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

空间偏移拉曼光谱(SORS)是一种用于对被不透明的层或容器遮挡的物体进行准确和可靠的化学分析的方法，例如用于筛选机场集装箱中的爆炸物。它包括用入射激光询问样品，并在距照明区域一定距离处测量散射光，这允许从样品内部的深度获得拉曼响应。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SOR的结合，称为SESORS。由于可实现增强的拉曼响应，这为在更深的地方检测许多分析物开辟了道路。我们最近的论文引入了SESORS的概念，通过展示从埋在或注入到组织中的SERS纳米粒子探测信号的可能性，达到了深度拉曼光谱的一个关键里程碑。我们与DSTL首次合作使用的手助SOR设备也是最近公布的。这个项目将与DSTL合作，使用DSTL提供的便携式SOR系统来评估检测一系列屏障后面的SERS纳米标记的能力，这些屏障包括厚塑料(1-5毫米厚)、彩色玻璃和纸板。这将涉及开发适当标记的SERS活性纳米标记，在785 nm及以上给出强烈的SERS响应。这将需要合成不同类型的金属纳米颗粒，这些纳米颗粒对电磁纳米颗粒的红外区具有吸收作用，并为纳米颗粒开发涂层，这些纳米颗粒在用作标签的环境中是稳定的。这将涉及探索将标记的纳米颗粒包裹在例如不同的聚合物或二氧化硅中。然后，这些材料将被用于不同的、不同的、已知的厚度的屏障材料中，并用于优化每种材料的SOR/SESORS系统。一旦该系统被优化为在深度提供最大的SERS响应，该系统也将用于检测生物材料内的纳米标签。目的(1)探索具有红移吸收的金属纳米标签的合成方法。这将涉及合成不同尺寸、形状和外壳结构的纳米颗粒。(2)评估可用于保护或包裹标记的纳米颗粒并使其免受环境影响的基质，并研究它们在785 nm及更高波长激光激励下的用途。(3)使用各种容器中的SOR对分析物和SERS活性纳米标签进行拉曼检测。容器的厚度也将有所不同。(4)对生物材料(例如组织样本)中深度纳米标签的检测。

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.