Parallel manipulation of individual magnetic microbeads for lab-on-a-chip applications

Many scientists and engineers are turning to lab-on-a-chip systems for cheaper and high throughput analysis of chemical reactions and biomolecular interactions. In this work, we developed several lab-on-a-chip modules based on novel manipulations of individual microbeads inside microchannels. The first manipulation method employs arrays of soft ferromagnetic patterns fabricated inside a microfluidic channel and subjected to an external rotating magnetic field. We demonstrated that the system can be used to assemble individual beads (1-3µm) from a flow of suspended beads into a regular array on the chip, hence improving the integrated electrochemical detection of biomolecules bound to the bead surface. In addition, the microbeads can follow the external magnet rotating at very high speeds and simultaneously orbit around individual soft magnets on the chip. We employed this manipulation mode for efficient sample mixing in continuous microflow. Furthermore, we discovered a simple but effective way of transporting the microbeads on-chip in the rotating field. Selective transport of microbeads with different size was also realized, providing a platform for effective sample separation on a chip. The second manipulation method integrates magnetic and dielectrophoretic manipulations of the same microbeads. The device combines tapered conducting wires and fingered electrodes to generate desirable magnetic and electric fields, respectively. By externally programming the magnetic attraction and dielectrophoretic repulsion forces, out-of-plane oscillation of the microbeads across the channel height was realized. Furthermore, we demonstrated the tweezing of microbeads in liquid with high spatial resolutions by fine-tuning the net force from magnetic attraction and dielectrophoretic repulsion of the beads. The high-resolution control of the out-of-plane motion of the microbeads has led to the invention of massively parallel biomolecular tweezers.Ph.D.Committee Chair: Hesketh, Peter; Committee Member: Allen, Mark; Committee Member: Degertekin, Levent; Committee Member: Lu, Hang; Committee Member: Yoda, Minam

Cell Manipulations with Dielectrophoresis

Biological sample analysis is a costly and time-consuming process. It involves highly trained technicians operating large and expensive instruments in a temperature and dust controlled environment. In the world of rising healthcare cost, the drive towards a more cost-effective solution calls for a point-of-care device that performs accurate analyses of human blood samples. To achieve this goal, today's bulky laboratory instruments need to be scaled down and integrated on a single microchip of only a few square centimeters or millimeters in size. Dielectrophoresis (DEP), a phenomenon where small particles such as human blood cells are manipulated by non-uniform electric fields, stands to feature prominently in the point-of-care device. An original device that enhances DEP effect through novel geometry of the electrodes is presented. When activated with two inverting sinusoidal waveforms, the novel-shaped electrodes generate horizontal bands of increasing electric fields on the surface of the microchip. With these bands of electric fields, particles can be manipulated to form a straight horizontal line at a predictable location. Experimental results showing the collection, separation, and transportation of mammalian cells are presented. A strategy for simultaneous processing of two or more types of particles is also demonstrated. With capabilities for an accurate position control and an increased throughput by parallel processing, the novel microchip device delivers substantial improvements over the existing DEP designs. The research presented here explores the effects of novel electrode geometries in cell manipulations and contributes to the overall progress of an automated blood analysis system

Manipulation of Polystyrene Microparticles on a Microchannel Glass

Bulk quantities of spherical microbeads have various applications in research and industrial fields. Simple techniques are required to be developed in order to manipulate and modify large numbers of these beads simultaneously. In our experiment, a microchannel glass-based microfluidic device is used to actuate large numbers of microbeads in parallel. The microchannel glass used in these experiments contains channels 4.1 μm in diameter. The microbeads are polystyrene beads which are superparamagnetic in nature and 5-6 μm in diameter. An aqueous suspension of microbeads is injected into a 2-chamber fluid cell that contains a separator, microchannel glass. The beads are reversibly immobilized on the surface of the microchannel glass by the application of suction with the help of a syringe pump. Assessment of bead movement is performed using optical microscopy. Optical micrographs and the live video for various experimental results are presented. Several experiments were performed by varying flow rates in order to manipulate the beads and the data of flow rates is tabulated. The speed of the beads is calculated and is correlated with flow rates in different chambers. The results were studied by plotting the flow rates and speed of the beads. Microbeads are also immobilized by applying pressure in fluid cell. The pressure is applied by weights suspended and held on syringes at respective positions. Several experiments are performed by applying varied pressures in different chambers and these pressures are plotted. Optical micrographs and the live video for various applied pressures are presented

Development of a PDMS Based Micro Total Analysis System for Rapid Biomolecule Detection

The emerging field of micro total analysis system powered by microfluidics is expected to revolutionize miniaturization and automation for point-of-care-testing systems which require quick, efficient and reproducible results. In the present study, a PDMS based micro total analysis system has been developed for rapid, multi-purpose, impedance based detection of biomolecules. The major components of the micro total analysis system include a micropump, micromixer, magnetic separator and interdigitated electrodes for impedance detection. Three designs of pneumatically actuated PDMS based micropumps were fabricated and tested. Based on the performance test results, one of the micropumps was selected for integration. The experimental results of the micropump performance were confirmed by a 2D COMSOL simulation combined with an equivalent circuit analysis of the micropump. Three designs of pneumatically actuated PDMS based active micromixers were fabricated and tested. The micromixer testing involved determination of mixing efficiency based on the streptavidin-biotin conjugation reaction between biotin comjugated fluorescent microbeads and streptavidin conjugated paramagnetic microbeads, followed by fluorescence measurements. Based on the performance test results, one of the micromixers was selected for integration. The selected micropump and micromixer were integrated into a single microfluidic system. The testing of the magnetic separation scheme involved comparison of three permanent magnets and three electromagnets of different sizes and magnetic strengths, for capturing magnetic microbeads at various flow rates. Based on the test results, one of the permanent magnets was selected. The interdigitated electrodes were fabricated on a glass substrate with gold as the electrode material. The selected micropumps, micromixer and interdigitated electrodes were integrated to achieve a fully integrated microfluidic system. The fully integrated microfluidic system was first applied towards biotin conjugated fluorescent microbeads detection based on streptavidin-biotin conjugation reaction which is followed by impedance spectrum measurements. The lower detection limit for biotin conjugated fluorescent microbeads was experimentally determined to be 1.9 x 106 microbeads. The fully integrated microfluidic system was then applied towards immuno microbead based insulin detection. The lower detection limit for insulin was determined to be 10-5M. The total detection time was 20 min. An equivalent circuit analysis was performed to explain the impedance spectrum results

Fundamental studies of AC/DC electrokinetic phenomena for the realization of microchip capillary electrophoresis for single-cell analysis

The goal of this research was to investigate AC and DC electrokinetic phenomena to better understand their individual and combined effects on particle and fluid motions in microchannels in order to realize microchip capillary electrophoresis for single cell analysis. AC-DC electroosmotic flow interaction was studied by observing the motions of polystyrene microbeads suspended in deionized water in a microchannel as the main AC and DC electrokinetics parameters were varied.Particle-particle interactive dielectrophoretic (DEP) force under electrohydrodynamic flow conditions was studied by performing experiments on a microchannel - microelectrode system containing polystyrene beads and comparing the experimental results with numerical simulation results using the Maxwell stress tensor calculation. Efficient sample injection and separation is another key to successful microchip CE. Accurate numerical studies were performed for understanding 3-D characteristics of the dispersion of sample species that is injected and carried by electroosmotic flow in diverse microchannel geometries. The following three cases were investigated; 1) non-rectangular cross section of microchannels, 2) different zeta potential for the top and bottom microchannel substrates, and 3) development of internal pressure gradient by variation of electric or electrokinetic properties along the channel direction. The results of the numerical study for the aforementioned 3 cases showed that 3-D modeling is crucial for accurate predictions of sample injection and migration in microchip electrophoresis system. Finally, continuous cell lysis in microchip CE devices was investigated experimentally by adopting a combination of electrical and osmotic cell lysis methods. The concept of continuous single cell lysis and CE was proven by analysis of single red blood cells labeled with FITC.Ph.D., MechanicalEngineering and Mechanics -- Drexel University, 201

Particles Separation in Microfluidic Devices, Volume II

Microfluidic platforms are increasingly being used for separating a wide variety of particles based on their physical and chemical properties. In the past two decades, many practical applications have been found in chemical and biological sciences, including single cell analysis, clinical diagnostics, regenerative medicine, nanomaterials synthesis, environmental monitoring, etc. In this Special Issue, we invited contributions to report state-of-the-art developments in the fields of micro- and nanofluidic separation, fractionation, sorting, and purification of all classes of particles, including, but not limited to, active devices using electric, magnetic, optical, and acoustic forces; passive devices using geometries and hydrodynamic effects at the micro/nanoscale; confined and open platforms; label-based and label-free technology; and separation of bioparticles (including blood cells), circulating tumor cells, live/dead cells, exosomes, DNA, and non-bioparticles, including polymeric or inorganic micro- and nanoparticles, droplets, bubbles, etc. Practical devices that demonstrate capabilities to solve real-world problems were of particular interest

Micro-Particle Operations Using Asymmetric Traps

Micro-particles are a great tool to detect biomolecules for their high multiplexing capability, wide options of materials, and scalability. Currently, most of the platforms utilizing micro-particles are bench-top scale instruments equipped with bulky devices for fine spatiotemporal control of micro-particles. This requirement for resources restricts the environment where micro-particles can be applied. To this problem, microfluidic techniques are an attractive solution because of its inherent capability of fine controlling of micro-particle due to scale matching. This dissertation describes the development of the micro-particle operations using the asymmetric trap, a new mechanical trap that has flow direction dependent particle capturing behavior. Based on the theory of deterministic lateral displacement of micro-particle in periodic obstacle array and mass balance relationships, we provide a model that connects characteristic trap-particle interactions to critical dimensions including particle diameter and the gaps of the asymmetric traps. We theoretically predicted and experimentally observed five different trap-particle interactions including one-way particle transport, symmetric passage, symmetric capturing, trap skipping in zig-zag mode, and trap skipping in bump mode. Our model could explain most of the experimental results (particle diameter = 20.3 µm, Re < 0.01). Based on our modeling of particle dynamics in the asymmetric traps, we explore micro-particle operations using the asymmetric traps. One-way particle transport, the basic transport function using asymmetric traps, could displace hundreds of micro-particles across trap rows in only a few fluid oscillations (<500 ms per oscillation). On top of that, the segregation, medium exchange, and focusing and splitting of micro-particle in oscillatory flow were accomplished by capitalizing on two features: difference in the transport speeds of the trap-particle interaction dynamics and transport polarity of the asymmetric traps. At first, segregation of micro-particle mixture was achieved by utilizing the difference in transport speeds of trap-particle interaction dynamics. In the investigation of factors of the segregation performance, we found that the number of rows is the critical factor for a high performance of the segregation. Next, medium exchange of the particles in oscillatory flow was successfully demonstrated. At modest amplitude and number of fluid oscillations, the particle could be displaced into a new medium over the mixing region. Lastly, we could focus and split of groups of micro-particles in a few fluid oscillations by exploiting transport polarity of the asymmetric traps.PHDChemical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/138628/1/netjigi_1.pd

Investigation of dielectrophoresis and its applications in micro/nano fluidics, electronics and fabrications

In this thesis, the author investigated the phenomenon of dielectrophoresis and its applications in electronics, microfluidics and optofluidics. Different configurations of microelectrodes, which were employed for such applications, were designed and fabricated. Their functionalities in producing dielectrophoretic (DEP) forces were evaluated through the simulation of electric fields. It is believed that dielectrophoresis is one of the best approaches for depositing nanomaterials for device applications, since dielectrophoretically assembled materials are highly aligned and concentrated in desired locations; such characteristics ensure intimate contacts between interfaces and hence guarantee exceptional device reliability and functionality. To develop nanostructured electronic devices using dielectrophoresis, finger-paired electrodes were first employed to reveal the ability of AC electric fields in aligning and assembling nanomaterials. After that, micro-tip electrode arrays were utilized to develop electronic devices such as conductometric sensors and field effect transistors using dielectrophoretically deposited nanomaterials. To realize the ability of DEP forces for manipulating particles in stationary liquid, a DEP-microfluidic device with micro-tip electrodes was utilized to comprehensively investigate the DEP behaviors of polystyrene microparticles using different AC electric fields. In a further study, the separation of carbon nanotubes (CNTs) from polystyrene particles was demonstrated using the same system. In order to achieve the most efficient DEP manipulation within liquid flows, curved electrodes were developed. With devices that use such a design, the author successfully conducted the following tasks in flowing liquid: the separation of polystyrene microparticles from CNTs, controllable focusing of polystyrene microparticles, sorting of polystyrene particles according to their dimensions, sorting of live and dead cells, trapping of polystyrene particles using pre-patterned CNTs, and the development of optofluidic waveguide using dielectrophoretically controlled silica particles. Within this PhD research, the author achieved the following outcomes: 1. The DEP separation of nanostructures from microstructures was demonstrated for the first time. 2. For the first time, curved electrodes were developed to manipulate particles in flowing liquid using dielectrophoresis 3. The DEP trapping of polystyrene microparticles using pre-patterned CNTs was demonstrated for the first time. 4. An optofluidics waveguide, which was achieved using dielectrophoretically controlled silica particles, was demonstrated for the first time. 5. Gas sensors, which are fabricated using dielectrophoretically assembled and aligned NCNTs and NCNTs/Pt:Ni nanoparticles, were developed for the first time. 6. Field effect transistors were developed using dielectrophoretically deposited hybrid organic-inorganic materials and demonstrated for the first time

Cell Separations and Sorting

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Analytical Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.analchem.9b05357.NIBIB Grant P41-EB020594COBRE Grant 5P20GM13042

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