Robotic dual-arm patch clamp for neuron excitability research under mechanical stimulation

The dual-arm patch clamp technique, using one micropipette electrode to patch the target cell to record its electric signals with the other micropipette mechanically stimulating the target cell, is a significant technique in neuroscience for studying neuron excitability under mechanical stimulation. A key step for dual-arm patch clamp operation is to coordinate two micropipettes to reach the target cells in the narrow brain tissue environment. The traditional manual operations face issues such as inaccurate workspace estimation, clumsy movements, and collision risks of the two micropipettes, resulting in low operational efficiency. Addressing the above issues, a robotic dual-arm patch clamp method was developed for neuron excitability research under mechanical stimulation in this paper. First, the reachable workspace of the dual-arm was calculated based on a kinematics model. Then, a robotic dual arm patch clamp operation procedure is proposed to approach, whole-cell patch, and mechanically stimulate the target cell. The experiment results on neurons in mouse brain slices show that the success rate of dual micropipette contacting cell surface reaches up to $90 \%(18 / 20)$ at an average speed of 6 mins/cell, which are both significantly improved in comparison to manual operation. An increase in neuron excitability in the primary visual cortex (V1) was found under the mechanical stimulation, proving the feasibility of the proposed system for studying the impact of mechanical stimulation on ion channel activities.