Publications

Charge exchange is the fundamental process that sustains cellular respiration and photosynthesis by shuttling electrons in a cascade of electron transfer (ET) steps between redox cofactors. While intraprotein charge exchange is well characterized in protein complexes bearing multiple redox sites, interprotein processes are less understood due to the lack of suitable experimental approaches and the dynamic nature of the interactions. Proteins constrained between electrodes are known to support electron transport (ETp) through the protein matrix even without redox cofactors, as the charges housed by the redox sites in ET are furnished by the electrodes. However, it is unknown whether protein ETp mechanisms apply to the interprotein medium present under physiological conditions. We study interprotein charge exchange between plant photosystem I (PSI) and its soluble redox partner plastocyanin (Pc) and address the role of the Pc copper center. Using electrochemical scanning tunneling spectroscopy (ECSTS) current-distance and blinking measurements, we quantify the spatial span of charge exchange between individual Pc/PSI pairs and ETp through transient Pc/PSI complexes. Pc devoid of the redox center (Pcapo) can exchange charge with PSI at longer distances than with the copper ion (Pcholo). Conductance bursts associated with Pcapo/PSI complex formation are higher than in Pcholo/PSI. Thus, copper ions are not required for long-distance Pc/PSI ETp but regulate its spatial span and conductance. Our results suggest that the redox center that carries the charge in Pc is not necessary to exchange it in interprotein ET through the aqueous solution and question the canonical view of tight complex binding between redox protein partners.

JTD Keywords: azurin, binding, blinking, crystal-structure, cupredoxin, current distance spectroscopy, electrochemical tunneling microscopy, proteinconductance, reduction, single metalloprotein, single molecule measurements, site, spectroscopy, Blinking, Cupredoxin, Current distance spectroscopy, Electrochemical tunneling microscopy, Interprotein electron transfer, Protein conductance, Single molecule measurements, State electron-transport

Photosynthesis is a fundamental process that converts photons into chemical energy, driven by large protein complexes at the thylakoid membranes of plants, cyanobacteria, and algae. In plants, water-soluble plastocyanin (Pc) is responsible for shuttling electrons between cytochrome b6f complex and the photosystem I (PSI) complex in the photosynthetic electron transport chain (PETC). For an efficient turnover, a transient complex must form between PSI and Pc in the PETC, which implies a balance between specificity and binding strength. Here, we studied the binding frequency and the unbinding force between suitably oriented plant PSI and Pc under redox control using single molecule force spectroscopy (SMFS). The binding frequency (observation of binding-unbinding events) between PSI and Pc depends on their respective redox states. The interaction between PSI and Pc is independent of the redox state of PSI when Pc is reduced, and it is disfavored in the dark (reduced P700) when Pc is oxidized. The frequency of interaction between PSI and Pc is higher when at least one of the partners is in a redox state ready for electron transfer (ET), and the post-ET situation (PSIRed-PcOx) leads to lower binding. In addition, we show that the binding of ET-ready PcRed to PSI can be regulated externally by Mg2+ ions in solution.

JTD Keywords: architecture, binding-site, complexes, ferredoxin, force spectroscopy, induced structural-changes, interprotein electron transfer, light-dependent interaction, mg2+ concentration, photosystem i, plastocyanin, probe, recognition, reduction, Force spectroscopy, Interprotein electron transfer, Light-dependent interaction, Photosynthetic reaction-center, Photosystem i, Plastocyanin, Single molecule measurements

Assessing tidal volume during mechanical ventilation is critical to improving gas exchange while avoiding ventilator-induced lung injury. Conventional flow and volume measurements are usually carried out by built-in pneumotachographs in the ventilator or by stand-alone flowmeters. Such flow/volume measurement devices are expensive and thus usually unaffordable in low-resource settings. Here, we aimed to design and test low-cost and technically-simple calibration and assembly pneumotachographs. The proposed pneumotachographs are made by manual perforation of a plate with a domestic drill. Their pressure-volume relationship is characterized by a quadratic equation with parameters that can be tailored by the number and diameter of the perforations. We show that the calibration parameters of the pneumotachographs can be measured through two maneuvers with a conventional resuscitation bag and by assessing the maneuver volumes with a cheap and straightforward water displacement setting. We assessed the performance of the simplified low-cost pneumotachographs to measure flow/volume during mechanical ventilation as carried out under typical conditions in low-resource settings, i.e., lacking gold standard expensive devices. Under realistic mechanical ventilation settings (pressure- and volume-control; 200-600 mL), inspiratory tidal volume was accurately measured (errors of 2.1% on average and <4% in the worst case). In conclusion, a simple, low-cost procedure facilitates the construction of affordable and accurate pneumotachographs for monitoring mechanical ventilation in low- and middle-income countries.

JTD Keywords: calibration, flow measurement, low- and middle-income countries, mechanical ventilation, pneumotachograph, Calibration, Flow, Flow measurement, Low- and middle-income countries, Lung injury, Mechanical ventilation, Pneumotachograph, Pressure-drop, Resistance, Tidal volume

This study explored the use of parasternal second intercostal space and lower intercostal space surface electromyogram (sEMG) and surface mechanomyogram (sMMG) recordings (sEMGpara and sMMGpara, and sEMGlic and sMMGlic, respectively) to assess neural respiratory drive (NRD), neuromechanical (NMC) and neuroventilatory (NVC) coupling, and mechanical efficiency (MEff) noninvasively in healthy subjects and chronic obstructive pulmonary disease (COPD) patients. sEMGpara, sMMGpara, sEMGlic, sMMGlic, mouth pressure (Pmo), and volume (Vi) were measured at rest, and during an inspiratory loading protocol, in 16 COPD patients (8 moderate and 8 severe) and 9 healthy subjects. Myographic signals were analyzed using fixed sample entropy and normalized to their largest values (fSEsEMGpara%max, fSEsMMGpara%max, fSEsEMGlic%max, and fSEsMMGlic%max). fSEsMMGpara%max, fSEsEMGpara%max, and fSEsEMGlic%max were significantly higher in COPD than in healthy participants at rest. Parasternal intercostal muscle NMC was significantly higher in healthy than in COPD participants at rest, but not during threshold loading. Pmo-derived NMC and MEff ratios were lower in severe patients than in mild patients or healthy subjects during threshold loading, but differences were not consistently significant. During resting breathing and threshold loading, Vi-derived NVC and MEff ratios were significantly lower in severe patients than in mild patients or healthy subjects. sMMG is a potential noninvasive alternative to sEMG for assessing NRD in COPD. The ratios of Pmo and Vi to sMMG and sEMG measurements provide wholly noninvasive NMC, NVC, and MEff indices that are sensitive to impaired respiratory mechanics in COPD and are therefore of potential value to assess disease severity in clinical practice. Author

JTD Keywords: biomedical measurement, chronic obstructive pulmonary disease, couplings, diaphragm, disease severity, efficiency, electromyography, exacerbations, healthy volunteers, inspiratory muscles, loading, mechanomyography, obstructive pulmonary-disease, pressure measurement, protocols, respiratory mechanics, respiratory muscles, responsiveness, spirometry, stimulation, volume measurement, At rests, Biomedical measurement, Biomedical measurements, Chronic obstructive pulmonary disease, Couplings, Disease severity, Efficiency ratio, Electromyography, Healthy subjects, Healthy volunteers, Loading, Mechanical efficiency, Mechanomyogram, Muscle, Muscles, Neural respiratory drive, Noninvasive medical procedures, Pressure measurement, Protocols, Pulmonary diseases, Surface electromyogram, Volume measurement

Under intrauterine growth restriction (IUGR), abnormal attainment of the nutrients and oxygen by the fetus restricts the normal evolution of the prenatal causing in many cases high morbidity being one of the top-ten causes of neonatal death. The current gold standards in hospitals to detect this relevant problem is the clinical observation by echography, cardiotocography and Doppler. These qualitative techniques are not conclusive and requires risky invasive fetal scalp blood testing and/or amniocentesis. We developed micro-implantable multiparametric electrochemical sensors for measuring ischemia in real time in fetal tissue and vascular. This implantable technology is designed to continuous monitoring for an early detection of ischemia to avoid potential fetal injury. Two miniaturized electrochemical sensors were developed based on oxygen and pH detection. The sensors were optimized in vitro under controlled concentration, to assess the selectivity and sensitivity required. The sensors were then validated in vivo in the ewe fetus model, by means of their insertion in the muscle leg and inside the iliac artery of the fetus. Ischemia was achieved by gradually obstructing the umbilical cord to regulate the amount of blood reaching the fetus. An important challenge in fetal monitoring is the detection of low levels of oxygen and pH changes under ischemic conditions, requiring high sensitivity sensors. Significant differences were observed in both; pH and pO(2) sensors under changes from normoxia to hypoxia states in the fetus tissue and vascular with both sensors. Herein, we demonstrate the feasibility of the developed sensors for future fetal monitoring in medical applications.

JTD Keywords: electrochemical biosensor, implantable sensor, in vivo validation, ischemia detection, tissue and vascular monitoring, Animal experiment, Animal model, Animal tissue, Article, Blood-gases, Brain, Classification, Controlled study, Diagnosis, Doppler, Early diagnosis, Electrochemical analysis, Electrochemical biosensor, Ewe, Feasibility study, Female, Fetus, Fetus disease, Fetus monitoring, Gestational age, Hypoxemia, Iliac artery, Implantable sensor, In vivo validation, Intrauterine growth restriction, Intrauterine growth retardation, Ischemia detection, Leg muscle, Management, Nonhuman, Oxygen consumption, Ph, Ph and oxygen detection, Ph measurement, Process optimization, Sheep, Tissue and vascular monitoring, Umbilical-cord occlusion

© 1964-2012 IEEE. Surface electromyography (sEMG) can be used for the evaluation of respiratory muscle activity. Recording sEMG involves the use of surface electrodes in a bipolar configuration. However, electrocardiographic (ECG) interference and electrode orientation represent considerable drawbacks to bipolar acquisition. As an alternative, concentric ring electrodes (CREs) can be used for sEMG acquisition and offer great potential for the evaluation of respiratory muscle activity due to their enhanced spatial resolution and simple placement protocol, which does not depend on muscle fiber orientation. The aim of this work was to analyze the performance of CREs during respiratory sEMG acquisitions. Respiratory muscle sEMG was applied to the diaphragm and sternocleidomastoid muscles using a bipolar and a CRE configuration. Thirty-two subjects underwent four inspiratory load spontaneous breathing tests which was repeated after interchanging the electrode positions. We calculated parameters such as (1) spectral power and (2) median frequency during inspiration, and power ratios of inspiratory sEMG without ECG in relation to (3) basal sEMG without ECG (Rins/noise), (4) basal sEMG with ECG (Rins/cardio) and (5) expiratory sEMG without ECG (Rins/exp). Spectral power, Rins/noise and Rins/cardio increased with the inspiratory load. Significantly higher values (p < 0.05) of Rins/cardio and significantly higher median frequencies were obtained for CREs. Rins/noise and Rins/exp were higher for the bipolar configuration only in diaphragm sEMG recordings, whereas no significant differences were found in the sternocleidomastoid recordings. Our results suggest that the evaluation of respiratory muscle activity by means of sEMG can benefit from the remarkably reduced influence of cardiac activity, the enhanced detection of the shift in frequency content and the axial isotropy of CREs which facilitates its placement.

JTD Keywords: atmospheric measurements, concentric ring electrodes, electrocardiography, electrodes, electromyography, laplacian potential, non-invasive respiratory monitoring, particle measurements, respiratory muscles, surface electromyography, Concentric ring electrodes, Laplacian potential, Muscles, Non-invasive respiratory monitoring, Respiratory muscles, Surface electromyography

Low-cost gas sensors allow for large-scale spatial monitoring of air quality in the environment. However they require calibration before deployment. Methods such as multivariate regression techniques have been applied towards sensor calibration. In this work, we propose instead, the use of deep learning methods, particularly, recurrent neural networks for predicting the gas concentrations based on the outputs of these sensors. This paper presents a first study of using Gated Recurrent Unit (GRU) neural network models for gas concentration prediction. The GRU networks achieve on average, a 44.69% and a 25.17% RMSE improvement in concentration prediction on a gas dataset when compared with Support Vector Regression (SVR) and Multilayer Perceptron (MLP) models respectively. With the current advances in deep network hardware accelerators, these networks can be combined with the sensors for a compact embedded system suitable for edge applications.

JTD Keywords: Robot sensing systems, Predictive models, Logic gates, Gas detectors, Training, Temperature measurement, Support vector machines

Modern optical sensors coupled with time-lapse microscopy devices and dedicated software tools allow the miniaturization of laboratories for biological experiments leading to the Organ-On-Chip (OoC) framework. OoCs allow performing massive measurements on a large number of cells under the assumption of reproducibility conditions, permitting to investigate the cell dynamics in terms of motility and shape changes over time. In this work, we present the OoC platform used in a preliminary study of the Rare Haemolytic Anaemia (RHA) disease, a group of rare diseases characterized by haemolysis, which is the premature loss of red blood cells (RBCs). Preliminary results demonstrate the effectiveness of shape measurement for the diagnosis of RHA.

JTD Keywords: Anaemia diagnosis, Cell tracking, Plasticity measurement, Time-lapse microscopy

Diaphragm neuromechanical coupling (NMC), which reflects the efficiency of conversion of neural activation to transdiaphragmatic pressure (Pdi), is increasingly recognized to be a useful clinical index of diaphragm function and respiratory mechanics in neuromuscular weakness and cardiorespiratory disease. However, the current gold standard assessment of diaphragm NMC requires invasive measurements of Pdi and crural diaphragm electromyography (oesEMGdi), which complicates the measurement of diaphragm NMC in clinical practice. This is the first study to compare invasive measurements of diaphragm NMC (iNMC) using the relationship between Pdi and oesEMGdi, with noninvasive assessment of NMC (nNMC) using surface mechanomyography (sMMGlic) and electromyography (sEMGlic) of lower chest wall inspiratory muscles. Both invasive and noninvasive measurements were recorded in twelve healthy adult subjects during an inspiratory threshold loading protocol. A linear relationship between noninvasive sMMGlic and sEMGlic measurements was found, resulting in little change in nNMC with increasing inspiratory load. By contrast, a curvilinear relationship between invasive Pdi and oesEMGdi measurements was observed, such that there was a progressive increase in iNMC with increasing inspiratory threshold load. Progressive recruitment of lower ribcage muscles, serving to enhance the mechanical advantage of the diaphragm, may explain the more linear relationship between sMMGlic and sEMGlic (both representing lower intercostal plus costal diaphragm activity) than between Pdi and crural oesEMGdi. Noninvasive indices of NMC derived from sEMGlic and sMMGlic may prove to be useful indices of lower chest wall inspiratory muscle NMC, particularly in settings that do not have access to invasive measures of diaphragm function.

JTD Keywords: Cardiovascular system, Diaphragms, Diseases, Electromyography, Medical signal processing, Neurophysiology, Patient monitoring, Pneumodynamics, Inspiratory muscle neuromechanical coupling, Diaphragm neuromechanical coupling, Neural activation, Transdiaphragmatic pressure, Diaphragm function, Respiratory mechanics, Diaphragm NMC, Invasive measurements, Crural diaphragm electromyography, iNMC, Noninvasive assessment, nNMC, Lower chest wall inspiratory muscles, Inspiratory threshold loading protocol, Noninvasive sMMGlic measurements, sEMGlic measurements, oesEMGdi measurements, Inspiratory threshold load, Lower ribcage muscles, Lower intercostal plus costal diaphragm activity, Crural oesEMGdi, Noninvasive indices, sEMGlic sMMGlic, Lower chest wall inspiratory muscle NMC, Surface mechanomyography, Electromyography, Inspiratory threshold loading, Mechanomyography, Neuromechanical coupling, Respiratory muscles

Fixed sample entropy (fSampEn) has been successfully applied to myographic signals for inspiratory muscle activity estimation, attenuating interference from cardiac activity. However, several values have been suggested for fSampEn parameters depending on the application, and there is no consensus standard for optimum values. This study aimed to perform a thorough evaluation of the performance of the most relevant fSampEn parameters in myographic respiratory signals, and to propose, for the first time, a set of optimal general fSampEn parameters for a proper estimation of inspiratory muscle activity. Different combinations of fSampEn parameters were used to calculate fSampEn in both non-invasive and the gold standard invasive myographic respiratory signals. All signals were recorded in a heterogeneous population of healthy subjects and chronic obstructive pulmonary disease patients during loaded breathing, thus allowing the performance of fSampEn to be evaluated for a variety of inspiratory muscle activation levels. The performance of fSampEn was assessed by means of the cross-covariance of fSampEn time-series and both mouth and transdiaphragmatic pressures generated by inspiratory muscles. A set of optimal general fSampEn parameters was proposed, allowing fSampEn of different subjects to be compared and contributing to improving the assessment of inspiratory muscle activity in health and disease.

JTD Keywords: Electromyography, Fixed sample entropy, Mechanomyography, Non-invasive physiological measurements, Oesophageal electromyography, Respiratory muscle

Bioimpedance is known for its linear relation with volume during normal breathing. For that reason, bioimpedance can be used as a noninvasive and comfortable technique for measuring respiration. The goal of this study is to analyze the temporal behavior of bioimpedance measured in four different electrode configurations during inspiratory loaded breathing. We measured four bioimpedance channels and airflow simultaneously in 10 healthy subjects while incremental inspiratory loads were imposed. Inspiratory loading threshold protocols are associated with breathing pattern changes and were used in respiratory mechanics studies. Consequently, this respiratory protocol allowed us to induce breathing pattern changes and evaluate the temporal relationship of bioimpedance with volume. We estimated the temporal delay between bioimpedance and volume respiratory cycles to evaluate the differences in their temporal behavior. The delays were computed as the lag which maximize the cross-correlation of the signals cycle by cycle. Six of the ten subjects showed delays in at least two different inspiratory loads. The delays were dependent on electrode configuration, hence the appearance of the delays between bioimpedance and volume were conditioned to the location and geometry of the electrode configuration. In conclusion, the delays between these signals could provide information about breathing pattern when breathing conditions change.

JTD Keywords: Bioimpedance, Delays, Electrodes, Protocols, Loading, Electrocardiography, Atmospheric measurements

Emerging nanobiotechnologies can offer solutions to the current and future challenges in medicine. By covering topics from regenerative medicine, tissue engineering, drug delivery, bionanofabrication, and molecular biorecognition, this Special Issue aims to provide an update on the trends in nanomedicine and drug delivery using biomimetic approaches, and the development of novel biologically inspired devices for the safe and effective diagnosis, prevention, and treatment of disease.

JTD Keywords: Bioinspired nanotechnologies, Bionanofabrication, Bio-nano measurement and microscopy, Nanomaterials for biological and medical applications, Nanoassemblies, Nanostructured surfaces, Drug delivery, Nanobioelectronics, Integrated systems/nanobiosensors, Nanotoxicology, Graphene-based applications

We present a novel lab-on-a-chip (LOC) device for the simultaneous detection of multiple biomarkers using simple voltage measurements. The biosensor functionalization is performed in-situ, immediately before its use, facilitating reagents storage and massive devices fabrication. Sensitivity, limit of detection (LOD) and limit of quantification (LOQ) are tunable depending on the in-chip flown sample volumes. As a proof-of-concept, the system has been tested and adjusted to quantify two proteins found in blood that are susceptible to be used combined, as a screening tool, to diagnose prostate cancer (PCa): prostate-specific antigen (PSA) and spondin-2 (SPON2). This combination of biomarkers has been reported to be more specific for PCa diagnostics than the currently accepted but rather controversial PSA indicator. The range of detection for PSA and SPON2 could be adjusted to the clinically relevant range of 1 to 10. ng/ml. The system was tested for specificity to the evaluated biomarkers. This multiplex system can be modified and adapted to detect a larger quantity of biomarkers, or different ones, of relevance to other specific diseases.

JTD Keywords: Adjustable sensing, Impedance measurements, In situ functionalization, Microfluidics, Prostate specific antigen, Self-assembled monolayers

An array with all-solid-state, potentiometric, miniaturized sensors for pH and potassium was developed to be introduced into the stomach or other sectors of the digestive tract by means of flexible endoscopy. These sensors perform continuous and simultaneous measurement of extracellular pH and potassium. This detection seeks to sense ischemia in the gastric mucosa inside the stomach, an event indicative of local microvascular perfusion and tissue oxygenation status. Our array is proposed as a medical tool to identify the occurrence of the ischemia after gastrointestinal or gastroesophageal anastomosis. The stability and feasibility of the miniaturized working and reference electrodes integrated in the array were studied under in vitro conditions, and the behavior of the potassium and pH ion-selective membranes were optimized to work under acidic gastric conditions with high concentrations of HCl. The array was tested in vivo in pigs to measure the ischemia produced by clamping the blood flow into the stomach. Our results indicate that ischemic and reperfusion states can be sensed in vivo and that information on tissue damage can be collected by this sensor array. The device described here provides a miniaturized, inexpensive, and mass producible sensor array for detecting local ischemia caused by unfavorable anastomotic perfusion and will thus contribute to preventing anastomotic leakage and failure caused by tissue necrosis.

JTD Keywords: Endoscopy, Surgery, Tissue, Gastric anastomosis, Gastric conditions, Ion selective sensors, Ischemia, pH detection, Reference electrodes, Simultaneous measurement, Tissue oxygenation, Sensors

Among the most common sleep disorders are those related to disruptions in airflow (apnea) or reductions in the breath amplitude (hypopnea) with or without obstruction of the upper airway (UA). One of the most important sleep disorders is obstructive sleep apnea (OSA). This sleep-disordered breathing, quantified by the apnea-hypopnea index (AHI), can produce a significant reduction of oxygen saturation and an abnormal elevation of carbon dioxide levels in the blood. Apnea and hypopnea episodes are associated with arousals and sleep fragmentation during the night and compensatory response of the autonomic nervous system.

JTD Keywords: Biomedical engineering, Biomedical measurements, Biomedical monitoring, Breathing disorders, Medical conditions, Medical treatment, Sleep, Sleep apnea

Automated signal processing in analytical instrumentation is today required for the analysis of highly complex biomedical samples. Baseline estimation techniques are often used to correct long term instrument contamination or degradation. They are essential for accurate peak area integration. Some methods approach the baseline estimation iteratively, trying to ignore peaks which do not belong to the baseline. The proposed method in this work consists of a modification of the Asymmetric Least Squares (ALS) baseline removal technique developed by Eilers and Boelens. The ALS technique suffers from bias in the presence of intense peaks (in relation to the noise level). This is typical of diverse instrumental techniques such as Gas Chromatography-Mass Spectrometry (GC-MS) or Gas Chromatography-Ion Mobility Spectrometry (GC-IMS). In this work, we propose a modification (named psalsa) to the asymmetry weights of the original ALS method in order to better reject large peaks above the baseline. Our method will be compared to several versions of the ALS algorithm using synthetic and real GC signals. Results show that our proposal improves previous versions being more robust to parameter variations and providing more accurate peak areas.

JTD Keywords: Gas chromatography, Instruments, Radioactivity measurement, Signal processing, Analytical instrument, Analytical Instrumentation, Asymmetric least squares, Baseline estimation, Baseline removal, Gas chromatography-mass spectrometries (GC-MS), Instrumental techniques, Noise levels, Iterative methods

Non-invasive evaluation of respiratory activity is an area of increasing research interest, resulting in the appearance of new monitoring techniques, ones of these being based on the analysis of the diaphragm mechanomyographic (MMGdi) signal. The MMGdi signal can be decomposed into two parts: (1) a high frequency activity corresponding to lateral vibration of respiratory muscles, and (2) a low frequency activity related to excursion of the thoracic cage. The purpose of this study was to apply the empirical mode decomposition (EMD) method to obtain the low frequency of MMGdi signal and selecting the intrinsic mode functions related to the respiratory movement. With this intention, MMGdi signals were acquired from a healthy subject, during an incremental load respiratory test, by means of two capacitive accelerometers located at left and right sides of rib cage. Subsequently, both signals were combined to obtain a new signal which contains the contribution of both sides of thoracic cage. Respiratory rate (RR) measured from the mechanical activity (RR_Mmg) was compared with that measured from inspiratory pressure signal (RR_P). Results showed a Pearson's correlation coefficient (r = 0.87) and a good agreement (mean bias = -0.21 with lower and upper limits of -2.33 and 1.89 breaths per minute, respectively) between RR_mmg and RR_P measurements. In conclusion, this study suggests that RR can be estimated using EMD for extracting respiratory movement from low mechanical activity, during an inspiratory test protocol.

JTD Keywords: Accelerometers, Band-pass filters, Biomedical measurement, Empirical mode decomposition, Estimation, IP networks, Muscles

Ischemic and dilated cardiomyopathy are associated with disorders of myocardium. Using the blood pressure (BP) signal and the values of the ventricular ejection fraction, we obtained parameters for stratifying cardiomyopathy patients as low- and high-risk. We studied 48 cardiomyopathy patients characterized by NYHA ≥2: 19 patients with dilated cardiomyopathy (DCM) and 29 patients with ischemic cardiomyopathy (ICM). The left ventricular ejection fraction (LVEF) percentage was used to classify patients in low risk (LR: LVEF > 35%, 17 patients) and high risk (HR: LVEF ≤ 35%, 31 patients) groups. From the BP signal, we extracted the upward systolic slope (BP_sl), the difference between systolic and diastolic BP (BPA), and systolic time intervals (STI). When we compared the LR and HR groups in the time domain analysis, the best parameters were standard deviation (SD) of 1=STI, kurtosis (K) of BP_sl, and K of BPA. In the frequency domain analysis, very low frequency (VLF) and high frequency (HF) bands showed statistically significant differences in comaprisons of LR and HR groups. The area under the curve of power spectral density was the best parameter in all classifications, and particularly in the very-low-and high- frequency bands (p <; 0.001). These parameters could help to improve the risk stratification of cardiomyopathy patients.

JTD Keywords: blood pressure measurement, cardiovascular system, diseases, medical disorders, medical signal processing, statistical analysis, time-domain analysis, BP signal, HR groups, LR groups, blood pressure signal analysis, cardiomyopathy patients, diastolic BP, dilated cardiomyopathy, frequency domain analysis, high-frequency bands, ischemic cardiomyopathy, left ventricular ejection fraction, low-frequency bands, myocardium disorders, patient characterization, power spectral density curve, standard deviation, statistical significant differences, systolic BP, systolic slope, systolic time intervals, time domain analysis, ventricular ejection fraction, Abstracts, Databases, Parameter extraction, Telecommunication standards, Time-frequency analysis

Due to its environmental, economical and safety implications, methane leak detection is a crucial task to address in the biogas production industry. In this paper, we introduce Gasbot, a robotic platform that aims to automatize methane emission monitoring in landfills and biogas production sites. The distinctive characteristic of the Gasbot platform is the use of a Tunable Laser Absorption Spectroscopy (TDLAS) sensor. This sensor provides integral concentration measurements over the path of the laser beam. Existing gas distribution mapping algorithms can only handle local measurements obtained from traditional in-situ chemical sensors. In this paper we also describe an algorithm to generate 3D methane concentration maps from integral concentration and depth measurements. The Gasbot platform has been tested in two different scenarios: an underground corridor, where a pipeline leak was simulated and in a decommissioned landfill site, where an artificial methane emission source was introduced.

JTD Keywords: Laser beams, Measurement by laser beam, Mobile robots, Robot kinematics, Robot sensing systems

In this work we report the fabrication and characterization of a label-free impedimetric immunosensor based on a silicon nitride (Si 3N 4) surface for the specific detection of human serum albumin (HSA) proteins. Silicon nitride provides several advantages compared with other materials commonly used, such as gold, and in particular in solid-state physics for electronic-based biosensors. However, few Si 3N 4-based biosensors have been developed; the lack of an efficient and direct protocol for the integration of biological elements with silicon-based substrates is still one of its the main drawbacks. Here, we use a direct functionalization method for the direct covalent binding of monoclonal anti-HSA antibodies on an aldehyde-functionalized Si-p/SiO 2/Si 3N 4 structure. This methodology, in contrast with most of the protocols reported in literature, requires less chemical reagents, it is less time-consuming and it does not need any chemical activation. The detection capability of the immunosensor was tested by performing non-faradaic electrochemical impedance spectroscopy (EIS) measurements for the specific detection of HSA proteins. Protein concentrations within the linear range of 10 -13-10 -7M were detected, showing a sensitivity of 0.128ΩμM -1 and a limit of detection of 10 -14M. The specificity of the sensor was also addressed by studying the interferences with a similar protein, bovine serum albumin. The results obtained show that the antibodies were efficiently immobilized and the proteins detected specifically, thus, establishing the basis and the potential applicability of the developed silicon nitride-based immunosensor for the detection of proteins in real and more complex samples.

JTD Keywords: Aldehyde, Electrochemical impedance spectroscopy, Human serum albumin, Immunosensor, Silicon nitride, Bovine serum albumins, Chemical reagents, Complex samples, Covalent binding, Detection capability, Electrochemical impedance, Electrochemical impedance spectroscopy measurements, Functionalizations, Human serum albumins, Impedimetric immunosensors, Label free, Limit of detection, Linear range, Protein concentrations, Silicon-based, Specific detection, Aldehydes

The self-assembly of peptides and proteins into amyloid fibrils of nanometric thickness and up to several micrometres in length, a phenomenon widely observed in biological systems, has recently aroused a growing interest in nanotechnology and nanomedicine. Here we have applied atomic force microscopy and single molecule force spectroscopy to study the amyloidogenesis of a peptide derived from human amylin and of its reverse sequence. The spontaneous formation of protofibrils and their orientation along well-defined directions on graphite and DMSO-coated graphite substrates make the studied peptides interesting candidates for nanotechnological applications. The measured binding forces between peptides correlate with the number of hydrogen bonds between individual peptides inside the fibril structure according to molecular dynamics simulations.

JTD Keywords: Amyloid fibril, Amyloidogenesis, Binding forces, Fibril structure, Graphite substrate, Molecular dynamics simulations, Nanometrics, Protofibrils, Single molecule force spectroscopy, Spontaneous formation, Atomic force microscopy, Atomic spectroscopy, Graphite, Hydrogen bonds, Medical nanotechnology, Molecular dynamics, Molecular physics, Self assembly, Thickness measurement, Peptides

Signal and data processing are essential elements in electronic noses as well as in most chemical sensing instruments. The multivariate responses obtained by chemical sensor arrays require signal and data processing to carry out the fundamental tasks of odor identification (classification), concentration estimation (regression), and grouping of similar odors (clustering). In the last decade, important advances have shown that proper processing can improve the robustness of the instruments against diverse perturbations, namely, environmental variables, background changes, drift, etc. This article reviews the advances made in recent years in signal and data processing for machine olfaction and chemical sensing.

JTD Keywords: Chemical sensors, Electronic nose, Intelligent sensors, Measurement techniques, Sensor arrays, Sensor systems

Biosensors' research filed has clearly been changing towards the production of multifunctional and innovative design concepts to address the needs related with sensitivity and selectivity of the devices. More recently, waveguide biosensors, that do not require any label procedure to detect biomolecules adsorbed on its surface, have been pointed out as one of the most promising technologies for the production of biosensing devices with enhanced performance. Moreover the combination of optical and electrochemical measurements through the integration of transparent and conducting oxides in the multilayer structures can greatly enhance the biosensors' sensitivity. Furthermore, the integration of polymeric substrates may bring powerful advantages in comparison with silicon based ones. The biosensors will have a lower production costs being possible to disposable them after use ("one use sensor chip"). This research work represents a preliminary study about the influence of substrate temperature on the overall properties of ITO thin films deposited by DC magnetron sputtering onto 0,5 mm thick PMMA sheets.

JTD Keywords: ITO thin films, PMMA sheets, Waveguide biosensing devices, Biosensing devices, Conducting oxides, Dc magnetron sputtering, Electrochemical measurements, Enhanced performance, Innovative design, ITO thin films, Multilayer structures, Overall properties, PMMA sheets, Polymeric substrate, Production cost, Sensor chips, Silicon-based, Substrate temperature, Biosensors, Deposition, Design, Film preparation, Optical multilayers, Thin films, Vapor deposition, Waveguides, Substrates

The design of mechanical joints that kinematically behave as their biological counterparts is a challenge that if not addressed properly can cause inadequate forces transmission between robot and patient. This paper studies the interaction forces in rehabilitation therapies of the elbow joint. To measure the effect of orthosis-patient misalignments, a force sensor with a novel distributed architecture has been designed and used for this study. A test-bed based on an industrial robot acting as a virtual exoskeleton that emulates the action of a therapist has been developed and the interaction forces analyzed.

JTD Keywords: Force, Force measurement, Force sensors, Joints, Medical treatment, Robot sensing systems, Force sensors, Medical robotics, Patient rehabilitation, Biological counterparts, Distributed architecture, Elbow joint, Force sensor, Inadequate forces transmission, Industrial robot, Mechanical joints design, Orthosis-patient misalignments, Patient-orthosis interaction forces, Rehabilitation therapies, Robot, Test-bed, Virtual exoskeleton

Background: Epidermal Growth Factor (EGF) is a key regulatory growth factor activating many processes relevant to normal development and disease, affecting cell proliferation and survival. Here we use a combined approach to study the EGF dependent transcriptome of HeLa cells by using multiple long oligonucleotide based microarray platforms (from Agilent, Operon, and Illumina) in combination with digital gene expression profiling (DGE) with the Illumina Genome Analyzer. Results: By applying a procedure for cross-platform data meta-analysis based on RankProd and GlobalAncova tests, we establish a well validated gene set with transcript levels altered after EGF treatment. We use this robust gene list to build higher order networks of gene interaction by interconnecting associated networks, supporting and extending the important role of the EGF signaling pathway in cancer. In addition, we find an entirely new set of genes previously unrelated to the currently accepted EGF associated cellular functions. Conclusions: We propose that the use of global genomic cross-validation derived from high content technologies (microarrays or deep sequencing) can be used to generate more reliable datasets. This approach should help to improve the confidence of downstream in silico functional inference analyses based on high content data.

JTD Keywords: Gene-expression measurements, Quality-control maqc, Cancer-cell-lines, Real-time pcr, Oligonucleotide microarrays, Phosphorylation dynamics, In-vivo, Networks, Signal, Technologies

JTD Keywords: Biomedical measurement, Cancer, Cellular biophysics, Force sensors

Inspired by sensory diversity and redundancy at the olfactory epithelium, we have built a large chemical sensor array based on commercial MOX sensors. Different sensor families along with temperature modulation accounts for sensory diversity, whereas sensors of the same family combined with different load resistors provide redundancy to the system. To study the encoding of odor mixtures, a data collection consisting on the response of the array to 3 binary mixtures of ethanol, acetone, and butanone with 18 different concentration ratios is obtained.

JTD Keywords: Chemioception, Sensors, Data acquisition, Temperature measurement

The differentiation of obstructive and central respiratory events is a major challenge in the diagnosis of sleep disordered breathing. Esophageal pressure (Pes) measurement is the gold-standard method to identify these events but its invasiveness deters its usage in clinical routine. Flattening patterns appear in the airflow signal during episodes of inspiratory flow limitation (IFL) and have been shown with invasive techniques to be useful to differentiate between central and obstructive hypopneas. In this study we present a new method for the automatic non-invasive differentiation of obstructive and central hypopneas solely with nasal airflow. An overall of 36 patients underwent full night polysomnography with systematic Pes recording and a total of 1069 hypopneas were manually scored by human experts to create a gold-standard annotation set. Features were automatically extracted from the nasal airflow signal to train and test our automatic classifier (Discriminant Analysis). Flattening patterns were non-invasively assessed in the airflow signal using spectral and time analysis. The automatic non-invasive classifier obtained a sensitivity of 0.71 and an accuracy of 0.69, similar to the results obtained with a manual non-invasive classification algorithm. Hence, flattening airflow patterns seem promising for the non-invasive differentiation of obstructive and central hypopneas.

JTD Keywords: Practical, Experimental/ biomedical measurement, Feature extraction, Flow measurement, Medical disorders, Medical signal processing, Patient diagnosis, Pneumodynamics, Pressure measurement, Signal classification, Sleep, Spectral analysis/ automatic noninvasive differentiation, Obstructive hypopnea, Central hypopnea, Inspiratory flow limitation, Nasal airflow, Esophageal pressure, Polysomnography, Feature extraction, Discriminant analysis, Spectral analysis

Sleep science and respiratory engineering as medical subspecialties and research areas grew up side-by-side with biomedical engineering. The formation of EMBS in the 1950's and the discovery of REM sleep in the 1950's led to parallel development and interaction of sleep and biomedical engineering in diagnostics and therapeutics.

JTD Keywords: Practical/ biomedical equipment, Biomedical measurement, Patient diagnosis, Patient monitoring, Patient treatment, Pneumodynamics, Sleep/ sleep engineering, Respiratory engineering, Automatic sleep analysis, Automatic sleep interpretation systems, Breathing, Biomedical, Engineering, Diagnostics, Therapeutics, REM sleep, Portable, Measurement, Ambulatory measurement, Monitoring

The study of mechanomyographic (MMG) signals of respiratory muscles is a promising noninvasive technique in order to evaluate the respiratory muscular effort and efficiency. In this work, the MMG signal of the diaphragm muscle it is evaluated in order to assess the respiratory muscular function in Chronic Obstructive Pulmonary Disease (COPD) patients. The MMG signals from left and right hemidiaphragm were acquired using two capacitive accelerometers placed on both left and right sides of the costal wall surface. The MMG signals and the inspiratory pressure signal were acquired while the COPD patients carried out an inspiratory load respiratory test. The population of study is composed of a group of 6 patients with severe COPD (FEV1>50% ref and DLCO<50% ref). We have found high positive correlation coefficients between the maximum inspiratory pressure (IPmax) developed in a respiratory cycle and different amplitude parameters of both left and right MMG signals (RMS, left: 0.68+/-0.11 - right: 0.69+/-0.12; Re nyi entropy, left: - 0.73+/-0.10 - right: 0.77+/-0.08; Multistate Lempel-Ziv, left: 0.73+/-0.17 - right: 0.74+/-0.08), and negative correlation between the Pmax and the maximum frequency of the MMG signal spectrum (left: -0.39+/-0.19 - right: -0.65+/-0.09). Furthermore, we found that the slope of the evolution of the MMG amplitude parameters, as the load increases during the respiratory test, has positive correlation with the %FEV1/FVC pulmonary function test parameter of the six COPD patients analyzed (RMS, left: 0.38 - right: 0.41; Re nyi entropy, left: 0.45 - right: 0.63; Multistate Lempel-Ziv, left: 0.39 - right: 0.64). These results suggest that the information provided by MMG signals could be used in order to evaluate the respiratory effort and the muscular efficiency in COPD patients.

JTD Keywords: Accelerometers, Biomechanics, Biomedical measurement, Diseases, Medical signal processing, Muscle

Sleep Apnea-Hypopnea Syndrome (SAHS) diagnosis is still done with an overnight multi-channel polysomnography. Several efforts are being made to study profoundly the snore mechanism and discover how it can provide an opportunity to diagnose the disease. This work introduces the concept of regular snores, defined as the ones produced in consecutive respiratory cycles, since they are produced in a regular way, without interruptions. We applied 2 thresholds (TH/sub adaptive/ and TH/sub median/) to the time interval between successive snores of 34 subjects in order to select regular snores from the whole all-night snore sequence. Afterwards, we studied the effectiveness that parameters, such as time interval between successive snores and the mean intensity of snores, have on distinguishing between different levels of SAHS severity (AHI (Apnea-Hypopnea Index)<5h/sup -1/, AHI<10 h/sup -1/, AHI<15h/sup -1/, AHI<30h/sup -1/). Results showed that TH/sub adaptive/ outperformed TH/sub median/ on selecting regular snores. Moreover, the outcome achieved with non-regular snores intensity features suggests that these carry key information on SAHS severity.

JTD Keywords: Practical, Experimental/ acoustic signal processing, Bioacoustics, Biomedical measurement, Diseases, Feature extraction, Medical signal processing, Patient diagnosis, Pneumodynamics, Sleep/ nonregular snore features, SAHS markers, Sleep apnea hypopnea syndrome, Overnight multichannel polysomnography, Snore mechanism

A considerable number of patients in weaning process have problems to keep spontaneous breathing during the trial and after it. This study proposes to extract characteristic parameters of the RR series and respiratory flow signal according to the patients' condition in weaning test. Three groups of patients have been considered: 93 patients with successful trials (group S), 40 patients that failed to maintain spontaneous breathing (group F), and 21 patients who had successful weaning trials, but that had to be reintubated before 48 hours (group R). The characterization was performed using spectral analysis of the signals, through the power spectral density, cross power spectral density and Coherence method. The parameters were extracted on the three frequency bands (VLF, LF and HF), and the principal statistical differences between groups were obtained in bands of VLF and HF. The results show an accuracy of 76.9% in the classification of the groups S and F.

JTD Keywords: Biomedical measurement, Electrocardiography, Medical signal processing, Pneumodynamics, Spectral analysis, RR series, Coherence method, Cross power spectral density, Electrocardiography, Principal statistical differences, Respiratory flow signal, Spectral analysis, Spontaneous breathing, Weaning test

In this study, we compare for the first time the nanomechanical properties of lipid bilayer islands on flat and porous surfaces. 1,2-Dimyzistoyl-sn-glycero-3-phosphatidylcholine (DMPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) bilayers were deposited on flat (silicon and mica) and porous silicon (pSi) substrate surfaces and examined using atomic force spectroscopy and force volume imaging. Force spectroscopy measurements revealed the effects of the underlying substrate and of the lipid phase on the nanomechanical properties of bilayers islands. For mica and silicon, significant differences in breakthrough force between the center and the edges of bilayer islands were observed for both phospolipids. These differences were more pronounced for DMPC than for DPPC, presumably due to melting effects at the edges of DMPC bilayers. In contrast, bilayer islands deposited on pSi yielded similar breakthrough forces in the central region and along the perimeter of the islands, and those values in turn were similar to those measured along the perimeter of bilayer islands deposited on the flat substrates. The study also demonstrates that pSi is suitable solid support for the formation of pore-spanning phospholipid bilayers with potential applications in transmembrane protein studies, drug delivery, and biosensing.

JTD Keywords: Black lipid-membranes, Gold surfaces, Supported bilayers, Channel activity, Micro-BLMS, Silicon, Proteins, Vesicles, AFM, Temperature measurement

The authors are working toward the design of a device for the detection of oxygen, following a discrete and an integrated instrumentation implementation. The discrete electronics are also used for preliminary analysis, to confirm the validity of the conception of system, and its set-up would be used in the characterization of the integrated device, waiting for the chip fabrication. This paper presents the design of a small and portable potentiostat integrated with electrodes, which is cheap and miniaturized, which can be applied for on-site measurements for the simultaneous detection of O/sub 2/ and temperature in water systems. As a first approach a discrete PCB has been designed based on commercial discrete electronics and specific oxygen sensors. Dissolved oxygen concentration (DO) is an important index of water quality and the ability to measure the oxygen concentration and temperature at different positions and depths would be an important attribute to environmental analysis. Especially, the objective is that the sensor and the electronics can be integrated in a single encapsulated device able to be submerged in environmental water systems and be able to make multiple measurements. For our proposed application a small and portable device is developed, where electronics and sensors are miniaturized and placed in close proximity to each other. This system would be based on the sensors and electronics, forming one module, and connected to a portable notebook to save and analyze the measurements on-line. The key electronics is defined by the potentiostat amplifier, used to fix the voltage between the working (WE) and reference (RE) electrodes following an input voltage (Vin). Vin is a triangular signal, programmed by a LabView/sup c / interface, which is also used to represent the CV transfers. To obtain a smaller and compact solution the potentiostat amplifier has also been integrated defining a full custom ASIC amplifier, which is in progress, looking for a point-of-care device. These circuits have been designed with a 0.13 mu m technology from ST Microelectronics through the CMP-TIMA service.

JTD Keywords: Amplifiers, Application specific integrated circuits, Chemical sensors, Electrodes, Portable instruments, Temperature measurement, Water sources

Ion implanted Insulator-Semiconductor (IS) sensor that specifically detects Na+ ions have been developed using ion implantation technique. Na+ ions were directly implanted with ion energies 30, 45, and 60 keV into the IS (oxidized Si3N4/Si3N4/SiO2/P-Si) structures previously covered with a thin aluminum layer. X-ray photoelectron spectroscopy (XPS) characterization shows that sodium and aluminum ions were implanted into the oxidized Si3N4 insulating layer surface. Their atomic percentage depending on energy, fluence of the implanted ion and of the annealing temperature. The sen sitivity of the ion-implanted IS structure for Na+ and of some interfering (K+, Li+, H+, and NH4+) ions was investigated using high frequency capacitance-voltage measurements. Under optimal i mplantation conditions such as energy, fluence and annealing temperature, the developed sodium microsensor demonstrates quasi-nernstian sensitivity (50 +/- 2 mV/pNa) in the concentration range from 10(-3.7) to 10(-1) M and high lifetime greater than 16 months without any loss of sensitivity.

JTD Keywords: Na+ microsensor, Ion implantation, XPS, C-V measurements