Invasive brain implants and tethered optical fibres are typically used in restrained or motion-impaired animals, limiting the control and the decoding of the neural circuitry in freely behaving ones. Here we report the implant- and tether-free optical neurostimulation of deep brain regions by locally injected and untargeted photothermal transducers. The macromolecular transducers, comprising a semiconducting polymer core and an amphiphilic polymer shell, have an average diameter of 40 nanometres and achieve a photothermal conversion of 71% (at 1064 nm), activating the transient receptor potential cation channel subfamily V member 1 (TRPV1) ectopically expressed by an adeno-associated virus in dopaminergic neurons of tyrosine hydroxylase-driven Cre recombinase transgenic mice. The near-transparency of biological tissue in the second near-infrared window enabled the light source to be placed at 50 centimetres above the mouse, at a low incident power density of 10 milliwatt/square millimetre, resulting in the activation, through the scalp and skull, of the dopaminergic neurons in the ventral tegmental area, with minimal thermal damage. The approach is suitable for the neurostimulation of socially interacting mice.

We present a device that can achieve controlled transport of colloidal microparticles using an array of micro-electrodes. By exciting the micro-electrodes in regular sequence with an AC voltage, a time-varying moving dielectrophoretic force-field is created. This force propels colloidal microparticles along the electrode array. Using this method, we demonstrate bidirectional transport of polystyrene micro-spheres. Electromagnetic simulation of the device is performed, and the dielectrophoretic force profile around the electrode array is mapped. We develop a Brownian dynamics model of the trajectory of a particle under the influence of the time-varying force-field. Numerical and experimental results showing controlled particle transport are presented. The numerical model is found to be in good agreement with experimental data. The developed numerical framework can be useful in designing and modeling lab-on-a-chip devices that employ external non-contact forces for micro-/nanoparticle manipulation.

Neural modulation techniques with electricity, light and other forms of energy have enabled the deconstruction of neural circuitry. One major challenge of existing neural modulation techniques is the invasive brain implants and the permanent skull attachment of an optical fiber for modulating neural activity in the deep brain. Here we report an implant-free and tether-free optical neuromodulation technique in deep-brain regions through the intact scalp with brain-penetrant second near-infrared (NIR-II) illumination. Macromolecular infrared nanotransducers for deep-brain stimulation (MINDS) demonstrate exceptional photothermal conversion efficiency of 71% at 1064 nm, the wavelength that minimizes light attenuation by the brain in the entire 400-1700 nm spectrum. Upon widefield 1064-nm illumination >50 cm above the mouse head at a low incident power density of 10 mW/mm2, deep-brain neurons are activated by MINDS-sensitized TRPV1 channels with minimal thermal damage. Our approach could open opportunities for simultaneous neuromodulation of multiple socially interacting animals by remotely irradiating NIR-II light to stimulate each subject individually.