FlatScope, a lensless microscope as thin as a credit card and small enough to sit on a fingertip, captures 3D fluorescence images.

Soft and conductive nanomaterials like carbon nanotubes, graphene, and nanowire scaffolds have expanded the family of ultraflexible microelectrodes that can bend and flex with the natural movement of the brain, reduce the inflammatory response, and improve the stability of long-term neural recordings. However, current methods to implant these highly flexible electrodes rely on temporary stiffening agents that temporarily increase the electrode size and stiffness thus aggravating neural damage during implantation, which can lead to cell loss and glial activation that persists even after the stiffening agents are removed or dissolve. A method to deliver thin, ultraflexible electrodes deep into neural tissue without increasing the stiffness or size of the electrodes will enable minimally invasive electrical recordings from within the brain. Here we show that specially designed microfluidic devices can apply a tension force to ultraflexible electrodes that prevents buckling without increasing the thickness or stiffness of the electrode during implantation. Additionally, these "fluidic microdrives" allow us to precisely actuate the electrode position with micron-scale accuracy. To demonstrate the efficacy of our fluidic microdrives, we used them to actuate highly flexible carbon nanotube fiber (CNTf) microelectrodes for electrophysiology. We used this approach in three proof-of-concept experiments. First, we recorded compound action potentials in a soft model organism, the small cnidarian Hydra. Second, we targeted electrodes precisely to the thalamic reticular nucleus in brain slices and recorded spontaneous and optogenetically evoked extracellular action potentials. Finally, we inserted electrodes more than 4 mm deep into the brain of rats and detected spontaneous individual unit activity in both cortical and subcortical regions. Compared to syringe injection, fluidic microdrives do not penetrate the brain and prevent changes in intracranial pressure by diverting fluid away from the implantation site during insertion and actuation. Overall, the fluidic microdrive technology provides a robust new method to implant and actuate ultraflexible neural electrodes.

Electrical measurements from large populations of animals would help reveal fundamental properties of the nervous system and neurological diseases. Small invertebrates are ideal for these large-scale studies; however, patch-clamp electrophysiology in microscopic animals typically requires low-throughput and invasive dissections. To overcome these limitations, we present nano-SPEARs: suspended electrodes integrated into a scalable microfluidic device. Using this technology, we have made the first extracellular recordings of body-wall muscle electrophysiology inside an intact roundworm, Caenorhabditis elegans. We can also use nano-SPEARs to record from multiple animals in parallel and even from other species, such as Hydra littoralis. Furthermore, we use nano-SPEARs to establish the first electrophysiological phenotypes for C. elegans models for Amyotrophic Lateral Sclerosis and Parkinson’s disease, and show a partial rescue of the Parkinson’s phenotype through drug treatment. These results demonstrate that nano-SPEARs provide the core technology for microchips that enable scalable, in vivo studies of neurobiology and neurological diseases.

Microfluidic devices allow scalable and customizable solutions for multi-modal interrogation of these soft, deformable Hydra.

In this work we investigate the presence of a torsional instability in single-wall carbon nanotubes which causes small diameter chiral carbon nanotubes to show natural torsion. To obtain insight into the nature of this instability, the natural torsion is calculated using an extended tight-binding model and is found to decrease as the inverse cube of the diameter. The dependence of the natural torsion on chiral angle is found to be different for metallic and semiconducting nanotubes, specially for near-armchair nanotubes, for which the behavior of semiconducting nanotubes deviates from the simple sin͑6͒ behavior observed for metallic nanotubes. The presence of this natural torsion implies a revision of the calculation of the chiral angle of the nanotubes.

Objective. Recording electrical activity from individual cells in vivo is a key technology for basic neuroscience and has growing clinical applications. To maximize the number of independent recording channels as well as the longevity, and quality of these recordings, researchers often turn to small and flexible electrodes that minimize tissue damage and can isolate signals from individual neurons. One challenge when creating these small electrodes, however, is to maintain a low interfacial impedance by applying a surface coating that is stable in tissue and does not significantly complicate the fabrication process. Approach. Here we use a high-pressure Pt sputtering process to create low-impedance electrodes at the wafer scale using standard microfabrication equipment. Main results. We find that direct-sputtered Pt provides a reliable and well-controlled porous coating that reduces the electrode impedance by 5–9 fold compared to flat Pt and is compatible with the microfabrication technologies used to create flexible electrodes. These porous Pt electrodes show reduced thermal noise that matches theoretical predictions. In addition, we show that these electrodes can be implanted into rat cortex, record single unit activity, and be removed all without disrupting the integrity of the coating. We also demonstrate that the shape of the electrode (in addition to the surface area) has a significant effect on the electrode impedance when the feature sizes are on the order of tens of microns. Significance. Overall, porous Pt represents a promising method for manufacturing low-impedance electrodes that can be seamlessly integrated into existing processes for producing flexible neural probes.

The cnidarian Hydra vulgaris provides an exciting opportunity to discover the relationship between animal behavior and the activity of every neuron in highly plastic, diffuse network of spiking cells. However, Hydra's deformable and contractile body makes it difficult to manipulate the local environment while recording neural activity. Here, we present a suite of microfluidic was not peer-reviewed) in the Public Domain. It is no longer restricted by copyright. Anyone can legally share, reuse, remix, or adapt thisThe copyright holder has placed this preprint (which . http://dx.doi.org/10.1101/257691 doi: bioRxiv preprint first posted online Jan. 31, 2018; 2 this technology may help reveal how highly plastic networks of neurons provide robust control of animal behavior.

Ultra-flexible microelectrodes that can bend and flex with the natural movement of the brain reduce the inflammatory response and improve the stability of long-term neural recordings.1-5 However, current methods to implant these highly flexible electrodes rely on temporary stiffening agents that increase the electrode size6-10 thus aggravating neural damage during implantation, which leads to cell loss and glial activation that persists even after the stiffening agents are removed or dissolve.11-13 A method to deliver thin, ultra-flexible electrodes deep into neural tissue without increasing the stiffness or size of the electrodes will enable minimally invasive electrical recordings from within the brain. Here we show that specially designed microfluidic devices can apply a tension force to ultra-flexible electrodes that prevents buckling without increasing the thickness or stiffness of the electrode during implantation. Additionally, these “fluidic microdrives” allow us to precisely actuate the electrode position with micron-scale accuracy. To demonstrate the efficacy of our fluidic microdrives, we used them to actuate highly flexible carbon nanotube fiber (CNTf) microelectrodes11,14 for electrophysiology. We used this approach in three proof-of-concept experiments. First, we recorded compound action potentials in a soft model organism, the small cnidarian Hydra. Second, we targeted electrodes precisely to the thalamic reticular nucleus in brain slices and recorded spontaneous and optogenetically-evoked extracellular action potentials. Finally, we inserted electrodes more than 4 mm deep into the brain of rats and detected spontaneous individual unit activity in both cortical and subcortical regions. Compared to syringe injection, fluidic microdrives do not penetrate the brain and prevent changes in intracranial pressure by diverting fluid away from the injection site during insertion and actuation. Overall, the fluidic microdrive technology provides a robust new method to implant and actuate ultra-flexible neural electrodes.