The thesis aims to study the motion of individual fluorescent molecules in the gel environments, and applies to the sensitive electrophoretic and dielectrophoretic studies. Firstly, dye molecules (Rhodamine B and DiI) are dispersed, and investigate the individual fluorescent spots. Later on, we study the motion of individual B-phycoerythrin molecules under external electrical field driving. Due to the porosity, agarose gel is used to contain the liquid, and the dye molecules can freely move within the pores. Thus, one can easily observe the motion of individual dye molecules under high numerical aperture objectives. B-phycoerythrin is chosen for the high extinction coefficient, native charge, and good fluorescent properties. Our results indicate most dye molecules are attached in the rigid structure of the gel. Only very limited molecular motions are observed. Moreover, we study the dielectrophoretic interaction of the dye molecules. Nano-electrodes are fabricated by electrolysis to have sub-micron aperture silver tips. Due to the high gradient of the electric field, it is used to have strong enough attractive forces around the apex of the tip, to overcome the thermal fluctuations. It allows us further trapping and manipulating small non-charged objects, up to single dye molecules.

Low-cost, highly-sensitivity, and minimally invasive tests for the detection and monitoring of life-threatening cancers can reduce the worldwide disease burden. The disease diagnosis community is constantly working to improve the detection capabilities of the deadly cancers (e.g.: pancreatic and lung) at their early stages. Still there were many cancers cannot be detected at their early stages due to lack of early diagnosis techniques. One of the reason being, many cancers that occur in the body release minute amounts of biomarker molecules during the initial stages (e.g.: DNA, RNA, miRNA and antigens) in the body fluids such as blood and serum. Since the traditional bio-sensing techniques have reached their maximum capacity in terms of critical performance parameters (sensitivity, detection time, reproducibility and limit of detection) there is an urgent need for innovative approaches that can fill this gap. To address this unmet need, here we report on developing a novel bio-sensing technique for detecting and quantifying biomolecules from the patients’ plasma/serum samples at point-of-care settings. Here we have investigated the novel interactions between biomolecules and externally applied fields to effectively manipulate and specifically concentrate them at a certain detection spots near electrodes on the detection device. Then the near-field interactions between the fluorophores and the free electrons on metal surfaces were successfully integrated with the externally applied low frequency (<10MHz) electric field, to achieve maximum florescence enhancement, that produces the detection limit of target-biomolecules in the rage of femto molars (fM). Moreover, the externally applied electric potential produces dielectrophoretic and thermophoretic force on the biomolecules, together with these forces we were able to separate the fluorophore-labelled rare target-biomolecules from the others in a sample. The novel integrated technique is tested and proved to be superior to the current gold standards (qRT-PCR and ELISA) for target-biomolecules detection in critical performance parameters. Finally the technique was used to analyze healthy and pancreatic cancer patients’ samples and further it has been proved that we can differentiate the healthy individuals and cancer patients. In addition, this technique is being applied to the other diseases such as obesity, opioid addiction and other types of cancers.

This thesis presents an analysis of the signal-to-noise ratio in liquid core anti-resonant reflecting optical waveguides (ARROWs) and the application of hydrodynamic focusing to the waveguides. These concepts are presented as a method to improve the detection capabilities of the ARROW platform. The improvements are specifically targeted at achieving single molecule detection (SMD) with the devices. To analyze the SNR of the waveguides a test platform was designed and fabricated. This test platform was then used to examine relationship between the SNR and the location of the excitation region. It was determined that the excitation region should be moved closer to the solid-core. By moving the excitation region closer to the solid-core the distance the signal was required to travel in the hollow-core was reduced. This reduction led to a decrease in optical signal loss and resulted in a more than 2x increase in the SNR. Hydrodynamic focusing in the waveguides was developed as a method to increase the consistency of detection of the devices. In hydrodynamic focusing particles in the sample are forced towards the center of the waveguide with a buffer solution. With the particles focused to the center of the channel the percentage that passed through the excitation region can be increased improving the detection consistency of the device. ARROW chips designed for hydrodynamic focusing were simulated, fabricated, and preliminary testing was performed. Initial results have shown a more than 30% increase in particle focusing.

This work presents detailed numerical calculations of the dielectrophoretic force in octupolar traps designed for single-cell trapping. A trap with eight planar electrodes is studied for spherical and ellipsoidal particles using an indirect implementation of the boundary element method (BEM). Multipolar approximations of orders one to three are compared with the full Maxwell stress tensor (MST) calculation of the electrical force on spherical particles. Ellipsoidal particles are also studied, but in their case only the dipolar approximation is available for comparison with the MST solution. The results show that the full MST calculation is only required in the study of non-spherical particles. / Singapore-MIT Alliance (SMA)

Transparent electrodes (TEs) have become important components of displays, touch screens, and solar photovoltaic (PV) energy conversion devices. As electrodes, they must be electrically conductive while being transparent. Transparent materials are normally poor conductors and materials with high electrical conductivity, such as metals, are typically not transparent. From the few candidate materials, indium tin oxide (ITO) is currently the best available, but indium is an expensive material and ITO cost has risen with increasing demand. Therefore, alternative materials or methods are sought to encourage production needs of applications and help in reducing their price. This thesis presents and discusses results of experimental work for a method, field-directed chaining, to produce a TE device which is nanowire-based, with a figure of merit FoM= 2.39 x10E-4 Ohm E-1, comparable to ITO but with potential for far lower cost. Using electric field-directed chaining, multiple parallel long chains of metal nanowires are assembled on inexpensive transparent materials such as glass by field directed nanowire chaining, using methods first demonstrated in our laboratory. In this work, we have improved the fraction of functional chains, by tuning the field/voltage, a key step in increasing the FoM and lowering the cost. The effect of operating parameters on TE optical and electrical properties has been studied and identified as well. From experiments with twenty seven substrates, each with a range of electric field and nanowire concentration, the highest light transmission achieved is 78% and the lowest sheet resistance achieved is 100 Ohm/sq. Among all the operating parameters, the electric field has the most significant influence on the fraction of nanowire chains that are functional. In the operating range of electric field strength available to us, we observed a monotonic increase in the fraction of functional nanowire chains. We found a counter-intuitive change in TE properties in a sub-range of nanowire concentration, associated with a change in the structure of chained patterns. / Graduate

Les travaux présentés dans ce manuscrit de thèse concernent le développement d’une méthode de caractérisation électrique de cellules biologiques, sans marquage, basée sur la diélectrophorèse Ultra Haute Fréquence (DEP-UHF). Sous l’action d’un champ électrique alternatif non uniforme, les cellules biologiques sont soumises à des forces de déplacement essentiellement liées à leurs propriétés diélectriques. En particulier, aux hautes fréquences, le champ électrique pénètre à l’intérieur de la cellule et interagit donc avec son contenu intracellulaire. Il est donc possible d’accéder à une «signature diélectrophorétique» de la cellule représentative de ses propriétés biologiques internes mais aussi de mécanismes physiologiques tels que l’apoptose ou encore la différenciation. Ce manuscrit présente le développement d’un microsystème innovant, implémenté à partir des couches passives d’une puce BiCMOS et couplé à un réseau microfluidique, pour la caractérisation, à l’échelle cellulaire, par DEP-UHF. Le microsystème développé permet une analyse fine et précise du comportement DEP haute fréquence d’une cellule. Un banc expérimental dédié aux caractérisations cellulaires, capable de générer des signaux hautes fréquences dans la gamme 10 MHz – 1 GHz pour des amplitudes allant jusqu’à 18 Vpp, a été développé. Ces travaux exploratoires ont pour but de démontrer le potentiel de discrimination de cette méthode entre différentes lignées cellulaires cancéreuses humaines à des stades tumoraux différents, dans l’objectif de développer de nouveaux outils d’aide au diagnostic. L’existence de différences significatives entre les signatures de certains types cellulaires ouvre des perspectives très intéressantes notamment pour le développement d’outils de tri cellulaire originaux basés uniquement sur les propriétés diélectriques intracellulaires. / The work presented in this dissertation concerns the development of an original label-free electrical characterization method dedicated to biological cells based on Ultra High Frequency dielectrophoresis (DEP-UHF). Under the action of a non-uniform alternative electric field, the biological cells are subjected to displacement forces related to their own dielectric properties. In particular, at high frequencies, the electric field penetrates inside the cell and thus interacts with its intracellular content. Therefore, it is possible to access to a «dielectrophoretic signature» of the cell that it is representative of its internal biological properties but also of physiological mechanisms such as apoptosis or differentiation. This dissertation presents the development of an innovative microsystem, implemented in the passive layer stack of a BiCMOS chip and associated with microfluidic, dedicated to biological characterization, at the cellular level. The developed microsystem allows an accurate analysis of a single cell DEP-UHF behaviour. An experimental bench, dedicated to cell characterization, and able to generate high frequency signals from 10 MHz to 1 GHz up to 18 Vpp magnitude, has been also developed accordingly. Actually, the led exploratory work achieved was focused on evaluating the discrimination potential of this method between different human cancer cells at different tumor stages with the objective to envision new kind of diagnostic tools. Finally, the existence of significant differences between the signatures of different cell types leads to very interesting perspectives, particularly for the development of new cell sorting tools based especially on the intracellular dielectric properties.

Fluid suspended biological particles (bioparticles) flowing through a non-uniform electric field are actuated by the induced dielectrophoretic (DEP) force, known to be dependent upon the bioparticles’ dielectric phenotypes. In this work: a 10-1000 kHz DEP actuation potential applied to a co-planar microelectrode array (MEA) induces a DEP force, altering passing bioparticle trajectories as monitored using: (1) an optical assay, in which the lateral bioparticle velocities are estimated from digital video; and (2) a capacitive cytometer, in which a 1.478 GHz capacitance sensor measures the MEA capacitance perturbations induced by passing bioparticles, which is sensitive to the bioparticles’ elevations. The experimentally observed and simulated lateral velocity profiles of actuated polystyrene microspheres (PSS) and viable and heat shocked Saccharomyces cerevisiae cells verify that the bioparticles’ dielectric phenotypes can be inferred from the resultant trajectories due to the balance between the DEP force and the viscous fluid drag force.

Fluid suspended biological particles (bioparticles) flowing through a non-uniform electric field are actuated by the induced dielectrophoretic (DEP) force, known to be dependent upon the bioparticles’ dielectric phenotypes. In this work: a 10-1000 kHz DEP actuation potential applied to a co-planar microelectrode array (MEA) induces a DEP force, altering passing bioparticle trajectories as monitored using: (1) an optical assay, in which the lateral bioparticle velocities are estimated from digital video; and (2) a capacitive cytometer, in which a 1.478 GHz capacitance sensor measures the MEA capacitance perturbations induced by passing bioparticles, which is sensitive to the bioparticles’ elevations. The experimentally observed and simulated lateral velocity profiles of actuated polystyrene microspheres (PSS) and viable and heat shocked Saccharomyces cerevisiae cells verify that the bioparticles’ dielectric phenotypes can be inferred from the resultant trajectories due to the balance between the DEP force and the viscous fluid drag force.