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用于落射荧光单分子传感的双波长片上集成超构透镜

Dual-Wavelength On-Chip Integrated Metalens for Epi-Fluorescence Single-Molecule Sensing.

作者信息

Barulina Elena, Nguyen Dang Du, Shuklin Fedor, Podobrii Mikhail, Novikov Sergey, Chernov Alexander, Kim Inki, Barulin Aleksandr

机构信息

Moscow Center for Advanced Studies, Kulakova str. 20, 123592 Moscow, Russia.

Department of Biophysics, Institute of Quantum Biophysics, Sungkyunkwan University, Suwon 16419, Republic of Korea.

出版信息

Sensors (Basel). 2024 Dec 5;24(23):7781. doi: 10.3390/s24237781.

Abstract

Single-molecule fluorescence spectroscopy offers unique capabilities for the low-concentration sensing and probing of molecular dynmics. However, employing such a methodology for versatile sensing and diagnostics under point-of-care demands device miniaturization to lab-on-a-chip size. In this study, we numerically design metalenses with high numerical aperture (NA = 1.1), which are composed of silicon nitride nanostructures deposited on a waveguide and can selectively focus guided light into an aqueous solution at two wavelengths of interest in the spectral range of 500-780 nm. Despite the severe chromatic focal shift in the lateral directions owing to the wavelength-dependent propagation constant in a waveguide, segmented on-chip metalenses provide perfectly overlapping focal volumes that meet the requirements for epi-fluorescence light collection. We demonstrate that the molecule detection efficiencies of metalenses designed for the excitation and emission wavelengths of ATTO 490LS, Alexa 555, and APC-Cy7 tandem fluorophores are sufficient to collect several thousand photons per second per molecule at modest excitation rate constants. Such sensitivity provides reliable diffusion fluorescence correlation spectroscopy analysis of single molecules on a chip to extract their concentration and diffusion properties in the nanomolar range. Achromatic on-chip metalenses open new avenues for developing ultra-compact and sensitive devices for precision medicine and environmental monitoring.

摘要

单分子荧光光谱技术为低浓度分子动力学传感和探测提供了独特的能力。然而,在即时检测(point-of-care)的需求下,要将这种方法用于通用传感和诊断,就需要将设备小型化到芯片实验室的尺寸。在本研究中,我们通过数值方法设计了具有高数值孔径(NA = 1.1)的超构透镜,其由沉积在波导上的氮化硅纳米结构组成,并且能够在500 - 780 nm光谱范围内的两个感兴趣波长处将导光选择性地聚焦到水溶液中。尽管由于波导中与波长相关的传播常数,在横向方向上存在严重的色差焦移,但片上分段超构透镜提供了完美重叠的焦体积,满足落射荧光光收集的要求。我们证明,针对ATTO 490LS、Alexa 555和APC - Cy7串联荧光团的激发和发射波长设计的超构透镜的分子检测效率,足以在适度的激发速率常数下每秒每分子收集数千个光子。这种灵敏度为芯片上单个分子的可靠扩散荧光相关光谱分析提供了可能,以提取它们在纳摩尔范围内的浓度和扩散特性。无色差片上超构透镜为开发用于精准医学和环境监测的超紧凑且灵敏的设备开辟了新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4ea/11645079/79972d6ce51c/sensors-24-07781-g001.jpg

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