Overcoming the Impedance Range Limitations of Portable Bioelectrical Impedance Spectroscopy Clinical Devices.

Several portable commercial bioimpedance spectroscopy (BIS) devices are used in clinical research, but are limited by their reduced impedance measuring range to less demanding four-electrode configuration measurements. Some of these devices provide raw bioimpedance data for research purposes. The SFB7 device from ImpediMed® is a typical portable clinical device which perform 256 measurement points from 3 kHz to 1 MHz, providing for each point the resistance R and the reactance X. Its main drawback is its impedance range, limited to only 1100 Ω, making it less suitable for more demanding, higher impedance, two-electrode measurements which are potentially of great clinical interest. Some benchtop reference devices have larger frequency and impedance ranges than the SFB7 but are not portable and are not designed specifically for BIS measurement on humans.This article proposes a method to overcome the impedance range limitation of the SFB7 by connecting in parallel to the investigated bioimpedance a fixed and known impedance, whose value (and hence that of the total measured impedance) is within the device's range. The investigated impedance is then calculated by eliminating the contribution of the known impedance via a post processing of the data.This concept has been successfully tested on a physical model, and an in vivo example has validated the practicality of performing demanding two-electrode measurements on individuals using a SFB7, with relative errors of R and X inferior to 2.5% and 7% respectively.Clinical Relevance- Using the proposed setup and after post processing of the data, the SFB7 BIS device can now be used to perform demanding two-electrode measurements, hitherto impossible, enabling a range of novel clinical, high-impedance studies, for example for localized skin characterization.

The challenges facing wearable sensor systems.

It has been pointed out that, in spite of significant national and international funding programmes, there is a dearth of successfully commercialised wearable monitoring systems. Although problems such as financial reimbursement, device interoperability and the present lack of the required connected healthcare infrastructure are major hurdles to the provision of remote clinical monitoring of home-based patients, the "Mount Everest" of monitoring applications, why are wearable systems not already commercialised and used in less demanding applications? The numerous wearable systems which appear on the Web and even in the literature are, for the most part, basic prototypes unsuited to the demands of real-life applications. SMEs which do seek to commercialise clinically promising systems are unfortunately faced with many challenges and few as yet have survived long enough to successfully commercialise their innovations.

Recording of bruxism events in sleeping humans at home with a smart instrumented splint.

Objective: The aim of this paper is to report quantitative and qualitative characteristics of bruxism events recorded in sleeping humans with a new smart ambulatory system specifically designed to measure dental clenching and grinding forces. The device is wireless and rechargeable, which enables its use over extended periods.Methods: Thirty recordings were obtained from volunteer subjects who wore the device at home during 10 consecutive nights (Clinicaltrials.gov N° NCT03363204).Results: The recordings showed that the system was able to successfully monitor bruxism during 10 consecutive nights, allowing a quantitative (number, duration, intensity, distribution during the night), as well as a qualitative characterization of the bruxism events (clenching vs. grinding).Discussion: This system could offer new perspectives in the field of bruxism, either as a research tool for clinical studies or as a medical device for the ambulatory home-based monitoring of bruxism.

Comparison between bioelectrical impedance spectroscopy measurements and water volume displacement of ankle oedema variations during the course of a day.

OBJECTIVE: The purpose of this study was to find relationships between variations in bioelectrical impedance spectroscopy (BIS) measurements and those obtained by water displacement (WD) and calf (C) and ankle (A) perimetry on legs of patients with venous insufficiency and lower limb oedema, some with positive pitting test (PPT), others with negative pitting test (NPT). APPROACH: Twenty-nine (29) female subjects were clinically examined prior to inclusion in the trial. Measurements were taken once in the morning and then 6 h later, using perimetry, WD, and then BIS; subjects were standing. Leg volume was assessed using two WD volumeters, one 'Tall' (TWD) and one 'Short' (SWD). BIS was performed using a SFB7 impedance meter device (Impedimed®). MAIN RESULTS: Forty-three (43) legs with oedema were included. The results showed that 61% of the TWD variations variance was explained by SWD variations; less than 30% of the TWD variations variance was explained using BIS or perimetry alone, and 45% at best when used in combination. R0, related to extracellular water, was the key BIS parameter. For NPT subpopulation (32 legs), the composite parameter (C2 - A2)/R0 explained more than 60% of the TWD variations variance. For PPT subpopulation (11 legs), small or statistically non-significant variance explanations were found. SIGNIFICANCE: Combination of anthropometric and BIS parameters gave a better forecast of WD results than using only one or other. A novel composite parameter, (C2 - A2)/R0, better predicted TWD changes than other parameters hitherto used in literature, with improved estimates for the NPT subpopulation. Study n°ANSM 2017-A01063-50.

Ambulatory sensor for circumference monitoring of lower limbs.

The continuous monitoring of edema in the lower limbs of the human body is presently not possible as suitable devices are not available. This paper presents the characterization and the testing of a novel ambulatory device dedicated to the monitoring of circumference variations in the lower limb. The sensor, based on an inductive loop integrated into a textile band, is connected to a miniaturized electronic system which wirelessly sends the calculated perimeter value of the leg to a smart mobile device. In-vitro tests have demonstrated that the device enables the measurement of perimeters ranging from 25 cm to 33 cm with an accuracy of 0.3 cm. This result was obtained using a circular loop, which assumes that the shape of the leg remains circular at the location where the loop is positioned. To investigate the influence of the loop shape on the sensor response, three physical models of different shapes (circular, elliptic and triangular) were tested. It was found that self-inductance values of the loop can be predicted in an acceptable way using a theoretical model for the three different shapes. Experimental tests showed that the error in the perimeter value is around 5% of the full scale when changing the geometry from circular to elliptic but can reach 11 % from circular to triangular. The application interface developed for a smartphone is presented, which will enable the ambulatory monitoring of leg edemic swelling during daily activity and facilitate its assessment by the clinician.

Design and development of an impedimetric-based system for the remote monitoring of home-based dialysis patients.

A key clinical challenge is to determine the desired 'dry weight' of a patient in order to terminate the dialysis procedure at the optimal moment and thus avoid the effects of over- and under-hydration. It has been found that the effects of haemodialysis on patients can be conveniently monitored using whole-body bioimpedance measurements. The identified need of assessing the hydrational status of patients undergoing haemodialysis at home gave rise to the present Dialydom (DIALYse à DOMicile) project. The aim of the project is to develop a convenient miniaturised impedance monitoring device for localised measurements (on the calf) in order to estimate an impedimetric hydrational index of the home-based patient, and to transmit this and other parameters to a remote clinical site. Many challenges must be overcome to develop a robust and valid home-based device. Some of these are presented in the paper.

Nickel hexacyanoferrate modified screen-printed carbon electrode for sensitive detection of ascorbic acid and hydrogen peroxide.

Electrochemically modified screen-printed carbon electrode (SPCE) has been prepared by electrodepositing nickel hexacyanoferrate(III) (NiHCF) onto the electrode surface using cyclic voltammetry (CV). The performance of NiHCF-SPCE sensor was characterized and optimized by controlling several operational parameters. The NiHCF film has been proven to remain stable after CV scanning from 0 to +1.0 V vs. Ag/AgCl in the pH range of 3 to 10 and is re-useable. The most favourable supporting electrolyte solution exhibiting the optimum electroanalytical performance of the NiHCF-SPCE sensor was found to be 0.2 mol/L sodium nitrate. The electrochemical response toward ascorbic acid (AA) and H2O2 in 0.2 mol/L sodium nitrate solution was studied by using CV and the results showed that both analytes were electrocatalytically oxidized at approximately +0.4 V, while H2O2 also revealed a reduction signal at -0.8 V vs. Ag/AgCl. The NiHCF-SPCE sensor exhibited highly linear response for AA and H2O2 in the examined concentration range from 5.0x10-5 to 1.5x10-3 mol/L and from 2.0x10-5 to 1.0x10-3 mol/L (at +0.4 V), with the correlation coefficients of 0.999 and 0.998, respectively. The reproducibility of the NiHCF-SPCE sensor was followed for the determination of AA by using four individual electrodes, and the relative standard deviation of CV peak currents varied between 0.9 % and 2.2 %. The proposed NiHCF-SPCE has been shown to be a very attractive electrochemical sensor for AA and H2O2, also in a view of inexpensive mass production of disposable single-use sensors. The NiHCF-SPCE sensor was tested by measuring AA in multivitamin tablets, with recoveries obtained between 94.4 % and 108.2 % (n=5).

Flexible technologies and smart clothing for citizen medicine, home healthcare, and disease prevention.

Improvement of the quality and efficiency of healthcare in medicine, both at home and in hospital, is becoming more and more important for patients and society at large. As many technologies (micro technologies, telecommunication, low-power design, new textiles, and flexible sensors) are now available, new user-friendly devices can be developed to enhance the comfort and security of the patient. As clothes and textiles are in direct contact with about 90% of the skin surface, smart sensors and smart clothes with noninvasive sensors are an attractive solution for home-based and ambulatory health monitoring. Moreover, wearable devices or smart homes with exosensors are also potential solutions. All these systems can provide a safe and comfortable environment for home healthcare, illness prevention, and citizen medicine.

Non-mediated glucose biosensing using nanostructured TiO2.

Insufficient insulin production in diabetics can be controlled by discontinuous measurement and insulin therapy. Ideally, an artificial pancreas system would be a closed loop system measuring glucose levels, and administering insulin as required, to minimise patient contribution. This paper presents an investigation into the use of titanium dioxide as an electrochemical transducer for the detection of hydrogen peroxide. Hydrogen peroxide is the product of glucose oxidation by the enzyme glucose oxidase in the presence of oxygen. The results show that peroxide can be quantitatively detected by electrochemical reduction on titanium dioxide electrodes without interference due to dissolved oxygen. When tested for the indirect amperometric measurement of glucose (with free glucose oxidase) it was found that the electrodes responded linearly over the range of glucose concentration found in human blood. With further development, these electrodes may be suitable for implantable glucose sensors.

Detection and removal of pathogenic biofilms on medical implant surfaces.

Advances in sensor technology have had a significant impact in medical research and practice in the last decade. However, within the hospital environment problems still exist where the application of sensing technology could provide the solution. The presence of antibiotic resistant bacteria within hospitals and the risk of serious infection that they pose is a cause for concern. This paper describes a research project that has recently started at the University of Ulster investigating the potential of "Sense and Destroy" tactics to reduce the spread of medical device related infections. It is proposed that Electrical Impedance Spectroscopy (EIS) probes implanted within a catheter may be used to detect subclinical biofilm formation. Furthermore, if the presence of a biofilm is detected, activation of a photocatalytic coating on the catheter wall may be used to inactivate the responsible microorganisms.

Amperometric detection of phenolic compounds by polypyrrole-based composite carbon paste electrodes.

This contribution describes new composite carbon paste electrodes (CPEs) for the determination of phenolic compounds. The composite CPEs were prepared by in situ generation of polypyrrole (PPy) within a paste containing the enzyme polyphenol oxidase (PPO). The best paste composition (enzyme/pyrrole monomer/carbon particles/Nujol) was determined for a model enzyme, glucose oxidase (GOx) according to the enzymatic activity of the resulting electrodes and to the enzyme leakage from the paste during storage in phosphate buffer. The in situ electrogenerated PPy improves the enzyme immobilisation within the paste since practically no enzyme was lost in solution after 72 h of immersion. Moreover, the enzyme activity remains particularly stable under storage since the biocomposite structure conserves 80% of its activity after 1 month of storage. Following the optimisation of the paste composition, PPO-based carbon paste biosensors were prepared and presented excellent analytical properties toward catechol detection with a sensitivity of 4.7 A M(-1) cm(-2) and a response time lower than 20 s. The resulting biosensors were applied to the determination of polyphenolic compounds (e.g., epicatechin and ferulic acid).

Thin film platinum cuff electrodes for neurostimulation: in vitro approach of safe neurostimulation parameters.

Thin film technology takes more and more importance in the development of biomedical devices dedicated to functional neurostimulation. Our research about the design of implant neurostimulating electrode is oriented toward thin film cuff electrodes based on a polyimide substrate covered by a chromium/gold/Pt film. The chromium/gold sputtered film serves as adhesion layer and current collector whereas platinum acts as an electrochemical actuator. The electrode surface has been designed to obey safe stimulation criteria (i.e. chemically inert noble metal, low electrode-electrolyte impedance, high electrochemical reversibility, high corrosion stability). The electrochemical behaviour of such platinum electrodes has been assessed and compared to a foil of platinum. Extensive in vitro characterisations of the both electrode types were carried out using AFM, SEM and electrochemical techniques. The role of enhanced surface roughness enabling high double layer capacitances to be achieved was clearly highlighted. The obtained results are discussed, with particular reference to thin film electrodes stability under in vitro electrical stimulation in NaCl 0.9% (physiological serum). Therefore, these thin film devices showed reversible PtOH formation and decomposition making them potentially attractive for the fabrication of implant stimulation cuff electrodes.

Local effect of compression stockings on skin microcirculatory activity through the measurement of skin effective thermal conductivity.

This paper presents a preliminary study to demonstrate the instantaneous local effect of compression stocking (Class 2) on skin microcirculatory activity. The measurement needs to be carefully performed as the sensor is placed under the garment. To assess the local effect of compression stockings, we use the ambulatory device Hematron located on the calf under the garment. Skin microcirculatory activity is assessed through the skin's effective thermal conductivity measurement. A specific housing for the sensor has been designed to avoid excessive pressure induced by the sensor when squeezed by stockings. The experiment, conducted on ten healthy subjects, comprised two stages: without and with compression stockings. Skin effective thermal conductivity was recorded at three successive positions (supine, sitting and standing). Significant improvement in skin microcirculatory activity was recorded by the Hematron device for the three positions. We have also demonstrated that Hematron sensor can be used under compression stockings.

ActimedARM - design of a wearable system to monitor daily actimetry.

We developed a low power kinematic sensor, ActimedARM, incorporating three-axis accelerometer and magnetometer, a microcontroller ARM3, a ZigBee wireless communication and µSD memory storage. With embedded algorithms it can detect in real time the postures of the subject. A preliminary assessment conducted on 12 subjects reached a 97% correct classification rate. The device exhibits 32 days of autonomy on a 3600 mAh capacity battery, which makes it convenient for field experiments in true daily life.

Objective evaluation of stress with the blind by the monitoring of autonomic nervous system activity.

Accessibility for the blind in an urban space must be studied under real conditions in their daily environment. A new approach for evaluating the impact of environmental conditions on blind pedestrians is the objective measure of stress by the monitoring of the autonomic nervous system (ANS) activity. Original techniques of data analysis and spatial representation are proposed for the detection of the ANS activity through the assessment of the electrodermal activity. Skin resistance was recorded with an EmoSense system on 10 blind subjects who followed a charted course independently. The course was 1065 meters long and consisted of various environmental conditions in an urban space. The spatial frequency of the non-specific skin resistance responses was used to provide a more relevant representation of geographic hotspots. Results of statistical analysis based on this new parameter are discussed to conclude on phenomena causing mental stress with the blind moving in an urban space.

Introducing knowledge of wearing compression stockings on the skin blood flow by using microHematron device.

The aim of this preliminary study was to review the actual state of knowledge concerning the mechanisms underlying compression medical stockings action on the skin blood flow (SBF) in capillaries. SBF was assessed by measuring the thermal conductivity of living-tissues using microHematron ambulatory device. The investigation was performed for different postures using three standard French classes (10-15 mmHg, 15-20 mmHg and 20-36 mmHg) of Medical compression stockings (MCS) on six healthy subjects without chronic venous insufficiency. The experiment was divided into four stages (supine, sitting, standing and walking) and was repeated for each class of compression stockings and without MCS. The results showed a significant improvement of SBF depending on the class of MCS used. Best results were obtained for the Class III, which exerts to the highest level of pressure exerted around the ankle. Due to the low number of subjects, which therefore reduces the statistical relevance of results, a non-significant difference in SBF due to the subject's posture was observed. Nonetheless, a positive action by all the classes of MCS on SBF was measured for the supine position. This is a very important result; with patients with chronic venous insufficiency have often some mobility reduction, MCS may enhance their microcirculation even at rest.

Remote wound monitoring of chronic ulcers.

Chronic wounds or ulcers are wounds that do not heal in the usual manner. This type of wound is most common in the elderly and in paraplegic patients with an estimated 1% of the population suffering from leg ulcers and the costs adding up to 4% of the annual National Health Service budget in the U.K. There is an identified need to develop a device capable of remote wound monitoring that enables patients to take charge of their wound management under clinical guidance. A new ¿wound mapping¿ device has been developed, which is based on electrical impedance spectroscopy and involves the multifrequency characterization of the electrical properties of wound tissue under an electrode array. A key feature of the prototype device is the anticipated incorporation of the measuring array into standard commercial occlusive dressings, thereby protecting the wound from interference and contamination, and thus, promoting wound healing, while monitoring the protected wound. Further development is planned including wireless transmission, thus enabling telewound monitoring as described earlier.

Design and validation of an ambulatory system for the measurement of the microcirculation in the capillaries: microHematron device.

The non-invasive Hematron sensor is an active sensor used in studying skin blood flow (SBF) by measuring thermal conductivity of living tissues. Up to now, the Hematron device was composed of the Hematron probe and a heavy analog conditioning electronics. This paper presents the design, realization and validation of an ambulatory device (microHematron) associated with the original Hematron probe. The electronic architecture is based on a Programmable System on Chip (PSoC), which contributes in reducing the number of discrete components, and consequently, the electronic conditioning circuit of Hematron. The microHematron device can be worn on the wrist of the patient thanks to its size (4x3x1cm3) compared to the non-ambulatory conditioning electronics sized 20x30x20cm3. In addition, data can be stored in a microSD card or transmitted using a ZigBee module. The validation of the microHematron device was performed using the analog conditioning electronics as a reference. Experiments were performed first on a physical model reproducing microcirculation in order to characterize the linearity of the thermal conductivity as a function of water flow. Then, two experiments were hold in-vivo conditions highlighting the performances of this new device. In a first experiment, effects of mental calculation on effective tissue perfusion were measured and in a second one, effects of an anti-cellulite cream on micro-vascularisation and skin temperature were studied.

A wearable, low-power, health-monitoring instrumentation based on a Programmable System-on-Chip.

Improvement in quality and efficiency of health and medicine, at home and in hospital, has become of paramount importance. The solution of this problem would require the continuous monitoring of several key patient parameters, including the assessment of autonomic nervous system (ANS) activity using non-invasive sensors, providing information for emotional, sensorial, cognitive and physiological analysis of the patient. Recent advances in embedded systems, microelectronics, sensors and wireless networking enable the design of wearable systems capable of such advanced health monitoring. The subject of this article is an ambulatory system comprising a small wrist device connected to several sensors for the detection of the autonomic nervous system activity. It affords monitoring of skin resistance, skin temperature and heart activity. It is also capable of recording the data on a removable media or sending it to computer via a wireless communication. The wrist device is based on a Programmable System-on-Chip (PSoC) from Cypress: PSoCs are mixed-signal arrays, with dynamic, configurable digital and analogical blocks and an 8-bit Microcontroller unit (MCU) core on a single chip. In this paper we present first of all the hardware and software architecture of the device, and then results obtained from initial experiments.

Evaluation of the autonomic nervous system for fall detection.

Studies show that the proportion of elderly will reach 30% of the total population by 2050 in developed countries, such as France. The elderly live generally alone, thus many health problems related to age are under reported. Falling is one of these problems and several devices have been developed recently, based on accelerometers, in order to detect it and alert carers. In order to improve the detection success of these devices, we propose quantifying autonomic nervous system activity (ANS) using a wearable ambulatory device developed for this purpose. We studied the A.N.S's response on 7 adult subjects during simulated falls and standing-lying transitions. We implemented a classification method using the Support Vector Machine in order to classify these two situations using measured heart rate variability and electrodermal response. Good results (sensibility = 70.37%, specificity = 80%, positive predictor = 73.8%) were obtained using a Polynomial kernel (p = 5) for the support vector machine implementation.