A photonic resonator interferometric scattering microscope for label-free detection of nanometer-scale objects with digital precision in point-of-use environments
A photonic resonator interferometric scattering microscope for label-free detection of nanometer-scale objects with digital precision in point-of-use environments
复制标题
光子谐振器干涉散射显微镜，用于在使用点环境中以数字精度对纳米级物体进行无标记检测
DOI：
10.1016/j.bios.2023.115197
复制
发表时间：
2023
影响因子：
12.6
通讯作者：
Cunningham, Brian T.
中科院分区：
文献类型：
--
作者：
Liu, Leyang;Tibbs, Joseph;Li, Nantao;Bacon, Amanda;Shepherd, Skye;Lee, Hankeun;Chauhan, Neha;Demirci, Utkan;Wang, Xing;Cunningham, Brian T.
纳米级物体（如纳米颗粒、病毒、细胞外囊泡和蛋白质分子）的无标记检测和数字计数可在癌症诊断、病原体检测和生命科学研究中实现广泛的应用。在这里，我们报告的设计，实施和表征的一个紧凑的光子谐振器干涉散射显微镜（PRISM）设计的使用点的环境和应用。干涉散射显微镜的对比度通过光子晶体表面放大，在光子晶体表面上，来自物体的散射光与来自单色光源的照明相结合。使用光子晶体基板的散射显微镜的结果在降低高强度激光或油浸物镜的要求，从而打开了一条通往仪器，更适合于光学实验室以外的环境。该仪器结合了两个创新的元素，方便不具备光学专业知识的用户在普通实验室环境中的桌面上操作。首先，由于散射显微镜对振动非常敏感，我们采用了一种廉价但有效的解决方案，即使用弹性带将仪器的主要组件悬挂在刚性金属框架上，与办公桌相比，振动幅度平均降低28.7 dBV。其次，基于全内反射原理的自动对焦模块保持了图像对比度随时间和空间位置的稳定性。在这项工作中，我们通过测量直径在10-40 nm范围内的金纳米颗粒的对比度，并通过观察各种生物分析物，包括HIV病毒，SARS-CoV-2病毒，外泌体和铁蛋白来表征系统的性能。
Label-free detection and digital counting of nanometer-scaled objects such as nanoparticles, viruses, extracellular vesicles, and protein molecules enable a wide range of applications in cancer diagnostics, pathogen detection, and life science research. Here, we report the design, implementation, and characterization of a compact Photonic Resonator Interferometric Scattering Microscope (PRISM) designed for point-of-use environments and applications. The contrast of interferometric scattering microscopy is amplified through a photonic crystal surface, upon which scattered light from an object combines with illumination from a monochromatic source. The use of a photonic crystal substrate for interferemetric scattering microscopy results in reduced requirements for high-intensity lasers or oil-immersion objectives, thus opening a pathway toward instruments that are more suitable for environments outside the optics laboratory. The instrument incorporates two innovative elements that facilitate operation on a desktop in ordinary laboratory environments by users that do not have optics expertise. First, because scattering microscopes are extremely sensitive to vibration, we incorporated an inexpensive but effective solution of suspending the instrument’s main components from a rigid metal framework using elastic bands, resulting in an average of 28.7 dBV reduction in vibration amplitude compared to an office desk. Second, an automated focusing module based on the principle of total internal reflection maintains the stability of image contrast over time and spatial position. In this work, we characterize the system's performance by measuring the contrast from gold nanoparticles with diameters in the 10–40 nm range and by observing various biological analytes, including HIV virus, SARS-CoV-2 virus, exosome, and ferritin protein.