Chem. J. Chinese Universities

#br#

2021, 42(11): 0.

Asbtract ( )

PDF (316KB) ( )

Related Articles | Metrics

Recent Progress in Controlled Synthesis of Persistent Luminescence Nanomaterials for Diagnosis Applications

XI Jing, CHEN Na, YANG Yanbing, YUAN Quan

2021, 42(11): 3247-3264. doi:10.7503/cjcu20210509

Asbtract ( )

HTML ( )

PDF (3085KB) ( )

Figures and Tables | References | Related Articles | Metrics

Persistent luminescence nanomaterials with special optical characteristics can remain luminescent after cessation of excitation. By collecting the persistent luminescence signal after autofluorescence decays， autofluorescence interference can be efficiently eliminated. Additionally， the interference of light scattering can also be avoided since in situ light excitation is not involved， leading to improved sensitivity in biodetection and bioimaging. Owing to the distinct optical properties， persistent luminescence nanoparticles opened a new door to the biological applications from biosensing/bioimaging to theranostics. Recently， controlled synthesis of persistent luminescence nanomaterials with improved luminescent properties and biocompatibility has attracted great attention with the increasing need for in vitro biodetection and in vivo bioimaging. In this review， we firstly summarize the controlled synthesis method for persistent luminescence nanomaterials， such as sol-gel method， hydrothermal method， thermal decomposition method， template method， etc. Secondly， the application of the persistent luminescence nanomaterials for diagnosis both in vitro and in vivo are further discussed. Given the potential of persistent luminescence nanomaterials in biosensing， the current challenges and future perspective are also discussed.

Research Progress of Bacterial Infection Imaging

ZHANG Yaqing, LI Linyao, HAO Mengqi, LUO Qin, DENG Siyu, YANG Yun, LIANG Xuewei, FANG Weiwei, SONG Erqun

2021, 42(11): 3265-3276. doi:10.7503/cjcu20210461

Asbtract ( )

HTML ( )

PDF (2095KB) ( )

Figures and Tables | References | Related Articles | Metrics

As one of the major causes for death， bacterial infection is caused by pathogenic bacteria or opportunistic pathogens that invade the human body and proliferate， producing toxins and other metabolites. Early diagnosis of infectious diseases is an important approach to effective treatment and control of infectious diseases. The rapid development of molecular imaging technology has brought unprecedented changes and opportunities to the evaluation of bacterial infection in vivo. This article reviews the research progress and the future development direction of imaging of bacterial infection in vivo based on the imaging methods such as computed tomography， ultrasound imaging， magnetic resonance imaging， fluorescence imaging， photoacoustic imaging， and others， aiming to provide reference for the development of detecting bacterial infection in vivo.

Progress in Aptamer-targeted Membrane Protein Recognition and Functional Regulation

LIU Xuejiao, YANG Fan, LIU Shuang, ZHANG Chunjuan, LIU Qiaoling

2021, 42(11): 3277-3283. doi:10.7503/cjcu20210465

Asbtract ( )

HTML ( )

PDF (904KB) ( )

Figures and Tables | References | Related Articles | Metrics

Membrane protein plays an important role in various biological process. Modulation the structural and functional property of membrane protein would help to clarify the fundamental molecular mechanisms and provide basis for drug discovery and efficient therapeutic strategy. Aptamer is a special kind of oligonucleotide which can bind to its target efficiently. Due to its unique properties， aptamer is widely used in biosensing application. As a biological material， DNA molecule possesses the advantages of programmable design and facile functionalization. Thus， the combination of aptamer with DNA nanotechnology would provide a powerful tool for studying the interactions between membrane proteins. This review summarizes the recent research progress on aptamer-targeted membrane protein recognition and functional regulation utilizing DNA nanotechnology. The promising prospects and challenges in the future application of aptamer-targeted membrane protein recognition and functional regulation are also highlighted.

Regulation of Cell-cell Interactions Based on DNA Nanostructures

HU Ling, YIN Yao, KE Guoliang, ZHANG Xiaobing

2021, 42(11): 3284-3294. doi:10.7503/cjcu20210451

Asbtract ( )

HTML ( )

PDF (1486KB) ( )

Figures and Tables | References | Related Articles | Metrics

Cells exchange materials and information with each other through chemical signals， electronic exchange and direct contact， to regulate the growth and development of living organisms. Therefore， the research and regulation of cell-cell interaction are great significance in mechanism study of cell functions and the diagnosis and treatment of diseases. DNA nanostructures have the advantages of easy synthesis， easy modifi- cation， programmable design， and high biological safety， which are promising for cell-cell interactions research with simple operation， precise adjustment， and intelligent response. In this review， we summarized the DNA nanostructure-based cell assembly strategies such as oligonucleotide hybridization， receptor-ligand binding， and aptamer targeted recognition， then introduced some regulation means such as pH， metal ions， and DNA triggers. The discussion also focused on some applications of cell-cell interactions， including intercellular force measurement and imaging， in vitro tissue construction， cell-cell communication and cellular immunotherapy. Finally， the opportunity and challenge in this field were discussed.

Coordination Porous Polymers for Targeting Subcellular Organelles： Bio-imaging， Diagnosis and Therapy

KE Mengting, YUAN Jiangpei, ZHANG Heng, FANG Yu

2021, 42(11): 3295-3309. doi:10.7503/cjcu20210464

Asbtract ( )

HTML ( )

PDF (3186KB) ( )

Figures and Tables | References | Related Articles | Metrics

Due to the changes in the external environment and living habits， the incidence and mortality rate of cancer are increasing day by day， so the problem of cancer prevention and treatment needs to be solved urgently. In recent years， a variety of targeted drugs for tumor cells in vivo have been reported based on the properties of porous nanomaterials. Metal-organic framework（MOF） and porous coordination cage（PCC） can be modified to some extent due to their diverse structures， high design ability， and certain modifiability. Therefore， it has received the favor of many researchers and obtained considerable development. Although metal- organic frameworks and porous coordination cages have been extensively studied in the fields of gas adsorption separation， chiral separation， catalysis， fluorescence and sensing， and electrical conductivity， their applications in biomedical applications have not been fully explored. In this paper， the research work of metal-organic framework and porous coordination cage in imaging and diagnosis and treatment of organisms is summarized， and some problems existing in the application of coordinated porous polymers in the biomedical field are pointed out.

Recent Advances in Fabricating the Multifunctional Aβ Small Organic Molecule Probes for Theranostic Application

CHEN Xiaoyu, LIU Yisheng, HE Mu, SHANGGUAN Ping, HAN Lulu, WANG Jiefei, SHI Bingyang

2021, 42(11): 3310-3320. doi:10.7503/cjcu20210452

Asbtract ( )

HTML ( )

PDF (2035KB) ( )

Figures and Tables | References | Related Articles | Metrics

Alzheimer’s disease（AD） is one of the most important progressive neurological diseases， which is characterized by the formation， misfolding， and aggregation of β-amyloid protein（Aβ）. Based on the special blood brain barrier（BBB） system and protein structure of Aβ， a variety of multifunctional Aβ fluorescent probes with high sensitivity， facile operation， and low toxicity， were developed for the detection and treatment of AD. This review respectively focused on the imaging detection and therapy of Aβ， and systematically reviewed the chemical regulation strategy for brain-target design， wavelength regulation， and integration of diagnosis with treatment. In the end， the perspective for the multifunctional fluorescent Aβ probes was also discussed.

Recent Advance in Light-controlled CRISPR Technology

LIU Hong, JIANG Jinghong, DUAN Zhijuan, XU Shijun, HUANG Fujian, XIA Fan

2021, 42(11): 3321-3333. doi:10.7503/cjcu20210420

Asbtract ( )

HTML ( )

PDF (1947KB) ( )

Figures and Tables | References | Related Articles | Metrics

The CRISPR-Cas system provides a versatile tool for programmable genome editing. The collision of CRISPR with optogenetics and photochemical biology has produced a brilliant spark. The photoactivated CRISPR-Cas system enables better spatial and temporal regulation of RNA-guided nuclease activity. In recent years， scientists have developed a range of light-activated CRISPR tools using a combination of CRISPR and a variety of optical techniques. These tools allow researchers to conduct high-resolution studies of life activities in spatial， temporal and genomic coordinates. In this review， research progress of the CRISPR system， gene editing technology， optogenetics and photochemical biology are briefly summarized， and the development of light-induced CRISPR technology is prospected.

Advances of Multifunctional Deoxyribozyme in Biomedical Analysis

WANG Qing, HE Yuqiu, WANG Fuan

2021, 42(11): 3334-3356. doi:10.7503/cjcu20210449

Asbtract ( )

HTML ( )

PDF (4427KB) ( )

Figures and Tables | References | Related Articles | Metrics

Deoxyribozymes（DNAzymes） are synthetic deoxynucleotide oligomers with enzyme-like activities identified through in vitro SELEX selection technology. DNAzymes have been widely explored in a broad range of applications， notably in biosensing and biomedical devices， owing to their easy synthesis and modification， stable chemical structure and excellent catalytic activity. Regulating the activity of DNAzymes is the key for exploring its potential utilization in many fields， and the flexible control will dramatically promote the application of DNAzymes. In this review， we summarize some methods for the regulation of DNAzymes activity and introduce their main applications in biomedical analysis. It is believed that DNAzymes will play a critical role in chemistry and medicine in the future.

Synthesis of Melanin and Its Function Regulation by Small Molecules

PENG Haiyue, WANG Ting, LI Guorui, HUANG Jing

2021, 42(11): 3357-3366. doi:10.7503/cjcu20210410

Asbtract ( )

HTML ( )

PDF (1445KB) ( )

Figures and Tables | References | Related Articles | Metrics

Melanin， as a natural pigment， can be roughly classified into eumelanin and pheomelanin. They are widely found in microorganisms， animals and plants， and have functions of radical scavenging， radiation protection and thermal regulation. In humans， melanin is responsible for the color of skin， hair and eyes， and plays an important role in protecting skin from harmful damage caused by ultraviolet radiation. Abnormal functioning of melanocytes can lead to a range of skin problems， such as melanoma， vitiligo and other diseases. Therefore， regulating the synthesis of melanin is a significant strategy for pigmentation-related disease therapy. Melanogenesis is a catalytic and chemical process that involves many enzymes such as tyrosinase， tyrosinase-related proteins. It’s an effective way to regulate the synthesis of melanin by changing tyrosinase activity and expression. In living organisms， melanin is biosynthesized. Because of its unique function， some artificial chemical synthesis methods of melanin have been also developed. In terms of small molecules regulating melanin function， many small molecules that inhibit melanin formation have been found. They have opened new minds for the treatment of melanin-related diseases. In this review， we discussed the biosynthesis and artificial synthesis process of melanin， its inhibition and regulation mechanisms by small molecule. It might provide a theoretical basis for the development of safe and efficient melanin-related drugs.

Investigations upon the Bioconjugation-based Construction Technologies and Applications of Aptamer-drug Conjugates

ZHAO Zhuo, WANG Xueqiang

2021, 42(11): 3367-3378. doi:10.7503/cjcu20210460

Asbtract ( )

HTML ( )

PDF (2061KB) ( )

Figures and Tables | References | Related Articles | Metrics

Aptamers are called “chemical antibodies” and have similar or superior specificity and affinity as antibodies. And it can precisely target the target protein and specifically bind to the target protein. In addition， aptamers possess many advantages such as simple acquisition and synthesis， easy chemical modification， not easy to denature， a wide range of targets， low immunogenicity， and fast cell internalization. Therefore， aptamers have been widely utilized in various research fields. In the area of cancer therapy， aptamers， as an excellent target identification tool and drug delivery vehicle， can precisely deliver anticancer drugs to tumor tissues. By coupling the nucleic acid aptamer to the drug molecule， we can make the drug molecule enter the targeted cells along with the aptamer through the targeting effect of the aptamer， so as to achieve the enrichment of the drug molecule in the targeted cells， and then produce the growth inhibitory effect on the targeted cells. In recent years， aptamer-drug conjugates have evolved into a frontier emerging field of cancer targeted therapy. It is hoped that through the study of nucleic acid aptamer conjugated drugs， new perspectives in targeted cancer treatment will be provided. This article reviewed the studies on aptamer-drug conjugates constructed by bioconjugation technologies and their applications.

Research Progress of Molecular Recognition and Interaction of Crystallins Linking Cataract

LIN Ningqin, YAO Ke, CHEN Xiangjun

2021, 42(11): 3379-3389. doi:10.7503/cjcu20210441

Asbtract ( )

HTML ( )

PDF (1268KB) ( )

Figures and Tables | References | Related Articles | Metrics

Cataract formation is the leading cause of blindness across the globe. The eye lens is the onset site of cataract. The eye lens is densely packed with crystallins at a high concentration. Crystallins are categorized into 3 distinct families： α?， β?， and γ-CRYs. The α-CRYs are known to function as a small molecule chape- rone， recognizing misfolded proteins and maintaining protein homeostasis in the lens. While the β?/γ-CRYs serve a key structural role in lens formation through intramolecular and intermolecular interactions. Crystallins are arranged in transiently short-range order within the lens fibers. In addition， the molecular recognition and dynamic protein interactions that are medicated by crystallins serve a critical role in maintaining the transpa-rency of the eye lens. Protein homeostasis disorder in eye lens is the main pathogenic factors causing cataract. The crystallins have a long half-life and no longer renewed after protein synthesis. Therefore， the crystallins are highly susceptible to both the extracellular and intracellular factors， such as pH， metal ions， radiation damage and post-translational modifications. These factors disrupt molecular recognition of the crystallins or alter protein-protein interactions， resulting in cataract formation. Identifying the chemical regulatory principles of molecular recognition and protein interactions of the crystallins can help elucidate the molecular mechanisms that maintain or disrupt lens transparency， along with developing innovative treatment strategies for cataract. In this review， based on recent progress in crystallins and cataracts， we comprehensively summarized the way of molecular recognition and protein interaction in the crystallins， as well as the regulatory factors. Recent technological innovations that were enabling us to characterize interactions between the crystallins were further discussed. In addition， we investigated the application values and challenges of protein-protein interaction networks that were dominated by the crystallins in the anti-cataract drug development.

Lateral Flow Assay Based on Molecular Recognition for Diagnosis of Corona Virus Disease 2019 Infection

LIU Yuan, DENG Jinqi, ZHAO Shuai, TIAN Fei, LI Yi, SUN Jiashu, LIU Chao

2021, 42(11): 3390-3405. doi:10.7503/cjcu20210257

Asbtract ( )

HTML ( )

PDF (2017KB) ( )

Figures and Tables | References | Related Articles | Metrics

The novel coronavirus disease 2019（COVID-19） pandemic caused by severe acute respiratory syndrome coronavirus 2（SARS-CoV-2） is still spreading worldwide. Rapid screening and isolation of infected individuals， including asymptomatic individuals， is one of the key steps to control the epidemic. Lateral flow assay is a mature technique for point-of-care detection. Owing to its advantages of simple operation， fast response and robustness， lateral flow assay has been a powerful tool for rapid detection of biomarkers. This paper summarized the recent research progresses of lateral flow assays for the diagnosis of COVID-19 infection， with antibody， protein， or nucleic acid as detection targets， and the advantages and limitations of different detection methodologies were shortly discussed. Finally， we briefly introduced the currently commercialized lateral flow test strips for COVID-19 diagnostics.

Recent Progress of Aptamer Functionalized Two-dimensional Materials Field Effect Transistor Sensors

XIE Chen, CHEN Na, YANG Yanbing, YUAN Quan

2021, 42(11): 3406-3420. doi:10.7503/cjcu20210510

Asbtract ( )

HTML ( )

PDF (2564KB) ( )

Figures and Tables | References | Related Articles | Metrics

Two-dimensional materials field-effect transistor sensors with adjustable electrical properties have been viewed as potential candidates for the design of high performance sensors for disease diagnosis and environmental monitoring. As a kind of nucleic acid molecules with recognition capability， aptamer exhibits high specificity and excellent stability for target molecules. In recent years， remarkable progress has been achieved in the field of aptamer functionalized two-dimensional materials field-effect transistor sensors. In this review， the latest research progress of aptamer functionalized two-dimensional materials field-effect transistor sensors is summarized. The structure and sensing principle of field-effect transistor sensors are illustrated. The preparation methods of two-dimensional materials and the design principle of aptamer functionalized sensors are comprehensively reviewed. For a further step， the application of aptamer functionalized two-dimensional materials field-effect transistor sensors in the field of disease diagnosis and environmental monitoring is summarized. Finally， the challenges and prospects of aptamer functionalized two-dimensional materials field-effect transistor sensors are discussed.

Research Progress of Multiplex Immunoassay

LUO Cheng, PENG Yamei, SHEN Hong, FANG Qun, PAN Jianzhang

2021, 42(11): 3421-3432. doi:10.7503/cjcu20210455

Asbtract ( )

HTML ( )

PDF (2478KB) ( )

Figures and Tables | References | Related Articles | Metrics

Clinically， immunoassay is the main method to detect physiologically related protein indicators. Compared with the singleplex immunoassay， clinical in vitro diagnosis has a greater demand for the multiplex immunoassay of physiologically related proteins. The heterogeneous immunoassay method that complete the immune reaction on a solid-phase carrier has the advantage of high sensitivity， and has become the main method of multiplex immunoassay at present. According to the different solid-phase， the research progress of multiplex immunoassay systems in recent years has been reviewed in terms of technical principles， methods， and characteristics. Finally， the advantages and disadvantages of different systems are compared and summarized， and the development of microfluidic multiplex immunoassay in the point of caring testing（POCT） field is prospected.

Fluorescent Probe for Hypoxia-triggered Imaging and Cancer Therapy

CHEN Weiju, CHEN Shiya, XUE Caoye, LIU Bo, ZHENG Jing

2021, 42(11): 3433-3444. doi:10.7503/cjcu20210394

Asbtract ( )

HTML ( )

PDF (3063KB) ( )

Figures and Tables | References | Related Articles | Metrics

The insufficient oxygen supply， known as hypoxia， is one of the most obvious features of tumors. In tumor regions， caused by the exaggerated growth of solid tumor， the depletion of oxygen in interior cells far exceeds their blood supply. Hypoxia will lead to a series of problems in tumor microenvironment， including increased tumor metastasis， drug resistance and pro-survival changes in gene expression. Thus， the construction of hypoxia-responsive fluorescent probe is vital to tumor diagnosis and prognosis. In this review， we discussed recent progress in fluorescent probe for hypoxia-triggered living cells imaging and cancer therapy. At first， we introduced three main sensing moieties which were sensitive to oxygen or oxygen-related enzymes， such as azoreductase， nitroreductase， quinone reductase and so on. Then， the latest progress in fluorescent probes for imaging under hypoxia conditions was summarized， including imaging for hypoxia-related parameter and hypoxia-related metabolic process. Third， based on different therapeutic strategies， including gene therapy， chemotherapy， photodynamic therapy and synergistic therapy， we discussed the research progress of hypoxia-responsive fluorescent probe for cancer therapy. In the future， we look forwarded to develop probe with excellent ability of targeting and selecting for hypoxia-activated imaging and cancer therapy， which could further facilitate cancer diagnosis and treatment in clinical area.

Research Progress on RNA⁃cleaving DNAzyme for the Detection of Pathogenic Bacteria

MAO Yu, QU Hao, ZHENG Lei

2021, 42(11): 3445-3456. doi:10.7503/cjcu20210450

Asbtract ( )

HTML ( )

PDF (1778KB) ( )

Figures and Tables | References | Related Articles | Metrics

DNAzymes， produced through in vitro selection process， are single-stranded oligonucleotides that have catalytic functions. With the development of in vitro selection technology， more and more DNAzymes have been selected. Among them， RNA-cleaving DNAzyme（RCD） has the functions of molecular recognition and catalytic signal amplification， and has the advantages of flexible design， easy preparation and low modification cost， etc.， which has gained widespread attention and application in the field of detection of pathogenic bacteria， providing a new molecular tool for early detection and prevention of pathogenic bacteria. In this paper， the research and application of RNA-cleavage deoxyribozyme in the detection of pathogenic bacteria were systematically summarized， and the problems and future development prospects of RNA-cleavage deoxyribozyme were also prospected.

Selection of Functionalized Aptamers and Their Applications in Molecular Recognition

JI Cailing, CHENG Xing, TAN Jie, YUAN Quan

2021, 42(11): 3457-3467. doi:10.7503/cjcu20210442

Asbtract ( )

HTML ( )

PDF (1379KB) ( )

Figures and Tables | References | Related Articles | Metrics

Aptamers are single-stranded oligonucleotides selected from oligonucleotide libraries. Due to their specific molecular binding ability， aptamers have been employed as molecular recognition tools and have been widely used in biomedicine. The finite chemical composition of natural nucleic acid libraries limits the structure and function of aptamers， thus restricting the applications of aptamers in molecular recognition. Functionalized aptamers introduce specific chemical functional groups to endow nucleic acid sequences with rich spatial conformation and new properties， enhancing their molecular recognition capabilities. However， functionalized nucleic acids are difficult to be compatible with nucleic acid amplification methods， making it difficult for traditional selection protocols to screen functionalized nucleic acids. Therefore， optimizing the selection strategies is essential to obtain functionalized aptamers with excellent performance. This review summarizes the selection methods of functionalized aptamers， and introduces the application of functionalized aptamers as molecular recognition tools in the field of biomedicine.

Advances in Bacteria Biosensing Based on Molecular Recognition

ZHANG Xiaorong, CHEN Lanlan, HU Shanwen

2021, 42(11): 3468-3476. doi:10.7503/cjcu20210425

Asbtract ( )

HTML ( )

PDF (1309KB) ( )

Figures and Tables | References | Related Articles | Metrics

Bacteria widely exist in the natural environment and are closely related to human health. The identification and detection of bacteria are of great significance for public health and medical health. Recently， more attention has been attracted in molecular recognition-based bacteria biosensing with high specificity and sensitivity. Herein， recent progresses of bacterial detection based on molecular recognition are reviewed. Molecular recognition methods are classified into three kinds of interactions： antibody-antigen immune interaction， nucleic acid recognition based on Watson-Crick base-pairing， and aptamer-ligand interaction. Finally， the existing bottlenecks of bacterial detection related research are summarized， and the potential of this field is inspiring.

Research Progress on Improving the Binding Affinity of Aptamers through Chemical Modification

LIU Ke, JIN Yu, LIANG Jiangong, WU Yuan

2021, 42(11): 3477-3492. doi:10.7503/cjcu20210292

Asbtract ( )

HTML ( )

PDF (2381KB) ( )

Figures and Tables | References | Related Articles | Metrics

Aptamers are short single-stranded DNA or RNA oligonucleotides obtained through in vitro systematic evolution of ligands by exponential enrichment（SELEX）. They possess high specificity and high affinity equivalent to or better than those of antibody. Moreover， they have been studied widely in food， environment， and biomedical fields due to many other advantages， such as wide range of targets， easy preparation， flexible and controllable modification， low immunogenicity， small batch variation， and easy storage. But so far， commercial applications of aptamers are still limited. Researchers have conducted numerous chemical modifications to enhance the performance of aptamers. This review focused on the non-covalent or covalent chemical modification of aptamers pre- and post-SELEX to increase the binding affinity of aptamer towards the target. It systematically summarized the research progress of chemical modification of aptamers in recent years and discussed the prospective of the future development.

Advances in Molecular Recognition of Exosomes Based on Aptamers

HUANG Ling, ZHUANG Zijian, LI Xiang, SHI Muling, LIU Gaoqiang

2021, 42(11): 3493-3508. doi:10.7503/cjcu20210458

Asbtract ( )

HTML ( )

PDF (1442KB) ( )

Figures and Tables | References | Related Articles | Metrics

Exosomes are globular bodies with lipid bilayer membrane structure secreted by living cells. Since researchers have confirmed that the exosomes undertake the function of extracellular RNA transportation， the research on the origin and function of exosomes is in the ascendant. In recent years， exosomes have been found to have the potential to be disease biomarkers， which makes exosomes with specific surface proteins and specific carriers become valuable detection objects in biomedical science. From the perspective of chemical essence， the acquisition and analysis of exosomes need to rely on specific molecular recognition process. Aptamers， as molecular recognition units， are characterized by high specificity， high affinity， steady bioactivity， easy synthesis and preservation， as well as facile design and modification. Aptamers have been successfully applied in biosensors for exosomes. In this review， based on the chemical composition of exosomes and their components with physiological and pathological significance， we introduce representative work in the field of extracellular vesicle analysis using aptamers as molecular recognition units， and summarize the existing apta-mer sequence information and application scenarios targeting exosomes. In particular， the latest progress of chemical regulation methods to enhance the recognition performance of aptamers is surveyed. We expect that the future progress in the selection and modification of aptamers will open up new and exciting avenues for molecular recognition of exosomes.

Multicolor Immunodiagnostic for Semiquantitative Visual Detection Syndrome Coronavirus 2 Specific Antibody： A Prospect Strategy for On-site COVID-19 Therapeutic Process Monitoring

CHEN Zhonghui, LI Jinqiu, LIN Wei, YU Liumin, TU Haijian, CHEN Yu, CAI Zongwei, LIN Zhenyu

2021, 42(11): 3509-3518. doi:10.7503/cjcu20210363

Asbtract ( )

HTML ( )

PDF (1136KB) ( )

Figures and Tables | References | Related Articles | Metrics

Rapid detection of body fluid severe acute respiratory syndrome coronavirus 2（SARS-CoV-2） antibody is an effective strategy for infection therapeutic effect of coronavirus disease（COVID-19）. Most detection methods require relatively large equipment， which limited their on-site application. Lateral flow immunoassay（LFIA） can be used to qualitative antibody detection based on the aggregation of gold nanoparticles （Au NPs）， which exhibits just one-color change and cannot realize rapid quantitative detection without the help of additional equipment. In this study， a high-resolution multicolor colorimetric strategy was developed and applied to assessing antibody concentration at a glance based on etching of gold nanorods（Au NRs）. Firstly， SARS-CoV-2 recombinant antigen was immobilized on the surface of the 96-wells. Then， horseradish peroxidase（HRP）-labeled second antibody combined with antibody to form an antigen-antibody-secondary antibody complex on the well surface， which has direct relationship with antibody concentration in the sample and can be used to oxidize 3，3′，5，5′-tetramethylbenzidine（TMB） to form TMB²⁺ at the presence of HRP. The generation of TMB²⁺ efficiently etch Au NRs to produce multicolor solution. The etching result in vivid color changes in the system has a relationship with the amount of SARS-CoV-2 IgM antibody. Under the optimal conditions， the proposed strategy exhibited a linear response in the 5.00―200 IU concentration range， and a detection limit of 1.29 IU for SARS-CoV-2 IgM antibody， with high sensitivity and specificity. This assay is prospective for the on-site semi-quantitative visual detection of SARS-CoV-2 IgM antibody concentration in the COVID-19 therapeutic process.

Construction of Electrochemiluminescence Sensing Interface Based on Silver Nanoclusters-Silica Nanoparticles and Biomolecular Recognition

WANG Bodong, PAN Meichen, ZHUO Ying

2021, 42(11): 3519-3525. doi:10.7503/cjcu20210392

Asbtract ( )

HTML ( )

PDF (1332KB) ( )

Figures and Tables | References | Related Articles | Metrics

A highly sensitive L-Cys（L-cysteine） biosensor was constructed via silver nanoclusters loaded on the surface of silica nanoparticles（Ag NCs-SiO₂ NPs） as an electrochemiluminescence（ECL） nanocomposite modified on the surface of glassy carbon electrode. The surface of silica nanoparticles（SiO₂ NPs） was functio-nalized with amino and sulfhydryl groups by bovine serum protein（BSA）， and then silver nanoclusters （Ag NCs） were in situ reduced on the surface of SiO₂ NPs by using BSA as a template and a reducing agent， which realized the stable load of silver nanoclusters. The Ag NCs-SiO₂ NPs electrochemiluminescence nanocomposites with the enhanced cathodic ECL signal were successfully obtained. With the existence of L-Cys in the solution， it covalently binds to Ag NCs forming Ag—S bond and quenching the ECL signal. Based on the above principle， a biosensor with the on-off signal response mode is constructed for the detection of L-Cys. The concentration range of L-Cys detected by the biosensor is 50 nmol/L—50 μmol/L. At the same time， the detection limit is 13.7 nmol/L， which can realize the sensitivity and specificity analysis of L-Cys. The biosensor constructed above is expected to be extensively applied in biological， medical and other fields.

Synthesis of Crosslinked Micelles and Ring-like Colloids via a Cyclic Template with Multivalency

ZHANG Miao, PENG Jinlei, LIU Ying, LIU Fangjun, MA Wei, WEI Hua

2021, 42(11): 3526-3536. doi:10.7503/cjcu20210370

Asbtract ( )

HTML ( )

PDF (1805KB) ( )

Figures and Tables | References | Related Articles | Metrics

The pendant hydroxyl groups of c-P（HEMA）₅₀ were first decorated with ferrocene（Fc） by click coupling to afford c-P（HEMA-Fc）₅₀， which was then used as a core template to direct the supramolecular comple-xation with β-cyclodextrin（β-CD） functionalized with both hydrophilic poly（ethylene glycol）（PEG） and lipoic acid（LA）（β-CD-PEG-LA） viaβ-CD/Fc host-guest inclusion complexation. The resulting supramolecular micelle formed by c-P（HEMA-Fc）₅₀/β-CD-PEG-LA could be crosslinked via dithiothreitol（DTT）-catalyzed intramolecular self-crosslinking of the decorated LA units to serve as a precursor of the ring-like colloids of crosslinked β-CD-PEG-LA. The advantage of this cyclic polymer over the previously used three-arm star-shaped polymer as a template lies in the multivalent structure of the cyclic polymer with greater stability and steric hindrance， which results in a significantly increased preparation concentration of 1.0 mg/mL for the ring-like colloids.

Preparation of Water-soluble Coumarin Fluorescent Substrate and Its Application in Droplet Based Digital Detection

KUANG Xiaojun, YI Jingwei, FANG Xiaoxia, LAI Dongmei, XU Hong

2021, 42(11): 3537-3546. doi:10.7503/cjcu20210459

Asbtract ( )

HTML ( )

PDF (2717KB) ( )

Figures and Tables | References | Related Articles | Metrics

4-Methylumbelliferyl phosphate is one of the most important fluorescent substrate， but its application in the droplet based microfluidic field is limited by its high hydrophobicity and diffusion property between droplets. In this paper， a novel high water solubility fluorescent substrate 7-（dihydroxyphosphoryloxyl） coumarin-4-acetic acid methyl ester was synthesized by modifying 7-hydroxycoumarin-4-acetic acid. The droplet microfluidics based single SP-AKP digital detection system was established with prepared 7-（dihydroxyphosphoryloxyl） coumarin-4-acetic acid methyl ester as the fluorescent substrate， and the spherical brush enzyme（polyelectrolyte nanoparticals loaded with a large number of alkaline phosphatases， SP-AKP） prepared by our research group as the model enzyme. The results showed that the new water-soluble coumarin fluorescent substrate had similar fluorescence spectroscopy and enzyme catalytic performance to traditional 4-MUP substrate. Compared with the enzyme-catalyzed fluorescent product of traditional substrate 4-MUP， which diffused signi- ficantly in droplets within 5 min， the enzyme-catalyzed fluorescent product（7-hydroxycoumarin-4-acetic acid） of the new fluorescent substrate had excellent diffusion suppression performance， which was stable in the droplet within 24 h with no obvious diffusion phenomenon. Further application in droplet based digital enzyme-linked immunosorbent assay of single SP-AKP indicated this new substrate could reach a low limit of detection of 29.9 amol/L， with flexible detection time and high signal accuracy. This new water-soluble coumarin fluorescent substrate was expected to replace 4-MUP in the applications such as ultrasensitive droplet based biological detection and many other fields that require enzymatic reaction in the droplet partitions.

Table of Content