Capacitive and Efficient Near-Infrared Stimulation of Neurons via an Ultrathin AgBiS2 Nanocrystal Layer.

Colloidal nanocrystals (NCs) exhibit significant potential for photovoltaic bioelectronic interfaces because of their solution processability, tunable energy levels, and inorganic nature, lending them chemical stability. Silver bismuth sulfide (AgBiS2) NCs, free from toxic heavy-metal elements (e.g., Cd, Hg, and Pb), particularly offer an exceptional absorption coefficient exceeding 105 cm-1 in the near-infrared (NIR), surpassing many of their inorganic counterparts. Here, we integrated an ultrathin (24 nm) AgBiS2 NC layer into a water-stable photovoltaic bioelectronic device architecture that showed a high capacitive photocurrent of 2.3 mA·cm-2 in artificial cerebrospinal fluid (aCSF) and ionic charges over 10 µC·cm-2 at a low NIR intensity of 0.5 mW·mm-2. The device without encapsulation showed a halftime of 12.5 years under passive accelerated aging test and did not show any toxicity on neurons. Furthermore, patch-clamp electrophysiology on primary hippocampal neurons under whole-cell configuration revealed that the device elicited neuron firing at intensity levels more than an order of magnitude below the established ocular safety limits. These findings point to the potential of AgBiS2 NCs for photovoltaic retinal prostheses.

A Retina-Inspired Optoelectronic Synapse Using Quantum Dots for Neuromorphic Photostimulation of Neurons.

Neuromorphic electronics, inspired by the functions of neurons, have the potential to enable biomimetic communication with cells. Such systems require operation in aqueous environments, generation of sufficient levels of ionic currents for neurostimulation, and plasticity. However, their implementation requires a combination of separate devices, such as sensors, organic synaptic transistors, and stimulation electrodes. Here, a compact neuromorphic synapse that combines photodetection, memory, and neurostimulation functionalities all-in-one is presented. The artificial photoreception is facilitated by a photovoltaic device based on cell-interfacing InP/ZnS quantum dots, which induces photo-faradaic charge-transfer mediated plasticity. The device sends excitatory post-synaptic currents exhibiting paired-pulse facilitation and post-tetanic potentiation to the hippocampal neurons via the biohybrid synapse. The electrophysiological recordings indicate modulation of the probability of action potential firing due to biomimetic temporal summation of excitatory post-synaptic currents. These results pave the way for the development of novel bioinspired neuroprosthetics and soft robotics, and highlight the potential of quantum dots for achieving versatile neuromorphic functionality in aqueous environments.

A Retina-Inspired Optoelectronic Synapse Using Quantum Dots for Neuromorphic Photostimulation of Neurons.

Neuromorphic electronics, inspired by the functions of neurons, have the potential to enable biomimetic communication with cells. Such systems require operation in aqueous environments, generation of sufficient levels of ionic currents for neurostimulation, and plasticity. However, their implementation requires a combination of separate devices, such as sensors, organic synaptic transistors, and stimulation electrodes. Here, a compact neuromorphic synapse that combines photodetection, memory, and neurostimulation functionalities all-in-one is presented. The artificial photoreception is facilitated by a photovoltaic device based on cell-interfacing InP/ZnS quantum dots, which induces photo-faradaic charge-transfer mediated plasticity. The device sends excitatory post-synaptic currents exhibiting paired-pulse facilitation and post-tetanic potentiation to the hippocampal neurons via the biohybrid synapse. The electrophysiological recordings indicate modulation of the probability of action potential firing due to biomimetic temporal summation of excitatory post-synaptic currents. The results pave the way for the development of novel bioinspired neuroprosthetics and soft robotics and highlight the potential of quantum dots for achieving versatile neuromorphic functionality in aqueous environments.

MnO2 Nanoflower Integrated Optoelectronic Biointerfaces for Photostimulation of Neurons.

Optoelectronic biointerfaces have gained significant interest for wireless and electrical control of neurons. Three-dimentional (3D) pseudocapacitive nanomaterials with large surface areas and interconnected porous structures have great potential for optoelectronic biointerfaces that can fulfill the requirement of high electrode-electrolyte capacitance to effectively transduce light into stimulating ionic currents. In this study, the integration of 3D manganese dioxide (MnO2 ) nanoflowers into flexible optoelectronic biointerfaces for safe and efficient photostimulation of neurons is demonstrated. MnO2 nanoflowers are grown via chemical bath deposition on the return electrode, which has a MnO2 seed layer deposited via cyclic voltammetry. They facilitate a high interfacial capacitance (larger than 10 mF cm-2 ) and photogenerated charge density (over 20 µC cm-2 ) under low light intensity (1 mW mm-2 ). MnO2 nanoflowers induce safe capacitive currents with reversible Faradaic reactions and do not cause any toxicity on hippocampal neurons in vitro, making them a promising material for biointerfacing with electrogenic cells. Patch-clamp electrophysiology is recorded in the whole-cell configuration of hippocampal neurons, and the optoelectronic biointerfaces trigger repetitive and rapid firing of action potentials in response to light pulse trains. This study points out the potential of electrochemically-deposited 3D pseudocapacitive nanomaterials as a robust building block for optoelectronic control of neurons.

Physical mechanisms of emerging neuromodulation modalities.

One of the ultimate goals of neurostimulation field is to design materials, devices and systems that can simultaneously achieve safe, effective and tether-free operation. For that, understanding the working mechanisms and potential applicability of neurostimulation techniques is important to develop noninvasive, enhanced, and multi-modal control of neural activity. Here, we review direct and transduction-based neurostimulation techniques by discussing their interaction mechanisms with neurons via electrical, mechanical, and thermal means. We show how each technique targets modulation of specific ion channels (e.g. voltage-gated, mechanosensitive, heat-sensitive) by exploiting fundamental wave properties (e.g. interference) or engineering nanomaterial-based systems for efficient energy transduction. Overall, our review provides a detailed mechanistic understanding of neurostimulation techniques together with their applications toin vitro, in vivo, and translational studies to guide the researchers toward developing more advanced systems in terms of noninvasiveness, spatiotemporal resolution, and clinical applicability.

Optical neuromodulation at all scales: from nanomaterials to wireless optoelectronics and integrated systems.

Light-based neuromodulation systems offer exceptional spatiotemporal resolution combined with the elimination of physical tether to communicate with neurons. Currently, optical neuromodulation systems ranging from the nano to the centimeter scale enable neural activity control from the single cell to the organ level in retina, heart, spinal cord, and brain, facilitating a wide range of experiments in intact and freely moving animals in different contexts, such as during social interactions and behavioral tasks. Nanotransducers (e.g., metallic nanoparticles, silicon nanowires, and polymeric nanoparticles) and microfabricated photodiodes convert light to electrical, thermal, and mechanical stimuli that can allow remote and non-contact stimulation of neurons. Moreover, integrated devices composed of nano and microscale optoelectronic components comprise fully implantable and wirelessly powered smart optoelectronic systems that exhibit multimodal and closed-loop operation. In this review, we first discuss the material platforms, stimulation mechanisms, and applications of passive systems, i.e., nanotransducers and microphotodiodes. Then, we review the use of organic and inorganic light-emitting diodes for optogenetics and implantable wireless optoelectronic systems that enable closed-loop optogenetic neuromodulation through the use of light-emitting diodes, wireless power transfer circuits, and feedback loops. Exploration of materials and mechanisms together with the presented applications from both research and clinical perspectives in this review provides a comprehensive understanding of the optical neuromodulation field with its advantages and challenges to build superior systems in the future.

Electrical Stimulation of Neurons with Quantum Dots via Near-Infrared Light.

Photovoltaic biointerfaces offer wireless and battery-free bioelectronic medicine via photomodulation of neurons. Near-infrared (NIR) light enables communication with neurons inside the deep tissue and application of high photon flux within the ocular safety limit of light exposure. For that, nonsilicon biointerfaces are highly demanded for thin and flexible operation. Here, we devised a flexible quantum dot (QD)-based photovoltaic biointerface that stimulates cells within the spectral tissue transparency window by using NIR light (λ = 780 nm). Integration of an ultrathin QD layer of 25 nm into a multilayered photovoltaic architecture enables transduction of NIR light to safe capacitive ionic currents that leads to reproducible action potentials on primary hippocampal neurons with high success rates. The biointerfaces exhibit low in vitro toxicity and robust photoelectrical performance under different stability tests. Our findings show that colloidal quantum dots can be used in wireless bioelectronic medicine for brain, heart, and retina.

Optoelectronic Neural Interfaces Based on Quantum Dots.

Optoelectronic modulation of neural activity is an emerging field for the investigation of neural circuits and the development of neural therapeutics. Among a wide variety of nanomaterials, colloidal quantum dots provide unique optoelectronic features for neural interfaces such as sensitive tuning of electron and hole energy levels via the quantum confinement effect, controlling the carrier localization via band alignment, and engineering the surface by shell growth and ligand engineering. Even though colloidal quantum dots have been frontier nanomaterials for solar energy harvesting and lighting, their application to optoelectronic neural interfaces has remained below their significant potential. However, this potential has recently gained attention with the rise of bioelectronic medicine. In this review, we unravel the fundamentals of quantum-dot-based optoelectronic biointerfaces and discuss their neuromodulation mechanisms starting from the quantum dot level up to electrode-electrolyte interactions and stimulation of neurons with their physiological pathways. We conclude the review by proposing new strategies and possible perspectives toward nanodevices for the optoelectronic stimulation of neural tissue by utilizing the exceptional nanoscale properties of colloidal quantum dots.

Nanoengineering InP Quantum Dot-Based Photoactive Biointerfaces for Optical Control of Neurons.

Light-activated biointerfaces provide a non-genetic route for effective control of neural activity. InP quantum dots (QDs) have a high potential for such biomedical applications due to their uniquely tunable electronic properties, photostability, toxic-heavy-metal-free content, heterostructuring, and solution-processing ability. However, the effect of QD nanostructure and biointerface architecture on the photoelectrical cellular interfacing remained unexplored. Here, we unravel the control of the photoelectrical response of InP QD-based biointerfaces via nanoengineering from QD to device-level. At QD level, thin ZnS shell growth (∼0.65 nm) enhances the current level of biointerfaces over an order of magnitude with respect to only InP core QDs. At device-level, band alignment engineering allows for the bidirectional photoelectrochemical current generation, which enables light-induced temporally precise and rapidly reversible action potential generation and hyperpolarization on primary hippocampal neurons. Our findings show that nanoengineering QD-based biointerfaces hold great promise for next-generation neurostimulation devices.

Quantum dot and electron acceptor nano-heterojunction for photo-induced capacitive charge-transfer.

Capacitive charge transfer at the electrode/electrolyte interface is a biocompatible mechanism for the stimulation of neurons. Although quantum dots showed their potential for photostimulation device architectures, dominant photoelectrochemical charge transfer combined with heavy-metal content in such architectures hinders their safe use. In this study, we demonstrate heavy-metal-free quantum dot-based nano-heterojunction devices that generate capacitive photoresponse. For that, we formed a novel form of nano-heterojunctions using type-II InP/ZnO/ZnS core/shell/shell quantum dot as the donor and a fullerene derivative of PCBM as the electron acceptor. The reduced electron-hole wavefunction overlap of 0.52 due to type-II band alignment of the quantum dot and the passivation of the trap states indicated by the high photoluminescence quantum yield of 70% led to the domination of photoinduced capacitive charge transfer at an optimum donor-acceptor ratio. This study paves the way toward safe and efficient nanoengineered quantum dot-based next-generation photostimulation devices.

Bidirectional optical neuromodulation using capacitive charge-transfer.

Artificial control of neural activity allows for understanding complex neural networks and improving therapy of neurological disorders. Here, we demonstrate that utilization of photovoltaic biointerfaces combined with light waveform shaping can generate safe capacitive currents for bidirectional modulation of neurons. The differential photoresponse of the biointerface due to double layer capacitance facilitates the direction control of capacitive currents depending on the slope of light intensity. Moreover, the strength of capacitive currents is controlled by changing the rise and fall time slope of light intensity. This approach allows for high-level control of the hyperpolarization and depolarization of membrane potential at single-cell level. Our results pave the way toward advanced bioelectronic functionalities for wireless and safe control of neural activity.

Plasmon-Coupled Photocapacitor Neuromodulators.

Efficient transduction of optical energy to bioelectrical stimuli is an important goal for effective communication with biological systems. For that, plasmonics has a significant potential via boosting the light-matter interactions. However, plasmonics has been primarily used for heat-induced cell stimulation due to membrane capacitance change (i.e., optocapacitance). Instead, here, we demonstrate that plasmonic coupling to photocapacitor biointerfaces improves safe and efficacious neuromodulating displacement charges for an average of 185% in the entire visible spectrum while maintaining the faradic currents below 1%. Hot-electron injection dominantly leads the enhancement of displacement current in the blue spectral window, and the nanoantenna effect is mainly responsible for the improvement in the red spectral region. The plasmonic photocapacitor facilitates wireless modulation of single cells at three orders of magnitude below the maximum retinal intensity levels, corresponding to one of the most sensitive optoelectronic neural interfaces. This study introduces a new way of using plasmonics for safe and effective photostimulation of neurons and paves the way toward ultrasensitive plasmon-assisted neurostimulation devices.

Biocompatible Quantum Funnels for Neural Photostimulation.

Neural photostimulation has high potential to understand the working principles of complex neural networks and develop novel therapeutic methods for neurological disorders. A key issue in the light-induced cell stimulation is the efficient conversion of light to bioelectrical stimuli. In photosynthetic systems developed in millions of years by nature, the absorbed energy by the photoabsorbers is transported via nonradiative energy transfer to the reaction centers. Inspired by these systems, neural interfaces based on biocompatible quantum funnels are developed that direct the photogenerated charge carriers toward the bionanojunction for effective photostimulation. Funnels are constructed with indium-based rainbow quantum dots that are assembled in a graded energy profile. Implementation of a quantum funnel enhances the generated photoelectrochemical current 215% per unit absorbance in comparison with ungraded energy profile in a wireless and free-standing mode and facilitates optical neuromodulation of a single cell. This study indicates that the control of charge transport at nanoscale can lead to unconventional and effective neural interfaces.

Ecofriendly and Efficient Luminescent Solar Concentrators Based on Fluorescent Proteins.

In recent years, luminescent solar concentrators (LSCs) have received renewed attention as a versatile platform for large-area, high-efficiency, and low-cost solar energy harvesting. So far, artificial or engineered optical materials, such as rare-earth ions, organic dyes, and colloidal quantum dots (QDs) have been incorporated into LSCs. Incorporation of nontoxic materials into efficient device architectures is critical for environmental sustainability and clean energy production. Here, we demonstrated LSCs based on fluorescent proteins, which are biologically produced, ecofriendly, and edible luminescent biomaterials along with exceptional optical properties. We synthesized mScarlet fluorescent proteins in Escherichia coli expression system, which is the brightest protein with a quantum yield of 61% in red spectral region that matches well with the spectral response of silicon solar cells. Moreover, we integrated fluorescent proteins in an aqueous medium into solar concentrators, which preserved their quantum efficiency in LSCs and separated luminescence and wave-guiding regions due to refractive index contrast for efficient energy harvesting. Solar concentrators based on mScarlet fluorescent proteins achieved an external LSC efficiency of 2.58%, and the integration at high concentrations increased their efficiency approaching to 5%, which may facilitate their use as "luminescent solar curtains" for in-house applications. The liquid-state integration of proteins paves a way toward efficient and "green" solar energy harvesting.