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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This article was originally published in our sister publication Pharmaceutical Manufacturing

Disposable bioprocess bags are increasingly being used in biopharmaceutical operations for buffer storage, buffer and media prep, bioreactors, product pooling and storage of bulk drug substance. Disposables offer certain advantages over stainless steel tanks: elimination of CIP/SIP, reduced labor, reduced validation requirements and increased operational flexibility.

Most bag films are multi-layer with a polyethylene or ethyl vinyl acetate fluid contacting layer.  Small bags (≤ 20L) can be handled and stored in a simple tray, but larger bags are typically housed in a bioprocess container—a plastic or stainless steel bin that supports the filled bag.  Bioprocess containers greater than 500L are often stationary while smaller bins are typically portable. New sensor technologies for pH, DO, conductivity, temperature and pressure have recently been developed that are compatible with disposable bag systems. However, one technology that has lagged behind is volume measurement for portable bioprocess containers.

There are several existing methods for volume measurement, including load cells, pressure transducers, graduation marks and floor scales, but all have limitations. Load cells are extremely accurate, but not a robust option for portable systems. Pressure transducers located on the base of bioprocess containers are susceptible to damage and their signals tend to drift over time. In an unpublished study at Genentech, the pressure transducer’s signal drifted up to 5% over 24 hours for a 2500-L bioprocess container system.

This phenomenon is not well understood at the moment. Graduation marks have limited accuracy since the volume is read subjectively by the operator and automated measurement technology does not currently exist.  Floor scales are not always available in the operation area, are relatively expensive and may present a safety risk when transporting heavy containers on and off the scale, especially if the scale has a ramp.

An alternate, novel method for non-invasive volume measurement in bags is guided wave radar (GWR), which will be the focus of this article. An approximate equipment price comparison of these various volume measurement options is provided in:

Table 1: Equipment prices for volume measurement options (2008 prices, w/o installation).

Measurement Method Equipment Price
GWR $2,400(a)
Floor Scale $11,400(b)
Pressure Transducer $1,800(c)
Load Cells $2,600(d)
Graduation Marks $0

 

(a) Magnetrol Eclipse Guided Wave Radar Level Transmitter (705-510A-110) with 50” 316L SS probe
(b)Mettler Toledo Vertex 4’ x 4’ 304L SS floor scale with guard rails, ramp, and transmitter
(c) Rosemount 3051S 2” tri-clamp pressure transducer with transmitter
(d) Kistler Morse LD3-02K-X-015-X-X (4 load cells)

Guided wave radar is based upon the principle of time domain reflectometry (TDR). TDR is a measurement technique used to determine the characteristics of electrical lines by observing reflected waveforms Pulses of electromagnetic energy are transmitted down a probe and the pulse is reflected when it reaches a liquid surface. The distance to the reflecting surface is determined by the return time of the pulse to the source [1].

GWR technology is commonly used for fluid volume measurements in traditional stainless steel tanks. However, GWR can also be used non-invasively for disposable bioprocess bags. If the probe is in close contact with the external surface of a filled bag, the electromagnetic pulse from the probe can penetrate the plastic film barrier to detect the air/liquid interface without being in direct contact with the liquid. Therefore, in bioprocessing applications where sterility is important or non-disposable instruments cannot contact the fluid, GWR may be a viable option.

Experimental Procedure

To test the accuracy of a GWR system with bioprocess bags, we installed a GWR probe and transmitter on a ConeCraft 500-L 304L stainless steel portable bioprocess container (Figure 1). 

Genetech 500-L portable bioprocess container

Figure 1: 500-L portable
bioprocess container

The probe (Model 7XF-E) was made of 316L stainless steel with a ½-inch diameter and 50.3-inch length. The transmitter was a Magnetrol Eclipse Enhanced Model 705. The probe was bent to a right angle and routed through a hole drilled into the back left corner of the bioprocess container (Figure 2). The vertical section of the probe extended from the top of the bin to the base, maximizing the volume measurement range. Two plastic spacers were used to create a 3-cm gap between the probe and the back wall of the bioprocess container, improving contact between the bag film and probe. This also eliminated interference between the GWR’s electromagnetic pulses and the back wall. The GWR transmitter was mounted on the outside of the container.

GWR Calibration Procedure:

A 500-L gamma-irradiated Sartorius-Stedim Flexel 3-D bag with Stedim-40 film was installed in the 500-L bioprocess container.

Stedim-40 is a 200 +/- 25-µm thick film constructed from the co-extrusion of seven layers, including ultra-low density polyethylene (fluid contact layer), ethyl vinyl alcohol, polyamide, polyethylene terephthalate, and several tie layers.

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