Augmenting insect olfaction performance through nano-neuromodulation.

Biological olfactory systems are highly sensitive and selective, often outperforming engineered chemical sensors in highly complex and dynamic environments. As a result, there is much interest in using biological systems to build sensors. However, approaches to read-out information from biological systems, especially neural signals, tend to be suboptimal due to the number of electrodes that can be used and where these can be placed. Here we aim to overcome this suboptimality in neural information read-out by using a nano-enabled neuromodulation strategy to augment insect olfaction-based chemical sensors. By harnessing the photothermal properties of nanostructures and releasing a select neuromodulator on demand, we show that the odour-evoked response from the interrogated regions of the insect olfactory system can not only be enhanced but can also improve odour identification.

Neuronal maturation-dependent nano-neuro interaction and modulation.

Nanotechnology-enabled neuromodulation is a promising minimally-invasive tool in neuroscience and engineering for both fundamental studies and clinical applications. However, the nano-neuro interaction at different stages of maturation of a neural network and its implications for the nano-neuromodulation remain unclear. Here, we report heterogeneous to homogeneous transformation of neuromodulation in a progressively maturing neural network. Utilizing plasmonic-fluors as ultrabright fluorescent nanolabels, we reveal that negative surface charge of nanoparticles renders selective nano-neuro interaction with a strong correlation between the maturation stage of the individual neurons in the neural network and the density of the nanoparticles bound on the neurons. In stark contrast to homogeneous neuromodulation in a mature neural network reported so far, the maturation-dependent density of the nanoparticles bound to neurons in a developing neural network resulted in a heterogeneous optical neuromodulation (i.e., simultaneous excitation and inhibition of neural network activity). This study advances our understanding of nano-neuro interactions and nano-neuromodulation with potential applications in minimally-invasive technologies for treating neuronal disorders in parts of the mammalian brain where neurogenesis persists throughout aging.

Plasmon-Enhanced Expansion Microscopy.

Expansion microscopy (ExM) is a rapidly emerging super-resolution microscopy technique that involves isotropic expansion of biological samples to improve spatial resolution. However, fluorescence signal dilution due to volumetric expansion is a hindrance to the widespread application of ExM. Here, we introduce plasmon-enhanced expansion microscopy (p-ExM) by harnessing an ultrabright fluorescent nanoconstruct, called plasmonic-fluor (PF), as a nanolabel. The unique structure of PFs renders nearly 15000-fold brighter fluorescence signal intensity and higher fluorescence retention following the ExM protocol (nearly 76%) compared to their conventional counterparts (<16% for IR-650). Individual PFs can be easily imaged using conventional fluorescence microscopes, making them excellent "digital" labels for ExM. We demonstrate that p-ExM enables improved tracing and decrypting of neural networks labeled with PFs, as evidenced by improved quantification of morphological markers (nearly a 2.5-fold increase in number of neurite terminal points). Overall, p-ExM complements the existing ExM techniques for probing structure-function relationships of various biological systems.