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Page 18 of 44 Jung et al. Soft Sci 2024;4:15 https://dx.doi.org/10.20517/ss.2024.02

with GO and inner layers of Nafion and an electropolymerized film of 1,3-diaminobenzene/resorcinol for
X
enhancing the selectivity of glucose. The developed glucose sensor demonstrated a sensitivity of
0.032 nA/μM with a low detection limit of 1.5 μM. Furthermore, a correlation between tear and blood
glucose levels was examined by simultaneously measuring the concentration of tear and blood glucose in
anesthetized rabbits. In addition to needle-type sensors, a flexible and soft biosensor integrated with a
contact lens was developed [Figure 5B]. The biosensor was composed of three electrodes on 2-
methacryloyloxyethyl phosphorylcholine (MPC) polymer and polydimethylsiloxane (PDMS) to ensure the
biocompatibility and flexibility. With minimum irritations, the biosensor demonstrated a rapid response
with a range of 0.03~5.0 mM. Also, Preclinical ocular tear monitoring with the contact lens biosensor
[221]
exhibited temporal monitoring of tear glucose and tear dynamics . Yao et al., from the group led by
Parviz, proposed the first platform of biosensors embedded in a contact lens [Figure 5C]. A titania sol-gel
film was used to immobilize GO on the WE, and Nafion was employed to reduce the electroactive
X
interferences in tears, such as ascorbic acid, lactate, and urea. The biosensor achieved a rapid response of 20
s and sensitivity of 240 μA·cm ·mM with a minimum detection limit of less than 0.01 mM tear glucose .
[222]
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In addition to glucose sensing, Kim et al., from the group led by Park, developed a multifunctional contact
lens biosensor to simultaneously measure intraocular pressure and glucose in tears [Figure 5D]. The contact
lens based on graphene and metallic NWs provided unobstructed vision by ensuring transparency of 91%
and stretchability of 25%. Intraocular pressure was measured in-vitro by changing resonance frequencies
during ocular hyperextension. Furthermore, a resistor-inductor-capacitor (RLC) circuit with a slightly
[223]
visible spiral antenna was used to transmit wirelessly glucose levels in the rabbit eye . By advancing the
developed contact lens, Park et al. from the same group reported a smart contact lens biosensor with a
display pixel that acts as feedback [Figure 5E]. This display pixel indicated that the tear glucose reaches
0.9 mM. Moreover, the smart contact lens was formed with stress-tunable hybrid substrates composed of
the elastomer and reinforced island. Rigid electronic components, such as the display pixel and rectifier
circuit for wireless power transfer, are attached on the mechanically reinforced island patterned by a
[224]
photocurable optical polymer . Beyond the function to display tear glucose levels, a more sophisticated
smart lens was reported, which enables continuous tear glucose monitoring and electrically on-demand
drug delivery [Figure 5F]. The loaded drugs, such as antiangiogenic genistein and metformin capable of
topical and ocular delivery applications, were delivered by applying an electrical voltage of 1.8 V. In-vivo
experiment was carried out on diabetic rabbits to monitor tear glucose with a real-time, wireless data
[225]
transfer system and deliver drugs on demand . Although contact lens-based electrochemical biosensors
are developing rapidly due to direct tear sampling, the safety of contact lenses remains a major concern. For
this reason, a wearable eyeglasses platform was developed to mitigate drawbacks of systems involving direct
eye contact [Figure 5G]. A biosensing fluidic system into the nose-bridge pad of eyeglasses allowed tear
collection and tear glucose measurement outside the eye. Monitoring alcohol intake, vitamins and glucose
demonstrated that the wearable platform is fully portable and easy to use by integrating the functional
circuit into the eyeglasses frame .
[226]
Saliva
Saliva is a key and easily accessible biofluid for non-invasive health monitoring, containing diverse
biomarkers such as glucose, lactate, hormones, and electrolytes [227,228] . It primarily originates from salivary
glands, reflecting contributions from various sources. Establishing correlations between blood and saliva
analyte concentrations is a common practice [229,230] . Recent research focuses on developing wearable
electrochemical biosensors for real-time saliva monitoring, particularly in glucose analysis for diabetes
diagnostics. Salivary glucose levels correlate with plasma levels, suggesting a potential painless and non-
intrusive approach to diabetes monitoring . However, challenges include the need for highly sensitive
[231]
sensors due to lower glucose concentrations in saliva, ensuring full biocompatibility for oral placement, and
addressing potential interference from elevated protein content or active compounds of saliva from food