Quantification of caffeine in coffee cans using electrochemical measurements, machine learning, and boron-doped diamond electrodes.

Electrochemical measurements, which exhibit high accuracy and sensitivity under low contamination, controlled electrolyte concentration, and pH conditions, have been used in determining various compounds. The electrochemical quantification capability decreases with an increase in the complexity of the measurement object. Therefore, solvent pretreatment and electrolyte addition are crucial in performing electrochemical measurements of specific compounds directly from beverages owing to the poor measurement quality caused by unspecified noise signals from foreign substances and unstable electrolyte concentrations. To prevent such signal disturbances from affecting quantitative analysis, spectral data of voltage-current values from electrochemical measurements must be used for principal component analysis (PCA). Moreover, this method enables highly accurate quantification even though numerical data alone are challenging to analyze. This study utilized boron-doped diamond (BDD) single-chip electrochemical detection to quantify caffeine content in commercial beverages without dilution. By applying PCA, we integrated electrochemical signals with known caffeine contents and subsequently utilized principal component regression to predict the caffeine content in unknown beverages. Consequently, we addressed existing research problems, such as the high quantification cost and the long measurement time required to obtain results after quantification. The average prediction accuracy was 93.8% compared to the actual content values. Electrochemical measurements are helpful in medical care and indirectly support our lives.

Metal deposition and shape reproduction at biological temperatures on cell-level samples.

The use of metal deposition has been limited to a limited number of applicable samples due to the increased temperature caused by accelerated electron impact on the substrate surface. The surfaces of various biological samples have a nanoscale structure with specific properties, which have been simulated in numerous studies. However, no examples of nano/microscale reproductions of biological surface features have used moulds. In this study, a mould that imitates the surface shape of a cellular-level biological material was fabricated, for the first time, and the shape was successfully reproduced using the mould. Al thin films were deposited on bovine sperm using magnetron sputtering without thermal denaturation with a cathode operating at a biological temperature. It is difficult to deposit films used as metal coatings on pre-treated biological materials at temperatures below 40 °C during evaporation. The Al thin film was peeled off and used as a mould to reproduce the shape of the sperm with high accuracy using a polymer. The results of this study represent a major innovation in reproducible biomimetic moulding technology, demonstrating biological temperature sputtering. We expect our non-destructive metal deposition and metal nano-moulding methods for biological samples to be the basis for the effective utilization of various biological structures.

Reversible Thermo-Responsive Valve for Microfluidic Paper-Based Analytical Devices.

Fluid control on a paper channel is necessary for analysis with multiple reagents, such as enzyme-linked immunosorbent assay (ELISA) in microfluidic paper-based analytical devices (µPADs). In this study, a thermo-responsive valve was fabricated by polymerizing N-isopropylacrylamide on a PVDF porous membrane by plasma-induced graft polymerization. The polymerized membrane was observed by scanning electron microscopy (SEM), and it was confirmed that more pores were closed at temperatures below 32 °C and more pores were opened at temperatures above 32 °C. Valve permeability tests confirmed that the proposed polymerized membrane was impermeable to water and proteins at temperatures below 32 °C and permeable to water at temperatures above 32 °C. The valve could also be reversibly and repeatedly opened and closed by changing the temperature near 32 °C. These results suggest that plasma-induced graft polymerization may be used to produce thermo-responsive valves that can be opened and closed without subsequent loss of performance. These results indicate that the thermo-responsive valve fabricated by plasma-induced graft polymerization could potentially be applied to ELISA with µPADs.

High-Density and Monodisperse Electrochemical Gold Nanoparticle Synthesis Utilizing the Properties of Boron-Doped Diamond Electrodes.

Owing to its simplicity and sensitivity, electrochemical analysis is of high significance in the detection of pollutants and highly toxic substances in the environment. In electrochemical analysis, the sensitivity of the sensor and reliability of the obtained signal are especially dependent on the electrode characteristics. Electrodes with a high density of nanomaterials, which exhibit excellent activity, are useful as sensor substrates for pollutant detection. However, the effective placement of high-density nanomaterials requires a high degree of control over the particle size, particle shape, and distance between the particles on the substrate. In this study, we exploited the properties of boron-doped diamond (BDD) electrodes, which have a wide potential window, and succeeded in coating a highly dense layer of gold nanoparticles (AuNPs) at high potential. The AuNP-modified BDD (AuNP-BDD) electrodes comprising less than 100 nm AuNPs at a density of 125 particles/µm were electrochemically synthesized over a short period of 30-60 s. The AuNP-BDD electrodes were applied for detecting arsenic, which is one of the most abundant elements, and exhibited a limit of detection of 0.473 ppb in solution.

Surface Plasmon Resonance (SPR)- and Localized SPR (LSPR)-Based Virus Sensing Systems: Optical Vibration of Nano- and Micro-Metallic Materials for the Development of Next-Generation Virus Detection Technology.

The global damage that a widespread viral infection can cause is evident from the ongoing COVID-19 pandemic. The importance of virus detection to prevent the spread of viruses has been reaffirmed by the pandemic and the associated social and economic damage. Surface plasmon resonance (SPR) in microscale and localized SPR (LSPR) in nanoscale virus sensing systems are thought to be useful as next-generation detection methods. Many studies have been conducted on ultra-sensitive technologies, especially those based on signal amplification. In some cases, it has been reported that even a low viral load can be measured, indicating that the virus can be detected in patients even in the early stages of the viral infection. These findings corroborate that SPR and LSPR are effective in minimizing false-positives and false-negatives that are prevalent in the existing virus detection techniques. In this review, the methods and signal responses of SPR and LSPR-based virus detection technologies are summarized. Furthermore, this review surveys some of the recent developments reported and discusses the limitations of SPR and LSPR-based virus detection as the next-generation detection technologies.

Plasmon Nanocomposite-Enhanced Optical and Electrochemical Signals for Sensitive Virus Detection.

The social impact of virus spread is immeasurable. Vaccine prophylaxes take considerable time to develop because clinical trials are required. The best initial response to an emerging virus is establishing a virus detection technology adapted by simply preparing virus-specific antibodies. A virus detection system that detects two signals from one analyte has been developed to detect the target virus more sensitively and reliably. Plasmon regions on the surface of nanoparticles are effective in enhancing optical and electrochemical signals. Thus, CdSeTeS quantum dots (QDs) have been used as optical and electrochemical signal-generating materials. In contrast, gold nanoparticle-magnetic nanoparticle-carbon nanotube (AuNP-MNP-CNT) nanocomposites are used for the magnetic separation of the virus from interferences and for signal enhancement. In the presence of the target virus, the QDs optically show a virus concentration-dependent fluorescence enhancement effect due to the localized surface plasmon resonance (LSPR) of AuNPs. Regarding the electrochemical signal, Cd ions eluted by acid degradation of the QDs in solution show a virus concentration-dependent increase in the current peak on an electrode whose electrochemical properties are improved by the deposition of these nanocomposites. Both nanomaterials are conjugated with antibodies specific to influenza virus A (IFV/A), binding this target in a sandwich structure. We are successfully detecting the virus from these two signals during actual virus detection, even when the virus particles are in a human serum matrix. The limit of detection is 2.16 fg/mL for optical detection and 13.66 fg/mL for electrochemical detection.

Cargo encapsulated hepatitis E virus-like particles for anti-HEV antibody detection.

Viral capsid-nanoparticle hybrid structures incorporating quantum dots (QDs) into virus-like particles (VLPs) constitute an emerging bioinspired type of nanoarchitecture paradigm used for various applications. In the present study, we packed inorganic QDs in vitro into the hepatitis E virus-like particle (HEV-LP) and developed a fluorometric biosensor for HEV antibody detection. Firstly, for the preparation of QDs-encapsulated HEV-LPs (QDs@HEV-LP), the HEV-LPs produced by a recombinant baculovirus expression system were disassembled and reassembled in the presence of QDs using the self-assembly approach. Thus, the prepared QDs@HEV-LP exhibited excellent fluorescence properties similar to QDs. Further, in the presence of HEV antibodies in the serum samples, when mixed with QDs@HEV-LP, bind together and further bind to anti-IgG-conjugated magnetic nanoparticles (MNPs). The target-specific anti-IgG-MNPs and QDs@HEV-LP enrich the HEV antibodies by magnetic separation, and the separated QDs@HEV-LP-bound HEV antibodies are quantified by fluorescence measurement. This developed method was applied to detect the HEV antibody from sera of HEV-infected monkey from 0 to 68 days-post-infection and successfully diagnosed for HEV antibodies. The viral RNA copies number from monkey fecal samples by RT-qPCR was compared to the HEV antibody generation. This study first used QDs-encapsulated VLPs as useful fluorescence emitters for biosensing platform construction. It provides an efficient route for highly sensitive and specific antibody detection in clinical diagnosis research.

Ni-modified magnetic nanoparticles for affinity purification of His-tagged proteins from the complex matrix of the silkworm fat body.

Purification of recombinant proteins is often a challenging matter because high purity and high recovery are desired. If the expressed recombinant protein is also in a complex matrix, such as from the silkworm expression system, purification becomes more challenging. Even if purification from the silkworm expression system is troublesome, it benefits from a high capacity for the production of recombinant proteins. In this study, magnetic nanoparticles (MNPs) were investigated as a suitable tool for the purification of proteins from the complex matrix of the silkworm fat body. The MNPs were modified with nickel so that they have an affinity for His-tagged proteins, as the MNP purification protocol itself does not need special equipment except for a magnet. Among the three different kinds of investigated MNPs, MNPs with sizes of 100 nm to 200 nm and approximately 20 nm-thick nickel shells were the most suitable for our purpose. With them, the total protein amount was reduced by up to at least approximately 77.7%, with a protein recovery of around 50.8% from the silkworm fat body. The minimum binding capacity was estimated to be 83.3 µg protein/mg MNP. Therefore, these MNPs are a promising tool as a purification pretreatment of complex sample matrices.

Controlling distance, size and concentration of nanoconjugates for optimized LSPR based biosensors.

In this report, we have examined the distance- and size-dependent localized surface plasmon resonance (LSPR) between fluorescent quantum dots (QDs) and adjacent gold nanoparticles (AuNPs) to provide a comprehensive evaluation, aiming for practical application in biosensing platform. A series of peptides with different chain lengths, connected between QDs and AuNPs is initially applied to prepare various CdSe QDs-peptide-AuNP systems to optimize LSPR signal. Separation distance between two nanoparticles of these systems before and after conjugation is also confirmed by quantum mechanical modeling and corroborated with their LSPR influenced fluorescence variations. After detailed optimizations, it can be noted that larger sized AuNPs make strong quenching of QDs, which gradually shows enhancement of fluorescence with the increment of distance and the smaller sized AuNPs. Depending on the requirement, it is possible to tune the optimized structure of the CdSe QD-peptide-AuNP nanostructures for the application. In this work, two different structural designs with different peptide chain length are chosen to construct two biosensor systems, observing their fluorescence enhancement and quenching effects, respectively. Using different structural orientation of these biosensors, two nanoconjugates has applied for detection of norovirus and influenza virus, respectively to confirm their application in sensing.

Electrochemical detection of white spot syndrome virus with a silicone rubber disposable electrode composed of graphene quantum dots and gold nanoparticle-embedded polyaniline nanowires.

BACKGROUND: With the enormous increment of globalization and global warming, it is expected that the number of newly evolved infectious diseases will continue to increase. To prevent damage due to these infections, the development of a diagnostic method for detecting a virus with high sensitivity in a short time is highly desired. In this study, we have developed a disposable electrode with high-sensitivity and accuracy to evaluate its performances for several target viruses. RESULTS: Conductive silicon rubber (CSR) was used to fabricate a disposable sensing matrix composed of nitrogen and sulfur-co-doped graphene quantum dots (N,S-GQDs) and a gold-polyaniline nanocomposite (AuNP-PAni). A specific anti-white spot syndrome virus (WSSV) antibody was conjugated to the surface of this nanocomposite, which was successfully applied for the detection of WSSV over a wide linear range of concentration from 1.45 × 102 to 1.45 × 105 DNA copies/ml, with a detection limit as low as 48.4 DNA copies/ml. CONCLUSION: The engineered sensor electrode can retain the detection activity up to 5 weeks, to confirm its long-term stability, required for disposable sensing applications. This is the first demonstration of the detection of WSSV by a nanofabricated sensing electrode with high sensitivity, selectivity, and stability, providing as a potential diagnostic tool to monitor WSSV in the aquaculture industry.

Plasmonic/magnetic molybdenum trioxide and graphitic carbon nitride quantum dots-based fluoroimmunosensing system for influenza virus.

A novel magnetic/plasmonic-assisted fluoro-immunoassay system is developed for the detection of influenza virus using magnetic-derivatized plasmonic molybdenum trioxide quantum dots (MP-MoO3 QDs) as the plasmonic/magnetic agent and fluorescent graphitic carbon nitride quantum dots (gCNQDs) as the monitoring probe. Specific antibody against influenza A virus was conjugated onto the surface of MP-MoO3 QDs and gCNQDs, respectively. In the presence of influenza A virus (as the test virus), a core-satellite immunocomplex is formed between the antibody-conjugated nanomaterials (Ab-MP-MoO3 QDs and Ab-gCNQDs) and their interaction resulted in the modulation and gradual enhancement of the fluorescence intensity of the detection probe with the influenza virus concentration-dependent increase. In addition, PL change without influenza A virus was not observed. Limits of detection of 0.25 and 0.9 pg/mL were achieved for Influenza virus A/New Caledonia (20/99/IVR/116) (H1N1) detection in deionized water and human serum, respectively. Clinically isolated influenza virus A/Yokohama (110/2009) (H3N2) was detected in the range of 45 - 25,000 PFU/mL, with a limit of detection ca 45 PFU/mL (as opposed to a minimum of 5000 PFU/mL for a commercial test kit). This developed biosensor provides a robust, sensitive as well as a selective platform for influenza virus detection.

Preparation of divalent antigen-displaying enveloped virus-like particles using a single recombinant Bombyx mori nucleopolyhedrovirus bacmid in silkworms.

Silkworms have been used as a host for the production of recombinant proteins in a baculovirus expression system using Bombyx mori nucleopolyhedrovirus (BmNPV). To coexpress several recombinant proteins, a silkworm must be coinfected with several recombinant BmNPVs, which requires a difficult DNA manipulation procedure. In this study, we constructed recombinant BmNPVs containing three expression cassettes, Rous sarcoma virus (RSV) Gag protein, surface antigen 1 of Neospora caninum (NcSAG1) and SAG1-related sequence 2 of N. caninum (NcSRS2), by Gibson assembly and the Bac-to-Bac system, designated BmNPV/SAG-SRS-Gag and BmNPV/SAG-Gag-SRS. BmNPV/SAG-SRS-Gag was expressed in silkworms and characterized. NcSAG1 and NcSRS2 were purified with RSV Gag proteins using sucrose density gradient centrifugation and affinity chromatography. RSV Gag formed virus-like particles (RSV-LPs) at a diameter of 20-30 nm based on transmission electron microscopy (TEM). Immuno-TEM analysis showed that both NcSAG1 and NcSRS2 were displayed on the surface of the RSV-LPs. These results indicate that RSV-LPs displaying two different kinds of proteins were produced in the hemolymph of silkworm larvae by the single polycistronic strategy. This expression platform is efficient for generating multiantigen-displaying VLPs and facilitates the development of vaccines against infectious diseases.

Fluorometric virus detection platform using quantum dots-gold nanocomposites optimizing the linker length variation.

In this study, a tunable biosensor using the localized surface plasmon resonance (LSPR), controlling the distance between fluorescent CdZnSeS/ZnSeS quantum dots (QDs) and gold nanoparticles (AuNPs) has been developed for the detection of virus. The distance between the AuNPs and QDs has been controlled by a linkage with a peptide chain of 18 amino acids. In the optimized condition, the fluorescent properties of the QDs have been enhanced due to the surface plasmon effect of the adjacent AuNPs. Successive virus binding on the peptide chain induces steric hindrance on the LSPR behavior and the fluorescence of QDs has been quenched. After analyzing all the possible aspect of the CdZnSeS/ZnSeS QD-peptide-AuNP nanocomposites, we have detected different concentration of influenza virus in a linear range of 10-14 to 10-9 g mL-1 with detection limit of 17.02 fg mL-1. On the basis of the obtained results, this proposed biosensor can be a good alternative for the detection of infectious viruses in the various range of sensing application.

Dual modality sensor using liposome-based signal amplification technique for ultrasensitive norovirus detection.

Sensitive and accurate detection methods for infectious viruses are the pressing need for effective disease diagnosis and treatment. Herein, based on V2O5 nanoparticles-encapsulated liposomes (VONP-LPs) we demonstrate a dual-modality sensing platform for ultrasensitive detection of the virus. The sensing performance relies on intrinsic peroxidase and electrochemical redox property of V2O5 nanoparticles (V2O5 NPs). The target-specific antibody-conjugated VONP-LPs and magnetic nanoparticles (MNPs) enrich the virus by magnetic separation and the separated VONP-LPs bound viruses are hydrolyzed to release the encapsulated V2O5 NPs. These released nanoparticles from captured liposomes act as peroxidase mimics and electrochemical redox indicator resulting in noticeable colorimetric and robust electrochemical dual-signal. Utilizing the superiority of dual-modality sensor with two quantitative analysis forms, norovirus like particles (NoV-LPs) can be detected by electrochemical signals with a wide linear range and low detection limit. To verify the applicability in real samples, norovirus (NoV) collected from actual clinical samples are effectively-identified with excellent accuracy. This proposed detection method can be a promising next-generation bioassay platform for early-stage diagnosis of virus disease and surveillance for public health.

The detection and identification of dengue virus serotypes with quantum dot and AuNP regulated localized surface plasmon resonance.

The dengue hemorrhagic fever or dengue shock syndrome has become a severe human fatal disease caused by infection with one of the four closely related but serologically distinct dengue viruses (DENVs). All four dengue serotypes are currently co-circulating throughout the subtropics and tropics. Since the fatality rate increases severely when a secondary infection occurs by a virus serotype different from that of the initial infection, serotype identification is equally important as virus detection. In this study, the development and validation of a rapid and quantitative DENV serotype-specific (serotypes 1-4) biosensor are reported by optimizing the stable system between cadmium selenide tellurium sulphide fluorescent quantum dots (CdSeTeS QDs) and gold nanoparticles (AuNPs). Four different nanoprobes are designed using each primer-probe serotype-specific hairpin single-stranded DNA covalently bound at different positions to CdSeTeS QDs, which generates an altered fluorescence signal for each serotype of DENV. In fourplex reactions with free functionalized AuNPs and the four nanoprobes, the standard dilutions of the target virus DNA from 10-15 to 10-10 M were successfully detected. The limit of detection was found to be in the femtomolar range for all four serotypes, where the serotype detection ability was undoubtedly established. To confirm the applicability of this sensing performance in long chained complex RNAs, the sensor was also applied successfully to RNAs extracted from DENV culture fluids for serotype identification as well as quantification, which can lead to a potential diagnostic probe for point-of-care detection.

Electrical pulse-induced electrochemical biosensor for hepatitis E virus detection.

Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis worldwide. In this work, a pulse-triggered ultrasensitive electrochemical sensor was fabricated using graphene quantum dots and gold-embedded polyaniline nanowires, prepared via an interfacial polymerization and then self-assembly approach. Introducing an external electrical pulse during the virus accumulation step increases the sensitivity towards HEV due to the expanded surface of the virus particle as well as the antibody-conjugated polyaniline chain length, compared to other conventional electrochemical sensors. The sensor was applied to various HEV genotypes, including G1, G3, G7 and ferret HEV obtained from cell culture supernatant and in a series of fecal specimen samples collected from G7 HEV-infected monkey. The sensitivity is similar to that detected by real-time quantitative reverse transcription-polymerase chain (RT-qPCR). These results suggests that the proposed sensor can pave the way for the development of robust, high-performance sensing methodologies for HEV detection.

A localized surface plasmon resonance-amplified immunofluorescence biosensor for ultrasensitive and rapid detection of nonstructural protein 1 of Zika virus.

Among the members of flaviviruses, the Zika virus (ZIKV) remains a potent infectious disease agent, with its associated pandemic prompting the World Health Organization (WHO) to declare it a global public health concern. Thus, rapid and accurate diagnosis of the ZIKV is needed. In this study, we report a new immunofluorescence biosensor for the detection of nonstructural protein 1 (NS1) of the ZIKV, which operates using the localized surface plasmon resonance (LSPR) signal from plasmonic gold nanoparticles (AuNPs) to amplify the fluorescence intensity signal of quantum dots (QDs) within an antigen-antibody detection process. The LSPR signal from the AuNPs was used to amplify the fluorescence intensity of the QDs. For ultrasensitive, rapid, and quantitative detection of NS1 of the ZIKV, four different thiol-capped AuNPs were investigated. Our biosensor could detect the ZIKV in a wide concentration range from 10-107 RNA copies/mL, and we found that the limit of detection (LOD) for the ZIKV followed the order Ab-L-cysteine-AuNPs (LOD = 8.2 copies/mL) > Ab-3-mercaptopropionic acid-AuNPs (LOD = 35.0 copies/mL). Immunofluorescence biosensor for NS1 exhibited excellent specificity against other negative control targets and could also detect the ZIKV in human serum.

Enhanced colorimetric detection of norovirus using in-situ growth of Ag shell on Au NPs.

Norovirus (NoV) is a leading cause of acute gastroenteritis. The low infectious dose and environmental stability of NoV facilitate its effective transmission through a variety of modes such as food, water and person-to-person. The available enzyme-linked immunosorbent assay (ELISA) for NoV detection has low sensitivity due to the low catalytic activity of the peroxidase used, and thus, a reliable ultrasensitive bioassay is needed. In this study, we apply the enhanced peroxidase-like activity of silver ion-incorporated gold nanoparticles (Au/Ag NPs) in a colorimetric bioassay for NoV detection. NoV was captured by anti-NoV genogroup II antibodies, which were immobilized on the surface of a 96-well microtiter plate and formed a sandwich structure among anti-NoV Ab, NoV and Ab-Au NP. Then, Ag ion-containing hydroquinone was added to form Au/Ag core/shell NPs. When H2O2/3,3',5,5'-tetramethylbenzidine (TMB) solution was added to the wells, Ag ions were liberated from the surface of Au/Ag NPs and enhanced the oxidation of TMB. These reactions enhanced the oxidation of TMB and developed an intense blue color. The Au/Ag NPs were shown to exhibit higher affinity and catalytic efficiency for H2O2 and higher catalytic velocity based on the kcat of up to 7-fold compared with Au NPs. The bioassay was then optimized to detect clinically isolated NoV using NoV-like particles (NoV-LPs). NoV-LPs were detected with a limit of detection of 10.8 pg/mL, corresponding to 1000- and 100-fold higher sensitivity compared to the gold-immunoassay and horseradish peroxidase-based ELISA, respectively. Clinically isolated NoV GII.4 and NoV GII.3 were detected in the range of 102-106 copies of viral RNA/mL fecal solution with a detection limit of 13.2 copies/mL fecal solution for NoV GII.4, equivalent to 132 copies of viral RNA/g feces and indicating significantly higher sensitivity compared to commercial immunoassay kits. This bioassay represents a workable detection assay for low concentrations of NoV that is applicable for early-stage diagnosis for public hygiene.

Femtomolar Detection of Dengue Virus DNA with Serotype Identification Ability.

Dengue surveillance trusts only on reverse transcription-polymerase chain reaction (RT-PCR) type methodologies for confirmation of dengue virus serotypes; however, its real time application is restricted due to the expensive, complicated, and time-consuming process. In search of a new sensing system, here, we have reported a two-way-detection method for Dengue virus (DENV) serotype identification along with DNA quantification by using a new class of nanocomposite of gold nanoparticles (AuNP) and nitrogen, sulfur codoped graphene quantum dots (N,S-GQDs). The N,S-GQDs@AuNP has been used for serotype detection via a simple fluorescence technique using four dye-combined probe DNAs which is further validated by confocal microscopy. The quantification of the DNA has been measured by the differential pulse voltammetric (DPV) technique using methyelene blue as a redox indicator. Results obtained in this study, clearly demonstrate that the N,S-GQDs@AuNP can efficiently detect the four serotypes of DENV individually in the concentration range of 10-14 to 10-6 M with the LOD of 9.4 fM. In addition, to confirm its applicability in long chained complex DNA system, the sensor was also applied to the clinically isolated DENV DNA and showed satisfactory performances for serotype identification as well as quantification. We hope this simple and reliable method can pave an avenue for the development of sensitive and robust sensing probes in biomedical applications.

Single-step detection of norovirus tuning localized surface plasmon resonance-induced optical signal between gold nanoparticles and quantum dots.

A new method of label free sensing approach with superior selectivity and sensitivity towards virlabel-freeon is presented here, employing the localized surface plasmon resonance (LSPR) behavior of gold nanoparticles (AuNPs) and fluorescent CdSeTeS quantum dots (QDs). Inorganic quaternary alloyed CdSeTeS QDs were capped with L-cysteine via a ligand exchange reaction. Alternatively, citrate stabilized AuNPs were functionalized with 11-mercaptoundecanoic acid to generate carboxylic group on the gold surface. The carboxylic group on the AuNPs was subjected to bind covalently with the amine group of L-cysteine capped CdSeTeS QDs to form CdSeTeS QDs/AuNPs nanocomposites. The fluorescence of CdSeTeS QDs/AuNPs nanocomposite shows quenched spectrum of CdSeTeS QDs at 640 nm due to the close interaction with AuNPs. However, after successive addition of norovirus-like particles (NoV-LPs), steric hindrance-induced LSPR signal from the adjacent AuNPs triggered the fluorescence enhancement of QDs in proportion to the concentration of the target NoV-LPs. A linear range of 10-14 to 10-9 g mL-1 NoV-LPs with a detection limit of 12.1 × 10-15 g mL-1 was obtained. This method was further applied on clinically isolated norovirus detection, in the range of 102-105 copies mL-1 with a detection limit of 95.0 copies mL-1, which is 100-fold higher than commercial ELISA kit. The superiority of the proposed sensor over other conventional sensors is found in its ultrasensitive detectability at low virus concentration even in clinically isolated samples. This proposed detection method can pave an avenue for the development of high performance and robust sensing probes for detection of virus in biomedical applications.