Manufacture of silicon microneedles for drug & vaccine delivery

该项目将开发用于专门护理点（POC）健康应用的大批量、质量控制、低成本、定制的硅微针（MN）设备。设备规格将通过对人体皮肤参数（弹性、变形、不同部位和不同年龄人群之间的表皮厚度）的全面表征和分析来定义，关于MN的输送。一系列新型MN产品将在临床皮肤模型中进行测试，以证明它们在药物和疫苗输送中易于应用和无痛透皮注射的实用性。硅纳米颗粒的主要优点是制造的灵活性和可扩展性；这是我们在这个应用程序中关注的方面，为个性化药物开发个性化但可扩展的制造。该项目将微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设备比任何皮下注射器针头都要细和短，相对来说是无痛的（它们不会刺入皮肤足够深以刺激疼痛），并且对皮肤造成的损伤也比传统的皮下注射器要小得多。这对于需要常规治疗的病人来说是至关重要的。MNs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（皮肤顶部75-150微米），将提供对疫苗的强大全身免疫反应。靶向这一区域可能导致更有效的免疫反应（可能不需要潜在有害的佐剂），从而节省制造疫苗的难度。将使用一种全新的等离子蚀刻和掩蔽工艺（SU / SPTS）来制造一系列长度达1mm的锋利空心纳米管。目前，锋利的纳米颗粒是使用湿化学蚀刻或湿和等离子相结合的蚀刻工艺生产的。根据皮肤参数测试的结果，我们新的灵活、经济高效的等离子蚀刻工艺将用于制造一系列不同高度的纳米颗粒，用于个性化药物和疫苗的输送。我们新颖的斜面MN设计-使用SPTS的深硅蚀刻技术开发-将以低注射力促进MN蒙皮渗透。新的、简单的MN药物/疫苗递送系统可能会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。优化中空MN设计将允许注射可行的药物和疫苗剂量。制造空心硅纳米颗粒也开辟了一个全新的领域，在流体采样与传感器诊断相结合的新应用。提取足够量的组织间液用于分析，将有助于对小分析物分子进行“无痛”测试。初步研究将评估该项目产生的新型MN产品在葡萄糖检测中的潜在用途。通过集成合作伙伴SPTS的晶圆盒加载、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器件的制造方法和材料在大规模生产中具有成本效益。锰市场已经成熟，可以使用新的锰设计进行开发，能够批量生产。

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.