This patent document relates to microelectrode arrays and methods of fabrication, and particularly to a microelectrode array, such as a neural interface, with an integrated stiffening shank, and methods of fabrication thereof.
Micro-electrode array neural probes and interfaces are essential tools in neuroscience. They provide a direct electrical interface with the neurons of a biological entity's nervous system to stimulate and/or record neural activity. Such neural probes enable researchers and clinicians to better explore and understand neurological diseases, neural coding, neural modulations, and neural topologies, and ultimately treat debilitating conditions of the nervous system, such as for example depression, Parkinson's disease, epilepsy, and deafness. In more recent years, their applications have increased from cochlear implants and pain modulation to use in more complex systems such as brain-machine interfacing and deep brain stimulation.
The most common neural probes are thin-film micromachined probes fabricated on silicon substrates using MEMS fabrication techniques. Neuronal stimulation and recording is conducted at discrete sites (metal pads) along the probes. The metal pads are connected, via metal traces, to output leads or to other signal processing circuitry. Silicon is the most widely used substrate for this type of probe because of its unique physical/electrical characteristics. The prevalence of silicon in the microelectronics industry ensures the neural probes can be relatively easily and efficiently fabricated in large numbers utilizing common MEMS fabrication techniques. There is, however, concern regarding the suitability of these silicon-based neural probes for long-term chronic) studies as the silicon will corrode over time when implanted in a body. Furthermore, the continuous micro-motion of the brain can induce strain between the brain tissue and implanted electrode promoting chronic injury and glial scarring at the implant site. Therefore, there are outstanding questions regarding the long-term safety and functionality of these silicon-based neural probes.
Polymer-based neural probes are an attractive alternative. First, they are flexible, thereby minimizing strain between the brain tissue and the implanted probe. Second, they are fully biocompatible and thus suitable for chronic implantation with no loss of functionality or safety. Finally, these polymer-based neural probes can be easily fabricated in large numbers using existing microfabrication techniques. Unfortunately, the inherent flexibility of the polymer-based neural probes means the probes also have a low mechanical stiffness causing the devices to buckle and fold during insertion. To counteract this, separate stiffening shanks are typically fabricated and then attached to individual neural probes. This procedure is very time-consuming, and in most cases, where the stiffening shanks are extremely thin (<50 μm thick), also very difficult.
As the use of MEA neural interfaces expand, the demand for multi-functionality and chronic biocompatibility also increases. As such, there is also a growing need to develop a single device capable of recording and stimulating both electrically and chemically in vivo. Most multi-electrode array (MEA) neural interfaces currently in the market or in use at academic institutions are only capable of one or two functionalities, mainly recording and stimulation of electrical signals.
Methods of drug delivery or chemical recording are often done using separate devices, in different regions of the brain if done simultaneously, and often require two different sets of equipment. This set up makes it impossible to gather electrical and chemical data from the same brain region during the same experiment. The same is true in clinical settings. Currently available neural stimulators, recorders, or drug delivery systems are all separate devices. In addition, most of these devices are constantly on or rely on timed control method, not based on the biophysical response of the body.
There is therefore a need for an improved flexible microelectrode having a stiffening shank that facilitates insertion into tissue. And there is also a need for a single device with chemical and electrical multi-functionality could provide a feedback capability that would increase the lifetime and efficacy of a medical device.
One aspect of the present invention includes a microelectrode array, comprising: an electrically conductive layer having one or more electrodes, and one or more metal traces connected to the one or more electrodes; a plurality of polymer layers together surrounding the electrically conductive layer to at least partially encapsulate the one or more metal traces and the one or more electrodes so that the one or more electrodes are exposed; and a stiffening shank embedded in the polymer layers adjacent at least a portion of the electrically conductive layer to mechanically support said portion.
Another aspect of the present invention includes a method of fabricating a microelectrode array, comprising: forming an electrically conductive layer having one or more electrodes, and one or more metal traces connected to the one or more electrodes; forming a plurality of polymer layers to together surround the electrically conductive layer to at least partially encapsulate the one or more metal traces and the one or more electrodes so that the one or more electrodes are exposed; and forming a stiffening shank embedded in the polymer-layers adjacent at least a portion of the electrically conductive layer to mechanically support said portion.
Other aspects of the present invention include, in addition to the aspects described above for the microelectrode array, one or more of the following: a microfluidic channel formed in the polymer layers with openings therethrough leading into the microfluidic channel to communicate fluids to or from an area of interest near the one or more electrodes; a microfluidic tube connected to the polymer layers to communicate fluids to or from an area of interest near the one or more electrodes; wherein the electrodes include electrochemical sensors.
And other aspects of the present invention include, in addition to the aspects described above for the method of fabricating the microelectrode array, one or more of the following: forming a microfluidic channel in the polymer layers with openings therethrough leading into the microfluidic channel to communicate fluids to or from an area of interest near the one or more electrodes; wherein the microfluidic channel is formed by: depositing and patterning a sacrificial material for the microfluidic channel on a first one of said polymer layers, depositing a second one of said polymer layers on the sacrificial material, forming openings through the second one of said polymer layers to the sacrificial material, and releasing the sacrificial material through the openings to form the microfluidic channel; connecting a microfluidic tube to the polymer layers to communicate fluids to or from an area of interest near the one or more electrodes; and forming electrochemical sensors to the exposed one or more electrodes.
Generally, the present invention is directed to a microelectrode array having a stiffening shank integrated into its body, and an integrated, wafer-level process of fabricating the microelectrode array which incorporates the stiffening shank into its otherwise flexible body so that no post-fabrication attachment is required. With this process, polymer-based neural probes are created with a stiffened area suitable for insertion into tissue but also with a flexible cable to minimize tissue damage. Utilizing existing microfabrication techniques, large numbers of stiffened polymer-based neural probes can be created easily and efficiently. Furthermore, additional functionalities may be incorporated into the microelectrode array with integrated stiffening shank to enable additional functionalities beyond electrical sensing/recording and stimulation, such as chemical sensing, and chemical delivery as well. The general structure of the neural probes described herein have a flexible, polymer-based cable, which runs the length of the probe and contains the electrodes, interconnection traces, the stiffening shank, and optionally a microfluidic channel.
The flexible neural interface with integrated stiffening shank is suitable for implantation in both humans and animals for either acute or chronic studies of various neurological disorders and as interfaces between neural tissue and prosthetics. The neural probes described here have a flexible, polymer-based cable, which runs the length of the probe and contains the electrodes and interconnection traces and a stiffening shank at the tip (where the electrodes are located). The stiffening shank is built into the device utilizing standard microfabrication techniques, and requires no post-fabrication attachment. The flexible neural interface may be fabricated with the stiffening shank either fully encapsulated in the surrounding polymer material or partially encapsulated in the surrounding polymer material. Furthermore, these neural interfaces can be created with electrodes on the “top,” the “bottom,” or on both the “top” and “bottom.”
Further, the process is not limited to vapor-deposited (e.g. sputtering, electron-beam/thermal evaporation, atomic layer deposition, chemical vapor deposition, physical vapor deposition) materials and thicknesses.
Furthermore, the present invention provides a single device capable of multi-functionalities to improve a researcher's capability to simultaneously study multiple phenomena in the nervous system and to provide a feedback mechanism for clinical medical devices. The microfabricated multi-functional array (MFA) will be capable of electrical stimulation and recording, chemical sensing, and chemical delivery all on a minimally-sized biocompatible platform designed for in vivo implantations. One aspect of the invention includes an implantable multi-functional multi-electrode array neural interface with microfluidic channel. The polymer-based MFA described here is suitable for implantation in both humans and animals for either acute or chronic studies of various neurological disorders and as interfaces between neural tissue and prosthetics. (This assumes the materials comprising the device have been properly chosen with regards to their biocompatibility.)
In generally, the fabrication method of the present invention is independent of the array dimensions (length, width, thickness, overall shape), the electrode properties (number, spatial arrangement, thickness, shape, material), interconnection trace metal (material, thickness, shape, spatial arrangement), and the microfluidic channel dimensions (length, diameter, connections). Further, the process is not limited to vapor-deposited (e.g. sputtering, electron-beam/thermal evaporation, atomic layer deposition, chemical vapor deposition, physical vapor deposition) materials and thicknesses.
The fabrication process is also independent of the specific material used for the stiffening shank, or the thickness/dimensions of the stiffening shank. And the stiffening shank is not limited to silicon. Other materials, with varying mechanical properties, can also be used, such as other semiconductors, dielectrics (e.g. glass/quartz/silicon-dioxide, sapphire), ceramics (e.g. alumina), metals (e.g. titanium, tungsten), and others (e.g. silicon-carbide, diamond). Preferably, any material that can be etched can be used. Ultimately, the mechanical properties and the thickness of the material used dictate the stiffness of the neural interface. It is appreciated that the stiffener may be made of various types of rigid materials, including for example silicon, glass, ceramic, metal, etc. For the fully-encapsulated embodiment of the present invention, the final device will be biocompatible and suitable for chronic and acute implantation studies, regardless of whether the stiffening shank material is biocompatible (provided the chosen polymer is biocompatible). And for the partially-encapsulated embodiment of the present invention, unless the stiffening shank material is biocompatible, the neural interface created may not be suitable for chronic and/or acute implantation studies. Furthermore, various thin film MEMS fabrication methods (e.g. photolithography) may be employed to fabricate the structure of the stiffener. The stiffener fabrication process is also independent of the thickness of the stiffening shank.
The fabrication process is independent of the specific type of polymer used to create the neural interface. Polymides and parylenes (poly(p-xylylene) are the two most commonly used polymers due to their biocompatibility. Other polymers can be used (provided these materials can be deposited and etched), although these other polymers may not be biocompatible and, thus, the neural interfaces created with these materials may not be suitable for chronic and/or acute implantation studies.
The accompanying drawings, which are incorporated into and form a part of the disclosure, are as follows:
Turning now to the drawings,
As shown in particular in
Optionally, chemical sensors may be deposited on the electrode 14 or other electrodes formed (not shown). For chemical sensing capability, electrochemical methods may be employed. Electrochemical sensing of analytes will be accomplished by applying appropriate current or voltage waveforms (including constant current and constant potential) to the sensing electrode. Sensitivity and selectivity will be optimized by varying applied waveforms and by chemically and physically modifying individual electrode sites. Sensitivity can be increased by increasing the effective surface area of the electrode sites and by reducing noise. This can be done by various physical and chemical methods including but not limited to roughening by plasma attack, using microfabrication techniques to deposit a highly porous electrode, deposition of conductive nanoparticles to increase surface area, and electroplating such that a high surface area electrode is formed. Selectivity can be improved by optimizing the applied waveforms and by size or electrostatic exclusion using semi-permeable thin film polymers. Depending on the properties of the analytes of interest and known interferents, the appropriate polymers will be deposited via dip-coating, electrochemical methods, or MEMS methods. The polymers could include but are not limited to Nafion, polypyrrole, and phenylenediamine.
While particular operational sequences, materials, temperatures, parameters, and particular embodiments have been described and or illustrated, such are not intended to be limiting. Modifications and changes may become apparent to those skilled in the art, and it is intended that the invention be limited only by the scope of the appended claims.
This patent document claims the benefit and priority of U.S. Provisional Application No. 61/713,416, filed on Oct. 12, 2012, and U.S. Provisional Application No. 61/802,382, filed on Mar. 15, 2013, both of which are hereby incorporated by reference.
The United States Government has rights in this invention pursuant to Contract No. DE-AC52-07NA27344 between the United States Department of Energy and Lawrence Livermore National Security, LLC for the operation of Lawrence Livermore National Laboratory.
Number | Date | Country | |
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61802382 | Mar 2013 | US | |
61713416 | Oct 2012 | US |