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.

下一代护理免疫测定的Optofluidic纳米质生物传感器 摘要：建立免疫力的预测模型需要对复合物的全面理解 免疫系统的动态功能行为。有许多理解的需求是显而易见的 当前无法使用可行治疗的免疫相关疾病。细胞因子经过充分研究 免疫细胞分泌的蛋白质，对于细胞间信号传导至关重要，以调节成熟，生长， 和特定细胞群体的响应能力。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有关的临床和免疫学上有用的信息， 癌症，自身免疫性疾病和过敏移植。基本生物学的持续革命， 免疫学和临床发现批判性地取决于能够分散的诊断工具的可用性 护理点测量可在床边或IN立即提供细胞因子水平的定量信息 诊所。当前现有的临床技术主要基于酶联免疫吸附测定法（ELISA）。 复杂的标签和洗涤过程需要总测定时间长达几个小时，并且 每位患者的样本体积为0.1-2 mL，这极大地阻碍了其免疫监测的应用 护理点。因此，对变革平台有一个新兴的临床需求，可以执行多种多样 参数细胞因子检测，以了解患者在快速和 准确的方式。这需要收集可能按照离子传输秒数的时间序列数据， 到达蛋白质水平变化的数小时，以及具有传感器灵敏度的宿主体内表型变化的天数 从生物学相关浓度到使用最小样品体积的单分子水平。解决这个问题 需求，此MIRA应用的主要目标是开发集成的Optofluidic纳米质。 生物传感平台，用于快速，高通量，敏感和多重细胞因子从全血到 单细胞水平朝着下一代保健点的免疫测定水平。 PI提出以下三个 项目：1）无标签，超敏感，高吞吐量纳米质血清免疫测定，用于实时免疫 监视； 2）个性化的多参数蜂窝功能免疫表型测定 免疫调节疗法； 3）直接可视化单细胞细胞因子分泌和 细胞间通信。计划的多尺度研究在实验和理论上都将桥接 对免疫系统的基本理解的差距并增强了适用性，诊断和预测 免疫系统疾病的功率。拟议的平台最终将使生物学家和临床医生装备 有能力实时监控患者的免疫状况，这是一种变革性成就 对基础研究和临床应用的巨大影响。

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

Near-infrared light triggered activation of pro-drug combination cancer therapy and induction of immunogenic cell death.

• DOI: 10.1016/j.ijpharm.2021.120972
• 发表时间: 2021-09-25
• 期刊: International journal of pharmaceutics
• 影响因子: 5.8
• 作者: Kang X;Cai Y;Wang Q;Wang C;Chen W;Yang W;Suryawanshi A;Zhou G;Chen P;Li F
• 通讯作者: Li F

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

• DOI: 10.3390/pharmaceutics15061567
• 发表时间: 2023-05-23
• 期刊: Pharmaceutics
• 影响因子: 5.4
• 作者: Kang X;Jadhav S;Annaji M;Huang CH;Amin R;Shen J;Ashby CR Jr;Tiwari AK;Babu RJ;Chen P
• 通讯作者: Chen P

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

• DOI: 10.3390/biom13050744
• 发表时间: 2023-04-25
• 期刊: Biomolecules
• 影响因子: 5.5