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1
Garland, M. J. "Optimisation of microneedle array design for microneedle mediated ionophoretic transdermal drug delivery". Thesis, Queen's University Belfast, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.557417.
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The present study was designed to identify the most suitable polymeric microneedle (MN) array design for use as an electrically responsive device capable of providing both sustained and on-demand percutaneous drug delivery both in vitro and in vivo. Soluble MN arrays loaded with a range of small to large molecules were fabricated from aqueous blends of 20% w/w poly(methyl vinyl ether eo maleic acid) (PMVEIMA). Novel hydrogel forming MN arrays were fabricated from aqueous blends containing 15% w/w PMVEIMA and 7.5% w/w poly(ethyleneglycol) (PEG, M; = 10 kDa). MN arrays were fabricated in a laser-engineered micro-moulding process. Hydrogel MN arrays were integrated with drug loaded reservoir patches. Whilst the combination of iontophoresis with both polymeric MN systems led to enhanced transdermal delivery of all drug molecules investigated in vitro, the electro- responsive nature of the hydrogel forming MN arrays enabled the sustained passive delivery and the electrically stimulated bolus delivery of the proteins insulin and bovine serum albumin in vivo. As such, this system may have great potential for the pulsatile transdermal delivery of therapeutic peptide/protein agents.
2
Zhao, Tianxin Zhao. "Silk Based Porous Microneedle Array for Programmable Drug Delivery". University of Akron / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=akron1468852925.
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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.
4
Guvanasen, Gareth Sacha. "Stretchable microneedle electrode array for stimulating and measuring intramuscular electromyographic activity". Diss., Georgia Institute of Technology, 2015. http://hdl.handle.net/1853/54392.
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The advancement of technologies that interface with electrically excitable tissues, such as the cortex and muscle, has the potential to lend greater mobility to the disabled, and facilitate the study of the central and peripheral nervous systems. Myoelectric interfaces are currently limited in their signal fidelity, spatial resolution, and interfacial area. Such interfaces are either implanted in muscle or applied to the surface of the muscle or skin. Thus far, the former technology has been limited in its applications due to the stiffness (several orders of magnitude greater than muscle) of its substrates, such as silicon and polyimide, whereas the latter technology suffers from poor spatial resolution and signal quality due to the physical separation between the electrodes and the signal source. We have developed a stretchable microneedle electrode array (sMEA) that can function while stretching and flexing with muscle tissue, thereby enabling multi-site muscle stimulation and electromyography (EMG) measurement across a large interfacial area.
The scope of this research encompassed: (i) the development of a stretchable and flexible array of penetrating electrodes for the purposes of stimulating and measuring the electrical activity of excitable tissue, (ii) the characterization of the electrical, mechanical, and biocompatibility properties of this electrode array, (iii) the measurement of regional electrical activity of muscle via the electrode array, (iv) the study of the effect of spatially distributed stimulation of muscle on the fatigue and ripple of muscle contractions, and (v) the assessment of the extent to which the stretch response of electrically stimulated muscle behaves in a physiological manner.
5
Held, Jochen. "Microneedle electrode arrays for cellular recording applications". Tönning Lübeck Marburg Der Andere Verl, 2009. http://d-nb.info/1001047702/04.
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6
Thakur, R. R. S. "Swellable Hydogel Microneedle Arrays for Transdermal Drug Delivery". Thesis, Queen's University Belfast, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.527897.
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Coulman, Sion Andrew. "Gene delivery to human skin using microneedle arrays". Thesis, Cardiff University, 2006. http://orca.cf.ac.uk/54257/.
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Cutaneous delivery of macromolecules is significantly impeded by the inherent barrier properties of the stratum corneum (SC). Within the last decade sophisticated engineering techniques have enabled the manufacture of microneedle arrays. These are innovative devices consisting of micron-sized needles which when inserted into the skin create physical conduits across the SC but do not impinge upon underlying nerve fibres or blood vessels. This study assessed the ability of microfabricated silicon microneedle arrays to penetrate the SC of ex vivo human skin for the localised delivery and subsequent expression of non-viral gene therapy formulations. Cutaneous gene therapy may represent a new method for the treatment of, or vaccination against, a range of candidate diseases. Microneedle arrays of variant geometries and morphologies, created using dry- and wet-etch microfabrication methods, were characterised by scanning electron microscopy. The potential of these devices for the cutaneous delivery of gene therapy formulations was initially demonstrated by permeation of a size and surface representative fluorescent nanoparticle across microneedle treated human epidermal membrane and observation of these nanoparticles in micron-sized conduits created in excised human skin. The ability to express exogenous genes within ex vivo human skin was subsequently proven by intradermal injection of the pCMVp reporter plasmid. However, a non-viral gene therapy vector failed to enhance cutaneous transfection. Cutaneous plasmid DNA delivery using the microneedle device facilitated effective, if somewhat limited and irreproducible, transfection of epidermal cells proximal to microchannels created in the skin. These investigations confirmed the ability of a silicon microneedle device to deliver macromolecular formulations, including plasmid DNA, to the viable epidermis and have demonstrated exogenous gene expression within human skin. However, limited and unpredictable gene expression following microneedle mediated delivery indicate that further studies to optimise the microneedle array morphology, its method of application and the plasmid DNA formulation are warranted.
8
Hamilton, Jordan David. "Fabrication and analysis of injection molded plastic microneedle arrays". Thesis, Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/39481.
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This thesis describes the fabrication of plastic microneedle devices, their fabrication by injection molding, and analysis of the penetration mechanics. Injection molding is an economical mass-production technique that may encourage widespread adoption of microneedles for drug delivery.
Four polymers were injection molded into hexagonal and square patterns of between 91 and 100 needles per array. The patterns and geometries were chosen to study the effect of needle spacing and array design on penetration force. Two needle spacings of approximately 1 mm and 1.5 mm were employed for both patterns. Molded parts showed tip radii below 15 microns, heights of 600 to 750 microns, and an included angle of approximately 30 degrees.
An economic analysis performed of the injection molded polymer devices showed that they can be manufactured for approximately $0.10 - $0.179 per part, which should be low enough to gain market acceptance. The added benefits of low pain perception, improved drug delivery for certain treatments, and the possibly of being recyclable make
injection molded micro-needle devices a desirable alternative to silicon or metal microneedles.
Penetration tests were performed with plastic micro-needle arrays and arrays of steel needles of the same spacings and patterns. Silicone rubber with mechanical properties similar to human skin was used as a skin simulant. The results showed that the micro-needles penetrated skin to depths between 120 and 185 microns depending on
pattern, spacing, tip radius and needle length. This depth is sufficient to deliver drug therapies, but not so far that they stimulate the nerve endings present beyond 130 microns inside the dermis layer in human skin.
An analytical model was developed to estimate the effects of various microneedle and skin characteristics on penetration force. The model was based on literature sources and derived from test results. The model accounted for coefficient of friction, tip radius, tip angle, and needle spacing, as well as the skin mimic's mechanical properties such as elastic modulus, mode I fracture toughness, and puncture fracture toughness. A Monte Carlo simulation technique was used to correct for errors in needle length and testing angle. Comparison of the experiments to the model showed good agreement.
9
Eltayib, Eyman Mohamed. "Hydrogel-forming microneedle arrays for minimally-invasive therapeutic monitoring". Thesis, Queen's University Belfast, 2016. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.705914.
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Hydrogel-forming microneedles (MN) were fabricated and evaluated for transdermal therapeutic monitoring of glucose as an endogenous biomarker model and two drugs, sodium valproate, as an anion model drug, and lithium as a cation model drug. A range of hydrogel-forming materials were characterized and evaluated to identify the most suitable formulation for fabrication of MN suitable for transdermal TM. MN contain no drugs themselves, upon insertion into skin they can rapidly imbibe ISF and undergo a transition to form discrete in situ hydrogel bulbs while maintaining their structural integrity and removed intact from the skin. Drug can thus diffuse through the swollen MN, which act as a continuous unblockable conduit between ISF and MN matrix. Hydrogel-forming MN were prepared from an optimised aqueous blend containing 11.1% w/w poly (methyl vinyl ether maleic anhydride) (Gantrez AN139), 5.6% w/w poly (ethylene glycol) (PEG 10,000). Successful transdermal extraction and detection of glucose was achieved in vitro through neonatal porcine skin and in vivo from healthy human volunteers. In vitro glucose was detected following application for 5 minutes but in vivo glucose was detected from MN applied for 1 hr. Results showed good correlation to blood glucose concentration with a lag time of 1 hr. Sodium valproate extraction was unsuccessful in vitro and was limited by the chemical nature of the drug, the MN fabrication material and the negative charge of the skin, in addition to the sensitivity of the analytical method. Finally, lithium was successfully extracted in vitro and in vivo from Sprague Dawley rats and gave a good reflection of picture of lithium serum level. In the view of these promising findings, with current work focusing on further optimisation of this technology, the future seems bright for a hydrogel-forming microneedle-based diagnostic and monitoring tool.
10
Justin, Richard. "Chitosan-graphene nanocomposite microneedle arrays for transdermal drug delivery". Thesis, University of Sheffield, 2015. http://etheses.whiterose.ac.uk/9544/.
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The project focused on the hypothesis that degradable, polymer microneedle arrays are a promising alternative to traditional drug delivery routes, offering the patient a painless, high concentration, and quick delivery of therapeutics through the skin. This project explored chitosan-graphene nanocomposites as potential materials for microneedle arrays; the addition of graphene to chitosan is believed to yield improved mechanical properties and electrical conductivity over pristine chitosan, which will allow for long and slender microneedles and for electrically stimulated drug delivery, and may positively affect the degradation and drug delivery properties of chitosan. Graphene derivatives, such as graphene oxide, reduced graphene oxide, graphene quantum dots, and magnetic graphene quantum dots were synthesised and then characterised, before they were used as the filler within chitosan nanocomposites. Their effect at varying concentrations upon the mechanical properties, electrical conductivity, drug release, and enzymatic degradation rate of chitosan were assessed. It was determined that reduced graphene oxide was the optimum nanoparticle to reinforce chitosan, achieving the best mechanical and electrical conductivity properties of the nanocomposites. Chitosan-graphene nanocomposite microneedle arrays were shown to passively release small molecular weight drugs at a high delivery quantity and rate. Conductive chitosan-graphene nanocomposite microneedles were tested to determine the effect of electrical stimulation on the release of large molecular weight drugs from the nanocomposite, with substantial improvements in the release rate of large molecular weight drugs when compared to passive diffusion. The microneedle arrays were shown to survive the force of insertion through compressive loading. The depth of penetration of the microneedles was determined through cross-sectional analysis of chicken skin.
11
Mantha, Satya Nymisha. "Fabrication of PPF Based Drug Containing Microneedle Arrays by Microstereolithography". University of Akron / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=akron1374434592.
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Alzahrani, Sharifah Yahya. "Dissolving microneedle arrays for enhanced transcutaneous delivery of a model antigen". Thesis, Queen's University Belfast, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.602410.
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Vaccination remains the most important approach to offering protection from infectious diseases. However, using needles and syringes for vaccine administration continues to be a matter of concern, especially in developing countries. Re-use of needles, needle stick injuries and improper disposal of needles in these regions of the world increase the risk of spreading blood-borne pathogens among health care workers, patients and the wider community. The concerns about the safe vaccination practice have led to an intensive effort to develop safe delivery methods for vaccines and replace hypodermic injections. The opportunity to develop a safe and effective method of vaccination using a minimally invasive method is becoming real. The most promising approaches is microneedle (MN) array which has proven to be a safe and cost effective method for vaccination. The current thesis was focus on dissolvable MNs fabricated from 20%w/w poly(methyl vinyl ether/maleic acid) loaded with a model antigen, ovalbumin (OVA). Various experiments were carried out during this thesis to investigate the feasibility and efficacy of using MNs for vaccine delivery. The in vitro studies showed that MNs loaded with OVA were strong enough to avoid breaking under high compression force. The integrity of the primary and secondary structure of OVA loaded into MN arrays successfully ensured. Further, MNs enhanced the release of OVA into the skin compared to passive permeation. In in vivo studies, the OVA released from the MNs' matrix upon insertion into mouse skin targeted dendrite cells (DCs). This thesis showed that av A was engulfed by DCs, processed and migrated to the lymph nodes. Consequently, the processed antigen encountered naive T cells, which led to initiation of robust humoral and cellular immune responses indicated by production of IgG, IgG 1, IgG2a, IFN-γ and IL-4. Interestingly, the PMVE/MA copolymer used to fabricate MNs seems to have adjuvant effects, indicated by the higher IgG level of mice immunized using MNs fabricated from PMVE/MA loaded with OVA compared with MNs fabricated from PMVE/MA and loaded with OVA plus adjuvant imiquimod.
13
Fung, Peter W. (Peter Waitak). "Evaluation of polyelectrolyte multilayer thin-film coated microneedle arrays for transcutaneous vaccine delivery". Thesis, Massachusetts Institute of Technology, 2011. http://hdl.handle.net/1721.1/69787.
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Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2011.Cataloged from PDF version of thesis.
Includes bibliographical references (p. 43-46).
The skin is an ideal organ for the safe and convenient delivery of vaccines, small molecules, and other biologics. Members of the Irvine and Hammond groups have developed a polyelectrolyte multilayer thin film-coated microneedle platform that can achieve simultaneous DNA and nanoparticle delivery. This delivery platform has the advantage of direct delivery of DNA or polymer nanoparticles to immune-active cells at the interface between the dermis and epidermis, enhancing uptake of the delivered cargo by resident immune cells. Ideal for the delivery of DNA vaccines, this platform aims to bridge the gap in the lack of efficient delivery platforms hampering the effectiveness of DNA vaccines. The ability to co-deliver polymer nanoparticles can serve as a conduit for delivering immune stimulating adjuvants or other drugs for therapeutic applications. An overview of current vaccine and delivery system research is presented. Market factors for the commercialization of the polyelectrolyte multilayer thin film-coated microneedle delivery platform are considered along with the risk factors in bringing this invention to market. An assessment of the intellectual property surrounding the platform is performed and a preliminary market entry strategy is developed for minimizing the risks commercialization.
by Peter W. Fung.
M.Eng.
14
Choi, Yoonsu. "A Three-Dimensional Coupled Microelectrode and Microfluidic Array for Neuronal Interfacing". Diss., Georgia Institute of Technology, 2005. http://hdl.handle.net/1853/11638.
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The objective of this research is to develop a three-dimensional (3-D) microfluidic/ electronic interface system for sustaining and monitoring 3-D neuronal networks. This research work is divided into two parts. One is the development of a 3-D multi-electrode array (MEA) with integrated microfluidic channels. The other is a microneedle array with embedded microelectrodes and microfluidic channels.
The 3-D MEA is composed of three elements that are essential for the development and monitoring of 3-D cultures of neurons. These components consist of scaffolds for cellular growth and structural stability, microfluidic channels for cell maintenance and chemical stimulation, and electrodes for electrical stimulation and recording. Two kinds of scaffold structures have been fabricated. The first scaffolding scheme employs a double exposure technique that embeds SU-8 towers into an SU-8 substrate. The second scaffolding mechanism introduces interconnects between towers for the purpose of mechanically supporting 3-D cell cultures and facilitating 3-D synaptic connections. Microfluidic channels are combined for fine control of the cellular microenvironment by means of diffusive and convective fluidic processes. Hollow towers with three-layer side ports were developed by using double exposure techniques and excimer laser ablation. The electrodes are combined into an integrated system that is capable of monitoring electrical activities and the cellular impedances of neurons which are attached to the electrodes.
The second part of this research is to fabricate a microneedle array for monitoring brain slices, which will directly detect electrical signals from living brain slices. Although the microneedle array is targeting different 3-D neuronal networks, it also has three components and the fabrication steps are the same as those for the 3-D MEA. To generate the sharp tip, isotropic reactive ion etching (RIE) is performed on tapered SU-8 towers. High aspect ratio tower structures can be effectively generated with SU-8 and tapered shapes are created by backside exposure.
The resulting systems will enable a new field of neurobiological research, in which the collective properties of 3-D neuronal circuits can be observed and manipulated with unprecedented detail and precision, and at a level of control not possible in living animals.
15
Wang, Po-Chun. "Fabrication, packaging, and application of micromachined hollow polymer needle arrays". Diss., Georgia Institute of Technology, 2013. http://hdl.handle.net/1853/50283.
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Micromachined needles have been shown to successfully transport biological molecules into the body with minimal invasiveness and pain, following the insertion of needles into the skin. The aim of this research is to demonstrate that micromachined hollow polymer needle arrays fabricated using UV lithography into micromolds, a potential batch-manufacturable process, can exhibit comparable insertion and injection performance to conventional hypodermic needles for drug delivery into skin.
A dual-exposure-and-single-development process flow is proposed for the above-mentioned UV lithography into micromolds approach to construct a pyramidal-tip hollow microneedle array with an integral baseplate and fluidic manifold. The developed process ultimately resulted in the ability to fabricate a 10×10 array of hollow SU-8 microneedles measuring 825 μm in height, 400 μm in width, and possessing a lumen of 120 μm in diameter. The tip diameter of the microneedles ranges from 15 μm to 25 μm. The insertion force of single needles characterized using excised porcine skin as a substrate is 2.4±1.2 N. Nevertheless, the high insertion force of 2.4 N per needle may cause a significant concern when a large number of needles are required to insert into skin for drug delivery.
Conventional hypodermic needles have two key structural characteristics: a sharp beveled tip and a large side-terminated lumen. Integration of these two key characteristics of hypodermic needles into microneedle design can potentially enhance microneedle performance. To reduce the insertion force and to incorporate the two key characteristics of hypodermic needles into the design of microneedles, a new needle tip design, namely the hypodermic-needle-like design, is presented. A 6×6 array of hypodermic-needle-like microneedles of 1 mm in height, approximate 350 μm in width, and with a lumen of 150 μm in diameter is demonstrated with successful insertion of the needle array into skin and an 85% lumen openness yield. The insertion force is significantly reduced by an order of magnitude with the new needle tip design and is 0.275±0.113 N per needle, comparable to that of hypodermic needles, i.e., 0.284±0.059 N. The hypodermic-needle-like microneedles exhibit a margin of safety of 180 for successful needle insertion into skin prior to needle fracture. A successful manual fluid injection into skin using single microneedle is demonstrated.
The micromachined hypodermic-needle-like polymer needle arrays presented in this dissertation are fabricated using UV lithography into micromolds, a potentially batch-manufacturable process, and exhibit comparable insertion performance to conventional hypodermic needles. Injection capability into skin is also demonstrated with a hypodermic-needle-like microneedle, illustrating the utility of these devices.
16
Pearton, Marc. "Delivery of pDNA to human skin facilitated by microneedle arrays : potential for DNA vaccination". Thesis, Cardiff University, 2007. http://orca.cf.ac.uk/55676/.
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The skin presents an attractive target for the delivery and expression of plasmid DNA pDNA. Potential therapeutic benefits from cutaneous gene therapy approaches include the correction or alleviation of inherited skin disorders genodermatoses and genetic vaccination. The skin is a particularly suitable portal for genetic vaccination due to its innate immunogenic capabilities. However, delivery of pDNA to the epidermis is severely constrained by the stratum corneum SC, low transfection efficiency and rapid loss of pDNA associated with epidermal cells. Microfabricated microneedles are employed as a means of penetrating the SC for macromolecular delivery. Solid silicon microneedles with different heights and tip morphologies were made by careful manipulation of the etching process, along with hollow silicon microneedles and solid polymer microneedles. To address the low transfection efficiency and rapid loss of pDNA in skin, hydrogels formed from smart polymers were investigated to provide sustained release reservoirs of pDNA. Gene delivery studies were performed in freshly maintained ex vivo human skin delivery formulations of reporter plasmid pCMVp and pEGFP-Nl and a therapeutic plasmid pCMV.M were applied to skin prior to microneedle application and maintenance in an optimized organ culture system. The results indicate that it is possible to deliver and express genes in the epidermis using microneedles. However, morphology of microneedles, their application protocol, and pDNA formulation all contribute to the efficiency of trans-gene expression.
17
Korkmaz, Emrullah. "Biodissolvable Microneedle Arrays for Effective Transdermal and Intradermal Delivery of Vaccines and Therapeutics: Manufacturing and Cutaneous Applications". Research Showcase @ CMU, 2016. http://repository.cmu.edu/dissertations/761.
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Transdermal delivery of biologically active molecules offers many attractive advantages over prevailing oral and parenteral drug delivery approaches toward addressing the low bioavailability of oral drugs and the inconvenience of hypodermic needle injections. However, transdermal delivery is hampered by the inability of the vast majority of drugs to penetrate through skin due to the physical barrier imposed by the skin’s outer layer, stratum corneum (SC), which allows only very small molecules (< 500 Da) to pass through. This places significant limits on the types of vaccines and therapeutics that can be directly delivered through skin. To mitigate these limitations while retaining the advantages of transdermal delivery, microneedle arrays (MNAs) have been developed to mechanically penetrate the SC for enabling the delivery of bioactive micro- and macromolecules through skin. In addition to transdermal applications of MNA technology that deliver drugs systemically through the skin’s microvasculature and lymphatic flow, MNAs have been used for intradermal applications to deliver drugs locally to the targeted skin microenvironments. Specifically, dissolvable MNAs that incorporate drug (and dissolve when inserted into skin) provide an effective and minimally-invasive means to deliver vaccines and therapeutics to and through skin. Despite recent advancements in MNA technology, there still remain considerable challenges in design and manufacturing, which hinders rapid and low cost fabrication of dissolvable MNAs with clinically-relevant materials and geometries, thereby limiting optimal skin-targeting immunization and treatment strategies.
In this Ph.D. research, to address the issues with the current MNA fabrication technologies, which impose strict limitations on manufacturable MNA designs, a novel micro- manufacturing technique based on mechanical diamond micromilling and micromolding is proposed. The overarching objective of this Ph.D. thesis research is to design and evaluate a new and comprehensive manufacturing strategy for successful creation of dissolvable MNA-based trans/intradermal delivery platforms that enable efficient, precise, and reproducible delivery of bioactive molecules to and through skin toward effective vacci- nation strategies and skin-targeted therapies. The specific objectives include: (1) to devise a novel micromilling/elastomer molding/spin-casting based fabrication approach for accurate and reproducible manufacturing of dissolvable MNAs with diverse and unique geometries, and from a myriad of biodissolvable and biodegradable materials, (2) to investigate the intradermal delivery characteristics of the created dissolvable MNAs through ex vivo and in vivo studies in mouse and human skin, and (3) to evaluate the use of the fabricated dissolvable MNAs for effective intradermal delivery of a number of vaccines (e.g., antigens and adjuvants), therapeutics (e.g., anti-cytokine biologics), and genetic materials (e.g., recombinant DNA and RNA) relevant to a broad range of novel cutaneous applications, including enhanced intradermal immunization strategies and skin-targeted therapies.
18
Lu, Yanfeng. "A Study on Liquid Bridge Based Microstereolithography (LBMSL) System". University of Akron / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=akron1468252608.
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Gülçür, Mert, J.-M. Romano, P. Penchev, Timothy D. Gough, Elaine C. Brown, S. Dimov i Benjamin R. Whiteside. "A cost-effective process chain for thermoplastic microneedle manufacture combining laser micro-machining and micro-injection moulding". Elsevier, 2021. http://hdl.handle.net/10454/18446.
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YesHigh-throughput manufacturing of transdermal microneedle arrays poses a significant challenge due to the high precision and number of features that need to be produced and the requirement of multi-step processing methods for achieving challenging micro-features. To address this challenge, we report a flexible and cost-effective process chain for transdermal microneedle array manufacture that includes mould production using laser machining and replication of thermoplastic microneedles via micro-injection moulding (micromoulding). The process chain also incorporates an in-line manufacturing data monitoring capability where the variability in the quality of microneedle arrays can be determined in a production run using captured data. Optical imaging and machine vision technologies are also implemented to create a quality inspection system that allows rapid evaluation of key quality indicators. The work presents the capability of laser machining as a cost-effective method for making microneedle moulds and micro-injection moulding of thermoplastic microneedle arrays as a highly-suitable manufacturing technique for large-scale production with low marginal cost.
This research work was undertaken in the context of MICRO-MAN project (“Process Fingerprint for Zero-defect Net-shapeMICROMANufacturing”, http://www.microman.mek.dtu.dk/).MICROMAN is a European Training Network supported byHorizon 2020, the EU Framework Programme for Research andInnovation (Project ID: 674801). This research has also receivedfunding and support from two other Horizon 2020 projects:HIMALAIA (Grant agreement No. 766871) and Laser4Fun (GA no.675063).
The full-text of this article will be released for public view at the end of the publisher embargo on 04 Feb 2022.
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Hu, Hung-Chieh, i 胡宏杰. "Fabrication of CMC Microneedle Array". Thesis, 2012. http://ndltd.ncl.edu.tw/handle/mv9zxj.
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碩士國立臺北科技大學
有機高分子研究所
100
Micro Electro Mechanical System fabrication technology（MEMS） has been used to be miniaturization of the microneedle array. The microneedle array can penetrate the stratum corneum of the skin without stimulation to the deep tissue of nerve. The literatures have reported that biodegradable and water-soluble polymer microneedle arrays can be completely dissolved in the skin, and non-toxic. Therefore, users do not have to worry about permanent residual from fracture of microneedle, and unsafety of reuse. There is also not any medical waste generated by using microneedle. In this study, we present the frabrication microneedles of water-soluble polymer, Carboxymethylcellulose（CMC）, which is approved to be biocompatible by the Food and Drug Agency（FDA）of the United States. We used micro-electromechanical system and micromold technique to fabricate CMC microneedles. First, microneedle master structure was created using etching technique with controlled process parameters to produce cylindrical array on silicon wafer. SU-8 was then coated on the mold to create the SU-8 master structure of depth 250um. The SU-8 master structure was then coated with polydimethylsiloxane（PDMS）to make PDMS molds for replication. Finally, the PDMS molds were covered with CMC solution. The CMC microneedle can be removed from the PDMS mold after thermal curing.
21
Yang, Yi-Cheng, i 楊益成. "Topography Optimization and Manufacture of Soluble Microneedle Array". Thesis, 2015. http://ndltd.ncl.edu.tw/handle/95s8a3.
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碩士明志科技大學
機械工程系機械與機電工程碩士班
103
The present study aimed to design a drug-delivery microneedle that could facili-tate painless drug administration using soluble materials exhibiting specific shapes and robustness. To achieve these specifications, ANSYS software was employed to ana-lyze the mechanical strength and lateral deflection critical load of the designs (pyra-mid column, triangular column, pentagon column and cone cloumn). The structural design was examined using the Taguchi method combined with critical buckling anal-ysis to identify the optimal size for the microneedle array. Mechanical strength analysis showed that when applying the same pressure, the stress among each shape of the tip was near 70 MPa error of ± 0.5 MPa, it can not dis-tinguish the difference, buckling analysis showed that the buckling load of pyramid column is 0.117 N, triangular column is 0.091 N, pentagon column was 0.087 N and cone column is 0.068 N, The analysis results indicated that pyramidal column exhib-ited superior cirtical load strength. An inclined exposure technique and micro molding method were used to fabri-cate the microneedle array. Carboxymethyl cellulose was selected as the constituents of the microneedle array. For the manufacturing process, the inclined exposure tech-nique was first employed in a laboratory to produce a pyramidal column-shaped sam-ple (base length = 320 μm, microneedle height = 650 μm, needle tip width = 15 μm) and an equilateral triangular column-shaped sample (base length = 396 μm, micronee-dle height = 650 μm, needle tip width = 15 μm). Then, high precision micro molding was employed using polydimethylsiloxane material to fabricate the female mold. Lastly, centrifugal casting was used to produce the microneedle structures. Microneedles degradation test consists of in vitro and in vivo tests, in vitro tests using Hank solution asbhuman body solution, microneedle are completely degraded within a minute,in vivo test inserts microneedles into rabbit and observe the degradation, the result was showed that it’s completely degraded in twenty-five minutes. In needle buckling load tests when pyra-mid column is forced 0.307 N which produce buckling; triangular column is forced 0.1257 N which produce buckling. Through this study confirmed that the pyramid shape needles have the better design of critical load and achieve the purpose of miceoneedles imme-diately degradation after piercing the skin.
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Chung, Yueh-Ching, i 鍾岳錦. "Research on Fabrication and Strength of Microneedle Array". Thesis, 2005. http://ndltd.ncl.edu.tw/handle/35848412876030598259.
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碩士國立臺灣大學
機械工程學研究所
93
How to fabricate microneedle array is the purpose of the research,. There are two kinds of microneedle array that we can find, one is in-plan microneedle arrays and another is out-of-plan microneedle arrays. In the early almost people focus on in-plan microneedle. Because we need smaller chips and to improve probability of getting blood, now people pay more attention on the application and research of out-of plan microneedle arrays. Using dry etching to fabricate out-of-plan micronedle arryas is the purpose of this research. Using this way can save time and escape unnecessary dangerous. In general people use wet etching to fabricate microneedle arrays. Isotropic etching liquid is HNA which include HF. HF is the most dangerous sour in chemical. Almost material can’t resist HF. So if we use HNA to fabricated microneedle array, we should be more carefully. In order to improve this problem, we use inductively couple plasma (ICP) to complete isotropic etching in this research. And we can try to collocate anisotropic etching to fabricated microneedle arrays that save more space and more height. After fabricating, we should measure the strength of microneedle arrays. This will be helpful to Integrate bio-chip.
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Li, Chun-Hsien, i 黎俊賢. "The Application of polymethylmethacrylate Microneedle Array for Cells Delivery". Thesis, 2016. http://ndltd.ncl.edu.tw/handle/78806304976883338656.
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碩士國立臺灣大學
醫學工程學研究所
104
Cell therapy is a kind of treatment method that delivers cells which are cultured in vitro into the human body in order to recover missing or damaged cells. In the past, cells are delivered by injection, but this way may make patients painful, have the possibility for patients to get infected, need trained personnel to operate and have the possibility of forming hematoma or bleeding. In this study, we used microneedle array as a carrier for cells delivering. With its small size, the subcutaneous wound is smaller and it will not touch nerves under the skin, so improvement of patients’ comfort can be easily achieved. Besides, using microneedle array will not require trained personnel to assist operating. Finally, it will reduce the risk of infection and hematoma formation. We used polymethyl-methacrylate (PMMA) as the material for fabricating microneedle array due to its adequate mechanical strength, excellent biocompatibility, stability and lower price. We are looking forward to using microneedle array made of PMMA to act as a carrier for cells delivering in order to treat missing or damaged cells in the human body. In this study, we used polydimethylsiloxane(PDMS) mold for fabricating PMMA microneedle array. Biocompatibility and cell viability were evaluated by MTT assay. Cell adhesion and proliferation on microneedle array were examined by Live/Dead Staining and SEM. Moreover, we used collagen, alginate and acellular skin as a delivered material to observe whether the cells can deliver from microneedle array to another place. The results show that PMMA microneedle array has good biocompatibility and cells can attach and grow on it. Besides, cells on the microneedle array can successfully deliver to collagen, alginate and acellular skin. Therefore, microneedle array with cell therapy is a new and highly potential treatment method.
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Fong, Zeng-Bing, i 曾秉豐. "The Study on Design and Fabrication for Hollow Microneedle Array". Thesis, 2016. http://ndltd.ncl.edu.tw/handle/06425464664181746460.
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碩士國立臺灣科技大學
機械工程系
104
In order to not easily make patients feel pain during insertion. There are many researchs have explored the geometric design and fabrication of microneedle array, but fewer explore inserting destruct. In the dynamically penetrating simulation, the basic geometry of the octagon, hexagon, taper , and pyramid could be obtained by using finite element software ANSYS in this study. The results showed that pyramidal microneedle array are the best design of penetrating.The hollow microneedle array is fabricated successfully by contacting exposure with three-dimensional mask. It is found that the geometry of the fabricated microneedle array are affected by square metal aperture stop and the altitude of photoresist. When the photoresist coating thickness is higher, the bottom corner will be more close to predict.
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Ming-TaLee i 李明達. "Fabrication of Microneedle Array: Inductively Coupled Plasma Etching and Spin Coating". Thesis, 2012. http://ndltd.ncl.edu.tw/handle/54030595026255628554.
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碩士國立成功大學
化學工程學系碩博士班
100
In this study, we have investigated fabrication of silicon microneedles which were then used to generate polydimethyl siloxane (PDMS) negative relief for subsequent usage of making polymeric microneedles via casting and spin coating. The silicon microneedles with different geometric shapes and sizes were fabricated by inductively coupled plasma- reactive ion etching (ICP-RIE) process. It is found that the conical shaped microneedles with aspect ratio around 0.5 were obtained by one step direct etching. When applying the proposed two-step approach, i.e. making micropillars, followed by lateral etching, the spear-like or nail-like microneedles with aspect ratio between 5-10 were obtained. The polymeric microneedles can be produced by both casting and spin coating processes. Spin coating provides a better alternative in terms of shorter processing time and better control of film thickness. For the spin coating process, it is found that the spin-rate dependent film thickness is highly associated with the rheological property of the polymer solution. By using the proper rheological model, the relationship between the film thickness and spin rate can be estimated, which is in a relatively good agreement with the experimental results.
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Yang, Chieh-Cheng, i 楊傑丞. "Process Parameter Study of Dip-drawing Technology for Making Microneedle Array". Thesis, 2019. http://ndltd.ncl.edu.tw/handle/69ktww.
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碩士國立彰化師範大學
機電工程學系
107
This paper presents a parameter study of the dip-drawing process of making high aspect-ratio polymeric microneedles. The process involves dip-pad spin coating, dip-drawing, UV-curing, necking, and breaking. To gain more insight into the process, we study three major process parameters including curing time, drawing speed, dip-mold’s tip diameter, they are critical parameters of the microneedle fabrication process. We also make different microneedles by setting a series of process parameters through dip-drawing platform. To prepare the experiment, we design an automatic dipping and drawing platform. The platform consists of a dip-mold holder, a dip-pad holder, a UV LED array, two stepping-motors, two threaded shaft systems, and a single board computer. The dip-mold is constructed of an acupuncture needle array. The dip-pad is prepared by spin-coating SU-8 (SU-2025). The single board computer acts as a human interface platform for a user to set up the dip-drawing process parameters including dip-drawing speed and curing time. User can operate this automatic platform to make various microneedles. The experiment results show that the dip-drawing process would yield sharpened high-aspect-ratio microneedles. At different drawing speeds, the radius of the microneedle tips gradually decreased with the increasing of the drawing speed. Under different UV curing time, the needle diameter decreased with the decreasing of curing time.
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Gao, Shao Syuan, i 高紹軒. "Feasibility Assessment of Fabricating Polymeric Microneedle Array by Stepwise Drawing Technique". Thesis, 2016. http://ndltd.ncl.edu.tw/handle/99r99r.
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碩士長庚大學
生化與生醫工程研究所
104
In this study, we expected to fabricate polymer-made microneedles (MNs) by stepwise drawing technique (SDT). The impact of morphology of MNs depends on the optimization of SDT, which includes the optimization of dispensing condition of peristaltic pump and drawing process. Multi-parameters adjustment of dispensing condition of MNs array was selected by model test and area of the base analysis. The characteristics of MN fabricated by different composition of dextran/maltose materials were investigated by stereomicroscope and scanning electron microscope. The results show that MNs with 875.83±54.3μm in height, 801.94±47μm in width and aspect ratio of 1.09 were fabricated by the polymer solution composed of 39% dextran and 1% maltose during 60 second of controlled drawing. MNs fabricated successfully via controlled drawing method were inserted into porcine cadaver skin to test the insertion capability and it is revealed that the insertion ratio was closed to 100%. In addition, optical coherence tomography (OCT) was used to observe the depth of MN puncture in real-time, the results showed that the penetration depth was about 400μm, which performed the sufficient mechanical strength to penetrate stratum corneum barrier. Furthermore, the skin recovery of porcine cadaver skin after puncture was also investigated by OCT, illustrating that indentation of the porcine cadaver skin tissue induced by MNs can recover after 260 minute. Rhodamine 6G (R6G)-loaded MN and FITC–insulin loaded MN were inserted into to porcine cadaver skins and to observe the in vitro transdermal delivery profiles by using confocal laser scanning microscope (CLSM). It is showed that the diffusion depth of R6G and FITC–insulin were about 460μm and 300μm after puncture for 10 min, respectively. Furthermore, in vitro transdermal delivery was performed by Franz diffusion cell to determine accumulated release profile of insulin. The result revealed that 88.2±2.69% of insulin was released within 7 hours from MN. SDT provides easy, convenient, and high-speed fabrication which could reduce MNs drying time and overcome the drawback of volume and drug loss in the 3D mold cavity. Optimization of the parameters of this technique may supply the possibility of MNs mass production in the future.
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Lee, Horn-Chin, i 李鴻慶. "Fabrication of a Hollow Metallic Microneedle Array and a Micro-Electroporation Chip". Thesis, 2006. http://ndltd.ncl.edu.tw/handle/80404571397871122332.
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碩士國立臺灣海洋大學
機械與機電工程學系
94
This thesis is focused on the design and fabrication of a hollow metallic microneedle array and electroporation chip using micro-electro-mechanical system (MEMS) technique. The fabrication process of the hollow metallic microneedle array was fairly simple and the expensive inductively coupled plasma etching was not required. Oxide and nitride was deposited on the Si substrate. The definition of square matrix pattern using reactive ion etching was used as the mask for wet etching. After the wet etching, array of solid microneedles with height of 300 �慆 was then electroformed and de-molded to complete the fabrication process. A drug reservoir made of PDMS was bonded together with the microneedle array to form a micro-injection system. The micro-injection system was tested on chicken skin tissue. Experimental results showed that the microneedles were robust and the system can be used for drug delivery The electroporation chip was demolded from a mold made from PMMA. A circular microchannel of diameter 250 �慆 was made possible by combining a optic fiber and the mold. Experimental result shows that the chip can fix a fish embryo cell by negative pressure through the channel. The associated deformation of the cell can increase the transmembrane potential and help form transient aqueous pores for better electroporation. Keywords: Hollow metallic microneedle array, electroporation chip
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Indermun, Sunaina. "Pharma-engineering of multifunctional microneedle array device for application in chronic pain". Thesis, 2015. http://hdl.handle.net/10539/17385.
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Chronic pain poses a major concern to modern medicine and is frequently undertreated, causing suffering and
disability. Transdermal delivery is the pivot to which analgesic research in drug delivery has centralized especially
with the confines of needle phobias and associated pain related to traditional injections, and the existing
limitations associated with oral drug delivery. Highlighted within this thesis is the possibility of further developing
transdermal drug delivery for chronic pain treatment using an Electro-Modulated Hydrogel- Microneedle array
(EMHM) prototype device for the delivery of analgesic medication
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Chan, Yong-Shi, i 陳詠欣. "The Fabrication of Hollow Microneedle Array with Controlled Microstructure for Cell Delivery". Thesis, 2018. http://ndltd.ncl.edu.tw/handle/257xd3.
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碩士國立臺灣大學
醫學工程學研究所
107
Microneedles are micro-scale needles that pierce into epidermis of skin to create micro-channel for drug delivery in a painless, minimally invasive way. With this micro-channel, we can address the limitation of transdermal method, which is the molecule of the drug must be small and oil-soluble to penetrate the stratum corneum barrier. The advantages of microneedles are avoiding drug degradation in stomach and liver, reducing the risk of infection, improving patient compliance due to minimal skin trauma, less pain, and sustaining drug release. The current types of microneedles include solid microneedles, coated microneedles, hollow microneedles, degradable microneedles, and hydro-forming microneedles. Cellular therapy is one of therapeutic medical therapy, which involves culturing and modifying cells in an in vitro sterilized environment. The cells will deliver to the body to restore damaged or missing cells and tissues in the body. Nowadays, the therapy mainly delivers the cells to the body by injection. In addition, there are some limitations by traditional injection. For example, the injection has a risk of infection, the patient''s compliance is low due to pain at injection, and injections could also cause cells are no room for growth. Therefore, in combining the advantages and disadvantages of the above two, in this study, polydimethylsiloxane (PDMS) was used as a material, engraved by laser engraving machine, to produce a hollow microneedle array mold. Polymethylmethacrylate (PMMA) was then used for filling, polymerization and demolding. Hollow microneedle arrays with different microstructures were successfully fabricated. The cells were cultured on the hollow microneedles. We used MTT Assay to test cell viability and the biocompatibility of the material. Then we used Live/Dead Staining to test the survival rate of the cells and we also observed the attachment of the cells on the hollow microneedles. The results show that PMMA hollow microneedles have good biocompatibility and the cells can be successfully attached to the microstructure of hollow microneedles. At the same time, the hollow microneedles were used as a carrier for cell delivery, and the cells were delivered to acellular tissue scaffolds prepared by a comprehensive acellular processing program in sequence of freeze-thaw, detergent and biological enzyme. This study confirmed that the cells can effectively enter the tissue via hollow microneedle carrier and growth well.
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HUANG, MIN-HUI, i 黃敏惠. "Evaluation of dissolving microneedle array patch for transdermal delivery of antipsychotic drugs". Thesis, 2019. http://ndltd.ncl.edu.tw/handle/x264t5.
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碩士元培醫事科技大學
生物科技暨製藥技術系碩士班
107
Drugs developed as transdermal delivery dosage form have advantages of easy to carry, ease for administration, avoiding first pass effect as well as providing topical or systemic therapeutic. However, low bioavailability is always occurred due to the hindrance of stratum corneum that is existed on the outer surface of skin. Strategies that could overcome the physiological barrier of stratum corneum on the outer surface of skin and harmless to tissue are the most important issues. In this study, we have developed a dissolving microneedle array patch with 10×10 microneedles on 8 mm×8 mm area. The shape of each microneedle was tetrahedral cone with 100×100 μm2 of basal area and 300 μm in length. The physical parameters with regard to hardness was measured as 24.93±3.12 N. The drug loaded patch with this hardness was confirmed could pierce the stratum corneum of the nude mouse skin. The melting point of model drug loaded in microneedle array patch was analyzed by differential scanning calorimetry (DSC). Similar melting point at 147-148 ℃ was observed when comparing Aripiprazole alone to formulated one. In addition, the results of Fourier-transform infrared spectroscope (FTIR) evaluation showed the wavenumber of model drug did not shift after formulated with patch excipients represented there no structure interaction between drug and excipients molecules. Loaded model drug may follow zero order released with the release rate of 244.31±30.71 ng/hr. The results of in vitro skin permeation study using Franz cell showed significant increase in apparent permeability coefficient of model drug loaded in microneedle array patch for 1.93×10-8 cm/sec compared to model drug alone. After patching drug loaded microneedle array on nude mice skin, blood samples were quantified by HPLC analysis. The results showed model drug behave sustained release properties. The pharmacokinetic parameters were analyzed with the non-compartment model and the conpartment model by using PK solver software. The results showed two-compartment mode was the best match. In vivo tissue analysis, the results show that the drug is distributed to various tissues, it also conforms to the two-compartment mode in the compartmental mode and the blood-tissue barrier system. In addition, model drug was quantified to distributed in the heart, lung, liver, spleen, stomach, kidney, duodenum, testis, brain and spinal cord. Among those issues, model drug showed relative slow distribution to blood-tissue barrier existed tissues including brain, spinal cord and testis.
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Vinaya, Kumar K. B. "Design, Development and Performance Study of Microneedle & Micropump-based Transdermal Drug Delivery System". Thesis, 2015. http://etd.iisc.ac.in/handle/2005/4092.
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Transdermal drug delivery is the most preferred drug delivery method, due to its high efficiency and less side effects. In conventional transdermal drug delivery, the delivery of macromolecular drugs (ex: Insulin, vaccines etc.) is limited by skin barrier. Several possible approaches have been proposed to overcome this limitation (chemical, electrical, ultrasound, microneedle etc.). Among these, the microneedle approach is considered as one of the best method to improve the effective delivery of drug. These microneedles penetrate into the outermost skin layers namely stratum corneum and epidermis. The thickness of the above mentioned skin layers will impose the constraints on the design of microneedle for the successful delivery of drug. On the other hand, along with the microneedle, the micropump is one more important functional module essential for a continuous drug delivery application such as insulin delivery for diabetic patients.
The aim of the present work is to improve the transdermal drug delivery using microneedle and micropump technology. Details on the fabrication, evaluation of both solid and hollow microneedle structures have been presented. Issues such as penetration reliability, liquid delivery into the skin and microneedle packaging are also discussed. Peristaltic micropump was developed to achieve a controlled flow of drug through the microneedle array. The developed micropump was successfully characterized to meet the typical drug delivery pump requirements such as: fail-safe mechanisms, adequate delivery of drug against blood pressure, ease of tubing and flow control over wide range. The micropump was integrated with necessary electronics and characterized for the complete drug delivery operation. Finally, the microneedle and micropump
-based system was tested and studied in vivo for insulin delivery. Results obtained were compared with the standard subcutaneous delivery with the same dose rate and found that they are in good agreement. The thesis is divided into seven chapters.
Chapter 1
The present chapter discusses a general brief introduction along with literature survey about microneedle and micropump for drug delivery applications. Information on fabrication of the microneedle array using different methods and their characterization to improve the transdermal drug delivery has been discussed. It also includes the information on the usage of micropump in drug delivery application.
Chapter 2
This chapter discusses the design, fabrication and characterization of cup shaped solid silicon microneedle array for leak proof drug delivery application. The mechanical stability of the fabricated microneedle to insert into the skin has been studied. The drug filled cup shaped microneedles were inserted into mice skin and drug dissolution was confirmed using fluorescence imaging technique.
Chapter 3
In this chapter, details on the fabrication of out-of-plane Si microneedle array using both isotropic and anisotropic etching processes has been presented. The fabricated microneedles were coated with Ti by sputtering and Au by electroplating method to make it suitable for implantable bio-devices. The mechanical failure mechanism of the microneedles was experimented using the in-house developed experimental setup. Fluid flow through the microneedle array was studied for different inlet pressures.
Chapter 4
Development of a tapered hollow stainless steel microneedle array using femto second laser machining process has been presented in this chapter. The mechanical stability of the fabricated microneedle array was studied for axial and transverse loading. The skin histology was carried out to study the microneedle penetration into the rat skin. Fluid flow through the microneedle array was studied for different inlet pressures. Information on the packaging of the microneedle array to protect the microneedle bore blockage from dust and other atmospheric contamination has also been included.
Chapter 5
This chapter reports on the design, development, testing and precision flow controlling of the peristaltic pump. A geared DC-motor was used to drive the fluid filled silicone tube to achieve the squeezing action. Variation of the flow rate due to different back pressures has been studied. The fail-safe property of the developed pump showed a low leak rate of ~ 0.14 % for a maximum inlet pressure of 140 kPa. Finally, the precision flow controlling was achieved by close-loop controlling of the DC motor driven peristaltic pump.
Chapter 6
This chapter discusses the integration of important sub-systems (microneedle, micropump and necessary electronics) for the minimally invasive, continuous and precision insulin delivery system. Using this microneedle and micropump-based system, successfully delivered insulin into a diabetic rat. The results obtained were comparable with the subcutaneous delivery of insulin with the same dose rate.
Chapter 7
In this chapter, the first section summarizes the salient features of the work presented in this thesis. The last section reports a scope for carrying out further work.
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Lin, Chuan, i 林雋. "The design and fabrication of 3-D electroplated microneedle array with oblique shape". Thesis, 2002. http://ndltd.ncl.edu.tw/handle/45604204310873727951.
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34
Yu-LuenDeng i 鄧宇倫. "Investigation of Particle Movement Induced by AC Electrokinetics inside Microchannel with Microneedle Array". Thesis, 2010. http://ndltd.ncl.edu.tw/handle/91229944832227210907.
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碩士國立成功大學
化學工程學系碩博士班
98
In the microfluidic systems, AC electrokinetics has been a common strategy to manipulate the fluid flow and particle motion, which leads to various applications such as separation, sample concentration and so on. From the literature, most of the electrode pair fabricated is two dimensional. Since the dielectrophoretic (DEP) force is proportional to the gradient of the square of electric field, 3-D design could extend the electrodes into the microchannel and provide the electric field inside the entire microchannel. In this study, we used an array of microneedles along with ITO glass to form the 3-D electrode pairs. The results show that, at lower particle concentration, the fluorescent particles aggregate faster at the tips of microneedles and the fluorescent intensity reaches the maximum in 10 seconds when only the tip of microneedles is conductive. AC electro-osmotic flow is observed at the lower frequency. As the particle concentration increases, an array of the pearl chain-like structure can be formed. Although the pearl chain-like structure can be formed when using the plane electrode, the distribution is not uniform.
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PAI, YU-CHUAN, i 白育全. "A Novel Method To Fabricate IrOx Microneedle Array For Application On Electrophysiological Devices". Thesis, 2019. http://ndltd.ncl.edu.tw/handle/zyb355.
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碩士國立臺北科技大學
材料科學與工程研究所
107
Medicine injection has raised attention in recent years. The skin compose by stratum corneum, dermis, and hypodermis layer. The requirement of microneedle arrays must have high aspect ratio, biocompatibility, and easy pirece the skin arrived at dermis layer of the length. In this work, we use three expose method of photolithography process to fabrication microneedle array, and we investigate relationship with the spin coating, photoresist viscosity, and exposure energy. It will influence the microneedle arrays structure. In addition, we utilize iridium and parylene C as the electrode and passivation materals, respectively. Subsequently we compare platinum and iridium oxide electrochemical characteristic, and use the optical microscope and scanning electron microscope to observe the surface morphology. Otherwise, we utilize the charge storage capacity(CSC) and electrochemical impedance spectroscopy to evaluate the reliability by soaking test. In addition, we characterized the resistivity of the platinum and iridium oxide film electrode by hall effect measuring. Finally, we would like to fabricate of the microneedle arrays can instead of the traditional needles and easy to pirece the skin into the dermis layer to achieve the purpose of painless injection. We also can obtain the electroencephalography(EEG), electrocardiography(ECG), electromyography(EMG) signal detection.
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Lin, Yi-Jou, i 林儀柔. "A Two-Step Controlled Release System Based on The Microneedle array filled with pH-sensitive PLGA hollow microspheres (HMS) for transdermal drug delivery". Thesis, 2011. http://ndltd.ncl.edu.tw/handle/28118117724661515154.
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碩士國立清華大學
奈米工程與微系統研究所
99
Transdermal delivery is an attractive alternative of drug delivery. Comparing to the conventional drug delivery techniques using pills or injections, this approach avoids degradation in the gastrointestinal tract and the pain of injections. But it is limited by the low permeability of skin because the stratum corneum (SC) in the upper skin (10-20 μm) is the main barrier. Hence, we used the Bio-MEMS technique to make microneedle array patch to inset into skin. This microneelde array patch could easily cross the SC but not so long that reach the deeper tissue and simulate nerves to developed a convenient, pain-free, and high efficient transdermal delivery patch. In this study, we present a novel approach to transdermal drug delivery that is two-step controlled-release system based on the skin cancer application. We used fluorescent dyes as model drugs to simulate the slow effect of anti-cancer drug and short half-time of anesthesia and vasoconstrictor. First, we used backside exposure technology of UV-lithography to fabricate microneedle array mold and bio-available PVP polymer with 1st model drug as the microneedle array materal. Second, we used double emulsion technology to fabricate pH-sensitive PLGA HMS (Hollow Micro-Spheres) with 2nd model drug. Sequentially, we combined these two techniques to fabricate the two-step controlled-release microneedle patch. This microneedle patch was shown two-step releasing profiles in vitro, the insertion capability ex vivo, and the transcutaneous delivery in vivo. As a consequence, we conclude that the two-step controlled-release can release two drugs with a time difference to the skin.
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Wu, Jia-Yong, i 吳嘉鏞. "Design and Fabrication of Microneedle Arrays for Drug Delivery". Thesis, 2014. http://ndltd.ncl.edu.tw/handle/38578235678897763356.
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碩士國立高雄應用科技大學
機械與精密工程研究所
102
With advances in technology and medicine, the microneedles for painless treatment are used to pierce the skin for drug delivery and vaccination. Some scholars found that the microneedle of less than 150 μm in length would not cause pain form patients in use. With the drug patches the hydrophilic drug molecules can pass the stratum corneum to deliver the drug quickly. In this study, we investigated the use of micro-electromechanical systems (MEMS) technology for fabrication of micron nickel metal needles. Using positive photoresist (AZ4620) and negative photoresist (SU8-50), different combination of photoresists were explored for the fabrication process. Photolithography was applied to fabricate the SU-8 photoresist mold in the stainless steel sheet, and then nickel metal was electroformed onto the photoresist mold. Finally Remover PG removed the photoresist SU-8 and then nickel microneedles were released. We successfully fabricated microneedle patches. The microneedles were in array of 5×5, in which the center spacing of two needles was 2.25 mm, the inner diameter of microneedle was 0.1 mm, the outside diameter of microneedle was 0.75 mm, and the length of microneedle was 100 ~ 150 μm. The microneedle layer and nozzle plate did not separate under bending tests. In the liquid transport experiment, the microneedle patch transmitted liquid successfully.
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Jhou, San-Jie, i 周三傑. "A Mathematical Two-Dimensional Model Accounting for Transdermal Diffusion with Microneedles Array". Thesis, 2014. http://ndltd.ncl.edu.tw/handle/66062259120277439401.
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碩士國立中興大學
化學工程學系所
102
In transdermal drug delivery, the stratum corneum is the enormous resistance. To effectively permeate the drug into the human skin, the studies had been proposed after the approaches of permeable enhancement had researched. These approaches was categorized to chemical and physical. Recently, the dramatical approach which was physical enhancement, can pierce the stratum corneum with microneedles. Because it directly crossed the permeability barrier, accompanied the coated drug can effectively get into the human body. Literature reported that used the biodegradability materials to fabricate the microneedles and the drug was encapsulated within the microneedles. In this way, it can not only assist the drug delivery, but also control drug release at targeting site. And it was without pain or biohazardous in human body. By this literature, the approach with microneedles can pierce the stratum corneum such that the drug get into the body without resistance. If used dissolved microneedles, then increased the controlled drug release function and without pain and hurt for human. Therefore, this work used a mathematicl two-dimensional model accounting for drug diffusion with microneedles array and fixed the number of microneedles to compare that increased the points in one direction more than other will have the best effective, as well as, compared to single microneedle. Among of different arrangements, the diffusion with increasing the number of microneedles in the direction of ρ was more effectively than the direction of θ. Finally, all of the arrangement with many microneedles were better than the model with single microneedle.
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Ching-FengLai i 賴鏡峰. "Design and Simulation of Microneedle Arrays for Transdermal Drug Delivery by Electroporation". Thesis, 2019. http://ndltd.ncl.edu.tw/handle/y7ky97.
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碩士國立成功大學
生物醫學工程學系
107
Transdermal drug delivery is one of the most efficiency way in transporting drug into human body. Compared to traditional method, transdermal drug delivery features in fast, less side effect, specific drug control. In modern medicine, the main idea not only focus on the efficiency of treatment but also puts emphasize at patient’s feeling. Microneedle can reduce painful feeling apparently compares to traditional subcutaneous injection due to its small diameter. Furthermore, microneedle is an effective tool which has been under developed in past decades. Besides drug delivery, microneedle can applied to gene therapy, target treatment against cancer especially for carcinoma and for vaccine. Microneedle can be divided into several types due to its pathway such as hollow, coat and poke, dissolving. Hollow microneedle combines with microfluidic and microneedle patch form a whole device. Although hollow microneedle reveals good efficiency in drug delivery, there are still some disadvantages. In this article, the aim is addressing design concept of “coat and poke” microneedle which combines with electric field. “Coat and poke” microneedle type is with protein-based drug coated or DNA-based vaccine at the surface of microneedle. As microneedle is made of metal material which is electrically conductive, it can exert electric field in human skin conducts electroporation to enhance efficiency of drug delivery. Furthermore, microneedle is in micro diameter (100~500μm) while it provides sufficient mechanical strength to penetrate skin without mechanical fracture and prevent patient feeling painful. In this study, microneedle with shorter length(〈200 μm) and larger wall angle(〉8°) show the greater ability to resist mechanical failure. Besides diameter, material selection is also a critical factor of design. Three types of material are chosen which are, Titanium Beta-21S, Stainless Steel 316L, Ni-Co-Cr-Mo alloy. Among these materials, Titanium Beta-21S shows the widest range of application so this material is recommended to microneedle application. To evaluate efficiency of drug delivery, diluted species and electric field distribution are important things for indicating which kinds of microneedle is better. Three kinds of design are applied, rectangular array, hexagon array with 4 potentials and hexagon array with 6 potentials. From the simulation result, hexagon array with 4 potentials can provide the largest effective volume formed by concentration and electric field at time=9s so that it reveals the appropriate moment to conduct electric field to reach greater efficiency. Combined with different physics, this study addresses design concept of microneedle array and hope that it can be applied in future.
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Guo, Ming-Sheng, i 郭銘勝. "Study on the microneedle arrays for transdermal drug delivery using wet etch technology". Thesis, 2005. http://ndltd.ncl.edu.tw/handle/25695538350383571465.
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碩士國立臺灣海洋大學
輪機工程系
93
Generally for treatment, it may use the syringes to inject drug but always cause human body to get pain. Therefore there were many successive studies of microneedles for human body to avoid getting pain and also to deliver drug. There is no pain of human body due to microneedle without exciting the end of nerve. The great number of blood capillaries of the human body increases the absorption of medicine. To use the silicon wafer with crystalline grain direction (100) and simple mark, the out-of-plane microneedle arrays with 460 μm in height can be done by the technology of MEMS. The PDMS (polydimethylsilox -ane) container, a reservoir of the transdermal drug, can be used with the microneedle arrays having a vias on the silicon to deliver the medicine.
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Hsu, Wei Chieh, i 徐偉傑. "Fast fabrication methods with controllable height and width of microneedle arrays for transdermal drug delivery". Thesis, 2014. http://ndltd.ncl.edu.tw/handle/32503184518996863218.
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碩士長庚大學
電子工程學系
102
Transdermal drug delivery system is new method to deliver drugs to human body by Diffusion, however the high-molecular-weight drugs isdifficult to go through the skin due to stratum corneum, the purpose of the stratum corneum is to form a barrier to protect underlying tissue from infection, dehydration, chemicals and mechanical stress, in order to overcome this skin barrier, microneedles offer a minimally invasive method, Microneedles are physical enhancers for transdermal drug delivery designed to increase the permeability of drugs into the skin by passing the stratum corneum. In this study, we use UV glue droplet combine with actuator to fabricate microneedle, we use different baking time to transform Viscosity of UV glue droplet and control actuator’s path and velocity to fabricate different length and width of microneedle. According to the results, baking time 3min can fabricate about 700 µm microneedle, we believe 700 µm microneedle can insert human skin to overcome stratum corneum barrier. Compare with tradition method, we purpose very easy method to fabricate microneedle and fabrication time is very short, we only need 30 minutes to complete the process. We believe that the approach we provided in this research was a easy and quick method for the microneedle fabrication.