Lu Haoliang, Rakhymzhanov Almas, Buttner Ulrich, Alsulaiman Dana
Division of Physical Science & Engineering, King Abdullah University of Science and Technology (KAUST), Thuwal, Makkah Province 23955-6900, Kingdom of Saudi Arabia.
Nanofabrication Core Lab, King Abdullah University of Science and Technology (KAUST), Thuwal, Makkah Province 23955-6900, Kingdom of Saudi Arabia.
ACS Omega. 2024 Aug 23;9(36):38096-38106. doi: 10.1021/acsomega.4c05196. eCollection 2024 Sep 10.
Microfluidics offers transformative potential in healthcare by enabling miniaturized, user-friendly, and cost-effective devices for disease diagnostics among other biomedical applications; however, their meaningful adoption is severely hindered, especially in developing countries and resource-limited settings, by the cost, time, and complexity of their fabrication. To overcome this barrier of access, this work develops a novel approach for highly efficient (<4 h), cost-effective, and clean-room-free fabrication of functional polydimethylsiloxane (PDMS)-based microfluidic devices based on coupling stereolithography three-dimensional (3D) printing with hot embossing. The strategy exhibits high fidelity between the digital design and final device, remarkable transfer accuracy between the 3D print and poly(methyl methacrylate) (PMMA) mold, in addition to highly smooth surfaces ( < 1 μm). To establish the versatility of the approach and performance quality of the fabricated devices, three advanced microfluidics-driven biosensing platforms are developed: a microsphere droplet generator, a stop-flow lithography-based hydrogel microparticle synthesizer, and a hydrogel postembedded microfluidic device for multiplexed biomarker detection. As a proof-of-concept, the latter platform was applied to the multiplexed detection of microRNA, a highly promising class of liquid biopsy biomarkers for many diseases including cancer. Notably, the ability to demonstrate multiplexed sensing of disease biomarkers within devices made through a facile, rapid, and clean-room-free strategy demonstrates the immense potential of this fabrication approach to accelerate the adoption and advancement of biomedical microfluidic devices in practice and in resource-limited settings.
微流控技术在医疗保健领域具有变革潜力，可实现小型化、用户友好且经济高效的疾病诊断设备以及其他生物医学应用；然而，其在实际应用中的推广受到严重阻碍，尤其是在发展中国家和资源有限的环境中，这是由于其制造的成本、时间和复杂性所致。为克服这一应用障碍，本研究开发了一种新颖的方法，用于基于立体光刻三维（3D）打印与热压印相结合，高效（<4小时）、经济高效且无需洁净室制造基于聚二甲基硅氧烷（PDMS）的功能性微流控设备。该策略在数字设计与最终设备之间展现出高保真度，在3D打印与聚甲基丙烯酸甲酯（PMMA）模具之间具有显著的转移精度，此外表面高度光滑（<1μm）。为验证该方法的通用性和所制造设备的性能质量，开发了三种先进的微流控驱动生物传感平台：微球液滴发生器、基于停流光刻的水凝胶微粒合成器以及用于多重生物标志物检测的水凝胶后嵌入微流控设备。作为概念验证，后一平台被应用于微小RNA的多重检测，微小RNA是一类极有前景的液体活检生物标志物，可用于包括癌症在内的多种疾病的检测。值得注意的是，通过简便、快速且无需洁净室的策略制造的设备能够实现疾病生物标志物的多重传感，这证明了这种制造方法在加速生物医学微流控设备在实际应用和资源有限环境中的应用及发展方面具有巨大潜力。
