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An Integrated Fluorescent Biosensor, Imaging, and Analysis Toolkit for Islet Biologics

用于胰岛生物制品的集成荧光生物传感器、成像和分析工具包

基本信息

批准号：
10613923
负责人：
Huiwang Ai
金额：
$ 40.38万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10613923
关键词：
Affect American Beta Cell Biological Assay Biological Products Biosensor Cell Line Cell Therapy Cell secretion Cells Cellular Phone Chemicals Clinical Collection Color Computer software Development Disease Economics Encapsulated Evaluation Family suidae Funding Future Generations Glucose Glutathione Disulfide Green Fluorescent Proteins Human Hypoxia Image Immune Immune response Immunosuppressive Agents Insulin Insulin-Dependent Diabetes Mellitus Ion Channel Islet Cell Islets of Langerhans Islets of Langerhans Transplantation Metabolic Metabolism Methods Microfluidics Monitor Mus NADP Oranges Organ Transplantation Outcome Oxidation-Reduction Patients Penetration Phenotype Phototoxicity Physiological Physiological Processes Physiology Preparation Productivity Proteins Quality Control Research Research Personnel Screening procedure Secretory Vesicles Serotonin Signal Transduction Source Standardization Systems Integration Tissues Toxic effect Transplantation United States Food and Drug Administration Work Youth allotransplant autocrine cell replacement therapy diabetes mellitus therapy fluorescence imaging fluorescence microscope genetic element glycemic control human stem cells improved in vitro Assay innovation islet manufacture minimally invasive multiparametric imaging multiplexed imaging next generation novel paracrine public health relevance red fluorescent protein research clinical testing response sensor spatiotemporal stem cells success synergism tool transplant centers

项目摘要

Abstract The objective of this 4-year R01 project is to develop an innovative and comprehensive toolkit, including a collection of fluorescent protein (FP) based biosensors, a microfluidic Islet-On-a-Chip, a smartphone fluorescence microscope, and an imaging analysis application, optimized for the potency evaluation of human islets as cell-based therapy in Type 1 diabetes (T1D), as well as for characterization of the phenotype and physiology of emerging new biologics for future T1D treatment. We propose to use genetically encoded fluorescent biosensors to evaluate key physiological parameters of β- cells and islets, and furthermore, to define the potency, phenotype, and physiology of various promising biologics for T1D cell replacement therapy. Leveraging the complementary expertise of our strong team and our extensive preliminary results, we will pursue the following two Specific Aims: 1. Develop and optimize fluorescent biosensors to monitor key physiological processes in β-cells and islets. 2. Integrate biosensors with microfluidic arrays, a smartphone fluorescence microscope, a customized imaging analysis application for standardized, high-content characterization of islet biologics. The outcome of this project will be an economic and integrated system for convenient and reliable characterization of human islets, xenogeneic islets, encapsulated islets, and stem-cell-derived β-cells. These in vitro assays, which innovatively evaluate several key physiological parameters of β-cells and islets, can not only be used for standardization and quality control, but also be important screening tools to improve the generation, storage, and transport of next-generation biologics. Our proposed work will generate significant impacts on development of current and future cell replacement therapy for diabetes.

摘要这个为期4年的R 01项目的目标是开发一个创新和全面的工具包，包括一系列基于荧光蛋白（FP）的生物传感器，微流体芯片上的胰岛，智能手机荧光显微镜和成像分析应用程序，优化用于人胰岛作为1型糖尿病（T1 D）的细胞治疗，以及表征表型和用于未来T1 D治疗的新兴生物制剂的生理学。我们建议使用基因编码的荧光生物传感器来评估β- 细胞和胰岛，并进一步定义各种有前途的生物制剂的效力、表型和生理学 T1 D细胞替代疗法凭借我们强大的团队和广泛的专业知识，根据初步结果，我们将追求以下两个具体目标： 1.开发和优化荧光生物传感器，以监测β细胞和胰岛中的关键生理过程。 2.将生物传感器与微流控阵列、智能手机荧光显微镜、定制的用于胰岛生物制品的标准化、高含量表征的成像分析应用。本项目的成果将是一个经济和集成的系统，方便和可靠本发明提供了人胰岛、异种胰岛、包封的胰岛和干细胞衍生的β细胞的表征。这些在体外试验创新性地评估了β细胞和胰岛的几个关键生理参数，可用于标准化和质量控制，也可作为重要的筛选工具，以提高生成，储存和运输下一代生物制剂。我们建议的工作将产生重大影响，目前和未来的糖尿病细胞替代疗法的发展。

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Illuminating lactate in cells, mice, and patient samples.

阐明细胞、小鼠和患者样本中的乳酸。

DOI：
10.1016/j.cmet.2022.12.007
发表时间：
2023
期刊：
Cell metabolism
影响因子：
29
作者：
Li,Zefan;Ai,Hui-Wang
通讯作者：
Ai,Hui-Wang

A luciferase prosubstrate and a red bioluminescent calcium indicator for imaging neuronal activity in mice.

DOI：
10.1038/s41467-022-31673-x
发表时间：
2022-07-08
期刊：
Nature communications
影响因子：
16.6
作者：
通讯作者：

Smartphone-microfluidic fluorescence imaging system for studying islet physiology.

DOI：
10.3389/fendo.2022.1039912
发表时间：
2022
期刊：
FRONTIERS IN ENDOCRINOLOGY
影响因子：
5.2
作者：
Yu, Xiaoyu;Xing, Yuan;Zhang, Yiyu;Zhang, Pu;He, Yi;Ghamsari, Farid;Ramasubramanian, Melur K.;Wang, Yong;Ai, Huiwang;Oberholzer, Jose
通讯作者：
Oberholzer, Jose

A fast, high-affinity fluorescent serotonin biosensor engineered from a tick lipocalin.

一种由蜱脂质运载蛋白设计而成的快速、高亲和力荧光血清素生物传感器。