近日，华中科技大学袁菁团队研究了利用数字阵列调制显微镜进行背景抑制的三维超分辨率成像。该项研究成果发表在2026年3月26日出版的《自然—光子学》杂志上。
尽管超分辨率结构光照明显微镜在生物医学研究中的价值已得到证实，但其在图像重建保真度和成像速度方面仍面临挑战。严重的背景干扰会引入伪影并降低分辨率，而计算密集的图像重建和照明模式切换则限制了成像通量。
研究组提出数字阵列调制显微技术（DaMo），该方法将数字阵列调制与单光谱重建算法相结合。高斯照明调制与数字探测调制的联用，实现了对比度达100%的外差探测。因此，DaMo在强背景干扰下可实现高保真重建（皮尔逊相关系数0.99±0.01），且重建速度比现有最先进的超分辨率结构光照明显微镜处理快102倍。DaMo的轴向分辨率达300 nm，横向分辨率达100 nm，在全细胞三维成像中信背比提升1,284倍。
该系统无需额外调制器或图像增强处理，以精简的工作流程实现了无伪影的精准成像。研究组通过肌动蛋白动力学的定量活细胞成像、级联丝状伪足融合事件追踪、细胞周期分析的多色全涂片成像以及肠上皮损伤线粒体组织病理评估，验证了DaMo的多功能性。DaMo为跨生物体系的大规模背景抑制超分辨率成像开辟了新途径。
附：英文原文
Title: Three-dimensional super-resolution imaging with suppressed background via digital array modulation microscopy
Author: Li, Sijie, Jin, Rui, Lu, Mengqi, Zhang, Ning, Zhang, Meng, Wei, Yunfei, Zhang, Zhan, Guo, Shirui, Zhang, Yu-Hui, Wang, Fengchao, Gong, Hui, Luo, Qingming, Yuan, Jing
Issue&Volume: 2026-03-26
Abstract: Despite its proven value for biomedical research, super-resolution structured illumination microscopy still faces challenges in both fidelity of image reconstruction and imaging speed. Substantial background interference introduces artefacts and degrades resolution, while computationally intensive image reconstruction and illumination pattern switching limit imaging throughput. Here we present digital array modulation microscopy (DaMo), which combines digital array modulation with a single-spectrum reconstruction algorithm. Gaussian illumination modulation combined with digital detection modulation enables heterodyne detection with a 100% contrast. Therefore, DaMo achieves high-fidelity reconstruction (Pearson correlation coefficient 0.99±0.01) under substantial background interference, with a 102× faster reconstruction speed than state-of-the-art super-resolution structured illumination microscopy processing. DaMo offers an axial resolution of 300nm and a lateral resolution of 100nm while achieving a 1,284-fold improvement in the signal-to-background ratio in whole-cell three-dimensional imaging. DaMo operates without additional modulators or extra image enhancement, providing artefact-free precision with a streamlined workflow. We demonstrate the versatility of DaMo via quantitative live-cell imaging of actin dynamics, tracking of cascaded filopodia fusion events, multicolour whole-smear imaging for cell cycle profiling, and tissue pathology assessment of intestinal epithelial injury in mitochondria. DaMo paves the way for large-scale, background-suppressed super-resolution imaging across diverse biological systems.
DOI: 10.1038/s41566-026-01869-4
Source: https://www.nature.com/articles/s41566-026-01869-4