System Integration - A Major Step toward Lab on a Chip

Microfluidics holds great promise to revolutionize various areas of biological engineering, such as single cell analysis, environmental monitoring, regenerative medicine, and point-of-care diagnostics. Despite the fact that intensive efforts have been devoted into the field in the past decades, microfluidics has not yet been adopted widely. It is increasingly realized that an effective system integration strategy that is low cost and broadly applicable to various biological engineering situations is required to fully realize the potential of microfluidics. In this article, we review several promising system integration approaches for microfluidics and discuss their advantages, limitations, and applications. Future advancements of these microfluidic strategies will lead toward translational lab-on-a-chip systems for a wide spectrum of biological engineering applications

Localized Surface Plasmon Resonance Sensing and its Interplay with Fluidics

In this Feature Article, we discuss the interplay between fluidics and the localized surface plasmon resonance (LSPR) sensing technique, primarily focusing on its applications in the realm of bio/chemical sensing within fluidic environments. Commencing with a foundational overview of LSPR principles from a sensing perspective, we subsequently showcase the development of a streamlined LSPR chip integrated with microfluidic structures. This integration opens the doors to advanced experiments involving fluid dynamics, greatly expanding the scope of LSPR-based research. Our discussions then turn to the practical implementation of LSPR and microfluidics in real-time biosensing, with a specific emphasis on monitoring DNA polymerase activity. Additionally, we illustrate the direct sensing of biological fluids, exemplified by the analysis of urine, while also shedding light on a unique particle assembly process that occurs on LSPR chips. We not only discuss the significance of LSPR sensing but also explore its potential to investigate a plethora of phenomena at liquid–liquid and solid–liquid interfaces. This is particularly noteworthy, as existing transduction methods and sensors fall short in fully comprehending these interfacial phenomena. Concluding our discussion, we present a futuristic perspective that provides insights into potential opportunities emerging at the intersection of fluidics and LSPR sensing

Characterization and modelling of micro and nanofluidic systems

Lab-on-a-chip arrangements are ever more frequently used for the miniaturization of chemical and biochemical analysis. In these arrangements, all the manipulations of analyte transport, separation, mixing with reactants and detection are integrated and implemented at the scale of a microchip of several cm in size. This makes possible a dramatic reduction in the required amounts of analytes and reactants, as well as in the time of analysis. Besides that, automation and high-throughput operations (due to parallelization) become much easier than in the conventional "macro-laboratory" environments. According to the great interest in the development of new porous materials including their subsequent integration into biomedical devices and industrial applications, the description of the characteristics of nanoporous media (for example membranes) and the development of characterization techniques are crucial for controlling the behavior of systems that include separation and purification processes with such technologies. Within this thesis various developments in the field of microfluidics, separation and purification of substances has been carried out: For the field of microfluidics, this study may be useful for the description of the first stages of the concentration polarization in microfluidic systems coupling membrane technology or micro/nano interfaces. Furthermore, it was shown that for such systems, Taylor-Aris theory is applicable locally in large open microchannels within a range of Peclet numbers. Furthermore, it was possible to derive a simple analytical approach for internal concentration gradient within long channels in terms of only a few parameters, determined numerically. This approach is useful for developing future experimental studies. In equipment used for measuring the zeta potential of porous media, the variation in the channel height is technically possible. This thesis shows that under such conditions, the fluid flow can become undeveloped turbulent, which provokes that conventional approaches to the interpretation of electrokinetic measurements should be changed accordingly. A mathematical model for arbitrary electrolytes mixtures has been defined to describe the transport phenomena occurring in several osmotic separation processes. The limited number of adjustable parameters contained in this model makes possible its unequivocal determination from a limited set of experimental data. According to the results of this work, hollow fibers membrane contactors are useful as a polishing step for removing low levels of ammonia in water. It has been determined and validated experimentally a mathematical model which helps to describe the influence of operating conditions, such as flow, ammonia concentration and pH of the system for both configurations, closed and open loop. These results are important for designing production systems of ultrapure water that can be used in the production of hydrogen by water electrolysis. The application of microfluidics technologies at industrial scale is one of the main challenges faced on this knowledge field; however, there are some devices that are already being used systematically at industrial level for separation purposes that fulfil the criteria for being considered within that group of technologies. This thesis establishes patterns and basic concepts that can serve as basis for the characterization and description of miniature versions of well-known separation processes, which in turn, can be used for the development of processes in new biochemical applications.La miniaturización de los análisis químicos y bioquímicos está cada vez utiliza más utilizada. Todas las manipulaciones de transporte de las muestras, la separación, la mezcla con los reactivos y la detección se integren y apliquen a escala de un microchip de varios centímetros de tamaño. Esto hace posible una reducción dramática en las cantidades requeridas de muestra y reactivos, así como en el tiempo del análisis. Además de eso, las operaciones de automatización y de alto rendimiento se vuelven mucho más fáciles que en los entornos convencionales "macro-laboratorio". De acuerdo con el gran interés en el desarrollo de nuevos materiales porosos incluyendo su posterior integración en dispositivos biomédicos y aplicaciones industriales, la descripción de las particularidades de los medios nanoporosos (por ejemplo membranas) y el desarrollo de técnicas de caracterización son cruciales para controlar el comportamiento de los sistemas que incluyen procesos de separación y purificación con dichas tecnologías. En esta tesis se han llevado a cabo diferentes avances en el campo de la microfluídica, la separación y purificación de sustancias: Para el campo de la microfluídica, este estudio puede ser útil para la descripción de las primeras etapas de la polarización en los sistemas microfluídicos que acoplan tecnología de membranas o micro/nano interfaces. Por otro lado, se demostró que para tales sistemas, la teoría de Taylor-Aris es aplicable localmente dentro de microcanales abiertos en una amplia gama de números de Péclet. Además, fue posible derivar una aproximación analítica sencilla para el gradiente de concentración interno dentro de canales largos en términos de sólo unos pocos parámetros, determinados numéricamente. Esta aproximación es útil para desarrollar futuros estudios experimentales. En algunos equipos usados para la medición del potencial zeta de medios porosos, la variación de la altura del canal es técnicamente posible. En esta tesis se muestra que en estas condiciones, el flujo de fluido puede llegar a ser de transición a turbulento y los enfoques convencionales para la interpretación de las mediciones electrocinéticas debe modificarse en consecuencia. Se definió un modelo matemático que permite describir de manera sencilla, fenómenos de transporte que ocurren en diversos procesos de separación osmóticos, para mezclas de electrolitos arbitrarias. El número limitado de parámetros ajustables que contiene este modelo hace factible su determinación inequívoca a partir de un conjunto limitado de datos experimentales. De acuerdo con los resultados de esta tesis, los contactores de membrana con fibras huecas son útiles como etapa de pulido para la eliminación de bajos niveles de amonio en agua. Se ha determinado y validado experimentalmente un modelo matemático el cual ha ayudado a describir la influencia de las condiciones de funcionamiento, tales como flujo, concentraciones de amonio y pH del sistema para ambas configuraciones, de lazo cerrado y abierto. Dichos resultados son útiles para el diseño de sistemas de producción de agua ultra pura que puede ser usada en la producción de hidrogeno por electrolisis. La aplicación de las tecnologías de microfluidos a escala industrial es uno de los principales retos que enfrentar en este campo del conocimiento; sin embargo, existen algunos dispositivos que ya se están utilizando de forma sistemática a nivel industrial para fines de separación que cumplen criterios necesarios para considerarlos dentro del grupo de las tecnologías de microfluídica. Acotando a los resultados presentados en microfluídica, con este trabajo se han establecido patrones y definido conceptos básicos, dentro de este campo de la ciencia, que pueden servir como bases en la caracterización y la descripción de versiones en miniatura de procesos de separación bien conocidos, los cuales se pueden usar para el desarrollo de procesos en nuevas aplicaciones bioquímicas

Operando Single Particle Catalysis - Combining a Nanoreactor and Plasmonic Nanospectroscopy

Heterogeneous catalysis is an important cornerstone of modern society with strong ties to the development of sustainable sources of energy and products. Catalysts are typically realized as supported metal nanoparticles that offer active sites that can accelerate chemical reactions by providing energetically more favorable reaction paths. Despite their broad use, the scrutiny of catalysts under realistic application conditions, such as high pressure and temperature, is a major experimental challenge. This difficulty is further amplified by the complexity present in real catalysts, often consisting of large ensembles of nanoparticles that all are unique. Furthermore, reactors used in catalysis studies often give rise to ill-defined reaction conditions in terms of catalyst distribution, reactant concentration and temperature. To mitigate these challenges, techniques are being developed to enable studies of catalytic nanoparticles under relevant operation conditions, so-called operando techniques. In this context, down-sized chemical reactors can be utilized to achieve precise control of both the catalyst, and the operating conditions. In this thesis, I have performed in situ studies of chemical reactions in/on nanoparticles by utilizing plasmonic nanospectroscopy based on the localized surface plasmon resonance (LSPR) phenomenon. The resonance condition for LSPR depends on both nanoparticle properties (size, shape, material) and the surrounding medium, which makes it possible to determine the physical and chemical state of individual nanoparticles optically. The LSPR response was used to study the oxidation of Cu nanoparticles, revealing the complex nature of nanoparticle oxidation kinetics, as well as particle specific oxidation mechanisms. Furthermore, a nanoreactor platform was developed and used in combination with plasmonic nanospectroscopy to perform operando characterization of individual Cu and Pt catalyst nanoparticles during CO oxidation. The obtained results illustrate how the oxidation of Cu results in catalyst deactivation and how reactant gradients formed inside the catalyst bed strongly affects the state of the catalyst, and thus its activity. Moreover, the nanoreactor enabled operando characterization of catalyst beds comprising 1000 well defined nanoparticles that could be individually addressed

Methods for immobilizing receptors in microfluidic devices: A review

In this review article, we discuss state-of-the-art methods for immobilizing functional receptors in microfluidic devices. Strategies used to immobilize receptors in such devices are essential for the development of specific, sensitive (bio)chemical assays that can be used for a wide range of applications. In the first section, we review the principles and the chemistry of immobilization techniques that are the most commonly used in microfluidics. We afterward describe immobilization methods on static surfaces from microchannel surfaces to electrode surfaces with a particular attention to opportunities offered by hydrogel surfaces. Finally, we discuss immobilization methods on mobile surfaces with an emphasis on both magnetic and non-magnetic microbeads, and finally, we highlight recent developments of new types of mobile supports

DEVELOPING NANOPORE ELECTROMECHANICAL SENSORS WITH TRANSVERSE ELECTRODES FOR THE STUDY OF NANOPARTICLES/BIOMOLECULES

This study concerns development of a technology of utilizing metallic nanowires for a sensing element in nanofluidic single molecular (nanoparticle) sensors formed in plastic substrates to detect the translocation of single molecules through the nanochannel. We aimed to develop nanofluidic single molecular sensors in plastic substrates due to their scalability towards high through and low cost manufacturing for point-of-care applications. Despite significant research efforts recently on the technologies and applications of nanowires, using individual nanowires as electric sensing element in nanofluidic bioanalytic devices has not been realized yet. This dissertation work tackles several technical challenges involved in this development, which include reduction of nanowire agglomerates in the deposition of individual nanowires on a substrate, large scale alignment/assembly of metallic nanowires, placement of single nanowires on microelectrodes, characterization of electrical conductance of single nanowire, bonding of a cover plate to a substrate with patterned microelectrodes and nanowire electrodes. Overcoming the abovementioned challenges, we finally demonstrated a nanofluidic sensor with an in-plane nanowire electrode in poly(methyl methacrylate) substrates for sensing single biomolecules. In the first part of this study, we developed the processes for separation and large-scale assembly of individual NiFeCo nanowires grown using an electrodeposition process inside a porous alumina template. A method to fabricate microelectrode patterns on plastic substrates using flexible stencil masks was developed. We studied electrical and magnetic properties of new composite core-shell nanowires by measuring the electrical transport through individual nanowires. The core-shell nanowires were composed of a mechanically stable FeNiCo core and an ultrathin shell of a highly conductive Au gold (FeNiCo-Au nanowires). In the second part of this study, we simulated the effects of the nanopore geometry on the current drop signal of the translocation through a nanopore via finite element method using COMSOL. Using the above techniques, we developed for the fabrication and alignment of the microelectrodes and nanowires, we studied the optimum conditions to integrate the transverse nanoelectrode with the nanochannel on plastic substrates. The main challenge was to find the conditions to embed the micro-/nanoelectrodes into the nanochannel substrate as well as the nanochannel cover sheet