Method of manufacturing a sensor for sensing analytes

• US 9,182,368 B2
• Filed: 03/14/2014
• Issued: 11/10/2015
• 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
• Primary Examiner(s): CAZAN, LIVIUS RADU
• Application Number:
  US14/211,404
• Publication Number:
  US 20140259652A1
• Time in Patent Office: 606 Days
• US Class Current: 1/1
• 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 method of manufacturing a sensor for sensing analytes, the method including: with a dicing saw, removing material from a substrate, thereby forming an array of columnar protrusions at a first surface of the substrate; forming an insulating layer coupled to exposed surfaces of the substrate and exposed surfaces of the array of columnar protrusions; removing a portion of the insulating layer at a second surface of the substrate, directly opposed to the first surface of the substrate; with the dicing saw, removing material from a distal end of each columnar protrusion in the array of columnar protrusions, thereby defining a sharp tip, uncovered by the insulating layer, at the distal end of each columnar protrusion in the array of columnar protrusions; and coupling a conductive layer to the sharp tip of each columnar protrusion in the array of columnar protrusions.

Claims

1. A method of manufacturing a sensor for sensing analytes, the method comprising:

with a dicing saw, removing material from a substrate, thereby forming an array of columnar protrusions at a first surface of the substrate;

forming an insulating layer coupled to exposed surfaces of the substrate and exposed surfaces of the array of columnar protrusions;

removing a portion of the insulating layer at a second surface of the substrate, directly opposed to the first surface of the substrate;

with the dicing saw, removing material from a distal end of each columnar protrusion in the array of columnar protrusions, thereby defining a sharp tip, uncovered by the insulating layer, at the distal end of each columnar protrusion in the array of columnar protrusions; and

coupling a conductive layer to the sharp tip of each columnar protrusion in the array of columnar protrusions.

2. The method of claim 1, wherein at least one of forming the array of columnar protrusions and defining the sharp tip at the distal end of each columnar protrusion in the array of columnar protrusions comprises passing the dicing saw in a first direction and in a second direction perpendicular to the first direction.

3. The method of claim 2, wherein forming the insulating layer comprises inducing thermal oxide growth at a temperature between 900°

C. and 1050°

C., and wherein coupling the conductive layer comprises electroplating at least one of gold, nickel, and platinum to the sharp tip of each columnar protrusion in the array of columnar protrusions.

4. The method of claim 1, further comprising applying a sensing layer, characterized by reversible redox reaction behavior, superficial to the conductive layer of the sensor and coupling a selective layer, comprising a distribution of a molecules complementary to a target analyte, superficial to the sensing layer of the sensor.

5. The method of claim 4, further including coupling an intermediate selective layer superficial to the conductive layer of the sensor, wherein coupling the intermediate selective layer includes electropolymerizing a phenylenediamene material.

6. The method of claim 4, further including coupling an intermediate protective layer superficial to the sensing layer of the sensor and deeper than the selective layer of the sensor, wherein the intermediate protective layer includes a functional compound configured to provide a protective barrier.

7. The method of claim 6, wherein coupling the intermediate protective layer includes coupling at least one of polytetrafluoroethylene, a chlorinated polymer, a tetrafluoroethylene-based fluoropolymer-copolymer, and polyethylene glycol, and wherein the functional compound includes at least one of a lipid and a charged chemical specie.

8. The method of claim 4, further including defining a notch at the sharp tip of at least at one columnar protrusion of the array of columnar protrusions, and performing at least one of isolating a portion of the sensing layer within the notch, depositing a calibration material within the notch, and depositing a therapeutic substance within the notch.

9. The method of claim 1, further including providing a biocompatible layer superficial to the conductive layer, wherein providing the biocompatible layer includes depositing a biocompatible polymer having anti-inflammatory and anti-microbial characteristics.