Spinal cord stimulator device and methods of manufacture and use thereof

A spinal cord stimulator device, including an implantation paddle, a connection segment and an encapsulant. The implantation paddle includes at least one pair of electrode stimulation pads, each of the electrode stimulation pads connected to ends of separate thin film electrode leads, wherein the electrode stimulation pads and the thin film electrode leads are sandwiched between softening polymer layers. The connection segment includes insulated wire leads, one end of each of the wire leads can be connected to contact pads on opposite ends of each one of the thin film leads at separated coupling joints. The encapsulant encompasses portions of the implantation paddle, including encompassing portions of the softening polymer layers surrounding the contact pads, the coupling joints and portions of the connection segment including portions of the wire leads next to the coupling joints. Methods of manufacturing device and using the device for spinal cord stimulation are also described.

TECHNICAL FIELD

This application is directed, in general, to electrical devices, and more specifically, spinal cord stimulator devices, including methods of manufacturing and using such devices.

BACKGROUND

Electrical devices that can stimulate nerves in the spinal cord have the potential to improve the lives of patients suffering from pain and paralysis. Important technological barriers to overcome toward achieving such goals include the ability to provide spinal cord stimulating devices that can be implanted with a minimum of tissue damage during and after implantation, and, provide stable electrical potentials for nerve stimulation over chronic implantation periods (e.g., weeks or months).

SUMMARY

One embodiment can be a spinal cord stimulator device. Embodiments of the device can comprise an implantation paddle including at least one pair of electrode stimulation pads, each of the electrode stimulation pads connected to ends of separate thin film electrode leads, wherein the electrode stimulation pads and the thin film electrode leads are sandwiched between softening polymer layers. Embodiments of the device can comprise a connection segment, including insulated wire leads, one end of each of the wire leads can be connected to contact pads on opposite ends of each one of the thin film leads at separated coupling joints. Embodiments of the device can comprise an encapsulant encompassing portions of the implantation paddle, including encompassing portions of the softening polymer layers surrounding the contact pads, the coupling joints and portions of the connection segment including portions of the wire leads next to the coupling joints.

Another embodiment can be a method of manufacturing a spinal cord stimulator device. Embodiments of the method can comprise providing an implantation paddle, the implantation paddle including at least one pair of electrode stimulation pads, each of the electrode stimulation pads connected to ends of separate thin film electrode leads, wherein the electrode stimulation pads and the thin film electrode leads are sandwiched between softening polymer layers. Embodiments of the method can comprise connecting one end of insulated wire leads to contact pads of the opposite ends of each one of the thin film electrode leads by forming separated coupling joints. Embodiments of the method can comprise encompassing portions of the thin film electrode leads and portions of the insulated wire leads in the vicinity of the coupling joints with an encapsulant.

Another embodiment can be a method of spinal cord stimulation. Embodiments of the method can comprise passing the implantation paddle of the spinal cord stimulator device between two vertebrae of a spinal cord. Embodiments of the method can comprise inserting the implantation paddle into an epidural or a subdural space between the spinal cord and the vertebra, wherein a long axis of the implanted implantation paddle is aligned with a long dimension of the spinal cord, and after implantation, the two softening polymer layers soften and wrap around part of a circumference of the spinal cord. Embodiments of the method can comprise connecting ends of the wire leads to a voltage source. Embodiments of the method can comprise applying a voltage from the voltage source across the ends of the wire leads to generate an electric field between the pair of electrode pads.

DETAILED DESCRIPTION

The spinal cord stimulating devices disclosed herein have a combination of design features conducive to chronic spinal implantation. The softening polymer layers of an implantation paddle portion of the device are rigid enough to allow implantation of the paddle into the epidural or subdural space between the spinal cord and vertebra without buckling or bending the paddle during implantation. As disclosed herein the paddle is thin and has a width:length aspect ratio that is conducive to implantation while still minimizing tissue damage.

The softening polymer layers of the paddle, once implanted, substantially soften (e.g. an order of magnitude or more decrease in elastic modulus) thereby reducing the likelihood of chronic tissue damage. Additionally, softening facilitates the implantation paddle hugging the dura without excessive force on the spinal cord. We believe that such an arrangement helps reduce stimulation electrode lead migration as compared to paddles composed of material that stays rigid after implantation. Surprisingly, the implanted thin softening polymer layers of the paddle are able to withstand the mechanical force exerted inside the epidural or subdural space.

We believe that these features are in contrast to and non-obvious in view of certain conventional spinal cord stimulating devices which have been designed to be thick and rigid so as to facilitate implantation and withstand the mechanical forces associated with spinal cord bending, twisting and stretching. Such conventional spinal cord stimulating devices retain their rigidity after implantation and often have larger thickness dimensions than the devices disclosed herein. Due to their continued rigidity after implantation, such devices tend not to hug the dura of the naturally curved circumference of the spinal cord. Consequently, such rigid devices can deform and cause tissue damage to the spinal cord in the vicinity of implantation. Moreover, over time, the stimulation electrodes of such rigid devices tend to migrate away from their originally implanted location thereby changing the electrical potential required for nerve stimulation.

These features are also in contrast and non-obvious in view of certain conventional spinal cord stimulating devices that include soft paddle materials, e.g., silicone, which can be difficult to implant into the epidural or subdural space without buckling or bending.

Additionally, as disclosed herein, to reduce the possibility of shearing damage to the softening polymer layer, embodiments of the implantation paddle can be limited to a length that can substantially fully implanted in the epidural or subdural space and lay parallel to target portion of the spinal cord to be stimulated. While not limiting the scope of the disclosure by theoretical considerations, we believe that such implantation paddles are subject to a lesser number and/or lower severity of mechanical forces associated with back or neck movement, e.g., as compared to a paddle length where substantial portions of the paddle reside outside of the epidural or subdural space.

We have discovered, as disclosed herein, that the mechanical forces associated with back and neck movement are better tolerated by a connection segment of the device that includes insulated wire leads that are connected to thin film leads of the implantation paddle. Such insulated wire leads extending up between vertebra are more tolerant to the large mechanical forces associated with back and neck movement that can occur. The coupling joints between the wire leads and thin film leads can be surrounded by an encapsulant as disclosed herein to mitigate against breakage of the joints, e.g., due to back and neck movement.

Consequently, embodiments of the spinal cord stimulator device disclosed herein can be implanted with a minimum of tissue damage during and after implantation, and, provide stable electrical potentials for nerve stimulation over chronic implantation periods (e.g., weeks or months).

One embodiment of the disclosure is a spinal cord stimulator device.

FIG. 1Ashows a plan view of an example spinal cord stimulator device100of the disclosure andFIG. 1Bshows a detailed plan view of part of the example spinal cord stimulator device100shown inFIG. 1A.FIGS. 1C and 1Dshow cross-sectional views of the example spinal cord stimulator device100shown inFIG. 1Aalong view lines1C-1C and1D-1D, respectively, as depicted inFIG. 1B.

With continuing reference toFIGS. 1A-1Dthroughout, embodiments of the device100can comprise an implantation paddle105, a connection segment107and an encapsulant110. The implantation paddle105can include at least one pair of electrode stimulation pads (e.g., pads112a, . . . and pads113a, . . . ), each of the electrode stimulation pads connected to ends (e.g., end115) of separate thin film electrode leads (e.g., leads116a, . . . , and leads117a,117b,117c, . . . ). As illustrated inFIGS. 1C and 1D, the electrode stimulation pads (e.g., pads112aand113a) and the thin film electrode leads (e.g., thin film leads116aand117acan be sandwiched between softening polymer layers (e.g., layers120,122).

The connection segment107can include insulated wire leads (e.g., wire leads124a, . . . and wire leads125a, . . . ). One end (e.g., end126) of each of the wire leads is connected to contact pads (e.g., contact pads127a, . . . and contact pads128a, . . . ) on opposite ends (e.g., end129) of each one of the thin film leads at separated coupling joints130(e.g., each coupling joint separated from all other coupling joints).

The encapsulant110can encompass portions of the implantation paddle105, including portions of the softening polymer layers120,122surrounding the contact pads contact pads127a, the coupling joints130, and, encompassing portions of the connection portion107include portions of the wire leads124a. . . ,125a, . . . next to the coupling joints130.

As noted above, the softening polymer layers120,122are more rigid under ex vivo pre-implantation conditions (e.g., room temperature and air environment) than under in vivo implanted conditions (e.g., 37° C. and aqueous environment). For example, embodiments of the softening polymer layers120,122can be composed of a polymer, designated SMP6, formed from a stoichiometric combination of the monomers Tris[2-(3-mercaptopropionyloxy)ethyl] isocyanurate (TMICN) and 1,3,5-triallyl-1,2,5-triazine-2,4,6 (1H,3H,5H)-trione (TATATO) combined with 31 mol % Tricyclo[5.2.1.02,6]decanedimethanol diacrylate (TCMDA) polymerized in the presence of the photocuring agent 2,2-Dimethoxy-2-phenylacetophenone. Layers of SMP6 can have an elastic modulus of about 1.8 GPa at 21° C. and air environment. After about 5 hours in water at 37° C., the elastic modulus drops by nearly two orders of magnitude to about 50 MPa.

Other embodiments of the softening polymer layers can be composed of polymers formed from combinations of monomers functionalized with thiol-enes, thiol-ene or acrylates) can have a glassy modulus of 1-3 GPa (e.g., at room temperature in air) and exhibit a rubbery plateau in modulus (e.g., at 37° C. in water) that can range from 100 MPa down to as low as 0.03 MPa, which is at or below the modulus of tissue.

As illustrated inFIG. 1C, to maintain sufficient paddle rigidity pre-implantation and toughness during implantation, embodiments of the softening polymer layers120,122can have a thickness132,134in a range from 20 to 100 microns, e.g., about 25, 50 or 75 microns in some embodiments. Having about a same thickness132,134can facilitate placing the pads112a, . . .113a. . . and the thin film electrode leads116a, . . . ,117a, . . . at or near a mechanical neutral plane of the implantation paddle105and thereby help prevent delamination of these pads and leads from the soften layer132, e.g., when the paddle105is bent during and/or following implantation.

Embodiments of the spinal cord implantation paddle105can have a long and narrow aspect ratio to facilitate implantation in the epidural space. For example, in some embodiments as illustrated inFIG. 1B, a width137to long axis length135aspect ratio can range from 1:6 to 1:8. For example, in some embodiments, when the length135of the paddle105equals 130 mm or 65 mm the paddle's width137can equal 20 mm or 10 mm, respectively. For example, in some embodiments, when the length135of the paddle105equals 15 mm, the paddle's width137can equal 2 mm.

In some embodiments, to facilitate having the implanted paddle105to wrap around and hug a target portion of the spinal cord dura or spinal cord subdurally, the width137of the paddle105can be in a range from 5 to 30 percent of the circumference of the spine. For example, when the target portion of the human spine has an average diameter (e.g., average of transverse and anteroposterior diameters) of about 10 mm, then the circumference equals about 31 mm, and for a paddle width137equal to 10 mm, the paddle wraps around about 31 percent of the circumference of the spinal cord. Of course, other factors, such as the number and distribution of electrode stimulation pads112a, . . . ,113a, . . . and thin film electrode leads116a, . . .117a, . . . , can also affect the minimum width137dimensions of the paddle105.

As illustrated inFIG. 1B, to facilitate implantation, some embodiments of the paddle105can have a leading segment138that includes the softening polymer layers120,122and is free of the electrode stimulation pads112a, . . .113a, . . . and the thin film traces116a, . . .117a, . . . . Providing such a leading segment138, free of electronic components, allows bending of the segment138at large angles (e.g., greater than 90 degree angles) to facilitate placing the paddle under vertebra in the epidural or subdural space while mitigating the risk of breaking or delaminating the pads or traces from the softening polymer layers during such implantation maneuvers. For example, in some embodiments the leading segment138can have a length139(e.g., from a curved leading edge of the paddle105to the edge of the most forward located pads112a,113a) in a range from 5 mm to 20 mm.

As illustrated inFIG. 1C, some embodiments of the electrode stimulation pads (e.g., pad112a) can include a titanium nitride layer140deposited (e.g., sputter deposited) on a portion of the thin film layer116a, e.g., to facilitate producing a large charge injection capacity, which in turn, can facilitate nerve stimulation via a capacitive stimulation mechanism well understood by those skilled in the pertinent art. To facilitate the ability to carry sufficient current to generate a large charge injection density for such spinal nerve stimulation, embodiments of the electrode stimulation pads112acan have a area perimeter142(FIG. 1B) in a range from about 2 mm2to 6 mm2(e.g., about 2 mm×3 mm) and can have a thickness144(FIG. 1C) in a range from about 5 to 2000 nanometers.

As illustrated inFIG. 1C, facilitate the ability to carry sufficient current, some embodiments of the thin film leads can be composed of gold deposited on the softening polymer layer having a thickness146in a range from about 100 to 5000 nanometers.

Other embodiments of thin film leads can be composed of copper, nickel, aluminum, platinum, PEDOT, carbon nanotubes, graphene, ultrananocrystalline diamond, chromium, alloys of several materials including palladium/nickel/gold.

As illustrated inFIG. 1B, in some embodiments, each of the thin film leads (e.g., lead116a) can be rectilinear structures each having a width148in a range from 20 to 200 microns and length150(FIG. 1B) sufficient to place the contact pads under the targeted portion of the spinal cord. For example, in some embodiments, the thin film leads can range in length150from about 1 to 15 cm, e.g., so as to extend along an about 1 to 15 cm length portion of the long dimension of the spinal cord (e.g., any portion of the length of the spinal cord extending from the foramen magnum to the upper part of the lumbar region).

In some embodiments, the paired electrode stimulation pads (e.g., pads112aand113a), are configured as positive and negative voltage leads, respectively, to generate the nerve stimulating electric field. Embodiments of the paired electrode pads112a,113acan be separated a sufficient distance (e.g., edge-to-edge distance152) to facilitate generating an electric field (e.g., comprising field line154) that can penetrate into the spinal cord and thereby stimulate the targeted nerves of the spinal cord. For example, in some embodiments, the edge-to-edge distance152is in a range from about 1 to 10 mm, and in some embodiments about 2 to 5 mm.

FIGS. 1A and 1Bdepict an example device100embodiment having 8 electrode stimulation pads (e.g., four pairs of pads) and associated separate thin film electrode leads and wire leads. Based upon the present disclosure, one skilled in the pertinent art would understand how similar devices100could be constructed with 16, 32, 64, etc . . . , stimulation pads and associated separate thin film electrode leads and wire leads.

Yet other embodiments include devices100that can be fabricated with backplanes that allow a limited number of traces to address more than 4 electrodes, such as 16, 32, 64, 128, 256, 512, 1024, 2048, 4096, 8192 or more than 10,000 electrodes or some other number of electrodes that are addressed in this way.

As illustrated inFIG. 1D, embodiments of the wire leads124a, . . . ,125a, . . . of the connection segment107can include a cylindrical wire160surrounded by an insulator layer162. In some embodiments, for example, the cylindrical wire160can be composed of steel (e.g., stainless steel) and have a diameter164in a range from 25 to 50 microns). In some embodiments, for example, the insulator layer162can be composed of a non-electrically conducting polymer such as parylene-C, polyether ether ketone, polyimide and the like.

As illustrated inFIG. 1D, the coupling joints130can lay on the contact pad (e.g., contact pads127a,128a) and portions of the thin film electrode leads (e.g., leads116a,117a). To provide a bonding base for the wire160, some embodiments of the contact pads127ahave a perimeter (e.g., perimeter166,FIG. 1B) of with an area in a range from about 700 to 3000 microns. In some embodiments a portion of the wire160(e.g., removed of insulator layer162) of the wire lead124a, . . . ,125a, . . . can be inserted into, and bonded to, a solder paste of the coupling joint130, e.g., via a melt-reflow process. Some embodiments of the coupling joint130can include a lead-free (e.g., less than about 0.1% lead) solder paste such an indium silver solder paste.

As illustrated inFIGS. 1B and 1D, to mitigate breakage of the coupling joints130, some embodiments of the encapsulant110encompass the implantation paddle105around portions of the thin film leads116a, . . .117a, . . . and the insulated wire leads124a, . . .125a, . . . , in the vicinity of the coupling joints130. For example, some embodiments of the encapsulant110can have a substantially spherical shape with an average diameter170in a range of from about 1 to 10 mm. For example, a 1 mm diameter170droplet of the encapsulant110, may be applied in the vicinity of the coupling joints130such that about 0.4 mm lengths172of the paddle105around the thin film leads and about 0.4 mm lengths around of the insulated wire leads are surrounded by the encapsulant110. For example, a 6 mm diameter170droplet of the encapsulant110, can be applied in the vicinity of the coupling joints130such that about 2.5 mm lengths172of the paddle105around the thin film leads and about 2.5 mm lengths around the insulated wire leads are surrounded by the encapsulant110.

Some embodiments of the encapsulant110are composed of a silicone epoxy polymer.

As illustrated inFIG. 1A, some embodiments of the device100can further include a voltage source180. Opposite ends (e.g., end182) of the wire leads124a, . . .125a, . . . can be connected the voltage source180. One skilled in the pertinent art would understand how the ends182of the wire leads124a, . . .125a, . . . could to be fashioned with connectors (e.g., pins) to interface with the voltage source180.

The voltage source180can be configured to apply separate voltage potentials between any pair of the electrode stimulation pads (e.g., paired pads112s,113a). In some embodiments, the voltage source180can be implanted, e.g., under the skin, while in other embodiments the voltage source180can be outside of the body of the subject implanted with the implantation paddle105and ends182of the wire leads of the connection segment107can connect to the voltage source180outside of the body.

One skilled in the pertinent art would be familiar with how to configure the voltage source180as a pulse generator to generate repeating pulses of positive or negative voltage potential across the pairs of electrodes at a frequency from 20 to 120 Hz, and in some embodiment 50 to 60 Hz, or, in some embodiments, greater than 6 kHz, e.g., to facilitate nerve blocking, or, to mitigate pain associated with sciatica or other forms of chronic or acute pain.

Some embodiments of the voltage source180can be configured to generate and apply such voltage pulses to produce currents through the lead wires and the thin film electrode leads connected to the paired electrode pads, up to 26 mA over a range of voltages up to ±16 volts. In some such embodiments, the voltage pulses can be applied for durations (e.g., a pulse width) in a range of about 100 to 500 microsecond.

To mitigate tissue heating and damage, some embodiments of the voltage source180can be configured to generate and apply a biphasic pulse such that the positive and negative potentials across paired electrode stimulation pads alternately reverse. Some embodiments of the voltage source180can be configured to have a pulse-free interval between pulse, e.g., to allow a capacitive discharge of the stimulated tissue between pulses. Some embodiments of the voltage source can be configured to generate variable voltage pulse widths and/or various pulse shapes, such as square or sinusoidal pulse shapes.

FIG. 1Eshows a plan view of another example spinal cord stimulator device100of the disclosure, andFIG. 1Fshows a detailed plan view of part of the device100, e.g., serpentine thin film electrode leads.

Embodiments of the device100depicted inFIG. 1Ecan have the same embodiments of implantation paddle105dimensions, polymer layers120,122, electrode stimulation pads and thin film electrode lead dimensions and compositions, thin film connection segment107, encapsulant110and voltage source180, as disclosed in the context ofFIGS. 1A-1D. However, as illustrated inFIG. 1E, embodiments of electrode stimulation pads112a,113acan be circularly shaped (e.g., 50 micron diameter circles having an area of about 2000 microns). In other embodiments, however, the stimulation pads112a,113aof the device depicted inFIG. 1Ehaving rectilinear-shaped pads could be used.

As illustrated inFIG. 1E, in some embodiments of the device100, to facilitate having a narrower width paddle105, the pair of pads112a,113acan be substantially aligned with each other and with a long axis184of the paddle105.

As illustrated inFIG. 1E, to provide greater resistance to shear fracturing, for some embodiments of the device100, the separate thin film electrode leads116a,117athat are separately connected to electrode stimulation pads112a,113acan include a serpentine profile, e.g., the profile in a plane parallel to the major surface186of the paddle105.

For example, as illustrated inFIG. 1F, portions of the thin film electrode leads116a,117acan have a sinusoidal profile. In some embodiments, for example, the pitch188of the sinusoid can equal a value in a range from about 500 to 600 microns and the amplitude190of the sinusoid can equal a value in a range from about 250 to 300 microns. Embodiments of the film electrode leads116a,117acan have the same width148and edge-to-edge separation distance152as disclosed in the context ofFIG. 1C.

Another embodiment of the disclosure is a method of manufacturing a spinal cord stimulator device.FIG. 2presents a flow diagram of an example method200of manufacturing a spinal cord stimulator device such as any of the embodiments of the example devices100disclosed herein, e.g., such as discussed in the context ofFIGS. 1A-1F.

With continuing reference toFIGS. 1A-1E, as illustrated inFIG. 2, the method200can include providing an implantation paddle105(step210). As discussed in the context ofFIGS. 1A-1E, the implantation paddle105can include at least one pair of electrode stimulation pads112a, . . . ,113a, . . . each of the electrode stimulation pads connected to ends115of separate thin film electrode leads116a, . . .117a, . . . and the electrode stimulation pads and the thin film electrode leads sandwiched between softening polymer layers120,122.

In some embodiments, providing the implantation paddle105(step210) can include manufacturing procedures such as described in the experiment section herein. One skilled in the pertinent art would understand how to adapt such procedures to provide any of the embodiments of the paddle105in accordance with step210.

In some embodiments, connecting the ends126of insulated wire leads124a, . . . ,125a, . . . to the contact pads127a, . . .128a, . . . (step220) includes removing the insulation from one end126of the wires, placing the end126into a solder paste located in the openings (e.g., openings192,FIG. 1D) formed in the second softening polymer layer122and then subjecting the device to a solder reflow process to reflow the solder paste and thereby form solder joints130to bond the contact pads and wire leads together.

The method200can further include encompassing portions (e.g., lengths172) of the thin film leads and portions (e.g., length174) of the insulated wire leads124a, . . . ,125a, . . . in the vicinity of the coupling joints130with an encapsulant110(step230).

In some embodiments, encompassing (step230) includes placing one or more droplets of a silicone epoxy polymer in the vicinity of the coupling joints130and allowing the silicone epoxy polymer to cure.

Another embodiment is a method of spinal cord stimulation.FIG. 3presents a flow diagram of an example method of spinal cord stimulation, using any of the example spinal cord stimulator devices100disclosed herein, e.g., such as discussed in the context ofFIGS. 1A-2.

With continuing reference toFIGS. 1A-2, the method300can comprise passing the implantation paddle105of the spinal cord stimulator device100between two vertebrae of a spinal cord (step310).

For example, the paddle105, as well as parts of the connection segment107and the encapsulant110, can be passed between two vertebrae in the cervical spine, the thoracic spine or the lumbar spine, e.g., between two vertebrae at the C3, C4 interspace in the cervical spinal column in order to wrap the paddle around the cervical enlargement on the spinal cord between areas C5 through T1.

The method300can further comprise inserting the implantation paddle105into an epidural or a subdural space between the spinal cord and the vertebra (step320). A long axis184of the implantation paddle105can be aligned with a long dimension of the spinal cord. After implantation, the two softening polymer layers120,122spontaneously soften and wrap around part of a circumference of the spinal cord.

For example, in some embodiments, as part of step320the paddle105can be inserted adjacent to the spinal column above the dura mater, while in other embodiments, the paddle105can be inserted subdurally, to facilitate closer proximity of the stimulation electrode pads to spinal nerves. Inserting the paddle subdurally can include cutting a slit in the dura, and inserting the rigid paddle through the slit under the dura.

Aspects of step320are further illustrated inFIGS. 4A and 4B, which present perspective partial view sketches of an implantation paddle105of the spinal cord stimulator device100of the disclosure: (A) immediately after inserting the implantation paddle105into an epidural or a subdural space between the spinal cord410and the vertebra (vertebra not shown for clarity) and (B) after a period time following implantation, respectively.

As illustrated inFIG. 4A, immediately following implantation a long axis184of the implantation paddle105is aligned with a long dimension420of the spinal cord410(e.g., part of the length of the spinal from the foramen magnum to the upper part of the lumbar region) and the major surface186of the paddle105including layers120,122is still in its original, e.g., planar shape. As illustrated inFIG. 4B, after a period time following implantation (e.g., about 5 hours for some embodiments) the long axis184of the implantation paddle105is still aligned with a long dimension420of the spinal cord410but due to softening of the softening polymer layers120,122the major surface186of the paddle105has wrapped around part of a circumference530of the spinal cord410. E.g., portions440,445of the paddle105lateral to the long axis184have curled to hug and conform to the shape of the spinal cord410.

The method300can further comprise connecting one end (e.g., opposite ends182) of the insulated wire leads124a, . . .125a, . . . to a voltage source180(step330).

For example the encapsulant110and portions of the insulated wire leads124a, . . .125a, . . . can reside in between the two vertebrae and the ends182of the wire leads124a, . . .125a, . . . can reside in an interstitial space of the body, e.g., between the skin and spinal cord, and be connected to an implanted voltage source180, e.g., implantable pulse generator. For example, the ends182of the wire leads124a, . . .125a, . . . can exit the body to connect to an external voltage source e.g., a non-implantable pulse generator (step340).

The method300can further comprise applying a voltage from the voltage source180across the ends (e.g., opposite ends182) of the wire leads124a, . . .125a, . . . to generate an electric field (e.g., field line154) between the pair of electrode pads112a, . . . ,113a, . . . (step350).

For example, as disclosed elsewhere herein, the voltage source180can be configured to apply a series of voltage pulses between the pair of electrode pads.

EXPERIMENTS

To further illustrate various features of the disclosure, various prototype spinal cord simulator devices were manufactured and tested for their ability to be chronically implanted along the spinal cord of rats and to provide reproducible stimulation thresholds or sub-thresholds, as disclosed below.

Manufacture of Implantation Paddles

The monomers of SMP6 were spun onto a sacrificial glass slide and then the monomers were photo cured to form SMP6 (e.g., layer120,FIG. 1C). The SMP6 layer and the sacrificial glass slide were post cured in a vacuum oven for 12 hours at a temperature of 120° C. A layer of gold (e.g., a 300 nm thick layer) was formed by e-beam evaporation onto the layer of post cured SMP6. After the gold deposition, a positive photoresist was spun onto the gold layer. The photoresist was patterned with a photomask to outline thin film electrode leads (e.g., leads116a, . . .117a, . . .FIG. 1B), including contact pads (e.g., pads127a, . . .128a, . . .FIG. 1B) and bases for the electrode stimulation pads (e.g., pads112a, . . . ,113a, . . .FIG. 1B). The positive photoresist was not crosslinked in regions where the thin film electrode leads are to be located through a positive chrome mask (e.g., a serpentine pattern in some embodiments). The chrome mask and the excess crosslinked photoresist were removed, and then the partially constructed paddle was submerged in an etchant (e.g., developer MF-319, Shipley MA) to remove portions of the gold layer that were not covered. The etchant was diluted 10:1 with distilled deionized water such that the paddle soaked in the solution for between 28 and 32 seconds. The paddle was then removed and placed in a flood exposure such that the remaining photoresist was broken down and washed away.

A 250 nm thick layer (e.g., layer140FIG. 1C) of titanium nitride was sputtered onto the partially constructed paddle using a RF magnetron sputtering system from a Ti target, with oxygen and nitrogen ratios in the sputtering chamber controlled to control the ratio of titanium oxy-nitride to titanium nitride, which affects the final charge injection capacity of the device.

A positive photoresist was spun onto the partially constructed paddle and patterned through another chrome mask to define target locations of the electrode stimulation pads. The positive resist was degraded through a mask similar in size and location as the target locations of the electrode stimulation pads. The areas of the device where the TiN layer was to be removed were exposed to a developer (e.g., MF-319, Shipley MA) for 55 seconds during which some of the photoresist was etched back, and, titanium nitride was removed in all areas except where the target electrode stimulation pads were to reside by using a TiN etcher. The remaining photoresist covering the TiN electrodes was removed by placing the partially constructed paddle under 365 nm UV light during a flood exposure and submerging it to a developer.

A second SMP6 layer (e.g., layer122FIG. 1C) was formed by spinning monomers of SMP6 onto the partially constructed paddle and then photocuring and post curing. A hard mask of SiNi was deposited on the second SMP layer and then patterned to form a mask with openings over the electrode stimulation pad and contact pad locations. The device was then exposed to a reaction ion etch to remove overlying portions of the second SMP6 layer to form opening in the second SMP6 layer (e.g., opening192FIG. 1D) and thereby expose the electrode stimulation pads and the contact pads.

Manufacture of Spinal Cord Stimulation Device

The contact pads (e.g., pads127a, . . .128aFIG. 1D) of the paddle (e.g., paddle105,FIG. 1E) were connected to insulated wire leads (e.g.,124a, . . .125a,FIG. 1D) by removing the insulation from one end (e.g., end126FIG. 1A) of the wires and placing the end126into a solder paste located in the openings (e.g., openings192formed in the second SMP6 layer122,FIG. 1D). The insulated wire lead was composed of stainless steel and had a diameter of 114.3 microns (CAT. 790500, A-M Systems, LLC, Carlsborg, Wash.). The solder paste was a lead free indium silver solder paste (e.g., indium:silver equal to about 97:3, from Indium Corporation, Clinton, N.Y.).

The device was then subject to a solder reflow process to reflow the solder paste and thereby form solder joints (e.g., joints130,FIG. 1E) to bond the contact pads and wire leads together.

A silicone epoxy polymer (LOCTITE® M-21HP, Henkel, Rocky Hill, Conn.) was then placed in the vicinity of the solder joints to form the encapsulant (e.g., encapsulant110FIG. 1E).

Prototype Spinal Cord Stimulator Devices and Spinal Cord Implantation

FIGS. 5A-5Cpresent photographs of different prototype spinal cord stimulator devices of the disclosure manufactured as described above. The device shown in5A was constructed to have an about 50 micron thick paddle (e.g., two 25 micron thick softening polymer layers), while the devices ofFIGS. 5A and 5Bwere constructed to have an about 100 micron thick paddles (e.g., two 50 micron thick softening polymer layers).

The devices illustrated inFIGS. 5A and 5Bwere designed to have implantation paddles several times longer than the length target portion of the spinal cord to be stimulated in rat subjects. Thus, portions of these implantation paddles not implanted adjacent to the spinal cord, were extended between two vertebra and past the neck of the rat subjects such that ends of the thin film leads were coupled to connectors (e.g., pins510or leads515, e.g., mounted to a head cap, not shown) which in turn were connected to a voltage source (not shown).

We discovered that prototype devices such as shown inFIG. 5Awere subject to shearing damage, either in the region of the paddle that extended between the vertebra (e.g., region520) and/or in the region of the paddle in the vicinity of the neck (e.g., region525), e.g., due substantial movement in these regions. Prototype devices such as shown inFIG. 5B, with double the thickness of paddle, were more resistant to shearing but still, after a period of time (e.g., days), would also tend to shear in these same regions520,525.

To mitigate against such shearing damage, prototype devices such as shown inFIG. 5Cwere constructed to have a short paddle length which could be fully or near fully implanted in the epidural or subdural space and thus lay fully or near fully parallel to target portion of the spinal cord. The thin film electrode leads in the paddle were connected to the insulated wire leads as described elsewhere herein. While not limiting the disclosure by theoretical considerations, we believe that such wires are not as prone to shearing because they composed of a material, steel, resistant to shearing forces, and because the wires are relatively freer to rotate, bend and twist, e.g., during spinal cord or neck movement, than the devices shown in5A and5B with extended paddle lengths.

Spinal Cord Stimulator Device Implantation and Nerve Stimulation Testing

FIG. 6Ashows a plan view photograph of an example spinal cord stimulator device of the disclosure during implantation under the C2 through C6 vertebra of a rat spinal cord andFIG. 6Bpresents a plan view photograph of the example spinal cord stimulator device depicted inFIG. 6A, prior to implantation.

FIGS. 7A and 7Bpresent axial MRI views of implanted spinal cord stimulator devices of the disclosure that include implantation paddles105having softening polymer layers or parylene-C layers, respectively, three weeks after implantation adjacent to the spinal cords of rats.

As illustrated inFIG. 7A, the width (e.g., width137FIG. 1B) of the paddle105, due to the softening of the softening polymer layers, curved to conform to the natural curvature of the spine, and hugged a portion of the curving circumference430of the spine. In contrast, as shown inFIG. 7B, the implanted paddle105having parylene-C layers, remained planar and did not conform the natural curvature of the spine. Rather, such paddles105, having parylene-C layers, distorted a portion the spine's circumference so as to become flattened and more planar.

FIGS. 8A and 8Bshow post-mortem anterior posterior pictures of portions of rat spinal cord (e.g., spanning a length adjacent to T1 to C3 vertebra) one week post-implantation with dummy paddles (e.g., paddles without electrode stimulation pads or thin film electrode leads) having: (A) softening polymer layers or (B) parylene-C layers. As illustrated, there was more visible tissue damage to spinal cord implanted with the dummy paddles having parylene-C layers as compared to the spinal cord implanted with the dummy paddles having softening polymer layers.

Histopathology conducted on such spinal cord tissue post-implantation showed that GFAP (astrocyte) and ED-1 (macrophage) staining indicated no astrogliosis or macrophage reaction to implantation after 3 weeks with paddles having softening polymer layers.

Experiments were performed to test the function and electrical stability, both intraoperatively and postoperatively, in vivo in rats implanted with prototype devices similar to that depicted inFIG. 5Cusing paddles having softening polymer layers or parylene-C layers.

A laminectomy was performed at C3 and the implantation paddle was inserted into the epidural space to the C5-C6 level. The paddle was not anchored in the epidural space after insertion. Insulated wire leads (e.g., of the connection segment) were run up from the laminectomy through muscle and secured to the top of the rat's skull with dental cement. An A-M Systems Isolated Pulse Stimulator (A-M Systems, Carlsborg, Wash.) was used to stimulate the cervical spinal cord.

As illustrated inFIGS. 9-13Bthe results of these tests demonstrate that the disclosed spinal cord stimulator devices performs safely and reliably as expected in vivo over an extended period of time, and, devices with paddles having softening polymer layers were more sensitive then devices with paddles having parylene-C layers.

FIG. 9presents an example electromyogram of the muscle response from a rat implanted with a spinal cord stimulator device of the disclosure when stimulated above a stimulation threshold in accordance with the disclosure.

FIG. 10shows example the spinal cord stimulation thresholds (“spinal threshold”) to evoke a muscle response measured via electromyography, measured in rats implanted with spinal cord stimulator devices that include implantation paddles having softening polymer layers (“softening electrode”) or parylene-C layers (“parylene-C”), respectively. As illustrated rats implanted with paddles having softening polymer layers required substantial lower threshold than rats implanted with paddles having parylene-C layers.

FIG. 11shows spinal cord stimulation thresholds, generated similar to that described in the context ofFIGS. 9-10, over time for two rat subjects (S1, S2) implanted with spinal cord stimulator devices that include implantation paddles having softening polymer layers. As illustrated, spinal threshold remained substantially constant for several weeks post-implantation. This suggests no or minimal migration of the electrode stimulation pads from their originally implanted locations.

FIG. 12Ashow example changes in the electromyogram measured muscle response (“% change in EMG”), in rats implanted with spinal cord stimulator devices that include implantation paddles having softening polymer layers (“softening electrode”) or parylene-C layers (“parylene-C”), respectively.FIG. 12Bpresents a sketch illustrating aspects of a method of stimulating the spinal cord of rats implanted with spinal cord stimulator devices after paired brain and spinal cord sub-threshold stimulation to evoke the EMG responses such as depicted inFIG. 12A.

As illustrated inFIG. 12Bpaired brain and spinal cord sub-threshold stimulation included sub-threshold stimulation of cortical regions of rat brain that map to forelimb function using conventional cortical electrodes, followed by an about 8 to 12 ms delay (e.g., 10 ms in some embodiments) and then subthreshold stimulation of nerves of the spinal cord using the implanted spinal cord stimulator device. As illustrated inFIG. 12A, much greater evoked muscle responses from such paired sub-threshold stimulation was obtained from rats implanted with paddles having softening polymer layers as compared to rates implanted with paddles having parylene-C layers.

FIG. 13Apresents example changes in the electromyogram measured muscle response (“% change in EMG”), in rats implanted with spinal cord stimulator devices that include stimulating electrode portions having softening polymer layers (“softening electrode”) or parylene-C layers (“paralene-C”), respectively, for different times after paired brain and spinal cord sub-threshold stimulation.FIG. 13Bpresents a sketch illustrating aspects of stimulating the spinal cord of rats implanted with spinal cord stimulator devices with different timing to evoke the EMG responses such as depicted inFIG. 13A.