Tag Archives: University of Montreal

Faster, cheaper, and just as good—nanoscale device for measuring cancer drug methotrexate

Lots of cancer drugs can be toxic if the dosage is too high for individual metabolisms, which can vary greatly in their ability to break drugs down. The University of Montréal (Université de Montréal) has announced a device that could help greatly in making the technology to determine toxicity in the bloodstream faster and cheaper according to an Oct. 27, 2014 news item on Nanowerk,

In less than a minute, a miniature device developed at the University of Montreal can measure a patient’s blood for methotrexate, a commonly used but potentially toxic cancer drug. Just as accurate and ten times less expensive than equipment currently used in hospitals, this nanoscale device has an optical system that can rapidly gauge the optimal dose of methotrexate a patient needs, while minimizing the drug’s adverse effects. The research was led by Jean-François Masson and Joelle Pelletier of the university’s Department of Chemistry.

An Oct. 27, 2014 University of Montréal news release, which originated the news item, provides more specifics about the cancer drug being monitored and the research that led to the new device,

Methotrexate has been used for many years to treat certain cancers, among other diseases, because of its ability to block the enzyme dihydrofolate reductase (DHFR). This enzyme is active in the synthesis of DNA precursors and thus promotes the proliferation of cancer cells. “While effective, methotrexate is also highly toxic and can damage the healthy cells of patients, hence the importance of closely monitoring the drug’s concentration in the serum of treated individuals to adjust the dosage,” Masson explained.

Until now, monitoring has been done in hospitals with a device using fluorescent bioassays to measure light polarization produced by a drug sample. “The operation of the current device is based on a cumbersome, expensive platform that requires experienced personnel because of the many samples that need to be manipulated,” Masson said.

Six years ago, Joelle Pelletier, a specialist of the DHFR enzyme, and Jean-François Masson, an expert in biomedical instrument design, investigated how to simplify the measurement of methotrexate concentration in patients.

Gold nanoparticles on the surface of the receptacle change the colour of the light detected by the instrument. The detected colour reflects the exact concentration of the drug in the blood sample. In the course of their research, they developed and manufactured a miniaturized device that works by surface plasmon resonance. Roughly, it measures the concentration of serum (or blood) methotrexate through gold nanoparticles on the surface of a receptacle. In “competing” with methotrexate to block the enzyme, the gold nanoparticles change the colour of the light detected by the instrument. And the colour of the light detected reflects the exact concentration of the drug in the blood sample.

The accuracy of the measurements taken by the new device were compared with those produced by equipment used at the Maisonneuve-Rosemont Hospital in Montreal. “Testing was conclusive: not only were the measurements as accurate, but our device took less than 60 seconds to produce results, compared to 30 minutes for current devices,” Masson said. Moreover, the comparative tests were performed by laboratory technicians who were not experienced with surface plasmon resonance and did not encounter major difficulties in operating the new equipment or obtaining the same conclusive results as Masson and his research team.

In addition to producing results in real time, the device designed by Masson is small and portable and requires little manipulation of samples. “In the near future, we can foresee the device in doctors’ offices or even at the bedside, where patients would receive individualized and optimal doses while minimizing the risk of complications,” Masson said. Another benefit, and a considerable one: “While traditional equipment requires an investment of around $100,000, the new mobile device would likely cost ten times less, around $10,000.”

For those who prefer to read the material in French here’s a link to ‘le 27 Octobre 2014 communiqué de nouvelles‘.

Here’s a prototype of the device,

Les nanoparticules d’or situées à la surface de la languette réceptrice modifient la couleur de la lumière détectée par l’instrument. La couleur captée reflète la concentration exacte du médicament contenu dans l’échantillon sanguin. Courtesy  Université de Montréal

Les nanoparticules d’or situées à la surface de la languette réceptrice modifient la couleur de la lumière détectée par l’instrument. La couleur captée reflète la concentration exacte du médicament contenu dans l’échantillon sanguin. Courtesy Université de Montréal

There is no indication as to when this might come to market, in English  or in French.

The evolution of molecules as observed with femtosecond stimulated Raman spectroscopy

A July 3, 2014 news item on Azonano features some recent research from the Université de Montréal (amongst other institutions),

Scientists don’t fully understand how ‘plastic’ solar panels work, which complicates the improvement of their cost efficiency, thereby blocking the wider use of the technology. However, researchers at the University of Montreal, the Science and Technology Facilities Council, Imperial College London and the University of Cyprus have determined how light beams excite the chemicals in solar panels, enabling them to produce charge.

A July 2, 2014 University of Montreal news release, which originated the news item, provides a fascinating description of the ultrafast laser process used to make the observations,

 “We used femtosecond stimulated Raman spectroscopy,” explained Tony Parker of the Science and Technology Facilities Council’s Central Laser Facility. “Femtosecond stimulated Raman spectroscopy is an advanced ultrafast laser technique that provides details on how chemical bonds change during extremely fast chemical reactions. The laser provides information on the vibration of the molecules as they interact with the pulses of laser light.” Extremely complicated calculations on these vibrations enabled the scientists to ascertain how the molecules were evolving. Firstly, they found that after the electron moves away from the positive centre, the rapid molecular rearrangement must be prompt and resemble the final products within around 300 femtoseconds (0.0000000000003 s). A femtosecond is a quadrillionth of a second – a femtosecond is to a second as a second is to 3.7 million years. This promptness and speed enhances and helps maintain charge separation.  Secondly, the researchers noted that any ongoing relaxation and molecular reorganisation processes following this initial charge separation, as visualised using the FSRS method, should be extremely small.

As for why the researchers’ curiosity was stimulated (from the news release),

The researchers have been investigating the fundamental beginnings of the reactions that take place that underpin solar energy conversion devices, studying the new brand of photovoltaic diodes that are based on blends of polymeric semiconductors and fullerene derivatives. Polymers are large molecules made up of many smaller molecules of the same kind – consisting of so-called ‘organic’ building blocks because they are composed of atoms that also compose molecules for life (carbon, nitrogen, sulphur). A fullerene is a molecule in the shape of a football, made of carbon. “In these and other devices, the absorption of light fuels the formation of an electron and a positive charged species. To ultimately provide electricity, these two attractive species must separate and the electron must move away. If the electron is not able to move away fast enough then the positive and negative charges simple recombine and effectively nothing changes. The overall efficiency of solar devices compares how much recombines and how much separates,” explained Sophia Hayes of the University of Cyprus, last author of the study.

… “Our findings open avenues for future research into understanding the differences between material systems that actually produce efficient solar cells and systems that should as efficient but in fact do not perform as well. A greater understanding of what works and what doesn’t will obviously enable better solar panels to be designed in the future,” said the University of Montreal’s Carlos Silva, who was senior author of the study.

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

Direct observation of ultrafast long-range charge separation at polymer–fullerene heterojunctions by Françoise Provencher, Nicolas Bérubé, Anthony W. Parker, Gregory M. Greetham, Michael Towrie, Christoph Hellmann, Michel Côté, Natalie Stingelin, Carlos Silva & Sophia C. Hayes. Nature Communications 5, Article number: 4288 doi:10.1038/ncomms5288 Published 01 July 2014

This article is behind a paywall but there is a free preview available vie ReadCube Access.

Canada’s ‘nano’satellites to gaze upon luminous stars

The launch (from Yasny, Russia) of two car battery-sized satellites happened on June 18, 2014 at 15:11:11 Eastern Daylight Time according to a June 18, 2014 University of Montreal (Université de Montréal) news release (also on EurekAlert).

Together, the satellites are known as the BRITE-Constellation, standing for BRIght Target Explorer. “BRITE-Constellation will monitor for long stretches of time the brightness and colour variations of most of the brightest stars visible to the eye in the night sky. These stars include some of the most massive and luminous stars in the Galaxy, many of which are precursors to supernova explosions. This project will contribute to unprecedented advances in our understanding of such stars and the life cycles of the current and future generations of stars,” said Professor Moffat [Anthony Moffat, of the University of Montreal and the Centre for Research in Astrophysics of Quebec], who is the scientific mission lead for the Canadian contribution to BRITE and current chair of the international executive science team.

Here’s what the satellites (BRITE-Constellatio) are looking for (from the news release),

Luminous stars dominate the ecology of the Universe. “During their relatively brief lives, massive luminous stars gradually eject enriched gas into the interstellar medium, adding heavy elements critical to the formation of future stars, terrestrial planets and organics. In their spectacular deaths as supernova explosions, massive stars violently inject even more crucial ingredients into the mix. The first generation of massive stars in the history of the Universe may have laid the imprint for all future stellar history,” Moffat explained. “Yet, massive stars – rapidly spinning and with radiation fields whose pressure resists gravity itself – are arguably the least understood, despite being the brightest members of the familiar constellations of the night sky.” Other less-massive stars, including stars similar to our own Sun, also contribute to the ecology of the Universe, but only at the end of their lives, when they brighten by factors of a thousand and shed off their tenuous outer layers.

BRITE-Constellation is both a multinational effort and a Canadian bi-provincial effort,

BRITE-Constellation is in fact a multinational effort that relies on pioneering Canadian space technology and a partnership with Austrian and Polish space researchers – the three countries act as equal partners. Canada’s participation was made possible thanks to an investment of $4.07 million by the Canadian Space Agency. The two new Canadian satellites are joining two Austrian satellites and a Polish satellite already in orbit; the final Polish satellite will be launched in August [2014?].

All six satellites were designed by the University of Toronto Institute for Aerospace Studies – Space Flight Laboratory, who also built the Canadian pair. The satellites were in fact named “BRITE Toronto” and “BRITE Montreal” after the University of Toronto and the University of Montreal, who play a major role in the mission.  “BRITE-Constellation will exploit and enhance recent Canadian advances in precise attitude control that have opened up for space science  the domain of very low cost, miniature spacecraft, allowing a scientific return that otherwise would have had price tags 10 to 100 times higher,” Moffat said. “This will actually be the first network of satellites devoted to a fundamental problem in astrophysics.”

Is it my imagination or is there a lot more Canada/Canadian being included in news releases from the academic community these days? In fact, I made a similar comment in my June 10, 2014 posting about TRIUMF, Canada’s National Laboratory for Particle and Nuclear Physics where I noted we might not need to honk our own horns quite so loudly.

One final comment, ‘nano’satellites have been launched before as per my Aug. 6, 2012 posting,

The nanosatellites referred to in the Aug.2, 2012 news release on EurekALert aren’t strictly speaking nano since they are measured in inches and weigh approximately eight pounds. I guess by comparison with a standard-sized satellite, CINEMA, one of 11 CubeSats, seems nano-sized. From the news release,

Eleven tiny satellites called CubeSats will accompany a spy satellite into Earth orbit on Friday, Aug. 3, inaugurating a new type of inexpensive, modular nanosatellite designed to piggyback aboard other NASA missions. [emphasis mine]

One of the 11 will be CINEMA (CubeSat for Ions, Neutrals, Electrons, & MAgnetic fields), an 8-pound, shoebox-sized package which was built over a period of three years by 45 students from the University of California, Berkeley, Kyung Hee University in Korea, Imperial College London, Inter-American University of Puerto Rico, and University of Puerto Rico, Mayaguez.

This 2012 project had a very different focus from this Austrian-Canadian-Polish effort. From the University of Montreal news release,

The nanosatellites will be able to explore a wide range of astrophysical questions. “The constellation could detect exoplanetary transits around other stars, putting our own planetary system in context, or the pulsations of red giants, which will enable us to test and refine our models regarding the eventual fate of our Sun,” Moffatt explained.

Good luck!

Biosensing cocaine

Amusingly, the Feb. 13, 2013 news item on Nanowerk highlights the biosensing aspect of the work in its title,

New biosensing nanotechnology adopts natural mechanisms to detect molecules

(Nanowerk News) Since the beginning of time, living organisms have developed ingenious mechanisms to monitor their environment.

The Feb. 13, 2013 news release from the University of Montreal (Université de Montréal) takes a somewhat different tack by focusing on cocaine,

Detecting cocaine “naturally”

Since the beginning of time, living organisms have developed ingenious mechanisms to monitor their environment. As part of an international study, a team of researchers has adapted some of these natural mechanisms to detect specific molecules such as cocaine more accurately and quickly. Their work may greatly facilitate the rapid screening—less than five minutes—of many drugs, infectious diseases, and cancers.

Professor Alexis Vallée-Bélisle of the University of Montreal Department of Chemistry has worked with Professor Francesco Ricci of the University of Rome Tor Vergata and Professor Kevin W. Plaxco of the University of California at Santa Barbara to improve a new biosensing nanotechnology. The results of the study were recently published in the Journal of American Chemical Society (JACS).

The scientists have provided an interesting image to illustrate their work,

Artist's rendering: the research team used an existing cocaine biosensor (in green) and revised its design to react to a series of inhibitor molecules (in blue). They were able to adapt the biosensor to respond optimally even within a large concentration window. Courtesy: University of Montreal

Artist’s rendering: the research team used an existing cocaine biosensor (in green) and revised its design to react to a series of inhibitor molecules (in blue). They were able to adapt the biosensor to respond optimally even within a large concentration window. Courtesy: University of Montreal

The news release provides some insight into the current state of biosensing and what the research team was attempting to accomplish,

“Nature is a continuing source of inspiration for developing new technologies,” says Professor Francesco Ricci, senior author of the study. “Many scientists are currently working to develop biosensor technology to detect—directly in the bloodstream and in seconds—drug, disease, and cancer molecules.”

“The most recent rapid and easy-to-use biosensors developed by scientists to determine the levels of various molecules such as drugs and disease markers in the blood only do so when the molecule is present in a certain concentration, called the concentration window,” adds Professor Vallée-Bélisle. “Below or above this window, current biosensors lose much of their accuracy.”

To overcome this limitation, the international team looked at nature: “In cells, living organisms often use inhibitor or activator molecules to automatically program the sensitivity of their receptors (sensors), which are able to identify the precise amount of thousand of molecules in seconds,” explains Professor Vallée-Bélisle. “We therefore decided to adapt these inhibition, activation, and sequestration mechanisms to improve the efficiency of artificial biosensors.”

The researchers put their idea to the test by using an existing cocaine biosensor and revising its design so that it would respond to a series of inhibitor molecules. They were able to adapt the biosensor to respond optimally even with a large concentration window. “What is fascinating,” says Alessandro Porchetta, a doctoral student at the University of Rome, “is that we were successful in controlling the interactions of this system by mimicking mechanisms that occur naturally.”

“Besides the obvious applications in biosensor design, I think this work will pave the way for important applications related to the administration of cancer-targeting drugs, an area of increasing importance,” says Professor Kevin Plaxco. “The ability to accurately regulate biosensor or nanomachine’s activities will greatly increase their efficiency.”

The funders for this project are (from the news release),

… the Italian Ministry of Universities and Research (MIUR), the Bill & Melinda Gates Foundation Grand Challenges Explorations program, the European Commission Marie Curie Actions program, the U.S. National Institutes of Health, and the Fonds de recherche du Québec Nature et Technologies.

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

Using Distal-Site Mutations and Allosteric Inhibition To Tune, Extend, and Narrow the Useful Dynamic Range of Aptamer-Based Sensors by Alessandro Porchetta, Alexis Vallée-Bélisle, Kevin W. Plaxco, and Francesco Ricci. J. Am. Chem. Soc., 2012, 134 (51), pp 20601–20604 DOI: 10.1021/ja310585e Publication Date (Web): December 6, 2012

Copyright © 2012 American Chemical Society

This article is behind a paywall.

One final note, Alexis Vallée-Bélisle has been mentioned here before in the context of a ‘Grand Challenges Canada programme’ (not the Bill and Melinda Gates ‘Grand Challenges’) announcement of several fundees  in my Nov. 22, 2012 posting. That funding appears to be for a difference project.

Self-assembling protein inspires University of Montreal’s researchers to smaller efforts

Protein folding doesn’t seem all that exciting to me and the notion that it might lead to self-assembled, living machines isn’t all that new (see my May 31, 2012 posting about a Living Foundries project). So the June 10, 2012 news item on Nanowerk left me with a flat feeling, initially,

Enabling bioengineers to design new molecular machines for nanotechnology applications is one of the possible outcomes of a study by University of Montreal researchers that was published in Nature Structural and Molecular Biology today (“Visualizing transient protein folding intermediates by tryptophan scanning mutagenesis” [behind a paywall]). The scientists have developed a new approach to visualize how proteins assemble, which may also significantly aid our understanding of diseases such as Alzheimer’s and Parkinson’s, which are caused by errors in assembly.

“In order to survive, all creatures, from bacteria to humans, monitor and transform their environments using small protein nanomachines made of thousands of atoms,” explained the senior author of the study, Prof. Stephen Michnick of the university’s department of biochemistry. “For example, in our sinuses, there are complex receptor proteins that are activated in the presence of different odor molecules. Some of those scents warn us of danger; others tell us that food is nearby.” Proteins are made of long linear chains of amino acids, which have evolved over millions of years to self-assemble extremely rapidly – often within thousandths of a split second – into a working nanomachine.

My ears pricked up when the talk turned to capturing images of action, which occurs in a “fleetingly short time,”

“To understand how a protein goes from a linear chain to a unique assembled structure, we need to capture snapshots of its shape at each stage of assembly said Dr. Alexis Vallée-Bélisle, first author of the study. “The problem is that each step exists for a fleetingly short time and no available technique enables us to obtain precise structural information on these states within such a small time frame. We developed a strategy to monitor protein assembly by integrating fluorescent probes throughout the linear protein chain so that we could detect the structure of each stage of protein assembly, step by step to its final structure.” The protein assembly process is not the end of its journey, as a protein can change, through chemical modifications or with age, to take on different forms and functions. “Understanding how a protein goes from being one thing to becoming another is the first step towards understanding and designing protein nanomachines for biotechnologies such as medical and environmental diagnostic sensors, drug synthesis or delivery,” Vallée-Bélisle said.

Here’s an image of protein self-assembly from the University of Montreal (Université de Montréal) website (Montréal, Québec, Canada),

Vallée-Bélisle and Michnick have developed a new approach to visualize how proteins assemble, which may also significantly aid our understanding of diseases such as Alzheimer's and Parkinson's, which are caused by errors in assembly. Here shown are two different assembly stages (purple and red) of the protein ubiquitin and the fluorescent probe used to visualize these stage (tryptophan: see yellow). Credit: Peter Allen

I would have liked a little more detail (e.g. how little time is there to capture the images?) but there isn’t always time either for the people who write these news releases or for me to follow up with questions. Given the huge political unrest amongst students over the proposed tuition fees and the Québec government’s attempts (sometimes described as draconian) to impose order, I’m impressed this news release was pulled together.