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What is Chromatography?

Chromatography is a complex downstream purification process in biopharma manufacturing that involves the separation of components in a mixture. In other words, it is used to separate and then purify the biopharmaceutical drug or target molecule (e.g., monoclonal antibody) from other molecules and impurities in the mixture. This purification takes place in a chromatography column, which is a cylindrical vessel fully packed with small 50-100μm chromatography beads, also called resin or sorbent, that is immobilized inside the column.

During the purification process, the mixture of product and impurities (called the mobile phase) enters the column and passes through the packed bed of the resin (stationary phase). The separation is caused by selective binding (adsorption) of the target molecules to the beads, which can be influenced by such factors as conductivity, pH, salt type and other operating conditions.

Under ideal conditions, the target molecules (the product) bind to the resin while impurities and other unwanted molecules pass through the column and will be washed away. Those separation conditions are defined by the composition of the liquid phase and can be changed dynamically in so called gradients. After the washing step, the target molecules are released (eluted) from the resin and are separated from impurities.

Picking the Right Downstream Pump for the Job

Realizing the importance for pumping equipment that feature the design and performance characteristics required for chromatography systems, Quattroflow® offers quaternary (four-piston) diaphragm pump technology. Specifically designed for critical biopharma applications, Quattroflow pumps help ensure a reliable production and a safe end product thanks to a variety of features and benefits, including:

Pressure capability
Pumping liquid through a chromatography column requires a relatively high pressure of 3 bar or more. This is caused by the back pressure from the chromatography column. Quattroflow pumps offer pressures up to 6 bar for multiple-use and up to 4 bar for single-use processes.

Flow characteristics
The flow rate of the pump is proportional to the motor speed, which simplifies the accurate control using PID control loops. In addition, the stability of the flow rate with changing discharge pressures is relatively low.

High turndown
Using a powerful and accurate servo motor, Quattroflow downstream pumps offer a broad flow-range and allow stable operation even at lower flow rates. This is especially essential in gradient chromatography where the composition of the liquid phase is changed continuously, which is typically achieved with two or more pumps running in parallel.

Low pulsation
Due to the consecutive actuation of four diaphragms, the pulsation is minimized to attain stable and repeatable flow conditions while achieving controlled conditions.

Q-Control Pumps

How Quattroflow Quaternary Diaphragm Pumps Work


The main advantage for using a Quattroflow pump is its unique form of operation: The four diaphragms are driven one after another by a connector plate, which moves b ack and forth out of its central position in a stroke that is generated by an eccentric shaft, with the length of the stroke determined by the angle of the eccentricity. In other words, the Quattroflow technology has been modeled on the operation of the human heart – which is capable of pumping whole human blood, one of the most shear-sensitive products in the world – with its four pumping chambers and check valves keeping product flow constantly moving forward. The pump chambers also do not require a mechanical seal or wetted rotating parts that can be subject to friction, ensuring total product containment without abrasion and minimum particle generation. Additionally, the four-piston pumping principle provides risk-free dry running and self-priming.

Hygienic and Precise Flow Measurement

Chromatography systems also require a hygienic and precise measurement of flow rates. Em-tec, part of PSG®, a Dover company, offers flow measurement systems based on the ultrasonic transit time method: media-contact free and in accordance with the strict hygienic requirements of the biopharmaceutical industry. Depending on the variant, several flow rates can be measured simultaneously using one system.

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