Nolte David D, An Ran, Turek John, Jeong Kwan
Department of Physics, Purdue University, West Lafayette, IN 47907, USA.
J Lab Autom. 2011 Dec;16(6):431-42. doi: 10.1016/j.jala.2011.05.002. Epub 2011 Jun 29.
Tissue dynamics spectroscopy combines dynamic light scattering with short-coherence digital holography to capture intracellular motion inside multicellular tumor spheroid tissue models. The cellular mechanical activity becomes an endogenous imaging contrast agent for motility contrast imaging. Fluctuation spectroscopy is performed on dynamic speckle from the proliferating shell and hypoxic core to generate drug-response spectrograms that are frequency versus time representations of the changes in spectral content induced by an applied compound or an environmental perturbation. A combination of 28 reference compounds and conditions applied to rat osteogenic UMR-106 spheroids generated spectrograms that were crosscorrelated in a similarity matrix used for unsupervised hierarchical clustering of similar compound responses. This work establishes the feasibility of tissue dynamics spectroscopy for three-dimensional tissue-based phenotypic profiling of drug response as a fully endogenous probe of the response of tissue to reference compounds.
组织动力学光谱技术将动态光散射与短相干数字全息术相结合,以捕捉多细胞肿瘤球体组织模型内的细胞内运动。细胞机械活动成为用于运动对比成像的内源性成像造影剂。对增殖外壳和缺氧核心的动态散斑进行波动光谱分析,以生成药物反应光谱图,该光谱图是频率与时间的表示,反映了应用化合物或环境扰动引起的光谱内容变化。将28种参考化合物和条件应用于大鼠成骨UMR - 106球体,生成的光谱图在相似性矩阵中进行互相关,该矩阵用于对相似化合物反应进行无监督层次聚类。这项工作确立了组织动力学光谱技术用于基于三维组织的药物反应表型分析的可行性,作为组织对参考化合物反应的完全内源性探针。