Nanoscale topological imaging using atomic force microscopy (AFM) combined with infrared (IR) spectroscopy (AFM-IR) is a rapidly emerging modality to record correlated structural and chemical images. Although the expectation is that the spectral data faithfully represents the underlying chemical composition, the sample mechanical properties affect the recorded data (known as the probe–sample-interaction effect). Although experts in the field are aware of this effect, the contribution is not fully understood. Further, when the sample properties are not well-known or when AFM-IR experiments are conducted by nonexperts, there is a chance that these nonmolecular properties may affect analytical measurements in an uncertain manner. Techniques such as resonance-enhanced imaging and normalization of the IR signal using ratios might improve fidelity of recorded data, but they are not universally effective. Here, we provide a fully analytical model that relates cantilever response to the local sample expansion which opens several avenues. We demonstrate a new method for removing probe–sample-interaction effects in AFM-IR images by measuring the cantilever responsivity using a mechanically induced, out-of-plane sample vibration. This method is then applied to model polymers and mammary epithelial cells to show improvements in sensitivity, accuracy, and repeatability for measuring soft matter when compared to the current state of the art (resonance-enhanced operation). Understanding of the sample-dependent cantilever responsivity is an essential addition to AFM-IR imaging if the identification of chemical features at nanoscale resolutions is to be realized for arbitrary samples.

中文翻译：

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探针-样品相互作用无关的原子力显微镜-红外光谱：迈向鲁棒的纳米级成分映射

使用原子力显微镜（AFM）结合红外（IR）光谱（AFM-IR）进行纳米级拓扑成像是一种快速出现的记录相关结构和化学图像的方法。尽管期望光谱数据能忠实地代表潜在的化学成分，但样品的机械性能会影响记录的数据（称为探针-样品-相互作用效应）。尽管本领域的专家已经意识到了这种影响，但是其贡献还没有被完全理解。此外，当样品特性不为人所知时或由非专家进行AFM-IR实验时，这些非分子特性可能会以不确定的方式影响分析测量。诸如共振增强成像和使用比率对IR信号进行归一化之类的技术可能会提高记录数据的保真度，但并不是普遍有效的。在这里，我们提供了一个完整的分析模型，该模型将悬臂响应与局部样本扩展相关联，从而打开了几种途径。我们演示了一种新方法，该方法通过使用机械感应的平面外样品振动测量悬臂响应度来消除AFM-IR图像中的探针-样品相互作用效应。然后，将该方法应用于聚合物和乳腺上皮细胞模型，以显示与现有技术（共振增强操作）相比，在测量软物质方面的灵敏度，准确性和可重复性得到改善。