Hao Shuang, Suebka Sartanee, Su Judith
Wyant College of Optical Sciences, University of Arizona, Tucson, AZ, 85721, USA.
Wyant College of Optical Sciences and Department of Biomedical Engineering, University of Arizona, Tucson, AZ, 85721, USA.
Light Sci Appl. 2024 Aug 19;13(1):195. doi: 10.1038/s41377-024-01536-9.
Label-free detection techniques for single particles and molecules play an important role in basic science, disease diagnostics, and nanomaterial investigations. While fluorescence-based methods are tools for single molecule detection and imaging, they are limited by available molecular probes and photoblinking and photobleaching. Photothermal microscopy has emerged as a label-free imaging technique capable of detecting individual nanoabsorbers with high sensitivity. Whispering gallery mode (WGM) microresonators can confine light in a small volume for enhanced light-matter interaction and thus are a promising ultra-sensitive photothermal microscopy platform. Previously, microtoroid optical resonators were combined with photothermal microscopy to detect 250 nm long gold nanorods and 100 nm long polymers. Here, we combine microtoroids with photothermal microscopy to spatially detect single 5 nm diameter quantum dots (QDs) with a signal-to-noise ratio exceeding 10. Photothermal images were generated by point-by-point scanning of the pump laser. Single particle detection was confirmed for 18 nm QDs by high sensitivity fluorescence imaging and for 5 nm QDs via comparison with theory. Our system demonstrates the capability to detect a minimum heat dissipation of 0.75 pW. To achieve this, we integrated our microtoroid based photothermal microscopy setup with a low amplitude modulated pump laser and utilized the proportional-integral-derivative controller output as the photothermal signal source to reduce noise and enhance signal stability. The heat dissipation of these QDs is below that from single dye molecules. We anticipate that our work will have application in a wide variety of fields, including the biological sciences, nanotechnology, materials science, chemistry, and medicine.
用于单颗粒和单分子的无标记检测技术在基础科学、疾病诊断和纳米材料研究中发挥着重要作用。虽然基于荧光的方法是单分子检测和成像的工具,但它们受到可用分子探针以及光闪烁和光漂白的限制。光热显微镜已成为一种无标记成像技术,能够高灵敏度地检测单个纳米吸收体。回音壁模式(WGM)微谐振器可以将光限制在小体积内以增强光与物质的相互作用,因此是一个很有前景的超灵敏光热显微镜平台。此前,微环光学谐振器与光热显微镜相结合,用于检测250纳米长的金纳米棒和100纳米长的聚合物。在此,我们将微环与光热显微镜相结合,以空间方式检测直径为5纳米的单个量子点(QD),信噪比超过10。通过对泵浦激光进行逐点扫描生成光热图像。通过高灵敏度荧光成像确认了18纳米量子点的单颗粒检测,并通过与理论比较确认了5纳米量子点的单颗粒检测。我们的系统展示了检测最低0.75皮瓦热耗散的能力。为实现这一点,我们将基于微环的光热显微镜装置与低振幅调制泵浦激光集成,并利用比例积分微分控制器输出作为光热信号源,以降低噪声并增强信号稳定性。这些量子点的热耗散低于单个染料分子的热耗散。我们预计我们的工作将在包括生物科学、纳米技术、材料科学、化学和医学在内的广泛领域得到应用。