Incyte Arc Applications
Intelligent, Real-Time VCD Measurement
The long-awaited Incyte Arc sensor combines the benefits of a reliable and continuous viable cell density (VCD) measurement with the intelligence of the Arc platform. Real-time measurement provides immediate detection of changes to viable cell density and cell physiology, enabling immediate process events and automated process control.
Arc sensors contain all required electronics in the head of the sensor itself, minimizing space requirements and eliminating transmitter and preamplifier costs. This functionality is exploited in Incyte Arc to store the precision of a factory calibration for a virtually maintenance-free sensor. The intelligence in the sensor provides information on the sensor status at all times, even throughout a run, for easy diagnostics and troubleshooting. Modbus and OPC communication can be employed for complete SCADA integration. 4-20 mA is also available for simplified permittivity signal integration. The range of outputs allows the same sensor to be used at all process scales.
“The Incyte Arc sensor is perfectly suited for the biopharma industry,” states Dr. Knut Georgy, Senior Market Segment Manager Process Analytics at Hamilton Bonaduz AG, referring to the hygienic design and sterilizability, in addition to the advanced measurement technology. The robust real-time measurement is not affected by dead cells, media debris, or composition changes, providing a direct measurement of viable cell density. This allows for optimization of the cell culture towards consistent, reproducible growth. Users of this technology have gained higher yields, lower costs, improved automation, and many other benefits. The following are specific examples of how Incyte is being used to benefit processes across the industry.
Seed Train Transfer for Increased Productivity
Automated transfers ensure that tight transfer windows are hit precisely every time. Removing imprecision of off-line sampling, human efforts, and run-to-run variations guarantees the seed train is rolled at the optimal density. Automated control also means that nobody has to come in when a transfer happens at night or over the weekend.
Perfusion Control Maximizes Efficiency
Feed: Precise measurement of VCD allows the exact amount of media feed needed for optimal growth. When employed with growth rate calculations, Incyte data can be used to increase the rate of feed corresponding to drops in growth rate. Such a dynamic feeding approach can be used to substantially increase the length of the production phase. Nutrient limitations caused by underfeeding can lead to diminished productivity, while overfeeding can lead to unnecessarily high costs and media accumulation in the reactor, especially over a weeks long run.
Bleed: Perfusion processes have the deciency of dead cell accumulation as cell densities rise. Bleed rates of dead cells and spent media can be controlled through inline measurements of VCD. The precision allows optimal reactor conditions for maximum productivity.
Easy Transition for Many Cell Types
Incyte can be used with almost any cell line, as long as it has a polarizable membrane (typical in mammalian, bacterial, and many other types of cells), making it an ideal technology for CMOs and other groups working with many different cell lines or types. This is especially useful for cells on microcarriers or other difficult-to-sample organisms. Seamlessly transition viable cell density analysis with a single instrument and output type.
Extended Production Phase with Beta Dispersion Curves
Data from the beta dispersion curve and fitted Cole-Cole parameters can be used to identify changes in cell physiology resulting from process conditions such as nutrient limitation. With advanced process understanding this information can be used to predict the onset of apoptosis long before it is evident in off-line data. This allows process actions, such as feeding, to be adjusted sooner, thereby extending the production phase.
More Process Information Through Virtual Sensing and Calculations
Incyte data can be used in calculations of specic growth rate, doubling time, viability, and many other important parameters. It can be used as a virtual (or soft) sensor when combined with other data. For example, permittivity can be used as a part of predictive models of glucose consumption that can be used in real time or as a sensor for viability when used with other inputs.
More Efficient Scale Transfer
Incyte can be used in small benchtop reactors all the way up to full scale manufacturing. The continuous permittivity data can be used to efficiently scale up (or down) by providing a real time profile of culture events, enabling straightforward and informed comparisons between process scales.
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