Quantitative phase imaging based on holography: trends and new perspectives
Huang and Cao Light: Science & Applications (2024)13:145
https://doi.org/10.1038/s41377-024-01453-x
REVIEW ARTICLE
Official journal of the CIOMP 2047-7538
www.nature.com/lsa
Open Access
Quantitative phase imaging based on holography:
trends and new perspectives
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Zhengzhong Huang1 and Liangcai Cao
1✉
Abstract
In 1948, Dennis Gabor proposed the concept of holography, providing a pioneering solution to a quantitative
description of the optical wavefront. After 75 years of development, holographic imaging has become a powerful tool
for optical wavefront measurement and quantitative phase imaging. The emergence of this technology has given
fresh energy to physics, biology, and materials science. Digital holography (DH) possesses the quantitative advantages
of wide-field, non-contact, precise, and dynamic measurement capability for complex-waves. DH has unique
capabilities for the propagation of optical fields by measuring light scattering with phase information. It offers
quantitative visualization of the refractive index and thickness distribution of weak absorption samples, which plays a
vital role in the pathophysiology of various diseases and the characterization of various materials. It provides a
possibility to bridge the gap between the imaging and scattering disciplines. The propagation of wavefront is
described by the complex amplitude. The complex-value in the complex-domain is reconstructed from the intensityvalue measurement by camera in the real-domain. Here, we regard the process of holographic recording and
reconstruction as a transformation between complex-domain and real-domain, and discuss the mathematics and
physical principles of reconstruction. We review the DH in underlying principles, technical approaches, and the
breadth of applications. We conclude with emerging challenges and opportunities based on combining holographic
imaging with other methodologies that expand the scope and utility of holographic imaging even further. The
multidisciplinary nature brings technology and application experts together in label-free cell biology, analytical
chemistry, clinical sciences, wavefront sensing, and semiconductor production.
Introduction
An accurate depiction of how waves spread in space and
time is essential to the investigation of physical objects
and their interactions with waves. In 1948, Dennis Gabor
proposed the concept of holography1. After 75 years of
development, holography has become a powerful tool for
quantitative phase measurement. By using the reference
wave, the sensor records the corresponding interference
with the unknown object wave. The amplitude and phase
of the object can be numerically reconstructed. Holographic recording and playback of waves have been used
in numerous applications, including biological sample
analysis, material representation, and material structure
analysis2,3.
Correspondence: Liangcai Cao ()
1
Department of Precision Instrument, Tsinghua University, Beijing 100084,
China
Phase refers to measuring the optical path length shift
at each point in the field of view introduced by a specimen. The light absorption value of various semitransparent objects is low because most of the light is
scattering from the object, such as biological samples,
resulting in a low-intensity-contrast image obtained by
bright-field microscopy. The propagation of wavefront is
described by the complex amplitude. Phase enables
quantitative visualization of the inner structure or
refractive index (RI) distribution of scattering samples
with weak absorption. The main information can be
reflected in the phase of the transmission wave due to the
differences in the RI of cell liquid and external media. It is
difficult for existing commercial cameras to achieve
direct detection of phase in the visible light regime. To
render the structures visible, one solution was to convert
them into ‘amplitude objects’ using various stains or
fluorescent tags with molecular specificity4,5. However,
© The Author(s) 2024
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Huang and Cao Light: Science & Applications (2024)13:145
they are qualitative and sample-preparation-dependent,
and the photobleaching and phototoxicity limit the
fluorescent imaging of live cells. Furthermore, the use of
exogenous labeling agents, such as fluorescent proteins
or dyes, may alter the normal physiology of cells. The
labeled cells cannot be re-injected into the human body.
Another method is intrinsic contrast imaging occurred in
the 1930s when Zernike invented a technique capable of
imaging phase objects with high contrast and without the
need for tagging6. The principle of Zernike’s phase contrast microscopy builds on Abbe’s understanding of
imaging as an interference process7. To boost the contrast of the resulting interferogram and thus the image,
Zernike added a phase shift of π/2. The additional phase
shift places the scattered field in the antiphase with
respect to the incident field. The resulting phase contrast
field converts the phase into amplitude modulation.
Phase contrast microscopes also balance the power of the
two fields by attenuating the incident field. These simple
modifications provides the microscope with the ability to
visualize live, label-free cells and other weak absorption
objects in rich detail.
Gabor showed that recording the intensity of the light
emerging from an object at an out-of-focus plane incorporates both amplitude and phase information about the
field at the image plane. After the publication of holography by Dennis Gabor in 1948 which led to receiving a
Nobel Prize in 1971, several important holography-related
inventions occurred in the 1960s. E. Leith’s work on offaxis holography8 had a substantial impact in making
holography a much more practical and popular discipline.
The invention of the laser made holography even more
practical. A. Lohmann’s introduction of computergenerated holograms used computers to numerically
generate holograms to be printed and photographed for
optical reconstruction2,9. In the late 1960s, there was the
invention of digital holography (DH) by J. W. Goodman,
who proposed usin (...truncated)