Chemist develops X-ray vision for quality assurance

July 24, 2014
Two different crystal forms of the protein insulin. The illustration to the right shows two different crystal forms of insulin using single crystal diffraction, while the graphs to the left present two different insulin ‘fingerprints’ taken using powder diffraction. Credit: Technical University of Denmark

It is seldom sufficient to read the declaration of contents if you need to know precisely what substances a product contains. In fact, to do this you need to be a highly skilled chemist or to have genuine X-ray vision so that you can look directly into the molecular structure of the various substances. Christian Grundahl Frankær, a Postdoc at DTU Chemical Engineering, is almost both, as he has developed a method that allows him to use X-rays to look deep into biological samples.

The 'Fingerprints' of a Substance

The technique is called 'powder diffraction' and involves subjecting a sample to an intense beam of X-rays. When the beam hits the sample, it disseminates in the same way as light does when reflected by a disco ball. This generates a pattern that reflects the structure of the material. Each individual substance has its own unique pattern—a kind of 'fingerprint'—which makes it readily identifiable when the results are run through a database.

Powder diffraction is currently used to identify simple substances such as sugar, salts and minerals, but the idea of using the same technique to characterize advanced biological molecules such as proteins is truly innovative. It is for this reason that the method has enormous potential in both food production and the pharmaceutical industry, where more and more attention is being devoted to -based medicines.

"I have tested different types of infant milk formula, protein powders and detergents. By taking a small sample of powder and bombarding it with X-rays, I can determine what substances the powder contains—and in what concentrations—within ten minutes. In addition, the analysis will typically reveal some information about how the product was made," relates Christian Grundahl Frankær. The method is therefore ideal for quality assurance of new products on the market.

Crystal Forms Determine Properties

Proteins are large molecules with complex 3D structures. The shape of a protein—or its crystal structure—can significantly alter its properties. A protein such as insulin may have many different crystal forms, and the form the substance appears in may affect its solubility or level of activity. This, in turn, may be of significance to how the protein will react when it enters the human body. For this reason, it makes a lot of sense to analyse the crystal forms of different proteins both during production and in the quality assurance of protein-based medicines, but this has simply not been practical nor financially viable until now. Christian Grundahl Frankær explains:

"We have now demonstrated that can actually be used on biological substances such as proteins. The results are not as detailed as in single crystal diffraction, which makes it possible to decode the entire structure of the protein, but they do allow us to 'lift fingerprints' quickly and easily so that we can identify the protein and its crystal structure. This is valuable knowledge when you are working with the production of proteins."

Quick Answer

The method has great potential in the context of optimizing both quality and production processes in all production set-ups that involve solid substances. Applying the new method will make it possible to check continuously for changes in—or transformations of—different substances used in the production process.

"The advantage of our method is that it allows you to take samples directly from a production line. You then have the results within 15 minutes and can tell precisely what crystalline material is involved. In addition, the X-ray beams we use can easily be generated using standard laboratory equipment," relates Christian Grundahl Frankær. The encouraging results are only the beginning.

"What we want to do now is to test how far we can push the method. We have already established that it works on proteins, but will it also work on other complex products? And what happens if we take the samples to the synchrotron in Grenoble, where the X-ray beam is a million times more powerful than the one we have in our laboratory?" asks Christian Grundahl Frankær.

Explore further: Investigating the detailed structure of large biomolecules with a non-damaging X-ray technique

Related Stories

Powders show their strength

October 9, 2007

[PIC=:left]Growing a single crystal of a protein can be very difficult. Thanks to recent developments, a powder sample may be enough to solve a structure.

A new approach for solving protein structures

September 6, 2012

(—Using synchrotron x-ray beams to solve the molecular structures of proteins and other large biological molecules has yielded many advances in medicine, such as drug therapies for cancer. Improvements in the techniques ...

Tiny crystals could revolutionize structural biology studies

November 20, 2013

For structural biologists, the first step in determining a protein's precise molecular structure is often the hardest: coaxing the protein to grow into the orderly, three-dimensional crystals that are the starting material ...

Recommended for you

How the Earth stops high-energy neutrinos in their tracks

November 22, 2017

Neutrinos are abundant subatomic particles that are famous for passing through anything and everything, only very rarely interacting with matter. About 100 trillion neutrinos pass through your body every second. Now, scientists ...

Lightning, with a chance of antimatter

November 22, 2017

A storm system approaches: the sky darkens, and the low rumble of thunder echoes from the horizon. Then without warning... Flash! Crash!—lightning has struck.

Quantum internet goes hybrid

November 22, 2017

In a recent study published in Nature, ICFO researchers led by ICREA Prof. Hugues de Riedmatten report an elementary "hybrid" quantum network link and demonstrate photonic quantum communication between two distinct quantum ...

Enhancing the quantum sensing capabilities of diamond

November 22, 2017

Researchers have discovered that dense ensembles of quantum spins can be created in diamond with high resolution using an electron microscopes, paving the way for enhanced sensors and resources for quantum technologies.

Study shows how to get sprayed metal coatings to stick

November 21, 2017

When bonding two pieces of metal, either the metals must melt a bit where they meet or some molten metal must be introduced between the pieces. A solid bond then forms when the metal solidifies again. But researchers at MIT ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.