Nanoplasmonic Aptasensing Enables Real-Time Optical Monitoring of Neurotransmitters in Living Brainstem Organoids.

Disruption of dopamine signaling is central to Parkinson's disease (PD) pathology and a primary target of symptomatic therapy. However, direct measurement of dopamine dynamics in human neural tissue with high sensitivity, temporal resolution, and compatibility with three-dimensional models remains technically challenging. Here, an organoid-on-a-chip platform that integrates a cavity-coupled nanoplasmonic aptasensor with human brainstem organoids (hBSOs) and microfluidic control is employed for label-free monitoring of the extracellular dopamine response. The plasmonic aptasensor achieves a limit of detection of 8.3 pM with minimal cross-reactivity with related catecholamines. Under static conditions, dopamine secretion from healthy- and PD-line hBSOs is quantified, revealing reduced basal secretion in PD-line organoids and selective enhancement by PD-targeted drugs compared with non-PD agents. Under perfused microfluidic conditions, L-DOPA-induced dopamine changes are monitored continuously over 12 h, and real-time spectral peak shifts are reconstructed into dopamine concentration-time profiles to assess kinetic responses to drug treatment. This real-time, nanoplasmonic neurotransmitter sensing framework links controlled drug dosing to extracellular dopamine dynamics in human neural organoid-on-chip systems for preclinical evaluation of PD therapies and other neuroactive perturbations.