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Biomedical Optics Express · 2022 ·Vol. 13 ·期 9 ·4592-4605 · IF 3.562

High sensitivity detection of SARS-CoV-2 by an optofluidic hollow eccentric core fiber

Qin Tan,Shengnan Wu,Shengnan Wu,Shengnan Wu,Shengnan Wu,Zhenchao Liu,Xun Wu,Erik Forsberg,Sailing He,Sailing He,Sailing He,Sailing He

Since the outbreak of coronavirus disease 2019 (COVID-19), efficient real-time monitoring has become one of the challenges faced in SARS-CoV-2 virus detection. A compact all-fiber Mach-Zehnder interferometer optofluidic sensor based on a hollow eccentric core fiber (HECF) for the detection and real-time monitoring of SARS-CoV-2 spike glycoprotein (SARS-CoV-2 S2) is proposed, analyzed and demonstrated. The sensor is comprised of fusion splicing single mode fiber (SMF), hollow core fiber (HCF) and HECF. After the incident light passes through the HCF from the SMF, it uniformly enters the air hole and the suspended micrometer-scale fiber core of the HECF to form a compact all-fiber Mach-Zehnder interferometer (MZI). HECF is side polished to remove part of the cladding that the suspended fiber core can contact the external environment. Subsequently, the mouse anti SARS-CoV-2 S2 antibody is fixed on the surface of the suspended-core for the sake of achieving high sensitivity and specific sensing of SARS-CoV-2 S2. The limit of detection (LOD) of the sensor is 26.8 pM. The proposed sensor has high sensitivity, satisfactory selectivity, and can be fabricated at low cost making it highly suitable for point-of-care testing and high-throughput detection of early stage of COVID-19 infection.

研究领域: 光学传感 · 生物医学工程 · 病毒学 · 光纤技术 · 即时诊断
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SENSORS AND ACTUATORS B-CHEMICAL · 2026 · IF 8.3

Multi-phase SERS detection of SARS-CoV-2 from liquids to aerosols and pseudovirus

Zhenle Qin,Xiaohui Fang,Yansheng Liu,Guofu Wang,Yang Li,Xinping Zhang

Rapid, ultrasensitive, and specific detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains challenging, particularly for micro-volume samples. This study presents a capillary-based three-dimensional Ag/ZnO nanorod surface-enhanced Raman spectroscopy (SERS) biosensing platform that enables dual-mode (liquid and aerosol) viral detection within the same device. The capillary configuration inherently provides a large surface-to-volume ratio and acts as a confined reaction chamber, eliminating the need for external liquid or gas cells while minimizing sample consumption. Vertically aligned Ag/ZnO nanorod arrays grown on the inner wall further increase the density of electromagnetic hotspots, achieving an enhancement factor of 1.07 × 10 ¹ ¹ with excellent signal uniformity (RSD = 4.65%). After ACE2 functionalization, the biosensor enables label-free, direct detection of the 2019-nCoV antigen S protein in phosphate-buffered saline (PBS) and pharyngeal swabs solution (PSS), with a limit of detection (LOD) of 1 fg/mL. In addition, a sandwich-structured sensing configuration was designed to further amplify the Raman response. Importantly, without additional instrumentation, the same capillary SERS platform also enables direct detection of the 2019-nCoV antigen S protein aerosol with a LOD of 10 fg/mL and the SARS-CoV-2 Spike Pseudovirus at 100 fg/mL. This biosensor integrates sampling, enrichment, and readout in a low-volume device, reduces the risk of cross-contamination, and maintains high analytical performance.

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ANALYTICAL AND BIOANALYTICAL CHEMISTRY · 2023 · IF 4.3

Highly sensitive digital detection of SARS-CoV-2 nucleocapsid protein through single-molecule counting

Dou Xuechen,Zhang Zhiwei,Liu Bo,Li Chao,Du Yaohua,Tian Feng

Nucleocapsid protein (NP) is one of the structural proteins of SARS-CoV-2 which is stable, well-conserved, highly immunogenic, and abundantly expressed due to the host’s adaptive immune response, making it a promising antigenic biomarker for the early and rapid identification and diagnosis of SARS-CoV-2. Traditional antigen analytical methods with NP as the detection marker often have insufficient sensitivity. To achieve rapid and highly sensitive detection of NP, we constructed a novel single-molecule (digital) fluorescence-linked immunosorbent assay (FLISA) based on streptavidin-modified transparent 96-well microplates. Streptavidin was immobilized on the microplate under optimized conditions with a 15 mM carbonate buffer solution (pH 9.6) as the coating solution, biotinylated antibodies conjugated with streptavidin as capture probes, and carboxylated fluorescent microsphere-conjugated monoclonal antibodies (FMs-mAbs) as fluorescent probes. Individual sandwich immunolabeled complexes of the SARS-CoV-2 diagnostic marker NP were detected and counted though wide-field inverted fluorescence microscopy (1.1 × 1.4 mm 2 ). FLISA had a linear detection range of 0.2 pg/mL to 200 ng/mL and a limit of detection (LOD) of 0.73 fg/mL and 8 fg/mL for NP in phosphate buffer saline and spiked nasal swab samples, respectively. The sensitivity was much higher than commercial antigen detection kits, providing wide detection prospects in future clinical diagnosis, environmental monitoring, and other fields.

CAS / MDL: 9005-38-3
✓ 已验证 产品关联 DOI PubMed 高影响因子
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TALANTA · 2022 · IF 6.556

Hybridization chain reaction circuit-based electrochemiluminescent biosensor for SARS-cov-2 RdRp gene assay

Kai Zhang,Zhenqiang Fan,Yue Huang,Yuedi Ding,Minhao Xie,Minghe Wang

In this work, we designed an ECL ratiometric biosensor with a three-stranded Y-type DNA (Y-DNA) probe and induced a hybridization chain reaction (HCR) for the highly sensitive detection of SARS-CoV-2 nucleic acid. The important component of this system is the self-assembled Y-Shaped probe based on three nucleic acids. Y1, Y2, and Y3 can be linked by complementary base pairing to Hairpin1 (H1), Hairpin2 (H2), and Ru modified DNA (Ru1), respectively. H1 and H2 can trigger the HCR reaction when activated by the SARS-CoV-2 RdRp gene and the 5′ end of Ru1. The 5′ end of Ru1 is modified with the Ru complex, which can produce a strong electrochemiluminescence luminescence signal at 620 nm under an applied voltage. Through the amplification of Y-DNA-induced HCR reaction, Ru1 on the electrode surface gradually increased, the ECL signal at 460 nm was gradually quenched, and the signal at 620 nm was steadily generated. The SARS-CoV-2 RdRp gene can be quantified according to the degree of decrease of ECL signal at 460 nm and the increase of ECL signal at 620 nm. Combining the two signal amplification strategies, this ratiometric ECL biosensor can accurately and efficiently detect the target gene with a detection limit of 59 aM.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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CARBOHYDRATE POLYMERS · 2022 · IF 10.723

Inhibitory activity of a sulfated oligo-porphyran from Pyropia yezoensis against SARS-CoV-2

Lihua Geng,Quanbin Zhang,Qishan Suo,Jing Wang,Yingxia Wang,Cong Wang,Ning Wu

COVID-19 caused by SARS-CoV-2 has spread around the world at an unprecedented rate. A more homogeneous oligo-porphyran with mean molecular weight of 2.1 kD, named OP145, was separated from Pyropia yezoensis . NMR analysis showed OP145 was mainly composed of →3)-β- d -Gal-(1 → 4)-α- l -Gal (6S) repeating units with few replacement of 3,6-anhydride, and the molar ratio was 1:0.85:0.11. MALDI-TOF MS revealed OP145 contained mainly tetrasulfate-oligogalactan with Dp range from 4 to 10 and with no more than two 3,6-anhydro-α- l -Gal replacement. The inhibitory activity of OP145 against SARS-CoV-2 was investigated in vitro and in silico. OP145 could bind to Spike glycoprotein (S-protein) through SPR result, and pseudovirus tests confirmed that OP145 could inhibite the infection with an EC50 of 37.52 μg/mL. Molecular docking simulated the interaction between the main component of OP145 and S-protein. All the results indicated that OP145 had the potency to treat and prevent COVID-19.

CAS / MDL: 127-09-3
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TALANTA · 2021 · IF 6.057

Anti-SARS-CoV-2 IgG and IgM detection with a GMR based LFIA system

Qiaoge Bayin,Lei Huang,Chunhui Ren,Yusheng Fu,Xing Ma,Jinhong Guo

Since December 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused millions of deaths and seriously threatened the safety of human life; indeed, this situation is worsening and many people are infected with the new coronavirus every day. Therefore, it is very important to understand patients’ degree of infection and infection history through antibody testing. Such information is useful also for the government and hospitals to formulate reasonable prevention policies and treatment plans. In this paper, we develop a lateral flow immunoassay (LFIA) method based on superparamagnetic nanoparticles (SMNPs) and a giant magnetoresistance (GMR) sensing system for the simultaneously quantitative detection of anti -SARS-CoV-2 immunoglobulin M (IgM) and G (IgG). A simple and time-effective co-precipitation method was utilized to prepare the SMNPs, which have good dispersibility and magnetic property, with an average diameter of 68 nm. The Internet of Medical Things-supported GMR could transmit medical data to a smartphone through the Bluetooth protocol, making patient information available for medical staff. The proposed GMR system, based on SMNP-supported LFIA, has an outstanding advantage in cost-effectiveness and time-efficiency, and is easy to operate. We believe that the suggested GMR based LFIA system will be very useful for medical staff to analyze and to preserve as a record of infection in COVID-19 patients.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2023 · IF 5.8

Bivalent mRNA vaccines against three SARS-CoV-2 variants mediated by new ionizable lipid nanoparticles

Ji Wang,Yanhao Zhang,Shuo Dong,Wenhui Zha,Chao Liu,Yang Wang,Yuhao Jiang,Hanlei Xing,Xinsong Li

Lipid nanoparticles (LNPs)-based mRNA vaccines have shown great potential in the fight against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. However, it remains still a challenge to improve the delivery efficiency of LNPs and the long-term stability of their mediated mRNA vaccines. Herein, a novel ionizable lipid 2-hexyldecyl 6-(ethyl(3-((2-hexyldecyl)oxy)-2-hydroxypropyl)amino)hexanoate (HEAH) derived LNPs were developed for delivering the receptor binding domain (RBD) mRNAs. In vitro cell assays confirmed that the ionizable lipid HEAH with one ether bond and one ester bond derived LNPs possessed higher mRNA delivery efficiency compared with the approved ALC-0315 with two ester bonds used in the BNT162b2 vaccine. Notably, the HEAH-derived LNPs powder lyophilized did not significantly change for 30 days after storage at 37 °C indicating good thermostability. After two RBD mRNAs of Delta and Omicron variants were encapsulated into the HEAH-derived LNPs, a bivalent mRNA vaccine was obtained as a nanoparticle formulation. Importantly, the bivalent mRNA vaccine not only resisted Delta and Omicron and also generated protective antibodies against ancestral SARS-CoV-2. The HEAH-mediated bivalent vaccine induced stronger humoral and cellular immunity than those of the ALC-0315 group. Taken together, the ionizable lipid HEAH-derived LNPs show outstanding potential in improving the delivery efficiency of mRNA and the stability of mRNA vaccine.

研究领域: 药学 · 分子生物学 · 病毒学 · 纳米技术
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ACS Sensors · 2023 · IF 8.9

Next-Generation Rapid and Ultrasensitive Lateral Flow Immunoassay for Detection of SARS-CoV-2 Variants

Chenglong Lin,Zhenzhen Liu,Fanghao Fang,Shuai Zhao,Yanyan Li,Meimei Xu,Yusi Peng,Hongyou Chen,Fang Yuan,Wanju Zhang,Xi Zhang,Zheng Teng,Rui Xiao,Yong Yang

The coronavirus disease 2019 (COVID-19) pandemic highlighted the need for rapid and accurate viral detection at the point-of-care testing (POCT). Compared with nucleic acid detection, lateral flow immunoassay (LFIA) is a rapid and flexible method for POCT detection. However, the sensitivity of LFIA limits its use for early identification of patients with COVID-19. Here, an innovative surface-enhanced Raman scattering (SERS)-LFIA platform based on two-dimensional black phosphorus decorated with Ag nanoparticles as important antigen-capturing and Raman-signal-amplification unit was developed for detection of SARS-CoV-2 variants within 5–20 min. The novel SERS-LFIA platform realized a limit of detection of 0.5 pg/mL and 100 copies/mL for N protein and SARS-CoV-2, demonstrating 1000 times more sensitivity than the commercial LFIA strips. It could reliably detect seven different SARS-CoV-2 variants with cycle threshold (Ct) < 38, with sensitivity and specificity of 97 and 100%, respectively, exhibiting the same sensitivity with q-PCR. Furthermore, the detection results for 48 SARS-CoV-2-positive nasopharyngeal swabs (Ct = 19.8–38.95) and 96 negative nasopharyngeal swabs proved the reliability of the strips in clinical application. The method also had good specificity in double-blind experiments involving several other coronaviruses, respiratory viruses, and respiratory medications. The results showed that the innovative SERS-LFIA platform is expected to be the next-generation antigen detection technology. The inexpensive amplification-free assay combines the advantages of rapid low-cost POCT and highly sensitive nucleic acid detection, and it is suitable for rapid detection of SARS-CoV-2 variants and other pathogens. Thus, it could replace existing antigens and nucleic acids to some extent.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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TALANTA · 2023 · IF 6.1

PdPtRu trimetallic nanozymes and application to electrochemical immunosensor for sensitive SARS-COV-2 antigen detection

Ying Li,Jian Xue,Rongjun Yu,Siling Chen,Xiangyu Deng,Anyi Chen,Jingfu Qiu

Herein, a ternary PdPtRu nanodendrite as novel trimetallic nanozyme was reported, which possessed excellent peroxidase-like activity as well as electro-catalytic activity on account of the synergistic effect between the three metals. Based on the excellent electro-catalytic activity of trimetallic PdPtRu nanozyme toward the reduction of H 2 O 2 , the trimetallic nanozyme was applied to construct a brief electrochemical immunosensor for SARS-COV-2 antigen detection. Concretely, trimetallic PdPtRu nanodendrite was used to modify electrode surface, which not only generated high reduction current of H 2 O 2 for signal amplification, but also provided massive active sites for capture antibody (Ab 1 ) immobilization to construct immunosensor. In the presence of target SARS-COV-2 antigen, SiO 2 nanosphere labeled detection antibody (Ab 2 ) composites were introduced on the electrode surface according sandwich immuno-reaction. Due to the inhibitory effect of SiO 2 nanosphere on the current signal, the current signal was decreased with the increasing target SARS-COV-2 antigen concentration. As a result, the proposed electrochemical immunosensor presented sensitive detection of SARS-COV-2 antigen with linear range from 1.0 pg/mL to 1.0 μg/mL and limit of detection down to 51.74 fg/mL. The proposed immunosensor provide a brief but sensitive antigen detection tool for rapid diagnosis of COVID-19.

CAS / MDL: 50-81-7 10049-07-7
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ANALYST · 2023 ·Vol. 148 ·期 15 ·3603-3609 · IF 4.2

Post-synthetic modification-driven ZIF reconstruction and functionalization for efficient SARS-CoV-2 ECL detection

Ju-Zheng Wang,Yi-Xuan Li,Qiaoting Yang,Junji Li,Jérome Chauvin,Xue-Ji Zhang,Serge Cosnier,Robert S. Marks,Dan Shan

The emergence of novel pathogens, as well as their frequent variants, raises the significance of developing superior and versatile sensing materials and techniques. Herein, a post-modified zeolitic imidazolate framework (pm-ZIF) was synthesized by using ZIF-67 as a parent MOF, and zinc(II) meso-tetra (4-carboxyphenyl) porphine (ZnTCPP) as a successive exchange ligand. Due to the preservation of the tetrahedral Co–N4 units from the ZIF precursor and the introduced porphyrin luminophores, this hybrid material pm-ZIF/P(Zn) enables the linear electrochemiluminescence (ECL) signal conversion of the target DNA concentration. An efficient biosensor that can be used to quantitatively detect SARS-CoV-2 was therefore constructed. The linear range of the sensor was 10−12–10−8 M, with a limit of detection (LOD) reaching 158 pM. Compared with the traditional amplification-based methods, the duration time of our method is significantly shortened and the quantitation of the SARS-Cov-2 RdRp gene can be completed within twenty minutes at room temperature.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2023 · IF 5.8

Functionalized protein microparticles targeting hACE2 as a novel preventive strategy for SARS-CoV-2 infection

Yujia Li,Yike Huang,Kehui Zhu,Xiaoqiong Duan,Shilin Li,Min Xu,Chunhui Yang,Jiaxin Liu,Hans Bäumler,Pin Yu,He Xie,Bin Li,Ye Cao,Limin Chen

The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), resulting in a serious burden on public health and social economy worldwide. SARS-CoV-2 infection is mainly initialized in the nasopharyngeal cavity through the binding of viral spike (S) protein to human angiotensin-converting enzyme 2 (hACE2) receptors which are widely expressed in many human cells. Thus, blockade of the interaction between viral S protein and hACE2 receptor in the primary entry site is a promising prevention strategy for the management of COVID-19. Here we showed protein microparticles (PMPs) decorated with hACE2 could bind and neutralize SARS-CoV-2 S protein-expressing pseudovirus (PSV) and protect host cells from infection in vitro. In the hACE2 transgenic mouse model, administration of intranasal spray with hACE2-decorated PMPs markedly decreased the viral load of SARS-CoV-2 in the lungs though the inflammation was not attenuated significantly. Our results provided evidence for developing functionalized PMPs as a potential strategy for preventing emerging air-borne infectious pathogens, such as SARS-CoV-2 infection.

CAS / MDL: 111-30-8
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Foods · 2022 ·Vol. 11 ·期 18 ·2865 · IF 5.561

A Sulfated Abalone Polysaccharide Inhibited SARS-CoV-2 Infection of Vero E6 Cells In Vitro

Jinghe Sun,Shuang Song,Chunqing Ai,Beiwei Zhu,Jingfeng Yang

Sulfate polysaccharides, such as heparin sulfate, have been found to have inhibitory activity against SARS-CoV-2. An abalone polysaccharide, AGSP, was deeply sulfate modified using the chlorosulfonic acid/pyridine method, yielding S-AGSP. AGSP and S-AGSP inhibitions of SARS-CoV-2 infection of Vero E6 cells were tested in vitro. The interference of AGSP or S-AGSP on the binding interaction between the SARS-CoV-2 spike protein and angiotensin-converting enzyme was tested using a biolayer interferometry assay. Results showed that S-AGSP, above a concentration of 1.87 µg/mL, significantly inhibited SARS-CoV-2 infection of Vero E6 cells. Compared with AGSP, S-AGSP obviously weakened the affinity between the SARS-CoV-2 spike protein and ACE2. The polysaccharide’s sulfate content played a vital role in influencing the binding affinity of spike protein to ACE2. Therefore, S-AGSP has potential as a COVID-19 competitive inhibitor as well as a candidate to be repurposed as a prophylactic COVID-19 therapeutic.Keywords:sulfated;polysaccharide;SARS-CoV-2;biolayer interferometry;ACE2

CAS / MDL: 631-61-8
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