ON-BODY MICROSENSOR FOR BIOMONITORING

• US 20140275897A1
• Filed: 03/14/2014
• Published: 09/18/2014
• Est. Priority Date: 03/14/2013
• Status: Active Grant

• Current Assignee: One Health Biosensing Incorporated
• Original Assignee: Sano Intelligence, Inc. (Informed Data Systems, Inc.)
• Inventors: Pushpala, Ashwin, Szmodis, Alan, Chapman, Matthew, Hall, Weldon, Miller, Scott, Hafezi, Hooman
• Granted Patent: US 9,008,745 B2
• Time in Patent Office: Days
• US Class Current: 600/347
• 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 2562/125 characterised by the manufacture of electrodes
• 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 5/14514 using means for aiding extraction of interstitial fluid, e.g. microneedles or suction
• 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 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: A61B 5/150022 for capillary blood or interstitial fluid
• CPC Class Codes: A61B 5/150282 for piercing elements, e.g. blade, lancet, canula, needle
• CPC Class Codes: A61B 5/150427 Specific tip design, e.g. for improved penetration characteristics
• CPC Class Codes: A61B 5/150969 Low-profile devices which resemble patches or plasters, e.g. also allowing collection of blood samples for testing
• CPC Class Codes: A61B 5/150984 Microneedles or microblades
• CPC Class Codes: A61B 5/4839 combined with drug delivery
• CPC Class Codes: A61B 5/685 Microneedles
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/0046 Solid microneedles
• CPC Class Codes: A61M 2037/0053 Methods for producing microneedles
• CPC Class Codes: A61M 25/00 Catheters; Hollow probes dilators A61M29/00; peritoneal catheters A61M1/285; tracheal tubes A61M16/04; for drainage A61M27/00; for uterus, vagina or rectum A61M31/00 ; for measuring or testing A61B; materials for catheters A61L29/00
• CPC Class Codes: A61M 37/0015 : by using microneedles
• CPC Class Codes: C12Q 1/006 : for glucose
• CPC Class Codes: G01N 27/3271 : Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood amperometry per se G01N27/49; aspects concerning the enzyme reagent C12Q1/001
• CPC Class Codes: Y10T 29/49117 : Conductor or circuit manufacturing

Abstract

A microsensor and method of manufacture for a microsensor, comprising an array of filaments, wherein each filament of the array of filaments comprises a substrate and a conductive layer coupled to the substrate and configured to facilitate analyte detection. Each filament of the array of filaments can further comprise an insulating layer configured to isolate regions defined by the conductive layer for analyte detection, a sensing layer coupled to the conductive layer, configured to enable transduction of an ionic concentration to an electronic voltage, and a selective coating coupled to the sensing layer, configured to facilitate detection of specific target analytes/ions. The microsensor facilitates detection of at least one analyte present in a body fluid of a user interfacing with the microsensor.

Claims

1. A sensor for sensing analytes present in a body fluid of a user, the sensor comprising:

a substrate composed of a semiconducting material; and

a filament including;

a substrate core defined at the substrate, the substrate core including a base end coupled to the substrate and a tip that facilitates access to the body fluid of the user;

a conductive layer, coupled to the tip of the substrate core as an active region that enables transmission of electronic signals generated upon detection of an analyte,

an insulating layer ensheathing the substrate core and exposing a portion of the conductive layer, thereby defining a boundary of the active region;

a sensing layer, in communication with the active region, characterized by reversible redox behavior for transduction of an ionic concentration of the analyte into an electronic signal;

an intermediate selective layer superficial to the conductive layer and deeper than the sensing layer that facilitates detection of the analyte,

an intermediate protective layer, superficial to the intermediate selective layer, including a functional compound that promotes generation of a protective barrier; and

a selective coating superficial to the intermediate protective layer, having a distribution of molecules that respond to presence of the analyte, superficial to the sensing layer.

2. The sensor of claim 1, wherein the conductive layer includes at least one of gold, nickel, and platinum, wherein the insulating layer includes 0.1-10 μ

m of a thermal oxide.

3. The sensor of claim 2, wherein the intermediate selective layer includes phenylenediamene and the intermediate protective layer includes at least one of urethane, parylene, and nafion.

4. The sensor of claim 3, wherein the sensing layer includes phenylenediamene and distributions of tyramine, glucose oxidase, and poly-lysine.

5. The sensor of claim 1, further including an intermediate active layer, superficial to the conductive layer and deeper than the sensing layer, including at least one of iron hexacyanoferrate and nano-Platinum for facilitating signal transduction upon detection of the analyte.

6. The sensor of claim 1, further including a biocompatible layer, superficial to the selective coating and composed of least one of urethane, parylene, Teflon, and a fluorinated polymer.

7. The sensor of claim 1, wherein the filament is one of an array of filaments at the substrate, and wherein each filament of the array of filaments has a length from 150-500 μ

m.

8. The sensor of claim 1, wherein the filament comprises a columnar protrusion with a rectangular cross section, coupled to a pyramidal tip region defining the tip, wherein the conductive layer is isolated to the pyramidal tip region.

9. The sensor of claim 8, wherein the pyramidal tip region is defined by an irregular pyramid, having a first pair of orthogonal faces, substantially contiguous with two faces of the columnar protrusion, and a second pair of orthogonal faces, angled relative to the first pair of orthogonal faces, such that the tip is substantially aligned with a vertex of the rectangular cross section of the columnar protrusion.

10. A sensor for sensing analytes present in a body fluid of a user, the sensor comprising:

a substrate composed of a semiconducting material; and

an array of filaments, each filament in the array of filaments including;

a substrate core defined at the substrate, the substrate core including a base end coupled to the substrate and a tip that facilitates access to the body fluid of the user;

a conductive layer, coupled to the tip of the substrate core as an active region that enables transmission of electronic signals generated upon detection of an analyte;

an insulating layer ensheathing the substrate core and exposing a portion of the conductive layer, thereby defining a boundary of the active region;

a sensing layer, in communication with the active region, characterized by reversible redox behavior for transduction of an ionic concentration of the analyte into an electronic signal; and

a selective coating, having a distribution of molecules that respond to presence of the analyte, coupled to the sensing layer.

11. The sensor of claim 10, wherein the substrate comprises boron-doped <

100>

orientation silicon, the conductive layer comprises at least one of a nickel-based, a gold-based, and a platinum-based material, and the insulating layer comprises an oxide layer of at least 1 μ

m thickness.

12. The sensor of claim 10, wherein each filament of the array of filaments comprises a columnar protrusion with a rectangular cross section, coupled to a pyramidal tip region defining the tip, wherein the conductive layer is isolated to the pyramidal tip region.

13. The sensor of claim 12, wherein the pyramidal tip region is defined by an irregular pyramid, having a first pair of orthogonal faces, substantially contiguous with two faces of the columnar protrusion, and a second pair of orthogonal faces, angled relative to the first pair of orthogonal faces, such that the tip is substantially aligned with a vertex of the rectangular cross section of the columnar protrusion.

14. The sensor of claim 10, wherein the sensing layer comprises a conducting polymer and the selective layer comprises a complementary molecule to a target analyte, distributed uniformly throughout a polymer matrix.

15. The sensor of claim 10, wherein every filament of the array of filaments is substantially identical in geometric configuration.

16. The sensor of claim 15, wherein the array of filaments comprises a first array configured to detect a concentration of a first analyte and a second array configured to detect a concentration of a second analyte, different from the first analyte.

17. The sensor of claim 10, further comprising an adhesion layer configured to facilitate coupling between at least two of the substrate core, the conductive layer, the insulating layer, the sensing layer, and the selective coating.

18. The sensor of claim 10, further comprising a temporary functional layer, superficial to the selective coating, that facilitates penetration of the sensor into the body of the user, wherein the temporary functional layer is configured to dissolve during contact with the body fluid of the user and configured to release an ion concentration upon dissolvement to facilitate calibration of the sensor.

19. The sensor of claim 10, further including a notch defined at the tip of at least one filament of the array of filaments.

20. The sensor of claim 19, wherein the notch performs one or more of:

isolating at least a portion of the sensing layer, receiving a calibration material configured to release an analyte for calibration of the sensor, and receiving a therapeutic substance to facilitate delivery of the therapeutic substance to the user.