Collaborative Research: A Stacked Plasmonic Nanopore for Tether-Free Stretching and Label-Free Sensing of hSTf Dynamics and Complex Formation at Ultra-Low Concentrations

合作研究：堆叠式等离子体纳米孔，用于超低浓度下 hSTf 动力学和复杂形成的无绳拉伸和无标记传感

基本信息

批准号：
2022374
负责人：
MinJun Kim
金额：
$ 28.73万
依托单位：
Southern Methodist University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2025-08-31
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2022374&HistoricalAwards=false
关键词：
Collaborative Research Stacked Plasmonic Nanopore

项目摘要

Fundamental knowledge of protein structures and their dynamic responses to stimuli or other molecules is important for many applications, including medical diagnosis and therapy. This research aims to develop a highly sensitive approach for studying the human serum transferrin protein (hSTf), which is a vital iron carrier in blood and of clinical importance. The sensing technique would allow differentiation of the free hSTf protein from the iron-bound protein and evaluation of iron deficiency or iron overload from very small blood samples. Successful development of this sensor would also enable profiling of a wide range of other proteins and biological molecules, e.g., DNA. This project offers excellent opportunities for interdisciplinary research training as it combines biochemistry, nanoengineering, photonics, and electrical engineering. The outreach efforts to K-12 schools through various programs at the Southern Methodist University and the University of Texas at Arlington help to inspire more students to pursue science, technology, engineering and mathematics (STEM) degrees.The stacked plasmonic nanosensor is based on the self-induced back-action (SIBA) actuated nanopore electrophoresis (SANE) sensing concept. The stacked nanopores are uniquely designed to enable 1) controlled trapping, releasing, and recapturing of proteins or the substrate-bound protein complexes, 2) transient deformation of the biological molecules, which can be induced by thermal effect or a combination of optical and electrical techniques, and 3) study of their deformation dynamics. The SANE concept implemented in the stacked nanopore sensor allows investigation of protein interactions at concentrations 1000-fold below the equilibrium dissociation constant in bulk solution, making this technique ultra-sensitive. An important aim of this research is the study of the properties of free-hSTf protein and the iron-bound protein complex using the SANE sensor. Optical signature profiles are established for each of the species to enable selective admission of bound complexes over unbound proteins in a mixed solution to the underlying pore. It uses symmetric (VCapture = VRecapture), followed by asymmetric (VCapture ≠ VRecapture) voltage conditions to facilitate the investigation of the strength and kinetic parameters associated with protein-substrate binding, protein relaxation times, and whether voltage-induced protein unfolding is reversible or not.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

蛋白质结构及其对刺激或其他分子的高度动态反应的基础知识对于许多应用都很重要，包括医学诊断和治疗。这项研究旨在开发一种敏感的方法来研究人血清转铁蛋白 (hSTf)，这是至关重要的。该传感技术将能够区分游离 hSTf 蛋白和铁结合蛋白，并从非常小的血液样本中评估铁缺乏或铁过载。多种其他蛋白质该项目结合了生物化学、纳米工程、光子学和电气工程，通过南卫理公会大学和大学的各种项目向 K-12 学校进行推广工作。德克萨斯州阿灵顿分校帮助激励更多学生攻读科学、技术、工程和数学 (STEM) 学位。堆叠等离子体纳米传感器基于自感应反作用 (SIBA) 驱动纳米孔电泳 (SANE) 传感概念。堆叠纳米孔经过独特设计，可实现 1) 蛋白质或底物结合蛋白质复合物的受控捕获、释放和重新捕获，2) 热效应引起的生物分子瞬时变形。或光学和电学技术的组合，以及 3) 研究其变形动力学在堆叠纳米孔传感器中实施的 SANE 概念允许研究浓度低于平衡解离 1000 倍的蛋白质相互作用。在散装溶液中恒定，使得该技术超灵敏，这项研究的一个重要目的是使用 SANE 传感器研究游离 hSTf 蛋白和铁结合蛋白复合物的特性。它使用对称（VCapture = VRecapture），然后是不对称（VCapture ≠ VRecapture）电压条件来促进强度的研究。以及与蛋白质-底物结合、蛋白质弛豫时间以及电压诱导的蛋白质展开是否可逆相关的动力学参数。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查进行评估，被认为值得支持标准。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Nanopore Data Analysis: Baseline Construction and Abrupt Change-Based Multilevel Fitting

纳米孔数据分析：基线构建和基于突变的多级拟合

DOI：
10.1021/acs.analchem.1c01646
发表时间：
2021-08
期刊：
Analytical Chemistry
影响因子：
7.4
作者：
Bandara, Y. M.;Saharia, Jugal;Karawdeniya, Buddini I.;Kluth, Patrick;Kim, Min Jun
通讯作者：
Kim, Min Jun

Label-free alternating-current plasmonic nanopore sensing of nanoparticles

纳米粒子的无标记交流等离子体纳米孔传感

DOI：
10.1117/12.2607884
发表时间：
2022-03-03
期刊：
Biomaterials
影响因子：
14
作者：
Scott Renkes;Minjun Kim;G. Ale;rakis;rakis
通讯作者：
rakis

Use of a solid‐state nanopore for profiling the transferrin receptor protein and distinguishing between transferrin receptor and its ligand protein

使用固态纳米孔分析转铁蛋白受体蛋白并区分转铁蛋白受体及其配体蛋白

DOI：
10.1002/elps.202200147
发表时间：
2022-12
期刊：
ELECTROPHORESIS
影响因子：
2.9
作者：
O'Donohue, Matthew;Saharia, Jugal;Bandara, Nuwan;Alexandrakis, Georgios;Kim, Min Jun
通讯作者：
Kim, Min Jun

Multi-physics simulations and experimental comparisons for the optical and electrical forces acting on a silica nanoparticle trapped by a double-nanohole plasmonic nanopore sensor

双纳米孔等离子体纳米孔传感器捕获的二氧化硅纳米颗粒上的光力和电力的多物理模拟和实验比较

DOI：
10.1016/j.sbsr.2023.100581
发表时间：
2023-08
期刊：
Sensing and Bio-Sensing Research
影响因子：
5.3
作者：
Asadzadeh, Homayoun;Renkes, Scott;Kim, MinJun;Alexandrakis, George
通讯作者：
Alexandrakis, George

Over One Million DNA and Protein Events Through Ultra‐Stable Chemically‐Tuned Solid‐State Nanopores

通过超稳定化学调谐固态纳米孔进行超过一百万个 DNA 和蛋白质事件

DOI：
10.1002/smll.202300198
发表时间：
2023-04
期刊：
Small
影响因子：
13.3
作者：
Saharia, Jugal;Bandara, Yapa Mudiyanselage Nuwan Dhananjaya Yapa;Karawdeniya, Buddini Iroshika;Dwyer, Jason Rodger;Kim, Min Jun
通讯作者：
Kim, Min Jun