Size-selective microfluidics delineate the effects of combinatorial immunotherapy on T-cell response dynamics at the single-cell level  

作　　者：Ayan Chatterjee Aniket Bandyopadhyay Tapas Kumar Maiti Tarun Kanti Bhattacharyya 

机构地区：[1]Advanced Technology Development Centre,Indian Institute of Technology Kharagpur,Kharagpur,India [2]Institute of Cell Dynamics and Imaging,University of Münster,Münster,Germany [3]Department of Biotechnology,Indian Institute of Technology Kharagpur,Kharagpur,India [4]Department of Electronics and Electrical Communication Engineering,Indian Institute of Technology Kharagpur,Kharagpur,India

出　　处：《Microsystems & Nanoengineering》2024年第6期249-265,共17页微系统与纳米工程(英文)

基　　金：funded by the Science and Engineering Research Board(SERB)in the Department of Science and Technology of the Government of India as a part of a core research grant(grant number:CRG/2019/006780).

摘　　要：Cellular communication at the single-cell level holds immense potential for uncovering response heterogeneity in immune cell behaviors.However,because of significant size diversity among different immune cell types,controlling the pairing of cells with substantial size differences remains a formidable challenge.We developed a microfluidic platform for size-selective pairing(SSP)to pair single cells with up to a fivefold difference in size,achieving over 40%pairing efficiency.We used SSP to investigate the real-time effects of combinatorial immunotherapeutic stimulation on macrophage T-cell interactions at the single-cell level via fluorescence microscopy and microfluidic sampling.While combinatorial activation involving toll-like receptor(TLR)agonists and rapamycin(an mTOR inhibitor)has improved therapeutic efficacy in mice,its clinical success has been limited.Here,we investigated immune synaptic interactions and outcomes at the single-cell level in real time and compared them with bulk-level measurements.Our findings,after tracking and computationally analyzing the effects of sequential and spatiotemporal stimulations of primary mouse macrophages,suggest a regulatory role of rapamycin in dampening inflammatory outputs in T cells.

关 键 词：STIMULATION fluid PAIRING 

分 类 号：R318[医药卫生—生物医学工程] Q25[医药卫生—基础医学]