SeedEZ^TMInterdigitated Electrodes and Multifunctional Layered Biosensor Composites (MLBCs): A Paradigm Shift in the Development ofIn VitroBioMicrosystems

Abstract

We have developed a new technology for the realization of composite biosensor systems, capable of measuring electrical and electrophysiological signals from electrogenic cells, using SeedEZ™ 3D cell culture-scaffold material. This represents a paradigm-shift for BioMEMS processing; 'Biology-Microfabrication' versus the standard 'Microfabrication-Biology' approach. An Interdigitated Electrode (IDE) developed on the 3D cell-scaffold was used to successfully monitor acute cardiomyocyte growth and controlled population decline. We have further characterized processability of the 3D scaffold, demonstrated long-term biocompatibility of the scaffold with various cell lines and developed a multifunctional layered biosensor composites (MLBCs) using SeedEZ™ and other biocompatible substrates for future multilayer sensor integration.

A 3D Cell Culture Organ-on-a-Chip Platform With a Breathable Hemoglobin Analogue Augments and Extends Primary Human Hepatocyte Functions in vitro

“…SeedEZ is optimized for long-term growth of 3D cell cultures and complex 3D co-culture models of brain, cancer, liver, bone, connective tissues, etc. (Roberts et al, 2018;Shoemaker et al, 2018;Vukasinovic et al, 2018;Lang et al, 2019;Xiong et al, 2019;Didier et al, 2020;Jensen and Teng, 2020), and as shown herein for weeks-long growth of HepG2 cells, a hepatocellular carcinoma liver cell line (Figure 2). SeedEZ scaffolds are easy to handle.…”

“…9,334,473), that is fixed in place at approximately mid-height of the well. SeedEZ is a 500 µm thick, transparent, hydrophilic, glass micro-fiber scaffold in which cells can be seeded in medium or hydrogel to encourage both cadherinmediated cell-cell and integrin-mediated cell-extracellular matrix (ECM) signaling (Didier et al, 2020). SeedEZ is optimized for long-term growth of 3D cell cultures and complex 3D co-culture models of brain, cancer, liver, bone, connective tissues, etc.…”

Microfabricated Polymer-Metal Biosensors For Multifarious Data Collection From Electrogenic Cellular Models

“…Together, this work serves to demonstrate accessible approaches to the development of polymer-metal fabrications for biosensor applications, and how impedimetric data coupled with equivalent circuit analysis can result in novel multifarious data from the platform technology. The authors acknowledge that all modalities described herein are not utilized in a combinatorial fashion, however interested readers may nd them practically utilized in other collaborative works from our group 5,13,35 . COMSOL micro uidic modelling of the device with a constant 8Pa applied pressure.…”

“…With respect to compound sensing modalities, electrical impedance 2 , electrochemical 12 and electrophysiological 13,14 measurements could increase the collection of data from a single platform chip utilizing similar readout methodologies (such as impedimetric frequency sweeps). 3D microelectrodes are a common component of next generation toolsets for cellular interrogation 4,15 .…”

Microfabricated polymer-metal biosensors for multifarious data collection from electrogenic cellular models

“…With respect to compound sensing modalities, electrical impedance 2 , electrochemical 12 , and electrophysiological 13 , 14 measurements utilizing similar readout methodologies (such as impedimetric frequency sweeps) increase the collection of data from a single platform chip. Three-dimensional (3D) microelectrodes are a common component of next-generation toolsets for cellular interrogation 4 , 15 .…”