Bottom-Up Engineering of Responsive Hydrogel Materials for Molecular Detection and Biosensing

Molecular sensors respond to target molecules in their surroundings to detect and sometimes even quantify their concentrations. Traditionally comprised of small organic molecules or metal complexes, these technologies have been essential to biomedical and environmental monitoring, ensuring human health, safety, and general well-being. In the past two decades, analyte-responsive hydrogels have been an emerging technology receiving vast research attention worldwide. Hydrogels capable of detecting a vast array of analytes, including inorganic ions, carbohydrates, thiols, gases, biomolecules (nucleic acids and proteins), and even microorganisms such as bacteria and viruses, have been developed. With the added advantages of bottom-up design at the molecular level and biocompatibility, molecular detection using hydrogel sensors is typically simple to perform, and hydrogels can be integrated with electronic devices to enhance detection sensitivity, or with biomedical devices for in vitro and in vivo studies. Herein, we discuss a range of innovative strategies that have been developed for engineering hydrogel molecular sensors, with emphasis on “bottom-up” molecular engineering to achieve analyte selectivity and sensitivity.