A MEMS fabricated cell electrophysiology biochip for in silico calcium measurements

For the last 50 years the state-of-the-art for studying electrophysiological activity of single cells has been based on an investigator using a single microprobe, and attempting to make relevant recordings, one cell at a time. Here we report the design, fabrication and characterization of a MEMS-based lab-on-a-chip system for measuring Ca2+ ion concentrations and currents around single cells. This device has been designed around specific science objectives of measuring real-time multidimensional calcium flux patterns around 16 Ceratopteris richardii fern spores in microgravity flight experiments and ground studies. The 16 microfluidic cell holding pores are 150 μm × 150 μm each and have 4 Ag/AgCl electrodes leading into them. An SU-8 structural layer is used for insulation and packaging purposes. The in silico cell physiology lab is wire bonded onto a custom PCB for easy interface with a state-of-the-art data acquisition system. The electrodes are coated with a Ca2+ ion-selective membrane based on ETH-5234 ionophore and operated against an Ag/AgCl reference electrode. Characterization results have shown Nernst slopes of 30 mV/decade that were stable over a number of measurement cycles, and actual fern spore Ca2+ measurements have been recorded with high repeatability and reproducibility. While this work is focused on technology to enable basic research on C. richardii spores, we anticipate that this type of cell electrophysiology lab-on-a-chip will be broadly applied in biomedical and pharmacological research by making minor modifications to the electrode material and the measurement technique.