On May 12, 2026, the 【NanGaoShi·Physics Lecture】was held at Classroom 209 of Xueming Building, School of Physical Science and Technology. Prof. Chao Zuo, the academic leader of Smart Computational Imaging Laboratory (SCILab) at Nanjing University of Science and Technology, was invited to deliver an academic lecture entitled "Computational Optical Phase Imaging: Principles, Methods and Instruments" for the faculty and students of our school. Hosted by Prof. Caojin Yuan from the School of Physical Science and Technology, the lecture was attended by numerous graduate and undergraduate students of relevant majors.

How to achieve high-contrast and quantitative observation of transparent samples (such as living cells) without exogenous labeling has long been a challenge in the fields of biological imaging and medical diagnosis. Centering on this theme, starting from the basic concepts of light fields, Prof. Zuo systematically elaborated on the core principles, mainstream technical methods and the development progress of domestic instruments of computational optical phase imaging.

Prof. Zuo first started with the basic concept of phase. He pointed out that phase is the relative position in a periodic function—for a periodic function, the phase determines the position of a point within the period. In optics, a light field contains two components: amplitude and phase. Amplitude determines brightness, while phase carries optical path difference information. When light passes through a transparent object (such as a cell), the amplitude remains almost unchanged, but the phase varies with the thickness and refractive index of the object. If the phase distribution can be measured, the three-dimensional morphology or refractive index distribution of the object can be deduced. However, conventional cameras can only record intensity (amplitude), and phase information is directly lost. How to "see" the invisible phase has become the core issue of computational optical imaging.

Historically, Frits Zernike was awarded the Nobel Prize in 1953 for the invention of phase-contrast microscopy. By introducing a phase plate in the microscope, he converted phase changes into intensity changes, realizing the first observation of transparent living cells without staining. This technique is still in use today, but it only allows qualitative observation and cannot quantitatively measure phase values. Later, Digital Holographic Microscopy (DHM) enabled accurate recording of phase distribution and digital focusing by introducing reference light interference—refocusing can be performed later in software without mechanical movement. Nevertheless, holographic systems are sensitive to vibration and have complex optical paths, limiting their popularization.

Prof. Zuo focused on the breakthroughs of his team in non-interferometric quantitative phase imaging. The method based on the Transport of Intensity Equation (TIE) only requires capturing several intensity images of the sample at different defocus planes to directly calculate the phase distribution, without interference or laser, and can use ordinary white light sources. The team further extended TIE from coherent light to partially coherent light scenarios, proposed the Generalized Transport of Intensity Equation, and established the phase retrieval theory under incoherent illumination. This work laid a mathematical foundation for subsequent wide-field and high-throughput phase imaging.

In terms of improving spatial resolution and field of view, Prof. Zuo introduced Fourier Ptychographic Microscopy (FPM). This method uses an LED array to illuminate the sample from different angles, captures a series of low-resolution images, and finally reconstructs high-resolution, large-field-of-view phase images through iterative synthesis in the frequency domain. Its equivalent numerical aperture can exceed the physical limit of conventional objective lenses, achieving "the performance of a large lens with a small lens". The team applied this technique to perform high-resolution phase imaging of thousands of cells simultaneously, and further developed it into three-dimensional diffraction tomography—by rotating the illumination angle or the sample, collecting phase information of multiple projections, and using CT-like reconstruction algorithms to obtain the three-dimensional refractive index distribution inside cells. This technique requires no fluorescent labeling, enables long-term observation of physiological processes such as cell division, mitochondrial dynamics, and synaptic transport, and avoids phototoxicity and photobleaching.

Prof. Zuo emphasized that the core of computational imaging lies in the organic integration of front-end optical modulation + back-end computational reconstruction. Conventional imaging only converts light intensity into digital images, whereas computational imaging empowers the front-end optical system with encoding and modulation capabilities, and the back-end algorithms are co-designed with the front-end physical model, ultimately breaking through many limitations of classical imaging. Based on the above principles, Prof. Chao Zuo's team has developed a variety of domestic label-free live-cell microscopes, with all core components (including LED arrays, imaging modules, and software algorithms) independently controllable. The instruments have been applied to biomedical research such as gastric cancer organoids, brain organoids, and endometrial models, and successfully realized label-free observation of subcellular organelles such as mitochondria and lipid droplets.

At the end of the lecture, Prof. Zuo compared the complementary relationship between label-free phase imaging and fluorescence imaging: fluorescence labeling has excellent specificity but is not universal for all samples and suffers from phototoxicity; label-free methods are universal and suitable for long-term observation but lack specificity. The collaborative development of the two will be an important direction for future in vivo imaging. He encouraged students to master the basic knowledge of optics and signal processing, while paying attention to the domestic development of high-end optical instruments, and contribute to breaking foreign monopolies and developing China's own "precision eyes".

The lecture was systematic, in-depth and cutting-edge, covering both the combing of basic knowledge of phase imaging and the complete research chain from algorithm innovation to instrument implementation, providing a valuable academic exchange platform for the faculty and students of the school.

Speaker Biography：

Prof. Chao Zuo is a Zijin Distinguished Professor at Nanjing University of Science and Technology, a national high-level talent, the academic leader of Smart Computational Imaging Laboratory (SCILab), and the Dean & Chief Scientist of the Intelligent Computational Imaging Research Institute. He presides over projects including the Major Instrument Program, Key Program of the National Natural Science Foundation of China, and the National Key R&D Program, focusing on the basic theory, key technologies and advanced instruments of "computational optical phase imaging". He has published more than 300 SCI papers, over 50 of which are selected as cover papers in journals such as eLight, Light, Optica, AP, PhotoniX, 26 papers are listed as ESI Highly Cited/Hot Papers, with a total citation of over 20,000 times. He is a Fellow of SPIE, Optica and IOP, and has received the ICO Prize and EPS-QEOD Fresnel Prize. He serves as an editor for journals including eLight, PhotoniX, and Optics Letters, and has been continuously selected as a Clarivate Highly Cited Researcher.