Continuous processing and single-use applications with SONOFLOW CO.55 Flow Sensors

Non-invasive SONOFLOW CO.55 Flow Sensors in Continuous Processing & Single-Use Applications to fulfil PAT-Requirements in Biopharma Production

The ever-running trend for supporting closed operations with flexible single-use solutions (SUS) designed for continuous processing reflects a paradigm shift in biopharmaceutical facility design. Utilized in almost all new products in early clinical trials so far, SUS are progressively applied in GMP environments as well. The combination of SUS and continuous bioprocessing is changing the industry’s conception of itself, having a significant impact on facility design by offering a smaller equipment footprint and substantially lower cleaning requirements. The implementation of a continuous process monitoring, in turn, guarantees to keep process stability and to raise overall efficiency.

Flow sensors placed at critical points in upstream and downstream processes

Fulfilling regulatory goals of the Process Analytical Technology (PAT) framework

As PAT has been defined as a mechanism to design, analyze, and control biotechnical and pharmaceutical manufacturing processes through the measurement of Critical Process Parameters (CPP), a constant flow monitoring can fundamentally support its overall targets:

  • reducing production cycling time
  • preventing rejection of batches
  • enabling real time release
  • increasing automation and control
  • improving energy and material use
  • facilitating continuous processing

Continuous Processing: reflecting a paradigm shift in biopharmaceutical facility design

As continuous processing is closely linked to the presence of moving fluids through the system and operates different volume and flow rates fed by peristaltic pumps, non-invasive flow sensors can reliably assume the requirements of PAT. Within upstream and downstream processes, clamp-on flow meters have been successfully placed at the following critical points:

  • Media Prep: replacing scales for volume measurement
  • Inoculation: injecting cell lines into the reactor
  • Bioreactor: feeding media/nutrients, control flow into and out of the bioreactor and ATF filters
  • Centrifugation: determining flow/no flow
  • Buffer Prep: replacing scales for volume measurement
  • Chromatography: balancing acid/base delivery to the system
  • Filtration: controlling process conditions during filtration
  • Tangential Flow Filtration: measuring flow rates on feed, permeate or retentate lines
  • Fill/Finish: measuring volume of fluid dispensed into containers

SONOFLOW CO.55 Clamp-On flow meters in bioprocessing applications

Media and/or Buffer Prep

Non-invasive flow sensors have effectively replaced lab scales in upstream and downstream bioprocessing such as in media and/or buffer prep. As both, scales and ultrasonic flow sensors perform highly accurate volumetric measurement, flow sensors have some considerable advantages over scales. Once calibrated to a certain environment and flow regime, the sensor operates reliably and accurately.

Their application is time-, space- and money-saving since it is highly flexible in use. A modern flow meter is ready for automation and largely insensitive to outer influences such as vibrations and air flow. Its non-contact to the measured liquid underlines the need to keep sensitive systems closed and prevent from contamination throughout all processes in biopharma production.


High performance liquid chromatography (HPLC) is widely used as the first separation step in downstream processing. As a constant and reproducible flow rate is important in chromatography, flow sensors can assume a number of important tasks such as to monitor and to provide feedback for pumps. Furthermore, they are used to monitor feeding lines of buffer solutions and can be applied on solvent lines.

Tangential Flow Filtration

Tangential flow filtration (TFF) or cross flow filtration is widely used in up and downstream processes such as for steps in cell harvesting, cell/lysate clarification, fractionation, concentration or diafiltration. The liquids to be filtered are fed in parallel to the filter. This allows solids to be kept in solution and to minimize the buildup of a "filter cake".

Clamp-on flow meters placed at the permeate line of hollow fiber cartridges record flow rate changes during pressure and exhaust cycles or fulfil volume totalizing tasks in place of scales. Further to these tasks, flow meters can be used for flow control on feeding and retentate lines.

Continuous/Perfusion Reactors

Continuous/perfusion reactors are key in keeping a reliable upstream process flow. As fresh media flows into the bioreactor continuously, and media is removed from the bioreactor at the same flow rate, highly accurate flow measurement systems are essentially needed to monitor these critical parameters. Non-invasive flow sensors can control inflow and removal rate and assure that they are equal. Yet again, the sensors flexibility and low equipment footprint is one of its most valuable advantages. Flow meters can be easily used on flexible tubing sets, maintain reactor sterility, guarantee a stable calibration, and are easy to automate.


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Mandy Reber

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