Neurotransmitters, for instance dopamine (DA), are significant endogenous signals in the central nervous system (CNS), as they play vital roles in modulating neurophysiological processes including cognition, emotion, memory, and other behaviors. Therefore, fast, ultra-sensitive, non-destructive and robust detection of neurotransmitters during stem cell differentiation and neuromodulation processes in the CNS would be of paramount importance for gaining an insight into how neural interactions regulate brain functions, developing better molecular diagnostics and therapeutics for neurological disorders. To this end, upconversion nanoparticles (UCNPs) have recently gained extensive attention as optical biosensors due to their excellent photo-stability, narrow emission bandwidths, as well as high signal to noise ratio, showing great potential in various applications; however, the relatively weak luminescence intensity due to low quantum efficiencies compromises the further development of UCNP-based applications.
Addressing this challenge, scientists from the Prof. Ki-Bum Lee's Lab (Hudifah Rabie, Yixiao Zhang, Nicholas Pasquale) develop novel "sandwich" structured UCNPs that use spatial separation of dopants to mitigate energy back transfer to allow for brighter emissions at lower excitation densities. Compared to previous core-shell designs, our "sandwich" structured UCNPs have several innovations: i) mitigating a significant deleterious photon back transfer pathway that has not been addressed, ii) exhibiting significantly higher luminescence, despite identical active components, and iii) having brighter overall luminescence in response to lower excitation power densities, especially for desired visible emissions. Furthermore, we utilized our advanced core-shell-shell UCNP for developing a highly sensitive biosensor for the ultrasensitive detection of dopamine released from stem cell-derived dopaminergic-neurons. Compared to conventional and commercially available biosensors, whose lower detection limits range in the nanomolar ranges, our biosensor provides sensing with up to 3 orders of magnitude higher sensitivity, in response to low power NIR excitation, thereby not only mitigating autofluorescence, light scattering, phototoxicity, but also thermal toxicity due to the lower power density of the NIR excitation. Given the challenges of in situ detection of neurotransmitters, our developed NIR-based biosensing of neurotransmitters in stem cell-derived neural interfaces present a unique tool for investigating single-cell mechanisms associated with dopamine, or other neurotransmitters, and their roles in neurological processes.
This work was recently published in Advanced Materials (Rabie, H. et al. 2019, 31: 1806991, DOI: 10.1002/adma.201806991) and was highlighted and selected for the cover.
Professor KiBum Lee