Quaternary
ammonium (QA) plays multiple roles in biological functions,
whose dysregulation may result in multiple diseases. However, how
to efficiently detect QA-based materials such as acetylcholine (ACh)
still remains a great challenge, especially in complex biological
environments. Here, a new effect [called quaternary-ammonium-modulated
surface-enhanced Raman spectroscopy (QAM-SERS) effect] is discovered,
showing that the existence of QA will modulate the intensity of SERS
signals in a concentration-dependent manner. When the QAM-SERS effect
is used, a new method is easily developed for in vitro detection of ACh with an extremely high sensitivity and an ultrawide
dynamic range. Particularly, the linear dynamic range can be freely
tuned to adapt for various physiological samples. As a proof-of-concept
experiment, the time-dependent secretion of ACh from PC12 cells was
successfully monitored using the QAM-SERS method, which were under
either the stimulation of potassium ions or the incubation of drugs.
The discovery of the QAM-SERS effect provides an easy and universal
strategy for detecting ACh as well as other QA-contained molecules,
which can also inspire new insights into the roles that QA could play
in biology and chemistry.