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Page 2 of 12                              Luo et al. Soft Sci 2024;4:7   https://dx.doi.org/10.20517/ss.2023.40



               INTRODUCTION
               Glucose, a vital molecule in the human body, plays a key role in biological cellular processes and clinical
               diagnoses. Usually, the human body maintains a blood glucose concentration of 4.4-6.6 mM, and
               excessively high or low blood glucose concentrations can cause various diseases, such as diabetes and
                           [1]
               hypoglycemia . Thus far, numerous glucose-detection approaches have been studied to fulfill the standard
               of clinical diagnosis and facilitate daily disease prevention. Among them, electrochemical glucose sensors
               are considered a promising approach to convert chemical signals into electrical signals owing to their good
                                                      [2,3]
               selectivity, high sensitivity, and compact size . Most of the existing electrochemical glucose biosensors
               utilize an enzyme (normally glucose oxidase enzyme) as the active component that reacts with and detects
               glucose molecules. However, these enzyme-based electrochemical biosensors are usually limited by enzyme
               conditions (for example, enzyme activity is directly affected by even slight changes in temperature or pH
               value) . Recently, non-enzyme-based electrochemical glucose biosensors that can easily detect glucose
                    [4,5]
               through electrochemical redox reactions have attracted considerable attention. These sensors are more
               robust and cost-effective compared to enzyme-based electrochemical biosensors .
                                                                                  [6,7]
               In the case of non-enzyme-based glucose sensors, development of electrode materials with good
               electrochemical activity and effective construction of the electrode system are key challenges from the
               perspective of improving their glucose detection performance. Notably, two-dimensional (2D) oxides offer
               attractive advantages in glucose-sensing applications owing to their unique electrochemical capabilities,
               relatively high surface area, and rapid electron mobility . Nevertheless, high energy consumption at the
                                                               [8,9]
               mechanically and electrically mismatched interface between active 2D oxides and the conductive substrate
               usually degrades the conversion rate of chemical signals to electrical signals, which limits the sensitivity and
               application range of 2D-oxide-based biosensors . We anticipate that these challenges can be addressed by
                                                        [10]
               directly growing 2D oxides on conductive substrates through physical/chemical deposition or wet chemical
                       [11]
               synthesis . However, the need for extreme fabrication conditions, including high temperatures and
               excessive chemical treatment, limits the practical application potential of these sensors.

               Recently, Ga-based liquid metals (Ga-LM) and related low-melting-point alloys with good fluidity, high
               conductivity, and good biocompatibility have attracted considerable attention for use in diverse
               applications, especially flexible electrodes and wearable sensors [12-14] . Particularly, the active and smooth
               surface of Ga-LM offers an ideal platform for the synthesis of 2D materials under mild growing
                        [15]
               conditions . For example, various 2D oxides can be grown on the LM surface by inducing a galvanic
               reaction between the metal atoms on the LM surface and the surrounding ions . Owing to the chemical
                                                                                   [16]
               compatibility of the galvanic reaction and extensibility of post-processing, the 2D oxides synthesized on LM
               templates are rich and diverse in species. Notably, a 2D oxide layer grown in this manner covers and
               naturally comes into contact with the highly conductive LM, resulting in the formation of a perfect
               mechanically and electrically matched interface between the 2D oxides and the conductive substrate [17-20] .
               This construction scheme can be applied directly to form an integrated electrode decorated with active
               materials in electrochemical devices. In addition, the deformability of LM imparts high flexibility to the
               integrated electrode. Therefore, through this strategy, it is believed that a high-performance electrochemical
               glucose biosensor with good interfacial interaction and flexibility can be achieved based on the combination
               of 2D oxides and LM.


               To validate this concept, cuprous oxide, a representative semiconductive 2D oxide used in glucose sensors
               owing  to  its  strong  catalytic  activity,  stable  structure,  and  non-toxicity [21,22] , is  selected  as  the
               electrochemically  active  material  herein  to  construct  a  non-enzyme-based  glucose  sensor.  The
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