Tag Archives: biophotonics

Non-viral ocular gene therapy with gold nanoparticles and femtosecond lasers

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I love the stylistic choice the writer made (pay special attention to the second paragraph) when producing this November 19, 2018 Polytechnique Montréal news release (also on EurekAlert),

A scientific breakthrough by Professor Michel Meunier of Polytechnique Montréal and his collaborators offers hope for people with glaucoma, retinitis or macular degeneration.

In January 2009, the life of engineer Michel Meunier, a professor at Polytechnique Montréal, changed dramatically. Like others, he had observed that the extremely short pulse of a femtosecond laser (0.000000000000001 second) could make nanometre-sized holes appear in silicon when it was covered by gold nanoparticles. But this researcher, recognized internationally for his skills in laser and nanotechnology, decided to go a step further with what was then just a laboratory curiosity. He wondered if it was possible to go from silicon to living matter, from inorganic to organic. Could the gold nanoparticles and the femtosecond laser, this “light scalpel,” reproduce the same phenomenon with living cells?

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A very pretty image illustrating the work,

Caption: Gold nanoparticles, which act like “nanolenses,” concentrate the energy produced by the extremely short pulse of a femtosecond laser to create a nanoscale incision on the surface of the eye’s retina cells. This technology, which preserves cell integrity, can be used to effectively inject drugs or genes into specific areas of the eye, offering new hope to people with glaucoma, retinitis or macular degeneration. Credit and Copyright: Polytechnique Montréal

The news release goes on to describe the technology in more detail,

Professor Meunier started working on cells in vitro in his Polytechnique laboratory. The challenge was to make a nanometric incision in the cells’ extracellular membrane without damaging it. Using gold nanoparticles that acted as “nanolenses,” Professor Meunier realized that it was possible to concentrate the light energy coming from the laser at a wavelength of 800 nanometres. Since there is very little energy absorption by the cells at this wavelength, their integrity is preserved. Mission accomplished!

Based on this finding, Professor Meunier decided to work on cells in vivo, cells that are part of a complex living cell structure, such as the eye for example.

The eye and the light scalpel

In April 2012, Professor Meunier met Przemyslaw Sapieha, an internationally renowned eye specialist, particularly recognized for his work on the retina. “Mike”, as he goes by, is a professor in the Department of Ophthalmology at Université de Montréal and a researcher at Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l’Est-de-l’Île-de-Montréal. He immediately saw the potential of this new technology and everything that could be done in the eye if you could block the ripple effect that occurs following a trigger that leads to glaucoma or macular degeneration, for example, by injecting drugs, proteins or even genes.

Using a femtosecond laser to treat the eye–a highly specialized and fragile organ–is very complex, however. The eye is part of the central nervous system, and therefore many of the cells or families of cells that compose it are neurons. And when a neuron dies, it does not regenerate like other cells do. Mike Sapieha’s first task was therefore to ensure that a femtosecond laser could be used on one or several neurons without affecting them. This is what is referred to as “proof of concept.”

Proof of concept

Mike and Michel called on biochemistry researcher Ariel Wilson, an expert in eye structures and vision mechanisms, as well as Professor Santiago Costantino and his team from the Department of Ophthalmology at Université de Montréal and the CIUSSS de l’Est-de-l’Île-de-Montréal for their expertise in biophotonics. The team first decided to work on healthy cells, because they are better understood than sick cells. They injected gold nanoparticles combined with antibodies to target specific neuronal cells in the eye, and then waited for the nanoparticles to settle around the various neurons or families of neurons, such as the retina. Following the bright flash generated by the femtosecond laser, the expected phenomenon occurred: small holes appeared in the cells of the eye’s retina, making it possible to effectively inject drugs or genes in specific areas of the eye. It was another victory for Michel Meunier and his collaborators, with these conclusive results now opening the path to new treatments.

The key feature of the technology developed by the researchers from Polytechnique and CIUSSS de l’Est-de-l’Île-de-Montréal is its extreme precision. With the use of functionalized gold nanoparticles, the light scalpel makes it possible to precisely locate the family of cells where the doctor will have to intervene.

Having successfully demonstrated proof of concept, Professor Meunier and his team filed a patent application in the United States. This tremendous work was also the subject of a paper reviewed by an impressive reading committee and published in the renowned journal Nano Letters in October 2018.

While there is still a lot of research to be done–at least 10 years’ worth, first on animals and then on humans–this technology could make all the difference in an aging population suffering from eye deterioration for which there are still no effective long-term treatments. It also has the advantage of avoiding the use of viruses commonly employed in gene therapy. These researchers are looking at applications of this technology in all eye diseases, but more particularly in glaucoma, retinitis and macular degeneration.

This light scalpel is unprecedented.

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

In Vivo Laser-Mediated Retinal Ganglion Cell Optoporation Using KV1.1 Conjugated Gold Nanoparticles by Ariel M. Wilson, Javier Mazzaferri, Éric Bergeron, Sergiy Patskovsky, Paule Marcoux-Valiquette, Santiago Costantino, Przemyslaw Sapieha, Michel Meunier. Nano Lett.201818116981-6988 DOI: https://doi.org/10.1021/acs.nanolett.8b02896 Publication Date: October 4, 2018  Copyright © 2018 American Chemical Society

This paper is behind a paywall.

What is Dr. Who’s sonic screwdriver?

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Dr. Who, a British Broadcasting Corporation science fiction television programme, has an enormous following worldwide. I am not one of those followers as you might have guessed from the headline, which means I didn’t understand this pop culture reference, from the April 23, 2012 news item on Nanowerk,

For fans of the hit series Doctor Who, the Sonic Screwdriver will be a familiar device. But now an international team of EU-funded researchers has taken equipment designed for magnetic resonance imaging (MRI)-guided focused ultrasound surgery and demonstrated a real Sonic Screwdriver, lifting and spinning a free-floating 10 cm-diameter rubber disk with an ultrasound beam.

I’m going to concentrate on the project first since this EU (European Union) funded project has a somewhat confusing configuration, which I’ll try to tease apart later in this posting. From the news item,

Dr Mike MacDonald, of the Institute for Medical Science and Technology (IMSAT) in the [University of Dundee, Scotland] United Kingdom, comments: ‘This experiment not only confirms a fundamental physics theory but also demonstrates a new level of control over ultrasound beams which can also be applied to non-invasive ultrasound surgery, targeted drug delivery and ultrasonic manipulation of cells.’

The theory the team were testing had not previously been proved in a single experiment; it is valid for both sound and light, and is used in fields like quantum communications and biophotonics. The theory states that the ratio of angular momentum to energy in a vortex beam is equal to the ratio of the number of intertwined helices to the frequency of the beam.

Dr Christine Demore from IMSAT comments: ‘For the first time, our experimental results confirm directly the validity of this fundamental theory. Previously this ratio could only be assumed from theory as the angular momentum and power in a beam had only ever been measured independently.’

The ultrasound beam generated by the researchers resembles the ‘double-helix’ structure of DNA but with many more twisted strands, or helices. This vortex beam generates a rotating, angular component of momentum that can exert torque on an object. In the recent publication, they showed how they could generate vortex beams with many intertwined helices, using a 1 000-element ultrasound transducer array as an acoustic hologram. These beams are so powerful they can levitate and spin the 90 g-disk made of ultrasonic absorber in water.

Here’s a 30 secs. video of the ‘sonic screwdriver’,

Ray Walters in his April 20, 2012 article  for Geek.com offers a description using measurements that are more commonly used in Canada and the US for what we’re seeing in the video [I have removed a link from the following passage],

Depicted in the video above, the “Sonotweezers” [aka, sonic screwdriver] project as it’s officially known, uses an ultrasound beam that is structured like a strand of DNA. The difference being that there are many more twisted strands that can be used to bring torque to bear on objects for movement. The team has used its device to levitate and spin a 3.17 ounce, 10cm diameter rubber disk that was suspended in water.

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To make this happen, the research team used a 1000-element ultrasound transducer array to create what’s called an acoustic hologram.

The project known as ‘Sonotweezers’ at the University of Dundee,  is part of a larger European Union project, Nanoporation, which is investigating drug delivery to cancer cell using MRI (magnetic resonance imaging) and guided focused ultrasound. The larger project includes a couple of Israeli teams, neither of which seem to be involved with the Sonotweezers/sonic screwdriver project. I gather some of the funding for the Sonotweezers project comes from the UK’s Engineering and Physical Sciences Ressearch Council (EPSRC). You can find out more about the Scottish team at the University of Dundee, Sonotweezers, and EPSRC in the April 19, 2012 press release on the University of Dundee website.