Laser microscope for investigating the elasticity of cells using the stimulated scat-tering of acoustic and optical waves

生物细胞的力学性能与其功能能力密切相关。因此，它们被认为在理解生物学的各种基本方面和疾病起源方面发挥着关键作用。此外，弹性等机械特性是疾病的有效标记，可以提供强大的诊断，例如肿瘤学。原子力显微镜能够以亚细胞空间分辨率确定弹性，但它们需要直接接触和制备样品。为了克服这些限制，从触觉技术到光学方法的范式转变被追求。布里渊散射，基于声子和光子的相互作用，允许无接触，无标签和三维体内弹性测量。到目前为止，测量是基于自发布里渊散射，它只表现出较差的信噪比（SNR），因此需要很长的平均时间。在“新型仪器研究”资助项目中，实现了基于受激布里渊散射评价的激光显微镜，将信噪比和测量速度提高了几个数量级。高度跨学科方法的目的在于建立，研究和验证受激布里渊激光显微镜与激光计量和系统工程的方法，以及实现一个示范，为以后在生物学和医学上的使用。测量原理的验证将通过生物力学的参考测量来执行。关于细胞弹性的时空相关性研究的新可能性将在这个项目中对血细胞的流式细胞术进行研究。新型受激布里渊激光显微镜作为一种非接触测量方法，用于亚细胞弹性研究，在医学上开辟了广泛的应用范围，从贴壁细胞的生物力学成像，流式细胞术到肿瘤学，再到有关生命物理学的基本问题。

The mechanical properties of biological cells are closely related with their functional capabilities. Hence, they are considered to play a key role in the understanding of a variety of fundamental aspects in biology and of the origin of diseases. Moreover, mechanical properties like elasticity are effective markers for diseases, which can provide powerful diagnostics e.g. for oncology. Atomic force microscopes are able to determine elasticity with subcellular spatial resolution, but they require a direct contact to and preparation of the sample. To overcome these limitations, a paradigm shift from tactile techniques to optical methods is pursued. Brillouin scattering, based on the interaction of acoustical phonons and photons, allows for contact-free, label-free and three-dimensional in-vivo measurements of the elasticity. So far, measurements were based on spontaneous Brillouin scattering, which exhibits only a poor signal-to-noise ratio (SNR) and hence requires long averaging times.Within the funding program "New Instrumentation for Research", a laser microscope based on the evaluation of stimulated Brillouin scattering is realized, whereby the SNR and the measure-ment speed can be increased by several orders of magnitude.The aim of the highly interdisciplinary approach lies in the setup, the investigation and validation of a stimulated Brillouin laser microscope with methods from laser metrology and systems engi-neering as well as the realization of a demonstrator for the later use in biology and medicine. The validation of the measurement principle will be performed by reference measurements of the biomechanics. New possibilities for research concerning spatio-temporal correlations of the elas-ticity of cells will be investigated already in this project for the case of flow cytometry of blood cells.The novel stimulated Brillouin laser microscope for subcellular investigations of elasticity as a contact-free measurement approach opens a broad spectrum of applications in medicine, rang-ing from biomechanical imaging of adherent cells, flow cytometry over oncology towards fun-damental questions concerning the physics of life.