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Jung et al. Soft Sci 2024;4:15 https://dx.doi.org/10.20517/ss.2024.02 Page 23 of 44

Yao et al. presented a non-invasive blood glucose sensor featuring a flexible and wearable design
[Figure 7C]. Utilizing a graphene (G)/CNTs/GO composites textile as the WE and a G/CNTs/Ag/AgCl as
x
[244]
the CE , the device was evaluated for its effectiveness in non-invasively measuring glucose levels in
humans. This assessment involved placing the sensors on the wrists of three healthy volunteers [Figure 7C].
The response current densities of the wrist-mounted sensors indicated that the calculated blood glucose
concentrations closely matched those measured by a standard glucose meter for all three volunteers.
Notably, the two-electrode non-invasive glucose sensors exhibited the capability for intermittent glucose
monitoring over an extended period of more than 8 h.

De la Paz et al. reported a flexible platform for non-invasive ISF extraction and detection, resembling a
temporary tattoo, with an extended sensing operation time of 8 h . The platform integrates with an
[245]
electronic board for controlling the RI-sensing operation and enables real-time wireless transmission,
making it suitable for extended daily glucose monitoring. This was demonstrated in a clinical investigation
involving individuals with diabetes [Figure 7D]. The wearable glucose patch was tested for 4 h in diabetic
patients, with blood and ISF glucose recordings following protocols used in initial eight-hour tests. During
fasting, all blood glucose measurements exceeded 100 mg/dL [Figure 7D], indicating higher ISF glucose
levels than healthy volunteers. The experiments showed minimal changes in glucose levels during the first
two measurements (0:20 and 1:00 h), followed by a significant rise 1 h after food ingestion (2:00 h). The
consistent agreement between ISF and blood readings confirms the reliability of non-invasive glucose
measurements for extended monitoring.

MULTIPLEXED WEARABLE SENSOR FOR DIABETES MELLITUS
Multiplexed analysis of wearable sensor
In recent years, significant strides have been taken in developing multiplexed wearable sensors for DM
monitoring. These advanced platforms enable the simultaneous analysis of various diabetes biomarkers,
providing a comprehensive picture of the individual health status. One direction of multiplexed analysis
involves the integration of electrochemical and physiological biomarkers including cardiovascular and/or
physical parameters. This multiplexed approach offers real-time insights into not only DM management but
also complications resulting from it. Another promising avenue of multiplexed analysis centers on
simultaneously measuring multiple electrochemical biomarkers. These sensors enable the concurrent
monitoring of glucose and other vital biomarkers in single- or multi-human biofluid. Such simultaneous
monitoring is necessary to understand the potential synergistic effects and complicated fluctuation of DM-
related biomarkers.

Electrochemical and physiological biomarkers
As the pioneering study for multiplexed analysis of electrochemical and physiological biomarkers, the
hybrid wearable patch was developed to simultaneously measure biochemical and electrophysiological
parameters [Figure 8A]. Patch-type electrodes for the lactate biosensor and electrocardiogram were
fabricated by leveraging a screen-printing method on the polyester sheet. Human experiments collecting the
hybrid signals during 15-30 min cycling activity demonstrated concurrent lactate and heart rate
measurement, extracted from electrocardiogram data, with negligible cross-talk . In addition to patch-
[246]
type wearable sensors, an integrated wearable health management system with a glucose sensing strip and
smart band was reported in 2018 [Figure 8B]. A sweat-based glucose sensing strip was attached on the
forehead, and a smart band with an electronic circuit was worn on the wrist for measuring physiological
signals, such as blood oxygen saturation level, heart rate, and physical activity. The sensing strip, which