With COVID-19 widespread worldwide, people are still struggling to develop faster and more accurate diagnostic methods. Here we demonstrated the label-free detection of SARS-CoV-2 spike protein by employing a SARS-CoV-2 spike antibody-conjugated phase-shifted long-period fiber grating (PS-LPFG) inscribed with a CO
2
laser. At a specific cladding mode, the wavelength separation (
λ
D
) between the two split dips of a PS-LPFG varies with the external refractive index, although it is virtually insensitive to ambient temperature variations. To detect SARS-CoV-2 spike protein, SARS-CoV-2 spike antibodies were immobilized on the fiber surface of the fabricated PS-LPFG functionalized through chemical modification. When exposed to SARS-CoV-2 spike protein with different concentrations, the antibody-immobilized PS-LPFG exhibited the variation of
λ
D
according to the protein concentration, which was caused by bioaffinity binding-induced local changes in the refractive index at its surface. In particular, we also confirmed the potential of our sensor for clinical application by detecting SARS-CoV-2 spike protein in virus transport medium. Moreover, our sensor could distinguish SARS-CoV-2 spike protein from those of MERS-CoV and offer efficient properties such as reusability and storage stability. Hence, we have successfully fabricated a promising optical transducer for the detection of SARS-CoV-2 spike protein, which can be unperturbed by external temperature disturbances.
We measured and analyzed the brain waves to observe the characteristics of human drowsiness. The basic method is to analyze the EEG(Electroencephalography) signals from subjects according to the frequency bands. It has been reported that alpha waves are related to a wakefulness state, an eye closure state and a state that begins to sleep. In this study, therefore, we restricted the frequency band for analyzing to between 8 and 13Hz called brain's alpha waves. We observed which components had a stronger influence on human drowsiness among the restricted frequency band and represented the experimental results to analyze using the power spectrum method.
The label-free detection of SARS-CoV-2 spike protein is demonstrated by using slightly tapered no-core fiber (ST-NCF) functionalized with ACE2. In the fabricated sensor head, abrupt changes in the mode-field diameter at the interfaces between single-mode fiber and no-core fiber excite multi-guided modes and facilitate multi-mode interference (MMI). Its slightly tapered region causes the MMI to be more sensitive to the refractive index (RI) modulation of the surrounding medium. The transmission minimum of the MMI spectrum was selected as a sensor indicator. The sensor surface was functionalized with ACE2 bioreceptors through the pretreatment process. The ACE2-immobilized ST-NCF sensor head was exposed to the samples of SARS-CoV-2 spike protein with concentrations ranging from 1 to 10
4
ng/mL. With increasing sample concentration, we observed that the indicator dip moved towards a longer wavelength region. The observed spectral shifts are attributed to localized RI modulations at the sensor surface, which are induced by selective bioaffinity binding between ACE2 and SARS-CoV-2 spike protein. Also, we confirmed the capability of the sensor head as an effective and simple optical probe for detecting antigen protein samples by applying saliva solution used as a measurement buffer. Moreover, we compared its detection sensitivity to SARS-CoV-2 and MERS-CoV spike protein to examine its cross-reactivity. In particular, we proved the reproducibility of the bioassay protocol adopted here by employing the ST-NCF sensor head reconstructed with ACE2. Our ST-NCF transducer is expected to be beneficially utilized as a low-cost and portable biosensing platform for the rapid detection of SARS-CoV-2 spike protein.
Graphical abstract
Supplementary Information
The online version contains supplementary material available at 10.1007/s00604-022-05413-3.
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