Minimally invasive continuous analyte monitoring for closed-loop treatment applications

A closed-loop drug-analyte monitoring and delivery system, comprising:

• a substrate;
• a microneedle sensor contingent configured to detect a plurality of analytes in interstitial fluid (ISF), comprising:
• a plurality of microneedle structures coupled to the substrate, each of the microneedle structures including an exterior wall spanning outward from a base surface of a microneedle structure and forming an apex at a terminus point of the exterior wall, wherein, at a portion of the exterior wall, the microneedle structure has an opening leading in to a hollow region of the microneedle structure that is defined by an interior wall,
• three or more working electrodes at least partially disposed in the hollow region of at least three of the plurality of microneedle structures, the three or more working electrodes including a first working electrode configured to sense a first analyte by a first electrochemical detection technique, a second working electrode configured to sense the first analyte by a second electrochemical detection technique different from the first electrochemical detection technique, and a third working electrode configured to sense a second analyte different than the first analyte, wherein the first working electrode includes a first functionalization material disposed on or integrated with a surface of the first working electrode to facilitate an electrochemical reaction involving the analyte and a chemical species of the first functionalization material, and
• at least one counter or reference electrode at least partially disposed in the hollow region of at least a third microneedle structure of the three or more microneedle structures, the at least one counter or reference electrode configured to apply or measure a voltage difference between the at least one counter or reference electrode and at least one of the two or more working electrodes,
• wherein the first analyte includes levodopa (L-Dopa) and the second analyte includes carbidopa (C-Dopa), wherein the three or more working electrodes are configured to concurrently sense the first analyte L-Dopa and the second analyte C-Dopa, wherein the first electrochemical detection technique to sense the first analyte L-Dopa includes chronoamperometry, wherein the second electrochemical detection technique to sense the first analyte L-Dopa includes square-wave voltammetry (SWV), and wherein the third working electrode is configured to sense the second analyte C-Dopa by SWV, and wherein the SWV is operable to concurrently detect L-Dopa and C-Dopa based on their different peak potentials, and
• wherein the first functionalization material includes tyrosinase enzyme immobilized to the first working electrode by a permselective anti-interference film and configured to biocatalyze the first analyte L-Dopa;
• a microneedle actuator contingent, comprising:
• one or more actuator microneedle structures coupled to the substrate, the one or more actuator microneedle structures each including an exterior wall spanning outward from a base surface of the actuator microneedle structure and forming an apex at a terminus point of the exterior wall, wherein, at a portion of the exterior wall, the actuator microneedle structure has an opening leading in to a hollow region of the microneedle structure that is defined by an interior wall,
• one or more containment chambers having an interior volume to contain a drug, the one or more containment chambers disposed within a corresponding one or more actuator microneedle structures, wherein a containment chamber includes at least one opening from the interior volume that interfaces with the hollow region of the actuator microneedle structure, and
• one or more polymer barriers coupled to the corresponding one or more containment chambers at an interface with the hollow region of the actuator microneedle structure, wherein the polymer barrier includes pores of a reversibly tunable porosity;
• and
• a data processing unit including a processor and memory and in communication with the two or more working electrodes and the at least one counter or reference electrode of the microneedle sensor contingent and in communication with the one or more polymer barriers of the microneedle actuator contingent, the data processing unit configured to process electrical signals detected by the microneedle sensor contingent to determine a parameter associated with the detected analyte, and the data processing unit is further configured to, based on the determined parameter, generate a control signal to actuate an expansion of pores of the one or more polymer barriers to an open state or a contraction the pores of the one or more polymer barriers to a closed state.