Review—Nanozyme-Based Immunosensors and Immunoassays: Recent Developments and Future Trends

Since the first report in the 1950s, immunosensors and immunoassays with good specificity have got extensive applications in clinical diagnosis, food safety, and environmental monitoring. As a typical type of immunosensors, enzyme-linked immunosorbent assays (ELISAs) are able to offer high sensitivity for target sensing because of the catalytically amplified readouts produced by their enzyme labels (horseradish peroxidase, alkaline phosphatase, et al.). However, the use of these natural enzymes brings some undesired defects to traditional ELISAs, including high cost and short shelflife. Fortunately, the discovery of nanomaterials with enzyme-like catalytic features (nanozymes) provides a potential way to overcome the above shortcomings. By replacing natural enzymes with artificial nanozymes, the developed immunosensors exhibit lower cost, better stability, and easier production along with comparable sensitivity and selectivity. In this regard, the past few years have witnessed the booming development of nanozyme-based immunosensors. Herein, we make a review on currently developed immunosensors and immunoassays where nanozymes are used as promising alternatives to natural enzymes. Progress of nanozyme-based immunosensors made in recent years is summarized according to various signaling modes. Some trends in the field, like the exploration of high-activity single-atom nanozymes to further improve the sensitivity, are discussed as well, hoping to provide some guides for future research. © The Author(s) 2019. Published by ECS. This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives 4.0 License (CC BY-NC-ND, http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is not changed in any way and is properly cited. For permission for commercial reuse, please email: oa@electrochem.org. [DOI: 10.1149/2.0082003JES]

[1]  Chengzhou Zhu,et al.  When Nanozymes Meet Single-Atom Catalysis. , 2019, Angewandte Chemie.

[2]  Dan Du,et al.  Emerging applications of nanozymes in environmental analysis: Opportunities and trends , 2019, TrAC Trends in Analytical Chemistry.

[3]  Yuehe Lin,et al.  Single-Atom Nanozyme Based on Nanoengineered Fe-N-C Catalyst with Superior Peroxidase-Like Activity for Ultrasensitive Bioassays. , 2019, Small.

[4]  Dan Du,et al.  2D Graphene Oxide/Fe-MOF Nanozyme Nest with Superior Peroxidase-Like Activity and Its Application for Detection of Woodsmoke Exposure Biomarker. , 2019, Analytical chemistry.

[5]  Dan Du,et al.  Oxidase-Like Fe-N-C Single-Atom Nanozymes for the Detection of Acetylcholinesterase Activity. , 2019, Small.

[6]  Yuehe Lin,et al.  Unprecedented peroxidase-mimicking activity of single-atom nanozyme with atomically dispersed Fe-Nx moieties hosted by MOF derived porous carbon. , 2019, Biosensors & bioelectronics.

[7]  Da-Wen Sun,et al.  Development of Nanozymes for Food Quality and Safety Detection: Principles and Recent Applications. , 2019, Comprehensive reviews in food science and food safety.

[8]  Chengzhou Zhu,et al.  Fe-N-C Single-Atom Nanozyme for the Intracellular Hydrogen Peroxide Detection. , 2019, Analytical chemistry.

[9]  Peng Huang,et al.  Nanozyme: new horizons for responsive biomedical applications. , 2019, Chemical Society reviews.

[10]  Dan Du,et al.  Pt-Ni(OH)2 nanosheets amplified two-way lateral flow immunoassays with smartphone readout for quantification of pesticides. , 2019, Biosensors & bioelectronics.

[11]  Xiyun Yan,et al.  Nanozymes: From New Concepts, Mechanisms, and Standards to Applications. , 2019, Accounts of chemical research.

[12]  Zeynep Altintas,et al.  Graphene Quantum Dots as Nanozymes for Electrochemical Sensing of Yersinia enterocolitica in Milk and Human Serum , 2019, Materials.

[13]  Q. Wei,et al.  A nanozyme-linked immunosorbent assay for dual-modal colorimetric and ratiometric fluorescent detection of cardiac troponin I , 2019, Sensors and Actuators B: Chemical.

[14]  Chengzhou Zhu,et al.  Self-Assembly of All-Inclusive Allochroic Nanoparticles for the Improved ELISA. , 2019, Analytical chemistry.

[15]  Bing Zhang,et al.  TiO2/SnOx‐Au nanocomposite catalyzed photochromic reaction for colorimetric immunoassay of tumor marker , 2019, Journal of pharmaceutical and biomedical analysis.

[16]  Xueji Zhang,et al.  Gold-platinum nanoflowers as a label and as an enzyme mimic for use in highly sensitive lateral flow immunoassays: application to detection of rabbit IgG , 2019, Microchimica Acta.

[17]  A. A. Abd El-Aty,et al.  Colorimetric bio-barcode immunoassay for parathion based on amplification by using platinum nanoparticles acting as a nanozyme , 2019, Microchimica Acta.

[18]  Chengzhou Zhu,et al.  Au@Pt nanodendrites enhanced multimodal enzyme-linked immunosorbent assay. , 2019, Nanoscale.

[19]  S. Dong,et al.  Single-atom nanozymes , 2019, Science Advances.

[20]  Yingju Liu,et al.  Double-integrated mimic enzymes for the visual screening of Microcystin-LR: Copper hydroxide nanozyme and G-quadruplex/hemin DNAzyme. , 2019, Analytica chimica acta.

[21]  M. Melendez,et al.  Novel enzyme-free immunomagnetic microfluidic device based on Co0.25Zn0.75Fe2O4 for cancer biomarker detection. , 2019, Analytica chimica acta.

[22]  Qiaorong Tang,et al.  Ratiometric fluorescent immunoassay for the cardiac troponin-I using carbon dots and palladium-iridium nanocubes with peroxidase-mimicking activity , 2019, Microchimica Acta.

[23]  Black oxidized 3,3′,5,5′-tetramethylbenzidine nanowires (oxTMB NWs) for enhancing Pt nanoparticle-based strip immunosensing , 2019, Analytical and Bioanalytical Chemistry.

[24]  Shichao Lin,et al.  Design of high performance nanozymes: a single-atom strategy , 2019, Science China Life Sciences.

[25]  Xinghua Shi,et al.  A Single-Atom Nanozyme for Wound Disinfection Applications. , 2019, Angewandte Chemie.

[26]  Xiaogang Qu,et al.  Nanozymes: Classification, Catalytic Mechanisms, Activity Regulation, and Applications. , 2019, Chemical reviews.

[27]  Yadong Li,et al.  Unraveling the enzyme-like activity of heterogeneous single atom catalyst. , 2019, Chemical communications.

[28]  Nam-Trung Nguyen,et al.  Avoiding Pre-Isolation Step in Exosome Analysis: Direct Isolation and Sensitive Detection of Exosomes Using Gold-Loaded Nanoporous Ferric Oxide Nanozymes. , 2019, Analytical chemistry.

[29]  C. Chuang,et al.  A colorimetric immunosensor based on self-linkable dual-nanozyme for ultrasensitive bladder cancer diagnosis and prognosis monitoring. , 2019, Biosensors & bioelectronics.

[30]  Kaiwei Wan,et al.  Recent Advances in Nanozyme Research , 2018, Advanced materials.

[31]  Juan Li,et al.  A nanozyme tag enabled chemiluminescence imaging immunoassay for multiplexed cytokine monitoring. , 2018, Chemical communications.

[32]  Hongyang Ke,et al.  Enzyme-free ECL immunesensor based on PbS nanocrystals for highly sensitive detection of alpha fetoprotein , 2018, Sensors and Actuators B: Chemical.

[33]  Chengzhou Zhu,et al.  Hierarchical manganese dioxide nanoflowers enable accurate ratiometric fluorescence enzyme-linked immunosorbent assay. , 2018, Nanoscale.

[34]  Xin Li,et al.  Surface charge engineering of nanosized CuS via acidic amino acid modification enables high peroxidase-mimicking activity at neutral pH for one-pot detection of glucose. , 2018, Chemical communications.

[35]  Xin Li,et al.  Histidine-mediated tunable peroxidase-like activity of nanosized Pd for photometric sensing of Ag+ , 2018, Sensors and Actuators B: Chemical.

[36]  A. Salimi,et al.  Mimicking peroxidase activity of Co2(OH)2CO3-CeO2 nanocomposite for smartphone based detection of tumor marker using paper-based microfluidic immunodevice. , 2018, Talanta.

[37]  M. Ahmed,et al.  Supporting Information Recent developments in Colorimetric Immunoassays using Nanozymes and plasmonic nanoparticles , 2018 .

[38]  Yuming Huang,et al.  Recent advances in the construction and analytical applications of metal-organic frameworks-based nanozymes , 2018, TrAC Trends in Analytical Chemistry.

[39]  Shaojun Dong,et al.  Nanozyme: An emerging alternative to natural enzyme for biosensing and immunoassay , 2018 .

[40]  Min Liu,et al.  Biominerized gold-Hemin@MOF composites with peroxidase-like and gold catalysis activities: A high-throughput colorimetric immunoassay for alpha-fetoprotein in blood by ELISA and gold-catalytic silver staining , 2018, Sensors and Actuators B: Chemical.

[41]  Tao Zhang,et al.  Diagnosis of rubella virus using antigen-conjugated Au@Pt nanorods as nanozyme probe , 2018, International journal of nanomedicine.

[42]  Xiaogang Qu,et al.  Carbon Nanozymes: Enzymatic Properties, Catalytic Mechanism, and Applications. , 2018, Angewandte Chemie.

[43]  J. Ren,et al.  Hydrogen-producing hyperthermophilic bacteria synthesized size-controllable fine gold nanoparticles with excellence for eradicating biofilm and antibacterial applications. , 2018, Journal of materials chemistry. B.

[44]  M. Ahmed,et al.  Enzyme-free Gold-silver Core-shell Nanozyme Immunosensor for the Detection of Haptoglobin , 2018, Analytical sciences : the international journal of the Japan Society for Analytical Chemistry.

[45]  Kun Xu,et al.  Colorimetric immunoassay for Listeria monocytogenes by using core gold nanoparticles, silver nanoclusters as oxidase mimetics, and aptamer-conjugated magnetic nanoparticles , 2018, Microchimica Acta.

[46]  Xin Li,et al.  A smartphone-integrated ready-to-use paper-based sensor with mesoporous carbon-dispersed Pd nanoparticles as a highly active peroxidase mimic for H2O2 detection , 2018, Sensors and Actuators B: Chemical.

[47]  A. Tang,et al.  Standardized assays for determining the catalytic activity and kinetics of peroxidase-like nanozymes , 2018, Nature Protocols.

[48]  Yuting Zhao,et al.  A Nanozyme- and Ambient Light-Based Smartphone Platform for Simultaneous Detection of Dual Biomarkers from Exposure to Organophosphorus Pesticides. , 2018, Analytical chemistry.

[49]  Sourav Ghosh,et al.  Nanoisozymes: Crystal-Facet-Dependent Enzyme-Mimetic Activity of V2 O5 Nanomaterials. , 2018, Angewandte Chemie.

[50]  Xiaolin Huang,et al.  Multi-branched gold nanoflower-embedded iron porphyrin for colorimetric immunosensor. , 2018, Biosensors & bioelectronics.

[51]  Lizeng Gao,et al.  In vivo guiding nitrogen-doped carbon nanozyme for tumor catalytic therapy , 2018, Nature Communications.

[52]  Dong Kyu Lee,et al.  Magnetic Nanozyme-Linked Immunosorbent Assay for Ultrasensitive Influenza A Virus Detection. , 2018, ACS applied materials & interfaces.

[53]  M. Kim,et al.  Highly sensitive colorimetric detection of allergies based on an immunoassay using peroxidase-mimicking nanozymes. , 2018, The Analyst.

[54]  Juan Li,et al.  Efficient label-free chemiluminescent immunosensor based on dual functional cupric oxide nanorods as peroxidase mimics. , 2018, Biosensors & bioelectronics.

[55]  P. Skládal,et al.  Prussian Blue Nanoparticles as a Catalytic Label in a Sandwich Nanozyme-Linked Immunosorbent Assay. , 2018, Analytical chemistry.

[56]  Yadong Li,et al.  A single-atom Fe-N4 catalytic site mimicking bifunctional antioxidative enzymes for oxidative stress cytoprotection. , 2018, Chemical communications.

[57]  Ronghua Yang,et al.  Filling in the Gaps between Nanozymes and Enzymes: Challenges and Opportunities. , 2017, Bioconjugate chemistry.

[58]  M. Trau,et al.  Simple and rapid colorimetric detection of melanoma circulating tumor cells using bifunctional magnetic nanoparticles. , 2017, The Analyst.

[59]  Yang Song,et al.  Nanozyme-Mediated Dual Immunoassay Integrated with Smartphone for Use in Simultaneous Detection of Pathogens. , 2017, ACS applied materials & interfaces.

[60]  Chengzhou Zhu,et al.  Single-Atom Electrocatalysts. , 2017, Angewandte Chemie.

[61]  Jinwoo Lee,et al.  Pt-Decorated Magnetic Nanozymes for Facile and Sensitive Point-of-Care Bioassay. , 2017, ACS applied materials & interfaces.

[62]  Wentao Xu,et al.  Ultrasensitive Detection of Viable Enterobacter sakazakii by a Continual Cascade Nanozyme Biosensor. , 2017, Analytical chemistry.

[63]  Lizeng Gao,et al.  Iron Oxide Nanozyme: A Multifunctional Enzyme Mimetic for Biomedical Applications , 2017, Theranostics.

[64]  Mingdang Li,et al.  A novel sandwich-type electrochemical immunosensor for PSA detection based on PtCu bimetallic hybrid (2D/2D) rGO/g-C3N4. , 2017, Biosensors & bioelectronics.

[65]  Highly photosensitive colorimetric immunoassay for tumor marker detection based on Cu2+ doped Ag-AgI nanocomposite. , 2017, Talanta.

[66]  Suresh Neethirajan,et al.  Amplified visual immunosensor integrated with nanozyme for ultrasensitive detection of avian influenza virus , 2017, bioRxiv.

[67]  D. Tang,et al.  High-index {hk0} faceted platinum concave nanocubes with enhanced peroxidase-like activity for an ultrasensitive colorimetric immunoassay of the human prostate-specific antigen. , 2017, The Analyst.

[68]  Kai Cai,et al.  Near–infrared electrochemiluminesence biosensor for high sensitive detection of porcine reproductive and respiratory syndrome virus based on cyclodextrin-grafted porous Au/PtAu nanotube , 2017 .

[69]  Guonan Chen,et al.  High peroxidase-like activity of iron and nitrogen co-doped carbon dots and its application in immunosorbent assay. , 2017, Talanta.

[70]  Bing Zhang,et al.  Photoresponsive colorimetric immunoassay based on chitosan modified AgI/TiO2 heterojunction for highly sensitive chloramphenicol detection. , 2017, Biosensors & bioelectronics.

[71]  Wei Wen,et al.  Recent Advances in Electrochemical Immunosensors. , 2017, Analytical chemistry.

[72]  Juewen Liu,et al.  Iron oxide nanozyme catalyzed synthesis of fluorescent polydopamine for light-up Zn(2+) detection. , 2016, Nanoscale.

[73]  Juan Li,et al.  Smart CuS Nanoparticles as Peroxidase Mimetics for the Design of Novel Label-Free Chemiluminescent Immunoassay. , 2016, ACS applied materials & interfaces.

[74]  Lizeng Gao,et al.  Nanozymes: an emerging field bridging nanotechnology and biology , 2016, Science China Life Sciences.

[75]  Xingyu Jiang,et al.  Integration of nanomaterials for colorimetric immunoassays with improved performance: a functional perspective. , 2016, The Analyst.

[76]  Xiaoyu Wang,et al.  Nanozymes in bionanotechnology: from sensing to therapeutics and beyond , 2016 .

[77]  Yang Liu,et al.  Nanozyme-strip for rapid local diagnosis of Ebola. , 2015, Biosensors & bioelectronics.

[78]  Z. Chai,et al.  Peptide-Conjugated Gold Nanoprobe: Intrinsic Nanozyme-Linked Immunsorbant Assay of Integrin Expression Level on Cell Membrane. , 2015, ACS nano.

[79]  D. Tang,et al.  Mesoporous carbon-enriched palladium nanostructures with redox activity for enzyme-free electrochemical immunoassay of brevetoxin B. , 2015, Analytica chimica acta.

[80]  Li Li,et al.  Microfluidic paper-based multiplex colorimetric immunodevice based on the catalytic effect of Pd/Fe₃O₄@C peroxidase mimetics on multiple chromogenic reactions. , 2015, Analytica chimica acta.

[81]  Zhifei Wang,et al.  Peroxidase-like activity of mesoporous silica encapsulated Pt nanoparticle and its application in colorimetric immunoassay. , 2015, Analytica chimica acta.

[82]  Chengzhou Zhu,et al.  Electrochemical Sensors and Biosensors Based on Nanomaterials and Nanostructures , 2014, Analytical chemistry.

[83]  E. Wang,et al.  Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes. , 2013, Chemical Society reviews.

[84]  Guonan Chen,et al.  Irregular-shaped platinum nanoparticles as peroxidase mimics for highly efficient colorimetric immunoassay. , 2013, Analytica chimica acta.

[85]  C. Suri,et al.  Palladium@gold bimetallic nanostructures as peroxidase mimic for development of sensitive fluoroimmunoassay. , 2012, Analytica chimica acta.

[86]  Juyoung Yoon,et al.  Fluorescent and colorimetric sensors for detection of lead, cadmium, and mercury ions. , 2012, Chemical Society reviews.

[87]  W. Marsden I and J , 2012 .

[88]  Xiaolei Zuo,et al.  Design of a carbon nanotube/magnetic nanoparticle-based peroxidase-like nanocomplex and its application for highly efficient catalytic oxidation of phenols , 2009 .

[89]  Yuehe Lin,et al.  Nanomaterial labels in electrochemical immunosensors and immunoassays. , 2007, Talanta.

[90]  Yu Zhang,et al.  Intrinsic peroxidase-like activity of ferromagnetic nanoparticles. , 2007, Nature nanotechnology.

[91]  R. Lequin Enzyme immunoassay (EIA)/enzyme-linked immunosorbent assay (ELISA). , 2005, Clinical chemistry.

[92]  B. Gould,et al.  Use of enzymes in immunoassay techniques. A review , 1984 .

[93]  M. Kronick,et al.  Immunoassay techniques with fluorescent phycobiliprotein conjugates. , 1983, Clinical chemistry.

[94]  S. Berson,et al.  Assay of Plasma Insulin in Human Subjects by Immunological Methods , 1959, Nature.