Premier Control Technologies Logo
Premier Control Technologies Fluid Solutions

Bioreactor and a Mass Flow Controller go hand in hand

Tuesday, 12th November 2024

Introduction to a Bioreactor, what does a Reactor do?

A Bioreactor is the name given to a piece of equipment that can help with the growth or cells. The Bioreactor consists of a closed chamber, the chamber will usually have a stirrer for mixing liquids, the liquid is where the cells and nutrients (food) is held and grown. Above the liquid is a gas atmosphere. The chamber will need to keep the liquid at a steady temperature. There will be sensors to monitor the environment such as temperature sensors, pH sensors and even the gas concentrations. The conditions are adjusted for optimum growth of the cells in the liquid. The liquid provides feed for the cells too.

The chamber must initially be sterilised usually via steam passing through the chamber, or a single use bag reactor that has been sterilised by radiation. The cells and nutrients (food) are added to the vessel and it is held at a steady temperature whilst being stirred in a controlled way to optimise cell growth and duplication. Stirring ensures the cells have access to the nutrients as they will be well dispersed. Stirring is also vitally important to adding gases to the liquid. Gas is added to the chamber at the bottom the bubbles are mixed with the liquid by the stirring. These gases aid the ideal conditions for rapid growth of cells and keeping them heathy.

Bioreactors

The gases used in bioreactor are commonly Air, Oxygen, Nitrogen and Carbon Dioxide.

What is Sparging?

Sparging is the introduction of gases such as Air or and O2 into the liquid. This is for the introduction of Oxygen into the liquid, known as dissolved Oxygen. The design of the bioreactor is important that the amount of dissolved oxygen is adequate for the cell growth.

Dissolved Oxygen

Typically, lots of tiny bubbles are best for getting the oxygen to dissolve into the liquid aided with the stirrer. The longer the oxygen bubble is moving through the liquid the more uptake into the liquid, too big a bubble and not enough stirring the bubbles simply rise through the liquid too fast and exit into the top of the chamber. Likewise, too much Oxygen can cause the liquid solution to degrade.

The correct levels of Carbon Dioxide (CO2) and Oxygen (O2) in the liquid, Dissolved CO2 and Dissolved O2 is vital in growth performance. Too little or too much of either will result in failed batches.

How to measure the Levels of Dissolved Oxygen and Dissolved CO2 in the Bioreactor?

Sensors are used to measure pH for the CO2 levels and an Oxygen sensor for Dissolved O2.

"Thus the accurate flow control of gas to a Bioreactor is very important for the cell to flourish."

Here's where Premier Control Technologies can assist manufacturers and end users with flow control to a Bioreactor. Mass Flow Controllers are instruments that adjust the flow rate of the gas according to what you input, they will automatically adjust (by controlling a valve) to maintain a steady flow and keep it stable regardless of changes in temperature or pressure.

What is the best MFC for Bioreactors?

There are a few options of the types of Mass Flow Controller from the Bio Series, MC series and the all-new BASIS OEM Model. Here’s a breakdown of each.

  1. The Bio Series

    The Bio Series is well suited to delivering accurate gas flow in the Bio and Pharmaceutical markets, with its Mass Flow and Volumetric flow rates reported on it’s built in display. What’s more impressive is the Bio Series as offers the parameters of Temperature and Pressure of the gas all in 1 device.

    • Control via local display, analogue, serial, or industrial communications
    • Lock screen to protect process parameters
    • Valve drive % for redundancy in preventative maintenance
    • Change control & management processes for GMP environments
    • USP Class VI certified elastomers & 316L stainless steel flow body; various materials options for sensor and valve per ASME BPE-2016
    • Oxygen cleaning available
    • ATEX Class 1 Div 2 available; IP66, IP67 & IS certifications coming soon
    • Lifetime warranty on all devices
    BIO Series

    Alicat Bio Series have an impressive 10,000 turn down, let me explain this: Turn Down is the factor from max Flow the device can deliver to the minimum flow it can deliver whilst maintaining the accuracy statement for the device. A simple calculation illustrates this well.

    For a Max Flow of 10SLPM (Standard Litres Per Minute) to minimum accurately controlled flow would be: 10SLPM/10,000= 0.001SLPM. Thus, a range of 0.001 to 10SLPM which is world beating.

    There are many flow rates available depending on the flow required for the specific Bioreactor from research (small size) reactors requiring very low flows to larger batch or continuous production of the bio media.

    These Alicat Mass Flow Controllers are multigas enabled, (98 Gas types) preloaded in the device memory, simply select the gas you wish to control the flow accurately of that particular gas.

    Data such as Flow, Temperature and Pressure is display on the built-in screen and can be transferred to a centralised system via one of the many communication protocols available.

    View the Bio Series product page

  2. The MC Series

    The most popular model and the model that launched Alicat as a global MFC manufacturer. Built in Display showing Volumetric Flow, Mass Flow, Temperature and Pressure with an unrivalled 10,000 turn down!

    Summary of features as follows:

    • Mass Flow Range: 0 SCCM–5000 SLPM
    • Accuracy: Up to ±0.5% of reading
    • Measurement Range: 0.01–100% of full scale
    • Response Time: 10 ms measurement response; 30ms control response
    • Multi-gas Calibration: 98+ pre-loaded gases
    • Repeatability: Greater of ±0.1% of reading or ±0.02% of full scale
    • Analog Outputs: 0–5 Vdc, 0–10 Vdc, 4–20 mA
    • Digital Communications: RS–232, RS–485, DeviceNet, EtherCAT, EtherNet/IP, Modbus RTU, TCP/IP, PROFIBUS, IO-LINK
    Alicat MFC MC Series

    View the MC Series product page

  3. The BASIS 2.0 OEM MFC

    The BASIS 2.0 OEM Mass Flow Controllers for larger quantities of Bioreactors suited to manufactures.

    Alicat Basis 2.0 Series
    Alicat Basis 2.0 Series in a Manifold

    The Alicat BASIS 2.0 is a small footprint OEM Priced Mass Flow Controller, which can be used as a single MFC or as part of a customer specified Manifold. The Basis is well suited to Bioreactors as it is multigas with the following gas types loaded in to its memory: Air, N2, O2, CH4, He, H2, Ar, CO2 and N2O. Full scale flow ranges 100 SCCM to 100 SLPM with a measurement and control range of 0.1% to 100% of full scale (1000:1 turndown). Communication options: RS-232 or RS-485, or 4-20mA or 0-5v. The device operates within an ambient and gas temperature range of 0 to 50°C and can handle up to 95% non-condensing humidity.

    View the Basis 2.0 MFC product page

Additional Equipment that may be useful

Back Pressure control using Equilibar BPRs

Here we have 2 options 'Permanent' and 'Single use':

  • Permanent Back Pressure Control

    Equilibar FD Series

    The Equilibar FD Series has been specifically for biotechnology and pharmaceutical and whilst its’ principle of operation is similar to other Equilibar Back Pressure Regulators, the FD series meets the ASME BPE requirements. Some of these requirements are listed below:

    • USP class 6
    • EU 1935/2004 (on request)
    • Crevice free design
    • Electropolished
    • Surface roughness Ra < 0.5 µm

    View the FD Series product page

  • Single use Back Pressure Control

    Equilibar SD series

    The SD series acknowledges the rapidly expanding requirements of Biopharmaceutical Industry for single use, lower cost components, that can be sterilized through irradiation and disposed of after use. The Equilibar SD Series offers USP Class VI polymers that can be sterilized as a complete assembly with the wetted components and diaphragm being disposable whilst the permanent support housing can be retained. By use of sanitary clamp connections for quick and easy assembly these regulators combine ease of use with excellent stability, smooth control and seamless automation. Options include a sterilised version (Gamma radiation) and Sanitary Certifications.

    View the SD Series product page

Pressure Regulators

Pumps

Liquid Pumps: The Longer Peristaltic, Fluid Metering Piston Pumps or Alicat Coriolis and Micro gear pumps can be utilized of best practice.

Related article

The Best gas Mixer in The World

Get in touch

If you have any questions rest assured PCT are a leading UK distributor and your enquiry will be handled with the utmost professionalism. Please contact us on 01953 609930 or email sales@pctflow.com.