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.

项目摘要 我们的研究计划是针对创新和先进的光学工具的可视化和 跨多个生物组织水平的潜在生物分子过程的量化。The Mira 一个项目将支持和改善我们的分析工具包，其中包括表面增强拉曼 光谱（Sers）为基础的分子成像探针，以自我激励的单细胞分析平台， 用于细胞机械定型的仿生结构。关键是，在MIRA提案的支持下，我们将 开发三个新的互补平台，以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，我们计划将Sers与相干振动拉曼光谱相结合，实现一种新型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，实现振动强 基态分子振动和光腔之间的耦合（VSC）仍然是难以捉摸的。 结合Sers纳米探针与合理设计的法布里-珀罗腔，我们提出了一个实用的方案， 使VSC同时增强拉曼散射的强度并丰富其光谱 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，以探测生物分子中的自旋效应， 生物系统中一种重要但知之甚少的量子效应。我们将实施DNA辅助的 自组装方法将纳米金刚石中的氮空位中心（NVnD）与等离子体纳米腔配对。 伴随的NVnD灵敏度和时空分辨率的增强将允许检测 目前无法检测的离子通量诱导的弱磁场（WMF），并检查WMF的作用， 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的点击缩合反应来创造一类新的合成药物。 涉及酶调节的细胞内自组装的基于肽的拉曼成像纳米探针。我们 纳米探针为靶向细胞成像提供了多种优势：更高的积累和减少的流出 由于原位探针组装;由于存在π共轭的重复单元， 功能团在单一结构;和精致的特异性，由于容易区分的振动 在小区静默频谱区域中的模式。