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”With CoSAXS we can develop more stable formulations for protein pharmaceuticals”

05 March 2021, 15:31

MAX IV Laboratory in Lund is one of the strongest X-ray sources in the world. Experimental stations, or beamlines as they are called, are ready for use. New beamlines are being commissioned every year, and one of them is CoSAXS.

At CoSAXS information is collected about how X-rays are scattered from different materials, so-called small-angle X-ray scattering (SAXS), and this is used to conclude material properties and molecular structure. It is possible to study a wide range of materials at CoSAXS, from proteins and other macromolecules in solution to foam, clay, paper, plastic, and another type of polymers, both solid and in solution.

Around the world, there are many other synchrotrons that produce X-rays and that house beamlines where researchers can study materials and processes. What separates CoSAXS from similar beamlines at other synchrotrons is the unusually high X-ray coherence. The high coherence creates unique possibilities to develop and use X-ray Photon Correlation Spectroscopy (XPCS) at CoSAXS. XPCS is like dynamic light scattering, but measures scattering from coherent X-rays. Using this technique, we can study diffusion, reorganization, relaxation, slower dynamics in solution equilibrium and non-equilibrium processes.

The intense X-ray radiation at CoSAXS makes it possible to measure samples that would otherwise give too weak signals. The intense beam also makes it possible to perform time-resolved studies down to 100 milliseconds time resolution, in current sample environments. The beam size at beamlines like CoSAXS is generally around 100 micrometers in diameter. However, that are cases where an even smaller beam size is needed, e.g. while measuring a heterogeneous material or if local structural changes are to be investigated. It is then possible to tune the beam size down to around 10 micrometers.

Most materials can be measured at CoSAXS, as long as X-ray radiation can sufficiently penetrate it. Material properties and processes that are measurable depending on the sample environment wherein the sample are placed during measurement. CoSAXS offers a variety of different sample environments to visiting researchers, but it is also possible for them to bring their own. Sample environments at CoSAXS include an automatic sample changer for soluble samples with space for 192 samples at a time. The sample changer is combined with a flowcell wherein the sample resides during the actual measurement. An HPLC is available at CoSAXS that can be connected to the same flow cell and enables separation of particles, usually protein, before measurement. There are also Linkam cells that enable the measurement of samples during heating. These cells change the temperature up to 80 °C/min and can span a temperature range of -195 °C to +300 °C. Sample environments under development include one for time-resolved measurement using stopped-flow, and one using microfluidics. There will also be a rheometer at the beamline for combination with SAXS.

As a multi-purpose beamline, with its ability to measure a wide range of samples, CoSAXS will contribute to academic research as well as industry research in many ways. The possibility to measure 100s of samples efficiently and automatically can help the pharmaceutical industry in finding new and more stable solutions to store drugs in, but also to understand the way other solutions fail to work. Nanoparticles are recurring in different types of industries, with wide use. SAXS has successfully been used to characterize the structure and properties of nanoparticles. The packaging industry can use CoSAXS to study the material properties of plastic and paper in various environments to improve resistance to wear and tear. It is also possible to study porous materials to get an understanding of pore sizes and the ordering of particles inside.

NextBioForm has been using SAXS to study protein pharmaceuticals. One of the studies was recently published in PLOS One and describe the structure of a protein in a solution using SAXS. It was possible to in part describe the internal dynamics of the protein and its interaction with other proteins. In a longer perspective, this can help up understand why under some circumstances this protein starts to destabilize. Further measurements on this protein will be performed at CoSAXS to get a more complete understanding of how and why it is destabilized during e.g. storage at room temperature.

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