Tag Archives: University of Innsbruck

Skin-based vaccination delivery courtesy of nanotechnology

A May 28, 2019 news item on Nanowerk announced research targeting Langerham cells and the immune system (Note: A link has been removed),

Researchers at the Max Planck Institute of Colloids and Interfaces in Potsdam developed targeted nanoparticles that are taken up by certain immune cells of the human skin (ACS Central Science, “A specific, glycomimetic Langerin ligand for human Langerhans cell targeting”). These so-called Langerhans cells coordinate the immune response and alert the body when pathogens or tumors occur.

This new nanoparticle technology platform enables targeted drug delivery of vaccines or pharmaceuticals to Langerhans cells, triggering a controlled immune response to naturally eradicate the pathogen or tumor.

Internalized nanoparticles (red) in a Langerhans cell (green membrane marker). Specific targeting of these skin immune cells may lead to novel approaches for skin vaccination [weniger] © Langerhans Zellforschung Labor an der Medizinischen Universität Innsbruck Courtesy: Max Planck Institute

A May 28,2019 Max Planck Institute (MPI) press release, which originated the news item, provides further explanations,

The skin is a particularly attractive place for the application of many drugs that affect the immune system, as the appropriate target cells lie directly beneath the skin. These Langerhans cells are able to elicit an immune reaction in the entire body of the patient after local application of an active substance.

Langerhans Cells – Experts of pathogen defense

To develop a targeted drug delivery system, which guides drugs directly to Langerhans cells, one can make use of their natural function: as professional, antigen-presenting cells they detect pathogens, internalize them and present components of these pathogens to effector cells of the immune system (T cells). For detection and uptake, Langerhans cells use receptors on their surface that search the environment for microbes. They especially recognize pathogens by the unique coating of sugar structures on their surface. Langerin, a protein of the C-type lectins family, is such a receptor on Langerhans cells that can detect viruses and bacteria. The specific expression of Langerin on Langerhans cells allows a targeted drug delivery encapsulated in nanoparticleswhile minimizing the side effects.

The research team of Dr. Christoph Rademacher at the Max Planck Institute of Colloids and Interfaces has now been able to exploit the knowledge of the underlying detection mechanisms with atomic resolution: “Based on our insight how immune cells recognize sugars, we developed a synthetic, sugar-like substance that enables nanoparticles to specifically bind to Langerhans cells”, says Dr. Christoph Rademacher. In collaboration with a scientific team from the Laboratory for Langerhans Cell Research of the Medical University of Innsbruck, nanoparticles have been developed that can be incorporated into Langerhans cells of the human skin through this interaction. The researchers thus lay the foundation for further developments, for example to deliver vaccines directly through the skin to the immune cells. “Imagine avoiding needles for vaccination in the future or directly activating the body’s immune system against infections and maybe even cancer”, adds Dr. Christoph Rademacher. Langerhans cells are responsible for activating the immune system systemically. Based on these findings, it may be possible in the future to develop novel vaccines against infections or immunotherapies for the treatment of cancer or autoimmune diseases.

The starting points for this work were the pioneering contributions from Ralph M. Steinman (Nobel Prize 2011) and other scientists who showed the potential of dendritic cells. Langerhans cells are one subset of these cells and are able to trigger an immune response. These findings were subsequently refined for use in cancer therapy. It has been shown that an immune response can be achieved via artificially introduced antigens. Later work confirmed these findings and also demonstrated that human Langerhans cells are also able to activate the immune system, which is particularly interesting for skin vaccination. Targeted delivery of immunomodulators to Langerhans cells would thus be desirable. However, this is often hindered or even prevented by the complex environment of the skin, especially by competing phagocytes in this tissue, such as macrophages. Consequently, pharmaceuticals not taken up by the Langerhans cells, but internalized into bystander cells may lead to unwanted side effects.

Recognition through synthetic sugars

Based on insights on the interaction between Langerin and its natural sugar ligands Christoph Rademacher and his team developed a synthetic ligand, which binds specifically to the receptor on Langerhans cells. For this purpose, synthetic sugars were produced in the laboratory and their interactions with the receptor were examined by nuclear magnetic resonance spectroscopy. With this method the researchers were able to determine which atoms of the ligand interact with which parts of the receptor. By using this structure-based approach they found out that a compound can be anchored and tested on these nanoparticles. These particles are liposomes, which have been used for many years in the clinic in the absence of such targeting ligands as a carrier for various drugs. The difference with existing systems is that the sugar-like ligand now allows specific binding to Langerhans cells. The investigations on these immune cells were carried out in collaboration with the research group of Assoz. Prof. Patrizia Stoitzner at the Langerhans Cell Research Laboratory of the Medical University of Innsbruck. Together they could show that the specific uptake of liposomes is possible even in the complex environment of human skin. The scientists used different methods such as flow cytometry and confocal microscopy for their findings.

These liposomal particles may now provide a common platform for researchers at the MPI of Colloids and Interfaces to work on the development of novel vaccines in the future.

Here’s a link to and a citation for the paper,

A Specific, Glycomimetic Langerin Ligand for Human Langerhans Cell Targeting by Eike-Christian Wamhoff, Jessica Schulze, Lydia Bellmann, Mareike Rentzsch, Gunnar Bachem, Felix F. Fuchsberger, Juliane Rademacher, Martin Hermann, Barbara Del Frari, Rob van Dalen, David Hartmann, Nina M. van Sorge, Oliver Seitz, Patrizia Stoitzner, Christoph Rademacher. ACS Cent. Sci.201955808-820 DOI: https://doi.org/10.1021/acscentsci.9b00093 Publication Date: May 10, 2019 Copyright © 2019 American Chemical Society

This paper appears to be open access.

Simulating elementary physics in a quantum simulation (particle zoo in a quantum computer?)

Whoever wrote the news release used a very catchy title “Particle zoo in a quantum computer”; I just wish they’d explained it. Looking up the definition for a ‘particle zoo’ didn’t help as much as I’d hoped. From the particle zoo entry on Wikipedia (Note: Links have been removed),

In particle physics, the term particle zoo[1][2] is used colloquially to describe a relatively extensive list of the then known “elementary particles” that almost look like hundreds of species in the zoo.

In the history of particle physics, the situation was particularly confusing in the late 1960s. Before the discovery of quarks, hundreds of strongly interacting particles (hadrons) were known, and believed to be distinct elementary particles in their own right. It was later discovered that they were not elementary particles, but rather composites of the quarks. The set of particles believed today to be elementary is known as the Standard Model, and includes quarks, bosons and leptons.

I believe the writer used the term to indicate that the simulation undertaken involved elementary particles. If you have a better explanation, please feel free to add it to the comments for this post.

Here’s the news from a June 22, 2016 news item on ScienceDaily,

Elementary particles are the fundamental buildings blocks of matter, and their properties are described by the Standard Model of particle physics. The discovery of the Higgs boson at the CERN in 2012 constitutes a further step towards the confirmation of the Standard Model. However, many aspects of this theory are still not understood because their complexity makes it hard to investigate them with classical computers. Quantum computers may provide a way to overcome this obstacle as they can simulate certain aspects of elementary particle physics in a well-controlled quantum system. Physicists from the University of Innsbruck and the Institute for Quantum Optics and Quantum Information (IQOQI) at the Austrian Academy of Sciences have now done exactly that: In an international first, Rainer Blatt’s and Peter Zoller’s research teams have simulated lattice gauge theories in a quantum computer. …

A June 23, 2016 University of Innsbruck (Universität Innsbruck) press release, which seems  to have originated the news item, provides more detail,

Gauge theories describe the interaction between elementary particles, such as quarks and gluons, and they are the basis for our understanding of fundamental processes. “Dynamical processes, for example, the collision of elementary particles or the spontaneous creation of particle-antiparticle pairs, are extremely difficult to investigate,” explains Christine Muschik, theoretical physicist at the IQOQI. “However, scientists quickly reach a limit when processing numerical calculations on classical computers. For this reason, it has been proposed to simulate these processes by using a programmable quantum system.” In recent years, many interesting concepts have been proposed, but until now it was impossible to realize them. “We have now developed a new concept that allows us to simulate the spontaneous creation of electron-positron pairs out of the vacuum by using a quantum computer,” says Muschik. The quantum system consists of four electromagnetically trapped calcium ions that are controlled by laser pulses. “Each pair of ions represent a pair of a particle and an antiparticle,” explains experimental physicist Esteban A. Martinez. “We use laser pulses to simulate the electromagnetic field in a vacuum. Then we are able to observe how particle pairs are created by quantum fluctuations from the energy of this field. By looking at the ion’s fluorescence, we see whether particles and antiparticles were created. We are able to modify the parameters of the quantum system, which allows us to observe and study the dynamic process of pair creation.”

Combining different fields of physics

With this experiment, the physicists in Innsbruck have built a bridge between two different fields in physics: They have used atomic physics experiments to study questions in high-energy physics. While hundreds of theoretical physicists work on the highly complex theories of the Standard Model and experiments are carried out at extremely expensive facilities, such as the Large Hadron Collider at CERN, quantum simulations may be carried out by small groups in tabletop experiments. “These two approaches complement one another perfectly,” says theoretical physicist Peter Zoller. “We cannot replace the experiments that are done with particle colliders. However, by developing quantum simulators, we may be able to understand these experiments better one day.” Experimental physicist Rainer Blatt adds: “Moreover, we can study new processes by using quantum simulation. For example, in our experiment we also investigated particle entanglement produced during pair creation, which is not possible in a particle collider.” The physicists are convinced that future quantum simulators will potentially be able to solve important questions in high-energy physics that cannot be tackled by conventional methods.

Foundation for a new research field

It was only a few years ago that the idea to combine high-energy and atomic physics was proposed. With this work it has been implemented experimentally for the first time. “This approach is conceptually very different from previous quantum simulation experiments studying many-body physics or quantum chemistry. The simulation of elementary particle processes is theoretically very complex and, therefore, has to satisfy very specific requirements. For this reason it is difficult to develop a suitable protocol,” underlines Zoller. The conditions for the experimental physicists were equally demanding: “This is one of the most complex experiments that has ever been carried out in a trapped-ion quantum computer,” says Blatt. “We are still figuring out how these quantum simulations work and will only gradually be able to apply them to more challenging phenomena.” The great theoretical as well as experimental expertise of the physicists in Innsbruck was crucial for the breakthrough. Both Blatt and Zoller emphasize that they have been doing research on quantum computers for many years now and have gained a lot of experience in their implementation. Innsbruck has become one of the leading centers for research in quantum physics; here, the theoretical and experimental branches work together at an extremely high level, which enables them to gain novel insights into fundamental phenomena.

Here’s a link to and a citation for the paper,

Real-time dynamics of lattice gauge theories with a few-qubit quantum computer by Esteban A. Martinez, Christine A. Muschik, Philipp Schindler, Daniel Nigg, Alexander Erhard, Markus Heyl, Philipp Hauke, Marcello Dalmonte, Thomas Monz, Peter Zoller, & Rainer Blatt.  Nature 534, 516–519 (23 June 2016)  doi:10.1038/nature18318 Published online 22 June 2016

This paper is behind a paywall.

There is a soundcloud audio file featuring an explanation of the work from the lead author, Esteban A. Martinez,

Viewing quantum entanglement with the naked eye

A Feb. 18, 2016 article by Bob Yirka for phys.org suggests there may be a way to see quantum entanglement with the naked eye,

A trio of physicists in Europe has come up with an idea that they believe would allow a person to actually witness entanglement. Valentina Caprara Vivoli, with the University of Geneva, Pavel Sekatski, with the University of Innsbruck and Nicolas Sangouard, with the University of Basel, have together written a paper describing a scenario where a human subject would be able to witness an instance of entanglement—they have uploaded it to the arXiv server for review by others.
Entanglement, is of course, where two quantum particles are intrinsically linked to the extent that they actually share the same existence, even though they can be separated and moved apart. The idea was first proposed nearly a century ago, and it has not only been proven, but researchers routinely cause it to occur, but, to date, not one single person has every actually seen it happen—they only know it happens by conducting a series of experiments. It is not clear if anyone has ever actually tried to see it happen, but in this new effort, the research trio claim to have found a way to make it happen—if only someone else will carry out the experiment on a willing volunteer.

A Feb. 17, 2016 article for the MIT (Massachusetts Institute of Technology) Technology Review describes this proposed project in detail,

Finding a way for a human eye to detect entangled photons sounds straightforward. After all, the eye is a photon detector, so it ought to be possible for an eye to replace a photo detector in any standard entanglement detecting experiment.

Such an experiment might consist of a source of entangled pairs of photons, each of which is sent to a photo detector via an appropriate experimental setup.

By comparing the arrival of photons at each detector and by repeating the detecting process many times, it is possible to determine statistically whether entanglement is occurring.

It’s easy to imagine that this experiment can be easily repeated by replacing one of the photodetectors with an eye. But that turns out not to be the case.

The main problem is that the eye cannot detect single photons. Instead, each light-detecting rod at the back of the eye must be stimulated by a good handful of photons to trigger a detection. The lowest number of photons that can do the trick is thought to be about seven, but in practice, people usually see photons only when they arrive in the hundreds or thousands.

Even then, the eye is not a particularly efficient photodetector. A good optics lab will have photodetectors that are well over 90 percent efficient. By contrast, at the very lowest light levels, the eye is about 8 percent efficient. That means it misses lots of photons.

That creates a significant problem. If a human eye is ever to “see” entanglement in this way, then physicists will have to entangle not just two photons but at least seven, and ideally many hundreds or thousands of them.

And that simply isn’t possible with today’s technology. At best, physicists are capable of entangling half a dozen photons but even this is a difficult task.

But the researchers have come up with a solution to the problem,

Vivoli and co say they have devised a trick that effectively amplifies a single entangled photon into many photons that the eye can see. Their trick depends on a technique called a displacement operation, in which two quantum objects interfere so that one changes the phase of another.

One way to do this with photons is with a beam splitter. Imagine a beam of coherent photons from a laser that is aimed at a beam splitter. The beam is transmitted through the splitter but a change of phase can cause it to be reflected instead.

Now imagine another beam of coherent photons that interferes with the first. This changes the phase of the first beam so that it is reflected rather than transmitted. In other words, the second beam can switch the reflection on and off.

Crucially, the switching beam needn’t be as intense as the main beam—it only needs to be coherent. Indeed, a single photon can do this trick of switching more intense beam, at least in theory.

That’s the basis of the new approach. The idea is to use a single entangled photon to switch the passage of more powerful beam through a beam splitter. And it is this more powerful beam that the eye detects and which still preserves the quantum nature of the original entanglement.

… this experiment will be hard to do. Ensuring that the optical amplifier works as they claim will be hard, for example.

And even if it does, reliably recording each detection in the eye will be even harder. The test for entanglement is a statistical one that requires many counts from both detectors. That means an individual would have to sit in the experiment registering a yes or no answer for each run, repeated thousands or tens of thousands of times. Volunteers will need to have plenty of time on their hands.

Of course, experiments like this will quickly take the glamor and romance out of the popular perception of entanglement. Indeed, it’s hard to see why anybody would want to be entangled with a photodetector over the time it takes to do this experiment.

There is a suggestion as to how to make this a more attractive proposition for volunteers,

One way to increase this motivation would be to modify the experiment so that it entangles two humans. It’s not hard to imagine a people wanting to take part in such an experiment, perhaps even eagerly.

That will require a modified set up in which both detectors are human eyes, with their high triggering level and their low efficiency. Whether this will be possible with Vivoli and co’s setup isn’t yet clear.

Only then will volunteers be able to answer the question that sits uncomfortably with most physicists. What does it feel like to be entangled with another human?

Given the nature of this experiment, the answer will be “mind-numbingly boring.” But as Vivoli and co point out in their conclusion: “It is safe to say that probing human vision with quantum light is terra incognita. This makes it an attractive challenge on its own.”

You can read the arXiv paper,

What Does It Take to See Entanglement? by Valentina Caprara Vivoli, Pavel Sekatski, Nicolas Sangouard arxiv.org/abs/1602.01907 Submitted Feb. 5, 2016

This is an open access paper and this site encourages comments and peer review.

One final comment, the articles reminded me of a March 1, 2012 posting which posed this question Can we see entangled images? a question for physicists in the headline for a piece about a physicist’s (Geraldo Barbosa) challenge and his arXiv paper. Coincidentally, the source article was by Bob Yirka and was published on phys.org.

So, you found a quantum trimer. What is it, again?

The University of Innsbruck produced a rather intriguing May 13, 2014 news release (also a May 13, 2014 news item on Nanowerk and on EurekAlert),

Eight years ago Rudolf Grimm’s research group was the first to observe an Efimov state in an ultracold quantum gas. The Russian physicist Vitali Efimov theoretically predicted this exotic bound state of three particles in the 1970s. He forecast that three particles would form a bound state due to their quantum mechanical properties, under conditions when a two-body bound state would be absent. What is even more astounding: When the distance between the particles is increased by factor 22.7, another Efimov state appears, leading to an infinite series of these states. Until now this essential ingredient of the famous scenario has remained elusive and experimentally proving the periodicity of the famous scenario has presented a challenge. “There have been some indications that particles continuously create three-body states if the distance is increased by this factor,” says Rudolf Grimm from the Institute of Experimental Physics of the University of Innsbruck and the Institute of Quantum Physics and Quantum Optics of the Austrian Academy of Sciences. “Proving the scenario was very difficult but we have finally been successful.”

I think the second Efimov state is the quantum trimer but the news release provides no explanation, mentioning the trimer in its headline only.  On the plus side, there’s a very ‘cool’ explanation of quantum gases,

Ultracold quantum gases are highly suited for studying and observing quantum phenomena of particle systems experimentally as the interaction between atoms are well tunable by a magnetic field. However, Rudolf Grimm’s research group got very close to the limits of what is possible experimentally when they had to increase the distance between the particles to one micrometer to be able to observe the second Efimov state. “This corresponds to 20,000 times the radius of a hydrogen atom,” explains Grimm. “Compared to a molecule, this is a gigantic structure.” This meant that the physicists had to be particularly precise with their work. What greatly helped the researchers in Innsbruck was their extensive experience with ultracold quantum gases and their great technical expertise. Their final result shows that the second Efimov state is larger than the first one by a factor of 21.0 with a measurement uncertainty of 1.3. “This small deviation from the factor 22.7 may be attributed to the physics beyond the ideal Efimov state, which is also an exciting topic,” explains Rudolf Grimm.

As for why this Efimov state holds such interest, I found the explanation perplexing but remain intrigued,

The scientific community’s interest in this phenomenon lies in its universal character. The law is equally applicable to nuclear physics, where strong interaction is responsible for the binding of particles in the atomic nucleus, and to molecular interactions that are based on electromagnetic forces. “Interaction between two particles and between many particles is well studied,” says Grimm. “But we still need to investigate and learn about phenomena that arise from the interaction between only a few particles. The Efimov states are the basic example for this.”

Here’s a link to and a citation for the paper,

Observation of the Second Triatomic Resonance in Efimov’s Scenario by
Bo Huang, Leonid A. Sidorenkov, Rudolf Grimm, and Jeremy M. Hutson. Phys. Rev. Lett. 112, 190401 – Published 12 May 2014 DOI: http://dx.doi.org/10.1103/PhysRevLett.112.190401
© 2014 American Physical Society

This article is behind a paywall.

The university provided an illustration of an Efimov state,

The mysterious Efimov scenario (Illustration: IQOQI/Harald Ritsch)

The mysterious Efimov scenario (Illustration: IQOQI/Harald Ritsch)

Beautiful, isn’t it?