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PuK - Process Technology & Components 2024

A technical trade magazine with a history of more than 60 years.

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Pumps and Systems<br />

Diaphragm metering pumps<br />

Fig. 2: The inline dilution systems use multihead<br />

diaphragm metering pumps specially<br />

designed for pharmaceutical applications.<br />

(Source: LEWA)<br />

luted to achieve the desired working<br />

concentration. The choice of solution<br />

depends on the subsequent steps in<br />

the downstream process. After the<br />

actual chemical synthesis, in which<br />

the nucleotides are added one after<br />

the other to a growing chain, the<br />

synthesized products undergo what<br />

is known as deprotection and purification<br />

steps to remove unwanted<br />

by-products. Accompanying process<br />

and quality control, e. g. in the form<br />

of mass spectrometry, ensures that<br />

the end product is within the defined<br />

specification window.<br />

Continuous flow regulation<br />

and keep the fluid quantity constant<br />

by controlling the speed of the metering<br />

pumps precisely. Pressure control<br />

valves with integrated electronically<br />

controlled pneumatic damping installed<br />

in the output-side manifold<br />

maintain low fluctuation and keep<br />

the mixing flow almost constant. This<br />

also applies to the pressure: Fluctuations<br />

are undesirable for the built-in<br />

measuring chains and interfere with<br />

the separation processes in the chromatography<br />

columns. Gas phase<br />

components and any temperature increase<br />

also have to be prevented.<br />

After the mixing result is combined<br />

in the manifold, the ratio is analyzed<br />

using appropriate measurement<br />

technology, e. g. via the pH<br />

value and electrical conductivity. After<br />

programming the stored target<br />

values in the higher-level control system,<br />

these are available as different<br />

methods for system control. The recorded<br />

measured values are determined<br />

at a high sampling rate and<br />

continuously evaluated centrally. The<br />

pumps used must be corrosion-resistant,<br />

hygienic and have a robust design<br />

for continuous use. LEWA has detailed<br />

knowledge and many years of<br />

experience in high-precision metering<br />

and mixing thanks to its de cades in<br />

the field of pump supply for the process<br />

chromatography of major OEMs.<br />

And this has also benefited the design<br />

of correspon ding mixing and metering<br />

systems for oligo synthesis customers<br />

for some years now.<br />

Fig. 4: Pressure control valve with damping<br />

properties equipped with an electronic pilot<br />

valve for automatic control.<br />

(Source: EQUILIBAR)<br />

Package units for individual<br />

dilution tasks<br />

The dilution systems designed and<br />

described are not standard systems,<br />

but customized inline metering and<br />

dilution systems that are designed<br />

and constructed as package units<br />

(PU) for the respective downstream<br />

process. A system of this type can<br />

have up to five process inlets and<br />

outlets – sometimes more – as well<br />

as various other connections, for example<br />

for flushing or waste water, to<br />

ensure flexible and continuous fluid<br />

transport. A cycle of chemical reactions<br />

is initiated by feeding in the<br />

respective synthesis fluids. Individual<br />

nucleotides are coupled and the<br />

desired modified chain sequence is<br />

In order to meet increased demand<br />

by expanding production capacities,<br />

precise and continuously operating<br />

inline dilution systems must be provided.<br />

One of the biggest challenges<br />

here is maintaining a consistently reproducible<br />

quality of the required<br />

buffer within the narrow window for<br />

permissible concentration deviations.<br />

Among other things, continuous<br />

monitoring of the flow rates and the<br />

resulting dilution ratios is essential<br />

for this. Therefore, inline dilution systems<br />

typically consist of several channels<br />

with valves, where each channel<br />

is equipped with a multi-head<br />

diaphragm pump and a Coriolis flow<br />

meter. They measure the mass flow<br />

Fig. 3: Pressure control valves with integrated electronically controlled pneumatic damping<br />

installed in the output-side manifold maintain low fluctuation and keep the mixing flow almost<br />

constant. (Source: LEWA)<br />

PROCESS TECHNOLOGY & COMPONENTS <strong>2024</strong><br />

21

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