Resolving the heterogeneity of particle populations by size is important when the particle size is a signature of abnormal biological properties leading to disease. Accessing size heterogeneity in the sub-micrometer regime is particularly important to resolve populations of subcellular species or diagnostically relevant bioparticles. Here, we demonstrate a ratchet migration mechanism capable of separating sub-micrometer sized species by size and apply it to biological particles. The phenomenon is based on a deterministic ratchet effect, is realized in a microfluidic device, and exhibits fast migration allowing separation in tens of seconds. We characterize this phenomenon extensively with the aid of a numerical model allowing one to predict the speed and resolution of this method. We further demonstrate the deterministic ratchet migration with two sub-micrometer sized beads as model system experimentally as well as size-heterogeneous mouse liver mitochondria and liposomes as model system for other organelles. We demonstrate excellent agreement between experimentally observed migration and the numerical model.

中文翻译：

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亚微米级（生物）颗粒分离的确定性棘轮

当粒度是导致疾病的异常生物学特性的标志时，按粒度解决粒子群体的异质性很重要。在亚微米范围内获得大小异质性对于解析亚细胞物种或诊断相关的生物粒子的种群特别重要。在这里，我们演示了一种棘轮迁移机制，该机制能够按大小分离亚微米大小的物种，并将其应用于生物颗粒。该现象基于确定性的棘轮效应，是在微流体设备中实现的，并且显示出快速迁移，可在数十秒内分离。我们借助于一个数值模型来广泛地描述这种现象，从而可以预测这种方法的速度和分辨率。我们进一步证明了确定性的棘轮迁移与两个亚微米大小的珠子作为模型系统进行实验，以及大小不均一的小鼠肝线粒体和脂质体作为其他细胞器的模型系统。我们证明了实验观察到的迁移和数值模型之间的极好的一致性。