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

Abstract

COVID-19 (or SARS-CoV-2) has deeply affected human beings worldwide for over two years, and its flexible mutations indicate the unlikeliness of its termination in a short time. Therefore, it is important to develop a quantitative platform for direct COVID-19 detection and human status monitoring. Such a platform should be simpler than nucleic acid amplification techniques such as polymerase chain reaction, and more reliable than the disposable test kits that are based on immunochromatography. To fulfill these requirements, we conducted proof-of-concept experiments for the quantitative detection of spike glycoprotein peptides and antibodies in one platform, i.e., all-dielectric metasurface fluorescence (FL) sensors. The high capability to enhance FL intensity enabled us to quantitatively measure the glycoproteins and antibodies more efficiently compared with the previous methods reported to date. Furthermore, the intrinsic limit of detection in the metasurface FL sensors was examined via confocal microscopy and found to be less than 0.64 pg/mL for glycoprotein peptides. Moreover, the sensors had a dynamic range more than five orders that of the target concentrations, indicating extremely high sensitivity. These two-way functions of the metasurface FL sensors can be helpful in reducing daily loads in clinics and in providing quantitative test values for proper diagnosis and cures.

Robust Detection of Cancer Markers in Human Serums Using All-Dielectric Metasurface Biosensors

“…In the semi-log plots, it is difficult to see the changes in FL intensity at low concentrations below 1 ng/mL; however, the linear plots in the insets exhibit the scaled responses of the metasurface biosensors, even at the range that is 25-fold smaller than the clinical criterion. We refer to that of the dynamic range, which is mainly limited by the performance of the uncooled CCD camera; indeed, a confocal FL microscopy enabled us to access much lower concentrations when we detected the spike proteins of SARS-CoV-2 [ 21 ].…”

“…Unbound CEA-sandwich bodies were rinsed with the PBS-T. Afterwards, the FL imaging was conducted from the top of metasurface biosensor; the optical configuration of the biosensor has been described in previous publications [ 20 , 21 ].…”

“…The MF chip was made of polydimethylsiloxane (PDMS), which was transparent to visible light and was designed to have six MF paths in accordance with the six metasurface areas ( Figure 1 c). Inlet and outlet holes were introduced at both ends of each MF path to facilitate connecting from the outside; this can be seen in previous reports [ 20 , 21 ]. The PDMS was naturally absorbed on the metasurface substrate, enabling us to flow the liquid reagents.…”

“…Accordingly, biosensors applicable to cancer markers were often tested for their robustness using human serums [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. All-dielectric metasurface biosensors [ 18 , 19 , 20 , 21 ] and plasmon–photon hybrid metasurface biosensors [ 22 ] were recently reported as efficient fluorescence (FL) biosensors. Figure 1 a,b illustrates two situations where sandwich complexes of antibody (Ab)—antigen—Ab are formed.…”

Metasurface Biosensors Enabling Single-Molecule Sensing of Cell-Free DNA

“…34 Furthermore, robust detections of CEA and PSA in human serums were recently shown. 33 Thus, it is expected that the metasurface FL biosensors can significantly reinforce the efficiency of FL detection when they are combined with other biosensing techniques, such as ordinary PCR. However, it has not yet been examined whether the metasurface biosensors are capable of detecting a single target molecule.…”