SYSTEM AND METHODS FOR WIRELESS DRUG DELIVERY ON COMMAND

• US 20170020416A1
• Filed: 07/21/2016
• Published: 01/26/2017
• Est. Priority Date: 07/23/2015
• Status: Active Grant

• Current Assignee: California Institute of Technology, The Trustees of Dartmounth College (Dartmouth College)
• Original Assignee: California Institute of Technology, The Trustees of Dartmounth College (Dartmouth College)
• Inventors: NAZARI, Meisam Honarvar, MUJEEB-U-RAHMAN, Muhammad, SENCAN, Mehmet, GAUR, Arti, SCHERER, Axel
• Granted Patent: US 10,368,788 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61B 17/3468 for implanting or removing devices, e.g. prostheses, implants, seeds, wires devices for implanting seeds A61M37/0069
• CPC Class Codes: A61B 2560/0219 of externally powered implanted units
• CPC Class Codes: A61B 2562/0209 Special features of electrodes classified in A61B5/24, A61B5/25, A61B5/283, A61B5/291, A61B5/296, A61B5/053
• CPC Class Codes: A61B 2562/028 Microscale sensors, e.g. electromechanical sensors [MEMS]
• CPC Class Codes: A61B 2562/04 Arrangements of multiple sensors of the same type
• CPC Class Codes: A61B 2562/125 characterised by the manufacture of electrodes
• CPC Class Codes: A61B 5/0031 Implanted circuitry
• CPC Class Codes: A61B 5/076 Permanent implantations telemetry using implanted circuitry A61B5/0031; implanted stimulators for therapy A61N1/3605, A61N1/362, A61N1/372
• CPC Class Codes: A61B 5/1451 for interstitial fluid
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/1473 invasive, e.g. introduced into the body by a catheter A61B5/1482 takes precedence
• CPC Class Codes: A61B 5/14735 comprising an immobilised reagent
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61B 5/4839 combined with drug delivery
• CPC Class Codes: A61M 2205/3523 using telemetric means
• CPC Class Codes: A61M 2205/8237 Charging means
• CPC Class Codes: A61M 2207/00 Methods of manufacture, assembly or production
• CPC Class Codes: A61M 5/14276 specially adapted for implantation
• CPC Class Codes: A61M 5/172 : electrical or electronic A61M5/16804, A61M5/16831 take precedence
• CPC Class Codes: A61M 5/1723 : using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00

Abstract

A fully integrated small size implantable sensing device is described, which can include a sensor and an electronic circuit to interface with the sensor and communicate with an external device. Various fabrication methods for the sensing device are described, including provision of wells, created using same fabrication technology as the electronic circuit, to contain electrodes of the sensor and corresponding functionalization chemicals. Such implantable sensing device can be used for a variety of electrochemical measuring applications within a living body as well as actuation by injecting a current into the living body.

Claims

1. A method for fabricating a miniaturized implantable device:

fabricating an electronic system by monolithically integrating the electronic system on a first face of a substrate, the electronic system comprising an energy storage element adapted to be charged through a wireless communication link;

fabricating a coil by monolithically integrating the coil on the first face of the substrate, the coil being configured to provide the wireless communication link; and

fixating at least one hermetic package, containing a liquid payload, on the first surface of the substrate, a portion of the hermetic package being positioned above the coil,

wherein the energy storage element is configured to provide energy to rupture a seal of the hermetic package, thereby dispensing the liquid payload.

2. The method according to claim 1, wherein the rupture of the seal is provided by applying heat to the seal.

3. The method according to claim 2, wherein the heat is provided by injecting current in the coil, the current provided by the energy storage element.

4. The method according the claim 1, wherein the rupture of the seal is provided by applying internal pressure to the hermetic package.

5. The method according to claim 4, wherein the internal pressure is provided by gases released through an electrochemical dissociation reaction of an electrolyte solution contained in the hermetic package, energy for the electrochemical dissociation being provided by the energy storage element.

6. The method according to claim 5, wherein the hermetic package comprises one chamber containing a mixture of the electrolyte solution and the liquid payload.

7. The method according to claim 5, wherein the hermetic package comprises two separate chambers, a first chamber containing the electrolyte solution and a second chamber containing the liquid payload.

8. The method according to claim 1, further comprising:

fabricating a plurality of electrodes of an electrochemical sensor by monolithically integrating the plurality of electrodes on the first face of the substrate, the plurality of electrodes being configured to provide electrical interface between the electrochemical sensor of the implantable device and the electronic system.

9. The method according to claim 8, wherein the fabricating the plurality of electrodes further comprises fabricating the plurality of electrodes on a first metal layer separate from metal layers used to fabricate the electronic system.

10. The method according to claim 8, wherein the fabricating the plurality of electrodes further comprises creating a plurality of wells in correspondence of the plurality of electrodes.

11. The method according to claim 1, wherein the energy storage element is a bank of capacitors charged through power extracted from the wireless communication link.

12. The method according to claim 1, wherein the fabricating of the coil comprises fabricating a plurality of concentric patterns on a first metal layer separate from metal layers used to fabricate the electronic system.

13. A method for wireless drug delivery on command, the method comprising:

providing a miniaturized implantable device fabricated using the method of claim 1, the liquid payload of the miniaturized implantable device comprising a drug to be delivered;

injecting the miniaturized implantable device in the mammal; and

based on the injecting, completely embedding the miniaturized implantable device within tissue of the mammal.

14. The method according to claim 13, wherein the injecting is performed using an appropriate gauge needle or an appropriate gauge trocar.

15. The method according to claim 13, further comprising:

powering the implantable device via an external coil inductively coupled to the implantable device;

based on the powering, charging the energy storage element of the electronic system of the implantable device; and

based on the charging, actuating rupture of the seal of the hermetic package of the implantable device; and

based on the actuating, delivering the drug to the tissue of the mammal.

16. An integrated miniaturized implantable device comprising:

a substrate for monolithic integration comprising a plurality of metal layers separated via a plurality of insulating layers;

a monolithically integrated electronic system comprising an energy storage element adapted to be charged through a wireless communication;

a monolithically integrated coil configured to provide the wireless communication link; and

a hermetic package, containing a liquid payload, fixated on the substrate, a portion of the hermetic package being positioned above the coil,

wherein during operation of the implantable device, the electronic system is configured to;

communicate with an external device over the wireless communication link provided by the coil,

extract power for the miniaturized implantable device from the wireless communication link,

charge the energy storage element based on the extracted power, and

energize an actuator via the energy storage element to rupture a seal of the hermetic package.

17. The miniaturized implantable device according to claim 16, wherein the actuator is the monolithically integrated coil energized by current injected from the energy storage element to provide heat to the seal for rupturing of the seal.

18. The miniaturized implantable device according to claim 16, wherein the actuator is an electrolyte solution contained in the hermetic package energized by current from the energy storage element to provide internal pressure for rupturing of the seal via gas released from an electrochemical dissociation reaction of the electrolyte.

19. The miniaturized implantable device according to claim 18, wherein the hermetic package comprises one chamber containing a mixture of the electrolyte solution and the liquid payload.

20. The miniaturized implantable device according to claim 18, wherein the hermetic package comprises two separate chambers, a first chamber containing the electrolyte solution and a second chamber containing the liquid payload.

21. The miniaturized implantable device according to claim 16, further comprising a monolithically integrated electrochemical sensor comprising a plurality of electrodes.

22. The miniaturized implantable device of claim 21, further comprising a plurality of wells in correspondence of the plurality of electrodes, wherein a depth of a well of the plurality of wells extends across one or more metal layers of the plurality of metal layers and/or one or more insulating layers of the plurality of insulating layers.

23. The miniaturized implantable device according to claim 22, wherein the depth is in a range of 4 μ

m to 6 μ

m.

24. The miniaturized implantable device according to claim 22, wherein the well comprises an electrode metal different from a metal of the one or more metal layers.

25. The miniaturized implantable device according to claim 16, wherein the energy storage element is a bank of capacitors charged through power extracted from the wireless communication link.

26. The miniaturized implantable device according to claim 16, wherein a larger side of the miniaturized implantable device is not larger than 1 mm.

27. The miniaturized implantable device according to claim 16, wherein a capacity of the hermetic package is about 1 microliter of liquid payload.

28. The miniaturized implantable device according to claim 16, wherein the coil comprises a plurality of concentric patterns fabricated on a first metal layer separate from metal layers used to fabricate the electronic system.

29. The miniaturized implantable device according to claim 16, wherein fabrication of the miniaturized implantable device comprises a CMOS fabrication technology.

30. The miniaturized implantable device according to claim 16, wherein the wireless communication link operates at a frequency band of the industrial, scientific and medical (ISM) radio band.

31. The miniaturized implantable device according to claim 16, wherein the wireless communication link operates at a frequency band used for standard cellular communication.