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

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

5 Scopus Citations
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Author(s)

  • Weikang Nicholas Lin
  • Matthew Zirui Tay
  • Joel Xu En Wong
  • Chia Yin Lee
  • Siew-Wai Fong
  • And 5 others
  • Cheng-l Wang
  • Lisa Fong Poh Ng
  • Laurent Renia
  • Chia-Hung Chen
  • Lih Feng Cheow

Detail(s)

Original languageEnglish
Pages (from-to)2578-2589
Journal / PublicationLab on a Chip
Volume22
Issue number13
Online published13 Jun 2022
Publication statusPublished - 7 Jul 2022
Externally publishedYes

Link(s)

Abstract

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 via 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 via sequential delivery of viruses and host cells via 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 (similar to 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.

Research Area(s)

  • DROPLET, INFECTION

Citation Format(s)

Rapid microfluidic platform for screening and enrichment of cells secreting virus neutralizing antibodies. / Lin, Weikang Nicholas; Tay, Matthew Zirui; Wong, Joel Xu En et al.
In: Lab on a Chip, Vol. 22, No. 13, 07.07.2022, p. 2578-2589.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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