量子点闪烁与MINFLUX技术结合在生物成像中的突破

First Application of Quantum Dots in MINFLUX Nanoscopy for Biological Imaging

摘要: 在超分辨显微技术中，最小荧光光子纳米显微镜(MINFLUX)以其卓越的空间分辨率和光子利用效率成为近年来的重大突破。然而，该方法对荧光探针的光物理特性提出了极为严格的要求，尤其是在发射稳定性、闪烁动态的可控性以及与生物标记体系的兼容性方面。半导体量子点(QDs)凭借其出色的光稳定性、宽光谱可调性和长时间成像能力，为满足这些要求并拓展MINFLUX的应用潜力提供了理想的候选。本研究首次将QDs应用于MINFLUX，并利用抗体标记的量子点纳米探针对固定U-2OS细胞微管蛋白实现了二维成像。结果表明，基于QDs的探针在MINFLUX下可实现约1.2 nm的定位精度(原始数据中位数)，清晰呈现了微管的基本结构特征。本研究验证了QDs在MINFLUX成像中的可行性，显示出其作为新型超分辨探针在单分子定位显微与纳米尺度生物学研究中的应用潜力。

Abstract: In the field of super-resolution microscopy, minimal photon fluxes nanoscopy (MINFLUX) has emerged as a major breakthrough due to its outstanding spatial resolution and photon efficiency. However, this method imposes stringent requirements on the photophysical properties of fluorescent probes, particularly in terms of emission stability, controllable blinking dynamics, and compatibility with biological labeling systems. Semiconductor quantum dots (QDs), with their exceptional photostability, broad spectral tunability, and long-term imaging capability, represent promising candidates to meet these demands and further extend the applicability of MINFLUX. In this study, we demonstrate for the first time the application of QDs in MINFLUX by employing antibody-conjugated QD nanoprobes to achieve two-dimensional imaging of microtubules in fixed U-2OS cells. The results show that QD-based probes can achieve a localization precision of approximately 1.2 nm (median value of raw data) under MINFLUX, clearly resolving the fundamental structural features of microtubules. This work validates the feasibility of QDs as novel probes for MINFLUX and highlights their potential in single-molecule localization microscopy and nanoscale biological research.