Impact of contact overlap on transconductance and noise in organic electrochemical transistors

Abstract Organic electrochemical transistors (OECTs) from poly(3,4-ethylenedioxythiophene) doped with polystyrene sulfonate (PEDOT:PSS) are used as amplifying transducers for bioelectronics. Although the impact on performance of device geometry parameters such as channel area and thickness has been widely explored, the overlap between the semiconductor film and the source and drain contacts has not been considered. Here we vary this overlap and explore its impact on transconductance and noise. We show that increasing contact overlap does not alter the magnitude of the steady-state transconductance but it does decreases the cut-off frequency. Noise was found to be independent of contact overlap and to vary according to the charge noise model. The results show that high-quality contacts can be established in PEDOT:PSS OECTs with minimal overlap.</jats:p

Effect of channel thickness on noise in organic electrochemical transistors

Organic electrochemical transistors (OECTs) have been widely used as transducers in electrophysiology and other biosensing applications. Their identifying characteristic is a transconductance that increases with channel thickness, and this provides a facile mechanism to achieve high signal amplification. However, little is known about their noise behavior. Here, we investigate noise and extract metrics for the signal-to-noise ratio and limit of detection in OECTs with different channel thicknesses. These metrics are shown to improve as the channel thickness increases, demonstrating that OECTs can be easily optimized to show not only high amplification, but also low noise.</jats:p

A Na+ conducting hydrogel for protection of organic electrochemical transistors.

Organic electrochemical transistors (OECTs) are being intensively developed for applications in electronics and biological interfacing. These devices rely on ions injected in a polymer film from an aqueous liquid electrolyte for their operation. However, the development of solid or semi-solid electrolytes are needed for future integration of OECTs into flexible, printed or conformable bioelectronic devices. Here, we present a new polyethylene glycol hydrogel with high Na+ conductivity which is particularly suitable for OECTs. This novel hydrogel was synthesized using cost-effective photopolymerization of poly(ethylene glycol)-dimethacrylate and sodium acrylate. Due to the high water content (83% w/w) and the presence of free Na+, the hydrogel showed high ionic conductivity values at room temperature (10-2 S cm-1) as characterized by electrochemical impedance spectroscopy. OECTs made using this hydrogel as a source of ions showed performance that was equivalent to that of OECTs employing a liquid electrolyte. They also showed improved stability, with only a 3% drop in current after 6 h of operation. This hydrogel paves the way for the replacement of liquid electrolytes in high performance OECTs bringing about advantages in terms of device integration and protection

3D Printed Microfluidic Device with Integrated Biosensors for Online Analysis of Subcutaneous Human Microdialysate

We thank the EPSRC (EP/H009744/1) and Wellcome Trust DOH (HICF-0510-080) for fundin

A planar impedance sensor for 3D spheroids.

Three dimensional cell culture systems have witnessed rapid expansion in the fields of tissue engineering and drug testing owing to their inherent ability to mimic native tissue microenvironments. High throughput technologies have also facilitated rapid and reproducible generation of spheroids and subsequently their use as in vitro tissue models in drug screening platforms. However, drug screening technologies are in need of monitoring platforms to study these 3D culture models. In this work we present a novel platform to measure the electrical impedance of 3D spheroids, through the use of a planar organic electrochemical transistor (OECT) and a novel circular-shaped microtrap. A new strategy was generated to overcome incompatibility of the integration of polydimethylsiloxane (PDMS) microdevices with OECT fabrication. The impedance platform for 3D spheroids was tested by using spheroids formed from mono-cultures of fibroblast and epithelial cells, as well as co-culture of the two cell types. We validated the platform by showing its ability to measure the spheroid resistance (Rsph) of the 3D spheroids and differences in Rsph were found to be related to the ion permeability of the spheroid. Additionally, we showed the potential use of the platform for the on-line Rsph monitoring when a co-culture spheroid was exposed to a porogenic agent affecting the integrity of the cell membrane

Quantitative Assessment of Whole-Body Tumor Burden in Adult Patients with Neurofibromatosis

Patients with neurofibromatosis 1 (NF1), NF2, and schwannomatosis are at risk for multiple nerve sheath tumors and premature mortality. Traditional magnetic resonance imaging (MRI) has limited ability to assess disease burden accurately. The aim of this study was to establish an international cohort of patients with quantified whole-body internal tumor burden and to correlate tumor burden with clinical features of disease.We determined the number, volume, and distribution of internal nerve sheath tumors in patients using whole-body MRI (WBMRI) and three-dimensional computerized volumetry. We quantified the distribution of tumor volume across body regions and used unsupervised cluster analysis to group patients based on tumor distribution. We correlated the presence and volume of internal tumors with disease-related and demographic factors.WBMRI identified 1286 tumors in 145/247 patients (59%). Schwannomatosis patients had the highest prevalence of tumors (P = 0.03), but NF1 patients had the highest median tumor volume (P = 0.02). Tumor volume was unevenly distributed across body regions with overrepresentation of the head/neck and pelvis. Risk factors for internal nerve sheath tumors included decreasing numbers of café-au-lait macules in NF1 patients (P = 0.003) and history of skeletal abnormalities in NF2 patients (P = 0.09). Risk factors for higher tumor volume included female gender (P = 0.05) and increasing subcutaneous neurofibromas (P = 0.03) in NF1 patients, absence of cutaneous schwannomas in NF2 patients (P = 0.06), and increasing age in schwannomatosis patients (p = 0.10).WBMRI provides a comprehensive phenotype of neurofibromatosis patients, identifies distinct anatomic subgroups, and provides the basis for investigating molecular biomarkers that correlate with unique disease manifestations

Nf2/Merlin controls spinal cord neural progenitor function in a Rac1/ErbB2-dependent manner

Objective: Individuals with the neurofibromatosis type 2 (NF2) cancer predisposition syndrome develop spinal cord glial tumors (ependymomas) that likely originate from neural progenitor cells. Whereas many spinal ependymomas exhibit indolent behavior, the only treatment option for clinically symptomatic tumors is surgery. In this regard, medical therapies are unfortunately lacking due to an incomplete understanding of the critical growth control pathways that govern the function of spinal cord (SC) neural progenitor cells (NPCs). Methods: To identify potential therapeutic targets for these tumors, we leveraged primary mouse Nf2-deficient spinal cord neural progenitor cells. Results: We demonstrate that the Nf2 protein, merlin, negatively regulates spinal neural progenitor cell survival and glial differentiation in an ErbB2-dependent manner, and that NF2-associated spinal ependymomas exhibit increased ErbB2 activation. Moreover, we show that Nf2-deficient SC NPC ErbB2 activation results from Rac1-mediated ErbB2 retention at the plasma membrane. Significance: Collectively, these findings establish ErbB2 as a potential rational therapeutic target for NF2-associated spinal ependymoma

A planar impedance sensor for 3D spheroids.

Three dimensional cell culture systems have witnessed rapid expansion in the fields of tissue engineering and drug testing owing to their inherent ability to mimic native tissue microenvironments. High throughput technologies have also facilitated rapid and reproducible generation of spheroids and subsequently their use as in vitro tissue models in drug screening platforms. However, drug screening technologies are in need of monitoring platforms to study these 3D culture models. In this work we present a novel platform to measure the electrical impedance of 3D spheroids, through the use of a planar organic electrochemical transistor (OECT) and a novel circular-shaped microtrap. A new strategy was generated to overcome incompatibility of the integration of polydimethylsiloxane (PDMS) microdevices with OECT fabrication. The impedance platform for 3D spheroids was tested by using spheroids formed from mono-cultures of fibroblast and epithelial cells, as well as co-culture of the two cell types. We validated the platform by showing its ability to measure the spheroid resistance (Rsph) of the 3D spheroids and differences in Rsph were found to be related to the ion permeability of the spheroid. Additionally, we showed the potential use of the platform for the on-line Rsph monitoring when a co-culture spheroid was exposed to a porogenic agent affecting the integrity of the cell membrane

Molecularly selective nanoporous membrane-based wearable organic electrochemical device for noninvasive cortisol sensing

Wearable biosensors have emerged as an alternative evolutionary development in the field of healthcare technology due to their potential to change conventional medical diagnostics and health monitoring. However, a number of critical technological challenges including selectivity, stability of (bio)recognition, efficient sample handling, invasiveness, and mechanical compliance to increase user comfort must still be overcome to successfully bring devices closer to commercial applications. We introduce the integration of an electrochemical transistor and a tailor-made synthetic and biomimetic polymeric membrane, which acts as a molecular memory layer facilitating the stable and selective molecular recognition of the human stress hormone cortisol. The sensor and a laser-patterned microcapillary channel array are integrated in a wearable sweat diagnostics platform, providing accurate sweat acquisition and precise sample delivery to the sensor interface. The integrated devices were successfully used with both ex situ methods using skin-like microfluidics and on human subjects with on-body real-sample analysis using a wearable sensor assembly

When Bio Meets Technology: Biohybrid Neural Interfaces

The development of electronics capable of interfacing with the nervous system is a rapidly advancing field with applications in basic science and clinical translation. Devices containing arrays of electrodes can be used in the study of cells grown in culture or can be implanted into damaged or dysfunctional tissue to restore normal function. While devices are typically designed and used exclusively for one of these two purposes, there have been increasing efforts in developing implantable electrode arrays capable of housing cultured cells, referred to as biohybrid implants. Once implanted, the cells within these implants integrate into the tissue, serving as a mediator of the electrode–tissue interface. This biological component offers unique advantages to these implant designs, providing better tissue integration and potentially long-term stability. Herein, an overview of current research into biohybrid devices, as well as the historical background that led to their development are provided, based on the host anatomical location for which they are designed (CNS, PNS, or special senses). Finally, a summary of the key challenges of this technology and potential future research directions are presented