Two-Photon Targeted, Quad Whole-Cell Patch Clamping Robot

Neurological disorders have devastating consequences in the lives of millions of people, and as the global population continues to age, the prevalence of these disorders will inevitably increase. To address their impact, it is crucial to understand the brain's normal and abnormal behaviour, beginning with the study of its fundamental unit: the cell. The gold standard technique for investigating the type and function of electrically active cells is whole-cell patch-clamp. When performed simultaneously in multiple neurons, this technique allows for precise measurement of the connectivity between cells, providing valuable insights into cell communication and function. However, multi-patch-clamp is a laborious and low throughput method with a steep learning curve, requiring extensive training. Consequently, only a handful of laboratories worldwide perform it.

What sets our system apart is its ability to target specific neurons using two-photon technology, facilitating investigations into how microcircuits involving particular cells or cell types behave in both normal brain function and dysfunction. Extensive testing of the instrumentation robot has been conducted on ex vivo mouse brain slices. The success rates achieved for targeted and non-targeted modes are 54% and 68%, respectively (Vera Gonzalez et al., 2023). These rates are comparable to manual patching performed by trained researchers, but our automated system offers significantly higher speed and throughput. Moreover, it opens up the possibility of utilizing multiple robots simultaneously, thus potentially multiplying the throughput while minimizing the experimenter's attention and time demands. Importantly, the instrumentation system also alleviates the mental strain on researchers, as learning and performing the technique manually can be demanding and frustrating. Lastly, given the recent emphasis on health precautions, our instrumentation robot provides a more health-conscious approach to conducting research.

However, we want to emphasize that we are not looking to substitute the very hard-working scientists that are already proficient in patch-clamp, but rather make their lives easier by automating other parts of the process (recording and note taking, pipette movements, pipette reuse, etc) and most importantly, making this technique available to all the laboratories in the world that currently do not perform the technique because they don't have a senior scientist that can teach them.