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This is a copy of the author 's final draft version of an article published in the journal Analytical and bioanalytical chemistry. The final publication is available at Springer via http://dx.doi.org/10.1007/s00216-016-9629-2, Direct-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. The aim of this study is to provide a first geometrical relationship of the post array that independent of the particles and/or medium, maximizes the trapping. A novel figure of merit is proposed to maximize the particle trapping in the post array while minimizing the required voltage, with a similar footprint and channel thickness. Different post array models with the variation of transversal distance (10 to 60 µm), longitudinal distance (10 to 80 µm), and post radius (10 to 150 µm) were analyzed using COMSOL Multiphysics finite element software. The obtained results indicated that a post radius of 40 µm larger than the transversal distance between posts could enhance the trapping condition between 56 % (for a transversal distance of 10 µm) and 341 % (for a transversal distance of 60 µm). For the validation of the numerical results, several microchannels with embedded post arrays were manufactured in polydimethylsiloxane (PDMS) and the particle trapping patterns of 6-µm-diameter polystyrene particles were measured experimentally. The experiments confirm the same trends as pointed out by the numerical analysis. The results show that this new figure of merit and geometrical relationship 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. The main advantage of these results is that they depend only on the geometry of the micropost array and are valid for trapping different particles suspended in different media., Peer Reviewed, Postprint (author's final draft)

Copyright 2015 AIP Publishing. This article may be downloaded for personal use only. Any other use requires prior permission of the author and AIP Publishing., 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¿µl) almost 10% of this (approx 1¿µl) 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., Peer Reviewed, Postprint (author's final draft)

There is currently a growing need for lab-on-a-chip devices for use in clinical analysis and diagnostics, especially in the area of patient care. The first step in most blood assays is plasma extraction from whole blood. This paper presents a novel, self-driven blood plasma separation microfluidic chip, which can extract more than 0.1 µl plasma from a single droplet of undiluted fresh human blood (~5 µl). This volume of blood plasma is extracted from whole blood with high purity (more than 98%) in a reasonable time frame (3 to 5 min), and without the need for any external force. This would be the first step towards the realization of a single-use, self-blood test that does not require any external force or power source to deliver and analyze a fresh whole-blood sample, in contrast to the existing time-consuming conventional blood analysis. The prototypes are manufactured in polydimethylsiloxane that has been modified with a strong nonionic surfactant (Silwet L-77) to achieve hydrophilic behavior. The main advantage of this microfluidic chip design is the clogging delay in 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-deep 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 maximum pumping efficiency without disturbing the red blood cells' trajectory through the use of different hydrodynamic principles, such as a constriction effect and a symmetrical filtration mode. To demonstrate the microfluidic chip's functionality, we designed and fabricated a novel hybrid microdevice that exhibits the benefits of both microfluidics and lateral flow immunochromatographic tests. The performance of the presented hybrid microdevice is validated using rapid detection of thyroid stimulating hormone within a single droplet of whole blood., Peer Reviewed, Postprint (author's final draft)

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-mu L 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 mu L blood plasma from a 2-mu L 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., Postprint (published version)

Tesi per compendi de publicacions. La consulta íntegra de la tesi, inclosos els articles no comunicats públicament per drets d'autor, es pot realitzar prèvia petició a l'Arxiu UPC, Premi extraordinari doctorat 2013-2014, Recently, the emergence of lab-on-a-chip devices has seen in a variety of applications especially in clinical analys is and diagnostics. ln particular the lack of suitable microdevices for separation of plasma from whole blood is a barrier to achieve a reliable lab on a chip (LOC) blood test. In order to address this issue, a novel self-driven high throughput blood plasma separator microchip is introduced as a first step to a miniaturized blood analys is. PDMS (Polydim ethylsiloxane) is utilized as the base material for the microdevice fabrication to ens ure the biocompatibility, the disposability (single-use to avoid contamination) and the low cost ofthe system for the mass-manufacturing. One of the characteristic features ofthe presented m icrodevice is that it needs to work just by capillary pressure eliminating the need of external sources. The requested capillary pressure to drive blood through the microdevice is derived via PDMS modification byanalyzing different surfactants, which are mixed with pre-cured PDMS to achieve a stable hydrophilic character. Furthermore, a diamond microchannel integrated micropillar (dMIMP) pump with high throughput and with a resistance flow 35.5% lower than a circular based micropillar pump (cMIMP) has been developed. For this purpose, the pressure drop and flow resistance of a lam inar flow through low aspect ratio MIMPs with different shapes and geometrical parameters are experim entally, numerically and analytically determined. In order to characterize the fabricated microcapillarypumps in PDMS, a novel and simple fabrication technique is introduced to overcome the PDMS deform ation under high-pressure operation. The presented fabrication technique combines the use of stiff PDMS (1 0:2, the ratio between polymer base and cross liking agent) and a thin coating layer of the UV curable thiolene resin as supporter (Norland Optical Adhesive 63) on the fabricated PDMS microchannel. Finally, using all the achieved results in the mate, Recientemente, la aparición de dispositivos de laboratorio en un chip (Lab on a chip) ha generado una gran variedad de nuevas aplicaciones especialmente en análisis clínicos y diagnóstico. En particular, la falta de micro dispositivos adecuados para la separación del plasma de la sangre es una barrera para lograr un dispositivo portátil que pueda realizar una análisis de sangre. Con el fin de abordar esta cuestión, un microsistema auto impulsado que pueda obtener una cantidad importante de plasma sanguíneo de una gota de sangre seria un primer paso para un análisis de sangre miniaturizado. En esta tesis se utiliza PDMS (Polydimethylsiloxane ) como material de base para la fabricación del microdispositivo debido a su biocompatibilidad y su bajo coste. Uno de los rasgos característicos del dispositivo presentado es que trabaja solo con presión capilar que elimina la necesidad de fuentes externas. La presión capilar solicitada para conducir sangre a través del microdispositivo se obtiene mediante la modificación del PDMS mediante diferentes agentes tensioactivos, que se mezclan con PDMS pre-curado para lograr un carácter hidrófilo estable. El proceso de filtración se basará en una estructura de columnas con baja relación de aspecto. Estás estructuras se han analizado numéricamente, analíticamente y experimentalmente, para obtener un diseño con baja resistencia al flujo. En concreto, se ha diseñado un conjunto de microcolumnas base diamante (dMIMP) que se utilizará como bomba de alto rendimiento y baja resistencia al flujo (35.5 % menor que una bomba microcolumnas circulares (cMIMP)). Para realizar esta caracterización se ha desarrollado un sistema de fabricación que permita caracterizar las estructruas de PDMS, a alta presión sin que se deformen. Por último, se ha utilizado el PDMS modificado y la bomba capilar optimizada para realizar un diseño de microfiltro de plasma sanguíneo de alto rendimiento. El microdispositivo presentado puede separar más de 0.11microL de pla, Award-winning, Postprint (published version)

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 Reviewed, Postprint (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., Peer Reviewed, Postprint (published version)

Peer Reviewed, Postprint (published version)