MICRONEEDLE ARRAYS FOR BIOSENSING AND DRUG DELIVERY

• US 20160095541A1
• Filed: 12/10/2015
• Published: 04/07/2016
• Est. Priority Date: 09/02/2011
• Status: Active Grant

• Current Assignee: National Technology & Engineering Solutions Of Sandia LLC (Honeywell International Inc.), Regents of the University of California (University of California), North Carolina State University (University of North Carolina System)
• Original Assignee: Sandia Corporation (Martin Marietta Corporation), Regents of the University of California (University of California), North Carolina State University (University of North Carolina System)
• Inventors: Wang, Joseph, Windmiller, Joshua Ray, Narayan, Roger, Polsky, Ronen, Edwards, Thayne L., Miller, Philip
• Granted Patent: US 9,743,870 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61B 10/0045 Devices for taking samples of body liquids devices for taking blood samples A61B5/15
• CPC Class Codes: A61B 2010/008 Interstitial fluid
• CPC Class Codes: A61B 2562/028 Microscale sensors, e.g. electromechanical sensors [MEMS]
• CPC Class Codes: A61B 2562/046 in a matrix array
• 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 5/1473 invasive, e.g. introduced into the body by a catheter A61B5/1482 takes precedence
• 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 5/150984 Microneedles or microblades
• CPC Class Codes: A61B 5/157 Devices characterised by integrated means for measuring characteristics of blood
• CPC Class Codes: A61B 5/276 Protection against electrode failure
• CPC Class Codes: A61B 5/4845 Toxicology, e.g. by detection of alcohol, drug or toxic products A61B5/4848 takes precedence
• CPC Class Codes: A61B 5/6833 Adhesive patches
• CPC Class Codes: A61B 5/685 Microneedles
• CPC Class Codes: A61B 5/7282 Event detection, e.g. detecting unique waveforms indicative of a medical condition A61B5/4094, A61B5/4818, A61B5/349, A61B5/0823 take precedence
• CPC Class Codes: A61M 2005/1726 the body parameters being measured at, or proximate to, the infusion site
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/003 having a lumen
• CPC Class Codes: A61M 5/158 Needles for infusions; Accessories therefor, e.g. for inserting infusion needles, or for holding them on the body
• CPC Class Codes: A61M 5/1723 : using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00
• CPC Class Codes: G01N 33/48785 : Electrical and electronic details of measuring devices for physical analysis of liquid biological material not specific to a particular test method, e.g. user interface or power supply

Abstract

Methods, structures, and systems are disclosed for biosensing and drug delivery techniques. In one aspect, a device for detecting an analyte and/or releasing a biochemical into a biological fluid can include an array of hollowed needles, in which each needle includes a protruded needle structure including an exterior wall forming a hollow interior and an opening at a terminal end of the protruded needle structure that exposes the hollow interior, and a probe inside the exterior wall to interact with one or more chemical or biological substances that come in contact with the probe via the opening to produce a probe sensing signal, and an array of wires that are coupled to probes of the array of hollowed needles, respectively, each wire being electrically conductive to transmit the probe sensing signal produced by a respective probe.

Claims

1-43. -43. (canceled)

44. A method for in situ measurement of one or more target chemical species present in a physiological fluid, the method comprising:

applying a stimulus signal to an electrically conductive structure disposed on a substrate, wherein the electrically conductive structure is disposed in a spatially-defined region separate from an array of protrusions attached to and extending from an anterior surface of the substrate, each protrusion possessing a vertical extent of between 20 and 1500 micrometers from said substrate to a distal extent of each protrusion, and

reading a resultant signal arising at an interface between the physiological fluid and an electrically-conducting probe disposed in a defined exposed region on each protrusion by providing an isolated electrical communication with said probe using a spatially-defined conducting channel in contact with the probe and the electrically conductive structure located in the spatially-defined region separate from said protrusion,

wherein a property of said resultant signal is indicative of a concentration of the one or more target chemical species present in said physiological fluid.

45. The method according to claim 44, comprising:

processing the resultant signal to determine whether the concentration of the one or more target chemical species present in said physiological fluid reflects a healthy or disease state.

46. The method according to claim 45, wherein processing the resultant signal includes comparing the resultant signal to a threshold value.

47. The method according to claim 45, wherein processing the resultant signal includes determining a pattern in the resultant signal.

48. The method according to claim 44, wherein the property of said resultant signal includes magnitude of the resultant signal.

49. The method according to claim 44, wherein the property of said resultant signal includes an impedimetric property.

50. The method according to claim 49, wherein the impedimetric property is associated with a phase or a frequency of the resultant signal.

51. A device for in situ measurement of one or more target chemical species present in a physiological fluid, the device comprising:

a substrate;

an array of protrusions attached to and extending from an anterior surface of the substrate, each protrusion possessing a vertical extent of between 20 and 1500 micrometers from the substrate to a distal extent of each protrusion;

an electrically-conducting probe disposed in a defined exposed region on each protrusion;

an electrically conductive structure disposed on the substrate configured to receive an excitation signal; and

a spatially-defined conducting channel in contact with each probe and the electrically conductive structure, the spatially-defined conducting channel located in a spatially-defined region separate from the protrusions to provide an electrical communication with each probe.

52. The device of claim 51, wherein the device is configured to measure a resultant signal at an interface between each probe and the physiological fluid;

and

wherein a property of said resultant signal is indicative of a concentration of the one or more target chemical species present in said physiological fluid.

53. The device according to claim 51, wherein said array of protrusions include at least one of a conal, columnar, triangular, pyramidal, rectangular, or polygonal geometric shape.

54. The device according to claim 51, wherein said defined exposed region is located on at least one exterior surface of each protrusion or within an interior of an aperture or void located on a surface of each protrusion.

55. The device according to claim 51, wherein said substrate is planar and comprises one of a polymer, semiconductor, metal, glass, or film.

56. The device according to claim 51, wherein said electrically-conducting probe includes a chemical species-selective layer deposited on a surface of said probe and facilitates quantification of the target species.

57. The device according to claim 51, wherein said electrically-defined conducting channel comprises an electrically-conducting trace in ohmic contact with each protrusion and terminating at a periphery of the substrate or an electrically-conducting via providing ohmic contact from the anterior to posterior surfaces of said substrate.

58. The device according to claim 51, wherein said physiological fluid includes liquids originating from a living human body and lying beneath biological tissues or membranes.

59. The device according to claim 51, wherein the physiological fluid comprises one of interstitial fluid, intracellular fluid, extracellular fluid, blood, plasma, serum, cerebrospinal fluid, mucus, intraocular, or vitreous humor.

60. The device according to claim 51, wherein said chemical species includes one of a metabolite, electrolyte, ion, pathogen, microorganism, hormone, protein, enzyme, vitamin, anti-oxidant, nucleic acid, antibodies, neurotransmitter, acid, or drug.

61. The device according to claim 51, wherein the chemical species-selective layer comprises one of an ion-selective membrane, enzyme-loaded membrane, conducting polymer, diffusion-limiting polymer, electrostatically-bound biocatalyst, covalently-bound biocatalyst, or surface-adsorbed biocatalyst.

62. The device according to claim 51, wherein the property of said resultant signal includes magnitude of the resultant signal.

63. The method according to claim 51, wherein the property of said resultant signal includes an impedimetric property.

64. The method according to claim 63, wherein the impedimetric property is associated with a phase or a frequency of the resultant signal.