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

利用声波和光波的受激散射研究细胞弹性的激光显微镜

• 批准号: 416519410
• 负责人: Professor Dr.-Ing. Jürgen W. Czarske, since 6/2019
• 金额: --
• 依托单位: Max-Planck-Institut für die Physik des Lichts
• 依托单位国家: 德国
• 项目类别: New Instrumentation for Research
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/416519410?language=en
• 关键词: Laser; microscope; investigating; elasticity; cells

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.

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的起源方面发挥着关键作用。此外，弹性等机械性能是疾病的有效标志物，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测定弹性，但它们需要直接接触样品并进行样品制备。为了克服这些限制，从触觉技术到光学方法的范式转变。布里渊散射，基于声学声子和光子的相互作用，允许无接触，无标记和三维体内测量的弹性。到目前为止，测量都是基于自发布里渊散射，其信噪比（SNR）很低，因此需要很长的平均时间。在“新研究仪器”的资助计划中，实现了基于受激布里渊散射评估的激光显微镜，由此SNR和测量速度可以提高几个数量级。高度跨学科方法的目的在于设置，利用激光计量学和系统工程的方法对受激布里渊激光显微镜进行了研究和验证，并实现了用于生物学和医学的演示器。将通过生物力学的参考测量来验证测量原理。本项目将以血细胞流式细胞术为例，研究细胞弹性时空相关性的新可能性。新型受激布里渊激光显微镜作为非接触测量方法，用于亚细胞弹性研究，开辟了医学领域的广泛应用，从粘附细胞的生物力学成像，流式细胞术在肿瘤学上对生命物理学基本问题的研究。