Conjugated polymers have emerged as a versatile platform for biosensing due to their unique electronic, optical, and electrochemical properties. Their ability to facilitate charge transport, amplify signals, and interface with biological molecules makes them particularly suitable for electrochemical, optical, and field-effect transistor (FET)-based biosensors. The functionalization of these polymers with biorecognition elements, such as DNA, enzymes, or antibodies, further enhances their specificity and sensitivity in detecting target analytes.

Electrochemical biosensors leverage the conductive properties of conjugated polymers to transduce biochemical interactions into measurable electrical signals. The polymer backbone serves as both a scaffold for immobilizing bioreceptors and a medium for electron transfer. Polyaniline (PANI), polypyrrole (PPy), and poly(3,4-ethylenedioxythiophene) (PEDOT) are commonly used due to their high conductivity and environmental stability. Functionalization strategies often involve covalent bonding or electrostatic interactions to attach biorecognition elements. For example, PANI can be modified with carboxylic acid groups to enable covalent coupling with amine-terminated DNA probes. Enzymes such as glucose oxidase can also be entrapped within the polymer matrix during electropolymerization, allowing for direct electron transfer between the enzyme and electrode. Signal amplification is achieved through redox cycling or the incorporation of conductive nanomaterials like gold nanoparticles, which enhance electron transfer kinetics.

Optical biosensors based on conjugated polymers exploit their strong light-matter interactions, including fluorescence and absorbance changes upon binding with target molecules. Conjugated polymers with high quantum yields, such as polyfluorenes and polythiophenes, are particularly effective. These polymers exhibit amplified quenching or emission upon interaction with analytes due to exciton migration along the polymer chain. For DNA detection, single-stranded DNA probes labeled with a quencher can hybridize with target DNA, restoring fluorescence when displaced. Enzymatic reactions can also modulate optical signals; for instance, horseradish peroxidase catalyzes the oxidation of a substrate, producing a colored product detectable via absorbance changes. To improve sensitivity, Förster resonance energy transfer (FRET) pairs can be integrated, where energy transfer between the polymer and a fluorophore-labeled bioreceptor provides a ratiometric signal.

Field-effect transistor-based biosensors utilize conjugated polymers as the active channel material, where binding events modulate charge carrier mobility. Organic thin-film transistors (OTFTs) and electrolyte-gated transistors (EGTs) are common configurations. In these devices, bioreceptors are immobilized on the polymer surface, and analyte binding induces electrostatic or conformational changes that alter channel conductivity. For example, DNA hybridization can introduce negative charges, depleting hole carriers in a p-type polymer like PEDOT:PSS. Enzymatic reactions that generate ionic species, such as the production of H+ during urea hydrolysis by urease, further modulate the threshold voltage. Signal amplification is achieved through the inherent gain of transistors or by incorporating nanostructured polymers that increase surface area and interaction sites.

Functionalization strategies are critical for ensuring specificity and minimizing non-specific binding. Covalent immobilization via carbodiimide chemistry or click reactions provides stable linkages, while non-covalent methods like π-π stacking or avidin-biotin interactions offer flexibility. DNA aptamers, engineered for high affinity, are often preferred over antibodies due to their thermal stability and ease of synthesis. Enzymes are typically crosslinked onto the polymer surface or entrapped within hydrogels to retain activity. Additionally, molecular imprinting creates synthetic recognition sites within the polymer matrix, mimicking natural bioreceptors.

Signal amplification techniques are essential for detecting low-abundance analytes. In electrochemical sensors, catalytic nanomaterials like platinum nanoparticles or carbon nanotubes enhance redox reactions. Optical sensors benefit from plasmonic nanoparticles that locally enhance electromagnetic fields, while FET-based sensors exploit the high transconductance of polymers to amplify small interfacial changes. Multi-enzyme cascades and DNA walkers further improve sensitivity by generating multiple signal outputs per binding event.

Challenges remain in optimizing polymer stability, reproducibility, and integration into portable devices. Environmental factors such as pH, temperature, and ionic strength can affect performance, necessitating robust polymer designs. Future advancements may focus on multi-functional polymers that combine sensing, amplification, and self-calibration in a single material. By tailoring conjugated polymers for specific biosensing applications, their potential in diagnostics, environmental monitoring, and personalized medicine can be fully realized.

The versatility of conjugated polymers in biosensing lies in their tunable electronic and optical properties, compatibility with diverse functionalization strategies, and ability to amplify signals across different transduction mechanisms. Continued research into polymer synthesis, bioreceptor integration, and device engineering will further expand their applications in sensitive and selective biosensing platforms.