Microdevices and Microsystems for Cell Manipulation

Microfabricated devices and systems capable of micromanipulation are well-suited for the manipulation of cells. These technologies are capable of a variety of functions, including cell trapping, cell sorting, cell culturing, and cell surgery, often at single-cell or sub-cellular resolution. These functionalities are achieved through a variety of mechanisms, including mechanical, electrical, magnetic, optical, and thermal forces. The operations that these microdevices and microsystems enable are relevant to many areas of biomedical research, including tissue engineering, cellular therapeutics, drug discovery, and diagnostics. This Special Issue will highlight recent advances in the field of cellular manipulation. Technologies capable of parallel single-cell manipulation are of special interest

Micro/Nano-Chip Electrokinetics

Micro/nanofluidic chips have found increasing applications in the analysis of chemical and biological samples over the past two decades. Electrokinetics has become the method of choice in these micro/nano-chips for transporting, manipulating and sensing ions, (bio)molecules, fluids and (bio)particles, etc., due to the high maneuverability, scalability, sensitivity, and integrability. The involved phenomena, which cover electroosmosis, electrophoresis, dielectrophoresis, electrohydrodynamics, electrothermal flow, diffusioosmosis, diffusiophoresis, streaming potential, current, etc., arise from either the inherent or the induced surface charge on the solid-liquid interface under DC and/or AC electric fields. To review the state-of-the-art of micro/nanochip electrokinetics, we welcome, in this Special Issue of Micromachines, all original research or review articles on the fundamentals and applications of the variety of electrokinetic phenomena in both microfluidic and nanofluidic devices

Micromanipulation in microfluidics using optoelectronic and acoustic tweezing

The thesis introduces a concept for a unified platform that enables the use of acoustic and electric fields for particle manipulations in microfluidic environments. In particular, optoelectronic tweezing (OET), also known as light induced dielectrophoresis is fused with acoustic tweezing, also known as acoustophoresis, on a versatile system. The system can be divided into two individual physical units. The first one represents the OET unit which integrates light induced electric fields into a robust microfluidic chip. The OET chip not only operates as a device for electric field generation but also as a transverse resonator to confine acoustic fields. These fields are the result of travelling surface acoustic waves excited by a piezoelectric transducer which defines the second unit. The developed platform is applied to a range of applications such as particle trapping, transporting, focussing, sorting as well particle alterations in form of cell lysis and microbubble insonation

The Effect of Proteome and Lipidome on the Behavior of Membrane Bound Systems in Thermally-Assisted Acoustophoresis

Changes in the biomechanical properties of cells accompanying the development of various pathological conditions have been increasingly reported as biomarkers for various diseases, including cancers. In cancer cells, the membrane properties have been altered compared to their healthy counterparts primarily due to proteomic and lipidomic dysregulations conferred by the underlying pathology. The separation and selective recovery of these cells or extracellular vesicles secreted from such cells is of high diagnostic and prognostic value. In this dissertation, the research builds on thermally-assisted acoustophoresis technique which was developed in our laboratory for the separation of vesicles of the same size, charge and shape yet with varying physical properties. This technique uses the inherent thermotropic behavior of lipid membrane to identify a distinct acoustic contrast temperature (Tϕ) for each individual composition under acoustophoresis. By tuning the temperature, the acoustic contrast factor (Φ) of vesicle systems experience a signature temperature at which sign of Φ switches from positive to negative. This temperature is defined as the acoustic contrast temperature, Tϕ. Since various vesicles systems have distinct Tϕ values, it allowed the development of a separation method of vesicles based on their membrane properties, with target outlet purities exceeding 95%. Over-expression and under-expression of proteins play crucial roles in the functionality of cells and can be indicators of pathological disorders. Using systematic designed experiments, the effect of membrane protein content in vesicles was studies. Using three different transmembrane peptides (gramicidin, alamethicin and melittin), the thermo-acoustofluidic properties of vesicles were studied in an in-house built lab-on-chip to assess the separation efficiencies for various protein contents. To demonstrate the utility of this method and its performance on real biological samples, the effect of proteins on thermally-dependent acoustic properties of red blood cells were investigated. The separation of red blood cells based on expressed membrane proteins of different contents proved to yield to distinctive Tϕ values that afforded the separation of the cells. The simplicity, rapidity, and label-free nature of this approach holds promise as a diagnostic and separation tool for cells affected by diseases that affect the physical properties of membrane and extracellular vesicles such as exosomes and microvesicles

Microfluidics and Nanofluidics Handbook

The Microfluidics and Nanofluidics Handbook: Two-Volume Set comprehensively captures the cross-disciplinary breadth of the fields of micro- and nanofluidics, which encompass the biological sciences, chemistry, physics and engineering applications. To fill the knowledge gap between engineering and the basic sciences, the editors pulled together key individuals, well known in their respective areas, to author chapters that help graduate students, scientists, and practicing engineers understand the overall area of microfluidics and nanofluidics. Topics covered include Finite Volume Method for Numerical Simulation Lattice Boltzmann Method and Its Applications in Microfluidics Microparticle and Nanoparticle Manipulation Methane Solubility Enhancement in Water Confined to Nanoscale Pores Volume Two: Fabrication, Implementation, and Applications focuses on topics related to experimental and numerical methods. It also covers fabrication and applications in a variety of areas, from aerospace to biological systems. Reflecting the inherent nature of microfluidics and nanofluidics, the book includes as much interdisciplinary knowledge as possible. It provides the fundamental science background for newcomers and advanced techniques and concepts for experienced researchers and professionals

Self-powered mobile sensor for in-pipe potable water quality monitoring

Traditional stationary sensors for potable-water quality monitoring in a wireless sensor network format allow for continuous data collection and transfer. These stationary sensors have played a key role in reporting contamination events in order to secure public health. We are developing a self-powered mobile sensor that can move with the water flow, allowing real-time detection of contamination in water distribution pipes, with a higher temporal resolution. Functionality of the mobile sensor was tested for detecting and monitoring pH, Ca2+, Mg2+, HCO3-/CO32-, NH4+, and Clions. Moreover, energy harvest and wireless data transmission capabilities are being designed for the mobile sensor

New lab-on-a-chip strategies for enantio-selective and non-diffusion-limited biosensing

The race for fast and small that drives nowadays society has also reached the field of biosensing. Looking for efficient and cost effective biosensors for applications including screening and treatment monitoring, biomolecular engineering, drug design and food industry; plasmonics and microfluidics technologies have synergistically grown to offer the most attractive solutions. The recent progress in nano-optics has paved the route toward the development of highly sensitive and label-free optical transducers using the localized surface plasmon resonance (LSPR). Additionally, LSPR offer high-end miniaturization and high degree of tunability of both sensors’ spatial and spectral responses. These unique properties have recently been interfaced with microfluidics towards lab-on-a-chip (LOC) functional platforms which offer reduced sample volumes and multi-tasking operations on a single chip. Combining nano-optics, microfluidics and biochemical sensing makes this PhD project highly multidisciplinary. This blend aims at pushing the limits of LSPR sensing by addressing two significant problems in the biosensing community. On one hand, we went through chiral plasmonic sensing. Chiral molecules exhibit signatures in the ultraviolet frequency region. They are typically characterized by circular dichroism (CD), which suffers of low sensitivity and the need of big sample volumes and concentrations. Plasmonic nanostructures have the potential to enhance the sensitivity of chiral detection and translate the molecular signatures to the visible spectral range. However, to date, it remains unclear which properties plasmonic sensors should exhibit to maximize this effect and apply it to reliable enantiomer discrimination. As a consequence, a collection of results of difficult interpretation and cross comparison can be found in the literature. Here, we bring further insight into this complex problem and present a chiral plasmonic sensor composed of a racemic mixture of gammadions that enables us to directly differentiate enantiomers. We also present a plasmo-fluidic sensing platform, which allows the systematic study of chiral biomolecules by enabling multiple sensing assays on a single chip. On the other hand, we addressed one of the major challenges of plasmonic sensing in microfluidics environments; the transport of the analyte to the sensor surface, which due to the laminar flow that rules in micro-channels, is limited by Brownian diffusion. Hence, dictates the total duration of the sensing assay. Here, we use the electrothermoplasmonic (ETP) effect to overcome this limit through opto-electrical fluid convective flow generation. To this end, we designed a LSPR sensing chip that integrates ETP operation into state-of-the-art microfluidics. Our results demonstrate that ETP-LSPR has improved performances over standard LSPR.La continua carrera de la miniaturización y la velocidad, que gobierna la sociedad tecnológica de hoy en día, ha alcanzado también el campo de los bio-sensores. Plasmónica y micro-fluídica, dos tecnologías complementarías, han crecido durante sinérgicamente en las últimas. Juntas son capaces de atender la exigente demanda de soluciones más efectivas y económicas en campos como el diagnóstico y tratamiento médico personalizado, la ingeniería bio-molecular, el diseño de fármacos y la industria alimentaria. El reciente progreso del campo de la nano-óptica ha forjado el camino para el desarrollo de sensores ópticos altamente sensibles y sin requerimiento de marcadores moleculares. Los sensores basados en resonancias plasmónicas superficiales localizadas (LSPR) son de gran atractivo debido a sus posibilidades de miniaturización y versatilidad en la caracterización de sus respuestas espaciales y espectrales. Estas propiedades únicas se han combinado recientemente con la micro-fluídica, dando lugar a plataformas funcionales integradas, conocidas como laboratorios en un chip (LOC). Dichas plataformas permiten reducir significativamente los volúmenes de muestra, además de realizar multiples operaciones en un solo chip. La combinación de la nano-óptica, la microfluídica y la detección bioquímica hacen de este proyecto de doctorado una tarea altamente multidisciplinar. Esta mezcla opta por llevar los límites de los sensores LSPR enfrentando dos de los problemas más notables en las últimas décadas: la detección de moléculas quirales mediante plasmónica y transporte molecular en micro-canales. Las moléculas quirales muestran respuestas ópticas en el rango ultravioleta del espectro y son comúnmente caracterizadas mediante dicroísmo circular (CD). Sin embargo, dicha respuesta óptica es minúscula y requieres grandes concentraciones y volúmenes de muestra para ser media. La plasmónica tiene el potencial de aumentar sensibilidad de los métodos actuales y además trasladar la respuesta quiral al rango visible. Aunque hasta la fecha, no se han conseguido predecir las propiedades óptimas que deben poseer los sensores para realizar dicha tarea de forma eficiente. En consecuencia, existen una variedad de trabajos publicados difíciles de interpretar y de enlazar. En este sentido hemos conseguido desarrollar un sensor compuesto por una mezcla racémica de cruces gamadas que es capaz de diferenciar entre enantiómeros de forma directa. Además, también presentamos una plataforma plasmónica y fluídica que permite el estudio sistemático de moléculas quirales mediante la realización de multiples ensayos simultáneos en un solo chip. Por otro lado, abordamos la limitación del transporte de moléculas por difusión browniana en micro-canales. Un problema que limita la velocidad en la detección de los sistemas que integran sensores plasmónicos con la microfluídica. En este frente, utilizamos el efecto electro-termo-plasmónico (ETP) para rebasar este límite a través de la generación de flujos convectivos que alteran el flujo laminar que impera en los micro-canales. Con este fin, hemos diseñado un chip que integra el estado del arte de la microfluídica con el efecto ETP. Los resultados que ofrecemos demuestran que el rendimiento de un ensayo en el nuevo sistema ETP-LSPR es superior al realizado en un LSPR estándar.Postprint (published version

Development of a Lab-on-a-Chip Device for Rapid Nanotoxicity Assessment In Vitro

Increasing useof nanomaterials in consumer products and biomedical applications creates the possibilities of intentional/unintentional exposure to humans and the environment. Beyond the physiological limit, the nanomaterialexposure to humans can induce toxicity. It is difficult to define toxicity of nanoparticles on humans as it varies by nanomaterialcomposition, size, surface properties and the target organ/cell line. Traditional tests for nanomaterialtoxicity assessment are mostly based on bulk-colorimetric assays. In many studies, nanomaterials have found to interfere with assay-dye to produce false results and usually require several hours or days to collect results. Therefore, there is a clear need for alternative tools that can provide accurate, rapid, and sensitive measure of initial nanomaterialscreening. Recent advancement in single cell studies has suggested discovering cell properties not found earlier in traditional bulk assays. A complex phenomenon, like nanotoxicity, may become clearer when studied at the single cell level, including with small colonies of cells. Advances in lab-on-a-chip techniques have played a significant role in drug discoveries and biosensor applications, however, rarely explored for nanomaterialtoxicity assessment. We presented such cell-integrated chip-based approach that provided quantitative and rapid response of cellhealth, through electrochemical measurements. Moreover, the novel design of the device presented in this study was capable of capturing and analyzing the cells at a single cell and small cell-population level. We examined the change in exocytosis (i.e. neurotransmitterrelease) properties of a single PC12 cell, when exposed to CuOand TiO2 nanoparticles. We found both nanomaterials to interfere with the cell exocytosis function. We also studied the whole-cell response of a single-cell and a small cell-population simultaneously in real-time for the first time. The presented study can be a reference to the future research in the direction of nanotoxicity assessment to develop miniature, simple, and cost-effective tool for fast, quantitative measurements at high throughput level. The designed lab-on-a-chip device and measurement techniques utilized in the present work can be applied for the assessment of othernanoparticles\u27 toxicity, as well

Microfluidics for Biosensing and Diagnostics

Efforts to miniaturize sensing and diagnostic devices and to integrate multiple functions into one device have caused massive growth in the field of microfluidics and this integration is now recognized as an important feature of most new diagnostic approaches. These approaches have and continue to change the field of biosensing and diagnostics. In this Special Issue, we present a small collection of works describing microfluidics with applications in biosensing and diagnostics