Evaluation and diagnosis of blood alterations is a common request for clinical laboratories, requiring a complex technological approach and dedication of health resources. In this paper, we present a microfluidic device that owing to a novel combination of hydrodynamic and dielectrophoretic techniques can separate plasma from fresh blood in a microfluidic channel and for the first time allows optical real-time monitoring of the components of plasma without pre- or post-processing. The microchannel is based on a set of dead-end branches at each side and is initially filled using capillary forces with a 2-μL droplet of fresh blood. During this process, stagnation zones are generated at the dead-end branches and some red blood cells (RBCs) are trapped there. An electric field is then applied and dielectrophoretic trapping of RBCs is used to prevent more RBCs entering into the channel, which works like a sieve. Besides, an electroosmotic flow is generated to sweep the rest of the RBCs from the central part of the channel. Consequently, an RBC-free zone of plasma is formed in the middle of the channel, allowing real-time monitoring of the platelet behavior. To study the generation of stagnation zones and to ensure RBC trapping in the initial constrictions, two numerical models were solved. The proposed experimental design separates up to 0.1 μL blood plasma from a 2-μL fresh human blood droplet. In this study, a plasma purity of 99 % was achieved after 7 min, according to the measurements taken by image analysis. Graphical Abstract Schematics of a real-time plasma monitoring system based on a Hydrodynamic and direct-current insulator-based dielectrophoresis microfluidic channel.

The deflection of magnetic beads in a microfluidic channel through magnetophoresis can be improved if the particles are somehow focused along the same streamline in the device. We design and fabricate a microfluidic device made of two modules, each one performing a unit operation. A suspension of magnetic beads in a viscoelastic medium is fed to the first module, which is a straight rectangular-shaped channel. Here, the magnetic particles are focused by exploiting fluid viscoelasticity. Such a channel is one inlet of the second module, which is a H-shaped channel, where a buffer stream is injected in the second inlet. A permanent magnet is used to displace the magnetic beads from the original to the buffer stream. Experiments with a Newtonian suspending fluid, where no focusing occurs, are carried out for comparison. When viscoelastic focusing and magnetophoresis are combined, magnetic particles can be deterministically separated from the original streamflow to the buffer, thus leading to a high deflection efficiency (up to ~96%) in a wide range of flow rates. The effect of the focusing length on the deflection of particles is also investigated. Finally, the proposed modular device is tested to separate magnetic and non-magnetic beads.

Abstract:Recently, there is a growing need for lab-on-a-chip devices in clinical analysis and diagnostics especially near the patient care. First step, in the most blood assays is plasma extraction from whole blood. This paper presents a novel high throughput blood plasma separation microfluidic chip, which with just a single droplet of undiluted human blood (~5µL) can separate (more than 0.1µL) plasma from whole blood without the need of external forces with high purity (more than 98%) and reasonable time (3 to 5 minutes). This would be the first step towards the realization of single use, self-blood test which does not require any external forces or connection to deliver and analyze a fresh whole blood sample in contrast to the conventional blood analysis which have variable waiting times. Polydimethylsiloxane (PDMS) is utilized as the base material to manufacture the microchip due to its biocompatibility and outstanding characteristics. PDMS has been modified with a strong nonionic surfactant (Silwet L-77) to achieve a hydrophilic behavior. The main advantage of this microfluidic chip design is the clogging delay on the filtration area, which results in an increased amount of extracted plasma (0.1 µL). Moreover, the plasma can be collected in one or more 10-µm-depth channels to facilitate the detection and readout of multiple blood assays. This high volume of extracted plasma is achieved; thanks to a novel design that combines the maximum pumping efficiency without disturbing the red blood cells (RBCs) trajectory by the use of different hydrodynamic principles such as constriction effect and symmetrical filtration mode. To demonstrate the microfluidic chip functionality, a novel hybrid microdevice, exhibiting the benefits of both microfluidics and lateral flow Immuno-chromatographic tests, is designed and fabricated. The performance of the presented hybrid microdevice is validated utilizing rapid detection of the thyroid stimulating hormone (TSH) within a single droplet of whole blood. ABSTRACTRecently, there is a growing need for lab-on-a-chip devices in clinical analysis and diagnostics especially near the patient care. First step, in the most blood assays is plasma extraction from whole blood. This paper presents a novel high throughput blood plasma separation microfluidic chip, which with just a single droplet of undiluted human blood (~5µL) can separate (more than 0.1µL) plasma from whole blood without the need of external forces with high purity (more than 98%) and reasonable time (3 to 5 minutes). This would be the first step towards the realization of single use, self-blood test which does not require any external forces or connection to deliver and analyze a fresh whole blood sample in contrast to the conventional blood analysis which have variable waiting times. Polydimethylsiloxane (PDMS) is utilized as the base material to manufacture the microchip due to its biocompatibility and outstanding characteristics. PDMS has been modified with a strong nonionic surfactant (Silwet L-77) to achieve a hydro...

Aquesta és una còpia de la versió author's final draft d'un article publicat a la revista Analytical and bioanalytical chemistry.La publicació final està disponible a Springer a través de http://dx.doi.org/10.1007/s00216-016-9629-2 This is a copy of the author 's final draft version of an article published in the journal Analytical and bioanalytical chemistry. AbstractDirect-current insulator-based dielectrophoresis (DC-iDEP) is a well-known technique that benefits from the electric field gradients generated by an array of insulating posts to separate or trap biological particles. In this work, we propose a novel figure of merit to find an efficient design of the post-array distribution in a microfluidic channel. To characterization can be used to reduce the required electric field to achieve effective particle trapping and, therefore, avoid the negative effects of Joule heating in cells or viable particles.

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A wide range of diseases and conditions are monitored or diagnosed from blood plasma, but the ability to analyze a whole blood sample with the requirements for a point-of-care device, such as robustness, user-friendliness, and simple handling, remains unmet. Microfluidics technology offers the possibility not only to work fresh thumb-pricked whole blood but also to maximize the amount of the obtained plasma from the initial sample and therefore the possibility to implement multiple tests in a single cartridge. The microfluidic design presented in this paper is a combination of cross-flow filtration with a reversible electroosmotic flow that prevents clogging at the filter entrance and maximizes the amount of separated plasma. The main advantage of this design is its efficiency, since from a small amount of sample (a single droplet $10 ll) almost 10% of this (approx 1 ll) is extracted and collected with high purity (more than 99%) in a reasonable time (5-8 min). To validate the quality and quantity of the separated plasma and to show its potential as a clinical tool, the microfluidic chip has been combined with lateral flow immunochromatography technology to perform a qualitative detection of the thyroid-stimulating hormone and a blood panel for measuring cardiac Troponin and Creatine Kinase MB. The results from the microfluidic system are comparable to previous commercial lateral flow assays that required more sample for implementing fewer tests. V C 2015 AIP Publishing LLC. [http://dx

Prediction and reduction of pressure drop and resistance flow in micropillar arrays are important for the design of microfluidic circuits used in different lab-on-a-chip and biomedical applications. In this work, a diamond microchannel-integrated micropillar pump (dMIMP) with a resistance flow 35.5 % lower than a circular-based micropillar pump (cMIMP) has been developed via the optimization of the fluid dynamic behavior of different pillar shapes in a low aspect ratio (H/D ranged from 0.06 to 0.2) integrated pillar microchannel. The effect of different geometrical parameters (such as pillar shape and its distribution) has been considered to minimize the microchannel resistance flow. Six-micrometer-depth polidimetilsiloxane (PDMS) channels have been fabricated using a modified soft lithography process, which prevents the PDMS deformation under high-pressure operation. Flow through the fabricated samples has been numerically solved and experimentally measured, with an agreement higher than 90 %. The results have been used to validate the derived analytical formulation to determine the flow resistance in this type of channels, a fast approach to obtain the resistance flow in the design stage of microdevices. The analysis of the results indicates that, although porosity can be a determinant parameter to predict the resistance flow of MIMP, other geometrical parameters such as side distance between pillars and pillar shape play a major role in this scenario. Finally, a high-throughput optimized diamond MIMP pump has been designed, tested and validated as a capillary pump, showing that it can provide a flow rate 73 % higher than a circular MIMP pump.Peer ReviewedPostprint (published version

PDMS is one of the most common materials used for the flow delivery in the microfluidics chips, since it is clear, inert, nontoxic, and nonflammable. Its inexpensiveness, straightforward fabrication, and biological compatibility have made it a favorite material in the exploratory stages of the bio-microfluidic devices. If small footprint assays want to be performed while keeping the throughput, high pressure-rated channels should be used, but PDMS flexibility causes an important issue since it can generate a large variation of microchannel geometry. In this work, a novel fabrication technique based on the prevention of PDMS deformation is developed. A photo-sensible thiolene resin (Norland Optical Adhesive 63, NOA 63) is used to create a rigid coating layer over the stiff PDMS micropillar array, which significantly reduces the pressure-induced shape changes. This method uses the exact same soft lithography manufacturing equipment. The verification of the presented technique was investigated experimentally and numerically and the manufactured samples showed a deformation 70% lower than PDMS conventional samples.