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by Keyword: Biosensors


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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


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


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

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


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


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


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


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


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


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


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


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


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


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


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