Exploring Electrical Impedance Spectroscopy as an Innovative Tool for On-Chip Analysis of Human Trabecular Meshwork

This work reports the investigation of in vitro cultured human trabecular meshwork (TM) using electric impedance spectroscopy. The outflow facility of aqueous humor contains a three-dimensional network composed of TM endothelial cells and the extracellular matrix (ECM). The network is a critical determinant of intraocular pressure (IOP), the increase of which is the main cause of primary open angle glaucoma (POAG). Electric impedance spectroscopy was chosen over other technologies for on-chip TM cell study because of its non-invasive and label-free natures as well as the ease of on-chip integration. An array of interdigitated microelectrodes (IMEs) was fabricated for impedance sensing. Polydimethylsiloxane (PDMS) was used as the passivation layer and to form the cell culture wells. TM cell growth and proliferation under external stimuli can thus be in situ monitored. In this work, the utility of the impedance spectroscopy was demonstrated by treating TM cells with dexamethasone (DEX), a synthetic glucocorticoid which is found to increase the IOP. Electric impedance was monitored for 3 days during DEX treatment. The impedance measurement at 40 kHz showed that a smaller increase of impedance magnitude occurred in the DEX treated group than in the control group, which suggested that DEX inhibits the proliferation of TM cells. The higher the DEX concentration, the greater inhibition was observed. The measurement was validated using AlamarBlue proliferation assay and microscopic observation. The measurement provides a reasonable explanation of glucocorticoid induced glaucoma, where the glucocorticoid alters the metabolic and physiological functions of TM cells by inhibiting normal cell growth and proliferation.