Label-free microfluidic-based cell sorters leverage innate differences among cells (e.g., size and stiffness), to separate one cell type from another. This sorting step is crucial for many cell-based applications. Polystyrene-based microparticles (MPs) are the current gold standard for calibrating flow-based cell sorters and analyzers; however, the deformation behavior of these rigid materials is drastically different from that of living cells. Given this discrepancy in stiffness, an alternative calibration particle that better reflects cell elasticity is needed for the optimization of new and existing microfluidic devices. Here, we describe the fabrication of cell-like, mechanically tunable MPs and demonstrate their utility in quantifying differences in inertial displacement within a microfluidic constriction device as a function of particle elastic modulus, for the first time. Monodisperse, fluorescent, cell-like microparticles that replicate the size and modulus of living cells were fabricated from polyacrylamide within a microfluidic droplet generator and characterized via optical and atomic force microscopy. Trajectories of our cell-like MPs were mapped within the constriction device to predict where living cells of similar size/modulus would move. Calibration of the device with our MPs showed that inertial displacement depends on both particle size and modulus, with large/soft MPs migrating further toward the channel centerline than small/stiff MPs. The mapped trajectories also indicated that MP modulus contributed proportionally more to particle displacement than size, for the physiologically relevant ranges tested. The large shift in focusing position quantified here emphasizes the need for physiologically relevant, deformable MPs for calibrating and optimizing microfluidic separation platforms.

中文翻译：

---

弹性模量对微通道中细胞状颗粒惯性位移的影响。

基于无标记微流体的细胞分选器利用细胞之间的先天差异（例如，大小和刚度），将一种细胞类型与另一种细胞类型分开。此排序步骤对于许多基于单元格的应用程序至关重要。聚苯乙烯基微粒 (MP) 是当前校准流式细胞分选仪和分析仪的黄金标准；然而，这些刚性材料的变形行为与活细胞的变形行为截然不同。鉴于刚度的这种差异，需要一种更好地反映细胞弹性的替代校准粒子来优化新的和现有的微流体设备。在这里，我们描述了细胞样的制造，机械可调 MPs 并首次展示了它们在量化微流体收缩装置内惯性位移差异作为粒子弹性模量的函数中的效用。复制活细胞大小和模量的单分散、荧光、细胞样微粒是由聚丙烯酰胺在微流体液滴发生器中制造的，并通过光学和原子力显微镜进行表征。我们的细胞样 MP 的轨迹被映射在收缩装置内，以预测类似大小/模量的活细胞将移动的位置。使用我们的 MP 校准设备表明，惯性位移取决于颗粒大小和模量，大/软 MP 比小/硬 MP 更向通道中心线迁移。映射的轨迹还表明，对于测试的生理相关范围，MP 模量对粒子位移的贡献比对大小的贡献更大。此处量化的聚焦位置的大转变强调了需要生理相关的、可变形的 MP 来校准和优化微流体分离平台。