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3D cell models have made strides in the past decades in response to failures of 2D cultures to translate targets during the drug discovery process. Here, we report on a novel multiwell plate bioelectronic platform, namely, the e-transmembrane, capable of supporting and monitoring complex 3D cell architectures. Scaffolds made of PEDOT:PSS [poly(3,4-ethylenedioxythiophene):polystyrene sulfonate] are microengineered to function as separating membranes for compartmentalized cell cultures, as well as electronic components for real-time in situ recordings of cell growth and function. Owing to the high surface area-to-volume ratio, the e-transmembrane allows generation of deep, stratified tissues within the porous bulk and cell polarization at the apico-basal domains. Impedance spectroscopy measurements carried out throughout the tissue growth identified signatures from different cellular systems and allowed extraction of critical functional parameters. This platform has the potential to become a universal tool for biologists for the next generation of high-throughput drug screening assays.

The inherent specificity and electrochemical reversibility of enzymes poise them as the biorecognition element of choice for a wide range of metabolites. To use enzymes efficiently in biosensors, the redox centers of the protein should have good electrical communication with the transducing electrode, which requires either the use of mediators or tedious biofunctionalization approaches. We report an all-polymer micrometer-scale transistor platform for the detection of lactate, a significant metabolite in cellular metabolic pathways associated with critical health care conditions. The device embodies a new concept in metabolite sensing where we take advantage of the ion-to-electron transducing qualities of an electron-transporting (n-type) organic semiconductor and the inherent amplification properties of an ion-to-electron converting device, the organic electrochemical transistor. The n-type polymer incorporates hydrophilic side chains to enhance ion transport/injection, as well as to facilitate enzyme conjugation. The material is capable of accepting electrons of the enzymatic reaction and acts as a series of redox centers capable of switching between the neutral and reduced state. The result is a fast, selective, and sensitive metabolite sensor. The advantage of this device compared to traditional amperometric sensors is the amplification of the input signal endowed by the electrochemical transistor circuit and the design simplicity obviating the need for a reference electrode. The combination of redox enzymes and electron-transporting polymers will open up an avenue not only for the field of biosensors but also for the development of enzyme-based electrocatalytic energy generation/storage devices.

Despite recent interest in organic electrochemical transistors (OECTs), sparked by their straightforward fabrication and high performance, the fundamental mechanism behind their operation remains largely unexplored. OECTs use an electrolyte in direct contact with a polymer channel as part of their device structure. Hence, they offer facile integration with biological milieux and are currently used as amplifying transducers for bioelectronics. Ion exchange between electrolyte and channel is believed to take place in OECTs, although the extent of this process and its impact on device characteristics are still unknown. We show that the uptake of ions from an electrolyte into a film of poly(3,4-ethylenedioxythiophene) doped with polystyrene sulfonate (, Pedot: PSS) leads to a purely volumetric capacitance of 39 F/cm(3). This results in a dependence of the transconductance on channel thickness, a new degree of freedom that we exploit to demonstrate high-quality recordings of human brain rhythms. Our results bring to the forefront a transistor class in which performance can be tuned independently of device footprint and provide guidelines for the design of materials that will lead to state-of-the-art transistor performance.