Temporal and spatial changes in neurotransmitter concentrations are central to information processing in neural networks. Therefore, biosensors for neurotransmitters are essential tools for neuroscience. In this work, we applied a new technique, corona phase molecular recognition (CoPhMoRe), to identify adsorbed polymer phases on fluorescent single-walled carbon nanotubes (SWCNTs) that allow for the selective detection of specific neurotransmitters, including dopamine. We functionalized and suspended SWCNTs with a library of different polymers (n = 30) containing phospholipids, nucleic acids, and amphiphilic polymers to study how neurotransmitters modulate the resulting band gap, near-infrared (nIR) fluorescence of the SWCNT. We identified several corona phases that enable the selective detection of neurotransmitters. Catecholamines such as dopamine increased the fluorescence of specific single-stranded DNA-and RNAwrapped SWCNTs by 58−80% upon addition of 100 μM dopamine depending on the SWCNT chirality (n,m). In solution, the limit of detection was 11 nM [K d = 433 nM for (GT) 15 DNA-wrapped SWCNTs]. Mechanistic studies revealed that this turn-on response is due to an increase in fluorescence quantum yield and not covalent modification of the SWCNT or scavenging of reactive oxygen species. When immobilized on a surface, the fluorescence intensity of a single DNA-or RNA-wrapped SWCNT is enhanced by a factor of up to 5.39 ± 1.44, whereby fluorescence signals are reversible. Our findings indicate that certain DNA/ RNA coronae act as conformational switches on SWCNTs, which reversibly modulate the SWCNT fluorescence. These findings suggest that our polymer−SWCNT constructs can act as fluorescent neurotransmitter sensors in the tissue-compatible nIR optical window, which may find applications in neuroscience.

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Corona phase molecular recognition (CoPhMoRe) uses a heteropolymer adsorbed onto and templated by a nanoparticle surface to recognize a specific target analyte. This method has not yet been extended to macromolecular analytes, including proteins. Herein we develop a variant of a CoPhMoRe screening procedure of single-walled carbon nanotubes (SWCNT) and use it against a panel of human blood proteins, revealing a specific corona phase that recognizes fibrinogen with high selectivity. In response to fibrinogen binding, SWCNT fluorescence decreases by >80% at saturation. Sequential binding of the three fibrinogen nodules is suggested by selective fluorescence quenching by isolated sub-domains and validated by the quenching kinetics. The fibrinogen recognition also occurs in serum environment, at the clinically relevant fibrinogen concentrations in the human blood. These results open new avenues for synthetic, non-biological antibody analogues that recognize biological macromolecules, and hold great promise for medical and clinical applications.

Molecular recognition is central to the design of therapeutics, chemical catalysis and sensors. Motifs for doing so most commonly involve biological structures such as antibodies and aptamers. The key to such biological recognition consists of a folded and constrained heteropolymer that, via intra-molecular forces, forms a unique three dimensional structure that creates a binding pocket or an interface able to recognize a specific molecule. In this work, we demonstrate that synthetic heteropolymers can be alternatively constrained by adsorption around a nanoparticle, and specifically a single walled carbon nanotube (SWNT), forming a corona phase and resulting in a new form of molecular recognition of specific molecules. The phenomenon is shown to be generic, with new heteropolymer recognition complexes demonstrated for three distinct examples: Riboflavin, l-thyroxine, and estradiol, each predicted using a 2D thermodynamic model of surface interactions. The dissociation constants are continuously tunable by perturbing the chemical structure of the heteropolymer. Moreover, these complexes can be used as new types of spatial-temporal sensors based on modulation of SWNT photoemission in the near-infrared, as we show by tracking riboflavin diffusion in murine macrophages.

Intercellular communication via chemical signaling proceeds with both spatial and temporal components, but analytical tools, such as microfabricated electrodes, have been limited to just a few probes per cell. In this work, we use a nonphotobleaching fluorescent nanosensor array based on single-walled carbon nanotubes (SWCNTs) rendered selective to dopamine to study its release from PC12 neuroprogenitor cells at a resolution exceeding 20,000 sensors per cell. This allows the spatial and temporal dynamics of dopamine release, following K + stimulation, to be measured at exceedingly high resolution. We observe localized, unlabeled release sites of dopamine spanning 100 ms to seconds that correlate with protrusions but not predominately the positive curvature associated with the tips of cellular protrusions as intuitively expected. The results illustrate how directionality of chemical signaling is shaped by membrane morphology, and highlight the advantages of nanosensor arrays that can provide high spatial and temporal resolution of chemical signaling.sensors | imaging | dopamine | carbon nanotubes | chemical signaling