Over the past decades, biosensors, a class of physicochemical detectors sensitive to biological analytes, have drawn increasing interest, particularly in light of growing concerns about human health. Functional polymeric materials have been widely researched for sensing applications because of their structural versatility and significant progress that has been made concerning their chemistry, as well as in the field of nanotechnology. Polymeric nanoparticles are conventionally used in sensing applications due to large surface area, which allows rapid and sensitive detection. On the macroscale, hydrogels are crucial materials for biosensing applications, being used in many wearable or implantable devices as a biocompatible platform. The performance of both hydrogels and nanoparticles, including sensitivity, response time, or reversibility, can be significantly altered and optimized by changing their chemical structures; this has encouraged us to overview and classify chemical design strategies. Here, we have organized this review into two main sections concerning the use of nanoparticles and hydrogels (as polymeric structures) for biosensors and described chemical approaches in relevant subcategories, which act as a guide for general synthetic strategies.

Stress biomarkers such as hormones and neurotransmitters in bodily fluids can indicate an individual’s physical and mental state, as well as influence their quality of life and health. Thus, sensitive and rapid detection of stress biomarkers (e.g., cortisol) is important for management of various diseases with harmful symptoms, including post-traumatic stress disorder and depression. Here, we describe rapid and sensitive cortisol detection based on a conducting polymer (CP) nanotube (NT) field-effect transistor (FET) platform. The synthesized polypyrrole (PPy) NT was functionalized with the cortisol antibody immunoglobulin G (IgG) for the sensitive and specific detection of cortisol hormone. The anti-cortisol IgG was covalently attached to a basal plane of PPy NT through an amide bond between the carboxyl group of PPy NT and the amino group of anti-cortisol IgG. The resulting field-effect transistor-type biosensor was utilized to evaluate various cortisol concentrations. Cortisol was sensitively measured to a detection limit of 2.7 × 10⁻¹⁰ M (100 pg/mL), with a dynamic range of 2.7 × 10⁻¹⁰ to 10⁻⁷ M; it exhibited rapid responses (<5 s). We believe that our approach can serve as an alternative to time-consuming and labor-intensive health questionnaires; it can also be used for diagnosis of underlying stress-related disorders.

Organic interfacial compounds (OICs) are required as linkers for the highly stable and efficient immobilization of bioprobes in nanobiosensors using 2D nanomaterials such as graphene. Herein, we first demonstrated the fabrication of a field‐effect transistor (FET) via a microelectromechanical system process after covalent functionalization on large‐scale graphene by introducing oligo(phenylene‐ethynylene)amine (OPE). OPE was compared to various OICs by density functional theory simulations and was confirmed to have a higher binding energy with graphene and a lower band gap than other OICs. OPE can improve the immobilization efficiency of a bioprobe by forming a self‐assembly monolayer via anion‐based reaction. Using this technology, Magainin I‐conjugated OGMFET (MOGMFET) showed a high sensitivity, high selectivity, with a limit of detection of 10⁰ cfu mL⁻¹. These results indicate that the OPE OIC can be applied for stable and comfortable interfacing technology for biosensor fabrication.