Integrating CRISPR-Cas diagnostics into organic electronics for point-of-care genotyping

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Gentamicin is an aminoglycoside antibiotic commonly used to treat neonatal infections. Each year in the UK, approximately 90,000 babies are administered gentamicin on Neonatal Intensive Care Units (7 million worldwide). National and international guidelines stress the importance of rapid antibiotic administration, ideally within an hour for cases of suspected sepsis. In high doses, or with protracted regimens, aminoglycosides causes ototoxicity that can manifest as hearing or balance impairment. However, certain individuals have a genetic predisposition to aminoglycoside induced ototoxicity (AIO), whereby just a single dose causes profound and irreversible hearing loss. These individuals have a variant in the mitochondrial RNR1 gene (m.1555AG), which has a prevalence of 0.2% (1 in 500) in the general population. A method to rapidly (within minutes) determine a patient's genetic status from a buccal swab sample would therefore be of significant clinical value, by establishing if alternative antibiotics should be used instead to avoid AIO.This project aims to develop a bioelectronic device to detect the m.1555 variant from human buccal samples. Currently, a patient's genetic status is determined by PCR-based methods that require complex laboratory equipment, expensive reagents, specialist personnel, and are insufficiently rapid for this clinical scenario. The proposed device will biochemically detect the presence of the variant and deliver an easily interpretable digital read-out. Such an electronic output can then be transferred to a patient's electronic records, without the need for manual interpretation and transcription of the results, thus saving time and reducing the risk of human error.