Imaging neuromodulation with synthetic probes is an emerging technology for studying neurotransmission. However, most synthetic probes are developed through conjugation of fluorescent signal transducers to preexisting recognition moieties such as antibodies or receptors. We introduce a generic platform to evolve synthetic molecular recognition on the surface of near-infrared fluorescent single-wall carbon nanotube (SWCNT) signal transducers. We demonstrate evolution of molecular recognition toward neuromodulator serotonin generated from large libraries of ~6.9 × 10¹⁰ unique ssDNA sequences conjugated to SWCNTs. This probe is reversible and produces a ~200% fluorescence enhancement upon exposure to serotonin with a K_d = 6.3 μM, and shows selective responsivity over serotonin analogs, metabolites, and receptor-targeting drugs. Furthermore, this probe remains responsive and reversible upon repeat exposure to exogenous serotonin in the extracellular space of acute brain slices. Our results suggest that evolution of nanosensors could be generically implemented to develop other neuromodulator probes with synthetic molecular recognition.

Photoacoustic imaging using endogenous chromophores as a contrast has been widely applied in biomedical studies owing to its functional imaging capability at the molecular level. Various exogenous contrast agents have also been investigated for use in contrast-enhanced imaging and functional analyses. This review focuses on contrast agents, particularly in the wavelength range, for use in photoacoustic imaging. The basic principles of photoacoustic imaging regarding light absorption and acoustic release are introduced, and the optical characteristics of tissues are summarized according to the wavelength region. Various types of contrast agents, including organic dyes, semiconducting polymeric nanoparticles, gold nanoparticles, and other inorganic nanoparticles, are explored in terms of their light absorption range in the near-infrared region. An overview of the contrast-enhancing capacity and other functional characteristics of each agent is provided to help researchers gain insights into the development of contrast agents in photoacoustic imaging.