Scalable mesenchymal stem cell enrichment from bone marrow aspirate using deterministic lateral displacement (DLD) microfluidic sorting

The growing interest in regenerative medicine has opened new avenues for novel cell therapies using stem cells. Bone marrow aspirate (BMA) is an important source of stromal mesenchymal stem cells (MSCs). Conventional MSC harvesting from BMA relies on archaic centrifugation methods, often leading to...

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Main Authors: Tan Kwan Zen, Nicholas, Zeming, Kerwin Kwek, Teo, Kim Leng, Loberas, Mavis, Lee, Jialing, Goh, Chin Ren, Yang, Da Hou, Oh, Steve, Hui Hoi Po, James, Cool, Simon M., Hou, Han Wei, Han, Jongyoon
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Published: Royal Society of Chemistry 2024
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Online Access:https://hdl.handle.net/1721.1/154144
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author Tan Kwan Zen, Nicholas
Zeming, Kerwin Kwek
Teo, Kim Leng
Loberas, Mavis
Lee, Jialing
Goh, Chin Ren
Yang, Da Hou
Oh, Steve
Hui Hoi Po, James
Cool, Simon M.
Hou, Han Wei
Han, Jongyoon
author_facet Tan Kwan Zen, Nicholas
Zeming, Kerwin Kwek
Teo, Kim Leng
Loberas, Mavis
Lee, Jialing
Goh, Chin Ren
Yang, Da Hou
Oh, Steve
Hui Hoi Po, James
Cool, Simon M.
Hou, Han Wei
Han, Jongyoon
author_sort Tan Kwan Zen, Nicholas
collection MIT
description The growing interest in regenerative medicine has opened new avenues for novel cell therapies using stem cells. Bone marrow aspirate (BMA) is an important source of stromal mesenchymal stem cells (MSCs). Conventional MSC harvesting from BMA relies on archaic centrifugation methods, often leading to poor yield due to osmotic stress, high centrifugation force, convoluted workflow, and long experimental time (∼2–3 hours). To address these issues, we have developed a scalable microfluidic technology based on deterministic lateral displacement (DLD) for MSC isolation. This passive, label-free cell sorting method capitalizes on the morphological differences between MSCs and blood cells (platelets and RBCs) for effective separation using an inverted L-shaped pillar array. To improve throughput, we developed a novel multi-chip DLD system that can process 2.5 mL of raw BMA in 20 ± 5 minutes, achieving a 2-fold increase in MSC recovery compared to centrifugation methods. Taken together, we envision that the developed DLD platform will enable fast and efficient isolation of MSCs from BMA for effective downstream cell therapy in clinical settings.
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spelling mit-1721.1/1541442024-09-10T04:33:19Z Scalable mesenchymal stem cell enrichment from bone marrow aspirate using deterministic lateral displacement (DLD) microfluidic sorting Tan Kwan Zen, Nicholas Zeming, Kerwin Kwek Teo, Kim Leng Loberas, Mavis Lee, Jialing Goh, Chin Ren Yang, Da Hou Oh, Steve Hui Hoi Po, James Cool, Simon M. Hou, Han Wei Han, Jongyoon Biomedical Engineering General Chemistry Biochemistry Bioengineering The growing interest in regenerative medicine has opened new avenues for novel cell therapies using stem cells. Bone marrow aspirate (BMA) is an important source of stromal mesenchymal stem cells (MSCs). Conventional MSC harvesting from BMA relies on archaic centrifugation methods, often leading to poor yield due to osmotic stress, high centrifugation force, convoluted workflow, and long experimental time (∼2–3 hours). To address these issues, we have developed a scalable microfluidic technology based on deterministic lateral displacement (DLD) for MSC isolation. This passive, label-free cell sorting method capitalizes on the morphological differences between MSCs and blood cells (platelets and RBCs) for effective separation using an inverted L-shaped pillar array. To improve throughput, we developed a novel multi-chip DLD system that can process 2.5 mL of raw BMA in 20 ± 5 minutes, achieving a 2-fold increase in MSC recovery compared to centrifugation methods. Taken together, we envision that the developed DLD platform will enable fast and efficient isolation of MSCs from BMA for effective downstream cell therapy in clinical settings. National Research Foundation Singapore 2024-04-12T18:20:10Z 2024-04-12T18:20:10Z 2023 Article http://purl.org/eprint/type/JournalArticle 1473-0197 1473-0189 https://hdl.handle.net/1721.1/154144 Tan Kwan Zen, Nicholas, Zeming, Kerwin Kwek, Teo, Kim Leng, Loberas, Mavis, Lee, Jialing et al. 2023. "Scalable mesenchymal stem cell enrichment from bone marrow aspirate using deterministic lateral displacement (DLD) microfluidic sorting." Lab on a Chip, 23 (19). PUBLISHER_CC 10.1039/d3lc00379e Lab on a Chip Creative Commons Attribution https://creativecommons.org/licenses/by/3.0/ application/pdf Royal Society of Chemistry Royal Society of Chemistry
spellingShingle Biomedical Engineering
General Chemistry
Biochemistry
Bioengineering
Tan Kwan Zen, Nicholas
Zeming, Kerwin Kwek
Teo, Kim Leng
Loberas, Mavis
Lee, Jialing
Goh, Chin Ren
Yang, Da Hou
Oh, Steve
Hui Hoi Po, James
Cool, Simon M.
Hou, Han Wei
Han, Jongyoon
Scalable mesenchymal stem cell enrichment from bone marrow aspirate using deterministic lateral displacement (DLD) microfluidic sorting
title Scalable mesenchymal stem cell enrichment from bone marrow aspirate using deterministic lateral displacement (DLD) microfluidic sorting
title_full Scalable mesenchymal stem cell enrichment from bone marrow aspirate using deterministic lateral displacement (DLD) microfluidic sorting
title_fullStr Scalable mesenchymal stem cell enrichment from bone marrow aspirate using deterministic lateral displacement (DLD) microfluidic sorting
title_full_unstemmed Scalable mesenchymal stem cell enrichment from bone marrow aspirate using deterministic lateral displacement (DLD) microfluidic sorting
title_short Scalable mesenchymal stem cell enrichment from bone marrow aspirate using deterministic lateral displacement (DLD) microfluidic sorting
title_sort scalable mesenchymal stem cell enrichment from bone marrow aspirate using deterministic lateral displacement dld microfluidic sorting
topic Biomedical Engineering
General Chemistry
Biochemistry
Bioengineering
url https://hdl.handle.net/1721.1/154144
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