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by Keyword: Microfluidic


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Williams, I., Lee, S., Apriceno, A., Sear, R. P., Battaglia, G., (2020). Diffusioosmotic and convective flows induced by a nonelectrolyte concentration gradient Proceedings of the National Academy of Sciences of the United States of America 117, (41), 25263-25271

Glucose is an important energy source in our bodies, and its consumption results in gradients over length scales ranging from the subcellular to entire organs. Concentration gradients can drive material transport through both diffusioosmosis and convection. Convection arises because concentration gradients are mass density gradients. Diffusioosmosis is fluid flow induced by the interaction between a solute and a solid surface. A concentration gradient parallel to a surface creates an osmotic pressure gradient near the surface, resulting in flow. Diffusioosmosis is well understood for electrolyte solutes, but is more poorly characterized for nonelectrolytes such as glucose. We measure fluid flow in glucose gradients formed in a millimeter-long thin channel and find that increasing the gradient causes a crossover from diffusioosmosis-dominated to convection-dominated flow. We cannot explain this with established theories of these phenomena which predict that both scale linearly. In our system, the convection speed is linear in the gradient, but the diffusioosmotic speed has a much weaker concentration dependence and is large even for dilute solutions. We develop existing models and show that a strong surface-solute interaction, a heterogeneous surface, and accounting for a concentration-dependent solution viscosity can explain our data. This demonstrates how sensitive nonelectrolyte diffusioosmosis is to surface and solution properties and to surface-solute interactions. A comprehensive understanding of this sensitivity is required to understand transport in biological systems on length scales from micrometers to millimeters where surfaces are invariably complex and heterogeneous.

Keywords: Convection, Diffusioosmosis, Microfluidics


Ruiz-Vega, G., Arias-Alpízar, K., de la Serna, E., Borgheti-Cardoso, L. N., Sulleiro, E., Molina, I., Fernàndez-Busquets, X., Sánchez-Montalvá, A., del Campo, F. J., Baldrich, E., (2020). Electrochemical POC device for fast malaria quantitative diagnosis in whole blood by using magnetic beads, Poly-HRP and microfluidic paper electrodes Biosensors and Bioelectronics 150, 111925

Malaria, a parasitic infection caused by Plasmodium parasites and transmitted through the bite of infected female Anopheles mosquitos, is one of the main causes of mortality in many developing countries. Over 200 million new infections and nearly half a million deaths are reported each year, and more than three billion people are at risk of acquiring malaria worldwide. Nevertheless, most malaria cases could be cured if detected early. Malaria eradication is a top priority of the World Health Organisation. However, achieving this goal will require mass population screening and treatment, which will be hard to accomplish with current diagnostic tools. We report an electrochemical point-of-care device for the fast, simple and quantitative detection of Plasmodium falciparum lactate dehydrogenase (PfLDH) in whole blood samples. Sample analysis includes 5-min lysis to release intracellular parasites, and stirring for 5 more min with immuno-modified magnetic beads (MB) along with an immuno-modified signal amplifier. The rest of the magneto-immunoassay, including sample filtration, MB washing and electrochemical detection, is performed at a disposable paper electrode microfluidic device. The sensor provides PfLDH quantitation down to 2.47 ng mL−1 in spiked samples and for 0.006–1.5% parasitemias in Plasmodium-infected cultured red blood cells, and discrimination between healthy individuals and malaria patients presenting parasitemias >0.3%. Quantitative malaria diagnosis is attained with little user intervention, which is not achieved by other diagnostic methods.

Keywords: Electrochemical magneto-immunosensor, Malaria quantitative diagnosis, Paper microfluidic electrode, Plasmodium LDH, Point-of-care (POC) testing


Sala-Jarque, Julia, Mesquida-Veny, Francina, Badiola-Mateos, Maider, Samitier, Josep, Hervera, Arnau, del Río, José Antonio, (2020). Neuromuscular activity induces paracrine signaling and triggers axonal regrowth after injury in microfluidic lab-on-chip devices Cells 9, (2), 302

Peripheral nerve injuries, including motor neuron axonal injury, often lead to functional impairments. Current therapies are mostly limited to surgical intervention after lesion, yet these interventions have limited success in restoring functionality. Current activity-based therapies after axonal injuries are based on trial-error approaches in which the details of the underlying cellular and molecular processes are largely unknown. Here we show the effects of the modulation of both neuronal and muscular activity with optogenetic approaches to assess the regenerative capacity of cultured motor neuron (MN) after lesion in a compartmentalized microfluidic-assisted axotomy device. With increased neuronal activity, we observed an increase in the ratio of regrowing axons after injury in our peripheral-injury model. Moreover, increasing muscular activity induces the liberation of leukemia inhibitory factor and glial cell line-derived neurotrophic factor in a paracrine fashion that in turn triggers axonal regrowth of lesioned MN in our 3D hydrogel cultures. The relevance of our findings as well as the novel approaches used in this study could be useful not only after axotomy events but also in diseases affecting MN survival.

Keywords: Neuromuscular junction, Microfluidics, Axotomy, Paracrine signaling


del Rio, Jose A., Ferrer, Isidre, (2020). Potential of microfluidics and lab-on-chip platforms to improve understanding of “prion-like” protein assembly and behavior Frontiers in Bioengineering and Biotechnology 8, 570692

Human aging is accompanied by a relevant increase in age-associated chronic pathologies, including neurodegenerative and metabolic diseases. The appearance and evolution of numerous neurodegenerative diseases is paralleled by the appearance of intracellular and extracellular accumulation of misfolded proteins in affected brains. In addition, recent evidence suggests that most of these amyloid proteins can behave and propagate among neural cells similarly to infective prions. In order to improve understanding of the seeding and spreading processes of these “prion-like” amyloids, microfluidics and 3D lab-on-chip approaches have been developed as highly valuable tools. These techniques allow us to monitor changes in cellular and molecular processes responsible for amyloid seeding and cell spreading and their parallel effects in neural physiology. Their compatibility with new optical and biochemical techniques and their relative availability have increased interest in them and in their use in numerous laboratories. In addition, recent advances in stem cell research in combination with microfluidic platforms have opened new humanized in vitro models for myriad neurodegenerative diseases affecting different cellular targets of the vascular, muscular, and nervous systems, and glial cells. These new platforms help reduce the use of animal experimentation. They are more reproducible and represent a potential alternative to classical approaches to understanding neurodegeneration. In this review, we summarize recent progress in neurobiological research in “prion-like” protein using microfluidic and 3D lab-on-chip approaches. These approaches are driven by various fields, including chemistry, biochemistry, and cell biology, and they serve to facilitate the development of more precise human brain models for basic mechanistic studies of cell-to-cell interactions and drug discovery.

Keywords: Lab-On-Chip, Amyloid propagation, Microfluidics, Fibril, Seeding, Spreading, Prion-like, Prionoid


Kaang, Byung Kwon, Mestre, Rafael, Kang, Dong-Chang, Sánchez, Samuel, Kim, Dong-Pyo, (2020). Scalable and integrated flow synthesis of triple-responsive nano-motors via microfluidic Pickering emulsification Applied Materials Today 21, 100854

Artificial micro-/nano-motors are tiny machines as newly emerging tools capable of achieving numerous tasks. In principle, the self-phoretic motions require asymmetric structures in geometry and chemistry. However, conventional production techniques suffered from complex and time consuming multi-step process in low uniformity, and difficult to endow multi-functions into motors. This work disclosed a continuous-flow synthesis of triple-responsive (thermophoretic, chemical and magnetic movement) nano-motors (m-SiO2/Fe3O4-Pdop/Pt) via microfluidic Pickering emulsification in a process of integrated and scalable manner. The droplet microfluidic process allows efficient self-assembly of the silica nanoparticles surrounding the spherical interface of resin droplet, rendering excellent Pickering efficiency and reproducibility, and followed by anisotropic decoration of polydopamine (Pdop) and Pt catalyst in a serial flow process. The obtained Janus nanoparticles reveal double- or triple-responsive self-propulsions with synergic mobility by combining thermophoresis powered by light, catalytic driven motion in H2O2 or magnetic movement by magnet. Further, a non-metallic polydopamine based thermophoretic motion as well as an automated nano-cleaner for rapid water purification by dye removal are convincingly functioned. Finally, this novel integrated flow strategy proves a scalable manufacturing production (> 0.7 g hr−1) of the nano-motors using inexpensive single microreactor, fulfilling quantitative and qualitative needs for versatile applications.

Keywords: Microfluidics Pickering emulsions, Triple-responsive motor, Adsorbent


Sierra, J., Marrugo-Ramírez, J., Rodriguez-Trujillo, R., Mir, M., Samitier, J., (2020). Sensor-integrated microfluidic approaches for liquid biopsies applications in early detection of cancer Sensors 20, (5), 1317

Cancer represents one of the conditions with the most causes of death worldwide. Common methods for its diagnosis are based on tissue biopsies—the extraction of tissue from the primary tumor, which is used for its histological analysis. However, this technique represents a risk for the patient, along with being expensive and time-consuming and so it cannot be frequently used to follow the progress of the disease. Liquid biopsy is a new cancer diagnostic alternative, which allows the analysis of the molecular information of the solid tumors via a body fluid draw. This fluid-based diagnostic method displays relevant advantages, including its minimal invasiveness, lower risk, use as often as required, it can be analyzed with the use of microfluidic-based platforms with low consumption of reagent, and it does not require specialized personnel and expensive equipment for the diagnosis. In recent years, the integration of sensors in microfluidics lab-on-a-chip devices was performed for liquid biopsies applications, granting significant advantages in the separation and detection of circulating tumor nucleic acids (ctNAs), circulating tumor cells (CTCs) and exosomes. The improvements in isolation and detection technologies offer increasingly sensitive and selective equipment’s, and the integration in microfluidic devices provides a better characterization and analysis of these biomarkers. These fully integrated systems will facilitate the generation of fully automatized platforms at low-cost for compact cancer diagnosis systems at an early stage and for the prediction and prognosis of cancer treatment through the biomarkers for personalized tumor analysis.

Keywords: Cancer, Circulant tumor cells (CTC), Circulant tumor DNA (ctDNA), Exosomes, Liquid biopsy, Microfluidic, Sensors


Lakey, A., Ali, Z., Scott, S. M., Chebil, S., Korri-Youssoufi, H., Hunor, S., Ohlander, A., Kuphal, M., Samitier, J., (2019). Impedimetric array in polymer microfluidic cartridge for low cost point-of-care diagnostics Biosensors and Bioelectronics 129, 147-154

Deep Vein Thrombosis and pulmonary embolism (DVT/PE) is one of the most common causes of unexpected death for hospital in-patients. D-dimer is used as a biomarker within blood for the diagnosis of DVT/PE. We report a low-cost microfluidic device with a conveniently biofunctionalised interdigitated electrode (IDE) array and a portable impedimetric reader as a point-of-care (POC) device for the detection of D-dimer to aid diagnosis of DVT/PE. The IDE array elements, fabricated on a polyethylenenaphtalate (PEN) substrate, are biofunctionalised in situ after assembly of the microfluidic device by electropolymerisation of a copolymer of polypyrrole to which is immobilised a histidine tag anti-D-Dimer antibody. The most consistent copolymer films were produced using chronopotentiometry with an applied current of 5μA for a period of 50 s using a two-electrode system. The quality of the biofunctionalisation was monitored using optical microscopy, chronopotentiometry curves and impedimetric analysis. Measurement of clinical plasma sample with a D-dimer at concentration of 437 ng/mL with 15 biofunctionalised IDE array electrodes gave a ratiometric percentage of sample reading against the blank with an average value of 124 ± 15 at 95% confidence. We have demonstrated the concept of a low cost disposable microfluidic device with a receptor functionalised on the IDE array for impedimetric detection towards POC diagnostics. Changing the receptor on the IDE array would allow this approach to be used for the direct detection of a wide range of analytes in a low cost manner.

Keywords: Electropolymerisation, Impedimetric sensing, Interdigitated electrodes, Microfluidics, Point-of-care diagnostics


Badiola-Mateos, M., Hervera, A., del Río, J. A., Samitier, J., (2018). Challenges and future prospects on 3D in-vitro modeling of the neuromuscular circuit Frontiers in Bioengineering and Biotechnology 6, Article 194

Movement of skeletal-muscle fibers is generated by the coordinated action of several cells taking part within the locomotion circuit (motoneurons, sensory-neurons, Schwann cells, astrocytes, microglia, and muscle-cells). Failures in any part of this circuit could impede or hinder coordinated muscle movement and cause a neuromuscular disease (NMD) or determine its severity. Studying fragments of the circuit cannot provide a comprehensive and complete view of the pathological process. We trace the historic developments of studies focused on in-vitro modeling of the spinal-locomotion circuit and how bioengineered innovative technologies show advantages for an accurate mimicking of physiological conditions of spinal-locomotion circuit. New developments on compartmentalized microfluidic culture systems (cμFCS), the use of human induced pluripotent stem cells (hiPSCs) and 3D cell-cultures are analyzed. We finally address limitations of current study models and three main challenges on neuromuscular studies: (i) mimic the whole spinal-locomotion circuit including all cell-types involved and the evaluation of independent and interdependent roles of each one; (ii) mimic the neurodegenerative response of mature neurons in-vitro as it occurs in-vivo; and (iii) develop, tune, implement, and combine cμFCS, hiPSC, and 3D-culture technologies to ultimately create patient-specific complete, translational, and reliable NMD in-vitro model. Overcoming these challenges would significantly facilitate understanding the events taking place in NMDs and accelerate the process of finding new therapies.

Keywords: 3D-culture, Compartmentalized microfluidic culture systems (cμFCS), HiPSC, In-vitro models, Neuromuscular circuit


Urrea, L., Segura, Miriam, Masuda-Suzukake, M., Hervera, A., Pedraz, L., Aznar, J. M. G., Vila, M., Samitier, J., Torrents, E., Ferrer, Isidro, Gavín, R., Hagesawa, M., Del Río, J. A., (2018). Involvement of cellular prion protein in α-synuclein transport in neurons Molecular Neurobiology 55, (3), 1847-1860

The cellular prion protein, encoded by the gene Prnp, has been reported to be a receptor of β-amyloid. Their interaction is mandatory for neurotoxic effects of β-amyloid oligomers. In this study, we aimed to explore whether the cellular prion protein participates in the spreading of α-synuclein. Results demonstrate that Prnp expression is not mandatory for α-synuclein spreading. However, although the pathological spreading of α-synuclein can take place in the absence of Prnp, α-synuclein expanded faster in PrPC-overexpressing mice.

Keywords: Amyloid spreading, Microfluidic devices, Prnp, Synuclein


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


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


Seo, K. D., Kwak, B. K., Sánchez, S., Kim, D. S., (2015). Microfluidic-assisted fabrication of flexible and location traceable organo-motor IEEE Transactions on Nanobioscience , 14, (3), 298-304

In this paper, we fabricate a flexible and location traceable micromotor, called organo-motor, assisted by microfluidic devices and with high throughput. The organo-motors are composed of organic hydrogel material, poly (ethylene glycol) diacrylate (PEGDA), which can provide the flexibility of their structure. For spatial and temporal traceability of the organo-motors under magnetic resonance imaging (MRI), superparamagnetic iron oxide nanoparticles (SPION; Fe3O4) were incorporated into the PEGDA microhydrogels. Furthermore, a thin layer of platinum (Pt) was deposited onto one side of the SPION-PEGDA microhydrogels providing geometrical asymmetry and catalytic propulsion in aqueous fluids containing hydrogen peroxide solution, H2O2. Furthermore, the motion of the organo-motor was controlled by a small external magnet enabled by the presence of SPION in the motor architecture.

Keywords: Flexible, Hydrogel, Magnetic resonance imaging, Microfluidics, Micromotor, Microparticle, Organo-motor, Poly (ethylene glycol) diacrylate, Self-propulsion, Superparamagnetic iron oxide nanoparticles


Castillo-Fernandez, O., Rodriguez-Trujillo, R., Gomila, G., Samitier, J., (2014). High-speed counting and sizing of cells in an impedance flow microcytometer with compact electronic instrumentation Microfluidics and Nanofluidics , 16, (1-2), 91-99

Here we describe a high-throughput impedance flow cytometer on a chip. This device was built using compact and inexpensive electronic instrumentation. The system was used to count and size a mixed cell sample containing red blood cells and white blood cells. It demonstrated a counting capacity of up to ~500 counts/s and was validated through a synchronised high-speed optical detection system. In addition, the device showed excellent discrimination performance under high-throughput conditions.

Keywords: Electronics, Impedance, Microcytometry, Microfluidics, Red blood cells (RBCs), White blood cells (WBCs)


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


Salerno, A., Levato, R., Mateos-Timoneda, M. A., Engel, E., Netti, P. A., Planell, J. A., (2013). Modular polylactic acid microparticle-based scaffolds prepared via microfluidic emulsion/solvent displacement process: Fabrication, characterization, and in vitro mesenchymal stem cells interaction study Journal of Biomedical Materials Research - Part A , 101A, (3), 720-732

The present study reports a novel approach for the design and fabrication of polylactic acid (PLA) microparticle-based scaffolds with microstructural properties suitable for bone and cartilage regeneration. Macroporous PLA scaffolds with controlled shape were fabricated by means of a semicontinuous process involving (1) microfluidic emulsification of a PLA/ethyl lactate solution (5% w/v) in a span 80/paraffin oil solution (3% v/v) followed by (2) particles coagulation/assembly in an acetone/water solution for the development of a continuous matrix. Porous scaffolds prepared from particles with monomodal or bimodal size distribution, overall porosity ranges from 93 to 96%, interparticles porosity from 41 to 54%, and static compression moduli from 0.3 to 1.4 MPa were manufactured by means of flow rate modulation of of the continuous phase during emulsion. The biological response of the scaffolds was assessed in vitro by using bone marrow-derived rat mesenchymal stem cells (MSCs). The results demonstrated the ability of the scaffolds to support the extensive and uniform three-dimensional adhesion, colonization, and proliferation of MSCs within the entire construct.

Keywords: Green solvent, Microfluidic, Microstructure, Stem cells, Scaffold


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


Comelles, J., Hortigüela, V., Samitier, J., Martinez, E., (2012). Versatile gradients of covalently bound proteins on microstructured substrates Langmuir 28, (38), 13688-13697

In this work, we propose an easy method to produce highly tunable gradients of covalently bound proteins on topographically modified poly(methyl methacrylate). We used a rnicrofluidic approach to obtain linear gradients with high slope (0.5 pmol.cm(-2).mm(-1)), relevant at the single-cell level. These protein gradients were characterized using fluorescence microscopy and surface plasmon resonance. Both experimental results and theoretical modeling on the protein gradients generated have proved them to be highly reproducible, stable up to 7 days, and easily tunable. This method enables formation of versatile cell culture platforms combining both complex biochemical and physical cues in an attempt to approach in vitro cell culture methods to in vivo cellular microenvironments.

Keywords: Cell-migration, Microfluidic channel, Surface, Streptavidin, Molecules, Topography, Mechanisms, Generation, Responses, Guidance


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, 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


Rodriguez-Trujillo, R., Castillo-Fernandez, O., Arundell, M., Samitier, J., Gomila, G., (2008). Yeast cells detection in a very fast and highly versatile microfabricated cytometer MicroTAS 2008 12th International Conference on Miniaturized Systems for Chemistry and Life Sciences , Chemical and Biological Microsystems Society (San Diego, USA) , 1888-1890

A novel microfluidic chip able to detect a wide range of different cell sizes at very high rates is reported. The device uses two-dimensional hydrodynamic focusing [1] of the sample (conducting) flow by three non-conducting flows and high-speed differential impedance detection electronics. High-speed counting of 15μm polystyrene particles and 5μm yeast cells with a rate of up to 1000 particles/s has been demonstrated. Using of two-dimensional focusing effect turn out to be essential in a device with very large cross-sectional area (100x43 μm2) in which particles result undetectable in the absence of focusing.

Keywords: Coulter-counter, Impedance, Microfluidics, Polydimethylsiloxane