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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Genetech bioprocess container

Figure 2. GWR probe installed in bioprocess container

The bioprocess container with bag was transported to a Mettler Toledo Vertex floor scale (+/- 0.1-kg accuracy; calibration range: 0.0-800.0 kg), which recorded the tare weight. The bag was slowly filled with purified water through the bottom inlet line. The GWR probe was calibrated by recording the GWR output current (mA) and the corresponding floor scale weight using a total of 17 strapping points. The bag film surrounding the GWR probe was manipulated during each measurement to eliminate creases and folds. A picture of the bioprocess container with filled bag is shown in Figure 3.

Water Fill Studies:

A 500-L gamma-irradiated Sartorius-Stedim bag was installed in the bioprocess container and tared on the floor scale. While resting on the floor scale, the bag was slowly filled with purified water to 475L and subsequently drained. GWR and floor-scale volumes were recorded every 25L while filling and draining the bag. This procedure was repeated three times for a total of four runs (Runs #1-4) and a fresh bag was installed after each drain. The floor scale provided a stable, level surface so variability due to floor slope was not a factor.

Genetech bioprocess bag

Figure 3. Container with filled bioprocess bag

During Run #1, the bag was not manipulated or touched, except during the initial fill of the first 25L. GWR readings during the fill and drain for Run #1 are plotted in Figure 4.

During Runs #2-4, the bag film was manipulated between each reading to eliminate creases and folds in the area surrounding the GWR probe, which otherwise could have contributed to error in the GWR reading. Average GWR readings for these three runs, including 95% confidence bars, are plotted in Figures 5 and 6.

Cell Culture Harvest Studies:

The GWR system was also tested in pilot plant operations where we performed eleven fills with Chinese Hamster Ovary harvested cell culture fluid (HCCF), each time using a fresh bag.  The fill volumes varied from 165.4L to 445.1L. After each fill, the bioprocess container was transported to the floor scale and the net weight of the liquid was recorded, taking into account the tare weight of the bioprocess container and empty bag. The volume of liquid measured by GWR was also recorded.  The bag film surrounding the GWR probe was not manipulated in any way prior to recording the volume.  The results were tabulated and the percent deviation between the floor scale and GWR measurements was calculated (Table 2).

The data points were also plotted next to the water fill study average for Runs #2-4 and are shown in Figure 7. The conversion of floor-scale weight to volume was based on an HCCF density of 1.017 kg/L.


Water Fill Studies:

Genetech Figure 4

Figure 4. GWR readings for Run #1 (fill & drain)—no bag manipulation

Genentech Fig 5

Figure 5. Average GWR readings while filling for Runs #2-4

 Genentech Fig 6

Figure 6. Average GWR readings while draining for Runs #2-4

Genetech Fig 7

Figure 7. Cell culture harvest data points (Runs #1-11) 

Cell Culture Harvest Studies:

Table 2. Results from GWR vs. floor-scale comparison study

Click image for full-size table.


Water Fill Studies:

The following observations were made from the water fill studies:

  • Variability in GWR volume measurement was greater when the bag film was not manipulated, such as Run #1, compared to Runs #2-4 where it was manipulated.  Without tugging on the corners of the bioprocess bag during the fill, the bag does not always fill uniformly, especially at fill volumes less than 250 L. Also, by not adjusting the bag film surrounding the GWR probe, the film would trap pockets of water as it folded over, leading to erroneous signals. If the fold extended upward, the liquid level at the GWR probe was above the bulk liquid level and the GWR reading was artificially high (Figure 8). If the fold extended downward, the GWR reading was artificially low.  The best way to mitigate this issue was to manually manipulate the bag film to remove the fold.
    Genetech GWR

    Figure 8. Bag with

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