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

下一代光学纳米探针：从量子生物传感到细胞监测

• 批准号: 10622691
• 负责人: ISHAN BARMAN
• 金额: $ 40.94万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10622691
• 关键词: Address; Advocate; Affect; Biological; Biomimetics; Biosensing Techniques; Cells; Cellular Structures; Coupling; DNA; Detection; Development; Engineering; Enzymes; In Situ; Ions; Machine Learning; Magnetism; Methods; Molecular; Molecular Analysis; Monitor; Nitrogen; Optics; Peptides; Physical condensation; Process; Raman Spectrum Analysis; Reaction; Research; Resolution; Role; Scheme; Specificity; Spectrum Analysis; Structure; Surface; Tissues; Visualization software; biological systems; biomaterial compatibility; cellular imaging; cellular targeting; cryptochrome; design; functional group; imaging probe; improved; innovation; magnetic field; molecular imaging; nanodiamond; nanofabrication; nanoimaging; nanoprobe; nanoscale; next generation; novel; plasmonics; programs; quantum; quantum sensing; rational design; self assembly; single cell analysis; spatiotemporal; synthetic peptide; targeted imaging; vibration

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.

项目概要 我们的研究计划旨在创新和推进光学工具的可视化和 MIRA 跨多个生物组织层面的潜在生物分子过程的量化。 该项目将支持和改进我们的分析工具包，其中包括表面增强拉曼 基于光谱（SERS）的分子成像探针到自驱动单细胞分析平台和 至关重要的是，在 MIRA 提案的支持下，我们将实现细胞机械分型的仿生结构。 开发三个新的互补平台来解决多重分子分析中的紧迫问题， 细胞内磁传感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颖的拉曼光谱传感方法 强耦合状态下的极化子相互作用虽然非常理想，但实现了强振动。 基态分子振动和光学腔之间的耦合（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，我们提出了一个实用的方案 渲染 VSC，同时增强拉曼散射强度并丰富其光谱 这些功能为超灵敏和高度多重分析物检测铺平了道路。 其次，我们的目标是开发一种超灵敏的纳米级磁力计来探测生物分子中的自旋效应， 生物系统中一个重要但知之甚少的量子效应我们将实施 DNA 辅助的量子效应。 自组装方法将纳米金刚石（NVnD）中的氮空位中心与等离子体纳米腔配对。 NVnD 灵敏度和时空分辨率的随之增强将允许检测 目前无法检测到的离子通量感应弱磁场 (WMF) 并检查 WMF 在 影响隐花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性点击缩合反应来创建一类新型合成材料 基于肽的拉曼成像纳米探针涉及酶调节的细胞内自组装。 纳米探针为靶向细胞成像提供多种优势：更高的积累和更少的外排 由于存在 π 共轭重复单元，因此具有高灵敏度； 单一结构中的官能团；由于易于区分的振动而具有精致的特异性 细胞沉默光谱区域中的模式。