in-vitro-multiparametric-cellular-analysis-micro-organic-charge

<em>In Vitro</em> Multiparametric Cellular Analysis by Micro Organic Charge-modulated Field-effect Transistor Arrays

Modern electrophysiology has been constantly fueled by the parallel development of increasingly sophisticated tools and materials. In turn, discoveries in ...

University of Cagliari

In this study, a novel approach to the fabrication of a multimodal temperature and force sensor on ultrathin, conformable and flexible substrates is presented. This process involves coupling a charge-modulated organic field-effect transistor (OCMFET) with a pyro/piezoelectric element, namely a commercial film of poly-vinylene difluoride (PVDF). The proposed device is able to respond to both pressure stimuli and temperature variations, demonstrating the feasibility of the approach for the development of low-cost, highly sensitive and conformable multimodal sensors. The overall thickness of the device is 1.2 μm, being thus able to conform to any surface (including the human body), while keeping its electrical performance. Furthermore, it is possible to discriminate between simultaneously applied temperature and pressure stimuli by coupling sensing surfaces made of poled and unpoled spin-coated PVDF-trifluoroethylene (PVDF-TrFE, a PVDF copolymer) with OCMFETs. This demonstrates the possibility of creating multimodal sensors that can be employed for applications in several fields, ranging from robotics to wearable electronics.

Ultrathin, flexible and multimodal tactile sensors based on organic field-effect transistors.

Since their introduction in the early 1970s, microelectrode arrays (MEAs) have been dominating the electrophysiology market thanks to their reliability, extreme robustness, and usability. Over the past 40 years, silicon technology has also played a role in the advancement of the field, and CMOS-based in vitro and in vivo systems are now able to achieve unprecedented spatial resolutions, giving the possibility to unveil hidden behavior of cellular aggregates down to the subcellular level. However, both the MEAs and silicon-based electronic devices present unavoidable problems such as their expensiveness, the usual rigidity of the employed materials, and the need of an (usually bulky) external reference electrode. Possible interesting alternatives to these incredibly useful devices unexpectedly lie in the field of organic electronics, thanks to the fast-growing pace of improvement that this discipline has undergone in the last 10-15 years. In this chapter, a particular organic transistor called organic charge-modulated field-effect transistor (OCMFET) will be presented as a promising bio-electronic interface, and a complete description of its employment as a detector of cellular electrical activity and as an ultrasensitive pH sensor will be provided, together with the discussion about the possibility of using such a device as an innovative multisensing tool for both electrophysiology and (neuro)pharmacology.

From MEAs to MOAs: The Next Generation of Bioelectronic Interfaces for Neuronal Cultures.

The ability to modify substrates with thin polymer films allows for the tailoring of surface properties, and through combination of patterning finds use in a large variety of applications such as electronics and lab-on-chip devices. Although many techniques can be used to afford polymer-modified surfaces such as surface-initiated polymerization or layer-by-layer methodologies, their stability in a wide range of environments as well as their ability to target specific chemistry are critical factors to enable their successful application. In this paper, we report a facile technique in creating nanoscale polymer thin films using solid-state continuous assembly of polymers via ring-opening metathesis polymerization (ssCAP) directly from surfaces functionalized through silanization. Using a polymeric precursor that includes norbornene moieties, a highly dense cross-linked network of polymer can be grown in a bottom-up fashion to afford thin films from an olefin-terminated silanized planar surface. Such nanotechnology affords films retaining the desirable qualities of previously reported methods while, at the same time, being covalently bound to the substrate: they are virtually pinhole free and can be reinitiated multiple times. By combining this process with microcontact printing, patterned films can be created by either the patterned deposition of a catalyst or by controlling the surface silanization chemistry and placement of olefin-terminated and nonreactive silanes. Additionally, patterned ssCAP films were grown from SU-8 by selectively functionalizing the surface through masking and lift-off processes after the silanization step, thereby spatially controlling the surface-initiation, and subsequent polymer film formation. These patterned films expand the capabilities of the CAP process and offer advantages over other film formation techniques in processes where patterned substrates and modified but robust surface chemistries are utilized.

Growing Patterned, Cross-linked Nanoscale Polymer Films from Organic and Inorganic Surfaces Using Ring-Opening Metathesis Polymerization.

The ability of field effect transistors (FETs) to detect charge variations on the gate may be exploited for realizing chemo- and bio-sensors. In this paper, we focus our attention on a particular kind of field effect device, named organic charge modulated FETs, whose features can be optimized for charge detection in liquid solutions. The results of the measurement of different bio-related effects are shown. In particular, DNA hybridization and pH detection in liquid media are proposed. Finally, preliminary considerations about the applicability of these devices to the detection of the electrical activity of cells are also provided. The device has considerable potential for being employed as a reliable, high sensitivity, low cost technology for sensing signals derived from living systems.

Charge sensing by organic charge-modulated field effect transistors: application to the detection of bio-related effects.

In this paper, we report on the development of an easy-to-fabricate three-dimensional Micro-Electrode Array (3D-MEA) specifically designed for brain-on-a-dish applications.

A three-dimensional micro-electrode array for in-vitro neuronal interfacing.

Recently, organic bioelectronics has attracted considerable interest in the scientific community. The impressive growth that it has undergone in the last 10 years has allowed the rise of the completely new field of cellular organic bioelectronics, which has now the chance to compete with consolidated approaches based on devices such as micro-electrode arrays and ISFET-based transducers both in in vitro and in vivo experimental practice. This review focuses on cellular interfaces based on organic active devices and has the intent of highlighting the recent advances and the most innovative approaches to the ongoing and everlasting challenge of interfacing living matter to the "external world" in order to unveil the hidden mechanisms governing its behavior. Device-wise, three different organic structures will be considered in this work, namely the organic electrochemical transistor (OECT), the solution-gated organic transistor (SGOFET - which is presented here in two possible different versions according to the employed active material, namely: the electrolyte-gated organic transistor - EGOFET, and the solution gated graphene transistor - gSGFET), and the organic charge modulated field effect transistor (OCMFET). Application-wise, this work will mainly focus on cellular-based biosensors employed in in vitro and in vivo cellular interfaces, with the aim of offering the reader a comprehensive retrospective of the recent past, an overview of the latest innovations, and a glance at the future prospects of this challenging, yet exciting and still mostly unexplored scientific field.

Article	Year
Ultrathin, flexible and multimodal tactile sensors based on organic field-effect transistors. Scientific reports\| PubMed ID: 29795264	2018
From MEAs to MOAs: The Next Generation of Bioelectronic Interfaces for Neuronal Cultures. Advances in neurobiology\| PubMed ID: 31073935	2019
Growing Patterned, Cross-linked Nanoscale Polymer Films from Organic and Inorganic Surfaces Using Ring-Opening Metathesis Polymerization. ACS applied materials & interfaces\| PubMed ID: 31741381	2020
Charge sensing by organic charge-modulated field effect transistors: application to the detection of bio-related effects. Journal of materials chemistry. B\| PubMed ID: 32261134	2013
A three-dimensional micro-electrode array for in-vitro neuronal interfacing. Journal of neural engineering\| PubMed ID: 32480394	2020
Interfacing cells with organic transistors: a review of in vitro and in vivo applications. Lab on a chip\| PubMed ID: 33565540	2021

Andrea Spanu

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