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European Inventor Armed with Lab-on-a-Chip Fights Infectious Disease

Some argue antimicrobial resistance (AMR), the ability of microbes to develop resistance to antimicrobial drugs, is a growing threat. Others say superbugs are already here, citing the increase in strains of antibiotic-resistant tuberculosis worldwide and the spread of staph infections.

There's little argument about this fact, however: if we are not in a post-antibiotic era now, we will be soon. Such an era would see patients dying from common infections caused by bacteria, parasites, virus and fungi, and from minor injuries.

In a study commissioned by British Prime Minister David Cameron, it was found that drug-resistant infections will reach global costs of $100 trillion and will add 10 million deaths a year, by 2050.

In the overall war against antibiotic resistance, the battle against hospital-acquired infections plays a major role. While infections can be caught anywhere, many of the antibiotic-resistant infections occur in hospitals and other medical facilities. Resistance is inevitable, but overly-broad prescriptions, inaccurate prescriptions and misuse of antibiotics exacerbate the problem. According to the Infectious Disease Society, up to 50 percent of antibiotic use is unnecessary or improperly used.

These infections that attack patients, making them sicker than they were when they came in with a previous illness, derail the name and purpose of health care. They cost billions of dollars. They cost thousands of lives.

While a recent report from the Centers for Disease Control and Prevention (CDC) in the U.S. reported a noticeable reduction in some cases of hospital-acquired infections, other infectious diseases, such as influenza and malaria, are becoming increasingly resistant to antibiotics and remain at large.

To be able to slow the development of drug-resistance, medical professionals must treat infections with accurate and specific antimicrobial drugs. The problem here, however, lies in the unknown. If the specific source of the problem (i.e. the bug causing the infection) isn't known, physicians often prescribe an overly-broad antibiotic, hoping it will eliminate the problem. Often it doesn't - it just puts the patient at risk and adds to the factors spurring on drug resistance.

To inspire companies to develop technology that would help physicians isolate the cause of infections and prescribe the right drugs in the right doses, Nesta and Innovate UK launched the Longitude Prize 2014. With a £10 million prize fund, the contest is an effort to combat the growing problem with a "cost-effective, accurate, rapid and easy-to-use test for bacterial infections that will allow health professionals worldwide to administer the right antibiotics at the right time."

One contender for the prize is Professor Chris Toumazou, winner of the European Inventor Award in 2014, and his company, DNA Electronics (DNAe). His semiconductor DNA sequencing technology, Genalysis, is a microchip that turns chemically encoded DNA into digital information that can help treat hospital-acquired infections - in particular, sepsis.

An increasingly problematic infection, sepsis, which results in inflammatory responses in the body triggered by chemicals in the bloodstream, can lead to severe organ failure and death. In the U.K. alone, sepsis kills over 37,000 people a year. The key to preventing this is early treatment of the infection with antibiotics and fluids.  

To ensure physicians use the correct drugs to treat these infections, Toumazou developed his semiconductor DNA sequencing technology around a small device the size of a USB stick.

"It was a eureka moment when I just took a microchip, and instead of putting electricity on [it], I put DNA, and the microchip turned on. It was sort of 'wow, I've got a really neat way now of sequencing DNA,' " Toumazou said excitedly.

The microchip technology is more than just neat, it's brilliant. On the surface of the microchip, when the electrical gate is peeled off, a chemically sensitive layer of silicon nitride is revealed. Immobilizing the DNA onto the surface and putting down the nucleotides, the building blocks of nucleic acids such as DNA, releases pyrophosphate, which brings on a pH change. The change essentially "turns on" the semiconductor, similar to how a pH probe works, except with the chip the nucleotide bases must be matching. While the chip is detecting the mutations, the DNA is also getting amplified.

"If the DNA matches, you got the mutation and it turns on the semiconductor, and if it doesn't match, it doesn't work," Toumazou explained.

So how can this device, smaller than a thumb, help fight sepsis infections in hospitals? It goes back to isolating the right bug, or the correct source of the problem, and eliminating the bug with a specific antibiotic rather than a broad one. But in the case of sepsis, isolating the bug needs to happen quickly.

"It's really all about speed," he says. The faster you can isolate the DNA of the bug, the sooner the proper antibiotic can be prescribed. It takes too long for hospitals to send cultures to the lab to identify the bug. While the culture is being developed, infections can turn deadly. The semiconductor microchip isolates the DNA of the bug in under an hour, giving physicians time to prescribe the correct, tailored antibiotic, often before pre-sepsis turns into full-blown sepsis.

The quicker the bug is isolated for any infection, the higher the chance the correct antibiotic will be prescribed. If broad or incorrect antibiotics are prescribed less often, medical professionals will contribute less to the development of antibiotic-resistant strains ringing in the post-antibiotic era.

"It's all down to making sure that you've got the right tailored medicine for that individual," Toumazou says. That's why he focuses on personalizing medicine based on quickly identifying mutations. He was inspired to develop tools for personal genetics after his son, Marcus, was found to have a genetic predisposition to renal disease. Marcus lost his kidneys at a young age. Toumazou believes that knowing about the predisposition earlier would have helped him manage Marcus's lifestyle and make it more comfortable. Marcus later received a kidney transplant, but went through a challenging period of time beforehand living with monitors and a dialysis machine.

If his son's medical difficulties were the motivators for Toumazou's interest in personalized genetics, Toumazou's experience as a professor at Imperial College London was the inspiration for his semiconductor microchip. Much of the idea for a device that combines speed and cost to fight infectious disease came from his encounters with clinicians at the school's hospital. These clinicians faced the nightmare of hospital-acquired infections everyday and he heard about the problem firsthand. He realized personalization was not only helpful, it was essential.

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