A microfluidic oxygen sink to create a targeted cellular hypoxic microenvironment under ambient atmospheric conditions

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Barmaki , S , Jokinen , V , Obermaier , D , Blokhina , D , Korhonen , M , Ras , R H A , Vuola , J , Franssila , S & Kankuri , E 2018 , ' A microfluidic oxygen sink to create a targeted cellular hypoxic microenvironment under ambient atmospheric conditions ' , Acta Biomaterialia , vol. 73 , pp. 167-179 . https://doi.org/10.1016/j.actbio.2018.04.007

Title: A microfluidic oxygen sink to create a targeted cellular hypoxic microenvironment under ambient atmospheric conditions
Author: Barmaki, Samineh; Jokinen, Ville; Obermaier, Daniela; Blokhina, Daria; Korhonen, Matti; Ras, Robin H. A.; Vuola, Jyrki; Franssila, Sami; Kankuri, Esko
Contributor organization: Medicum
Department of Pharmacology
University of Helsinki
Plastiikkakirurgian yksikkö
Doctoral Programme in Drug Research
Esko Markus Kankuri / Principal Investigator
HUS Musculoskeletal and Plastic Surgery
Date: 2018-06
Language: eng
Number of pages: 13
Belongs to series: Acta Biomaterialia
ISSN: 1742-7061
DOI: https://doi.org/10.1016/j.actbio.2018.04.007
URI: http://hdl.handle.net/10138/303668
Abstract: Physiological oxygen levels within the tissue microenvironment are usually lower than 14%, in stem cell niches these levels can be as low as 0-1%. In cell cultures, such low oxygen levels are usually mimicked by altering the global culture environment either by O-2 removal (vacuum or oxygen absorption) or by N-2 supplementation for O-2 replacement. To generate a targeted cellular hypoxic microenvironment under ambient atmospheric conditions, we characterised the ability of the dissolved oxygen-depleting sodium sulfite to generate an in-liquid oxygen sink. We utilised a microfluidic design to place the cultured cells in the vertical oxygen gradient and to physically separate the cells from the liquid. We demonstrate generation of a chemical in-liquid oxygen sink that modifies the surrounding O-2 concentrations. O-2 level control in the sink-generated hypoxia gradient is achievable by varying the thickness of the polydimethylsiloxane membrane. We show that intracellular hypoxia and hypoxia response element-dependent signalling is instigated in cells exposed to the microfluidic in-liquid O-2 sink-generated hypoxia gradient. Moreover, we show that microfluidic flow controls site-specific microenvironmental kinetics of the chemical O-2 sink reaction, which enables generation of intermittent hypoxia/re-oxygenation cycles. The microfluidic O-2 sink chip targets hypoxia to the cell culture microenvironment exposed to the microfluidic channel architecture solely by depleting O-2 while other sites in the same culture well remain unaffected. Thus, responses of both hypoxic and bystander cells can be characterised. Moreover, control of microfluidic flow enables generation of intermittent hypoxia or hypoxia/re-oxygenation cycles. (C) 2018 Published by Elsevier Ltd on behalf of Acta Materialia Inc.
Subject: Hypoxia
Cell culture
Microfluidic chip
Oxygen depletion
220 Industrial biotechnology
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: acceptedVersion

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