Top-down fabrication is widely used for producing micro to nanometer scale features for biomedical applications. Opposed to
bottom-up approach, it is superior to control geometry, structure and composition of the product. Traditional top-down fabrication
techniques usually suffer from utility of clean room, harsh processing procedures and high cost. This dissertation is focused on
developing a novel top-down fabrication technique based on soft lithography to fabricate functional microdevices and micropatterns for
cell-borne drug delivery, biosensing and cell-tracking. The first chapter overviews the major top-down fabrication methods and their
applications in biomedical science, as well as introduces recent advances in cell-borne drug delivery, biosensing and cell-tracking. The
second chapter reports on the development of a novel type of particulate structures called microdevices for cell-borne drug delivery. The
microdevices were fabricated by soft lithography with a disklike shape. Each microdevice was composed of a layer of biodegradable
thermoplastic. One face of the thermoplastic layer was covalently grafted with a cell-adhesive polyelectrolyte such as poly-L-lysine. This
asymmetric structure allowed the microdevices to bind to live cells through bulk mixing without causing cell aggregation. Moreover, the
cell−microdevice complexes were largely stable, and the viability and proliferation ability of the cells were not affected by the
microdevices over a week. In addition, sustained release of a mock drug from the microdevices was demonstrated. This type of microdevice
promises to be clinically useful for sustained intravascular drug delivery. The third chapter extended the work in the second chapter to
fabricate enzyme-laden microdevices for cell-borne enzyme delivery. Enzymes have been used to treat various human diseases and traumas.
However, therapeutic utility of free enzymes is impeded by their short circulation time, lack of targeting ability, immunogenicity, and
inability to cross biological barriers. Cell-mediated drug delivery approach offers unique capability for overcoming these limitations but
the traditional cell-mediated enzyme delivery techniques suffer from drawbacks such as risk of intracellular degradation of and low
loading capacity for the payload enzyme. This chapter presents development of a novel cell-mediated enzyme delivery technique featured by
the use of micrometer-sized disk-shaped particles termed microdevices. The microdevices are fabricated by layer-by-layer assembly and soft
lithography with catalase being used as a model therapeutic enzyme. The amount of catalase in the microdevices can be controlled with
number of catalase layers. Catalase in the microdevices is catalytically active and active catalase is slowly released from the
microdevices. Moreover, cell-microdevice complexes are produced by attaching the catalase-laden microdevices to the external surface of
both K562 cells and mouse embryonic stem cells. This technique is potentially applicable to other enzymes and cells, and promises to be
clinically useful. The fourth chapter describes fabrication of disk-shaped microdevices containing densely packed Carbon nanotubes (CNTs)
for Raman labelling of macrophages. Capability to detect or track macrophages in vivo is important for developing macrophage-based
therapies. Dispersed carbon nanotubes (CNTs) have been used for Raman labelling of cells and a top-down approach has been developed to
fabricate disk-shaped microparticles for the same application. The fabrication is featured by the use of spray coating of CNTs to produce
the microdevices. Raman detection of a single microdevice at a centimeter-scale working distance and the feasibility of using chemically
modified CNTs for multiplexed Raman labelling were demonstrated. Macrophages were stably labelled with the microdevices by simply adding
the microdevices to cultivated macrophages. The labelling slightly reduced viability of the macrophages and the labelled macrophages
retained their ability to capture foreign particles. Moreover, Raman detection of a single macrophage was demonstrated. This technique
promises to be useful for detection or tracking of macrophages in vivo as well as for other biomedical applications. The fifth chapter
presents a simple strategy to construct a micrometer-sized self-referenced fluorescence sensor for detecting Cu2+. The method relies on
microcontact printing of bovine serum albumin-stabilized gold nanocluster (BSA-AuNC) and poly(propyl methacrylate) (PPMA) stripes on a
glass slide. The PPMA stripes are printed on the BSA-AuNC stripes to form a crossbar array, with its cell unit being composed of four
distinct regions: BSA-AuNC, plain glass, PPMA, and BSA-AuNC covered by PPMA. The BSA-AuNC region is fluorescent and its fluorescence
intensity is changeable upon contacting with analyte solution. The BSA-AuNC covered by PPMA is also fluorescent but insensitive to the
analyte solution due to the presence of PPMA which prevents the analyte solution from contacting the BSA-AuNC. This region can thus be
used as an internal reference for sensing. This self-referenced sensor is able to detect Cu2+ in a highly specific and
concentration-dependent manner. The sixth chapter summarizes the major achievements of abovementioned studies. / A Dissertation submitted to the Department of Chemical and Biomedical Engineering in partial
fulfillment of the Doctor of Philosophy. / Fall Semester 2016. / September 19, 2016. / Biosensing, Cell-borne Drug Delivery, Cell-tracking, Fabrication, Soft lithography / Includes bibliographical references. / Jingjiao Guan, Professor Directing Dissertation; Steven Lenhert, University Representative; Yan
Li, Committee Member; Samuel C. Grant, Committee Member.
| Identifer | oai:union.ndltd.org:fsu.edu/oai:fsu.digital.flvc.org:fsu_405644 |
| Contributors | Xia, Junfei (authoraut), Guan, Jingjiao, 1973- (professor directing dissertation), Lenhert, Steven, 1977- (university representative), Li, Yan (committee member), Grant, Samuel C. (committee member), Florida State University (degree granting institution), College of Engineering (degree granting college), Department of Chemical and Biomedical Engineering (degree granting departmentdgg) |
| Publisher | Florida State University, Florida State University |
| Source Sets | Florida State University |
| Language | English, English |
| Detected Language | English |
| Type | Text, text |
| Format | 1 online resource (136 pages), computer, application/pdf |
| Rights | This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). The copyright in theses and dissertations completed at Florida State University is held by the students who author them. |
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