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. 2025 Aug 19;15(36):29267–29283. doi: 10.1039/d5ra03897a

Table 1. Classification and performance characteristics of biosensors for infectious disease detection.

Type Specification Advantages Disadvantages References
Electrochemical
Voltametric Measures current while varying the potential over time also includes Differential pulse voltammetry (DPV) and Cyclic voltammetry (CV) These systems offer high sensitivity, low cost, portability, and fast response with minimal sample use Stable surface modifications and complex protocols are needed, and biological components may limit performance and need complex indicators 1
Amperometric Measures current at constant potential, proportional to electroactive species concentration Facilitates the measurement of analytes. Retains the general benefits of electrochemical biosensors Shares general disadvantages: complexity in production, signal interference, and potential enzyme inhibition 1, 4 and 50
Potentiometric Measures potential between electrodes at zero current, reflecting analyte concentration or activity Good selectivity, sensitive, stable reference systems, low power consumption, noninvasive potential Limited to ions and certain analytes, affected by ionic strength or matrix composition, production and calibration complexity 1, 4 and 5
Impedimetric Measures impedance of electrode-solution interface (e.g., Electrochemical impedance spectroscopy (EIS)) Label-free detection allows sensitive, real-time biomolecular analysis and is suitable for miniaturization and adaptable use Temperature and matrix effects, complex interpretation, surface modification required and exposure to environmental noise 1, 18 and 51
Conductometric Measures changes in conductivity near the electrode due to biochemical reaction Easy setup, rapid feedback, wide detection range, ideal for small sample sizes and complex matrices Requires signal amplification, limited specificity, temperature and pH dependent 1 and 5
Other types (Organic electrochemical transistor (OECT), photoelectrochemical, and electrochemiluminescent sensors) Each uses specialized electrical or light-based detection principles Enhanced sensitivity, integration with optical/electronic systems, suitable for multiplexed detection and portable formats Integration and design complexity, high cost of specialized parts, need for advanced production 1
Optical
Surface plasmon resonance (SPR) Measures refractive index shifts at a metal–liquid interface due to biomolecular binding High sensitivity, real-time monitoring, label-free, kinetic, and affinity analysis possible Expensive instrumentation, limited to surface interactions, requires stable surface functionalization, sensitive to temperature and bulk refractive index changes 52
Ellipsometry Measures changes in light polarization upon binding, precise surface analysis Ultrasensitive to thin layers, label-free, suitable for surface binding studies Requires clean, reflective surfaces, complex data interpretation 53
Absorbance/reflectance Measures light absorbed/reflected due to analyte–enzyme/color interaction Simple setup, cost-effective, compatible with basic lab equipment Lower sensitivity, prone to interference, limited dynamic range 54
Scanning angle reflectometry (SAR) Measures angle-dependent reflectance to analyze refractive index and layer thickness High precision for layer thickness and surface concentration, label-free Needs angular scanning setup, less portable, sensitive to vibrations 55
Chemiluminescence/luminescence Detects light emitted from enzyme-catalyzed chemiluminescence or bioluminescent reactions Very high sensitivity, low background noise, does not require excitation source Limited enzyme stability, single-use, reagent dependent, short-lived signal duration 56
Fluorescence resonance energy transfer (FRET) Monitors energy transfer between two fluorophores in close proximity Excellent for molecular interaction mapping, real-time detection, high spatial resolution Requires dual labeling, distance dependent, expensive reagents, photobleaching of fluorophores affects performance 57
Total internal reflection fluorescence (TIRF) Uses evanescent field to excite fluorophores near surface only High surface specificity, low background noise, excellent for membrane or surface studies Only detects events near surface (∼100–200 nm), requires precise optical alignment 58
Optical waveguide light mode spectroscopy (OWLS) Measures refractive index changes at waveguide surface Real-time, label-free, suitable for kinetic and concentration measurements Requires waveguide integration, niche applications, costly instruments 59
Interferometry (Mach–Zehnder interferometer, biolayer interferometry) Measures phase shifts due to biomolecular binding on surface Real-time, label-free, highly sensitive, suitable for kinetic profiling Sensitive to temperature fluctuations and optical drift, requires stable operating environment 60 and 61
Piezoelectric
Bulk acoustic wave (BAW) (includes QCM, TSM, PQC) Utilizes shear or longitudinal acoustic waves that propagate through the piezoelectric substrate; binding of biomolecules induces a frequency shift proportional to mass High sensitivity to mass changes, real-time and label-free detection, suitable for biochemical liquid samples Fragile at high frequency, sensitive to viscosity and temperature, requires surface functionalization 62, 63 and 43
QCM: measures changes in resonance frequency on crystal surface
TSM: detects changes through shear vibration, suited for liquids
PQC: variant of QCM using AT-cut crystals, often interchangeable in biosensing. Used interchangeably with QCM in biosensing literature due to shared operational principles
Surface acoustic wave (SAW) Surface-propagated acoustic waves interact with biomolecules on the sensor surface, changes in wave velocity/attenuation indicate binding Extremely sensitive to surface interactions, fast response time, ideal for small molecule/pathogen detection, label-free Sensitive to ambient temperature and humidity, complex and costly fabrication, limited robustness 62