IMPLANTABLE AND BIORESORBABLE SENSORS

• US 20170020402A1
• Filed: 05/04/2016
• Published: 01/26/2017
• Est. Priority Date: 05/04/2015
• Status: Abandoned Application

• Current Assignee: Board of Trustees of The University of Illinois, Washington University In St Louis
• Original Assignee: Board of Trustees of The University of Illinois, Washington University In St Louis
• Inventors: MURPHY, Rory KJ, KANG, Seung Kyun, LEE, Seung Min, RAY, Wilson Z., ROGERS, John A., HARBURG, Daniel Vincent
• Application Number:
  US15/146,629
• Publication Number:
  US 20170020402A1
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61B 2503/40 Animals
• CPC Class Codes: A61B 2503/42 for laboratory research
• CPC Class Codes: A61B 2560/0219 of externally powered implanted units
• CPC Class Codes: A61B 2560/0223 of calibration, e.g. protocols for calibrating sensors
• CPC Class Codes: A61B 2562/0261 Strain gauges
• CPC Class Codes: A61B 2562/125 characterised by the manufacture of electrodes
• CPC Class Codes: A61B 5/0028 Body tissue as transmission medium, i.e. transmission systems where the medium is the human body
• CPC Class Codes: A61B 5/0031 Implanted circuitry
• CPC Class Codes: A61B 5/02055 Simultaneously evaluating both cardiovascular condition and temperature
• CPC Class Codes: A61B 5/031 Intracranial pressure
• CPC Class Codes: A61B 5/11 Measuring movement of the entire body or parts thereof, e.g. head or hand tremor, mobility of a limb for measuring pulse A61B5/02 ;A61B5/1038 takes precedence; motion detection to correct for motion artifacts in physiological signals A61B5/721
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14539 for measuring pH
• CPC Class Codes: A61B 5/14542 for measuring blood gases A61B5/14551 takes precedence

Abstract

Provided herein are implantable and bioresorbable sensors that are specifically designed to be implanted, function for an operational lifetime, and at some point after the operational lifetime to be resorbed by the body in such a manner so as to avoid having to remove any part of the sensor. This avoids a second impact on the patient otherwise associated with sensor removal. The sensors have a substrate and an electronic device supported by the substrate. A barrier layer isolates the electronic device from surrounding environment, including a biofluid, during use. Each of the substrate, electronic device, and barrier layer have a bioresorption rate during use to provide controlled bioresorption such reliable measure of one or more parameters occur over and an operational lifetime, and after a bioresorption lifetime greater than the operational lifetime, no detectable portion of the implantable and bioresorbable sensor remains at an implantation site.

Claims

1. An implantable and bioresorbable sensor comprising:

a substrate;

an electronic device supported by the substrate, wherein the electronic device comprises a semiconductor or metallic component;

a barrier layer that isolates the electronic device from a surrounding environment during use; and

wherein each of the substrate, electronic device, and barrier layer have a bioresorption rate during use to provide controlled bioresorption of the implantable and bioresorbable sensor, configured so that the implantable and bioresorbable sensor operates for an operational lifetime and has a bioresorption lifetime that is greater than the operational lifetime, and no detectable portion of the implantable and bioresorbable sensor remains at an implantation site after the bioresorption lifetime.

2. The implantable and bioresorbable sensor of claim 1, wherein the barrier layer fluidically, electrically and chemically isolates the electronic device from a surrounding fluid during use.

4. The implantable and bioresorbable sensor of claim 1, wherein the semiconductor or metallic component has a thickness less than or equal to 10 μ

m.

5. The implantable and bioresorbable sensor of claim 1, wherein the electronic device comprises a sensor selected from the group consisting of:

a pressure sensor;

a temperature sensor;

a motion sensor;

a flow sensor;

a thermal conductivity sensor;

a diffusivity sensor;

a pH sensor;

an electrical sensor;

an optical sensor;

a glucose sensor, oxygen sensor and a biomolecule sensor.

6. The implantable and bioresorbable sensor of claim 1 that is multi-functional, with the electronic device comprising a first electronic device that senses a first physical parameter and a second electronic device that senses a second physical parameter, wherein the physical parameters are selected from the group consisting of pressure, temperature, acceleration, electric potential, impedance, fluid flow-rate, thermal conductivity, pH, glucose level, oxygen level, and biomolecule detection.

7. The implantable and bioresorbable sensor of claim 1, wherein the electronic device comprises a pressure sensor, the pressure sensor comprising:

a cavity disposed in the substrate;

a deformable layer supported by the substrate and that covers the cavity; and

a strain gauge supported by the deformable layer and adjacent to the cavity, wherein deflection of the deformable layer by a pressure in a fluid surrounding the deformable layer and strain gauge generates an electrical output from the pressure sensor strain gauge that depends on the fluid pressure.

8. The implantable and bioresorbable sensor of claim 7, wherein the strain gauge is made from a material selected from the group consisting of:

a Si-nanomembrane;

a polycrystalline Si;

germanium;

silicon-germanium; and

a metal or alloy thereof.

12. The implantable and bioresorbable sensor of claim 7, wherein the stain gauge comprises a Si-nanomembrane with a distal piezoresistive end having a serpentine geometry and a cavity volume that is greater than 0.1 mm³ and less than 2 mm³.

15. The implantable and bioresorbable sensor of claim 1, further comprising an at least partially resorbable wireless data-transmitter electrically connected to the electronic device, wherein the electronic device further comprises:

a near-field communication (NFC) microchip;

an electronic circuit comprising;

electrical interconnects, resistors, and capacitors that electrically connect the NFC chip and semiconductor or metallic component for data acquisition, processing and transmission; and

an inductive coil or radiofrequency receiver for powering the implantable and bioresorbable sensor from an externally-positioned or subdermally-implanted electronic component.

23. The implantable and bioresorbable sensor of claim 1, further comprising an encapsulation layer that encapsulates the implantable and bioresorbable sensor, the encapsulation layer comprising a bioresorbable polymer layer, a bioresorbable inorganic layer, or both a bioresorbable polymer layer and a bioresorbable inorganic layer, wherein the bioresorbable polymer layer and the bioresorbable inorganic layer have a thickness selected to provide a desired operational lifetime.

25. The implantable and bioresorbable sensor of claim 1, further comprising:

an electrical interconnect;

a wireless transmitter, wherein the electrical interconnect electrically connects the wireless transmitter to the electronic device; and

wherein the electrical interconnect comprises a bioresorbable metal wire having a thickness less than 50 μ

m and a width less than 500 μ

m.

26. The implantable and bioresorbable sensor of claim 1 wherein the operational lifetime is greater than or equal to one week, wherein for the bioresorption lifetime that is greater than the operational lifetime, each of the substrate, the barrier layer and the electronic device are configured for bioresorption by a patient in which the implantable and bioresorbable sensor is implanted.

27. The implantable and bioresorbable sensor of claim 26, wherein constituents of the implantable and bioresorbable sensor are configured to dissolve by any one or more of hydrolysis, enzyme reaction, or metabolic reaction after implantation in a programmed timeframe.

28. The implantable and bioresorbable sensor of claim 27, wherein the constituents are configured to dissolve within 14 months after implantation.

29. The implantable and bioresorbable sensor of claim 28, further comprising electrical interconnects to electrically connect the electronic device to a wireless transmitter, wherein the electrical interconnects comprise biodegradable metal wires having a thickness less than 50 μ

m and configured to have a dissolution rate when in contact with a biofluid during use that is between 0.2 nm/day and 20 nm/day.

30. The implantable and bioresorbable sensor of claim 29, further comprising a polymer layer supported by the substrate, the polymer layer configured to have a dissolution rate when in contact with a biofluid such that after a time period that is greater than three weeks the polymer layer has dissolved.

31. The implantable and bioresorbable sensor of claim 29, wherein a barrier layer composition and a barrier layer thickness are selected to provide a desired operational lifetime that is between 1 day and 12 months.

35. The implantable and bioresorbable sensor of claim 1, for monitoring two or more parameters selected from the group consisting of:

pressure;

temperature;

motion;

fluid flow;

conductivity;

diffusivity;

pH;

oxygen level;

electric potential;

impedance;

optical image;

presence of a biomolecule of interest;

glucose presence or concentration; and

lactate presence or concentration.

36. The implantable and bioresorbable sensor of claim 1, configured for implantation into a cavity of a living animal, wherein after a bioresorption lifetime, no detectable portion of the implantable and bioresorbable sensor remains in the living animal.

37. The implantable and bioresorbable sensor of claim 36, configured to adhere to a tissue, body cavity or organ wall selected from the group consisting of:

a luminal facing blood vessel wall;

an external-facing blood vessel wall, brain, heart, lung, eye, esophagus, stomach, sphincter, liver, urinary bladder, and spinal cord.

3. (canceled)

9-11. -11. (canceled)

13-14. -14. (canceled)

16-22. -22. (canceled)

24. (canceled)

32-34. -34. (canceled)

38. (canceled)

39. An implantable and bioresorbable pressure sensor comprising:

a substrate;

a cavity disposed in the substrate;

a deformable layer supported by the substrate and that covers the cavity;

an electronic device supported by the substrate, wherein the electronic device comprises a strain gauge supported by the deformable layer and adjacent to the cavity, wherein deflection of the deformable layer by a fluid pressure in a fluid surrounding a top surface of the deformable layer and strain gauge generates an electrical output from the strain gauge that depends on a magnitude of the fluid pressure; and

a barrier layer that fluidically isolates the electronic device during use.

40. The implantable and bioresorbable pressure sensor of claim 39, wherein the deformable layer comprises a polymer layer, an inorganic layer, or both a polymer and inorganic layer.

43. The implantable and bioresorbable pressure sensor of claim 39, wherein the strain gauge comprises a bioresorbable nanomembrane formed of:

Si, polycrystalline Si, Ge, Si—

Ge, a-IGZO, Mg, Mo, Zn, W, Fe, or alloys thereof, wherein the nanomembrane has a thickness less than 1 μ

m.

44. The implantable and bioresorbable pressure sensor of claim 43 that is a Si-nanomembrane strain gauge that comprises a distal piezoresistive end having a serpentine geometry.

45. The implantable and bioresorbable pressure sensor of claim 39, further comprising an additional sensor electrically connected to the electronic device to provide a multi-functional sensor that detects pressure and at least one additional physical parameter.

41-42. -42. (canceled)

46. An extraction-free method of remotely sensing one or more physical parameters in a living animal, the method comprising the steps of:

inserting into a living animal an implantable and bioresorbable sensor operably connected to a wireless transmitter;

electrically coupling the inserted implantable and bioresorbable sensor to an externally located electronic component to power the sensor and wireless transmitter;

outputting to the wireless transmitter from the implantable and bioresorbable sensor an electrical output, wherein the electrical output depends on the one or more physical parameters;

wirelessly transmitting the electrical output to the externally located electronic component; and

hydrolyzing the implantable and bioresorbable sensor so that after an operational lifetime no observable or detectable portion of the implantable and bioresorbable sensor remains in the living animal,

thereby providing the extraction-free method of remotely sensing one or more physical parameters.