dissolved oxygen in bioreactor

How to Control Dissolved Oxygen (DO) in Bioreactor

DO, or dissolved oxygen, is the amount of oxygen that is dissolved in the liquid medium of a bioreactor. DO is an important parameter for aerobic bioprocesses, such as cell culture or fermentation, that involve the growth and metabolism of microorganisms that require oxygen. DO affects the viability, productivity, and quality of the microorganisms and their products.

Controlling DO in a bioreactor is a challenging and essential task that requires careful monitoring and adjustment of various factors and variables that influence the oxygen transfer and consumption in the bioreactor. In this article, we will explain what are the factors and variables that affect DO in a bioreactor, how to measure and control DO in a bioreactor, and what are the benefits and challenges of controlling DO in a bioreactor.

What are the Factors and Variables that Affect DO in Bioreactor?

The DO in a bioreactor is determined by the balance between the oxygen transfer from the gas phase to the liquid phase and the oxygen consumption by the microorganisms in the liquid phase. The oxygen transfer rate (OTR) and the oxygen uptake rate (OUR) are two key parameters that quantify the oxygen transfer and consumption in a bioreactor.

The OTR depends on several factors and variables, such as:

  • The physical properties of the liquid medium, such as viscosity, density, solubility, etc.
  • The geometry and size of the bioreactor vessel, such as height, diameter, aspect ratio, etc.
  • The agitation system of the bioreactor, such as impeller type, speed, number, location, etc.
  • The aeration system of the bioreactor, such as sparger type, flow rate, pressure, gas composition, etc.
  • The presence of baffles or other devices that enhance mixing and prevent vortex formation in the bioreactor.

The OUR depends on several factors and variables, such as:

  • The type and strain of the microorganisms, such as bacteria, yeast, fungi, mammalian cells, etc.
  • The growth rate and biomass concentration of the microorganisms in the bioreactor.
  • The metabolic activity and product formation of the microorganisms in the bioreactor.
  • The availability and concentration of nutrients (such as sugars, nitrogen sources, vitamins, minerals, etc.) and inhibitors (such as ethanol, lactic acid, etc.) in the bioreactor.

How to Measure and Control DO in Bioreactor?

The measurement and control of DO in a bioreactor are usually performed by using a DO sensor and a DO controller. A DO sensor is a device that measures the DO concentration in the liquid medium of a bioreactor. A DO controller is a device or a software that adjusts the variables that affect OTR or OUR to maintain the DO concentration at a desired setpoint.

A common type of DO sensor is an electrochemical sensor that consists of an anode (usually platinum), a cathode (usually silver), an electrolyte (usually potassium chloride), and a membrane (usually Teflon). The sensor works by applying a voltage between the anode and the cathode and measuring the current that flows through them. The current is proportional to the amount of oxygen that diffuses through the membrane and reacts at the electrodes. The sensor output is calibrated against a standard solution with known DO concentration.

A common type of DO controller is a proportional-integral-derivative (PID) controller that uses a feedback loop mechanism to adjust the variables that affect OTR or OUR based on the error between the measured DO concentration and the setpoint. The PID controller consists of three terms: proportional (P), integral (I), and derivative (D). The P term adjusts the variables proportionally to the error; the I term adjusts the variables based on the accumulated error over time; and the D term adjusts the variables based on the rate of change of error. The PID controller parameters (P, I, and D values) can be tuned manually or automatically to optimize the performance of the controller.

A common way to control DO in a bioreactor is to use a DO cascade that involves two or more controllers that adjust different variables that affect OTR or OUR. For example, a typical DO cascade for cell culture consists of:

  • A primary controller that adjusts the gas flow rate or pressure to control OTR.
  • A secondary controller that adjusts the agitation speed or impeller type to control OTR.
  • A tertiary controller that adjusts the gas composition or pure oxygen flow rate to control OTR.

The primary controller is activated first when there is an error between the measured DO concentration and the setpoint. If the primary controller cannot correct the error, the secondary controller is activated. If the secondary controller cannot correct the error, the tertiary controller is activated. The DO cascade can be set up in and executed by the bioprocess control software.

What are the Benefits and Challenges of Controlling DO in Bioreactor?

The benefits of controlling DO in a bioreactor are:

  • It improves the productivity and quality of the microorganisms and their products by providing optimal oxygen availability and demand for their growth and metabolism.
  • It reduces the cost and waste of the bioprocess by optimizing the gas and power consumption and preventing accumulation of toxic metabolites or excess heat in the bioreactor.
  • It facilitates the scale up and technology transfer of the bioprocess by standardizing the DO control strategy and parameters for different scales and types of bioreactors.

The challenges of controlling DO in a bioreactor are:

  • It requires accurate and reliable measurement and control devices and software that can handle the complexity and variability of the bioprocess and the bioreactor.
  • It requires careful tuning and optimization of the DO control parameters (such as PID values, cascade levels, setpoints, etc.) that can vary depending on the type and stage of the bioprocess and the bioreactor.
  • It requires coordination and integration of the DO control with other control systems (such as temperature, pH, nutrient delivery, etc.) that can affect or be affected by the DO control in the bioreactor.

Conclusion

DO is an important parameter for aerobic bioprocesses that involve the growth and metabolism of microorganisms that require oxygen. DO affects the viability, productivity, and quality of the microorganisms and their products. Controlling DO in a bioreactor is a challenging and essential task that requires careful monitoring and adjustment of various factors and variables that influence the oxygen transfer and consumption in the bioreactor. There are different methods and devices for measuring and controlling DO in a bioreactor, such as DO sensor, DO controller, PID controller, DO cascade, etc. Controlling DO in a bioreactor has several benefits and challenges that need to be considered and addressed for optimal bioprocess performance.

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