Small volume bioreactors with substantially constant working volumes and associated systems and methods
US-2016215246-A1 · Jul 28, 2016 · US
US10071378B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-10071378-B2 |
| Application number | US-201414775285-A |
| Country | US |
| Kind code | B2 |
| Filing date | Feb 24, 2014 |
| Priority date | Mar 13, 2013 |
| Publication date | Sep 11, 2018 |
| Grant date | Sep 11, 2018 |
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A microchannel device includes: an upstream channel portion configured to allow an upstream liquid plug and a gas to flow therethrough; a downstream channel portion configured to allow a downstream liquid plug and a gas to flow therethrough; a liquid holding portion provided between a downstream end portion of the upstream channel portion and an upstream end portion of the downstream channel portion, the liquid holding portion being configured to hold a main liquid plug therein; and a gas bypass channel portion provided so as to bypass the liquid holding portion from the downstream end portion of the upstream channel portion to the upstream end portion of the downstream channel portion, the gas bypass channel portion being configured to allow the gas to flow therethrough in a state in which the liquid holding portion holds the main liquid plug.
Opening claim text (preview).
The invention claimed is: 1. A method, comprising the following (a) to (g): (a) providing a microchannel device comprising an upstream channel portion, a downstream channel portion, a liquid holding portion provided between a downstream end portion of the upstream channel portion and an upstream end portion of the downstream channel portion, and a gas bypass channel portion provided so as to bypass the liquid holding portion from the downstream end portion of the upstream channel portion to the upstream end portion of the downstream channel portion; (b) filling the gas bypass channel portion with a gas and holding a main liquid plug in the liquid holding portion; (c) causing a first upstream liquid plug and a second upstream liquid plug to sequentially flow through the upstream channel portion toward the liquid holding portion; (d) causing the first upstream liquid plug to flow into the liquid holding portion to merge the first upstream liquid plug with the main liquid plug, and pushing out a part of the main liquid plug after the merging to the downstream channel portion; (e) causing a gas in the upstream channel portion, which is following the first upstream liquid plug to flow into the gas bypass channel portion to push out a part of the gas in the gas bypass channel portion to the upstream end portion of the downstream channel portion, to thereby cut the part of the main liquid plug, which is pushed out in the item (d), to form a first downstream liquid plug; (f) causing the second upstream liquid plug to flow into the liquid holding portion to merge the second upstream liquid plug with the main liquid plug and pushing out a part of the main liquid plug after the merging to the downstream channel portion; and (g) causing a gas in the upstream channel portion, which is following the second upstream liquid plug to flow into the gas bypass channel portion to push out a part of the gas in the gas bypass channel portion to the upstream end portion of the downstream channel portion, to thereby cut the part of the main liquid plug, which is pushed out in the item (f), to form a second downstream liquid plug, wherein an upstream end portion of the gas bypass channel portion is open at the downstream end portion of the upstream channel portion, and the liquid holding portion is provided downstream of the upstream end portion of the gas bypass channel portion. 2. The method according to claim 1 , further comprising the following (h): (h) recovering the first downstream liquid plug and the second downstream liquid plug. 3. The method according to claim 1 , wherein the item (c) comprises causing the first upstream liquid plug and the second upstream liquid plug to flow so that the second downstream liquid plug is formed in the item (g) within a time shorter than 1 second after the formation of the first downstream liquid plug in the item (e). 4. The method according to claim 1 , wherein the item (c) comprises causing the first upstream liquid plug and the second upstream liquid plug to flow so that the second upstream liquid plug is merged with the main liquid plug in the item (f) within a time shorter than 1 second after the first upstream liquid plug is merged with the main liquid plug in the item (d). 5. The method according to claim 1 , wherein the volume of each of the first upstream liquid plug, the second upstream liquid plug, the first downstream liquid plug, and the second downstream liquid plug, is smaller than 1 μL. 6. The method according to claim 1 , wherein: the main liquid plug held in the liquid holding portion in the item (b) contains a first factor; and one or both of the first upstream liquid plug and the second upstream liquid plug that is caused to flow through the upstream channel portion in the item (c) contain a second factor which directly or indirectly acts on the first factor. 7. The method according to claim 6 , wherein: the first factor is a cell body; and the second factor is a substance which directly or indirectly acts on the cell body.
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