Guided Wave Radar at Genentech

A Novel Technique for Non-invasive Volume Measurement in Disposable Bioprocess Bags

By Bryan Bean, Tim Matthews, Neria Daniel, Steve Ward, Brad Wolk, Genentech, Inc.

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upward fold

This was done for Runs #2-4 and the results from Figures 4 and 5 indicate improved GWR accuracy.
  • The GWR accuracy improved as the fill volume increased, likely due to greater static head pressure inside the bag. The increased pressure naturally eliminated major creases and folds and helped draw the bag film tightly against the inside walls of the bioprocess container and GWR probe, leading to extremely accurate and consistent GWR readings between 250-475L as seen in Figures 5 and 6.
  • It was difficult to measure volumes under 50L accurately using GWR, especially during the fill. With a low static head pressure, the bag did not press tightly against the GWR probe or conform to any consistent shape, thus GWR liquid measurements within this range were typically inconsistent.
  • Some of the largest deviations in GWR accuracy occurred within the range of 150L-200L. Since the GWR reading was consistently low for all four runs, accuracy may be improved by recalibrating within this range or incorporating additional strapping points.
  • GWR consistency improved with the presence of an air pocket above the liquid surrounding the GWR probe (Figure 9). The air pocket prevented liquid from drawing into the upward fold and impacting the GWR signal. Under these conditions, the liquid level at the probe was fully representative of the bulk liquid level.
  • Overall, the GWR was accurate and consistent as seen by the 95% confidence bars in Figures 5 and 6. GWR appears to be a reliable method for liquid volume measurement as long as the calibration is done carefully.
  • 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%.

    Genentech electron beam

    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.

    GWR Limitations:

    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. 


    References

    1. http://en.wikipedia.org/wiki/Time_domain_reflectometer

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