Rapid fabrication of highly customizable solid microneedle arrays

快速制造高度可定制的实心微针阵列

基本信息

批准号：
RTI-2022-00028
负责人：
Dalton, Colin
金额：
$ 10.6万
依托单位：
University of Calgary
依托单位国家：
加拿大
项目类别：
Research Tools and Instruments
财政年份：
2021
资助国家：
加拿大
起止时间：
2021-01-01 至 2022-12-31
项目状态：
已结题

来源：
https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=743015
关键词：
Rapid fabrication highly customizable solid

项目摘要

There are many drawbacks to hypodermic needles, such as insertion pain, tissue trauma, and expertise needed to perform an injection. Microfabricated microneedle arrays promise painless blood extraction and drug infusion by penetrating only the upper part of the skin, avoiding the nerves. Solid microneedles are coated with a therapeutic agent, allowing the drug molecules to dissolve into the surrounding tissue after penetrating the skin barrier. The dosage depends on the microneedle area and therefore the yield is limited. Microfabrication methods are ideal to create solid microneedle arrays, as the materials are biocompatible, robust and designed for large-scale integration with other micro manufacturing processes. We have demonstrated a new method to make solid microneedle arrays. This proof of concept manual fabrication method is tedious, unreliable and greatly impedes the innovation cycle, taking ~5 minutes to make a single microneedle when hundreds are needed. Working with vendors of automated wire bonders, we have shown that the process can be decreased to ~1 second per microneedle. However, having a sample made by a vendor is costly (several thousand dollars per device), and takes up to a month for delivery. This greatly impedes the experimental investigation needed for this research, where hundreds of device iterations need to be tested and experimentally validated. The requested automated wire bonder will provide dedicated access for my students, allowing for efficient and reliable fabrication of new designs of large area, high-density arrays in a repeatable, reliable, cost efficient, and extremely timely process (devices can be made and tested the same day). This will greatly increase our research productivity and maintain our competitive edge. The requested automated wire bonder will directly support the training of my HQP who are investigating methods to overcome the solid microneedle yield issue through integrating microfluidic channels next to the base of the solid microneedles, in part supported by my Discovery Grant. Without this equipment we will not be able to investigate large scale arrays for the delivery of relevant amounts of liquid into the area next to the perforated skin. As our microneedles are metal and individually electrically addressable, the ability to increase the uptake of drugs through the process of electroporation and iontophoresis will be investigated. The bonder will be housed in a multi-user cleanroom facility, with experienced technicians maintaining the equipment, extending its operational lifetime and facilitating HQP training. The equipment will be utilized extensively for the current research program and, when idle, will be available to other researchers thereby increasing their research productivity. Long-term this research will move from the bench to the bedside, by creating a solid microneedle system that can be used without direct medical supervision, thus reducing healthcare expenditure.

皮下注射针有许多缺点，例如插入疼痛、组织创伤以及进行注射所需的专业知识。微型制造的微针阵列仅穿透皮肤的上部，避开神经，从而实现无痛采血和药物输注。实心微针涂有治疗剂，使药物分子穿透皮肤屏障后溶解到周围组织中。剂量取决于微针面积，因此产量有限。微加工方法是制造固体微针阵列的理想选择，因为这些材料具有生物相容性、坚固性，并且专为与其他微制造工艺大规模集成而设计。我们展示了一种制造固体微针阵列的新方法。这种概念验证的手动制造方法非常繁琐、不可靠，并且极大地阻碍了创新周期，当需要数百根微针时，需要约 5 分钟才能制造一根微针。我们与自动焊线机供应商合作，证明该过程可以缩短至每微针约 1 秒。然而，由供应商制作样品的成本很高（每台设备数千美元），并且最多需要一个月的时间才能交货。这极大地阻碍了这项研究所需的实验研究，其中需要测试和实验验证数百次设备迭代。所要求的自动焊线机将为我的学生提供专用通道，允许以可重复、可靠、成本效益高且极其及时的过程高效可靠地制造大面积、高密度阵列的新设计（可以制造和测试设备）同一天）。这将大大提高我们的研究生产力并保持我们的竞争优势。所要求的自动焊线机将直接支持我的 HQP 的培训，他们正在研究通过在实心微针底座旁边集成微流体通道来克服实心微针产量问题的方法，部分由我的发现补助金支持。如果没有这种设备，我们将无法研究将相关量的液体输送到穿孔皮肤附近区域的大规模阵列。由于我们的微针是金属的并且可单独电寻址，因此将研究通过电穿孔和离子电渗疗法过程增加药物吸收的能力。粘合机将安装在多用户洁净室设施中，由经验丰富的技术人员维护设备，延长其使用寿命并促进 HQP 培训。这些设备将广泛用于当前的研究计划，闲置时可供其他研究人员使用，从而提高他们的研究生产力。从长远来看，这项研究将从实验室转向临床，通过创建一个无需直接医疗监督即可使用的坚固微针系统，从而减少医疗支出。