近日，英国圣安德鲁斯大学的Malte C. Gather及其研究小组与德国科隆大学的Marcel Schubert等人合作并取得一项新进展。经过不懈努力，他们实现可变形微激光力传感。相关研究成果已于2024年6月5日在国际知名学术期刊《光：科学与应用》上发表。

据悉，机械力是细胞行为和功能的关键调节因子，影响许多基本的生物过程，如细胞迁移、胚胎发生、免疫反应和病理状态。专门的力传感器和成像技术已经被开发出来，以量化这些在单细胞和体内不可见的力。然而，目前的技术严重依赖于高分辨率显微镜，并且不允许对光学致密组织进行检查，从而减少了它们在二维细胞培养和高度透明的生物组织中的应用。

该研究团队引入DEFORM，可变形微激光力传感，一种以前所未有的时空分辨率检测亚纳米牛顿力的光谱技术。DEFORM技术依赖于染料掺杂的油微滴激光发射光谱分析，并通过监测这些微滴中激光模式因力作用而发生的简并提升，来检测纳米级别的形变。经过原子力显微镜的严格验证，并结合激光光谱变化与施加力的关联模型的开发，DEFORM已成功地应用于测量三维结构、肿瘤球体和晚期果蝇幼虫内部数百微米深处的力。

研究人员更进一步展示了DEFORM在单细胞空间分辨率，和毫秒时间分辨率下的连续力传感能力，这为在胚胎形成、组织重塑以及肿瘤侵袭的晚期阶段，进行生物力学力的非侵入性研究开辟了新的道路。

附：英文原文

Title: Deformable microlaser force sensing

Author: Dalaka, Eleni, Hill, Joseph S., Booth, Jonathan H. H., Popczyk, Anna, Pulver, Stefan R., Gather, Malte C., Schubert, Marcel

Issue&Volume: 2024-06-05

Abstract: Mechanical forces are key regulators of cellular behavior and function, affecting many fundamental biological processes such as cell migration, embryogenesis, immunological responses, and pathological states. Specialized force sensors and imaging techniques have been developed to quantify these otherwise invisible forces in single cells and in vivo. However, current techniques rely heavily on high-resolution microscopy and do not allow interrogation of optically dense tissue, reducing their application to 2D cell cultures and highly transparent biological tissue. Here, we introduce DEFORM, deformable microlaser force sensing, a spectroscopic technique that detects sub-nanonewton forces with unprecedented spatio-temporal resolution. DEFORM is based on the spectral analysis of laser emission from dye-doped oil microdroplets and uses the force-induced lifting of laser mode degeneracy in these droplets to detect nanometer deformations. Following validation by atomic force microscopy and development of a model that links changes in laser spectrum to applied force, DEFORM is used to measure forces in 3D and at depths of hundreds of microns within tumor spheroids and late-stage Drosophila larva. We furthermore show continuous force sensing with single-cell spatial and millisecond temporal resolution, thus paving the way for non-invasive studies of biomechanical forces in advanced stages of embryogenesis, tissue remodeling, and tumor invasion.

DOI: 10.1038/s41377-024-01471-9

Source: https://www.nature.com/articles/s41377-024-01471-9