Sensing local biomolecular environments with coherent optical nanoscopy

使用相干光学纳米镜感测局部生物分子环境

• 批准号: 1941129
• 金额: --
• 依托单位: CARDIFF UNIVERSITY
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1941129
• 关键词: Sensing; local; biomolecular; environments; coherent

The development of novel imaging tools and technologies, including super-resolution optical microscopy, has revolutionised our understanding of biological processes in living cells. Combining high resolution imaging capability with chemical sensing in living cells has the potential to unravel processes virtually impossible to follow with available techniques, such as for example defining the local environment at the specific entry site of endocytic routes of key importance for drug delivery.The main aim of this project is to demonstrate and quantify the applicability of novel optical microscopy techniques beyond state-of-the-art for local biosensing of single biomolecules directly within living cells. Specifically, the method will feature a unique combination of coherent anti-Stokes Raman scattering (CARS) [1] microscopy of endogenous biomolecules and Four-Wave Mixing (FWM) imaging of metallic nanoparticles [2], with the aim to exploit the local field enhancement effect of CARS in the vicinity of a plasmonic nanoparticle for bio-sensing at the nanoscale [3,4]. A unique home-built CARS/FWM microscope is available in Borri's laboratory [4,5], therefore the main emphasis of this project will be to push its applicability for sensing directly in living cells.[1] A Zumbusch, W Langbein, P Borri "Nonlinear vibrational microscopy applied to lipid biology" Progress in lipid research 52 (4), 615-632 (2013).[2] F. Masia, et al., Opt. Lett. 34, 1816 (2009).; ibid Phys Rev B 85, 235403 (2012).[3] H Xu et al "Electromagnetic contribution to single-molecule sensitivity in surface enhanced Raman scattering" Phys. Rev. E 62, 4318 (2000).[4] Lukas Payne, et al. "Optical micro-spectroscopy of single metallic nanoparticles: quantitative extinction and transient resonant four-wave mixing", Faraday Discussions 184, 305 (2015).[5] I Pope, et al. "Simultaneous hyperspectral differential-CARS, TPF and SHG microscopy with a single 5 fs Ti: Sa laser" Optics express 21 (6), 7096-7106 (2013).

新型成像工具和技术（包括超分辨率光学显微镜）的发展彻底改变了我们对活细胞生物过程的理解。将高分辨率成像能力与活细胞中的化学传感相结合，有可能揭示现有技术几乎不可能遵循的过程，例如定义对于药物输送至关重要的内吞途径的特定进入位点的局部环境。该项目的目的是证明和量化新型光学显微镜技术的适用性，超越最先进的技术，直接对活细胞内的单个生物分子进行局部生物传感。具体来说，该方法将内源性生物分子的相干反斯托克斯拉曼散射（CARS）[1]显微镜和金属纳米粒子的四波混合（FWM）成像[2]独特地结合在一起，旨在开发局部场CARS 在等离激元纳米粒子附近的增强效应，用于纳米级生物传感 [3,4]。 Borri 的实验室拥有独特的自制 CARS/FWM 显微镜 [4,5]，因此该项目的主要重点将是推动其在活细胞中直接传感的适用性。 [1] A Zumbusch、W Langbein、P Borri “非线性振动显微镜应用于脂质生物学”脂质研究进展 52 (4), 615-632 (2013)。 [2] F. Masia 等人，选项。莱特。 34, 1816 (2009).;同上 Phys Rev B 85, 235403 (2012).[3] H Xu 等人“电磁对表面增强拉曼散射中单分子灵敏度的贡献”Phys。修订版 E 62, 4318 (2000).[4]卢卡斯·佩恩等人。 “单个金属纳米粒子的光学显微光谱：定量消光和瞬态共振四波混合”，法拉第讨论 184, 305 (2015)。 [5]我教皇等人。 “使用单个 5 fs Ti: Sa 激光器同时进行高光谱微分 CARS、TPF 和 SHG 显微镜”Opticsexpress 21 (6), 7096-7106 (2013)。