Application note A072-ME01

Microspheres for liver cancer treatment

Patients who suffer from liver tumours that
cannot be surgically removed nor respond to
chemotherapy, may benefit from a local treatment
with radioactive particles.

Quirem Medical manufactures polylactic acid
microspheres containing radioactive holmium,
suitable for such treatment. These microspheres are
injected in the hepatic artery and are carried along
by the blood flow. The radioactive microspheres will
lodge within the small blood vessels near the liver
tumour where they deliver their radiation locally,
with the aim to kill the tumour cells. Quirem Medical
manufactures the non-radioactive microspheres.
Subsequently, the microspheres are enriched by
neutron bombardment. An essential step in the
synthesis is the controlled evaporation of a solvent
that has been used in a previous step. Bronkhorst
mass flow controllers deliver the nitrogen flow to
enhance and control the solvent evaporation.


Application requirements

Nitrogen is needed to evaporate the solvent, as it
acts as an inert carrier gas that sweeps off the
evaporated solvent and accordingly determines the
evaporation rate. So the correct nitrogen flow is a
very important parameter in the production
process to obtain the right size of the microspheres.

Important topics

  • Correct and stable nitrogen flow rate
  • Monitoring of process conditions
  • FDA approved seals
  • Cleanroom production

Process solution

To evaporate the solvent in the microsphere synthesis, classic type EL-FLOW mass flow controllers are used. There are five batch processes in parallel, each with its own mass flow controller and with a Hepa filter upstream. All of these mass flow controllers have FDA approved seals, to anticipate future use of the product in the USA. These mass flow controllers were manufactured in the cleanroom, and were double packed and sealed delivered. This delivery included all necessary certifications, including a TSE/BSE declaration to demonstrate that no animal fats have been used in the device. Moreover, Bronkhorst MASS-VIEW has been included, to monitor if the mass flow controllers will deviate in due time, which may be a trigger to send the devices to Bronkhorst for recalibration. The correct nitrogen flow is a very important parameter in the production process. The scale of the flow is for Quirem Medical more important than its accuracy. Furthermore, a high quality flow controller (and meter) is necessary: to establish a stable flow, and also to be able to monitor the process conditions - for read out and data storage. They are pleased with the mass flow controller, and satisfied with Bronkhorst’s fast service.

The currently used flow is very suitable to produce microspheres that are used to treat patients. Perhaps in the future will be investigated if a different nitrogen flow rate results in an improvement of the production process.

Flow scheme
Flow scheme

Nitrogen controllers
From raw materials to end product

Bronkhorst High-Tech B.V.

Nijverheidsstraat 1A
NL-7261 AK Ruurlo (NL)
Tel. +31 573 45 88 00

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