Rational Design of Trifunctional Polyen Dyes for Highly Sensitive, Multiplexed Bioanalytics with Surface-Enhanced Resonance Raman Scattering

功能化的贵金属胶体具有用于定量、高灵敏度、多路复用的具有表面增强（共振）拉曼散射（SE（R）RS）的生物分析的巨大潜力。这种SE（R）RS颗粒的多路复用能力、定量、灵敏度和稳定性很大程度上取决于金属胶体表面上的拉曼报告分子的性质。然而，定制的拉曼报告分子的概念，其中表现出所有所需的物理和化学性质，在一个单一的分子铅结构，目前还没有。该项目的中心目标是合理设计和合成三官能拉曼染料，这些染料具有高度局部对称性、对标记峰位置的控制、最大拉曼散射截面、最小距离的高表面亲和力、最大表面覆盖率以及用于亲水稳定和生物缀合的单元。至少10种不同的拉曼报告染料的选择和合成由基于相应振动光谱的DFT计算的理论指导。首先在确定的胶体混合物中测试新SERRS颗粒的信号强度、再现性和定量，然后在10重免疫SERRS测定中测试。

Functionalized noble metal colloids have an enormous potential for quantitative, highly sensitive, multiplexed bioanalytics with surface-enhanced (resonance) Raman scattering (SE(R)RS). Multiplexing capacity, quantification, sensitivity, and stability of such SE(R)RS particles largely depend on the properties of the Raman reporter molecules on the surface of the metal colloid. However, concepts for tailor-made Raman reporters, which exhibit all desired physical and chemical properties in a single molecular lead structure, are currently not available. The central goal of this project is the rational design and synthesis of trifunctional Raman dyes with high local symmetry, control over the position of marker peaks, maximum Raman scattering cross sections, high surface affinity with minimal distance, maximum surface coverage and units for hydrophilic stabilization and bioconjugation. The selection and synthesis of at least 10 different Raman reporter dyes is guided by theory based on DFT calculations of the corresponding vibrational spectrum. Signal strength, reproducibility, and quantification of the new SERRS particles are tested first in defined colloidal mixtures and then in a 10-plex-immuno-SERRS assay.