A photonic chip that makes it possible to carry out superresolution light microscopy with conventional microscopes

New imaging potential: standard resolution (left) compared to (centre, right) high resolution and superresolution obtained with the chip-based technique. Photo: Bielefeld University/Robin Diekmann

New invention at Bielefeld University and the University of Tromsø (Norway)

Physicists at Bielefeld University and tThe Arctic University of Norway in Tromsø have developed a photonic chip that makes it possible to carry out superresolution light microscopy, also called ‘nanoscopy’, with conventional microscopes. In nanoscopy, the position of single fluorescent molecules can be determined with a precision of just a few nanometres, that is, to a millionth of a millimetre. This information can be used to produce images with a resolution of about 20 to 30 nanometres, and thereby ten times that of conventional light microscopy. Until now, this method has required the use of expensive special instruments. Bielefeld University and the University of Tromsø have filed a patent for this new ‘chip-based nanoscopy’ procedure. On the 24th of April 2017 the researchers will be publishing the accompanying study in the journal ‘Nature Photonics’.

Dr. Mark Schüttpelz from Bielefeld University and Dr. Balpreet Singh Ahluwalia (University of Tromsø) are the inventors of this photonic waveguide chip. Professor Dr. Thomas Huser and Robin Diekmann from Bielefeld University’s Biomolecular Photonics Group also worked on developing this new concept. The invention makes experiments much easier to perform: a probe is illuminated directly on a chip about the size of a specimen slide. A lens and a camera record the signal perpendicular to the chip. The measurement data obtained can be reconstructed as superresolved images with a markedly higher resolution than that obtained with conventional microscopy.

The chip-based nanoscopy technique can also be applied with conventional microscopes. Photo: Bielefeld University/Matthias Simonis

The chip-based nanoscopy technique can also be applied with conventional microscopes. Photo: Bielefeld University/Matthias Simonis

Whereas the images that can be obtained simultaneously with established nanoscopy techniques range from only parts of cells up to just a few cells, the use of photonic chips now makes it possible to visualise more than 50 cells in one superresolution image. ‘The invention of the new chip-based superresolution technique is a paradigm shift in microscopy, and it will now permit a much broader use of nanoscopy in science, research, and everyday applications,’ says Dr. Mark Schüttpelz.

Current nanoscopic techniques are extremely complex, expensive, and require intensively trained technicians. Up to now, these limitations have restricted the use of nanoscopy to only highly specialized institutes throughout the world and prevented its spread to standard laboratories in biology and medicine let alone to hospitals and analytical laboratories.

The invention of the ‘chip-based nanoscopy’ procedure by researchers at Bielefeld and Tromsø will take its place in the long history of developments in microscopy and nanoscopy:

  • In 1609, Galileo Galilei invented light microscopy.
  • In 1873, Ernst Abbe discovered the fundamental property that limits the resolution of an optical system for visible light to roughly 250 nanometres.
  • In recent years, several optical methods have been developed concurrently in order to overcome the diffraction   limit  of light. In 2014, the Nobel Prize for Chemistry was awarded for the development of a superresolution in the range of roughly 20 to 30 nanometres.

Learn more: Chip-based nanoscopy: Microscopy in HD quality



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Optical tractor beam holds bacteria for a superresolution closeup

Picture of the distribution of the genetic information in an Escherichia coli bacterial cell: Physicists at Bielefeld University are the first to photograph this distribution at the highest optical resolution without anchoring the cells on a glass substrate. Photo: Bielefeld University

Up to now, if scientists wanted to study blood cells, algae, or bacteria under the microscope, they had to mount these cells on a substrate such as a glass slide. Physicists at Bielefeld and Frankfurt Universities have developed a method that traps biological cells with a laser beam enabling them to study them at very high resolutions. In science fiction books and films, the principle is known as the ‘tractor beam’. Using this procedure, the physicists have obtained superresolution images of the DNA in single bacteria.

One of the problems facing researchers who want to examine biological cells microscopically is that any preparatory treatment will change the cells. Many bacteria prefer to be able to swim freely in solution. Blood cells are similar: They are continuously in rapid flow, and do not remain on surfaces. Indeed, if they adhere to a surface, this changes their structure and they die.

‘Our new method enables us to take cells that cannot be anchored on surfaces and then use an optical trap to study them at a very high resolution. The cells are held in place by a kind of optical tractor beam. The principle underlying this laser beam is similar to the concept to be found in the television series “Star Trek”,’ says Professor Dr. Thomas Huser. He is the head of the Biomolecular Photonics Research Group in the Faculty of Physics. ‘What’s special is that the samples are not only immobilized without a substrate but can also be turned and rotated. The laser beam functions as an extended hand for making microscopically small adjustments.’

The Bielefeld physicists have further developed the procedure for use in superresolution fluorescence microscopy. This is considered to be a key technology in biology and biomedicine because it delivers the first way to study biological processes in living cells at a high scale – something that was previously only possible with electron microscopy. To obtain images with such microscopes, researchers add fluorescent probes to the cells they wish to study, and these will then light up when a laser beam is directed towards them. A sensor can then be used to record this fluorescent radiation so that researchers can even gain three-dimensional images of the cells.

In their new method, the Bielefeld researchers use a second laser beam as an optical trap so that the cells float under the microscope and can be moved at will. ‘The laser beam is very intensive but invisible to the naked eye because it uses infrared light,’ says Robin Diekmann, a member of the Biomolecular Photonics Research Group. ‘When this laser beam is directed towards a cell, forces develop within the cell that hold it within the focus of the beam,’ says Diekmann. Using their new method, the Bielefeld physicists have succeeded in holding and rotating bacterial cells in such a way that they can obtain images of the cells from several sides. Thanks to the rotation, the researchers can study the three-dimensional structure of the DNA at a resolution of circa 0.0001 millimetres.

Professor Huser and his team want to further modify the method so that it will enable them to observe the interplay between living cells. They would then be able to study, for example, how germs penetrate cells.

Learn more: Optical tractor beam traps bacteria



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Robots Might Be Able to Help Germany Integrate Refugee Kids

A child with language robot Nao. CITEC / University Bielefeld

A child with language robot Nao. CITEC / University Bielefeld

Can a robot help Germany integrate its influx of migrants? A new research project thinks the answer might be yes.

More than 1 million refugees reached Germany last year. Children represent around 25 percent of the refugees and migrants arriving in Europe, according to the International Organization for Migration.

That’s where “Nao” comes in. Researchers at Germany’s Bielefeld University are testing whether the high-tech, wide-eyed robot can help teach migrant children language skills.

“Kids respond very positively to the small humanoid robot Nao that we are programming,” said Stefan Kopp, an artificial intelligence expert working on the project. “They are highly motivated and its fun for them to interact with the technology.”

The “El Tutor” project aims to explore how social robots can assist with second language teaching at pre-schools, like being used for classroom exercises.

“The robot might actually ask the child for help at times,” Kopp said. It also can offer fun responses when a child performs well.

Learn more: Robots Might Be Able to Help Germany Integrate Refugees



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New open source software for high resolution microscopy

The images show a liver cell before and after processing the data with the software developed at Bielefeld University. CREDIT Photo: Bielefeld University

The images show a liver cell before and after processing the data with the software developed at Bielefeld University.
Photo: Bielefeld University

With their special microscopes, experimental physicists can already observe single molecules. However, unlike conventional light microscopes, the raw image data from some ultra-high resolution instruments first have to be processed for an image to appear. For the ultra-high resolution fluorescence microscopy that is also employed in biophysical research at Bielefeld University, members of the Biomolecular Photonics Group have developed a new open source software solution that can process such raw data quickly and efficiently. The Bielefeld physicist Dr. Marcel Müller reports on this new open source software in the latest issue of Nature Communications published on 21 March.

Conventional light microscopy can attain only a defined lower resolution limit that is restricted by light diffraction to roughly 1/4 of a micrometre. High resolution fluorescence microscopy makes it possible to obtain images with a resolution markedly below these physical limits. The physicists Stefan Hell, Eric Betzig, and William Moerner were awarded the Nobel Prize in 2014 for developing this important key technology for biomedical research. Currently, one of the ways in which researchers in this domain are trying to attain a better resolution is by using structured illumination.

At present, this is one of the most widespread procedures for representing and presenting dynamic processes in living cells. This method achieves a resolution of 100 nanometres with a high frame rate while simultaneously not damaging the specimens during measurement. Such high resolution fluorescence microscopy is also being applied and further developed in the Biomolecular Photonics Group at Bielefeld’s Faculty of Physics. For example, it is being used to study the function of the liver or the ways in which the HI virus spreads.

However, scientists cannot use the raw images gained with this method straight away. ‘The data obtained with the microscopy method require a very laborious mathematical image reconstruction. Only then do the raw data recorded with the microscope result in a high-resolution image,’ explains Professor Dr. Thomas Huser, head of the Biomolecular Photonics Group. Because this stage requires a complicated mathematical procedure that has been accessible for only a few researchers up to now, there was previously no open source software solution that was easily available for all researchers. Huser sees this as a major obstacle to the use and further development of the technology. The software developed in Bielefeld is now filling this gap.

Dr. Marcel Müller from the Biomolecular Photonics Group has managed to produce such universally implementable software. ‘Researchers throughout the world are working on building new, faster, and more sensitive microscopes for structured illumination, particularly for the two-dimensional representation of living cells. For the necessary post-processing, they no longer need to develop their own complicated solutions but can use our software directly, and, thanks to its open source availability, they can adjust it to fit their problems,’

Müller explains. The software is freely available to the global scientific community as an open source solution, and as soon as its availability was announced, numerous researchers, particularly in Europe and Asia, requested and installed it. ‘We have already received a lot of positive feedback,’ says Marcel Müller. ‘That also reflects how necessary this new development has been.’

Learn more: New open source software for high resolution microscopy



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Carrying a Table Together with a Robot

The small humanoid robot COMAN still has some “growing” to do before it can interact “eye to eye” with human adults. Professor Dr. Jochen Steil is leading the new research project. Photo: Bielefeld University.

The small humanoid robot COMAN still has some “growing” to do before it can interact “eye to eye” with human adults. Professor Dr. Jochen Steil is leading the new research project. Photo: Bielefeld University.


From a robot’s perspective, humans are normally a nuisance: when robots and humans have to work together, it often leads to problems.

Researchers on CogIMon, a new project starting at Bielefeld University, want to teach robots how to interact with humans and work together to accomplish tasks. CogIMon stands for “cognitive compliant interaction in motion.” This research group is working on humanoid as well as industrial robots. The project is coordinated by Professor Dr. Jochen Steil of CoR-Lab, the research institution on cognition and robotics at Bielefeld University. Together with six other international partners, the joint project will run from 2015–2018 and is funded with 7 million Euros from Horizon 2020, a framework programme for research and innovation of the European Union.

“The goal of CogIMon is to teach robots to understand the forces during the movement of objects and how to appropriately react to changes in weight or contact with the object while carrying it,” explains Jochen Steil. Humans have no problem estimating the weight of an object, as they can see how heavy something is in the body language of another person. This makes it easy for humans to correspondingly adjust the force exerted when lifting. Currently, however, robots lack this ability. “Robots can measure their own force and regulate it to a certain degree. They can stop their movements or ease off, but they have not yet been able to understand forces or actively control them to take part in a joint effort. We want to change that.”

“Understanding active forces is a big challenge because it entails complex, highly skilled interaction that combines abilities from a number of different areas. Perception, the ability to move objects, controlling flexibility and body motion are a few examples,” says Steil. At this time, there is little theory to help explain how robots can move objects together with humans. For this reason, project partners in Italy and the Great Britain are conducting basic research using interaction experiments with humans. Meanwhile, Steil’s group is developing new controlling and programming methods for the robots. A classic example for moving objects can be seen when a human and a robot or two robots carry a table together. In this action, it is important to adjust one’s forces: the one carrying leads the way, the other follows. When changing who leads and who follows, it is necessary that one is able to predict their partner’s motions and adjust their own movements accordingly.

To research human interaction with humanoid robots, researchers can draw on the humanoid robot prototype COMAN (COmpliant huMANoid platform). COMAN was developed at the Italian Institute of Technology in Genua. It is 95 cm tall and weighs 31 kg. For the CogIMon project, it must “grow” in size by about 25 percent so that it can also interact with human adults. In the future, COMAN is supposed to learn how to “read” human body language. This could allow the robot to be used, for instance, in physical rehabilitation, where it could help train motor skills and coordination by playing catch with patients. While throwing and catching the ball, the robot would have to be able to react directly to its human partners and even fake a shot. This group interaction should be so open, though, that both humans and robots would be able to leave and return to the group at any time without this causing confusion.

Read more: Carrying a Table Together with a Robot


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