Abstract

Using integrated silicon micromachining and thin-film technology, the fabrication of electrically functionalized microsieves for the study of 3D neuronal cell networks in vitro was a major challenge and is still very expensive at the current scale of device production, which is limited to fundamental research. Also, thin-film sidewall electrodes are in contact with the neurons and the microsieves need to be rigorously cleaned prior to reuse or the expensively integrated culture platform must be discarded. To simplify such microsieve studies on neuronal cell networks, we started analysis by optical techniques on polymer microsieves, which also proved to be valuable in our previous studies. Knowing the distribution of cells throughout the pores of the sieve, however, will enhance statistical relevance of these biological experiments. Hence, here, we present the feasibility study on a new technical concept for a cost-effective, fast, and reusable electrical platform to monitor the cell placement distribution in single-use 3D microsieves by a hybrid assembly approach in a label-free manner. The proposed system, having 3D electrodes integrated with microsieves, was compared with the thin-film sidewall electrodes that touch cells in a 3D simulation platform. Although a relatively thick and tapered insulating layer exists between cells and electrodes in the proposed 3D pluggable system, an impedance variation ratio of 3.4% on a measurable based impedance of ∼59 kΩ was obtained in these simulations and is very similar to the values for sidewall electrodes.

Highlights

  • The first technique to achieve in vitro cell culture was developed by Ross Harrison in the first decade of the twentieth century

  • In the past three decades, achievement of cell culturing on microelectromechanical systems (MEMS)-based devices, such as early developments of microelectrode arrays (MEAs), micro total analysis systems, and lab-on-a-chip, offers a great number of interactive analysis techniques to unravel tissue physiology

  • The polymer-based microsieve part will be pluggable and cost-effective, which means that it can complement a relatively expensive 3D electrode apparatus used for the impedance measurement in a high-throughput and robust cell culture microenvironment

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Summary

INTRODUCTION

The first technique to achieve in vitro cell culture was developed by Ross Harrison in the first decade of the twentieth century. In the past three decades, achievement of cell culturing on microelectromechanical systems (MEMS)-based devices, such as early developments of microelectrode arrays (MEAs), micro total analysis systems, and lab-on-a-chip, offers a great number of interactive analysis techniques to unravel tissue physiology This type of integrated devices enables far more efficient analytical methods than conventional cell culture systems.. In this study, the concept and feasibility of a rapid and label-free platform to monitor the cell placement distribution in a real-time manner by containing 3D electrodes is introduced In this platform, the polymer-based microsieve part will be pluggable and cost-effective, which means that it can complement a relatively expensive 3D electrode apparatus used for the impedance measurement in a high-throughput and robust. The designed impedance sensors will be reusable for the large number of microsieve cultures that are generally needed in a biological study without any rigorous cleaning steps by means of the elimination of cell-electrode touching interfaces

Concept of the proposed platform
Working principle of the proposed platform
FEM simulations
SUMMARY AND CONCLUSIONS
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