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Covalent organic frameworks (COFs) are gaining growing interest owing to their various structures and versatility. Since their specific physical–chemical characteristics endow them great usage potentiality in biosensing, we herein have synthesized spherical COFs with regular shape and good dispersion, which are further used for the design of a novel nanoprobe by modifying Histostar on the surface of the COFs. Moreover, we have applied a nanoprobe for the fabrication of an electrochemical biosensor to detect exosomes. Since Histostar is a special polymer, conjugated with many secondary antibodies (IgG), and HRP can increase the availability of HRP at the antigenic site, the biosensor can have a strong signal amplification ability. Meanwhile, since COFs with high porosity can be loaded with a huge amount of Histostar, the sensitivity of the biosensor can be further improved. With such a design, the proposed biosensor can achieve a low exosomes detection limit of 318 particles/µL, and a wide linear detection range from 103 particles/µL to 108 particles/µL. So, this work may offer a promising platform for the ultrasensitive detection of exosomes. [ABSTRACT FROM AUTHOR]

Programmed death-ligand 1 protein positive (PD-L1+) exosome is one of the most prospective biomarkers for the diagnosis of cancer. However, the current methods for the detection of PD-L1+ exosomes are usually laborious, time-consuming and require numerous samples. Herein, we report in this paper an electrochemical biosensor for PD-L1+ exosomes detection based on ultra-thin two-dimensional covalent organic framework nanosheets (2D COF NSs) coupled with clustered regularly interspaced short palindromic repeats (CRISPR) Cas 12a for signal amplification. Firstly, COF-367 NSs functionalized with gold nanoparticles (AuNPs) have been synthesized for the modification of the working electrode, thus the proposed sensor can show highly improved electrochemical performance. Secondly, by utilizing the trans-cleavage activity of Cas12a, this sensor can achieve very high sensitivity for the detection of PD-L1+ exosomes. With such design, the biosensor can have a linear range from 1.2 × 102 to 1.2 × 107 particles/μL with a detection limit of 38 particles/μL. Moreover, this sensor can be employed to analyze non-small cell lung cancer (NSCLC) patient serum samples, and successfully identify NSCLC patients, demonstrating the great potential in clinical applications. [Display omitted] • An ultra-thin 2D COF NSs-based biosensor was designed. • It can exhibit excellent analytical performance for the detection of PD-L1+ exosomes. • The low detection limits of 38 particles/μL was achieved. • The proposed method has been used to analyze the clinical serum samples. [ABSTRACT FROM AUTHOR]

[Display omitted] • SARS-CoV-2 PLpro as a new biomarker is used to diagnose COVID-19. • A novel PLpro-activated peptide-DNA smart nanoprobe is designed for sensitive and specific detection of SARS-CoV-2. • The fabricated biosensor can be used for the detection of SARS-CoV-2 in blood, saliva, and clinical samples. • The biosensor can be used to screen and validate inhibitors of SARS-CoV-2 PLpro. The persistent coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still infecting hundreds of thousands of people every day. Enriching the kits for SARS-CoV-2 detection and developing the drugs for patient treatments are still urgently needed for combating the spreading virus, especially after the emergence of various mutants. Herein, an electrochemical biosensor has been fabricated in this work for the detection of SARS-CoV-2 via its papain-like cysteine protease (PLpro) and the screening of protease inhibitor against SARS-CoV-2 by using our designed chimeric peptide-DNA (pDNA) nanoprobes. Utilizing this biosensor, the sensitive and specific detection of SARS-CoV-2 PLpro can be conducted in complex real environments including blood and saliva. Five positive and five negative patient throat swab samples have also been tested to verify the practical application capability of the biosensor. Moreover, we have obtained a detection limit of 27.18 fM and a linear detection range from 1 pg mL−1 to 10 μg mL−1 (I = 1.63 + 4.44 lgC). Meanwhile, rapid inhibitor screening against SARS-CoV-2 PLpro can be also obtained. Therefore, this electrochemical biosensor has the great potential for COVID-19 combating and drug development. [ABSTRACT FROM AUTHOR]

• Covalent organic frameworks conjugated with DNA and horseradish peroxidase (HRP-DNA-COFs, HDCs) are successfully prepared. • The prepared HDCs can recognize exosomes and catalyze the oxidation of 1, 3, 5-trimethylbenzene (TMB) substrate. • An HDCs-based electrochemical biosensor is constructed for exosome detection. • The HDCs-based biosensor achieves good performance to detect exosomes with simplicity and sensitivity. Quantification of trace exosomes in biofluids is helpful for the early diagnosis of cancers. Electrochemical biosensors have attracted special attentions for exosome detection, while the employment of nanoconjugates in the construction of electrochemical biosensors can achieve better performance. So, in this work, we have designed and fabricated HRP-DNA-COF nanoconjugates (HDCs) that involve covalent organic frameworks (COFs) as the scaffold, cholesterol-tagged DNA to recognize exosomes and horseradish peroxidase (HRP) to amplify the signal readout. The successful preparation of HDCs have been verified experimentally, based on which an electrochemical biosensor has been constructed for exosome detection. Attributed to the specific recognition ability and excellent catalytic ability of HDCs, the biosensor achieves good performance to detect exosomes with simplicity and sensitivity in the linear range from 104 to 107 particles/μL. Besides, the strategy proposed in this work to construct COF-based nanoconjugates may promote the wider application of COFs in biomedical research. [ABSTRACT FROM AUTHOR]