Scientists at the Braunschweig University of Technology have developed tiny adapters that allow the coupling of molecules to nanostructures and their precise positioning on the scale of a millionth of a millimeter.
This development is of relevance especially for DNA sequencing, which is considered the key technology for the analysis of inherited diseases. The latest results are presented in the current issue of the journal “Nano Letters”.
Immobilization strategy: DNA origami (grey rectangles) equipped with a fluorescent dye (red) occupy the small holes in the metal film (ZMWs) in a way that only one adapter fits per cavity.
Comparison between optimal Poisson distribution and the experimentally measured distribution in ZMWs of 200 nm.
For DNA sequencing, individual nucleotides are analyzed which are the building blocks of DNA. “Monitoring the incorporation of single nucleotides into a full DNA strand in real-time is a revolutionary method”, Prof. Philip Tinnefeld explains. “It’s almost a live broadcast”.
Special proteins, the so-called DNA polymerases, incorporate the nucleotides in a zipper like fashion to build a double stranded DNA strand. In order to observe this process and extract the order of nucleotides, scientists employ special cover slides. A glass slide is coated with a thin metal film that contains tiny holes, so-called zeromode waveguides (ZMWs).
“The challenge for this application is to equip each of these nano-holes with exactly one polymerase that utilize the nucleotides”, Prof. Philip Tinnefeld says. Usually, these biomolecules are deposited randomly in the ZMWs, which results in many empty ZMWs while others contain multiple polymerase molecules. Even for the optimal situation, only 37 % of the holes can be used, as the expert for Nano-Bio-Sciences explains.
Coupling and positioning of molecules
His research group now achieved a more efficient usage of the ZMWs by developing a new binding strategy. For this, the nano-experts from the Institute for Physical and Theoretical Chemistry in the Laboratory of Emerging Nanometrology (Braunschweig University of Technology) could use their experience of working with the so-called DNA origami technique: the Braunschweig scientists literally fold precisely fitting structures from single viral DNA strands.
The nano-adapters were designed such that exactly one DNA origami can bind in every ZMW. The nano-adapters additionally provide docking points for functional units, like fluorescent dyes or the polymerase molecules that are used for DNA sequencing. “With our novel strategy, we connect single molecules via DNA origami with the lithographically fabricated ZMWs. This procedure can improve the efficiency of DNA sequencing and also be beneficial for applications in other areas of research like molecular electronics”, Prof. Tinnefeld summarizes.
About the project
This research project of the NanoBioSciences group of Prof. Philip Tinnfeld (Institute for Physical and Theoretical Chemistry) was conducted at the new Laboratory of Emerging Nanometrology of the Braunschweig University of Technology and was funded by a Starting Grant of the European Research Council (SiMBA).
E. Pibiri, P. Holzmeister, B. Lalkens, G.P. Acuna, P. Tinnefeld (2014):Single-Molecule Positioning in Zeromode Waveguides by DNA Origami Nano-Adapters - Nano Lett.
Prof. Philip Tinnefeld
Dr. Guillermo Acuna
Institut für Physikalische und Theoretische Chemie
Laboratory of Emerging Nanometrology
Technische Universität Braunschweig
Tel: 0531 391 5330
Stephan Nachtigall | idw - Informationsdienst Wissenschaft
Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.
The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
20.07.2018 | Power and Electrical Engineering
20.07.2018 | Information Technology
20.07.2018 | Materials Sciences