Patent Publication Number: US-2020281489-A1

Title: Agent-Delivering Neural Probe Devices And Related Systems And Methods

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
     This application claims the benefit under 35 U.S.C. § 119(e) to U.S. Provisional Application 62/815,530, filed Mar. 8, 2019 and entitled “Agent-Delivering Neural Probe Devices and Related Systems and Methods,” which is hereby incorporated herein by reference in its entirety. 
    
    
     FIELD 
     The various embodiments herein relate to neural probes, including agent-delivering neural probes and other neurological treatment devices, including, for example, agent-eluting devices, and related systems and methods for detection and/or stimulation. 
     BACKGROUND 
     Known neural probes and devices have relatively thick profiles that can result in damage to the patient&#39;s brain tissue during use. Further, any procedure that accesses the human brain triggers a defensive response known as the foreign body response or reaction (“FBR”). This reaction mechanism is a complex signaling system that tells the body to encapsulate the foreign entity and triggers an edema response. The encapsulation isolates the foreign body element from the rest of the surrounding tissue. 
     There is a need in the art for improved neural probes and related devices and technologies that incorporate agent delivery, including, for example, agent elution. 
     BRIEF SUMMARY 
     Discussed herein are various neural probe devices with agent delivery components, including, for example, agent coatings, agent delivery lumens, agent delivery structures disposed over the devices, and other such delivery components, along with related methods of delivering various agents to a patient via such a probe device. 
     In Example 1, a neural electrode comprises an electrode body, at least one electrode array associated with the electrode body, and a dissolvable agent delivery structure disposed over at least a portion of the electrode body. Example 2 relates to the neural electrode according to Example 1, wherein the dissolvable agent delivery structure is removably disposed over the at least a portion of the electrode body such that the dissolvable agent delivery structure is separable from the electrode body. 
     Example 3 relates to the neural electrode according to Example 1, wherein the dissolvable agent delivery structure comprises a dissolvable scaffold comprising at least one treatment agent. 
     Example 4 relates to the neural electrode according to Example 3, wherein the at least one treatment agent is releasable over time as the dissolvable scaffold dissolves. 
     Example 5 relates to the neural electrode according to Example 3, wherein the at least one treatment agent comprises a cannabinoid. 
     Example 6 relates to the neural electrode according to Example 1, wherein the electrode body comprises an elongate, unitary tubular body, wherein the at least one electrode array is disposed on an outer surface of the tubular body, and wherein the neural electrode is a depth electrode. 
     Example 7 relates to the neural electrode according to Example 1, further comprising an elongate structure coupled to the electrode body, wherein the electrode body comprises a thin film pad, wherein the at least one electrode array is disposed in the thin film pad, and wherein the neural electrode is a cortical electrode. 
     In Example 8, a neural electrode comprises an electrode body, at least one electrode array associated with the electrode body, and a drug delivery component comprising an agent elution coating disposed on the electrode body or a drug delivery lumen defined through a portion of the electrode body. 
     Example 9 relates to the neural electrode according to Example 8, wherein the electrode body comprises an elongate, unitary tubular body, wherein the at least one electrode array is disposed on an outer surface of the tubular body, and wherein the neural electrode is a depth electrode. 
     Example 10 relates to the neural electrode according to Example 9, wherein the drug delivery component is the drug delivery lumen, wherein the drug delivery lumen is defined within the elongate tubular body such that the lumen is coaxial with a longitudinal axis of the elongate tubular body, 
     Example 11 relates to the neural electrode according to Example 10, further comprising a drug delivery opening defined at a distal end of the tubular body, wherein the drug delivery opening is in fluidic communication with the drug delivery lumen. 
     Example 12 relates to the neural electrode according to Example 10, further comprising a plurality of openings defined in the outer surface of the tubular body, wherein the plurality of openings are in fluidic communication with the drug delivery lumen. 
     Example 13 relates to the neural electrode according to Example 9, wherein the drug delivery component is the agent elution coating, wherein the agent elution coating is disposed on the tubular body. 
     Example 14 relates to the neural electrode according to Example 13, wherein the agent elution coating comprises at least one treatment agent, wherein the at least one treatment agent is releasable over time. 
     Example 15 relates to the neural electrode according to Example 8, further comprising an elongate structure coupled to the electrode body, wherein the electrode body comprises a thin film pad, wherein the at least one electrode array is disposed in the thin film pad, and wherein the neural electrode is a cortical electrode. 
     Example 16 relates to the neural electrode according to Example 15, wherein the drug delivery component is the drug delivery lumen, wherein the drug delivery lumen is defined within the thin film pad. 
     Example 17 relates to the neural electrode according to Example 15, wherein the drug delivery component is the agent elution coating, wherein the agent elution coating is disposed on the thin film pad. 
     In Example 18, a method of implanting an intracranial electrode device comprises forming at least one hole in a skull of a patient, urging the intracranial electrode device through the at least one hole, positioning the intracranial electrode device at the target intracranial position, actuating the electrode device to stimulate tissue at the target intracranial position, and delivering an agent to the target intracranial position. 
     Example 19 relates to the method according to Example 18, wherein the delivering the agent comprises delivering the agent via a dissolvable agent delivery structure, an agent elution coating, or a drug delivery lumen. 
     Example 20 relates to the method according to Example 18, wherein the agent reduces the inflammation of brain tissue or minimizes or eliminates a seizure. 
     In Example 21, a neural probe and drug delivery system comprises a neural probe comprising a probe body, a cavity defined in the probe body, and a deployable cover disposed adjacent to the cavity, wherein the deployable cover comprises an open position and a closed configuration in which the deployable cover is disposed over the cavity. Further, the system comprises a magnetic actuation member configured to be disposable near the neural probe, wherein the magnetic actuation member can be in magnetic communication with the deployable cover. 
     Example 22 relates to the system according to Example 21, wherein an agent is disposable within the cavity. 
     In Example 23, a neural probe comprises a probe body, a cavity defined in the probe body, a contact disposed within the cavity, an electrical lead operably coupled to the contact, wherein the electrical lead is configuration to allow for transmission of an electrical current, and an ionically polarized agent disposable within the cavity, wherein application of the electrical current is configured to iontophoretically urge the ionically polarized agent out of the cavity. 
     In Example 24, a neural probe comprises a probe body and a cavity defined in the probe body, the cavity comprising an opening defined in an outer surface of the probe body, wherein the opening provides fluidic access to the cavity, and an agent channel defined within the cavity. The probe further comprises a contact disposed within the cavity, and an agent disposable within the agent channel. 
     Example 25 relates to the neural probe according to Example 24, wherein the agent channel is disposed around an outer circumference of the cavity. 
     Example 26 relates to the neural probe according to Example 24, wherein the agent is deliverable via contact with body fluids in fluidic communication with the cavity. 
     In Example 27, a positionable cortical electrode comprises a thin film pad, a plurality of electrode contacts disposed in the thin film pad, at least one delivery lumen defined in the thin film pad, a plurality of openings defined in an outer surface of the thin film pad, wherein the plurality of openings are in fluidic communication with the at least one delivery lumen, an elongate structure coupled to the thin film pad, and a fluid channel defined in the elongate structure, wherein the fluid channel is in fluidic communication with the at least one delivery lumen. 
     In Example 28, a neural probe comprises a probe body and a drug reservoir associated with the probe body, the drug reservoir comprising a reservoir body, a reservoir interior defined within the reservoir body, wherein the interior is configured to receive an agent, and an actuable gate disposed along an exterior wall of the reservoir body. 
     Example 29 relates to the neural probe according to Example 28, wherein the actuable gate comprises a conduit defined within the actuable gate, an opening defined in the actuable gate, wherein the opening is in fluid communication with the conduit, and a moveable flap disposed adjacent to the opening, wherein the moveable flap comprises an open position and a closed position in which the moveable flap is disposed over the opening. 
     While multiple embodiments are disclosed, still other embodiments will become apparent to those skilled in the art from the following detailed description, which shows and describes illustrative embodiments. As will be realized, the various implementations are capable of modifications in various obvious aspects, all without departing from the spirit and scope thereof. Accordingly, the drawings and detailed description are to be regarded as illustrative in nature and not restrictive. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1A  is a top view of a cortical electrode, according to one embodiment. 
         FIG. 1B  is a perspective view of depth electrode, according to one embodiment. 
         FIG. 10  is a perspective view of an electrode array, according to one embodiment. 
         FIG. 2  is a side view of an outer surface of a neural probe device having an agent coating coated thereon, according to one embodiment. 
         FIG. 3A  is a top view of a cortical electrode with a drug delivery structure disposed thereon, according to one embodiment. 
         FIG. 3B  is a perspective view of a depth electrode with a drug delivery structure disposed thereon, according to one embodiment. 
         FIG. 4  is a perspective view of a depth electrode with a drug delivery lumen, according to one embodiment. 
         FIG. 5  is a perspective view of a depth electrode with small openings for delivery of an agent, according to one embodiment. 
         FIG. 6  is a cross-sectional side view of a drug delivery system that includes a neural probe device and a magnetic actuation member, according to one embodiment. 
         FIG. 7  is a cross-sectional side view of a iontophoretic drug delivery device, according to one embodiment. 
         FIG. 8  is a cross-sectional side view of a kinetic energy drug delivery device, according to one embodiment. 
         FIG. 9A  is a cross-sectional side view of a drug delivery device with a cavity having an agent channel, according to one embodiment. 
         FIG. 9B  is a top view of the drug delivery device of  FIG. 9A , according to one embodiment. 
         FIG. 10A  is a top view of a cortical electrode with a fluidic agent delivery mechanism, according to one embodiment. 
         FIG. 10B  is a side view of a portion of a delivery channel of a fluidic agent delivery mechanism, according to one embodiment. 
         FIG. 11A  is a cross-sectional side view of a drug delivery reservoir, according to one embodiment. 
         FIG. 11B  is a side view of the actuable gate of the reservoir of  FIG. 11A , according to one embodiment. 
         FIG. 12A  is a schematic view of a drug delivery system having a neural probe coupled to a controller, according to one embodiment. 
         FIG. 12B  is a front view of a known controller for use with the system of  FIG. 12A , according to one embodiment. 
     
    
    
     DETAILED DESCRIPTION 
     Discussed herein are various neural probes in the form of electrodes and other related devices, methods, and technologies that incorporate agent delivery of various kinds, including agent or drug elution. More specifically, the various embodiments disclosed or contemplated herein relate to improved systems, devices, and methods, and various components thereof, for monitoring, stimulating, and/or ablating brain tissue while also delivering an agent of some kind, and various components of such systems and devices. The agent can be delivered contemporaneously via drug delivery or over time (elution) via a coating or bioresorbable delivery of some kind, and can be a pharmaceutical drug or an agent for providing benefits to the patient, including, for example, enhancing the electrical features of the device. In some embodiments, the agent can be delivered or provided over time on the surface of the brain (via a cortical electrode, for example) or into the tissue of the brain (via a depth electrode, for example). In those implementations in which the agent is delivered or provided over time, it is understood that that it can be any known period of time, from a relatively short period to a relatively long period. In addition, the controlled delivery or providing of the agent according to any embodiment herein can be self-controlled by a patient, doctor, other user, or computer or can be controlled autonomously. For purposes of this application, it is understood that the term “drug delivery” includes elution. 
     The various drug delivery device embodiments disclosed or contemplated herein include any type of neural electrode, including, for example, a cortical electrode  10  as shown in  FIG. 1A , a depth electrode  12  as depicted in  FIG. 1B , or an electrode array  14  as shown in  FIG. 10 . Other exemplary devices can include, for example, a scalp electrode (not shown). Alternatively, the implementations herein are not limited to those specific, exemplary devices. Rather, any of the drug delivery features or components disclosed or contemplated herein can be incorporated into any known neural probe or electrode. In each of these device embodiments as shown or any other known device, the drug delivery can be in the form of a coating disposed on at least a portion of the device (such as any of devices  10 ,  12 ,  14 ), with the coating containing a treatment agent or drug of some kind. Alternatively, as will be described in further detail below, the drug delivery can be accomplished via a sheath or other separate component that can be disposed over at least a portion of the device prior to implantation, deployed with the device, and released upon removal of the device to remain in position to continue to deliver a treatment agent over a predetermined period of time after the device has been removed. In a further alternative, the device itself can have an agent delivery component or feature, such as delivery openings in the device that allow for continual delivery over time or delivery upon actuation by a user. These agent delivery and elution embodiments and other such components or features are described in additional detail herein. 
     In one embodiment as best shown in  FIG. 2 , the neural probe device  20  has an outer surface  22  with an agent coating  24  coated on the outer surface  22 . It is understood that the neural probe device  20  can be any type of neural probe, including any of the exemplary devices discussed above, and it is further understood that the agent coating  24  embodiments as described herein can be incorporated into any device embodiment disclosed or contemplated herein. The outer surface  22  as shown can be any portion of the device  20 , such that the entire outer surface  22  of the device  20  can be coated, or any portion thereof. 
     In one embodiment, the outer surface  22  of the device  20  is made of a polyimide, such as, for example, Kapton. In a further implementation, the outer surface  22  is made of parylene C, which is a coating that can be coated over the device  20  (including over a polyimide such as Kapton) to create the outer surface  22  made of parylene C. Alternatively, the outer surface  22  can be made of any known material that can be incorporated into a neural probe device  20 . 
     In one specific embodiment, the coating  24  includes nitric oxide, and at least one treatment agent. That is, the treatment agent is coated onto the outer surface  22 , and then the nitric oxide is coated over the treatment agent, thereby creating a two-layered agent coating  24  made up of the agent layer and the nitric oxide layer. After deployment of the device  20  to its desired location in the patient, the nitric oxide begins to slowly resolve over time, resulting in the slow release (elution) of the treatment agent. Alternatively, the coating  24  can include any composition that can slowly dissolve when the device  20  is deployed to slowly release the treatment agent over time. For example, the coating  24  can be a dissolvable coating, a hydrophilic coating, a patterned coating with time release, or any other type of coating. Alternatively, the coating  24  can including any composition that allows for release of the treatment agent via any period of time, including immediately. 
     In another exemplary implementation, the coating  24  is made up of a layer of time-release microspheres that contain the treatment agent and can release the treatment agent over a predetermined period of time that can be selected. That is, the microspheres can be engineered to release the agent over the desired time period, including, for example, a range from about one week to about one year. One specific example of such a microsphere that can be coated on the device  20  to create the coating  24  is the Chroniject microsphere technology, which is commercially available from Oakwood. 
     In use, the device  20  would be positioned on or in the brain tissue of the patient, depending on the type of device  20 . For example, a depth electrode device would be inserted into the brain tissue, while a cortical electrode would be positioned onto the surface of the brain tissue. Regardless of the type of device  20 , the coating  24  with the treatment agent(s) contained therein is disposed on the outer surface  22  in a location on the device  20  so as to maximize the contact between the coating  24  and the brain tissue in contact with the device  20 . 
     In one embodiment, the treatment agent included in the coating  24  is intended to curtail the body&#39;s response to the presence of the device in the body. For example, the treatment agent can be Slipskin™ 90/10 or Medikote™ PVD Coating. In certain implementations, the coating  24  provides for extended time-release of the treatment agent during the period of time that the device  20  is in the brain, thereby preventing or reducing the body&#39;s natural response to the presence of the device  20  throughout the time that the device  20  is present. The time-release feature of the coating  24  can be accomplished by the specific nitric oxide or microsphere technologies and similar technologies as discussed above, or by any other known time-release technology. 
     Alternatively, the treatment agent can be any known agent that could be beneficial for a neural probe in contact with brain tissue for any period of time. For example, the treatment agent can be heparin. 
     In addition to the desired benefits of the treatment agent included in the coating  24 , additional benefits can arise from incorporation of the coating  24  onto the outer surface  22  of the device  20 . For example, in certain embodiments, the coating  24  can increase contact between the brain tissue and the device  20  by causing the brain tissue to be attracted to the coating  24 , thereby causing attraction of the brain tissue to the device  20 . For example, in one embodiment, the coating  24  can be hydrophilic such that the coating attracts water, thereby causing the water in the brain tissue to be drawn toward and/or adhere to the device  20 . 
     According to another implementation, the coating  24  can be used to influence or change the behavior of the electrical activity of a neuron. For example, in one embodiment, the coating  24  can influence the way ion channels in a neuron function. More specifically, the coating  24  can include a composition that contains ions, such as ions in the form of sodium or potassium, for example. Alternatively, the ion composition can be any known composition containing ions. A seizure is caused by neuron cells “firing” as a result of an increase in the action potential of the cells. The “firing” is a spark created by each cell as the cell is reset to bring the action potential back to a normal state. In this specific embodiment, the ion composition is delivered to the neuron cells such that the ions can change the ionic state outside the target neuron cells, thereby reducing or eliminating the risk of the cells firing. That is, the ions can bring the action potential of the cells back to a normal state without the cells firing. Thus, the coating  24  containing ions can decrease the electrical activity of one or more neurons, thereby reducing or eliminating the risk of a seizure. In certain embodiments, the coating  24  can contain a treatment agent that has both at least one drug in combination with ions. 
     In accordance with an alternative implementation as shown in  FIGS. 10A and 10B , a device  160  is provided that can deliver a fluidic agent/composition via a delivery mechanism to slow seizure activity in a fashion similar to the delivery of ions as described above, but this embodiment utilizes cold saline or similar fluids instead of ions. As best shown in  FIG. 10A , the device  160  in this implementation is a cortical electrode  160  having a connection structure  162  and an electrode array pad  164 . Further, the device has a fluid channel  166  defined through the connection structure  162  and a delivery channel  168  defined in the electrode array pad  164  to provide for passage of the fluid agent through the channel  166  and delivery of the agent to the target area of the brain via the delivery channel  168 . Further, the fluid channel  166  extends proximally from the connection structure  162  and has a connector  170  on its proximal end to allow for coupling to a syringe or other source of agent fluid. 
     In one implementation as shown, the delivery channel  168  has four branches extending across the pad  164  as shown. Alternatively, the delivery channel  168  can have one, two, three, or five or more branches. In a further alternative, the channel  168  can have any configuration that provides for effective delivery of the fluidic agent to the target area of the brain. As best shown in  FIG. 10B , which depicts an expanded view of a portion of a delivery channel  168  according to one embodiment, the delivery channel  168  has a plurality of holes  172  formed therein such that the inner lumen (not shown) of the channel  168  is in fluidic communication with the area adjacent to the channel  168 . As such, the fluidic agent being delivered through the fluid channel  166  and into the delivery channel  168  can pass through the holes  172  and thereby be delivered to the target area adjacent to the pad  164 . It is understood that the holes  172  can be formed in the channel  168  along its entire length and all of its branches. Alternatively, the holes  172  can be formed in only a predetermine portion or length of the channel  168  and/or its branches. 
     According to certain embodiments, the fluidic agent is cold saline that can slow seizure activity by delivery to the area of the brain that is the source of that activity. Alternatively, any other fluidic agent that can slow seizure activity can be used. 
     In certain alternative implementations, the coating  24  can be added to or incorporate onto any type of neural tools (such that the outer surface  22  described above is an outer surface  22  of a related neural tool  20 , rather than any of the probe or electrode embodiments discussed herein) that are used with or during use of neural probes, such as wands, spatulas, or other such known tools and devices. Thus, the various embodiments and features as described herein with respect to  FIG. 2  can also apply to a coating  24  on any such tool, including any coating embodiment with any treatment agent as described or contemplated herein. 
       FIGS. 3A and 3B  depict two embodiments of neural probe devices  30 ,  36  having drug delivery components (or “structures”)  34 ,  40  disposed thereon. More specifically, the device  30  in  FIG. 3A  is a cortical electrode  30  having a contact array  32 , and the drug delivery structure  34  is disposed over the contact array  32 . Further, the device  36  in  FIG. 3B  is a depth electrode  36  having an elongate body  38 , and the drug delivery structure  40  is disposed over the elongate body  38 . It is understood that a similar structure can be disposed over any neural probe device disclosed herein or any other known neural probe device. In these exemplary embodiments, in use, each structure  34 ,  40  can be a sheath, scaffold, or sheath-like structure  34 ,  40  that can be physically disposed over the device (such as device  30  or  36 ) prior to placement of the device on or in the patient&#39;s brain as necessary. Thus, when the device  30 ,  36  is positioned in the patient, the structure  34 ,  40  is also positioned in the patient. Further, in certain implementations, the structure  34 ,  40  can be maintained in place in the patient when the device  30 ,  36  is removed, thereby allowing the structure  34 ,  40  to continue to deliver the desired treatment agent to the area after the device  30 ,  36  is removed. 
     In certain embodiments, the structure  34 ,  40  (or any such structure for any type of neural probe device) can be a sheath or scaffold  34 ,  40  made of dissolvable material containing a treatment agent such that the treatment is steadily released over time as the material dissolves. For example, in one implementation, the structure  34 ,  40  is a commercially-available bioresorbable scaffold such as, or similar to, Igaki-Tamai, DeSolve, DeSolve 100, IDEAL biostent, REVA, ReZolve, ReZolve 2, Fantom, Fortitude, Mirage BRMS, MeRes, Xinsorb, or ART 18AZ. Alternatively, the structure  34 ,  40  can be any structure that can be made of any known dissolvable material for timed release of a treatment agent. 
     According to certain further implementations, any of the various device embodiments disclosed or contemplated herein can include a drug delivery component, structure, or feature that is integral to the device. For example, in one embodiment, a neural probe device  50  as depicted in  FIG. 4  has a drug delivery lumen  54  defined in the body  52  of the device  50  such that the treatment agent can be delivered to the target area of the brain tissue via the drug delivery lumen  54  in the device  50  as shown. Further, as will be discussed in further detail below, in certain variations of this implementation, the device  50  can also have a delivery controller (similar to the controller/actuator  214  discussed in further detail below in relation to  FIGS. 12A and 12B ) associated with the device  50  that is in fluidic communication with the drug delivery lumen  54  such that the controller can actuate delivery of the treatment agent to the target area of the tissue via the lumen  54 . Various exemplary controller implementations are discussed in further detail below. 
     It is understood that any device similar to device  50  having an agent delivery lumen such as lumen  54  can also be used for other types of fluid flow. That is, the fluidic access lumen  54  can be used to not only deliver a treatment agent, but also flush the treatment area with an appropriate known flushing fluid, or retract fluid from the treatment area via the lumen  54 . In one specific exemplary embodiment, the fluidic access lumen  54  can be used to apply suction, thereby assisting with retaining the device  50  in place via the suction. 
     In further alternatives, instead of a delivery lumen (such as lumen  54  as discussed above), any device embodiment herein can have an array of small openings defined in the body of the device such that the treatment agent can be delivered to the treatment area via the small openings. One such exemplary device  60  is depicted in  FIG. 5 , in which the device  60  has openings  64  defined in the body  62  as shown. In use, any agent disclosed or contemplated herein can be delivered to the brain tissue via the openings  64 . It is understood that the delivery can be accomplished via any delivery method or mechanism disclosed or contemplated herein. For example, any of the embodiments herein having small agent delivery openings can also have a controller/actuator similar to any of the exemplary embodiments discussed elsewhere herein such that delivery of the agent via the delivery openings can be controlled and actuated with precision. 
     According to the various embodiments herein, the treatment agent can be provided in any of several different forms for use with any of the device implementations disclosed or contemplated herein. For example, as described above, the agent can be provided in a liquid form that can vary in viscosity in the coating embodiments discussed above with respect to  FIG. 2 . Continuing with the coating embodiments of  FIG. 2 , it is understood that the agent can also be provided in a slurry form, a solid form, or any other form that a coating is known to take in the art. Alternatively, the agent can be provided in structured, water-soluble, non-fluid form in those embodiments in which the device has a drug delivery structure removably disposed thereon as discussed above with respect to  FIGS. 3A and 3B . Alternatively, the agent can be provided in liquid form in those embodiments in which the device has a drug delivery structure, component, or feature integral to device as discussed above with respect to  FIGS. 4 and 5 . In a further embodiment, in the devices of  FIGS. 4 and 5  (or any devices with any type of delivery structures), the treatment agent can be formed into a solid or dry form, such as a pellet or a powder. For example, in certain embodiments, the treatment agent is formed into a solid, water soluble pellet that can be delivered to the target area in the patient via the delivery lumen  54  of the device  50  in  FIG. 4 . In another example relating to the device  60  depicted in  FIG. 5 , the solid form of the treatment agent can be disposed within the device  60  such that fluid from the patient can come into contact with the solid treatment agent via the openings  64 , thereby causing the solid treatment agent to begin to dissolve and thereby deliver the treatment agent to the target tissue via the openings  64 . In accordance with another implementation similar to the water-soluble solid form as described above, the treatment agent can be in a liquid or dry form and disposed within a capsule. According to a further alternative, the agent can take any known form. 
     Other forms of drug delivery actuation are contemplated herein. For example, in certain implementations such as the exemplary implementation shown in  FIG. 6 , a system  70  is provided that includes a magnetic actuation member  74  that can operate in combination with the neural probe device  72  such that the magnetic actuation member  74  is in magnetic communication with the device  72 . The magnetic communication allows the actuation member  74  to actuate the device  72  to release the treatment agent for delivery to the target area of the tissue. In this specific exemplary embodiment as shown, the probe  72  is a cortical electrode probe  72  having three layers  78 A,  78 B,  78 C that are coupled together to form the body  78  of the probe  72 . More specifically, the body  78  is made up of a first outer layer  78 A, a middle or inner layer  78 B, and a second outer layer  78 C such that the middle layer  78 B is disposed between and attached to the first and second outer layers  78 A,  78 C. The body  78  also has a cavity (also referred to herein as an “agent receptacle”)  80  defined therein. More specifically, in this particular embodiment, the cavity  80  is formed via the absence of a length of the middle layer  70 B, thereby resulting in a cavity  80  defined by the first layer  78 A and the two opposing ends of the middle layer  70 B on both sides of the cavity  80 . Any treatment agent  82  according to any embodiment herein can be disposed in the cavity  80  as shown. The body  78  also has a deployable cover (or “flap”)  84  that is disposed over the cavity  80  such that the cover  84  can be used to enclose the cavity  80  and thereby retain the agent  82  therein. Further, the flap  84  can be rotatably coupled to the body  78  by a joint  86  at one end of the flap  84 . In a further alternative, the deployable cover  84  can be any known device or mechanism for covering an opening and being actuable to move into an open position. 
     In one embodiment, the flap  84  is tensioned such that the flap  84  is continuously urged toward the body  78  (in the direction indicated by arrow “A” toward the “closed” position in which the flap  84  is in contact with the body  78  and encloses the cavity  80 ) by the tension. Thus, as the flap  84  is urged away from the body  78  (in the direction indicated by arrow “B”), the force urging the flap  84  toward the body  78  increases. In one specific implementation, the tensioning component (not shown) is a spring or piston-like component (not shown). Alternatively, the tensioning component (not shown) can be any known tensioning component. 
     Further, the flap  84  in this implementation can be made of a magnetic material or can have a magnet or other magnetic material disposed therein (not shown) such that the magnetic actuation member  74  can communicate magnetically with the flap  84 . Thus, in use, the device  72  can be positioned as needed in relation to the brain  76  of the patient. More specifically, in this example, the device  72  is disposed along the surface of the brain  76 . Once the device  72  is positioned as desired, the treatment agent (or the composition containing the treatment agent)  82  in the cavity  80  can be released by application of a magnetic field via the magnetic actuation member  74 . It is understood that the treatment agent  82  remains unreleased, or undelivered until the magnetic field is applied to the device  72 . For example, as best shown in  FIG. 6 , the magnetic actuation member  74  is either moved by a user toward and into closer proximity with the device  72  or otherwise is actuated such that a magnetic field is generated by the actuation member  74  that extends to the flap  84 . The flap  84  is repelled by the magnetic field, thereby causing the flap  84  to rotate on its hinge  86  away from the body  78  (in the direction indicated by arrow “B”). Thus, the rotation away from the body  78  causes the flap  84  to move into its open position or configuration, which results in fluidic access to the cavity  80 . As a result, the magnetic actuation member  74  can be used to magnetically actuate the flap  84  to move into its open position, thereby releasing the agent  82  in the cavity  80 . 
     In accordance with another drug delivery actuation embodiment, the treatment agent or the composition containing the treatment agent can be propelled or otherwise actuated to be delivered to the treatment area via iontophoresis. In one specific exemplary embodiment as depicted in  FIG. 7 , a device  100  is provided that has a device body  102  with a contact  104  that is also an electrical actuation member  104  that is in electrical communication with the treatment agent/composition  106  to be delivered to the target area of the brain  108 . In this specific embodiment, the body  102  is made up of three layers: a first outer layer  102 A, a middle or inner layer  102 B, and a second outer layer  102 C such that the middle layer  102 B is disposed between and attached to the first and second outer layers  102 A,  102 C. A portion of the middle layer  102 B is made up of the contact  104  and an electrical lead  110  coupled to the contact  104 , as shown, such that an electrical current as represented by arrow D can be transmitted to the contact  104  via the lead  110 . Alternatively, the contact and the electrical actuation member can be two different components. The body  102  also has a cavity (also referred to herein as an “agent receptacle”)  112  defined therein. More specifically, in this particular embodiment, the cavity  112  is formed via the absence of a length of the second outer layer  102 C, thereby resulting in a cavity  112  defined by the electrical actuation member/contact  104  and the two opposing ends of the second outer layer  102 C on both sides of the cavity  112  such that the cavity  112  contains the contact  104 , as discussed above. Any treatment agent  106  according to any embodiment herein that can be delivered via iontophoresis or any application of electrical current can be disposed in the cavity  112  as shown. 
     Thus, in the instant implementation as shown, the treatment agent/composition  106  is disposed in or on the device  100  such that actuation of the contacts (including contact  104 ) on the body  102  by providing an electrical current as represented by arrow D can interact with the ionically polarized treatment agent/composition  106  to propel the agent/composition  106  toward the treatment area of the brain  108 , as represented by arrows C. Alternatively, it need not be the contacts of the electrode that propel the agent/composition. Instead, the device  100  can have any known component that can apply an electrical current to the agent/composition to propel the agent/composition in a similar fashion. In certain embodiments, regardless of the source of the actuation, the amount of current and/or time can be varied to control the speed and distance that the ionically polarized treatment agent/composition travels. Various iontophoretic delivery device embodiments can be scalp electrodes that are positioned on the external scalp of the patient, rather than inside the skull or in direct contact with the brain tissue. In these specific embodiments, the iontophoretic delivery makes it possible to deliver the treatment agent through the skull. 
     In a further alternative embodiment of a drug delivery actuation embodiment as shown in  FIG. 8 , the treatment agent or the composition containing the treatment agent can be propelled or otherwise actuated to be delivered to the treatment area via kinetic energy. More specifically, a device  120  is provided that has a device body  122  with a contact  124  that is also an kinetic actuation member  124  that is in contact with or otherwise in communication with the treatment agent/composition  126  to be delivered to the target area of the brain  128 . In this specific embodiment, the body  122  is made up of three layers: a first outer layer  122 A, a middle or inner layer  122 B, and a second outer layer  122 C such that the middle layer  122 B is disposed between and attached to the first and second outer layers  122 A,  122 C. A portion of the middle layer  122 B is made up of the contact  124  that can be made of a material that is responsive to kinetic energy such that kinetic energy as represented by arrow E can be transmitted to the contact  124  and cause the contact/kinetic actuation member  124  to urge the agent/composition  126  toward the brain  128 . Alternatively, the contact and the kinetic actuation member can be two different components. The body  122  also has a cavity (also referred to herein as an “agent receptacle”)  130  defined therein. More specifically, in this particular embodiment, the cavity  130  is formed via the absence of a length of the second outer layer  122 C, thereby resulting in a cavity  130  defined by the kinetic actuation member/contact  124  and the two opposing ends of the second outer layer  122 C on both sides of the cavity  130  such that the cavity  130  contains the contact  124 , as discussed above. Any treatment agent  126  according to any embodiment herein that can be delivered via kinetic energy or any application of kinetic energy—such as vibration, tuned vibration, ultrasound, etc.—can be disposed in the cavity  130  as shown. 
     Thus, in the instant implementation as shown, the treatment agent/composition  126  is disposed in or on the device  120  such that actuation of the contacts (including contact  124 ) on the body  122  by providing kinetic energy as represented by arrow E can interact with the treatment agent/composition  126  to propel the agent/composition  126  toward the treatment area of the brain  128 , as represented by arrows F. Alternatively, it need not be the contacts of the electrode that propel the agent/composition. Instead, the device  120  can have any known component that can apply kinetic energy to the agent/composition to propel the agent/composition in a similar fashion. In certain embodiments, regardless of the source of the actuation, the amount of energy and/or time can be varied to control the speed and distance that the treatment agent/composition travels. 
     Another embodiment of a drug delivery device is contemplated that doesn&#39;t require external actuation, but simply provides for delivery of the agent via fluidic access to the agent such that the agent is dissolved over time into the brain fluids that contact the agent. More specifically, as shown in  FIGS. 9A  (cross-sectional side view) and  9 B (top view), a device  140  is provided that has a device body  142  with a contact  144  disposed within a cavity  150  that defines an agent channel  152  within the cavity  150  such that an agent/composition  146  can be disposed within the channel  152 . Please note that the agent/composition  146  is only depicted in a portion of the channel  152  in  FIG. 9A  in order to be able to better depict the channel  152  in the portion not containing any agent  146 . In this specific embodiment, the body  142  is made up of four layers: a first outer layer  142 A, a middle or inner layer  142 B, a lead and contact layer  142 C, and a second outer layer  142 D such that the middle layer  142 B and the lead/contact layer  142 C are disposed between and attached to the first and second outer layers  142 A,  142 D. The lead/contact layer  142 C is made up of the contact  144  and a lead component  148  that is coupled to the contact  144  and delivers electrical stimulation thereto. The cavity  150  is formed via the absence of a length of the first outer layer  142 A and a length of the middle layer  142 B, thereby resulting in a cavity  150  defined by the contact  144  and the two opposing ends of the first outer layer  142 A and of the middle layer  142 B on both sides of the cavity  150  such that the cavity  150  contains the contact  144 , as discussed above. Further, the agent channel  152  defined within the cavity  150  such that the channel  152  encircles the cavity  150  is formed by the lip  154  that is formed via the first outer layer  142 A. More specifically, the first outer layer  142 A extends further towards the center of the cavity  150  in comparison to the middle layer  142 B such that the lip  154  is formed around the circumference of the cavity  150 . As such, the lip  154  forms the channel  152  such that the agent  146  can be disposed within the channel  152  and thereby be disposed around the outer circumference of the cavity  150  (and the contact  144 ). Any treatment agent  146  according to any embodiment herein that can be delivered via fluidic access can be disposed in the cavity  150  as shown. 
     Thus, in the instant implementation as shown, the treatment agent/composition  146  is disposed with the channel  154  in the device  140  as described above such that liquid in the brain tissue can enter the cavity  150  and interact with the treatment agent/composition  146 , causing the agent/composition  146  to dissolve over some predetermined period of time and thereby be delivered to the target area of the brain adjacent to the cavity  150 . Alternatively, this device  140  can incorporate iontophoretic or kinetic energy delivery technology similar to that described above into the device  140  such that the agent/composition  146  in the channel  154  can be delivered by iontophoretic or kinetic energy actuation. 
     Another form of drug delivery, according to a further implementation, relates to timed release of an agent via an agent reservoir, as depicted with respect to one example in  FIGS. 11A and 11B . In this exemplary implementation, a drug reservoir  180  is provided that can be integrated into a contact of any neural probe or alternatively can be disposed elsewhere on the probe. The reservoir  180  has an enclosure (or “body”)  182  with a wall  184  that defines an interior  186  that contains the desired agent  188 . Further, an actuable gate  190  is provided at some point along the wall  184  such that the gate  190  can be actuated to allow for release of some portion (or all) of the agent from the reservoir  180  at the desired time. As best shown in  FIG. 11B , according to one embodiment, the gate  190  has a body  192 , a conduit  194  defined through the body  192 , and a moveable flap  196 . The movable flap  196  has a hinge  198  such that it is rotatably coupled to the body  192  and can move between a closed position (or “configuration) in which it is disposed over the conduit  194  and thereby seals the conduit  194  closed and an open position (or “configuration”) in which it is positioned away from the body  192  as depicted, thereby allowing fluidic access to the conduit  194  and thus allowing passage of agent out of the interior  186 , through the conduit  194 , and out to the target tissue. 
     In one embodiment, the flap  196  is operated magnetically and is tensioned to return to its closed position when any external forces are removed, in a fashion similar to the flap  84  described above. Alternatively, the flap  196  can be operated mechanically, electrically, or via any form of force. Further, while the specific gate  190  has been described in detail, it is understood that any type of known port or door that can provide both open and closed configurations can be incorporated into the reservoir for use herein. In addition, it is understood that an external actuation mechanism is in communication with the gate  190  such that a user can utilize the external actuation mechanism to control the gate  190  via any form of communication, including wired or wireless communication. 
     Another drug delivery system  210  is depicted in  FIGS. 12A and 12B , according to one exemplary implementation. The system  210  has a neural probe  212  that is coupled to a controller  214  via a connection line  216 . In one exemplary embodiment, the controller  214  is a known drug pump  214  as best shown in  FIG. 12B . The drug pump  214  can be any known drug/infusion pump  214  that can be used to deliver any agent to a patient over time and further can provide precise control of said delivery. Alternatively, any known controller/actuation device can be incorporated into the system  210 . The controller  214  is coupled with the neural probe  212  via the connection line  216  such that the controller  214  can control the operation of the probe  212 , including controlling the delivery of an agent from the probe  212  to the brain of the patient. In one embodiment, the connection line  216  has at least one communication line (not shown) and at least one agent delivery lumen (not shown) disposed therein, such that the connection line  216  can be used to transmit electronic or electrical communications via the communication line and further can be used to transfer an agent via the agent delivery lumen. In one embodiment, the neural probe  212  is a depth electrode  212 . Alternatively, the neural probe  212  can be any known probe, including a cortical electrode or any other known probe. 
     It is understood that any of the device embodiments with a drug delivery lumen as disclosed or contemplated herein, including those in  FIGS. 4, 5, 10A, 10B, 11A, and 11B , can be coupled with and operate in conjunction with a controller/actuator such as the controller/actuator  214  described above. Further, any other embodiment having an actuable component can also be coupled with an operate in conjunction with a controller/actuator, including those in  FIGS. 6-9B . As such, any of the device implementations disclosed or contemplated herein can be incorporated into the system  210  or any similar system having a controller/actuator. 
     It is further understood that any of the various embodiments disclosed or contemplated in  FIGS. 2-12B  can be incorporated into or used in conjunction with any known neural probe embodiment, including the embodiments depicted in  FIGS. 1A-1C . 
     In use, the various devices disclosed or contemplated herein, including those having a delivery lumen, delivery openings, iontophoretic delivery, kinetic energy delivery, fluidic access delivery, agent reservoirs, or similar structures or features, can be used to treat a seizure in real-time. That is, if a patient feels a seizure coming on, the patient can actuate a controller/actuator (similar to any of the controller/actuator embodiments discussed above, for example), or the controller can otherwise be triggered to actuate the implanted probe to deliver a treatment agent into the brain tissue via the agent delivery component (such as an agent delivery lumen or agent delivery openings as described above, for example) to eliminate or minimize the seizure. Alternatively, the various delivery components can be utilized in any known manner to deliver a treatment agent via a neural probe device as disclosed or contemplated herein. 
     Various treatment agents can be incorporated into any of the various drug delivery device embodiments disclosed or contemplated herein. For example, some of the exemplary treatment agents can include, but are not limited to, paclitaxel (available as Elutax, Biostream, Pantera Lux, etc.), acetazolamide, brivaracetam (available as Briviact), carbamazepine (also available as Carbagen, Tegretol, Tegretol Prolonged Release), clobazam (also available as Frisium, Perizam, Tapclob, Zacco), clonazepam, eslicarbazepine acetate (available as Zebinix), ethosuximide, gabapentin (also available as Neurontin), lacosamide (available as Vimpat), lamotrigine (also available as Lamitcal), levetiracetam (also available as Desitrend, Keppra) oxcarbazepine (also available asTrileptal), perampanel (available as Fycompa), phenobarbital, phenytoin (also available as Epanutin, Phenytoin Sodium Flynn), piracetam (available as Nootropil), pregabalin (also available as Alzain, Axalid, Lecaent, Lyrica, Rewisca), primidone, rufinamide (available as Inovelon), sodium valproate (also available as Epilim, Epilim Chrono, Epilim Chronosphere, Episenta, Epival), stiripentol (also available as Diacomit), tiagabine (available as Gabitril), topiramate (also available as Topamax), valproic acid (available as Convulex, Epilim Chrono, Epilim Chronosphere), vigabatrin (available as Sabril), zonisamide (also available as Zonegran), any cannabinoid, any antibiotic, and any stem cell composition. It is further understood that the agent can be any known seizure treatment agent or any other treatment agent that could benefit a patient into which an electrode device is being implanted. 
     In certain embodiment, the treatment agent can be a seizure treatment agent that is attracted to electrical activity. For example, the agent can have an ionic attraction to the misfiring cells in the brain tissue, thereby resulting in the agent being drawn to the area that is the source of the seizure. In one example, the agent is an electrically charged molecule polarized agent (similar to the types of agents used in iontophoretic delivery). Alternatively, the agent takes the form of an electrically charged sphere coated with the agent. In a further alternative, the agent can be any known seizure treatment agent that is attracted to electrical activity, including any agents that have been polarized to be drawn to electrical potentials in a tissue. In these embodiments, the agent can be released or delivery by any of the device embodiments disclosed or contemplated herein and then will be attracted to an area of electrical activity, which is likely to be a seizure. Further, it is understood that, according to various implementations, the agent is an agent that helps to normalize the neuron action potential of the misfiring cells. As such, the agent is drawn to the seizure, where it treats the seizure. 
     In further implementations, the agent is not a treatment agent, but instead is an indication agent or other type of agent that can be incorporated into or delivered via any embodiment disclosed or contemplated herein. In one specific example, the agent is a blood indication agent. That is, the agent is a composition that changes color in the presence of protein, thereby indicating the presence of blood. In one example, the blood indication agent can change color to notify a surgeon that there is blood present in the surgical area of the patient. 
     Although the present invention has been described with reference to preferred embodiments, persons skilled in the art will recognize that changes may be made in form and detail without departing from the spirit and scope of the invention.