Lab-on-a-chip Thermoelectric and Solid-phase Immunodetection of Biochemical Analytes and Extracellular Vesicles: Experimental and Computational Analysis

Microfluidics is the technology of controlling and manipulating fluids at the microscale. Microfluidic platforms provide precise fluidic control coupled with low sample volume and an increase in the speed of biochemical reactions. Lab-on-a-chip platforms are used for detection and quantification of biochemical analytes, capture, and characterization of various proteins, sensitive analysis of cytokines, and isolation and detection of extracellular vesicles (EVs). This study focuses on the development of microfluidic and solid-phase capture pin platforms for the detection of cytokines, extracellular vesicles, and cell co-culture. The fabrication processes of the devices, experimental workflows, numerical analysis to identify optimal design parameters, and reproducibility studies have been discussed. Layer-by-layer assembly of polyelectrolytes has been developed to functionalize glass and stainless-steel substrates with biotin for the immobilization of streptavidinconjugated antibodies for selective capture of cytokines or EVs. Microstructure characterization techniques (SEM, EDX, and fluorescence microscopy) have been implemented to assess the efficiency of substrate functionalization. A detailed overview of current methods for purification and analysis of EVs is discussed as well. Additionally, the dissertation demonstrates the feasibility of a calorimetric microfluidic immunosensor with an integrated antimony-bismuth (Sb/Bi) thermopile sensor for the detection of cytokines with picomolar sensitivity. The developed platform can be used for the universal detection of both exothermic or endothermic reactions. A three-dimensional numerical model was developed to define the critical design parameters that enhance the sensitivity of the platform. Mathematical analyses identified the optimal combinations of substrate material and dimensions that will maximize the heat transfer to the sensor. Lab-on-a-chip cell co-culture platform with integrated pneumatic valve was designed, numerically characterized, and fabricated. This device enables the reversible separation of two cell culture chambers and serves as a tool for the effective analysis of cell-to-cell communication. Intercellular communication is mediated by extracellular vesicles. A protocol for the functionalization of stainless-steel probe with exosomespecific CD63 antibody was developed. The efficiency of the layer-by-layer deposition of polyelectrolytes and the effectiveness of biotin and streptavidin covalent boding were characterized using fluorescent and scanning electron microscopy

Toward roll-to-roll transfer of large-scale graphene for flexible electronics fabrication

textGraphene is a promising material for flexible electronics due to its extraordinary electrical, mechanical, and optical properties. One of the biggest challenges today is to transfer large-scale graphene sheet to flexible substrates with minimal quality degradation. In this thesis, a bilayer polymer support for graphene transfer is proposed. Liquid PDMS (polydimethylsiloxane) is first coated on graphene to conform to its surface morphology. A flexible plastic substrate is then pressed on PDMS as a durable support. After PDMS is cured, electrochemical delamination is used to separate graphene from the copper foil. Due to the extremely low work of adhesion between graphene and PDMS, the graphene film on PDMS can be further transferred onto silicon wafer or other flexible substrates by simple adhesion. An added benefit of the PDMS layer is its strain isolation effect, which could protect graphene-based devices from breaking under external loads applied on the flexible substrate. The strain isolation effect of PDMS is verified with an analytical model and finite element analysis. The design of a prototype roll-to-roll graphene transfer machine is also presented.Mechanical Engineerin

Textile UHF-RFID antenna sensors based on material features, interfaces and application scenarios

Tesi en modalitat de compendi de publicacions, amb una secció retallada per drets de l'editor. In reference to IEEE copyrighted material which is used with permission in this thesis, the IEEE does not endorse any of Universitat Politècnica de Catalunya's products or services. Internal or personal use of this material is permitted. If interested in reprinting/republishing IEEE copyrighted material for advertising or promotional purposes or for creating new collective works for resale or redistribution, please go to http://www.ieee.org/publications_standards/publications/rights/rights_link.html to learn how to obtain a License from RightsLink.Radio frequency identification over measurable ultra-high frequency textile substrates (UHF-RFID) is a promising technology to develop new applications in the field of health and the Internet of Things (IOT), due to the massive use of fabrics and the technological maturity of embroidery techniques. This thesis is the result of a compendium of publications on this topic. First, as a result of the analysis of the state of art, a systematic review entitled 'Wearable textile UHF-RFID sensors: A systematic review' has been published. The thesis aims to improve research on UHF-RFID textile-based sensor technology. Thanks to the analysis of the state of art, three novel research objectives have been set that are worth exploring. The first is to study novel detection functions for textile UHF-RFID based sensor technology; the second is to find a connection/interface solution between textile antennas and integrated circuit (IC) chips and the third is to reduce the costs of such technology to promote future commercial applications. To contextualize the thesis, it includes the necessary theoretical fundamentals and the manufacturing and characterization methods used during it. As a result of the work derived from the first objective, a scientific article entitled “Textile UHF-RFID Antenna Sensor for Measurements of Sucrose Solutions in Different Levels of Concentration” has been published. In this work, a textile UHF-RFID tag with two detection positions is proposed for sucrose solution measurements. The two detection positions with the different detection functions show good performance and can offer two options for future full applications. In addition, another scientific article entitled “ Textile UHF-RFID Antenna Embroidered on Surgical Masks for Future Textile Sensing Applications” has been published to support the first objective. The inspiration for this work came from the current pandemic situation. This work develops three progressive designs of textile UHF-RFID antennas over surgical masks due to the current global epidemic situation. Reliability testing demonstrated that the proposed designs can be used for human healthcare focused applications. As a result of the second objective, a research article entitled 'Experimental Comparison of Three Electro-textile Interfaces for Textile UHF-RFID Tags on Clothes' has been published. This work proposes three electro-textile interfaces integrated with the corresponding textile UHF-RFID antennas and provides the chip-textile connection solutions (through sewing, push buttons and insertion). As a result of this objective, an electro-textile interconnect system has been proposed together with its electrical model, which allows the correct adaptation of impedances between the RFID antennas and the integrated circuit. It is worth noting that the mixed-use feasibility of the proposed electro-textile interfaces and the designed textile UHF-RFID antennas has been verified, reducing the cost in the design procedure in applications where the read range requirements of the order of 1 meter. The third objective has been achieved and exposed by a scientific article entitled 'Electro-textile UHF-RFID Compression Sensor for Health-caring Applications'. It proposes a single UHF-RFID based compression textile sensor that can be used simultaneously in two different healthcare application scenarios, which directly impacts on cost reduction.La identificación por radiofrecuencia sobre substratos textiles de ultra alta frecuencia (UHF-RFID) con capacidad de medida es una tecnología prometedora para desarrollar nuevas aplicaciones en el campo de la salud y el Internet de las cosas (IOT), debido a la masiva utilización de los tejidos y a la madurez tecnológica de las técnicas de bordado. Esta tesis es el resultado de un compendio de publicaciones sobre dicha temática. En primer lugar, como resultado del análisis del estado del arte se ha publicado una revisión sistemática titulada 'Wearable textile UHF-RFID sensors: A systematic review'. La tesis tiene como objetivo mejorar la investigación sobre la tecnología de sensores basada en textiles UHF-RFID. Gracias al análisis del estado del arte se han fijado tres objetivos de investigación novedosos que vale la pena explorar. El primero es estudiar funciones de detección novedosas para la tecnología de sensores basada en UHF-RFID textiles; el segundo es encontrar una solución de conexión/interfaz entre antenas textiles y chips de circuito integrado (IC) y el tercero es la reducción de costes de dicha tecnología para promover futuras aplicaciones comerciales. Para contextualizar la tesis, ésta incluye los fundamentos teóricos necesarios y los métodos de fabricación y caracterización utilizados durante la misma. Como resultado del trabajo derivado del primer objetivo, se ha publicado un artículo científico titulado “Textile UHF-RFID Antenna Sensor for Measurements of Sucrose Solutions in Different Levels of Concentration”. En este trabajo, se propone una etiqueta UHF-RFID textil con dos posiciones de detección para mediciones de solución de sacarosa. Las dos posiciones de detección con las diferentes funciones de detección muestran un buen rendimiento y pueden ofrecer dos opciones para futuras aplicaciones completas. Además, se ha publicado otro artículo científico titulado "Textile UHF-RFID Antenna Embroidered on Surgical Masks for Future Textile Sensing Applications" para respaldar el primer objetivo. La inspiración para este trabajo vino de la actual situación de pandemia. En este trabajo se desarrollan tres diseños progresivos de antenas UHF-RFID textiles sobre mascarillas quirúrgicas debido a la situación epidémica mundial actual. Las pruebas de fiabilidad demostraron que los diseños propuestos se pueden usar para aplicaciones centradas en el cuidado de las personas. Como resultado del segundo objetivo, se ha publicado un artículo de investigación titulado 'Experimental Comparison of Three Electro-textile Interfaces for Textile UHF-RFID Tags on Clothes'. En este trabajo se proponen tres interfaces electro-textiles integradas con las correspondientes antenas UHF-RFID textiles y se aportan las soluciones de conexión chip-textil (mediante costura, botones a presión e inserción). Como resultado de este objetivo, se ha propuesto un sistema de interconexión electro-textil junto con su modelo eléctrico, lo que permite la correcta adaptación de impedancias entre las antenas RFID y el circuito integrado. Vale la pena señalar que se ha verificado la viabilidad de uso mixto de las interfaces electro-textiles propuestas y las antenas UHF-RFID textiles diseñadas, lo que reduce el coste en el procedimiento de diseño en aplicaciones donde los requerimientos de rango de lectura del orden de 1 metro. El tercer objetivo se ha alcanzado y expuesto mediante un artículo científico titulado 'Electro-textile UHF-RFID Compression Sensor for Health-caring Applications'. En él, se propone un único sensor textil de compresión basado en UHF-RFID que puede ser utilizado a la vez en dosPostprint (published version

Silicon - polymer hybrid integrated microwave photonic devices for optical interconnects and electromagnetic wave detection

textThe accelerating increase in information traffic demands the expansion of optical access network systems that require high-performance optical and photonic components. In short-range communication links, optical interconnects have been widely accepted as a viable approach to solve the problems that copper based electrical interconnects have encountered in keeping up with the surge in the data rate demand over the last decades. Low cost, ease of fabrication, and integration capabilities of low optical-loss polymers make them attractive for integrated photonic applications to support futuristic data communication networks. In addition to passive wave-guiding components, electro-optic (EO) polymers consisting of a polymeric matrix doped with organic nonlinear chromophores have enabled wide-RF-bandwidth and low-power active photonic devices. Beside board level passive and active optical components, on-chip micro- or nano-photonic devices have been made possible by the hybrid integration of EO polymers onto the silicon platform. In recent years, silicon photonics have attracted a significant amount of attentions, because it offers compact device size and the potential of complementary metal–oxide–semiconductor (CMOS) compatible photonic integrated circuits. The combination of silicon photonics and EO polymers can enable miniaturized and high-performance hybrid integrated photonic devices, such as electro-optic modulators, optical interconnects, and microwave photonic sensors. Silicon photonic crystal waveguides (PCWs) exhibit slow-light effects which are beneficial for device miniaturization. Especially, EO polymer filled silicon slotted PCWs further reduce the device size and enhance the device performance by combining the best of these two systems. The potential applications of these silicon-polymer hybrid integrated devices include not only optical interconnects, but also optical sensing and microwave photonics. In this dissertation, the design, fabrication, and characterization of several types of silicon-polymer hybrid photonic devices will be presented, including EO polymer filled silicon PCW modulators for on-chip optical interconnects, antenna-coupled optical modulators for electromagnetic wave detections, and low-loss strip-to-slot PCW mode converters. In addition, some polymer-based devices and silicon-based photonic devices will also be presented, such as traveling wave electro-optic polymer modulators based on domain-inversion directional couplers, and silicon thermo-optic switches based on coupled photonic crystal microcavities. Furthermore, some microwave (or RF) components such as integrated broadband bowtie antennas for microwave photonic applications will be covered. Some on-going work or suggested future work will also be introduced, including in-device pyroelectric poling for EO polymer filled silicon slot PCWs, millimeter- or Terahertz-wave sensors based on EO polymer filled plasmonic slot waveguide, low-loss silicon-polymer hybrid slot photonic crystal waveguides fabricated by CMOS foundry, logic devices based on EO polymer microring resonators, and so on.Electrical and Computer Engineerin

Dual-Wave Acoustofluidic Centrifuge for Ultrafast Concentration of Nanoparticles and Extracellular Vesicles

Extracellular vesicles (EVs) are secreted nanostructures that play various roles in critical cancer processes. They operate as an intercellular communication system, transferring complex sets of biomolecules from cell to cell. The concentration of EVs is difficult to decipher, and there is an unmet technological need for improved (faster, simpler, and gentler) approaches to isolate EVs from complex matrices. Herein, an acoustofluidic concentration of extracellular vesicles (ACEV) is presented, based on a thin-film printed circuit board with interdigital electrodes mounted on a piezoelectric substrate. An angle of 120° is identified between the electrodes and the reference flat of the piezoelectric substrate for simultaneous generation of Rayleigh and shear horizontal waves. The dual waves create a complex acoustic field in a droplet, resulting in effective concentration of nanoparticles and EVs. The ACEV is able to concentrate 20 nm nanospheres within 105 s and four EV dilutions derived from the human prostate cancer (Du145) cell line in approximately 30 s. Cryo-electron microscopy confirmed the preservation of EV integrity. The ACEV device holds great potential to revolutionize investigations of EVs. Its faster, simpler, and gentler approach to EV isolation and concentration can save time and effort in phenotypic and functional studies of EVs

Chemical vapor deposited two-dimensional material based high frequency flexible field-effect transistors

Flexible nanoelectronics have attracted great attention due to interesting concepts such as wearable electronics and internet of things, which requires high speed and low power consumption flexible smart system with functions ranging from sensing, computing to wireless communicating. In this dissertation, transparent and solution processable nanoscale polyimide film for highly flexible gate dielectrics is demonstrated by in-situ opto-electro-mechanical measurement and utilized for two-dimensional nanomaterials based field-effect transistors (FETs). Graphene thin film transistor with the nanoscale polyimide dielectric on flexible glass is operated in extremely high frequency regime and shows the highest experimental saturation velocity (~8.4 × 10⁶ cm/s) in any materials in any flexible transistors. Molybdenum disulfide (MoS₂) based transistors with embedded gate structure on rigid substrate are demonstrated with enhancement mode operation, ON/OFF ratio over 10⁸, the highest transconductance (~ 70 µS/µm) and saturation velocity (~1.8 × 10⁶ cm/s). CVD MoS₂ FETs on flexible plastic substrates are also demonstrated, showing enhancement mode operation, ON/OFF radio over 10¹⁰ and transconductance (~6 µS/µm). The flexible CVD MoS₂ transistors with embedded gate structure were employed to study effects of substoichiometric doping by HfO [subscript 2-x]. After the doping layer, the flexible MoS₂ transistors show ×8 higher source-drain current density as well as more than ×2 mobility improvements. For the another first demonstration, GHz operation and flexibility of graphene and MoS₂ based FETs are realized on commercial available paper substrates, which indicates flexible two-dimensional material based nanoelectronics can be implemented on paper substrates for systems, sensors, and Internet of Things.Electrical and Computer Engineerin

Self-Assembly of Iron Oxide-Poly(ethylene glycol) Core–Shell Nanoparticles at Liquid–Liquid Interfaces

Nanoparticles (NPs) play an increasingly important role in the fabrication of functional advanced materials. Two major steps need to be carried out in order to achieve control of the material properties. First of all, the properties of the single NPs have to be under control, especially in relation to colloidal stability; aggregation and corrosion negate all the benefits associated to the nanoscopic dimensions. Secondly, the assembly process has to be controlled to achieve a material with the desired properties. We propose here to use stabilized ceramic NPs consisting of a magnetite core, coated by a poly(ethylene glycol) (PEG) shell and study their assembly at polar/non-polar liquid interfaces, en route to fabricating functional NP membranes. These NPs show extraordinary stability in aqueous solutions achieved by anchoring linear PEG chains through an end-terminating nitroDOPA group to their surface. Furthermore, the core and shell sizes of these NPs can be independently varied with ease. We first describe the details of the NP synthesis and stabilization in bulk solutions, discussing the PEG molecular weight needed to achieve bulk stability. Subsequently, we demonstrate self-assembly of these particles at liquid–liquid interfaces (SALI) into monolayers of stable properties. SALI has been chosen as path for the assembly given its suitability for fabricating two-dimensional materials. We report here results from pendant drop tensiometry which illustrate the kinetics of NP adsorption at the liquid–liquid interface and highlight the role played by the molecular weight of the PEG shell in the interfacial assembly. In particular we show that the requisites to ensure particle stability at a liquid interface are more stringent compared to the bulk case

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

Carbon nanotubes micro-arrays: characterization and application in biosensing of free proteins and label-free capture of breast cancer cells

Circulating tumor cells (CTCs) are cells released into the bloodstream from primary tumors and are suspected to be one of the main causes behind metastatic spreading of cancer. The ability to capture and analyze circulating tumor cells in clinical samples is of great interest in prevailing patient prognosis and clinical management of cancer. Carbon nanotubes, individual rolled-up graphene sheets, have emerged as exciting materials for probing the biomolecular interactions. With diameter of about 1 nm, they can attach themselves to cell surface receptors through specific antibodies and hold a great potential for diagnostic cellular profiling. Carbon nanotubes can be either semiconducting or metallic, and the electronic properties of either type rivals the best known materials. Small size of nanotubes and the ability to functionalize their surface using 1-Pyrenebutanoic Acid, Succinimidyl Ester (PASE), enables a versatile probe for developing a platform for capture and analysis of cancer biomarkers and circulating tumor cells. Although nanotubes have previously been used to electrically detect a variety of molecules and proteins, here for the first time we demonstrate the label free capture of spiked breast cancer cells using ultra-thin carbon nanotube film micro-array devices in a drop of buffy coat and blood. A new statistical approach of using Dynamic Time Warping (DTW) was used to classify the electrical signatures with 90% sensitivity and 90% specificity in blood. These results suggest such label free devices could potentially be useful for clinical capture and further analysis of circulating tumor cells. This thesis will go in-depth the properties of carbon nanotubes, device fabrication and characterization methodologies, functionalization protocols, and experiments in buffy coats and in blood. Combination of nano and biological materials, functionalization protocols and advanced statistical classifiers can potentially enable clinical translation of such devices in the future