Queensland Micro- and Nanotechnology Centre, Griffith University, Nathan, Queensland 4111, Australia.
School of Engineering and Built Environment, Griffith University, Nathan, Queensland 4111, Australia.
Nanoscale. 2024 Feb 15;16(7):3560-3570. doi: 10.1039/d3nr05410a.
Manipulation, focusing, and separation of submicron- and nanoparticles such as extracellular vesicles (EVs), viruses and bacteria have broad applications in disease diagnostics and therapeutics. Viscoelastic microfluidic technology emerges as a promising technique, and it shows an unparalleled capacity to manipulate and separate submicron particles in a high resolution based on the elastic effects of non-Newtonian mediums. The maximum particle separation resolution for the reported state-of-the-art viscoelastic microfluidics is around 200 nm. To further enhance the reseparation resolution, this work develops a viscoelastic microfluidic device that can achieve a finer separation resolution up to 100 nm, by optimising the operating conditions such as flow rate, flow rate ratio and polyethylene oxide (PEO) concentration. With these optimised conditions, we separated a ternary mixture of 100 nm, 200 nm and 500 nm polystyrene particles, with purities above 90%, 70% and 82%, respectively. Furthermore, we also applied the developed viscoelastic microfluidic device for the separation of cancer cell-secreted extracellular vesicles (EVs) into three different size groups. After single processing, the separation efficiencies for small EVs (sEVs, <150 nm), medium EVs (mEVs, 150-300 nm), and large EVs (>300 nm) were 86%, 80% and 50%, respectively. The enrichment factors for the three EV groups were 2.4, 1.1 and 1.3, respectively. Moreover, we observed an unexpected effect of high PEO concentrations (2000-5000 ppm) on the lateral migration of nanoparticles where nanoparticles of up to 50 nm surprisingly can migrate and concentrate at the middle of the microchannel. This simple and label-free viscoelastic microfluidic device possesses excellent potential for sorting submicron particles for various chemical, biological, medical and environmental applications.
微纳粒子（如细胞外囊泡（EVs）、病毒和细菌）的操控、聚焦和分离在疾病诊断和治疗中有广泛的应用。粘弹性微流控技术是一种很有前途的技术，它基于非牛顿介质的弹性效应，具有无与伦比的在高分辨率下操控和分离亚微米颗粒的能力。报道的最先进的粘弹性微流控技术的最大粒子分离分辨率约为 200nm。为了进一步提高再分离分辨率，本工作开发了一种粘弹性微流控装置，通过优化操作条件（如流速、流速比和聚氧化乙烯（PEO）浓度），可以实现高达 100nm 的更精细的分离分辨率。在这些优化条件下，我们成功地将 100nm、200nm 和 500nm 的聚苯乙烯粒子的三元混合物分离，纯度分别高于 90%、70%和 82%。此外，我们还将开发的粘弹性微流控装置应用于分离癌细胞分泌的细胞外囊泡（EVs）成三个不同的大小组。经过单次处理，小细胞外囊泡（sEVs，<150nm）、中细胞外囊泡（mEVs，150-300nm）和大细胞外囊泡（>300nm）的分离效率分别为 86%、80%和 50%。三个 EV 组的富集因子分别为 2.4、1.1 和 1.3。此外，我们观察到高 PEO 浓度（2000-5000ppm）对纳米粒子侧向迁移的意外影响，高达 50nm 的纳米粒子令人惊讶地可以迁移并集中在微通道的中间。这种简单且无标记的粘弹性微流控装置具有出色的潜力，可用于对各种化学、生物、医学和环境应用中的亚微米颗粒进行分类。
