# US 10,368,788 B2 · System and methods for wireless drug delivery on command

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- Number: US 10,368,788 B2
- Document ID: US10368788B2
- Status: Granted
- Kind: B2
- Application number: 15/216,675
- Filed: 2016-07-21
- Published: 2017-01-26
- Granted: 2019-08-06
- Earliest claimed: 2015-07-23
- Assignees: California Institute of Technology; Trustees of Dartmouth College
- Applicants: California Institute of Technology; The Trustees of Dartmouth College
- Inventors: Axel Scherer; Meisam Honarvar Nazari; Muhammad Mujeeb-U-Rahman; Mehmet Sencan; Arti Gaur
- Web page: https://patentgrep.com/patent/US10368788B2

## CPC

- A61B 5/1473: invasive, e.g. introduced into the body by a catheter
- A61B 5/0031: {Implanted circuitry}
- A61B 5/076: {Permanent implantation}
- A61B 5/1451: {for interstitial fluid}
- A61B 5/14532: {for measuring glucose, e.g. by tissue impedance measurement}
- A61B 5/1459: invasive, e.g. introduced into the body by a catheter
- A61B 5/14865: {invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors}
- A61B 5/4839: {combined with drug delivery}
- A61B 17/3468: {for implanting or removing devices, e.g. prostheses, implants, seeds, wires (devices for implanting seeds A61M37/0069)}
- A61M 5/14276: {specially adapted for implantation}
- A61M 5/172: electrical or electronic
- A61M 5/1723: {using feedback of body parameters, e.g. blood sugar or pressure}
- A61B 5/14546: {for measuring analytes not otherwise provided for, e.g. ions, cytochromes}
- A61B 5/14735: {comprising an immobilised reagent}
- A61B 2560/0219: of externally powered implanted units
- A61B 2562/0209: Special features of electrodes classified in A61B5/24, A61B5/25, A61B5/283, A61B5/291, A61B5/296, A61B5/053
- A61B 2562/028: Microscale sensors, e.g. electromechanical sensors [MEMS]
- A61B 2562/04: Arrangements of multiple sensors of the same type
- A61B 2562/125: characterised by the manufacture of electrodes
- A61M 2205/3523: using telemetric means
- A61M 2205/8237: Charging means
- A61M 2207/00: Methods of manufacture, assembly or production
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}

## 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

### Claim 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.

### Claim 2 (depends on 1)

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.

### Claim 3 (depends on 1)

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.

### Claim 4 (depends on 3)

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.

### Claim 5 (depends on 3)

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.

### Claim 6 (depends on 1)

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

### Claim 7 (depends on 6)

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.

### Claim 8 (depends on 7)

The miniaturized implantable device according to claim 7, wherein the depth is in a range of 4 μm to 6 μm.

### Claim 9 (depends on 7)

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.

### Claim 10 (depends on 1)

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.

### Claim 11 (depends on 1)

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

### Claim 12 (depends on 1)

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

### Claim 13 (depends on 1)

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.

### Claim 14 (depends on 1)

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

### Claim 15 (depends on 1)

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.

### Claim 16 (depends on 1)

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