Facility for coupling a bioreactor with a device for physicochemically analysing or collecting samples

Patent metadata

Field	Value
Publication number	US-9963669-B2
Application number	US-201415101255-A
Country	US
Kind code	B2
Filing date	Dec 1, 2014
Priority date	Dec 6, 2013
Publication date	May 8, 2018
Grant date	May 8, 2018

Abstract

The invention concerns a facility for coupling a bioreactor for culturing bio-organisms, in dynamic mode, with at least one device for physicochemically analyzing a fluid from this bioreactor or collecting samples of this fluid, the device being equipped with a pump and an injector, the bioreactor being equipped with means for supplying culture medium and xenobiotic(s). The facility is remarkable in that the bioreactor is connected to a closed perfusion loop provided with a pump, fitted with a sampling loop and in that the facility comprises:
a device for injecting a cleaning product into said sampling loop, two six-way valves, the first valve being connected to the closed perfusion loop, to the sampling loop and to a cleaning loop, the second valve being connected to the cleaning loop and an injection loop that connects the injector to at least one of the devices.

First claim

The invention claimed is:

1. A coupling facility of a bioreactor for culturing bio-organisms, in dynamic mode, with at least one unit for physicochemical analysis of fluid coming from this bioreactor or one unit for collecting samples of this fluid, said unit being equipped with a pump and an injector, the bioreactor being equipped with means of supplying culture medium and xenobiotic(s), wherein the bioreactor is connected to a closed perfusion loop provided with a pump, this perfusion loop being fitted with a derivation loop, so-called “sample loop” and in that the facility comprises:
an injection device of a cleaning product into said sample loop,
a first valve comprising six ways,
and a second valve comprising six ways,
wherein the first and second valves each have first, second, third, fourth, fifth and sixth connecting orifices, the first and second valves are movable between a first position in which the first connecting orifice is connected to the second connecting orifice, the third connecting orifice to the fourth connecting orifice and the fifth connecting orifice to the sixth connecting orifice, and a second position, in which the first connecting orifice is connected to the sixth connecting orifice, the second connecting orifice to the third connecting orifice and the fourth connecting orifice to the fifth connecting orifice,
wherein for the first valve, its first and second connecting orifices are connected to the closed perfusion loop of the bioreactor, its third and sixth connecting orifices are connected to the sample loop, its fourth connecting orifice to the third connecting orifice of the second valve through a cleaning loop and its fifth connecting orifice to the sixth connecting orifice of the second valve through the cleaning loop, and
wherein for the second valve, its first connecting orifice is connected to a drain tank, its second connecting orifice to the injection device of a cleaning product, its fifth connecting orifice to the injector and its fourth connecting orifice to at least one of the units for physicochemical analysis or collecting samples, through an injection loop.

2. The facility according to claim 1 , wherein it comprises a third valve fitted with at least one input and two outputs, this third valve being positioned on the injection loop such that its input is connected to the injector through the fourth connecting orifice and the fifth connecting orifice of the second valve, its first output is connected to at least one of the units for physicochemical analysis or collecting samples and its second output is connected to a drain tank, said third valve occupying either a first position in which the input is connected to its first output, or a second position in which the input is connected to its second output.

3. The facility according to claim 1 , wherein the sample loop includes a trapping column.

4. The facility according to claim 1 , wherein a filter is present on the perfusion loop between the bioreactor and the first valve.

5. The facility according to claim 1 , wherein the bioreactor is placed inside an enclosure in which the rate of carbon dioxide and the temperature are controlled.

6. The facility according to claim 1 , wherein the physicochemical analysis unit is a liquid chromatography unit.

7. The facility according to claim 6 , wherein the physicochemical analysis unit is a high-performance liquid chromatography unit (HPLC).

8. The facility according to claim 1 , wherein the physicochemical analysis unit is selected from a mass spectrometer, especially a mass spectrometer provided with a source of ionisation for liquid of type ESI, APCI or APPI, a nuclear magnetic resonance unit (NMR), a fluorometric detector, a spectrophotometer or an online coupling unit MALDI TOF.

9. The facility according to claim 1 , wherein the unit is a collector of fractions for collecting samples of fluid coming from the bioreactor.

10. The facility according to claim 1 , wherein it comprises one or more physicochemical analysis units, mounted in series after a first physicochemical analysis unit, this first unit being especially a liquid chromatography unit.

11. The facility according to claiml, wherein the bioreactor is a multi-reactor box.

12. The facility according to claim 1 , wherein the bioreactor is a biochip.

13. The facility according to claim 12 , wherein the biochip is of micro-fluidic type.

14. A process for online physicochemical analysis of a biological fluid coming from a bioreactor or for collecting samples of this fluid, with the facility according to claim 1 , wherein it consists of performing at least once the following cycle of steps:
a) putting the first valve in its first position and the second valve in its second position, so as to clean and dry the sample loop,
b) putting the first valve and the second valve in their second position, so as to collect a sample in the sample loop and inject an internal standard in at least one of a first unit for physicochemical analysis of fluid coming from the bioreactor or a second unit for collecting samples of this fluid from the injector,
c) putting the first valve and the second valve in their first position, so as to inject the sample collected into the sample loop, in said first or second unit, by means of an eluent provided by the injector.

Assignees

• Univ Technologie De Compiegne—Utc
• Centre Nat Rech Scient

Inventors

• Leclerc Eric
• Paullier Patrick
• Merlier Franck

Classifications

• C12M29/04 Primary

  Filters; Permeable or porous membranes or plates, e.g. dialysis · CPC title

• C12M41/34

  of gas · CPC title

• C12M33/04 Primary

  by injection or suction, e.g. using pipettes, syringes, needles (pipettes in general B01L3/02) · CPC title

• C12M41/12

  of temperature (controlling the temperature of chemical or physical processes B01J19/0013, heating or cooling apparatus for laboratory use B01L7/00) · CPC title

• C12Q1/02

  involving viable microorganisms · CPC title