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Conference paperYoshizaki S, Serb A, Liu Y, et al., 2014,
Octagonal CMOS Image Sensor with Strobed RGB LED Illumination for Wireless Capsule Endoscopy
, IEEE International Symposium on Circuits and Systems (ISCAS), Publisher: IEEE, Pages: 1857-1860 -
Conference paperReverter F, Prodromakis T, Liu Y, et al., 2014,
Design Considerations for a CMOS Lab-on-Chip Microheater Array to Facilitate the in vitro Thermal Stimulation of Neurons
, IEEE International Symposium on Circuits and Systems (ISCAS), Publisher: IEEE, Pages: 630-633 -
Journal articleRamachandran A, Snehalatha C, Ram J, et al., 2013,
Efficacy of mobile phone messaging in prevention of type 2 diabetes by lifestyle change in men at high risk - A randomised clinical trial in India
, Journal of Association of Physicians of India, Vol: 61, Pages: 951-952, ISSN: 0004-5772- Cite
- Citations: 1
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Journal articleRamachandran A, Snehalatha C, Ram J, et al., 2013,
Effectiveness of mobile phone messaging in prevention of type 2 diabetes by lifestyle modification in men in India: a prospective, parallel-group, randomised controlled trial
, The Lancet Diabetes & Endocrinology, Vol: 1, Pages: 191-198, ISSN: 2213-8587 -
Journal articleTrantidou T, Payne DJ, Tsiligkiridis V, et al., 2013,
The dual role of Parylene C in chemical sensing: Acting as an encapsulant and as a sensing membrane for pH monitoring applications
, Sensors and Actuators B - Chemical, Vol: 186, Pages: 1-8, ISSN: 0925-4005In this work, we demonstrate a new property of Parylene C emphasizing on its application in pH sensing technologies. For many decades the material has been extensively used as a biocompatible inert encapsulant of implantable micro-devices. Toward a new understanding of the material's potential, we explore the transformation of Parylene C from a passive encapsulation membrane into an active H+ sensing membrane using discrete MOSFETs to evaluate its chemical sensing performance. We employ oxygen plasma treatment to functionalize Parylene's H+ sensing capacity and enhance the chemical sensitivity, drift rates, and reliability of the sensing devices. Moreover, we demonstrate a versatile technique that enables the deployment of the material both as an encapsulant and as a sensing membrane in a single platform, in order to benefit from distinguishable and consistent sensitivities, and low leakage currents during pH measurements. Our investigation reveals that the selective modification of Parylene's surface chemistry yields reliable pH sensing devices, ensuring the best combination of sensitivity (16.3 mV/pH) and leakage currents (6–10 nA) over a reasonably wide pH range (4–10), while drift rates remain in low levels (2.5–20 mV/h). We believe that this study opens up new application horizons for Parylene, which is a new promising material in the emerging field of flexible electronics able to deliver low film thicknesses and high biocompatibility, while facilitating the application of mechanical stimulus.
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Conference paperWilliams I, Constandinou TG, 2013,
Modelling muscle spindle dynamics for a proprioceptive prosthesis
, Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBS), Publisher: IEEEMuscle spindles are found throughout our skeletalmuscle tissue and continuously provide us with a sense of our limbs position and motion (proprioception). This paper advances a model for generating artificial muscle spindle signalsfor a prosthetic limb, with the aim of one day providing amputees with a sense of feeling in their artificial limb. By utilising the Opensim biomechanical modelling package the relationship between a joints angle and the length of surrounding muscles is estimated for a prosthetic limb. This is then applied to the established Mileusnic model to determine the associated muscle spindle firing pattern. This complete system model is then reduced to allow for a computationallyefficient hardware implementation. This reduction is achieved with minimal impact on accuracy by selecting key monoarticular muscles and fitting equations to relate joint angle to muscle length. Parameter values fitting the Mileusnic modelto human spindles are then proposed and validated against previously published human neural recordings. Finally, a model for fusimotor signals is also proposed based on data previously recorded from reduced animal experiments.
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Journal articleHerrero P, Georgiou P, Oliver N, et al., 2013,
A composite model of glucagon-glucose dynamics for in silico testing of bihormonal glucose controllers.
, J Diabetes Sci Technol, Vol: 7, Pages: 941-951BACKGROUND: The utility of simulation environments in the development of an artificial pancreas for type 1 diabetes mellitus (T1DM) management is well established. The availability of a simulator that incorporates glucagon as a counterregulatory hormone to insulin would allow more efficient design of bihormonal glucose controllers. Existing models of the glucose regulatory system that incorporates glucagon action are difficult to identify without using tracer data. In this article, we present a novel model of glucagon-glucose dynamics that can be easily identified with standard clinical research data. METHODS: The minimal model of plasma glucose and insulin kinetics was extended to account for the action of glucagon on net endogenous glucose production by incorporating a new compartment. An existing subcutaneous insulin absorption model was used to account for subcutaneous insulin delivery. The same model of insulin pharmacokinetics was employed to model the pharmacokinetics of subcutaneous glucagon absorption. Finally, we incorporated an existing gastrointestinal absorption model to account for meal intake. Data from a closed-loop artificial pancreas study using a bihormonal controller on T1DM subjects were employed to identify the composite model. To test the validity of the proposed model, a bihormonal controller was designed using the identified model. RESULTS: Model parameters were identified with good precision, and an excellent fitting of the model with the experimental data was achieved. The proposed model allowed the design of a bihormonal controller and demonstrated its ability to improve glycemic control over a single-hormone controller. CONCLUSIONS: A novel composite model, which can be easily identified with standard clinical data, is able to account for the effect of exogenous insulin and glucagon infusion on glucose dynamics. This model represents another step toward the development of a bihormonal artificial pancreas.
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Journal articleLui KW, Murphy OH, Toumazou C, 2013,
A Wearable Wideband Circularly Polarized Textile Antenna for Effective Power Transmission on a Wirelessly-Powered Sensor Platform
, IEEE TRANSACTIONS ON ANTENNAS AND PROPAGATION, Vol: 61, Pages: 3873-3876, ISSN: 0018-926X- Author Web Link
- Cite
- Citations: 69
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Journal articleToumazou C, Shepherd LM, Reed S, et al., 2013,
Simultaneous DNA amplification and detection using a pH-sensing semiconductor system
, Nature Methods, Vol: 10, ISSN: 1548-7105We developed an integrated chip for real-time amplification and detection of nucleic acid using pH-sensing complementary metal-oxide semiconductor (CMOS) technology. Here we show an amplification-coupled detection method for directly measuring released hydrogen ions during nucleotide incorporation rather than relying on indirect measurements such as fluorescent dyes. This is a label-free, non-optical, real-time method for detecting and quantifying target sequences by monitoring pH signatures of native amplification chemistries. The chip has ion-sensitive field effect transistor (ISFET) sensors, temperature sensors, resistive heating, signal processing and control circuitry all integrated to create a full system-on-chip platform. We evaluated the platform using two amplification strategies: PCR and isothermal amplification. Using this platform, we genotyped and discriminated unique single-nucleotide polymorphism (SNP) variants of the cytochrome P450 family from crude human saliva. We anticipate this semiconductor technology will enable the creation of devices for cost-effective, portable and scalable real-time nucleic acid analysis.
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Journal articleThanapitak S, Toumazou C, 2013,
A Bionics Chemical Synapse
, IEEE TRANSACTIONS ON BIOMEDICAL CIRCUITS AND SYSTEMS, Vol: 7, Pages: 296-306, ISSN: 1932-4545- Author Web Link
- Cite
- Citations: 16
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Journal articleGrossman N, Simiaki V, Martinet C, et al., 2013,
The spatial pattern of light determines the kinetics and modulates backpropagation of optogenetic action potentials
, JOURNAL OF COMPUTATIONAL NEUROSCIENCE, Vol: 34, Pages: 477-488, ISSN: 0929-5313- Author Web Link
- Open Access Link
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- Citations: 30
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Conference paperLeene LB, Luan S, Constandinou TG, 2013,
A 890fJ/bit UWB transmitter for SOC integration inhigh bit-rate transcutaneous bio-implants
, IEEE International Symposium on Circuits and Systems (ISCAS)The paper presents a novel ultra low power UWBtransmitter system for near field communication in transcutaneous biotelemetries. The system utilizes an all-digital architecture based on minising the energy dissipated per bit transmitted by efficiently encoding a packet of pulses with multiple bits and utilizing oscillator referenced delays. This is achieved by introducing a novel bi-phasic 1.65 pJ per pulse UWB pulse generator together with a 72uμW DCO that provide a transmission bandwidth of 77.5 Mb/s with an energy efficiency of 890fJ per bit from a 1.2V supply. The circuit core occupies a compact silicon footprint of 0.026mm2 in a 0.18 μm CMOS technology.
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Conference paperBarsakcioglu DY, Eftekhar A, Constandinou TG, 2013,
Design Optimisation of Front-End Neural Interfaces for Spike Sorting Systems
, IEEE International Symposium on Circuits and Systems (ISCAS)This work investigates the impact of the analoguefront-end design (pre-amplifier, filter and converter) on spike sorting performance in neural interfaces. By examining key design parameters including the signal-to-noise ratio, bandwidth,filter type/order, data converter resolution and sampling rate, their sensitivity to spike sorting accuracy is assessed. This is applied to commonly used spike sorting methods such as template matching, 2nd derivative-features, and principle component analysis. The results reveal a near optimum set of parameters to increase performance given the hardware-constraints. Finally, the relative costs of these design parameters on resource efficiency (silicon area and power requirements) are quantified through reviewing the state-of-the-art.
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Conference paperKoutsos E, Paraskevopoulou SE, Constandinou TG, 2013,
A 1.5μW NEO-based Spike Detector with Adaptive-Threshold for Calibration-free Multichannel Neural Interfaces
, IEEE International Symposium on Circuits and Systems (ISCAS)This paper presents a novel front-end circuit for detecting action potentials in extracellular neural recordings. By implementing a real-time, adaptive algorithm to determine an effective threshold for robustly detecting a spike, the need for calibration and/or external monitoring is eliminated. The input signal is first pre-processed by utilising a non-linear energy operator (NEO) to effectively boost the signal-to-noise ratio (SNR) of the spike feature of interest. The spike detection threshold is then determined by tracking the peak NEO response and applying a non-linear gain to realise an adaptive response to different spike amplitudes and background noise levels. The proposed algorithm and its implementation is shown to achieve both accurate and robust spike detection, by minimising falsely detected spikes and/or missed spikes. The system has been implemented in a commercially available 0.18μm technology requiring a total power consumption of 1.5μW from a 1.8V supply and occupying a compact footprint of only 0.03$\,$mm$^2$ silicon area. The proposed circuit is thus ideally suited for high-channel count, calibration-free, neural interfaces.
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Conference paperPagkalos I, Herrero P, Georgiou P, et al., 2013,
An Analogue Implementation of the Beta-Cell Insulin Release Model
, IEEE International Symposium on Circuits and SystemsThis paper presents the implementation of a low-power analogue circuit, which replicates the granular release of insulin from beta-cell of the pancreas, to control the blood glucose. Results show that the circuit with a power consumption of 1.667 mW can achieve the same physiological responses with the designed model developed in Matlab. It is therefore expected that in a future implementation of the circuit in silicon, the same quality of blood glucose control can be achieved and therefore can be used as part of the Artificial Pancreas to support the treatment of Diabetes.
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Journal articleWilliams I, Constandinou TG, 2013,
An Energy-Efficient, Dynamic Voltage Scaling Neural Stimulator for a Proprioceptive Prosthesis
, IEEE Transactions on Biomedical Circuits and Systems, Vol: 7, Pages: 129-139This paper presents an 8 channel energy-efficient neural stimulator for generating charge-balanced asymmetric pulses. Power consumption is reduced by implementing a fully integrated DC-DC converter that uses a reconfigurable switched capacitor topology to provide 4 output voltages for Dynamic Voltage Scaling (DVS). DC conversion efficiencies of up to 82% are achieved using integrated capacitances of under 1 nF and the DVS approach offers power savings of up to 50% compared to the front end of a typical current controlled neural stimulator. A novel charge balancing method is implemented which has a low level of accuracy on a single pulse and a much higher accuracy over a series of pulses. The method used is robust to process and component variation and does not require any initial or ongoing calibration. Measured results indicate that the charge imbalance is typically between 0.05% - 0.15% of charge injected for a series of pulses. Ex-vivo experiments demonstrate the viability in using this circuit for neural activation. The circuit has been implemented in a commercially-available 0.18μm HV CMOS technology and occupies a core die area of approximately 2.8mm² for an 8 channel implementation.
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Journal articleParaskevopoulou SE, Barsakcioglu D, Saberi M, et al., 2013,
Feature Extraction using First and Second Derivative Extrema (FSDE), for Real-time and Hardware-Efficient Spike Sorting
, Journal of Neuroscience Methods, Vol: 215, Pages: 29-37, ISSN: 0165-0270Next generation neural interfaces aspire to achieve real-time multi-channel systems by integrating spike sorting on chip to overcome limitations in communication channel capacity. The feasibility of this approach relies on developing highly-efficient algorithms for feature extraction and clustering with the potential of low-power hardware implementation. We are proposing a feature extraction method, not requiring any calibration, based on first and second derivative features of the spike waveform. The accuracy and computational complexity of the proposed method are quantified and compared against commonly used feature extraction methods, through simulation across four datasets (with different single units) at multiple noise levels (ranging from 5 to 20% of the signal amplitude). The average classification error is shown to be below 7% with a computational complexity of 2N-3, where N is the number of sample points of each spike. Overall, this method presents a good trade-off between accuracy and computational complexity and is thus particularly well-suited for hardware-efficient implementation.
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Journal articleMurphy OH, Bahmanyar MR, Borghi A, et al., 2013,
Continuous in vivo blood pressure measurements using a fully implantable wireless SAW sensor
, Biomedical Microdevices, Vol: 15, Pages: 737-749, ISSN: 1572-8781In this paper, the development of a fully implantable wireless sensor able to provide continuous real-time accurate pressure measurements is presented. Surface Acoustic Wave (SAW) technology was used to deposit resonators on crystalline quartz wafers; the wafers were then assembled to produce a pressure sensitive device. Excitation and reading via a miniature antenna attached to the pressure sensor enables continuous external interrogation. The main advantages of such a configuration are the long term stability of quartz and the low power necessary for the interrogation, which allows 24/7 interrogation by means of a hand-held, battery powered device. Such data are of vital importance to clinicians monitoring and treating the effects of hypertension and heart failure. A prototype was designed and tested using both a bio-phantom test rig and an animal model. The pressure traces for both compare very well with a commercially available catheter tip pressure transducer. The work presented in this paper is the first known wireless pressure data from the left ventricle of the heart of a living swine.
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Journal articleWoods SP, Constandinou TG, 2013,
Wireless Capsule Endoscope for Targeted Drug Delivery: Mechanics and Design Considerations
, IEEE Transactions on Biomedical Engineering, Vol: 60, Pages: 945-953, ISSN: 0018-9294This paper describes a platform to achieve targeted drug delivery in next generation wireless capsule endoscopy. The platform consists of two highly novel sub-systems: one is a micro-positioning mechanism which can deliver 1ml of targeted medication and the other is a holding mechanism which gives the functionality of resisting peristalsis. The micro-positioning mechanism allows a needle to be positioned within a 22.5⁰ segment of a cylindrical capsule and be extendible by up to 1.5mm outside the capsule body. The mechanism achieves both these functions using only a single micro-motor and occupying a total volume of just 200mm³. The holding mechanism can be deployed diametrically opposite the needle in 1.8s and occupies a volume of just 270mm³. An in-depth analysis of the mechanics is presented and an overview of the requirements necessary to realise a total system integration is discussed. It is envisaged that the targeted drug delivery platform will empower a new breed of capsule micro-robots for therapy in addition to diagnostics for pathologies such as ulcerative colitis and small intestinal Crohn's disease.
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Journal articleKalofonou M, Toumazou C, 2013,
Semiconductor technology for early detection of DNA methylation for cancer: From concept to practice
, SENSORS AND ACTUATORS B-CHEMICAL, Vol: 178, Pages: 572-580, ISSN: 0925-4005The electrical detection of DNA methylation based biomarkers using semiconductor technology shows great promise for early cancer screening. Presented is the very first proof-of-concept example of using CMOS-based technology for real-time DNA methylation detection using Ion-Sensitive Field-Effect Transistors (ISFETs). An electrochemical label-free approach was applied in two gene assays, each one of which incorporated the sequences of DAPK1 and CDKN2A/p16-INK4 (p16) gene promoters at a both methylated and unmethylated state, performing isothermal methylation-specific amplification and detection both in-tube and on-chip (real-time). Good discrimination was shown between the two states, achieving a very good average pH signal change for the methylated state of 1.91 for DAPK1 assay and of 1.58 for p16 assay in the tube test. The real-time on-chip test showed similarly good real-time differential signal change in favour of methylated DNA, reaching 37 mV for DAPK1 assay and 23 mV for p16 assay, validating the results from the proof-of-concept test of pH-LAMP in-tube while confirming the sensitivity of real-time methylation-specific pH-LAMP on-chip.
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