Attomolar-level detection of respiratory virus long-chain oligonucleotides based on FRET biosensor with upconversion nanoparticles and Au–Au dimer

Abstract

<p>Upconversion <a href="https://www-sciencedirect-com.eproxy.lib.hku.hk/topics/agricultural-and-biological-sciences/nanoparticle" title="Learn more about nanoparticles from ScienceDirect's AI-generated Topic Pages">nanoparticles</a> (UCNPs) are promising <a href="https://www-sciencedirect-com.eproxy.lib.hku.hk/topics/chemical-engineering/nanoprobe" title="Learn more about nanoprobes from ScienceDirect's AI-generated Topic Pages">nanoprobes</a> in DNA/RNA detection, such as respiratory viral <a href="https://www-sciencedirect-com.eproxy.lib.hku.hk/topics/biochemistry-genetics-and-molecular-biology/rna" title="Learn more about RNAs from ScienceDirect's AI-generated Topic Pages">RNAs</a>, and <a href="https://www-sciencedirect-com.eproxy.lib.hku.hk/topics/biochemistry-genetics-and-molecular-biology/small-interfering-rna" title="Learn more about siRNA from ScienceDirect's AI-generated Topic Pages">siRNA</a> in cancer. However, recent studies have indicated that the sensitivity of UCNP-based <a href="https://www-sciencedirect-com.eproxy.lib.hku.hk/topics/physics-and-astronomy/bioinstrumentation" title="Learn more about biosensors from ScienceDirect's AI-generated Topic Pages">biosensors</a> is restricted, ranging from picomolar to femtomolar level. Moreover, most of existing UCNP-based probes are only able to detect short-chain <a href="https://www-sciencedirect-com.eproxy.lib.hku.hk/topics/biochemistry-genetics-and-molecular-biology/oligonucleotide" title="Learn more about oligonucleotides from ScienceDirect's AI-generated Topic Pages">oligonucleotides</a>, which are not suitable for detection of long-chain <a href="https://www-sciencedirect-com.eproxy.lib.hku.hk/topics/chemistry/oligonucleotide" title="Learn more about oligonucleotides from ScienceDirect's AI-generated Topic Pages">oligonucleotides</a> in many real applications. In this work, we introduced a new UCNP-based <a href="https://www-sciencedirect-com.eproxy.lib.hku.hk/topics/physics-and-astronomy/resonance-fluorescence" title="Learn more about fluorescence resonance from ScienceDirect's AI-generated Topic Pages">fluorescence resonance</a> energy transfer (FRET) nanoprobe design composed of NaGdF₄:Yb³⁺, Er³⁺@NaGdF₄ core-shell UCNPs (csUCNPs) linking with Au–Au dimer to detect long-chain <a href="https://www-sciencedirect-com.eproxy.lib.hku.hk/topics/agricultural-and-biological-sciences/oligonucleotide" title="Learn more about oligonucleotides from ScienceDirect's AI-generated Topic Pages">oligonucleotides</a> of SARS-CoV-2 N-gene. Compared with typical single <a href="https://www-sciencedirect-com.eproxy.lib.hku.hk/topics/materials-science/gold-nanoparticle" title="Learn more about gold nanoparticles from ScienceDirect's AI-generated Topic Pages">gold nanoparticles</a> (AuNPs) in FRET biosensors, our theoretical investigation shows that a stronger <a href="https://www-sciencedirect-com.eproxy.lib.hku.hk/topics/chemistry/electromagnetic-field" title="Learn more about electromagnetic field from ScienceDirect's AI-generated Topic Pages">electromagnetic field</a> is generated in the Au–Au dimer where the <a href="https://www-sciencedirect-com.eproxy.lib.hku.hk/topics/physics-and-astronomy/plasmon" title="Learn more about plasmon from ScienceDirect's AI-generated Topic Pages">plasmon</a> resonance can enhance FRET efficiency and increase the working distance. Thus, the synergetic effect of plasmonic resonance and FRET enables a greater quenching efficiency (QE) of Au–Au dimer to UCNPs, which leads to more remarkable <a href="https://www-sciencedirect-com.eproxy.lib.hku.hk/topics/chemical-engineering/upconversion-luminescence" title="Learn more about upconversion luminescence from ScienceDirect's AI-generated Topic Pages">upconversion luminescence</a> (UCL) recovery for each target gene recognition. Importantly, our design significantly improved the limit of detection (LOD) to attomolar level, with a linear response ranging from 2 aM to 2 fM. Moreover, the clinical detection with inactivated SARS-CoV-2 samples was successfully performed with excellent specificity within 30 min using the developed UCNPs biosensors incorporated with Au–Au dimer. This UCNP biosensor based on Au–Au dimer strategy with ultra-sensitivity and good <a href="https://www-sciencedirect-com.eproxy.lib.hku.hk/topics/physics-and-astronomy/selectivity" title="Learn more about selectivity from ScienceDirect's AI-generated Topic Pages">selectivity</a> opens a new path for clinical diagnosis without target amplification and plays an instructive role in other virus diagnosis.</p>