Development and in-vitro validation of an ultrasensitive multianalyte biosensing patch for real-time monitoring of brain injury and infection severity

Innovation description Wearable and wireless ultrasensitive multianalyte biosensing device to monitor brain injury and infection severity Biomarkers: Tau, glial fibrillary acidic protein (GFAP), lactate, C-reactive protein (CRP), IL-6 Unmet patient need There is an unmet need for longitudinal monitoring and early recognition of brain injury during infection. Brain injury occurs through neurological disorders secondary to infection such as stroke, and the impact of inflammation on the brain (1). Neurological disorders affected 1/3 people with COVID-19 in 2020, have poor functional outcomes, and cost the UK economy £96 billion per year (2–4). I demonstrated in the national COVID-CNS study acutely raised brain injury biomarkers in COVID-19 that persisted for one year (Tau, GFAP and Neurofilament light chain), and were associated with cognitive deficits equivalent to 20 years of ageing and reduced grey matter volume (Nature Med 2024 (5,6)). Crucially, neurological disorders can be subtle, which means lasting damage can occur before they are diagnosed. We want to develop a biosensor to rapidly identify brain injury. Patient benefit Early intervention for brain injury in infection has the potential to reduce the burden of neurological disorders in the NHS. We anticipate initially using the biosensor in patients admitted to hospital and expanding to the community. There is value to underserved communities, especially patients who are less able to communicate their problems or travel to seek healthcare. Alignment with call We will answer a single question to bring our innovative healthcare technology for acquired brain injury in infection to the next stage of development and ready for further investment. Robust evidence generated We have developed a low-cost prototype of transdermal devices for personalised healthcare monitoring (7). Almost all biomarkers that are present in blood are also present in interstitial fluid (ISF) (8). Our minimally invasive patch uses functionalised microneedle electrodes, enabling highly sensitive, selective and stable real-time determination of metabolites (lactate, glucose), cytokines (IL-6), and drugs (theophylline, B-lactam antibiotics) (9–12). This has been validated in vitro and tested on healthy volunteers. Separately, a point of care voltametric sensor has been validated in vitro for the detection of p-tau (441) in ISF and plasma, employing a Tau-specific molecularly imprinted polymer (13). There is proof-of-concept for GFAP and CRP (14,15). Capturing additional value from artificial intelligence (AI) We have successfully integrated AI-based calibration algorithms, reducing artefact-induced distortions and improving accuracy and reliability (Figure 1, Prepared - embargoed). Figure 1: Schematic diagram of the subdermal patch and AI. Evidence gap We want to develop and validate an advanced prototype, detecting biomarkers of brain injury (Tau, GFAP) and infection (lactate, IL-6, CRP) on the same patch. Input from patients and public The initial transdermal patch was developed with and by the Microprobe Glucose Sensor PPI Advisory Group. The group wanted a small, painless patch, an accessible display, and data readily available (16). This proposal was written in collaboration with the COVID-CNS PPI panel (17). The panel raised concerns about late diagnosis of neurological disorders, motivating development of technology for early recognition. COVID-CNS successfully reached under-represented groups (18,19).