Smartphones to diagnose diseases in real time

Date: Mar-11-2014A team from the US is developing a disease diagnostic system based on nanotechnology that will

only require a smartphone and a $20 lens attachment to read results. While there are still some

challenges to overcome, they are hopeful the end result will be an affordable diagnostic tool

that can be used in the field.

The new system is the creation of Jiming Bao, assistant professor of electrical and computer

engineering, and Richard Willson, professor of chemical and biomolecular engineering, at the

University of Houston in Texas.

The journal ACS Photonics recently published a paper they and other colleagues wrote

about the nanotechnology biosensing method at the heart of the system.

The essential design of the system is a biosensing device coupled with a simple microscope

that can read the results. Nanotechnology features in the biosensing part and the smartphone -

enhanced with an affordable lens - could be the microscope part, say the researchers.

In their study, they describe how they developed a high-throughput biosensing technique that

combines optical transmission of nanoholes with silver staining.

Essentially, the device works like all diagnostic tools - it detects the result of a chemical

reaction between a pathogen and a molecule that bonds uniquely with it.

The pathogen could be a virus or bacterium, and the molecule could be a disease-fighting

antibody. A good example of an ironclad diagnosis is the reaction that occurs when a strep

bacterium reacts with a unique anti-strep antibody. The diagnostic system allows the reaction to

happen and then senses the result in a way so it cannot be confused with any other.

The challenge is to devise a system that works quickly, cheaply and easily: both on the

biosensing side of allowing the reactions and the results to happen uniquely, and on the

interpretation side, so they can be viewed and analyzed.

Thin glass slide with transparent nanoholes that can be filled with bacteria and

viruses

For the biosensing side, the team at Houston created a simple glass slide and a thin film of

gold with thousands of nanoholes punched in it. This in itself was a technological achievement

involving several stages, such as using lasers to cut "interference fringes" on a plate coated

with a photoresist material, washing it, then exposing it to evaporated gold.

The result is a glass slide coved with a thin film of gold with ordered rows and columns of

transparent nanoholes - each measuring only 600 nanometers - that let light pass through them.

To put that in perspective, consider that human hair measures about 60,000 nanometers in

diameter.

The stage was set to get the pathogens - bacteria and viruses - to populate the nanoholes and

allow the chemical reactions to take place inside the holes. But here came another challenge.

When the pathogens reacted with antibodies (plus a few added ingredients) in the

nanoholes to produce the required diagnostic chemical reaction, the bond was not enough to block

out the light.

As Prof. Willson explains:

"The thing that binds to the antibody is probably not big and grey enough to darken this

hole, so you have to find a way to darken it up somehow."

They finally got there by using antibodies carrying enzymes that produce silver

particles when exposed to certain chemicals.

With this second round of antibodies now attached to any pathogens in the holes, the whole

slide can then be exposed to chemicals that encourage silver production. The

slide can be rinsed off 15 minutes later, and thanks to the gold, the silver particles remain in their holes and

block the light.

And there you have the required diagnostic: you place a sample of pathogen on the slide, you bathe the slide in a solution containing antibodies that you know react

uniquely with various pathogens, then you shine a light through the holes and if they are blocked you have a positive result.

Smartphone with camera, flash and attached lens becomes a microscope

Now all that is needed is a microscope to look at the holes and see which ones do not let

light through. Prof. Willson says a basic microscope used in elementary schools would be good

enough. And with a few small tweaks, there is no reason why a smartphone camera with a flash and

an extra lens attached could not do the job.

"Some of the more advanced diagnostic systems need $200,000 worth of instrumentation to read

the results," he explains, yet "with this, you can add $20 to a phone you already have and

you're done."

The team acknowledges there is still a way to go before they can start rolling the system

out. For example, they still need to find a way to drive the
bacteria and viruses

in the sample down to the surface of the slide to get sufficiently accurate results.

But they are hopeful of overcoming these challenges and being able to give health care

providers in the field a portable, cheap, accurate and fast way to diagnose diseases.

The researchers give a practical example of how the smartphone system could help in an industrial accident. With the nanohole slide

and smartphone system, it would be possible to analyzed up to 10 contaminants at a time and get

nearly instant readouts, allowing respondents to assess the danger very quickly.

Another area they foresee such a system as being useful for is in poor regions where large

groups of people could be screened for widespread and serious disease, like diabetes. As Prof.

Willson explains:

"There are a lot of situations where an affordable diagnostic tool that is simple to use and

simple to interpret could be very useful. If both your disposables and your reader are cheap,

that makes it a lot easier to extend your system out into the real world."

The National Institutes of Health and The Welch Foundation helped to fund the study.

In September 2013, Medical News Today reported on a study where a

smartphone system was devised for diagnosing

eye diseases. The easy-to-use system captures high-quality photos of retinas, and could

bring the advantages of affordable telemedicine to ophthalmology clinics.

Written by Catharine Paddock PhD




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