Using white noise to gate organic transistors for dynamic monitoring of cultured cell layers.

Jonathan Rivnay,Roisin M Owens,Miriam Huerta,Marc Ramuz,Pierre Leleux,George G Malliaras,Adel Hama

doi:10.1038/srep11613

Abstract

Impedance sensing of biological systems allows for monitoring of cell and tissue properties, including cell-substrate attachment, layer confluence, and the “tightness” of an epithelial tissue. These properties are critical for electrical detection of tissue health and viability in applications such as toxicological screening. Organic transistors based on conducting polymers offer a promising route to efficiently transduce ionic currents to attain high quality impedance spectra, but collection of complete impedance spectra can be time consuming (minutes). By applying uniform white noise at the gate of an organic electrochemical transistor (OECT), and measuring the resulting current noise, we are able to dynamically monitor the impedance and thus integrity of cultured epithelial monolayers. We show that noise sourcing can be used to track rapid monolayer disruption due to compounds which interfere with dynamic polymerization events crucial for maintaining cytoskeletal integrity, and to resolve sub-second alterations to the monolayer integrity.

Highlights

Usually exposure time required by the experiment/camera which may be in the millisecond range for more routine techniques, but in the second range for newer techniques such as PALM or STORM which attempt to improve the spatial resolution into the low nanometer range[6]
This is interesting for monitoring of cellular responses to stimuli that may occur on the msec or sec time regime, where important information may be lost due to limitations in the measurement techniques
The geometry (50 × 50 μ m2, ~130 nm thick) of the organic electrochemical transistors (OECTs) is selected such that the maximum transconductance is attained at VG = 0 V, so that the applied gate noise requires no offset, and excessive biasing across the cell monolayer can be minimized[23]

Summary

Introduction

Usually exposure time required by the experiment/camera which may be in the millisecond range for more routine techniques, but in the second range for newer techniques such as PALM (photo-activated localization microscopy) or STORM (stochastical optical reconstruction microscopy) which attempt to improve the spatial resolution into the low nanometer range[6]. Applying a signal which instantaneously contains a broad frequency range is advantageous for dynamic monitoring In this case, a pulse, step, or white noise can be most beneficial. Our group demonstrated the ability to combine measurements of gate and drain current of an OECT to assemble broad-band impedance spectra of cultured epithelial monolayers[20]. Such an approach relies on harmonic frequency sweeps common to most EIS implementations. The data collection and analysis described allows for detection of early, fast (subsecond), and potentially subtle biological changes/disruption in response to internal/external stresses or toxic compounds

Methods

Results

Conclusion