Implants using ultrasonic backscatter for sensing physiological conditions

• US 10,300,310 B2
• Filed: 09/25/2018
• Issued: 05/28/2019
• Est. Priority Date: 07/07/2016
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Maharbiz, Michel M., Carmena, Jose M., Anwar, Mekhail, Ozilgen, Burak A., Seo, Dongjin, Fava, Federica
• Primary Examiner(s): Chao, Elmer M
• Application Number:
  US16/141,930
• Publication Number:
  US 20190022428A1
• Time in Patent Office: 245 Days
• CPC Class Codes: A61B 2505/05 Surgical care
• CPC Class Codes: A61B 2560/0219 of externally powered implanted units
• CPC Class Codes: A61B 2562/028 Microscale sensors, e.g. electromechanical sensors [MEMS]
• CPC Class Codes: A61B 2562/12 Manufacturing methods specially adapted for producing sensors for in-vivo measurements
• 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 5/279 specially adapted for particular uses
• CPC Class Codes: A61B 5/686 Permanently implanted devices, e.g. pacemakers, other stimulators, biochips A61B5/6861 takes precedence
• CPC Class Codes: A61B 6/4258 for detecting non x-ray radiation, e.g. gamma radiation A61B6/037 takes precedence
• CPC Class Codes: A61B 8/0808 for diagnosis of the brain
• CPC Class Codes: A61B 8/085 for locating body or organic structures, e.g. tumours, calculi, blood vessels, nodules
• CPC Class Codes: A61B 8/0875 for diagnosis of bone A61B5/4504 takes precedence
• CPC Class Codes: A61B 8/48 Diagnostic techniques A61B8/13 takes precedence
• CPC Class Codes: A61M 2205/04 implanted
• CPC Class Codes: A61M 2205/825 using mechanical generation of electricity, e.g. hand cranked generators
• CPC Class Codes: A61M 39/0208 Subcutaneous access sites for injecting or removing fluids transcutaneous access sites A61M39/0247; implantable infusion devices A61M5/14276
• CPC Class Codes: A61N 1/0534 Electrodes for deep brain stimulation
• CPC Class Codes: A61N 1/3605 Implantable neurostimulators for stimulating central or peripheral nerve system
• CPC Class Codes: A61N 1/372 Arrangements in connection with the implantation of stimulators
• CPC Class Codes: A61N 1/37205 Microstimulators, e.g. implantable through a cannula
• CPC Class Codes: A61N 1/3787 : from an external energy source
• CPC Class Codes: A61N 2005/1087 : Ions; Protons
• CPC Class Codes: A61N 2007/0021 : Neural system treatment
• CPC Class Codes: A61N 5/1071 : for verifying the dose delivered by the treatment plan
• CPC Class Codes: B06B 1/06 : operating with piezoelectric effect or with electrostriction piezoelectric or electrostrictive devices per se H10N30/00
• CPC Class Codes: G01N 27/327 : Biochemical electrodes , e.g. electrical or mechanical details for in vitro measurements

Abstract

Described herein is an implantable device having a sensor configured to detect an amount of an analyte, a pH, a temperature, strain, or a pressure; and an ultrasonic transducer with a length of about 5 mm or less in the longest dimension, configured to receive current modulated based on the analyte amount, the pH, the temperature, or the pressure detected by the sensor, and emit an ultrasonic backscatter based on the received current. The implantable device can be implanted in a subject, such as an animal or a plant. Also described herein are systems including one or more implantable devices and an interrogator comprising one or more ultrasonic transducers configured to transmit ultrasonic waves to the one or more implantable devices or receive ultrasonic backscatter from the one or more implantable devices. Also described are methods of detecting an amount of an analyte, a pH, a temperature, a strain, or a pressure.

Claims

1. A system, comprising:

(a) an implantable device, comprising;

a sensor configured to detect a pH; and

an ultrasonic transducer with a length of 5 mm or less in the longest dimension, the ultrasonic transducer configured to receive ultrasonic waves that power the implantable device, receive a current modulated based on the pH detected by the sensor, and emit a pH-dependent ultrasonic backscatter based on the current received by the ultrasonic transducer; and

(b) an interrogator comprising one or more ultrasonic transducers configured to transmit the ultrasonic waves that power the implantable device, and receive the ultrasonic backscatter from the implantable device.

2. The system of claim 1, wherein the sensor is an optical sensor.

3. The system of claim 2, wherein the optical sensor comprises a light source and an optical detector.

4. The system of claim 2, wherein the optical sensor comprises a matrix comprising a fluorophore, and wherein fluorescence intensity or fluorescence lifetime of the fluorophore depends on the pH.

5. The system of claim 2, wherein the optical sensor comprises a matrix comprising a fluorophore and an oscillating or pulsating light source, where a phase shift or time delay between light emitted from the light source and fluorescence detected by a fluoresce sensor is based on the pH.

6. The system of claim 1, wherein the sensor is a potentiometric chemical sensor or an amperometric chemical sensor.

7. The system of claim 1, wherein the ultrasonic transducer is a bulk piezoelectric transducer, a piezoelectric micro-machined ultrasonic transducer (PMUT) or a capacitive micro-machined ultrasonic transducer (CMUT).

8. The system of claim 1, wherein the implantable device is 5 mm or less in the longest dimension.

9. The system of claim 1, wherein the volume of the implantable device is 5 mm³ or less.

10. The system of claim 1, wherein the implantable device is implanted in a subject.

11. The system of claim 10, wherein the subject is an animal or a plant.

12. The system of claim 1, wherein the implantable device further comprises an integrated circuit.

13. The system of claim 12, wherein the integrated circuit comprises a power circuit.

14. The system of claim 12, wherein the integrated circuit comprises a driver configured to provide current to the sensor.

15. The system of claim 12, wherein the integrated circuit comprises a front end configured to receive a signal from the sensor.

16. The system of claim 12, wherein the integrated circuit comprises a digital circuit.

17. The system of claim 16, wherein the digital circuit is configured to operate a modulation circuit.

18. The system of claim 17, wherein the digital circuit is configured to transmit a digitized signal to the modulation circuit, and wherein the digitized signal is based on the detected pH.

19. The system of claim 1, wherein the implanted device is at least partially encapsulated by a biocompatible material.

20. The system of claim 1, wherein the implantable device comprises two or more sensors.

21. The system of claim 1, wherein the interrogator is configured to be wearable by a subject.

22. A method of detecting a pH, comprising:

powering one or more implantable devices implanted in a subject using ultrasonic waves emitted from an interrogator comprising one or more transducers, wherein the one or more implantable devices comprise an ultrasonic transducer with a length of 5 mm or less in the longest dimension and a sensor configured to measure the pH;

converting energy from the ultrasonic waves into an electrical current;

transmitting the electrical current to the sensor;

measuring the amount of the pH using the sensor;

modulating the electrical current based on the measured pH;

transducing the modulated electrical current into an ultrasonic backscatter that encodes the measured pH;

emitting the ultrasonic backscatter to the interrogator; and

receiving the ultrasonic backscatter.

23. The method of claim 22, wherein the one or more implantable devices are implanted in a subject.

24. The method of claim 22, wherein the interrogator is worn by the subject.

25. The method of claim 22, wherein the sensor is an optical sensor that comprises a matrix comprising a fluorophore and an oscillating or pulsating light source, and the method further comprises:

determining a phase shift or time delay between light emitted from the light source and fluorescence emitted by the fluorophore, wherein the phase shift or time delay is based on the pH.

26. A method of detecting a pH, comprising:

powering one or more implantable devices implanted in a subject using ultrasonic waves emitted from an interrogator comprising one or more transducers, wherein the one or more implantable devices each comprise an ultrasonic transducer with a length of 5 mm or less in the longest dimension and a sensor configured to measure the pH;

converting energy from the ultrasonic waves into an electrical current;

measuring the pH using the sensor;

modulating the electrical current based on the measured pH;

transducing the modulated electrical current into an ultrasonic backscatter that encodes the measured pH; and

emitting the ultrasonic backscatter to the interrogator; and

receiving the ultrasonic backscatter.

27. The method of claim 26, wherein the one or more implantable devices are implanted in a subject.

28. The method of claim 26, wherein the interrogator is worn by the subject.

29. The method of claim 26, comprising analyzing the ultrasonic backscatter to determine the measured pH.

30. The method of claim 26, wherein the sensor is an optical sensor that comprises a matrix comprising a fluorophore and an oscillating or pulsating light source, and the method further comprises:

determining a phase shift or time delay between light emitted from the light source and fluorescence emitted by the fluorophore, wherein the phase shift or time delay is based on the pH.