Nanophotonics has been widely utilized in enhanced molecularspectroscopy or mediated chemical reaction, which has major applications in the field of enhancing sensing and enables opportunities in developing healthcare monitoring. This review presents an updated overview of the recent exciting advances of plasmonic biosensors in the healthcare area. Manufacturing, enhancements and applications of plasmonic biosensors are discussed, with particular focus on nanolisted main preparation methods of various nanostructures, such as chemical synthesis, lithography, nanosphere lithography, nanoimprint lithography, etc., and describing their respective advances and challenges from practical applications of plasmon biosensors. Based on these sensing structures, different types of plasmonic biosensors are summarized regarding detecting cancer biomarkers, body fluid, temperature, gas and COVID-19. Last, the existing challenges and prospects of plasmonic biosensors combined with machine learning, mega data analysis and prediction are surveyed.

The synthesis of nanostructured surfaces and thin films has potential applications in the field of plasmonics, including plasmon sensors, plasmon-enhanced molecular spectroscopy (PEMS), plasmon-mediated chemical reactions (PMCRs), and so on. In this article, we review various nanostructured surfaces and thin films obtained by the combination of nanosphere lithography (NSL) and physical vapor deposition. Plasmonic nanostructured surfaces and thin films can be fabricated by controlling the deposition process, etching time, transfer, fabrication routes, and their combination steps, which manipulate the formation, distribution, and evolution of hotspots. Based on these hotspots, PEMS and PMCRs can be achieved. This is especially significant for the early diagnosis of hepatocellular carcinoma (HCC) based on surface-enhanced Raman scattering (SERS) and controlling the growth locations of Ag nanoparticles (AgNPs) in nanostructured surfaces and thin films, which is expected to enhance the optical and sensing performance.

In the present study, a sunflower-like nanostructure array composed of a series of synaptic nanoparticles and nanospheres was manufactured through an efficient and low-cost colloidal lithography technique. The primary electromagnetic field contribution generated by the synaptic nanoparticles of the surface array structures was also determined by a finite-difference time-domain software to simulate the hotspots. This structure exhibited high repeatability and excellent sensitivity; hence, it was used as a surface-enhanced Raman spectroscopy (SERS) active substrate to achieve a rapid detection of ultra-low concentrations of Alpha-fetoprotein (AFP). This study demonstrates the design of a plasmonic structure with strong electromagnetic coupling, which can be used for the rapid detection of AFP concentration in clinical medicine.