4.8 Review

Immunochromatographic enhancement strategy for SARS-CoV-2 detection based on nanotechnology

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FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY (2022)

Review Chemistry, Analytical

Challenges in the Detection of SARS-CoV-2: Evolution of the Lateral Flow Immunoassay as a Valuable Tool for Viral Diagnosis

Nayeli Shantal Castrejon-Jimenez et al.

Summary: This review summarizes the advantages, limitations, and evolution of lateral flow immunoassays (LFIA) during the SARS-CoV-2 pandemic and the challenges of improving these diagnostic devices.

BIOSENSORS-BASEL (2022)

Review Medicine, Research & Experimental

The role of SARS-CoV-2 accessory proteins in immune evasion

Milad Zandi et al.

Summary: The accessory proteins of SARS-CoV-2 play significant roles in immune evasion and viral pathogenesis, making them potential targets for drug development. The IFN-I and IFN-III responses are essential for clearing the infection. Several SARS-CoV-2 accessory proteins, such as ORF3a, ORF7a, and ORF7b, inhibit the host's IFN-beta response.

BIOMEDICINE & PHARMACOTHERAPY (2022)

Article Chemistry, Analytical

A sample-to-answer COVID-19 diagnostic device based on immiscible filtration and CRISPR-Cas12a-assisted detection

Bongkot Ngamsom et al.

Summary: In response to the disparities of vaccination coverage in low-and middle-income countries, this study presents a lab-on-a-chip device called 'IFAST-LAMP-CRISPR', which provides an affordable, rapid, and high-precision molecular diagnostic means for detecting SARS-CoV-2. The device integrates RNA extraction, amplification, molecular detection, and lateral flow readout in one device, offering a simple, cost-effective, and integrated platform for COVID-19 diagnostics in low-resource settings.

TALANTA OPEN (2022)

Article Chemistry, Analytical

Nanozyme enhanced magnetic immunoassay for dual-mode detection of gastrin-17

Chujun Zheng et al.

Summary: In this study, a novel magnetic lateral flow assay was developed for dual-mode detection of gastrin-17 (G-17), an important biomarker for early gastric cancer diagnosis. The assay utilized iron oxide decorated with platinum probes, which exhibited magnetic properties and peroxidase activity. The assay showed high sensitivity and specificity, and results were consistent with the enzyme-linked immunosorbent assay method. The entire testing process was simple, rapid, and suitable for portable diagnostic applications.

ANALYST (2022)

Article Chemistry, Multidisciplinary

A wearable AIEgen-based lateral flow test strip for rapid detection of SARS-CoV-2 RBD protein and N protein

Guo-Qiang Zhang et al.

Summary: This study developed test strips for the detection of SARS-CoV-2 using AIE luminogens as reporters, achieving high sensitivity and specificity with limits of detection as low as 6.9 ng/mL for RBD protein and 7.2 ng/mL for N protein. The integration of the test strips onto N95 masks simplified the sampling procedures and showed high anti-interference capacity in complex biosamples.

CELL REPORTS PHYSICAL SCIENCE (2022)

Article Biochemical Research Methods

Tetra-primer ARMS-PCR combined with dual-color fluorescent lateral flow assay for the discrimination of SARS-CoV-2 and its mutations with a handheld wireless reader

Yunxiang Wang et al.

Summary: A low-cost and highly sensitive diagnostic platform is reported, which can simultaneously distinguish wild-type (WT) SARS-CoV-2 and its two mutations within 2 hours. The platform utilizes PCR amplification and a dual-color fluorescent test strip to detect the specific nucleic acid fragments, with results interpreted by the naked eye or a smartphone-connected device. This method provides a simple, accurate, and affordable approach for screening SARS-CoV-2 and its variants, even in resource-limited settings.

LAB ON A CHIP (2022)

Review Immunology

Review Article Genotype and phenotype of COVID-19: Their roles in pathogenesis

Leila Mousavizadeh et al.

Summary: COVID-19 is a novel coronavirus belonging to the Betacoronavirus genus, with similarities and differences in genomic structure compared to other human Betacoronaviruses. It contains at least six open reading frames and important structural proteins are encoded near the one-third of the genome.

JOURNAL OF MICROBIOLOGY IMMUNOLOGY AND INFECTION (2021)

Article Biophysics

Controlled copper in situ growth-amplified lateral flow sensors for sensitive, reliable, and field-deployable infectious disease diagnostics

Yaofeng Zhou et al.

Summary: The PEI-CISG technology introduced in this study controls the growth of copper nanoshells on the surface of gold nanoparticles in AuNP-LFS, effectively enhancing the detection sensitivity for various infectious diseases.

BIOSENSORS & BIOELECTRONICS (2021)

Review Chemistry, Multidisciplinary

Recent advances in the development of colorimetric analysis and testing based on aggregation-induced nanozymes

Honghong Rao et al.

Summary: This article explores the importance of aggregation-induced nanozymes in enhancing the activity of nanozymes and improving the colorimetric sensing performance, as well as the future prospects and challenges in this field.

CHINESE CHEMICAL LETTERS (2021)

Article Chemistry, Analytical

Comparative Study of In Situ Techniques to Enlarge Gold Nanoparticles for Highly Sensitive Lateral Flow Immunoassay of SARS-CoV-2

Vasily G. Panferov et al.

Summary: Three techniques were compared to lower the LOD of SARS-CoV-2 LFIA, with gold enhancement being the most optimal, increasing the maximum dilution of samples by 500 times and providing highly sensitive and rapid testing.

BIOSENSORS-BASEL (2021)

Article Biophysics

Dual lateral flow optical/chemiluminescence immunosensors for the rapid detection of salivary and serum IgA in patients with COVID-19 disease

Aldo Roda et al.

Summary: The study developed a noninvasive and highly sensitive immunosensor for IgA in saliva and serum, which can be used for diagnosing and monitoring COVID-19 infection. The immunosensor demonstrated the capability to detect salivary IgA in infected individuals and correlated with disease severity and infection time.

BIOSENSORS & BIOELECTRONICS (2021)

Article Biophysics

A novel rapid detection for SARS-CoV-2 spike 1 antigens using human angiotensin converting enzyme 2 (ACE2)

Jong-Hwan Lee et al.

Summary: This study presents a novel rapid detection method for the SARS-CoV-2 S1 antigen using a matched pair of ACE2 and antibody. The detection method showed high specificity and sensitivity without cross-reactivity, making it a valuable tool in detecting the S1 antigen from COVID-19 patients.

BIOSENSORS & BIOELECTRONICS (2021)

Review Chemistry, Multidisciplinary

Discussion of the protein characterization techniques used in the identification of membrane protein targets corresponding to tumor cell aptamers

Zhukang Guo et al.

Summary: Aptamers are oligonucleotide chains with specific binding ability to protein and other targets, and can be used to discover novel tumor markers. Further characterization of newly acquired membrane proteins is essential for their clinical use as tumor markers.

CHINESE CHEMICAL LETTERS (2021)

Article Medical Laboratory Technology

IgG antibodies against SARS-CoV-2 decay but persist 4 months after vaccination in a cohort of healthcare workers

Giulia Brisotto et al.

Summary: The study showed that SARS-CoV-2 mRNA vaccines can induce a lasting IgG response for at least 4 months, even beyond the parameters of clinical trials. The observed antibody decay at follow-up suggests further research is needed to characterize the immune response and identify individuals with low anti-SARS-CoV-2 immunity who may require a vaccination booster.

CLINICA CHIMICA ACTA (2021)

Article Immunology

Structural and functional insights into non-structural proteins of coronaviruses

Mohammed A. Rohaim et al.

Summary: Coronaviruses, due to their zoonotic nature, have caused various diseases in both humans and animals. The recent emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 has resulted in high morbidity and mortality. Understanding the structure and function of coronaviruses' RNA synthesizing machinery and replication strategies is crucial for developing effective control strategies.

MICROBIAL PATHOGENESIS (2021)

Article Biochemistry & Molecular Biology

Monoclonal Antibodies against Nucleocapsid Protein of SARS-CoV-2 Variants for Detection of COVID-19

Ruei-Min Lu et al.

Summary: Mitigation strategies for the COVID-19 pandemic have been hindered by the emergence of SARS-CoV-2 variants. A panel of 41 monoclonal antibodies against SARS-CoV-2 NP was generated, with 9 high-binding antibodies used in a new rapid diagnostic test showing high sensitivity and specificity for detecting viral variants. The developed LFIA strips have the capability to detect 10 NP mutants, including the alpha, beta, gamma, and delta variants.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Article Medical Laboratory Technology

A rapid lateral flow immunoassay strip for detection of SARS-CoV-2 antigen using latex microspheres

Lin Shen et al.

Summary: In third-world countries, the lateral flow immunoassay strip (LFIA) may be a better method for detecting SARS-CoV-2, and this study developed a highly specific LFIA with a sensitivity and specificity of 98.22% and 97.93%, respectively.

JOURNAL OF CLINICAL LABORATORY ANALYSIS (2021)

Article Biophysics

Development of a SARS-CoV-2-specific biosensor for antigen detection using scFv-Fc fusion proteins

Hye-Yeon Kim et al.

Summary: This study presents the development of a specific LFIA-based biosensor for COVID-19 using phage display technology to generate antibodies targeting SARS-CoV-2 NP antigen, allowing rapid and specific detection of the virus. The newly developed rapid diagnostic test shows potential for use in the diagnosis of COVID-19.

BIOSENSORS & BIOELECTRONICS (2021)

Article Biophysics

Nanozyme chemiluminescence paper test for rapid and sensitive detection of SARS-CoV-2 antigen

Dan Liu et al.

Summary: The nanozyme-based chemiluminescence paper assay offers a new method for rapid and sensitive detection of SARS-CoV-2 antigen. The test is specific to the SARS-CoV-2 antigen and can be completed within 16 minutes.

BIOSENSORS & BIOELECTRONICS (2021)

Article Biochemistry & Molecular Biology

Comparative research on nucleocapsid and spike glycoprotein as the rapid immunodetection targets of COVID-19 and establishment of immunoassay strips

Dan Liu et al.

Summary: The outbreak of COVID-19 has posed a significant challenge to healthcare systems worldwide, necessitating the urgent development of low-cost and convenient testing technologies.

MOLECULAR IMMUNOLOGY (2021)

Article Environmental Sciences

Prospects of nanomaterials-enabled biosensors for COVID-19 detection

Manish Srivastava et al.

Summary: This study provides an overview of the COVID-19 pandemic and nanomaterials-enabled biosensing approaches for the diagnosis of SARS-CoV-2. Despite limited research on nanomaterials-enabled biosensing techniques, the review summarizes nanomaterials-mediated improved biosensing strategies and possible mechanisms for diagnosing COVID-19.

SCIENCE OF THE TOTAL ENVIRONMENT (2021)

Article Chemistry, Analytical

SERS-based lateral flow immunoassay for sensitive and simultaneous detection of anti-SARS-CoV-2 IgM and IgG antibodies by using gap-enhanced Raman nanotags

Shiliang Chen et al.

Summary: The newly developed SERS-based LFIA strip using GERTs achieved highly sensitive detection of anti-SARS-CoV-2 IgM and IgG, with detection limits 100 times lower compared to conventional LFIA strips, improving the accuracy and reliability of early diagnosis.

SENSORS AND ACTUATORS B-CHEMICAL (2021)

Article Chemistry, Analytical

Development of a SERS-based lateral flow immunoassay for rapid and ultra-sensitive detection of anti-SARS-CoV-2 IgM/IgG in clinical samples

Haifeng Liu et al.

Summary: This study reported a surface-enhanced Raman scattering-based lateral flow immunoassay method for the high sensitivity simultaneous detection of anti-SARS-CoV-2 IgM/IgG. The method utilized custom SERS tags and dual layers of Raman dye, with signal intensities easily recorded by a portable Raman instrument for high sensitivity analysis. Validation on samples from COVID-19 patients and healthy individuals showed high accuracy and specificity.

SENSORS AND ACTUATORS B-CHEMICAL (2021)

Article Chemistry, Multidisciplinary

Handheld Microfluidic Filtration Platform Enables Rapid, Low-Cost, and Robust Self-Testing of SARS-CoV-2 Virus

Jiang Xu et al.

Summary: The novel microfluidic test kit combines ultra-high throughput hydrodynamic filtration and sandwich immunoassay techniques for rapid separation and enrichment of antigens, demonstrating high detection sensitivity, low cost, and suitability for areas with inadequate medical infrastructure and limited laboratory resources.

SMALL (2021)

Review Chemistry, Analytical

Point-of-care COVID-19 diagnostics powered by lateral flow assay

Yaofeng Zhou et al.

Summary: The global COVID-19 pandemic caused by the novel coronavirus has posed a serious threat to human life and health since its discovery in December 2019. Lateral flow assay (LFA) has been widely accepted as a critical point-of-care diagnostic platform for the rapid diagnosis of COVID-19, although it faces challenges and requires continuous improvement to enhance its efficiency in clinical diagnostics.

TRAC-TRENDS IN ANALYTICAL CHEMISTRY (2021)

Article Chemistry, Multidisciplinary

Early Detection of SARS-CoV-2 Seroconversion in Humans with Aggregation-Induced Near-Infrared Emission Nanoparticle-Labeled Lateral Flow Immunoassay

Rui Chen et al.

Summary: A new serological diagnostic method was designed for early detection of COVID-19 using AIE nanoparticles. The method showed comparable or higher sensitivity to ELISA and outperformed a commercial colloidal gold nanoparticle test strip. Early detection of IgM and IgG was achieved within 1-7 days of symptom onset with the AIE nanoparticle-based test strip.

ACS NANO (2021)

Article Pathology

Performance comparison of the Cobas® Liat® and Cepheid® GeneXpert® systems on SARS-CoV-2 detection in nasopharyngeal swab and posterior oropharyngeal saliva

Hin Fung Tsang et al.

Summary: The study compared the performance of cepheid (R) Xpress SARS-CoV-2 assay and cobas (R) Liat (R) SARS-CoV-2 & Influenza A/B assay in detecting SARS-CoV-2, demonstrating excellent concordance between the two systems. The study is limited by the small number of SARS-CoV-2 positive and weak-positive specimens.

EXPERT REVIEW OF MOLECULAR DIAGNOSTICS (2021)

Review Immunology

A Recent Update on Advanced Molecular Diagnostic Techniques for COVID-19 Pandemic: An Overview

Akanksha Roberts et al.

Summary: A vaccine is crucial, but rapid and precise diagnostic methods are also essential in monitoring and combating the spread of SARS-CoV-2 and its variants. A variety of conventional and modern diagnostic methods have been developed, with ongoing research focusing on developing more economical tools to tackle the COVID-19 pandemic.

FRONTIERS IN IMMUNOLOGY (2021)

Review Biochemistry & Molecular Biology

Potential drug targets of SARS-CoV-2: From genomics to therapeutics

Anas Shamsi et al.

Summary: The emergence of SARS-CoV-2 has posed a global threat due to the continuous rise in COVID-19 cases. The complex mechanism of the virus pathogenesis hinders the development of effective therapeutics, but in-depth analysis of the genome architecture and pathogenesis may lead to potential treatment options.

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES (2021)

Review Biotechnology & Applied Microbiology

Paper-Based Point-of-Care Testing of SARS-CoV-2

Yuan Jia et al.

Summary: Paper-based point-of-care tests have gained interest for their rapid, low-cost, and instrument-free detection capabilities. This review focuses on the development of paper-based POC devices for detecting SARS-CoV-2, discussing principles, performance, advantages, drawbacks, limitations, and prospects of existing devices in the field.

FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY (2021)

Article Medicine, General & Internal

Development and Efficacy of Lateral Flow Point-of-Care Testing Devices for Rapid and Mass COVID-19 Diagnosis by the Detections of SARS-CoV-2 Antigen and Anti-SARS-CoV-2 Antibodies

Wen-Yeh Hsieh et al.

Summary: The COVID-19 pandemic, caused by SARS-CoV-2, poses a significant challenge to the global healthcare system. Early detection and treatment of infected cases are crucial, with rapid and cost-effective immunoassays like LFIA being utilized for quick and large-scale testing.

DIAGNOSTICS (2021)

Article Nanoscience & Nanotechnology

fM-aM Detection of the SARS-CoV-2 Antigen by Advanced Lateral Flow Immunoassay Based on Gold Nanospheres

Yilin Liu et al.

Summary: The study developed an advanced LFA technology based on gold nanospheres and thermal contrast amplification for highly sensitive detection of SARS-CoV-2 virus, achieving visual detection sensitivity comparable to PCR for the first time. The use of a fast TCA reading algorithm further improved the accuracy of detection.

ACS APPLIED NANO MATERIALS (2021)

Article Chemistry, Analytical

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

Qiaoge Bayin et al.

Summary: The study introduces a novel lateral flow immunoassay method based on superparamagnetic nanoparticles and giant magnetoresistance sensing system for simultaneous quantitative detection of anti-SARS-CoV-2 immunoglobulin M and G. This method offers advantages in cost-effectiveness, time efficiency, and ease of operation.

TALANTA (2021)

Review Infectious Diseases

COVID-19 Pandemic: Review of Contemporary and Forthcoming Detection Tools

Mumtarin Jannat Oishee et al.

Summary: This review elaborates on various diagnostic tools available or under investigation for COVID-19, including cell culture, immunofluorescent antibody, radiologic imaging, RT-PCR assay, CRISPR-Cas, microfluidics, and immunoassays like ELISA and LFIA. Advancements in NGS and metagenomics are further improving viral detection in this global challenge.

INFECTION AND DRUG RESISTANCE (2021)

Review Chemistry, Analytical

Paper-Based Biosensors: Frontiers in Point-of-Care Detection of COVID-19 Disease

Riccarda Antiochia

Summary: This review summarizes the current state of paper-based biosensors (PBBs) used in the detection of COVID-19, specifically focusing on three categories for SARS-CoV-2 diagnostics. It highlights the characteristics, analytical performance, advantages and drawbacks of each type of biosensor compared to traditional methods, with the hope of assisting scientists in developing novel PBB platforms with enhanced performance to help contain the COVID-19 outbreak.

BIOSENSORS-BASEL (2021)

Article Nanoscience & Nanotechnology

Ultrasensitive and Simultaneous Detection of Two Specific SARS-CoV-2 Antigens in Human Specimens Using Direct/Enrichment Dual-Mode Fluorescence Lateral Flow Immunoassay

Chongwen Wang et al.

Summary: A dual-mode lateral flow immunoassay biosensor was developed for high-sensitivity simultaneous detection of SARS-CoV-2 spike and nucleocapsid protein antigens, offering enhanced accuracy and efficiency in viral infection screening. The system demonstrated superior performance in detecting SARS-CoV-2 antigens in saliva and nasal swab samples, with detection limits of 1 and 0.5 pg/mL for the spike and nucleocapsid protein antigens, respectively.

ACS APPLIED MATERIALS & INTERFACES (2021)

Article Chemistry, Analytical

Rapid and Sensitive SERS-Based Lateral Flow Test for SARS-CoV2-Specific IgM/IgG Antibodies

Supriya Srivastav et al.

Summary: The study compared the performance of a conventional lateral flow assay (LFA) with a surface-enhanced Raman scattering (SERS)-based LFA test in detecting SARS-CoV-2-specific IgM/IgG in sera of COVID-19 patients. The custom-built SERS reader showed at least an order of magnitude higher sensitivity than conventional LFAs with naked-eye detection. SERS detection in a purified system showed a sensitivity that is 7 orders of magnitude higher than naked-eye detection, indicating the high potential of SERS-based LFAs in point-of-care testing.

ANALYTICAL CHEMISTRY (2021)

Review Chemistry, Multidisciplinary

The point-of-care-testing of nucleic acids by chip, cartridge and paper sensors

Yuyue Xu et al.

Summary: Point-of-care nucleic acid testing (POCNAT) plays a crucial role in infectious disease outbreaks, offering rapid, simple, and automated detection of nucleic acid. Leveraging advancements in technology, novel experimental carriers like chips, cartridges, and papers have been employed for automated nucleic acid detection, marking significant progress in the field.

CHINESE CHEMICAL LETTERS (2021)

Article Immunology

Rapid and Visual Detection of SARS-CoV-2 Using Multiplex Reverse Transcription Loop-Mediated Isothermal Amplification Linked With Gold Nanoparticle-Based Lateral Flow Biosensor

Xu Chen et al.

Summary: The novel molecular diagnosis technique, multiplex reverse transcription loop-mediated isothermal amplification (mRT-LAMP) combined with a nanoparticle-based lateral flow biosensor, demonstrated high sensitivity and specificity in detecting the SARS-CoV-2 virus. The mRT-LAMP-LFB method is a simple, rapid, and reliable assay for identifying SARS-CoV-2, especially in resource-constrained regions for prevention and control of COVID-19.

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY (2021)

Review Engineering, Biomedical

CRISPR-based diagnostics

Michael M. Kaminski et al.

Summary: This Review summarizes the rapidly expanding toolbox of CRISPR-based diagnostics, highlighting their applications in real-time diagnosis. It mentions that nucleic acid-based diagnostics are sensitive and specific, but most require expensive equipment and trained personnel.

NATURE BIOMEDICAL ENGINEERING (2021)

Article Chemistry, Analytical

On-demand nanozyme signal enhancement at the push of a button for the improved detection of SARS-CoV-2 nucleocapsid protein in serum

Daniel W. Bradbury et al.

Summary: The innovative 3D printed casing incorporates lateral-flow immunoassay, dehydrated signal enhancement reagents, and a sealed buffer chamber, allowing for easy detection of the SARS-CoV-2 N-protein in undiluted serum in just 40 minutes.

ANALYST (2021)

Article Chemistry, Analytical

Immunoassay of SARS-CoV-2 nucleocapsid proteins using novel red emission-enhanced carbon dot-based silica spheres

Lai-Di Xu et al.

Summary: This method utilizes red emission-enhanced CD-based silica spheres to ultrasonically detect SARS-CoV-2 NP, demonstrating fast detection speed, high specificity, and ease of operation.

ANALYST (2021)

Article Chemistry, Analytical

Development of spike protein-based fluorescence lateral flow assay for the simultaneous detection of SARS-CoV-2 specific IgM and IgG

Chongwen Wang et al.

Summary: The study introduced a lateral flow immunoassay method using quantum dot nanotags for simultaneous detection of SARS-CoV-2-specific IgM and IgG in patient serum, demonstrating high sensitivity and specificity. The method showed great potential for rapid and accurate identification of infected individuals, as validated by clinical samples.

ANALYST (2021)

Review Chemistry, Analytical

Rapid developments in lateral flow immunoassay for nucleic acid detection

Chujun Zheng et al.

Summary: This review discusses two main research directions of lateral flow nucleic acid tests, one involving the incorporation of isothermal amplification methods for increased sensitivity, and the other focusing on the development of novel labeling materials for improved quantifiability. Future research will focus on integrating the entire testing process into microfluidic systems and combining with molecular diagnostic tools to facilitate rapid and accurate testing.

ANALYST (2021)

Review Chemistry, Multidisciplinary

Diagnosing COVID-19: The Disease and Tools for Detection

Buddhisha Udugama et al.

ACS NANO (2020)

Editorial Material Pathology

Real-time RT-PCR in COVID-19 detection: issues affecting the results

Alireza Tahamtan et al.

EXPERT REVIEW OF MOLECULAR DIAGNOSTICS (2020)

Article Medicine, General & Internal

Rapid Large-Scale COVID-19 Testing during Shortages

Christian Beetz et al.

DIAGNOSTICS (2020)

Article Chemistry, Multidisciplinary

Rapid, ultrasensitive and highly specific biosensor for the diagnosis of SARS-CoV-2 in clinical blood samples

Lu Zeng et al.

MATERIALS CHEMISTRY FRONTIERS (2020)

Article Nanoscience & Nanotechnology

Machine Learning Approach to Enhance the Performance of MNP-Labeled Lateral Flow Immunoassay

Wenqiang Yan et al.

NANO-MICRO LETTERS (2019)

Review Materials Science, Biomaterials

A review of fluorescent signal-based lateral flow immunochromatographic strips

Xiaoqun Gong et al.

JOURNAL OF MATERIALS CHEMISTRY B (2017)

Article Chemistry, Physical

Absorption and scattering microscopy of single metal nanoparticles

M. A. van Dijk et al.

PHYSICAL CHEMISTRY CHEMICAL PHYSICS (2006)