A pin-based pyro-electrohydrodynamic jet sensor for tuning the accumulation of biomolecules down to sub-picogram level detection

The detection of low abundant biomarkers is of great interest in different clinical cases, such as the early diagnosis of Alzheimer's disease. Here we present what we call pin-based pyro-electrohydrodynamic jet (p-jet) sensor that can linearly tune the accumulation rate of biomolecules in tiny droplets. In this newly revealed pin-based configuration we demonstrate the ability to detect biomolecules down to sub-picogram concentration. Two different fluorescent probes at a varying number of accumulated droplets, up to 50, have been used to investigate the p-jet sensor. Moreover, a comparative study with a commercial piezo-driven bio-spotter has been performed. The spots of biomolecules exhibit high reproducibility by achieving a coefficient of variation <10%, both in diameter and fluorescence intensity, respectively. Remarkably, the spot intensity increases linearly with the number of accumulated droplets, thus showing the effective inherent additive functionality of this technique. Such accumulation effect allowed us to reach a limit of detection down to sub-picogram level. The p-jet sensor was applied to detect the Aβ1–42 protein, a typical Alzheimer's disease biomarker, through an immunoreaction protocol carried out on the p-jet spots. The results demonstrate the compatibility of the p-jet with immunoassay procedures, opening the route to the development of a highly sensitive device able to detect low abundant biomarkers for early diagnosis applications.