Capacitance is used to monitor "biomass" in cell culture and fermentation processes. The present work explores various ways to support good manufacturing practices (GMP) use and create robust methods that can assure proper performance of capacitance equipment. An at-line capacitance measurement method is particularly valuable as it can be used to correct or confirm online measurements from bioreactors. To obtain consistent predictions of online capacitance, the at-line method requires appropriate control of culture temperature, vessel geometry, mixing, and timing. The at-line method yields values that differ systematically from online values, but the variation is ≤11% for two cell lines tested. A cell line-specific conversion factor addresses the difference and enables accurate predictions of online capacitance values. In addition to the at-line method, verification of equipment performance is further enabled by using formaldehyde-treated cell standards. The cell-derived standards create a stabilized system for studying capacitance and recapitulate the performance of metabolically active cell culture. The formaldehyde-treated cells, however, require a much greater conversion factor to predict online outputs. The stabilized system proves useful for evaluation and calibration of capacitance measuring systems. The at-line method and stabilized cell-derived suspensions support use of capacitance for process control in large scale mammalian cell culture.

Portions of this document may be illegible in electronic image products. Images are produced from the best available original document. FOREWORD w Development and comnercialization of hydrothermal resources for electrical energy production is recognized as a complex political, environmental, and economic undertaking. Substantial uncertainty exists concerning the degree t o which the economic climate, environmental changes, and political actions w i l l influence development and ultimate comnercialization. d This research report is one of a series being prepared as part of the Department of Energy's project entitled "Economic Valuation of Geothermal Environmental Impacts." The goal of this project is t o provide information and support for program planning, research, and marketing activities directed toward the comnercialization o f hydrothermal resources. A primary objective of t h i s work includes developing ways to identify, estimate, and mitigate the nonmarket cost impediments t o the commercialization of hydrothermal resources. Pacific Northwest Laboratory (PNL) is conducting this project for the Department of Energy, Office of Hydrothermal C m e r c i a1 i zati on, under Contract No. AE-30-03-02.

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