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A Sensitive, Compact, In Situ Biomass Measurement System

November 19, 2009

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A Sensitive, Compact, In Situ Biomass Measurement System

By Christian Kaiser, John P. Carvell, and Reiner Luttmann

Of all available on-line biomass assays, the radio-frequency impedance (RFI) method has a clear advantage for process development and manufacturing: It is an unambiguous reflection of viable cell biovolume rather than the total number of cells. Viable cell concentration is of prime importance in metabolic studies and others relating to the efficiency of target protein production. RF impedance is also suitable for measuring live cell densities in bioreactors when cells are attached to microcarriers or inert discs.

Measuring optical density (OD) using light absorption (usually at the 600 nm wavelength) is widely used to monitor biomass off-line during bacterial fermentations. In-line optical sensors have been developed for that purpose, and they rely on transmittance, absorbance, and/or backscattering measurements. In general, their performance is acceptable for high-viability cell culture applications, but light-based probes do not distinguish between the viable and nonviable cells. They will also detect debris, aggregates, and other noncellular particles that can collect during fermentation (1, 2). Moreover, the optical sensors are prone to fouling from the attachment of proteins over extensive production runs. In highly aerated fermentors, light-based sensors are prone to interference from gas bubbles during aeration, and calibration must be conducted by polynomial approximation of the relationship between in-line and off-line optical density.

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A Sensitive, Compact, In Situ Biomass Measurement System

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