Microfluidics Integration into Low-Noise Multi-Electrode Arrays.

Mafalda Ribeiro,Paulo R F Rocha,Pamela Ali,Benjamin Metcalfe,Despina Moschou

doi:10.3390/mi12060727

Mafalda Ribeiro, Paulo R F Rocha + Show 3 more

Open Access

https://doi.org/10.3390/mi12060727

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Journal: Micromachines	Publication Date: Jun 20, 2021
Citations: 6	License type: CC BY 4.0

Affiliation: University of Bath, University of Coimbra

Abstract

Organ-on-Chip technology is commonly used as a tool to replace animal testing in drug development. Cells or tissues are cultured on a microchip to replicate organ-level functions, where measurements of the electrical activity can be taken to understand how the cell populations react to different drugs. Microfluidic structures are integrated in these devices to replicate more closely an in vivo microenvironment. Research has provided proof of principle that more accurate replications of the microenvironment result in better micro-physiological behaviour, which in turn results in a higher predictive power. This work shows a transition from a no-flow (static) multi-electrode array (MEA) to a continuous-flow (dynamic) MEA, assuring a continuous and homogeneous transfer of an electrolyte solution across the measurement chamber. The process through which the microfluidic system was designed, simulated, and fabricated is described, and electrical characterisation of the whole structure under static solution and a continuous flow rate of 80 µL/min was performed. The latter reveals minimal background disturbance, with a background noise below 30 µVpp for all flow rates and areas. This microfluidic MEA, therefore, opens new avenues for more accurate and long-term recordings in Organ-on-Chip systems.

Highlights

The microfluidic multi-electrode array (MEA) developed for the purposes of this study was designed to ensure both continuous and uniform flow of growth medium across the complete surface of the chip
Alternative geometries were designed via COMSOL, and the concentration profile was modelled considering an inlet flow rate of 100 μL/min
Electrical characterisation were performed on the chip under both static and continuous flow, indicating that an tests were performed on the chip under both static and continuous flow, indicating that increase in flow rate did not significantly influence the recoding background noise, where a an increase in flow rate did not significantly influence the recoding background noise, plateau of 30 μVpp was maintained

Summary

Introduction

The high cost of drug development commonly arises from the low success rate of clinically applicable drugs during the development stage. It takes on average 10–12 years [1] to develop a new drug, with two-thirds of the total costs ascribed to the clinical trial stage [2]. In order to reduce these costs and, allow the more rapid introduction of effective drugs in clinical practice, it is critical that the accuracy and throughput of pre-clinical screening is significantly improved [3]. The traditional drug development route mostly relies on animal testing, which is costly, ethically contentious, and often offers poor predictive power for human response to drugs due to interspecific discrepancies [4]

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