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

Abstract

Benchtop tissue cultures have become increasingly complex in recent years, as more “on-a-chip” biological technologies such as Microphysiological Systems (MPSs) work to incorporate cellular constructs that more accurately represent their respective biological systems. Such MPSs have begun providing major breakthroughs in biological research and are poised to shape the field in the coming decades. These biological systems necessitate integrated sensing modalities to procure complex, multiplexed datasets, with unprecedented combinatorial biological detail. In this work we expand on our polymer-metal biosensor approach by demonstrating a facile technology towards compound biosensing which are characterized through custom modeling approaches. Herein we develop a compound chip with 3D microelectrodes, 3D microfluidics, Interdigitated Electrodes (IDEs) and a micro-heater. The chip is subsequently tested using electrical/electrochemical characterization of 3D microelectrodes with 1kHz impedance and phase recordings, and IDE-based high frequency (~ 1MHz frequencies) impedimetric analysis of differential localized temperature recordings, both of which are modelled through equivalent electrical circuits for process parameter extraction. Additionally, a simplified antibody-conjugation strategy was employed for a similar IDE-based analysis of the implications for a key analyte (L-Glutamine) binding on the equivalent electrical circuit. Lastly, acute microfluidic perfusion modelling was performed to demonstrate ease of microfluidics integration into such a polymer-metal biosensor platform for potential complimentary localized chemical stimulation. Combined, our work demonstrates the design, development, and characterization of an accessibly designed, polymer-metal compound biosensor for electrogenic cellular constructs, geared towards comprehensive MPS data collection.

Advances in sensor developments for cell culture monitoring

“…[17][18][19]34,[58][59][60][61] However, the most common approaches toward the cell-to-culture ware interface impedimetric sensing target involve cell contact or motile ability. [47,62,63] One example is Rapier et al reported a simple and intrinsic microfluidic sensory system based on impedimetric sensing for determining cell location and confluency. [23] The developed method was integrated with four bands of gold electrodes spanning the width of 500-μm-widemicrofluidic channels.…”