Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells
Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells
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DOI：
10.1073/pnas.0804723105
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发表时间：
2008-12-23
影响因子：
11.1
通讯作者：
Backman, Vadim
中科院分区：
文献类型：
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作者：
Subramanian, Hariharan;Pradhan, Prabhakar;Backman, Vadim
最近，人们大力推动在纳米尺度上理解生物过程。光学显微镜在细胞微结构成像中非常有用。然而，由于缺乏在这些小尺度上进行细胞分析的实用手段，纳米尺度上细胞组织的表征受到了阻碍。为了满足这一需求，我们开发了一种显微光谱技术，即单细胞部分波光谱（PWS），它提供了对生物细胞纳米级结构统计特性的深入了解，超出了传统显微镜所揭示的范围。结合介观光传输理论，PWS 量化了细胞内结构的无序强度。为了说明该技术的潜力，在结肠癌发生的细胞系和动物模型的实验中，我们表明，细胞纳米结构紊乱程度的增加与显微镜下/组织学上正常的细胞中癌发生早期阶段的遗传事件相似。这些数据表明，以 PWS 为代表的单细胞光学的这一进步可能具有重要的生物医学应用。
Recently, there has been a major thrust to understand biological processes at the nanoscale. Optical microscopy has been exceedingly useful in imaging cell microarchitecture. Characterization of cell organization at the nanoscale, however, has been stymied by the lack of practical means of cell analysis at these small scales. To address this need, we developed a microscopic spectroscopy technique, single-cell partial-wave spectroscopy (PWS), which provides insights into the statistical properties of the nanoscale architecture of biological cells beyond what conventional microscopy reveals. Coupled with the mesoscopic light transport theory, PWS quantifies the disorder strength of intracellular architecture. As an illustration of the potential of the technique, in the experiments with cell lines and an animal model of colon carcinogenesis we show that increase in the degree of disorder in cell nanoarchitecture parallels genetic events in the early stages of carcinogenesis in otherwise microscopically/histologically normal-appearing cells. These data indicate that this advance in single-cell optics represented by PWS may have significant biomedical applications.