MICRONEEDLE ARRAYS FOR BIOSENSING AND DRUG DELIVERY

• US 20170347925A1
• Filed: 08/25/2017
• Published: 12/07/2017
• 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: 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)
• Inventors: Wang, Joseph, Windmiller, Joshua Ray, Narayan, Roger, Miller, Phillip, Polsky, Ronen, Edwards, Thayne L.
• Granted Patent: US 10,136,846 B2
• Time in Patent Office: Days
• 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. An analyte-selective sensor device for measuring an analyte in a physiological fluid, comprising:

a substrate having an anterior surface and a posterior surface;

an array of electrically-insulating protruded needle structures arranged perpendicularly and extending from the anterior surface of the substrate to a distal extent of 1500 micrometers or less from the posterior surface of the substrate;

an array of electrically-conductive probes, each probe disposed within and circumscribed by a corresponding electrically-insulating protruded needle structure, wherein the electrically-conductive probes extend perpendicularly from the anterior surface of the substrate to a region beyond the distal extent of the electrically-insulating protruded needle structures;

an array of electrically-conductive interconnects, each interconnect coupled to a corresponding electrically-conductive probe at the anterior surface of the substrate; and

an array of electrodes, each electrode disposed on a surface of a corresponding electrically-conductive probe in the region beyond the distal extent of the electrically-insulating protruded needle structure, wherein at least one electrode of the array is functionalized by a coating to interact with an analyte in a physiological fluid and produce a sensing signal at the electrode, wherein the produced sensing signal includes an electrical signal that transfers through the probe to the corresponding electrically-conductive interconnect.

2. The device of claim 1, wherein the analyte includes at least one of a biochemical, a metabolite, an electrolyte, an ion, a pathogen, or a microorganism.

3. The device of claim 1, wherein the physiological fluid includes interstitial fluid, dermal interstitial fluid, extracellular fluid, intracellular fluid, transdermal fluid, cerebrospinal fluid, synovial fluid, mucosa, or blood.

4. The device of claim 1, wherein the substrate includes a semiconductor, a glass, a dielectric, a polymer, or an organic material.

5. The device of claim 1, wherein the electrically-insulating protruded needle structures are structured to include a shape including at least one of pyramidal, triangular, cylindrical, quadrilateral, or polygonal.

6. The device of claim 1, wherein the electrically-insulating protruded needle structures comprises a semiconductor, a glass, a polymer, a plastic, a crystal, or a dielectric.

7. The device of claim 1, wherein the electrically-conductive probes are structured to include a shape including at least one of cylindrical, circular, triangular, quadrilateral, or polygonal.

8. The device of claim 1, wherein the electrically-conductive probes comprises a semiconductor, a metal, a polymer, or an organic material.

9. The device of claim 1, wherein the coating functionalized on the at least one electrode includes at least one of a film, a membrane, a polymer, or an entrapped bio-recognition element.

10. The device of claim 9, wherein the bio-recognition element includes an enzyme, an antibody, an aptamer, a cell, a nucleic acid, an ionophore, a molecularly-imprinted polymer, a biocatalyst, and a synthetic catalyst.

11. The device of claim 1, wherein the array of electrically-conductive electrodes includes a subset of electrodes that are working electrodes.

12. The device of claim 11, wherein the array of electrically-conductive electrodes includes a second subset of electrodes that are counter electrodes.

13. The device of claim 11, wherein the array of electrically-conductive electrodes includes a third subset of electrodes that are reference electrodes.

14. The device of claim 13, wherein the reference electrodes include a functionalized coating, and wherein the functionalized coating includes at least one of a film, a membrane, a polymer, or an entrapped bio-recognition element.

15. The device of claim 14, wherein the bio-recognition element includes an enzyme, an antibody, an aptamer, a cell, a nucleic acid, an ionophore, a molecularly-imprinted polymer, a biocatalyst, and a synthetic catalyst.

16. The device of claim 1, wherein the interaction between the coating and the analyte is detected using at least one of amperometry, voltammetry, potentiometry, coulometry, polarography, or electrochemical impedance spectroscopy.

17. The device of claim 1, wherein the sensing signal is at least one of an electrical voltage, current, resistance, capacitance, inductance, conductance, charge, or impedance.

26. The method of claim 11, wherein the array of electrically-conductive electrodes includes a first subset of electrodes that are working electrodes, a second subset of electrodes that are counter electrodes, and a third subset of the electrically-conductive electrodes that are reference electrodes.

27. The method of claim 26, wherein at the third subset of electrodes include a functionalized coating, and wherein the functionalized coating includes at least one of a film, a membrane, a polymer, or an entrapped bio-recognition element.

18. An analyte-selective sensor device for measuring an analyte in a physiological fluid, comprising:

a substrate having an anterior surface and a posterior surface;

an array of electrically-insulating protruded needle structures arranged perpendicularly and extending from the anterior surface of the substrate to a distal extent of 1500 micrometers or less from the posterior surface of the substrate;

an array of electrically-conductive probes, each probe disposed within and circumscribed by a corresponding electrically-insulating protruded needle structure, wherein the electrically-conductive probes extend perpendicularly from the anterior surface of the substrate to a region beyond the distal extent of the electrically-insulating protruded needle structures;

an array of electrically-conductive interconnects, each interconnect coupled to a corresponding probe at the anterior surface of the substrate; and

an array of electrodes, each electrode disposed on a surface of a corresponding electrically-conductive probe in the region beyond the distal extent of the electrically-insulating protruded needle structures, wherein at least one electrode of the array is operable to produce a sensing signal corresponding to a measurement of an analyte within a physiological fluid, and wherein the corresponding probe is operable to transfer the sensing signal through the probe to the electrically-conductive interconnect.

19. A method for measuring an analyte within a physiological fluid, comprising:

contacting an analyte-selective sensor device with a physiological fluid, wherein the analyte-selective sensor device includes (i) a substrate having an anterior surface and a posterior surface, (ii) an array of electrically-insulating protruded needle structures arranged perpendicularly and extending from the anterior surface of the substrate to a distal extent of 1500 micrometers or less from the posterior surface of the substrate, (iii) an array of electrically-conductive probes, each probe disposed within and circumscribed by a corresponding electrically-insulating protruded needle structure, wherein the electrically-conductive probes extend perpendicularly from the anterior surface of the substrate to a region beyond the distal extent of the electrically-insulating protruded needle structures, (iv);

an array of electrically-conductive interconnects, each interconnect coupled to a corresponding electrically-conductive probe at the anterior surface of the substrate, and (v) an array of electrodes, each electrode disposed on and electrically coupled to a surface of a corresponding electrically-conductive probe in the region beyond the distal extent of the electrically-insulating protruded needle structures, wherein at least one electrode of the array is functionalized by a coating;

applying an electrical stimulus signal to at least one of the electrically-conductive probes that electrically conducts the applied electrical stimulus signal to the electrodes;

measuring a resultant sensing signal arising by an interaction between the coating functionalized on the at least one electrode and an analyte present in the physiological fluid, wherein a property of the measured sensing signal is indicative of a concentration of the analyte in the physiological fluid, and wherein the measured resultant sensing signal includes an electrical signal that transfers through the probe to the electrically-conductive interconnect; and

receiving the measured resultant sensing signal at a circuit electrically coupled to the electrically-conductive interconnect.

20. The method of claim 19, wherein the analyte includes at least one of a biochemical, a metabolite, an electrolyte, an ion, a pathogen, or a microorganism.

21. The method of claim 20, wherein the metabolite includes at least one of glucose, lactate, ketone, uric acid, ascorbic acid, bilirubin, glutathione, or glutamate.

22. The method of claim 20, wherein said ion includes at least one of hydrogen, sodium, potassium, magnesium, calcium, chloride, phosphate, nitrate, sulfide, or sulfate.

23. The method of claim 19, wherein the physiological fluid includes interstitial fluid, dermal interstitial fluid, extracellular fluid, intracellular fluid, transdermal fluid, cerebrospinal fluid, synovial fluid, mucosa, or blood.

24. The method of claim 19, wherein the array of electrically-conductive electrodes includes a first subset of electrodes that are working electrodes, and a second subset of electrodes that are counter electrodes, reference electrodes, or a set including both.

25. The method of claim 24, wherein at least some of the second subset of electrodes include a functionalized coating, and wherein the functionalized coating includes at least one of a film, a membrane, a polymer, or an entrapped bio-recognition element.

28. The method of claim 19, wherein the functionalized coating includes at least one of a film, a membrane, a polymer, and an entrapped biorecognition element including an enzyme, antibody, aptamer, cell, nucleic acid, ionophore, molecularly-imprinted polymer, biocatalyst, and a synthetic catalyst.

29. The method of claim 19, interaction between the coating and the analyte is detected using at least one of amperometry, voltammetry, potentiometry, coulometry, polarography, or electrochemical impedance spectroscopy.

30. A method for measuring an analyte within a physiological fluid, comprising:

contacting an analyte-selective sensor device with a physiological fluid, wherein the analyte-selective sensor device includes (i) a substrate having an anterior surface and a posterior surface, (ii) an array of electrically-insulating protruded needle structures arranged perpendicularly and extending from the anterior surface of the substrate to a distal extent of 1500 micrometers or less from the posterior surface of the substrate, (iii) an array of electrically-conductive probes, each probe disposed within and circumscribed by a corresponding electrically-insulating protruded needle structure, wherein the electrically-conductive probes extend perpendicularly from the anterior surface of the substrate to a region beyond the distal extent of the electrically-insulating protruded needle structures, (iv);

an array of electrically-conductive interconnects, each interconnect coupled to a corresponding electrically-conductive probe at the anterior surface of the substrate, and (v) an array of electrodes, each electrode disposed on and electrically coupled to a surface of a corresponding electrically-conductive probe in the region beyond the distal extent of the electrically-insulating protruded needle structures, wherein at least one electrode of the array is operable to produce a sensing signal corresponding to a measurement of an analyte within a physiological fluid, and wherein the corresponding probe is operable to transfer the sensing signal through the probe to the electrically-conductive interconnect;

applying an electrical stimulus signal to at least one of the electrically-conductive probes that electrically conducts the applied electrical stimulus signal to the electrodes;

measuring a resultant sensing signal arising by an interaction between the coating functionalized on the at least one electrode and an analyte present in the physiological fluid, wherein a property of the measured sensing signal is indicative of a concentration of the analyte in the physiological fluid, and wherein the measured resultant sensing signal includes an electrical signal that transfers through the probe to the electrically-conductive interconnect; and

receiving the measured resultant sensing signal at a circuit electrically coupled to the electrically-conductive interconnect.