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Rapid Antimicrobial Resistance Diagnostics System Advances

MRSA bacteria

Scanning electron micrograph of methicillin-resistant Staphylococcus aureus, or MRSA, in brown spheres, surrounded by cellular debris. (NIAID, NIH)

2 Nov. 2018. Developers of a system that uses high-speed genomic analysis with standard semiconductor chips say they demonstrated an ability to sequence bacterial DNA directly from raw blood samples. This advance, says DNA Electronics in London meets the first stage of a contract with the Biomedical Advanced Research and Development Authority, or BARDA, to develop a system for rapid diagnosis of antimicrobial resistant infections and influenza.

DNA Electronics, or DNAe, is a spin-off enterprise from the biomedical engineering lab of Chris Toumazou at Imperial College London and the company’s scientific founder, which studies semiconductor technology for medical diagnostics and therapies. In that lab, Toumazou and colleagues developed devices such as cochlear implants for born-deaf children, an artificial pancreas for type 1 diabetics, and wireless heart monitors for personalized ambulatory health monitoring.

DNAe’s technology, known as LiDia uses a single semiconductor chip to perform high-throughput genomic sequencing, sometimes called next-generation sequencing, of blood samples to detect infections. Nucleotides, the basic building blocks of nucleic acids in DNA, says the company, release hydrogen ions that can be detected as electrical signals. The LiDia system recognizes specific patterns of those signals using standard CMOS semiconductor chip, without the need for added fluorescent dyes or precision optics that add time and cost. The company says it can identify a targeted infection in about 3 hours, faster than most other tests on the market that require a day or more.

DNAe’s first product analyzes blood samples for sepsis infections, a continuing concern for medical facilities. In their work for BARDA, an agency of the U.S. Department of Health and Human Services responsible for medical countermeasures against terrorist and public health threats, DNAe is extending the system to diagnose antimicrobial resistant infections. Among the bacteria with antibiotic resistant strains, often found in health care facilities, are E. coli, Klebsiella pneumoniae, Enterococcus faecium, Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus, or MRSA.

The antimicrobial resistance problem, notes World Health Organization is global and growing. The organization says new mechanisms of resistance to antibiotics are emerging that threaten our ability to combat infections from pneumonia, tuberculosis, blood poisoning, gonorrhea, and foodborne diseases. The company cites data showing at least 2 million people in the U.S. become infected with bacteria that are resistant to antibiotics and at least 23,000 people die each year as a direct result of these infections.

The first stage of the BARDA contract calls for DNAe to sequence the DNA of target bacteria from raw, unprocessed blood samples. The company says its technology successfully demonstrated that capability. The contract, signed in September 2016, has a total payout of nearly $52 million.The company says it received approval from BARDA to proceed with the second stage of the contract to develop a prototype device.

Toumazou says in a company statement that DNAe’s system can help make antibiotic prescriptions more precise and effective than today’s practices. “The relative speed, simplicity, scalability and cost-effectiveness of semiconductor sequencing,” he notes, “allow it to be used in a much wider range of settings than previously possible for DNA sequencing, and make it particularly suited to application in diagnosis.”

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