Architectures and methods for electrochemical neuromodulation
A prosthetic device includes a closed loop system for maintaining a predetermined concentration of a target ion in a region in proximity to a cell, such as a nerve cell. The device includes a controller and an ion-selective electrode assembly operatively connected to the controller, wherein the ion-selective electrode configuration is configured to sense the concentration of the target ion by potentiometric measurement and to convey the concentration to the controller. The controller is configured to modulate the current to the ion-selective electrode assembly based on the concentration of the target ion to control the concentration of the target ion so as to maintain the predetermined concentration of the target ion.
1 . A prosthetic device comprising a closed loop system for maintaining a predetermined concentration of a target ion in a region in proximity to a cell, the device comprising:
a controller; and
an ion-selective electrode assembly operatively connected to the controller, wherein the ion-selective electrode assembly is configured to sense the concentration of the target ion by potentiometric measurement and to convey the concentration to the controller, wherein
the controller is configured to repeat a sequence of using the ion-selective electrode assembly to (a) sense the concentration of the target ion and (b) modulate application of current to the ion-selective electrode assembly based on the sensed concentration of the target ion to control the concentration of the target ion so as to maintain the predetermined concentration of the target ion in the closed-loop system, wherein the controller is further configured to operate a feedback system including the ion-selective electrode assembly that both senses, via potentiometric measurement, and modulates, via applied electric field, the concentration of the target ion by repeatedly: (i) shutting off the current during short intervals to take a potentiometric measurement of the target ion concentration, and (ii) determining, using a mathematical model updated based on the measured target ion concentration, the magnitude of electric field to apply to maintain the predetermined concentration of the target ion and applying the electric field of the determined magnitude through the ion-selective electrode assembly.
2 . The prosthetic device of claim 1 , wherein the ion-selective electrode assembly comprises:
a first ion-selective electrode that is configured to sense the concentration of the target ion; and
a second ion-selective electrode that is configured to control the concentration of the target ion via the modulation of the current by the controller.
3 . The prosthetic device of claim 1 , wherein the ion-selective electrode assembly comprises a single ion-selective electrode configured both (a) to sense the concentration of the target ion and (b) to control the concentration of the target ion via the modulation of the current by the controller.
4 . The prosthetic device of claim 1 , further comprising a power source configured to supply a voltage to the ion-selective electrode assembly.
5 . The prosthetic device of claim 4 , wherein the power source is configured to supply DC electrical current to the ion-selective electrode assembly.
6 . The prosthetic device of claim 4 , wherein the ion-selective electrode assembly is implanted in a subject sufficiently close to a nerve in the subject to change the concentration of ions at the nerve when voltage from the power source is delivered to the ion-selective electrode assembly.
7 . The prosthetic device of claim 1 , wherein the ion-selective electrode assembly comprises an electrode core coated with an ion-selective membrane, wherein the composition of the ion-selective membrane is tailored such that the membrane loses transfer selectivity at the predetermined concentration, thereby maintaining the predetermined concentration of the target ion.
8 . The prosthetic device of claim 7 , wherein the target ion is Ca 2+ and the ion-selective membrane is a Ca 2+ -selective membrane.
9 . The prosthetic device of claim 7 , wherein the target ion is Na + and the ion-selective membrane is a Na + -selective membrane.
10 . The prosthetic device of claim 7 , wherein the target ion is K + and the ion-selective membrane is a K + -selective membrane.
11 . The prosthetic device of claim 7 , wherein the electrode core is less than 1 mm in diameter.
12 . The prosthetic device of claim 1 , wherein the ion-selective electrode assembly is deposited on a flexible biocompatible substrate.
13 . The prosthetic device of claim 1 , wherein the prosthetic device is sized to enclose a nerve.
14 . The prosthetic device of claim 1 , wherein the ion-selective electrode assembly comprises a porous electrode layer sandwiched between a first and second membrane wherein the first membrane is an electrochemical diode and the second membrane is selected from an electrochemical diode and an ion-selective membrane (ISM) operably connectable to a power supply.
15 . The prosthetic device of claim 14 , wherein the electrochemical diode is a bipolar ion-exchange membrane.
16 . The prosthetic device of claim 14 , wherein the prosthetic device is further configured for electrochemical rectification.
17 . A method of modulating neural activity in a subject in need thereof, comprising:
implanting the ion-selective electrode assembly of the prosthetic device of claim 1 sufficiently proximate to a nerve cell in a subject to deliver electrical current to the nerve cell;
applying an electrical current through the ion-selective electrode assembly to deliver that electrical current to the nerve cell; and
repeatedly (i) shutting off the current during short intervals to take potentiometric measurements of the target ion concentration using the ion-selective electrode assembly, and (ii) determining, using the mathematical model updated based on the measured concentration, the magnitude of electric field to apply to maintain the predetermined concentration of the target ion, and issuing a command to apply the electric field of the determined magnitude through the ion-selective electrode assembly in the closed-loop system.
18 . The method of claim 17 , wherein the ion-selective electrode assembly comprises an electrode core coated with an ion-selective membrane, wherein the composition of the ion-selective membrane is tailored such that the membrane loses transfer selectivity at the predetermined concentration, thereby maintaining the predetermined concentration of the target ion.
19 . The method of claim 18 , wherein the electrical current delivered to the nerve cell is less than 1 uA.
20 . The method of claim 18 , wherein the electric field applied to the ion-selective electrode assembly is less than 2V.
21 . The method of claim 18 , wherein the subject is in need of treatment of a neurological disease or condition.
22 . The method of claim 21 , wherein the neurological disease or condition is selected from the group consisting of epilepsy, chronic pain, Parkinson's disease and other movement disorders.
23 . The method of claim 21 , wherein the neurological condition is a neuropathic pain disorder.
24 . The method of claim 23 , wherein the neuropathic pain disorder is Trigeminal Neuralgia.
25 . The method of claim 21 , wherein the modulation is selected from stimulation or inhibition of nerve signal propagation.
26 . The method of claim 18 , wherein the ion-selective membrane offers single-ion selectivity, passing the target ion while blocking all other ions, and wherein the target ion is Ca 2+ , Na + , or K + .
27 . The method of claim 26 , wherein the ion-selective membrane separates the target ion from other ions of identical charge.
28 . The method of claim 17 , wherein the prosthetic device is in the form of a cuff, and wherein the cuff is wrapped around the nerve cell in vivo.