Characterization of cell physical biomarkers is vital to understand cell properties and applicable for disease diagnostics. Current methods used to analyze physical phenotypes involve external forces to deform the cells. Alternatively, internal tension forces via osmotic swelling can also deform the cells. However, an established assumption contends that the forces generated during hypotonic swelling concentrated on the plasma membrane are incapable of assessing the physical properties of nucleated cells. Here, we utilized an osmotic swelling approach to characterize different types of nucleated cells. Using a microfluidic device for cell trapping arrays with truncated hanging micropillars (CellHangars), we isolated single cells and evaluated the swelling dynamics during the hypotonic challenge at 1 s time resolution. We demonstrated that cells with different mechanical phenotypes showed unique swelling dynamics signature. Different types of cells can be classified with an accuracy of up to ∼99%. We also showed that swelling dynamics can detect cellular mechanical property changes due to cytoskeleton disruption. Considering its simplicity, swelling dynamics offers an invaluable label-free physical biomarker for cells with potential applications in both biological studies and clinical practice.

中文翻译：

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表征新物理生物标记的单细胞渗透溶胀动力学。

细胞物理生物标志物的表征对于了解细胞特性至关重要，并适用于疾病诊断。用于分析物理表型的当前方法涉及外力使细胞变形。或者，通过渗透溶胀产生的内部张力也会使细胞变形。但是，已经建立的假设认为，在低渗溶胀期间集中在质膜上产生的力不能评估有核细胞的物理性质。在这里，我们利用渗透溶胀法来表征不同类型的有核细胞。使用微流体装置将细胞截断的微柱（CellHangars）捕获到细胞中，我们分离了单个细胞，并以1 s的时间分辨率评估了低渗刺激期间的肿胀动力学。我们证明了具有不同机械表型的细胞显示出独特的溶胀动力学特征。可以对不同类型的细胞进行分类，精度最高可达〜99％。我们还表明，溶胀动力学可以检测到由于细胞骨架破坏而引起的细胞力学特性变化。考虑到其简单性，溶胀动力学为细胞提供了无价的无标记物理生物标记，在生物研究和临床实践中都有潜在的应用。