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 我们的研究计划致力于创新，并推进视觉工具以进行可视化和 跨多个生物组织的潜在生物分子过程的量化。 mira 项目将支持和改善我们的分析工具包，该工具包涵盖了表面增强的拉曼 基于光谱（SERS）的分子成像问题，用于自我激活的单细胞分析平台和 细胞机械分型的仿生结构。在Conccuctife，在Mira提案的支持下，我们将 开发三个新的完整平台，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，我们计划通过将SER与连贯的氛围融合来实现一种新型的拉曼光谱传感方法 强度耦合方案中的偏振子相互作用。虽然高度可取，但要实现振动强大 地面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Fabry-Perot腔相结合，我们提出了一个实用的方案 渲染VSC只会增强拉曼散射的强度并丰富其光谱 特征为超敏感和高度多重分析物检测的方式粘贴了道路。 其次，我们旨在开发超敏感的纳米级磁力计，以探测生物分子中的自旋效应，即 在生物系统中的重要但不了解的量子效应。我们将实施DNA辅助 在纳米座（NVND）中将氮空位中心配对的自组装方法与等离子纳米腔。 NVND敏感性和时空分辨率的参与增强功能将允许检测 目前无法检测到的离子通量诱导的弱磁场（WMF）的数量，并检查WMF在 影响加密粉状生成的自由基对的自旋动力学。 第三，我们试图利用生物相容性的点击凝结反应以创建新的合成类 基于肽的拉曼成像纳米探针涉及酶调节的细胞内自组装。我们的 纳米探针为靶向细胞成像提供了多个优点：较高的积累和减少的排出 由于原位探针组件；高灵敏度由于存在π连接的重复单位 单个结构中的功能组；以及由于易于区分的振动而获得的独家特异性 细胞静默光谱区域中的模式。