Highly sensitive detection of a neurodegenerative protein biomarker by using the pyro-electrohydrodynamic jet

A set of protein biomarkers are largely recognized as responsible of neurodegeneration mechanisms and hence as potential targets to be detected in low abundant concentrations in body fluids for performing early diagnosis. As an example, the Tau protein experiences a transition phase from a native disorder conformation into a preaggregation state, which leads to fibrillization processes. Here we show the possibility to detect Tau in urine samples at sub-picogram level, through the concentration effect of the pyro-electrohydrodynamic (p-jet) technique. An immunofluorescence protocol is applied to concentrated p-jet spots able to reduce drastically the diffusion effects in the antibody-antigen reaction. A set of diluted samples were prepared, and the fluorescence signal was detected by a confocal scanner. We achieved an excellent linear response with a significant signal-to-noise ratio down to 0.25 pg/mL. In perspective, the technique could be integrated into a compact device to be used for monitoring the early stage associated to neurodegenerative syndromes in different scenarios such as for example in long-term human space exploration missions.