The site‐selective C−H amination reaction of 7‐azaindoles with various benzisoxazoles as amination surrogates under cationic rhodium(III) catalysis is described. This transformation efficiently ...provides a range of ortho‐aminated N‐aryl‐7‐azaindoles with excellent site‐selectivity and functional group compatibility. The formed ortho‐aminated 7‐azaindoles were readily transformed into biologically relevant heterocycles such as azaindoloacridine, azaindoloacridone, and bis‐indole compounds. Moreover, the synthetic derivatives were tested for in vitro anticancer activity against human breast adenocarcinoma cells (MCF‐7), human renal carcinoma cells (786‐O), and human prostate adenocarcinoma cells (DU145). Notably, some synthetic compounds were found to display most potent anticancer activity, compared to that of anticancer doxorubicin as a positive control.
Organic electrochemical transistors (OECTs) are successfully used for sensitive and selective detection of sarcosine, which is recognized as a potential non-invasive specific biomarker for prostate ...cancer. The sensitivity and selectivity of OECT-based sarcosine sensors are significantly improved by modifying sarcosine oxidase (SOx) on platinum-plated anodized aluminum oxide (AAO) gate electrodes. The device with Nafion-SOx/Pt/AAO gate electrode shows the excellent sensing performance and the sarcosine can be detected in a linear range from 50 nM to 100 μM with a detection limit of 50 nM, which is satisfied with the clinical range of prostate cancer levels in human urine (20 nM–5 μM) and much lower than that of conventional electrochemical methods. Meanwhile, the selectivity of the sensor is also well proved. This work indicates a novel OECT-based sarcosine biosensor with high sensitivity and selectivity for the first time, which has the prospect of a wide range of routine testing.
Display omitted
Magnetic covalent organic frameworks (COFs) are useful mesoporous materials for the enrichment and separation of analytes, and are utilized in the pretreatment of samples. However, the use of ...magnetic COFs in electrochemical immunosensors has rarely reported. Herein, a novel electrochemical assay for the determination of prostate specific antigen (PSA) was developed using black phosphorene (BPene) as a platform and magnetic COFs for signal amplification. BPene was prepared via water-phase exfoliation. BPene nanocomposite (Au@BPene) was prepared by depositing Au nanoparticles (Au NPs) onto BPene. This nanocomposite was utilized as an immunsensing platform to bind primary antibodies and improve electron transfer. Subsequently, an Au NP-loaded magnetic COF was used to immobilize the secondary antibodies and abundant electronic signals of methylene blue (MB). The fabricated sensor exhibited linearity ranging from 0.0001 ng mL-1 to 10 ng mL−1 with the detection limit of 30 fg mL−1. The sensor could determine the PSA in a real sample with excellent specificity, good stability, and desirable reproducibility. The effective signal amplification of the proposed sensor is attributed to the good electron transfer of Au@BPene, excellent enrichment capacity of signal molecules (MB) of the COF, and efficient catalytic activity of Fe3O4. This work not only provides an effective electrochemical assay to detect PSA in real sample, but also broadens the utilization scope of magnetic COFs in immunosensing.
•An ultrasensitive electrochemical immunosensor for prostate specific antigen was developed.•The sensor was based on phosphorene and magnetic covalent organic framework.•The detection limit of the sensor was 30 fg mL-1.•The sensor was successfully adopted to determine PSA in real sample.•The sensor showed excellent specificity, good stability, and desirable reproducibility.
An ultrasensitive and highly selective electrochemiluminescence (ECL) immunosensor is proposed for the detection of prostate specific antigen (PSA) based on multiple amplification via glucose oxidase ...(GOx) and platinum nanoparticles (Pt NPs) conjugated with polyglutamic acid (PGA). The proposed immunosensor has a wide linear range (1.0 pg/mL–150 ng/mL) and low detection limit (0.6 pg/mL) for PSA detection, which is due in part to the excellent catalytic activity of the Ab2-GOx-PGA-Pt NPs probe toward the luminol ECL reaction.
Display omitted
•Ab2-GOx-PGA-Pt NPs as signal-amplifying probe and Au NPs-luminol-LDH as ECL emitter were used to construct an immunosensor.•Ab2-GOx-PGA-Pt NPs have high catalytic activity to luminol ECL and increase the ECL signal.•The proposed ECL immunosensor achieved highly sensitive detection of PSA with a wide linear range.
Early stage detection of prostate cancer, one of the main causes of mortality among men, is of great importance for better treatment of the patients. Prostate specific antigen (PSA) is a glycoprotein ...which has been considered as the most potential serological biomarker for the detection of prostate cancer. Among the various techniques employed for PSA detection, aptamer-based biosensors (aptasensors) have achieved notable attention because of their unique features and great potentials as diagnostic tools. A variety of strategies such as integration of nanomaterials (NMs) into the structure of aptasensors have also been applied for enhancing the sensitivity of PSA detection. This article reviews recent advances in various optical and electrochemical aptasensors used for PSA detection.
•PSA has been proved to be the most potential biomarker for diagnosis of prostate cancer.•This review mainly focuses on recent developed aptasensors and nano-aptasensors for PSA detection.•This review covers the prominent roles of nanomaterials in the development of PSA aptasensors.•Future perspectives and challenges of PSA aptasensors are discussed briefly.
Extracellular vesicles (EVs) offer many opportunities in early-stage disease diagnosis, treatment monitoring, and precision therapy owing to their high abundance in bodily fluids, accessibility from ...liquid biopsy, and presence of nucleic acid and protein cargo from their cell of origin. Despite their growing promise, isolation of EVs for analysis remains a labor-intensive and time-consuming challenge given their nanoscale dimensions (30-200 nm) and low buoyant density. Here, we report a simple, size-based EV separation technology that integrates 1024 nanoscale deterministic lateral displacement (nanoDLD) arrays on a single chip capable of parallel processing sample fluids at rates of up to 900 μL h-1. Benchmarking the nanoDLD chip against commonly used EV isolation technologies, including ultracentrifugation (UC), UC plus density gradient, qEV size-exclusion chromatography (Izon Science), and the exoEasy Maxi Kit (QIAGEN), we demonstrate a superior yield of ∼50% for both serum and urine samples, representing the ability to use smaller input volumes to achieve the same number of isolated EVs, and a concentration factor enhancement of up to ∼3× for both sample types, adjustable to ∼60× for urine through judicious design. Further, RNA sequencing was carried out on nanoDLD- and UC-isolated EVs from prostate cancer (PCa) patient serum samples, resulting in a higher gene expression correlation between replicates for nanoDLD-isolated EVs with enriched miRNA, decreased rRNA, and the ability to detect previously reported RNA indicators of aggressive PCa. Taken together, these results suggest nanoDLD as a promising alternative technology for fast, reproducible, and automatable EV-isolation.
A novel dual-signal enzyme-linked immunosorbent assay (ELISA) has been developed based on Fe(III)-containing metal–organic frameworks (Fe-MOFs) as an ascorbic acid (AA)-responsive fluorescent probe ...and oxidase mimic that catalyze the coloration of TMB. The mechanism of AA-induced emission enhancement of Fe-MOFs is also investigated systematically.
Display omitted
•Ascorbic acid (AA)-induced Fe-MOFs emission enhancement and its mechanism has been systematically investigated.•A novel dual-mode ELISA platform has been developed using Fe-MOFs as an optical probe.•A sensitive PSA detection is realized by integration of AA-induced dual-signal generation and ALP-linked ELISA.
A novel dual-mode enzyme-linked immunosorbent assay (ELISA) has been developed based on Fe(III)-containing metal–organic frameworks (Fe-MOFs), which possesses unique properties of an ascorbic acid (AA)-responsive fluorescence emission and an oxidase-like activity inhibition. In this design, bimodal signals, a remarkable emission enhancement and a noticeable color change from the oxidation inhibition of a chromogenic substrate 3,3′,5,5′-tetramethylbenzidine (TMB), are generated from the Fe-MOFs probe with the increase of AA concentration. The change in the fluorescent and colorimetric signal is easily regulated by controlling AA level, which in turn is catalytically adjusted by the alkaline phosphatase (ALP) used in ELISA. Under an optimal condition, a limit of detection (LOD) at 180 pg mL−1 is achieved with the proposed dual-mode ELISA using human prostate specific antigen (PSA) as a model analyte. Furthermore, the mechanism of AA-induced emission enhancement of Fe-MOFs is also investigated systematically. The results show that the enhancement is attributed the AA-induced inhibition of ligand-metal charge transfer (LMCT) from the fluorescent ligand 2-amino-1, 4-benzenedicarboxylic acid (BDC-NH2) to Fe(III). When Fe(III) in Fe-MOF is reduced into Fe(II) by AA, the LMCT is partially inhibited and the fluorescence of BDC-NH2 is consequently recovered, thus resulting in a fluorescence enhancement of the Fe-MOFs.
Efficient separation of electron–hole pairs is vitally crucial to enhancing the analytical performance of paper-based photoelectrochemical (PEC) bioanalysis. Herein, a simple but effective strategy ...is developed to modulate the effective separation of photogenerated electrons and holes via introducing a polar charge carriers-created (PCC) electric field induced by a classical perovskite ferroelectric BaTiO3 (BTO). By inserting it between the n-type WO3 nanoflakes and p-type Cu2O (WO3 nanoflakes/BTO/Cu2O), the photoelectrode is endowed with a renewable PCC electric field, as a sustaining driving force, to guarantee the realization of directional separation of charge carrier (DSCC) strategy in PEC bioanalysis. The enduring PCC electric field can attract the electrons of Cu2O and holes of WO3, respectively, thereby regulating the directional migration of charge carriers and achieving an enhanced PEC photocurrent for the ultrasensitive quantification based on the highly efficient separation of electron–hole pairs. Consequently, with respect to WO3 nanoflakes/Cu2O and WO3 nanoflakes photoelectrode, the polarized WO3 nanoflakes/BTO/Cu2O photoelectrode exhibits 1.7 and 10.9 times higher photocurrent density, respectively. Benefiting from this, the prominent photocurrent density is obtained which is extremely beneficial for enhancing the sensitivity of PEC bioanalysis. Ultimately, the ultrasensitive detection of model prostate specific antigen (PSA) is realized and presents a linear range of 0.1 pg/mL–50 ng/mL with the detection limitation of 0.036 pg/mL. This work provides the basis for understanding the role of the polarized electric field induced by ferroelectric in tuning the charge separation as well as insights on strategies for constructing high-performance paper-based PEC bioanalysis.
Present work demonstrates the fabrication of new and facile sandwich‐type electrochemical immunosensor based on palladium nanoparticles (PdNPs), polyaniline (PANI) and fullerene‐C60 nanocomposite ...film modified glassy carbon electrode (PdNP@PANI‐C60/GCE) for ultrasensitive detection of Prostate‐specific antigen (PSA) biomarker. PdNP@PANI‐C60 was electrochemically synthesized on GCE and used as an electroactive substrate. PdNP@PANI‐C60 was characterized by scanning electron microscopy (SEM), energy‐dispersive X‐ray spectroscopy (EDS), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Primary antibody anti‐PSA (Ab1) was covalently immobilized on PdNP@PANI‐C60/GCE using NHS/EDC linkers. In the presence of PSA antigen, horseradish peroxidase secondary antibody (HRP‐Ab2) was brought into the surface of the electrode, developing stable amplified signals of H2O2 reduction. Under the optimal conditions, a linear curve for determination of PSA at the proposed immunosensor was 1.6×10−4 ng.mL−1 to 38 ng.mL−1 with a limit of detection (LOD) of 1.95×10−5 ng.mL−1. The proposed immunosensor was successfully validated in serum and urine samples towards PSA detection with satisfactory and acceptable results.
Display omitted
•Easy elaboration of graphene-based aptasensor for PSA detection.•MB as a redox center for potentio-amperometric detection of PSA.•Sensitive, Selective and specific detection.•The ...biosensor served to detect PSA in spiked human serum.
A novel and disposable potentio-amperometric aptasensor for the prostate specific antigen (PSA) was constructed using functionalized graphene-modified carbon screen-printed electrodes as transducing surface. The PSA specific DNA aptamer was covalently tethered to the graphene through amide bond between the aptamer-terminated amine and the carboxylic acid-enriched graphene casted on the electrode surface. A further hybridization of a partially complementary DNA (cDNA) was followed by intercalation of methylene blue into the double-stranded DNA sequences. The detection approach was based on a competitive assay between the antigen and the cDNA. In fact, the detection relies on the PSA biorecognition by its aptamer, triggering the release of the loosely bound DNA strand and the intercalated dye molecules, which was monitored by differential pulse voltammetry. The aptasensor allowed selective and specific detection of PSA over a wide range of concentrations from 1 pg·mL−1 to 100 ng·mL−1 with a low detection limit of 0.064 pg·mL-1. This electroanalytical device also exhibited high reproducibility and storage stability, and was successfully validated in spiked human blood serum samples.
PDF
