biophysics community, as well as to the industry branch of AFM and patch-clamp.
For the scientific impact, we have EU COST actions where this method will be disseminated as well as international technological conferences like IEEE and EuMW (EU Microwave Conference) where the partners are platinum sponsors. On the business side, the addressable market volume is 500 MEuros/year, and assuming a 10% market share in 5 years timeframe this results in 50 MEuros/year revenue. The partners of this project developed the technology in recent years and published it in high-impact journals, while the industrial partner is a leading electronics technology provider to allow for efficient development of demonstrators and prototypes.
Technologywise, the new hardware module integrates nanotechnology and high frequency RF (radiofrequency) technology, as such it is a unique combination of two established fields, which will disrupt the patch-clamp community. Patch-clamp is a well-established technology for characterisation and investigation of ion channels through direct measurements of the small ionic currents that flow through the channels acting as gates in our cells. The ion-channels are of fundamental importance for the function of biological processes in humans and therefore the target of almost a quarter of all currently available drugs for medical treatment. However, due to physically and technical limitations, patch clamp only allows the measurement of ionic currents in a time domain down to 1μs.
In this project, we will overcome these fundamental limitations by shrinking the sensing electrodes of the device to the ultimate nanometre level and by application of a new pump-probe detection scheme. This is achieved by implementation of a smart nano-electrode platform into a commercial AFM. The nanoelectrodes serve as back electrodes and immobilise the ion-channel while forming the Gigaseal required to measure only the current flowing through the channel. Dedicated high frequency RF electronics and adequate integration allows application and sensing of ultra sharp potential pulses to AFM probe and nano-electrode substrate. The AFM probe positioned directly above the channel senses locally the ionic current with high temporal resolution. Successful implementation of the new device will open a completely new domain for the study of ion channel dynamics for scientists in life science and pharmacological applications.