Collaborative Research: Plasmofluidic Nanoantenna-Superlens Biosensor for Single-Cell Functional Immunophenotyping

合作研究：用于单细胞功能免疫表型分析的质流控纳米天线-超级透镜生物传感器

• 批准号: 1701363
• 负责人: Pengyu Chen
• 金额: $ 17.09万
• 依托单位: Auburn University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1701363&HistoricalAwards=false
• 关键词: Collaborative; Research; Plasmofluidic; Nanoantenna; Superlens

Accurate and real-time analysis of the functions of different disease-fighting blood cells is very useful for monitoring the immune status of the human body, as well as evaluating the disease stage and drug efficacy. The objective of this research is to develop a new method that enables single-cell functional immune analysis from droplets of human blood. Such a platform would ultimately provide clinicians a new measurement for quantitatively characterizing the disease-fighting blood cells. The proposed educational plans will have broad impacts on students from various educational levels (K-12, undergraduate, and graduate), genders, and ethnicities. Accurate and real-time analysis of the functions of different immune cell subsets is needed for monitoring the immune status of patients, as well as for evaluating the disease stage and drug efficacy. In particular, quantitative and dynamic profiling of the cytokine secretions from individual immune cells is useful for determining the cellular functional immune phenotype in patients. However, the heterogeneity of the immune cells makes such quantitative characterization challenging especially when dealing with human blood samples. The objective of this research is to develop a new integrated plasmofluidic nanoantenna-superlens biosensing platform that enables single-cell, multi-subset, multiplex functional immune analysis from microliters of human blood. The approach combines an efficient on-chip single immune cell isolation technique and a parallel cell cytokine secretion assay based on the label-free plasmonic nanoantenna-superlens biosensor. The proposed research will be achieved by pursuing the following objectives. 1) development of plasmonic nanoantenna-superlens biosensing platform for rapid and sensitive on-chip cytokine detection; 2) development of microfluidic single cell isolation technique to achieve purification of leukocyte subsets from a heterogeneous mixture found in whole blood; and 3) demonstration of an integrated plasmofluidic nanoantenna-superlens barcode microarray biosensor for multiplex functional immunophenotyping of single immune cells. The analysis performed using the proposed platform for a large number of individual immune cells will establish a new approach that permits immunophenotypical screening of leukocyte subsets by detecting differences and time-dependent variations of their immune functions. Such a platform would ultimately provide clinicians a new tool for quantitatively characterizing the immunophenotypes of patients and would, therefore, allow precise disease diagnosis, monitoring, and risk stratification. The proposed educational plan will have broad impacts on students from different educational levels (K-12, undergraduate, and graduate), genders, and ethnicities. Technologies developed in the proposal will be used as effective vehicles for education and outreach activities. Extending research opportunities to K-12 students and undergraduates will expose them to the rewarding scientific discoveries and encourage them to pursue future studies and careers in engineering.

准确、实时地分析不同抗病血细胞的功能，对于监测人体的免疫状态，以及评估疾病分期和药物疗效非常有用。这项研究的目的是开发一种新的方法，使单细胞功能免疫分析从人的血液滴。这样的平台最终将为临床医生提供一种新的定量表征抗病血细胞的测量方法。此次教育改革方案将对各教育阶段（K-12、本科、研究生）、性别、种族的学生产生广泛的影响。准确、实时地分析不同免疫细胞亚群的功能，是监测患者免疫状态、评估疾病分期和药物疗效的重要手段。特别是，个体免疫细胞的细胞因子分泌的定量和动态分析对于确定患者的细胞功能免疫表型是有用的。然而，免疫细胞的异质性使得这种定量表征具有挑战性，特别是在处理人类血液样本时。本研究的目的是开发一种新的集成等离子流体纳米天线-超透镜生物传感平台，使单细胞，多亚群，多重功能免疫分析从微升人体血液。该方法结合了高效的片上单免疫细胞分离技术和基于无标记等离子纳米天线-超透镜生物传感器的平行细胞细胞因子分泌测定。拟议的研究将通过追求以下目标来实现。1)基于等离子体纳米天线-超透镜生物传感平台的芯片上细胞因子快速灵敏检测；2)开发微流控单细胞分离技术，从全血中的异质混合物中纯化白细胞亚群；3)展示了一种集成等离子流控纳米天线-超透镜条形码微阵列生物传感器，用于单个免疫细胞的多重功能免疫表型。使用所提出的平台对大量个体免疫细胞进行的分析将建立一种新的方法，通过检测其免疫功能的差异和时间依赖性变化来允许白细胞亚群的免疫表型筛选。这样的平台最终将为临床医生提供一种定量表征患者免疫表型的新工具，从而实现精确的疾病诊断、监测和风险分层。该教育计划将对不同教育水平（K-12、本科、研究生）、性别、种族的学生产生广泛的影响。建议中发展的技术将被用作教育和外联活动的有效工具。扩大对K-12学生和本科生的研究机会将使他们接触到有益的科学发现，并鼓励他们在未来的工程研究和职业生涯中继续努力。

项目成果

Soft and Condensed Nanoparticles and Nanoformulations for Cancer Drug Delivery and Repurpose

• DOI: 10.1002/adtp.201900102
• 发表时间: 2020-01
• 期刊: Advanced Therapeutics
• 影响因子: 4.6
• 作者: Wen Yang;Hanitrarimalala Veroniaina;Xiaole Qi;Pengyu Chen;Feng Li;P. Ke

Biomimetic metal-organic nanoparticles prepared with a 3D-printed microfluidic device as a novel formulation for disulfiram-based therapy against breast cancer

• DOI: 10.1016/j.apmt.2019.100492
• 发表时间: 2020-03-01
• 期刊: APPLIED MATERIALS TODAY
• 影响因子: 8.3
• 作者: Chang, Ya;Jiang, Jizong;Li, Feng
• 通讯作者: Li, Feng

Probing the Aggregation and Immune Response of Human Islet Amyloid Polypeptides with Ligand-Stabilized Gold Nanoparticles

• DOI: 10.1021/acsami.8b19506
• 发表时间: 2019-03-20
• 期刊: ACS APPLIED MATERIALS & INTERFACES
• 影响因子: 9.5
• 作者: Javed, Ibrahim;He, Jiacheng;Chen, Pengyu
• 通讯作者: Chen, Pengyu

Disulfiram Copper Nanoparticles Prepared with a Stabilized Metal Ion Ligand Complex Method for Treating Drug-Resistant Prostate Cancers

• DOI: 10.1021/acsami.8b14940
• 发表时间: 2018-12-05
• 期刊: ACS APPLIED MATERIALS & INTERFACES
• 影响因子: 9.5
• 作者: Chen, Wu;Yang, Wen;Li, Feng
• 通讯作者: Li, Feng