Publications

Conference paper

Ghoreishizadeh S, Haci D, Liu Y, Constandinou Tet al., 2017,

A 4-wire interface SoC for shared multi-implant power transfer and full-duplex communication

, IEEE Latin American symposium on Circuits and Systems (LASCAS), Publisher: IEEE, Pages: 49-52, ISSN: 2473-4667

This paper describes a novel system for recovering power and providing full-duplex communication over an AC-coupled 4-wire lead between active implantable devices. The target application requires a single Chest Device be connected to a Brain Implant consisting of multiple identical optrodes that record neural activity and provide closed loop optical stimulation. The interface is integrated within each optrode SoC allowing full-duplex and fully-differential communication based on Manchester encoding. The system features a head-to-chest uplink data rate (1.6 Mbps) that is higher than that of the chest-to-head downlink (100kbps) superimposed on a power carrier. On-chip power management provides an unregulated 5 V DC supply with up to 2.5 mA output current for stimulation, and a regulated 3.3 V with 60 dB PSRR for recording and logic circuits. The circuit has been implemented in a 0.35 μm CMOS technology, occupying 1.4 mm 2 silicon area, and requiring a 62.2 μA average current consumption.

Journal article

Leene L, Constandinou TG, 2017,

A 0.016² 12b ΔΣSAR With 14fJ/conv. for ultra low power biosensor arrays

, IEEE Transactions on Circuits and Systems. Part 1: Regular Papers, Vol: 64, Pages: 2655-2665, ISSN: 1549-8328

The instrumentation systems for implantable brain-machine interfaces represent one of the most demanding applications for ultra low-power analogue-to-digital-converters (ADC) to date. To address this challenge, this paper proposes a ΔΣSAR topology for very large sensor arrays that allows an exceptional reduction in silicon footprint by using a continuous time 0-2 MASH topology. This configuration uses a specialized FIR window to decimate the ΔΣ modulator output and reject mismatch errors from the SAR quantizer, which mitigates the overhead from dynamic element matching techniques commonly used to achieve high precision. A fully differential prototype was fabricated using 0.18 μm CMOS to demonstrate 10.8 ENOB precision with a 0.016 mm² silicon footprint. Moreover, a 14 fJ/conv figure-of-merit can be achieved, while resolving signals with the maximum input amplitude of ±1.2,Vpp sampled at 200 kS/s. The ADC topology exhibits a number of promising characteristics for both high speed and ultra low-power systems due to the reduced complexity, switching noise, sampling load, and oversampling ratio, which are critical parameters for many sensor applications.

Conference paper

Mirza K, Zuliani C, Hou B, Ng FS, Peters NS, Toumazou Cet al., 2017,

An Individually Addressable Microneedle Device for Real-Time Wireless pH Monitoring

, 9th Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC'17)

This paper describes the development of an array of individually addressable pH sensitive microneedles using injection moulding and their integration within a portable device for real-time wireless recording of pH distributions in biological samples. The fabricated microneedles are subjected to gold pat- terning followed by electrodeposition of iridium oxide to sensitize them to 0.07 units of pH change. Miniaturised electronics suitable for the sensors readout, analog-to-digital conversion and wireless transmission of the potentiometric data are embodied within the device, enabling it to measure real-time pH of soft biological samples such as muscles. In this paper, real-time recording of the cardiac pH distribution, during ischemia followed by reperfusion cycles in cardiac muscles of male Wistar rats has been demonstrated by using the microneedle array.

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Conference paper

Mirza K, Zuliani C, Hou B, Ng FS, Peters N, Toumazou Cet al., 2017,

An Individually Addressable Microneedle Device for Real-Time Wireless pH Monitoring

, 39th Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC'17)

This paper describes the development of an array of individually addressable pH sensitive microneedles using injection moulding and their integration within a portable device for real-time wireless recording of pH distributions in biological samples. The fabricated microneedles are subjected to gold pat- terning followed by electrodeposition of iridium oxide to sensitize them to 0.07 units of pH change. Miniaturised electronics suitable for the sensors readout, analog-to-digital conversion and wireless transmission of the potentiometric data are embodied within the device, enabling it to measure real-time pH of soft biological samples such as muscles. In this paper, real-time recording of the cardiac pH distribution, during ischemia followed by reperfusion cycles in cardiac muscles of male Wistar rats has been demonstrated by using the microneedle array.

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Conference paper

Luan S, Williams I, De-Carvalho F, Grand L, Jackson A, Quian Quiroga R, Constandinou TGet al., 2017,

Standalone headstage for neural recording with real-time spike sorting and data logging

, BNA Festival of Neuroscience, Publisher: The British Neuroscience Association Ltd

Conference paper

Sundarasaradula Y, Constandinou TG, Thanachayanont A, 2017,

A 6-bit, two-step, successive approximation logarithmic ADC for biomedical applications

, IEEE International Conference on Electronics, Circuits and Systems (ICECS), Publisher: IEEE, Pages: 25-28

This paper presents the design and realization of a novel low-power 6-bit successive approximation logarithmic ADC for biomedical applications. A two-step successive approximation method is proposed to obtain a piecewise-linear approximation of the desired logarithmic transfer function. The proposed ADC has been designed and simulated using process parameters from a standard 0.35 μm 2P4M CMOS technology with a single 1.8 V power supply voltage. Simulation results show that, at a sampling rate of 25 kS/s, the proposed ADC consumes 4.36 μW to 14.6 μW (proportional to input amplitudes). The proposed ADC achieves 18.6 pJ/conversion-step, maximum INL of 0.45 LSB, an ENOB of 4.97-bits, and SNDR of 31.7 dB with 1 V full-scale input range.

Conference paper

Leene L, Constandinou TG, 2017,

A 0.45V continuous time-domain filter using asynchronous oscillator structures

, IEEE International Conference on Electronics, Circuits and Systems (ICECS), Publisher: IEEE, Pages: 49-52

This paper presents a novel oscillator based filter structure for processing time-domain signals with linear dynamics that extensively uses digital logic by construction. Such a mixed signal topology is a key component for allowing efficient processing of asynchronous time encoded signals that does not necessitate external clocking. A miniaturized primitive is introduced as analogue time-domain memory that can be modelled, synthesized, and incorporated in closed loop mixed signal accelerators to realize more complex linear or non-linear computational systems. This is contextualized by demonstrating a compact low power filter operating at 0.45 V in 65 nm CMOS. Simulation results are presented showing an excess of 50 dB dynamic range with a FOM of 7fJ/pole which promises an order of magnitude improvement on state-of-the-art filters in nanometre CMOS.

Conference paper

Herrero Vinas P, Pesl P, Reddy M, El Sharkawy M, Toumazou Cet al., 2017,

Safety layer for an insulin delivery system

, Advanced Technologies & Treatments for Diabetes, Publisher: Mary Ann Liebert, ISSN: 1520-9156

Conference paper

Lauteslager T, Tommer M, Kjelgard KG, Lande TS, Constandinou TGet al., 2017,

Intracranial Heart Rate Detection Using UWB Radar

, IEEE Biomedical Circuits and Systems (BioCAS) Conference, Publisher: IEEE, Pages: 119-122

Microwave imaging is a promising technique for noninvasive imaging of brain activity. A multistatic array of body coupled antennas and single chip pulsed ultra-wideband radars should be capable of detecting local changes in cerebral blood volume, a known indicator for neural activity. As an initialverification that small changes in the cerebrovascular system can indeed be measured inside the skull, we recorded the heart rate intracranially using a single radar module and two body coupled antennas. The obtained heart rate was found to correspond to ECG measurements. To confirm that the measured signal was indeed from within the skull, we performed simulations to predict the time-of-flight of radar pulses passing through differentanatomical structures of the head. Simulated time-of-flight through the brain corresponded to the measured delay of heart rate modulation in the radar signal. The detection of intracranial heart rate using microwave techniques has not previously been reported, and serves as a first proof that functional neuroimaging using radar could lie within reach.

Conference paper

Leene L, Constandinou TG, 2017,

A 2.7uW/Mips, 0.88GOPS/mm^2 Distributed Processor for Implantable Brain Machine Interfaces

, IEEE Biomedical Circuits and Systems (BioCAS) Conference, Publisher: IEEE, Pages: 360-363

This paper presents a scalable architecture in 0.18u m CMOS for implantable brain machine interfaces (BMI) that enables micro controller flexibility for data analysis at the sensor interface. By introducing more generic computational capabilities the system is capable of high level adaptive function to potentially improve the long term efficacy of invasive implants. This topology features a compact ultra low power distributedprocessor that supports 64-channel neural recording system on chip (SOC) with a computational efficiency of 2.7uW/MIPS with a total chip area of 1.37mm2. This configuration executes 1024 instructions on each core at 20MHz to consolidate full spectrum high precision recordings from 4 analogue channels for filtering, spike detection, and feature extraction in the digital domain.

Conference paper

Williams I, Rapeaux A, Liu Y, Luan S, Constandinou TGet al., 2017,

A 32-channel bidirectional neural/EMG interface with on-chip spike detection for sensorimotor feedback

, IEEE Biomedical Circuits and Systems (BioCAS) Conference, Publisher: IEEE, Pages: 528-531

This paper presents a novel 32-channel bidirectional neural interface, capable of high voltage stimulation and low power, low-noise neural recording. Current-controlled biphasic pulses are output with a voltage compliance of 9.25V, user configurable amplitude (max. 315 uA) & phase duration (max. 2 ms). The low-voltage recording amplifiers consume 23 uW per channel with programmable gain between 225 - 4725. Signals are10-bit sampled at 16 kHz. Data rates are reduced by granular control of active recording channels, spike detection and event-driven communication, and repeatable multi-pulse stimulation configurations.

Conference paper

Frehlick Z, Williams I, Constandinou TG, 2017,

Improving Neural Spike Sorting Performance Using Template Enhancement

, IEEE Biomedical Circuits and Systems (BioCAS) Conference, Publisher: IEEE, Pages: 524-527

This paper presents a novel method for improving the performance of template matching in neural spike sorting for similar shaped spikes, without increasing computational complexity. Mean templates for similar shaped spikes are enhanced to emphasise distinguishing features. Template optimisation is based on the variance of sample distributions. Improved spike sorting performance is demonstrated on simulated neural recordings with two and three neuron spike shapes. The method is designed for implementation on a Next Generation Neural Interface (NGNI) device at Imperial College London.

Conference paper

Luan S, Liu Y, Williams I, Constandinou TGet al., 2017,

An Event-Driven SoC for Neural Recording

, IEEE Biomedical Circuits and Systems (BioCAS) Conference, Publisher: IEEE, Pages: 404-407

This paper presents a novel 64-channel ultra-low power/low noise neural recording System-on-Chip (SoC) featuring a highly reconfigurable Analogue Front-End (AFE) and block-selectable data-driven output. This allows a tunable bandwidth/sampling rate for extracting Local Field Potentials (LFPs)and/or Extracellular Action Potentials (EAPs). Realtime spike detection utilises a dual polarity simple threshold to enable an event driven output for neural spikes (16-sample window). The 64-channels are organised into 16 sets of 4-channel recording blocks, with each block having a dedicated 10-bit SAR ADC that is time division multiplexed among the 4 channels. Eachchannel can be individually powered down and configured for bandwidth, gain and detection threshold. The output can thus combine continuous-streaming and event-driven data packets with the system configured as SPI slave. The SoC is implemented in a commercially-available 0.35u m CMOS technology occupying a silicon area of 19.1mm^2 (0.3mm^2 gross per channel) and requiring 32uW/channel power consumption (AFE only).

Journal article

Pesl P, Herrero P, Reddy M, Oliver N, Johnston DG, Toumazou C, Georgiou Pet al., 2017,

Case-Based Reasoning for Insulin Bolus Advice.

, J Diabetes Sci Technol, Vol: 11, Pages: 37-42

BACKGROUND: Insulin bolus calculators assist people with Type 1 diabetes (T1D) to calculate the amount of insulin required for meals to achieve optimal glucose levels but lack adaptability and personalization. We have proposed enhancing bolus calculators by the means of case-based reasoning (CBR), an established problem-solving methodology, by individualizing and optimizing insulin therapy for various meal situations. CBR learns from experiences of past similar meals, which are described in cases through a set of parameters (eg, time of meal, alcohol, exercise). This work discusses the selection, representation and effect of case parameters used for a CBR-based Advanced Bolus Calculator for Diabetes (ABC4D). METHODS: We analyzed the usage and effect of selected parameters during a pilot study (n = 10), where participants used ABC4D for 6 weeks. Retrospectively, we evaluated the effect of glucose rate of change before the meal on the glycemic excursion. Feedback from study participants about the choice of parameters was obtained through a nonvalidated questionnaire. RESULTS: Exercise and alcohol were the most frequently used parameters, which was congruent with the feedback from study participants, who found these parameters most useful. Furthermore, cases including either exercise or alcohol as parameter showed a trend in reduction of insulin at the end of the study. A significant difference ( P < .01) was found in glycemic outcomes for meals where glucose rate of change was rising compared to stable rate of change. CONCLUSIONS: Results from the 6-week study indicate the potential benefit of including parameters exercise, alcohol and glucose-rate of change for insulin dosing decision support.

Conference paper

Mirza KB, Wildner K, Kulasekeram N, Cork S, Bloom S, Nikolic K, Toumazou Cet al., 2017,

Live Demo: Platform for Closed Loop Neuromodulation Based on Dual Mode Biosignals

, IEEE Biomedical Circuits and Systems Conference (BioCAS), Publisher: IEEE, ISSN: 2163-4025

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Journal article

Cooke GS, Gurrala R, Harrison E, Shepherd L, Davidson D, McClure M, Kaye S, Toumazou Cet al., 2016,

Novel pH sensing semiconductor for point-of-care detection of HIV-1 viremia

, Scientific Reports, Vol: 6, ISSN: 2045-2322

The timely detection of viremia in HIV-infected patients receiving antiviral treatment is key to ensuring effective therapy and preventing the emergence of drug resistance. In high HIV burden settings, the cost and complexity of diagnostics limit their availability. We have developed a novel complementary metal-oxide semiconductor (CMOS) chip based, pH-mediated, point-of-care HIV-1 viral load monitoring assay that simultaneously amplifies and detects HIV-1 RNA. A novel low-buffer HIV-1 pH-LAMP (loop-mediated isothermal amplification) assay was optimised and incorporated into a pH sensitive CMOS chip. Screening of 991 clinical samples (164 on the chip) yielded a sensitivity of 95% (in vitro) and 88.8% (on-chip) at >1000 RNA copies/reaction across a broad spectrum of HIV-1 viral clades. Median time to detection was 20.8 minutes in samples with >1000 copies RNA. The sensitivity, specificity and reproducibility are close to that required to produce a point-of-care device which would be of benefit in resource poor regions, and could be performed on an USB stick or similar low power device.

Journal article

De Marcellis A, Palange E, Nubile L, Faccio M, Di Patrizio Stanchieri G, Constandinou Tet al., 2016,

A pulsed coding technique based on optical UWB modulation for high data rate low power wireless implantable biotelemetry

, Electronics, Vol: 5, Pages: 1-10, ISSN: 2079-9292

This paper reports on a pulsed coding technique based on optical Ultra-wideband (UWB)modulation for wireless implantable biotelemetry systems allowing for high data rate link whilstenabling significant power reduction compared to the state-of-the-art. This optical data codingapproach is suitable for emerging biomedical applications like transcutaneous neural wirelesscommunication systems. The overall architecture implementing this optical modulation techniqueemploys sub-nanosecond pulsed laser as the data transmitter and small sensitive area photodiode asthe data receiver. Moreover, it includes coding and decoding digital systems, biasing and drivinganalogue circuits for laser pulse generation and photodiode signal conditioning. The complete systemhas been implemented on Field-Programmable Gate Array (FPGA) and prototype Printed CircuitBoard (PCB) with discrete off-the-shelf components. By inserting a diffuser between the transmitterand the receiver to emulate skin/tissue, the system is capable to achieve a 128 Mbps data rate with abit error rate less than 10 9 and an estimated total power consumption of about 5 mW correspondingto a power efficiency of 35.9 pJ/bit. These results could allow, for example, the transmission of an800-channel neural recording interface sampled at 16 kHz with 10-bit resolution.

Conference paper

De Marcellis A, Palange E, Faccio M, Nubile L, Di Patrizio Stanchieri G, Constandinou TGet al., 2016,

A new optical UWB modulation technique for 250Mbps wireless link in implantable biotelemetry systems

, Eurosensors, Publisher: Elsevier: Creative Commons Attribution Non-Commercial No-Derivatives License, Pages: 1676-1680, ISSN: 1877-7058

We propose a new UWB modulation technique for wireless optical communications in transcutaneous biotelemetry. The solution, based on the generation of sub-nanoseconds laser pulses, allows for a high data rate link whilst achieving a significant power reduction (energy per bit) compared to the state-ofthe- art. These features make this particularly suitable for emerging biomedical applications such as implantable neural/biosensor systems. The relatively simple architecture consists of a transmitter and receiver that can be integrated in a standard CMOS technology in a compact Silicon footprint (lower than 1mm^2 in a 0.18μm technology). These parts, optimised for low-voltage/low-power operation, include coding and decoding digital systems, biasing and driving analogue circuits for laser pulse generation and photodiode signal conditioning. Experimental findings with prototype PCBs have validated the new paradigm showing the system capabilities to achieve a BER less than 10^-9 with data rate up to 250Mbps and estimated total power consumption lower than 5mW.

Journal article

Moser N, Lande TS, Toumazou C, Georgiou Pet al., 2016,

ISFETs in CMOS and Emergent Trends in Instrumentation: A Review

, IEEE Sensors Journal, Vol: 16, Pages: 6496-6514, ISSN: 1530-437X

Over the past decade, ion-sensitive field-effect transistors (ISFETs) have played a major role in enabling the fabrication of fully integrated CMOS-based chemical sensing systems. This has allowed several new application areas, with the most promising being the fields of ion imaging and full genome sequencing. This paper reviews the new trends in front-end topologies toward the design of ISFET sensing arrays in CMOS for these new applications. More than a decade after the review of the ISFET by Bergveld which summarized the state of the art in terms of device and early readout circuity, we describe the evolution in terms of device macromodel and identify the main sensor challenges for current designers. We analyze the techniques that have been reported for both ISFET instrumentation and compensation, and conclude that topologies are focusing on device adaptation for offset and drift cancellation, as opposed to system compensation which are often not as robust. Guidelines are provided to build a tailored CMOS ISFET array, emphasizing that the needs in terms of applications are the keys to selecting the right pixel architecture. Over the next few years, the race for the largest and densest array is likely to be put on hold to allow the research to focus on new pixel topologies, ultimately leading to the development of reliable and scalable arrays. A wide range of new applications are expected to motivate this paper for at least another decade.

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Conference paper

Zhao H, Dehkhoda F, Ramezani R, Sokolov D, Constandinou TG, Liu Y, Degenaar Pet al., 2016,

A CMOS-Based Neural Implantable Optrode for Optogenetic Stimulation and Electrical Recording

, IEEE Biomedical Circuits and Systems (BioCAS) Conference, Publisher: IEEE, Pages: 286-289

This paper presents a novel integrated optrode for simultaneous optical stimulation and electrical recording for closed -loop optogenetic neuro-prosthetic applications. The design has been implemented in a commercially available 0.35μm CMOS process. The system includes circuits for controlling the optical stimulations; recording local field potentials (LFPs); and onboard diagnostics. The neural interface has two clusters of stimulation and recording sites. Each stimulation site has a bonding point for connecting a micro light emitting diode (μLED) to deliver light to the targeted area of brain tissue. Each recording site is designed to be post-processed with electrode materials to provide monitoring ofneural activity. On-chip diagnostic sensing has been included to provide real-time diagnostics for post-implantation and during normal operation.

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An Individually Addressable Microneedle Device for Real-Time Wireless pH Monitoring

An Individually Addressable Microneedle Device for Real-Time Wireless pH Monitoring

Standalone headstage for neural recording with real-time spike sorting and data logging

Live Demo: Platform for Closed Loop Neuromodulation Based on Dual Mode Biosignals

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