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Torras, N., García-Díaz, M., Fernández-Majada, V., Martínez, E., (2018). Mimicking epithelial tissues in three-dimensional cell culture models Frontiers in Bioengineering and Biotechnology 6, Article 197

Epithelial tissues are composed of layers of tightly connected cells shaped into complex three-dimensional (3D) structures such as cysts, tubules, or invaginations. These complex 3D structures are important for organ-specific functions and often create biochemical gradients that guide cell positioning and compartmentalization within the organ. One of the main functions of epithelia is to act as physical barriers that protect the underlying tissues from external insults. In vitro, epithelial barriers are usually mimicked by oversimplified models based on cell lines grown as monolayers on flat surfaces. While useful to answer certain questions, these models cannot fully capture the in vivo organ physiology and often yield poor predictions. In order to progress further in basic and translational research, disease modeling, drug discovery, and regenerative medicine, it is essential to advance the development of new in vitro predictive models of epithelial tissues that are capable of representing the in vivo-like structures and organ functionality more accurately. Here, we review current strategies for obtaining biomimetic systems in the form of advanced in vitro models that allow for more reliable and safer preclinical tests. The current state of the art and potential applications of self-organized cell-based systems, organ-on-a-chip devices that incorporate sensors and monitoring capabilities, as well as microfabrication techniques including bioprinting and photolithography, are discussed. These techniques could be combined to help provide highly predictive drug tests for patient-specific conditions in the near future.

Keywords: 3D cell culture models, Biofabrication, Disease modeling, Drug screening, Epithelial barriers, Microengineered tissues, Organ-on-a-chip, Organoids


Agusil, Juan Pablo, Torras, Núria, Duch, Marta, Esteve, Jaume, Pérez-García, Lluïsa, Samitier, Josep, Plaza, José A., (2017). Highly anisotropic suspended planar-array chips with multidimensional sub-micrometric biomolecular patterns Advanced Functional Materials 27, 1605912

Suspended planar-array (SPA) chips embody millions of individual miniaturized arrays to work in extremely small volumes. Here, the basis of a robust methodology for the fabrication of SPA silicon chips with on-demand physical and chemical anisotropies is demonstrated. Specifically, physical traits are defined during the fabrication process with special focus on the aspect ratio, branching, faceting, and size gradient of the final chips. Additionally, the chemical attributes augment the functionality of the chips with the inclusion of complete coverage or patterns of selected biomolecules on the surface of the chips with contact printing techniques, offering an extremely high versatility, not only with the choice of the pattern shape and distribution but also in the choice of biomolecular inks to pattern. This approach increases the miniaturization of printed arrays in 3D structures by two orders of magnitude compared to those previously demonstrated. Finally, functional micrometric and sub-micrometric patterned features are demonstrated with an antibody binding assay with the recognition of the printed spots with labeled antibodies from solution. The selective addition of physical and chemical attributes on the suspended chips represents the basis for future biomedical assays performed within extremely small volumes.

Keywords: Microcontact printing, Microparticles, Molecular multiplexing, Polymer pen lithography, Silicon chip technology


Torras, Núria, Agusil, Juan Pablo, Vázquez, Patricia, Duch, Marta, Hernández-Pinto, Alberto M., Samitier, Josep, de la Rosa, Enrique J., Esteve, Jaume, Suárez, Teresa, Pérez-García, Lluïsa, Plaza, José A., (2016). Suspended planar-array chips for molecular multiplexing at the microscale Advanced Materials , 28, (7), 1449–1454

A novel suspended planar-array chips technology is described, which effectively allows molecular multiplexing using a single suspended chip to analyze extraordinarily small volumes. The suspended chips are fabricated by combining silicon-based technology and polymer-pen lithography, obtaining increased molecular pattern flexibility, and improving miniaturization and parallel production. The chip miniaturization is so dramatic that it permits the intracellular analysis of living cells.

Keywords: Chip-in-a-cell, Suspended-arrays, Planar-arrays, Silicon chips, Single-cell analysis


Campillo, N., Jorba, I., Schaedel, L., Casals, B., Gozal, D., Farré, R., Almendros, I., Navajas, D., (2016). A novel chip for cyclic stretch and intermittent hypoxia cell exposures mimicking obstructive sleep apnea Frontiers in Physiology 7, Article 319

Intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), plays a critical role in the pathogenesis of OSA-associated morbidities, especially in the cardiovascular and respiratory systems. Oxidative stress and inflammation induced by IH are suggested as main contributors of end-organ dysfunction in OSA patients and animal models. Since the molecular mechanisms underlying these in vivo pathological responses remain poorly understood, implementation of experimental in vitro cell-based systems capable of inducing high-frequency IH would be highly desirable. Here, we describe the design, fabrication, and validation of a versatile chip for subjecting cultured cells to fast changes in gas partial pressure and to cyclic stretch. The chip is fabricated with polydimethylsiloxane (PDMS) and consists of a cylindrical well-covered by a thin membrane. Cells cultured on top of the membrane can be subjected to fast changes in oxygen concentration (equilibrium time ~6 s). Moreover, cells can be subjected to cyclic stretch at cardiac or respiratory frequencies independently or simultaneously. Rat bone marrow-derived mesenchymal stem cells (MSCs) exposed to IH mimicking OSA and cyclic stretch at cardiac frequencies revealed that hypoxia-inducible factor 1a (HIF-1a) expression was increased in response to both stimuli. Thus, the chip provides a versatile tool for the study of cellular responses to cyclical hypoxia and stretch.

Keywords: Cell stretch, Hypoxia-inducible factor, Intermittent hypoxia, Lab-on-a-chip, Obstructive sleep apnea


Páez-Avilés, C., Juanola-Feliu, E., Punter-Villagrasa, J., Del Moral Zamora, B., Homs-Corbera, A., Colomer-Farrarons, J., Miribel-Català , P. L., Samitier, J., (2016). Combined dielectrophoresis and impedance systems for bacteria analysis in microfluidic on-chip platforms Sensors 16, (9), 1514

Bacteria concentration and detection is time-consuming in regular microbiology procedures aimed to facilitate the detection and analysis of these cells at very low concentrations. Traditional methods are effective but often require several days to complete. This scenario results in low bioanalytical and diagnostic methodologies with associated increased costs and complexity. In recent years, the exploitation of the intrinsic electrical properties of cells has emerged as an appealing alternative approach for concentrating and detecting bacteria. The combination of dielectrophoresis (DEP) and impedance analysis (IA) in microfluidic on-chip platforms could be key to develop rapid, accurate, portable, simple-to-use and cost-effective microfluidic devices with a promising impact in medicine, public health, agricultural, food control and environmental areas. The present document reviews recent DEP and IA combined approaches and the latest relevant improvements focusing on bacteria concentration and detection, including selectivity, sensitivity, detection time, and conductivity variation enhancements. Furthermore, this review analyses future trends and challenges which need to be addressed in order to successfully commercialize these platforms resulting in an adequate social return of public-funded investments.

Keywords: Bacteria, Dielectrophoresis, Impedance, Microfluidics, On-chip


Paoli, R., Samitier, J., (2016). Mimicking the kidney: A key role in organ-on-chip development Micromachines , 7, (7), 126

Pharmaceutical drug screening and research into diseases call for significant improvement in the effectiveness of current in vitro models. Better models would reduce the likelihood of costly failures at later drug development stages, while limiting or possibly even avoiding the use of animal models. In this regard, promising advances have recently been made by the so-called "organ-on-chip" (OOC) technology. By combining cell culture with microfluidics, biomedical researchers have started to develop microengineered models of the functional units of human organs. With the capacity to mimic physiological microenvironments and vascular perfusion, OOC devices allow the reproduction of tissue- and organ-level functions. When considering drug testing, nephrotoxicity is a major cause of attrition during pre-clinical, clinical, and post-approval stages. Renal toxicity accounts for 19% of total dropouts during phase III drug evaluation-more than half the drugs abandoned because of safety concerns. Mimicking the functional unit of the kidney, namely the nephron, is therefore a crucial objective. Here we provide an extensive review of the studies focused on the development of a nephron-on-chip device.

Keywords: Disease model, Drug discovery, Kidney, Nephron-on-chip, Organ-on-chip


del Moral Zamora, Beatriz, Manuel Álvarez Azpeitia, Juan, Brañas, Ana Ma Oliva, Colomer-Farrarons, Jordi, Castellarnau, Marc, Miribel-Català, Pere Ll, Homs-Corbera, Antoni, Juárez, Antonio, Samitier, Josep, (2015). Dielectrophoretic concentrator enhancement based on dielectric poles for continuously flowing samples Electrophoresis , 36, (13), 1405-1413

We describe a novel continuous-flow cell concentrator micro-device based on dielectrophoresis (DEP), and its associated custom-made control unit. The performances of a classical interdigitated metal electrode-based DEP microfluidic device and this enhanced version, that includes insulator-based pole structures, were compared using the same setup. Escherichia coli (E. coli) samples were concentrated at several continuous flows and the device's trapping efficiencies were evaluated by exhaustive cell counts. Our results show that pole structures enhance the retention up to 12.6%, obtaining significant differences for flow rates up to 20 μl/min, when compared to an equivalent classical interdigitated electrodes setup. In addition, we performed a subsequent proteomic analysis to evaluate the viability of the biological samples after the long exposure to the actuating electrical field. No E. coli protein alteration in any of the two systems was observed.

Keywords: Concentrator, Dielectrophoresis, Escherichia coli, Lab- on- a- chip


del Moral Zamora, B., Azpeitia, J. M. Á, Farrarons, J. C., Català, P. L. M., Corbera, A. H., Juárez, A., Samitier, J., (2014). Towards point-of-use dielectrophoretic methods: A new portable multiphase generator for bacteria concentration Micro and Nanosystems , 6, (2), 71-78

This manuscript presents a portable and low cost electronic system for specific point-of-use dielectrophoresis applications. The system is composed of two main modules: a) a multiphase generator based on a Class E amplifier, which provides 4 sinusoidal signals (0°, 90°, 180°, 270°) at 1 MHz with variable output voltage up to 10 Vpp (Vm) and an output driving current of 1 A; and b) a dielectrophoresis-based microfluidic chip containing two interdigitated electrodes. The system has been validated by concentrating Escherichia coli (E. coli) at 1 MHz while applying a continuous flow of 5 µL/min. The device functionalities were verified under different conditions, achieving an 83% trapping efficiency when counter-phased signals are used.

Keywords: Cell Concentrator, Class E amplifier, Dielectrophoresis, Electronics, Lab-on-a-chip (LOC), Low cost, Portable device


Rigat, L., Elizalde, A., Del Portillo, H. A., Homs-Corbera, A., Samitier, J., (2014). Selective cell culturing step using laminar co-flow to enhance cell culture in splenon-on-a-chip biomimetic platform MicroTAS 2014 18th International Conference on Miniaturized Systems for Chemistry and Life Sciences , CBMS (San Antonio, USA) , 769-771

Constant evolution and improvements on areas such as tissue engineering, microfluidics and nanotechnology have made it possible to partially close the gap between conventional in vitro cell cultures and animal model-based studies. A step forward in this field concerns organ-on-chip technologies, capable of reproducing the most relevant physiological features of an organ in a microfluidic platform. In this work we have exploited the capabilities of laminar co-flow inside our biomimetic platform, the splenon-on-a-chip, in order to enhance cell culture inside its channels to better mimic the spleen's environment. © 14CBMS.

Keywords: Cell culture, Co-flow, Laminar flow, Organ-on-a-chip, Spleen


Rigat, L., Bernabeu, M., Elizalde, A., de Niz, M., Martin-Jaular, L., Fernandez-Becerra, C., Homs-Corbera, A., del Portillo, H. A., Samitier, J., (2014). Human splenon-on-a-chip: Design and validation of a microfluidic model resembling the interstitial slits and the close/fast and open/slow microcirculations IFMBE Proceedings XIII Mediterranean Conference on Medical and Biological Engineering and Computing 2013 (ed. Roa Romero, Laura M.), Springer (Seville, Spain) 41, 884-887

Splenomegaly, albeit variably, is a landmark of malaria infection. Due to technical and ethical constraints, however, the role of the spleen in malaria remains vastly unknown. The spleen is a complex three-dimensional branched vasculature exquisitely adapted to perform different functions containing closed/rapid and open/slow microcirculations, compartmentalized parenchyma (red pulp, white pulp and marginal zone), and sinusoidal structure forcing erythrocytes to squeeze through interstitial slits before reaching venous circulation. Taking into account these features, we have designed and developed a newfangled microfluidic device of a human splenon-on-a-chip (the minimal functional unit of the red pulp facilitating blood-filtering and destruction of malarial-infected red blood cells). Our starting point consisted in translating splenon physiology to the most similar microfluidic network, mimicking the hydrodynamic behavior of the organ, to evaluate and simulate its activities, mechanics and physiological responses and, therefore, enable us to study biological hypotheses. Different physiological features have been translated into engineering elements that can be combined to integrate a biomimetic microfluidic spleen model. The device is fabricated in polydimethylsiloxane (PDMS), a biocompatible polymer, irreversibly bonded to glass. Microfluidics analyses have confirmed that 90% of the blood circulates through a fast-flow compartment whereas the remaining 10% circulates through a slow compartment, equivalently to what has been observed in a real spleen. Moreover, erythrocytes and reticulocytes going through the slow-flow compartment squeeze at the end of it through 2μm physical constraints resembling interstitial slits to reach the closed/rapid circulation.

Keywords: Malaria, Microfluidics, Organ-on-a-chip, Spleen


del Moral Zamora, B., Azpeitia, J. M. Á, Farrarons, J. C., Català, P. L. M., Corbera, A. H., Juárez, A., Samitier, J., (2014). Towards point-of-use dielectrophoretic methods: A new portable multiphase generator for bacteria concentration IFMBE Proceedings XIII Mediterranean Conference on Medical and Biological Engineering and Computing 2013 (ed. Roa Romero, Laura M.), Springer International Publishing (London, UK) 41, 856-859

This manuscript presents portable and low cost electronic system for specific point-of-use dielectrophoresis applications. The system is composed of two main modules: a) a multiphase generator based on a Class E amplifier, which provides 4 sinusoidal signals (0º, 90º, 180º, 270º) at 1 MHz with variable output voltage up to 10 Vpp (Vm) and an output driving current of 1 A; and b) a dielectrophoresis-based microfluidic chip containing two interdigitated electrodes. The system has been validated by concentrating Escherichia Coli at 1 MHz while applying a continuous flow of 5 μL/min. Device functionalities were verified under different conditions achieving a 83% trapping efficiency in the best case.

Keywords: Cell Concentrator, Class E amplifier, Dielectrophoresis, Electronics, Lab-on-a-chip (LOC), Low cost, Portable device


Esquivel, Juan Pablo , Castellarnau, Marc , Senn, Tobias , Löchel, Bernd , Samitier, Josep , Sabaté, Neus , (2012). Fuel cell-powered microfluidic platform for lab-on-a-chip applications Lab on a Chip 12, (1), 74-79

The achievement of a higher degree of integration of components – especially micropumps and power sources – is a challenge currently being pursued to obtain portable and totally autonomous microfluidic devices. This paper presents the integration of a micro direct methanol fuel cell (mDMFC) in a microfluidic platform as a smart solution to provide both electrical and pumping power to a Lab-on-a-Chip system. In this system the electric power produced by the fuel cell is available to enable most of the functionalites required by the microfluidic chip, while the generated CO2 from the electrochemical reaction produces a pressure capable of pumping a liquid volume through a microchannel. The control of the fuel cell operating conditions allows regulation of the flow rate of a liquid sample through a microfluidic network. The relation between sample flow rate and the current generated by the fuel cell is practically linear, achieving values in the range of 4–18 mL min 1 while having an available power between 1–4 mW. This permits adjusting the desired flow rate for a given application by controlling the fuel cell output conditions and foresees a fully autonomous analytical Lab-on-a-Chip in which the same device would provide the electrical power to a detection module and at the same time use the CO2 pumping action to flow the required analytes through a particular microfluidic design.

Keywords: micro direct methanol fuel cell (mDMFC), Lab-on-a-chip (LOC), Microfluidic device


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


Ivon Rodriguez-Villarreal, Angeles, Tarn, Mark D., Madden, Leigh A., Lutz, Julia B., Greenman, John, Samitier, Josep, Pamme, Nicole, (2011). Flow focussing of particles and cells based on their intrinsic properties using a simple diamagnetic repulsion setup Lab on a Chip 11, (7), 1240-1248

The continuous flow focussing and manipulation of particles and cells are important factors in microfluidic applications for performing accurate and reproducible procedures downstream. Many particle focussing methods require complex setups or channel designs that can limit the process and its applications. Here, we present diamagnetic repulsion as a simple means of focussing objects in continuous flow, based only on their intrinsic properties without the requirement of any label. Diamagnetic polystyrene particles were suspended in a paramagnetic medium and pumped through a capillary between a pair of permanent magnets, whereupon the particles were repelled by each magnet into the central axis of the capillary, thus achieving focussing. By investigating this effect, we found that the focussing was greatly enhanced with (i) increased magnetic susceptibility of the medium, (ii) reduced flow rate of the suspension, (iii) increased particle size, and (iv) increased residence time in the magnetic field. Furthermore, we applied diamagnetic repulsion to the flow focussing of living, label-free HaCaT cells.

Keywords: Feeble magnetic substances, On-chip, Blood-cells, Microfluidic device, Separation, Field, Levitation, Magnetophoresis, Fractionation, Nanoparticles


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


Rodriguez-Villarreal, A. I., Arundell, M., Carmona, M., Samitier, J., (2010). High flow rate microfluidic device for blood plasma separation using a range of temperatures Lab on a Chip 10, (2), 211-219

A hybrid microfluidic device that uses hydrodynamic forces to separate human plasma from blood cells has been designed and fabricated and the advantageous effects of temperature and flow rates are investigated in this paper. The blood separating device includes an inlet which is reduced by approximately 20 times to a small constrictor channel, which then opens out to a larger output channel with a small lateral channel for the collection of plasma. When tested the device separated plasma from whole blood using a wide range of flow rates, between 50 mu l min(-1) and 200 mu l min(-1), at the higher flow rates injected by hand and at temperatures ranging from 23 degrees C to 50 degrees C, the latter resulting in an increase in the cell-free layer of up to 250%. It was also tested continuously using between 5% and 40% erythrocytes in plasma and whole blood without blocking the channels or hemolysis of the cells. The mean percentage of plasma collected after separation was 3.47% from a sample of 1 ml. The percentage of cells removed from the plasma varied depending on the flow rate used, but at 37 degrees C ranged between 95.4 +/- 1% and 97.05 +/- 05% at 100 mu l min(-1) and 200 mu l min(-1), respectively. The change in temperature also had an effect on the number of cells removed from the plasma which was between 93.5 +/- 0.65% and 97.01 +/- 0.3% at 26.9 degrees C and 37 degrees C, respectively, using a flow rate of 100 mu l min(-1). Due to its ability to operate in a wide range of conditions, it is envisaged that this device can be used in in vitro 'lab on a chip' applications, as well as a hand-held point of care (POC) device.

Keywords: On-a-chip, Cells, Viscosity, Membrane


Darwish-, N., Caballero, D., Moreno, M., Errachid, A., Samitier, J., (2010). Multi-analytic grating coupler biosensor for differential binding analysis Sensors and Actuators B: Chemical 144, (2), 413-417

In this paper, a multiple-channel extension of a dual-grating Coupler biosensor is presented as a Solution for the problem of resolving different selectivities, Usual when heterogeneous samples are analyzed. Several differently functionalized channels can perform quantitative analysis of competiting recognition events, Suppress shifts due to buffer changes and even monitorize drifts coming from the light Source. Here, the multiple-channel approach is developed and proven for a four-channel configuration, providing a resolution limit of 10(-5) Refractive index Units (RIU) and with an a potentially Unlimited scalability. Finally, a differential HSA recognition event is monitored, at both an IgG functionalized channel and at a blocked one.

Keywords: Optical grating coupler, Multi-channel biorecognition, On-chip reference


Tort, N., Salvador, J. P., Eritja, R., Poch, M., Martinez, E., Samitier, J., Marco, M. P., (2009). Fluorescence site-encoded DNA addressable hapten microarray for anabolic androgenic steroids Trac-Trends in Analytical Chemistry , 28, (6), 718-728

We report a new strategy for immunochemical screening of small organic molecules based on the use of a hapten microarray. Using DNA-directed immobilization strategies, we have been able to convert a DNA chip into a hapten microarray by taking advantage of all the benefits of the structural and electrostatic homogeneous properties of DNA. The hapten microarray uses hapten-oligonucleotide probes instead of proteins, avoiding the limitations of preparing stochiometrically-defined protein-oligonucleotide bioconjugates. As proof of concept, we show here the development of a microarray for analysis of anabolic androgenic steroids. The microchip is able to detect several illegal substances with sufficient detectability to be used as a screening method, according to the regulations of the World Anti-Doping Agency for sport and the European Commision for food safety. The results that we show corroborate the universal possibilities of the DNA chip, and, in this case, they open the way to develop hapten microarrays for the immunochemical analysis of small organic molecules.

Keywords: Anti-doping, DNA chip, DNA-directed immobilization (DDI), Fluorescence, Food safety, Hapten microarray, Immunochemical screening, Proof of concept, Small organic molecule, Steroid


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


Rodriguez-Trujillo, R., Castillo-Fernandez, O., Garrido, M., Arundell, M., Valencia, A., Gomila, G., (2008). High-speed particle detection in a micro-Coulter counter with two-dimensional adjustable aperture Biosensors and Bioelectronics 24, (2), 290-296

This article presents the fabrication and characterisation of a high-speed detection micro-Coulter counter with two-dimensional (2D) adjustable aperture and differential impedance detection. The developed device has been fabricated from biocompatible and transparent materials (polymer and glass) and uses the principle of hydrodynamic focusing in two dimensions. The use of a conductive solution for the sample flux and non-conductive solutions for the focalising fluxes provides an adjustable sample flow where particles are aligned and the resistive response concentrated, consequently enhancing the sensitivity and versatility of the device. High-speed counting of 20 mu m polystyrene particles and 5 mu m yeast cells with a rate of up to 1000 particles/s has been demonstrated. Two-dimensional focusing conditions have been used in devices with physical cross-sectional areas of 180 mu m x 65 mu m and 100 mu m x 43 mu m, respectively, in which particles resulted undetectable in the absence of focusing. The 2D-focusing conditions have provided, in addition, increased detection sensitivity by a factor of 1.6 as compared to 1 D-focusing conditions.

Keywords: Impedance, Chip, Microfluidics