Organic transistor platform with integrated microfluidics for in-line multi-parametric in vitro cell monitoring

Abstract

Future drug discovery and toxicology testing could benefit significantly from more predictive and multi-parametric readouts from in vitro models. Despite the recent advances in the field of microfluidics, and more recently organ-on-a-chip technology, there is still a high demand for real-time monitoring systems that can be readily embedded with microfluidics. In addition, multi-parametric monitoring is essential to improve the predictive quality of the data used to inform clinical studies that follow. Here we present a microfluidic platform integrated with in-line electronic sensors based on the organic electrochemical transistor. Our goals are twofold, first to generate a platform to host cells in a more physiologically relevant environment (using physiologically relevant fluid shear stress (FSS)) and second to show efficient integration of multiple different methods for assessing cell morphology, differentiation, and integrity. These include optical imaging, impedance monitoring, metabolite sensing, and a wound-healing assay. We illustrate the versatility of this multi-parametric monitoring in giving us increased confidence to validate the improved differentiation of cells toward a physiological profile under FSS, thus yielding more accurate data when used to assess the effect of drugs or toxins. Overall, this platform will enable high-content screening for in vitro drug discovery and toxicology testing and bridges the existing gap in the integration of in-line sensors in microfluidic devices.

Real‐Time Monitoring of Glucose Export from Isolated Chloroplasts Using an Organic Electrochemical Transistor

“…Until now no direct detection of biomolecules from cells or organelles has been reported. In in vitro cell studies, for example, the sensor is decoupled from the cell culture and is used as a stand‐alone system …”

Balancing Ionic and Electronic Conduction for High‐Performance Organic Electrochemical Transistors

“…An OECT is an electrochemical device that shows great technological potential for sensing biochemical molecules, monitoring or stimulating cell activity, and also for use as a building block in neuromorphic devices . OECTs are three‐terminal devices in which a conjugated polymer thin‐film channel is patterned between two metal electrodes (drain and source) ( Figure a).…”

Three‐Dimensional (3D) cell culture monitoring: Opportunities and challenges for impedance spectroscopy

“…Field effect transistors (FETs) and light‐addressable potentiometric sensors (LAPs) have emerged as useful sensors capable of detecting cellular metabolic products and provide effective spatial resolution within 2D cell culture systems. FETs are generally comprised of an ion‐permeable membrane that is integrated between the source and drain to allow for measurement of extracellular ion concentrations and cellular respiration, while LAPs allow for pH measurements of cells by recording changes in photocurrent (Curto et al, 2017; Dantism, Takenaga, Wagner, Wagner, & Schöning, 2015; Poghossian, Ingebrandt, Offenhäusser, & Schöning, 2009). Photocurrent changes measured by LAPs have also been used to monitor wound healing 2D cultures (Wagner et al, 2016).…”