Microscale Material Processing for Drug Delivery and Biosensing Applications

Rapid prototyping and additive manufacturing techniques have become more prevalent in recent years and their use in microscale medical device fabrication is of interest. In this thesis, a variety of rapid prototyping and microscale fabrication techniques are investigated to determine if they can be utilized in the creation of polymeric microneedle devices for drug delivery and biosensing applications. The photopolymerization technique dynamic mask microstereolithography is investigated to this end. Micromolding replication of structures created from this photopolymerization technique is highlighted. Furthermore, a combination of injection molding and drawing lithography are utilized for manipulation of a thermoplastic polymer material for microneedle fabrication. Inkjet printing, which is a noncontact deposition technique, is investigated as a means of applying surface coatings of therapeutic agents to microneedle arrays.;Initially, an investigation was undertaken to evaluate the ability to fabricate microneedle arrays using dynamic mask microstereolithography in order to produce polymer master structures that are suitable for silicone mold creation and subsequent structure replication with poly(methyl vinyl ether -- co -- maleic anhydride) (PMVE/MA) material. The antimicrobial properties of microneedles fabricated using this technique were assessed in modified-disk diffusion agar plating studies. Early tests were conducted to assess the ability to deposit inkjet coatings of fluorescent quantum dot model drug solutions onto the surfaces of the microneedles. The material properties of the fabricated structures were investigated and the delivery of model drug to cadaveric porcine skin was investigated iii with multiphoton microscopy. Microneedle arrays created out of PMVE/MA using the combination of dynamic mask microstereolithography and soft lithography were modified by inkjet printed drug coatings. Piezoelectric inkjet printing was utilized to deposit the antifungal drugs amphotericin B and miconazole onto the surfaces of the microneedles. The antifungal properties of the drug coatings on the microneedle arrays were assessed.;Microneedle arrays were also fabricated by using a combination of injection molding and drawing lithography out of the biodegradable polymer, poly(glycolic acid) (PGA). Surface coatings of voriconazole (antifungal agent) were applied to the microneedle arrays using piezoelectric inkjet printing. Examination of the microneedles and print coatings with microscopy, energy dispersive x-ray spectrometry, and Fourier transform infrared spectroscopy were conducted. Assessment of the porcine skin penetration by the microneedle arrays and the antimicrobial properties of the inkjet-modified arrays with agar plating studies were conducted. Modification of this technique was undertaken to create microneedle devices with multiple surface coatings. Drug release layers were applied to the microneedles with inkjet printing, followed by deposition of the poorly aqueously soluble drug, itraconazole. These devices were assessed for the chemical composition of the printcoatings, antimicrobial properties, and penetration into skin.;Furthermore, while microneedles are heavily investigated for drug delivery applications, they have also more recently sought attention as biosensing devices, particularly in transdermal sensing applications. These approaches may also have value in applications of food-based biosensing. Early tests were conducted to fabricate and test microneedles for fluid sampling of tuna in determination of histamine-spoilage with a commercially available lateral flow test for histamine. The results of these microneedle sampled tests were compared to the manufacturer's protocol to assess the efficacy of the technique in foodstuff testing.;Overall, these fabrication techniques proved effective in the production of microneedle arrays out of different materials, including PMVE/MA and poly(glycolic acid). Inkjet printing proved to be a useful process to create microscale coatings on microneedle surfaces, serving as a process that can be utilized for creation of accurately applied drug release layers and low-dose drug coatings. The microneedle sampling technique for use in biosensing/screening of histamine from fish samples also proved effective, with test results in good agreement with a commercial protocol for screening histamine-spoilage in tuna samples.