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New opportunities for proteins identification using nanotechnology

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Published on Friday, 22 November 2019

Physicists from the University of Luxembourg and their international research partners have reported a comprehensive perspective on how novel nanoscale tools called plasmonic nanopores might improve in an unprecedented manner the way we can discriminate single-molecule DNA bases, and even identify single proteins components, that is amino acids, coming from specific patients.

The scientists have published a Mini Review in Nano Letters, the prestigious journal of the American Chemical Society reporting the latest and most breakthrough advances of fundamental research in all branches of the theory and practice of nanoscience and nanotechnology. The article was produced in cooperation with researchers at Northeastern University in Boston (US) and the Italian Institute of Technology (Italy).

The human proteome is the whole set of proteins that a human can express. Most of the human proteome is known. In fact, along the years, bio-informatics reconstructed the human proteome by correlating different databases coming from mass spectrometry, genome analyses, and other techniques. However the proteome, being the set of proteins potentially expressed, does not give information regarding the protein really expressed in a specific person or a patient, which own a specificity as due to post-translational modifications and alternative splicing. “To access this fundamental information is necessary to develop new and even more sensitive techniques for single protein identification able to work with small samples and low molecular concentration,” explains Nicolò Maccaferri, Researcher in the Ultrafast Phenomena in Condensed Matter Group led by Prof. Daniele Brida at the Physics and Materials Science Research Unit at the University of Luxembourg.

Plasmonic nano-pores for single molecule detection

Solid-state nanopore-based sensors are promising platforms for next-generation sequencing technologies, featuring label-free single-molecule sensitivity, rapid detection, and low-cost manufacturing. In recent years, solid-state nanopores have been explored due to their miscellaneous fabrication methods and their use in a wide range of sensing applications.

“We focus on a novel family of solid-state nanopores which have recently appeared, namely plasmonic nanopores. The use of plasmonic nanopores to engineer electro-magnetic fields around a nanopore sensor allows for enhanced optical spectroscopies, local control over temperature, thermophoresis of molecules and ions to/from the sensor, and trapping of entities,” explains Maccaferri.

In order to achieve this result, the scientists design and synthetise these nano-pores which exploit surface plasmon resonances (SPRs), the collective oscillations of the conduction electrons in metallic nanostructures. These nanoscale objects have found applications in several fields such as light harvesting, photocatalysis, subwavelength imaging, metamaterials, and nanomedicine. Among others, one specific family of plasmonic platforms is based on plasmonic nanohole arrays and the more recently implemented plasmonic nanopores, sub-100 nm apertures connecting two compartments, for sensing applications. Plasmonic-based solid-state nanopore sensors present new opportunities for biomolecular sensing.

In fact, a plasmonic nanostructure can enhance and focus electro-magnetic radiation to a nanoscale volume (hotspot) localised at the nanopore, in which biomolecules can be “scanned” as they translocate through the pore. “This approach is very powerful for the following reasons because the measurement is independent from electrical sensing as in commercially available biological or solid-state nano-pore bio-sensors, and relies on detection of photons rather than electrons. Moreover the optical detection can be performed in the far-field, as photons freely travel in the aqueous media surrounding the nano-pores,” says Maccaferri, who is now dreaming to build a team of scientists here in Luxembourg working on this topic by using light-based nanotechnologies. “It would be wonderful to have a multi-disciplinary  working group of physicists, chemists, biologists and, in the future, even companies and hospitals interested in implementing this promising technology to bring it to the market to have an affordable sensing platform which can be used at patients’ homes.”

“Since my arrival at the University, I realised that Luxembourg can be a great place to bring forward visionary ideas. I hope we can start an activity where we combine our experimental knowledge on light-matter interactions and the huge amount of possibilities offered by this University, which is investing a lot of efforts in harnessing biology and physics,” concludes Maccaferri, who is very excited about the new stimulating challenges offered by this topic.

Publication: "Plasmonic Nanopores for Single-Molecule Detection and Manipulation: Toward Sequencing Applications", Nano Letters, October 2019