Namgung Bumseok, Lee Taewoo, Tan Justin Kok Soon, Poh Daren Kiat How, Park Soyeon, Chng Kevin Ziyang, Agrawal Rupesh, Park Sung-Yong, Leo Hwa Liang, Kim Sangho
Department of Biomedical Engineering, National University of Singapore, 9 Engineering Drive 1, 117575, Singapore.
Department of Ophthalmology, National Healthcare Group Eye Institute, Tan Tock Seng Hospital, 308433, Singapore.
Lab Chip. 2020 Oct 27;20(21):3930-3937. doi: 10.1039/d0lc00619j.
Human red blood cells (RBCs) aggregate under low shear conditions, which significantly modulates flow resistance and tissue perfusion. A higher aggregation tendency in blood thus serves as an important clinical indicator for the screening of cardiovascular disorders. Conventional ways of measuring RBC aggregation still require large sample volumes, cumbersome manual procedures, and expensive benchtop systems. These inconvenient and high-cost measurement methods hamper their clinical applicability. Here, we propose a low-cost, miniaturized system to overcome the limitations of these methods. Our system utilizes a coin vibration motor (CVM) to generate a localized vortex for disaggregating RBCs in a disposable fluidic chip. The design of the chip was optimized with fluid dynamics simulations to ensure sufficient shear flow in the localized vortex for RBC disaggregation. The time-dependent increase in light transmittance from an LED light source through the plasma gap while the RBCs re-aggregate is captured with a CMOS camera under stasis conditions to quantify the level of RBC aggregation. Our CVM-based aggregometer was validated against a commercial benchtop system for human blood samples under physiological and pathological conditions, and showed an excellent performance with a high intraclass correlation coefficient of 0.995. In addition, we were able to achieve a rapid measurement (<4 min) with the CVM-based aggregometer, requiring only a 6 μl blood sample. These illustrate the potential of our CVM-based aggregometer for low-cost point-of-care diagnostics without compromising the measurement sensitivity.
人类红细胞（RBCs）在低剪切条件下会聚集，这会显著调节血流阻力和组织灌注。因此，血液中较高的聚集倾向是筛查心血管疾病的重要临床指标。传统的测量红细胞聚集的方法仍然需要大量样本、繁琐的手动操作以及昂贵的台式系统。这些不便且成本高昂的测量方法阻碍了它们的临床应用。在此，我们提出一种低成本的小型化系统来克服这些方法的局限性。我们的系统利用硬币振动电机（CVM）在一次性微流控芯片中产生局部涡流来使红细胞解聚。通过流体动力学模拟对芯片设计进行了优化，以确保局部涡流中有足够的剪切流来使红细胞解聚。在静态条件下，用CMOS相机捕捉红细胞重新聚集时LED光源透过血浆间隙的透光率随时间的增加，以量化红细胞聚集水平。我们基于CVM的凝集仪在生理和病理条件下针对人血样本与商用台式系统进行了验证，在类内相关系数高达0.995时表现出优异的性能。此外，我们使用基于CVM的凝集仪能够实现快速测量（<4分钟），仅需6微升血样。这些说明了我们基于CVM的凝集仪在不影响测量灵敏度的情况下用于低成本即时诊断的潜力。
