Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Self-aligning microscope smashes limits of super-resolution microscopy

20.04.2020

UNSW medical researchers have achieved unprecedented resolution capabilities in single-molecule microscopy to detect interactions between individual molecules within intact cells.

The 2014 Nobel Prize in Chemistry was awarded for the development of super-resolution fluorescence microscopy technology that afforded microscopists the first molecular view inside cells, a capability that has provided new molecular perspectives on complex biological systems and processes.


A T cell with precise localisation of T cell receptors (pink) and CD45 phosphatase (green).

Credit: Single Molecule Science, UNSW Sydney

Now the limit of detection of single-molecule microscopes has been smashed again, and the details are published in the current issue of Science Advances.

While individual molecules could be observed and tracked with super-resolution microscopy already, interactions between these molecules occur at a scale at least four times smaller than that resolved by existing single-molecule microscopes.

"The reason why the localisation precision of single-molecule microscopes is around 20-30 nanometres normally is because the microscope actually moves while we're detecting that signal. This leads to an uncertainty.

With the existing super-resolution instruments, we can't tell whether or not one protein is bound to another protein because the distance between them is shorter than the uncertainty of their positions," says Scientia Professor Katharina Gaus, research team leader and Head of UNSW Medicine's EMBL Australia Node in Single Molecule Science.

To circumvent this problem, the team built autonomous feedback loops inside a single-molecule microscope that detects and re-aligns the optical path and stage.

"It doesn't matter what you do to this microscope, it basically finds its way back with precision under a nanometre. It's a smart microscope. It does all the things that an operator or a service engineer needs to do, and it does that 12 times per second," says Professor Gaus.

Measuring the distance between proteins

With the design and methods outlined in the paper, the feedback system designed by the UNSW team is compatible with existing microscopes and affords maximum flexibility for sample preparation.

"It's a really simple and elegant solution to a major imaging problem. We just built a microscope within a microscope, and all it does is align the main microscope. That the solution we found is simple and practical is a real strength as it would allow easy cloning of the system, and rapid uptake of the new technology," says Professor Gaus.

To demonstrate the utility of their ultra-precise feedback single-molecule microscope, the researchers used it to perform direct distance measurements between signalling proteins in T cells. A popular hypothesis in cellular immunology is that these immune cells remain in a resting state when the T cell receptor is next to another molecule that acts as a brake.

Their high precision microscope was able to show that these two signalling molecules are in fact further separated from each other in activated T cells, releasing the brake and switching on T cell receptor signalling.

"Conventional microscopy techniques would not be able to accurately measure such a small change as the distance between these signalling molecules in resting T cells and in activated T cells only differed by 4-7 nanometres," says Professor Gaus.

"This also shows how sensitive these signalling machineries are to spatial segregation. In order to identify regulatory processes like these, we need to perform precise distance measurements, and that is what this microscope enables. These results illustrate the potential of this technology for discoveries that could not be made by any other means."

Postdoctoral researcher, Dr Simao Pereira Coelho, together with PhD student Jongho Baek - who has since been awarded his PhD degree - led the design, development, and building of this system. Dr Baek also received the Dean's Award for Outstanding PhD Thesis for this work.

Media Contact

Isabelle Dubach
i.dubach@unsw.edu.au
61-432-307-244

 @UNSWnews

http://www.unsw.edu.au 

Isabelle Dubach | EurekAlert!
Further information:
https://newsroom.unsw.edu.au/news/science-tech/self-aligning-microscope-smashes-limits-super-resolution-microscopy
http://dx.doi.org/10.1126/sciadv.aay8271

More articles from Life Sciences:

nachricht Rising water temperatures could endanger the mating of many fish species
03.07.2020 | Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung

nachricht Moss protein corrects genetic defects of other plants
03.07.2020 | Rheinische Friedrich-Wilhelms-Universität Bonn

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Electrons in the fast lane

Solar cells based on perovskite compounds could soon make electricity generation from sunlight even more efficient and cheaper. The laboratory efficiency of these perovskite solar cells already exceeds that of the well-known silicon solar cells. An international team led by Stefan Weber from the Max Planck Institute for Polymer Research (MPI-P) in Mainz has found microscopic structures in perovskite crystals that can guide the charge transport in the solar cell. Clever alignment of these "electron highways" could make perovskite solar cells even more powerful.

Solar cells convert sunlight into electricity. During this process, the electrons of the material inside the cell absorb the energy of the light....

Im Focus: The lightest electromagnetic shielding material in the world

Empa researchers have succeeded in applying aerogels to microelectronics: Aerogels based on cellulose nanofibers can effectively shield electromagnetic radiation over a wide frequency range – and they are unrivalled in terms of weight.

Electric motors and electronic devices generate electromagnetic fields that sometimes have to be shielded in order not to affect neighboring electronic...

Im Focus: Gentle wall contact – the right scenario for a fusion power plant

Quasi-continuous power exhaust developed as a wall-friendly method on ASDEX Upgrade

A promising operating mode for the plasma of a future power plant has been developed at the ASDEX Upgrade fusion device at Max Planck Institute for Plasma...

Im Focus: ILA Goes Digital – Automation & Production Technology for Adaptable Aircraft Production

Live event – July 1, 2020 - 11:00 to 11:45 (CET)
"Automation in Aerospace Industry @ Fraunhofer IFAM"

The Fraunhofer Institute for Manufacturing Technology and Advanced Materials IFAM l Stade is presenting its forward-looking R&D portfolio for the first time at...

Im Focus: AI monitoring of laser welding processes - X-ray vision and eavesdropping ensure quality

With an X-ray experiment at the European Synchrotron ESRF in Grenoble (France), Empa researchers were able to demonstrate how well their real-time acoustic monitoring of laser weld seams works. With almost 90 percent reliability, they detected the formation of unwanted pores that impair the quality of weld seams. Thanks to a special evaluation method based on artificial intelligence (AI), the detection process is completed in just 70 milliseconds.

Laser welding is a process suitable for joining metals and thermoplastics. It has become particularly well established in highly automated production, for...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International conference QuApps shows status quo of quantum technology

02.07.2020 | Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

Aachen Machine Tool Colloquium AWK'21 will take place on June 10 and 11, 2021

07.04.2020 | Event News

 
Latest News

Rising water temperatures could endanger the mating of many fish species

03.07.2020 | Life Sciences

Risk of infection with COVID-19 from singing: First results of aerosol study with the Bavarian Radio Chorus

03.07.2020 | Studies and Analyses

Efficient, Economical and Aesthetic: Researchers Build Electrodes from Leaves

03.07.2020 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>