In situ quantitative measurement of neurotransmitter [e.g., dopamine (DA)] activities can provide useful insights into the underlying mechanisms of stem cell differentiation, the formation of neuronal networks, and neurodegenerative diseases such as Parkinson’s disease (PD). Currently, neurotransmitter detection methods suffer from poor spatial resolution, nonspecific detection, and a lack of in situ analysis. Although Raman spectroscopy has arisen as a powerful tool for analyzing biomolecules in a highly selective and non-destructive manner, it has suffered from low sensitivity and signal homogeneity.

Addressing these challenges, Prof. Ki-Bum Lee and his team in the Department of Chemistry and Chemical Biology at Rutgers developed a highly sensitive and selective in situ detection system to monitor neurotransmitters at the single-cell level using a surface-enhanced Raman spectroscopy (SERS) analytical method. As a proof-of-concept, the team focused on the detection of DA secreted from dopaminergic cells, including neural stem cells. To overcome the inherent drawback of high signal intensity variation in SERS biosensing, finely-tuned homogeneous gold nanoarrays with tooth-like structures fabricated by laser interferene lithography were used to uniformly enhance Raman signal. For the specific detection of DA, Raman dye-labeled aptamers were bound onto the surface of the hybrid nano-SERS array. The presence of DA released the aptamer from the GO surface by forming a DA-aptamer complex. The subsequent decrease of Raman intensity due to the detachment of Raman dye-labeled aptamer was found to be proportional to the DA concentration. As a result, the developed sensing platform can measure a wide range of DA concentrations (10–4 to 10–9 M) rapidly (within one hour). Additionally, the release of DA from single dopaminergic cells and NSCs was successfully measured. More specifically, neuronal differentiation was determined by measuring the decrease of Raman signals in situ in a spatially controlled and highly sensitive manner.

In summary, the demonstration of sensitive and selective DA detection in live cells could lead to breakthroughs in stem cell therapies for CNS diseases, such as PD, by validating the therapeutic effects of dopaminergic cells before their transplantation into patients. In general, our nano-SERS array represents a novel live-cell sensing platform and may pave new roads for understanding and treating many devastating neurological disorders. Publication: This work was recently published in Advanced Materials (DOI: 10.1002/adma.202004285).


CORRESPONDENCE: Prof. Ki-Bum Lee (Rutgers University); Prof. Jeong-Woo Choi (Sogang University)

Rutgers AUTHORS: Dr. Jin-Ha Choi, Dr. Letao Yang, Brian M. Conley

Group Members

Ki Bum Lee Ph 
             KiBum Lee, Ph.D.

Jin Ha Choi            
          Jin-Ha Choi, Ph.D.

Letao Yang Ph
            Letao Yang, Ph.D.

Brian Connely
              Brian M. Conley