NSF-GACR: An Optical Biosensing Platform for Simultaneous Detection and Quantification of Exosomes and Exosomal Cargo Biomarkers

NSF-GACR：用于同时检测和定量外泌体和外泌体货物生物标志物的光学生物传感平台

• 批准号: 2247222
• 负责人: Qiuming Yu
• 金额: $ 36万
• 依托单位: Cornell University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2247222&HistoricalAwards=false
• 关键词: NSF; GACR; Optical; Biosensing; Platform

Biosensors have proven extremely valuable in biomedical research, healthcare and pharmaceutics and are envisioned to become an integral part of modern medical diagnostics. Recently, circulating exosomes (tiny sac-like structures that were formed inside cells and contain some of the cell's proteins, DNA, and RNA) have emerged as promising biomarkers for medical diagnosis because they contain information about their cells of origin. Despite exosomes having been reported to be present in all major body fluids, effective detection and molecular analysis of exosomes remains particularly challenging due to the high variability in exosome subpopulations, small amounts of cargo molecules, and low recovery and reproducibility of exosome purification. This international collaborative project between Cornell University (Ithaca) and the Institute of Photonics and Electronics, Prague (IPE) will address these challenges by developing a new biosensing methodology that enables simultaneous detection and quantification of exosomes and exosomal cargo molecules to take full advantage of the richness of information contained in exosomes. Simultaneous identification and quantification of exosomes and exosomal cargo biomarkers have broader applications from biomedical diagnosis to the characterization of new drug delivery carriers based on exosomes. This project provides training opportunities for the next generation workforce in STEM fields in the US and the Czech Republic. Graduate and undergraduate students from underrepresented groups will receive training in this highly interdisciplinary research project. Graduate students will visit the collaborative labs each summer to foster the collaboration and gain experience on conducting research in a diverse environment.The goal of this project is to bring together two research institutions, one located in the US and the other in the Czech Republic, to develop a new biosensing methodology that enables simultaneous detection and quantification of exosomes and exosomal cargo molecules in order to take full advantage of the richness of information contained in exosomes. The biosensing platform will be based on optically excited surface plasmons that enable rapid and sensitive detection of biomolecules and investigation of biomolecular interactions in real time without the need for labeling. The specific objectives of the project are: (1) to develop a novel method for the capture, quantification, and profiling of selected exosomes based on a plasmonic biosensor; (2) to develop methods for controlled lysis of exosomes captured in the plasmonic biosensor and for the ultrasensitive detection of miRNA (microRNAs) and protein cargo molecules released from the lysed exosomes; and (3) to integrate these methods into a single biosensing platform for selective capture and profiling of exosomes and detection of multiple exosomal cargo miRNAs and proteins. The project will advance fundamental knowledge of utilizing exosomes as emerging biomarkers and nanoscience and nanotechnology in biosensing. The results of this work will make significant impacts not only in the field of biosensing but also in the fields of medical diagnosis, cell biology, biomaterials, surface chemistry and plasmonics.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.

事实证明，生物传感器在生物医学研究，医疗保健和药物方面非常有价值，并被设想成为现代医学诊断不可或缺的一部分。最近，循环外泌体（在细胞内形成并包含某些细胞蛋白质，DNA和RNA的细小囊样结构）已成为有希望的医学诊断生物标志物，因为它们包含有关其起源细胞的信息。 尽管据报道外泌体存在于所有主要体液中，但由于外泌体亚群，少量货物分子的较高可变性，较低的恢复和可重现的外泌体纯化，对外泌体的有效检测和分子分析仍然尤其具有挑战性。康奈尔大学（ITHACA）与光子与电子研究所之间的这个国际合作项目，布拉格（IPE）将​​通过开发一种新的生物传感方法来解决这些挑战，该方法能够同时检测和量化外部货物体分子，以充分利用包含外来中信息丰富的信息。外泌体和外泌体货物生物标志物的同时鉴定和定量具有更广泛的应用，从生物医学诊断到基于外泌体的新药递送载体的表征。该项目为美国和捷克共和国的STEM领域的下一代劳动力提供了培训机会。来自代表性不足的小组的研究生和本科生将接受这个高度跨学科的研究项目的培训。研究生将在每年夏天访问合作实验室，以促进在多元化环境中进行研究的协作和获得经验。该项目的目的是将两个位于美国的研究机构组合在一起，另一个位于美国，另一个研究机构，以开发一种新的生物膜方法，以同时检测和量身定量，以富于exosomes和exosomal carecomal carsosal carsosal carsosal carsosal sorecomal solecals opergo solecals的量外泌体。 生物传感平台将基于光学激发的表面等离子体，可快速，敏感地检测生物分子并实时研究生物分子相互作用，而无需标记。该项目的具体目标是：（1）开发一种基于等离子生物传感器的选定外泌体捕获，定量和分析的新方法； （2）开发用于在等离子生物传感器中捕获的外泌体以及对miRNA（microRNA）和从裂解外泌体释放的蛋白质货物分子的超敏化外泌体的方法的方法； （3）将这些方法集成到单个生物传感平台中，以选择性捕获和分析外泌体以及检测多个外泌体货物miRNA和蛋白质。该项目将促进利用外泌体作为新兴的生物标志物，纳米科学和纳米技术的基本知识。这项工作的结果不仅将在生物传感领域产生重大影响，而且还将在医学诊断，细胞生物学，生物材料，表面化学和等离子体学领域产生重大影响。这项奖项反映了NSF的法定任务，并被认为是值得通过基金会的智力功能和更广泛影响的评估来进行评估的支持。