CAREER: Ultrafast molecular separation and integrated near-field light-metal-fluorophore interactions for biomarker detection at point-of-care

职业：超快分子分离和集成近场光-金属-荧光团相互作用，用于护理点生物标志物检测

基本信息

批准号：
2310106
负责人：
Dharmakeerthi Nawarathna
金额：
$ 50万
依托单位：
Old Dominion University Research Foundation
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2022
资助国家：
美国
起止时间：
2022-10-01 至 2027-03-31
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2310106&HistoricalAwards=false
关键词：
CAREER Ultrafast molecular separation integrated

项目摘要

Cancer, obesity, and opioid abuse pose a combined threat to the health of the people in the United States, affecting a significant portion and costing more than $250 billion per year in medical expenses. The unavailability of sensing technologies addressing the fundamental molecular changes related to disease initiation, progression, and therapeutic interventions is a critical roadblock for successfully combating these diseases. MicroRNA (miRNAs) are short non-coding RNA fragments (~17–25 nucleotides) that are involved in post-transcriptional regulation of gene expression either by degrading or repressing translation of multiple target mRNAs. Since miRNAs are involved in early gene regulations that initiate biochemical cascades for many diseases, they could provide reliable and clinically relevant information earlier than other downstream biomarkers (e.g., antigens). Also, miRNA biomarkers are stably expressed in circulating blood and, therefore, miRNA detection could be used to develop sensitive, minimally invasive, and low-cost diagnostics tests. Unfortunately, miRNAs have not yet been translated or utilized in the clinical diagnosis of any disease. This is in part due to the lack of sensitive and low-cost miRNA detection approaches that are applicable at clinics, hospitals, and medical centers. The outcome of this research plan will be a complete, ready-to-go miRNA detection platform that includes data collection, quality control, and built-in statistical methods for data analysis. In addition, proposed broader impact activities aim to introduce research into the undergraduate electrical engineering curriculum of North Dakota State University. Also, outreach efforts will aim to attract underrepresented groups (middle school girls and Native American community college students) to the field of engineering by introducing biosensor concepts and providing an opportunity to produce a technical solution to a societal or community problem. The PI will also work with high school STEM teachers in Native American schools to help them develop learning plans for their students. These activities will broaden the participation of underrepresented groups in STEM education and the workforce. The research goals of this project are to study three fundamental concepts in the areas of small nucleic acid-field (electric and temperature) interactions and near-field light-to-metal-to-fluorophore energy transfer: (1) study of fundamental nucleic acid and field (electric and temperature) interactions to selectively separate fluorophore-labeled short (~17–25 nucleotide) miRNA-DNA duplex molecules from other single-stranded nucleic acid molecules of similar lengths and concentrate them near electrodes, (2) study of AC electric fields to maximize each near-field light-metal-fluorophore interaction that contributes to enhancing the fluorescence intensity of fluorophores, and 3) integration of multiple interactions to enhance the fluorescence intensity well beyond current capabilities. This new knowledge will be used to develop a template for a universal biosensor that detects any individual or combination of biomarker-types in any buffer. Specifically, the proposed 5-year project will develop miRNA-based point-of-care technology to address the critical need for the analysis of clinical samples.This project is jointly funded by the Electrical, Communications and Cyber Systems Division (ECCS), and the Established Program to Stimulate Competitive Research (EPSCoR).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.

癌症，肥胖和阿片类药物滥用对美国人民的健康构成了综合威胁，影响着很大的一部分，并且每年的医疗费用损失超过2500亿美元。敏感性技术无法获得与疾病起始，进展和热干预有关的基本分子变化，这是成功相互作用的关键障碍。 microRNA（miRNA）是短的非编码RNA片段（〜17–25个核动肽），与通过降解或反映多个靶mRNA的翻译来参与基因表达的转录后调节。由于miRNA参与了启动许多疾病生化级联反应的早期基因调节，因此与其他下游生物标志物（例如抗原）相比，它们可以提早提供可靠且临床相关的信息。同样，miRNA生物标志物在循环的血液中稳定表达，因此，miRNA检测可用于开发敏感，微创和低成本诊断测试。不幸的是，尚未在任何疾病的临床诊断中翻译或使用miRNA。这部分是由于缺乏适用于诊所，医院和医疗中心的敏感和低成本的miRNA检测方法。该研究计划的结果将是一个完整的，即时的miRNA检测平台，其中包括数据收集，质量控制和内置统计方法用于数据分析。此外，拟议的更广泛的影响活动旨在介绍北达科他州立大学的本科电气工程课程的研究。此外，外展工作将旨在通过引入生物传感器概念并提供机会解决社会或社区问题的技术解决方案，从而吸引代表性不足的团体（中学女生和美国原住民社区大学生）进入工程领域。 PI还将与美国原住民学校的高中STEM老师合作，以帮助他们为学生制定学习计划。这些活动将扩大代表性不足的团体参与STEM教育和劳动力的参与。该项目的研究目标是研究小型核酸场（电和温度）相互作用以及近场的光到金属对氟植物能量转移的三个基本概念：（1）研究基本的核酸和田间相互作用（电和温度）的研究，以选择性地分离荧光型荧光素酸（〜17-25核酸）的核酸酸盐（〜17-25核酸）的核酸菌酸（〜17–25核酸酯）的核酸含量（〜17-25-25核酸）。（2）对AC电场进行长度并将其集中在电极附近，以最大程度地提高每个近场光线荧光团相互作用，从而有助于增强荧光团的荧光强度，3）多种相互作用的整合以增强荧光强度超出电流功能。这些新知识将用于为通用生物传感器开发模板，该模板检测任何缓冲液中生物标志物类型的任何个体或组合。 Specifically, the proposed 5-year project will develop miRNA-based point-of-care technology to address the critical need for the analysis of clinical samples.This project is jointly funded by the Electrical, Communications and Cyber Systems Division (ECCS), and the Established Program to Stimulate Competitive Research (EPSCoR).This award reflects NSF's statutory mission and has been deemed precious of support through evaluation using the Foundation's intellectual merit and broader impacts review 标准。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Integrated Nano-Plasmonic and Dielectrophoretic Based Label Free DNA Biomarker Detection

基于集成纳米等离子体和介电泳的无标记 DNA 生物标志物检测

DOI：
10.1109/rapid54473.2023.10264745
发表时间：
2023
期刊：
IEEE
影响因子：
0
作者：
Lakshan, K. A.;Nawarathna, Dharmakeerthi
通讯作者：
Nawarathna, Dharmakeerthi

Label-free Biomarker Detection Using Dielectrophoresis and Localized Surface Plasmonic Resonance

使用介电泳和局部表面等离子共振进行无标记生物标志物检测

DOI：
10.1109/rapid54472.2022.9911547
发表时间：
2022
期刊：
IEEE RAPID
影响因子：
0
作者：
Lakshan, K. A.;Nawarathna, Dharmakeerthi
通讯作者：
Nawarathna, Dharmakeerthi

microRNA Detection in Heathy and Pancreatic Cancer Samples

健康癌症和胰腺癌样本中的 microRNA 检测

DOI：
10.1109/rapid54473.2023.10264765
发表时间：
2023
期刊：
IEEE
影响因子：
0
作者：
Velmanickam, Logeeshan;Chang, David H;Ganepola, Ganepola AP;Nawarathna, Dharmakeerthi
通讯作者：
Nawarathna, Dharmakeerthi

Label-Free Detection of Gamma-Aminobutryric Acid Biomarker Using Dielectrophoresis and Absorption

使用介电泳和吸收法无标记检测 γ-氨基丁酸生物标志物