The unique properties of stimuli-responsive polymers make them valuable for myriad applications, their use for biosensing and molecular diagnostics is reviewed here.

Stimuli-responsive polymer (SRP)-based nanoparticles and SRP/nanomaterial hybrids have myriad applications, we review their uses for chemical sensing and biosensing.

Poly(N-isopropylacrylamide)-co-(acrylic acid) (pNIPAm-co-AAc) microgels incorporated with CuS nanoparticles (CuSNPs) were synthesized and employed for nearinfrared (NIR) triggered photothermal killing of cancer cells. Cu 2+ was enriched in the microgels through deprotonation of the pNIPAm-co-AAc microgels at high solution pH. CuSNPs were subsequently generated within the pNIPAm-co-AAc microgels upon exposure to heat and S 2− . The solution of hybrid microgels showed an absorption peak in the NIR region (∼1000 nm). After demonstrating that the hybrid microgels were not cytotoxic, we showed that NIR excitation of the hybrid microgels could be used to kill HeLa cells. Almost 90% of the HeLa cells were killed when incubated with 400 μg/mL of the hybrid microgels and exposed to 808 nm laser light with a power density of 2 W/cm 2 for 10 min. While these materials show promise for photothermal therapy, they can also be incorporated into a hydrogel matrix that can be triggered to release small molecule drugs upon exposure to NIR wavelengths.

Silver nanoparticle (AgNP)-loaded poly(N-isopropylacrylamide)-co-acrylic acid (pNIPAm-co-AAc)-based microgels were generated and used to make etalons. The etalons were shown to exhibit optical properties that depended on the concentration of H2O2 in solution.

A sensor capable of quantifying both anti-SARS-CoV-2 spike receptor-binding domain (RBD) antibody levels and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus in saliva and serum was developed. This was accomplished by exploiting the enzymatic reaction of maltose and orthophosphate (PO 4 3− ) in the presence of maltose phosphorylase to generate an equivalent amount of glucose that was detected using a commercial glucometer test strip and a potentiostat. Important for this approach is the ability to generate PO 4 3− in an amount that is directly related to the concentration of the analytes. RBD-modified magnetic microparticles were used to capture anti-SARS-CoV-2 spike RBD antibodies, while particles modified with anti-SARS-CoV-2 nucleocapsid antibodies were used to capture SARS-CoV-2 nucleocapsid protein from inactivated virus samples. A magnet was used to isolate and purify the magnetic microparticles (with analyte attached), and alkaline phosphatase-conjugated secondary antibodies were bound to the analytes attached to the respective magnetic microparticles. Finally, through enzymatic reactions, specific amounts of PO 4 3− (and subsequently glucose) were generated in proportion to the analyte concentration, which was then quantified using a commercial glucometer test strip. Utilizing glucose test strips makes the sensor relatively inexpensive, with a cost per test of ∼US $7 and ∼US $12 for quantifying anti-SARS-CoV-2 spike RBD antibody and SARS-CoV-2, respectively. Our sensor exhibited a limit of detection of 0.42 ng/mL for anti-SARS-CoV-2 spike RBD antibody, which is sensitive enough to quantify typical concentrations of antibodies in COVID-19-infected or vaccinated individuals (>1 μg/mL). The limit of detection for the SARS-CoV-2 virus is 300 pfu/mL (5.4 × 10 6 RNA copies/mL), which exceeds the performance recommended by the WHO (500 pfu/ mL). In addition, the sensor exhibited good selectivity when challenged with competing analytes and could be used to quantify analytes in saliva and serum matrices with an accuracy of >94% compared to RT-qPCR.