Quantification of nanoscale density fluctuations using electron microscopy: Light-localization properties of biological cells

Abstract

We report a study of the nanoscale mass-density fluctuations of heterogeneous optical dielectric media, including nanomaterials and biological cells, by quantifying their nanoscale light-localization properties. Transmission electron microscope images of the media are used to construct corresponding effective disordered optical lattices. Light-localization properties are studied by the statistical analysis of the inverse participation ratio ͑IPR͒ of the localized eigenfunctions of these optical lattices at the nanoscale. We validated IPR analysis using nanomaterials as models of disordered systems fabricated from dielectric nanoparticles. As an example, we then applied such analysis to distinguish between cells with different degrees of aggressive malignancy. © 2010 American Institute of Physics. ͓doi:10.1063/1.3524523͔Quantifying the degree of nanoscale disorder is a major research interest in characterizing the optical ͑electronic͒ properties of disordered condensed-matter systems. 1 Statistical properties, such as the mean and standard deviation ͑std͒, of the inverse participation ratio ͑IPR͒ of the spatially localized optical eigenfunctions of these optical systems are important quantitative measures of the degree of disorder of these lattices, where IPR of an eigenfunction E is defined as IPR= ͉͐E͑r͉͒ 4 dr ជ ͓in units of inverse area in two dimension ͑2D͔͒. 2,3 The average value of the IPR of a uniform lattice is a fixed universal number ͑ϳ2.5 in 2D͒, but the value increases with an increasing degree of disorder ͑or degree of localization͒. IPR has been well-studied in condensed-matter physics for characterizing the degree of disorder of homogeneous and heterogeneous media in a single parameter. [4][5][6] In this paper, we report the study of light-localization properties of biological cells by first constructing optical lattices of these cells via transmission electron microscopy ͑TEM͒ imaging 7 and then studying the statistical properties of IPR of the eigenfunctions of these lattices. In our most recent optical experiments, we show that the degree of nanoscale disorder increases with the degree of carcinogenesis for both control and precancerous cells ͑in cell lines, mouse model, and different organs in human studies, such as pancreas, colon, and lung͒. [8][9][10] These nanoscale changes may result from the rearrangements of DNA, RNA, lipids, or proteins. We want to verify and quantify these nanoscale changes as observed in optical studies by TEM.It has been shown that the optical refractive index ͑n͒ is linearly proportional to the local density ͑ ͒ of intracellular macromolecules for a majority of the scattering substances found in living cells, such as proteins, lipids, DNA, or RNA, i.e., n = n 0 + ⌬n = n 0 + ␣ , where n 0 is the refractive index of the medium, is the local concentration of solids, with ␣ ϳ 0.18. 11 Furthermore, we consider that the absorption of the contrast agent by the cell is linearly proportional to the total mass present in the thin cell voxel. Therefore, if TEM imaging is perfo...

MUC13 interaction with receptor tyrosine kinase HER2 drives pancreatic ductal adenocarcinoma progression

“…For this, mass arrays and then dielectric arrays were created from the confocal imaging of the cells, then the normal modes of light waves were obtained. This was followed by the quantification of the amount of the morphological distortion, L md , by taking the average of the square of the intensity of the normal modes, using a very similar methodology described elsewhere 17–19 .…”

Quantification of nanoscale density fluctuations by electron microscopy: probing cellular alterations in early carcinogenesis

“…The result showed that << IPR ( L )> Pixel > value is proportional to the product of the amplitude of the refractive index fluctuation and its correlation. Overall, the validation study in (24) showed that nanoscale disorder can be quantified by the IPR technique, which can distinguish statistically significant differences between the two disordered systems of minute difference in disorder.…”

“…A short description was presented in (24) about the methodology, but here we present the methodology in detail (Section 2). Then we reviewed in brief our previous results (24) to provide a background for the present study (Section 3).…”

“…A short description was presented in (24) about the methodology, but here we present the methodology in detail (Section 2). Then we reviewed in brief our previous results (24) to provide a background for the present study (Section 3). Finally, for the first time, we report the results of the quantification of the nanoscale mass density fluctuations in human colon tissues and their alterations in early carcinogenesis (Section 4.1).…”

1036 MUC13 Interaction With Receptor Tyrosine Kinase HER2 Drives Pancreatic Ductal Adenocarcinoma Progression

“…For this, mass arrays and then dielectric arrays were created from the confocal imaging of the cells, then the normal modes of light waves were obtained. This was followed by the quantification of the amount of the morphological distortion, L md , by taking the average of the square of the intensity of the normal modes, using a very similar methodology described elsewhere [17][18][19] .…”