Department of Food Science, College of Agriculture and Life Sciences, Cornell University, Ithaca, NY 14853.
Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
Proc Natl Acad Sci U S A. 2018 Aug 14;115(33):8272-8277. doi: 10.1073/pnas.1800819115. Epub 2018 Jul 30.
The separation of motile sperm from semen samples is sought after for medical infertility treatments. In this work, we demonstrate a high-throughput microfluidic device that can passively isolate motile sperm within corrals inside a fluid channel, separating them from the rest of the diluted sample. Using finite element method simulations and proposing a model for sperm motion, we investigated how flow rate can provide a rheotaxis zone in front of the corral for sperm to move upstream/downstream depending on their motility. Using three different flow rates that provided shear rates above the minimum value within the rheotaxis zone, we experimentally tested the device with human and bovine semen. By taking advantage of the rheotactic behavior of sperm, this microfluidic device is able to corral motile sperm with progressive velocities in the range of 48-93 μm⋅s and 51-82 μm⋅s for bovine and human samples, respectively. More importantly, we demonstrate that the separated fractions of both human and bovine samples feature 100% normal progressive motility. Furthermore, by extracting the sperm swimming distribution within the rheotaxis zone and sperm velocity distribution inside the corral, we show that the minimum velocity of the corralled sperm can be adjusted by changing the flow rate; that is, we are able to control the motility of the separated sample. This microfluidic device is simple to use, is robust, and has a high throughput compared with traditional methods of motile sperm separation, fulfilling the needs for sperm sample preparation for medical treatments, clinical applications, and fundamental studies.
从精液样本中分离游动精子是医学不孕治疗的目标。在这项工作中，我们展示了一种高通量微流控装置，它可以在流体通道内的围栏内被动分离游动精子，将它们与稀释后的样本的其余部分分离。我们使用有限元方法模拟并提出了一种精子运动模型，研究了流速如何在前缘提供一个趋流区，使精子能够根据其运动性向上游/下游移动。我们使用三种不同的流速，提供了趋流区内的最小剪切率以上的剪切率，用人类和牛的精液对该装置进行了实验测试。通过利用精子的趋流行为，这种微流控装置能够以 48-93 μm⋅s 和 51-82 μm⋅s 的范围在牛和人样本中分别对具有渐进速度的游动精子进行围栏。更重要的是，我们证明了从人类和牛的样本中分离出的部分均具有 100%的正常渐进运动性。此外，通过提取趋流区内的精子游动分布和围栏内的精子速度分布，我们表明可以通过改变流速来调整被围栏困住的精子的最小速度；也就是说，我们能够控制分离样本的运动性。与传统的游动精子分离方法相比，这种微流控装置使用简单、稳健且具有高通量，满足了医学治疗、临床应用和基础研究中对精子样本制备的需求。
