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Neural interfacing and osseointegration are two largely independent fields of research that have gained significant momentum in the last few decades. Both osseointegration and neural interfaces have demonstrated the capacity to improve quality of life for amputees. How these technologies can benefit each other has been largely unexplored. Here we describe the development of an Osseointegrated Neural Interface (ONI) for prosthesis control in rabbits, combining current clinical practices for treating amputation neuromas, with neural interfacing and osseointegration. We performed experiments to test the bidirectional interfacing capacity of nerves transposed into bone over time. We found that nerves transposed into bone can be chronically interfaced for bi-directional communication, and that osseointegration can be leveraged to act as a percutaneous connection point for neural interfaces and a prosthesis. These results demonstrate proof of concept for an ONI to provide chronic, compact neural interfacing for improved prosthesis use.

Optimization of deep brain stimulation (DBS) parameters is a weeks to months-long process for many patients, due in part to the inflammatory response caused by electrode implantation. To investigate the effect of inflammation on current delivery. transgenic mice, expressing Thy1-GCaMP6f (a genetically-encoded calcium sensor), were implanted with a DBS electrode in the subthalamic nucleus (STN). Immediately following insertion, high frequency electrical stimulation of the STN was performed and we imaged changes in fluorescence elicited by stimulation to characterize the response of cortical neurons to STN DBS. Our result is consistent with the idea that the acute inflammatory response during the perioperative and early postoperative periods shunt current away from the desired target compared to the chronic inflammatory state weeks later.

An outstanding challenge for humanity is to continue to understand how our brain works and invent technology to restore neural circuit functionalities. Many neural interfaces used for neuron cell cultures are flat, open, rigid, and opaque, posing challenges to reflecting the native microenvironment of the brain and precise engagement with neurons. Here we present a novel neural interface consisting of silicon nitride microtube arrays formed by a new nanotechnology platform that simply relies on strain-induced self-rolled-up membrane (S-RUM) mechanism [1]. We have found that these microtubes provide robust physical confinement and unprecedented guidance effect towards outgrowth of primary cortical neurons [2]. What is more surprising is that a dramatic increase (20x) of the growth rate inside the microtube compared to regions outside the microtubes has been observed [2]. The outgrowth of hippocampal neurons is also explored using identical platforms with the intent of integrating both networks on the same chip. The unique characteristics of these S-RUM microtubes that enabled the cell guidance and acceleration will be discussed in detail: (1) True 3D geometrical confinement: the perfect cylindrical geometry of the S-RUM microtubes with tunable diameters and ultra-thin walls, the same type of small and confined spaces neurons grow in vivo, provides conformal 3D adhesion tailored to different kinds of cells. (2) Electrostatic adhesion: the deposited SiN x thin films are found to have a high density of trapped positive charges that naturally attract the axon towards the microtube opening. The ability of the microtube array to control the speed and direction of axonal extension provides a key element in arranging patterned neural networks that have both short and long range connections. (3) Optically transparent: having the ability to see through both the tube and the underlying substrate enabled direct observation of how cells transition from the flat regions to different parts of the tube.

Advancements in neural interfaces capable of neural stimulation have shown that neural implants may potentially target the central nervous system to treat neurological disorders. Unfortunately, many of the current technologies used to stimulate and record from the brain do not suffice for this purpose; those that provide a sufficient channel density, which is required for interfacing and chronic functionality in vivo, fail quickly, while others that last for an extended period of time in vivo are limited in recording and stimulation capabilities. Of the current methodologies available, electrocorticography (ECoG) based implants show promise for providing both high channel density interfaces as well as chronic functionality after implantation. This study evaluates the performance of a μECoG for the purpose of chronic stimulation.

Micro-electrocorticography (μECoG) displays advantages over traditional invasive methods. The μECoG electrode can record neural activity with high spatial-temporal resolution and it can reduce implantation side effects (e.g. vascular and local-neuronal damage, tissue encapsulation, infection). In this study, we propose a printable transparent μECoG electrode for optogenetic applications by using ultrasonic microfluid printing technique. The device is based on poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT: PSS) as a conductive polymer, polydimethylsiloxane (PDMS) as an insulating polymer and poly(chloro-para-xylylene) (Parylene-C) as the device substrate. We focus on ultrasonic microfluid printing due to its low production cost, excellent material handling capability, and its customizable film thickness (down to 5-20 microns). The ultrasonic fluid-printed μECoG displays high spatial resolution and records simulated signal (0-200 Hz sine wave) effectively with low electrode impedance (50-200 kOhms@1kHz). The μECoG also shows good biocompatibility suitable for customizable chronic implants. This new neural interfacing device could be combined with optogenetics and Brain-Computer Interface (BCI) applications for a possible future use in neurological disease diagnosis and rehabilitations.

Chronic imaging of the peripheral nervous system with contemporary techniques requires repetitive surgical procedures to reopen an area of interest in order to see underlying biological processes over time. The recurrence of surgical openings on an animal increases trauma, stress, and risk of infection. Such effects can greatly lessen the physiological relevance of any data recorded in this manner. In order to bypass repetitive surgery, a Peripheral Nerve Window (PNW) device has been created for chronic in vivo imaging purposes. Intravital imaging window devices have been used previously to image parts of the rodent model such as the brain, spinal cord, and mammary tissue, but currently have not been used in the peripheral nervous system because of lack of bone anchoring and access to deep nerve tissue. We demonstrate a novel surgical technique in a rat which transposes the sciatic nerve above the surrounding muscle tissue allowing the PNW access to an 8mm section of the nerve. Subsequent days of observation revealed increased vasculature development primarily around the nerve, showing that this preparation can be used to image nerve tissue and surrounding vasculature for up to one week post-implantation.

Integration of the Dasher text-entry program with a brain-computer interface (BCI) system may give individuals with severe motor disabilities the ability to write using their neural signals. Five able-bodied participants previously trained to control their neural signals using motor imagery in an electroencephalogram-based BCI study were trained to control the Dasher program using similar methods. The time to write simple phrases in Dasher using BCI and standard mouse inputs were compared. To compare with existing technology, four disabled participants wrote the same phrases using their own augmentative communication input. The time to input phrases with Dasher-BCI was greater than that for Dasher-mouse and other alternative inputs. However, as Dasher is optimized for BCI control, it will become increasingly useful for people with severe motor and speech disabilities.

For applications in cell biology, the ability to produce patterns of adhesion proteins for directing cell patterning is of particular interest. Often though, these patterns require extensive clean room facilities and intricate chrome masks to achieve very small feature sizes. We have developed a modified lift-off method for rapid prototyping of simple PLL structures that have features on a micron scale. The lift-off method is simple and easily adaptable to a variety of biological applications.

We describe a technique for the fabrication and use of a microfluidic flow device that has portions that are open to the external environment. Matching inlet and outlet flow rates in the device forms virtual walls through surface tension at the liquid-air interface. Traditional instrumentation, such as the patch-clamp pipette, can be introduced into the flow stream through the surface-tension walls, thereby combining decades of electrophysiology techniques with the benefits of microfluidic environmental control of in-vitro tissue samples such as neural cultures and brain slices.

Rejuvenation of iridium microelectrode sites, which involves applying a 1.5 V bias for 4 s, has been shown to reduce site impedances of chronically implanted microelectrode arrays. This study applied complex impedance spectroscopy measurements to an equivalent circuit model of the electrode-tissue interface. Rejuvenation was found to cause a transient increase in electrode conductivity through an IrO/sub 2/ layer and a decrease in the surrounding extracellular resistance by 85 /spl plusmn/ 1% (n=73, t-test p < 0.001) and a decrease in the immediate site resistance by 44 /spl plusmn/ 7% (n=73, t-test p

Advances in BioMBMS have provided researchers with the capabilities to look at a myriad of things with more detail and precision than ever before, and the brain is no exception to this. The brain is becoming more accessible and controllable on almost every level; the challenge lies in increasing the quality of the interface with the brain. To address this challenge, we must begin by optimizing to the best of our capabilities the implantable devices used. One method to help optimize these devices is to integrate active electronics on the microelectrode that will enhance the quality of the signals being extracted from brain. This paper describes a chronic silicon-substrate microelectrode with integrated analog-front end electronics capable of recording from nearby neurons in active and passive modes of operation. Six-channel 2-D arrays have been chronically implanted into barrel cortex of two rats and have recorded chronic unit activity with SNRs up to 8:1.

The capability of sensing catecholamine fluctuations in the brain is useful to determine how neurostimulation - both chemical and electrical - can affect catecholamine release and uptake. Here we report preliminary results on two multichannel neural probes capable of sensing dopamine through chronoamperometry methods. With a 16-channel microelectrode array and five-channel Michigan puffer probe with a microfluidic channel, we found that a 5-cycle dip coating process of Nafion, an ion-selective polymer, optimized sensitivity to dopamine and selectivity over ascorbic acid. In addition, through fluorescent microscopy, we have shown the suitability of Nafion as a "biocompatible" material for chronically implanted microelectrode probes. These findings support the ongoing work to develop chronic implantable chemical sensors.

Surgical techniques are a critical contributor to the level of success achieved with chronically implanted cortical neuroprosthetic devices. Many different factors contribute to the amount of irritation the tissue is exposed to from the implanted device. Factors include mechanical irritations, infectious pathogens, dural regrowth, etc. In this paper we describe a novel application of the hydrogel polymer, ALGEL/spl reg/ (Neural Intervention Technologies, Ann Arbor, MI), in conjunction with an implanted Michigan probe (CNCT, University of Michigan). This polymer contains many inherent properties that are beneficial to this type of procedure. Properties include: 1) ease of application, 2) biocompatibility, 3) exemplary mechanical properties, and 4) translucent clarity. We believe that ALGEL has been a large contributor to the high level of success achieved with our chronic electrode implantations.

The desire to perform chronic recordings from many channels in cortex is high among both neuroscientists and neural prosthesis researchers. The Michigan probe with integrated silicon ribbon cable has been used successfully for obtaining chronic cortical recordings in rodents. As these silicon devices are applied in larger animals and potentially in humans, however, a more mechanically robust, scalable system is required. Here we present a device that takes advantage of several existing, well-characterized technologies and methods and combines them to form a hybrid cortical assembly. The components of the assembly include thin-film multichannel silicon probes and polyimide cables that are electrically and mechanically coupled using thermocompression ball bonding. The resulting probe/cable assembly is low profile (

A finite element model has been developed to investigate the theoretical relationship between changes in extracellular resistivity and electrical potential in a chronic extracellular recording scenario. The inputs to the model are experimental results obtained from chronic recording and complex impedance measurements in cerebral cortex of adult guinea pigs. Using the measured tissue-electrode impedance to set the resistivity in the model provides simulated extracellular potentials that are consistent with the measured spike amplitudes. In both the experimental and theoretical paradigms it was found that increased extracellular resistivity results in an increased potential at the recording electrode tip. Although the results of the two methods could not be directly correlated, they do suggest that a certain amount of variance can be accounted for by the increased resistivity values. The methods presented offer a powerful theoretical tool for understanding some of the factors, which may affect chronic extracellular recording stability.