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Page 14 of 20 Li et al. Soft Sci 2023;3:37 https://dx.doi.org/10.20517/ss.2023.30

monitoring electrocorticogram (ECoG) signals [Figure 8H]. However, there is still a risk of leakage of raw
LMs in implantable bioelectrodes. Therefore, we propose that implantable bioelectrodes based on LM-
elastomer composites should be given more attention in future research, as they have the potential to
address the issue of LM leakage.

CONCLUSIONS AND OUTLOOKS
Unique properties such as fluidity, metallic electrical/thermal conductivity, and low toxicity of LMs
contribute to their broadening applications of biosensors in the healthcare area. This review illustrated the
recent advances in flexible and wearable LM-based biosensors, including interconnects, pressure sensors,
strain sensors, temperature sensors, and implantable electrodes. However, there remain some challenges
and opportunities associated with Ga-based biosensors, which are shown in Figure 9 and summarized
below:

(1) Despite that many works have reported the low cytotoxicity of Ga and its alloys, it deserves to be noted
that some reports revealed that Ga-based LMs are toxic at the cellular level [136,137] , and the threshold
concentrations of Ga, Ga-based alloys, and Ga ions need to be systematically investigated by conducting in
vitro/vivo experiments. An important consideration when using bulk Ga-based LMs in biomedical
applications is whether the Ga ions released from these materials can be absorbed through the skin . In
[127]
addition, further research is needed to investigate the metabolic process and potential toxicity mechanisms
of Ga ions in the body .For instance, further investigations are warranted to elucidate the mechanism by
[138]
which Ga ions induce damage to normal cellular components.

(2) Advanced connection technologies should be further developed to connect flexible LM biosensors to
rigid electrical components. Currently, most LM-based biosensors use rigid metal wires to connect the
encapsulated LM patterns with the external printed circuit board. However, the soft-rigid connection
between the LM patterns and the wires is a weak point due to the mechanical mismatch between the two
materials. For example, the rigid metal wire is very easy to be pulled out from the polymer. Besides, LMs
would leak along the interface between the rigid metal wire and polymer while the biosensor is under long-
term usage. Therefore, it is urgent to develop a more reliable encapsulation method to connect LM patterns
and rigid electrical components. We recommend that the conductive LM-elastomers possess the potential
to address the connection problem.

(3) The fluidic nature of LMs makes them susceptible to leakage from the encapsulating polymer, which can
lead to contamination. This risk is exacerbated by stress concentrations generated by external forces during
long-term stretching or folding. The leaked Ga-based LM can solder with electrical components without
heating, which is destructive for electronic circuits. To prevent leakage of LM during long-term usage,
effective encapsulation measures should be taken. Additionally, controlling the fluidity and wettability of
LMs through oxidation, mixing with solid metal microparticles, and the development of novel LM-
elastomer composites are effective strategies to address this problem.

(4) The resolution of LM-based biosensor patterns is another area that requires attention. Although LM
nano-patterns with ~500 nm line width have been fabricated using lithography, the resolution is relatively
lower than that achievable on a silicon wafer. High resolution is crucial for the integration of LM-based
biosensors into flexible electronics. Therefore, future research should focus on developing precision
instruments and optimizing processes, such as oxide formation and phase transition, during the patterning
process to improve the resolution of LM patterns.