Development of functionalised nanoparticles for cancer imaging using surface enhanced spatially offset resonance Raman spectroscopy

空间偏移拉曼光谱（SORS）是一种用于对内容物被不透明层或容器遮蔽的物体进行准确和稳健的化学分析的方法，例如用于在机场筛查容器的内容物以寻找爆炸物。它涉及用入射激光束询问样品，并在偏离照明区域的距离处测量散射光，这允许从样品内的深度处获得拉曼响应。深度拉曼技术的进一步发展导致了表面增强拉曼散射（Sers）和SORS两者的组合，称为SESORS。由于可实现增强的拉曼响应，这为在甚至更大的深度处检测许多分析物开辟了道路。我们最近的论文介绍了SESORS的概念，通过展示从埋在组织中的Sers纳米颗粒探测信号的可能性，达到了深度拉曼光谱学的一个关键里程碑，或从比以前在epi-拉曼方法中实现的深度更深（25 mm）注入组织。我们与Dstl的初步合作使用了一个手动SORS设备最近也发表了。该项目与Dstl合作，将使用Dstl提供的便携式SORS系统，以评估检测一系列障碍物后面Sers纳米标签的能力，例如厚塑料（1-5 mm厚），彩色玻璃和纸板。这将涉及开发适当标记的Sers活性纳米标签，其在785 nm及以上产生强Sers响应。这将需要合成不同类型的金属纳米颗粒，其具有朝向电磁纳米颗粒的红外区域的散射，并开发用于纳米颗粒的涂层，该涂层在它们将充当标签的环境中是稳定的。这将涉及探索在例如不同聚合物或二氧化硅中的标记纳米颗粒的封装。这些材料将用于不同厚度的不同屏障材料中，并用于优化每种材料的SORS/SESORS系统。一旦系统被优化为在深度处提供最大的Sers响应，该系统还将用于检测生物材料内部的纳米标签。例如，组织内纳米标签的检测，以模拟体内目标纳米标签的检测。目的（1）探索具有红移荧光的金属纳米标签的合成。这将涉及合成具有不同尺寸、形状和壳结构的纳米颗粒。(2)评价可用于保护或封装标记纳米颗粒并保护其免受环境影响的基质，并研究其在785 nm及以上激光激发下的用途。(3)在由例如塑料、玻璃、纸等制成的各种容器中使用SORS对分析物和Sers活性纳米标签进行拉曼检测。容器的厚度也将变化。(4)在生物材料（例如组织样品）内的深度处的纳米标签的SORS检测。

Spatially offset Raman spectroscopy (SORS) is a method used for accurate and robust chemical analysis of objects where the contents are obscured by an opaque layer or container for example for screening the contents of containers at airports for explosives. It involves interrogating a sample with an incident laser beam and measuring the scattered light at a distance offset from the illumination area, this allows Raman responses to be obtained from at depth within a sample. Further advances in deep Raman techniques have led to the combination of both surface enhanced Raman scattering (SERS) and SORS together, referred to as SESORS. This opens the way for detecting a number of analytes at even greater depths due to the enhanced Raman response achievable. Our recent paper introducing the concept of SESORS, reached a key milestone in deep Raman spectroscopy by demonstrating the possibility of probing signals from SERS nanoparticles buried, or injected into tissues from depths significantly deeper (25 mm) than that previously achieved in epi-Raman approaches. Our initial collaboration with Dstl using a hand help SORS device was also recently published.This project, in collaboration with Dstl will use a portable SORS system supplied by Dstl, to assess the ability to detect SERS nanotags behind a range of barriers, such as thick plastics (1-5 mm thick), coloured glass and cardboard. This will involve developing suitably labelled SERS active nanotags which give a strong SERS response at 785 nm and above. This will require synthesising different types of metal nanoparticles which have absorbances towards the infrared region of the electromagnetic nanoparticles and developing coatings for the nanoparticles which are stable in the environment in which they will act as a label. This will involve exploring the encapsulation of labelled nanoparticles in for example different polymers or silica. These will then be used inside different barrier materials, of varying, known, thickness, and used to optimise the SORS/SESORS system for each material.Once the system has been optimised to give maximum SERS response at depth, the system will also be used for the detection of nanotags inside biological material. For example, the detection of nanotags inside tissue to simulate the detection of target nanotags in vivo.Objectives(1) To explore the synthesis of metal nanotags with red shifted absorbances. This will involve synthesising nanoparticles with different sizes, shapes and shell structures.(2) Evaluate matrices which can be used to protect or encapsulate the labelled nanoparticles and protect them from the environment and investigate their use with 785 nm laser excitation and above.(3) Raman detection of analytes and SERS active nanotags using SORS in various containers made of for example plastic, glass, paper etc. The thickness of the containers will also be varied.(4) SORS detection of nanotags at depth within biological material e.g. tissue samples.