Spatial light interference microscopy: principle and applications to biomedicine

Abstract

In this paper, we review spatial light interference microscopy (SLIM), a commonpath, phase-shifting interferometer, built onto a phase-contrast microscope, with white-light illumination. As one of the most sensitive quantitative phase imaging (QPI) methods, SLIM allows for speckle-free phase reconstruction with sub-nanometer path-length stability. We first review image formation in QPI, scattering, holography, and microcopy. Then, we outline SLIM imaging from theory to instrumentation. Zernike's phase-contrast microscopy, phase retrieval in SLIM, and halo removal algorithms are discussed. Next, we discuss the requirements for operation, with a focus on software developed in-house for SLIM that high-throughput acquisition, whole slide scanning, mosaic tile registration, and imaging with a color camera. Lastly, we review the applications of SLIM in basic science and clinical studies. SLIM can study cell dynamics, cell growth and proliferation, cell migration, and mass transport, etc. In clinical settings, SLIM can assist with cancer studies, reproductive technology, and blood testing, etc. Finally, we review an emerging trend, where SLIM imaging in conjunction with artificial intelligence (AI) brings computational specificity and, in turn, offers new solutions to outstanding challenges in cell biology and pathology.

Machine Learning Assisted Classification of Cell Lines and Cell States on Quantitative Phase Images

“…Despite random errors arising in DHM-based morphology evaluation due to coherent noise, imperfect segmentation and variations of intracellular refractive index, we believe that the achieved accuracy was quite fair for analysis of individual cells and for distinguishing between cell types and states. Please note that the accuracy of cell morphology evaluation can be increased using high-NA microscopic objectives, using the synthetic aperture [43,44] and coherent noise suppression techniques [29,44,45]. The tolerable evaluation accuracy of morphological features provided by DHM indicates the validity of this technique for evaluation of morphology-dependent processes, such as necrosis/apoptosis cell death pathways.…”

“…Quantitative phase imaging (QPI) techniques using coherent or partially coherent radiation [29,30] allow for reconstruction of phase images of individual cells and for computation of a wide variety of cellular parameters, discussed and listed in [27,31] and elsewhere. The obtained optical parameters of cells depend on both morphological characteristics and refractive index distributions, related to dry mass density in different cellular compartments.…”

Label-free imaging of collagen fibers in tissue slices using phase imaging with computational specificity

“…SLIM imaging is achieved by connecting an external SLIM module (CellVista SLIM Pro, Phi Optics, Inc.) on the side port of a phase contrast microscope [38]. The SLIM principle of operation is presented Ref.…”

Numerical Modeling of Radiation Focusing by Dielectric Microcylinders with Several Layers

“…Ultra-narrow light spots or nanojets are widely used in modern optical instrumentation. The problems of nanojets formation and optimization of their parameters are being actively studied by the world scientific community due to their importance in different areas [3][4][5] and mostly in biomedicine [6][7][8]. They are used for micromanipulation [9,10], optical tweezers [11][12][13], for fluorescence enhancement in Raman spectroscopy [14], in histological studies [15], in vivo application [16].…”