Biosensors as alternative or supplementary solutions are being developed based on plasmonic nanomaterials. Yet there are false positive or negative reports, especially for the early stages. The reference diagnosis for SARS-CoV-2 is based on reverse transcription polymerase chain reaction (RT-PCR) 30.

With further biofunctionalization with antibody, we also demonstrated the performance of our devices for SARS-CoV-2 detection. These encoded agglomerates were further encapsulated with a silica shell to protect them from oxidation, contaminations and increase the stability for a long period of time thanks to the unique properties of the SiO 2 layer ( e.g., surface chemistry, biocompatibility, optical transparency, and colloidal stability). With the help of controlled agglomeration, we improved the percentage of hot spots which guaranteed the extremely high Raman enhancement. We systematically studied the fundamental aspects and optimized the thiol silver bonding for encoding silver nanoparticles. Here we present a controllable design and synthesis of a nanostructure confining encoded silver nano-agglomerates inside silica coating 2). The design and controllable synthesis of nanostructures are critical steps towards implementing SERS in medicine 12. However, producing homogenous, sensitive and reproducible SERS platforms is the main difficulty which hampers SERS bioapplications 26, with many efforts made in the design and synthesis of uniform nanomaterials 27, 28, 29. Thus SERS has been an effective tool to realize qualitative and quantitative detection of biological species 12, 17, 18, 19, including micro RNA analysis 20, enzyme 21, hydrogen peroxide 22, staphylococcal enterotoxin B 23 and other diseases biomarkers 24, 25 with gold nanowire, gold-silver alloy NPs and gold-MnO 2 coreвЂ“shell, hollow gold nanospheres and gold nanostar and nanosphere separately. SERS as a non-destructive technology provides chemical information in aqueous environments. Gold and silver are the most commonly applied materials for SERS substrates, as they offer high field enhancement in the visible to near infrared range due to their high density of electrons 16. Thus, hot spots have critical importance when designing a SERS nanostructure. Moreover, this enhancement can be further increased up to 10 15 orders of magnitude to SERS signal by hot spots 15, which are caused by the plasmonic coupling of the particles when they are very close to each other 14. In general, average enhancement factors for typical SERS substrates are amplified by 10 6 to 10 8 orders of magnitude comparing with their Raman signature 14. SERS signals can be collected from the molecules which are in close proximity of nanometallic surfaces with confined LSPR 13. Surface enhanced Raman spectroscopy (SERS) also depends on plasmonic platforms 12.

Based on their optical properties, flexible functionalized nanomaterials have already been applied in sensing varieties of biomolecules, including biomarkers for cancer 8, enzyme 9, DNA 10, and other biological species 11. This LSPR phenomenon limits nanomaterials absorbing specific region of light, and makes the nanomaterials sensitive to the modifications of physical properties of nanomaterials and their environments showing plasmonic absorption shifts 5, 6, 7. This diagnosis field takes benefits from the design and synthesis of nanomaterials 2, 3, 4, especially noble metal nanomaterials showing localized surface plasmon resonance (LSPR) properties. Nanosystems has been widely developed in sensor devices for diagnostics, in vitro and in vivo diagnosis 1.

The design for precise diagnosis is critical to human health as for preventing pandemics or other biothreads.

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