As part of established biomanufacturing development, screening and early phase bioprocess development occurs at bench scale (microplates and shake flasks) whereby conventional offline sampling can only provide limited feedback on fermentation bioprocess parameters including strain productivity. To address these limitations, a new sensitive and selective online analytical platform consisting entirely of commercially available components with a small footprint (valves, 2DLC hardware, LC separation, and online tandem mass spectrometry) was developed for online monitoring of chip-based microbioreactors. Fermentations of microbial cell factories (Saccharomyces cerevisiae) were cultivated in 20 μL bioreactors, requiring perfusion of cell culture media at low μL/min rates delivered by syringe pump modules, operated in a multiplexed configuration with a flow-through stream selection valve, and monitored with a 2DLC-MS/MS system adapted for microscale operation. This allows uninterrupted multiplexed microperfusions to be monitored with online measurements of metabolites from parallel fermentations without the occurrence of blockages or cross-contamination between independent fermentations. Fermentations of lactic-acid-producing strains ofS. cerevisiaewere continuously monitored over 5-24 h, demonstrating the suitability of the platform for online monitoring of product quantity and key metabolites for fermentation biotechnology. Offering minimal consumption of biological material and using <1.5 mL of cell culture media over 24 h per experiment, this new platform can be used for monitoring a broad range of biomolecules, rapid strain selection, and screening of microenvironmental factors and is adaptable for targeting other key biotechnology products.
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| Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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| Site | Modification | Modifier | Source | Reference |
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Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.
| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.
| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through its pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.
| Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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Increase the total number of rows displayed on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; download this table as a .txt file using the Download button;
| Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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