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Simplified Gas Line Configuration for Bioreactors and Bioprocess Systems

An example of how to reduce cost and complexity for gas inputs utilizing high controllable range mass flow control.

As the need for even more potent and specific pharmaceuticals grows, Pharma manufacturers have turned to Biologics to meet the increasing needs to solve complex and currently untreatable disease conditions (including cancer and myriad genetic diseases). Biologics, and Biosimilars, differ from conventional drugs in that they are grown in living cells, rather than manufactured using conventional chemical processes. This growth is carried out in a controlled environment typically termed a bioreactor or fermenter. The bioreactor environment poses some unique challenges to process and automation experts. The bioprocessing techniques required utilize unique control schemes, specific materials requirements and often complex gas control systems. As the organisms grow, mass flow needs within the reactor can scale radically, more so than in most chemical and industrial processes.

The diagram below shows a typical gas input schema for a global premier biologics manufacturer. Note that this design requires both high flow and low flow lines for both oxygen and process air.

Mass flow schematics for Bioreactor

Figure 1: Mass flow schematic for the inputs to a bioreactor from a typical large scale bioprocessing company.

This multiplicity of mass flow lines is required by the limited range of the mass flow meters used. For example, the Oxygen flow lines show one meter to be used for flow rates under 35 SLPM and another for flow rates under 100 SLPM. These flow ranges imply a controllable range of no more than 30:1 for the controller specified. Alicat recommended that this design could be simplified by utilizing Alicat’s mass flow controllers. The latest Alicat mass flow controllers have an amazing controllable range of up to 10:000:1, far in excess of the 30:1 required by a dual flow range design.

Low and High Mass Flow Lines

Figure 2: Zoomed view of the low and high mass flow lines for the original bioreactor mass flow schematic shown above and simplified design using an Alicat MFC

Bioreactors typically have pressures of approximately 50psi to atmosphere. Table 1 shows the performance of a typical Alicat Bio series 100SLPM controller from 100SLPM down to 10SCCM.

Desired Flow Rate (SLPM)Flow Rate Error (SLPM)Error as % Flow
100+/-.6.6%
20+/-.12.6%
5+/-.12%
1+/-.110%
.1+/-.1100%
.01+/-.11000%

Table 1: Alicat mass flow accuracy vs. flow rate for a typical Alicat 100 SLMP Mass Flow Controller

Virtually any mass flow controller can be adequately accurate within the middle and top of their specified flow range. The Alicat mass flow controller has a mass flow error of only .6% near the top of the scale, and only .3% error at 50 SLPM. What enables this flow range simplification is the high degree of accuracy at very low flow. An Alicat MFC has an error of less than 10% of the desired flow rate down to a turndown of 100:1. Even as low as 1000:1 the error in flow is an astonishing .1 SLPM for a 100 SLPM flow controller! The data and experience indicated that this manufacturer could reduce the total lines needed for this design from 6 lines to 4. This allows for a 33% cost savings in parts, construction time and control systems for this portion of the bioreactor. All the while simplifying the design, increasing redundancy and decreasing potential failure points.

Alicat’s BIO series controller and meters enable this type of simple and efficient design. And they do so with options for a fully BPE compliant design, certified USP VI elastomers, your choice of industrial protocol and much, much more. Utilizing the unprecedented controllable range in the Alicat BIO series mass flow controllers and meters can reduce your bioprocessing costs while increasing system performance and improving reliability.