As an application of low electric field to biomedical engineering, this paper attempts to study the dose-effect of biological effects caused by msPEF with experiments on HeLa cells. MTT assay was used to trace the cell electroporation and examine cell viability. It is observed that with the increasing electric field intensity and pulse numbers, IRE effects will occur successively.

A two-dimensional microarray of ten thousand (100100) chondrocyte-spheroids was successfully constructed with a 100-µm spacing on a micropatterned gold electrodes that were coated with poly(ethylene glycol) (PEG) hydrogels. The PEGylated surface as a cytophobic region was regulated by controlling the gel structure through photolithography. In this way, a PEG hydrogel was modulated enough to inhibit outgrowth of chondrocytes from cell adhering region in the horizontal direction. These structural control of PEG hydrogel was critical for inducing formation of three-dimensional chondrocyte condensations (spheroids) within 24 hours. We report noninvasive monitoring of the cellular functional change at the cell membrane using a chondrocyte-based field effect transistor (FET), which is based on detection of extracellular potential change induced as a result of the interaction between extracellular matrix (ECM) protein secreted from spheroid and substrate at the cell membrane. The interface potential change at the cell membrane/gate insulator interface can be monitored during the uptake of substrate without any labeling materials. Our findings on the time course of the interface potential would provide important information to understand the uptake kinetics for cellular differentiation.

A two-dimensional microarray of ten thousand (100100) hepatocyte hetero-spheroids, underlaid with non-parenchymal cells, was successfully constructed with a 100-µm spacing on micro-fabricated glass substrates that were coated with poly(ethylene glycol) (PEG). Co-cultivation of hepatocytes with endothelial cells was essential to stabilize hepatocyte viability and liver-specific functions, allowing us to obtain hepatocyte spheroids with a diameter of 100-µm, functioning as a miniaturized liver to secrete albumin for at least 1 month. The most important feature of this study is that these substrates are defined to provide an unprecedented control of substrate properties for modulating cell behavior, employing both surface engineering and synthetic polymer chemistry. The spheroid array constructed here is highly useful as a platform of tissue and cell-based biosensors (TBB and CBB), detecting a wide variety of clinically, pharmacologically, and toxicologically active compounds through a cellular physiological response.