Rapid microfluidic platform for screening and enrichment of cells secreting virus neutralizing antibodies

Lin, Weikang Nicholas, Tay, Matthew Zirui, Wong, Joel Xu En, Lee, Chia Yin, Fong, Siew-Wai, Cheng-I, Wang, Ng, Lisa Fong Poh ORCID: 0000-0003-4071-5222, Renia, Laurent, Chen, Chia-Hung and Cheow, Lih Feng
(2022) Rapid microfluidic platform for screening and enrichment of cells secreting virus neutralizing antibodies. LAB ON A CHIP, 22 (13). pp. 2578-2589.

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As part of the body's immune response, antibodies (Abs) have the ability to neutralize pathogenic viruses to prevent infection. To screen for neutralizing Abs (nAbs) from the immune repertoire, multiple screening techniques have been developed. However, conventional methods have a trade-off between screening throughput and the ability to screen for nAbs <i>via</i> their functional efficacy. Although droplet microfluidic platforms have the ability to bridge this disparity, the majority of such reported platforms still rely on Ab-binding assays as a proxy for function, which results in irrelevant hits. Herein, we report the multi-module Droplet-based Platform for Effective Antibody RetrievaL (DROP-PEARL) platform, which can achieve high-throughput enrichment of Ab-secreting cells (ASCs) based on the neutralizing activity of secreted nAbs against the a target virus. In this study, in-droplet Chikungunya virus (CHIKV) infection of host cells and neutralization was demonstrated <i>via</i> sequential delivery of viruses and host cells <i>via</i> picoinjection. In addition, we demonstrate the ability of the sorting system to accurately discriminate and isolate uninfected droplets from a mixed population of droplets at a rate of 150 000 cells per hour. As a proof of concept, a single-cell neutralization assay was performed on two populations of cells (nAb-producing and non-Ab producing cells), and up to 2.75-fold enrichment of ASCs was demonstrated. Finally, we demonstrated that DROP-PEARL is able to achieve similar enrichment for low frequency (∼2%) functional nAb-producing cells in a background of excess cells secreting irrelevant antibodies, highlighting its potential prospect as a first round enrichment platform for functional ASCs. We envision that the DROP-PEARL platform could potentially be used to accelerate the discovery of nAbs against other pathogenic viral targets, and we believe it will be a useful in the ongoing fight against biological threats.

Item Type: Article
Uncontrolled Keywords: Antibodies, Viral, Microfluidics, Antibodies, Neutralizing
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 18 Oct 2022 09:55
Last Modified: 18 Jan 2023 21:15
DOI: 10.1039/d2lc00018k
Open Access URL: https://doi.org/10.1039/D2LC00018K
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3165587