Electrochemical Immunosensor For Ultrasensitive Detection Research Articles

A dual-mode label-free electrochemical immunosensor for ultrasensitive detection of procalcitonin by on-site vulcanization of dual-MOF heterostructure

Detection of procalcitonin (PCT) is crucial for the early identification of sepsis. PCT is primarily utilized in the multiple diagnosis of bacterial and viral illnesses along with to guide the application of antibiotics. Considering their advantages of high specificity and straightforward usage, electrochemical immunosensors offer significant application prospects in the detection of disease indicators. A dual-mode electrochemical immunosensor was constructed in this study to reliably identify PCT. In light of the synergistic effect of the dual-MOF derived heterostructure, the immunosensor demonstrating excellent square wave voltammetry (SWV) signals as well as significant catalytic activity for the H2O2 redox process. In addition to maintaining a low detection limit (SWV: 0.31 fg/mL and i-t: 0.098 fg/mL), the immunosensor offers an extensive linear response range (0.000001–100 ng/mL). The excellent performance is on account of the introduction of the local on-site sulfurized dual-MOF heterostructure with abundant metal chalcogenides/MOF interfaces, which boosts the specific surface area, offers an abundance of active sites, enhances conductivity, and raises catalytic activity. Furthermore, the immunosensor exhibits outstanding specificity, stability and reproducibility for the determination of PCT in serum, which is of great crucial for the clinical screening and diagnosis of sepsis.

Dual-signaling electrochemical immunosensor for ultra-sensitive detection of procalcitonin based on the hydrogen evolution and photoelectric signals of AuPt/BP

In recent years, noble metal catalysts have been extensively studied in terms of hydrogen evolution reaction (HER), but there has been less research on the construction of immunosensor based on the catalytic signal amplification strategy of noble metal. Based on the excellent HER and photoelectric performance of AuPt nanoslices modified black phosphorus nanoflakes (AuPt/BP) in neutral medium, we reported a dual-signal electrochemical immunosensor, which uses AuPt/BP as signal amplification label for the detection of procalcitonin (PCT). Due to the charge transfer between AuPt and BP, AuPt/BP has better HER activity and photoelectric performance than single AuPt or BP, which realized the construction of dual-signal electrochemical immunosensors and the improvement of detection sensitivity. In addition, the presence of BP makes AuPt/BP has better dispersion and larger surface area, which can load more secondary antibody (Ab2) and realize the signal amplification of the immunosensor. The linear ranges of PCT detection based on HER and photoelectric signals are 1.96 fg mL−1 ∼ 0.196 ng mL−1 and 1.96 fg mL−1 ∼ 19.6 pg mL−1, and the detection limits of PCT with HER and photoelectric signals are 0.88 fg mL−1 and 0.99 fg mL−1.

Portable smartphone‐based microfluidic electrochemical immunosensor for ultrasensitive detection of alpha‐fetoprotein in human serum

AbstractRapid and accurate tracing of biomarkers is essential for early detecting and diagnosing of cancer. Therefore, a valid and convenient strategy needs to be developed for efficient monitoring of cancer biomarkers. Herein, we constructed a portable microfluidic electrochemical immunosensor based on three‐dimensional reduced graphene oxide (3D rGO) doped with gold nanoparticles (Au NPs) for ultrasensitive determination of alpha‐fetoprotein (AFP). The designed microfluidic chip, with the advantages of small injection volume, detachable structure and high integration, was fabricated by 3D printing, which only needed 9 μL of reagent to realize the high sensitivity detection. In addition, the 3D Au NPs‐rGO composites with high specific surface area and electrons transfer capacity can effectively increase electroactive sites and enhance electrochemical signals. Benefiting from these features, the 3D Au NPs‐rGO microfluidic electrochemical immunochip showed a wide detection range between 0.1 pg/mL–200 ng/mL and a best detection limit of 0.045 pg/mL with the high sensitivity of 175.008 μA (ng/mL)−1 cm−2. Meanwhile, the proposed immunosensor exhibited reliable AFP detection in human serum samples, which demonstrated that this portable smartphone‐based microfluidic electrochemical immunosensor hold great promises in clinical detection and huge potential in personalized healthcare.

Electrochemical immunosensor for ultrasensitive detection of human papillomaviruse type 16 L1 protein based on Ag@AuNPs-GO/SPA

Human papillomaviruse type 16 (HPV16) is a high-risk serotype. As the main protective antigen protein, L1 protein is also the target protein for diagnosis. A simple label free electrochemical immunosensor (ECIS) was fabricated for ultrasensitive detection of HPV16 L1 protein in this work. Quasi-spherical Ag@Au core-shell nanoparticles on graphene oxide (Ag@AuNPs-GO) was developed as current response amplifier and characterized by UV–Vis Spectroscopy, Transmission Electron Microscopy and energy dispersive X-ray spectroscopy. Staphylococcal protein A was decorated on the modified electrode and utilized to immobilized the Fc portion of the monoclonal antibody specific for HPV16 L1 protein. Cyclic Voltammetry, Differential Pulse Voltammetry and Electrochemical Impedance Spectroscopy were used to verify the electrochemical performance and interfacial kinetic property. The increased concentration of HPV16 L1 protein led to slow electron transport and linearly decreased differential pulse voltammetry peak current with a detection limit of 0.002 ng mL−1 and a wide linear relationship in the range of 0.005–400 ng mL−1at a regression coefficient (R2) of 0.9948. Furthermore, this ECIS demonstrated acceptable accuracy with good reproducibility, stability and selectivity, suggesting a promising immunological strategy for HPV typing and early screening.

Ultrasensitive sandwich-typed electrochemical immunoassay for detection of squamous cell carcinoma antigen based on highly branched PtCo nanocrystals and dendritic mesoporous SiO2@AuPt nanoparticles.

Squamous cell carcinoma antigen (SCCA) is one of the common squamous cell carcinomas (SCC) in women, which usually works as a tumor biomarker for cervical cancer in diagnostic applications. Herein, bimetallic PtCo highly branched nanocrystals (PtCo BNCs) acted as electrode substrates to construct sandwich-typed electrochemical immunosensor for ultrasensitive detection of SCCA, by using dendritic mesoporous SiO2@AuPt nanoparticles (DM-SiO2@AuPt NPs) to adsorb electroactive thionine (Thi) as a signal label. The PtCo BNCs enlarged the loading of the primary antibody (Ab1), showing effective improvement in conductivity and sensitivity. The DM-SiO2 had abundant pores to incorporate more Thi, on which the decorated AuPt NPs created a great number of active sites to immobilize the secondary antibodies (Ab2), thereby obviously amplifying the detection signals. The prepared sensor exhibited a broader linear range (0.001-120ngmL-1) and a lower detection limit (0.33pgmL-1, S/N = 3), combined with high reproducibility, a low relative standard deviation (below 2.5%) and acceptable recovery (from 98.5 to 110.0%) even in diluted human serum samples. This research provides a substantial platform for clinical diagnosis of SCCA in practice.

A novel portable label-free electrochemical immunosensor for ultrasensitive detection of Aeromonas salmonicida in aquaculture seawater

Infectious diseases caused by Aeromonas salmonicida (A. salmonicida) have a huge impact and produce significant losses in aquaculture and fish farming. Fish pathogen early detection is a critical step for the rapid identification and prevention of these problems. This work presents a novel portable label-free ultrasensitive electrochemical immunosensor for A. salmonicida detection in seawater. It consists of a fluidic integrated electrochemical-cell-chip (ECC) with independent chambers enclosing three electrochemical cells (ECs). Anti-A. salmonicida (AbSalm) antibodies were covalently attached to the gold surface of the microfabricated electrodes and were used for the sensitive detection of A. salmonicida. The antibody-antigen immunoreaction was studied by enzyme-linked immunosorbent assay (ELISA), and the surface functionalization was characterized by using quartz crystal microbalance (QCM), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS). The performance of the developed immunosensor, in terms of sensitivity, repeatability, and specificity, was also studied. The linear working range varied between 1 and 107CFUmL-1, with a limit of detection (LOD) as low as 1CFUmL-1. The suitability of the immunosensor for real sample detection was successfully demonstrated via recovery studies performed in spiked seawater samples. The proposed technology supports the use of low-cost and portable instrumentation that concedes the ultrasensitive, simple, and fast quantification of the A. salmonicida. To the best of our knowledge, this is the first portable sensing system for the detection of A. salmonicida in seawater samples, which provides a promising online monitoring platform for the detection of this bacterium in aquaculture facilities.

Morphologically Flex Sm-MOF Based Electrochemical Immunosensor for Ultrasensitive Detection of a Colon Cancer Biomarker.

Despite having the potential to synthesize stable metal-organic frameworks (MOFs), rare earth metal-based MOFs have not been exploited extensively. Owing to the high coordination numbers, the MOFs can generate a suitable coordination environment for various applications. Herein, samarium (Sm)-based MOFs were synthesized with three different organic linkers, namely, trimesic acid (TMA), meso-tetra(4-carboxyphenyl)porphine (TCPP), and 1,3,6,8-tetra(4-carboxylphenyl) pyrene(TBPy) by the solvothermal approach. The morphologies of Sm-TMA MOF, Sm-TCPP MOF, Sm-TBPy MOF were rod-shaped, cubic consisting of stacked 2D layers, and spherical made of small cubic structures, respectively. After the electrochemical properties of the synthesized MOFs were investigated, the MOFs were used to fabricate immunosensors for detection of carcinoembryonic antigen using a label-free signaling strategy. The immunosensors exhibited a wide linear detection range and a lower detection limit. The exhibited reproducibility and selectivity of the immunosensors were within the tolerable limits. The established label-free immunosensor has been successfully applied for detection of carcinoembryonic antigen in human serum samples, demonstrating that the rare earth metal-based MOFs are promising for construction of biosensors for medical diagnosis.

A novel electrochemical immunosensor for ultrasensitive detection of tumor necrosis factor α based on polystyrene - PAMAM dendritic polymer blend nanofibers

A simple, rapid, and highly sensitive label-free immunosensor based on polystyrene (PS)-polyamidoamine (PAMAM) dendritic polymer nanofibers (NFs) for detection of tumor necrosis factor-α (TNF-α) cytokine was developed. The choice of PAMAM was due to the possibility of designing the surface of NFs to create a novel interface with the high control ability of the density of amine groups at the surface by which capture antibody (anti-TNF-α) could be covalently attached to the surface of NFs through glutaraldehyde (GA) coupling chemistry. Evaluation of the electrode surface using cyclic voltammetry (CV) proved the electrode manufacturing stages were successful by decreasing the peak current values due to the blockage of electron transfer by the biomolecule layer on the surface of NFs, as well as the ability to precisely control the current peak by changing the diameter of the NFs and the concentration of dendrimer. Electrochemical impedance spectroscopy (EIS) was used to test the detection capability of the immunosensors and compare the role of the amount of PAMAM presented on the surface of NFs on their analytical performance. Increasing the concentration of dendrimer greatly increased the sensitivity of immunosensors due to the higher stabilization of the antibody on the nanofiber surface. The immunosensor had a very high affinity for TNF-α cytokines, with a linear response ranging from 10 to 200 pg/mL and a low limit of detection (LOD) of 669 fg/mL. Interference results with Interleukin-10 (IL-10) cytokine showed that the immunosensor was extremely specific and may be utilized to detect cytokines in clinical diagnosis.

3D carbonized wood-based integrated electrochemical immunosensor for ultrasensitive detection of procalcitonin antigen

This work presents a novel 3D carbonized wood-based integrated electrochemical immunosensor for ultrasensitive detection of procalcitonin (PCT) antigen at picogram level, achieving a wide linear detection range for PCT concentrations range from 0.05 to 90 pg mL−1 with a low detection limit of 0.014 pg mL−1 (S/N = 3), outperforming the previous reports. 3D carbonized wood as a new immunosensor matrix is used for electrochemical PCT biosensing, improving the stability of electrode and overcoming the disadvantages of traditional glassy carbon electrode (GCE). It obtained an excellent detection result, due to it has abundant mutual crisscross microchannels that promote the reactants and electrons transfer, greatly amplify the current signal. This novel sandwich-type electrochemical immunosensor is composed of 3D carbonized wood, carboxylic multi-walled carbon nanotube (cMWCNT), Au@Co3O4 core-shell nanosphere and Au/single layer nitrogen-doped graphene (Au/SL-NG), when it is applied for PCT detection in real clinical samples, it exhibits high accuracy same as enzyme-linked immunosorbent assay (ELISA) method.

Electrochemical immunosensor for ultra-sensitive detection of attomolar prostate specific antigen with sulfur-doped graphene quantum dot@gold nanostar as the probe

A novel sulfur-doped graphene quantum dot (S-GQD) decorated 3-dimensional gold nanostar (AuNS/S-GQD) nanocomposite has been developed as the actively electrochemical immunosensing material for ultra-sensitive and selective detection of attomolar prostate specific antigen (PSA) in phosphate buffer saline (PBS) and human serum. The S-GQDs were hydrothermally prepared at 180 °C for 10 h, and then AuNS/S-GQDs were fabricated by reducing Au precursor to AuNS in the presence of S-GQDs at room temperature. The electronic microscopic results indicate that 2 – 8 nm S-GQDs are homogenously deposited onto the 35 – 60 nm AuNS surface. The AuNS provides an excellent electric conductivity for electrochemical performance, while S-GQD serves as a sensing probe to bind prostate specific antibody (Ab) via amide bonding. After deposition of AuNS/S-GQDs onto screen-printed electrode (Es), the Es||AuNS/S-GQD/Ab immunosensor provides a stable, ultra-sensitive, and highly selective platform for PSA detection. The wide detection ranges of 10 fg mL−1 – 50 ng mL−1 and 100 fg mL−1 – 35 ng mL−1 with low limits of detection (LOD) of 0.29 (9.7 aM) and 26 fg mL−1 in PBS and neat human serum, respectively, are obtained. Moreover, the Es||AuNS/S-GQD/Ab immunosensor can effectively detect PSA in human serum with recovery of 97 – 107%. The high selectivity toward PSA detection over the other 8 interferences and low cytotoxic effect of Es||AuNS/S-GQD/Ab immunosensor are also observed. These excellent results demonstrate the potential of using AuNS/S-GQD nanocomposite as an electrochemically biosensing probe to effectively detect PSA and other cancer markers in human serum for clinically early diagnosis.

Functionalized graphene oxidein situ initiated ring-opening polymerization for highly sensitive sensing of cytokeratin-19 fragment.

Improving the sensitivity of detection is crucial to monitor biomarker, assess toxicity, and track therapeutic agent. Herein, a sensitivity-improved immunosensor is reported for the first timevia functionalized graphene oxide (GO) and a "grafting-to" ring-opening polymerization (ROP) dual signal amplification strategy. Through the ROP reaction using 2-[(4-ferrocenylbutoxy)methyl] oxirane (FcEpo) as the monomer, lots of electroactive tags are linked in situ from multiple initiation sites on the GO surface modified with ethanol amine (GO-ETA), thereby achieving high sensitivity even in the case of trace amounts of tumor markers. The utmost important factor for achieving this high sensitivity is to select functionalized GO as the initiator that contains a large number ofrepeated hydroxyl functional groups so as to trigger additional ROP reaction. Under the optimal conditions, the high sensitivity and applicability is demonstrated by the use of GO-ETA-mediated ROP-based immunosensor to detect non-small cell lung cancer (NSCLC)-specific biomarker down to 72.58 ag/mL (equivalent to ~6 molecules in a 5μL sample). Furthermore, the satisfactory results for the determination of biomarkers in clinical serum samples highlighted that this immunosensor holds a huge potential in practical clinical application. This work described an electrochemical immunosensor for ultrasensitive detection of CYFRA 21-1 via the functionalized graphene oxide (GO) and a "grafting-to" ring-opening polymerization (ROP) dual signal amplification strategy, which hold the merits of high sensitivity, applicability, selectivity, efficiency, easy operation and environmental friendliness.

Electrochemical ultrasensitive detection of CYFRA21-1 using Ti3C2Tx-MXene as enhancer and covalent organic frameworks as labels.

The concentration level of cytokeratin fragment antigen 21-1 (CYFRA21-1) can be used as an important indicator for predicting non-small cell lung cancer (NSCLC). Here, a sandwich-type electrochemical immunosensor for ultrasensitive detection of CYFRA21-1 is developed. The sensor based on a combination of gold nanoparticle (AuNPs) decorated Ti3C2Tx-MXene (Au-Ti3C2Tx) as the substrate enhancer, and toluidine blue (TB) modified AuNPs doped covalent organic framework (COF) polymer as the signal tag (TB-Au-COF). The Au-Ti3C2Tx is used to capture numerous primary antibodies and accelerate the electron transfer rate of the substrate, while the TB-Au-COF can be applied to provide a large number of signal units TB and secondary antibodies. These features of composites endow the proposed immunosensor with high sensitivity and current response to CYFRA21-1. Under optimum conditions, the immunosensor offers a wide current response for CYFRA21-1 from 0.5-1.0 × 104pg·mL-1 with a detection limit of 0.1pg·mL-1. Furthermore, the biosensing platform can be applied for CYFRA21-1 detection to analyze real serum samples, providing an effective and useful avenue for the applicability of Au-Ti3C2Tx and TB-Au-COF composite materials in biosensing field.

Dual labeled mesoporous silica nanospheres based electrochemical immunosensor for ultrasensitive detection of carcinoembryonic antigen

Carcinoembryonic antigen (CEA) is a well-known cancer biomarker for the detection of several malignancies. The development of ultrasensitive CEA diagnostic tools is crucial for early detection and progression observation of tumors. Herein, a dual signal amplified sandwich-type electrochemical immunoassay was developed based on dual-labeled mesoporous silica nanospheres as a signal amplifier, combined with NiO@Au decorated graphene as a conductive layer for ultrasensitive and rapid determination of CEA. The dual-labeled mesoporous silica (DLMS) nanosphere, which was synthesized by entrapping Au nanorod (Au NR) and horseradish peroxidase (HRP) in the channels of amine-functionalized SBA-15 followed by subordinate antibody (Ab2) conjugation which was denoted as Au NR@SBA-15/Ab2-HRP. The dual signal amplification from Au NR@SBA-15 and HRP enhanced the sensitivity of the proposed immunoassay. Consequently, the developed DLMS based immunosensor displayed ultra-low limits of detection of 5.25 fg/mL and a wide range of linearity (0.1–5 pg/mL), which was extended for CEA determination in real-time samples with improved recoveries of >98%. Therefore, this dual amplification prototype would cater to the clinical requirements for the ultrasensitive detection of CEA biomarkers.

A sandwich-type electrochemical immunosensor for ultrasensitive detection of multiple tumor markers using an electrical signal difference strategy

Traditional sandwich-type electrochemical immunosensors can only detect single tumor markers because signal interference occurs when detecting multiple tumor markers. In this work, an electrical signal difference strategy was proposed for the accurate detection of multiple tumor markers. We labeled PdAgCeO2 mesoporous nanospheres with a carcinoembryonic antigen (CEA) secondary antibody and MnO2 nanosheets labeled with an alpha-fetoprotein (AFP) secondary antibody. The two electrical signal tags were mixed and incubated on a prepared immunosensor to catalyze H2O2 and generate an electrical signal I1 (i-t ampere curve). When 2.5 mM ascorbic acid solution (AA) was added to 20 mL of PBS solution at pH = 6.5 for 180 s, an electrical signal I2 was generated. I2 was the current response of the CEA antigen concentration, and the electrical signal difference ΔI = I1–I2 was the current response of the AFP antigen. Thus, the immunosensor accurately detected the AFP and CEA tumor markers. This method was called the electrical signal difference strategy. The proposed single-use immunosensor detected CEA antigens in a range of 0.001 ng/mL-40 ng/mL, and the detection limit was 0.5 pg/mL; the detection range of the AFP antigen was 0.005 ng/mL-100 ng/mL, and the detection limit was 1 pg/mL. Therefore, this study provides new ideas and strategies for accurate clinical detection of multiple tumor markers.

A sandwich-type electrochemical immunosensor for ultrasensitive detection of CEA based on core–shell Cu2O@Cu-MOF@Au NPs nanostructure attached with HRP for triple signal amplification

A novel sandwich-type electrochemical immunosensor based on cuprous oxide (Cu2O)@copper-metal organic framework (Cu-MOF)@gold nanoparticles (Au NPs) core–shell structure was proposed. Cu2O@Cu-MOF@Au attached with horseradish peroxidase (HRP) triple-catalyzed hydrogen peroxide (H2O2) for detecting CEA antigen. In this work, 50 nm Cu2O nanospheres were prepared. Using Cu2O nanospheres as the core, Cu-MOF was coated on the surface of Cu2O nanospheres by reaction of Cu2O and ligands. Subsequently, chloroauric acid was reduced to Au NPs without adding any reducing agent and Au NPs dispersed on the surface of Cu-MOF. Finally, the Cu2O@Cu-MOF@Au-HRP-Ab2 nanoprobe was successfully prepared. Immunosensors had good performance due to the following reasons. Firstly, Cu2O, Cu-MOF and HRP have excellent catalytic properties for hydrogen peroxide. In addition, the synergistic effect of Cu2O, Cu-MOF and HRP promoted the reduction of hydrogen peroxide and tripled amplification of electrical signals. Here, the successfully prepared immunosensor detected carcinoembryonic antigen (CEA) sensitively, the detection range was 50 fg/mL–80 ng/mL, and the detection limit was 17 fg/mL. Besides, the proposed immunosensor had good stability, selectivity and specificity. Detection in human serum samples had good results without matrix effect. This provided a new idea for the clinical detection of tumor markers: "metal oxide—metal organic framework—precious metal nanoparticles" (MMP).

A self-assembled electrochemical immunosensor for ultra-sensitive detection of ochratoxin A in medicinal and edible malt

Trace residue of mycotoxins in complex medicinal and edible food matrices has brought huge challenges for the development of ultrasensitive analytical methods. Here, a green electrochemical immunosensor for the ultrasensitive detection of ochratoxin A (OTA) was fabricated by self-assembling a compact 2-mercaptoacetic (TGA) monolayer on the surface of the working Au electrode to form the Au/TGA/bovine serum aibumin (BSA)-OTA/anti-OTA monoclonal antibody composite probes for selective and ultra-sensitive detection of OTA based on indirect competitive principle and differential pulse voltammetry analysis. The electrochemical impedance spectroscopy and cyclic voltammetry methods were introduced to characterize the assemble situation of the TGA-modified Au electrode and optimize some critical parameters for the green electrochemical immunoseonsor. Under the optimal conditions, the developed immunosensor exhibited much lower limit of detection (0.08 ng/mL) in the range of 0.1–1.0 ng/mL for OTA compared with other direct or disposable electrochemical immunosensors. Real application in the spiked malt samples verified high accuracy with no matrix interferences of the proposed immunoseonsor. This is a meaningful study on a self-assembled electrochemical immunoseonsor for ultra-sensitive and rapid detection of OTA in malt samples, which suggested a general simple-to-use sensing platform and prospect as an economical and green tool for ultra-sensitive detection of much more trace-level of toxic small molecules in other complex matrices to ensure their quality and safety.

A novel electrochemical immunosensor for ultrasensitive detection of CA125 in ovarian cancer

In the current study, we report on the design and development of a novel electrochemical immunosensor for the detection of cancer antigen 125 (CA125) oncomarker. Polyamidoamine/gold nanoparticles (PAMAM/AuNPs) were used to increase the conductivity and enhance the number of antibodies (Abs) immobilized on the electrode surface. Three-dimensional reduced graphene oxide-multiwall carbon nanotubes (3DrGO-MWCNTs) were used to modify the glassy carbon electrode to improve the electrode conductivity and specific surface area. Ab and toluidine blue attached to O-succinyl-chitosan-magnetic nanoparticles (Suc-CS@MNPs) as a tracer. The poor solubility of chitosan (CS) was improved by succinic anhydride using a novel modification method. Under optimum condition, the developed immunosensor exhibited a wide linear range (0.0005–75 U/mL) and an excellent limit of detection around 6 μU/mL. The reliability of the engineered immunosensor in detecting CA125 was verified by standard addition recovery method, which was further compared to enzyme-linked immunosorbent assay (ELISA). The proposed immunosensor exhibited excellent stability, high selectivity and sensitivity, and good reproducibility. Based on the great performance of the engineered immunosensor, it is proposed as a robust and reliable diagnostic tool for the detection of CA125 in the clinic.

Gold and silver bio/nano-hybrids-based electrochemical immunosensor for ultrasensitive detection of carcinoembryonic antigen

Carcinoembryonic antigen (CEA) is an important oncomarker for the detection of breast cancer. For ultra-sensitive sensing of CEA with great specificity and accuracy, an innovative and reliable electrochemical immunosensor was developed using various nano-hybrids. A glassy carbon electrode (GC) was modified with thiolated graphene oxide (T-GO) to elevate the active surface area of the electrode. The streptavidin-coated gold nanoparticles (AuNPs) were used to increase the conductivity of the sensing area as well as the loading capacity of the biotinylated monoclonal antibody (mAb). A sandwich-on approach was developed to reach a low limit of detection (LOD). The biotinylated mAb, streptavidin coated silver nanoparticles (AgNPs) and horseradish peroxidase (HRP), altogether, formed the signaling probe of the proposed immunosensor. The electrochemical signal was significantly enhanced in the presence of hydroquinone (HQ) and hydrogen peroxide (H2O2). Under the optimized conditions, the proposed immunosensor presented an excellent performance in a linear range of 100 fg/mL to 5 pg/mL with a low detection limit of 75 fg/mL. The engineered immunosensor displayed excellent specificity for the detection of CEA even in the real human serum, upon which it is proposed for the early detection and monitoring of CEA in the clinic.

Trimetallic hybrid nanodendrites and magnetic nanocomposites-based electrochemical immunosensor for ultrasensitive detection of serum human epididymis protein 4

Alloy nanomaterials with various morphologies have showed their potential application in electrochemical signal amplification. However, it is still challenging to fabricate stable multimetallic nanomaterials with large surface area and strong electrochemical activity for the further enhancement of electrochemical sensors’ performance. Here, the trimetallic AgPtCo nanodendrites (NDs) were synthesized as powerful redox probe and highly efficient signal amplifier for electrochemical signal readout. A robust and ultrasensitive electrochemical immunosensor, based on AgPtCo NDs and magnetic nanocomposites (Fe3O4@SiO2@Au MNCs), was successfully developed to detect serum human epididymis protein 4 (HE4). The established method, drawing upon the strong electrochemical activity of AgPtCo NDs and the enrichment and separation effect of MNCs, exhibited a wide linear range (0.001–50 ng mL−1) and a low detection limit (0.487 pg mL−1). Besides, the developed sensor was applied to analyze the concentration of HE4 in real samples and the results achieved were consistent with those of clinical methods. Thus, this AgPtCo NDs and MNCs based electrochemical immunosensor might become a powerful alternative approach for ultrasensitive detection of various serum biomarkers associated with early diagnosis and treatment of diseases.

A label-free small molecular hydrogel-based electrochemical immunosensor for ultrasensitive detection of deoxynivalenol

A guanosine-based small-molecular hydrogel is developed as a label-free electrochemical immunosensing platform for ultrasensitive detection of deoxynivalenol.