In the Nano-Argovia project “NANOCREATE”, scientists from the Paul Scherrer Institute (PSI), in collaboration with the University of Applied Sciences (FHNW) and GratXray AG (Villigen, AG), are developing a cost-effective fabrication method for optical X-ray gratings. These gratings are used in a computed tomography (CT) scanner developed by GratXray that allows for high-resolution, high-contrast imaging of low absorbing tissues, such as the female breast.

Decisive advantages
In classic X-ray imaging, contrast between different tissue types get better the lower the X-ray energy. However, the lower the X-ray energy, the higher the radiation dose that is deposited in the patient. Therefore, classical X-ray imaging is physically limited by the image contrast that can be reached. This limitation can partially be overcome with grating interferometry, where not only the absorption, but also the refraction and scatter of X-ray can be measured. These additional signals are much stronger in soft tissue and thus, allow to significantly improve image contrast under dose control. Integrated in a dedicated breast CT, this technique allows for retrieving unprecedented image quality in 3D, ultimately leading to a more accurate diagnosis of breast cancer.

New fabrication method
Grating interferometry for medical diagnostics has been developed extensively in recent years, but the high production costs of specialized gratings remains a limiting factor for the technique’s broad application. The team behind the Nano Argovia project “NANOCREATE”, led by Dr. Konstantins Jefimovs (PSI), is therefore focusing on the development of alternative manufacturing method, to lower fabrication cost so that gratings can be produced on larger area and in higher volumes.

The scientists at PSI are developing a method based on metal assisted chemical etching to produce silicon structures of high aspect ratio, larger area and lower costs. These structures, which have low X-ray absorbance, are then filled with gold, strongly absorbing X-ray. They want to produce and test the grating performance manufactured by this new method on a lab CT-system. On the other hand, the team at FHNW is testing laser ablation as an alternative method to directly make the gratings from a metal foil. These techniques are now being examined in greater detail as part of the Nano Argovia project.

In addition to the project leader, Dr. Konstantins Jefimovs (PSI), the team consists of Professor Lucia Romano (PSI), Professor Ronald Holtz (FHNW), Dr. Bojan Resan (FHNW), as well as Dr. Martin Stauber and Dr. Zhentian Wang (both of GratXray AG). “The Nano Argovia project “NANOCREATE” will help us in our efforts to make grating interferometry available for a broad range of applications,” says Dr. Martin Stauber of GratXray, a spin-off company of PSI.

In the Nano Argovia project NanoGhip, an interdisciplinary team led by Dr. Martin Ostermaier from InterAx Biotech AG (Villigen, AG) is investigating a new screening method for active substances that could lead to the discovery of new medicines. The scientists aim to develop a new type of biochip that analyzes how the chemical and biological molecules in question react with protein complexes in real time. Even at this early stage, it could also provide information about the safety profile of the tested compounds.

Relaying signals
Membrane proteins play an important role in our cells. As well as being fundamental for our survival, they are involved in the development and treatment of diseases. In this context, G protein–coupled (GCP) receptors are particularly significant. Among other functions, they relay signals to the cell’s interior and thereby regulate a whole cascade of vital reactions. In doing so, many of these G protein–coupled receptors interact with a wide range of proteins to form protein complexes.

Searching for new active substances that influence these receptors is difficult because, instead of analyzing one individual protein, it is important to consider entire protein complexes in order to replicate the natural conditions in the cell as closely as possible. Given that these protein complexes are anchored within membranes in their natural environment, they must also be integrated into membranes for the screening process.

Tiny changes
In order to create a biochip, the researchers in the NanoGhip project incorporate natural protein complexes into synthetic membranes. These have very similar properties to the natural membranes but surpass their natural counterparts in terms of robustness. The researchers then use biosensors to monitor structural changes in the protein complexes when test substances come into contact with the system. These tiny conformational changes of the G protein–coupled receptors have a magnitude of just 0.1 to 1.4 nanometers. Using the protein-based biosensors, the scientists derive information about whether a test substance prevents the GPC receptors from relaying signals to the cell’s interior.

The Nano Argovia project NanoGhip is a close collaboration by scientists from InterAx (a start-up of the Paul Scherrer Institute and ETH Zurich), the Paul Scherrer Institute, and the Department of Chemistry and Biozentrum at the University of Basel, with each of them contributing their own very different areas of expertise. “In this project, we’ve brought together a unique combination of experts that allows us to exploit synergies and explore a new approach to the biological screening of substances on a chip,” summarizes project leader Martin Ostermaier.

In the Nano Argovia project “NanoTough”, scientists from the University of Applied Sciences and Arts Northwestern Switzerland (FHNW), the University of Basel, and the company Huntsman Advanced Materials GmbH (Basel) are investigating the use of block copolymers in composite materials. The aim is to make composites tougher without impairing their workability.

Room for improvement
Plastics that have been reinforced with carbon fibers (fiber-reinforced composites) stand out for their combination of extraordinary mechanical properties and low weight. They are primarily used for building vehicles, aircraft, and ships but also play an increasingly important role in the manufacturing of wind turbines. Their range of applications could be expanded further if the materials were less brittle and if their toughness could be improved. This can already be achieved today by adding thermoplastic powders, but the use of such additives increases the materials’ viscosity and therefore makes them harder to work.

Block copolymers as an additive
The teams of scientists working on the Nano Argovia project “NanoTough” begin by investigating the synthesis of various block copolymers, which they later add to an epoxy resin that acts as a matrix. Block copolymers are polymers assembled from at least two different monomers, with single molecules of the monomers linking up in long chains to form the individual blocks (e.g. AAAAABBBBB). The group led by Professor Wolfgang Meier from the Department of Chemistry first synthesizes a variety of block copolymers (BCPs) with different compositions and masses and then studies how these affect the morphology of the resulting nanostructures.

In addition, the researchers attempt to simulate the conditions found in an epoxy resin system by selecting different solvents and temperatures. Once the BCPs are synthesized and characterized, suitable candidates are selected and then tested in an epoxy resin system by the team working under project leader Dr. Sonja Neuhaus and Professor Clemens Dransfeld (FHNW School of Engineering, Windisch). Key factors include not only the conditions during curing but also the morphology of the block copolymers in fully cured samples. A thermoplastic material is then added, and the morphological characteristics of the new composite material are analyzed.

Lastly, partner company Huntsman works with the FHNW team to characterize the samples’ mechanical properties and compare them with leading commercially available materials. This work centers around experiments to test the fracture properties and the determination of the glass transition temperature under a variety of conditions.

In the NQsense project, the team working under project leader Professor Patrick Maletinsky plans to fabricate a fully integrated quantum sensor with significantly improved sensitivity. This sensor could be used, for example, to support basic scientific research in the areas of materials science or to perform failure analyses in the semiconductor industry.

Diamonds as sensors
The team of scientists from the Department of Physics at the University of Basel, the Paul Scherrer Institute, and the industrial partner Qnami – a start-up from the Department of Physics at the University of Basel – is basing its work on tiny quantum sensors made of diamonds.

These are created by deliberately removing two carbon atoms from the diamonds’ crystal lattice. One is replaced with a nitrogen atom, and the second is left as a vacant site in the lattice. These nitrogen-vacancy centers (NV centers) host individual electrons that can be excited and manipulated. The intrinsic angular momentum (spin) of these electrons, and their electric dipole, are extremely sensitive to tiny magnetic and electric fields. Exposing the diamond sensor to fields of this kind causes a change in the intensity of the NV center’s luminescence. This can be detected using an optical device and used to draw specific conclusions about the influencing field.

Ambitious goals
In recent years, the team has already achieved significant improvements in the tiny sensors’ complex and demanding production process. Now, the scientists are exploring ways to boost the sensitivity of their sensors. That is easier said than done, because diamonds have a high refractive index. As a result, most of the light emitted by the NV centers is reflected inwards by the outer surfaces, leaving it unavailable for measurements.

“At the moment, we can use about one to two percent of the emitted photons for our measurements. As part of the Nano Argovia project NQsense, we now want to design and produce structures that allow us to boost the yield to up to 50 percent,” comments Professor Patrick Maletinsky on the impending challenge.

“The Nano Argovia program offers the ideal framework for our product’s further development, as we can exploit synergies with our partners at the University of Basel and the Paul Scherrer Institute, as well as benefiting from our partners’ excellent technical equipment,” says Mathieu Munsch, CEO of the industrial partner, Qnami.