Origami diagnostic tests to aid disease elimination

Reducing the impact of diseases such as malaria, sleeping sickness, schistosomiasis and rabies is a global priority. Many agencies are working together on ambitious programs to eliminate many of them during the next decade.

The Head of the Foundation for Innovative New Diagnostics (FIND), Professor Joseph Ndung’u, neglected tropical disease (NTD) programme raises new and important challenges for a new generation of diagnostics.

To succeed in eliminating any of the NTDs, surveillance is critical. There is a pressing need to monitor emerging hot spots of re-emergence or screen communities who might be carrying sub-clinical reservoirs of the infections.

Professor Ndung’u not only proposes the need for very sensitive tests, but also that they need to be multiplexed (able to test for multiple pathogens from a single sample).

In practice, this means that, when testing for an endemic disease such as malaria, other sensors integrated in the same device can monitor and inform the progress towards elimination of another disease (or multiple diseases).

Such sensors must also be low cost and easily used by healthcare workers to test entire communities that are at risk to re-emergence, following interventions.

With funding from EPSRC ISF, Professor Jon Cooper and colleagues from the School of Engineering, including Dr Julien Reboud and Alice Garret (PhD student), have been developing a low-cost paper-based diagnostic device to meet these criteria.

Crucially, this test can quantify levels of infection using DNA. This provides species-specific information that quickly and accurately informs the appropriate treatment of the infection. DNA-based testing comes with many advantages over conventional immunodiagnosis (the detection of antigens and antibodies in the blood or serum).

For example, the ability to differentiate between current and historical infections means that the sensors can also quantify the decrease in prevalence within a community. This is crucial to monitoring the progress of a local or national elimination strategy.

DNA-based testing, which often has an associated amplification mechanism, is very sensitive and can also detect asymptomatic levels of infection. This enables the treatment of individuals who appear healthy but have the potential to infect others.

DNA testing has the potential to inform therapy. When more than one species of microbe is co-endemic, a multiplex DNA sensor can provide species-specific information.

In malaria diagnostics, for example, effective treatment may depend on this information. Similarly, as the global threat of antimicrobial resistance continues, the ability to detect the drug resistance status and directly inform treatment will become ever more important.

Paper is not only low cost, but it can support predictable microfluidic flows of samples and reagents. It is also easily disposable by burning. Importantly it is one of the few materials with the characteristic to crease and stay creased.

Folding paper in a manner similar to origami can bring reagents and samples together and can be used as an easy way of performing sample preparation and washing steps.

Flow of samples and reagents in the paper can be readily controlled using “channels” created by printing hydrophobic layers into the paper. This cheap method for device fabrication, using commercially available hot-wax printing, should enable the production of these tests in the countries where the disease elimination initiatives are taking place.

“Our Biomedical Engineering group at Glasgow has a history of technological innovation and expertise in biosensor technology. Being able to define and control the chemistries of paper using hot wax printing was really an enabling technology in this process.”

"Using our origami tests, we have now worked in Africa and India and explored multiplexed 'sample-to-answer' paper origami tests for infections, including those caused by trematodes, protozoa, bacteria and viruses, from a variety of samples including blood, sperm and faeces in humans and animals.

The recent involvement of a healthcare technology assessment team to explore the economic impact of potential interventions is an important development in our programme. It is one we hope will demonstrate the health and economic benefits of the programme."

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