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1
Heucke, Stephan F. "Advancing nanophotonic devices for biomolecular analysis". Diss., Ludwig-Maximilians-Universität München, 2013. http://nbn-resolving.de/urn:nbn:de:bvb:19-165294.
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2
Melli, Mauro. "Mechanical resonating devices and their applications in biomolecular studies". Doctoral thesis, SISSA, 2010. http://hdl.handle.net/20.500.11767/4646.
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To introduce the reader in the subjects of the thesis, Chapter 1 provides an overview on the
different aspects of the mechanical sensors. After a brief introduction to NEMS/MEMS, the
different approaches of mechanical sensing are provided and the main actuation and detection
schemes are described. The chapter ends with an introduction to microfabrication.
Chapter 2 deals with experimental details. In first paragraph the advantages of using a pillar
instead of common horizontal cantilever are illustrated. Then, the fabrication procedures and the
experimental setup for resonance frequencies measurement are described. The concluding
paragraph illustrates the technique, known as dip and dry, I used for coupling mechanical
detection with biological problems.
In Chapter 3, DNA kinetics of adsorption and hybridization efficiency, measured by means of pillar
approach, are reported.
Chapter 4 gives an overview of the preliminary results of two novel applications of pillar approach.
They are the development of a protein chip technology based on pillars and the second is the
combination of pillars and nanografting, an AFM based nanolithography.
Chapter 5 starts with an introduction about the twin cantilever approach and of the mechanically
induced functionalization. Fabrication procedure is described in the second paragraph. Then the
chemical functionalizations are described and proved. Cleaved surface analyses and the
spectroscopic studies of the mechanically induced functionalization are reported.
In Appendix A there is an overview of the physical models that are used in this thesis.
3
Sawlekar, Rucha. "Programming dynamic nonlinear biomolecular devices using DNA strand displacement reactions". Thesis, University of Warwick, 2016. http://wrap.warwick.ac.uk/91757/.
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Recent advances in DNA computing have greatly facilitated the design of biomolecular circuitry based on toehold-mediated DNA strand displacement (DSD) reactions. The synthesis of biomolecular circuits for controlling molecular-scale processes is an important goal of synthetic biology with a wide range of in vitro and in vivo applications. In this thesis, new results are presented on how chemical reaction networks (CRNs) can be used as a programming language to implement commonly used linear and nonlinear system theoretic operators that can be further utilised in combination to form complex biomolecular circuits. Within the same framework, the design of an important class of nonlinear feedback controller, i.e. a quasi sliding mode (QSM) feedback controller, is proposed. The closed loop response of the nonlinear QSM controller is shown to outperform a traditional linear proportional+integrator (PI) controller by facilitating much faster tracking response dynamics without introducing overshoots in the transient response. The resulting controller is highly modular and is less affected by retroactivity effects than standard linear designs. An important issue to consider in this design process for synthetic circuits is the effect of biological and experimental uncertainties on the functionality and reliability of the overall circuit. In the case of biomolecular feedback control circuits, such uncertainties could lead to a range of adverse effects, including achieving wrong concentration levels, sluggish performance and even instability. In this thesis, the robustness properties of two biomolecular feedback controllers; PI and QSM, subject to uncertainties in the experimentally implemented rates of their underlying chemical reactions, and to variations in accumulative time delays in the process to be controlled, are analysed. The simulation results show that the proposed QSM controller is significantly more robust against investigated uncertainties, highlighting its potential as a practically implementable biomolecular feedback controller for future synthetic biology applications. Finally, the thesis presents new results on the design of biomolecular feedback controllers using the set of chemical reactions underlying covalent modification cycles.
4
Kearns, Gregory Justin. "Engineering interfaces at the micro- and nanoscale for biomolecular and nanoparticle self-assembled devices /". view abstract or download file of text, 2007. http://proquest.umi.com/pqdweb?did=1417810561&sid=2&Fmt=2&clientId=11238&RQT=309&VName=PQD.
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Thesis (Ph. D.)--University of Oregon, 2007.Typescript. Includes vita and abstract. Includes bibliographical references (leaves 158-174). Also available for download via the World Wide Web; free to University of Oregon users.
5
Malmstadt, Noah. "Temperature-dependant [sic] smart bead adhesion : a versatile platform for biomolecular immobilization in microfluidic devices /". Thesis, Connect to this title online; UW restricted, 2003. http://hdl.handle.net/1773/8019.
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6
Tiwari, Purushottam Babu. "Multimode Analysis of Nanoscale Biomolecular Interactions". FIU Digital Commons, 2015. http://digitalcommons.fiu.edu/etd/1923.
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Biomolecular interactions, including protein-protein, protein-DNA, and protein-ligand interactions, are of special importance in all biological systems. These interactions may occer during the loading of biomolecules to interfaces, the translocation of biomolecules through transmembrane protein pores, and the movement of biomolecules in a crowded intracellular environment. The molecular interaction of a protein with its binding partners is crucial in fundamental biological processes such as electron transfer, intracellular signal transmission and regulation, neuroprotective mechanisms, and regulation of DNA topology. In this dissertation, a customized surface plasmon resonance (SPR) has been optimized and new theoretical and label free experimental methods with related analytical calculations have been developed for the analysis of biomolecular interactions.
Human neuroglobin (hNgb) and cytochrome c from equine heart (Cyt c) proteins have been used to optimize the customized SPR instrument. The obtained Kd value (~13 µM), from SPR results, for Cyt c-hNgb molecular interactions is in general agreement with a previously published result. The SPR results also confirmed no significant impact of the internal disulfide bridge between Cys 46 and Cys 55 on hNgb binding to Cyt c. Using SPR, E. coli topoisomerase I enzyme turnover during plasmid DNA relaxation was found to be enhanced in the presence of Mg2+. In addition, a new theoretical approach of analyzing biphasic SPR data has been introduced based on analytical solutions of the biphasic rate equations.
In order to develop a new label free method to quantitatively study protein-protein interactions, quartz nanopipettes were chemically modified. The derived Kd (~20 µM) value for the Cyt c-hNgb complex formations matched very well with SPR measurements (Kd ~16 µM). The finite element numerical simulation results were similar to the nanopipette experimental results. These results demonstrate that nanopipettes can potentially be used as a new class of a label-free analytical method to quantitatively characterize protein-protein interactions in attoliter sensing volumes, based on a charge sensing mechanism.
Moreover, the molecule-based selective nature of hydrophobic and nanometer sized carbon nanotube (CNT) pores was observed. This result might be helpful to understand the selective nature of cellular transport through transmembrane protein pores.
7
Hahn, Jaeseung. "Programmable biomolecular integration and dynamic behavior of DNA-based systems for development of biomedical nano-devices". Thesis, Massachusetts Institute of Technology, 2019. https://hdl.handle.net/1721.1/122213.
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Thesis: Ph. D. in Medical Engineering and Medical Physics, Harvard-MIT Program in Health Sciences and Technology, 2019Cataloged from PDF version of thesis.
Includes bibliographical references.
Departing from the traditional role as a carrier of genetic information, DNA has emerged as an engineering material for construction of nano-devices. The advances in the field of DNA nanotechnology have enabled design and synthesis of DNA nanostructures of arbitrary shapes and manipulation of the nanostructures' conformations in a programmable way. DNA-based systems offer potential applications in medicine by manipulating the biological components and processes that occur at the nanometer scale. To accelerate the translation of DNA-based systems for medical applications, we identified some of the challenges that are hindering our ability to construct biomedical nano-devices and addressed these challenges through advances in both structural and dynamic DNA nanotechnology. First, we tested the stability of DNA nanostructures in biological environments to highlight the necessity of and path towards protection strategies for prolonged integrity of biomedical nano-devices. Then, we constructed a platform for robust 3D molecular integration using DNA origami technique and implemented the platform for a nanofactory capable of production of therapeutic RNA to overcome the challenges in RNA delivery. Moreover, we established a mechanism to drive DNA devices by changing temperature with prolonged dynamic behavior that was previously challenging to accomplish without special modification of DNA and/or equipment not readily available in a typical lab setting. Together, the progress made in this thesis bring us another step closer to realization of medical applications of DNA nanotechnology by focusing on the challenges in both structural and dynamic aspects of the technology.
by Jaeseung Hahn.
Ph. D. in Medical Engineering and Medical Physics
Ph.D.inMedicalEngineeringandMedicalPhysics Harvard-MIT Program in Health Sciences and Technology
8
Razaq, Aamir. "Development of Cellulose-Based, Nanostructured, Conductive Paper for Biomolecular Extraction and Energy Storage Applications". Doctoral thesis, Uppsala universitet, Nanoteknologi och funktionella material, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-158444.
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Conductive paper materials consisting of conductive polymers and cellulose are promising for high-tech applications (energy storage and biosciences) due to outstanding aspects of environmental friendliness, mechanical flexibility, electrical conductivity and efficient electroactive behavior. Recently, a conductive composite paper material was developed by covering the individual nanofibers of cellulose from the green algae Cladophora with a polypyrrole (PPy) layer. The PPy-Cladophora cellulose composite paper is featured with high surface area (80 m2 g-1), electronic conductivity (~2 S cm-1), thin conductive layer (~50 nm) and easily up-scalable manufacturing process. This doctoral thesis reports the development of the PPy-Cladophora composite as an electrode material in electrochemically controlled solid phase ion-exchange of biomolecules and all-polymer based energy storage devices. First, electrochemical ion-exchange properties of the PPy-Cladophora cellulose composite were investigated in electrolytes containing three different types of anions, and it was found that smaller anions (nitrate and chloride) are more readily extracted by the composite than lager anions (p-toluene sulfonate). The influence of differently sized oxidants used during polymerization on the anion extraction capacity of the composite was also studied. The composites synthesized with two different oxidizing agents, i.e. iron (III) chloride and phosphomolybdic acid (PMo), were investigated for their ability to extract anions of different sizes. It was established that the number of absorbed ions was larger for the iron (III) chloride-synthesized sample than for the PMo-synthesized sample for all four electrolytes studied. Further, PPy-Cladophora cellulose composites have shown remarkable electrochemically controlled ion extraction capacities when investigated as a solid phase extraction material for batch-wise extraction and release of DNA oligomers. In addition, composite paper was also investigated as an electrode material in the symmetric non-metal based energy storage devices. The salt and paper based energy storage devices exhibited charge capacities (38−50 mAh g−1) with reasonable cycling stability, thereby opening new possibilities for the production of environmentally friendly, cost efficient, up-scalable and lightweight energy storage systems. Finally, micron-sized chopped carbon fibers (CCFs) were incorporated as additives to improve the charge-discharge rates of paper-based energy storage devices and to enhance the DNA release efficiency. The results showed the independent cell capacitances of ~60-70 F g-1 (upto current densities of 99 mA cm2) and also improved the efficiency of DNA release from 25 to 45%.
9
Heucke, Stephan F. Verfasser], i Hermann E. [Akademischer Betreuer] [Gaub. "Advancing nanophotonic devices for biomolecular analysis : force spectroscopy and nanopositioning of single molecules in zero-mode waveguides / Stephan F. Heucke. Betreuer: Hermann Gaub". München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2013. http://d-nb.info/1046785311/34.
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10
Absher, Jason Matthew. "THE DEVELOPMENT OF MICROFLUIDIC DEVICES FOR THE PRODUCTION OF SAFE AND EFFECTIVE NON-VIRAL GENE DELIVERY VECTORS". UKnowledge, 2018. https://uknowledge.uky.edu/cme_etds/85.
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Including inherited genetic diseases, like lipoprotein lipase deficiency, and acquired diseases, such as cancer and HIV, gene therapy has the potential to treat or cure afflicted people by driving an affected cell to produce a therapeutic protein. Using primarily viral vectors, gene therapies are involved in a number of ongoing clinical trials and have already been approved by multiple international regulatory drug administrations for several diseases. However, viral vectors suffer from serious disadvantages including poor transduction of many cell types, immunogenicity, direct tissue toxicity and lack of targetability. Non-viral polymeric gene delivery vectors (polyplexes) provide an alternative solution but are limited by poor transfection efficiency and cytotoxicity. Microfluidic (MF) nano-precipitation is an emerging field in which researchers seek to tune the physicochemical properties of nanoparticles by controlling the flow regime during synthesis. Using this approach, several groups have demonstrated the successful production of enhanced polymeric gene delivery vectors. It has been shown that polyplexes created in the diffusive flow environment have a higher transfection efficiency and lower cytotoxicity. Other groups have demonstrated that charge-stabilizing polyplexes by sequentially adding polymers of alternating charges improves transfection efficiency and serum stability, also addressing major challenges to the clinical implementation of non-viral gene delivery vectors.
To advance non-viral gene delivery towards clinical relevance, we have developed a microfluidic platform (MS) that produces conventional polyplexes with increased transfection efficiency and decreased toxicity and then extended this platform for the production of ternary polyplexes. This work involves first designing microfluidic devices using computational fluid dynamics (CFD), fabricating the devices, and validating the devices using fluorescence flow characterization and absorbance measurements of the resulting products. With an integrated separation mechanism, excess polyethylenimine (PEI) is removed from the outer regions of the stream leaving purified polyplexes that can go on to be used directly in transfections or be charge stabilized by addition of polyanions such as polyglutamic acid (PGA) for the creation of ternary polyplexes. Following the design portion of the research, the device was used to produce binary particle characterization was carried out and particle sizes, polydispersity and zeta potential of both conventional and MS polyplexes was compared. MS-produced polyplexes exhibited up to a 75% reduction in particle size compared to BM-produced polyplexes, while exhibiting little difference in zeta potential and polydispersity. A variety of standard biological assays were carried out to test the effects of the vectors on a variety of cell lines – and in this case the MS polyplexes proved to be both less toxic and have higher transfection efficiency in most cell lines. HeLa cells demonstrated the highest increase in transgene expression with a 150-fold increase when comparing to conventional bulk mixed polyplexes at the optimum formulation. A similar set of experiments were carried out with ternary polyplexes produced by the separation device. In this case it was shown that there were statistically significant increases in transfection efficiency for the MS-produced ternary polyplexes compared to BM-produced poyplexes, with a 23-fold increase in transfection activity at the optimum PEI/DNA ratio in MDAMB-231 cells. These MS-produced ternary polyplexes exhibited higher cell viability in many instances, a result that may be explained but the reduction in both free polymer and ghost particles.
11
Hou, Chih-Sheng Johnson. "An integrated microelectronic device for biomolecular amplification and detection". Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/38676.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2007.Includes bibliographical references (p. 133-154).
The extraordinarily high sensitivity, large dynamic range and reproducibility of polymerase chain reaction (PCR) have made it one of the most widely used techniques for analyzing nucleic acids. As a result, considerable effort has been directed towards developing miniaturized systems for PCR, but most rely on off-chip optical detection modules that are difficult to miniaturize into a compact analytical system and fluorescent product markers that can require extensive effort to optimize. This thesis presents a robust and simple method for direct label-free PCR product quantification using a microelectronic sensor. The thesis covers the design, fabrication, and characterization of the sensing technique and its integration with PCR microfluidics into a monolithic detection platform. The sensor used in this thesis study is an electrolyte-insulator-silicon (EIS) device fabricated on planar silicon substrates. Based on electronic detection of layer-by-layer assembly of polyelectrolytes, the sensing technique can specifically quantify double-stranded DNA product in unprocessed samples and monitor the product concentration at various stages of PCR to generate readout analogous to that of a real-time fluorescent measurement.
(cont.) Amplification is achieved with integrated metal resistive heaters, temperature sensors, and microfluidic valves. Direct electronic quantification of the product on-chip yields analog surface potential signals that can be converted to a digital true/false readout. A silicon field-effect sensor for direct detection of heparin by its intrinsic negative charge has also been developed. Detection of heparin and heparin-based drugs in buffer and serum has been studied, and a study demonstrating strong correlation between electronic heparin sensing measurements and those from a colorimetric assay for heparin-mediated anti-Xa activity has been performed.
by Chih-Sheng Johnson Hou.
Ph.D.
12
Kawabata, Tomohisa. "Studies on measurements of biomolecules using micro fluidic devices". Kyoto University, 2009. http://hdl.handle.net/2433/124023.
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13
Jönsson, Mats. "Microfluidic Devices for Manipulation and Detection of Beads and Biomolecules". Doctoral thesis, Uppsala universitet, Institutionen för teknikvetenskaper, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6746.
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This thesis summarises work towards a Lab-on-Chip (LOC). The request for faster and more efficient chemical and biological analysis is the motivation behind the development of the LOC-concept. Microfluidic devices tend to become increasingly complex in order to include, e.g. sample delivery, manipulation, and detection, in one chip. The urge for smart and simple design of robust and low-cost microdevices is addressed and discussed. Design, fabrication and characterization of such microdevices have been demonstrated using low-cost polymer and glass microfabrication methods. The manufacturing is feasible, to a large extent, to perform outside the clean-room, and has subsequently been the chosen technique for most of the work. Issues of bonding reliability are solved by using polymer adhesive tapes. A planar electrocapture device with LOC-compatibility is demonstrated where beads are immobilised and released in a flowing stream. Retention of nanoparticles by means of electric field-flow fractionation using transparent indium tin oxide electrodes is presented. Moreover, a cast PDMS 4-way crossing is enabling a combination of liquid chromatography and capillary electrophoresis to enhance separation efficiency. Sample transport issues and a new flow-cell design in a quartz crystal microbalance bioanalyzer are also investigated. Fast bacteria counting by impedance measurements, much requested by the pharmaceutical industry for biomass monitoring, is carried out successfully. In conclusion, knowledge in micro system technology to build microdevices have been utilised to manipulate and characterise beads and cells, taking one step further towards viable Lab-on-Chip instruments.
14
Jönsson, Mats. "Microfluidic devices for manipulation and detection of beads and biomolecules /". Uppsala : Acta Universitatis Upsaliensis : Universitetsbiblioteket [distributör], 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6746.
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Wang, Ying-Chih 1977. "Electrokinetic trapping of biomolecules : novel nanofluidic devices for proteomic applications". Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/40358.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2007.Includes bibliographical references (p. 135-141).
Sample preparation has long been the most important and costly process in bioanalyses. Conventional identification methods involve multiple purification steps combined with mass spectrometry or immunosensing. While well-developed and widely utilized, these methods require extensive human labor and exhibit limited resolving power for low abundance analytes. Due to the shear complexity and abundance variation of biosamples, rapid and ultra-sensitive diagnostic measurements of disease markers are still out of reach. To address this issue, we developed a novel nanofluidic concentrator, utilizing the unique concentration polarization effect of sub 50 nm nanofluidic filters. With the distinct ionic and molecular interaction at the nanoscale, nanofluidic systems can potentially outperform current sample preparation and molecular detection techniques. Aiming to investigate and expand the applications of these techniques, this thesis work involves the design and development of a highly efficient nanofluidic preconcentrator, which can achieve a million fold detectability enhancements without complex buffer arrangements. This thesis also includes an integrated preconcentration-immunosensing device.
(cont.) By manipulating analyte concentrations, this integrated device not only increases the detection sensitivity, but also expands the dynamic range of given antibody-antigen couples. In addition, we also investigated the ion transfer at the micro-/nano-fluidic interface. Depending on the strength of the applied electric field across the nanochannel array, various phenomena such as concentration polarization, charge depletion, and nonlinear electrokinetic flows in the adjacent microfluidic channel can be observed and studied in situ by fluorescent microscopy. In summary, the nanofluidic concentrator we developed in this thesis facilitates sample preparation and detection of biomolecules from complex biological matrices and facilitates a further understanding of nanoscale molecular/fluid/ion transport phenomena by providing a well-controlled experimental platform.
by Ying-Chih Wang.
Ph.D.
16
Branquinho, Rita. "Label-free detection of biomolecules with Ta2O5-based field effect devices". Doctoral thesis, Faculdade de Ciências e Tecnologia, 2012. http://hdl.handle.net/10362/9413.
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17
Holowacz, Markus, Annika Krans, Camilla Wallén, Alberto Martinez i Nadia Mohammadi. "A Survey of Commercial Biomolecules, Delimited to Pharmaceuticals and Medical Devices". Thesis, Uppsala universitet, Institutionen för teknikvetenskaper, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-324833.
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Biologics — biomolecule-based therapeutics — are predicted to become the next generation of therapeutical drugs. The pharmaceutical industry is investing a great amount of money into research in this medical field, which shows the importance and the need of analyses regarding biological drugs. This report is a survey of commercial biologics in which the market and trends regarding the past, present and future are analysed. The results are based on a literature study limited to commercial biologics — either as chemical entities, as conjugates to another class of biomolecules or as medical devices. The market for biomolecule-based therapeutics and medical devices is predicted to flourish as the new generations of peptides, proteins, oligonucleotides, carbohydrates and lipids increase in both approvals and sales. The fact that scientists have gained a broader comprehension on a molecular level due to advanced technologies has resulted in biologics reaching clinical maturity. The optimized pharmacokinetic properties, greater specificity, and the increased therapeutic window have led to reduced side effects compared to traditional therapeutical alternatives. Due to new development approaches — peptidomimetics — the stability of peptides has shown to increase. This results in a huge market and development potential. The protein therapeutics market is the largest among biologics, and their subgroup — the monoclonal antibody-based therapeutics market — is the fastest growing. With a high growth rate of novel therapeutics in development, the market will continue to expand. Conjugated monoclonal antibodies (ADC) and GalNAc conjugates to small interfering RNA are just a few examples of high potential drugs that are expected to increase on the market and in clinical development. Oncology is the dominating therapeutic area, where great success has been observed in both clinical and pre-clinical studies. Lipid conjugates have proven to be efficient in the treatment of tumour cells and the cytotoxic ADC grant great hope for the biomolecule-based therapeutics market. The market is also expected to grow for establishing biologics; for example the increasing need of anticoagulants is predicted to double the Heparin market to 2023 and the demand for novel treatment alternatives opens market opportunities for Heparin biosimilars. The biological vaccine market is also predicted to grow together with biologics, as mutated animal-spread diseases increase in number.
18
Martinez, Alberto, Nadia Mohammadi, Markus Holowacz, Annika Krans i Camilla Wallén. "A Survey of Commercial Biomolecules, Delimited to Pharmaceuticals and Medical Devices". Thesis, Uppsala universitet, Institutionen för teknikvetenskaper, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-324840.
Pełny tekst źródłaStreszczenie:
Biologics — biomolecule-based therapeutics — are predicted to become the next generation of therapeutical drugs. The pharmaceutical industry is investing a great amount of money into research in this medical field, which shows the importance and the need of analyses regarding biological drugs. This report is a survey of commercial biologics in which the market and trends regarding the past, present and future are analysed. The results are based on a literature study limited to commercial biologics — either as chemical entities, as conjugates to another class of biomolecules or as medical devices. The market for biomolecule-based therapeutics and medical devices is predicted to flourish as the new generations of peptides, proteins, oligonucleotides, carbohydrates and lipids increase in both approvals and sales. The fact that scientists have gained a broader comprehension on a molecular level due to advanced technologies has resulted in biologics reaching clinical maturity. The optimized pharmacokinetic properties, greater specificity, and the increased therapeutic window have led to reduced side effects compared to traditional therapeutical alternatives. Due to new development approaches — peptidomimetics — the stability of peptides has shown to increase. This results in a huge market and development potential. The protein therapeutics market is the largest among biologics, and their subgroup — the monoclonal antibody-based therapeutics market — is the fastest growing. With a high growth rate of novel therapeutics in development, the market will continue to expand. Conjugated monoclonal antibodies (ADC) and GalNAc conjugates to small interfering RNA are just a few examples of high potential drugs that are expected to increase on the market and in clinical development. Oncology is the dominating therapeutic area, where great success has been observed in both clinical and pre-clinical studies. Lipid conjugates have proven to be efficient in the treatment of tumour cells and the cytotoxic ADC grant great hope for the biomolecule-based therapeutics market. The market is also expected to grow for establishing biologics; for example the increasing need of anticoagulants is predicted to double the Heparin market to 2023 and the demand for novel treatment alternatives opens market opportunities for Heparin biosimilars. The biological vaccine market is also predicted to grow together with biologics, as mutated animal-spread diseases increase in number.
19
Greco, Pierpaolo <1977>. "Microfluidic device and interfacial transport: application to biomolecules and nanostructures". Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2009. http://amsdottorato.unibo.it/1663/1/Pierpaolo_Greco_PhD_thesis.pdf.
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The aim of my dissertation is to provide new knowledge and applications of microfluidics in a variety of problems, from materials science, devices, and biomedicine, where the control on the fluid dynamics and the local concentration of the solutions containing the relevant molecules (either materials, precursors, or biomolecules) is crucial. The control of interfacial phenomena occurring in solutions at dierent length scales is compelling in nanotechnology for devising new sensors, molecular electronics devices, memories.
Microfluidic devices were fabricated and integrated with organic electronics devices. The transduction involves the species in the solution which infills the transistor channel and confined by the microfluidic device. This device measures what happens on the surface, at few nanometers from the semiconductor channel. Soft-lithography was adopted to fabricate platinum electrodes, starting from platinum carbonyl precursor. I proposed a simple method to assemble these nanostructures in periodic arrays of microstripes, and form conductive electrodes with characteristic dimension of 600 nm. The conductivity of these sub-microwires is compared with the values reported in literature and bulk platinum. The process is suitable for fabricating thin conductive patterns for electronic devices or electrochemical cells, where the periodicity of the conductive pattern is comparable with the diusion length of the molecules in solution.
The ordering induced among artificial nanostructures is of particular interest in science. I show that large building blocks, like carbon nanotubes or core-shell nanoparticles, can be ordered and self-organised on a surface in patterns due to capillary forces. The eective probability of inducing order with microfluidic flow is modeled with finite element calculation on the real geometry of the microcapillaries, in soft-lithographic process.
The oligomerization of A40 peptide in microconfined environment represents a new investigation of the extensively studied peptide aggregation. The added value of the approach I devised is the precise control on the local concentration of peptides together with the possibility
to mimick cellular crowding. Four populations of oligomers where distinguished, with diameters ranging from 15 to 200 nm. These aggregates could not be addresses separately in fluorescence. The statistical analysis on the atomic force microscopy images together with a model of growth reveal new insights on the kinetics of amyloidogenesis as well as allows me to identify the minimum stable nucleus size. This is an important result owing to its implications in the understanding and early diagnosis and therapy of the Alzheimer’s disease
20
Greco, Pierpaolo <1977>. "Microfluidic device and interfacial transport: application to biomolecules and nanostructures". Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2009. http://amsdottorato.unibo.it/1663/.
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The aim of my dissertation is to provide new knowledge and applications of microfluidics in a variety of problems, from materials science, devices, and biomedicine, where the control on the fluid dynamics and the local concentration of the solutions containing the relevant molecules (either materials, precursors, or biomolecules) is crucial. The control of interfacial phenomena occurring in solutions at dierent length scales is compelling in nanotechnology for devising new sensors, molecular electronics devices, memories.
Microfluidic devices were fabricated and integrated with organic electronics devices. The transduction involves the species in the solution which infills the transistor channel and confined by the microfluidic device. This device measures what happens on the surface, at few nanometers from the semiconductor channel. Soft-lithography was adopted to fabricate platinum electrodes, starting from platinum carbonyl precursor. I proposed a simple method to assemble these nanostructures in periodic arrays of microstripes, and form conductive electrodes with characteristic dimension of 600 nm. The conductivity of these sub-microwires is compared with the values reported in literature and bulk platinum. The process is suitable for fabricating thin conductive patterns for electronic devices or electrochemical cells, where the periodicity of the conductive pattern is comparable with the diusion length of the molecules in solution.
The ordering induced among artificial nanostructures is of particular interest in science. I show that large building blocks, like carbon nanotubes or core-shell nanoparticles, can be ordered and self-organised on a surface in patterns due to capillary forces. The eective probability of inducing order with microfluidic flow is modeled with finite element calculation on the real geometry of the microcapillaries, in soft-lithographic process.
The oligomerization of A40 peptide in microconfined environment represents a new investigation of the extensively studied peptide aggregation. The added value of the approach I devised is the precise control on the local concentration of peptides together with the possibility
to mimick cellular crowding. Four populations of oligomers where distinguished, with diameters ranging from 15 to 200 nm. These aggregates could not be addresses separately in fluorescence. The statistical analysis on the atomic force microscopy images together with a model of growth reveal new insights on the kinetics of amyloidogenesis as well as allows me to identify the minimum stable nucleus size. This is an important result owing to its implications in the understanding and early diagnosis and therapy of the Alzheimer’s disease
21
Park, Jung Jin. "Development of bioMEMS device and package for a spatially programmable biomolecule assembly". College Park, Md. : University of Maryland, 2006. http://hdl.handle.net/1903/3871.
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Thesis (Ph. D.) -- University of Maryland, College Park, 2006.Thesis research directed by: Material Science and Engineering. Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.
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Choi, Seong-O. "An Electrically Active Microneedle Electroporation Array for Intracellular Delivery of Biomolecules". Diss., Georgia Institute of Technology, 2007. http://hdl.handle.net/1853/19710.
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The objective of this research is the development of an electrically active microneedle array that can deliver biomolecules such as DNA and drugs to epidermal cells by means of electroporation. Properly metallized microneedles could serve as microelectrodes essential for electroporation. Furthermore, the close needle-to-needle spacing of microneedle electrodes provides the advantage of utilizing reduced voltage, which is essential for safety as well as portable applications, while maintaining the large electric fields required for electroporation. Therefore, microneedle arrays can potentially be used as part of a minimally invasive, highly-localized electroporation system for cells in the epidermis layer of the skin.
This research consists of three parts: development of the 3-D microfabrication technology to create the microneedle array, fabrication and characterization of the microneedle array, and the electroporation studies performed with the microneedle array. A 3-D fabrication process was developed to produce a microneedle array using an inclined UV exposure technique combined with micromolding technology, potentially enabling low cost mass-manufacture. The developed technology is also capable of fabricating 3-D microstructures of various heights using a single mask.
The fabricated microneedle array was then tested to demonstrate its feasibility for through-skin electrical and mechanical functionality using a skin insertion test. It was found that the microneedles were able to penetrate skin without breakage. To study the electrical properties of the array, a finite element simulation was performed to examine the electric field distribution. From these simulation results, a predictive model was constructed to estimate the effective volume for electroporation. Finally, studies to determine hemoglobin release from bovine red blood cells (RBC) and the delivery of molecules such as calcein and bovine serum albumin (BSA) into human prostate cancer cells were used to verify the electrical functionality of this device.
This work established that this device can be used to lyse RBC and to deliver molecules, e.g. calcein, into cells, thus supporting our contention that this metallized microneedle array can be used to perform electroporation at reduced voltage. Further studies to show efficacy in skin should now be performed.
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Rani, Dipti [Verfasser]. "Label-free detection of biomolecules using silicon nanowire ion-sensitive field-effect transistor devices / Dipti Rani". Gießen : Universitätsbibliothek, 2018. http://d-nb.info/1156851343/34.
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Wöhrle, Johannes Verfasser], i Gerald A. [Akademischer Betreuer] [Urban. "Microfluidic device for the generation and replication of DNA microarrays and the label-free detection of biomolecular interactions on these arrays". Freiburg : Universität, 2020. http://d-nb.info/1236500385/34.
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Lao, Ieng Kin. "Mechanistic and experimental investigations of pulsed electric field flow fractionation micro device and its applications for nanoparticle and biomolecule separation /". View abstract or full-text, 2004. http://library.ust.hk/cgi/db/thesis.pl?CENG%202004%20LAO.
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Thesis (Ph. D.)--Hong Kong University of Science and Technology, 2004.Accompanying CD-ROM contains supporting information on avi formated video clips. Includes bibliographical references (leaves 172-183). Also available in electronic version. Access restricted to campus users.
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bhardwaj, vinay. "Label-free surface-enhanced Raman spectroscopy-linked immunosensor assay (SLISA) for environmental surveillance". FIU Digital Commons, 2015. http://digitalcommons.fiu.edu/etd/2321.
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The contamination of the environment, accidental or intentional, in particular with chemical toxins such as industrial chemicals and chemical warfare agents has increased public fear. There is a critical requirement for the continuous detection of toxins present at very low levels in the environment. Indeed, some ultra-sensitive analytical techniques already exist, for example chromatography and mass spectroscopy, which are approved by the US Environmental Protection Agency for the detection of toxins. However, these techniques are limited to the detection of known toxins. Cellular expression of genomic and proteomic biomarkers in response to toxins allows monitoring of known as well as unknown toxins using Polymerase Chain Reaction and Enzyme Linked Immunosensor Assays. However, these molecular assays allow only the endpoint (extracellular) detection and use labels such as fluorometric, colorimetric and radioactive, which increase chances of uncertainty in detection. Additionally, they are time, labor and cost intensive. These technical limitations are unfavorable towards the development of a biosensor technology for continuous detection of toxins. Federal agencies including the Departments of Homeland Security, Agriculture, Defense and others have urged the development of a detect-to-protect class of advanced biosensors, which enable environmental surveillance of toxins in resource-limited settings.
In this study a Surface-Enhanced Raman Spectroscopy (SERS) immunosensor, aka a SERS-linked immunosensor assay (SLISA), has been developed. Colloidal silver nanoparticles (Ag NPs) were used to design a flexible SERS immunosensor. The SLISA proof-of-concept biosensor was validated by the measurement of a dose dependent expression of RAD54 and HSP70 proteins in response to H2O2 and UV. A prototype microchip, best suited for SERS acquisition, was fabricated using an on-chip SLISA to detect RAD54 expression in response to H2O2. A dose-response relationship between H2O2 and RAD54 is established and correlated with EPA databases, which are established for human health risk assessment in the events of chemical exposure. SLISA outperformed ELISA by allowing RISE (rapid, inexpensive, simple and effective) detection of proteins within 2 hours and 3 steps. It did not require any label and provided qualitative information on antigen-antibody binding. SLISA can easily be translated to a portable assay using a handheld Raman spectrometer and it can be used in resource-limited settings. Additionally, this is the first report to deliver Ag NPs using TATHA2, a fusogenic peptide with cell permeability and endosomal rupture release properties, for rapid and high levels of Ag NPs uptake into yeast without significant toxicity, prerequisites for the development of the first intracellular SERS immunosensor.
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Sullivan, Sean Padraic. "Polymer microneedles for transdermal delivery of biopharmaceuticals". Diss., Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/33873.
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Biopharmaceuticals, including proteins, DNA and vaccines, are one of the fastest growing segments of the overall pharmaceutical market. While the hypodermic injection, the most common delivery method for these molecules, is effective, it also has limitations, including low patient compliance, need for medically trained personnel and biohazardous sharps after delivery. The overall goal of this thesis was to develop a new delivery system for biopharmaceuticals, based on dissolving polymer microneedles, which is effective and more patient compliant than the hypodermic needle.
Microneedles are microscopic needles that are large enough to insert into the skin to deliver drugs effectively, while being short enough to avoid the pain causing nerves deep in the skin. An additional benefit of polymer microneedles is that the needles completely dissolve in the skin, leaving behind no biohazardous sharps. There are significant material and fabrication issues that must be overcome in the development of this new device.
The first part of this thesis focused on the development of a new fabrication process, based on in situ photopolymerization, for the creation of polymer microneedles. These microneedles were shown to successfully insert into the skin, dissolving within a minute to deliver the encapsulated cargo, and retain full activity of encapsulated proteins.
Next, we applied the microneedle technology to the delivery of the influenza virus. We found that the reformulation process required to encapsulate the influenza virus in polymer microneedles did not affect the antigenicity or immunogenicity of the virus. In addition, we used coated metal microneedles to successfully immunize mice with the influenza virus, verifying the delivery capabilities of a microneedle system.
Finally, we used the dissolving polymer microneedles to successfully immunize mice with the influenza virus, resulting in full protection against lethal challenge after one immunization. This immune response was equivalent to the control intramuscular injection. In conclusion, we have developed dissolving polymer microneedles as an effective and patient compliant delivery system for biopharmaceuticals. This system could be especially applicable to mass immunization efforts or home use, since it can be self-administered and allows for easy disposal with no biohazardous sharps.
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Jalal, Ahmed Hasnain. "Multivariate Analysis for the Quantification of Transdermal Volatile Organic Compounds in Humans by Proton Exchange Membrane Fuel Cell System". FIU Digital Commons, 2018. https://digitalcommons.fiu.edu/etd/3886.
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In this research, a proton exchange membrane fuel cell (PEMFC) sensor was investigated for specific detection of volatile organic compounds (VOCs) for point-of-care (POC) diagnosis of the physiological conditions of humans. A PEMFC is an electrochemical transducer that converts chemical energy into electrical energy. A Redox reaction takes place at its electrodes whereas the volatile biomolecules (e.g. ethanol) are oxidized at the anode and ambient oxygen is reduced at the cathode. The compounds which were the focus of this investigation were ethanol (C2H5OH) and isoflurane (C3H2ClF5O), but theoretically, the sensor is not limited to only those VOCs given proper calibration.
Detection in biosensing, which needs to be carried out in a controlled system, becomes complex in a multivariate environment. Major limitations of all types of biosensors would include poor selectivity, drifting, overlapping, and degradation of signals. Specific detection of VOCs in multi-dimensional environments is also a challenge in fuel cell sensing. Humidity, temperature, and the presence of other analytes interfere with the functionality of the fuel cell and provide false readings. Hence, accurate and precise quantification of VOC(s) and calibration are the major challenges when using PEMFC biosensor.
To resolve this problem, a statistical model was derived for the calibration of PEMFC employing multivariate analysis, such as the “Principal Component Regression (PCR)” method for the sensing of VOC(s). PCR can correlate larger data sets and provides an accurate fitting between a known and an unknown data set. PCR improves calibration for multivariate conditions as compared to the overlapping signals obtained when using linear (univariate) regression models.
Results show that this biosensor investigated has a 75% accuracy improvement over the commercial alcohol breathalyzer used in this study when detecting ethanol. When detecting isoflurane, this sensor has an average deviation in the steady-state response of ~14.29% from the gold-standard infrared spectroscopy system used in hospital operating theaters.
The significance of this research lies in its versatility in dealing with the existing challenge of the accuracy and precision of the calibration of the PEMFC sensor. Also, this research may improve the diagnosis of several diseases through the detection of concerned biomarkers.
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Jia, Yuan. "Polymer-Based MEMS Calorimetric Devices for Characterization of Biomolecular Interactions". Thesis, 2017. https://doi.org/10.7916/D8M3372K.
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Biomolecular interactions are central to all biological functions as the execution of biological function usually depends on the concerted action of biomolecules existing in protein complexes, metabolic or signaling pathways or networks. Therefore, understanding biomolecular interactions, and the temperature dependence of biomolecular interactions is of critical importance for the study of fundamental science, therapeutic drug development, and biomolecule manipulation. Biocalorimetry, a process of measuring the heat involved in biomolecular interactions, has distinct advantages over other biomoelcualr interactions characterization methods as it is solution based, label free, universally applicable, and allows for determination of thermodynamic propoerties. However, the utility of available commercial instruments is limited by complex design, rather large sample consumption, and slow responses. Micro-electro-mechanical systems (MEMS) technology, as an alternative approach, potentially offers solutions to such limitations as it can potentially be fabricated at low cost, operated at high throughput with minimum sample consumption, and available for integration with various functional units. However, existing MEMS calorimeters either do not yet allow proper control of reaction conditions for thermodynamic characterization of biomolecular reaction systems or is not yet suitable for practical applications because of a lack of sensitivity, reliability, and high operating cost. This thesis will build upon our existing knowledge of the MEMS technology in biocalorimetry and develop new generation of polymer MEMS calorimetric devices that are economical, sensitive, and robust for studying biomolecular characterization in practical settings.
The development of such devices requires innovations in the fabrication process as the conventional photolithography process is largely incompatible with polymer substrates. To address that, this thesis first presents a novel method of fabricating polymer-based MEMS thermoelectric sensors using a thermally assisted lift-off approach, by which, thick metal or semiconductor films experience controlled breakup due to thermal reflow of the underlying lithographically defined patterns. The thick film MEMS thermoelectric sensors exhibit electric and thermoelectric performances comparable to those made from bulk materials. This allows the sensors to be useful in low-noise, high-efficiency thermoelectric measurements.
The polymer-based MEMS sensors fabrication approach is then implemented in making MEMS calorimetric devices for solution-based, quantitative thermodynamic characterization of biomolecular interactions. This thesis presents both polymer-based MEMS differential scanning calorimetry (DSC) and isothermal titration calorimetry (ITC) devices that are more robust, and cost lower. The polymer-based MEMS calorimeters eliminate the need for complex, fragile silicon freestanding structures and offer real-time, in-situ temperature control to biomolecules with well-defined miniature volume. Combining with the improved sensitivity, the polymer-based devices also reduce consumption of material and leads to substantially reduced thermal mass of the measurement system for a rapid response time and improved throughput. The interpretation of the DSC, ITC measurement results yielded complete thermodynamic information of several biomolecular interactions of critical scientific and therapeutic interest that include the characterization of the unfolding of protein (lysozyme) for the determination of its thermodynamic properties, and the binding parameters of interactions of 18-Crown-6 and barium chloride in practically applicable reagent concentrations.
In addition, PDMS-based microfluidic structures that are used in molecular biological analysis platforms, including MEMS calorimeters are known to be problematic due to its surface adsorption effects and high permeability. To address this, this thesis eliminates the use of PDMS microfluidic structures in MEMS calorimeters entirely by presenting the first demonstration of a miniaturized 3D-printed Lab-on-a-chip (LOC) platform that integrates the polymer-based MEMS calorimeter for quantitative ITC characterization of biomolecular interactions. Exploiting topographical flexibility offered by 3D printing, the platform design features fully isolated cantilever-like calorimetric measurement structures in a differential setup. This design layout improves thermal isolation and reduces overall platform thermal mass, thereby enhancing the measurement sensitivity and reducing the platform response time. The utility of the platform is demonstrated with ITC measurements of the binding of 18-Crown-6 with barium chloride and the binding of ribonuclease A with cytidine 2’-monophosphate in a reusable manner, and with practically relevant reagent concentrations.
Finally, some perspectives of how far away the devices are from commercializing are summarized, and future works in suggesting the strategies to achieve this goal are proposed.
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Huang, Ying-Ming. "Micro-scale hybrid biological-engineered devices powered by biomolecular motors". 2008. http://etda.libraries.psu.edu/theses/approved/WorldWideIndex/ETD-2484/index.html.
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Mihajlović, Goran. "InAs quantum well Hall devices for room-temperature detection of magnetic biomolecular labels". 2006. http://etd.lib.fsu.edu/theses/available/etd-09152006-145231.
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Thesis (Ph. D.)--Florida State University, 2006.Advisor: Stephan von Molnár, Florida State University, College of Arts and Sciences, Dept. of Physics. Title and description from dissertation home page (viewed Jan. 22, 2007). Document formatted into pages; contains xvii, 103 pages. Includes bibliographical references.
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Liao, Ke-Pan, i 廖克槃. "Development of Microfluid Devices and Study of Electrical Characterization in Biomolecular Aqueous Solution". Thesis, 2003. http://ndltd.ncl.edu.tw/handle/33136412176985979446.
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碩士國立臺灣大學
電機工程學研究所
91
This study attempts to design and fabricate several microfluid devices with different configurations, dimensions and structure by using the process of semiconductor and MEMS technology. We load a small amount of DNA aqueous solutions into the channel on the chips. In the meanwhile, we apply voltage from end to end of the channel and detect the electrical signals of th solution. With these datas, we can distinguish some charged molecules with different molecular weight by analyzing electrical characterization in biomolecular aqueous solution.
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Liu, Hao-Heng, i 劉皓恆. "Enhancement of biomolecular detection in selectively modified silicon nanobelt devices via localized Joule heating". Thesis, 2014. http://ndltd.ncl.edu.tw/handle/19493799222677198015.
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博士國立交通大學
材料科學與工程學系所
102
In this dissertation, a self-assembled monolayer (SAM) of methoxy poly (ethylene glycol) silane (mPEG-sil) was selectively modified on the surface of nanobelt devices (NBDs) to act as a passivation layer that inhibits non-specific binding of proteins, thus increasing the sensing rate and improving the limit of detection (LOD). The template for selective modification was achieved by localized Joule heating of NBDs, with the mPEG-sil on localized heating region being ablated. Two different characteristic NBDs, resistor-type (RNBD) and transistor-type (TNBD), were fabricated by a CMOS-compatible process. Localized Joule heating was achieved by producing a local high resistance in NBDs through an implantation process. The RNBD is designed as n+/n-/n+ structure, whereas the TNBD is designed as n+/p-/n+. The thermal distribution was simulated prior to experiments using COMSOL and TCAD for RNBD and TNBD, respectively. The results show that both NBDs exhibited localized heating phenomena in our design, and can reach the minimum temperature for removing SAM (673 K) by 40-V and 15-V pulse voltages in the RNBD and TNBD, respectively. AFM was used to investigate the removal of mPEG-sil, with the results demonstrating that the localized Joule heating is uniform in the n- region in RNBD and non-uniform in the p- region for TNBD due to the impact ionization mechanism. In addition, localized Joule heating was examined in both vacuum and ambient, and indicated that the removal region was longer in vacuum for the same pulse bias. The 3-aminopropyltrimethoxysilane (APTMS), NHS-biotin and dye-labeled streptavidin which were deposited selectively in the removal regions were characterized by fluorescence detection to substantiate the selective modification and the resistivity of mPEG-sil to the non-specific binding. The results showed that fluorescence is only apparent in the removal regions, which is consistent to the surface analysis via AFM. Moreover, the enhancements of sensing rate and LOD were demonstrated by time-lapse fluorescence detection of dye-labeled streptavidin for RNBD and real-time detection of streptavidin for TNBD. Both the results of time-lapse fluorescence detection and real-time detection showed the same trend, that of NBDs with selective modification exhibiting a higher sensing rate (>2x enhancement) and lower LOD (1-order improvement) when compared with NBDs with non-selective modification.
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"Breath figure plga films as implant coatings for controlled drug release". Tulane University, 2013.
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The breath figure method is a versatile and facile approach of generating ordered micro and nanoporous structures in polymeric materials. When a polymer solution (dissolved in a high vapor pressure organic solvent) is evaporated out in the presence of a moist air stream, the evaporative cooling effect causes the condensation and nucleation of water droplets onto the polymer solution surface. This leads to the formation of an imprinted porous structure upon removal of the residual solvent and water. The facile removal of the water droplet template leaving its structural imprint is a specifically appealing aspect of the breath figure film technology. The first part of the dissertation work involves the fabrication of drug loaded breath figure thin films and its utilization as a controlled drug release carrier and biomaterial scaffold. In a single fabrication step, single layer/multilayer porous thin films were designed and developed by combining the breath figure process and a modified spin or dip coating technique. Using biodegradable polymers such as poly (lactic-co-glycolic acid) (PLGA) and poly (ethylene glycol) (PEG), drug loaded films were fabricated onto FDA approved medical devices (the Glaucoma drainage device and the Surgical hernia mesh). The porosity of the films is in the range of 2-4 µm as characterized by scanning electron microscope. The drug coated medical implants were characterized for their surface and bulk morphology, the degradation rate of the film, drug release rate and cell cytotoxicity. The results suggest that the use of breath figure morphologies in biodegradable polymer films adds an additional level of control to drug release. In comparison to non-porous films, the breath figure films showed an increased degradation and enhanced drug release. Furthermore, the porous nature of the film was investigated as a biomaterial scaffold to construct three dimensional in vitro tissue model systems. The breath figure film with interconnected pores facilitates cell infiltration and tissue remodelling in vitro, suggesting its high potential in regenerative medicine and tissue engineering applications. In the second part of the dissertation, the versatility of breath figure polymers was explored as a reverse template to create micropatterned soft materials. Unlike traditional lithographic masters, the breath figure assembly is a simple and cost-effective approach to create micro/nano sized “bead†like uniform patterns on the surface of hydrogels and biopolymers. By incorporating iron nanoparticles into the pores, this technique was extended to form hydrogels decorated with nanoparticles specifically in the pattern. The morphology features and the functional characteristics were demonstrated through scanning electron microscopy. The potential applications of these micro-fabricated materials in biosensors and cell culture substrates are outlined.acase@tulane.edu
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Tsou, Pei-Hsiang. "Porous Membrane-Based Sensor Devices for Biomolecules and Bacteria Detection". Thesis, 2012. http://hdl.handle.net/1969.1/ETD-TAMU-2012-08-11878.
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Biological/biochemistry analyses traditionally require bulky instruments and a great amount of volume of biological/chemical agents, and many procedures have to be performed in certain locations such as medical centers or research institutions. These limitations usually include time delay in testing. The delays may be critical for some aspects such as disease prevention or patient treatment. One solution to this issue is the realization of point-of-care (POC) testings for patients, a domain in public health, meaning that health cares are provided near the sites of patients using well-designed and portable medical devices. Transportation of samples between local and central institutions can therefore be reduced, facilitating early and fast diagnosis. A closely related topic in engineering, lab-on-a-chip (LOC), has been discussed and practiced in recent years. LOC emphasizes integrating several functions of laboratory processes in a small portable device and performing analysis using only a very small amount of sample volume, to achieve low-cost and rapid analysis. From an engineer's point of view, LOC is the strategy to practice the idea of POC testing.
This dissertation aimed at exploring the POC potentials of porous membrane-base LOC devices, which can be used to simplify traditional and standard laboratory procedures. In this study, three LOC prototypes are shown and discussed. First the protein sensor incorporating with silica nanofiber membrane, which has shown 32 times more improvement of sensitivity than a conventional technique and a much shorter detection time; secondly the bacteria filter chip that uses a sandwiched aluminum oxide membrane to stabilize the bacteria and monitor the efficacy of antibiotics, which has reduced the test time from 1 day of the traditional methods to 1 hour; the third is the sensor combining microfluidics and silica nanofiber membrane to realize Surface Enhanced Raman Spectroscopy on bio-molecules, which has enhancement factor 10^9 and detection limit down to nanomolar, but simple manufacturing procedures and reduced fabrication cost. These results show the porous-base membrane LOC devices may have potentials in improving and replacing traditional detection methods and eventually be used in POC applications.
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Cheng, Fu-Yuan, i 鄭富元. "Fabrication of silicon nanowire device for biomolecules detection". Thesis, 2005. http://ndltd.ncl.edu.tw/handle/80645479326109631005.
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碩士國立暨南國際大學
生物醫學科技研究所
93
In this study, a silicon nanowire device was fabricated by using scanning probe lithography method(SPM lithography) for ultra-sensitive bio-molecules detection. With sample pretreated with 3-APTS 3-Amino-propyltrimethoxysilane(APTS) to get aminoderivitized surface and coating bis-sulfo-succinimidyl suberate(BS3) as protein-bindable sites, the antibody binding can be detected by changes in the device characteristics. Concentration-dependent measurements showed that sheep anti-rabbit IgG antibody can be detected. Furthermore we found that the regular shift of electrical property from low to high concentration which was due to the SiNW binding with different antibody concentration. Additionally, in this study a new technique for the selective formation of SAM monolayers was investigated. The selective oxidation induced by electric field in the vicinity of a conductive SPM probe which is called field-induced oxidation (FIO) is a promising method for fabricating nano-scale structure .We perform field induced oxidation by using SPM nano-lithography for patterning the silicon nanowire covered with silicon dioxide. After FIO patterning , the silicon nanowire covered with silicon dioxide was etched by TMAH .Then the sample was dip with HF solution. After that the silicon nanowire surface was become hydrogen terminal. And then 3-Amino-propyltrimethoxysilane(APTS) can be formed selectively with hydroxyl group on the native oxide surface. After the selective SAM formation, the scanned area of silicon nanowire surface was treated with amino-propyltrimethoxysilane to form a amino-termianted monolayer and then bis-sulfo-succinimidyl suberate were coating as protein-bindable sites. Selective coating of immobilized protein binding could be observed through electrical characteristics change.With different surface treatments, the SiNW device shows potential for other applications in biomedical detection. Finally ,we discuss the electrical properties of the silicon nanowire and the heterojunction of metal-semiconductor contact. We try to improve the electric properties of the silicon nanowire by doping the P-type dopant into the silicon nanowire. And then we improve the metal-silicon contact by rapid thermal annealing. We find that the schottky barrier was reduced and the output current of the silicon nanowire device was increased.
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Pimenta, Francisco Manuel Pinheiro. "Application of open-source software in the design of microfluidic devices for controlled deformation of biomolecules". Master's thesis, 2014. https://repositorio-aberto.up.pt/handle/10216/84698.
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Pimenta, Francisco Manuel Pinheiro. "Application of open-source software in the design of microfluidic devices for controlled deformation of biomolecules". Dissertação, 2014. https://repositorio-aberto.up.pt/handle/10216/84698.
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Zhuang, Ben-Yuan, i 莊本原. "High - Tc Superconducting Quantum Interference Device Vibrating Sample Magnetometer for the detection of biomolecules". Thesis, 2015. http://ndltd.ncl.edu.tw/handle/08969985910456682198.
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Li, Ying, i 李穎. "Fabrication and characterization of biomolecules composites for design and development of biomaterial devices, biosensors and energy applications". Thesis, 2013. http://ndltd.ncl.edu.tw/handle/f2baf2.
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博士國立臺北科技大學
工程科技研究所
101
The thesis work proposes was to synthesize novel nanomaterials like graphene, carbon nanotubes based biomolecules for application in fabrication of biosensors, biofuel cells and solar cells. The research includes the synthesis of carbon based nanocomposite and their different morphologies, biosynthesis of nanomaterials, bioelectrode modification, characterization of biomolecules modified electrodes, and their applications. The research focus will be mainly in selection of various suitable compounds/biomolecules for carbon nanotubes, Fullerene, graphene based on nanocomposite, and other morphology composites, and their characterization. The main work is the application for the prepared nanocomposite for electrode modification. The modified electrodes were tested for their electrocatalytic activities. CNT-based sensors generally have higher sensitivities, lower limits of detection, and faster electron transfer kinetics than traditional carbon electrodes. Many variables were tested and then optimized to create a CNT-based sensor. This study highlights different biomolecules and compares electrode design techniques for selective analyte detection. Carbon nanotubes possess similar dimensions to many biological molecules used within biosensors. MWCNTs can be oxidized to form surface carboxyl groups which can then be modified to allow covalent linking to enzymes or others. The design of biofuel cells involves the application of enzymes or microorganisms as catalyst for the targeted oxidation and reduction of specific fuel and oxidizer substrates at both electrodes to generate an electrical power output. The emergence of biofuel cells is driven by the need for clean methods of producing electricity from renewable fuel sources, and the ever-increasing depletion of fossil fuels. Dye molecules for sensor devices exhibits interesting enhancement in the electrocatalytic activity towards the oxidation or reduction of several biochemical and inorganic compounds. Dye for the functionalization of CNTs or Graphene leads to the construction of efficient electrochemical sensors. The above mentioned functional materials/ligands are both electrochemically active and photoactive. So, by using these dye molecules/polymers functionalized CNTs can enhance electrocatalysis and photoelectrocatalysis of various analyte reactions. This photoelectrocatalysis studies could be very helpful for developing new type of biosensors.