Biosensors & Computers Help Optimize Bioprocessing Systems

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clip from the Archives, MAY 1987, p16
From the Archives, MAY 1987, p16

EDITOR’S NOTE: Late last year, Brandessence Market Research and Consulting released a study (“Bioprocessing Analytics Equipment Market”) that raised two key points: First, devices that perform multiple functions and automate quality assurance are reducing error rates. Second, devices that incorporate “smart sampling” are improving the integration of upstream and downstream activities.

Such devices were at an early stage in 1987, when the text below first appeared. It comes from a GEN article that described how bioprocessors of the time were looking to electronics to improve the accuracy of monitoring and control. The article discussed several companies that introduced some of the first systems to bring sophisticated electronics to biomanufacturing.

Biotechnologists are turning increasingly to electronics for new solutions to bioprocess control requirements. Biosensors and computers, which monitor and keep records of the inflow of nutrients to the biological product as well as the outflow of metabolites, are helping bioprocess engineers reach their ultimate goal: the optimization of biological production.

Several companies are working on novel process monitoring and control systems that can be applied to the production of a range of biological products including monoclonal antibodies and recombinant cell culture proteins.

Perfusion cell culture systems, such as the OptiCell 5200R™ made by Charles River Biotechnical Services in Wilmington, MA, provides a very sensitive and reliable way to measure physiological parameters, according to Randall J. von Wedel, PhD, president of a San Francisco–based consulting firm, Cytoculture International. By monitoring and controlling a bioreactor’s oxygen consumption rate, the OptiCell can determine whether the cells are propagating efficiently.

The system uses six probes to monitor as many as 12 parameters. It measures oxygen in, oxygen out, pH in, pH out, media flow rate, percentage oxygen across the permeator, percentage nitrogen across the permeator, total gas flow, temperature in, temperature out, and run time.

Utilizing a patented ceramic substrate called OptiCore™, the closed-loop perfusion system enhances the viability of the culture by selectively removing dead cells from live cells. Cells adhere to the small cylindrical unit, which has a high surface area per unit of volume. The immobile culturing medium consists of a ceramic matrix encased in plastic.

Systems such as the OptiCell 5200R provide the advantages of instant, real-time readouts and constant information flow. In order to process biologicals continuously, the biotechnologist needs a custom-built electronic system to integrate various cell culture and bioprocess technologies. Ideally, such a system would have dedicated microprocessors monitoring and controlling all of the parameters and a master microprocessor overseeing the entire process, according to von Wedel.

Holtz Bioengineering (Morgan Hill, CA) has developed a flexible, easy-to-use, and relatively inexpensive cell culture/bioprocessing control system that evolved out of its own needs. The seven-year-old company, which manufactures fermentation products, built this system for its own use and then developed a commercial version, the Proteus-2000.

“We do fermentation for a living. We’re not an instrument manufacturer,” said Barry Holtz, PhD, president of the company. “It’s a case of a chemist telling an engineer how to make a system motivated by the actual needs of a scientist.”

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