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Issue 18, 2020
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Microfluidic label-free bioprocessing of human reticulocytes from erythroid culture

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Abstract

In vitro erythroid cultures from human hematopoietic stem cells produce immature red blood cells (RBCs) called reticulocytes, which are important for RBCs production, and are widely used in scientific studies of malaria pathology, hematological diseases and protein translation. However, in vitro reticulocyte cultures contain expelled cell nuclei and erythroblasts as undesirable by-products and current purification methods such as density gradient centrifugation and fluorescence-activated cell sorting (FACS) are not optimal for integrated bioprocessing and downstream therapeutic applications. Developments in Dean flow fractionation (DFF) and deterministic lateral displacement (DLD) microfluidic sorting methods are ideal alternatives due to label-free size sorting, throughput scalability and low manufacturing cost. DFF sorting of reticulocytes from whole erythroid culture showed a 2.4-fold increase in cell recovery compared to FACS albeit with a lower purity; DLD sorting showed comparable cell recovery and purity with FACS using an inverse-L pillar structure to emphasize size and deformability sorting of reticulocytes. The viability and functional assurance of purified reticulocytes showed conserved cell deformability and supported the propagation of malaria parasites. Collectively, our study on label-free RBCs isolation represents a significant technical advancement towards developing in vitro generated viable human RBCs, opening opportunities for close-loop cell manufacturing, downstream therapeutic and research purposes.

Graphical abstract: Microfluidic label-free bioprocessing of human reticulocytes from erythroid culture

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Supplementary files

Article information


Submitted
14 Nov 2019
Accepted
10 Aug 2020
First published
14 Aug 2020

This article is Open Access

Lab Chip, 2020,20, 3445-3460
Article type
Paper

Microfluidic label-free bioprocessing of human reticulocytes from erythroid culture

K. K. Zeming, Y. Sato, L. Yin, N. Huang, L. H. Wong, H. L. Loo, Y. B. Lim, C. T. Lim, J. Chen, P. R. Preiser and J. Han, Lab Chip, 2020, 20, 3445
DOI: 10.1039/C9LC01128E

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