Advanced Materials for Rapid Diagnostics in Food, Agriculture and Healthcare

Paper based devices are an emerging trend for micro total analysis systems due to their rapid, sensitive and specific attributes. Lateral flow assays (LFAs), the predecessor of paper-fluidic devices, are developed for many applications which range from nucleic acid and antibody detection to commercial home pregnancy tests. With growing interest in replacing conventional detection methods, multistep assays are needed. These assays require multiple test reagents, therefore, there is a need to control fluid flow for the development of complex paper-based devices. We were able fabricate paper-fluidic platforms where we used electrowetting-on-dielectrics to create valves on paper. With this method, we directly controlled the timing and flow of the fluid. However, the electrowetting valves required an external power source for actuation, thus we developed a passive fluid control method. To do this, passive delay valves/barriers were inkjet-printed, by altering the drop spacing of the ink creating effective delay barriers, which decreases the rate of capillary action of the throughput solution. The patterned devices were later used to create a paper based device where an amplified nucleic acid assay was performed. After creating a paper based platform and understanding the properties that control fluid flow on paper, it is important to discover applications that are suitable for the devices. Phage amplified LFAs were developed, where a genetically engineered phage that overexpresses alkaline phosphatase was used, in combination with phage amplification kinetics to detect for low levels of E. coli in a sample. In the end, we were able to fabricate a barcode style LFA that had a visually quantitative colorimetric readout. After understanding phage kinetics and amplification, their infectious and destructive mechanism was leveraged and applied to decontamination of agricultural rinse water. In general, bacteriophages are capable of infecting and lysing target bacteria and are kept viable by lyophilization, but freeze-drying is time consuming and requires large machinery. In our study, we dehydrated bacteriophages in electrospun nanofibers and studied the effects of excipients in polymeric solutions and different storage conditions on bacteriophage viability. Ultimately, electrospun nanofibers stored for eight weeks at ambient temperatures retained high phage viability which is sufficient for infection

Methods for immobilizing receptors in microfluidic devices: A review

In this review article, we discuss state-of-the-art methods for immobilizing functional receptors in microfluidic devices. Strategies used to immobilize receptors in such devices are essential for the development of specific, sensitive (bio)chemical assays that can be used for a wide range of applications. In the first section, we review the principles and the chemistry of immobilization techniques that are the most commonly used in microfluidics. We afterward describe immobilization methods on static surfaces from microchannel surfaces to electrode surfaces with a particular attention to opportunities offered by hydrogel surfaces. Finally, we discuss immobilization methods on mobile surfaces with an emphasis on both magnetic and non-magnetic microbeads, and finally, we highlight recent developments of new types of mobile supports

SURFACE ENABLED LAB-ON-A-CHIP (LOC) DEVICE FOR PROTEIN DETECTION AND SEPARATION

Sensitive and selective chemical/biological detection/analysis for proteins is essential for applications such as disease diagnosis, species phenotype identification, product quality control, and sample examination. Lab-on-a-chip (LOC) device provides advantages of fast analysis, reduced amount of sample requirements, and low cost, to magnificently facilitate protein detection research. Isoelectric focusing (IEF) is a strong and reliable electrophoretic technique capable of discerning proteins from complex mixtures based on the isoelectric point (pI) differences. It has experienced plenty of fruitful developments during previous decades which has given it the capability of performing with highly robust and reproducible analysis. This progress has made IEF devices an excellent tool for chemical/biological detection/analysis purposes. In recent years, the trends of simple instrument setting, rapid analysis, small sample requirement, and light labor intensity have inspired the LOC concept to be combined with IEF to evolve it into an “easily-handled chip with hours of analysis” from the earlier method of “working with big and heavy machines in a few days.” Although IEF is already a mature technique being applied, further LOC-IEF developments are still experiencing challenges related to its limitations such as miniaturizing the device scale without harming the resolving/discerning ability. With the facilitation of newly technologically advanced/improved fabrication tools, it is completely possible to address challenges and approach new limits of LOC-IEF. In this dissertation, a surface enabled printing technique, which can transfer liquid to a surface with prescribed patterns, was firstly introduced to IEF device fabrication. By employing surface enabled printing, a surface enabled IEF (sIEF) device running at a scale of 100 times smaller than those previously reported was designed and fabricated. Commercial carrier ampholytes (PharmalyteTM) with different pH range were engaged to generate a continuous pH gradient on sIEF device. Device design and optimized fabrication conditions were practically investigated; establishment of pH gradient was verified by fluorescent dyes; dependencies of electric field strength and carrier ampholytes concentration were systematically examined. To further optimize the sIEF system, dependencies of surface treatment and additive chemicals were explored. Fluorescent proteins and peptides were tested for the separation capability of sIEF. Finally, the well optimized sIEF system was used as a tool for real protein (hemoglobin variants and monoclonal antibody isoforms) separations. Hemoglobin variants test results revealed that sIEF is capable of separating amphoteric species with pI difference as small as 0.2. Monoclonal protein tests demonstrated the capability of sIEF to be a ready-to-use tool for protein structural change monitoring. In conclusion, this new sIEF approach has lower applied voltages, smaller sample requirements, a relatively quick fabrication process, and reusability, making it more attractive as a portable, user-friendly platform for qualitative protein detection and separation

Digital microfluidics on paper

This thesis is one of the first reports of digital microfluidics on paper and the first in which the chip’s circuit was screen printed unto the paper. The use of the screen printing technique, being a low cost and fast method for electrodes deposition, makes the all chip processing much more aligned with the low cost choice of paper as a substrate. Functioning chips were developed that were capable of working at as low as 50 V, performing all the digital microfluidics operations: movement, dispensing, merging and splitting of the droplets. Silver ink electrodes were screen printed unto paper substrates, covered by Parylene-C (through vapor deposition) as dielectric and Teflon AF 1600 (through spin coating) as hydrophobic layer. The morphology of different paper substrates, silver inks (with different annealing conditions) and Parylene deposition conditions were studied by optical microscopy, AFM, SEM and 3D profilometry. Resolution tests for the printing process and electrical characterization of the silver electrodes were also made. As a showcase of the applications potential of these chips as a biosensing device, a colorimetric peroxidase detection test was successfully done on chip, using 200 nL to 350 nL droplets dispensed from 1 μL drops

A frequency reconfigurable circularly polarized microstrip patch antenna using liquid metal microswitches

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2013.Cataloged from PDF version of thesis.Includes bibliographical references (p. 78-80).Reconfigurable antennas with adaptable frequency, pattern, and polarization offer flexibility and size reduction for wireless systems that must increasingly execute multiple missions with less volume. These antennas will also complement anticipated cognitive radio systems, which promise more efficient use of the electromagnetic spectrum. Microscale liquid metal switches are proposed to overcome the series loss, mechanical fatigue, and limited power handling reliability of common methods of antenna reconfiguration such as semiconductor diodes and microelectromechanical switches. The proposed microswitches consist of mercury droplets that selectively connect solid metal traces. Both fluidic and electrostatic switch actuation mechanisms are investigated, and an electrostatic switch is demonstrated. Electrostatically actuated switches are designed into a compact single-feed patch antenna configurable between two communication frequency bands and a GPS band with different circular polarizations. The antenna topology is based on a corner truncated square patch with switched sets of extensions to achieve resonant frequency and axial ratio control. Measurements of reconfigurable prototypes demonstrate frequency and polarization configurability in good agreement with full-wave simulations. The proposed reconfiguration mechanism is compared to other methods, and future directions for the integration of microfluidics in reconfigurable radio frequency systems are proposed.by Steven Christopher Yee.S.M

Self-contained microfluidic platform for general purpose lab-on-chip using pcb-mems technology.

El presente trabajo está centrado en la investigación de una nueva plataforma microfluídica autónoma para propósito general fabricada en PCBMEMS. En la vista de la proliferación en los últimos años de los sistemas microfluídicos Lab on Chip (LoC) y la multitud de aplicaciones en las que tienen cabida, surge la necesidad de creación de un sistema portable, autónomo y con una fabricación orientada hacia la producción masiva. En este contexto, se presenta el trabajo de esta tesis dentro de los proyectos de investigación de financiación nacional ISILAB (TEC2011-29045-C04-02) y BIOLOP (TEC2014-54449-C3-2- R). La tesis se encuentra organizada para cubrir los aspectos previamente propuestos. Primeramente, se presenta una introducción donde se explican los motivos para el desarrollo de este trabajo y cuáles son los objetivos específicos que se quieren cumplir. Seguidamente, se hace un breve estudio del arte. En este estudio se presenta la tecnología MEMS, los principios básicos de la microfluídica, que son los fundamentos de los sistemas LOCs y por último, se detalla un estudio de los principales elementos activos en la literatura que componen una plataforma microfluídica. Después de la introducción y revisión literaria del marco de esta tesis, se explican los resultados obtenidos. Esta tesis está desarrollada en dos fases principales: el desarrollo de todos los componentes que hacen un lab on chip autónomo de propósito general y el desarrollo de una tecnología basada en estándares para una producción masiva. En la primera fase se detallan los principales componentes que forman parte de una plataforma autónoma multifunción: microválvula, sistema de impulsión, circuito microfluídico y plataforma de sensado. Todos estos componentes son diseñados como un prototipo y están fabricados en SU-8 y PCBMEMS. El PCB permanece como sustrato y los canales y cámaras microfluídicas están fabricados en SU-8. La microválvula diseñada presenta una activación termoeléctrica, es de un solo uso y tiene una rápida activación y un consumo bajo de energía. Además, el diseño está pensado para ser altamente integrable en una plataforma microfluídica. El siguiente componente descrito es una sistema de impulsión basado en cámaras presurizadas, este sistema está integrado con la microválvula y su principal característica es la activación en el momento de uso, asegurando la ausencia de pérdidas. Para probar la validez de los componentes anteriores, se desarrolla un circuito microfluídico de propósito general. El circuito está diseñado para mezclar dos muestras y transportarlas a una cámara de detección. Finalmente, se desarrolla una plataforma para la detección de glucosa, integrable en el circuito microfluídico. Una vez desarrollado el prototipo, el siguiente objetivo de la tesis es el paso de la tecnología de prototipado hacía una de producción masiva. Para ello los materiales utilizados son el PMMA y el PCB. La tecnología PCBMEMS es conocida por su versatilidad para la integración de la electrónica, por lo que lo hace idóneo para la conexión con el exterior. El PMMA es un material también muy extendido en las aplicaciones microfluídicas, debido a su transparencia, bio compatibilidad y su fácil modelado. La unión de los dos componentes representa un desafío en el desarrollo de la tesis, debido a sus diferentes propiedades químicas. El proceso de fabricación se desarrolla integrando la microválvula y el sistema de impulsión, como partes de una plataforma microfluídica. Para terminar, se ha diseñado un pequeño circuito microfluídico para probar la viabilidad del sistema propuesto hacia una tecnología de gran escala. Finalmente, se exponen las conclusiones de la investigación, las posibles líneas futuras de este trabajo y los apéndices que complementan el trabajo de la tesis.The work presented is focused on the investigation of a new autonomous microfluidic platform manufactured using PCBMEMS technology for general purpose. With the proliferation of the microfluidic platforms, Lab on Chip (LoC), and the multitude of applications which have placed in the market, there is a need to create a self-contained microfluidic platform for general purpose with mass production-oriented manufacturing. Within this framework, the work of this thesis is presented. This is part of two national research project ISILAB (TEC2011-29045-C04-02) and BIOLOP (TEC2014-54449-C3-2- R). The thesis is organized to cover the aspects previously explained. Firstly, an introduction is presented with the motivation and objectives of this work. Subsequently, a study of the art is done. This study presents theMEMS technology, the basics principles of microfluidics, which are the pillars of the lab on chips and finally, a study of the main active elements presented in the literature. After the introduction and the literary revision of the framework of this thesis, the results obtained are presented. This thesis is developed in two main phases: the development of all components that make an autonomous general purpose lab on chip and the development of a standards-based technology for mass production. The first phase details the main components of an autonomous multifunction platform: microvalve, impulsion system, microfluidic circuit and sensing platform. All of these components are designed as a prototype and are manufactured in SU- 8 and PCBMEMS. The PCB remains as a substrate, and the microfluidic channels and chambers are manufactured in SU-8. The microvalve developed is a single use thermoelectrical microvalve with fast activation and low power consumption. In addition, the design is thought to be highly integrable in a microfluidic plat-form. The next component is a impulsion system based on pressurized chambers. The system is integrated with the microvalve and its main characteristic is the activation at the moment of use, ensuring the absence of losses. To test the validity of the above components, a general purpose microfluidic circuit is developed. The circuit is designed to mix two samples and transport those to a detection chamber. Finally, a platform for the detection of glucose, integrable in the microfluidic circuit, is developed. Once the prototype is achieved, the next objective of the thesis is the migration from prototyping technology to mass production. To this end, the materials used are PMMA and PCB. PCBMEMS technology is known for its versatility for the integration of electronics, making it suitable for electrical connection. PMMA is also widely used in microfluidic applications due to its transparency, bio compatibility and easy modeling. The union of the two components represents a challenge in the development of the thesis due to its different chemical properties. The manufacturing process is developed by integrating the microvalve and the drive system, as parts of a microfluidic platform. In conclusion, a small microfluidic circuit is designed by testing the feasibility of the proposed system towards large-scale technology. Finally, the conclusions of the research, the possible future lines of this work and the appendices that complement the work of the thesis are presented