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The material-enabled oxygen control in thiol-ene microfluidic channels and its feasibility for subcellular drug metabolism assays under hypoxia in vitro
- Source :
- Lab on a Chip. 21:1820-1831
- Publication Year :
- 2021
- Publisher :
- Royal Society of Chemistry (RSC), 2021.
-
Abstract
- Tissue oxygen levels are known to be critical to regulation of many cellular processes, including the hepatic metabolism of therapeutic drugs, but its impact is often ignored in in vitro assays. In this study, the material-induced oxygen scavenging property of off-stoichiometric thiol-enes (OSTE) was exploited to create physiologically relevant oxygen concentrations in microfluidic immobilized enzyme reactors (IMERs) incorporating human liver microsomes. This could facilitate rapid screening of, for instance, toxic drug metabolites possibly produced in hypoxic conditions typical for many liver injuries. The mechanism of OSTE-induced oxygen scavenging was examined in depth to enable precise adjustment of the on-chip oxygen concentration with the help of microfluidic flow. The oxygen scavenging rate of OSTE was shown to depend on the type and the amount of the thiol monomer used in the bulk composition, and the surface-to-volume ratio of the chip design, but not on the physical or mechanical properties of the bulk. Our data suggest that oxygen scavenging takes place at the polymer-liquid interface, likely via oxidative reactions of the excess thiol monomers released from the bulk with molecular oxygen. Based on the kinetic constants governing the oxygen scavenging rate in OSTE microchannels, a microfluidic device comprising monolithically integrated oxygen depletion and IMER units was designed and its performance validated with the help of oxygen-dependent metabolism of an antiretroviral drug, zidovudine, which yields a cytotoxic metabolite under hypoxic conditions.
- Subjects :
- Immobilized enzyme
Metabolite
Microfluidics
116 Chemical sciences
Biomedical Engineering
chemistry.chemical_element
Bioengineering
02 engineering and technology
Oxidative phosphorylation
Biochemistry
Oxygen
03 medical and health sciences
chemistry.chemical_compound
Humans
Sulfhydryl Compounds
Hypoxia
030304 developmental biology
0303 health sciences
318 Medical biotechnology
In vitro toxicology
General Chemistry
Metabolism
021001 nanoscience & nanotechnology
Pharmaceutical Preparations
chemistry
317 Pharmacy
Biophysics
Feasibility Studies
1182 Biochemistry, cell and molecular biology
Limiting oxygen concentration
0210 nano-technology
Drug metabolism
Subjects
Details
- ISSN :
- 14730189 and 14730197
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Lab on a Chip
- Accession number :
- edsair.doi.dedup.....0bd195c41abc5c86c9f6cc49c0cc76e3