ReyeS - Eye-safe Raman Spectroscopy for in-vivo ABI biomarkers monitoring

We propose the development of a compact spectroscopy system to be integrated into a handheld device for non-invasive, real-time, in vivo diagnostics and monitoring of ABI-specific biomarkers, utilising information obtained from the blood vessels in the eye. The proposed system will employ Raman Spectroscopy (RS) in conjunction with imaging and signal processing for both point-of-interest data acquisition and chemometric analysis of the collected spectral signatures. Our objective is to target the blood vessels visible on the anterior surface of the eye for spectroscopic analysis. In the final design of the instrument, a handheld probe will be positioned in front of the patient's eye, and the patient will be instructed to look sideways, thereby exposing the numerous blood vessels present in the choroidal region. The front of the eye will then be imaged using an onboard camera, which will identify the unique locations of the blood vessels in each patient and guide the beam steering for point-of-interest spectroscopy of blood-based biomarkers. This innovative approach offers several advantages over traditional retinal analysis, as it eliminates variations caused by the eye's lens affecting the laser beam, as well as the overall influence of the anterior segment of the eye, vitreous humor, and retina on the spectroscopic data. By focusing on the blood vessels in the choroid near the front of the eye, our system will only need to penetrate the scleral tissue, thereby minimising the complexity of the matrix and reducing signal losses. This innovation addresses the unmet need for in vivo, non-invasive diagnostic instruments that rapidly measure and analyse blood-based ABI biomarkers, enabling the examination of the temporal dynamics of their concentration following brain injury. There is substantial evidence in the literature supporting the feasibility of this concept. RS is considered a highly effective technique for biomarker-based ABI diagnostics. [1-10]. The presence of validated ABI biomarkers in the eye, such as elevated concentrations of tau (detected through immunohistochemistry), supports the potential of the ocular ABI diagnostic tool [11]. Eye-based RS has also been demonstrated ex vivo [11-14], as well as with eye-safe protocols in vivo [15-19]; however, it has not yet been applied to ABI diagnostics. Although in a completely different context, machine vision-enabled point-of-interest spectroscopy has also been demonstrated in our team's research [20]. The presented concept is currently in the early stages of hardware development; therefore, there have not yet been any extensive public and patient involvement (PPI) activities. This concept has been shared with several experts in the fields of neurology and brain injury, all of whom have expressed interest in the proposed solution. Professor Tom McMillan and Dr. Neil Graham have joined the project in an advisory capacity to guide the development of this innovation. Additionally, this innovation has been discussed with Professor Karen Faulds, an expert in RS for bioanalysis, who has also joined the project in an advisory role.