Research Update: Electrical monitoring of cysts using organic electrochemical transistors

M Huerta,M Ramuz,R M Owens,A Hama,J Rivnay

doi:10.1063/1.4915493

Abstract

Organotypic three-dimensional (3D) cell culture models have the potential to act as surrogate tissues in vitro, both for basic research and for drug discovery/toxicology. 3D cultures maintain not only 3D architecture but also cell-cell and cell extracellular matrix interactions, particularly when grown in cysts or spheroids. Characterization of cell cultures grown in 3D formats, however, provides a significant challenge for cell biologists due to the incompatibility of these structures with commonly found optical or electronic monitoring systems. Electronic impedance spectroscopy is a cell culture monitoring technique with great potential; however, it has not been possible to integrate 3D cultures with commercially available systems to date. Cyst-like 3D cultures are particularly challenging due to their small size and difficulty in manipulation. Herein, we demonstrate isolation of cyst-like 3D cultures by capillarity and subsequent integration with the organic electrochemical transistor for monitoring the integrity of these structures. We show not only that this versatile device can be adapted to the cyst format for measuring resistance and, therefore, the quality of the cysts, but also can be used for quantitative monitoring of the effect of toxic compounds on cells in a 3D format. The ability to quantitatively predict effects of drugs on 3D cultures in vitro has large future potential for the fields of drug discovery and toxicology.

Highlights

Organotypic three-dimensional (3D) cell culture models have the potential to act as surrogate tissues in vitro, both for basic research and for drug discovery/toxicology. 3D cultures maintain 3D architecture and cell-cell and cell extracellular matrix interactions, when grown in cysts or spheroids
There is an increasing awareness that growth of cells in 2D cultures does not accurately mimic the three dimensional (3D) environment found in vivo.1 3D culture models have been proposed as surrogate tissues, since these types of culture systems mimic both 3D architecture for cell growth and maintain cell-cell and cell-extracellular matrix (ECM) interactions
A number of commercially available electrical impedance spectroscopy (EIS) systems exist in a variety of different formats which can be roughly divided into two categories; the planar format where cells are grown directly on the top of two electrodes, and the non-planar format, where cells are grown in single or multiple layers on a porous support and electrodes are placed on either side of the cell culture.[8,10]