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Palacín, J., Martínez, D., Clotet, E., Pallejà, T., Burgués, J., Fonollosa, J., Pardo, A., Marco, Santiago, (2019). Application of an array of metal-oxide semiconductor gas sensors in an assistant personal robot for early gas leak detection Sensors 19, (9), 1957

This paper proposes the application of a low-cost gas sensor array in an assistant personal robot (APR) in order to extend the capabilities of the mobile robot as an early gas leak detector for safety purposes. The gas sensor array is composed of 16 low-cost metal-oxide (MOX) gas sensors, which are continuously in operation. The mobile robot was modified to keep the gas sensor array always switched on, even in the case of battery recharge. The gas sensor array provides 16 individual gas measurements and one output that is a cumulative summary of all measurements, used as an overall indicator of a gas concentration change. The results of preliminary experiments were used to train a partial least squares discriminant analysis (PLS-DA) classifier with air, ethanol, and acetone as output classes. Then, the mobile robot gas leak detection capabilities were experimentally evaluated in a public facility, by forcing the evaporation of (1) ethanol, (2) acetone, and (3) ethanol and acetone at different locations. The positive results obtained in different operation conditions over the course of one month confirmed the early detection capabilities of the proposed mobile system. For example, the APR was able to detect a gas leak produced inside a closed room from the external corridor due to small leakages under the door induced by the forced ventilation system of the building.

Keywords: Metal-oxide semiconductor, Gas sensor, Gas leak detection, Assistant personal robot, Mobile robot


Burgués, Javier, Hernández, Victor, Lilienthal, Achim J., Marco, Santiago, (2019). Smelling nano aerial vehicle for gas source localization and mapping Sensors 19, (3), 478

This paper describes the development and validation of the currently smallest aerial platform with olfaction capabilities. The developed Smelling Nano Aerial Vehicle (SNAV) is based on a lightweight commercial nano-quadcopter (27 g) equipped with a custom gas sensing board that can host up to two in situ metal oxide semiconductor (MOX) gas sensors. Due to its small form-factor, the SNAV is not a hazard for humans, enabling its use in public areas or inside buildings. It can autonomously carry out gas sensing missions of hazardous environments inaccessible to terrestrial robots and bigger drones, for example searching for victims and hazardous gas leaks inside pockets that form within the wreckage of collapsed buildings in the aftermath of an earthquake or explosion. The first contribution of this work is assessing the impact of the nano-propellers on the MOX sensor signals at different distances to a gas source. A second contribution is adapting the ‘bout’ detection algorithm, proposed by Schmuker et al. (2016) to extract specific features from the derivative of the MOX sensor response, for real-time operation. The third and main contribution is the experimental validation of the SNAV for gas source localization (GSL) and mapping in a large indoor environment (160 m2) with a gas source placed in challenging positions for the drone, for example hidden in the ceiling of the room or inside a power outlet box. Two GSL strategies are compared, one based on the instantaneous gas sensor response and the other one based on the bout frequency. From the measurements collected (in motion) along a predefined sweeping path we built (in less than 3 min) a 3D map of the gas distribution and identified the most likely source location. Using the bout frequency yielded on average a higher localization accuracy than using the instantaneous gas sensor response (1.38 m versus 2.05 m error), however accurate tuning of an additional parameter (the noise threshold) is required in the former case. The main conclusion of this paper is that a nano-drone has the potential to perform gas sensing tasks in complex environments.

Keywords: Robotics, Signal processing, Electronics, Gas source localization, Gas distribution mapping, Gas sensors, Drone, UAV, MOX sensor, Quadcopter


Romeo, Agostino, Moya, Ana, Leung, Tammy S., Gabriel, Gemma, Villa, Rosa, Sánchez, Samuel, (2018). Inkjet printed flexible non-enzymatic glucose sensor for tear fluid analysis Applied Materials Today , 10, 133-141

Here, we present a flexible and low-cost inkjet printed electrochemical sensor for enzyme-free glucose analysis. Versatility, short fabrication time and low cost make inkjet printing a valuable alternative to traditional sensor manufacturing techniques. We fabricated electro-chemical glucose sensors by inkjet printing electrodes on a flexible polyethylene terephthalate substrate. CuO microparticles were used to modify our electrodes, leading to a sensitive, stable and cost-effective platform for non-enzymatic detection of glucose. Selectivity, reproducibility, and life-time provided by the CuO functionalization demonstrated that these sensors are reliable tools for personalized diagnostics and self-assessment of an individual's health. The detection of glucose at concentrations matching that of tear fluid allows us to envisage applications in ocular diagnostics, where painless and non-invasive monitoring of diabetes can be achieved by analyzing glucose contained in tears.

Keywords: Inkjet printing, Non-enzymatic sensor, Glucose, Copper oxide, Tear analysis


Pérez, Judit, Dulay, Samuel, Mir, M., Samitier, Josep, (2018). Molecular architecture for DNA wiring Biosensors and Bioelectronics , 121, 54-61

Detection of the hybridisation events is of great importance in many different biotechnology applications such as diagnosis, computing, molecular bioelectronics, and among others. However, one important drawback is the low current of some redox reporters that limits their application. This paper demonstrates the powerful features of molecular wires, in particular the case of S-[4-[2-[4-(2-Phenylethynyl)phenyl]ethynyl]phenyl] thiol molecule and the key role that play the nanometric design of the capture probe linkers to achieve an efficient couple of the DNA complementary ferrocene label with the molecular wire for an effective electron transfer in co-immobilised self-assembled monolayers (SAMs) for DNA hybridisation detection. In this article, the length of the linker capture probe was studied for electron transfer enhancement from the ferrocene-motifs of immobilised molecules towards the electrode surface to obtain higher kinetics in the presence of thiolated molecular wires. The use of the right couple of capture probe linker and molecular wire has found to be beneficial as it helps to amplify eightfold the signal obtained.

Keywords: DNA hybridisation, Bioelectronics, Electron transfer rate constant, Molecular wires, Electrochemistry, Ferrocene, Biosensor


Solórzano, A., Rodríguez-Pérez, R., Padilla, M., Graunke, T., Fernandez, L., Marco, S., Fonollosa, J., (2018). Multi-unit calibration rejects inherent device variability of chemical sensor arrays Sensors and Actuators B: Chemical , 265, 142-154

Inherent sensor variability limits mass-production applications for metal oxide (MOX) gas sensor arrays because calibration for replicas of a sensor array needs to be performed individually. Recently, calibration transfer strategies have been proposed to alleviate calibration costs of new replicas, but they still require the acquisition of transfer samples. In this work, we present calibration models that can be extended to uncalibrated replicas of sensor arrays without acquiring new samples, i.e., general or global calibration models. The developed methodology consists in including multiple replicas of a sensor array in the calibration process such that sensor variability is rejected by the general model. Our approach was tested using replicas of a MOX sensor array in the classification task of six gases and synthetic air, presented at different background humidity and concentration levels. Results showed that direct transfer of individual calibration models provides poor classification accuracy. However, we also found that general calibration models kept predictive performance when were applied directly to new copies of the sensor array. Moreover, we explored, through feature selection, whether particular combinations of sensors and operating temperatures can provide predictive performances equivalent to the calibration model with the complete array, favoring thereby the existence of more robust calibration models.

Keywords: Gas sensor array, MOX sensor, Robust calibration, Calibration transfer, Machine olfaction


Burgués, J., Jiménez-Soto, J. M., Marco, S., (2018). Estimation of the limit of detection in semiconductor gas sensors through linearized calibration models Analytica Chimica Acta , 1013, 13-25

The limit of detection (LOD) is a key figure of merit in chemical sensing. However, the estimation of this figure of merit is hindered by the non-linear calibration curve characteristic of semiconductor gas sensor technologies such as, metal oxide (MOX), gasFETs or thermoelectric sensors. Additionally, chemical sensors suffer from cross-sensitivities and temporal stability problems. The application of the International Union of Pure and Applied Chemistry (IUPAC) recommendations for univariate LOD estimation in non-linear semiconductor gas sensors is not straightforward due to the strong statistical requirements of the IUPAC methodology (linearity, homoscedasticity, normality). Here, we propose a methodological approach to LOD estimation through linearized calibration models. As an example, the methodology is applied to the detection of low concentrations of carbon monoxide using MOX gas sensors in a scenario where the main source of error is the presence of uncontrolled levels of humidity.

Keywords: Semiconductor gas sensors, Metal-oxide sensors, Limit of detection, Non-linear, Humidity interference, Temperature modulation


Burgués, Javier, Marco, Santiago, (2018). Multivariate estimation of the limit of detection by orthogonal partial least squares in temperature-modulated MOX sensors Analytica Chimica Acta , 1019, 49-64

Metal oxide semiconductor (MOX) sensors are usually temperature-modulated and calibrated with multivariate models such as Partial Least Squares (PLS) to increase the inherent low selectivity of this technology. The multivariate sensor response patterns exhibit heteroscedastic and correlated noise, which suggests that maximum likelihood methods should outperform PLS. One contribution of this paper is the comparison between PLS and maximum likelihood principal components regression (MLPCR) in MOX sensors. PLS is often criticized by the lack of interpretability when the model complexity increases beyond the chemical rank of the problem. This happens in MOX sensors due to cross-sensitivities to interferences, such as temperature or humidity and non-linearity. Additionally, the estimation of fundamental figures of merit, such as the limit of detection (LOD), is still not standardized in multivariate models. Orthogonalization methods, such as Orthogonal Projection to Latent Structures (O-PLS), have been successfully applied in other fields to reduce the complexity of PLS models. In this work, we propose a LOD estimation method based on applying the well-accepted univariate LOD formulas to the scores of the first component of an orthogonal PLS model. The resulting LOD is compared to the multivariate LOD range derived from error-propagation. The methodology is applied to data extracted from temperature-modulated MOX sensors (FIS SB-500-12 and Figaro TGS 3870-A04), aiming at the detection of low concentrations of carbon monoxide in the presence of uncontrolled humidity (chemical noise). We found that PLS models were simpler and more accurate than MLPCR models. Average LOD values of 0.79 ppm (FIS) and 1.06 ppm (Figaro) were found using the approach described in this paper. These values were contained within the LOD ranges obtained with the error-propagation approach. The mean LOD increased to 1.13 ppm (FIS) and 1.59 ppm (Figaro) when considering validation samples collected two weeks after calibration, which represents a 43% and 46% degradation, respectively. The orthogonal score-plot was a very convenient tool to visualize MOX sensor data and to validate the LOD estimates.

Keywords: Metal oxide sensors, Partial least squares, Orthogonal projection to latent structures, Maximum likelihood principal component regression, Limit of detection, Temperature modulation


Fernandez, L., Yan, J., Fonollosa, J., Burgués, J., Gutierrez, A., Marco, S., (2018). A practical method to estimate the resolving power of a chemical sensor array: Application to feature selection Frontiers in Chemistry , 6, Article 209

A methodology to calculate analytical figures of merit is not well established for detection systems that are based on sensor arrays with low sensor selectivity. In this work, we present a practical approach to estimate the Resolving Power of a sensory system, considering non-linear sensors and heteroscedastic sensor noise. We use the definition introduced by Shannon in the field of communication theory to quantify the number of symbols in a noisy environment, and its version adapted by Gardner and Barlett for chemical sensor systems. Our method combines dimensionality reduction and the use of algorithms to compute the convex hull of the empirical data to estimate the data volume in the sensor response space. We validate our methodology with synthetic data and with actual data captured with temperature-modulated MOX gas sensors. Unlike other methodologies, our method does not require the intrinsic dimensionality of the sensor response to be smaller than the dimensionality of the input space. Moreover, our method circumvents the problem to obtain the sensitivity matrix, which usually is not known. Hence, our method is able to successfully compute the Resolving Power of actual chemical sensor arrays. We provide a relevant figure of merit, and a methodology to calculate it, that was missing in the literature to benchmark broad-response gas sensor arrays.

Keywords: Gas sensor array, MOX sensors, Resolving Power, Sensor resolution, Dimensionality reduction, Machine olfaction


Fonollosa, Jordi, Solórzano, Ana, Marco, Santiago, (2018). Chemical sensor systems and associated algorithms for fire detection: A review Sensors 18, (2), 553

Indoor fire detection using gas chemical sensing has been a subject of investigation since the early nineties. This approach leverages the fact that, for certain types of fire, chemical volatiles appear before smoke particles do. Hence, systems based on chemical sensing can provide faster fire alarm responses than conventional smoke-based fire detectors. Moreover, since it is known that most casualties in fires are produced from toxic emissions rather than actual burns, gas-based fire detection could provide an additional level of safety to building occupants. In this line, since the 2000s, electrochemical cells for carbon monoxide sensing have been incorporated into fire detectors. Even systems relying exclusively on gas sensors have been explored as fire detectors. However, gas sensors respond to a large variety of volatiles beyond combustion products. As a result, chemical-based fire detectors require multivariate data processing techniques to ensure high sensitivity to fires and false alarm immunity. In this paper, we the survey toxic emissions produced in fires and defined standards for fire detection systems. We also review the state of the art of chemical sensor systems for fire detection and the associated signal and data processing algorithms. We also examine the experimental protocols used for the validation of the different approaches, as the complexity of the test measurements also impacts on reported sensitivity and specificity measures. All in all, further research and extensive test under different fire and nuisance scenarios are still required before gas-based fire detectors penetrate largely into the market. Nevertheless, the use of dynamic features and multivariate models that exploit sensor correlations seems imperative

Keywords: Fire detection, Gas sensor, Pattern recognition, Sensor fusion, Machine learning, Toxicants, Carbon monoxide, Hydrogen cyanide, Standard test fires, Transducers, Smoke


Burgués, J., Marco, S., (2018). Low power operation of temperature-modulated metal oxide semiconductor gas sensors Sensors 18, (2), 339

Mobile applications based on gas sensing present new opportunities for low-cost air quality monitoring, safety, and healthcare. Metal oxide semiconductor (MOX) gas sensors represent the most prominent technology for integration into portable devices, such as smartphones and wearables. Traditionally, MOX sensors have been continuously powered to increase the stability of the sensing layer. However, continuous power is not feasible in many battery-operated applications due to power consumption limitations or the intended intermittent device operation. This work benchmarks two low-power, duty-cycling, and on-demand modes against the continuous power one. The duty-cycling mode periodically turns the sensors on and off and represents a trade-off between power consumption and stability. On-demand operation achieves the lowest power consumption by powering the sensors only while taking a measurement. Twelve thermally modulated SB-500-12 (FIS Inc. Jacksonville, FL, USA) sensors were exposed to low concentrations of carbon monoxide (0–9 ppm) with environmental conditions, such as ambient humidity (15–75% relative humidity) and temperature (21–27 ◦C), varying within the indicated ranges. Partial Least Squares (PLS) models were built using calibration data, and the prediction error in external validation samples was evaluated during the two weeks following calibration. We found that on-demand operation produced a deformation of the sensor conductance patterns, which led to an increase in the prediction error by almost a factor of 5 as compared to continuous operation (2.2 versus 0.45 ppm). Applying a 10% duty-cycling operation of 10-min periods reduced this prediction error to a factor of 2 (0.9 versus 0.45 ppm). The proposed duty-cycling powering scheme saved up to 90% energy as compared to the continuous operating mode. This low-power mode may be advantageous for applications that do not require continuous and periodic measurements, and which can tolerate slightly higher prediction errors.

Keywords: Smartphone, Metal-oxide semiconductor, Gas sensor, Low power, Temperature-modulation, Interferences


Burgués, Javier, Hernandez, Victor, Lilienthal, Achim J., Marco, Santiago, (2018). 3D Gas distribution with and without artificial airflow: An experimental study with a grid of metal oxide semiconductor gas sensors Proceedings EUROSENSORS 2018 , MDPI (Graz, Austria) 2, (13), 911

Gas distribution modelling can provide potentially life-saving information when assessing the hazards of gaseous emissions and for localization of explosives, toxic or flammable chemicals. In this work, we deployed a three-dimensional (3D) grid of metal oxide semiconductor (MOX) gas sensors deployed in an office room, which allows for novel insights about the complex patterns of indoor gas dispersal. 12 independent experiments were carried out to better understand dispersion patters of a single gas source placed at different locations of the room, including variations in height, release rate and air flow profiles. This dataset is denser and richer than what is currently available, i.e., 2D datasets in wind tunnels. We make it publicly available to enable the community to develop, validate, and compare new approaches related to gas sensing in complex environments.

Keywords: MOX, Metal oxide, Flow visualization, Gas sensors, Gas distribution mapping, Sensor grid, 3D, Gas source localization, Indoor


Vouloutsi, Vasiliki, Halloy, José, Mura, Anna, Mangan, Michael, Lepora, Nathan, Prescott, T. J., Verschure, P., (2018). Biomimetic and Biohybrid Systems 7th International Conference, Living Machines 2018, Paris, France, July 17–20, 2018, Proceedings , Springer International Publishing (Lausanne, Switzerland) 10928, 1-551

This book constitutes the proceedings of the 7th International Conference on Biomimetic and Biohybrid Systems, Living Machines 2018, held in Paris, France, in July 2018. The 40 full and 18 short papers presented in this volume were carefully reviewed and selected from 60 submissions. The theme of the conference targeted at the intersection of research on novel life-like technologies inspired by the scientific investigation of biological systems, biomimetics, and research that seeks to interface biological and artificial systems to create biohybrid systems.

Keywords: Artificial neural network, Bio-actuators, Bio-robotics, Biohybrid systems, Biomimetics, Bipedal robots, Earthoworm-like robots, Robotics, Decision-making, Tactile sensing, Soft robots, Locomotion, Insects, Sensors, Actuators, Robots, Artificial intelligence, Neural networks, Motion planning, Learning algorithms


Zaffino, R. L., Mir, M., Samitier, J., (2017). Oligonucleotide probes functionalization of nanogap electrodes Electrophoresis , 38, (21), 2712-2720

Nanogap electrodes have attracted a lot of consideration as promising platform for molecular electronic and biomolecules detection. This is mainly for their higher aspect ratio, and because their electrical properties are easily accessed by current-voltage measurements. Nevertheless, application of standard current-voltages measurements used to characterize nanogap response, and/or to modify specific nanogap electrodes properties, represents an issue. Since the strength of electrical fields in nanoscaled devices can reach high values, even at low voltages. Here, we analyzed the effects induced by different methods of surface modification of nanogap electrodes, in test-voltage application, employed for the electrical detection of a desoxyribonucleic acid (DNA) target. Nanogap electrodes were functionalized with two antisymmetric oligo-probes designed to have 20 terminal bases complementary to the edges of the target, which after hybridization bridges the nanogap, closing the electrical circuit. Two methods of functionalization were studied for this purpose; a random self-assembling of a mixture of the two oligo-probes (OPs) used in the platform, and a selective method that controls the position of each OP at selected side of nanogap electrodes. We used for this aim, the electrophoretic effect induced on negatively charged probes by the application of an external direct current voltage. The results obtained with both functionalization methods where characterized and compared in terms of electrode surface covering, calculated by using voltammetry analysis. Moreover, we contrasted the electrical detection of a DNA target in the nanogap platform either in site-selective and in randomly assembled nanogap. According to our results, a denser, although not selective surface functionalization, is advantageous for such kind of applications.

Keywords: Biosensor bioelectronics, DNA electrophoresis, Nanogap electrodes, Self-assembled monolayers, Site-selective deposition


Pomareda, V., Magrans, R., Jiménez-Soto, J., Martínez, D., Tresánchez, M., Burgués, J., Palacín, J., Marco, S., (2017). Chemical source localization fusing concentration information in the presence of chemical background noise Sensors 17, (4), 904

We present the estimation of a likelihood map for the location of the source of a chemical plume dispersed under atmospheric turbulence under uniform wind conditions. The main contribution of this work is to extend previous proposals based on Bayesian inference with binary detections to the use of concentration information while at the same time being robust against the presence of background chemical noise. For that, the algorithm builds a background model with robust statistics measurements to assess the posterior probability that a given chemical concentration reading comes from the background or from a source emitting at a distance with a specific release rate. In addition, our algorithm allows multiple mobile gas sensors to be used. Ten realistic simulations and ten real data experiments are used for evaluation purposes. For the simulations, we have supposed that sensors are mounted on cars which do not have among its main tasks navigating toward the source. To collect the real dataset, a special arena with induced wind is built, and an autonomous vehicle equipped with several sensors, including a photo ionization detector (PID) for sensing chemical concentration, is used. Simulation results show that our algorithm, provides a better estimation of the source location even for a low background level that benefits the performance of binary version. The improvement is clear for the synthetic data while for real data the estimation is only slightly better, probably because our exploration arena is not able to provide uniform wind conditions. Finally, an estimation of the computational cost of the algorithmic proposal is presented.

Keywords: Machine olfaction, Odor robots, Chemical sensors, Bayesian inference


Burgues, J., Fonollosa, J., Marco, S., (2017). Discontinuously operated MOX sensors for low power applications IEEE Conference Publications ISOCS/IEEE International Symposium on Olfaction and Electronic Nose (ISOEN) , IEEE (Montreal, Canada) , 1-3

Metal oxide semiconductor sensors are limited by their low selectivity, high power consumption and temporal drift. This paper proposes a novel discontinuous temperature modulation operation mode characterized by on-demand measurements and periodic warm-up cycles. The performance of two sets of FIS SB-500-12 sensors, one group continuously operated and the other group discontinuously operated, was compared in a scenario of carbon monoxide detection at low concentrations for five consecutive days. Results showed that the discontinuous operating mode moderately increased the prediction error and the limit of detection but was advantageous in terms of energy savings (up to 60% with respect to the continuous temperature modulation mode).

Keywords: Discontinuous operation, Duty-cycling, Low power, MOX sensors, Temperature modulation


Solorzano, A., Fonollosa, J., Fernandez, L., Eichmann, J., Marco, S., (2017). Fire detection using a gas sensor array with sensor fusion algorithms IEEE Conference Publications ISOCS/IEEE International Symposium on Olfaction and Electronic Nose (ISOEN) , IEEE (Montreal, Canada) , 1-3

Conventional fire alarms are based on smoke detection. Nevertheless, in some fire scenarios volatiles are released before smoke. Fire detectors based only on chemical sensors have already been proposed as they may provide faster response, but they are still prone to false alarms in the presence of nuisances. These systems rely heavily on pattern recognition techniques to discriminate fires from nuisances. In this context, it is important to test the systems according to international standards for fires and testing the system against a diversity of nuisances. In this work, we investigate the behavior of a gas sensor array coupled to sensor fusion algorithms for fire detection when exposed to standardized fires and several nuisances. Results confirmed the ability to detect fires (97% Sensitivity), although the system still produces a significant rate of false alarms (35%) for nuisances not presented in the training set.

Keywords: Fire alarm, Gas sensor array, Machine Olfaction, Multisensor system, Sensor fusion


Camara, M. A., Castillo, Y., Blanco-Almazan, D., Estrada, L., Jane, R., (2017). MHealth tools for monitoring Obstructive Sleep Apnea patients at home: Proof-of-concept Engineering in Medicine and Biology Society (EMBC) 39th Annual International Conference of the IEEE , IEEE (Seogwipo, South Korea) , 1555-1558

Obstructive Sleep Apnea (OSA) is a sleep disorder that affects mainly the adult and elderly population. Due to the high percentage of patients who remain undiagnosed and untreated because of limitations of current diagnosis methods, the management of OSA is an important social, scientific and economic problem that will be difficult to be assumed by health systems. On the other hand, smartphone platforms (mHealth systems) are being considered as an innovative solution, thanks to the integration of the essential sensors to obtain clinically relevant parameters in the same device or in combination with wireless wearable devices.

Keywords: Sleep apnea, Microphones, Monitoring, Sensors, Accelerometers, Biomedical monitoring, Band-pass filters


Fonollosa, J., Fernández, L., Gutiérrez-Gálvez, A., Huerta, R., Marco, S., (2016). Calibration transfer and drift counteraction in chemical sensor arrays using Direct Standardization Sensors and Actuators B: Chemical , 236, 1044-1053

Inherent variability of chemical sensors makes it necessary to calibrate chemical detection systems individually. This shortcoming has traditionally limited usability of systems based on metal oxide gas sensor arrays and prevented mass-production for some applications. Here, aiming at exploring calibration transfer between chemical sensor arrays, we exposed five twin 8-sensor detection units to different concentration levels of ethanol, ethylene, carbon monoxide, or methane. First, we built calibration models using data acquired with a master unit. Second, to explore the transferability of the calibration models, we used Direct Standardization to map the signals of a slave unit to the space of the master unit in calibration. In particular, we evaluated the transferability of the calibration models to other detection units, and within the same unit measuring days apart. Our results show that signals acquired with one unit can be successfully mapped to the space of a reference unit. Hence, calibration models trained with a master unit can be extended to slave units using a reduced number of transfer samples, diminishing thereby calibration costs. Similarly, signals of a sensing unit can be transformed to match sensor behavior in the past to mitigate drift effects. Therefore, the proposed methodology can reduce calibration costs in mass-production and delay recalibrations due to sensor aging. Acquired dataset is made publicly available.

Keywords: Calibration transfer, Chemical sensors, Direct Standardization, Electronic nose, MOX sensors, Public dataset


Fernandez, L., Guney, S., Gutierrez-Galvez, A., Marco, S., (2016). Calibration transfer in temperature modulated gas sensor arrays Sensors and Actuators B: Chemical , 231, 276-284

Abstract Shifts in working temperature are an important issue that prevents the successful transfer of calibration models from one chemical instrument to another. This effect is of special relevance when working with gas sensor arrays modulated in temperature. In this paper, we study the use of multivariate techniques to transfer the calibration model from a temperature modulated gas sensor array to another when a global change of temperature occurs. To do so, we built 12 identical master sensor arrays composed of three different types of commercial Figaro sensors and acquired a dataset of sensor responses to three pure substances (ethanol, acetone and butanone) dosed at 7 concentrations. The master arrays are then shifted in temperature (from −50 to 50 °C, ΔT = 10 °C) and considered as slave arrays. Data correction is performed for an increasing number of transfer samples with 4 different calibration transfer techniques: Direct Standardization, Piece-wise Direct Standardization, Orthogonal Signal Correction and Generalized Least Squares Weighting. In order to evaluate the performance of the calibration transfer, we compare the Root Mean Square Error of Prediction (RMSEP) of master and slave arrays, for each instrument correction. Best results are obtained from Piece-wise Direct standardization, which exhibits the lower RMSEP values after correction for the smaller number of transfer samples.

Keywords: Calibration transfer, Gas sensor array, MOX, Temperature modulation


Huerta, R., Mosqueiro, T., Fonollosa, J., Rulkov, N.F., Rodríguez-Lujan, I., (2016). Online decorrelation of humidity and temperature in chemical sensors for continuous monitoring Chemometrics and Intelligent Laboratory Systems , 157, 169-176

A method for online decorrelation of chemical sensor signals from the effects of environmental humidity and temperature variations is proposed. The goal is to improve the accuracy of electronic nose measurements for continuous monitoring by processing data from simultaneous readings of environmental humidity and temperature. The electronic nose setup built for this study included eight metal-oxide sensors, temperature and humidity sensors with a wireless communication link to external computer. This wireless electronic nose was used to monitor the air for two years in the residence of one of the authors and it collected data continuously during 537 days with a sampling rate of 1 sample per second. To estimate the effects of variations in air humidity and temperature on the chemical sensors' signals, we used a standard energy band model for an n-type metal-oxide (MOX) gas sensor. The main assumption of the model is that variations in sensor conductivity can be expressed as a nonlinear function of changes in the semiconductor energy bands in the presence of external humidity and temperature variations. Fitting this model to the collected data, we confirmed that the most statistically significant factors are humidity changes and correlated changes of temperature and humidity. This simple model achieves excellent accuracy with a coefficient of determination R2 close to 1. To show how the humidity–temperature correction model works for gas discrimination, we constructed a model for online discrimination among banana, wine and baseline response. This shows that pattern recognition algorithms improve performance and reliability by including the filtered signal of the chemical sensors.

Keywords: Electronic nose, Chemical sensors, Humidity, Temperature, Decorrelation, Wireless e-nose, MOX sensors, Energy band model, Home monitoring


Estrada, L., Torres, A., Sarlabous, L., Jané, R., (2016). Evaluating respiratory muscle activity using a wireless sensor platform Engineering in Medicine and Biology Society (EMBC) 38th Annual International Conference of the IEEE , IEEE (Orlando, USA) , 5769-5772

Wireless sensors are an emerging technology that allows to assist physicians in the monitoring of patients health status. This approach can be used for the non-invasive recording of the electrical respiratory muscle activity of the diaphragm (EMGdi). In this work, we acquired the EMGdi signal of a healthy subject performing an inspiratory load test. To this end, the EMGdi activity was captured from a single channel of electromyography using a wireless platform which was compared with the EMGdi and the inspiratory mouth pressure (Pmouth) recorded with a conventional lab equipment. From the EMGdi signal we were able to evaluate the neural respiratory drive, a biomarker used for assessing the respiratory muscle function. In addition, we evaluated the breathing movement and the cardiac activity, estimating two cardio-respiratory parameters: the respiratory rate and the heart rate. The correlation between the two EMGdi signals and the Pmouth improved with increasing the respiratory load (Pearson's correlation coefficient ranges from 0.33 to 0.85). The neural respiratory drive estimated from both EMGdi signals showed a positive trend with an increase of the inspiratory load and being higher in the conventional EMGdi recording. The respiratory rate comparison between measurements revealed similar values of around 16 breaths per minute. The heart rate comparison showed a root mean error of less than 0.2 beats per minute which increased when incrementing the inspiratory load. In summary, this preliminary work explores the use of wireless devices to record the muscle respiratory activity to derive several physiological parameters. Its use can be an alternative to conventional measuring systems with the advantage of being portable, lightweight, flexible and operating at low energy. This technology can be attractive for medical staff and may have a positive impact in the way healthcare is being delivered.

Keywords: Biomedical monitoring, Electrodes, Medical services, Monitoring, Muscles, Wireless communication, Wireless sensor networks


Ziyatdinov, Andrey, Fonollosa, Jordi, Fernández, Luis, Gutiérrez-Gálvez, Agustín, Marco, Santiago, Perera, Alexandre, (2015). Data set from gas sensor array under flow modulation Data in Brief , 3, 131-136

Abstract Recent studies in neuroscience suggest that sniffing, namely sampling odors actively, plays an important role in olfactory system, especially in certain scenarios such as novel odorant detection. While the computational advantages of high frequency sampling have not been yet elucidated, here, in order to motivate further investigation in active sampling strategies, we share the data from an artificial olfactory system made of 16 MOX gas sensors under gas flow modulation. The data were acquired on a custom set up featured by an external mechanical ventilator that emulates the biological respiration cycle. 58 samples were recorded in response to a relatively broad set of 12 gas classes, defined from different binary mixtures of acetone and ethanol in air. The acquired time series show two dominant frequency bands: the low-frequency signal corresponds to a conventional response curve of a sensor in response to a gas pulse, and the high-frequency signal has a clear principal harmonic at the respiration frequency. The data are related to the study in [1], and the data analysis results reported there should be considered as a reference point.

Keywords: Gas sensor array, MOX sensor, Flow modulation, Early detection, Biomimetics, Respiration, Sniffing


Galán, T., Prieto-Simón, B., Alvira, M., Eritja, R., Götz, G., Bäuerle, P., Samitier, J., (2015). Label-free electrochemical DNA sensor using "click"-functionalized PEDOT electrodes Biosensors and Bioelectronics , 74, 751-756

Here we describe a label-free electrochemical DNA sensor based on poly(3,4-ethylenedioxythiophene)-modified (PEDOT-modified) electrodes. An acetylene-terminated DNA probe, complementary to a specific "Hepatitis C" virus sequence, was immobilized onto azido-derivatized conducting PEDOT electrodes using "click" chemistry. DNA hybridization was then detected by differential pulse voltammetry, evaluating the changes in the electrochemical properties of the polymer produced by the recognition event. A limit of detection of 0.13. nM was achieved using this highly selective PEDOT-based genosensor, without the need for labeling techniques or microelectrode fabrication processes. These results are promising for the development of label-free and reagentless DNA hybridization sensors based on conducting polymeric substrates. Biosensors can be easily prepared using any DNA sequence containing an alkyne moiety. The data presented here reveal the potential of this DNA sensor for diagnostic applications in the screening of diseases, such as "Hepatitis C", and genetic mutations.

Keywords: Azido-EDOT, Click chemistry, Differential pulse voltammetry, DNA biosensor, Electrochemistry, Hepatitis C virus


Ziyatdinov, Andrey, Fonollosa, Jordi, Fernánndez, Luis, Gutierrez-Gálvez, Agustín, Marco, Santiago, Perera, Alexandre, (2015). Bioinspired early detection through gas flow modulation in chemo-sensory systems Sensors and Actuators B: Chemical , 206, 538-547

Abstract The design of bioinspired systems for chemical sensing is an engaging line of research in machine olfaction. Developments in this line could increase the lifetime and sensitivity of artificial chemo-sensory systems. Such approach is based on the sensory systems known in live organisms, and the resulting developed artificial systems are targeted to reproduce the biological mechanisms to some extent. Sniffing behaviour, sampling odours actively, has been studied recently in neuroscience, and it has been suggested that the respiration frequency is an important parameter of the olfactory system, since the odour perception, especially in complex scenarios such as novel odourants exploration, depends on both the stimulus identity and the sampling method. In this work we propose a chemical sensing system based on an array of 16 metal-oxide gas sensors that we combined with an external mechanical ventilator to simulate the biological respiration cycle. The tested gas classes formed a relatively broad combination of two analytes, acetone and ethanol, in binary mixtures. Two sets of low-frequency and high-frequency features were extracted from the acquired signals to show that the high-frequency features contain information related to the gas class. In addition, such information is available at early stages of the measurement, which could make the technique suitable in early detection scenarios. The full data set is made publicly available to the community.11 http://archive.ics.uci.edu/ml/datasets/Gas+sensor+array+under+flow+modulation.

Keywords: Gas sensor array, MOX sensor, Flow modulation, Early detection, Biomimetics, Sniffing


Fonollosa, J., Sheik, S., Huerta, R., Marco, S., (2015). Reservoir computing compensates slow response of chemosensor arrays exposed to fast varying gas concentrations in continuous monitoring Sensors and Actuators B: Chemical , 215, 618-629

Metal oxide (MOX) gas sensors arrays are a predominant technological choice to perform fundamental tasks of chemical detection. Yet, their use has been mainly limited to relatively controlled instrument configurations where the sensor array is placed within a closed measurement chamber. Usually, the experimental protocol is defined beforehand and it includes three stages: the array is first exposed to a gas reference, then to the gas sample, and finally to the reference again to recover the initial state. Such sampling procedure requires signal acquisition during the complete experimental protocol and usually delays the output prediction until the predefined measurement duration is complete. Due to the slow time response of chemical sensors, the completion of the measurement typically requires minutes. In this paper we propose the use of reservoir computing (RC) algorithms to overcome the slow temporal dynamics of chemical sensor arrays, allowing identification and quantification of chemicals of interest continuously and reducing measurement delays. We generated two datasets to test the ability of RC algorithms to provide accurate and continuous prediction to fast varying gas concentrations in real time. Both datasets - one generated with synthetic data and the other acquired from actual gas sensors - provide time series of MOX sensors exposed to binary gas mixtures where concentration levels change randomly over time. Our results show that our approach improves the time response of the sensory system and provides accurate predictions in real time, making the system specifically suitable for online monitoring applications. Finally, the collected dataset and developed code are made publicly available to the research community for further studies.

Keywords: Chemical sensors, Continuous gas prediction, Electronic nose, Real-time detection, Reservoir computing


Fernandez, L., Marco, S., Gutierrez-Galvez, A., (2015). Robustness to sensor damage of a highly redundant gas sensor array Sensors and Actuators B: Chemical , 218, 296-302

Abstract In this paper we study the role of redundant sensory information to prevent the performance degradation of a chemical sensor array for different distributions of sensor failures across sensor types. The large amount of sensing conditions with two different types of redundancy provided by our sensor array makes possible a comprehensive experimental study. Particularly, our sensor array is composed of 8 different types of commercial MOX sensors modulated in temperature with two redundancy levels: (1) 12 replicates of each sensor type for a total of 96 sensors and (2) measurements using 16 load resistors per sensors for a total of 1536 redundant measures per second. We perform two experiments to determine the performance degradation of the array with increasing number of damaged sensors in two different scenarios of sensor faults distributions across sensor types. In the first experiment, we characterize the diversity and redundancy of the array for increasing number of damaged sensors. To measure diversity and redundancy, we proposed a functional definition based on clustering of sensor features. The second experiment is devoted to determine the performance degradation of the array for the effect of faulty sensors. To this end, the system is trained to separate ethanol, acetone and butanone at different concentrations using a PCA–LDA model. Test set samples are corrupted by means of three different simulated types of faults. To evaluate the performance of the array we used the Fisher score as a measure of odour separability. Our results show that to exploit to the utmost the redundancy of the sensor array faulty sensory units have to be distributed uniformly across the different sensor types.

Keywords: Gas sensor arrays, Sensor redundancy, Sensor diversity, Sensor faults aging, Sensor damage, MOX sensors, Large sensor arrays


Barreiros dos Santos, M., Azevedo, S., Agusil, J. P., Prieto-Simón, B., Sporer, C., Torrents, E., Juárez, A., Teixeira, V., Samitier, J., (2015). Label-free ITO-based immunosensor for the detection of very low concentrations of pathogenic bacteria Bioelectrochemistry , 101, 146-152

Abstract Here we describe the fabrication of a highly sensitive and label-free ITO-based impedimetric immunosensor for the detection of pathogenic bacteria Escherichia coli O157:H7. Anti-E. coli antibodies were immobilized onto ITO electrodes using a simple, robust and direct methodology. First, the covalent attachment of epoxysilane on the ITO surface was demonstrated by Atomic Force Microscopy and cyclic voltammetry. The immobilization of antibody on the epoxysilane layer was quantified by Optical Waveguide Lightmode Spectroscopy, obtaining a mass variation of 12 ng cm− 2 (0.08 pmol cm− 2). Microcontact printing and fluorescence microscopy were used to demonstrate the specific binding of E. coli O157:H7 to the antibody-patterned surface. We achieved a ratio of 1:500 Salmonella typhimurium/E. coli O157:H7, thus confirming the selectivity of the antibodies and efficiency of the functionalization procedure. Finally, the detection capacity of the ITO-based immunosensor was evaluated by Electrochemical Impedance Spectroscopy. A very low limit of detection was obtained (1 CFU mL− 1) over a large linear working range (10–106 CFU mL− 1). The specificity of the impedimetric immunosensor was also examined. Less than 20% of non-specific bacteria (S. typhimurium and E. coli K12) was observed. Our results reveal the applicability of ITO for the development of highly sensitive and selective impedimetric immunosensors.

Keywords: E. coli O157:H7, Electrochemical Impedance Spectroscopy, Immunosensor, Indium tin oxide, Label-free detection


Pardo, W. A., Mir, M., Samitier, J., (2015). Signal enhancement in ultraflat electrochemical DNA biosensors Electrophoresis , 36, (16), 1905-1911

The ability of holding back the undesired molecules, but at the same time to provide the right distribution and orientation of the bioreceptors, are critical targets to reach an efficient hybridization and enhanced detection in electrochemical DNA biosensors. The main actors responsible of these key functions are the substrate of the sensor and the interface auto-assembled on it. In this paper we present the annealing as a method to improve commercial gold evaporated substrates for biosensor applications. The restructuring of granulated gold surface by means of annealing heating treatment leads to the formation of ultraflat gold lamellar terraces. The formation of terraces was characterized with scanning tunneling microscopy and optical interferometry. The performance of the sensor sensitivity on granular substrates and ultraflat substrates was studied, concerning the orientation and surface coverage of the bioreceptor interface applied in electrochemical biosensor. The hybridization efficiency of ferrocene-labeled DNA amplified by PCR was characterized with surface plasmon resonance and electrochemistry. The experimental results demonstrate that annealing process, positive influence on optical and voltammetric readings, due to a structured organization of the bioreceptors on the flat substrate, gaining more efficient immobilization and DNA hybridization. The results suggest the annealing as a powerful tool for improving gold substrates in biosensors applications.

Keywords: Annealing ultraflat surfaces, DNA biosensor, DNA hybridization, Electrochemistry, Self-assembled monolayer


Fonollosa, J., Neftci, E., Huerta, R., Marco, S., (2015). Evaluation of calibration transfer strategies between Metal Oxide gas sensor arrays Procedia Engineering EUROSENSORS 2015 , Elsevier (Freiburg, Germany) 120, 261-264

Abstract Inherent variability of chemical sensors makes necessary individual calibration of chemical detection systems. This shortcoming has traditionally limited usability of systems based on Metal Oxide (MOX) sensor arrays and prevented mass-production for some applications. Here, aiming at exploring transfer calibration between electronic nose systems, we exposed five identical 8-sensor detection units to controlled gas conditions. Our results show that a calibration model provides more accurate predictions when the tested board is included in the calibration dataset. However, we show that previously built calibration models can be extended to other units using a reduced number of measurements. While baseline correction seems imperative for successful baseline correction, among the different tested strategies, piecewise direct standardization provides more accurate predictions.

Keywords: Electronic nose, Calibration, MOX sensor, Machine Olfaction


Palleja, T., Balsa, R., Tresanchez, M., Moreno, J., Teixido, M., Font, D., Marco, S., Pomareda, V., Palacin, J., (2014). Corridor gas-leak localization using a mobile Robot with a photo ionization detector sensor Sensor Letters , 12, (6-7), 974-977

The use of an autonomous mobile robot to locate gas-leaks and air quality monitoring in indoor environments are promising tasks that will avoid risky human operations. However, these are challenging tasks due to the chaotic gas profile propagation originated by uncontrolled air flows. This paper proposes the localization of an acetone gas-leak in a 44 m-length indoor corridor with a mobile robot equipped with a PID sensor. This paper assesses the influence of the mobile robot velocity and the relative height of the PID sensor in the profile of the measurements. The results show weak influence of the robot velocity and strong influence of the relative height of the PID sensor. An estimate of the gas-leak location is also performed by computing the center of mass of the highest gas concentrations.

Keywords: Gas source detection, LIDAR sensor, Mobile robot, PID sensor, SLAM, Acetone, Air quality, Gases, Indoor air pollution, Mobile robots, Robots, Air quality monitoring, Autonomous Mobile Robot, Gas sources, Indoor environment, Leak localization, LIDAR sensors, Profile propagation, SLAM, Ionization of gases


Tahirbegi, I. B., Mir, M., Schostek, S., Schurr, M., Samitier, J., (2014). In vivo ischemia monitoring array for endoscopic surgery Biosensors and Bioelectronics , 61, 124-130

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.

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


Urbán, P., Fernàndez-Busquets, X., (2014). Nanomedicine against malaria Current Medicinal Chemistry , 21, (5), 605-629

Malaria is arguably one of the main medical concerns worldwide because of the numbers of people affected, the severity of the disease and the complexity of the life cycle of its causative agent, the protist Plasmodium sp. The clinical, social and economic burden of malaria has led for the last 100 years to several waves of serious efforts to reach its control and eventual eradication, without success to this day. With the advent of nanoscience, renewed hopes have appeared of finally obtaining the long sought-after magic bullet against malaria in the form of a nanovector for the targeted delivery of antimalarial drugs exclusively to Plasmodium-infected cells. Different types of encapsulating structure, targeting molecule, and antimalarial compound will be discussed for the assembly of Trojan horse nanocapsules capable of targeting with complete specificity diseased cells and of delivering inside them their antimalarial cargo with the objective of eliminating the parasite with a single dose. Nanotechnology can also be applied to the discovery of new antimalarials through single-molecule manipulation approaches for the identification of novel drugs targeting essential molecular components of the parasite. Finally, methods for the diagnosis of malaria can benefit from nanotools applied to the design of microfluidic-based devices for the accurate identification of the parasite's strain, its precise infective load, and the relative content of the different stages of its life cycle, whose knowledge is essential for the administration of adequate therapies. The benefits and drawbacks of these nanosystems will be considered in different possible scenarios, including cost-related issues that might be hampering the development of nanotechnology-based medicines against malaria with the dubious argument that they are too expensive to be used in developing areas.

Keywords: Dendrimers, Liposomes, Malaria diagnosis, Nanobiosensors, Nanoparticles, Plasmodium, Polymers, Targeted drug delivery


Zaffino, R. L., Mir, M., Samitier, J., (2014). Label-free detection of DNA hybridization and single point mutations in a nano-gap biosensor Nanotechnology , 25, (10), 105501 (8)

We describe a conductance-based biosensor that exploits DNA-mediated long-range electron transport for the label-free and direct electrical detection of DNA hybridization. This biosensor platform comprises an array of vertical nano-gap biosensors made of gold and fabricated through standard photolithography combined with focused ion beam lithography. The nano-gap walls are covalently modified with short, anti-symmetric thiolated DNA probes, which are terminated by 19 bases complementary to both the ends of a target DNA strand. The nano-gaps are separated by a distance of 50nm, which was adjusted to fit the length of the DNA target plus the DNA probes. The hybridization of the target DNA closes the gap circuit in a switch on/off fashion, in such a way that it is readily detected by an increase in the current after nano-gap closure. The nano-biosensor shows high specificity in the discrimination of base-pair mismatching and does not require signal indicators or enhancing molecules. The design of the biosensor platform is applicable for multiplexed detection in a straightforward manner. The platform is well-suited to mass production, point-of-care diagnostics, and wide-scale DNA analysis applications.

Keywords: Biosensor, DNA hybridization, Labelfree, Nanogap, Single nucleotide mutation


Marco, Santiago, (2014). The need for external validation in machine olfaction: emphasis on health-related applications Analytical and Bioanalytical Chemistry , Springer Berlin Heidelberg 406, (16), 3941-3956

Over the last two decades, electronic nose research has produced thousands of research works. Many of them were describing the ability of the e-nose technology to solve diverse applications in domains ranging from food technology to safety, security, or health. It is, in fact, in the biomedical field where e-nose technology is finding a research niche in the last years. Although few success stories exist, most described applications never found the road to industrial or clinical exploitation. Most described methodologies were not reliable and were plagued by numerous problems that prevented practical application beyond the lab. This work emphasizes the need of external validation in machine olfaction. I describe some statistical and methodological pitfalls of the e-nose practice and I give some best practice recommendations for researchers in the field.

Keywords: Chemical sensor arrays, Pattern recognition, Chemometrics, Electronic noses, Robustness, Signal and data processing


Bennetts, Victor, Schaffernicht, Erik, Pomareda, Victor, Lilienthal, Achim, Marco, Santiago, Trincavelli, Marco, (2014). Combining non selective gas sensors on a mobile robot for identification and mapping of multiple chemical compounds Sensors 14, (9), 17331-17352

In this paper, we address the task of gas distribution modeling in scenarios where multiple heterogeneous compounds are present. Gas distribution modeling is particularly useful in emission monitoring applications where spatial representations of the gaseous patches can be used to identify emission hot spots. In realistic environments, the presence of multiple chemicals is expected and therefore, gas discrimination has to be incorporated in the modeling process. The approach presented in this work addresses the task of gas distribution modeling by combining different non selective gas sensors. Gas discrimination is addressed with an open sampling system, composed by an array of metal oxide sensors and a probabilistic algorithm tailored to uncontrolled environments. For each of the identified compounds, the mapping algorithm generates a calibrated gas distribution model using the classification uncertainty and the concentration readings acquired with a photo ionization detector. The meta parameters of the proposed modeling algorithm are automatically learned from the data. The approach was validated with a gas sensitive robot patrolling outdoor and indoor scenarios, where two different chemicals were released simultaneously. The experimental results show that the generated multi compound maps can be used to accurately predict the location of emitting gas sources.

Keywords: Environmental monitoring, Gas discrimination, Gas distribution mapping, Service robots, Open sampling systems, PID, Metal oxide sensors


Juanola-Feliu, E., Miribel-Català, P. L., Avilés, C. P., Colomer-Farrarons, J., González-Piñero, M., Samitier, J., (2014). Design of a customized multipurpose nano-enabled implantable system for in-vivo theranostics Sensors 14, (10), 19275-19306

The first part of this paper reviews the current development and key issues on implantable multi-sensor devices for in vivo theranostics. Afterwards, the authors propose an innovative biomedical multisensory system for in vivo biomarker monitoring that could be suitable for customized theranostics applications. At this point, findings suggest that cross-cutting Key Enabling Technologies (KETs) could improve the overall performance of the system given that the convergence of technologies in nanotechnology, biotechnology, micro&nanoelectronics and advanced materials permit the development of new medical devices of small dimensions, using biocompatible materials, and embedding reliable and targeted biosensors, high speed data communication, and even energy autonomy. Therefore, this article deals with new research and market challenges of implantable sensor devices, from the point of view of the pervasive system, and time-to-market. The remote clinical monitoring approach introduced in this paper could be based on an array of biosensors to extract information from the patient. A key contribution of the authors is that the general architecture introduced in this paper would require minor modifications for the final customized bio-implantable medical device.

Keywords: Biocompatible, Biosensor, Biotelemetry, Implantable multi-sensor, Innovation, KET, Nanomedicine, Personalized medicine, Biotelemetry, Innovation, Medical nanotechnology, Biocompatible, Implantable system, In-vivo, KET, Multi sensor, Personalized medicines, Theranostics, Biosensors


Mir, M., Lugo, R., Tahirbegi, I. B., Samitier, J., (2014). Miniaturizable ion-selective arrays based on highly stable polymer membranes for biomedical applications Sensors 14, (7), 11844-11854

Poly(vinylchloride) (PVC) is the most common polymer matrix used in the fabrication of ion-selective electrodes (ISEs). However, the surfaces of PVC-based sensors have been reported to show membrane instability. In an attempt to overcome this limitation, here we developed two alternative methods for the preparation of highly stable and robust ion-selective sensors. These platforms are based on the selective electropolymerization of poly(3,4-ethylenedioxythiophene) (PEDOT), where the sulfur atoms contained in the polymer covalently interact with the gold electrode, also permitting controlled selective attachment on a miniaturized electrode in an array format. This platform sensor was improved with the crosslinking of the membrane compounds with poly(ethyleneglycol) diglycidyl ether (PEG), thus also increasing the biocompatibility of the sensor. The resulting ISE membranes showed faster signal stabilization of the sensor response compared with that of the PVC matrix and also better reproducibility and stability, thus making these platforms highly suitable candidates for the manufacture of robust implantable sensors.

Keywords: Biomedicine, Electrochemistry, Endoscope, Implantable device, Ion-selective electrode (ISE) sensor, Ischemia, pH detection, Biocompatibility, Chemical sensors, Electrochemistry, Electrodes, Electropolymerization, Endoscopy, Functional polymers, Implants (surgical), Ion selective electrodes, Medical applications, Polyvinyl chlorides, Stabilization, Biomedical applications, Biomedicine, Implantable devices, Ion selective sensors, Ischemia, Membrane instability, pH detection, Poly(3 ,4 ethylenedioxythiophene) (PEDOT), Ion selective membranes


Tahirbegi, I. B., Alvira, M., Mir, M., Samitier, J., (2014). Simple and fast method for fabrication of endoscopic implantable sensor arrays Sensors 14, (7), 11416-11426

Here we have developed a simple method for the fabrication of disposable implantable all-solid-state ion-selective electrodes (ISE) in an array format without using complex fabrication equipment or clean room facilities. The electrodes were designed in a needle shape instead of planar electrodes for a full contact with the tissue. The needle-shape platform comprises 12 metallic pins which were functionalized with conductive inks and ISE membranes. The modified microelectrodes were characterized with cyclic voltammetry, scanning electron microscope (SEM), and optical interferometry. The surface area and roughness factor of each microelectrode were determined and reproducible values were obtained for all the microelectrodes on the array. In this work, the microelectrodes were modified with membranes for the detection of pH and nitrate ions to prove the reliability of the fabricated sensor array platform adapted to an endoscope.

Keywords: Chemical sensors, Cyclic voltammetry, Electrochemistry, Endoscopy, Fabrication, Implants (surgical), Microelectrodes, Needles, Nitrates, Scanning electron microscopy, Biomedicine, Fabricated sensors, Fabrication equipment, Implantable devices, Implantable sensors, Optical interferometry, Planar electrode, Roughness factor, Ion selective electrodes


Sheik, S., Marco, S., Huerta, R., Fonollosa, J., (2014). Continuous prediction in chemoresisitive gas sensors using reservoir computing Procedia Engineering 28th European Conference on Solid-State Transducers (EUROSENSORS 2014) , Eurosensors (Brescia, Italy) 87, 843-846

Although Metal Oxide (MOX) sensors are predominant choices to perform fundamental tasks of chemical detection, their use has been mainly limited to relatively controlled scenarios where a gas sensor array is first exposed to a reference, then to the gas sample, and finally to the reference again to recover the initial state. In this paper we propose the use of MOX sensors along with Reservoir Computing algorithms to identify chemicals of interest. Our approach allows continuous gas monitoring in simple experimental setups without the requirement of acquiring recovery transient of the sensors, thereby making the system specifically suitable for online monitoring applications.

Keywords: Chemical sensing, Reservoir computing, Gas sensors, Dynamic gas mixtures, Electronic nose


Fernandez, L., Gutierrez-Galvez, A., Marco, S., (2014). Robustness to sensor damage of a highly redundant gas sensor array Procedia Engineering 28th European Conference on Solid-State Transducers (EUROSENSORS 2014) , Eurosensors (Brescia, Italy) 87, 851-854

Abstract In this paper we study the role of redundant sensory information to prevent the performance degradation of a chemical sensor array as the number of faulty sensors increases. The large amount of sensing conditions with two different types of redundancy provided by our sensor array makes possible a comprehensive experimental study. Particularly, our sensor array is composed of 8 different types of commercial MOX sensors modulated in temperature with two redundancy levels: 1) 12 replicates of each sensor type for a total of 96 sensors, and 2) measurements using 16 load resistors per sensors for a total of 1536 redundant measures per second. The system is trained to identify ethanol, acetone and butanone using a PCA-LDA model. Test set samples are corrupted by means of three different simulated types of faults. To evaluate the tolerance of the array against sensor failure, the Fisher Score is used as a figure of merit for the corrupted test set samples projected on the PCA-LDA model.

Keywords: Gas ensor arrays, sensor redundancy, MOX sensors, large sensor arrays.


Martínez, Dani, Pallejà, T., Moreno, Javier, Tresanchez, Marcel, Teixidó, M., Font, Davinia, Pardo, Antonio, Marco, Santiago, Palacín, Jordi, (2014). A mobile robot agent for gas leak source detection Advances in Intelligent Systems and Computing Trends in Practical Applications of Heterogeneous Multi-Agent Systems. The PAAMS Collection (ed. Bajo Perez, Javier, Corchado Rodríguez, Juan M., Mathieu, Philippe, Campbell, Andrew, Ortega, Alfonso, Adam, Emmanuel, Navarro, Elena M., Ahrndt, Sebastian, Moreno, Maríaa N., Julián, Vicente), Springer International Publishing 293, 19-25

This paper presents an autonomous agent for gas leak source detection. The main objective of the robot is to estimate the localization of the gas leak source in an indoor environment without any human intervention. The agent implements an SLAM procedure to scan and map the indoor area. The mobile robot samples gas concentrations with a gas and a wind sensor in order to estimate the source of the gas leak. The mobile robot agent will use the information obtained from the onboard sensors in order to define an efficient scanning path. This paper describes the measurement results obtained in a long corridor with a gas leak source placed close to a wall.

Keywords: Gas detection, Mobile robot agent, Laser sensor, Self-localization


Juanola-Feliu, Esteve, Colomer-Farrarons, Jordi, Miribel-Català, Pere, González-Piñero, Manel, Samitier, Josep, (2014). Nano-enabled implantable device for glucose monitoring Implantable Bioelectronics (ed. Katz, Evgeny), Wiley-VCH Verlag GmbH & Co. KGaA (Weinheim, Germany) , 247-263

This chapter contains sections titled: * Introduction * Biomedical Devices for In Vivo Analysis * Conclusions and Final Recommendations * References

Keywords: Technology transfer, Innovation management, Nanotechnology, Nanobiosensor, Diabetes, Biomedical device, Implantable biosensors


Gorostiza, Pau, Arosio, Daniele, Bregestovski, Piotr, (2013). Molecular probes and switches for functional analysis of receptors, ion channels and synaptic networks Frontiers in Molecular Neuroscience , 6, (Article 48), 1-2

Gustavsson, J., Planell, J., Engel, E., (2013). Ion-selective electrodes to monitor osteoblast-like cellular influence on the extracellular concentration of calcium Journal of Tissue Engineering and Regenerative Medicine , 7, (8), 609-620

In bone tissue engineering, the composition of the ionic extracellular environment (IEE) can determine both cellular fate and a biomaterial's development and performance. Therefore, precise control of the IEE and a perfect understanding of the dynamic changes that it can be subject to due to cellular activity is highly desired. To achieve this, we initially monitored how two standard osteoblast-like cell models that expressed either high or low alkaline phosphatase activity - SAOS-2 and MG63 cells, respectively - affected the extracellular concentrations of calcium and phosphate during long-term cultures. It was observed that cellular influence on the IEE varied greatly between the two models and could be linked to the capacity of cells to deposit calcium in the extracellular matrix. Miniaturized ion-selective electrodes that could allow for real-time monitoring of calcium in a minimally invasive way were then constructed. The electrodes were characterized in standard in vitro cell culture environments, prior to being successfully applied for periods of 24h, to record the dynamics of cell-induced deposition of calcium in the extracellular matrix, while using osteogenic media of either high or low concentrations of phosphate. As a result, this study provides the background and technological means for the non-destructive evaluation of the IEE in vitro and allows for the optimization and development of better models of bone tissue construction.

Keywords: Extracellular ions, Ion-selective electrode, MG63, Mineralization, Osteoblasts, Saos-2, Sensor, Tissue engineering


Ziyatdinov, A., Diaz, E. Fernández, Chaudry, A., Marco, S., Persaud, K., Perera, A., (2013). A software tool for large-scale synthetic experiments based on polymeric sensor arrays Sensors and Actuators B: Chemical , 177, 596-604

This manuscript introduces a software tool that allows for the design of synthetic experiments in machine olfaction. The proposed software package includes both, a virtual sensor array that reproduces the diversity and response of a polymer array and tools for data generation. The synthetic array of sensors allows for the generation of chemosensor data with a variety of characteristics: unlimited number of sensors, support of multicomponent gas mixtures and full parametric control of the noise in the system. The artificial sensor array is inspired from a reference database of seventeen polymeric sensors with concentration profiles for three analytes. The main features in the sensor data, like sensitivity, diversity, drift and sensor noise, are captured by a set of models under simplified assumptions. The generator of sensor signals can be used in applications related to test and benchmarking of signal processing methods, neuromorphic simulations in machine olfaction and educational tools. The software is implemented in R language and can be freely accessed.

Keywords: Gas Sensor Array, Conducting Polymers, Electronic Nose, Sensor Simulation, Synthetic Dataset, Benchmark, Educational Tool


Fonollosa, Jordi, Fernérndez, Luis, Huerta, Ramón, Gutiérrez-Gálvez, Agustín, Marco, Santiago, (2013). Temperature optimization of metal oxide sensor arrays using Mutual Information Sensors and Actuators B: Chemical , Elsevier 187, (0), 331-339

The sensitivity and selectivity of metal oxide (MOX) gas sensors change significantly when the sensors operate at different temperatures. While previous investigations have presented systematic approaches to optimize the operating temperature of a single MOX sensor, in this paper we present a methodology to select the optimal operating temperature of all the MOX sensors constituent of a gas sensor array based on the multivariate response of all the sensing elements. Our approach estimates a widely used Information Theory measure, the so-called Mutual Information (MI), which quantifies the amount of information that the state of one random variable (response of the gas sensor array) can provide from the state of another random variable representing the gas quality. More specifically, our methodology builds sensor models from experimental data to solve the technical problem of populating the joint probability distribution for the MI estimation. We demonstrate the relevance of our approach by maximizing the MI and selecting the best operating temperatures of a four-sensor array sampled at 94 different temperatures to optimize the discrimination task of ethanol, acetic acid, 2-butanone, and acetone. In addition to being applicable in principle to sensor arrays of any size, our approach gives precise information on the ability of the system to discriminate odors according to the temperature of the MOX sensors, for either the optimal set of temperatures or the temperatures that may render inefficient operation of the system itself.

Keywords: MOX gas sensor, Temperature optimization, Limit of detection, Mutual Information, E-nose, Sensor array, Information Theory, Chemical sensing


Marco, S., Gutiérrez-Gálvez, A., Lansner, A., Martinez, D., Rospars, J. P., Beccherelli, R., Perera, A., Pearce, T., Vershure, P., Persaud, K., (2013). Biologically inspired large scale chemical sensor arrays and embedded data processing Proceedings of SPIE - The International Society for Optical Engineering Smart Sensors, Actuators, and MEMS VI , SPIE Digital Library (Grenoble, France) 8763, 1-15

Biological olfaction outperforms chemical instrumentation in specificity, response time, detection limit, coding capacity, time stability, robustness, size, power consumption, and portability. This biological function provides outstanding performance due, to a large extent, to the unique architecture of the olfactory pathway, which combines a high degree of redundancy, an efficient combinatorial coding along with unmatched chemical information processing mechanisms. The last decade has witnessed important advances in the understanding of the computational primitives underlying the functioning of the olfactory system. EU Funded Project NEUROCHEM (Bio-ICT-FET- 216916) has developed novel computing paradigms and biologically motivated artefacts for chemical sensing taking inspiration from the biological olfactory pathway. To demonstrate this approach, a biomimetic demonstrator has been built featuring a large scale sensor array (65K elements) in conducting polymer technology mimicking the olfactory receptor neuron layer, and abstracted biomimetic algorithms have been implemented in an embedded system that interfaces the chemical sensors. The embedded system integrates computational models of the main anatomic building blocks in the olfactory pathway: The olfactory bulb, and olfactory cortex in vertebrates (alternatively, antennal lobe and mushroom bodies in the insect). For implementation in the embedded processor an abstraction phase has been carried out in which their processing capabilities are captured by algorithmic solutions. Finally, the algorithmic models are tested with an odour robot with navigation capabilities in mixed chemical plumes.

Keywords: Antennal lobes, Artificial olfaction, Computational neuroscience, Olfactory bulbs, Plume tracking, Abstracting, Actuators, Algorithms, Biomimetic processes, Chemical sensors, Conducting polymers, Data processing, Flavors, Odors, Robots, Smart sensors, Embedded systems


Fernandez, L., Gutierrez-Galvez, A., Marco, S., (2013). Multi-way analysis of diversity and redundancy factors in large MOX gas sensor data Metal Oxide-based Sensors 14th International Meeting on Chemical Sensors - IMCS 2012 , AMA Science Portal (Nuremberg, Germany) P2.07, 1279-1280

We propose the use of multi-way methods to analyze the contribution of diversity and redundancy to odor identification and concentration estimation in a large chemical sensor array. We use a chemical sensing system based on a large array of metal oxide sensors (MOX) and inspired on the diversity and redundancy of the olfactory epithelium. In order to analyze the role of diversity (different sensor type and temperature modulation) and redundancy (replicates of sensors and different load resistors) in odor quantification and discrimination tasks, we have acquired two datasets and modeled the data using multi-way techniques.

Keywords: Artificial Olfaction, Large array, MOX gas sensor, Multi-way methods


Diéguez, Lorena, Caballero, David, Calderer, Josep, Moreno, Mauricio, Martínez, Elena, Samitier, Josep, (2012). Optical gratings coated with thin Si3N4 layer for efficient immunosensing by optical waveguide lightmode spectroscopy Biosensors , 2, (2), 114-126

New silicon nitride coated optical gratings were tested by means of Optical Waveguide Lightmode Spectroscopy (OWLS). A thin layer of 10 nm of transparent silicon nitride was deposited on commercial optical gratings by means of sputtering. The quality of the layer was tested by x-ray photoelectron spectroscopy and atomic force microscopy. As a proof of concept, the sensors were successfully tested with OWLS by monitoring the concentration dependence on the detection of an antibody-protein pair. The potential of the Si3N4 as functional layer in a real-time biosensor opens new ways for the integration of optical waveguides with microelectronics.

Keywords: Silicon nitride, Optical gratings, Waveguide, Biosensor


Gustavsson, J., Ginebra, M. P., Planell, J., Engel, E., (2012). Electrochemical microelectrodes for improved spatial and temporal characterization of aqueous environments around calcium phosphate cements Acta Biomaterialia 8, (1), 386-393

Calcium phosphate compounds can potentially influence cellular fate through ionic substitutions. However, to be able to turn such solution-mediated processes into successful directors of cellular response, a perfect understanding of the material-induced chemical reactions in situ is required. We therefore report on the application of home-made electrochemical microelectrodes, tested as pH and chloride sensors, for precise spatial and temporal characterization of different aqueous environments around calcium phosphate-based biomaterials prepared from α-tricalcium phosphate using clinically relevant liquid to powder ratios. The small size of the electrodes allowed for online measurements in traditionally inaccessible in vitro environments, such as the immediate material-liquid interface and the interior of curing bone cement. The kinetic data obtained has been compared to theoretical sorption models, confirming that the proposed setup can provide key information for improved understanding of the biochemical environment imposed by chemically reactive biomaterials.

Keywords: Calcium phosphate, Hydroxyapatite, Ion sorption, Iridium oxide, Sensors, Animals, Biocompatible Materials, Bone Cements, Calcium Phosphates, Cells, Cultured, Chlorides, Electrochemical Techniques, Gold, Hydrogen-Ion Concentration, Hydroxyapatites, Iridium, Materials Testing, Microelectrodes, Powders, Silver, Silver Compounds, Water


Tort, N., Salvador, J. P., Avino, A., Eritja, R., Comelles, J., Martinez, E., Samitier, J., Marco, M. P., (2012). Synthesis of steroid-oligonucleotide conjugates for a DNA site-encoded SPR immunosensor Bioconjugate Chemistry , 23, (11), 2183-2191

The excellent self-assembling properties of DNA and the excellent specificity of the antibodies to detect analytes of small molecular weight under competitive conditions have been combined in this study. Three oligonucleotide sequences (N(1)up, N(2)up, and N(3)up) have been covalently attached to three steroidal haptens (8, hG, and 13) of three anabolic-androgenic steroids (AAS), stanozolol (ST), tetrahydrogestrinone (THG), and boldenone (B), respectively. The synthesis of steroid oligonucleotide conjugates has been performed by the reaction of oligonucleotides carrying amino groups with carboxyl acid derivatives of steroidal haptens. Due to the chemical nature of the steroid derivatives, two methods for coupling the haptens and the ssDNA have been studied: a solid-phase coupling strategy and a solution-phase coupling strategy. Specific antibodies against ST, THG, and B have been used in this study to asses the possibility of using the self-assembling properties of the DNA to prepare biofunctional SPR gold chips based on the immobilization of haptens, by hybridization with the complementary oligonucleotide strands possessing SH groups previously immobilized. The capture of the steroid oligonucleotide conjugates and subsequent binding of the specific antibodies can be monitored on the sensogram due to variations produced on the refractive index on top of the gold chip. The resulting steroid oligonucleotide conjugates retain the hybridization and specific binding properties of oligonucleotides and haptens as demonstrated by thermal denaturation experiments and surface plasmon resonance (SPR).

Keywords: Directed protein immobilization, Plasmon resonance biosensor, Self-assembled monolayers, Label-free, Serum samples, Assay, Immunoassays, Antibodies, Progress, Binding


Caballero, D., Martinez, E., Bausells, J., Errachid, A., Samitier, J., (2012). Impedimetric immunosensor for human serum albumin detection on a direct aldehyde-functionalized silicon nitride surface Analytica Chimica Acta , 720, 43-48

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.

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


Baccar, Z.M., Caballero, D., Eritja, R., Errachid, A., (2012). Development of an impedimetric DNA-biosensor based on layered double hydroxide for the detection of long ssDNA sequences Electrochimica Acta , 74, 123-129

DNA testing requires the development of sensitive and fast devices to measure the presence of nucleic acid sequences by DNA hybridization. In this paper, a simple and label-free DNA-biosensor has been investigated based on the detection of DNA hybridization on layered double hydroxide (LDH) nanomaterials with special emphasis on targeting long single stranded DNA sequences. First, the immobilization of a 20 bases long DNA probe on a thin layer of Mg2AlCO3 and Mg3AlCO3 LDH was studied. Then, DNA hybridization reaction was detected by means of Electrochemical Impedance Spectroscopy. The resulting biosensor showed a high sensitivity for the detection of 80 bases long DNA complementary sequences. The dynamic range was 18–270 ng/ml with a detection limit lower than 1.8 ng/ml.

Keywords: DNA-biosensor, Nanomaterials, Layered double hydroxide, Self-assembly


Udina, S., Carmona, M., Pardo, A., Calaza, C., Santander, J., Fonseca, L., Marco, S., (2012). A micromachined thermoelectric sensor for natural gas analysis: Multivariate calibration results Sensors and Actuators B: Chemical , 166-167, 338-348

The potential use of a micromachined thermopile based sensor device for analyzing natural gas is explored. The sensor consists of a thermally isolated hotplate which is heated by the application of a sequence of programmed voltages to an integrated heater. Once the hotplate reaches a stationary temperature, the thermopile provides a signal proportional to the hotplate temperature. These signals are processed in order to determine different natural gas properties. Sensor response is mainly dependent on the thermal conductivity of the surrounding gas at different temperatures. Seven predicted properties (normal density, Superior Heating Value, Wobbe index and the concentrations of methane, ethane, carbon dioxide and nitrogen) are calibrated against sensor signals by using multivariate regression, in particular Partial Least Squares. Experimental data have been used for calibration and validation. Results show property prediction capability with reasonable accuracy except for prediction of carbon dioxide concentration. A detailed uncertainty analysis is provided to better understand the metrological limits of the system. These results imply for the first time the possibility of designing unprecedented low-cost natural gas analyzers. The concept may be extended to other constrained gas mixtures (e.g. of a known number of components) to enable low-cost multicomponent gas analyzers.

Keywords: Gas sensor, Natural gas, MEMS, Superior Heating Value, density, PLS


Kuphal, M., Mills, C.A., Korri-Youssoufi, H., Samitier, J., (2012). Polymer-based technology platform for robust electrochemical sensing using gold microelectrodes Sensors and Actuators B: Chemical , 161, (1), 279-284

Rapid and inexpensive development of electrochemical sensors with good exploitation potential may be produced using a polymer as a substrate material. However, fabrication of polymer-based sensors is challenging. Using photolithography and etching of gold-coated poly(ethylene-2,6-naphthalate) (PEN), we have succeeded in fabricating disk-shaped and interdigitated microelectrodes (uEs). The electrodes have an excellent adhesion to the polymer and are encapsulated using a novel room-temperature process, applicable for low-cost, high-throughput fabrication. The PEN surface has been characterized in respect of wettability, surface energy and surface roughness. Finally, the electrodes give stable and reproducible electrochemical impedance spectroscopy and cyclic voltammetry responses, using the redox couple ferrocyanide and ruthenium hexamine. The results demonstrate the robustness and functionality of the polymer-based sensor platform with minimum feature sizes of 6 um.

Keywords: Poly(ethylene naphthalate), Photolithography, Microelectrodes, Interdigitated electrodes, Electrochemical characterization, Electrochemical sensor


Juanola-Feliu, E., Colomer-Farrarons, J., Miribel-Català , P., Samitier, J., Valls-Pasola, J., (2012). Market challenges facing academic research in commercializing nano-enabled implantable devices for in-vivo biomedical analysis Technovation , 32, (3-4), 193-204

This article reports on the research and development of a cutting-edge biomedical device for continuous in-vivo glucose monitoring. This entirely public-funded process of technological innovation has been conducted at the University of Barcelona within a context of converging technologies involving the fields of medicine, physics, chemistry, biology, telecommunications, electronics and energy. The authors examine the value chain and the market challenges faced by in-vivo implantable biomedical devices based on nanotechnologies. In so doing, they trace the process from the point of applied research to the final integration and commercialization of the product, when the social rate of return from academic research can be estimated. Using a case-study approach, the paper also examines the high-tech activities involved in the development of this nano-enabled device and describes the technology and innovation management process within the value chain conducted in a University-Hospital-Industry-Administration-Citizens framework. Here, nanotechnology is seen to represent a new industrial revolution, boosting the biomedical devices market. Nanosensors may well provide the tools required for investigating biological processes at the cellular level in vivo when embedded into medical devices of small dimensions, using biocompatible materials, and requiring reliable and targeted biosensors, high speed data transfer, safely stored data, and even energy autonomy.

Keywords: Biomedical device, Diabetes, Innovation management, Nanobiosensor, Nanotechnology, Research commercialization, Technology transfer, Academic research, Applied research, Barcelona, Biocompatible materials, Biological process, Biomedical analysis, Biomedical devices, Cellular levels, Converging technologies, Glucose monitoring, High-speed data transfer, Implantable biomedical devices, Implantable devices, In-vivo, Industrial revolutions, Innovation management, Medical Devices, Nanobiosensor, Rate of return, Research and development, Technological innovation, Value chains, Biological materials, Biomedical engineering, Biosensors, Commerce, Data transfer, Earnings, Engineering education, Glucose, Implants (surgical), Industrial research, Innovation, Medical problems, Nanosensors, Nanotechnology, Technology transfer, Equipment


Marco, S., Gutierrez-Galvez, A., (2012). Signal and data processing for machine olfaction and chemical sensing: A review IEEE Sensors Journal , 12, (11), 3189-3214

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.

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


Azevedo, S., Diéguez, L., Carvalho, P., Carneiro, J. O., Teixeira, V., Martínez, Elena, Samitier, J., (2012). Deposition of ITO thin films onto PMMA substrates for waveguide based biosensing devices Journal of Nano Research , 17, 75-83

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.

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


Amigo, L. E., Fernandez, Q., Giralt, X., Casals, A., Amat, J., (2012). Study of patient-orthosis interaction forces in rehabilitation therapies IEEE Conference Publications 4th IEEE RAS & EMBS International Conference on Biomedical Robotics and Biomechatronics (BioRob) , IEEE (Roma, Italy) , 1098-1103

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.

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


Mir, Monica, Martinez-Rodriguez, Sergio, Castillo-Fernandez, Oscar, Homs-Corbera, Antoni, Samitier, Josep, (2011). Electrokinetic techniques applied to electrochemical DNA biosensors Electrophoresis , 32, (8), 811-821

Electrokinetic techniques are contact-free methods currently used in many applications, where precise handling of biological entities, such as cells, bacteria or nucleic acids, is needed. These techniques are based on the effect of electric fields on molecules suspended in a fluid, and the corresponding induced motion, which can be tuned according to some known physical laws and observed behaviours. Increasing interest on the application of such strategies in order to improve the detection of DNA strands has appeared during the recent decades. Classical electrode-based DNA electrochemical biosensors with combined electrokinetic techniques present the advantage of being able to improve the working electrode's bioactive part during their fabrication and also the hybridization yield during the sensor detection phase. This can be achieved by selectively manipulating, driving and directing the molecules towards the electrodes increasing the speed and yield of the floating DNA strands attached to them. On the other hand, this technique can be also used in order to make biosensors reusable, or reconfigurable, by simply inverting its working principle and pulling DNA strands away from the electrodes. Finally, the combination of these techniques with nanostructures, such as nanopores or nanochannels, has recently boosted the appearance of new types of electrochemical sensors that exploit the time-varying position of DNA strands in order to continuously scan these molecules and to detect their properties. This review gives an insight into the main forces involved in DNA electrokinetics and discusses the state of the art and uses of these techniques in recent years.

Keywords: Electrochemical DNA biosensors, Lab-on-a-chip (LOC), Micro-total analysis systems (mu TAS), Nanopore


A. Mathur, P. Roca-Cusachs, O. M. Rossier, S. J. Wind, M. P. Sheetz, J. Hone, (2011). New approach for measuring protrusive forces in cells Journal of Vacuum Science & Technology B: Microelectronics and Nanometer Structures , 29, (6), 06FA02

Pomareda, Victor, Marco, Santiago, (2011). Chemical plume source localization with multiple mobile sensors using bayesian inference under background signals Olfaction and Electronic Nose: Proceedings of the 14th International Symposium on Olfaction and Electronic Nose AIP Conference Proceedings (ed. Perena Gouma, SUNY Stony Brook), AIP (New York City, USA) 1362, (1), 149-150

This work presents the estimation of a likelihood map for the location of a source of chemical plume using multiple mobile sensors and Bayesian Inference. Previously described methods use a single sensor and just binary detections (concentrations above or below a certain threshold). The main contribution of this work is to extend previous proposals to use concentration information while at the same time being robust against the presence of background signals. The algorithm has two parts. The first part, concerning Adaptive Background Estimation, uses robust statistics measurements to estimate the background level despite the intermittent presence of high concentrations due to plume statistics. The second part of the algorithm estimates likelihood functions for background and for condition plus plume. Then, the algorithm sequentially builds a likelihood probability map for the location of the source. The algorithm allows the use of multiple mobile sensors. The simulation results demonstrate that our algorithm estimates better the source location and is much more robust in the presence of false alarms.

Keywords: Sensors, Inference mechanisms, Probability, Simulation


Punter-Villagrasa, J., Colomer-Farrarons, J., Miribel-Catala, P., Puig-Vidal, M., Samitier, J., (2011). Discrete to full custom ASIC solutions for bioelectronic applications Proceedings of the SPIE - The International Society for Optical Engineering VLSI Circuits and Systems V , SPIE - The International Society for Optical Engineering (Prague, Czech Republic) 8067, 80670Q

This paper presents a first approach on multi-pathogen detection system for portable point-of-care applications on discrete electronics field. The main interest is focused on the development of custom built electronic solutions for bioelectronics applications, from discrete devices to ASICS solutions.

Keywords: Application specific integrated circuits, Biomedical electronics, Biosensors


Colomer-Farrarons, Jordi , Miribel-Català, Pedro Luís, Samitier, Josep , (2011). Low-voltage µpower CMOS subcutaneous biomedical implantable device for true/false applications Biomedical Engineering IASTED International Conference Biomedical Engineering (Biomed 2011) (ed. Baumgartner, C.), ACTA Press (Innsbruck, Austria) Biomedical Engineering, 424-428

A ±1.2V / 350μW integrated front-end architecture for a true/false in-vivo subcutaneous detection device is presented. The detection is focused on using three electrodes amperometric sensors. The powering and AM transcutaneous communication are based on an inductively coupled link working at 13.56 MHz. A prototype device (5.5 mm x 29.5 mm) has been implemented and fully validated.

Keywords: Implantable Device, Front-End architecture, Bioelectronics, Microelectronics Design, Biosensors


Gutierrez-Galvez, Agustin, Fernandez, Luis, Marco, Santiago, (2011). Study of sensory diversity and redundancy to encode for chemical mixtures Olfaction and Electronic Nose: Proceedings of the 14th International Symposium on Olfaction and Electronic Nose AIP Conference Proceedings (ed. Perena Gouma, SUNY Stony Brook), AIP (New York City, USA) 1362, (1), 147-148

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.

Keywords: Chemioception, Sensors, Data acquisition, Temperature measurement


Mir, M., (2011). Aptamers: The new biorecognition element for proteomic biosensing Biochemistry Research Updates (ed. Baginski, Simon J.), Nova Science Publishers, Inc (Hauppauge, USA) , -----

Aptamers are single stranded artificial nucleic acid ligands that can be generated against almost any kind of target, such as ions, metabolites aminoacids, drugs, toxins, proteins or whole cells. They are isolated from combinatorial libraries of synthetic nucleic acids by an iterative process of adsorption, recovery and amplification, know as SELEX (Systematic Evolution of Ligands by EXponential enrichment) process. Aptamers, the nucleic acid equivalent to antibodies, are easy to synthesise, is not required the use of animals for its synthesis, for this reason it can be developed again toxins and small molecules that do not produce immune response in animals and can be tuned for affinity in closer to assay conditions permitting recognition out of the physiological state. So, aptamers posses numerous advantages that make them preferred candidates as biorecognition elements. In view of the advantages and simple structure of aptamers, they have been used in a wide range of applications such as therapeutics, diagnosis, chromatography, environmental detection, among other.

Keywords: Aptamers, Biosensors, Protein recognition


Colomer-Farrarons, Jordi, Miribel-Català, Pere LI., Rodríguez-Villarreal, A. Ivón, Samitier, Josep, (2011). Portable bio-devices: Design of electrochemical instruments from miniaturized to implantable devices New perspectives in biosensors technology and applications (ed. Andrea Serra, Pier), InTech (Rijeka, Croatia) Biomedical Engineering, 373-400

A biosensor is a detecting device that combines a transducer with a biologically sensitive and selective component. Biosensors can measure compounds present in the environment, chemical processes, food and human body at low cost if compared with traditional analytical techniques. This book covers a wide range of aspects and issues related to biosensor technology, bringing together researchers from 12 different countries. The book consists of 20 chapters written by 69 authors and divided in three sections: Biosensors Technology and Materials, Biosensors for Health and Biosensors for Environment and Biosecurity.

Keywords: Bio-Devices, Electrochemical Instruments, Miniaturized Devices, Nanobiosensor


Prieto-Simón, B., Campà s, M., Marty, J. L., (2010). Electrochemical aptamer-based sensors Bioanalytical Reviews , 1, (2), 141-157

The valuable properties of aptamers, such as specificity, sensitivity, stability, cost-effectiveness and design flexibility, have favoured their use as biorecognition elements in biosensor development. These synthetic affinity probes can be developed for almost any target molecule, covering a wide range of applications in fields such as clinical diagnosis and therapy, environmental monitoring and food control. The combination of aptamers with high-performance electrochemical transducers, with their inherent high sensitivities, fast response times and simple equipment, has already provided several electrochemical aptamer-based sensors. Moreover, the small size and versatility of aptamers allow efficient immobilisations in high-density monolayers, an important feature towards miniaturisation and integration of compact electrochemical devices. This review describes the state-of-the-art of electrochemical aptamer-based sensors, entering into the details of the different strategies and types of electrochemical transduction and also considering their advantages when applied to the analysis of complex matrices.

Keywords: Aptabeacon, Aptamer, Biosensor, Electrochemical detection, Redox label


Ziyatdinov, A., Marco, S., Chaudry, A., Persaud, K., Caminal, P., Perera, A., (2010). Drift compensation of gas sensor array data by common principal component analysis Sensors and Actuators B: Chemical , 146, (2), 460-465

A new drift compensation method based on Common Principal Component Analysis (CPCA) is proposed. The drift variance in data is found as the principal components computed by CPCA. This method finds components that are common for all gasses in feature space. The method is compared in classification task with respect to the other approaches published where the drift direction is estimated through a Principal Component Analysis (PCA) of a reference gas. The proposed new method - employing no specific reference gas, but information from all gases -has shown the same performance as the traditional approach with the best-fitted reference gas. Results are shown with data lasting 7-months including three gases at different concentrations for an array of 17 polymeric sensors.

Keywords: Gas sensor array, Drift, Common principal component, Analysis, Component correction, Electronic nose


Perera, A., Pardo, A., Barrettino, D., Hierlermann, A., Marco, S., (2010). Evaluation of fish spoilage by means of a single metal oxide sensor under temperature modulation Sensors and Actuators B: Chemical , 146, (2), 477-482

In this paper the feasibility of using metal oxide gas sensor technology for evaluating spoilage process for sea bream (Sparus aurata) is explored. It is shown that a single sensor under temperature modulation is able to find a correlation with the fish spoilage process. Results are obtained in real frigorific storage conditions: that is, at low measurement temperatures with variations of relative humidity.

Keywords: Gas sensors, Electronic nose, Spoilage process, Temperature modulation, Bream sparus-aurata, Electronic nose, Freshness, Quality, Sardines, Storage


Montoliu, I., Tauler, R., Padilla, M., Pardo, A., Marco, S., (2010). Multivariate curve resolution applied to temperature modulated metal oxide gas sensors Sensors and Actuators B: Chemical , 145, (1), 464-473

Metal oxide (MOX) gas sensors have been widely used for years. Temperature modulation of gas sensors is as an alternative to increase their sensitivity and selectivity to different gas species. In order to enhance the extraction of useful information from this kind of signals, data processing techniques are needed. In this work, the use of self-modelling curve resolution techniques, in particular multivariate curve resolution-alternating least squares (MCR-ALS), is presented for the analysis of these signals. First, the performance of MCR in a synthetic dataset generated from temperature-modulated gas sensor response models has been evaluated, showing good results both in the resolution of gas mixtures and in the determination of concentration/sensitivity profiles. Secondly, experimental confirmation of previously obtained conclusions is attempted using temperature-modulated MOX sensors together with MCR-ALS for the analysis of carbon monoxide (CO) and methane (CH4) gas mixtures in dry air. Results allow confirming the possibility of using the proposed approach as a quantitative technique for gas mixtures analysis, and also reveal some limitations.

Keywords: Temperature modulation, Multivariate curve resolution, MCR-ALS, Metal oxide sensors


Padilla, M., Perera, A., Montoliu, I., Chaudry, A., Persaud, K., Marco, S., (2010). Drift compensation of gas sensor array data by orthogonal signal correction Chemometrics and Intelligent Laboratory Systems , 100, (1), 28-35

Drift is an important issue that impairs the reliability of gas sensing systems. Sensor aging, memory effects and environmental disturbances produce shifts in sensor responses that make initial statistical models for gas or odor recognition useless after a relatively short period (typically few weeks). Frequent recalibrations are needed to preserve system accuracy. However, when recalibrations involve numerous samples they become expensive and laborious. An interesting and lower cost alternative is drift counteraction by signal processing techniques. Orthogonal Signal Correction (OSC) is proposed for drift compensation in chemical sensor arrays. The performance of OSC is also compared with Component Correction (CC). A simple classification algorithm has been employed for assessing the performance of the algorithms on a dataset composed by measurements of three analytes using an array of seventeen conductive polymer gas sensors over a ten month period.

Keywords: Gas sensor array, Drift, Orthogonal signal correction, Component correction, Cross-validation, Electronic nose, Data shift


Padilla, M., Perera, A., Montoliu, I., Chaudry, A., Persaud, K., Marco, S., (2010). Fault detection, identification, and reconstruction of faulty chemical gas sensors under drift conditions, using Principal Component Analysis and Multiscale-PCA Theoretical or Mathematical; Experimental The 2010 International Joint Conference on Neural Networks (IJCNN 2010) , IEEE, Piscataway, NJ, USA (Barcelona, Spain) , 7 pp.

Statistical methods like Principal Components Analysis (PCA) or Partial Least Squares (PLS) and multiscale approaches, have been reported to be very useful in the task of fault diagnosis of malfunctioning sensors for several types of faults. In this work, we compare the performance of PCA and Multiscale-PCA on a fault based on a change of sensor sensitivity. This type of fault affects chemical gas sensors and it is one of the effects of the sensor poisoning. These two methods will be applied on a dataset composed by the signals of 17 conductive polymer gas sensors, measuring three analytes at several concentration levels during 10 months. Therefore, additionally to performance's comparison, both method's stability along the time will be tested. The comparison between both techniques will be made regarding three aspects; detection, identification of the faulty sensors and correction of faulty sensors response.

Keywords: Fault diagnosis, Gas sensors, Principal component analysis


Fernandez, L., Gutierrez-Galvez, A., Marco, S., (2010). Gas sensor array system inspired on the sensory diversity and redundancy of the olfactory epithelium Procedia Engineering Eurosensor XXIV Conference (ed. Jakoby, B., Vellekoop, M.J.), Elsevier Science BV (Linz, Austria) 5, (0), 25-28

This paper presents a chemical sensing system that takes inspiration from the combination of sensory diversity and redundancy at the olfactory epithelium to enhance the chemical information obtained from the odorants. The system is based on commercial MOS sensors and achieves, first, diversity trough different types of MOS along with modulation of their temperatures, and second redundancy including 12 MOS sensors for each type (12×8) combined with a high-speed multiplexing system that allows connecting 16 load resistors with each and every one of the 96 sensors in about two seconds. Exposition of the system to ethanol, ammonia, and acetone at different concentrations shows how the system is able to capture a large amount of information of the identity and the concentration of the odorant.

Keywords: Gas sensor array, Biologically inspired system, Redundancy, Diversity, MOX sensors, Temperature modulation


Sanmarti, M., Iavicoli, P., Pajot-Augy, E., Gomila, G., Samitier, J., (2010). Human olfactory receptors immobilization on a mixed self assembled monolayer for the development of a bioelectronic nose Procedia Engineering (EUROSENSOR XXIV CONFERENCE) 24th Eurosensor Conference (ed. Jakoby, B., Vellekoop, M.J.), Elsevier Science (Linz, Austria) 5, 786-789

The present work focuses on the development of an immunosensing surface to build a portable olfactory system for the detection of complex mixture of odorants. Homogeneous cell derived vesicles expressing the olfactory receptors were produced and immobilized with efficiency onto a gold substrate through an optimized surface functionalization method.

Keywords: Bioelectronic noses, Biosensors, Nanoproteoliposomes, Nanosomes, Olfactory receptors, SAMs


Caballero, D., Samitier, J., Bausells, J., Errachid, A., (2009). Direct patterning of anti-human serum albumin antibodies on aldehyde-terminated silicon nitride surfaces for HSA protein detection Small , 5, (13), 1531-1534

Silicon nitride surfaces are modified with a triethoxysilane aldehyde self-assembled monolayer for the direct immobilization of monoclonal antibodies and the detection of human serum albumin proteins, without any activation requirements. Surface modification and the specific recognition interaction between the HSA protein and its associated antibody are studied by fluorescence microscopy and atomic force microscopy.

Keywords: Aldehyde, Human serum albumin, Immunosensors, Microcontact printing, Silicon nitride


Mir, M., Homs, A., Samitier, J., (2009). Integrated electrochemical DNA biosensors for lab-on-a-chip devices Electrophoresis , 30, (19), 3386-3397

Analytical devices able to perform accurate and fast automatic DNA detection or sequencing procedures have many potential benefits in the biomedical and environmental fields. The conversion of biological or biochemical responses into quantifiable optical, mechanical or electronic signals is achieved by means of biosensors. Most of these transducing elements can be miniaturized and incorporated into lab-on-a-chip devices, also known as Micro Total Analysis Systems. The use of multiple DNA biosensors integrated in these miniaturized laboratories, which perform several analytical operations at the microscale, has many cost and efficiency advantages. Tiny amounts of reagents and samples are needed and highly sensitive, fast and parallel assays can be done at low cost. A particular type of DNA biosensors are the ones used based on electrochemical principles. These sensors offer several advantages over the popular fluorescence-based detection schemes. The resulting signal is electrical and can be processed by conventional electronics in a very cheap and fast manner. Furthermore, the integration and miniaturization of electrochemical transducers in a microsystem makes easier its fabrication in front of the most common currently used detection method. In this review, different electrochemical DNA biosensors integrated in analytical microfluidic devices are discussed and some early stage commercial products based on this strategy are presented.

Keywords: DNA, Electrochemical DNA biosensors, Electrochemistry, Lab-on-a-chip, Micro Total Analysis systems, Field-effect transistors, Sequence-specific detection, Chemical-analysis systems, Solid-state nanopores, Carbon nanotubes, Microfluidic device, Electrical detection, Hybridization, Molecules, Sensor


Fonollosa, J., Carmona, M., Santander, J., Fonseca, L., Moreno, M., Marco, S., (2009). Limits to the integration of filters and lenses on thermoelectric IR detectors by flip-chip techniques Sensors and Actuators A: Physical , 149, (1), 65-73

In the trend towards miniaturization, a detector module containing multiple IR sensor channels is being built and characterized. In its final form it contains thermopiles, narrow band filters and Fresnel lenses. An important feature of such module is the assembly by flip-chip of the IR filters on top of the thermopiles. The performance of the filter-thermopile ensemble has been assessed by physical simulation and experiments and it has been optimized by the use of an empirically validated model. It has been found that integration of filters (or lenses) too close to the IR detector may lead to degraded performance due to thermal coupling. The impact and extent of this degradation has been thoroughly explored, being the main parameter the distance between the IR sensor and the filter. To avoid such detrimental effects a possibility is to set the device in vacuum conditions, obtaining an improved output response and avoiding the influence of the filters. Another way is to increase the solder joint height. Beyond a certain height, the filter is considered to be isolated from the thermopile.

Keywords: Assembly, Infrared sensor, Infrared filter, Fresnel lenses, FEM simulation, Optimization


Colomer-Farrarons, J., Miribel-Catala, P. L., Samitier, J., Arundell, M., Rodriguez, I., (2009). Design of a miniaturized electrochemical instrument for in-situ O/sub 2/ monitoring Sensors and Signal Conditioning VLSI Circuits and Systems IV , SPIE (Desdren, Germany) 7363, 73630A

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.

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


Barreiros dos Santos, M., Sporer, C., Sanvicens, N., Pascual, N., Errachid, A., Martinez, E., Marco, M. P., Teixeira, V., Samiter, J., (2009). Detection of pathogenic Bacteria by Electrochemical Impedance Spectroscopy: Influence of the immobilization strategies on the sensor performance Procedia Chemistry 23rd Eurosensors Conference (ed. Brugger, J., Briand, D.), Elsevier Science, BV (Lausanne, Switzerland) 1, 1291-1294

Electrochemical impedance spectroscopy (EIS) is applied to detect pathogenic E. coli O157:H7 bacteria via a label free immunoassay-based detection method. Polyclonal anti-E.coli antibodies (PAb) are immobilized onto gold electrodes following two different strategies, via chemical bond formation between antibody amino groups and a carboxylic acid containing self-assembled molecular monolayer (SAM) and alternatively by linking a biotinylated anti-E. coli to Neutravidin on a mixed-SAM. Impedance spectra for sensors of both designs for increasing concentrations of E. coli are recorded in phosphate buffered saline (PBS). The Nyquist plots can be modeled with a Randle equivalent circuit, identifying the charge transfer resistance RCT as the relevant concentration dependent parameter. Sensors fabricated from both designs are able to detect very low concentration of E. coli with limits of detection as low as 10-100 cfu/ml. The influence of the different immobilization protocols on the sensor performance is evaluated in terms of sensitivity, dynamic range and resistance against nonspecific absorption.

Keywords: Bacteria detection, Biosensors, E-coli, Impedance spectroscopy


Perera, A., Pardo, A., Barrettino, D., Hierlermann, A., Marco, S., (2009). Evaluation of fish spoilage by means of a single metal oxide sensor under temperature modulation Olfaction and Electronic Nose: Proceedings of the 13th International Symposium on Olfaction and Electronic Nose 13th International Symposium on Olfaction and Electronic Nose (ed. Pardo, M., Sberveglieri, G.), Amer Inst Physics (Brescia, Italy) 1137, 483-486

In this paper the feasibility of using metal oxide gas sensor technology for evaluating spoilage process for sea bream (Sparus Aurata) is explored. It is shown that a single sensor under temperature modulation is able to find a correlation with the fish spoilage process

Keywords: Gas sensors, Electrochemical sensors, Chromatography


Marco, S., Gutierrez-Galvez, A., (2009). Recent developments in the application of biologically inspired computation to chemical sensing Olfaction Electronic Nose: Proceedings of the 13th International Symposium on Olfaction and Electronic Nose 13th International Symposium on Olfaction and the Electronic Nose (ed. Pardo, M., Sberveglieri, G.), Amer Inst Physics (Brescia, Italy) 1137, 151-154

Biological olfaction outperforms chemical instrumentation in specificity, response time, detection limit, coding capacity, time stability, robustness, size, power consumption, and portability. This biological function provides outstanding performance due, to a large extent, to the unique architecture of the olfactory pathway, which combines a high degree of redundancy, an efficient combinatorial coding along with unmatched chemical information processing mechanisms. The last decade has witnessed important advances in the understanding of the computational primitives underlying the functioning of the olfactory system. In this work, the state of the art concerning biologically inspired computation for chemical sensing will be reviewed. Instead of reviewing the whole body of computational neuroscience of olfaction, we restrict this review to the application of models to the processing of real chemical sensor data.

Keywords: Computational Intelligence, Chemical Sensors


Perera, A., Rock, F., Montoliu, I., Weimar, U., Marco, S., (2009). Total solvent amount and human panel test predictions using gas sensor fast chromatography and multivariate linear and non-linear processing Olfaction and Electronic Nose: Proceedings of the 13th International Symposium on Olfaction and Electronic Nose 13th International Symposium on Olfaction and the Electronic Nose (ed. Pardo, M., Sberveglieri, G.), Amer Inst Physics (Brescia, Italy) 1137, 572-573

Data from a Gas Sensor based Chromatography instrument is used in order to replicate output from a human panel and the estimation of the total solvent amount measured by and FID device in a packaging application. The system is trained on different packaging sample properties and validated with unseen combinations of materials, varnishes and production processes. This contribution will show the difficulties on the prediction of the output of the human panel, and the success on the prediction of the total amount of solvent in the sample

Keywords: Gas sensors, Solvent prediction


Baccar, Z. M., Caballero, D., Zine, N., Jaffrezic-Renault, N., Errachid, A., (2009). Development of urease/layered double hydroxides nanohybrid materials for the urea detection: Synthesis, analytical and catalytic characterizations Sensor Letters 6th Maghreb-Europe Meeting on Materials and Their Applications for Devices and Physical, Chemical and Biological Sensors , AMER SCIENTIFIC PUBLISHERS (Rabat, Morocco) 7, (5), 676-682

We developed new hybrid nanomaterials, urease/LDH (layered double hydroxides), for the urea detection. The LDH that were prepared by co-precipitation in constant pH and in ambient temperature are hydrotalcites (Mg2Al, Mg3Al) and zaccagnaite (Zn2Al and Zn3Al). The immobilization of urease in these various layered hybrid materials is realized by auto-assembly. The structures of hosted matrices were studied by X-ray diffraction, Absorbance Infrared spectroscopy in ATR mode and Atomic Force Microscopy (AFM). These techniques allowed the characterisation of the urease immobilization and its interactions with LDH chemical groups. The urease was adsorbed and its morphology was conserved in its new environment. Furthermore, the study of catalytic parameters of Urease/LDH biomembranes and of the kinetics reaction of urea hydrolysis shows a good conformation of the enzyme in hydrotalcite matrices and that the affinity is similar to free urease.

Keywords: Ldh hybrid nanomaterials, Surface properties, Urea biosensors, Urease thin films


Guaus, E., Torrent-Burgues, J., Zine, N., Errachid, A., (2009). Glassy carbon electrode modified with a langmuir-blodgett film of a thiomacrocyclic ionophore for Cu(II) recognition Sensor Letters 6th Maghreb-Europe Meeting on Materials and Their Applications for Devices and Physical, Chemical and Biological Sensors , AMER SCIENTIFIC PUBLISHERS (Rabat, Morocco) 7, (5), 1006-1011

Nanometric films of a thiomacrocyclic ionophore, 4-phenyl-4-sulfide-11(1- oxodecyl)-1,7-dithia-11-aza-4-phosphacyclotetradecane (ThM), have been deposited on the surface of a Glassy Carbon Electrode (GCE) by the Langmuir-Blodgett (LB) technique. The films have been characterised by using AFM. The influence of these modified electrodes (GCE-ThM) on the reduction of Cu(II) ions has been investigated by using Cyclic Voltammetry (CV) and Electrochemical Impedance Spectroscopy (EIS), and its sensor response has been checked. The CV and EIS responses of LB films on GCE indicate that these ThM films are sensitive to Cu(II) ions. The analysis by EIS of the interference of some other cations, as Mg(II) and Co(II), shows that LB films of ThM can be used for specific Cu(II) sensing applications.

Keywords: Cu(II) sensor, Cyclic voltammetry, Electrochemical impedance spectroscopy, Langmuir-blodgett films


Baccar, Z. M., Hidouri, S., El Bari, N., Jaffrezic-Renault, N., Errachid, A., Zine, N., (2009). Stable immobilization of anti-beta casein antibody onto layered double hydroxides materials for biosensor applications Sensor Letters 6th Maghreb-Europe Meeting on Materials and Their Applications for Devices and Physical, Chemical and Biological Sensors , AMER SCIENTIFIC PUBLISHERS (Rabat, Morocco) 7, (5), 647-655

This review presents the development of new kind of antibody/LDH (layered double hydroxides) hybrid nanomaterials for beta casein detection. The preparation method of the LDH is described. It is based on the co-precipitation of metallic salts in constant pH and temperature. The chosen LDH are hydrotalcites (Mg2AICO3, Mg3AICO3), Zaccagnaite: Zn2AICO3 and hydrocalumite: Ca 2AICI. Finally, the antibody is immobilized into the LDH materials using Layer-by-Layer method by autoassembly. In this work, we studied the surface properties of the prepared hybrid biomembranes using X-ray diffraction, Infrared spectroscopy in ATR mode and Atomic Force Microscopy (AFM). These techniques allow describing the antibody immobilization and its interactions with LDH. The antibody was adsorbed and its morphology was conserved in its new environment after more than 15 days continuously in PBS solution, promising a constant biosensor performance.

Keywords: Anti β-casein antibody, Antibody immobilization, Ldh hybrid biomaterials, Urea biosensors


Gutierrez, A., Marco, S., (2009). Biologically inspired signal processing for chemical sensing Studies in Computational Intelligence GOSPEL Workshop on Bio-inspired Signal Processing (ed. Gutierrez, A., Marco, S.), Springer (Barcelona, Spain) -----, (188), -----

This 167-page book is volume 188 in the series 'Studies in computational intelligence.' This volume contain 9 extensive chapters written in English. This volume presents a collection of research advances in biologically inspired signal processing for chemical sensing. The olfactory system, and the gustatory system to a minor extent, has been taken in the last decades as a source of inspiration to develop artificial sensing systems. The recognition of odors by the olfactory system entails a number of signal processing functions such as preprocessing, dimensionality reduction, contrast enhancement, and classification. Using mathematical models to mimic the architecture of the olfactory system, these processing functions can be applied to chemical sensor signals. This book provides background on the olfactory system including a review on information processing in the insect olfactory system along with a proposed signal processing architecture based on the mammalian cortex. It also provides some bio-inspired approaches to process chemical sensor signals such as an olfactory mucosa to improve odor separation and a model of olfactory receptor neuron convergence to correlated sensor responses to an odor and his organoleptic properties. This book will useful to those working or studying in the areas of sensory reception and computational biology.

Keywords: Nervous System (Neural Coordination), Computer Applications (Computational Biology), Sense Organs (Sensory Reception)


Cho, S., Castellarnau, M., Samitier, J., Thielecke, H., (2008). Dependence of impedance of embedded single cells on cellular behaviour Sensors 8, (2), 1198-1211

Non-invasive single cell analyses are increasingly required for the medical diagnostics of test substances or the development of drugs and therapies on the single cell level. For the non-invasive characterisation of cells, impedance spectroscopy which provides the frequency dependent electrical properties has been used. Recently, microfludic systems have been investigated to manipulate the single cells and to characterise the electrical properties of embedded cells. In this article, the impedance of partially embedded single cells dependent on the cellular behaviour was investigated by using the microcapillary. An analytical equation was derived to relate the impedance of embedded cells with respect to the morphological and physiological change of extracellular interface. The capillary system with impedance measurement showed a feasibility to monitor the impedance change of embedded single cells caused by morphological and physiological change of cell during the addition of DMSO. By fitting the derived equation to the measured impedance of cell embedded at different negative pressure levels, it was able to extrapolate the equivalent gap and gap conductivity between the cell and capillary wall representing the cellular behaviour.

Keywords: Frequency-domain, Spectroscopy, Erythrocytes, Biosensor, Membrane, System


Udina, S., Pardo, A., Marco, S., Santander, J., Fonseca, L., (2008). Thermoelectric MEMS sensors for natural gas analysis Electronic Proceedings of the Seventh IEEE Sensors Conference 2008 Sensors, 2008 IEEE (ed. Frech, P., Siciliano, P.), IEEE (Lecce, Italy) , 1364-1367

T Multivariate data analysis techniques have been used for the first time in thermoelectric MEMS sensors in order to determine the composition of natural gas mixtures. Experimental measurements with different thermoelectric devices have been performed, the gathered data have been used to calibrate the sensor responses to four main components of natural gas: CH4, C2H6, N2 and CO2. Presence of the three first components was predicted with good accuracy while CO2 prediction was poor. Presented results indicate that thremoelectric sensors operated at different heater temperatures open the possibility of low-cost natural gas analysis.

Keywords: Natural gas, Multivariate calibration, Thermal conductivity, Thermal sensor


Zazoua, A., Kherrat, R., Samar, M. H., Errachid, A., Jaffrezic-Renault, N., Bessueille, F., Leonard, D., (2008). Characterization of TBP containing polysiloxane membrane/insulator/semiconductor structures for hexavalent chromium detection Materials Science and Engineering: C-Biomimetic and Supramolecular Systems 5th Maghreb/Europe Meeting on Materials and Their Applications for Devices and Physical, Chemical and Biological Sensors (MADICA 2006) (ed. -----), Elsevier Science BV (Mahdia, Tunisia) 28, (5-6), 1014-1019

A hexavalent chromium-sensitive EMIS sensor (electrolyte membrane insulator semiconductor sensor) is prepared by deposition of a tributylphosphate (TBP) ionophore-containing siloprene membrane on a Si/SiO2/Si3N4 structure. The developed EMIS sensor was studied by means of impedance spectroscopy, capacitance-voltage, X-ray photoelectron spectrometry and FT-IR spectroscopy. From the flat-band shift of the EMIS structure, the nersntian response to the anionic species Cr2O7- was demonstrated. The linear range of detection is 10(-4) M to 10(-1) M and the detection limit is 10(-5) M. Sulfate and chloride anions are shown not to be interfering whereas carbonate ions present a pK(pot) equal to 0.19.

Keywords: Hexavalent chromium, EMIS sensor, Tributylphosphate, Siloprene membrane


Castellarnau, M., Zine, N., Bausells, J., Madrid, C., Juarez, A., Samitier, J., Errachid, A., (2008). ISFET-based biosensor to monitor sugar metabolism in bacteria Materials Science & Engineering C 5th Maghreb-Europe Meeting on Materials and their Applicatons for Devices and Physical, Chemical and Biological Sensors (ed. -----), Elsevier Science (Mahdia, Tunisia) 28, (5-6), 680-685

We report the use of ion-selective field effect transistor devices (ISFETs) with an integrated pseudo-reference electrode for on-line monitoring of bacterial metabolism by monitoring of the pH variation. As a model we tested the ability of Lactobacillus strains to ferment sugars, producing lactic acid, which results in a decrease in pH in the suspension medium. We have tested and compared sugar uptake by L. sakei and a L. curvatus strains. The results obtained show that it is possible to distinguish between both types of Lactobacillus strains through their pattern of ribose uptake. The use of ISFETs represents a non-invasive methodology that can be used to monitor biological activity in a wide variety of systems.

Keywords: Lactobacillus-sakei, Technology, Sensors, System, Growth, Cells, State, Meat


Barhoumi, H., Haddad, R., Maaref, A., Bausells, J., Bessueille, F., Leonard, D., Jaffrezic-Renault, N., Martelet, C., Zine, N., Errachid, A., (2008). Na+-implanted membrane for a capacitive sodium electrolyte-Insulator-Semiconductor microsensors Sensor Letters International Conference of Thermal, Mechanical and Multiphysics Simulation and Experiments in Microelectronics and Microsystems (ed. -----), Amer Scientific Publishers (Lombardy, Italy) 6, (1), 204-208

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.

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


Mills, C. A., Pla, M., Martin, C., Lee, M., Kuphal, M., Sisquella, X., Martinez, E., Errachid, A., Samitier, J., (2007). Structured thin organic active layers and their use in electrochemical biosensors Measurement & Control , 40, (3), 88-91

Rodriguez, Segui, Bucior, I., Burger, M. M., Samitier, J., Errachid, A., Fernàndez-Busquets, X., (2007). Application of a bio-QCM to study carbohydrates self-interaction in presence of calcium Transducers '07 & Eurosensors Xxi, Digest of Technical Papers 14th International Conference on Solid-State Sensors, Actuators and Microsystems , IEEE (Lyon, France) 1-2, 1995-1998

In the past years, the quartz crystal microbalance (QCM) has been successfully applied to follow interfacial physical chemistry phenomena in a label free and real time manner. However, carbohydrate self adhesion has only been addressed partially using this technique. Carbohydrates play an important role in cell adhesion, providing a highly versatile form of attachment, suitable for biologically relevant recognition events in the initial steps of adhesion. Here, we provide a QCM study of carbohydrates' self-recognition in the presence of calcium, based on a species-specific cell recognition model provided by marine sponges. Our results show a difference in adhesion kinetics when varying either the calcium concentration (with a constant carbohydrate concentration) or the carbohydrate concentration (with constant calcium concentration).

Keywords: Biomedical materials, Calcium, Cellular biophysics, Microbalances, Porous materials, Quartz, Surface chemistry/ bio-QCM, Carbohydrates self-interaction, Quartz crystal microbalance, Interfacial physical chemistry phenomena, Carbohydrate self adhesion, Biologically relevant recognition events, Marine sponges, Adhesion kinetics, Calcium concentration, Carbohydrate concentration, Biosensors, Biomedical materials, Surface chemistry, Cellular biophysics