Next-generation optical nanoprobes: From quantum biosensing to cellular monitoring

项目总结 我们的研究计划旨在创新和发展用于可视化和 跨生物组织多层次的潜在生物分子过程的量化。米拉 项目将支持和改进我们的分析工具包，该工具包涵盖了表面增强拉曼光谱 基于光谱(SERS)的分子成像探针到自驱动单细胞分析平台和 细胞机械分型的仿生结构。至关重要的是，在米拉提案的支持下，我们将 开发三个新的、互补的平台来解决多重分子分析中的紧迫问题， 细胞内磁感应，以及细胞和组织的靶向成像。 首先，我们计划通过将SERS与相干振动相融合来实现一种新的拉曼光谱传感方法。 强耦合区中的极化子相互作用。虽然非常可取，但实现强烈的振动 基态分子振动和光腔之间的耦合(VSC)仍然难以捉摸。 将SERS纳米探针与合理设计的法布里-珀罗腔相结合，提出了一种实用的方案 使VSC同时增强拉曼散射强度和丰富其光谱 这些特性为超灵敏和高度多样化的分析物检测铺平了道路。 第二，我们的目标是开发一种超灵敏的纳米磁强计来探测生物分子中的自旋效应， 生物系统中一种重要但鲜为人知的量子效应。我们将实施一种DNA辅助的 纳米金刚石(NVnD)中氮空位中心与等离子体纳米腔的自组装方法。 随之而来的NVnD灵敏度和时空分辨率的增强将允许检测到 目前无法检测到的离子通量诱导的弱磁场(WMF)，并研究WMF在 影响隐色素生成的自由基对的自旋动力学。 第三，我们寻求利用生物相容的点击缩合反应来创造一类新的合成 涉及酶调控的细胞内自组装的多肽拉曼成像纳米探针。我们的 纳米探针为靶向细胞成像提供了多种优势：更高的蓄积量和更少的外排 由于原位探针组装；由于存在π-共轭的重复单元而具有高灵敏度 单一结构中的官能团；由于易于区分的振动而具有精致的专一性 模式在细胞无声光谱区。

PROJECT SUMMARY Our research program is directed towards innovating and advancing optical tools for the visualization and quantification of latent biomolecular processes across multiple levels of biological organization. The MIRA project will support and improve our analytical toolkit, which spans from surface-enhanced Raman spectroscopic (SERS)-based molecular imaging probes to self-actuating single-cell analysis platforms and biomimetic structures for cellular mechanotyping. Crucially, with support from the MIRA proposal, we will develop three new, complementary platforms to address pressing questions in multiplexed molecular analysis, intracellular magnetic sensing, and targeted imaging of cells and tissues. First, we plan to realize a novel Raman spectroscopic sensing method by fusing SERS with coherent vibro- polariton interactions in the strong coupling regime. While highly desirable, achieving vibrational strong coupling (VSC) between ground-state molecular vibrations and an optical cavity has remained elusive. Combining SERS nanoprobes with rationally designed Fabry-Perot cavities, we present a practical scheme to render VSC that would simultaneously enhance the strength of Raman scattering and enrich its spectral features paving the way for ultrasensitive and highly multiplexed analyte detection. Second, we aim to develop an ultrasensitive nanoscale magnetometer to probe spin effects in biomolecules, an important but poorly understood quantum effect in biological systems. We will implement a DNA-assisted self-assembly approach to pair nitrogen vacancy-center in nanodiamond (NVnD) with plasmonic nanocavities. The accompanying enhancements in NVnD sensitivity and spatiotemporal resolution will permit the detection of currently undetectable ion flux-induced weak magnetic fields (WMF) and to examine the role of WMF in affecting the spin dynamics of cryptochrome-generated radical pairs. Third, we seek to harness biocompatible click condensation reactions to create a new class of synthetic peptide-based Raman imaging nanoprobes involving enzyme-regulated intracellular self-assembly. Our nanoprobes offer multiple advantages for targeted cellular imaging: higher accumulation and reduced efflux due to in situ probe assembly; high sensitivity due to the presence of repetitive units of a π-conjugated functional group in a single structure; and exquisite specificity owing to the easily distinguishable vibrational mode in the cell silent spectral region.