A microfluidics approach towards high-throughput pathogen removal from blood using margination

Sepsis is an adverse systemic inflammatory response caused by microbial infection in blood. This paper reports a simple microfluidic approach for intrinsic, non-specific removal of both microbes and inflammatory cellular components (platelets and leukocytes) from whole blood, inspired by the invivo...

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Main Authors: Hou, Han Wei, Gan, Hiong Yap, Bhagat, Ali Asgar S., Li, Leon Daliang, Lim, Chwee Teck, Han, Jongyoon
Other Authors: Harvard University--MIT Division of Health Sciences and Technology
Format: Article
Language:en_US
Published: American Institute of Physics 2014
Online Access:http://hdl.handle.net/1721.1/86903
https://orcid.org/0000-0001-7215-1439
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author Hou, Han Wei
Gan, Hiong Yap
Bhagat, Ali Asgar S.
Li, Leon Daliang
Lim, Chwee Teck
Han, Jongyoon
author2 Harvard University--MIT Division of Health Sciences and Technology
author_facet Harvard University--MIT Division of Health Sciences and Technology
Hou, Han Wei
Gan, Hiong Yap
Bhagat, Ali Asgar S.
Li, Leon Daliang
Lim, Chwee Teck
Han, Jongyoon
author_sort Hou, Han Wei
collection MIT
description Sepsis is an adverse systemic inflammatory response caused by microbial infection in blood. This paper reports a simple microfluidic approach for intrinsic, non-specific removal of both microbes and inflammatory cellular components (platelets and leukocytes) from whole blood, inspired by the invivo phenomenon of leukocyte margination. As blood flows through a narrow microchannel (20 × 20 µm), deformable red blood cells (RBCs) migrate axially to the channel centre, resulting in margination of other cell types (bacteria, platelets, and leukocytes) towards the channel sides. By using a simple cascaded channel design, the blood samples undergo a 2-stage bacteria removal in a single pass through the device, thereby allowing higher bacterial removal efficiency. As an application for sepsis treatment, we demonstrated separation of Escherichia coli and Saccharomyces cerevisiae spiked into whole blood, achieving high removal efficiencies of ∼80% and ∼90%, respectively. Inflammatory cellular components were also depleted by >80% in the filtered blood samples which could help to modulate the host inflammatory response and potentially serve as a blood cleansing method for sepsis treatment. The developed technique offers significant advantages including high throughput (∼1 ml/h per channel) and label-free separation which allows non-specific removal of any blood-borne pathogens (bacteria and fungi). The continuous processing and collection mode could potentially enable the return of filtered blood back to the patient directly, similar to a simple and complete dialysis circuit setup. Lastly, we designed and tested a larger filtration device consisting of 6 channels in parallel (∼6 ml/h) and obtained similar filtration performances. Further multiplexing is possible by increasing channel parallelization or device stacking to achieve higher throughput comparable to convectional blood dialysis systems used in clinical settings.
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spelling mit-1721.1/869032022-10-02T02:13:49Z A microfluidics approach towards high-throughput pathogen removal from blood using margination Hou, Han Wei Gan, Hiong Yap Bhagat, Ali Asgar S. Li, Leon Daliang Lim, Chwee Teck Han, Jongyoon Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Hou, Han Wei Gan, Hiong Yap Li, Leon Daliang Han, Jongyoon Sepsis is an adverse systemic inflammatory response caused by microbial infection in blood. This paper reports a simple microfluidic approach for intrinsic, non-specific removal of both microbes and inflammatory cellular components (platelets and leukocytes) from whole blood, inspired by the invivo phenomenon of leukocyte margination. As blood flows through a narrow microchannel (20 × 20 µm), deformable red blood cells (RBCs) migrate axially to the channel centre, resulting in margination of other cell types (bacteria, platelets, and leukocytes) towards the channel sides. By using a simple cascaded channel design, the blood samples undergo a 2-stage bacteria removal in a single pass through the device, thereby allowing higher bacterial removal efficiency. As an application for sepsis treatment, we demonstrated separation of Escherichia coli and Saccharomyces cerevisiae spiked into whole blood, achieving high removal efficiencies of ∼80% and ∼90%, respectively. Inflammatory cellular components were also depleted by >80% in the filtered blood samples which could help to modulate the host inflammatory response and potentially serve as a blood cleansing method for sepsis treatment. The developed technique offers significant advantages including high throughput (∼1 ml/h per channel) and label-free separation which allows non-specific removal of any blood-borne pathogens (bacteria and fungi). The continuous processing and collection mode could potentially enable the return of filtered blood back to the patient directly, similar to a simple and complete dialysis circuit setup. Lastly, we designed and tested a larger filtration device consisting of 6 channels in parallel (∼6 ml/h) and obtained similar filtration performances. Further multiplexing is possible by increasing channel parallelization or device stacking to achieve higher throughput comparable to convectional blood dialysis systems used in clinical settings. Singapore-MIT Alliance for Research and Technology (SMART) Centre (BioSyM IRG) Massachusetts Institute of Technology. Microsystems Technology Laboratories United States. Defense Advanced Research Projects Agency (DARPA DLT (Dialysis-Like Therapeutics) program, under SSC Pacific grant N66001-11-1-4182) 2014-05-09T15:02:10Z 2014-05-09T15:02:10Z 2012-05 2012-02 Article http://purl.org/eprint/type/JournalArticle 19321058 http://hdl.handle.net/1721.1/86903 Wei Hou, Han, Hiong Yap Gan, Ali Asgar S. Bhagat, Leon D. Li, Chwee Teck Lim, and Jongyoon Han. “A Microfluidics Approach Towards High-Throughput Pathogen Removal from Blood Using Margination.” Biomicrofluidics 6, no. 2 (2012): 024115. https://orcid.org/0000-0001-7215-1439 en_US http://dx.doi.org/10.1063/1.4710992 Biomicrofluidics Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Institute of Physics MIT web domain
spellingShingle Hou, Han Wei
Gan, Hiong Yap
Bhagat, Ali Asgar S.
Li, Leon Daliang
Lim, Chwee Teck
Han, Jongyoon
A microfluidics approach towards high-throughput pathogen removal from blood using margination
title A microfluidics approach towards high-throughput pathogen removal from blood using margination
title_full A microfluidics approach towards high-throughput pathogen removal from blood using margination
title_fullStr A microfluidics approach towards high-throughput pathogen removal from blood using margination
title_full_unstemmed A microfluidics approach towards high-throughput pathogen removal from blood using margination
title_short A microfluidics approach towards high-throughput pathogen removal from blood using margination
title_sort microfluidics approach towards high throughput pathogen removal from blood using margination
url http://hdl.handle.net/1721.1/86903
https://orcid.org/0000-0001-7215-1439
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