Optofluidic Nanoplasmonic Biosensors for Next Generation Point-of-Care Immunoassays

用于下一代护理点免疫测定的光流控纳米等离子体生物传感器

• 批准号: 10689037
• 负责人: Pengyu Chen
• 金额: $ 37.55万
• 依托单位: AUBURN UNIVERSITY AT AUBURN
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10689037
• 关键词: Achievement; Address; Autoimmune Diseases; Behavior; Biological; Biological Assay; Biology; Biosensing Techniques; Biosensor; Cell Communication; Cells; Clinic; Clinical; Communicable Diseases; Complex; Data; Decentralization; Detection; Diagnosis; Disease; Enzyme-Linked Immunosorbent Assay; Feedback; Fingerprint; Future; Growth; Hour; Hypersensitivity; Immune; Immune System Diseases; Immune response; Immune system; Immunity; Immunoassay; Immunologic Monitoring; Immunologics; Immunology; Immunophenotyping; Ion Transport; Label; Malignant Neoplasms; Measurement; Mediating; Molecular; Outcome; Patients; Phenotype; Physicians; Population; Process; Protein Secretion; Proteins; Research; Sampling; Series; Serum; Signal Transduction; System; Technology; Testing; Time; Transplantation; Visualization; Whole Blood; clinical application; cytokine; diagnostic tool; fundamental research; immune system function; immunological status; immunomodulatory therapies; nanoplasmonic; next generation; patient response; personalized immunotherapy; point of care; predictive modeling; real time monitoring; sensor; tool

Optofluidic Nanoplasmonic Biosensors for Next Generation Point-of-care Immunoassays Abstract: Building predictive models of immunity requires comprehensive understanding of the complex and dynamic functional behavior of immune system. A need for such understanding is obvious with a number of immune related diseases for which viable treatments are not currently available. Cytokines are well-studied proteins secreted by immune cells and essential for intercellular signaling to regulate the maturation, growth, and responsiveness of particular cell populations. Previous studies suggest that quantification of cytokine-based immune fingerprints provides clinically and immunologically useful information related to infectious diseases, cancer, autoimmune diseases, and allergy transplantation. The ongoing revolution in fundamental biology, immunology and clinical discovery critically hinges on the availability of diagnostic tools capable of decentralized point-of-care measurements to provide immediate quantitative information of cytokine levels at the bedside or in the clinic. Current existing clinical technology is mainly based on Enzyme-linked immunosorbent assay (ELISA). The complex labelling and washing processes require a total assay time up to more than a few hours and a sample volume of 0.1- 2 mL per test per patient, which greatly hinders its application for immune monitoring at the point of care. Thus, there is an emerging clinical demand for transformative platforms that can perform multi- parametric cytokine detection to understand the dynamical immune response of the patient in a rapid and accurate manner. This requires collecting time series data that could be on the order of seconds for ion transport, to hours for changes in protein levels, and to days for phenotypic changes in host body with sensor sensitivity from biological relevant concentration to single molecular level using minimum sample volume. To address this need, the central objectives of this MIRA application are to develop integrated optofluidic nanoplasmonic biosensing platforms for rapid, high throughput, sensitive and multiplex cytokine detection from whole blood to single-cell level towards next-generation point-of-care immunoassays. The PI proposes the following three projects: 1) Label free, ultra-sensitive, high throughput nanoplasmonic serum immunoassay for real-time immune monitoring; 2) Multi-parametric cellular functional immunophenotyping assay for personalized immunomodulatory therapy; 3) Nanoplasmon ruler for direct visualization of single-cell cytokine secretion and cell-to-cell communication. The planned multi-scale research both experimentally and theoretically will bridge the gap in fundamental understanding of immune system and enhance the applicability, diagnosis and prediction power for immune system diseases. The proposed platforms would ultimately gear the biologists and clinicians with capability to real-time monitor the immune status in patients, a transformative achievement that has enormous implications to fundamental research and clinical applications.

用于下一代护理点免疫测定的光流控纳米等离子体生物传感器 摘要：建立免疫预测模型需要全面了解复杂的和 免疫系统的动态功能行为。对于许多人来说，显然需要这种理解。 目前尚无可行治疗方法的免疫相关疾病。细胞因子已得到充分研究 由免疫细胞分泌的蛋白质，对于细胞间信号传递至关重要，以调节成熟、生长、 和特定细胞群的反应性。先前的研究表明基于细胞因子的定量 免疫指纹提供与传染病相关的临床和免疫学有用信息， 癌症、自身免疫性疾病和过敏移植。基础生物学正在进行的革命， 免疫学和临床发现关键取决于能够分散的诊断工具的可用性 床边或现场护理点测量可提供细胞因子水平的即时定量信息 诊所。目前现有的临床技术主要基于酶联免疫吸附测定（ELISA）。 复杂的标记和清洗过程需要长达几个小时的总检测时间和 每个患者每次检测的样本量为0.1-2 mL，这极大地阻碍了其在免疫监测中的应用 护理点。因此，对能够执行多种任务的变革性平台出现了新兴的临床需求。 参数细胞因子检测可快速、准确地了解患者的动态免疫反应 准确的方式。这需要收集离子传输的时间序列数据，这些数据可能是秒级的， 数小时内检测蛋白质水平的变化，数天内检测宿主体内表型的变化（具有传感器灵敏度） 使用最小的样品体积从生物相关浓度到单分子水平。为了解决这个问题 根据需要，该 MIRA 应用的中心目标是开发集成光流控纳米等离子体 生物传感平台，用于快速、高通量、灵敏和多重细胞因子检测，从全血到 单细胞水平的下一代护理点免疫测定。 PI提出以下三点 项目： 1) 用于实时免疫的无标记、超灵敏、高通量纳米等离子体血清免疫分析 监控； 2) 个性化的多参数细胞功能免疫表型分析 免疫调节治疗； 3) Nanoplasmon 标尺，用于直接可视化单细胞细胞因子分泌和 细胞间通讯。计划中的多尺度实验和理论研究将弥补 缩小对免疫系统基本认识的差距并提高其适用性、诊断和预测 免疫系统疾病的力量。拟议的平台最终将为生物学家和临床医生提供帮助 能够实时监测患者的免疫状态，这是一项变革性的成就 对基础研究和临床应用产生巨大影响。

项目成果

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

使用 3D 打印微流体装置制备的仿生金属有机纳米粒子，作为基于双硫仑的乳腺癌治疗的新型配方。

• 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: Ya;Jizong Jiang;Wu Chen;Wen Yang;Lili Chen;Pengyu Chen;Jianzhong Shen;Shizhi Qian;Teng Zhou;Linfeng Wu;L. Hong;Yongzhuo Huang;Feng Li
• 通讯作者: Feng Li

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

用于癌症药物输送和再利用的软和凝聚纳米颗粒和纳米制剂。

• 发表时间: 2020-01
• 影响因子: 4.6
• 作者: Yang, Wen;Veroniaina, Hanitrarimalala;Qi, Xiaole;Chen, Pengyu;Li, Feng;Ke, Pu Chun
• 通讯作者: Ke, Pu Chun

Advancing Cancer Therapy with Copper/Disulfiram Nanomedicines and Drug Delivery Systems.

利用铜/双硫仑纳米药物和药物输送系统推进癌症治疗。

• 发表时间: 2023-05-23
• 影响因子: 5.4
• 作者: Kang, Xuejia;Jadhav, Sanika;Annaji, Manjusha;Huang, Chung;Amin, Rajesh;Shen, Jianzhong;Ashby Jr, Charles R;Tiwari, Amit K;Babu, R Jayachandra;Chen, Pengyu
• 通讯作者: Chen, Pengyu

Novel Nanoplasmonic-Structure-Based Integrated Microfluidic Biosensors for Label-Free in Situ Immune Functional Analysis: A review of recent progress.

用于无标记原位免疫功能分析的新型纳米等离子体结构集成微流体生物传感器：最新进展综述。

• 发表时间: 2020-04
• 影响因子: 1.6
• 作者: Wang, Chuanyu;Cai, Yuxin;MacLACHLAN, Alana;Chen, Pengyu
• 通讯作者: Chen, Pengyu

Liposomal DQ in Combination with Copper Inhibits ARID1A Mutant Ovarian Cancer Growth.

脂质体 DQ 与铜结合可抑制 ARID1A 突变卵巢癌的生长。

• 发表时间: 2023-04-25
• 影响因子: 5.5
• 作者: Kang, Xuejia;Wang, Qi;Wu, Siqi;Wang, Chuanyu;Annaji, Manjusha;Huang, Chung;Shen, Jianzhong;Chen, Pengyu;Babu, R Jayachandra
• 通讯作者: Babu, R Jayachandra