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  • Journal article
    Herrero P, Delaunay B, Jaulin L, Georgiou P, Oliver N, Toumazou Cet al., 2016,

    Robust set-membership parameter estimation of the glucose minimal model

    , INTERNATIONAL JOURNAL OF ADAPTIVE CONTROL AND SIGNAL PROCESSING, Vol: 30, Pages: 173-185, ISSN: 0890-6327
  • Conference paper
    Murphy O, Bahmanyar MR, McLeod CN, Toumazou C, Yacoub Met al., 2016,

    Beyond RF ablation other uses for RF within the body

    , Pages: 1362-1364

    The use of high frequencies within the body is commonplace for treatment and imaging, but, other than a few examples very little exists in terms of RF sensors and for communication deep into the body. This paper will give an overview of an RF powered implantable blood pressure sensor for continuous monitoring and in doing so demonstrate the use of RF within the body.

  • Conference paper
    Ma D, Georgiou P, Toumazou C, 2016,

    A weak inversion ISFET current mirror for differential bio-sensing

    , 12th IEEE Biomedical Circuits and Systems Conference (BioCAS), Publisher: IEEE, Pages: 42-45, ISSN: 2163-4025
  • Conference paper
    Murphy O, Bahmanyar MR, McLeod CN, Toumazou C, Yacoub Met al., 2016,

    Beyond RF Ablation Other uses for RF within the body.

    , 11th European Microwave Integrated Circuits Conference (EuMIC), Publisher: IEEE, Pages: 433-435
  • Conference paper
    Pesl P, Herrero P, Reddy M, Oliver N, Toumazou C, Georgiou Pet al., 2016,

    Live Demonstration: Smartwatch Implementation of an Advanced Insulin Bolus Calculator for Diabetes

    , IEEE International Symposium on Circuits and Systems (ISCAS), Publisher: IEEE, Pages: 2370-2370, ISSN: 0271-4302
  • Conference paper
    Ma D, Georgiou P, Toumazou C, 2016,

    An ISFET-based switched current DNA integrator

    , IEEE International Symposium on Circuits and Systems (ISCAS), Publisher: IEEE, Pages: 329-332, ISSN: 0271-4302
  • Conference paper
    Reddy M, Herrero P, Sharkawy ME, Pesl P, Jugnee N, Pavitt D, Godsland IF, Alberti G, Toumazou C, Johnston DG, Georgiou P, Oliver NSet al., 2015,

    Metabolic Control With the Bio-inspired Artificial Pancreas in Adults With Type 1 Diabetes: A 24-Hour Randomized Controlled Crossover Study.

    , Pages: 405-413

    BACKGROUND: The Bio-inspired Artificial Pancreas (BiAP) is a closed-loop insulin delivery system based on a mathematical model of beta-cell physiology and implemented in a microchip within a low-powered handheld device. We aimed to evaluate the safety and efficacy of the BiAP over 24 hours, followed by a substudy assessing the safety of the algorithm without and with partial meal announcement. Changes in lactate and 3-hydroxybutyrate concentrations were investigated for the first time during closed-loop. METHODS: This is a prospective randomized controlled open-label crossover study. Participants were randomly assigned to attend either a 24-hour closed-loop visit connected to the BiAP system or a 24-hour open-loop visit (standard insulin pump therapy). The primary outcome was percentage time spent in target range (3.9-10 mmol/l) measured by sensor glucose. Secondary outcomes included percentage time in hypoglycemia (<3.9 mmol/l) and hyperglycemia (>10 mmol/l). Participants were invited to attend for an additional visit to assess the BiAP without and with partial meal announcements. RESULTS: A total of 12 adults with type 1 diabetes completed the study (58% female, mean [SD] age 45 [10] years, BMI 25 [4] kg/m(2), duration of diabetes 22 [12] years and HbA1c 7.4 [0.7]% [58 (8) mmol/mol]). The median (IQR) percentage time in target did not differ between closed-loop and open-loop (71% vs 66.9%, P = .9). Closed-loop reduced time spent in hypoglycemia from 17.9% to 3.0% (P < .01), but increased time was spent in hyperglycemia (10% vs 28.9%, P = .01). The percentage time in target was higher when all meals were announced during closed-loop compared to no or partial meal announcement (65.7% [53.6-80.5] vs 45.5% [38.2-68.3], P = .12). CONCLUSIONS: The BiAP is safe and achieved equivalent time in target as measured by sensor glucose, with improvement in hypoglycemia, when compared to standard pump therapy.

  • Conference paper
    Dehkhoda F, Soltan A, Ramezani R, Zhao H, Liu Y, Constandinou TG, Degenaar Pet al., 2015,

    Smart Optrode for Neural Stimulation and Sensing

    , 2015 IEEE Sensors Conference, Publisher: IEEE, Pages: 1-4

    Implantable neuro-prosthetics considerable clinical benefit to a range of neurological conditions. Optogenetics is a particular recent interest which utilizes high radiance light for photo-activation of genetic cells. This can provide improved biocompatibility and neural targeting over electrical stimuli. To date the primary optical delivery method in tissue for optogenetics has been via optic fibre which makes large scale multiplexing difficult. An alternative approach is to incorporate optical micro-emitters directly on implantable probes but this still requires electrical multiplexing. In this work, we demonstrate a fully active optoelectronic probe utilizing industry standard 0.35μm CMOS technology, capable of both light delivery and electrical recording. The incorporation of electronic circuits onto the device further allows us to incorporate smart sensors to determine diagnostic state to explore long term viability during chronic implantation.

  • Conference paper
    Williams I, Luan S, Jackson A, Constandinou TGet al., 2015,

    A scalable 32 channel neural recording and real-time FPGA based spike sorting system

    , IEEE Biomedical Circuits and Systems (BioCAS) Conference, Publisher: IEEE, Pages: 187-191

    This demo presents a scalable a 32-channel neuralrecording platform with real-time, on-node spike sorting ca-pability. The hardware consists of: an Intan RHD2132 neuralamplifier; a low power Igloo ® nano FPGA; and an FX3 USB3.0 controller. Graphical User Interfaces for controlling thesystem, displaying real-time data, and template generation witha modified form of WaveClus are demonstrated.

  • Conference paper
    De Marcellis A, Palange E, Liberatore V, Nubile L, Faccio M, Constandinou TGet al., 2015,

    A new modulation technique for high data rate low power UWB wireless optical communication in implantable biotelemetry systems

    , Eurosensors 2015

    We report on the development of a novel modulation technique for UWB wireless optical communication systems for application in a transcutaneous biotelemetry. The solution, based on the generation of short laser pulses, allows for a high data rate link whilst achieving a significant power reduction (energy per bit) compared to the state-of-the-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. These parts include circuits for bias and drive current generation, conditioning and processing, optimised for low-volt age/low-power operation. Preliminary experimental findings validate the new paradigm and show good agreement with expected results. The complete system achieves a BER less than 10-7, with maximum data rate of 125Mbps and estimated total power consumption of less than 3mW.

  • Patent
    Jackson A, Constandinou TG, Eftekhar A, Quiroga RQ, Navajas JAet al., 2015,

    System for a Brain-Computer Interface

  • Journal article
    Pesl P, Herrero P, Reddy M, Xenou M, Oliver N, Johnston D, Toumazou C, Georgiou Pet al., 2015,

    An Advanced Bolus Calculator for Type 1 Diabetes: System Architecture and Usability Results.

    , IEEE Journal of Biomedical and Health Informatics, Vol: 20, Pages: 11-17, ISSN: 2168-2208

    This paper presents the architecture and initial usability results of an advanced insulin bolus calculator for diabetes (ABC4D), which provides personalized insulin recommendations for people with diabetes by differentiating between various diabetes scenarios and automatically adjusting its parameters over time. The proposed platform comprises two main components: a smartphone-based patient platform allowing manual input of glucose and variables affecting blood glucose levels (e.g., meal carbohydrate content and exercise) and providing real-time insulin bolus recommendations; and a clinical revision platform to supervise the automatic adaptations of the bolus calculator parameters. The system implements a previously in silico validated bolus calculator algorithm based on case-based reasoning, which uses information from similar past events (i.e., cases) to suggest improved personalized insulin bolus recommendations and automatically learns from new events. Usability of ABC4D was assessed by analyzing the system usage at the end of a six-week pilot study (n = 10). Further feedback on the use of ABC4D has been obtained from each participant at the end of the study from a usability questionnaire. On average, each participant requested 115 ± 21 insulin recommendations, of which 103 ± 28 (90%) were accepted. The clinical revision software proposed a total of 754 case revisions, where 723 (96%) adaptations were approved by a clinical expert and updated in the patient platform.

  • Conference paper
    Woods S, Constandinou TG, 2015,

    A novel holding mechanism for next generation active wireless capsule endoscopy

    , 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Publisher: IEEE, Pages: 1181-1185

    This paper proposes that next generation wirelesscapsule endoscopy (WCE) technology will feature active me-chanical components (i.e. actuated) as opposed to current sys-tems that are predominantly passive (e.g. for imaging purposes).Future systems will integrate microsystems that use micro-actuators to, for example, perform micro-surgery, take tissuesamples, deliver medication, etc. In this paper we detail a novel,ultra-compact integrated mechanism for resisting peristalsisand describe how this can be fabricated in Nylon 6 usingCNC milling. The holding action is achieved by extendingan “anchor” spanning an effective 60.4 mm circumference, fora 11.0 mm diameter WCE. This function is achieved by amechanism that occupies only 347.0 mm3volume, includingmechanics and actuator. This shows how exploiting conventionalmanufacturing processes can result in a radical change in thecapabilities of WCE systems and empower the next generationof active devices.

  • Conference paper
    Rapeaux A, Nikolic K, Williams I, Eftekhar A, Constandinou TGet al., 2015,

    Fiber size-selective stimulation using action potential filtering for a peripheral nerve interface: A simulation study

    , 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Pages: 3411-3414

    Functional electrical stimulation is a powerfultool for restoration of function after nerve injury. Howeverselectivity of stimulation remains an issue. This paper presentsan alternative stimulation technique to obtain fiber size-selectivestimulation of nerves using FDA-approved electrode implants.The technique was simulated for the ventral roots ofXenopus Laevis, motivated by an application in bladder control. Thetechnique relies on applying a high frequency alternatingcurrent to filter out action potentials in larger fibers, resultingin selective stimulation of the smaller fibers. Results predict thatthe technique can distinguish fibers with only a 2 µm differencein diameter (for nerves not exceeding 2 mm in diameter). Thestudy investigates the behaviour of electrically blocked nervesin detail. Model imperfections and simplifications yielded someartefacts in the results, as well as unexpected nerve behaviourwhich is tentatively explained.

  • Journal article
    Woods S, Constandinou TG, 2015,

    Engineering Micro Mechanical Systems for the Next Generation Wireless Capsule Endoscopy

    , BioMed Research International, Vol: 2015, ISSN: 2314-6141

    Wireless capsule endoscopy (WCE) enables the detection and diagnosis of in ammatory bowel diseases such as Crohn's disease and ulcerative colitis. However treatment of these pathologies through the administering of therapy can only be achieved through conventional means. This paper describes the next generation wireless capsule endoscopy which has increased functionality to allow for targeted drug delivery in the small intestinal tract. A prototype microrobot fabricated in Nylon 6 is presented which is capable of resisting natural peristaltic pressure through the deployment of an integrated holding mechanism and delivering targeted therapy. The holding action is achieved by extending an \anchor" spanning an effective 60.4mm circumference, for a 11.0mm diameterWCE. This function is achieved by a mechanism that occupies only 347.0mm3 volume, including mechanics and actuator. A micro-positioning mechanism is described which utilises a single micromotor to radially position then deploy a needle 1.5mm outside the microrobot's body for the purpose of delivering a 1 ml dose of medication to a targeted site. An analysis of the mechanics required to drive the holding mechanism is presented and an overview of micro-actuators and the state of the art in WCE is discussed. The novel mechanisms offer increased functionality to WCE. It is envisaged that this increased ability to perform targeted therapy will empower the next generation of WCE to help diagnose and treat pathologies of the GI tract.

  • Conference paper
    Faliagkas K, Leene L, Constandinou TG, 2015,

    A Novel Neural Recording System Utilising Continuous Time Energy Based Compression

    , IEEE International Symposium on Circuits & Systems (ISCAS), Publisher: IEEE, Pages: 3000-3003

    This work presents a new data compression methodthat uses an energy operator to exploit the correlated energy inneural recording features in order to achieve adaptive sampling.This approach enhances conventional data converter topologieswith the power saving of asynchronous systems while maintaininglow complexity & high efficiency. The proposed scheme enablesthe transmission of 0:7kS/s, while preserving the features of thesignal with an accuracy of 95%. It is also shown that the operationof the system is not susceptible to noise, even for signals with 1dBSNR. The whole system consumes 3:94mWwith an estimated areaof 0:093mm2.

  • Journal article
    Hernandez-Silveira M, Ahmed K, Ang SS, Zandari F, Mehta T, Weir R, Burdett A, Toumazou C, Brett SJet al., 2015,

    Assessment of the feasibility of an ultra-low power, wireless digital patch for the continuous ambulatory monitoring of vital signs.

    , BMJ Open, Vol: 5, Pages: e006606-e006606, ISSN: 2044-6055

    BACKGROUND AND OBJECTIVES: Vital signs are usually recorded at 4-8 h intervals in hospital patients, and deterioration between measurements can have serious consequences. The primary study objective was to assess agreement between a new ultra-low power, wireless and wearable surveillance system for continuous ambulatory monitoring of vital signs and a widely used clinical vital signs monitor. The secondary objective was to examine the system's ability to automatically identify and reject invalid physiological data. SETTING: Single hospital centre. PARTICIPANTS: Heart and respiratory rate were recorded over 2 h in 20 patients undergoing elective surgery and a second group of 41 patients with comorbid conditions, in the general ward. OUTCOME MEASURES: Primary outcome measures were limits of agreement and bias. The secondary outcome measure was proportion of data rejected. RESULTS: The digital patch provided reliable heart rate values in the majority of patients (about 80%) with normal sinus rhythm, and in the presence of abnormal ECG recordings (excluding aperiodic arrhythmias such as atrial fibrillation). The mean difference between systems was less than ±1 bpm in all patient groups studied. Although respiratory data were more frequently rejected as invalid because of the high sensitivity of impedance pneumography to motion artefacts, valid rates were reported for 50% of recordings with a mean difference of less than ±1 brpm compared with the bedside monitor. Correlation between systems was statistically significant (p<0.0001) for heart and respiratory rate, apart from respiratory rate in patients with atrial fibrillation (p=0.02). CONCLUSIONS: Overall agreement between digital patch and clinical monitor was satisfactory, as was the efficacy of the system for automatic rejection of invalid data. Wireless monitoring technologies, such as the one tested, may offer clinical value when implemented as part of wider hospital systems that integrate and supp

  • Journal article
    Herrero P, Pesl P, Reddy M, Oliver N, Georgiou P, Toumazou Cet al., 2015,

    Advanced insulin bolus advisor based on run-to-run control and case-based reasoning

    , IEEE Journal of Biomedical and Health Informatics, Vol: 19, Pages: 1087-1096, ISSN: 2168-2194

    This paper presents an advanced insulin bolus advisor for people with diabetes on multiple daily injections or insulin pump therapy. The proposed system, which runs on a smartphone, keeps the simplicity of a standard bolus calculator while enhancing its performance by providing more adaptability and flexibility. This is achieved by means of applying a retrospective optimization of the insulin bolus therapy using a novel combination of run-to-run (R2R) that uses intermittent continuous glucose monitoring data, and case-based reasoning (CBR). The validity of the proposed approach has been proven by in-silico studies using the FDA-accepted UVa-Padova type 1 diabetes simulator. Tests under more realistic in-silico scenarios are achieved by updating the simulator to emulate intrasubject insulin sensitivity variations and uncertainty in the capillarity measurements and carbohydrate intake. The CBR(R2R) algorithm performed well in simulations by significantly reducing the mean blood glucose, increasing the time in euglycemia and completely eliminating hypoglycaemia. Finally, compared to an R2R stand-alone version of the algorithm, the CBR(R2R) algorithm performed better in both adults and adolescent populations, proving the benefit of the utilization of CBR. In particular, the mean blood glucose improved from 166 ± 39 to 150 ± 16 in the adult populations (p = 0.03) and from 167 ± 25 to 162 ± 23 in the adolescent population (p = 0.06). In addition, CBR(R2R) was able to completely eliminate hypoglycaemia, while the R2R alone was not able to do it in the adolescent population.

  • Journal article
    Herrero P, Pesl P, Bondia J, Reddy M, Oliver N, Georgiou P, Toumazou Cet al., 2015,

    Method for automatic adjustment of an insulin bolus calculator: In silico robustness evaluation under intra-day variability

    , COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE, Vol: 119, Pages: 1-8, ISSN: 0169-2607
  • Patent
    Reed S, Georgiou P, Constandinou TG, 2015,

    Method and Apparatus for Sensing a Property of a Fluid

    , 8,986,525 B2

    A device for sensing a property of a fluid comprising a first substrate having formed thereon a sensor configured in use to come into contact with a fluid in order to sense a property of the fluid, and a wireless transmitter for transmitting data over a wireless data link and a second substrate having formed thereon a wireless receiver for receiving data transmitted over said wireless link by said wireless transmitter. The first substrate is fixed to or within said second substrate. Additionally or alternatively, the device comprises a first substrate defining one or more microfluidic structures for receiving a fluid to be sensed and a second substrate comprising or having attached thereto a multiplicity of fluid sensors, the number of sensors being greater than the number of microfluidic structures. The second substrate is in contact with the first substrate such that at least one of the sensors is aligned with the or each microfluidic structure so as to provide an active sensor for the or each structure, and such that one or more of the sensors is or are not aligned with any microfluidic structure and is or are thereby redundant.

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