Table 3.

Summarized key information on the applicability of different sensing platforms.

Technique	Advantages	Disadvantages	Potential for WBE Applications	Challenges in implementation	References
Indirect sensing (PCR, LAMP, genome sequencing and CRISPR)	Most commonly used for detecting nucleic acids; Precise and sensitive detection; Established protocols and standards.	Require centralized facilities, specialized equipment, and trained personnel; High cost; Time consuming.	Established methods for nucleic acid detection; Detection of SARS-CoV-2 RNA; Analysis of complex matrices (e.g., wastewater, biofluids).	False negatives; Interpretation of findings in terms of disease propagation and human health risks; Variability of strains in samples vs reference strains.	[20,26,36,61]
SERS based sensing (liquid SERS, paper-based SERS, microfluidic SERS, magnetic SERS)	Rapid, highly sensitive and low-cost detection; Wide range of SERS nanotags are already available; Great potential for field deployment.	Requires plasmonic substrates; Nanomaterial and SERS tag orientation induce large variability in scattering response.	Single molecule detection capability; Detection at environmentally relevant concentrations; Low-cost SERS active substrates for wastewater monitoring; Field diagnosis using handheld Raman systems.	Heterogeneity of SERS substrates; Weak SERS signals and similarity of SERS profiles of biomolecules require additional data analysis; Reproducibility; Detection at sub nanomolar concentrations in complex media (e.g., wastewater, biofluids).	[37,42,62]
Electrical approaches (FET sensing, electrochemical sensing)	Rapid, highly sensitive, low cost and real-time detection; Simple and portable instrumentation; Electrical signals unaffected by factors such as sample turbidity or interference from fluorescing compounds.	Low stability and reproducibility in physiological environments; Reduced sensitivity and specificity due to non-specific adsorption of interfering species.	Detection at environmentally relevant concentrations; Easy lab on a chip integration due to low power requirements; Portable instrumentation and compatibility with microfabrication technology for on-site analysis; Real-time detection with simple operation.	Operation in complex media (e.g., wastewater, biofluids) has several challenges including non-specific adsorption of interfering molecules, Debye screening effect in FET nanosensors, and stability of electrochemical signals under changing physiological conditions.	[[51], [52], [53],63]
Combined approaches (SEC sensing)	Highly sensitive and selective due to simultaneous acquisition of complementary electrochemical and spectroscopic data; Improved spectroscopic modality (e.g., SERS).	Requires advanced understanding of SEC mechanisms for accurate data interpretation; Incident light beam can affect the electrochemical results.	Single molecule detection capability; Overlapping signals of interfering molecules can be resolved using complementary data allowing detection in complex media (e.g., wastewater, biofluids).	Reproducibility of devices (e.g., EC-SERS substrates); Complex data interpretation and analysis; Improvement and miniaturization of instrumentation for on-site analysis	[57,58,64]