Microdroplet Technology Based Functional Microcapsules Generation, Handling and Applications

制度:新 ; 報告番号:甲3593号 ; 学位の種類:博士(工学) ; 授与年月日:2012/2/25 ; 早大学位記番号:新593

Fabrication of Miniaturized Paper-Based Microfluidic Devices (MicroPADs)

Microfluidic paper-based analytical devices (microPADs) are emerging as cost-effective and portable platforms for point-of-care assays. A fundamental limitation of microPAD fabrication is the imprecise nature of most methods for patterning paper. The present work demonstrates that paper patterned via wax printing can be miniaturized by treating it with periodate to produce higher-resolution, high-fidelity microPADs. The optimal miniaturization parameters were determined by immersing microPADs in various concentrations of aqueous sodium periodate (NaIO4) for varying lengths of time. This treatment miniaturized microPADs by up to 80% in surface area, depending on the concentration of periodate and length of the reaction time. By immersing microPADs in 0.5-M NaIO4 for 48 hours, devices were miniaturized by 78% in surface area, and this treatment allowed for the fabrication of functional channels with widths as small as 301 µm and hydrophobic barriers with widths as small as 387 µm. The miniaturized devices were shown to be compatible with redox-based colorimetric assays and enzymatic reactions. This miniaturization technique provides a new option for fabricating sub-millimeter-sized features in paper-based fluidic devices without requiring specialized equipment and could enable new capabilities and applications for microPADs

MEMS Technology for Biomedical Imaging Applications

Biomedical imaging is the key technique and process to create informative images of the human body or other organic structures for clinical purposes or medical science. Micro-electro-mechanical systems (MEMS) technology has demonstrated enormous potential in biomedical imaging applications due to its outstanding advantages of, for instance, miniaturization, high speed, higher resolution, and convenience of batch fabrication. There are many advancements and breakthroughs developing in the academic community, and there are a few challenges raised accordingly upon the designs, structures, fabrication, integration, and applications of MEMS for all kinds of biomedical imaging. This Special Issue aims to collate and showcase research papers, short commutations, perspectives, and insightful review articles from esteemed colleagues that demonstrate: (1) original works on the topic of MEMS components or devices based on various kinds of mechanisms for biomedical imaging; and (2) new developments and potentials of applying MEMS technology of any kind in biomedical imaging. The objective of this special session is to provide insightful information regarding the technological advancements for the researchers in the community

Polymer-based device fabrication and applications using direct laser writing technology

Polymer materials exhibit unique properties in the fabrication of optical waveguide devices, electromagnetic devices, and bio-devices. Direct laser writing (DLW) technology is widely used for micro-structure fabrication due to its high processing precision, low cost, and no need for mask exposure. This paper reviews the latest research progresses of polymer-based micro/nano-devices fabricated using the DLW technique as well as their applications. In order to realize various device structures and functions, different manufacture parameters of DLW systems are adopted, which are also investigated in this work. The flexible use of the DLW process in various polymer-based microstructures, including optical, electronic, magnetic, and biomedical devices are reviewed together with their applications. In addition, polymer materials which are developed with unique properties for the use of DLW technology are also discussed

Optically Driven PH Gradient Generator Based on Self-Assembled Proton Pumps for Activating Hydrogel Microactuators

This dissertation presents a new approach for developing a biologically inspired photo-electro-chemo-mechanical microactuator by exploiting the ion pumping characteristics of bacteriorhodopsin (bR) proton pumps and the pH sensitivity of smart hydrogels. The ultimate goal of this project is to prove the viability of integrating bR monolayer into novel actuation applications using molecular level architectures. To accomplish this, the bR proton pumps are molecularly labelled, organized, and directionally immobilized on Au-coated substrate, and then integrated with pH sensitive hydrogel. When responding to an incident light beams, the internal proton pumping mechanism is mathematically modeled for quantifying the processing of the photonic energy into electro-chemical potential. Experimental and theoretical findings indicate that the photo-electric response of the dry bR is attributed to charge displacement and recombination; whereas, the response of the aqueous bR measured is a real proton pumping mechanism. The photo-electric properties, light source conditions all have influence on the observed photo-electric response characteristics. The presented technology is proven both experimentally and analytically through simulation. Experiments are conducted using acrylic acid (AA) monomer linked to 2-hydroxyethyl methacrylate (HEMA) monomer and the developed bR monolayer forming this hybrid microactuator. The light detecting part of the actuator is the bR monolayer. In this part the incident light beams are processed in the bR proton pumps through their photo-cycle to transport protons from the cytoplasmic side to the extracellular side of the bR protein. The bR monolayer is fabricated with molecular level recognition, labelling, and adsorption leading to a novel architecture able to transport protons through a porous substrate. Once protons are transported from one side to the other side of the membrane, the concentration of the hydrogen ions is changed. The change in the hydrogen ions concentration is expected theoretically and has been proved by monitoring pH changes in the ionic solution as pH gives direct indication on the hydrogen ions concentration. The change in the pH is exploited by integrating the light detecting part of the actuator to the pH-sensitive hydrogel which acts as the actuator shell that receives the pH changes and treat it as an input signal and then process it to undergo in an electric phase transition that leads to volume transition and associated mechanical work. The generated mechanical work is exploited in microactuation techniques with interest in microfluidic valves to control the flow in the microchannels. Based on the presented work the bR monolayer shows great potential for becoming a viable biomaterial for use in optical sensing and actuation. Many industrial and biomedical applications may benefit from the presented advances in generating higher performance micro-systems

An Optofluidic Lens Biochip and an x-ray Readable Blood Pressure Microsensor: Versatile Tools for in vitro and in vivo Diagnostics.

Three different microfabricated devices were presented for use in vivo and in vitro diagnostic biomedical applications: an optofluidic-lens biochip, a hand held digital imaging system and an x-ray readable blood pressure sensor for monitoring restenosis. An optofluidic biochip–termed the ‘Microfluidic-based Oil-Immersion Lens’ (mOIL) biochip were designed, fabricated and test for high-resolution imaging of various biological samples. The biochip consists of an array of high refractive index (n = 1.77) sapphire ball lenses sitting on top of an oil-filled microfluidic network of microchambers. The combination of the high optical quality lenses with the immersion oil results in a numerical aperture (NA) of 1.2 which is comparable to the high NA of oil immersion microscope objectives. The biochip can be used as an add-on-module to a stereoscope to improve the resolution from 10 microns down to 0.7 microns. It also has a scalable field of view (FOV) as the total FOV increases linearly with the number of lenses in the biochip (each lens has ~200 microns FOV). By combining the mOIL biochip with a CMOS sensor, a LED light source in 3D printed housing, a compact (40 grams, 4cmx4cmx4cm) high resolution (~0.4 microns) hand held imaging system was developed. The applicability of this system was demonstrated by counting red and white blood cells and imaging fluorescently labelled cells. In blood smear samples, blood cells, sickle cells, and malaria-infected cells were easily identified. To monitor restenosis, an x-ray readable implantable blood pressure sensor was developed. The sensor is based on the use of an x-ray absorbing liquid contained in a microchamber. The microchamber has a flexible membrane that is exposed to blood pressure. When the membrane deflects, the liquid moves into the microfluidic-gauge. The length of the microfluidic-gauge can be measured and consequently the applied pressure exerted on the diaphragm can be calculated. The prototype sensor has dimensions of 1x0.6x10mm and adequate resolution (19mmHg) to detect restenosis in coronary artery stents from a standard chest x-ray. Further improvements of our prototype will open up the possibility of measuring pressure drop in a coronary artery stent in a non-invasively manner.PhDMacromolecular Science and EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/111384/1/toning_1.pd

POLYMERIC MICRONEEDLES FOR TRANSDERMAL DRUG DELIVERY

Ph.DDOCTOR OF PHILOSOPH

Glassy Materials Based Microdevices

Microtechnology has changed our world since the last century, when silicon microelectronics revolutionized sensor, control and communication areas, with applications extending from domotics to automotive, and from security to biomedicine. The present century, however, is also seeing an accelerating pace of innovation in glassy materials; as an example, glass-ceramics, which successfully combine the properties of an amorphous matrix with those of micro- or nano-crystals, offer a very high flexibility of design to chemists, physicists and engineers, who can conceive and implement advanced microdevices. In a very similar way, the synthesis of glassy polymers in a very wide range of chemical structures offers unprecedented potential of applications. The contemporary availability of microfabrication technologies, such as direct laser writing or 3D printing, which add to the most common processes (deposition, lithography and etching), facilitates the development of novel or advanced microdevices based on glassy materials. Biochemical and biomedical sensors, especially with the lab-on-a-chip target, are one of the most evident proofs of the success of this material platform. Other applications have also emerged in environment, food, and chemical industries. The present Special Issue of Micromachines aims at reviewing the current state-of-the-art and presenting perspectives of further development. Contributions related to the technologies, glassy materials, design and fabrication processes, characterization, and, eventually, applications are welcome

Multipurpose platform based on LiNbO3 crystals for novel scenarios in soft matter manipulation

La possibilità di manipolare e dosare la cosiddetta “materia soffice” con tecniche che siano versatili ma anche dotate di elevata risoluzione spaziale, è di grande interesse per una vasta gamma di applicazioni. Questo lavoro di tesi si inserisce in questo contesto proponendo una piattaforma di tipo ferroelettrico in cui la polarizzazione spontanea di cristalli quali il niobato di litio (LiNbO3) è sfruttata ad arte per generare forze di tipo elettro-dinamico su scala micrometrica. Tali forze sono in grado di dosare e indirizzare opportunamente piccoli volumi di materiale fluido di tipo polimerico ma anche di tipo biologico. In particolare, i campi elettrici generati tramite effetto piroelettrico integrato su cristallo sono utilizzati qui per diversi tipi di applicazioni. I risultati mostrano come fluidi polimerici possono essere elettro-filati in modo controllato, evitando le instabilità tipiche dell’electrospinning tradizionale. Polimeri con proprietà ottiche opportune possono essere usati per stampare matrici di microlenti plastiche e versatili. L’energia solare può essere accumulata e sfruttata per sorgenti alternative di campi elettrici. Infine, la morfologia e le proprietà di adesione di cellule di fibroblasti viventi possono essere pilotate tramite le cariche di superficie espresse da tali supporti

A Novel Microbial Source Tracking DNA Microarray Used for Pathogen Detection in Environmental Systems

Pathogen detection and the identification of fecal contamination sources can be challenging in environmental and engineered treatment systems. Factors including pathogen diversity and ubiquity of fecal indicator bacteria hamper risk assessment and remediation of contamination sources. Therefore, a quick method that can detect and identify waterborne pathogens in environmental systems is needed. In this work, a custom microarray targeting pathogens (viruses, bacteria, protozoa), microbial source tracking (MST) markers, mitochondria DNA (mtDNA) and antibiotic resistance genes was used to detect over 430 selected gene targets in whole genome amplification (WGA) DNA and complementary DNA (cDNA) isolated from sewage and animal (avian, cattle, poultry and swine) feces, freshwater and marine water samples, sewage spiked surface water samples, treated wastewater and sewage contaminated produce.;A combination of perfect match and mismatch probes on the microarray reduced the likelihood of false positive detections, thus increasing the specificity of the microarray for various gene targets. A linear decrease in fluorescence of positive probes over a 1:10 dilution series demonstrated a semi-quantitative relationship between gene concentrations in a sample and microarray fluorescence. Various pathogens, including norovirus, Campylobacter fetus, Helicobacter pylori, Salmonella enterica, and Giardia lamblia were detected in sewage via the microarray, as well as MST markers and resistance genes to aminoglycosides, beta-lactams, and tetracycline. Sensitivity (percentage true positives) of MST results in sewage and animal waste samples (21--33%) was lower than specificity (83--90%, percentage of true negatives). Next generation sequencing (NGS) of DNA from the fecal samples revealed two dominant bacterial families that were common to all sample types: Ruminococcaceae and Lachnospiraceae. Five dominant phyla and 15 dominant families comprised 97% and 74%, respectively, of sequences from all fecal sources.;Waterborne pathogens were also detectable via the microarray in freshwater, marine water and sewage spiked surface water samples as well as treated wastewater. Ultrafiltration was used to concentrate microorganisms (bacteria, viruses, protozoa and parasites) from several liters of environmental and treated water samples. Dead-end ultrafiltration (DEUF) was shown to have a 61.4 +/- 47.8 % recovery efficiency and 46-fold concentration increasing ability. Then WGA was utilized to increase gene copies and lower the microarray detection limit. Viruses, including adenovirus, bocavirus, Hepatitis A virus, and polyomavirus were detected in human associated water samples as well as pathogens like Legionella pneumophila, Shigella flexneri, C. fetus and genes coding for resistance to aminoglycosides, beta-lactams, tetracycline. Microbial source tracking results indicate that sewage spiked freshwater and marine samples clustered separately from other fecal sources including wild and domestic animals via non-metric dimensional scaling. A linear relationship between qPCR and microarray fluorescence was found, indicating the semi-quantitative nature of the MST microarray.;Multiple displacement amplification (MDA), which is an important type of WGA, is a widely used tool to amplify genomic nucleic acids. The strong amplification efficiency of MDA and low initial template requirement make MDA an attractive method for environmental molecular and NGS studies. However, like other nucleic acid amplification techniques, various factors may influence MDA efficiency including template concentration (e.g. rare species swamping out), GC amplification bias and genome length favoring amplification of longer genomes. It was found that MDA increased nucleic acids in mixed environmental samples approximately 4.24 +/- 1.40 (log, average +/- standard deviation) for 16S rRNA gene of Enterococcus faecalis, 1.90 +/- 1.70 for RNA polymerase gene of human norovirus, 8.83 +/- 2.88 for T antigen gene of human polyomavirus, 3.83 +/- 0.93 for uidA gene of Escherichia coli, 4.96 +/- 0.32 for invA gene of S. enterica and 8.77 +/- 2.85 for 16S rRNA gene of human Bacteroidales. The template length, concentration and GC content were found to influence MDA efficiency. The results mainly show that the MDA will be more efficient the longer the template length, the greater the initial concentration of nucleic acids and the lower the GC content of the template.;Overall, the results of this work show that 1) the microarray and sample handling technique is suitable for pathogen detection from feces and sewage; 2) when combined with ultrafiltration techniques, the microarray can also be used as a pathogen detection tool in environmental waters; 3) template length, and initial concentration increase MDA efficiency, but higher GC content template negatively effects MDA efficiency. The proposed microarray can be used for pathogen detection in feces, wastewater treatment plant sewage, treated wastewater and environmental waters. Further the proposed method is potentially applicable to pathogen/microorganism detections on vegetables, seafood, in hospital settings, industrial wastewater, and aquaculture settings