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Cell Culture Harvest Studies:
The volume measured by GWR was comparable to the water fill studies for all 11 runs (Table 2 and Figure 7). The difference between floor-scale and GWR measurements varied from 0L to 12 L and the maximum deviation was 5.7%.
Figure 9. Air pocket in bag improves GWR accuracy
GWR accuracy improved at higher fill volumes, which is also consistent with the water fill studies. Accuracy could have been improved further by manipulating the bag film surrounding the GWR probe and incorporating an air pocket similar to Figure 9.
There are limitations for this particular GWR system, such as the minimum and maximum volume detection limits. Because of the location of a bioprocess bag’s heat-sealed edges, the top of the bag does not remain flat as the bag approaches its maximum fill volume. Instead, the top becomes “dome-like” and the bag film and liquid pull away from the GWR probe, preventing accurate measurement. Under this scenario, the GWR reading would be artificially low. There are very few applications where bioprocess bags are filled to capacity because of the danger of overpressurization and bag failure. Furthermore, this issue can be resolved by using slightly oversized bags. The limitation of maximum volume measurement of GWR must be assessed for each individual application.
There is also a minimum volume limitation for GWR since the bag must be in contact with the probe to obtain an accurate signal. A certain volume of liquid must be present in the bag for this to occur. This volume varies depending on the size of the bag and footprint of the bioprocess container. The minimum volume range may improve with different vessel geometries—for example, a tall, cylindrical vessel with conical bottom.
Another limitation of GWR is signal variability due to floor slope. Floor slope may be a factor for portable bioprocess containers whose volume is measured in more than one location. Since the GWR probe is not centered in the middle of the bag, any floor slope from front to back of the bioprocess container may result in some degree of error. Floor slope was not a factor for these experiments since GWR volume was measured on a stable, level floor scale.
A fourth limitation of GWR is that the bag must be manipulated to produce the most accurate and consistent volume readings, as seen in the water fill studies. Bag manipulation may not be realistic for large bioprocess containers (>1000L) in which the top of the bag is not readily accessible.
Recommendations and Future Work
Based on the results of this study, GWR appears to be a viable option for non-invasive volume measurement of liquid in bioprocess bags. GWR is robust and ideal for portable bioprocess containers, it provides relatively accurate, consistent volume readings, and it is relatively cheap and easy to install on new and existing bioprocess containers. Also, the stainless steel GWR probe can be bent to conform to the geometry of almost any vessel.
We recommend using GWR for portable bioprocess containers in place of load cells or pressure transducers. Floor scales are also a reliable option but are expensive, are not available in all facilities, and they present a safety risk when transporting heavy containers on and off the scale. In addition, the floor scale may not be positioned next to process skids. Since the GWR probe is installed on the actual bioprocess container, volume can be measured wherever the bioprocess container is being used.
GWR may also be suitable for bioprocess containers greater than 500L volume. We recommend conducting additional studies to support use of this technology for larger bags.
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