Dynamics and control of the two-pulse protocol in electroporation: numerical exploration

Externally applied voltages can create transient, non-selective pores in a cell's membrane, a phenomenon known as electroporation. Electroporation has reduced toxicity, is easy to perform, and does not induce the immune system. Therefore, the technique has a wide range of biological and medical applications. Previous experiments show that a two-pulse protocol, which consists of a fast, large-magnitude pulse and a slow, small-magnitude pulse, can increase the efficiency of drug delivery such as gene electrotransfer. In this work, we investigate the dynamics and control of the two-pulse protocol using a macroscopic model of electroporation. Numerical simulations show that there exists a range of pore radii that cannot be sustained using the conventional, open-loop, two-pulse protocol. As a result, one may need to use pores that are significantly larger than the sizes of the targeted molecules. Moreover, it is not possible to know the rate of delivery a priori. To ensure accurate drug delivery and avoid potential damage to the cell's membrane, we explore feedback mechanisms to eliminate the gap in sustainable pore radii and thus to precisely control the electroporation process. Numerical simulations show that a straightforward feedback algorithm can achieve robust control effects. Moreover, the control algorithm is effective without knowledge of the model and thus has the potential to be implemented in experiments.