Manufacture of silicon microneedles for drug & vaccine delivery

该项目将开发高容量、质量受控、低成本、定制的硅微针（MN）设备，用于专业的护理点（POC）健康应用。将通过对人体皮肤参数（不同部位和不同年龄的不同人群之间的弹性、变形、表皮厚度）的综合表征和分析来定义器械规格。将在临床皮肤模型中测试一系列新型MN产品，以证明其在药物和疫苗输送中易于应用和无痛经皮注射的实用性。硅MN的主要优点是制造的灵活性和可扩展性;我们在此应用中专注于此方面，为个性化医疗开发个性化但可扩展的制造。该项目将微细加工和制造专业知识（SU / SPTS）与卡迪夫大学（CU）的临床前和临床结果相结合。我们将开发新型中空MN阵列药物和疫苗递送系统，并展示其在临床实践中的潜力。MN装置比任何皮下注射器针头都要细和短得多，相对无痛（它们不会刺入皮肤足够深以刺激疼痛），并且对皮肤的损伤比传统皮下注射器要小得多。这对于需要定期治疗的患者至关重要。MN将为适当的皮肤隔室提供靶向治疗。例如，在疫苗接种中，将抗原施用于免疫处理朗格汉斯细胞所在的表皮（皮肤的顶部75-150 μ m）将提供对疫苗的稳健的全身免疫应答。靶向这一区域可能导致更有效的免疫应答（可能不需要潜在有害的佐剂），从而节省难以制造的疫苗的剂量。将使用一种全新的等离子体蚀刻和掩蔽工艺（SU / SPTS）来制造一系列长度达1 mm的尖锐中空MN。目前，使用湿法化学蚀刻或组合的湿法和等离子体蚀刻工艺来生产尖锐MN。基于皮肤参数测试结果，我们的新型灵活、经济高效的等离子体蚀刻工艺将用于制造一系列不同高度的MN，用于个性化药物和疫苗输送。我们采用SPTS的深硅蚀刻技术开发的新型斜面MN设计将有助于MN在低注射力下穿透皮肤。新的、简单的MN药物/疫苗递送系统可以彻底改变数十亿美元的药物递送市场，首次实现广泛的低分子量药物分子的有效经皮递送，包括：双氯芬酸、酮洛芬、甲氨蝶呤、舒马曲坦、烟酸甲酯和利多卡因，以及针对流感、丙型肝炎、麻疹、脊髓灰质炎、狂犬病和结核病的靶向疫苗递送。中空MN设计的优化将允许注射可行的药物和疫苗剂量。中空硅MN的制造也开辟了一个全新的领域，即结合传感器诊断的流体采样的新应用。提取足够用于分析的体积的组织液将促进小分析物分子的“无痛”测试。初步研究将评估该项目产生的新型MN产品在葡萄糖测试中的潜在用途。通过合作伙伴SPTS的晶圆盒装载式多工艺室工具，将实现从小样品到全晶圆，再到多晶圆生产的设备制造规模扩大。SPTS是半导体和MEMS工艺设备的全球领导者，是大批量、低成本制造专用硅MN产品的理想合作伙伴。SPTS将确保用于制造MN设备的制造方法和材料具有成本效益，可用于扩大生产。MN市场已经成熟，可以使用新的MN设计进行开发，能够批量制造。

This project will develop high-volume, quality controlled, low-cost, bespoke, silicon microneedle (MN) devices for specialised Point of Care (POC) health applications. Device specifications will be defined by a comprehensive characterisation and analysis of human skin parameters (elasticity, deformation, epidermal thickness at different sites and between different people of different ages), with respect to MN delivery A range of novel MN products will be tested in clinical skin models to demonstrate their utility for easy-application and painless transdermal injection in drug and vaccine delivery. The key benefit of silicon MNs is the flexibility, scalability of manufacturing; it is this aspect that we focus on in this application, developing personalised but scalable manufacture for personalised medicine.The project combines microfabrication and manufacturing expertise (SU / SPTS) with pre-clinical and clinical results from Cardiff University (CU). We will develop novel hollow MN array drug and vaccine delivery systems and demonstrate their potential in clinical practice. Considerably finer and shorter than any hypodermic syringe needle, MN devices are relatively painless, (they do not puncture deep enough into the skin to stimulate pain), and cause appreciably less damage to skin than traditional hypodermics. This is critical in where patients will require regular therapy.MNs will provide targeted therapy to the appropriate skin compartment. E.g. in vaccination, administering antigens to the epidermis (the top 75-150 um of skin) where the immune processing Langerhans cells reside will provide a robust,whole body immune response to the vaccine. Targeting of this zone may lead to a more efficient immune response (potentially without the need for potentially harmful adjuvants) and hence dose-sparing of the difficult to manufacture vaccine.A completely novel plasma etch and masking process will be used (SU / SPTS) to fabricate a range of sharp, hollow MNs up to 1mm in length. Currently, sharp MNs are produced using a wet chemical etch or a combined wet and plasma etch process. Our new flexible, cost-effective plasma etch process will be used to manufacture a range of MNs of different heights for personalised drug and vaccine delivery, based on the results of skin parameter testing.Our novel bevelled MN design - developed using SPTS' deep silicon etch technology - will facilitate MN skin penetration using low injection forces. The new, simple MN drug / vaccine delivery system could revolutionise the multi billion dollar drug delivery markets enabling for the first time the effective transcutaneous delivery of a wide range of low molecular weight drug molecules including: diclofenac, ketoprofen, methotrexate, sumatriptan, methyl nicotinate and lidocaine, and targeted vaccine delivery against influenza, hepatitis C, measles, polio, rabies and tuberculosis. Optimisation of hollow MN designs will allow injection of viable drug and vaccine dosages.Manufacture of hollow silicon MNs also opens up a whole new field of novel applications in fluid sampling combined with sensor diagnostics. Extracting interstitial fluid in volumes substantial enough for analysis will facilitate "pain free" testing of small analyte molecules. Preliminary studies will evaluate the novel MN products arising from this project for potential use in glucose testing .Scale-up of device fabrication from small samples to full wafers, to multi-wafer production, will be achieved through integral partner SPTS' wafer-cassette loaded, multi-process-chamber tools. SPTS, the global leader in semiconductor and MEMS process equipment, is the ideal partner for high-volume, low-cost manufacture of specialised silicon MN products. SPTS will ensure manufacturing methods and materials used to make the MN devices are cost effective for scale-up production. The MN market is ripe for exploitation using new MN designs, capable of being manufactured on a volume scale.