Accurate flow measurement for preparative chromatography

Manufacturers of preparative chromatography and supercritical fluid chromatography (SFC) systems therefore integrate advanced flow measurement solutions to ensure consistent product quality. For this purpose, they frequently rely on Bronkhorst flow instruments as part of their system design.

Application requirements

In pharmaceutical applications, equipment must comply with comprehensive User Requirement Specifications (URS), which require extensive monitoring and documentation of critical process parameters. Flow rate is one of the most critical parameters, as it directly influences product quality and yield. Deviations from the specified flow limits can result in batch rejection, potentially leading to significant financial losses. Preparative chromatography systems typically operate with small sample volumes, both in laboratory and industrial environments. As a result, flow instruments must be capable of measuring very low flow rates while maintaining accuracy over a wide dynamic range. In addition to conventional liquid solvents, supercritical fluids (most notably CO2) are increasingly used in preparative chromatography. CO2 acts as an efficient solvent and substantially reduces the consumption of petroleum-based solvents. Depending on the target compound, it may be combined with organic solvents or small amounts of water. When working with supercritical fluids, real-time monitoring of density and temperature is essential. The physical state of CO2 changes rapidly with variations in pressure and temperature, directly affecting process stability. Furthermore, the integration of HPLC pumps requires precise flow regulation. Accurate PID control, combined with continuous pump condition monitoring, is necessary to maintain stable operation, prevent process interruptions and support preventive maintenance strategies.

Important topics

Accurate and reliable measurement of low liquid and supercritical fluid flow rates.

Independent flow measurement for supercritical CO2, unaffected by fluid properties.

Integrated density and temperature monitoring for enhanced process stability.

Precise pump control using embedded PID functionality.

Seamless integration into automated systems via digital communication.

Process solution

For liquid-phase flow measurement and control, an ES-FLOW ultrasonic volumetric flow meter is used. This compact instrument is specifically designed for low-flow applications and provides accurate, repeatable measurements for solvents, co-solvents and water.

For supercritical fluid applications, a Coriolis mass flow meter is installed upstream of the feed pump. Coriolis technology is ideally suited for supercritical CO2, as the measurement principle is independent of fluid properties such as density or viscosity. In addition to mass flow, the instrument provides real-time density and temperature measurements, ensuring that the CO2 reaches the pump in the correct liquid state.

Bronkhorst instruments feature an integrated PID controller, enabling direct control of the upstream pump by adjusting pump speed to achieve the desired flow rate. Continuous monitoring of pump performance allows fine-tuning of control parameters, early detection of clogging or wear, and prevention of heat exchanger or pump failures.

All flow instruments are integrated into the automated control system via digital communication using the PROFINET protocol.

Without direct flow measurement, preparative chromatography systems would rely on theoretical flow curves, typically associated with uncertainties of up to 20%. Such inaccuracies make reproducible extractions and consistent production throughput unachievable.

By measuring the actual volumetric flow of liquids or the mass flow of supercritical CO2, consistent and reproducible yields can be achieved. The process can be fully automated and controlled in real time, providing reliable production quality assurance. This results in improved process robustness, reduced operational risk, and significant savings in time and costs.

“Bronkhorst flow meters give us exceptionally stable flow control — even with supercritical CO₂. Their accuracy and reliable PID control greatly improve extraction consistency and save us valuable time.”