Graphene Sensors from DARPA will be used to understand Brain from the neurons on up

New technology funded by DARPA’s RE-NET program enables monitoring and stimulation of neurons using optical and electronic methods simultaneously

Understanding the anatomical structure and function of the brain is a longstanding goal in neuroscience and a top priority of President Obama’s brain initiative. Electrical monitoring and stimulation of neuronal signaling is a mainstay technique for studying brain function, while emerging optical techniques—which use photons instead of electrons—are opening new opportunities for visualizing neural network structure and exploring brain functions. Electrical and optical techniques offer distinct and complementary advantages that, if used together, could offer profound benefits for studying the brain at high resolution. Combining these technologies is challenging, however, because conventional metal electrode technologies are too thick (over 500 nm) to be transparent to light, making them incompatible with many optical approaches.

DARPA has created a proof-of-concept tool that demonstrates much smaller, transparent contacts that can measure and stimulate neural tissue using electrical and optical methods at the same time.

Conventional metal electrode technologies (top left) are opaque, obstructing views of underlying neural tissue. DARPA’s RE-NET program has developed new graphene sensors that are electrically conductive but only 4 atoms thick—hundreds of times thinner than current contacts (top middle). Their extreme thinness enables nearly all light to pass through across a wide range of wavelengths. Placed on a flexible plastic backing that conforms to the shape of tissue (bottom), the sensors are part of a proof-of-concept tool that demonstrates much smaller, transparent contacts that can measure and stimulate neural tissue using electrical and optical methods at the same time (top right).

Nature Communications – Graphene-based carbon-layered electrode array technology for neural imaging and optogenetic applications

“This technology demonstrates potentially breakthrough capabilities for visualizing and quantifying neural network activity in the brain,” said Doug Weber, DARPA program manager. “The ability to simultaneously measure electrical activity on a large and fast scale with direct visualization and modulation of neuronal network anatomy could provide unprecedented insight into relationships between brain structure and function—and importantly, how these relationships evolve over time or are perturbed by injury or disease.”

The new device uses graphene, a recently discovered form of carbon, on a flexible plastic backing that conforms to the shape of tissue. The graphene sensors are electrically conductive but only 4 atoms thick—less than 1 nanometer and hundreds of times thinner than current contacts. Its extreme thinness enables nearly all light to pass through across a wide range of wavelengths. Moreover, graphene is nontoxic to biological systems, an improvement over previous research into transparent electrical contacts that are much thicker, rigid, difficult to manufacture and reliant on potentially toxic metal alloys.

The technology demonstration draws upon three cutting-edge research fields: graphene, which earned researchers the 2010 Nobel Prize in Physics; super-resolved fluorescent microscopy, which earned researchers the 2014 Nobel Prize in Chemistry; and optogenetics, which involves genetically modifying cells to create specific light-reactive proteins.

RE-NET seeks to develop new tools and technologies to understand and overcome the failure mechanisms of neural interfaces. DARPA is interested in advancing next-generation neurotechnologies for revealing the relationship between neural network structure and function. RE-NET, and subsequent DARPA programs in this field, plan to leverage this new tool by simultaneously measuring the function, physical motion and behavior of neurons in freely moving subjects. This technology provides the capability to modulate neural function, by applying programmed pulses of electricity or light to temporarily activate neurons. Therefore, it could not only provide better observation of native functionality but also, through careful modulation of circuit activity, enable exploration of causal relationships between neural signals and brain function.

“Historically, researchers have been limited to correlational studies that suggest, but do not prove causal linkages between neural activity and behavior,” Weber said. “Now, we have the opportunity to directly see, measure and stimulate neural circuits to explore these relationships and develop and validate models of brain circuit function. This knowledge could greatly aid how we understand and treat brain injury and disease.”

RE-NET is part of a broader portfolio of programs within DARPA that support President Obama’s brain initiative. These programs include ongoing efforts designed to advance fundamental understanding of the brain’s dynamics to drive applications (Revolutionizing Prosthetics, Restorative Encoding Memory Integration Neural Device, Reorganization and Plasticity to Accelerate Injury Recovery, Enabling Stress Resistance), manufacture sensing systems for neuroscience applications and therapies (Hand Proprioception and Touch Interfaces,Electrical Prescriptions) and analyze large data sets (Detection and Computational Analysis of Psychological Signals).

Abstract

Neural micro-electrode arrays that are transparent over a broad wavelength spectrum from ultraviolet to infrared could allow for simultaneous electrophysiology and optical imaging, as well as optogenetic modulation of the underlying brain tissue. The long-term biocompatibility and reliability of neural micro-electrodes also require their mechanical flexibility and compliance with soft tissues. Here we present a graphene-based, carbon-layered electrode array (CLEAR) device, which can be implanted on the brain surface in rodents for high-resolution neurophysiological recording. We characterize optical transparency of the device at over 90% transmission over the ultraviolet to infrared spectrum and demonstrate its utility through optical interface experiments that use this broad spectrum transparency. These include optogenetic activation of focal cortical areas directly beneath electrodes, in vivo imaging of the cortical vasculature via fluorescence microscopy and 3D optical coherence tomography. This study demonstrates an array of interfacing abilities of the CLEAR device and its utility for neural applications.

Reliable Neural-Interface Technology (RE-NET)

DARPA created the Reliable Neural-Interface Technology (RE-NET) program in 2010 to directly address the need for high performance neural interfaces to control dexterous functions made possible with advanced prosthetic limbs. Specifically, RE-NET seeks to develop the technologies needed to reliably extract information from the nervous system, and to do so at a scale and rate necessary to control many degree-of-freedom (DOF) machines, such as high-performance prosthetic limbs. Prior to the DARPA RE-NET program, all existing methods to extract neural control signals were inadequate for amputees to control high-performance prostheses, either because the level of extracted information was too low or the functional lifetime was too short. However, recent technological advances create new opportunities to solve both of these neural-interface problems. For example, it is now feasible to develop high-resolution peripheral neuromuscular interfaces that increase the amount of information obtained from the peripheral nervous system. Furthermore, advances in cortical microelectrode technologies are extending the durability of neural signals obtained from the brain, making it possible to create brain-controlled prosthetics that remain useful over the full lifetime of the patient.

For a decade now, DARPA has been leading efforts aimed at ‘revolutionizing’ the state-of-the-art in prosthetic limbs, recently debuting 2 advanced mechatronic limbs for the upper extremity. These new devices are truly anthropomorphic and capable of performing dexterous manipulation functions that finally begin to approach the capabilities of natural limbs. However, in the absence of a high bandwidth, intuitive interface for the user, these limbs will never achieve their full potential in improving the quality of life for the wounded soldiers that could benefit from this advanced technology.

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