A major issue facing the diagnosis of neurodegenerative disease is the availability of an accessible, scalable, and highly sensitive technology. Compelling evidence now suggests that the abundance of blood-based dementia biomarkers, including ß-amyloid (Aß) and tau, and their ratios, change considerably before clinical symptoms arise. Assessing these parameters via a straightforward blood test could facilitate early-stage diagnosis, recruitment of patients into clinical trials, and open a platform for at-home treatment monitoring. Current technologies for biomarker analysis are resource-intensive, rely on cerebrospinal fluid extraction, and are not widely adopted. Here, we demonstrate the detection of blood-based biomarkers using a next-generation, label-free photonic biosensor based on the principle of chirped guided mode resonance (GMR) spectroscopy. Our handheld GMR device is a low-cost optical biosensor suitable for the real-time, sensitive and parallel detection of dementia biomarkers. The technology utilizes wavelength scale grating structures to excite a standing wave that is sensitive to refractive index changes on the sensor surface. When target biomarkers bind to antibodies on the sensor surface, a refractive index change gives rise to a detectable shift in resonance wavelength. The chirped element of the GMR translates spectral information into spatial position, allowing biomarker binding to be detected by imaging the spatial position of the optical resonance on a simple camera detector. Our label-free technology outperforms competing modalities including surface plasmon approaches, has demonstrable sensitivity to pg/mL concentrations of low molecular weight protein biomarkers, offers a wide dynamic range, is mechanically and thermally stable, enables the real-time detection of at least eight biomarkers in parallel, and corrects for non-specific binding. By applying our biosensing approach to the detection of dementia biomarkers, we have demonstrated the real-time and quantitative detection of Aß in laboratory analytes, paving the way for further developments towards a blood test technology to support disease diagnosis, at-home treatment monitoring, and the democratization of testing.
