Microneedles hold the potential for enabling shallow skin penetration applications where biomarkers are extracted from the interstitial fluid (ISF) and drugs are injected in a painless and effective manner. To this purpose, needles must have an inner channel. Channeled needles were demonstrated using custom silicon microtechnology, having several needle tip geometries. Nevertheless, all the proposed fabrication sequences are not compatible with mass production based on mature, standard microfabrication techniques. Furthermore, ISF extraction was also demonstrated with channeled needles but under poorly controlled conditions and over long periods of time, the latter being impractical for medical use. A range of factors may impede or slow ISF extraction that require controlled experiments. In this work we address the above tasks in terms of microfabrication sequence design, tip geometry design and experimental validation under controlled conditions. We report the development and fabrication of a silicon channeled microneedle array using conventional, industrial micromechanic processes. With only 2 lithography steps, a hypodermic needle tip profile is achieved. Using the fabricated microneedles, fluid extraction is experimented on chicken skin mockups. Extraction tests are carried out by inducing a controlled pressure gradient between the two ends of the microneedle channels, generated by loading the chip or by applying vacuum to the chip's backside. The extraction of more than 1 μL of fluid in 20 minutes is demonstrated with a maximum applied pressure gradient of 500 mbar. A correlation between the extraction rate efficiency and needles' density is observed, both for short and long extraction times. These results provide the first demonstration of in vitro interstitial fluid collection under controlled experimental conditions using silicon hollow microneedles fabricated with standard micro electro mechanical systems (MEMS) fabrication technology and minimal steps. Based on the obtained data, a comparison is drawn between pressure load and vacuum as drivers for ISF extraction, according to modelling and controlled experiments.

中文翻译：

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斜面微针，带有用于透皮注射和采样的通道，以最少的步骤和标准 MEMS 技术制造。


微针具有实现浅层皮肤渗透应用的潜力，其中从间质液 （ISF） 中提取生物标志物，并以无痛和有效的方式注射药物。为此，针头必须有一个内通道。使用定制的硅微技术演示了通道针，具有多个针尖几何形状。然而，所有提议的制造序列都与基于成熟、标准微纳加工技术的大规模生产不兼容。此外，还证明了使用槽针提取 ISF，但在控制不佳的条件下和长时间提取，后者对于医疗用途不切实际。一系列因素可能会阻碍或减慢需要对照实验的 ISF 提取。在这项工作中，我们从微纳加工序列设计、尖端几何形状设计和受控条件下的实验验证方面解决了上述任务。我们报道了使用传统的工业微机械工艺开发和制造硅通道微针阵列。只需 2 个光刻步骤，即可实现皮下注射针尖轮廓。使用制造的微针，在鸡皮模型上进行液体提取实验。萃取测试是通过在微针通道的两端之间诱导受控的压力梯度来进行的，该梯度是通过加载芯片或对芯片背面施加真空产生的。结果表明，在 20 分钟内萃取超过 1 μL 的液体，最大施加压力梯度为 500 mbar。观察到提取速率效率和针密度之间的相关性，无论是短提取时间还是长提取时间。 这些结果首次证明了在受控实验条件下使用采用标准微机电系统 （MEMS） 制造技术和最小步骤制造的硅空心微针进行体外间质液收集。根据获得的数据，根据建模和对照实验，将压力负荷和真空作为 ISF 提取的驱动因素进行了比较。