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Jung et al. Soft Sci 2024;4:15 https://dx.doi.org/10.20517/ss.2024.02 Page 3 of 44

Table 1. Physiological reference range of metabolites and electrolytes in biofluids for individuals in good health (units: mM)
Biofluids Glucose Lactate Uric acid Sodium Potassium
Blood 3.9~5.6 [22,23] 0.5~1.5 [24,25] 0.2~0.42 [26,27] 135~150 [28-30] 5~6 [30-32]
[33-35] [36,37] [38] [28-30] [30-32]
Sweat 0.06~0.11 16~30 ~0.02 10~100 4~24
[38,39] [40] [41] [42,43] [42,43]
Saliva 0.03~0.1 0.09~0.13 0.17~0.23 8.7~217.3 2.6~18.3
[44] [45] [46] [47] [47]
Tear 0.06~0.3 1~5 0.07~0.16 120~170 6~42
[48-50] [51] [52,53] [54,55]
ISF 3.2~9.2 0.5~10 - 120~154 2.8~5.3
ISF: Interstitial fluid.

Table 2. Physiological reference range of metabolites and electrolytes in biofluids for individuals with diabetic chronic complications
(units: mM)
Biofluids Glucose Lactate Uric acid Sodium Potassium
Blood > 7 [22,23] 2~4 [25] > 0.42 (Men) [56] > 160 [57] > 5.1 [57]
[56] [57] [57]
> 0.34 (Women) < 135 < 3.5
[33-35] [36,37]
Sweat 0.01~1.00 0.01~1 - - -
[38,39] [43] [43]
Saliva 0.19~0.3 - - 23.9~271.9 7.2~24.5
[44]
Tear 0.4~1.4 - - - -
ISF 1.99~22.2 [50] - - - -
ISF: Interstitial fluid.

and renal diseases) [73-75] , and electrolytes [critical for identifying electrolyte disorders such as sodium (Na )
+
and potassium (K )] [76-78] . These sensors operate across various human biofluids, encompassing tears [79-82] ,
+
saliva, blood serum, interstitial fluid (ISF), and sweat [83,84] .

Among a number of methods for monitoring biomarkers related to DM, electrochemical analysis has been
[85]
widely investigated . This strategy, which offers a straightforward and quantitative approach, measures
electrochemical signals and converts them directly into concentrations of metabolites and electrolytes.
Consequently, it is the most commonly utilized method, generally relying on potentiometric [86-88] ,
amperometric [89-91] , and voltametric techniques [92-94] . Furthermore, electrochemical sensors are currently
gaining traction due to their miniaturization, low-power consumption instrumentation, and the potential
for implementation in wearable devices that enable simple, accurate, sensitive, selective, and low-cost
analytical procedures [95,96] .

This review offers a comprehensive overview of wearable sensor technology utilizing electrochemical
analysis for managing DM and its associated complications. The primary focus is on non-invasive and
minimally invasive electrochemical wearable sensors specifically engineered for detecting various
metabolites and electrolytes present in human biofluids. The initial section of the review delves into the
electrochemical sensing mechanisms applied to monitor biomolecules and electrolytes. This includes
discussions on the materials employed, such as enzymes, non-enzyme assays, polymer-based ion-selective
membranes (ISM), and the different sensing modes used for wearable electrochemical sensors. Following
that, the second section explored wearable electrochemical sensors, elucidating device designs specifically
designed for monitoring targeted metabolites and electrolytes in biofluids such as sweat, tears, saliva, and
ISF, aimed at enhancing the effectiveness of DM management. The subsequent section of the review focuses
on wearable sensor devices for a multiplexed monitoring platform. This involves chemical-
electrophysiological hybrid sensing systems, along with multiplexed electrochemical sensors that can
simultaneously monitor various biomarkers for effective DM management. Additionally, the review
explores machine learning (ML)-based multiplexed analysis methodologies specifically designed for the
efficient management of DM and its associated complications [Figure 1].