A housekeeping prognostic health management framework for microfluidic systems

Micro-Electro-Mechanical Systems (MEMS) and Microfluidics are becoming popular solutions for sensing, diagnostics and control applications. Reliability and validation of function is of increasing importance in the majority of these applications. On-line testing strategies for these devices have the potential to provide real-time condition monitoring information. It is shown that this information can be used to diagnose and prognose the health of the device. This information can also be used to provide an early failure warning system by predicting the remaining useful life. Diagnostic and prognostic outcomes can also be leveraged to improve the reliability, dependability and availability of these devices. This work has delivered a methodology for a “lightweight” prognostics solution for a microfluidic device based on real-time diagnostics. An oscillation based test methodology is used to extract diagnostic information that is processed using a Linear Discriminant Analysis based classifier. This enables the identification of current health based on pre-defined health levels. As the deteriorating device is periodically classified, the rate at which the device degrades is used to predict the devices remaining useful life

Nanoscale Manipulation, Probing, and Assembly Using Microfluidic Flow Control

Nanoparticles have unique properties that can be beneficial in fields ranging from quantum information to biological sensing. To take advantage of some of some of these benefits, techniques are required that can select single particles and place them at desired locations with nanoscale precision. This capability allows for bottom-up assembly of nanoparticle systems and facilitates development of improved tools for probing nanoscale physics. Current manipulation approaches are inadequate for positioning nanoparticles such as single quantum dots. Quantum dots can act as single photon sources, and are useful for applications in nanophotonics and quantum optics. In this thesis, I present a technique for manipulation of single quantum dots and other nano-objects. Using this technique, I demonstrate nanoparticle manipulation, assembly, and probing with nanoscale precision. The nanomanipulation approach I introduce employs electroosmotic flow to position colloidal nanoparticles suspended in an aqueous system. Single quantum dot manipulation is demonstrated with a precision better than 50 nm for holding times of up to one hour. This technique is useful for studying the behavior of single quantum dots and their interactions with the environment in real time. A fluid chemistry was developed for the deterministic immobilization of nanoparticles along a two-dimensional surface with 130 nm precision. In addition, a technique for assembling systems of silver nanowires is demonstrated. A method for imaging the local density of optical states of silver nanowires is presented using single quantum dots as probes, achieving an imaging accuracy of 12 nm. Spontaneous emission control is accomplished simultaneously by placing the quantum dot at various locations along the wire. Together, these experiments illustrate the versatility of microfluidics for the advancement of nanoscience research and engineering

Real-Time Bio Sensing Using Micro-Channel Encapsulated MEMS Resonators

This work presents a label-free bio-molecular detection technique based on realtime monitoring of the resonant frequency of micromechanical thermal-piezoresistive rotational mode disk resonators encapsulated in microfluidic channels. Mass loading via adsorption of molecular layers on the surface of such devices results in a frequency shift. In order to provide a reliable platform for sample-resonator interactions and to protect the resonators from contaminants, the resonators were encapsulated in PDMS-based microfluidic channels. Micro-channel encapsulation also allows insulation of electrical signals from the analyte solution. To characterize the performance of such devices as real-time label-free bio-molecular detectors, the strong non-covalent binding of Avidin with its ligand, biotin was utilized. To further validate the measured frequency shifts and confirm that the frequency shifts are due to molecular attachments to the resonator surfaces, fluorescent labeled molecules followed by fluorescent imaging was used confirming the existence of the expected molecular layers on the resonator surfaces

Actuation Of Droplets Using Transparent Graphene Electrodes For Tunable Lenses And Biomedical Applications

Variable focal length liquid microlenses are the next candidate for a wide variety of applications. Driving mechanism of the liquid lenses can be categorized into mechanical and electrical actuation. Among different actuation mechanisms, EWOD is the most common tool for actuation of the liquid lenses. In this dissertation, we have demonstrated versatile and low-cost miniature liquid lenses with graphene as electrodes. Tunable focal length is achieved by changing both curvature of the droplet using electrowetting on dielectric (EWOD) and applied pressure. Ionic liquid and KCl solution are utilized as lens liquid on the top of a flexible Teflon-coated PDMS/parylene membrane. Transparent and flexible, graphene allows transmission of visible light as well as large deformation of the polymer membrane to achieve requirements for different lens designs and to increase the field of view without damaging of electrodes. Another advantage of graphene compared to non-transparent electrodes is the larger lens aperture. The tunable range for the focal length is between 3 and 7 mm for a droplet with a volume of 3 μL. The visualization of bone marrow dendritic cells is demonstrated by the liquid lens system with a high resolution (more than 456 lp/mm). The Spherical aberration analysis is performed using COMSOL software to investigate the optical properties of the lens under applied voltages and pressure. We propose a prototype of compound eye with specific design of the electrodes using both tunable lenses and tunable supporting membrane. The design has many advantages including large field of view, compact size and fast response time. This work maybe applicable in the development of the next generation of cameras, endoscopes, cell phones on flexible platform. We also proposed here the design and concept of self-powered wireless sensor based on the graphene radio-frequency (RF) components, which are transparent, flexible, and monolithically integrated on biocompatible soft substrate. We show that a quad-ring circuit based on graphene transistors may simultaneously offer sensing and frequency modulation functions. This battery-free and transparent sensors based on newly discovered 2D nanomaterials may benefit versatile wireless sensing and internet-of-things applications, such as smart contact lenses/glasses and microscope slides

Sensing methods for real-time Loop-mediated Isothermal Amplification in Digital Microfluidic systems

Digital Microfluidics (DMF) is a technology capable of maneuvering picoliter to microliter droplets in an independent and individual manner, with a wide variety of uses for bioassays and biosensing. These systems are advantageous for their small volumes, higher portability and multiplex assay capabilities, proving to be very capable of lab-on-chip and point-of-care applications. One of these applications are DNA amplification assays, of which, Loop Mediated Isothermal Amplification (LAMP), that has received increased interest from the scientific community. This method is a sensitive and simple diagnostic tool for fast detection and identification of molecular biomarkers enabling real-time monitoring. Nevertheless, sensing methods coupled with DMF devices are still uncapable of measuring the progress of said reaction in real-time. This work explores two real-time LAMP measurement approaches to be coupled with a DMF system. The first approach uses an H-shaped device, where human c-Myc proto-oncogene and human 18S housekeeping gene are amplified and measured in real-time through fluorescence methods. The second approach uses interdigitated electrodes, where human c-Myc proto-oncogene is amplified and measured in real-time through Electrochemical Impedance Spectroscopy (EIS). Following development and characterization of both techniques, fluorescence measuring devices show 49% fluorescence signal difference between positive and negative controls end-points. EIS measuring devices indicate significant differences between commercial solutions with pH 4, 7 and 10, by Ciclic Voltammetry. This suggests that such devices could be used for real-time, label free, LAMP monitoring, since significant pH changes occur during a LAMP reactio

Micro-electro-opto-fluidic systems for biomedical drug screening and electromagnetic filtering and cloaking applications

Microfluidic is a multidisciplinary field that deals with the flow of liquid inside micro-meter size channels. In order to be considered as microfluidics, at least one dimension of the channel should be in the range of one micrometer or sub-millimeter. Microfluidic technology includes designing, manufacturing, formulating devices and processing the liquid. As numerous bio-science and engineering techniques have utilized microfluidics and highly integrated with this remarkable technology, the microfluidic platform technology has extended to several sub-techs: micro-scale analysis, soft-lithography fabrication, polymer science and processing, on-chip sensing and micro-scale fluid manipulation. Those sub-techs have been developed rapidly along with the booming microfluidics. The advance of those techniques has promoted microfluidic system diverse and widespread applications. Some examples that employ this technology include on-chip drug screening, micro-scale analysis, flexible electronics, biochemical assays. Many engineering field, such as optics, electronics, chemicals and electromagnetics, have been integrated with the microfluidic system to form a completed system for sensing, analyzing or realizing some specific applications. Through the fusion of those technologies with microfluidics, many emerging technologies are well initiated, such as optofluidics and electrofluidics. Despite of rapid advancement of each parent technology field, those intersected technologies are still in their infancy and many technological elements and even some fundamental concepts are just now being developed. Thus, it provides great opportunity to explore more about those emerging technologies. Some particular areas that mainly interest researchers including cost deduction, effective fabrication, highly integration, portability and applicability. Due to the wide and diversity nature of the microfluidic technology and numerous combinations from the integration with other fields, it is very difficult to choose a single aspect or particular subject to research. Hence, we would like to focus on the application orientated microfluidic techniques that integrated with other engineering areas, in particular optics and electronics. Correspondingly, I will present four microfluidic platforms that integrated with optics, electronics for different application purpose. First of all, fiber-optics was integrated into a microfluidic device to detect muscular force generation of microscopic nematodes. The integrated opto-fluidic device is capable of measuring the muscular force of nematode worms normal to the translational movement direction with high sensitivity, high data reliability, and simple device structure. The ability to quantify the muscular forces of small nematode worms will provide a new approach for screening mutants at single animal resolution. Secondly, electronic grids were integrated into a microfluidic chip to realize on-chip tracking of nematode locomotion. The micro-electro-fluidic approach is capable of real-time lens-less and image-sensor-less monitoring of the locomotion of microscopic nematodes. The technology showed promise for overcoming the constraint of the limited field of view of conventional optical microscopy, with relatively low cost, good spatial resolution, and high portability. Thirdly, electromagnetic spit ring resonator (SRR) structure was adopted as microfluidic channel filled with liquid metal to fabricate a tunable microfluidic microwave electronics called meta-atom. The presented meta-atom is capable of tuning its electromagnetic (EM) response characteristics over a broad frequency range via simple mechanical stretching. The meta-atom in this study presents a simple but effective building block for realizing mechanically tunable metamaterials. Finally, based on the meta-atom we previously developed, an array of electromagnetic SRR shaped microfluidic channels filled with liquid metal to form a flexible metamaterial-based microwave electronic “skin” or meta-skin. When stretched, the meta-skin performs as a tunable frequency selective surface with a wide resonance frequency tuning range. When wrapped around a curved dielectric material, the meta-skin functions as a flexible “cloaking” surface to significantly suppress scattering from the surface of the dielectric material along different directions. The microfluidic platform will find great applications when it integrates with other technologies. The development of such integration will greatly intersect different research areas and benefit all of the intersected technologies and fields, thus broadening the future applications

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

Comparative advantages of mechanical biosensors

Mechanical interactions are fundamental to biology. Mechanical forces of chemical origin determine motility and adhesion on the cellular scale, and govern transport and affinity on the molecular scale. Biological sensing in the mechanical domain provides unique opportunities to measure forces, displacements and mass changes from cellular and subcellular processes. Nanomechanical systems are particularly well matched in size with molecular interactions, and provide a basis for biological probes with single-molecule sensitivity. Here we review micro- and nanoscale biosensors, with a particular focus on fast mechanical biosensing in fluid by mass- and force-based methods, and the challenges presented by non-specific interactions. We explain the general issues that will be critical to the success of any type of next-generation mechanical biosensor, such as the need to improve intrinsic device performance, fabrication reproducibility and system integration. We also discuss the need for a greater understanding of analyte–sensor interactions on the nanoscale and of stochastic processes in the sensing environment

Processo de microfabricação de dispositivos microfluídicos passivos e ativos

Orientadores: Jacobus Willibrordus Swart, Stanislav MoshkalevTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Elétrica e de Computação em cocutela com Vrije Universiteit BrusselResumo: O processo de miniaturização permite reações de misturas líquidas e análises mais rápidas, em volumes menores, com dispositivos portáteis e mais confiáveis. Os principais desafios estão na fabricação com alta precisão e integração de microcanais com sensores. Nós desenvolvemos protocolos completos de obtenção de microcanais com atuadores e sensores integrados, envolvendo técnicas convencionais de microfabricação e caracterização compatíveis com instalações em sala limpa. Resultando em dispositivos fabricados em silício, vidro e polidimetilsiloxano (PDMS), com microcanais com largura entre 100 e 458 µm, profundidade entre 20 e 64 µm. Apresentamos novas metodologias para aplicações em Lab-On-a-Chip (LOC): 1) Sistema com microcanais integrados a um sensor capacitivo. 2) Misturador ativo com atuadores eletromagnéticos em microcanais. 3) Misturador passivo com sensor terahertz acoplado, para controle de concentração de etanol sob demanda. Apresentamos o sistema microfluídico completo de geração de micro gotas de água/óleo e micros sensor capacitivo para detecção e controle de volume e velocidade de gotas de até 1mm de comprimento. Apresentamos misturador ativo, com membrana de PDMS integrada com atuadores eletromagnéticos, estabelecendo a correlação entre a melhoria de mistura líquida e a frequência de oscilação. Apresentamos sensor sub-THz acoplado a plataforma microfluídica com medições não invasivas, sem contato e livre de rótulos para a determinação da concentração de etanol e controle sob demanda. Demonstramos sensoriamento on-line operando a 60 GHz, com faixa dinâmica de 2,79 dB, controle da concentração de etanol com variação de 0,32% (v / v) e micro misturador passivo com canais curvos operando em fluxo laminar, com número de Reynolds 25700. Em adição, apresentamos um estudo preliminar com simulação de método de elementos finitos (MEF) em comparação com modelos teóricos. Apresentamos a caracterização de fluidos e a aplicação de dispositivos microfluídicosAbstract: The miniaturization process allows reactions of liquid mixtures and faster analyzes, in smaller volumes, with portable and more reliable devices. The main challenges are in the manufacturing with high precision and integration of microchannels with sensors. We have developed complete protocols for obtaining microchannels with integrated actuators and sensors, involving conventional microfabrication and characterization techniques compatible with clean room facilities. Resulting in devices fabricated in silicon, glass and polydimethylsiloxane (PDMS), with microchannels widths between 100 and 458 ?m, depth between 20 and 64 µm. We present new methodologies for Lab-On-a-Chip (LOC) applications: 1) System with microchannels integrated to a capacitive sensor. 2) Active mixer with electromagnetic actuators in microchannels. 3) Passive mixer with coupled terahertz sensor for control of concentration of ethanol on demand. We present the complete microfluidic system for the micro droplets generation of water/oil and micro capacitive sensor, for detection and control of volume and droplet velocity up to 1mm in length. We present an active mixer, with integrated PDMS membrane with electromagnetic actuators, establishing the correlation between the liquid mixture improvement and the oscillation frequency. We present sub-THz sensor coupled to microfluidic platform with non-invasive, contactless and label-free measurements for determination of ethanol concentration and control on demand. We demonstrated on-line sensing, operating at 60 GHz, with a dynamic range of 2.79 dB, ethanol concentration control with a variation of 0.32% (v / v) and passive micro-mixer with curved channels operating in laminar flow with number of Reynolds 25700. In addition, we present a preliminary study with simulation of finite element method (FEM) in comparison with theoretical models. We presented the fluid characterization regime and application of microfluidic devicesDoutoradoEletrônica, Microeletrônica e OptoeletrônicaDoutor em Engenharia Elétrica001/2014FAPEA