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

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dc.contributor Aalto-yliopisto fi
dc.contributor Aalto University en
dc.contributor.author Barmaki, Samineh
dc.contributor.author Jokinen, Ville
dc.contributor.author Obermaier, Daniela
dc.contributor.author Blokhina, Daria
dc.contributor.author Korhonen, Matti
dc.contributor.author Ras, Robin H.A.
dc.contributor.author Vuola, Jyrki
dc.contributor.author Franssila, Sami
dc.contributor.author Kankuri, Esko
dc.date.accessioned 2019-06-20T13:17:31Z
dc.date.available 2019-06-20T13:17:31Z
dc.date.issued 2018-06
dc.identifier.citation 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 en
dc.identifier.issn 1742-7061
dc.identifier.other PURE UUID: f49f85ac-29a4-4f39-bf01-2c0c7a3c8bba
dc.identifier.other PURE ITEMURL: https://research.aalto.fi/en/publications/a-microfluidic-oxygen-sink-to-create-a-targeted-cellular-hypoxic-microenvironment-under-ambient-atmospheric-conditions(f49f85ac-29a4-4f39-bf01-2c0c7a3c8bba).html
dc.identifier.other PURE LINK: http://www.scopus.com/inward/record.url?scp=85045538984&partnerID=8YFLogxK
dc.identifier.other PURE FILEURL: https://research.aalto.fi/files/20846776/CHEM_Barmaki_et_al_microfluidic_oxygen_2018_Acta_Biomaterialia.pdf
dc.identifier.uri https://aaltodoc.aalto.fi/handle/123456789/38894
dc.description.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 O2 removal (vacuum or oxygen absorption) or by N2 supplementation for O2 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 O2 concentrations. O2 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-dependentsignalling is instigated in cells exposed to the microfluidic in-liquid O2 sink-generated hypoxia gradient. Moreover, we show that microfluidic flow controls site-specific microenvironmental kinetics of the chemical O2 sink reaction, which enables generation of intermittent hypoxia/re-oxygenation cycles. The microfluidic O2 sink chip targets hypoxia to the cell culture microenvironment exposed to the microfluidic channel architecture solely by depleting O2 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. Statement of Significance: Specific manipulation of oxygen concentrations in cultured cells’ microenvironment is important when mimicking low-oxygen tissue conditions and pathologies such as tissue infarction or cancer. We utilised a sodium sulfite-based in-liquid chemical reaction to consume dissolved oxygen. When this liquid was pumped into a microfluidic channel, lowered oxygen levels could be measured outside the channel through a polydimethylsiloxane PDMS membrane allowing only for gaseous exchange. We then utilised this setup to deplete oxygen from the microenvironment of cultured cells, and showed that cells responded to hypoxia on molecular level. Our setup can be used for specifically removing oxygen from the cell culture microenvironment for experimental purposes and for generating a low oxygen environment that better mimics the cells’ original tissue environments. en
dc.format.extent 167-179
dc.format.mimetype application/pdf
dc.language.iso en en
dc.publisher Elsevier BV
dc.relation.ispartofseries Acta Biomaterialia en
dc.relation.ispartofseries Volume 73 en
dc.rights openAccess en
dc.subject.other Biotechnology en
dc.subject.other Biomaterials en
dc.subject.other Biochemistry en
dc.subject.other Biomedical Engineering en
dc.subject.other Molecular Biology en
dc.subject.other 216 Materials engineering en
dc.title A microfluidic oxygen sink to create a targeted cellular hypoxic microenvironment under ambient atmospheric conditions en
dc.type A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä fi
dc.description.version Peer reviewed en
dc.contributor.department University of Helsinki
dc.contributor.department Department of Chemistry and Materials Science
dc.contributor.department PreSens Precision Sensing GmbH
dc.contributor.department Finnish Red Cross Blood Service
dc.contributor.department Soft Matter and Wetting
dc.contributor.department Department of Applied Physics en
dc.contributor.department Department of Bioproducts and Biosystems en
dc.subject.keyword Cell culture
dc.subject.keyword Hypoxia
dc.subject.keyword Microenvironment
dc.subject.keyword Microfluidic chip
dc.subject.keyword Oxygen depletion
dc.subject.keyword Biotechnology
dc.subject.keyword Biomaterials
dc.subject.keyword Biochemistry
dc.subject.keyword Biomedical Engineering
dc.subject.keyword Molecular Biology
dc.subject.keyword 216 Materials engineering
dc.identifier.urn URN:NBN:fi:aalto-201906203960
dc.identifier.doi 10.1016/j.actbio.2018.04.007
dc.date.embargo info:eu-repo/date/embargoEnd/2020-06-02

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