ASL Pichia Monitor

The yeast Pichia pastoris can be genetically engineered to express proteins for both basic research and industrial purposes. Pichia fermentations require glycerol and methanol for cell growth and protein production, respectively, and these cells are highly sensitive to metabolite concentrations. Currently, concentrations and cell density during Pichia fermentations must be monitored using manual sampling and off-line analyses, making reactor optimization difficult. No satisfactory on-line systems are commercially available.

The ASL Pichia Monitor provides a real-time, continuous monitor for controlling and optimizing metabolite concentrations during the production of bio-therapeutics and industrial enzymes with Pichia pastoris. The monitoring technology is based on non-destructive near infrared spectroscopic sensing. The targeted analytes for Pichia are glycerol, methanol, and biomass (cell density). Figures 1 and 2 display concentration results from representative Pichia fermentations. The results shown in Figure 2 display the ASL monitor’s automated feedback control capabilities. A schematic of the ASL monitor is shown in Figure 3.

Successful concentration measurements with the ASL monitor rely on “Constrained Variance”, an ASL innovation that:

• Reduces sources of spectral variance;

• Focuses the measurement on the molecular structure of the targeted analyte;

• Provides reliable and prospective analytical measurements.

Potential benefits to the user of the ASL Pichia monitor include:

• Maximized product yield

• Minimization of unwanted by-products

• Reduction in the extent of downstream processing

• Reduction in both the time & cost of drug development