无需染色的便携式分子显微镜,实现厘米级成像与单分子灵敏度。
Deep-ultraviolet ptychographic pocket-scope (DART): mesoscale lensless molecular imaging with label-free spectroscopic contrast
- 利用深紫外吸收指纹与无透镜叠栅成像技术
- 分辨率达308纳米,成像范围达厘米级,深度景深毫米级
- 适合临床诊断、太空生物探测等便携场景
传统生物样本中尺度表征需在分辨率、视场、景深和分子特异性间权衡,多数方法依赖外部标记。本文提出深紫外叠栅便携显微镜(DART),通过生物分子天然的深紫外吸收特征,结合无透镜叠栅显微技术,实现厘米级视场内308纳米线宽分辨率,同时保持毫米级深度景深。虚拟误差箱方法有效消除因时间相干性不足等光学缺陷导致的伪影,无需透镜即可获得高保真分子图像。在深紫外波段进行差异光谱成像,实现对核酸与蛋白质分布的定量映射,检测灵敏度达飞克级,提供可解释的虚拟染色基础。我们展示了在组织切片、细胞病理学样本、血细胞及神经元群体上的应用,无需外源标记即可揭示精细分子对比。该便携平台融合高分辨率分子图谱与大尺度成像能力,为快速临床诊断、组织分析及空间探索中的生物学表征开辟新路径。
原文摘要 · Abstract (English)
The mesoscale characterization of biological specimens has traditionally required compromises between resolution, field-of-view, depth-of-field, and molecular specificity, with most approaches relying on external labels. Here we present the Deep-ultrAviolet ptychogRaphic pockeT-scope (DART), a handheld platform that transforms label-free molecular imaging through intrinsic deep-ultraviolet spectroscopic contrast. By leveraging biomolecules' natural absorption fingerprints and combining them with lensless ptychographic microscopy, DART resolves down to 308-nm linewidths across centimeter-scale areas while maintaining millimeter-scale depth-of-field. The system's virtual error-bin methodology effectively eliminates artifacts from limited temporal coherence and other optical imperfections, enabling high-fidelity molecular imaging without lenses. Through differential spectroscopic imaging at deep-ultraviolet wavelengths, DART quantitatively maps nucleic acid and protein distributions with femtogram sensitivity, providing an intrinsic basis for explainable virtual staining. We demonstrate DART's capabilities through molecular imaging of tissue sections, cytopathology specimens, blood cells, and neural populations, revealing detailed molecular contrast without external labels. The combination of high-resolution molecular mapping and broad mesoscale imaging in a portable platform opens new possibilities from rapid clinical diagnostics, tissue analysis, to biological characterization in space exploration.
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