A stretchable Micro-Electrode Array for in vitro electrophysiology

Abstract

A novel stretchable Micro-Electrode Array (MEA) for biomedical applications with robust spiraled interconnects and radial micro-grooves for cell alignment is presented, enabling the unique combination of alignment, mechanical stimulation, and electrical characterization of living cells. Many of the problems normally associated with the fabrication of interconnects and electrodes on stretchable PDMS (Polydimethylsiloxane) membranes have been eliminated by first fabricating the interconnects and then spin-coating the PDMS. Experiments supported by Finite Element simulations demonstrate the robustness of the new spiraled interconnect design. The alignment of cells to micro-molded grooves is demonstrated, allowing for directional stretching of the cells.

Small molecule absorption by PDMS in the context of drug response bioassays

“…Soft polymer substrates like polydimethylsiloxane (PDMS) are preferred by bioengineers because they can be used to fabricate microfluidic channels, flexible membranes and provide topological cues to recapitulate blood vessels, mechanical tissue strain and induce cell orientation [8], [9], [10]. Furthermore, sensors that measure electrical activity, metabolic behavior, ion transport and force of contraction can be integrated as readouts [2], [11]. PDMS-based Organ-on-Chip devices can also be used for live cell imaging and are compatible with immunoassays, disease phenotyping and drug testing [12], [13].…”

“…Soft polymer-based microfluidic assays have long been used for multiple biological purposes [14] but PDMS most commonly because of its biocompatibility, transparency, ease of microfabrication, molding properties and tunable substrate mechanics [15]. Its elasticity has made it particularly useful in mimicking tissues that undergo cyclic stretch and strain in the body, such as the lungs or heart [2], [8], [11]. One of its drawbacks, however, is its absorption of compounds added to culture medium in bioassays, most particularly, hydrophobic small molecules like many drugs [16], [17], [18].…”

Cytostretch, an Organ-on-Chip Platform

“…A stretchable electrode-containing Cytostretch membrane can be inserted into culture devices [ 12 , 25 ]. The stretchable membrane consists of an array of 12 titanium nitride (TiN) electrodes embedded in the PDMS membrane.…”

“…The readout of the field potential of the hPSC-CMs is performed with a Multi Channel System (MCS) USB-MEA-System. Cytostretch interfaces with this system through a printed circuit board as presented in [ 12 , 25 ].…”

“…Twelve electrodes with a minimum geometric surface area (GSA) of 50 µm 2 can be fabricated, although, for this application, electrodes with a 110 µm 2 GSA were chosen. The maximum number of electrodes included in the Cytostretch membrane is defined by the width of the interconnect tracks in the dog-bone-shaped membrane, as presented by Pakazad et al [ 12 , 25 ]. The hPSC-CMs plated on the Cytostretch started beating spontaneously within three days, demonstrating their viability and functionality.…”