Tag Archives: hand-held diagnostics

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.

e-Gnosis chip (nanopore sensor) competition on Marblar—winning money and developing a reputation for brilliance

It’s probably best to explain Marblar, a creative ‘playground’ or, as it could be called, a ‘wisdom of the crowd initiative’, before describing the e-Gnosis chip project.

Basically, Marblar is inviting people to participate in an online game/conversation where competitors make suggestions to ‘host’ inventors about how to best commercialize their inventions. Anyone can register to join in; there are two types of incentives for ‘game players’. First, they can accumulate marbles/points by voting and/or contributing ideas. Second, they can win cash prizes. Here’s how the Marblar community describes itself, from the About page,

Marblar is a creative playground that takes over-looked technology and unleashes a crowd of multi-disciplined, brilliant Marblars to discover new applications.

It is like a big game where many minds work together to realise the promise of science. Working with tech holders, we find the best technology deserving of a second look and transform these into challenges for the crowd of Marblars. The best ideas win points, kudos, and prizes. Best yet anyone can tackle any challenge. We don’t care what your background is…we care about your applied brilliance.

There’s a very interesting list of organizations backing this initiative, heavily weighted towards UK institutions but with a solid international presence, from the Partners page,

University of Oxford
Oxford, England

MRC Laboratory of Molecular Biology
Cambridge, England

Svaya Nanotechnologies
California, USA

Imperial Innovations
London, England

Edinburgh Research and Innovation
Edinburgh, Scotland

King’s College London
London, UK

Exploit Technologies

Virginia Tech
Virginia, USA

Getting back to the game, for the hosted competitions, participants get to brainstorm ideas for a fixed period of time. These ideas are then refined over another fixed period of time with the inventor finally choosing a winner.

Now on to the specific game/project, the e-Gnosis chip (nanopore sensor). The inventor, Peter Kollensperger of the Imperial College London, has created a portable diagnostic device. There are many such diagnostic devices being developed all over the world, many of them designed for medical use. Kollensperger wants to find another market niche for his e-Gnosis chip device,

The vast majority of biosensors today are based on some form of optical readout to get the  results you want. You usually have a choice between inexpensive (but non-quantitative) methods such as lateral flow tests (e.g. pregnancy tests), which just show you a blue line if positive, or more sensitive tests that can tell you how much of the analyte is present using specialised optical equipment. These quantitative tests generally require several extra wash steps and additional reagents and are carried out by labs or on specialised microfluidic or robotic platforms. We wanted to develop a sensitive, quantitative technology that doesn’t require expensive platforms but instead:

  • Could be read using a low-cost smartphone or laptop accessory (<$20);
  • Works with a small amount of sample (~10 microlitre, such as a tiny drop of blood, urine or saliva)
  • Requires no (or just one) washing steps.
  • Runs several different tests on the same sample simultaneously.
  • Is as easy to use as a pregnancy test.

Here’s what the inventor is looking for (from the e-Gnosis chip page),

We’ve been looking at the field of medical diagnostics for a while, but the point-of-care market is highly competitive, fragmented into relatively small markets, with high entry barriers in the form of FDA [US Food and Drug Administration]/EMA [European Medicines Agency] approval. So for any medical diagnostic we’d need a large market, where our device’s unique features (multiplexing, rapid & simple point-of-care use without sample prep) offer a very significant competitive advantage, and can justify the high barrier costs for approval.

We’d be very interested to hear ideas about a consumer market to prove the device commercially, keeping in mind:

  • While the chip-manufacturing part of the process is cheap, the cost/test is unlikely to ever fall below $6-8 due to functionalization and assembly. We need an application where customers would pay enough to allow a reasonable profit margin.
  • Need a high-volume application to justify setup costs of chip-manufacture (>$300k). What’s your market size?
  • What would be the market entry route? Who’d be our commercial partners? What are the competing devices and their price? How would distinguish ourselves against these?

Here’s a little more about Kollensperger (from the e-Gnosis chip page),

I’m Peter Kollensperger and I’m working with Prof. Green in the Optical and Semiconductor Devices Group of the Electrical and Electronic Engineering Department at Imperial College London.

My research to date has focused on the use of nanotechnology for biosensing applications, but my overarching interest is in making diagnostic/sensing technologies more accessible both to doctors and the general public.

The combination of scalable nanotechnology and the hugely parallel processing of semiconductor foundries holds great promise for the area of biosensors and we are looking for applications where the end-user wants to get results on the go without spending a large upfront amount on a reader. This can be in medical diagnostics, but ideally would be in an underserved consumer market where the combination of properties of our chip can make a real difference.

The Marblar community offers video services for the inventors hosting competitions and this is Kollensperger’s

Diagnostics Array from Marblar on Vimeo.

There’s still time (20 days) to enter the competition. Good luck!

By the way, I owe a big thank you to Daniel Bayley for contacting me about the project and about Marblar.

Alberta’s diagnostic tool on a chip (aka point-of-care diagnostics)

2012 seems to be continuing a trend that 2011 enjoyed, the race to develop diagnostics-on-a-chip (aka handheld diagnostics or point-of-care diagnostics). The latest story is from Tannara Yelland for Canadian University Press in a Jan. 3, 2012 article titled, Where nanotechnology and medicine meet; University of Alberta researcher shrinks medical tests, makes them more affordable,

Researchers have made great strides in diagnostic tools for detecting the genetic abnormalities that lead to or signal cancers, but many of these remain solely the province of experimental labs because of practical impediments like the cost of equipment.

Aiming specifically to make clinical medicine easier and less expensive to conduct, Pilarski [Linda Pilarski, a University of Alberta oncology professor and Canada Research Chair in Biomedical Nanotechnology] and her team have created a microfluidic chip about the size of a thumbnail that can test for up to 80 different genetic markers of cancer.

“Most of the things we were doing were much too complicated to do in a clinical lab,” Pilarski said. “Their technology has to be far more regulated than what we’re doing in the lab. It may be feasible [to use current experimental tests] in a big research hospital, but not in Stony Plains [Alberta], in our little health care centre, for example.

“And with tests that are feasible, they’re feasible only because they study many samples at once.”

… They have reversed the normal procedure, studying several samples for one disease, in the hopes of making tests easier to do in more remote locations.

There are about 80 small posts attached to a glass chip, and each post carries out a different test for a different mutation. Unlike the currently used larger equipment, Pilarski says these chips should allow clinicians to perform the tests within an hour, and rather than make patients wait a nerve-wracking few days for their results, they can find out before they leave the lab.

While Pilarski’s work has focused on cancer, the chip she has developed could be used to test for any number of illnesses, which is precisely what medical equipment company Aquila Diagnostics plans to do with Pilarski’s technology.

“Some of the first things to come out might not be for cancer but for infectious diseases,” Pilarski said.

My most recent posting on handheld diagnostic tools, Dec. 22, 2011, noted the Grand Challenges grants (from the Bill & Melinda Gates Foundation and from the Canadian not-for-profit agency called Grand Challenges) awarded to researchers working on the problem of diagnosing infectious diseases in the developing world. From the posting,

The grants announced today are part of the Point-of-Care Diagnostics (POC Dx) Initiative [of the Bill & Melinda Gates Foundation], a research and development program with the goal of creating new diagnostic platforms that enable high-quality, low-cost diagnosis of disease, and also facilitate sustainable markets for diagnostic products, a key challenge in the developing world. This first phase of the POC Dx Initiative is focused on developing new technologies and identifying implementation issues to address the key barriers for clinical diagnostics in the developing world.

Getting back to  Pilarski and the Alberta initiative, the company mentioned in the article, Aquila Diagnostics is based in Edmonton, Alberta and is associated with the University of Alberta. From the company website home page,

Aquila is a medical device company focused on point-of-care diagnosis testing for blood borne infectious diseases and cancer. The Company is developing a portable diagnostic system that delivers rapid, low-cost, multiparameter tests without the need for highly-skilled operators. Aquila’s gel post PCR technology is protected and under licence from the University of Alberta.

I look forward to hearing more about these initiatives as they get closer to market.