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

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.

There are numerous beneficiaries of this Advanced Biomedical Materials CDT. Firstly and of short term impact are the PhD students themselves. They will receive extensive research specific and professional/transferable skills training throughout the 4 years of the programme. They will have access to state of the art facilties and world leading academics, industry and clinicians. The training and potential placements are designed to maximise the impact of their research in terms of dissemination and movement of their research along the translation pathway.

Longer term benefits are that this distinct cohort will become the future UK Biomedical Materials leaders and be able to use their bespoke training and network within the cohort to collaborate on future worldwide funding opportunities and drive UK research in this area.

UK and international academics will benefit as they will gain the next generation of highly skilled postdoctoral researchers with knowledge and expertise not only in their specific research area but of industry, regulatory and clinical aspects.

UK and international industry will benefit - in the short term they will gain academic based research to further develop products and in the longer term have a pool of highly skilled graduates.

Clinicians will benefit from collaborative research and also the development of new and novel products to enhance the treatment of a variety of trauma and disease based needs from biomaterials.

The public will benefit as end users as patients that will have their quality of life improved from the products developed in the CDT and will be educated in novel technologies and materials to repair the human body. The UK economy will benefit from the reduced healthcare costs associated with the new and improved medical products developed in this CDT and subsequently from the trained graduates. The UK economy will also benefit from the increased revenue from medical sales products from the UK industrial partners we will be working with.

The impact of this CDT will be realised by direct academic, clinical and industrial engagement with the students allowing efficient and state of the at training and fast translation of developing products. Students will also be trained in knowledge exchange and will use these skills to disseminate their research to, and liaise with, the key stakeholders - the academic, industrial, clinical and public sectors. We will ensure widening participation routes are addressed in this CDT in order to include equality and diversity not only in our initial CDT student cohort but in future researcher generations to come.