Bioprocessing & Bioreactors
Reliability and Reproducibility in Mass Flow Control

Bronkhorst,

YOUR Partner for Bioprocessing andBioreactor Applications

Why Bronkhorst?
Worldwide representation and service at factory level
Widest product portfolio for low ﬂows of gases and liquids
Fulﬁlling bioreactor application requirements
Stainless Steel SS316L wetted parts and FDA/USP elastomer sealing
Highest accuracy in the market (±0,5% of Reading plus ±0,1% of Full Scale)Widest range of communication interfaces available for MFMs/MFCs on the market
Standard and customised instruments to meet customer requirements
More than 40 years of experience in bioprocessing & bioreactor applications

www.bronkhorst.com

We understand bioreactors
We provide well-built solutions for bioreactor gas and liquid. Bronkhorst's flow instruments are suitable for benchtop and industrial bioreactors. They areaccurate, robust, reliable, and compact. As tailored manifold solutions or open frame installations, they can also be integrated into your equipment.
Long-term relationships with major and innovative biotechnology equipment manufacturers have demonstrated that our mass flow controllers are well suitedfor the job and have strengthened our portfolio with market-specific modifications.
Bioreactors are used to produce bioethanol and other biofuels, pharmaceuticals, fine chemicals, vitamins, vaccines, colorants etc. Because accurate dosing of
air, nitrogen, oxygen, and carbon dioxide into microbial and cell cultures is critical, the keywords are accuracy and reproducibility.
In this market brochure, we would like to show some of these applications and the solutions that our instruments can provide.

Examples of applications
Bioreactor gas dosing
Gas dosing for bacterial, yeast and mammalian cell growth
Flow control in pharmaceutical biotechnology
Controlled CO2 supply for algae growth
Gas mixing setup to calibrate oxygen sensor for monitoring beer quality
Bioreactor liquid dosing
Nutrient dosing
Buffer solution dosing
Reagent dosingReliable and reproducible gas control
Air, O2, N2, and CO2 are the four most commonly used gases for gassing bioreactors. Bacteria and cells are grown using air and oxygen. Typically, N2 is used tocalibrate the pO2 sensor and reduce the O2 content. CO2 is commonly used to control the pH value in the liquid phase.
To be able to deliver high-quality biological products over time, optimal conditions inside a bioreactor are required. These conditions can only be maintained
if the corresponding process is made reliable and reproducible. Bronkhorst instruments are among the most accurate instruments in the market. The physicalreliability can be expressed as a MTBF number, which is 130 years. Moreover, the digital parameters of our instruments can provide the user with diagnostic
information on the status of the process and of the meters or controllers themselves.
How the gassing of a bioreactor works:
Overlay

CO2AirSparger

CO2AirO2
N2

LiquidExhaust cooler
Waste
Pump
Pump

Weighing scale

Glucose Lactate
Pump

PO2Cells

TpH
Biomass

Cell retention
deviceWeighing scale

Pump

APPLICATION

Gas dosing for bioreactors
Bacteria are the workhorses of biotechnology, where they are used tocreate chemically, pharmaceutically, or biologically active substances suchas drugs, vaccines and other complex organic molecules. Bacteria havelong been used in the production of fermented foods and beverages
such as yoghurt and wine. Bacterial habitats are created in bioreactors
where bacteria can grow in a controlled environment by conditioning thetemperature, gas and liquid concentrations, and pH value.

Application requirements
Accurate and reproducible dosing of gases such as oxygen or carbon
dioxide to bioreactors is essential to control bacterial growth rate.
Moreover, for easy scaling-up, a full range of dosing equipment is available,
and be mutually interchangeable.
A reproducible and reliable gas flow is crucial for a safe operation ofbioreactors.

BIOREACTOR MASS FLOW CONTROLLER
DESCRIPTIONFEATURES (depending on model and flow range)
USP CLASS VI for FDA compliance

Biocompatibility of used sealing materials

ADI-freeAll sealing materials are free of Animal Derived Ingredients

Wetted parts

Stainless Steel 316L (or equivalent)

EN10204 3.1 material certificate

Inspection certificates of material laboratory analyses of all machined wetted parts

Degreased instrument

For use with Oxygen enriched media

Surface roughness

Ra 0.8 μm (micro meter)

Dynamic range

Dynamic range up to 1 : 200

Compact Flow Controller series (IP40)

IQ+FLOW and MANI-FLOW for compact bioreactor applications

General purpose Flow Controller series (IP40)

EL-FLOW Select and FLOW-SMS for broad range of bioreactor applications

Industrial Flow Controller series (IP65)

IN-FLOW and MASS-STREAM for industrial set-ups and open frame installations

Process connections

Compression type, Face seal, Tri-clamp DIN32676 (serie B)

Multi-Gas functionality

Up to 8 flow curves, for example Air, N2, O2 and CO2

Calibration on actual gas or with conversion model

Both methods available for optimization of process and economical aspects

Calibration certificate

Documented accuracy and repeatability of the instrument

Mean Time Between Failure (MBTF)

130 years
IN-FLOW F-113AI
Industrial Style Thermal Mass Flow Meter for Gases

APPLICATION

Liquid flow control for optimising growth of microorganisms
Mammalian cells and microorganisms are being used more than everbefore to produce pharmaceuticals and (bio)chemicals. Microorganisms in abioreactor need liquid nutrients, buffer solutions and reagents. Precise flow
control of these liquids ensures consistent growth and controllable results.
In case researchers in institutes or industry want to know what conditions
cause biological cells to grow faster or slower, flow control of liquid
nutrients or other additives can be used to optimise the cell growth.

ES-FLOW™ ES-103I
Ultrasonic flow meter for low flow rates

Application requirements
Many types of nutrients, buffer solutions and reagents are involved tocreate an optimal environment for microorganisms. Therefore, a wideliquid compatibility of instrumentation is needed. Also, liquid-independentmeasurement and control of mass or volume are necessary. Since small andlarge liquid doses could be needed in different situations, a large dynamic
range of dosing equipment is much desired. Bronkhorst instruments miniCORI-FLOW and ES-FLOW are dedicated to provide these requirements
and offer compact alternatives for weighting scales. ES-FLOW is specificallysuitable for several cleaning methods.

MINI CORI-FLOW™ M13V14I
Low Flow Coriolis Mass Flow Controller for Liquids and Gases

SMART maintenance and diagnostics for bioreactors
Bronkhorst digital Mass Flow Controllers and Meters provide a variety of parameters for enhanced measurement, control, and diagnostics functionality thatis useful in bioreactors. The internal microcontroller primarily supports the device's flow measurement and control functions, as well as digital or analogcommunication. Additional parameters are implemented for diagnostic purposes, such as use with bioreactors. Bronkhorst instrument parameters can provide
useful information for effective integration into maintenance systems, achieving optimal reliability, and minimising downtime.

Smart Functions of our gas and liquid instruments:	Response Alarm: together with a variably adjustable timer (max. valueof 255 s), this alarm reliably indicates whether the specified setpoint isreached within the pre-set time	Timer: with a variably adjustable timer (max. value of 255 s), this alarm
reliably indicates whether the specified setpoint is reached within thepre-set time	Measure: indicates the actual value of the flow	
Set Point: if the set point specified by the higher-level control was readin and accepted by the device at all	
Valve Output: (= coil current) allows a conclusion to be drawn about
contamination	Power-Up Alarm Message: can detect an unforeseen and time-critical
drop in the power supply
Hardware alarm and error messages: a possible malfunction of thedevice is signalled, which can be used on the plant side for corresponding
further alarm messages or specific actions by the plant control	
Operation Hours: indicates the total number of hours that an MFC has
been energised since it was first started up	
Calibration Date: is the date of the last calibration of the respective
instrument

Artist impression of a customised, multi-channel flow solution

Leader in low-flow measurement and control technology
Bronkhorst High-Tech is leading in the field low flow fluidics handlingtechnology. We offer an extensive product range of thermal, Coriolisand ultrasonic flow meters and controllers for low flow rates of gases
and liquids. Our flow instruments are used for a variety of applications
in laboratory, machinery, industrial and hazardous areas. By sharing ourknowledge and closely cooperating with OEM customers, we develop
customer specific low flow solutions, e.g. of multifunctional, pretested
modules or skids for gas, liquid of vapour flow control. With ourheadquarters based in Ruurlo (NL), Bronkhorst is represented by 12 wholly
owned subsidiaries in Europe, in the USA and in Asia and additionally by anetwork of distributors in more than 30 countries worldwide.

Facts & figures

Customer first
In addition to the extensive standard product range, Bronkhorst
collaborates with customers to develop the best customized process
measurement and flow control solution. Our global perspective, butwith local focus, ensures that our international distributor network is able
to provide on-site support and discuss the best solution to any given
application. This ethos also includes product adjustments to ensure thatthe finer details of your application will always be met with a bespoke
solution if necessary.

Worldwide support

More than 40 years experience in Mass Flow & Pressure
More than 1.000.000 instruments in the field
Approx. 460 employees at headquarters in the Netherlands

Support can be offered from many different locations around the globe.
You can find our nearest distributor/service office on our web pagewww.bronkhorst.com/distributors

12 branch offices; approx. 150 employees
Representation in >40 countries; >20 factory level service offices
20% of employees active in R&D and development
Cleanroom according to ISO 14644-1 Class 6 with Class 5 flow benchesFor urgent matters, our International Support Team is available 24/7 toanswer your request immediately or ensure appropriate further action.
Just call: +31 859 02 1866

ISO 9001 and ISO 14001 certifiedBronkhorst Calibration Center, ISO 17025:2017www.bronkhorst.com

Bronkhorst High-Tech B.V.
Nijverheidsstraat 1aNL-7261 AK Ruurlo, The Netherlands

Tel. +31 573 458800
info@bronkhorst.com

9.60.078A L2101586 ©Bronkhorst®