DE19710652A1 - Miniaturised modular bio-technical cell cultivation assembly - Google Patents

Abstract

A miniaturised bio-technical assembly for culture of microorganisms comprises a series of modular cylindrical glass vessels (4), a conical cultivation vessel, a cylindrical vessel holding a particulate substrate base, a cylindrical fluidised bed vessel, an upright (2) and a conical lid with connectors (6) and measuring devices (7). The components are interchangeable to assemble devices with different function The interchangeable parts are the lids (2), the cylindrical fluidised bed vessel, the cylindrical vessel holding a particulate substrate base, the conical cultivation vessel and the mixer (1). The devices which can be assembled from the range of standard component parts are a standard mixer-fermenter, a fluidised bed reactor, a miniature mixer-fermenter, a measurement and control device in a control housing consisting of a power-supply printed-circuit board (PCB), control, foil-covered push-button control panel, eight modular measurement device PCBs, a DMS weighing system, six miniature hose pumps, aerators, three proportional piezo-electric valves, a graphics display and a housing.

Description

Scope of the facility

The following components belong to the biotechnical system:

• - Measuring and control unit (MCU 3010) with control electronics, strain gauge weighing system, three Proportional valves in an ergonomic desk housing and five peristaltic pumps.
• - Modular bioreactor vessel with the possibility of four different ones To apply cultivation methods.

State of the art

In the laboratory, a cylindrical single or is usually used for cell cultivation Double jacket vessel used, the outer jacket vessel usually for tempering of the inner reaction vessel. Usable volumes of 2 and 5 liters are usually used offered, rarely orders of magnitude from 0.5 to 10 liters. The common cylinder shape the vessels do not allow the arrangement of a sufficient one for very small vessel volumes Number of measuring probes and fittings, due to the small vessel cover ∅, so that either controlled conditions have to be dispensed with, labor-intensive, external Measurements and analyzes have to be carried out, and are therefore delayed Process corrections arise. Another disadvantage of these standard stirred fermenters is that limited volume variation. Added to this is the inflexibility of the vessel configuration, e.g. B. need for different procedures such. B. general cultivation and cell cultivation in the Usually completely different and independent culture vessels are used, a simple one So far, inexpensive retrofitting has not been possible.

Common measuring control units are located in voluminous, box-shaped housings, that take up a lot of space on cramped laboratory tables. Additional Space is created by juxtaposing three units such as a housing Instrumentation, culture vessel, monitor or PC. The operation often has to be inconvenient stooped posture, even longer programming can never be sedentary like done on a computer.

The number of measurement control parameters is often only four, max. limited to six pieces. The Modular equipment options according to process requirements are often not available. The Number of peristaltic pumps limited to four.  

The invention relates to a miniaturized biotechnological plant for breeding of microorganisms.

Miniature reaction tube series

Reaction vessels of the type described in the introduction are known. In particular, the lid will with a variety of connecting pieces, measuring probes and. Like. provided that quite have different tasks to perform. These structures or internals are depending on Smaller or larger number of applications required, the lid being relatively tight is loaded and this results in a minimum lid diameter. By so determined With cylindrical (inner) vessels, the lid diameter results in a volume that for many Applications, especially in particularly cost-intensive crops, is too large. Through the The taper of the conical reaction vessel will have a sufficiently large lid diameter realized small volume at the same time. Probes and fittings are also conical in the lid arranged so that they are parallel to the vessel wall.

Due to the modular design of the individual vessel parts, there are conventional reaction vessels the possibility of using different cultivation methods. The standard assembly All four reactor vessels consist of the cylindrical reaction vessel with screwed on Outer ring.

The standard agitator consists of the standard assembly, the straight lid and the Agitator and various connecting pieces and measuring probes.

The fixed bed reactor consists of the standard assembly, the fixed bed container, the straight one Lid, individual parts for fixed bed fixation as well as various connecting pieces and measuring probes.

The fluidized bed reactor consists of the standard assembly, the straight cover, individual parts for fluidized bed fixation as well as various connecting pieces and measuring probes.

The miniature stirring fermenter consists of the standard assembly, the conical lid, the Agitator and various connecting pieces and measuring probes.

Measuring control unit

The measuring / control unit is housed in a splash-proof desk housing. The housing contains the power board, which provides the voltage supply for pump and agitator motors, the strain gauge weighing system as a bridge over the boards, a fan, the graphic display, the keyboard board and the control board, including the software for controlling the various parameters contains. There are slots on the control board for the different measured value conversion boards. The measured value conversion boards are designed as functional modules and can be easily plugged into the control board as required. The following function groups can currently be inserted:

• - Temperature control, complete with measuring amplifier, cold water valve, heating element and sensor
• - pH control, complete with measuring amplifier, sensor and proportional control valve
• - pO2 control, complete with measuring amplifier, sensor and proportional control valve
• - pH control, complete with measuring amplifier, sensor and proportional control valve
• - DMS weighing system with measuring amplifier
• - Anti-foam control, complete with measuring amplifier, sensor and proportional control valve
• - Gas flow measurement, complete with sensor.

The measured value conversion boards are in turn provided with pluggable cable connections commercially available plug sockets connected to the back of the measuring / control unit. The required sensors are connected to the sockets and are also as required insertable at any time. Similarly, on the back there are three proportional Piezo valves for continuous gas mixing. These are controlled via the MCU.

The main functions of the MCU are:

Process visualization

The current culture breeding process can be shown on the one hand using a bar chart by placing all control parameters as bars between the adjustable control limits is visible. On the other hand, all actual and target values can be used together or individually are displayed.

Regulator

The MCU has eight PID controllers that were implemented using software. The Controller parameters (gain, reset time, lead time, operating point setting, Min. Setpoint, Max. Setpoint, and command variable) can be changed as required.

Setpoint specification

The setpoint for the PID controller is either entered directly or by creating a program in which it is possible to temporally depend on ten setpoints to enter.

Analog outputs

An additional four analog outputs can be switched directly on and off and in their Output voltage can be set.

Digital outputs

An additional four digital outputs can be switched on or off directly.

Parameter backup

For three different process controls, all set parameters can be found under a certain name can be saved.

The MCU 3010 has a standardized serial interface RS232 and associated Application software. This enables process visualization using a personal computer (IBM compatible) possible.

The MCU 3010 is thus an autonomously operable measuring / control unit that can also be used with everyone other biotechnological reaction vessel can be operated. One on the top attached plate, connected to the strain gauge weighing system, holds the reaction vessel. This saves expensive laboratory space.

Due to the extensive miniaturization of the measuring / control unit with a particularly high Functional density results in a relatively small space requirement of the biotechnological Investment. This saves expensive laboratory space.  

The invention is further illustrated and described in several exemplary embodiments.

Show it:

Fig. 1 side view of the measuring / control unit MCU 3010 with miniature stirred fermenter,

Fig. 2 Front view of the measuring / control unit MCU 3010 with miniature stirred fermenter,

Fig. 3 top view of the measuring / control unit MCU 3010 with miniature stirred fermenter,

Fig. 4 sectional view of the standard Rührfermenters,

Fig. 5 sectional view of the fixed-bed reactor,

Fig. 6-sectional view of the fluidized bed reactor,

Fig. 7-sectional view of the miniature Rührfermenters,

Fig. 8 sectional view of the measuring / control unit MCU 3010,

Fig. 9 view of the standard Rührfermenters,

FIG. 10 view of the fixed-bed reactor,

FIG. 11 view of the fluidized-bed reactor,

Fig. 12 View of the miniature stirred fermenter.

Reference list

1

Agitator

2nd

straight lid

3rd

Outer ring

4th

Reactor vessel

5

Fumigation pipe

6

Through socket

7

pH electrode

8th

Fixed bed or fluidized bed containers

9

Fixed bed fixation

10th

Fluid bed fixation

11

conical lid

12th

conical reactor vessel

13

Pump head

14

Power board

15

Control board

16

Pump head with motor

17th

Fan

18th

Plate

19th

DMS weighing system

Claims (5)

1. Miniaturized, biotechnological plant for the cultivation of microorganisms consisting of a modular series of vessels, with a cylindrical glass container ( 4 ), a conical cultivation vessel ( 12 ), a cylindrical fixed bed container ( 8 ), a cylindrical fluidized bed container ( 8 ), a straight one ( 2 ), and a conical cover ( 11 ) for introducing arranging connection piece ( 6 ), measuring probes ( 7 ) and the like. characterized in that by exchanging the lid (2, 11) fixed bed container (8), fluidized-bed tank (8), conical culture vessel (12) and agitator (1) a standard stirred fermenter (Fig. 8), fixed-bed reactor (Fig. 9), fluidized bed reactor ( Fig. 10) or miniature stirring fermenter ( 11 ) and a measuring control unit in a desk housing ( Fig. 1) consisting of a power board, control board, membrane keyboard, eight modular transmitter boards, strain gauge weighing system ( 19 ), six miniature peristaltic pumps ( 16 ), fan ( 17 ), three proportional piezo valves, graphic display and a housing. 2. Series of reaction vessels according to claim 1, characterized in that by the conicity of the miniature reaction vessels has a small volume in relation to the lid diameter with a constant high occupancy density of connecting pieces, measuring probes and. the like arises. 3. series of reaction vessels according to claim 1, characterized in that by the modular construction creates the possibility of four different culture vessels on simple Way to put together. 4. Measuring / control unit according to claim 1, characterized in that it has functions such as:
Strain gauge weighing system, eight measurement / control parameters, six peristaltic pumps, three proportional gas mixing valves in a confined space and additionally has a display for process visualization. 5. Measuring / control unit according to claim 1, characterized in that a particularly Ergonomic housing the operation compared to conventional devices simplified and enables fatigue-free working and monitoring.