Ultrasensitive molecularly imprinted fluorescence sensor for simultaneous determination of CA125 and CA15-3 in human serum and OVCAR-3 and MCF-7 cells lines using Cd and Ni nanoclusters as new emitters.

In the clinical diagnosis of tumors, a single-marker immunoassay may lead to false results. Thus there is a need for an effective and valid method for the simultaneous measurement of multiple tumor markers. In this work, an efficient fluorescence immunosensor for the simultaneous measurement of CA125 and CA15-3 tumor markers was fabricated by utilizing the high selectivity of magnetic molecularly imprinted polymers (MMIPs) and the high sensitivity of a fluorescence (FL) method. Ni nanoclusters (Ni NCs) and noble Cd nanoclusters (Cd NCs) were introduced as efficient and economic emitters, and magnetic graphene oxide (GO-Fe3O4) was applied as a support material for surface molecularly imprinted polymers. Under the most favorable experimental conditions, the fluorescence intensity of the Cd NCs and Ni NCs gradually increased with increasing concentration of CA125 and CA15-3 antigens at a range of 0.0005-40 U mL-1, respectively, with a limit of detection (LOD) of 50 µU mL-1. The developed method had excellent properties including a broad linear range, good reproducibility, and simple operation for the clinical diagnosis of CA 125 and CA 15-3 tumor markers. This molecularly imprinted fluorescence sensor has the potential to be an effective clinical tool for the timely screening of breast cancer in human serum samples and OVCAR-3 and MCF-7 cell lines, and can be applied in clinical diagnostics.

Magnetic N-doped carbon derived from mixed ligands MOF as effective electrochemiluminescence coreactor for performance enhancement of SARS-CoV-2 immunosensor.

COVID-19 as an infectious disease with rapid transmission speed is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), so, early and accurate diagnostics of COVID-19 is quite challenging. In this work, the selective and sensitive self-enhanced ECL method to detect of SARS-CoV-2 protein was designed with magnetic N-doped carbon derived from dual-ligand metal-organic frameworks (MOF) (CoO@N-C) with the primary and tertiary amino groups as a novel coreactant that covalently combined with Ru(bpy)2(phen-NH2)2+ as electrochemiluminescence (ECL) emitter. Mixed-ligand strategy and selected nitrogen-containing ligands, 4,4',4''-((1,3,5-triazine-2,4,6-triyl) tris-(azanediyl)) tribenzoic acid (H3TATAB) with 2-aminoterephthalic acid (BDC-NH2) were used for synthesis of the proposed MOF. Also, magnetic CoO@N-C with high synergistically charge transfer kinetics and good stability can be used as an effective platform/coreactor on the ITO electrode which load more Ru-complex as signal producing compound and SARS-CoV-2 N protein antibody to increase the sensitivity of the immunosensor. Furthermore, (CoO@N-C) as coreactor improved the ECL signal of the Ru (II)-complex more than 2.1 folds compared to tripropylamine. In view of these competences, the novel "on-off" ECL biosensor performed with great stability and repeatability for detection of SARS-CoV-2 protein, which exhibited a broad linearity from 8 fg. mL-1 to 4 ng. mL-1 (6 order of magnitude) and an ultra-low limit of detection 1.6 fg. mL-1. Finally, this proposed method was successfully applied to detect of SARS-CoV-2 N protein in serum sample with satisfactory results, indicating the proposed immunosensor has the potential for quick analysis of SARS-CoV-2.

Graphdiyne nanosheet as a novel sensing platform for self-enhanced electrochemiluminescence of MOF enriched ruthenium (II) in the presence of dual co-reactants for detection of tumor marker.

Graphdiyne (GDY) is a new two-dimensional carbon material with high charge carrier mobility, excellent conductivity, more suitable band gap, and natural pores was introduced as a new electrochemiluminescent sensing platform. Herein, the metal organic framework (MOFs) used for enrichment of luminophore with grafting Ru(bpy)2(phen-NH2)2+(Ru-complex) and Ru-complex amine-rich nitrogen-doped carbon nanodots(Ru-NCNDs) via both encapsulating and external decoration and decoration of SmS2 QDs as coreactant. Then, the MOF enriched Ru-complex (Ru@MOF@NCNDs-Ru@SmS2 QD) located on a GDY modified ITO electrode developed as a novel and efficient ECL platform. According to the Density Functional Theory (DFT) calculation, the band gap of graphdiyne/Ru(bpy)2(phen-NH2)2+ system decreased compared to graphdiyne, Ru-complex and also graphene oxide/Ru(bpy)2(phen-NH2)2+system, which enhanced (2 folds) the signal response of the presented ECL platform. The ECL response signal of the suggested emitter with high ECL efficiency (13.34%) increased 8 and 4 folds compared to GDY/Ru-NCNDs and GDY/Ru@MOF@NCNDs-Ru as platforms, respectively. The proposed ECL platform applied for CA19-9 antigens detection at concentration range 0.0005 UmL-1 to 200 UmL-1 and detection limit of 0.00013 UmL-1.The development of GDY based platform for decorating nano luminophores, not only provides the design of ECL luminophores with high performance but also promises the application of the presented strategy for fabrication of ultrasensitive bio affinity sensors as candidates in clinical monitoring and diseases diagnostics.

Ratiometric fluorescence resonance energy transfer aptasensor for highly sensitive and selective detection of Acinetobacter baumannii bacteria in urine sample using carbon dots as optical nanoprobes.

Development of sensitive and selective analytical method for accurate diagnosis of Acinetobacter baumannii (Ab) bacteria in biological samples is a challenge. Herein, we developed an ingenious ratiometric fluorescent aptasensor for sensitive and selective detection of (Ab) bacteria based on fluorescence resonance energy transfer (FRET) between ortho-phenylenediamines carbon dot (o-CD), nitrogen-doped carbon nanodots (NCND) as donor's species and graphene oxide (GO) as acceptor. NCND that assembled onto the edge of graphene oxide (GO) exhibited quenched photoluminescence emission, and with the absorption of the modified o-CD with aptamer (o-CD-ssDNA) onto the graphene oxide surface the fluorescence of o-CD was efficiently quenched. The aptamer (ssDNA) as a biorecognition element is bound with A. baumannii specifically which releases the o-CD-ssDNA from GO and the recovery of the fluorescence signal of o-CD, while the fluorescence intensity of NCND only slightly altered and acted as the reference signal in ratiometric fluorescence assay. The fluorescence intensity ratio (I550 nm/I440nm) varied from 2.0 to 10.0 with the concentration of bacteria changing from 2.0 × 103 to 4.5 × 107 cfu/mL and the low detection limit of 3.0 × 102 cfu/mL (S/N = 3). The feasibility of the developed aptasensor for selective detection of A. baumannii in urine sample with satisfactory results was also demonstrated.

A self-enhanced ECL-RET immunosensor for the detection of CA19-9 antigen based on Ru(bpy)2(phen-NH2)2+ - Amine-rich nitrogen-doped carbon nanodots as probe and graphene oxide grafted hyperbranched aromatic polyamide as platform.

Electrochemiluminescence resonance energy transfer (ECL-RET) assay as an efficient analytical technique has aroused considerable interest in recognition and biosensing. In the present study, a novel self-enhanced ECL-RET of Ru(bpy)2(phen-NH2)2+ as an efficient luminophore to the MoS2 nanosheets as effective quencher was designed for CA19-9 antigen analysis. Herein, the graphene oxide grafted hyperbranched aromatic polyamide (GO-HBP) with high loading ability for Ru-complex was used as the sensing platform, while amine-rich nitrogen-doped carbon nanodots (NCNDs) which covalently linked to Ru(bpy)2(phen-NH2)2+ applied as co-reactant for enhancing of anodic ECL signal response. In this approach GO-HBP-Ru-complex-NCND-anti-CA19-9 Ab exhibited amplified ECL emissions ("on" state) and with formation of sandwiched immunocomplex between, immobilized CA19-9 Ab, CA19-9 antigen and MoS2 nanosheets modified with CA19 9 antibody, the ECL response of luminophore was efficiently quenched ("off" state). The signal response was doubly amplified by covalent attachment of more luminophore, co-reactant and CA19-9 antibody with hyperbranched aromatic polyamide. On the basis of all above features, the ECL intensity of Ru-NCND decreased with the increase of the concentration of CA19-9 antigen in a wide linear range of 2 mU mL-1- 50 U mL-1 with the detection limit of 0.25 mU mL-1 (S/N = 3). The application of the fabricated ECL-RET immunosensor for determination of CA19-9 antigen in human serum samples was appraised that the satisfactory results were found to be in admissible accord with those gained with the reference method (ELISA assay).The suggested method opens up a novel avenue for expanding high-performance ECL-RET immunosensors cancer markers detection in clinical monitoring.

Highly sensitive bioaffinity electrochemiluminescence sensors: Recent advances and future directions.

Electrogenerated chemiluminescence (also called electrochemiluminescence and abbreviated ECL) has attracted much attention in various fields of analysis due to the potential remarkably high sensitivity, extremely wide dynamic range and excellent controllability. Electrochemiluminescence biosensor, by taking the advantage of the selectivity of the biological recognition elements and the high sensitivity of ECL technique was applied as a powerful analytical device for ultrasensitive detection of biomolecule. In this review, we summarize the latest sensing applications of ECL bioanalysis in the field of bio affinity ECL sensors including aptasensors, immunoassays and DNA analysis, cytosensor, molecularly imprinted sensors, ECL resonance energy transfer and ratiometric biosensors and give future perspectives for new developments in ECL analytical technology. Furthermore, the results herein discussed would demonstrate that the use of nanomaterials with unique chemical and physical properties in the ECL biosensing systems is one of the most interesting research lines for the development of ultrasensitive electrochemiluminescence biosensors. In addition, ECL based sensing assays for clinical samples analysis and medical diagnostics and developing of immunosensors, aptasensors and cytosensor for this purpose is also highlighted.