The document describes mini bioreactors for small scale cell culture and microbial fermentation. It discusses various bioreactor models ranging from 250 ml to 1000 ml total volume with working volumes from 50 ml to 800 ml. Key features highlighted include integrated sensors for pH, temperature, oxygen, and foam, as well as actuators like pumps, gas mixers, and heating/cooling. Applications mentioned include discovery, process development, screening, and optimization. Larger scale systems and add-ons like feed controllers and mini bioseparators are also summarized.

1. Mini Bioreactors
Real Small
Real bioreactors

2. Full Range of Bioreactors
Micro
(200µl)
Autoclavable
1-20L
SIP/CIP
7-2,000L

3. Bioreactor Application
Autoclavable - Glass
Discovery Screening Process
Development
Process optimization
SIP Systems
Micro Flask
Appliflex
Mini Bioreactor
Production

4. Scale vs Throughput
SCALE
THROUGHPUT
As scale increases, throughput decreases

5. INFORMATION
THROUGHPUT
Throughput vs Information
• Traditionally, information increases as your throughput decreases
• Decisions must be made prior to fermentation
• Limited information available to make decisions

6. THROUGHPUT
Better Technology, More Information, Better Decisions
• The MiniBio increase your throughput
• The MiniBio provides more information prior to stirred vessels
• Higher throughput and more information = better decision making
INFORMATION

7. &

8. Small Scale Bioreactors
• Functions:
– Generate more data in less time
– Easy setup and operation
– Cultivate using less medium
– Cultivate using les bench space
– Generate scalable results
– Mimic lab scale bioreactors
– Easy data handling

10. Communication
Internet
Company
network

11. • Sensors
– Integrated amplifiers for Agitation, pH, DO2,
Temperature, Level and Foam
• Actuators
– up to 6 variable speed pumps or micro valve
additions (max 4 built in)
– Needle valve with solenoid per gas
– 3-channel Mass Flow Controller,
– Heating (via Peltier or heating blanket),
– Cooling (via Peltier)
– Condenser cooling (Peltier)

12. • Inputs / Outputs
– Spare I/O:
• 8 x digital output (0/5V)
• 4 x analog in (0 – 10 V)
• 4 x analog out (0/4 – 20 mA)
• USB connection for buglab, Balances,
Biomass, Fluorophor pH and DO2

13. • Software features
– Adaptive PID control, pH, DO, Temp
– Free configuration control loops
– Up to 15 different control loops
– Easily changed Cell to Microbial and vise
versa
– Integrated buglab and balances
– Feed control

14. MiniBio bioreactor range

15. Small Scale Bioreactors
• MiniBio
– 250 (290) ml total volume
• 50 ml .. 200 ml working volume
– 500 (550) ml total volume
• 100 ml .. 400 ml working volume
– 1000 (1030) ml total volume
• 200 ml .. 800 ml working volume

17. MiniBio 250
Modular topplate
Classic pH, Temperature and
Oxygen sensors
Micro valve for micro liter
additions

18. MiniBio 250
• 3x M12 ports for pH, DO2 sensor, Condenser
• 5x M8 port for septum, foam and level sensor,
microvalve, height adjustable sample pipe, etc.
• Thermowell for temperature sensor
• Sparger aeration (open pipe or sparger tip)
• 4 liquid inlets or 3 inlets + 1 overlay
• Fixed sample pipe
• Lipsealed stirrer with height adjustable impellers
(Rushton or Marine impellers 50 to 2000 RPM )

19. MiniBio 500
• 4x M12 ports for pH, DO2 sensor, Condenser,
BioSep or biomass
• 5x M8 port
• Thermowell for temperature sensor
• Sparger aeration (open pipe or sparger tip)
• 4 liquid inlets or 3 inlets + 1 overlay
• Fixed sample pipe
• Lipsealed stirrer with height adjustable impellers
(Rushton or Marine impellers 50 to 2000 RPM )

20. Special features
• Micro valve
• Mini BioSep
• Feed control

21. Additions
• 25 % / day addition
• WV 150 ml = 1.5 ml/hour
• 1 droplet = 0.025-0.05 ml
• 1.5 ml/hour = 30 - 60 droplets / hour
– No continuous feed

22. Microvalve

23. Microvalve
• Autoclavable
• Drops of 500 nL up to ±50 µL
• 1 drop per sec = continuous
• Flow of 1.8 ml/hour up to ±200 ml/hour
• Activated from my-Control as pump output

24. Microvalve control
PI
0.5 barg
Z370000010
Z811001919
Z310216030 +
Z310216040
Z8?

25. Mini BioSep
Principle of operation
• Cell culture
• Perfusion
• 0.1-1000L/day

26. Mini BioSep
• 1L/day unit
• Fits only on 500ml MiniBio
• 8 mm sensor holder
• No recirculation

27. Mini BioSep
Mini BioSep Controller
• Controls 1-4 biosep systems
• 4 slots for HF control board
• 1 power setting 0.1-1W
• 1 setting for run time and 1 for stop time
• Activates (start/stop) up to 4 pumps

28. MiniBioSep
Pump with prime rate reverse
• Backflush to return cells
• Up to 4 harvest lines per pump
Z375239000
Z375192000 4x Z3751985000

29. Feed controller
• Gravimetrical feed control
• Balance (SBI protocol)
• RS232 (balance) - USB (my)
• Internal or external variable speed pump

30. Feed controller
• Gravimetrical feed control
• Weight control based on average of first
derivative
• Not effected by environmental conditions

31. Feed controller
y = -0,4102x + 744,95
R² = 0,9997
0
0,5
1
1,5
2
2,5
3
3,5
4
725
725,5
726
726,5
727
727,5
728
728,5
729
729,5
730
41 43 45 47 49
Weight(grams)
Time (hours)
Flow Profile of 10g/ day
10g/day
output pump
Lineare (10g/day)

32. Bundles
• Bundle MiniBio
– 250 / 500 / 1000 MiniBio Bundle
– Cell or Microbial
• Bundle autoclavable
– 1, 2, 3 Autoclavable bundle with my-Control
– Cell or Microbial
– Silver band
– Data acquisition

33. Bundles
• Bundle Cell
– 1 pump (alkali)
– 2 gasses (Air, CO2, needle valve+solenoid)
– Heating blanket
– Stirrer
• Bundle Microbial
– 3 pump (alkali, acid, foam)
– 2 gasses (Air, O2, needle valve+solenoid)
– Peltier temperature control
– Stirrer

34. Bundles add-ons
• Internal pump(s)
• Microvalves
• Additional gas line, overlay output
• 3-channel MFC
• Analog inputs - sensors
• Analog outputs - pumps
• Full SCADA
• 22” Touchsceen PC
• Colored front panels

35. Add on packs bundles
• Other color front panel

36. Features
• Mechanically coupled agitator that allows mixing up to 2000 rpm even
in viscous media or high density cultures.
• Minimum working volume of 50 ml in our 250 ml system(with mixing
and measurement and control of pH, Temp, DO, foam and level.
• Autotuning adaptive PID control for accurate control even when the
process conditions change
• Up to 6 variable speed pumps per system
• Microdosing with flow rates down to 1.8 ml/hour continuously.
• Control any number from 1 to 16 or even 32 bioreactors from 1 pc.
• Very limited bench space 5 systems on 100x60 cm
• All electric connections (no water connections required)
• Additional inputs and outputs for external sensors and pumps
• Complete configurational freedom. Customer can connected any
actuator to any sensor input and create a new control loop.
• Software runs within each controller so if you loose connection with
the pc the process is not stopped.
• Individual coloring of the control units.

37. Questions
Thank you