Minimally invasive electrodes of cellular scale that approach a bio-integrative level of neural recording could enable the development of scalable brain machine interfaces that stably interface with the same neural populations over long period of time.In this paper, we designed and created NeuroRoots, a bio-mimetic multi-channel implant sharing similar dimension (10µm wide, 1.5µm thick), mechanical flexibility and spatial distribution as axon bundles in the brain. A simple approach of delivery is reported based on the assembly and controllable immobilization of the electrode onto a 35µm microwire shuttle by using capillarity and surface-tension in aqueous solution. Once implanted into targeted regions of the brain, the microwire was retracted leaving NeuroRoots in the biological tissue with minimal surgical footprint and perturbation of existing neural architectures within the tissue. NeuroRoots was implanted using a platform compatible with commercially available electrophysiology rigs and with measurements of interests in behavioral experiments in adult rats freely moving into maze. We demonstrated that NeuroRoots electrodes reliably detected action potentials for at least 7 weeks and the signal amplitude and shape remained relatively constant during long-term implantation.This research represents a step forward in the direction of developing the next generation of seamless brain-machine interface to study and modulate the activities of specific sub-populations of neurons, and to develop therapies for a plethora of neurological diseases.
We report a surface treatment for an elastomeric dry adhesive that improves adhesion, especially on surfaces with microscopic roughness. The process involves coating wedge-shaped polydimethylsiloxane (PDMS) features of the adhesive with a 50nm coating of poly (3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS). As compared to the uncoated adhesive, performance is 1.25x better on smooth surfaces like glass, with a maximum shear stress of 70kPa in shear and 25kPa in normal adhesion under controlled loading conditions. On slightly rough surfaces such as paper and panels painted with flat paint, it provides between 2.5x and over 12x greater shear stress than the uncoated adhesive. Moreover, the coating, being much stiffer than the underlying wedges, does not increase the tendency to become dirty and does not tend to self-stick, or clump. Durability tests show that the performance remains substantially unchanged for 80,000 attachment/loading/detachment cycles. We describe the coating process, present the test results, and discuss the reasons for the enhanced performance on a variety of materials.
Cold stimuli and the subsequent activation of β-adrenergic receptor (β-AR) potently stimulate adipose tissue thermogenesis and increase whole-body energy expenditure. However, systemic activation of the β3-AR pathway inevitably increases blood pressure, a significant risk factor for cardiovascular disease, and, thus, limits its application for the treatment of obesity. To activate fat thermogenesis under tight spatiotemporal control without external stimuli, here, we report an implantable wireless optogenetic device that bypasses the β-AR pathway and triggers Ca 2+ cycling selectively in adipocytes. The wireless optogenetics stimulation in the subcutaneous adipose tissue potently activates Ca 2+ cycling fat thermogenesis and increases whole-body energy expenditure without cold stimuli. Significantly, the light-induced fat thermogenesis was sufficient to protect mice from diet-induced body-weight gain. The present study provides the first proof-of-concept that fat-specific cold mimetics via activating non-canonical thermogenesis protect against obesity.
Communication between living brain tissue and engineered devices is the key link to understand brain function and restore neurological deficits from disease, injury, and old age. Enabled by new materials and device designs, a new generation of brain interface technologies is replacing bulkier systems, offering lower tissue damage, reduced immunogenicity, and long‐term stability. New electrode materials with improved chronic performance and increasing emphasis on multimodal capabilities are being integrated onto ultraflexible and mechanically compliant architectures. As these scale to smaller dimensions and higher channel counts, the goal of bidirectional, single‐cell interfaces is nearly within reach. However, promising, long‐term reliability, toxicity, and performance of these systems are still largely unknown. Here, the basics of electrode materials and in vivo technologies are reviewed, and recent advances in electronic and ionic materials are highlighted.
A biosensing platform based on an organic transistor circuit for metabolite detection in highly complex biological media is introduced. The sensor circuit provides inherent background subtraction allowing for highly specific, sensitive lactate detection in tumor cell cultures. The proposed sensing platform paves the way toward rapid, label-free, and cost-effective clinically relevant in vitro diagnostic tools.
Lipid bilayers are widely employed as a model system to investigate interactions between cells and their environment. Supported lipid bilayers (SLB) with integrated transmembrane proteins are emerging as a preferred platform for sensing applications. Challenges lie in the generation of SLB on surfaces which allow transduction of signals for characterization of lipid bilayer and incorporated transmembrane proteins. For the first time, the formation of SLBs is shown on films of the conducting polymer, poly(3,4‐ethylenedioxythiophene) doped with poly(styrene sulfonate) (PEDOT:PSS), using traditional methods for characterizing lipid bilayer quality and function (QCM‐D, FRAP) combined with impedance spectroscopy. Further, partial formation of SLBs on PEDOT:PSS based organic electrochemical transistors (OECTs) is successfully demonstrated, as well as the ability to integrate and sense the ion pore α‐hemolysin, confirming the sensitivity of the OECT as a transducer of biological membrane function. This work represents a highly promising first step toward the use of such OECTs for functional readout of transmembrane proteins in their native environment.
Organic electronic ion pumps (OEIPs) convert electrical current into ionic current. When in contact with neural tissue, this ionic current can be used to control the activity of neural networks. G. G. Malliaras, C. Bernard, and co-workers develop an OEIP capable of delivering the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), as described on page 3138. The ability of the OEIP to locally suppress epileptiform activity in the mouse hippocampus is demonstrated.
Despite recent interest in organic electrochemical transistors (OECTs), sparked by their straightforward fabrication and high performance, the fundamental mechanism behind their operation remains largely unexplored. OECTs use an electrolyte in direct contact with a polymer channel as part of their device structure. Hence, they offer facile integration with biological milieux and are currently used as amplifying transducers for bioelectronics. Ion exchange between electrolyte and channel is believed to take place in OECTs, although the extent of this process and its impact on device characteristics are still unknown. We show that the uptake of ions from an electrolyte into a film of poly(3,4-ethylenedioxythiophene) doped with polystyrene sulfonate (PEDOT:PSS) leads to a purely volumetric capacitance of 39 F/cm(3). This results in a dependence of the transconductance on channel thickness, a new degree of freedom that we exploit to demonstrate high-quality recordings of human brain rhythms. Our results bring to the forefront a transistor class in which performance can be tuned independently of device footprint and provide guidelines for the design of materials that will lead to state-of-the-art transistor performance.
In treating epilepsy, the ideal solution is to act at a seizure's onset, but only in the affected regions of the brain. Here, an organic electronic ion pump is demonstrated, which directly delivers on-demand pure molecules to specific brain regions. State-of-the-art organic devices and classical pharmacology are combined to control pathological activity in vitro, and the results are verified with electrophysiological recordings.
Organic electrochemical transistors are integrated on depth probes to achieve localized electrical stimulation of neurons. The probes feature a mechanical delamination process which leaves only a 4 μm thick film with embedded transistors inside the brain. This considerably reduces probe invasiveness and correspondingly improves future brain-machine interfaces.
An organic electrochemical transistor operates in accumulation mode with high transconductance. The channel comprises a thiophene-based conjugated polyelectrolyte, which is p-type doped by anions injected from a liquid electrolyte upon the application of a gate voltage. The use of ethylene glycol as a co-solvent dramatically improves the transconductance and the temporal response of the transistors.