This disclosure relates generally to devices, systems, and methods for magnetic stimulation of neurons.
Neuromodulation is an evolving therapy that can involve various types of electromagnetic stimuli including the application of a strong magnetic field or a small electric current to nerve structures.
Some embodiments are directed to an implantable magnetic neurostimulation probe. The magnetic neurostimulation probe includes at least one electrical conductor disposed on at least one substrate and arranged in at least one planar loop. At least one planar magnetic core comprising a magnetic material is disposed on the substrate and within the planar loop. A biocompatible coating is disposed over the substrate, the electrically conductive trace, and the magnetic core.
In accordance with some embodiments, a method involves applying an electrical current of about 10 mA to 60 mA to a magnetic probe having least one electrical conductor. The electrical conductor is disposed on the substrate and is arranged as at least one planar loop. At least one magnetic core comprising a magnetic material is disposed on the substrate and within the planar loop. In response to the applied electrical current, the magnetic probe produces an excitation volume having a boundary with a radius of about 50 μm such that an electric field gradient generated by the magnetic probe is greater than 11000 V/m2 within the boundary and is less than 11000 V/m2 at and beyond the boundary.
Some embodiments are directed to a system that comprises an implantable magnetic neurostimulation probe and an energizer electrically coupled to the probe. The implantable magnetic neurostimulation includes at least one substrate; at least one electrical conductor disposed on the substrate and arranged as at least one planar loop; at least one planar magnetic core comprising a magnetic material disposed on the substrate and within the planar loop; and a biocompatible coating is disposed over the substrate, coil, and magnetic core. The energizer is configured to apply the electrical current through the electrical conductor.
In accordance with some embodiments and magnetic probe includes at least one electrical conductor disposed on a substrate and arranged as at least one planar loop. At least one planar magnetic core comprising a magnetic material is disposed on the substrate and within the planar loop. When energized by an electric current through the loop, the probe is configured to produce an excitation volume having an boundary with a radius of about 50 μm such that at an electric field gradient generated by the probe is greater than 11000 V/m2 within the boundary and is less than 11000 V/m2 at and beyond the boundary.
The figures are not necessarily to scale. Like numbers used in the figures refer to like components. However, it will be understood that the use of a number to refer to a component in a given figure is not intended to limit the component in another figure labeled with the same number.
Neural stimulation has the potential to treat a large number of neurological disorders. However, it can be challenging to provide effective stimulation that activates the targeted neurons without concurrently activating nearby neurons that are not targeted. Unintentional activation of non-targeted neurons leads to the spread of activation beyond the target area with undesirable or unknown results.
When magnetically stimulated, neurons are activated by the spatial gradient of the electric field produced by an energized a magnetic coil. Magnetic coils suitable for neurostimulation can produce an electric field gradient that is sufficient to activate neurons, e.g., about 11000 V/m2, within an activation volume which extends outwardly in three dimensions from the location of the magnetic coil. The activation volume has a radius that defines the activation boundary of the spatial gradient of the electric field. The spatial gradient of the electric field is sufficient to activate neurons within the activation volume but is insufficient to activate neurons at the boundary or outside the boundary of the activation volume.
Magnetic stimulation of neurons using implanted magnetic probes potentially has several advantages when compared to conventional electrical stimulation of neurons. The electric fields generated by implanted micro coils can be spatially asymmetrical and therefore may be more amenable to selective activation of targeted neurons than neurostimulation using conventional neuroelectrical stimulation. Furthermore, in comparison to conventional neural stimulation by electrical probes, magnetic fields more readily pass through biologic materials without substantial attenuation. Magnetic stimulation coils do not need to be placed in direct contact with the targeted neurons and can be encapsulated in biocompatible materials.
Embodiments disclosed herein involve magnetic probes suitable for use in neural stimulation as well as other implementations. The magnetic probes incorporate micro coils which can have any suitable shape or configuration, e.g., planar or three dimensional (3D) coils. In some embodiments, the magnetic probes incorporate micro coils in the form of planar loops disposed on a substrate with high magnetic permeability cores disposed at least partially within the loops. The magnetic cores allow the planar loops to be energized by low currents that produce high electric field gradients which do not extend beyond relatively small activation volumes. The smaller activation volumes produced by the disclosed magnetic probes are useful to selectively target specific locations without affecting or minimally affecting other locations. For example, when the disclosed magnetic probes are used for magnetic neural stimulation, the activation volumes allow for activation of targeted neurons without activation of nearby non-targeted neurons. According to various implementations, the disclosed magnetic probes can produce electric field gradients greater than 1.1×104 V/m2 within the activation volume, thus providing a spatial electric field gradient that is sufficient for the stimulation of biological nerves. These electric field gradients can be produced using an energizing current through the micro coil on the order of about 50 mA at a voltage of about 1 V.
The substrate 110 may be flat and/or rigid and may comprise materials such as silicon, germanium, sapphire, quartz and/or fused silica, among other materials. According to some implementations, the electrical conductor 120 can be an electrically conductive trace deposited onto the substrate 110. The electrical conductor 120 can comprise various metals, including gold, silver, copper, aluminum, nickel, platinum and/or alloys thereof, for example. The magnetic core 130 may have magnetization change per cm3 mol−1 in a range of about 10 to 2000 G, for example. Suitable materials for the magnetic core 130 include ferromagnetic materials, including iron, cobalt, nickel, and/or alloys thereof. In additional examples, some ceramics, such as yttrium-based ceramics could be used. The substrate 110, electrical conductor 120, and magnetic core 130 may be at least partially or fully encapsulated by an encapsulant 140, e.g., a hermetic encapsulant and/or a biocompatible encapsulant. Suitable encapsulants include polyimide or silicon oxynitride (SiONx).
The magnetic probe 100 may have an overall length, Lp, in a range of about 2 mm to 5 mm, an overall width, Wp, in a range of 50 μm to 200 μm, and an overall probe thickness, Tp, (which includes the thickness of the substrate, electrical conductor, magnetic core, and encapsulant) in a range of about 55 μm to about 510 μm.
The substrate 110 can have a thickness, Ts, in a range of about 25 μm to 500 μm. The electrical conductor 120 may have a width, Wc, in a range of about 1 μm to about 20 μm and a thickness, Tc, in a range of about 1 μm to about 10 μm. The electrical conductor 120 that forms the loop can have an overall length, Lc, between about 5 mm and about 20 mm.
The loop 121 may be rectangular, as shown in
The magnetic core 130 may have a generally rectangular shape as depicted in
In some embodiments, the loop may have a more complex shape than the simple loop illustrated in
According to some embodiments, multiple magnetic cores may be disposed within a single loop of the electrical conductor, as illustrated in
The magnetic cores 231, 232, 233 are disposed within respective sections 221-1, 221-2, 221-3 of the magnetic loop 221. Magnetic core 231 is disposed within loop section 221-1; magnetic core 232 is disposed within loop section 221-2; and magnetic core 233 is disposed within loop section 221-3.
The magnetic probe 200 may have an overall length, in a range of about 2 mm to 5 mm, an overall width in a range of 50 μm to 200 μm, and a thickness in a range of about 2 μm to 10 μm. For example, the substrate 210 can have a thickness in a range of about 25 μm to 500 μm.
The electrical conductor 220 may have a width in a range of about 1 μm to 20 μm and a thickness in a range of about 1 μm to about 10 μm. The first loop section 221-1 may have a maximum length, L11, between about 2 mm and 5 mm and a maximum width, W11, between about 30 μm and 150 μm.
According to some embodiments, the second loop section, 221-2, may have a length, L12 that is about 50 to 75% of the length, L11, of the first loop section 221-1. The third loop section, 221-3, may have a length, L13 that is about 50 to 75% of the length, L12, of the second loop section 221-2. The widths, W11, W12, W13 of the first, second and third loop sections 221-1, 221-2, 221-3 can be about the same in some embodiments.
By virtue of the step-like pattern in the sawtooth profile, the different locations of the terminated tips 251a, 252a, 253a of the loop 221 give control over the transverse field gradient (in the x-y plane) depending upon the insertion into the biological tissue. The sawtooth shape shown in
In
A magnetic probe may include multiple magnetic cores disposed within multiple planar loops. In some embodiments, the multiple loops may be formed using a single electrically continuous electrical conductor, e.g., arranged in a spiral comprising multiple concentric loops. In some embodiments, the loops may be formed using multiple separate electrical conductors, e.g., multiple electrically separate concentric loops.
An example of a magnetic probe 300 having multiple concentric cores 332, 333, 334, 335 and multiple loops 351, 352, 353, 354, 355 is provided in
The magnetic probe 300 may have an overall length, in a range of about 2 mm to 5 mm, an overall width in a range of 50 μm to 200 μm, and an overall thickness (including the substrate, electrical conductor, core, and encapsulant) in a range of about 51 μm to about 501 The electrical conductors of loops 351-355 may have a width in a range of about 1 μm to 20 μm and a thickness in a range of about 1 μm to about 10 μm.
Loop 351 may have a maximum length, L11 between about 2 mm and 5 mm and a maximum width, W11, between about 30 μm and 150 μm.
According to some embodiments, the second loop, 352 may have a length that is about 75 to 90% of the length of the length of the first loop 351; loop 353 may have a length that is about 50 to 75% % of the length of the loop 352; loop 354 may have a length that is about 50 to 75% % of the length of loop 353; and loop 355 may have a length that is about 50 to 75% % of the length of loop. In some embodiments, the surface area of some of the cores can be the same, e.g., cores 332, 333, 334 in
In the configuration shown in
According to some embodiments, a magnetic probe can include multiple electrically non-continuous loops as illustrated by
The loops 451a, 452a, 453a may differ in geometry, e.g., as shown in
Magnetic core 431a is at least partially enclosed by loop 451a; magnetic core 432a is at least partially enclosed by loop 452a; and magnetic core 433a is at least partially enclosed by loop 453a. In the magnetic probe 400a, each core 431a, 432a, 433a is enclosed by only one of the loops 421a, 422a, 423a. As previously discussed, the geometry, surface area, shape, material, thickness, etc. of the magnetic cores may vary from core to core in some embodiments, Alternatively, at least some of these characteristics may not vary from core to core.
As illustrated in
Substrate, 411b, loop 451b, and core 431b form a first portion 461 of the magnetic probe 400b; substrate, 412b, loop 452b, and core 432b form a second portion 462 of the magnetic probe 400b; and substrate, 413b, loop 453b, and core 433b form a third portion 463 of the magnetic probe 400b. An encapsulant 440 can be disposed over each of the first, second, and third portions 461, 462, 463.
According to some embodiments, each of the first, second, and third portions 461, 462, 463 may comprise a single core within a single loop as described in connection with
In the technical application shown in
This design of the disclosed magnetic probe enables excitation at different locations within the spatial boundaries of a structure depending on the amplitude of the current injection in the loops.
The direct way to obtain a larger electric field gradient is to use a larger AC current excitation. However, one of the consequences of simply increasing the current in the micro coils is that the volume of excitation also increases. For example, increasing currents through a 10 μm wide Cu loop from 1 mA to 100 mA, generates an increase in a volume of excitation with radius >150 This can lead to stimulation of non-targeted regions. However, a micro-coil geometry with high permeability cores can still maintain a small excitation volume (within a radius of about 50 μm) with about 50 mA currents at electric field gradients of greater than 11000 V/m2 or even about 107 V/m2.
In the example illustrated in
Simulations were also performed for the multiple loop neural probe shown in
The width of the magnetic probe in this simulated example is 200 The magnetic probe 300 includes five electrically isolated concentric loops 351-355 having five different total lengths. The loops 351-355 at least partially enclose a different number of cores 332-335, from one core to four cores. The width of the loops 351-355 can be modified to obtain different decay depths away from the coils 332-335 of the electric field gradient at or above the gradient threshold value of 11000 V/m2. The edges of the loops are regions where there is a strong discontinuity in the dielectric constant of the materials across the interface. A wider loop spreads the field lines more than a narrower loop. However a narrower loop would also increase the resistance. Therefore an interplay between the current requirements and the field-narrowing requirements can be used to ascertain a loop width suitable for a particular application.
In this example, as shown in
The reason for such high electric-field gradients can be understood by considering that this design is similar to a 2D solenoid with a high permeability core. With the “length” of the solenoid approaching a very small number (2 μm in this case, or the corresponding thickness of the trace), when the number of loops around the core is increased which is similar to increasing the number of turns in the solenoid. From Ampere's Law and the functioning of a solenoid, it is known that the magnetic field strengths that can be generated are inversely proportional to the length of the solenoid and directly proportional to the number of turns in the solenoid. More precisely, the solenoid formula can be written as
B=μ0μrnI (Equation 1)
In Equation 1, μ0 is the magnetic permeability of free space and μr is the relative permeability of a ferrite core. In Equation 1, n is the number of turns per unit length of the solenoid and I is the current through the solenoid. Thus relatively large magnetic fields can be achieved which, when modulated via the modulation of the AC current, yields large electric field gradients as observed in the simulations. It can also be concluded from Equation 1 that the magnetic field created on-axis for a 2D current loop is as follows:
In Equation 2, z is the distance along the axis away from the coil, R is the radius of the coil, I is the current and N is the number of loops. At a given distance and for a given radius, the magnetic field can be increased by increasing the number of loops.
In
In general, the electric current through the loop formed by the electrical conductor 1120 may be less than about 500 mA, or less than 250 mA, or less than 100 mA, or less than 50 mA or even less than about 25 ma to obtain the electric field gradients discussed herein. When energized by an electric current in a range of about 25 mA to about 500 mA, e.g., a current of about 25 mA, 50 mA, about 100 mA, about 200 mA, or about 500 mA through the loop, the probe is configured to produce a spatial electric field gradient between about 104 V/m2 to about 107 V/m2 within a volume around the probe. The volume may have a radius less than 150 μm to less than about 25 for example. For example, the probe may produce an electric field gradient greater than 104 V/m2 inside the volume and a spatial electric field gradient less than 104 V/m2 at and beyond the boundary of the volume. In another example, the probe may produce a spatial electric field gradient greater than 105 V/m2 inside the volume and a spatial electric field gradient less than 105 V/m2 at and beyond the boundary of the volume. In another example, the probe may produce a spatial electric field gradient greater than 106 V/m2 inside the volume and a spatial electric field gradient less than 106 V/m2 outside the volume. In yet another example, the probe may produce a spatial electric field gradient greater than 107 V/m2 inside the volume and a spatial electric field gradient less than 107 V/m2 at and beyond the boundary of the volume. When compared to a substantially similar probe that does not include the at least one magnetic core, for the same energizing current and the same electric field gradient, the volume may be reduced by at least a few percent to about 60%.
As previously discussed, the magnetic probe disclosed herein finds application as a neural stimulation probe.
By using high permeability cores, the volume of activation can be confined above the threshold value for neural stimulation of 11000 V/m2. For example, for the same current values of 15 mA, simulations demonstrate a reduction of the radius of activation by up to 3 fold. This will thus permit driving larger currents into the loops and thus obtain larger electric field gradients, while not compromising on the selectivity of the excitation volume.
Extending the concept of a 3D solenoid or the 2D current loop to the 2D plane, multi-loop and multi-core magnetic probes have been designed that increase the electric field gradients produced by the probe. These designs can restrict activation depth of the probe by about 3 times when compared to probes without the cores for the same currents driven.
The foregoing description of various embodiments has been presented for the purposes of illustration and description and not limitation. The embodiments disclosed are not intended to be exhaustive or to limit the possible implementations to the embodiments disclosed. Many modifications and variations are possible in light of the above teaching.
This application is a divisional of U.S. Ser. No. 15/922,693, filed Mar. 15, 2018, which is incorporated herein by reference in its entirety.
This invention was made with Government support under government contract number 1U01NS099700-01 awarded by the NIH. The Government has certain rights in this invention.
Number | Date | Country | |
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Parent | 15922693 | Mar 2018 | US |
Child | 17400578 | US |