Ultra-Sensitive Surface Enhanced Raman Spectroscopy Sensor For In-Situ Monitoring Of Dopamine Release Using Zipper-Like Ortho-Nanodimers

Accurate quantitative detection of dopamine (DA) in blood is essential for the early diagnosis and the pathogenesis analysis of dopaminergic dysfunction, which still remains a great challenge because of the extremely low concentration in patients. Using our previously reported DNA-assisted synthesis of ortho-nanodimers (DaSON) strategy, a microfluidic surface enhanced Raman spectroscopy (SERS) biosensor for the ultrasensitive and reliable detection of DA in serum was demonstrated by modifying SERS probes with DA aptamers in a specific orientation to form zipper-like ortho-nanodimers. The uniform 1-nm gap in zipper-like ortho-nanodimers endows the SERS sensor with ultrahigh sensitivity and high accuracy for the detection of DA. The limit of detection is as low as 10 aM in phosphate buffer saline and 10 fM in serum, which is about two orders of magnitude lower than that of previous methods. Using a single microfluidic chip containing a 3D cell culture unit, quantitatively in-situ monitoring of extracellular DA released from living neurons under different medications was first realized. Quantification of DA in human blood samples was also achieved with the recoveries ranging from 87.5% to 123.7%. Given the difficulty of DA quantification in complex physiological samples, our developed SERS sensor provides an appealing tool for in-vitro investigating of neurological processes and clinical examination of dopaminergic disorders.