Scanning probe microscopy provides a unique window into the morphology, mechanics, and structure of proteins and their complexes on the nanoscale. Such measurements require, however, deposition of samples onto substrates. This process can affect conformations and assembly states of the molecular species under investigation and can bias the molecular populations observed in heterogeneous samples through differential adsorption. Here, we show that these limitations can be overcome with a single-step microfluidic spray deposition platform. This method transfers biological solutions to substrates as microdroplets with subpicoliter volume, drying in milliseconds, a timescale that is shorter than typical diffusion times of proteins on liquid-solid interfaces, thus avoiding surface mass transport and change to the assembly state. Finally, the single-step deposition ensures the attachment of the full molecular content of the sample to the substrate, allowing quantitative measurements of different molecular populations within heterogeneous systems, including protein aggregates.

中文翻译：

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用于解决单分子蛋白质结构和异质性的微流体沉积。

扫描探针显微镜为了解蛋白质及其复合物在纳米尺度上的形态、力学和结构提供了独特的窗口。然而，此类测量需要将样品沉积到基板上。这个过程可以影响正在研究的分子物种的构象和组装状态，并且可以通过差异吸附使在异质样品中观察到的分子群产生偏差。在这里，我们展示了这些限制可以通过单步微流体喷雾沉积平台来克服。该方法将生物溶液作为具有亚皮升体积的微滴转移到基板上，以毫秒为单位干燥，该时间尺度比蛋白质在液-固界面上的典型扩散时间短，从而避免了表面质量传递和转变为组装状态。最后，