System and methods for wireless drug delivery on command

• US 10,368,788 B2
• Filed: 07/21/2016
• Issued: 08/06/2019
• 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
• Inventors: Scherer, Axel, Nazari, Meisam Honarvar, Mujeeb-U-Rahman, Muhammad, Sencan, Mehmet, Gaur, Arti
• Primary Examiner(s): Vu, Quynh-Nhu H.
• Application Number:
  US15/216,675
• Publication Number:
  US 20170020416A1
• Time in Patent Office: 1,111 Days
• 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. 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 link;

a monolithically integrated coil on a first surface of the substrate, the monolithically integrated coil configured to provide the wireless communication link; and

a hermetic package comprising at least one chamber that contains a liquid payload, the hermetic package is in its entirety fixated on the first surface of the substrate, a portion of the hermetic package being positioned on the monolithically integrated 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 monolithically integrated 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.

2. The miniaturized implantable device according to claim 1, 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.

3. The miniaturized implantable device according to claim 1, 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 solution.

4. The miniaturized implantable device according to claim 3, wherein the hermetic package comprises one chamber containing a mixture of the electrolyte solution and the liquid payload.

5. The miniaturized implantable device according to claim 3, wherein the hermetic package comprises two separate chambers, a first chamber containing the electrolyte solution and a second chamber containing the liquid payload.

6. The miniaturized implantable device according to claim 1, further comprising a monolithically integrated electrochemical sensor comprising a plurality of electrodes.

7. The miniaturized implantable device of claim 6, further comprising a plurality of wells,

wherein each of the plurality of electrodes is formed in a respective well of the plurality of wells, and

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.

8. The miniaturized implantable device according to claim 7, wherein the depth is in a range of 4 μ

m to 6 μ

m.

9. The miniaturized implantable device according to claim 7, wherein at least one well of the plurality of wells comprises an electrode metal different from a metal of the one or more metal layers.

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

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

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

13. The miniaturized implantable device according to claim 1, 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.

14. The miniaturized implantable device according to claim 1, wherein fabrication of the miniaturized implantable device comprises a CMOS fabrication technology.

15. The miniaturized implantable device according to claim 1, wherein the wireless communication link operates at a frequency band of the industrial, scientific and medical (ISM) radio band.

16. The miniaturized implantable device according to claim 1, wherein the wireless communication link operates at a frequency band used for standard cellular communication.