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Open Access Review Issue
Advances in label-free dynamic imaging of live cells using fourier ptychographic microscopy
Biophysics Reports 2026, 12(4): 240-253
Published: 31 August 2026
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High-resolution and long-term dynamic imaging are essential for visualizing the spatial distribution and interaction networks of organelles within living cells. Although traditional super-resolution fluorescence microscopy achieves impressive resolutions of 20–100 nm, it faces significant challenges, including phototoxicity, photobleaching, and limited suitability for prolonged live-cell observation. These issues have driven the development of label-free imaging technologies that aim to minimize disruption to cellular physiology while providing high-resolution, non-destructive imaging. Among label-free approaches, Quantitative Phase Imaging (QPI) has emerged as a promising alternative for live-cell research by reconstructing cellular structures based on phase changes in transmitted light. In particular, Fourier ptychographic microscopy (FPM) achieves resolutions as fine as 150 nm while maintaining a large field of view, making it highly suitable for high-resolution, label-free imaging. Since its introduction in 2013, FPM has rapidly advanced, offering computational imaging capabilities that surpass conventional resolution limits. However, current systems are constrained by slow imaging speeds due to the sequential illumination of hundreds of LEDs. Here, we review the collective advancements in FPM that have transformed its capabilities over recent years. While numerous research groups have contributed to this progress, key innovations include the development of two-dimensional super-resolution FPM techniques that overcome the diffraction limit through iterative pattern optimization. Building upon these efforts, our group has introduced three-dimensional fast high-resolution Fourier microscopy, achieving 3D dynamic imaging at sub-micron resolution through computational refocusing algorithms. Collectively, these advancements establish FPM as a groundbreaking tool for real-time, high-resolution imaging of living cells, facilitating comprehensive analysis of organelle interactions and providing valuable insights into cellular functions and disease mechanisms.

Open Access Method Issue
Cell membrane sample preparation method of combined AFM and dSTORM analysis
Biophysics Reports 2022, 8(4): 183-192
Published: 25 July 2022
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A major role of cell membranes is to provide an ideal environment for the constituent proteins to perform their biological functions. A deep understanding of the membrane proteins assembly process under physiological conditions is quite important to elucidate both the structure and the function of the cell membranes. Along these lines, in this work, a complete workflow of the cell membrane sample preparation and the correlated AFM and dSTORM imaging analysis methods are presented. A specially designed, angle-controlled sample preparation device was used to prepare the cell membrane samples. The correlated distributions of the specific membrane proteins with the topography of the cytoplasmic side of the cell membranes can be obtained by performing correlative AFM and dSTORM measurements. These methods are ideal for systematically studying the structure of the cell membranes. The proposed method of the sample characterization was not only limited to the measurement of the cell membrane but also can be applied for both biological tissue section analysis and detection.

Open Access Review Issue
Studying structure and functions of cell membranes by single molecule biophysical techniques
Biophysics Reports 2021, 7(5): 384-398
Published: 31 October 2021
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Cell membranes are complicated multicomponent structures, related to many basic cellular processes, such as substance transporting, energy conversion, signal transduction, mechanosensing, cell adhesion and so on. However, cell membranes have long been difficult to study at a single-molecule level due to their complex and dynamic properties. During the last decades, biophysical imaging techniques, such as atomic force microscopy and super-resolution fluorescent microscopy, have been developed to study biological structures with unprecedented resolution, enabling researchers to analyze the composition and distribution of membrane proteins and monitor their specific functions at single cell/molecule level. In this review, we highlight the structure and functions of cell membranes based on up-to-date biophysical techniques. Additionally, we describe the recent advances in force-based detecting technology, which allow insight into dynamic events and quantitativelymonitoring kinetic parameters for trans-membrane transporting in living cells.

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