Electrical Impedance Spectroscopy for Microtissue Spheroid Analysis in Hanging-Drop Networks

Abstract

Electrical impedance spectroscopy (EIS) as a label-free and noninvasive analysis method receives growing attention for monitoring three-dimensional tissue constructs. In this Article, we present the integration of an EIS readout function into the hanging-drop network platform, which has been designed for culturing microtissue spheroids in perfused multitissue configurations. Two pairs of microelectrodes have been implemented directly in the support of the hanging drops by using a small glass inlay inserted in the microfluidic structure. The pair of bigger electrodes is sensitive to the drop size and allows for drop size control over time. The pair of smaller electrodes is capable of monitoring, on the one hand, the size of microtissue spheroids to follow, for example, the growth of cancer microtissues, and, on the other hand, the beating of cardiac microtissues in situ. The presented results demonstrate the feasibility of an EIS readout within the framework of multifunctional hanging-drop networks.

Spheroids-on-a-chip: Recent advances and design considerations in microfluidic platforms for spheroid formation and culture

“…The hanging droplets were in contact with hydrogels from their ceiling which enabled in situ monitoring of lactate ( Figure 17A). The mentioned microfluidic HD concept was integrated into another work by Schmid et al for electrical impedance spectroscopy [208]. Two pairs of platinum electrode inlays were deposited on a glass and placed in the HD culture similar to the previous design.…”

Inventions and Innovations in Preclinical Platforms for Cancer Research

“…For the real-time on-chip monitoring of the spheroids, several techniques have been developed including the electrode-based biosensors for oxygen [109], glucose and lactate concentration [110] and also pH and electrical impedance [111] measurements. These monitoring techniques alleviate the need for spheroid retrieval from the chip, which effectively reduces the time and cost.…”

Microsensor systems for cell metabolism – from 2D culture to organ-on-chip

“…Small tissue size and its position away from the electrodes, which can only be at the ceiling of the droplet, make them challenging however. 140 Reducing the droplet volume to bring the spheroid closer to the electrodes for measurement was necessary. Overall, the drawbacks of the hanging droplet approach are the complex liquid handling, necessary prevention of evaporation and limited robustness against mechanical shocks of the systems.…”