Research ArticleBIOENGINEERING

Skin-like biosensor system via electrochemical channels for noninvasive blood glucose monitoring

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Science Advances  20 Dec 2017:
Vol. 3, no. 12, e1701629
DOI: 10.1126/sciadv.1701629
  • Fig. 1 ETC principle and the skin-like biosensors.

    (A) Schematic of the ETCs, which perform HA penetration, glucose refiltration, and glucose outward transportation. (B) Schematic of the ultrathin skin-like biosensor multilayers. (C) Thin, flexible, and biocompatible paper battery attached to the skin surface for ETC measurement. (D) Selective electrochemically deposited dual electrodes of the biosensors (left). The biosensor completely conforms to the skin surface (right).

  • Fig. 2 Electrochemical and mechanical characterization of the device.

    (A) Scanning electron microscopy (SEM) micrograph of O-Au (left) and optical micrograph of broken O-PB (right). (B) SEM micrograph of N-Au (left) and optical micrograph of complete N-PB (right). (C) Schematic of surface nanostructure–induced inner flow during ECD (left). Fluid mechanics simulation of the velocity distribution when the inner flow passes over the surface of the nanostructure (right, top) and electrochemical simulation of the growth rate of PB during ECD on N-Au (right, bottom). (D) Deposition current of O-PB (blue) and N-PB (red). (E) CV scan of O-PB (blue) and N-PB (red). (Inset) CV curve of O-PB (−0.05 to 0.35 V versus Ag/AgCl reference electrode at a scan rate of 50 mV/s). (F) Nyquist plot of EIS of O-Au (black), N-Au (red), O-PB (green), and N-PB (blue). (G) Response of N-PB to the same density H2O2 as a function of deposition time (that is, thickness). (H) CV of freshly deposited N-PB and N-PB after 2 months of storage. (I) Young’s modulus and hardness of N-PB (blue) and O-PB (green).

  • Fig. 3 Bionic transfer printing and glucose measurement calibration.

    (A) Process of bionic ROSE transfer printing. (B) Serpentine (top) and interdigital (bottom) pattern biosensors transfer-printed by ROSE. (C) CV of a biosensor before and after transfer printing (−0.05 to 0.35 V versus reference electrode at a scan rate of 50 mV/s). Amperometric I-t results of (D) low-density and (E) moderate-density glucose as measured in a calibration experiment. (Inset) Biosensor response as a function of density. (F) The glucose measurement response for 50 to 100 μM at 10 μM per step was repeated four times. (G) Amperometric I-t result of the selective response to glucose (Glu) and other interfering substances: ascorbic acid (AA), HA, uric acid (UA), and lactic acid (LA). (H) Temperature calibration result (TCR) of the temperature sensor.

  • Fig. 4 In vivo clinical trials.

    (A) Paper battery being attached to the skin surface for ETC measurement (left), with HA sprayed under the paper battery anode (right). (B) Amperometric I-t result recorded from the biosensor attached to the skin surface. (C) Biosensing response current with (red) and without (blue) the ETC control test. (D) In vivo invasive blood glucose measurement by using a finger-prick glucometer (left) and a venous blood test with vein detained needles (right). (E) Results of hourly glucose monitoring in 1-day period from 10:00 to 23:00 by using a glucometer (red) and ETC devices (blue) (subject 1). (F) Results of 5-day glucose monitoring with the glucometer (red) and ETC devices (blue) (subject 1). (G) Results of blood glucose measured by using a plasma blood test with a vein detained needle (red) and ETC devices (blue) during the OGTT (subjects 2 and 3).

Supplementary Materials

  • Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/3/12/e1701629/DC1

    Supplementary Text

    fig. S1. Advantage of CGM over prevalent glucose monitoring and treatment.

    fig. S2. Thin and flexible biocompatible paper battery.

    fig. S3. Schematic of high-density HA penetration promoting filtration of glucose in the blood.

    fig. S4. Glucose biosensing principle.

    fig. S5. Different patterns for glucose biosensing dual electrode.

    fig. S6. Bending stiffness (that is, flexibility) as a function of device thickness.

    fig. S7. SEM micrographs of electrochemical deposited PB on different gold electrodes.

    fig. S8. PB sediments after the ECD of O-PB that are not attached to the electrodes.

    fig. S9. PB thickness measurement.

    fig. S10. Twenty times of CV scan (−0.05 to 0.35 V versus reference electrode at a scan rate of 50 mV/s).

    fig. S11. Bode plot of O-Au, N-Au, O-PB, and N-PB scan frequency of 1 × 10−2 to 1 × 10−4 Hz.

    fig. S12. Electrochemical characterization of the N-PB after 2 months’ storage.

    fig. S13. Mechanical property measurement of O-PB and N-PB.

    fig. S14. Biosensing device calibration experiment of high-density glucose.

    fig. S15. CV scan (−0.05 to 0.35 V versus reference electrode at a scan rate of 50 mV/s) of the device in four-time repeated glucose calibration experiments.

    fig. S16. Influence of pH value and temperature change on device’s performance.

    fig. S17. Skin surface temperature measurement in 20 min at room temperature with a Pt temperature sensor.

    fig. S18. Skin surface condition.

    movie S1. ROSE transfer printing.

  • Supplementary Materials

    This PDF file includes:

    • Supplementary Text
    • fig. S1. Advantage of CGM over prevalent glucose monitoring and treatment.
    • fig. S2. Thin and flexible biocompatible paper battery.
    • fig. S3. Schematic of high-density HA penetration promoting filtration of glucose in the blood.
    • fig. S4. Glucose biosensing principle.
    • fig. S5. Different patterns for glucose biosensing dual electrode.
    • fig. S6. Bending stiffness (that is, flexibility) as a function of device thickness.
    • fig. S7. SEM micrographs of electrochemical deposited PB on different gold electrodes.
    • fig. S8. PB sediments after the ECD of O-PB that are not attached to the electrodes.
    • fig. S9. PB thickness measurement.
    • fig. S10. Twenty times of CV scan (−0.05 to 0.35 V versus reference electrode at a scan rate of 50 mV/s).
    • fig. S11. Bode plot of O-Au, N-Au, O-PB, and N-PB scan frequency of 1 × 10−2 to 1 × 10−4 Hz.
    • fig. S12. Electrochemical characterization of the N-PB after 2 months’ storage.
    • fig. S13. Mechanical property measurement of O-PB and N-PB.
    • fig. S14. Biosensing device calibration experiment of high-density glucose.
    • fig. S15. CV scan (−0.05 to 0.35 V versus reference electrode at a scan rate of 50 mV/s) of the device in four-time repeated glucose calibration experiments.
    • fig. S16. Influence of pH value and temperature change on device’s performance.
    • fig. S17. Skin surface temperature measurement in 20 min at room temperature with a Pt temperature sensor.
    • fig. S18. Skin surface condition.
    • Legend for movie S1

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    Other Supplementary Material for this manuscript includes the following:

    • movie S1 (.mp4 format). ROSE transfer printing.

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