Abstract

Computational microscopy, as a subfield of computational imaging, combines optical manipulation and image algorithmic reconstruction to recover multi-dimensional microscopic images or information of micro-objects. In recent years, the revolution in light-emitting diodes (LEDs), low-cost consumer image sensors, modern digital computers, and smartphones provide fertile opportunities for the rapid development of computational microscopy. Consequently, diverse forms of computational microscopy have been invented, including digital holographic microscopy (DHM), transport of intensity equation (TIE), differential phase contrast (DPC) microscopy, lens-free on-chip holography, and Fourier ptychographic microscopy (FPM). These computational microscopy techniques not only provide high-resolution, label-free, quantitative phase imaging capability but also decipher new and advanced biomedical research and industrial applications. Nevertheless, most computational microscopy techniques are still at an early stage of “proof of concept” or “proof of prototype” (based on commercially available microscope platforms). Translating those concepts to stand-alone optical instruments for practical use is an essential step for the promotion and adoption of computational microscopy by the wider bio-medicine, industry, and education community. In this paper, we present four smart computational light microscopes (SCLMs) developed by our laboratory, i.e., smart computational imaging laboratory (SCILab) of Nanjing University of Science and Technology (NJUST), China. These microscopes are empowered by advanced computational microscopy techniques, including digital holography, TIE, DPC, lensless holography, and FPM, which not only enables multi-modal contrast-enhanced observations for unstained specimens, but also can recover their three-dimensional profiles quantitatively. We introduce their basic principles, hardware configurations, reconstruction algorithms, and software design, quantify their imaging performance, and illustrate their typical applications for cell analysis, medical diagnosis, and microlens characterization.

Highlights

  • The optical microscope is one of the most significant inventions in the history of humankind that witnessed the fundamental revolution in biomedicine, chemistry, material science, electronics, and other various fields of scientific society

  • In “Computational light microscopy: paradigms” section, we introduce four smart computational light microscopes (SCLMs) we have developed in four paradigms, and their working principles, system configurations, imaging algorithms, and typical applications are presented in detail

  • Computational light microscopy: paradigms we present four SCLMs developed in our lab that exemplify the basic ideas of computational light microscopy presented in the previous section and demonstrate their potential impact on the function and performance of microscopic instruments and the associated applications

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Summary

Introduction

The optical microscope is one of the most significant inventions in the history of humankind that witnessed the fundamental revolution in biomedicine, chemistry, material science, electronics, and other various fields of scientific society. These SCLMs are empowered by advanced computational microscopy techniques, including DHM, TIE, DPC, lensless holography, and FPM, which enable multi-modal observation for unstained specimens, and can recover their 3D shapes quantitatively We introduce their basic principles, hardware configurations, reconstruction algorithms, and software design, quantify their imaging performance, and illustrate their typical applications. (3) Inverse reconstruction algorithm the forward image formation model is inverted (by solving the corresponding inverse problem) to reconstruct the specimen image and, importantly, additional high dimensional information, such as phase, spectrum, polarization, optical field, coherence, RI, and 3D profile, which cannot be directly acquired using traditional methods. By replacing the light source of a conventional microscope with a coherent laser and introducing an additional reference beam path, the invisible phase information can be modulated into the visible interference fringes, and quantitatively reconstructed based on Fourier fringe analysis techniques. The USB Hub circuit’s function is to simplify the link between the microscope and the host computer, and all the parts of the microscope can be controlled through the PCB

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