Optimization of multiple-pulse ultra-low voltage Nanospike electroporation chips using feedback system control for efficient delivery of molecules to cancer cells

We present a rapid and efficient method to optimize the electric pulse parameters for multiple-pulse electroporation (EP) of cancer cells on Nano-spike EP chips to achieve high EP efficiencies (η_EP) and cell viabilities (φ_cell) at ultra-low voltages. In this paper, feedback system control (FSC) scheme was used for the optimization. The FSC scheme consists of an iterative closed-loop of three operations: combinatory inputs of electric pulse parameters, the experimental readouts, and stochastic search algorithm to find combinations for next iteration. We show that only 11 combinations were needed to obtain the optimized electric pulse parameters with high η_EP and φ_cell (> 90%) at ultra-low voltage (~ 1 V), much better than that of commercial electroporators. In addition, more than 80% of research time was saved.