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Quantum-enhanced nonlinear microscopy
Nature ( IF 42.778 ) Pub Date : 2021-06-09 , DOI: 10.1038/s41586-021-03528-w
Catxere A. Casacio, Lars S. Madsen, Alex Terrasson, Muhammad Waleed, Kai Barnscheidt, Boris Hage, Michael A. Taylor, Warwick P. Bowen

The performance of light microscopes is limited by the stochastic nature of light, which exists in discrete packets of energy known as photons. Randomness in the times that photons are detected introduces shot noise, which fundamentally constrains sensitivity, resolution and speed1. Although the long-established solution to this problem is to increase the intensity of the illumination light, this is not always possible when investigating living systems, because bright lasers can severely disturb biological processes2,3,4. Theory predicts that biological imaging may be improved without increasing light intensity by using quantum photon correlations1,5. Here we experimentally show that quantum correlations allow a signal-to-noise ratio beyond the photodamage limit of conventional microscopy. Our microscope is a coherent Raman microscope that offers subwavelength resolution and incorporates bright quantum correlated illumination. The correlations allow imaging of molecular bonds within a cell with a 35 per cent improved signal-to-noise ratio compared with conventional microscopy, corresponding to a 14 per cent improvement in concentration sensitivity. This enables the observation of biological structures that would not otherwise be resolved. Coherent Raman microscopes allow highly selective biomolecular fingerprinting in unlabelled specimens6,7, but photodamage is a major roadblock for many applications8,9. By showing that the photodamage limit can be overcome, our work will enable order-of-magnitude improvements in the signal-to-noise ratio and the imaging speed.



中文翻译:

量子增强非线性显微镜

光学显微镜的性能受到光的随机特性的限制,光存在于称为光子的离散能量包中。检测光子的时间随机性会引入散粒噪声,这从根本上限制了灵敏度、分辨率和速度1。虽然这个问题的长期解决方案是增加照明光的强度,但这在调查生命系统时并不总是可行的,因为明亮的激光会严重干扰生物过程2,3,4。理论预测,通过使用量子光子相关性,可以在不增加光强度的情况下改善生物成像1,5. 在这里,我们通过实验表明,量子相关性允许信噪比超出传统显微镜的光损伤极限。我们的显微镜是相干拉曼显微镜,可提供亚波长分辨率并结合明亮的量子相关照明。与传统显微镜相比,这种相关性允许对细胞内的分子键进行成像,信噪比提高 35%,相当于浓度灵敏度提高 14%。这使得观察原本无法解析的生物结构成为可能。相干拉曼显微镜允许在未标记的样本中进行高度选择性的生物分子指纹识别6,7,但光损伤是许多应用的主要障碍8,9. 通过证明可以克服光损伤限制,我们的工作将实现信噪比和成像速度的数量级改进。

更新日期:2021-06-09
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