Publications
551 results found
Trantidou T, Tariq M, Terracciano CM, et al., 2014, Parylene C-Based Flexible Electronics for pH Monitoring Applications, Sensors, Vol: 14, Pages: 11629-11639, ISSN: 1424-8239
Emerging materials in the field of implantable sensors should meet the needs for biocompatibility; transparency; flexibility and integrability. In this work; we present an integrated approach for implementing flexible bio-sensors based on thin Parylene C films that serve both as flexible support substrates and as active H+ sensing membranes within the same platform. Using standard micro-fabrication techniques; a miniaturized 40-electrode array was implemented on a 5 μm-thick Parylene C film. A thin capping film (1 μm) of Parylene on top of the array was plasma oxidized and served as the pH sensing membrane. The sensor was evaluated with the use of extended gate discrete MOSFETs to separate the chemistry from the electronics and prolong the lifetime of the sensor. The chemical sensing array spatially maps the local pH levels; providing a reliable and rapid-response (<5 s) system with a sensitivity of 23 mV/pH. Moreover; it preserves excellent encapsulation integrity and low chemical drifts (0.26–0.38 mV/min). The proposed approach is able to deliver hybrid flexible sensing platforms that will facilitate concurrent electrical and chemical recordings; with application in real-time physiological recordings of organs and tissues.
Eftekhar A, Juffali W, El-Imad J, et al., 2014, Ngram-derived Pattern Recognition for the Detection and Prediction of Epileptic Seizures, PLOS One, Vol: 9, Pages: 1-15
This work presents a new method that combines symbol dynamics methodologies with an Ngram algorithm for the detection and prediction of epileptic seizures. The presented approach specifically applies Ngram-based pattern recognition, after data pre-processing, with similarity metrics, including the Hamming distance and Needlman-Wunsch algorithm, for identifying unique patterns within epochs of time. Pattern counts within each epoch are used as measures to determine seizure detection and prediction markers. Using 623 hours of intracranial electrocorticogram recordings from 21 patients containing a total of 87 seizures, the sensitivity and false prediction/detection rates of this method are quantified. Results are quantified using individual seizures within each case for training of thresholds and prediction time windows. The statistical significance of the predictive power is further investigated. We show that the method presented herein, has significant predictive power in up to 100% of temporal lobe cases, with sensitivities of up to 70–100% and low false predictions (dependant on training procedure). The cases of highest false predictions are found in the frontal origin with 0.31–0.61 false predictions per hour and with significance in 18 out of 21 cases. On average, a prediction sensitivity of 93.81% and false prediction rate of approximately 0.06 false predictions per hour are achieved in the best case scenario. This compares to previous work utilising the same data set that has shown sensitivities of up to 40–50% for a false prediction rate of less than 0.15/hour.
Kalofonou M, Toumazou C, 2014, An ISFET based analogue ratiometric method for DNA methylation detection, IEEE International Symposium on Circuits and Systems (ISCAS), Publisher: IEEE, Pages: 1832-1835, ISSN: 0271-4302
This paper presents the concept of a ratiometric approach for DNA methylation detection using the “Methylation Cell” for the indication of epigenetic abnormalities related to cancer. The “Methylation Cell” allows real-time detection of pH signals resulting from DNA based reactions using ISFET sensors, performing continuous computation of the ratio of DNA methylation, giving a discrete output signal when DNA methylation exceeds a certain predefined percentage. Fabricated in a typical 0.35μm CMOS process, it uses current-mode translinear circuits to perform computation in low power. Experimental results are presented, demonstrating its capabilities through an integration in a Lab-on-Chip (LoC) set-up using a microfluidic assembly.
Trantidou T, Rao C, Barrett H, et al., 2014, Selective hydrophilic modification of Parylene C films: a new approach to cell micro-patterning for synthetic biology applications, Biofabrication, Vol: 6, ISSN: 1758-5090
We demonstrate a simple, accurate and versatile method to manipulate Parylene C, a material widely known for its high biocompatibility, and transform it to a substrate that can effectively control the cellular microenvironment and consequently affect the morphology and function of the cells in vitro. The Parylene C scaffolds are fabricated by selectively increasing the material's surface water affinity through lithography and oxygen plasma treatment, providing free bonds for attachment of hydrophilic biomolecules. The micro-engineered constructs were tested as culture scaffolds for rat ventricular fibroblasts and neonatal myocytes (NRVM), toward modeling the unique anisotropic architecture of native cardiac tissue. The scaffolds induced the patterning of extracellular matrix compounds and therefore of the cells, which demonstrated substantial alignment compared to typical unstructured cultures. Ca2+ cycling properties of the NRVM measured at rates of stimulation 0.5–2 Hz were significantly modified with a shorter time to peak and time to 90% decay, and a larger fluorescence amplitude (p < 0.001). The proposed technique is compatible with standard cell culturing protocols and exhibits long-term pattern durability. Moreover, it allows the integration of monitoring modalities into the micro-engineered substrates for a comprehensive interrogation of physiological parameters.
Lang Z, Gurrala R, Kaye S, et al., 2014, POC diagnostic test for HLA B<SUP>☆</SUP>5701 using pH-based label-free detection, HIV MEDICINE, Vol: 15, Pages: 71-71, ISSN: 1464-2662
Pagkalos I, Herrero P, Toumazou C, et al., 2014, Bio-Inspired Glucose Control in Diabetes Based on an Analogue Implementation of a β-Cell Model, IEEE TRANSACTIONS ON BIOMEDICAL CIRCUITS AND SYSTEMS, Vol: 8, Pages: 186-195, ISSN: 1932-4545
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- Citations: 13
Toumazou C, Thay TSLK, Georgiou P, 2014, A new era of semiconductor genetics using ion-sensitive field-effect transistors: the gene-sensitive integrated cell, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES, Vol: 372, ISSN: 1364-503X
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- Citations: 18
Reddy M, Oliver N, Herrero P, et al., 2014, GLYCAEMIC VARIABILITY AND QUALITY OF LIFE IN SUBJECTS WITH TYPE 1 DIABETES MELLITUS - IS THERE A CORRELATION?, Publisher: MARY ANN LIEBERT, INC, Pages: A59-A59, ISSN: 1520-9156
Herrero P, Liu C, Georgiou P, et al., 2014, HYPOGLYCEMIA PREDICTION BASED ON EXTENDED KALMAN FILTER USING A PHYSIOLOGICAL MODEL OF GLUCOSE REGULATION, Publisher: MARY ANN LIEBERT, INC, Pages: A82-A83, ISSN: 1520-9156
Reddy M, Oliver N, Herrero P, et al., 2014, THE IMPACT OF INSULIN INFUSION RATE VARIABILITY ON GLYCAEMIC VARIABILITY IN ADULTS WITH TYPE 1 DIABETES, Publisher: MARY ANN LIEBERT, INC, Pages: A59-A59, ISSN: 1520-9156
Pesl P, Herrero P, Reddy M, et al., 2014, Live Demonstration: An Advanced Bolus Calculator for Diabetes Management - A Clinical and Patient Platform, IEEE Biomedical Circuits and Systems Conference (BioCAS), Publisher: IEEE, Pages: 175-175, ISSN: 2163-4025
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- Citations: 2
Herrero P, El Sharkawy M, Pesl P, et al., 2014, Live Demonstration: A Handheld Bio-inspired Artificial Pancreas for Treatment of Diabetes, IEEE Biomedical Circuits and Systems Conference (BioCAS), Publisher: IEEE, Pages: 172-172, ISSN: 2163-4025
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- Citations: 3
Sohbati M, Toumazou C, 2014, A Temperature Insensitive Continuous Time Δ<i>pH</i> to Digital Converter, IEEE International Symposium on Circuits and Systems (ISCAS), Publisher: IEEE, Pages: 37-40, ISSN: 0271-4302
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- Citations: 6
Trantidou T, Tariq M, Pinto K, et al., 2014, A lab-on-chip approach for monitoring the electrochemical activity of biorealistic cell cultures, IEEE International Symposium on Circuits and Systems (ISCAS), Publisher: IEEE, Pages: 642-645, ISSN: 0271-4302
Ramachandran 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
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- Citations: 1
Kalofonou M, 2013, Semiconductor technology for detection of DNA methylation based biomarkers in early screening of cancer
The role of DNA methylation based biomarkers in several stages of cancer development is a rapidly advancing area of research. The aberrancies on the methylation profile of gene promoters play a critical role in gene silencing, thus contributing in different phases of tumour initiation, progression and recurrence, also associated with predicting the response to chemotherapeutic agents, therefore leading to a better assessment of the clinical effectiveness of cancer therapies and so of better prognosis. The need for detection of DNA methylation has become one of the most important assays in early cancer screening. This work introduces the use of semiconductor technology for detection of DNA methylation based biomarkers in CMOS for early screening of cancer using the Ion-Sensitive Field-Effect Transistor (ISFET). This enables label-free detection of DNA methylation in gene markers of interest associated with tumour development in different organs, ultimately enabling a Point-of-Care (PoC) system for early cancer diagnosis. Towards this goal, we introduce the concept of ratiometric detection using the "Methylation Cell" which allows continuous computation of the DNA methylation ratio. This was demonstrated through a Lab-on-Chip (LoC) system using low power current-mode translinear circuits fabricated in unmodified CMOS. Complementary to this, a novel implementation of the "Gilbert Gain Cell" integrated with ISFET sensors was proposed, referred to as the ISFET based Chemical Gilbert Cell, a current-mode circuit for differential reaction monitoring of pH signals derived from DNA methylation reactions. The Cell achieves elimination of common non-idealities of ISFETs such as drift reduction and temperature variations, while achieving gain tunability.
Ramachandran 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
Trantidou 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: 0925-4005
In 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.
Reddy M, Herrero P, Oliver N, et al., 2013, Clinical Evaluation of the Imperial College Bio-inspired Artificial Pancreas Overnight and After Breakfast in Adults with Type 1 Diabetes, European Association for the Study of Diabetes
Herrero 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: 941-951
BACKGROUND: 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.
Lui 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
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- Citations: 69
Toumazou C, Shepherd LM, Reed S, et al., 2013, Simultaneous DNA amplification and detection using a pH-sensing semiconductor system, Nature Methods, Vol: 10, ISSN: 1548-7105
We 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.
Grossman 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
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- Citations: 30
Thanapitak S, Toumazou C, 2013, A Bionics Chemical Synapse, IEEE TRANSACTIONS ON BIOMEDICAL CIRCUITS AND SYSTEMS, Vol: 7, Pages: 296-306, ISSN: 1932-4545
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- Citations: 16
Pagkalos I, Herrero P, Georgiou P, et al., 2013, An Analogue Implementation of the Beta-Cell Insulin Release Model, IEEE International Symposium on Circuits and Systems
This 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.
Murphy 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: 1572-8781
In 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.
Kalofonou 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: 0925-4005
The 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.
Reddy M, Herrero P, Oliver N, et al., 2013, Clinical Assessment of the Imperial College Bio-inspired Artificial Pancreas (BiAP) in Subjects With Type 1 Diabetes Mellitus, Advanced Technologies & Treatments for Diabetes, 2013
Pesl P, Herrero P, Reddy M, et al., 2013, Parameter Tuning of a Case-Based Reasoning Algorithm for Insulin Dosing Decision Support, Advanced Technologies & Treatments for Diabetes, 2013
Dassau E, Hennings T, Fazio J, et al., 2013, Closing the Loop, DIABETES TECHNOLOGY & THERAPEUTICS, Vol: 15, Pages: S29-S39, ISSN: 1520-9156
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