Development of Microfluidic Nano-Liter Platform for Single Cell Dynamic Monitorin

单细胞动态监测微流控纳升平台的开发

• 批准号: 8768527
• 负责人: Tania Tali Konry
• 金额: $ 18.73万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-13 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8768527
• 关键词: Antibodies; Antigen-Antibody Reactions; Antigen-Presenting Cells; Antigens; Biochemical; Biological; Biological Assay; Cause of Death; Cell Communication; Cell secretion; Cell surface; Cells; Collaborations; Communication; Custom; DNA amplification; Data; Dendritic Cell Vaccine; Dendritic Cells; Detection; Development; Eligibility Determination; Encapsulated; Event; Future; Generations; Goals; Image; Immune; Immune response; Immune system; Immunotherapy; Individual; Interleukin-10; Interleukin-12; Label; Learning; Life; Ligands; Liquid substance; Malignant Neoplasms; Measurement; Membrane Proteins; Methods; Microfluidics; Microscopic; Microspheres; Modeling; Monitor; Optics; Pathway interactions; Pattern; Phase; Phenotype; Play; Population; Procedures; Process; Protocols documentation; Public Health; Reaction; Research; Role; Signal Transduction; Specificity; Surface; Synapses; System; T-Cell Activation; T-Lymphocyte; TNFRSF5 gene; TNFSF5 gene; Techniques; Technology; Therapeutic; Time; Up-Regulation; Vaccines; Visual; Work; base; cell type; cytokine; design; immune function; immunological synapse; immunological synapse formation; improved; lymph nodes; nanolitre; novel; novel strategies; polydimethylsiloxane; response; sensor; single molecule; technique development; tumor; tumor immunology; tumor progression

DESCRIPTION (provided by applicant): One of the central processes regulating immune function involves T cells establishing cell-cell contacts with antigen-presenting cells (APCs) such as dendritic cells (DCs) via a contact zone known as the immunological synapse (IS). The importance of this synapse is considerable since interaction of T cells with DCs in lymph nodes is one of the critical steps in the generation of antigen specific immune responses which activate the na¿ve T cells. Despite great technical advances in microscopic imaging, the development of techniques to dynamically monitor the cellular and the induced secretion patterns at the IS interaction on a single cell level to avoid ambiguities that arise due to heterogeneous responses in cell populations is lagging. It is the goal of the proposed work to develop a microfluidic droplt approach for dynamic monitoring of the biochemical events that transpire upon cell-cell communication in this key event of the immune response. In particular, the current proposal outlines the integration of a novel approach to monitor live cell surface expression changes as well as the actual immunological synapse (IS) formed between DCs and T cells. In addition to cell surface studies, the microfluidic droplet approach developed herein will also allow us to collect data on secreted molecules during IS formation utilizing microsphere sensors incorporated in the microfluidic reaction droplets. Thus, live cell secretion and cell surface changes will be monitored on a single cell level simultaneously in a distinct microenvironment, feat not possible using conventional techniques.

描述（由申请人提供）：调节免疫功能的核心过程之一涉及 T 细胞与抗原呈递细胞 (APC) 建立细胞间接触，例如 作为树突状细胞（DC），通过称为免疫突触（IS）的接触区。这种突触的重要性相当大，因为 T 细胞与淋巴结中 DC 的相互作用是产生激活幼稚 T 细胞的抗原特异性免疫反应的关键步骤之一。尽管显微成像技术取得了巨大的进步，但在单细胞水平上动态监测细胞和 IS 相互作用诱导的分泌模式以避免由于细胞群中的异质反应而产生的模糊性的技术的发展仍然滞后。拟议工作的目标是开发一种微流体液滴方法，用于动态监测免疫反应这一关键事件中细胞间通讯所发生的生化事件。特别是，当前的提案概述了监测活细胞表面表达变化以及 DC 和 T 细胞之间形成的实际免疫突触 (IS) 的新方法的整合。除了细胞表面研究之外，本文开发的微流体液滴方法还允许我们利用微流体反应液滴中的微球传感器收集 IS 形成过程中分泌分子的数据。因此，将在不同的微环境中在单细胞水平上同时监测活细胞分泌和细胞表面变化，这是使用传统技术不可能实现的。

项目成果

Phenotypic drug profiling in droplet microfluidics for better targeting of drug-resistant tumors.

液滴微流体中的表型药物分析，以更好地靶向抗药性肿瘤。

• DOI: 10.1039/c5lc00923e
• 发表时间: 2015-12-07
• 期刊: Lab on a chip
• 影响因子: 6.1
• 作者: Sarkar S;Cohen N;Sabhachandani P;Konry T
• 通讯作者: Konry T

Generation and functional assessment of 3D multicellular spheroids in droplet based microfluidics platform.

基于液滴的微流体平台中 3D 多细胞球体的生成和功能评估。

• DOI: 10.1039/c5lc01139f
• 发表时间: 2016-02-07
• 期刊: Lab on a chip
• 影响因子: 6.1
• 作者: Sabhachandani P;Motwani V;Cohen N;Sarkar S;Torchilin V;Konry T
• 通讯作者: Konry T

Anti-myeloma activity and molecular logic operation by Natural Killer cells in microfluidic droplets.

• DOI: 10.1016/j.snb.2018.11.068
• 发表时间: 2019-03
• 期刊: Sensors and actuators. B, Chemical
• 作者: Saheli Sarkar;S. Mckenney;Pooja Sabhachandani;J. Adler;Xiaozhe Hu;Dina Stroopinksy;J. Rosenblatt;D. Avigan;T. Konry