Microneedle arrays for biosensing and drug delivery

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.

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. 
     
     
         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 .- 28 . (canceled) 
     
     
         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 . (canceled)