Transport of intensity equation: a tutorial

Quantitative phase imaging (QPI) of transparent samples plays an essential role in multiple biomedical applications, and miniaturizing these systems will enable their adoption into point-of-care and in vivo applications. Here, we propose a compact quantitative phase gradient microscope (QGPM) based on two dielectric metasurface layers, inspired by a classical differential interference contrast (DIC) microscope. Owing to the multifunctionality and compactness of the dielectric metasurfaces, the QPGM simultaneously captures three DIC images to generate a quantitative phase gradient image in a single shot. The volume of the metasurface optical system is on the order of 1 mm3. Imaging experiments with various phase resolution samples verify the capability to capture quantitative phase gradient data, with phase gradient sensitivity better than 92.3 mrad μm−1 and single-cell resolution. The results showcase the potential of metasurfaces for developing miniaturized QPI systems for label-free cellular imaging and point-of-care devices. Using two dielectric metasurface layers, a compact quantitative phase gradient microscope that can capture quantitative phase gradient images in a single shot is reported with phase gradient sensitivity better than 92.3 mrad μm−1 and single-cell resolution.

Single-shot quantitative phase gradient microscopy using a system of multifunctional metasurfaces

Metasurface is a recently developed nanophotonics concept to manipulate the properties of light by replacing conventional bulky optical components with ultrathin (more than 10 4 times thinner) flat optical components. Since the first demonstration of metasurfaces in 2011, they have attracted tremendous interest in the consumer optics and electronics industries. Recently, metasurface-empowered novel bioimaging and biosensing tools have emerged and been reported. Given the recent advances in metasurfaces in biomedical engineering, this review article covers the state of the art for this technology and provides a comprehensive interdisciplinary perspective on this field. The topics that we have covered include metasurfaces for chiral imaging, endoscopic optical coherence tomography, fluorescent imaging, superresolution imaging, magnetic resonance imaging, quantitative phase imaging, sensing of antibodies, proteins, DNAs, cells, and cancer biomarkers. Future directions are discussed in twofold: application-specific biomedical metasurfaces and bioinspired metasurface devices. Perspectives on challenges and opportunities of metasurfaces, biophotonics, and translational biomedical devices are also provided. The objective of this review article is to inform and stimulate interdisciplinary research: firstly, by introducing the metasurface concept to the biomedical community; and secondly by assisting the metasurface community to understand the needs and realize the opportunities in the medical fields. In addition, this article provides two knowledge boxes describing the design process of a metasurface lens and the performance matrix of a biosensor, which serve as a "crash-course" introduction to those new to both fields.

Metasurfaces for biomedical applications: imaging and sensing from a nanophotonics perspective

Due to its specificity, fluorescence microscopy has become a quintessential imaging tool in cell biology. However, photobleaching, phototoxicity, and related artifacts continue to limit fluorescence microscopy's utility. Recently, it has been shown that artificial intelligence (AI) can transform one form of contrast into another. We present phase imaging with computational specificity (PICS), a combination of quantitative phase imaging and AI, which provides information about unlabeled live cells with high specificity. Our imaging system allows for automatic training, while inference is built into the acquisition software and runs in real-time. Applying the computed fluorescence maps back to the quantitative phase imaging (QPI) data, we measured the growth of both nuclei and cytoplasm independently, over many days, without loss of viability. Using a QPI method that suppresses multiple scattering, we measured the dry mass content of individual cell nuclei within spheroids. In its current implementation, PICS offers a versatile quantitative technique for continuous simultaneous monitoring of individual cellular components in biological applications where long-term label-free imaging is desirable.

/pdf/phase-imaging-with-computational-specificity-pics-for-dqpkuof2l2.pdf

Phase imaging with computational specificity (PICS) for measuring dry mass changes in sub-cellular compartments

Relevance and Regulation of Cell Density.

Quantitative phase imaging, i.e., measuring the map of pathlength shifts due to the specimen of interest, has been developing rapidly over the past decade. The main methods and exciting applications to biomedicine will be reviewed.

Quantitative phase imaging in biomedicine

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Quantitative phase imaging in biomedicine