Research ArticleBIOENGINEERING

Wearable/disposable sweat-based glucose monitoring device with multistage transdermal drug delivery module

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Science Advances  08 Mar 2017:
Vol. 3, no. 3, e1601314
DOI: 10.1126/sciadv.1601314
  • Fig. 1 Wearable/disposable sweat monitoring device and microneedle-based transdermal drug delivery module.

    (A) Optical camera image (top; dotted line, edges of the patch) and schematic (bottom) of the wearable sweat monitoring patch. A porous sweat-uptake layer is placed on a Nafion layer and sensors. (B) Optical camera image (top) and schematic (bottom) of the disposable sweat monitoring strip. (C) Optical camera image (top; dotted line, edges of the patch) and schematic (bottom) of the transdermal drug delivery device. Replacement-type microneedles are assembled on a three-channel thermal actuator. (D) Schematic drawing of the glucose sensor in an exploded view. PB, prussian blue. (E) Minimum volume of the artificial sweat required for sensing with different sizes of the glucose sensor. (F) Scanning electron microscope (SEM) images before (left) and after (right) immobilization of the enzyme (enz.) on the porous gold electrode. (G) Comparison of the H2O2 sensitivity in the planar and porous gold electrode deposited with Prussian blue at different H2O2 concentrations. (H) Schematic of the drug-loaded microneedles. The right inset describes details of different PCNs. (I) SEM image of the microneedles. (J) Confocal microscope images of the released dye from microneedles (MN) (top view) into the 4% agarose gel (green, agar; red, dye). (K) Infrared (IR) camera image of the three-channel (ch) thermal actuator.

  • Fig. 2 Optimization of the sweat control and characterization of individual sensors.

    (A) Optical image of the wearable sweat analysis patch with a sweat-uptake layer and a waterproof band. The inset shows the magnified view of the porous sweat-uptake layer. (B) Optical image of the sweat analysis patch under deformation. (C) Optical image of the disposable sweat analysis strip on human skin with perspiration. (D) Glucose (glu.) concentration measurement at different sweat volumes (0.3 mM glucose in artificial sweat). (E) Optical image (top) and calibration curve (bottom) of the humidity sensor. Inset shows the image before and after wetting of the sensor. (F) Optical image (top) and calibration curve (bottom) of the glucose sensor. (G) Optical image (top) and calibration curve (bottom) of the pH sensor. (H) Optical image (top) and calibration curve (bottom) of the temperature sensor. (I) Changes of the relative sensitivity of the uncorrected glucose sensor at different pH levels. The relative sensitivity (S/So) is defined as measured sensitivity divided by sensitivity at pH 5. (J) In vitro monitoring of glucose changes with (green) and without (red) correction using simultaneous pH measurements (blue). (K) Calibration curves of the glucose sensor at different temperatures.

  • Fig. 3 Characterization of PCNs and PCN-loaded microneedles.

    (A) Schematic illustration of the PCN. HA, hyaluronic acid. (B) Cryo-TEM image of PCN1 (palm oil) below the melting temperature (left) and TEM image of PCN1 above the melting temperature (right). (C) Cryo-TEM image of PCN2 (tridecanoic acid) below the melting temperature (left) and TEM image of PCN2 above the melting temperature (right). (D) Dynamic light scattering size measurement of PCNs at 30° (skin temperature), 40°, and 45°C. (E) Optical image (left) and confocal fluorescence (FL) microscope image (right) of PCM-coated microneedles. Microneedles contain dye-loaded PCNs for imaging. (F) Microneedle dissolution test in PBS before (left) and after (right) the PCM coating. (G) Mechanical strength test of microneedles in their dry and wet states. (H) Confocal microscope image of microneedles penetrating into 4% agarose gel (left) and IR camera image of the thermal actuation on the gel (right). (I) Drug-release profile from microneedles. (J) IR camera images of eight different spatiothermal profiles using the three-channel thermal actuator for multistage drug delivery. (K) Multistage drug-release profile. a.u., arbitrary units.

  • Fig. 4 Sweat-based glucose monitoring and feedback therapy in vivo.

    (A) Optical camera image of the subject using a cycle ergometer for sweat generation with the wearable patch on the subject’s arm. (B) Real-time humidity monitoring to check the accumulation of sweat. (C) Multimodal glucose and pH sensing to improve detection accuracy. (D) Measured sweat glucose concentrations (n = 3), pH levels (n = 4), and corrected sweat glucose level (n = 3) based on the averaged pH (dotted line, glucose concentration measured by a commercial glucose assay). (E) Optical camera image of the disposable strip-type sensors connected to a zero insertion force (ZIF) connector. (F) Optical camera images of the sweat uptake via the fluidic channel of the strip. (G) Humidity monitoring of the disposable strip using impedance measurements. (H) Sweat glucose and pH monitoring using the disposable strip. (I) Ratio of sweat glucose concentrations (n = 3) measured by the patch and a commercial glucose assay with and without the pH-based correction before and after a meal. (J) Comparison of the sweat and blood glucose concentrations before and after a meal. (K) Optical camera image of the transdermal drug delivery device on the db/db mouse. (L) Blood glucose levels of the db/db mice for the treated groups (microneedles with the drugs) and control groups (without the patch, microneedle without the drugs) (*P < 0.05, **P < 0.01 versus control, Student’s t test).

Supplementary Materials

  • Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/3/3/e1601314/DC1

    Supplementary Text

    fig. S1. Optical camera images of the wearable diabetes patch.

    fig. S2. Device fabrication process.

    fig. S3. Schematic illustration of the operation sequence of the diabetes treatment system.

    fig. S4. Electrochemical analysis of the planar and porous gold electrode.

    fig. S5. Drug delivery from microneedles with integrated heaters.

    fig. S6. Effect of the sweat control layers and miniaturization of the glucose sensor.

    fig. S7. Characterization of the glucose sensor.

    fig. S8. Characterization of the pH sensor.

    fig. S9. Skin temperature and characterization of chlorpropamide-loaded PCNs.

    fig. S10. Characterization of hyaluronic acid, DOPA-conjugated hyaluronic acid.

    fig. S11. Characterization of the PCNs.

    fig. S12. Fabrication process of the microneedles.

    fig. S13. Characterization of the heater and temperature sensor and their cooperation.

    fig. S14. Portable electrochemical analyzer for the wearable diabetes patch.

    fig. S15. Reliability of the wearable diabetes patch under variable skin temperature and multiple reuses.

    fig. S16. Sweat uptake and calibration of the disposable strip-type sensors.

    fig. S17. Human sweat analysis.

    fig. S18. Feedback microneedle therapy.

  • Supplementary Materials

    This PDF file includes:

    • Supplementary Text
    • fig. S1. Optical camera images of the wearable diabetes patch.
    • fig. S2. Device fabrication process.
    • fig. S3. Schematic illustration of the operation sequence of the diabetes treatment system.
    • fig. S4. Electrochemical analysis of the planar and porous gold electrode.
    • fig. S5. Drug delivery from microneedles with integrated heaters.
    • fig. S6. Effect of the sweat control layers and miniaturization of the glucose sensor.
    • fig. S7. Characterization of the glucose sensor.
    • fig. S8. Characterization of the pH sensor.
    • fig. S9. Skin temperature and characterization of chlorpropamide-loaded PCNs.
    • fig. S10. Characterization of hyaluronic acid, DOPA-conjugated hyaluronic acid.
    • fig. S11. Characterization of the PCNs.
    • fig. S12. Fabrication process of the microneedles.
    • fig. S13. Characterization of the heater and temperature sensor and their cooperation.
    • fig. S14. Portable electrochemical analyzer for the wearable diabetes patch.
    • fig. S15. Reliability of the wearable diabetes patch under variable skin temperature and multiple reuses.
    • fig. S16. Sweat uptake and calibration of the disposable strip-type sensors.
    • fig. S17. Human sweat analysis.
    • fig. S18. Feedback microneedle therapy.

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