Thesis (Ph. D.)--Oregon State University, 2009. / Printout. Includes bibliographical references. Also available on the World Wide Web.

Thesis (Ph. D.)--West Virginia University, 2010. / Title from document title page. Document formatted into pages; contains xii, 124 p. : ill. (some col.). Includes abstract. Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 66-80).

Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 140-155).

Thesis (Ph. D.)--Oregon State University, 2008. / Printout. Includes bibliographical references (leaves 133-137). Also available on the World Wide Web.

The present thesis includes a series of studies on microfluidic technology from novel microfabrication methods in polymers to diverse microfluidic applications. Specifically, this study focuses on some key issues in microfluidics, regarding the development of microfluidic fabrication strategy, material selection for microfabrication, and applications, in particularly controllable reactions of novel polymer-based microfluidic devices. We have developed novel methods, which hold completely different idea/ concept with conventional approaches', for fabrication of microfluidic chips with polymer materials. While for the microfluidic applications, the thesis exhibits cell perfusion experiments with freestanding 3D microchannels made of alginate hydrogel, convenient and sensitive lead(Ⅱ) ions detection on a plastic membrane microfluidic chip which was fabricated by the proposed novel one-step strategy, as well as and microfluidic controllable synthesis of enzyme-embedded metal-organic frameworks in a laminar flow;In the first part, we proposed an inside-out fabrication strategy using a copper scaffold as the sacrificial template to create freestanding 3D microvascular structures containing branched tubular networks with alginate hydrogel. The microvascular structures produced with this method are strong enough to allow handling, biocompatible for cell culture, appropriately porous to allow diffusion of small molecules, while sufficiently dense to prevent blocking of channels when embedded in various types of gels. In addition, other materials and biomolecules could be pre-loaded in our hydrogel tubular networks by mixing them with alginate solution, and the thickness of tubule wall is tunable. Compared to other potential strategies of fabricating free-standing gel channel networks, our method is parallel processing using an industrially mass-producible template, making our method rapid, low-cost and scalable. We demonstrated cell culture in a nutrition gradient based on a microfluidic diffusion device made of agar, a hydrogel traditionally hard to microfabricate, by embedding the synthesized tubules into the agar gel. In this way, the freestanding hydrogel vascular network we produced is a universal functional unit that can be integrated with other gel-based devices to build up the supporting matrix for 3D cell culture outside the hydrogel vascular structure; allowing great convenience and flexibility 3D culture. The method is readily implementable to have broad applications in biomedicine and biology, such as vascular tissue regeneration, drug discovery, and delivery system in 3D culture.;The second part, we developed a one-step method to mass produce microfluidic chip with thermal plastic membranes. We used a perfluoropolymer perfluoroalkoxy (often called Teflon PFA) negative mold, which is very nonsticky and has ultrahigh melting point, as solid stamp to thermal-bond two pieces of plastic membranes, low density polyethylene (LDPE) and polyethylene terephthalate (PET) coated with ethylene-vinyl acetate copolymer (EVA), which have different coefficients of thermal expansion. During the short period of contact with the heated Teflon stamp, the pressed area of the membranes permanently bonded, while the LDPE membrane spontaneously rose up at the area not pressed, forming microchannels automatically. These two regions were clearly distinguishable even at micrometer scale so that we were able to fabricate microchannels with width down to 50 microns. By using thermal-bonding, the pattern of Teflon mold will be transferred to the plastic membrane forming channels while two membranes will be bonded at the same time. The method enables generation of microchannels and bonding process to accomplish in a single step without sophisticated instruments. One Teflon mold can be used to mass replicate many plastic membrane chips in a short time because each round needs only a few seconds. Our method can fabricate a plastic microfluidic chip rapidly (within 12 seconds per piece) at an extremely low price (less than 0.02{dollar} per piece). We also showed some identical microfluidic manipulations with the flexible plastic membrane chips including droplet formation, microfluidic capillary electrophoresis and squeezing-pump for quantitative injection. In addition, we demonstrated convenient on-chip detection of lead ion by a peristaltic-pumping design, as an example of the applications of the plastic membrane chips in resource-limited environment. Due to the fast production method and low-cost of plastic materials, this one-step method will hopefully lead to new opportunities for the commercial implementations of microfluidic technologies.;Finally, on the basis of preliminary study of microfluidic laminar flow synthesis of MOFs in aqueous system in Chapter 4, we successfully synthesized and investigated formation of enzyme-embedded metal-organic frameworks (MOFs) in a continuous laminar flow on a microfluidic chip. Resultant enzyme-MOF composites displayed higher enzymatic activity than enzyme-MOF composites from bulk solution synthesis. A possible reason was that the precisely controlled and yet changeable reaction conditions such as reaction time and diffusive mixing of reagents allowed the fast reaction to be isolated into controllable processes and studied with predesigned yet changing conditions. This, in return, led to distinct morphological characteristics and activities of the enzyme-MOF composites compared to those from bulk synthesis. The results indicated that the highest activity of enzyme-MOF composites was obtained when metal ions and organic ligands were first gradually mixed within a few seconds before enzyme molecules joined the gradual mixing process. We found that the crystallinity degree of as-produced enzyme-MOF composites was reduced via the microfluidic flow synthesis, containing more structural defects compared to those with high degree of crystallinity from bulk synthesis. The reduced crystallinity allowed more effective approaching of substrates with enzyme embedded in composites and therefore an increased enzyme activity compared to enzyme-MOF composites from bulk synthesis. We further demonstrated that enzyme-MOF composites showed enhanced stability against elevated temperature and protease digestion compared with free enzymes, allowing their wider utility in biotechnology.

Micro-fluid mixing is an important aspect of many of the various micro-fluidic systems used in biochemical production, biomedical industries, micro-energy systems and some electronic devices. Typically, because of size constraints and laminar flow conditions, different fluids may only have the opportunity to mix by diffusion, which is extremely rate limited. Therefore, active or highly effective passive mixing techniques are often required. In this study, two pulsed injectors are used to actively enhance mixing in a high aspect ratio microchannel (125 ��m deep and 1 mm wide). The main channel has two adjacent flowing streams with 100% dye and 0% dye concentrations, respectively. Two injectors (125 ��m deep and 250 ��m wide) are located on separate sides of the channel, with one downstream 2 mm (equivalent to two main channel widths or eight injector widths) from the other. This results in an asymmetric mixing as the flow proceeds downstream. A dye solution is used to map local mixing throughout the channel by measuring concentration variations as a function of both space and time. The primary flow rates are varied from 0.01 to 0.20 ml/min (Reynolds numbers of 0.3 to 26.6), the injector flow rate ratios are varied from 0.125 to 2, and the pulsing frequencies are varied from 5 to 15 Hz. Images of the concentration variations within the channel are used to quantify mixing by calibrating the intensity of the image with the concentration of the dye solution. The degree of mixing (DoM) is used as a measure of quality and is defined based on the integration across the channel of the difference between the local concentration and the 50% concentration values. DoM is normalized by the 50% concentration value and subtracted from one to yield a parameter that varies from 0 (no mixing) to 1 (perfect mixing). It is shown that there is a high degree of repeatability of concentration distribution as a function of phase of the pulsing cycle. A mixing map is constructed over the range of variables tested which indicates an optimum set of flow and pulsing conditions needed to achieve maximum mixing in the main channel flow. The flow rate ratio between the injectors and main channel is found to be the most influential parameter on overall mixing. The highest DoM in the main channel was found to be 0.89. It is also noticed that improved mixing can occur at very low flow ratios under a unique set of primary flow and low frequency pulsing conditions. In general, there is an inverse relationship between primary flow rate and pulsing frequency to achieve better overall mixing. / Graduation date: 2003

Thesis (M.S.)--Rutgers University, 2008. / "Graduate Program in Biomedical Engineering." Includes bibliographical references (p. 60-62).

Thesis (Ph. D.)--Ohio State University, 2009. / Title from first page of PDF file. Includes vita. Includes bibliographical references (p. 119-224).

University of Macau / Faculty of Science and Technology / Department of Electrical and Computer Engineering