Sensory chip targets dengue fever outbreak

New technology is coming to the aid of Brazil’s once-vaunted reputation for mastery of tropical public health challenges, which took a serious tumble in 2016 when the nation proved incapable of controlling a trio of mosquito-borne human diseases.

On the eve of the Rio Olympics, a massive outbreak of three diseases transmitted by the Aedes Aegyptii mosquito deterred some elite athletes from competing in the Games, and one year later travel advisories from foreign governments still warn pregnant women against entering the country.

Aedes Aegyptii mosquito  responsible for a trio of infectious diseases

Aedes Aegyptii mosquito responsible for a trio of infectious diseases

The diseases are dengue, which in 2016 affected 1.5 million people, chikungunya with 215,000 cases and Zika with 215,000 cases. The most worrying is Zika, responsible for almost 5,000 cases in Brazil of microcephaly (a birth defect involving an abnormally small head and incomplete brain development in infants whose others were infected).

According to the US CDC, (Centers for Disease Control and Prevention) Zika, which originated in Uganda in the 1940s and was first reported in Brazil in 2015, has the potential to become a pandemic across the Americas except for Canada and Chile, and across Asia.

Zika may have garnered far more alarmist headlines, but in epidemiological terms Brazil’s real villain is dengue. Nevertheless until now there was simply no way of stopping it.

The absence of any reliable test kit meant there was no way for local public health officers with limited budgets to track these diseases, or to easily differentiate dengue. Although Brazil put its armed forces to work educating the population on how to eradicate Aedes Aegyptii breeding grounds, healthcare workers still struggle with primary disease identification.

But things could soon change, thanks to the recent invention of a simple, low-cost biosensor that can detect the presence of an antigen that’s characteristic of infection by dengue.

A smart but simple immunochip — called a Piezoelectric sensor – uses the electrochemical ability of certain materials, especially quartz crystals, to generate a voltage when subjected to mechanical stress or vibration. Changes in pressure, acceleration, temperature, strain or force can be measured by converting them to an electrical charge.

Piezoelectric sensors use thin films of oxidized bacterial cellulose nanocrystals to detect the presence of certain molecules. The sensor is based on a technology known as quartz crystal microbalance (QCM), able to detect amounts of a molecule such as a protein on the order of nanograms (billionths of a gram). In this case the molecule detected by the microbalance is the antigen (NS1) for dengue in blood serum.

Eventually, commercially-available biosensor kits could test blood samples, providing results in approximately 15 minutes without any need for sophisticated medical laboratory support – a prerequisite in developing nations.

The immunochip breakthrough came from the Biopol group in the Chemistry and Biochemistry & Biology Departments of the Federal University of Paraná (UFPR) in Curitiba.

The group undertook a comparative study between two different quartz crystal microbalance devices to discover which would work best in tropical developing nations with limited healthcare budgets. In these countries, healthcare workers just need a binary yes/no answer to whether dengue is present in blood samples.

The first chip was a sophisticated and higher-cost quartz crystal microbalance with energy dissipation monitoring (QCM-D). The second was a simpler, cheaper quartz crystal microbalance without energy dissipation monitoring (QCM). The limits of NS1 recognition of the two devices were 0.1 μg mL−1 for QCM-D and 0.32 μg mL−1 for QCM. This means that while both have good clinical utility as fast diagnostic tools for the detection of several diseases, the simplicity and cost benefit of the QCM is “good enough” for countries like Brazil.

The results of the study showing the immunochip’s potential were published in the journal Biosensors and Bioelectronics.

Cleverton Pirich, a PhD student in biochemistry and one of the study authors, said the chip works indirectly by detecting an antigen “that’s characteristic of infection by dengue. This is done by means of antibodies immobilized on the biosensor, which rapidly detect the presence of the antigen in a blood sample, indirectly diagnosing infection.”

Pirich added: “The aim is a qualitative diagnosis, a positive or negative result. Our proposal paves the way for the development of simpler and more affordable equipment to fulfil this purpose.” He believes that a commercially available immunochip of this type could provide results in approximately 15 minutes.

But building reliable prototype sensors of this type requires nanotechnology expertise beyond the reach of many developing nations. The result from any quartz crystal microbalance with energy dissipation monitoring (QCM-D) requires highly expert interpretation.

So the Biopol team from Paraná came to São Paulo to have their work validated by Roberto Manuel Torresi, a professor in the University of São Paulo’s Chemistry Institute (IQ-USP). “The microbalance in our lab is far more sophisticated than the others in Brazil,” said Torresi, describing his laboratory’s sophisticated and precise QCM-D equipment.

Torresi’s laboratory has one of the most sophisticated and precise QCM-Ds in operation in Brazil. It was purchased with FAPESP’s support.

Torresi was able to confirm the presence of NS1 in all the blood samples contaminated by addition of the dengue antigen, thus validating the Biopol team’s scientific method and confirming the dengue detection microsensor using simpler QCM is indeed a viable blueprint for development into a commercial product that could save lives.

You can read a report by Brazilian journalist Peter Moon by clicking here.

You can read the article “Piezoelectric immunochip coated with thin films of bacterial cellulose nanocrystals for dengue detection” by clicking here.

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