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Parra-Cabrera, C., Samitier, J., Homs-Corbera, A., (2016). Multiple biomarkers biosensor with just-in-time functionalization: Application to prostate cancer detection Biosensors and Bioelectronics 77, 1192-1200

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

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

Morales, R., Badesa, F. J., Garcia-Aracil, N., Aranda, J., Casals, A., (2015). Autoadaptive neurorehabilitation robotic system assessment with a post-stroke patient Revista Iberoamericana de Automatica e Informatica Industrial , 12, (1), 92-98

This paper presents a new rehabilitation system that is able to adapt its performance to patient's psychophysiological state during the execution of robotic rehabilitation tasks. Using this approach, the motivation and participation of the patient during rehabilitation activity can be maximized. In this paper, the results of the study with healthy subjects presented in (Badesa et al., 2014b) have been extended for using them with patients who have suffered a stroke. In the first part of the article, the different components of the adaptive system are exposed, as well as a comparison of different machine learning techniques to classify the patient's psychophysiological state between three possible states: stressed, average excitation level and relaxed are presented. Finally, the results of the auto-adaptive system which modifies the behavior of the rehabilitation robot and virtual task in function of measured physiological signals are shown for a patient in the chronic phase of stroke.

Keywords: Physiological state multimodal interfaces rehabilitation robotics control

McLenachan, S., Menchon, C., Raya, A., Consiglio, A., Edel, M. J., (2012). Cyclin A(1) is essential for setting the pluripotent state and reducing tumorigenicity of induced pluripotent stem cells Stem Cells and Development , 21, (15), 2891-2899

The proper differentiation and threat of cancer rising from the application of induced pluripotent stem (iPS) cells are major bottlenecks in the field and are thought to be inherently linked to the pluripotent nature of iPS cells. To address this question, we have compared iPS cells to embryonic stem cells (ESCs), the gold standard of ground state pluripotency, in search for proteins that may improve pluripotency of iPS cells. We have found that when reprogramming somatic cells toward pluripotency, 1%-5% of proteins of 5 important cell functions are not set to the correct expression levels compared to ESCs, including mainly cell cycle proteins. We have shown that resetting cyclin A1 protein expression of early- passage iPS cells closer to the ground state pluripotent state of mouse ESCs improves the pluripotency and reduces the threat of cancer of iPS cells. This work is a proof of principle that reveals that setting expression of certain proteins correctly during reprogramming is essential for achieving ESC- state pluripotency. This finding would be of immediate help to those researchers in different fields of iPS cell work that specializes in cell cycle, apoptosis, cell adhesion, cell signaling, and cytoskeleton.

Keywords: Self-renewal, IPS cells, Ground-state, C-MYC, Generation, Pathway, Disease, Mice, Link, P53

Arimon, M., Sanz, F., Giralt, E., Carulla, N., (2012). Template-assisted lateral growth of amyloid-β42 fibrils studied by differential labeling with gold nanoparticles Bioconjugate Chemistry , 23, (1), 27-32

Amyloid-β protein (Aβ) aggregation into amyloid fibrils is central to the origin and development of Alzheimer’s disease (AD), yet this highly complex process is poorly understood at the molecular level. Extensive studies have shown that Aβ fibril growth occurs through fibril elongation, whereby soluble molecules add to the fibril ends. Nevertheless, fibril morphology strongly depends on aggregation conditions. For example, at high ionic strength, Aβ fibrils laterally associate into bundles. To further study the mechanisms leading to fibril growth, we developed a single-fibril growth assay based on differential labeling of two Aβ42 variants with gold nanoparticles. We used this assay to study Aβ42 fibril growth under different conditions and observed that bundle formation is preceded by lateral interaction of soluble Aβ42 molecules with pre-existing fibrils. Based on this data, we propose template-assisted lateral fibril growth as an additional mechanism to elongation for Aβ42 fibril growth.

Keywords: AFM, Beta-Amyloid Fibrils, Polymorphism, Association, Elongation, Dynamics, State

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

de Oliveira, I. A. M., Risco, D., Vocanson, F., Crespo, E., Teixidor, F., Zine, N., Bausells, J., Samitier, J., Errachid, A., (2008). Sodium ion sensitive microelectrode based on a p-tert-butylcalix[4]arene ethyl ester Sensors and Actuators B: Chemical 130, (1), 295-299

Planar sodium-selective potentiometric microelectrodes with a conducting polymer (polypyrrole doped with cobaltabis(dicarbollide) ions ([3,3'-Co(1,2-C2B9-H-11)(2)](-))) as solid contact layer between the polymeric sensitive membrane and the platinum substrate have been constructed. The p-tert-butylcalix[4]arene ethyl ester was used as ionophore for sodium recognition. The microelectrode shows a linear response for Na+ concentrations between 3.0 x 10(-6) and 1.0 x 10(-1) M with a Nernstian slope of 58.65 +/- 2 mV per decade and a detection limit of 1.45 x 10(-6) M. The response time was 14 s, and the electrode is suitable for use within the pH range of 3-10.

Keywords: Sodium, Polypyrrole, Calix[4]arene, Solid-state ion selective microelectrode, Potentiometric

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

Díez-Pérez, Ismael, Vericat, Carolina, Gorostiza, Pau, Sanz, Fausto, (2006). The iron passive film breakdown in chloride media may be mediated by transient chloride-induced surface states located within the band gap Electrochemistry Communications , 8, (4), 627-632

Despite its tremendous scientific and economic impact, the mechanism that triggers metal passive film breakdown in the presence of aggressive ions remains under discussion. We have studied the iron passive film in chloride media using X-ray photoelectron spectroscopy (XPS), electrochemical impedance spectroscopy and electrochemical tunneling spectroscopy (ECTS). Ex situ XPS reveal that the film consists exclusively of an Fe(III) oxide without chloride content. In situ ECTS has been used to build up conductance maps of the Fe electrode during its electrochemical oxidation in a borate buffer solution and its breakdown when the film is grown in the presence of chloride. This conductograms provide direct and in situ experimental evidence of chloride-induced surface states within the band gap of the oxide film (~3.3eV). These states enable new charge exchange pathways that allow hole capture at the surface of the n-type Fe(III) oxide. The blocking of VB processes that occurs in the iron passive film is no longer present in chloride media, and electrode corrosion can proceed through these new states. We propose a simple 3-step mechanism for the process, in which chloride anions form an oxidizing Fe(II) surface intermediate but do not participate directly in the reaction.

Keywords: Electrochemical tunneling spectroscopy, Electronic band structure, Fe passive film, Aqueous chloride corrosion, Semiconductor decomposition, Interface states