The cause of the hypodermic needle blockage was discovered

In very rare cases, injections of pre-filled syringes may be blocked. This can cause harmful effects if the patient's medication does not enter the body or the dosage is too low.

A team from the Paul Scherrer Institute PSI, led by the ANAXAM Technology Transfer Center in collaboration with MSS, has now been able to look inside such needles in detail. The researchers were able to determine the possible causes of blockages and create conditions to prevent them in the future.

Key is the combination of imaging techniques at the Swiss Light Source SLS and the neutron source SINQ. Both are located in close proximity to each other at the PSI site—a group that is unique in the world. As a result, chemical engineer Vladimir Novak and physicist and CEO of ANAXAM Christian Grunsweig say, „We have succeeded in seeing the inside of a needle in more detail.”

Prefilled syringes (PFS) are increasingly used for cancer therapy, for example, using monoclonal antibodies. However, in a small number of cases, the needles of pre-filled syringes become clogged. The risk of this is increased as therapeutic agents containing proteins and antibodies are highly concentrated, highly viscous, and offer greater resistance to fluid flow.

No reliable statistics are available on the mean frequency of obstruction. Researchers discuss fluctuating pressure or temperature conditions as possible causes, for example, when transporting blocks.

Pressure and temperature fluctuations are possible causes

A team led by chemical engineer Vladimir Novak, head of the project team and researcher at ANAXAM, tested this hypothesis in a series of measurements. For example, 31 PFSs were exposed to changes in temperature between 5 and 40 degrees and changes in pressure between 550 and 1010 millibars. Such conditions usually occur during flights carrying medical supplies. The team examined the needles using both synchrotron X-ray and neutron beams.

Both imaging modalities have certain advantages. Neutrons can penetrate metals well, but are deflected by hydrogen atoms, which occur in liquids, thus producing a clear contrast. „Neutron radiography allows visualization of the fluid inside the needle in 2D, thereby varying both ambient pressure and temperature while measuring the syringes,” explains David Mannes from PSI's Laboratory for Neutron Scattering and Imaging.

Conventional X-ray computed tomography typically cannot visualize low-density fluids within stainless steel in such detail because the transmitted light beam is insufficient. However, this can be achieved using partially coherent beams such as those available at PSI's SLS.

Synchrotron X-ray tomography provides high-resolution 3D imaging to study the detailed interfaces between air and fluids inside the needle. „The new application of this technique represents the first attempt by the scientific community to investigate the needle blockage problem using synchrotron X-ray tomography,” explains Margie Olbinado, industrial liaison scientist for SLS's Tomcat beamline at PSI.

The measurements clearly showed that fluctuations in ambient conditions led to deposits on the metal of the needle. Both pressure and temperature fluctuations force fluid into the needle, where air bubbles can also form. As the fluid dries, it leaves plugs or deposits inside the needle.

Manufacturers, distributors and users should ensure uninterrupted cold chain and constant pressure during transport and storage of PFS. „The combination of neutron imaging and synchrotron X-ray tomography clearly demonstrates this,” says Novak.

Findings are Published In the magazine Drug research.