PT  - JOURNAL ARTICLE
AU  - Alice J. Gillen
AU  - Alessandra Antonucci
AU  - Melania Reggente
AU  - Daniel Morales
AU  - Ardemis A. Boghossian
TI  - Distinguishing dopamine and calcium responses using XNA-nanotube sensors for improved neurochemical sensing
AID  - 10.1101/2021.02.20.428669
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.02.20.428669
4099  - http://biorxiv.org/content/early/2021/02/20/2021.02.20.428669.short
4100  - http://biorxiv.org/content/early/2021/02/20/2021.02.20.428669.full
AB  - To date, the engineering of single-stranded DNA-SWCNT (DNA-SWCNT) optical biosensors have largely focused on creating sensors for new applications with little focus on optimising existing sensors for in vitro and in vivo conditions. Recent studies have shown that nanotube fluorescence can be severely impacted by changes in local cation concentrations. This is particularly problematic for neurotransmitter sensing applications as spatial and temporal fluctuations in the concentration of cations, such as Na+, K+, or Ca2+, play a central role in neuromodulation. This can lead to inaccuracies in the determination of neurotransmitter concentrations using DNA-SWCNT sensors, which limits their use for detecting and treating neurological diseases.Herein, we present new approaches using locked nucleic acid (LNA) to engineer SWCNT sensors with improved stability towards cation-induced fluorescence changes. By incorporating LNA bases into the (GT)15-DNA sequence, we create sensors that are not only more resistant towards undesirable fluorescence modulation in the presence of Ca2+ but that also retain their capabilities for the label-free detection of dopamine. The synthetic biology approach presented in this work therefore serves as a complementary means for enhancing nanotube optoelectronic behavior, unlocking previously unexplored possibilities for developing nano-bioengineered sensors with augmented capabilities.Competing Interest StatementThe authors have declared no competing interest.