The portability of physiological monitoring has necessitated the biocompatibility of components used in circuitry local to biological environments. A key component in processing circuitry is the linear amplifier. Amplifier circuit topologies utilize transistors, and recent advances in bioelectronics have focused on organic electrochemical transistors (OECTs). OECTs have shown the capability to transduce physiological signals at high signal‐to‐noise ratios. In this study high‐performance interdigitated electrode OECTs are implemented in a common source linear amplifier topology. Under the constraints of OECT operation, stable circuit component parameters are found, and OECT geometries are varied to determine the best amplifier performance. An equation is formulated which approximates transistor behavior in the linear, nonlinear, and saturation regimes. This equation is used to simulate the amplifier response of the circuits with the best performing OECT geometries. The amplifier figures of merit, including distortion characterizations, are then calculated using physical and simulation measurements. Based on the figures of merit, prerecorded electrophysiological signals from spreading depolarizations, electrocorticography, and electromyography fasciculations are inputted into an OECT linear amplifier. Using frequency filtering, the primary features of events in the bioelectric signals are resolved and amplified, demonstrating the capability of OECT amplifiers in bioelectronics.

Objective Recording of local field potentials (LFPs) during deep brain stimulation (DBS) is necessary to investigate the instantaneous brain response to stimulation, minimize time delays for closed-loop neurostimulation and maximise the available neural data. To our knowledge, existing recording systems lack the ability to provide artefact-free high-frequency (>100 Hz) LFP recordings during DBS in real time primarily because of the contamination of the neural signals of interest by the stimulation artefacts. Approach To solve this problem, we designed and developed a novel, low-noise and versatile analog front-end (AFE) that uses a high-order (8th) analog Chebyshev notch filter to suppress the artefacts originating from the stimulation frequency. After defining the system requirements for concurrent LFP recording and DBS artefact suppression, we assessed the performance of the realised AFE by conducting both in vitro and in vivo experiments using unipolar and bipolar DBS (monophasic pulses, amplitude ranging from 3 to 6 V peak-to-peak, frequency 140 Hz and pulse width 100 μs). A full performance comparison between the proposed AFE and an identical AFE, equipped with an 8th order analog Bessel notch filter, was also conducted. Main results A high-performance, 4 nV (Hz)−1 AFE that is capable of recording nV-scale signals was designed in accordance with the imposed specifications. Under both in vitro and in vivo experimental conditions, the proposed AFE provided real-time, low-noise and artefact-free LFP recordings (in the frequency range 0.5–250 Hz) during stimulation. Its sensing and stimulation artefact suppression capabilities outperformed the capabilities of the AFE equipped with the Bessel notch filter. Significance The designed AFE can precisely record LFP signals, in and without the presence of either unipolar or bipolar DBS, which renders it as a functional and practical AFE architecture to be utilised in a wide range of applications and environments. This work paves the way for the development of externalized research tools for closed-loop neuromodulation that use low- and higher-frequency LFPs as control signals.

BackgroundIt is widely accepted by the scientific community that bioelectrical signals, which can be used for the identification of neurophysiological biomarkers indicative of a diseased or pathological state, could direct patient treatment towards more effective therapeutic strategies. However, the design and realisation of an instrument that can precisely record weak bioelectrical signals in the presence of strong interference stemming from a noisy clinical environment is one of the most difficult challenges associated with the strategy of monitoring bioelectrical signals for diagnostic purposes. Moreover, since patients often have to cope with the problem of limited mobility being connected to bulky and mains-powered instruments, there is a growing demand for small-sized, high-performance and ambulatory biopotential acquisition systems in the Intensive Care Unit (ICU) and in High-dependency wards. Finally, to the best of our knowledge, there are no commercial, small, battery-powered, wearable and wireless recording-only instruments that claim the capability of recording electrocorticographic (ECoG) signals.MethodsTo address this problem, we designed and developed a low-noise (8 nV/√Hz), eight-channel, battery-powered, wearable and wireless instrument (55 × 80 mm2). The performance of the realised instrument was assessed by conducting both ex vivo and in vivo experiments.ResultsTo provide ex vivo proof-of-function, a wide variety of high-quality bioelectrical signal recordings are reported, including electroencephalographic (EEG), electromyographic (EMG), electrocardiographic (ECG), acceleration signals, and muscle fasciculations. Low-noise in vivo recordings of weak local field potentials (LFPs), which were wirelessly acquired in real time using segmented deep brain stimulation (DBS) electrodes implanted in the thalamus of a non-human primate, are also presented.ConclusionsThe combination of desirable features and capabilities of this instrument, namely its small size (~one business card), its enhanced recording capabilities, its increased processing capabilities, its manufacturability (since it was designed using discrete off-the-shelf components), the wide bandwidth it offers (0.5–500 Hz) and the plurality of bioelectrical signals it can precisely record, render it a versatile and reliable tool to be utilized in a wide range of applications and environments.

Currently, there are no valid pre-operatively established biomarkers or algorithms that can accurately predict surgical and clinical outcome for patients with advanced epithelial ovarian cancer (EOC). In this study, we suggest that profiling of tumour parameters such as bioelectrical-potential and metabolites, detectable by electronic sensors, could facilitate the future development of devices to better monitor disease and predict surgical and treatment outcomes. Biopotential was recorded, using a potentiometric measurement system, in ex vivo paired non-cancerous and cancerous omental tissues from advanced stage EOC (n = 36), and lysates collected for metabolite measurement by microdialysis. Consistently different biopotential values were detected in cancerous tissue versus non-cancerous tissue across all cases (p < 0.001). High tumour biopotential levels correlated with advanced tumour stage (p = 0.048) and tumour load, and negatively correlated with stroma. Within our EOC cohort and specifically the high-grade serous subtype, low biopotential levels associated with poorer progression-free survival (p = 0.0179, p = 0.0143 respectively). Changes in biopotential levels significantly correlated with common apoptosis related pathways. Lactate and glucose levels measured in paired tissues showed significantly higher lactate/glucose ratio in tissues with low biopotential (p < 0.01, n = 12). Our study proposes the feasibility of biopotential and metabolite monitoring as a biomarker modality profiling EOC to predict surgical and clinical outcomes.

We present Myolink, a portable, modular, low-noise electrophysiology amplifier optimized for high-density surface electromyogram (HD sEMG) acquisition. Methods: Myolink consists of 4 modules. Each 10 × 8 cm module can concurrently acquire 32 unipolar electrode potentials at sampling rates of up to 8 kHz with 24-bit resolution. Modules may be stacked and operated synchronously, supporting the concurrent acquisition of up to 128 channels. A custom high-performance analog front-end provides an input-referred-noise < 0.4 µV RMS for a bandwidth of 23-524 Hz (tuneable by design choices), which is lower than current commercial systems. Digitized signals are processed by a custom on-board FPGA-based controller and subsequently transmitted to a PC via a medical-grade isolated USB 2.0 interface. Results: The system has been tested by recording experimental HD sEMG signals, which have been subsequently decomposed into motor unit action potentials. Compared to commercially available systems, the proposed recording system led to higher-quality surface EMG acquisition, as well as higher decomposition accuracy across a wide range of forces, with the greater gain for forces ≤ 20% of the maximum voluntary contraction. Significance: A portable, ultra-lownoise, HD sEMG amplifier design has been implemented and characterized. The system provides IRN performance beyond the capabilities of current state-of-the-art instrumentation and this improvement has a significant effect on HD sEMG decomposition.