Physiological Motion Compensation for Neuroscience Research Based on Electrical Bio-Impedance Sensing

Researchers have developed a large number of methods to study the brain’s function. One of the most effective techniques is in vivo whole-cell patch-clamp recording which allows the recording of intracellular neuronal activity. A major issue that drastically reduces the efficiency of in vivo patch clamping is the excessive movement of the brain primarily caused by heartbeat and breathing, which can be larger than the size of the neurons under investigation. Motion compensation techniques are complicated due to the lack of sensors to reliably measure local physiologically-induced motion. This work proposes the use of electrical bio-impedance (EBI) to the existing patch electrodes in the patching pipette as a proximity sensor. The study further develops an extended Kalman filter (EKF) to estimate overall motion and then establishes a motion compensation algorithm for the patch pipette. The proposed method was developed on a custom laboratory benchtop setup and validated during actual in vivo experiments. The results of the laboratory experiments show a real-time compensatory performance exceeding 80%. The in vivo experiments achieved a performance of over 75%, confirming the ability to compensate for real physiologically induced motion. Moreover, the method demonstrated dynamic continuous motion compensation while the electrode was advanced to a neuron, contacting the neuron membrane without damage illustrating the ability to improve neuronal patch clamping. As far as the authors are aware this is the first time that physiologically induced motion can be compensated for this application and this solely relies on EBI.