NIR Biosensing of Neurotransmitters in Stem Cell‐Derived Neural Interface Using Advanced Core–Shell Upconversion Nanoparticles

• Published in: Advanced materials (Weinheim) 2019-04, Vol.31 (14), p.e1806991-n/a
• Main Authors: Rabie, Hudifah, Zhang, Yixiao, Pasquale, Nicholas, Lagos, Maureen J., Batson, Philip E., Lee, Ki‐Bum
• Format: Article
• Language: English
• Subjects: Biomedical materials; Biosensing Techniques - methods; Biosensors; Cell Differentiation; core–shell nanostructures; Crystal structure; detection of dopamine; Differentiation (biology); Dopamine; Energy conservation; energy migration; Erbium; Fluorescence; Fluorides; Humans; Infrared Rays; Luminescence; Materials science; Migration; Models, Molecular; Molecular Conformation; Nanoparticles; Nanoparticles - chemistry; Neural Stem Cells - cytology; Neurological diseases; Neurons - cytology; Neurotransmitter Agents - metabolism; Neurotransmitters; NIR biosensors; Sodium compounds; stem cell differentiation; Stem cells; Tissue engineering; Upconversion; upconversion nanoparticles; Ytterbium
• ISSN: 0935-9648; 1521-4095; 1521-4095
• DOI: 10.1002/adma.201806991

Nondestructive neurotransmitter detection and real‐time monitoring of stem cell differentiation are both of great significance in the field of neurodegenerative disease and regenerative medicine. Although luminescent biosensing nanoprobes have been developed to address this need, they have intrinsic limitations such as autofluorescence, scattering, and phototoxicity. Upconversion nanoparticles (UCNPs) have gained increasing attention for various biomedical applications due to their high photostability, low auto‐fluorescent background, and deep tissue penetration; however, UCNPs also suffer from low emission intensities due to undesirable energy migration pathways. To address the aforementioned issue, a single‐crystal core–shell–shell “sandwich” structured UCNP is developed that is designed to minimize deleterious energy back‐transfer to yield bright visible emissions using low power density excitations. These UCNPs show a remarkable enhancement of luminescent output relative to conventional β‐NaYF4:Yb,Er codoped UCNPs and β‐NaYF4:Yb,Er@NaYF4:Yb “active shell” alike. Moreover, this advanced core–shell–shell UCNP is subsequently used to develop a highly sensitive biosensor for the ultrasensitive detection of dopamine released from stem cell‐derived dopaminergic‐neurons. Given the challenges of in situ detection of neurotransmitters, the 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. A novel “sandwich” structured upconversion nanoparticle (UCNP) is designed to minimize the detrimental energy back‐transfer from erbium to ytterbium, which promotes extremely bright green luminescence at low power densities. Based on the exceptional upconversion luminescence property, a GO‐LRET‐quenching‐based turn‐on optical sensor is constructed to detect dopamine in live cells to demonstrate its utility.