Tissue-integrating sensors

• US 10,463,287 B2
• Filed: 10/06/2011
• Issued: 11/05/2019
• Est. Priority Date: 10/06/2010
• Status: Active Grant

• Current Assignee: Profusa, Inc.
• Original Assignee: Profusa, Inc.
• Inventors: Wisniewski, Natalie A., Helton, Kristen, McMillan, William A.
• Primary Examiner(s): Winakur, Eric F
• Assistant Examiner(s): Fardanesh, Marjan
• Application Number:
  US13/267,741
• Publication Number:
  US 20120265034A1
• Time in Patent Office: 2,952 Days
• Field of Search: 600310-344
• CPC Class Codes: A61B 5/0004 characterised by the type of physiological signal transmitted
• CPC Class Codes: A61B 5/0017 transmitting optical signals transmission by light H04B10/00
• 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 5/14503 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors A61B5/1459, A61B5/1464, A61B5/1473, A61B5/1482, A61B5/14865 take precedence
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/14735 comprising an immobilised reagent
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: A61B 5/681 Wristwatch-type devices
• CPC Class Codes: A61B 5/7278 Artificial waveform generation or derivation, e.g. synthesising signals from measured signals A61B5/327 takes precedence

Abstract

Tissue-integrating biosensors, systems comprising these sensors and methods of using these sensors and systems for the detection of one or more analytes are provided.

Claims

1. A system for detecting an analyte, the system comprising:

a sensor, the entire sensor being devoid of electronics, the sensor including;

a sensing moiety configured to produce an emission signal in the presence of an analyte; and

a tissue-integrating scaffold including the sensing moiety, the tissue-integrating scaffold defining a plurality of hollow, interconnected pores;

a module, physically spaced apart from the sensor, the module configured to (1) send an excitation signal that diffuses through tissue to the sensor and excites the moiety and (2) receive the emission signal produced by the sensing moiety after the emission signal has diffused through the tissue.

2. The system of claim 1, wherein the tissue-integrating scaffold is configured such that capillaries grow directly into and through the tissue-integrating scaffold in close proximity to the sensing moiety when the apparatus placed into a tissue of a subject.

3. The system of claim 1, wherein the sensor is between 100-1000 microns in diameter.

4. The system of claim 1, wherein the plurality of hollow, interconnected pores are configured such that the sensing moiety is in close proximity to blood vessels when the tissue-integrating sensor is placed into a tissue of a subject.

5. The system of claim 1, wherein the plurality of hollow, interconnected pores are configures such that, when the tissue-integrating sensor is placed into tissue of a subject, the plurality of hollow, interconnected pores promote space-filling ingrowth of cells.

6. The system of claim 1, wherein the plurality of hollow, interconnected pores are configures such that, when the tissue-integrating sensor is placed into tissue of a subject, the plurality of hollow, interconnected pores promote tissue-ingrowth having a channel pattern.

7. The system of claim 1, wherein the sensor is configured to be completely enveloped by the tissue such the emission signal is received transcutaneously.

8. An apparatus, comprising:

a hydrogel scaffold defining a plurality of hollow, interconnected pores configured such that, when the hydrogel scaffold is placed into tissue of a subject, the plurality of hollow, interconnected pores promote space-filling ingrowth of tissue; and

a sensing moiety disposed within the hydrogel scaffold and configured to produce a signal in a presence of an analyte.

9. The apparatus of claim 8, wherein the hydrogel scaffold is porous around its periphery.

10. The apparatus of claim 8, wherein:

the sensing moiety is disposed within an interior of the hydrogel scaffold; and

the plurality of hollow, interconnected pores are configured such that, when the hydrogel scaffold is placed into tissue of the subject, the sensing moiety is in close proximity to blood vessels.

11. The apparatus of claim 8, wherein:

the hydrogel scaffold has a diameter of at least 300 micrometers; and

the plurality of interconnected pores are configured such that, when the hydrogel scaffold is placed into tissue of the subject, a distance between the sensing moiety and a blood vessel is no more than 100 microns greater than half the average distance between blood vessels in the tissue.

12. The apparatus of claim 8, wherein the hydrogel scaffold is between 100-1000 microns in diameter and between about 0.25 mm and 10 mm in length.

13. An apparatus, comprising:

a plurality of sensing moieties configured to produce a signal in a presence of an analyte;

a tissue-integrating scaffold containing the plurality of sensing moieties, the tissue-integrating scaffold defining a plurality of interconnected pores such that at least a subset of the sensing moieties from the plurality of sensing moieties that are disposed in an interior of the tissue-integrating scaffold are in close proximity to blood vessels when the tissue-integrating sensor placed into a tissue of a subject.

14. The apparatus of claim 13, wherein the tissue-integrating scaffold is constructed solely of the plurality of sensing moieties.

15. The apparatus of claim 13, wherein the tissue-integrating scaffold is constructed of a polymer.

16. The apparatus of claim 13, wherein the tissue-integrating scaffold is constructed of at least one of a hydrogel, a collagen, or a decellularized extracellular matrix.

17. The apparatus of claim 13, wherein the plurality of sensing moieties are embedded within the tissue-integrating scaffold.

18. The apparatus of claim 13, further comprising a calibration moiety.

19. The apparatus of claim 13, wherein the tissue-integrating scaffold is between 100-1000 microns in diameter and between about 0.25 mm and 10 mm in length.

20. The apparatus of claim 13, wherein the tissue-integrating scaffold is configured such that, when the tissue-integrating scaffold is placed into tissue of the subject, the plurality of interconnected pores promote space-filling ingrowth of tissue.