I-Corps: Add-on Brillouin Module for Confocal Microscopes

这个I-Corps项目的更广泛的影响/商业潜力是引入了一种新的显微镜模式，它可以实现非接触式机械映射，并开发了与商业共聚焦显微镜仪器兼容的相应附加模块。共聚焦显微镜仪器广泛应用于学术界和工业界，但不提供样品的力学信息;力学测试仪器在学术界和工业界也普遍存在，但基于接触。该项目为光学显微镜仪器带来了非接触式机械测试能力。除了能够以高时空分辨率进行传统的材料表征外，该仪器还将在生物医学研究中发挥重要作用。在过去的二十年里，人们越来越认识到细胞与其局部微环境之间的机械相互作用在调节细胞功能中的重要作用。一个广泛使用的光学显微镜细胞生物力学将加速我们的机械化学途径及其在控制生物过程中的作用的理解。因此，该仪器有望被工业界和学术界的生物医学研究人员和材料科学家广泛使用，以在不干扰样品的情况下获得细胞、组织和生物材料的机械性能，并具有高3D分辨率。 这个I-Corps项目探索了共焦显微镜的附加模块的商业化，该模块具有新颖的布里渊光谱学。 自20世纪70年代以来，布里渊光谱已广泛用于材料测试和环境传感，使用专用光谱仪进行单次测量需要10分钟至数小时。近年来，开发了一种新型光谱仪，以将采集速度提高几个数量级，并允许获得生物材料、生物细胞和组织的3D弹性图。由于商业共聚焦显微镜的集成，几个非常有影响力的领域（例如干细胞谱系分化，恶性肿瘤转化）将受益于这项技术，因为它能够在环境和设置中收集生物力学信息，例如模拟体内条件的3D微环境。 此外，该仪器将使微流体平台上的细胞生物力学研究，以控制微环境条件。该技术与传统的光学显微镜兼容，还可以与力映射模式相结合，从而能够研究细胞如何感知机械刺激并将其转化为生化信号。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this I-Corps project is the introduction of a new microscopy modality, which enables non-contact mechanical mapping, and the development of the corresponding add-on module compatible to commercial confocal microscopy instruments. Confocal microscopy instruments are widely used in academia and industry but do not provide mechanical information of samples; mechanical testing instruments are also ubiquitous in both academia and industry but are contact-based. This project brings the non-contact mechanical testing capability to optical microscopy instruments. Beyond enabling traditional material characterizations with high spatio-temporal resolution, the instrument will be highly impactful in biomedical research. The past two decades have seen increasing recognition of the prominent role of the mechanical interplay between cells and their local microenvironment to regulate cell function. A widely utilized optical microscope for cell biomechanics would accelerate our understanding of mechano-chemical pathways and their role in the control of biological processes. Thus, this instrument is expected to be broadly used by biomedical researchers and material scientists in industry and academia to access cell, tissue and biomaterial mechanical properties without perturbing the sample and with high 3D resolution. This I-Corps project explores the commercialization of an add-on module for confocal microscopes that features novel Brillouin spectroscopy. Brillouin spectroscopy has been widely used for material testing and environmental sensing since the 1970's using specialized spectrometers that required 10 min to hours for a single measurement. In recent years, a new type of spectrometer was developed to improve speed of acquisition by several orders of magnitude and allowed to obtain 3D elasticity maps of biomaterials, biological cells and tissues. Thanks to the integration in commercial confocal microscopes, several highly impactful areas (e.g. stem cell lineage differentiation, malignancy transformation) will benefit from this technology as it enables gathering biomechanical information in environments and settings such as 3D microenvironments that mimic the in vivo conditions. In addition, the instrument will enable the study of cell biomechanics on microfluidic platforms in order to control microenvironment conditions. Being compatible with traditional optical microscopes, this technology can also be combined with force mapping modalities thus enabling to investigate how cells sense mechanical stimuli and transduce them into biochemical signals.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.