Publications
180 results found
Tageldeen MK, Pagkalos I, Ghoreishizadeh SS, et al., 2023, Analogue circuit realisation of surface-confined redox reaction kinetics, BIOSENSORS & BIOELECTRONICS, Vol: 228, ISSN: 0956-5663
Kim MY, Nesbitt J, Koutsoftidis S, et al., 2023, Immunohistochemical characteristics of local sites that trigger atrial arrhythmias in response to high frequency stimulation, EP Europace, Vol: 25, Pages: 726-738, ISSN: 1099-5129
Introduction: The response to high frequency stimulation (HFS) is used to locate putative sites of ganglionated plexuses (GPs), which are implicated in triggering atrial fibrillation (AF). Objective: To identify topological and immunohistochemical characteristics of presumed GP sites functionally identified by HFS. Methods: 63 atrial sites were tested with HFS in 4 Langendorff-perfused porcine hearts. A 3.5mm tip quadripolar ablation catheter was used to stimulate and deliver HFS to the left and right atrial epicardium, within the local atrial refractory period. Tissue samples from sites triggering atrial ectopy/AF (ET) sites and non-ET sites were stained with choline acetyl transferase (ChAT) and tyrosine hydroxylase (TH), for quantification of parasympathetic and sympathetic nerves, respectively. The average cross-sectional area (CSA) of nerves was also calculated.Results: Histomorphometry of 6 ET sites (9.5%) identified by HFS evoking at least a single atrial ectopic was compared with non-ET sites. All ET sites contained ChAT-immunoreactive (ChAT-IR) and/or TH-immunoreactive nerves (TH-IR). Nerve density was greater in ET sites compared to non-ET sites (nerves/cm2: 162.3 ±110.9 vs 69.65 ±72.48; p=0.047). Overall, TH-IR nerves had larger CSA than ChAT-IR nerves (µm2: 11,196 ± 35,141 vs 2,070 ± 5,841; p<0.0001), but in ET sites, TH-IR nerves were smaller than in non-ET sites (µm2: 6,021±14,586 vs 25,254 ± 61,499; p<0.001).Conclusions: ET sites identified by HFS contained higher density of smaller nerves than non-ET sites. Majority of these nerves were within the atrial myocardium. This has important clinical implications on devising an effective therapeutic strategy for targeting autonomic triggers of AF.
Tyrrell JE, Petkos K, Drakakis EM, et al., 2021, Organic electrochemical transistor common‐source amplifier for electrophysiological measurements, Advanced Functional Materials, Vol: 31, Pages: 1-13, ISSN: 1616-301X
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.
Tageldeen MK, Gowers SAN, Leong CL, et al., 2020, Traumatic brain injury neuroelectrochemical monitoring: behind-the-ear micro-instrument and cloud application, Journal of NeuroEngineering and Rehabilitation, Vol: 17, ISSN: 1743-0003
BACKGROUND: Traumatic Brain Injury (TBI) is a leading cause of fatality and disability worldwide, partly due to the occurrence of secondary injury and late interventions. Correct diagnosis and timely monitoring ensure effective medical intervention aimed at improving clinical outcome. However, due to the limitations in size and cost of current ambulatory bioinstruments, they cannot be used to monitor patients who may still be at risk of secondary injury outside the ICU. METHODS: We propose a complete system consisting of a wearable wireless bioinstrument and a cloud-based application for real-time TBI monitoring. The bioinstrument can simultaneously record up to ten channels including both ECoG biopotential and neurochemicals (e.g. potassium, glucose and lactate), and supports various electrochemical methods including potentiometry, amperometry and cyclic voltammetry. All channels support variable gain programming to automatically tune the input dynamic range and address biosensors' falling sensitivity. The instrument is flexible and can be folded to occupy a small space behind the ear. A Bluetooth Low-Energy (BLE) receiver is used to wirelessly connect the instrument to a cloud application where the recorded data is stored, processed and visualised in real-time. Bench testing has been used to validate device performance. RESULTS: The instrument successfully monitored spreading depolarisations (SDs) - reproduced using a signal generator - with an SNR of 29.07 dB and NF of 0.26 dB. The potentiostat generates a wide voltage range from -1.65V to +1.65V with a resolution of 0.8mV and the sensitivity of the amperometric AFE was verified by recording 5 pA currents. Different potassium, glucose and lactate concentrations prepared in lab were accurately measured and their respective working curves were constructed. Finally,the instrument achieved a maximum sampling rate of 1.25 ksps/channel with a throughput of 105 kbps. All measurements were successfully received at the cl
Bashford J, Masood U, Wickham A, et al., 2020, Fasciculations demonstrate daytime consistency in amyotrophic lateral sclerosis, Muscle and Nerve, Vol: 61, Pages: 745-750, ISSN: 0148-639X
IntroductionFasciculations represent early neuronal hyperexcitability in amyotrophic lateral sclerosis (ALS). To aid calibration as a disease biomarker, we set out to characterize the daytime variability of fasciculation firing.MethodsFasciculation awareness scores were compiled from 19 ALS patients. In addition, 10 ALS patients prospectively underwent high‐density surface electromyographic (HDSEMG) recordings from biceps and gastrocnemius at three time‐points during a single day.ResultsDaytime fasciculation awareness scores were low (mean: 0.28 muscle groups), demonstrating significant variability (coefficient of variation: 303%). Biceps HDSEMG recordings were highly consistent for fasciculation potential frequency (intraclass correlation coefficient [ICC] = 95%, n = 19) and the interquartile range of fasciculation potential amplitude (ICC = 95%, n = 19). These parameters exhibited robustness to observed fluctuations in data quality parameters. Gastrocnemius demonstrated more modest levels of consistency overall (44% to 62%, n = 20).DiscussionThere was remarkable daytime consistency of fasciculation firing in the biceps of ALS patients, despite sparse and intermittent awareness among patients’ accounts.
Zafeiropoulos GC, Drakakis EM, 2020, The neoEEG board: A 3 nV/√<i>Hz</i> multi-channel wireless instrument for neonatal EEG monitoring, MEASUREMENT, Vol: 154, ISSN: 0263-2241
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Yue X, Kiely J, Gibson D, et al., 2020, Charge-Based Supercapacitor Storage Estimation for Indoor Sub-mW Photovoltaic Energy Harvesting Powered Wireless Sensor Nodes, IEEE TRANSACTIONS ON INDUSTRIAL ELECTRONICS, Vol: 67, Pages: 2411-2421, ISSN: 0278-0046
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Bashford J, Wickham A, Iniesta R, et al., 2020, Preprocessing surface EMG data removes voluntary muscle activity and enhances SPiQE fasciculation analysis, Clinical Neurophysiology, Vol: 131, Pages: 265-273, ISSN: 1388-2457
ObjectivesFasciculations are a clinical hallmark of amyotrophic lateral sclerosis (ALS). The Surface Potential Quantification Engine (SPiQE) is a novel analytical tool to identify fasciculation potentials from high-density surface electromyography (HDSEMG). This method was accurate on relaxed recordings amidst fluctuating noise levels. To avoid time-consuming manual exclusion of voluntary muscle activity, we developed a method capable of rapidly excluding voluntary potentials and integrating with the established SPiQE pipeline.MethodsSix ALS patients, one patient with benign fasciculation syndrome and one patient with multifocal motor neuropathy underwent monthly thirty-minute HDSEMG from biceps and gastrocnemius. In MATLAB, we developed and compared the performance of four Active Voluntary IDentification (AVID) strategies, producing a decision aid for optimal selection.ResultsAssessment of 601 one-minute recordings permitted the development of sensitive, specific and screening strategies to exclude voluntary potentials. Exclusion times (0.2–13.1 minutes), processing times (10.7–49.5 seconds) and fasciculation frequencies (27.4–71.1 per minute) for 165 thirty-minute recordings were compared. The overall median fasciculation frequency was 40.5 per minute (10.6–79.4 IQR).ConclusionWe hereby introduce AVID as a flexible, targeted approach to exclude voluntary muscle activity from HDSEMG recordings.SignificanceLongitudinal quantification of fasciculations in ALS could provide unique insight into motor neuron health.
Bashford J, Wickham A, Iniesta R, et al., 2020, SPiQE: An automated analytical tool for detecting and characterising fasciculations in amyotrophic lateral sclerosis (vol 130, pg 1083, 2019), Clinical Neurophysiology, Vol: 131, Pages: 350-350, ISSN: 1388-2457
[Correction to https://doi.org/10.1016/j.clinph.2019.03.032]
Petkos K, Koutsoftidis S, Guiho T, et al., 2019, A high-performance 8 nV/√Hz 8-channel wearable and wireless system for real-time monitoring of bioelectrical signals, Journal of NeuroEngineering and Rehabilitation, Vol: 16, Pages: 1-24, ISSN: 1743-0003
Background: It 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.Methods: To 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.Results: To 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.Conclusions: The combination of desirable features and capabilities of this instrum
Petkos K, Guiho T, Degenaar P, et al., 2019, A high-performance 4 nV (√Hz)−1 analog front-end architecture for artefact suppression in local field potential recordings during deep brain stimulation, Journal of Neural Engineering, Vol: 16, ISSN: 1741-2552
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 applica
Bashford J, Wickham A, Iniesta R, et al., 2019, THE SURFACE POTENTIAL QUANTIFICATION ENGINE INTEGRATES ACTIVE VOLUNTARY IDENTIFICATION TO ENHANCE FASCICULATION ANALYSIS IN AMYOTROPHIC LATERAL SCLEROSIS, Annual Meeting of the American-Association-of-Neuromuscular-and-Electrodiagnostic-Medicine (AANEM), Publisher: WILEY, Pages: S3-S3, ISSN: 0148-639X
Bashford J, Wickham A, Iniesta R, et al., 2019, SPiQE: An automated analytical tool for detecting and characterising fasciculations in amyotrophic lateral sclerosis, Clinical Neurophysiology, Vol: 130, Pages: 1083-1090, ISSN: 1388-2457
OBJECTIVES: Fasciculations are a clinical hallmark of amyotrophic lateral sclerosis (ALS). Compared to concentric needle EMG, high-density surface EMG (HDSEMG) is non-invasive and records fasciculation potentials (FPs) from greater muscle volumes over longer durations. To detect and characterise FPs from vast data sets generated by serial HDSEMG, we developed an automated analytical tool. METHODS: Six ALS patients and two control patients (one with benign fasciculation syndrome and one with multifocal motor neuropathy) underwent 30-minute HDSEMG from biceps and gastrocnemius monthly. In MATLAB we developed a novel, innovative method to identify FPs amidst fluctuating noise levels. One hundred repeats of 5-fold cross validation estimated the model's predictive ability. RESULTS: By applying this method, we identified 5,318 FPs from 80 minutes of recordings with a sensitivity of 83.6% (+/- 0.2 SEM), specificity of 91.6% (+/- 0.1 SEM) and classification accuracy of 87.9% (+/- 0.1 SEM). An amplitude exclusion threshold (100 μV) removed excessively noisy data without compromising sensitivity. The resulting automated FP counts were not significantly different to the manual counts (p = 0.394). CONCLUSION: We have devised and internally validated an automated method to accurately identify FPs from HDSEMG, a technique we have named Surface Potential Quantification Engine (SPiQE). SIGNIFICANCE: Longitudinal quantification of fasciculations in ALS could provide unique insight into motor neuron health.
Zafeiropoulos GC, Papadimitriou K, Drakakis EM, 2018, Performance ANd ACcuracy in Electrical BioActivity Recordings (PANACEA): a high-performance, wireless, multi-instrument for potentiometric and amperometric recording of biosignals, Measurement, Vol: 129, Pages: 128-141, ISSN: 0263-2241
This paper presents the design, testing and quantitative evaluation of a high-performance, low-power, portable multi-instrument (), capable of recording important biosignals accurately and in real-time. This highly versatile system has the ability to transmit the captured bio-data back to the user either in a wired (HDMI cable) or wireless (ZigBee protocol) manner, depending on the targeted application. The biological information that can be recorded by the proposed instrument spans a wide range of bio-potentials and bio-amperometric signals. The proposed instrument is split into two complementary “sub-instruments”, where one is operating as the front-end device, responsible for the accurate, low-noise signal detection and transmission, while the second “sub-instrument” is operating as the “base station”, responsible for the collection and further processing of the captured data. For wired transmission (e.g to the user’s PC) the front end module can operate independently, however, for wireless transmission both “sub-instruments” are required (transmitter-base station architecture). For wireless transmission, each of the two “sub-instruments” is equipped with dedicated 2 Mbps ZigBee radio transceivers and both parts are controlled by a small area embedded FPGA module. The front-end device features two distinct sections: (a) a current/voltage to voltage section comprising six potentiometry and two transimpedance amplifier-based amperometry channels. These eight in total analogue channels are converted into digital form by means of a 24 bit, voltage input, Analogue-to-Digital Converter (ADC) and (b) a four channel, commercially available switched-capacitor-based ADC Integrated Circuit (IC), which converts input charge to digital data with 16 or 20 bit resolution at 3.125 kSPS. The paper presents a plethora of measured wired and wireless experimental results, corresponding to most well-known biomedical an
Soleimani H, Drakakis EM, 2018, A low-power digital IC emulating intracellular calcium dynamics, International Journal of Circuit Theory and Applications, Vol: 46, Pages: 1929-1939, ISSN: 0098-9886
Low power/area cytomorphic chips may be interfaced and ultimately implanted in the human body for cell‐sensing and cell‐control applications of the future. In such electronic platforms, it is crucial to accurately mimic the biological timescales and operate in real time. This paper proposes a methodology where slow nonlinear dynamical systems describing the behaviour of naturally encountered biological systems can be efficiently realised in hardware. To this end, as a case study, a low power and efficient digital Application‐Specific Integrated Circuit capable of emulating slow intracellular calcium dynamics with timescales reaching to seconds has been fabricated in the commercially available AMS 0.35 μm technology and compared with its analog counterpart. The fabricated chip occupies an area of 1.5 mm2 (excluding the area of the pads) and consumes 18.93 nW for each calcium unit from a power supply of 3.3 V. The presented cytomimetic topology follows closely the behaviour of its biological counterpart, exhibiting similar time‐domain calcium ions dynamics. Results show that the implemented design has the potential to speed up large–scale simulations of slow intracellular dynamics by sharing cellular units in real time.
Cunnea P, Gorgy T, Petkos K, et al., 2018, Clinical value of bioelectrical properties of cancerous tissue in advanced epithelial ovarian cancer patients, Scientific Reports, Vol: 8, Pages: 1-12, ISSN: 2045-2322
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.
Peyton G, Farzaneh B, Soleimani H, et al., 2018, Quadrature synthetic aperture beamforming front-end for miniaturized ultrasound imaging, IEEE Transactions on Biomedical Circuits and Systems, Vol: 12, Pages: 871-883, ISSN: 1932-4545
A quadrature synthetic aperture front-end receiver for B-mode ultrasound imaging is presented. The receiver targets small-scale imaging applications such as capsule endoscopy and low-cost portable devices. System complexity, area, power consumption, and cost are minimized using synthetic aperture beamforming (SAB), whereby signals are processed in a sequential manner using only a single channel. SAB is combined with quadrature (I/Q) sampling, which further reduces the bandwidth and computational load. I/Q demodulation is carried out using a full custom analog front-end (AFE), which comprises a low-noise, variable gain preamplifier, followed by a passive mixer, programmable gain amplifier (PGA) and active lowpass filter. A novel preamplifier design is proposed, with quasi-exponential time-gain control and low noise (5.42 nV√Hz input-referred noise). Overall, the AFE consumes 7.8 mW (static power) and occupies 1.5 mm × 1.5 mm in AMS 0.35 μm CMOS. Real-time SAB is carried out using a Spartan-6 FPGA, which dynamically apodises and focuses the data by interpolating and applying complex phase rotations to the I/Q samples. For a frame rate of 7 Hz, the power consumption is 3.4 mW/channel across an aperture of 64 elements. B-mode images were obtained using a database of ultrasound signals (2.5 MHz center frequency) derived from a commercial ultrasound machine. The normalized root mean squared error between the quadrature SAB image and the RF reference image was 13%. Image quality/frame rate may be tuned by varying the degree of spatial compounding.
Peyton G, Boutelle MG, Drakakis EM, 2018, Comparison of synthetic aperture architectures for miniaturised ultrasound imaging front-ends, BioMedical Engineering OnLine, Vol: 17, ISSN: 1475-925X
BackgroundPoint of care ultrasonography has been the focus of extensive research over the past few decades. Miniaturised, wireless systems have been envisaged for new application areas, such as capsule endoscopy, implantable ultrasound and wearable ultrasound. The hardware constraints of such small-scale systems are severe, and tradeoffs between power consumption, size, data bandwidth and cost must be carefully balanced.MethodsIn this work, two receiver architectures are proposed and compared to address these challenges. Both architectures uniquely combine low-rate sampling with synthetic aperture beamforming to reduce the data bandwidth and system complexity. The first architecture involves the use of quadrature sampling to minimise the signal bandwidth and computational load. Synthetic aperture beamforming (SAB) is carried out using a single-channel, pipelined protocol suitable for implementation on an FPGA/ASIC. The second architecture employs compressive sensing within the finite rate of innovation framework to further reduce the bandwidth. Low-rate signals are transmitted to a computational back-end (computer), which sequentially reconstructs each signal and carries out beamforming.ResultsBoth architectures were tested using a custom hardware front-end and synthetic aperture database to yield B-mode images. The normalised root-mean-squared-error between the quadrature SAB image and the RF reference image was 13%while the compressive SAB error was 22% for the same degree of spatial compounding. The sampling rate is reduced by a factor of 2 (quadrature SAB) and 4.7 (compressive SAB), compared to the RF sampling rate. The quadrature method is implemented on FPGA, with a total power consumption of 4.1mW, which is comparable to state-of-the-art hardware topologies, but with significantly reduced circuit area.ConclusionsThrough a novel combination of SAB and low-rate sampling techniques, the proposed architectures achieve a significant reduction in data transmission
Zafeiropoulos G, O'Hare D, Drakakis E, 2018, PANACEA 2.0: A Wireless, High-Performance Multi-instrument for (Bio)Signals Recording, BioMedEng18
Koymen I, Drakakis EM, 2018, Current-input current-output analog half center oscillator and central pattern generator circuits with memristors, International Journal of Circuit Theory and Applications, Vol: 46, Pages: 1294-1310, ISSN: 0098-9886
The comparison of the memristor to the biological synapse has motivated the introduction of memristors to biomimetic circuits such as Central Pattern Generators (CPGs) and Half Center Oscillators (HCOs). The effects of the utilization of memristors in such systems have been investigated in this work. The HCO is a neural oscillator, and the CPG is made up of 4 HCOs producing oscillations corresponding to the locomotion of a 4‐limbed animal. Analog HCO and CPG circuits have been simulated using the Cadence Virtuoso platform and effects of using current‐driven and voltage‐driven memristors in different configurations with different parameters have been analyzed. Improvement in the stability of rhythm and variations in oscillation amplitudes have been observed.
Pagkalos I, Rogers M, Boutelle MG, et al., 2018, A high-performance application specific integrated circuit for electrical and neurochemical traumatic brain injury monitoring, ChemPhysChem: a European journal of chemical physics and physical chemistry, Vol: 19, Pages: 1215-1225, ISSN: 1439-4235
This paper presents the first application specific integrated chip (ASIC) for the monitoring of patients who have suffered a Traumatic Brain Injury (TBI). By monitoring the neuralphysiological (ECoG) and neurochemical (glucose, lactate and potassium) signals of the injured human brain tissue, it is possible to detect spreading depolarisations, which have been shown to be associated with poor TBI patient outcome. This paper describes the testing of a new 7.5mm2 ASIC fabricated in the commercially available AMS 0.35μm CMOS technology. The ASIC has been designed to meet the demands of processing the injured brain tissue's ECoG signals, recorded by means of depth or brain surface electrodes, and neurochemical signals, recorded using microdialysis coupled to microfluidics-based electrochemical biosensors. The potentiostats use switched-capacitor charge integration to record currents with 100fA resolution, and allow automatic gain changing to track the falling sensitivity of a biosensor. This work supports the idea of a "behind the ear" wireless microplatform modality, which could enable the monitoring of currently non-monitored mobile TBI patients for the onset of secondary brain injury.
Yue X, Huang JV, Krapp HG, et al., 2018, An implantable mixed-signal CMOS die for battery-powered in vivo blowfly neural recordings, Microelectronics Journal, Vol: 74, Pages: 34-42, ISSN: 0026-2692
A mixed-signal die containing two differential input amplifiers, a multiplexer and a 50 KSPS, 10-bit SAR ADC, has been designed and fabricated in a 0.35 μm CMOS process for in vivo neural recording from freely moving blowflies where power supplied voltage drops quickly due to the space/weight limited insufficient capacity of the battery. The designed neural amplifier has a 66 + dB gain, 0.13 Hz-5.3 KHz bandwidth and 0.39% THD. A 20% power supply voltage drop causes only a 3% change in amplifier gain and 0.9-bit resolution degrading for SAR ADC while the on-chip data modulation reduces the chip size, rendering the designed chip suitable for battery-powered applications. The fabricated die occupies 1.1 mm2 while consuming 238 μW, being suitable for implantable neural recordings from insects as small as a blowfly for electrophysiological studies of their sensorimotor control mechanisms. The functionality of the die has been validated by recording the signals from identified interneurons in the blowfly visual system.
Boutelle MG, Gowers SAN, Hamaoui K, et al., 2018, High temporal resolution delayed analysis of clinical microdialysate streams, Analyst, Vol: 143, Pages: 715-724, ISSN: 1364-5528
This paper presents the use of tubing to store clinical microdialysis samples for delayed analysis with high temporal resolution, offering an alternative to traditional discrete offline microdialysis sampling. Samples stored in this way were found to be stable for up to 72 days at −80 °C. Examples of how this methodology can be applied to glucose and lactate measurement in a wide range of in vivo monitoring experiments are presented. This paper presents a general model, which allows for an informed choice of tubing parameters for a given storage time and flow rate avoiding high back pressure, which would otherwise cause the microdialysis probe to leak, while maximising temporal resolution.
Soleimani H, Drakakis EM, 2018, An efficient and reconfigurable synchronous neuron model, IEEE Transactions on Circuits and Systems II: Express Briefs, Vol: 65, Pages: 91-95, ISSN: 1549-7747
This brief presents a reconfigurable and efficient 2-D neuron model capable of extending to higher dimensions. The model is applied to the Izhikevich and FitzHugh-Nagumo neuron models as 2-D case studies and to the Hindmarsh-Rose model as a 3-D case study. Hardware synthesis and physical implementations show that the resulting circuits can reproduce neural dynamics with acceptable precision and considerably low hardware overhead compared to previously published piecewise linear models.
Soleimani H, Drakakis EM, 2017, A compact synchronous cellular model of nonlinear calcium dynamics: simulation and FPGA synthesis results, IEEE Transactions on Biomedical Circuits and Systems, Vol: 11, Pages: 703-713, ISSN: 1932-4545
Recent studies have demonstrated that calcium is a widespread intracellular ion that controls a widerange of temporal dynamics in the mammalian body. The simulation and validation of such studies us-ing experimental data would bene t from a fast large scale simulation and modelling tool. This paperpresents a compact and fully recon gurable cellular calcium model capable of mimicking Hopf bifurcationphenomenon and various nonlinear responses of the biological calcium dynamics. The proposed cellularmodel is synthesized on a digital platform for a single unit and a network model. Hardware synthesis,physical implementation on FPGA, and theoretical analysis con rm that the proposed cellular model canmimic the biological calcium behaviors with considerably low hardware overhead. The approach has thepotential to speed up large{scale simulations of slow intracellular dynamics by sharing more cellular unitsin real{time. To this end, various networks constructed by pipelining 10k to 40k cellular calcium units arecompared with an equivalent simulation run on a standard PC workstation. Results show that the cellularhardware model is, on average, 83 times faster than the CPU version.
Jokar E, Soleimani H, Drakakis EM, 2017, Systematic computation of nonlinear bilateral dynamical systems with a novel low-power log-domain circuit, IEEE Transactions on Circuits and Systems I: Regular Papers, Vol: 64, Pages: 2013-2025, ISSN: 1549-8328
Simulation of large-scale nonlinear dynamical systems on hardware with a high resemblance to their mathematical equivalents has been always a challenge in engineering. This paper presents a novel current-input current-output circuit supporting a systematic synthesis procedure of log-domain circuits capable of computing bilateral dynamical systems with considerably low power consumption and acceptable precision. Here, the application of the method is demonstrated by synthesizing four different case studies: 1) a relatively complex 2-D nonlinear neuron model; 2) a chaotic 3-D nonlinear dynamical system Lorenz attractor having arbitrary solutions for certain parameters; 3) a 2-D nonlinear Hopf oscillator, including bistability phenomenon sensitive to initial values; and 4) three small neurosynaptic networks comprising three FHN neuron models variously coupled with excitatory and inhibitory synapses. The validity of our approach is verified by nominal and Monte Carlo simulated results with realistic process parameters from the commercially available AMS 0.35-μm technology. The resulting continuous-time, continuous-value, and low-power circuits exhibit various bifurcation phenomena, nominal time-domain responses in good agreement with their mathematical counterparts and fairly acceptable process variation results (less than 5% STD).
Soltan A, McGovern B, Drakakis E, et al., 2017, High density, high radiance mu LED matrix for optogenetic retinal Prostheses and planar neural stimulation, IEEE Transactions on Biomedical Circuits and Systems, Vol: 11, Pages: 347-359, ISSN: 1932-4545
Optical neuron stimulation arrays are important for both in-vitro biology and retinal prosthetic biomedical applications. Hence, in this work, we present an 8100 pixel high radiance photonic stimulator. The chip module vertically combines custom made gallium nitride μLEDs with a CMOS application specific integrated circuit. This is designed with active pixels to ensure random access and to allow continuous illumination of all required pixels. The μLEDs have been assembled on the chip using a solder ball flip-chip bonding technique which has allowed for reliable and repeatable manufacture. We have evaluated the performance of the matrix by measuring the different factors including the static, dynamic power consumption, the illumination, and the current consumption by each LED. We show that the power consumption is within a range suitable for portable use. Finally, the thermal behavior of the matrix is monitored and the matrix proved to be thermally stable.
Cunnea P, Gowers S, Moore JE, et al., 2017, Novel technologies in the treatment and monitoring of advanced and relapsed epithelial ovarian cancer, Convergent Science Physical Oncology, Vol: 3, ISSN: 2057-1739
Epithelial ovarian cancer (EOC) is the fifth most common cause of cancer death in females in the UK. It has long been recognized to be a set of heterogeneous diseases, with high grade serous being the most common subtype. The majority of patients with EOC present at an advanced stage (FIGO III–IV), and have the largest risk for disease recurrence from which a high percentage will develop resistance to chemotherapy. Despite continual advances in diagnostics, imaging, surgery and treatment of EOC, there has been little variation in the survival rates for patients with EOC. In this review we will introduce novel bioengineering advances in modelling the lymphatic system and real-time tissue monitoring to improve the clinical and therapeutic outcome for patients with EOC. We discuss the advent of the non-invasive 'liquid biopsy' in the surveillance of patients undergoing treatment and follow-up. Finally, we present new bioengineering advances for palliative care of patients to lessen symptoms of patients with ascites and improve quality of life.
Pagkalos I, Drakakis EM, 2017, An automatic transimpedance gain control circuit for analogue front-ends of drifting amperometric biosensors, Measurement, Vol: 102, Pages: 249-252, ISSN: 1873-412X
When amperometric biosensors drift, their sensitivity drops with time:the same difference in detected concentration value ∆Cresults in lower sen-sor output current ∆Ias the measurement/monitoring time progresses. Thislimitation affects the longevity of biosensors. To counterbalance for the dropin sensitivity, manual adjustment of the I-to-V transimpedance gain is usuallyapplied. This paper presents an automatic transimpedance gain control cir-cuit suitable for switched-capacitor-based current analogue front-ends. Thecircuit has been fabricated in the 0.35μmAMS technology, occupies an areaof 0.028mm2and consumes 14.5μWfrom a 3.3Vsupply. Measured resultsconfirm the automatic selection between three values of transimpedance gain,namely 1,10 and 100GΩ each optimised for sensor current range values of±1.65nA,±165pAand±16.5pArespectively. Though the reported topologyhas been tailored for glucose/lactate amperometric biosensors of slow tem-poral dynamics, its parameters can be made to match the conditions of otherphysiological/physical processes in need of monitoring.
Pedrigi RM, Papadimitriou KI, Kondiboyina A, et al., 2016, Disturbed cyclical stretch of endothelial cells promotes nuclear expression of the pro-atherogenic transcription factor NF-kappa B, Annals of Biomedical Engineering, Vol: 45, Pages: 898-909, ISSN: 1573-9686
Exposure of endothelial cells to low and multidirectional blood flow is known to promote a pro-atherogenic phenotype. The mechanics of the vessel wall is another important mechano-stimulus within the endothelial cell environment, but no study has examined whether changes in the magnitude and direction of cell stretch can be pro-atherogenic. Herein, we developed a custom cell stretching device to replicate the in vivo stretch environment of the endothelial cell and examined whether low and multidirectional stretch promote nuclear translocation of NF-κB. A fluid–structure interaction model of the device demonstrated a nearly uniform strain within the region of cell attachment and a negligible magnitude of shear stress due to cyclical stretching of the cells in media. Compared to normal cyclical stretch, a low magnitude of cyclical stretch or no stretch caused increased expression of nuclear NF-κB (p = 0.09 and p < 0.001, respectively). Multidirectional stretch also promoted significant nuclear NF-κB expression, comparable to the no stretch condition, which was statistically higher than the low (p < 0.001) and normal (p < 0.001) stretch conditions. This is the first study to show that stretch conditions analogous to atherogenic blood flow profiles can similarly promote a pro-atherogenic endothelial cell phenotype, which supports a role for disturbed vessel wall mechanics as a pathological cell stimulus in the development of advanced atherosclerotic plaques.
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