High-Sensitivity High-Throughput Detection of Nucleic Acid Targets on Metasurface Fluorescence Biosensors

Abstract

Worldwide infection disease due to SARS-CoV-2 is tremendously affecting our daily lives. High-throughput detection methods for nucleic acids are emergently desired. Here, we show high-sensitivity and high-throughput metasurface fluorescence biosensors that are applicable for nucleic acid targets. The all-dielectric metasurface biosensors comprise silicon-on-insulator nanorod array and have prominent electromagnetic resonances enhancing fluorescence emission. For proof-of-concept experiment on the metasurface biosensors, we have conducted fluorescence detection of single-strand oligoDNAs, which model the partial sequences of SARS-CoV-2 RNA indicated by national infection institutes, and succeeded in the high-throughput detection at low concentrations on the order of 100 amol/mL without any amplification technique. As a direct detection method, the metasurface fluorescence biosensors exhibit high performance.

Rapid Detection of Attomolar SARS-CoV-2 Nucleic Acids in All-Dielectric Metasurface Biosensors

“…We went through nanolithography from electron-beam drawing of dry etching of Si on insulator and prepared the metasurface substrates that were almost faithful to the design. The detailed procedures were described in the previous publications [ 18 , 19 ].…”

“…We examined two amplification methods of LAMP in Figure 1 b and PCR in Figure 1 c. The PCR and LAMP were one-step processes from the amplification to the FL-probe hybridization. We also incorporated the efficient FL-detection biosensors, that is, the all-dielectric metasurface biosensors [ 18 , 19 ]. In this comprehensive study, we reached an extremely low target concentration of 6 aM within 1 h amplification time, which strongly suggests that this scheme is capable of realizing sub-aM SARS-CoV-2 RNA detection.…”

Advanced high-throughput biosensor-based diagnostic approaches for detection of severe acute respiratory syndrome-coronavirus-2

“…Moreover, the meta -surface fluorescence biosensors show high performance due to the direct detection procedure. For the feasibility study, Iwanaga (2021) experimented on the meta -surface biosensors and exhibit the fluorescence detection of single-stranded oligo DNAs which are partly alike to SAR-CoV-2 RNA designated by national infection institutes. Furthermore, without any amplification techniques they are succeeded in high–throughput detection of a nucleic acid target at a low concentration level, that is, 100 amol/mL.…”

Two-Way Detection of COVID-19 Spike Protein and Antibody Using All-Dielectric Metasurface Fluorescence Sensors

“…Here, we address proof-of-concept experiments for the quantitative detection of COVID-19 spike proteins and Abs. When implementing sandwich assays to detect Ab–protein–Ab complexes, it becomes possible to set the proteins or Abs to be a target in the assay, meaning that two-way detection can be realized in one platform through the employment of all-dielectric metasurface fluorescence (FL) sensors [ 9 , 10 , 11 ]. The configurations of the two-way assay are schematically illustrated in Figure 1 a,b.…”