Abstract
A major challenge in the field of optical imaging of live cells is achieving rapid, 3D, and noninvasive imaging of isolated cells without labeling. If successful, many clinical procedures involving analysis and sorting of cells drawn from body fluids, including blood, can be significantly improved. A new label‐free tomographic interferometry approach is presented. This approach provides rapid capturing of the 3D refractive‐index distribution of single cells in suspension. The cells flow in a microfluidic channel, are trapped, and then rapidly rotated by dielectrophoretic forces in a noninvasive and precise manner. Interferometric projections of the rotated cell are acquired and processed into the cellular 3D refractive‐index map. Uniquely, this approach provides full (360°) coverage of the rotation angular range around any axis, and knowledge on the viewing angle. The experimental demonstrations presented include 3D, label‐free imaging of cancer cells and three types of white blood cells. This approach is expected to be useful for label‐free cell sorting, as well as for detection and monitoring of pathological conditions resulting in cellular morphology changes or occurrence of specific cell types in blood or other body fluids.
Highlights
Introduction sample viabilityStill, the widely used methods for detection and diagnosis of diseases such as cancer at the cellular levelThe ability to identify and characterize different cell types in a are based on indirect and subjective histological and cytological heterogeneous medium has an important role in biological and examination of tissues or samples from body fluids; procedures medical research, as well as in clinical practice
The experimental demonstrations presented include 3D, labelimaging methods, such as Zernike’s phase free imaging of cancer cells and three types of white blood cells. This approach is expected to be useful for label-free cell sorting, as well as for detection and monitoring of pathological conditions resulting in cellular morphology changes or occurrence of specific cell types in blood or other body fluids
The proposed system integrates wide-field interferometry for quantitative phase map acquisition with a microfluidic channel for cell flowing, trapping, and full rotation based on dielectrophoretic forces (DEP)
Summary
We imitated acquisition by full rotation of the cell around one axis (360° range), the angular spectrum coverage of which is shown in Figure 1c and the coinciding reconstructed refractive-index profile is shown in Figure 2d,h, as can be provided by the proposed method when rotating around one axis. In the reconstruction based on illumination rotation with 140° angular coverage (Figure 2c,g), due to the missing angles only one of the two organelles is visible and the second one, as well as the edges of the large shape, are heavily blurred This signifies the advantages of being able to fully cover the 3D spatial Fourier domain by using cell rotation around two axes. This is obtained here, for the first time for our knowledge, by combining tomographic interferometry with microfluidics and DEP to allow full angular coverage for suspended cells
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