Detection Of Human Epidermal Growth Factor Receptor-2 Research Articles

Multi-quenching electrochemiluminescence system based on resonance energy transfer from self-enhanced Ce(III, IV)-MOF@Ru to CuO@PDA@AuNPs for ultrasensitive detection of HER2

This study presents an innovative approach based on electrochemiluminescence resonance energy transfer (ECL-RET) through the introduction of a new pattern donor-acceptor couple. The donor of self-enhanced Ce(III, IV)-MOF@Ru is created by immobilizing Ru(bpy)32+ on Ce-based metal-organic frameworks (Ce(III, IV)-MOF). The acceptor of CuO@PDA@AuNPs is the CuO nanospheres polydopamine (PDA) framework grafted with gold nanoparticles (AuNPs). An ultrasensitive detection of human epidermal growth factor receptor-2 (HER2) was achieved through the development of a quenched ECL immunosensor. Ce(III, IV)-MOF, a unique 3D infinite extension framework, was recognized for its excellent nanostructure and remarkable capacity to greatly activate tripropylamine (TPrA) and generate abundant radicals. Fortunately, it was simultaneously utilized as a highly effective coreactant accelerator and encapsulation agent, thereby facilitating the immobilization of Ru(bpy)32+ and the generation of radicals for creating a self-enhanced emitter of Ce(III, IV)-MOF@Ru. Consequently, by effectively reducing the distance of electron transmission and minimizing the loss of energy, Ce(III, IV)-MOF@Ru achieved a significantly high efficiency in ECL. More importantly, CuO@PDA@AuNPs was prepared as a perfect quenching agent. The ultraviolet-visible (UV–vis) spectra of CuO@PDA@AuNPs exhibited partial overlap with ECL spectra of Ce(III, IV)-MOF@Ru, thus efficiently initiating the ECL-RET interaction between the donor and acceptor. With the purpose of demonstrating the superiority of newly obtained self-enhanced nanoemitter and donor-acceptor couple, an ECL immunoassay was proposed for the analysis of HER2 with range of 0.2 fg/mL ∼ 10 ng/mL and the limit of detection of 0.067 fg/mL. Therefore, this method supplies convenient and significant strategy for the clinical analysis.

Comparative study of optical fiber immunosensors based on traditional antibody or nanobody for detecting HER2

In this study, we present a novel biomarker detection platform employing a modified S-tapered fiber coated with gold nanoparticle/graphene oxide (GNP/GO) for quantifying human epidermal growth factor receptor-2 (HER2) concentrations, using antibodies as sensing elements. The fabrication of this device involves implementing an in-situ layer-by-layer technique coupled with a chemical adsorption step to achieve the self-assembly of GNP, GO, and antibodies on the STF surface. The detection mechanism relies on monitoring the refractive index changes induced by the adsorption of HER2 onto the immobilized antibodies. For comparative analysis, both monoclonal antibody (mAb) and the novel nanobody (Nb) were employed in constructing the STF immunosensor, referred to as the mAb immunosensor and Nb immunosensor, respectively. Spectral analysis results highlight that the Nb immunosensor exhibits twice the sensitivity of the mAb immunosensor. This enhanced sensitivity is attributed to the small size, high antigen affinity, strong specificity, and structural stability of Nb. The Nb immunosensor demonstrated an impressive detection limit of 0.001 nM for HER2, surpassing the detection limit of the mAb immunosensor. These findings underscore the potential of the proposed Nb immunosensor as a promising and sensitive tool for HER2 detection, contributing to the diagnosis and prognosis of breast cancer. Furthermore, the simplicity of production and excellent optical performance position the Nb immunosensor as a prospective real-time biosensor with minimal cytotoxicity.

Microfluidic Immunosensor Platform for Sensitive Detection of Human Epidermal Growth Factor Receptor-2 Based on Enhanced Cathode Electrochemiluminescence of Bimetallic Nanoclusters.

In this work, a microfluidic immunosensor chip was developed by incorporating microfluidic technology with electrochemiluminescence (ECL) for sensitive detection of human epidermal growth factor receptor-2 (HER2). The immunosensor chip can achieve robust reproducibility in mass production by integrating multiple detection units in a series. Notably, nanoscale materials can be better adapted to microfluidic systems, greatly enhancing the accuracy of the immunosensor chip. Ag@Au NCs closed by glutathione (GSH) were introduced in the ECL microfluidic immunosensor system with excellent and stable ECL performance. The synthesized CeO2-Au was applied as a coreaction promoter in the ECL signal amplification system, which made the result of HER2 detection more reliable. In addition, the designed microfluidic immunosensor chip integrated the biosensing system into a microchip, realizing rapid and accurate detection of HER2 by its high throughput and low usage. The developed short peptide ligand NARKFKG (NRK) achieved an effective connection between the antibody and nanocarrier for improving the detection efficiency of the sensor. The immunosensor chip had better storage stability and sensitivity than traditional detection methods, with a wide detection range from 10 fg·mL-1 to 100 ng·mL-1 and a low detection limit (LOD) of 3.29 fg·mL-1. In general, a microfluidic immunosensor platform was successfully constructed, providing a new idea for breast cancer (BC) clinical detection.

The unique monoclonal antibodies and immunochemical assay for comprehensive determination of the cell-bound and soluble HER2 in different biological samples

The expression of the HER2 (human epidermal growth factor receptor 2) protein in cancer cells is a well-established cancer marker used for diagnostic and therapeutic purposes in modern treatment protocols, especially in breast cancer. The gold-standard immunohistochemical diagnostic methods with the specific anti-HER2 antibodies are utilized in the clinic to measure expression level of the membrane-bound receptor. However, a soluble extracellular domain (ECD) of HER2 is released to the extracellular matrix, thus the blood assays for HER2 measurements present an attractive way for HER2 level determination. There is a need for accurate and validated assays that can be used to correlate the concentration of the circulating HER2 protein with disease clinical manifestations. Here we describe two monoclonal antibodies binding HER2 with a unique sequence of the complementarity-determining regions that recognize HER2 ECD. Development and validation of the sandwich enzyme-linked immunosorbent assay (ELISA) for quantification of the soluble HER2 in a variety of biological samples is also presented. The assay provides HER2 quantitation within a concentrations range from 1.56 to 100 ng/ml with sensitivity at the level of 0.5 ng/ml that meets the expectations for measurements of HER2 in the blood and tumor tissue samples. The method presents satisfactory intra- and inter-assay precision and accuracy for immunochemical quantification of biomarkers in biological samples. The utility of the generated monoclonal anti-HER2 antibodies has been confirmed for use in the precise measurement of HER2 (both cell-bound and soluble) in several types of biological material, including serum, solid tumor tissue, and cell culture medium. Additionally, the developed immunochemical tools have a potential for HER2 detection, not only in a wide range of sample types but also independently of the sample storage/pre-processing, allowing for comprehensive HER2 analysis in tissue (IHC), cultured cells (immunofluorescence) and blood (ELISA).

Ag nanorod@PEI-Ag nanohybrid as an excellent signal label for sensitive and rapid detection of serum HER2

The accurate detection of Human epidermal growth factor receptor-2 (HER2) as a critical breast cancer biomarker can be essential for the early selection of therapeutic approaches. HER2 is a prominent component of a signaling network. Overexpression of the HER2 protein due to amplification of its gene leads to the development of an aggressive subtype of breast cancer. Patients with tumors that overexpress HER2 are eligible for treatment that significantly reduces mortality rates. Herein, we present a fast and simple method for detecting serum HER2. A new electrochemical label has been developed using charged Ag nanorod@ polyethylenimine-Ag (Ag NR@ PEI-Ag) nanohybrid. The synthesized Ag NR@PEI-Ag nanohybrid simultaneously has the electroactive property of silver and the large surface area of the PEI, which results in the enhancement of the detection signal. So, using Ag NR@PEI-Ag nanohybrid as the electrochemical label, a simple, fast, and sensitive electrochemical biosensor was designed to detect HER2. This way, after immobilizing HER2 aptamer on the Au electrode surface, HER2 or human serum was exposed to the aptamer. Then, the positively charged Ag NR@PEI-Ag nanohybrid was adsorbed onto the negatively charged aptamer-HER2 complex, and the current that was produced due to the Ag/AgCl reaction was measured as the electrochemical signal. The aptasensor shows a broad linear response from 10–12 to 10–7 g, a low detection limit (LOD) of 10 pg, and a total assay time of ~ 30 min.

Liquid crystal-assisted optical biosensor for early-stage diagnosis of mammary glands using HER-2

Breast cancer (BC) is one of the most commonly diagnosed cancers and the second leading cause of cancer mortality among women around the world. The purpose of this study is to present a non-labeled liquid crystal (LC) biosensor, based on the inherent feature of nematic LCs, for the evaluation of BC using the human epidermal growth factor receptor-2 (HER-2) biomarker. The mechanism of this sensing is supported by surface modification with dimethyloctadecyl [3-(trimethoxysilyl) propyl] ammonium chloride (DMOAP) encouraging the long alkyl chains that induce a homeotropic orientation of the LC molecules at the interface. To enhance the binding efficacy of more HER-2 antibody (Ab) on LC aligning agents, a simple ultraviolet radiation-assisted method was also used to increase functional groups on the DMOAP coated slides, thereby improving binding affinity and efficiency onto HER-2 Abs. The designed biosensor makes use of the specific binding of HER-2 protein to HER-2 Ab and disruption of the orientation of LCs. This orientation change leads to a transition of the optical appearance from dark to birefringent, enabling the detection of HER-2. This novel biosensor exhibits a linear optical response to HER-2 concentration in the wide dynamic range of 10–6–102 ng/mL, with an ultra-low detection limit of 1 fg/mL. As a proof of concept, the designed LC biosensor was successfully investigated for the quantification of HER-2 protein in patients suffering from BC. Owing to the sensitivity, selectivity, and label-free detection, this biosensor may amplify the application of LC-based biosensors for the detection of most types of cancers.

Microswimmer-Based Ultrasensitive Dual-Signal Ratiometric Electrochemical Homogeneous Aptasensor with Functionalized Co-UiO-66 for the Single-Step Detection of HER2 in Whole Blood.

The ability to efficiently detect trace disease biomarkers in whole blood remains an enormous challenge. Researchers have paid more attention to the homogeneous electrochemical ratio biosensor due to its self-calibration capability and improved detection accuracy. However, proportional homogeneous electrochemical sensing is difficult to achieve and typically requires functional modification of the electrode or the preparation of complex materials. Herein, a dual-signal ratiometric aptamer homogeneous electrochemical microswimming detection device with active capture capability and one-step detection of human epidermal growth factor receptor-2 (HER2) is proposed. The homogeneous electrochemical biosensor is fabricated based on a functionalized nanocomposite double-stranded DNA({single-stranded DNA-ferrocene (Fc)-aptamer})@Co-UiO-66 with catalase properties and adsorptive properties to electroactive toluidine blue (TB) molecules. Encapsulation of Co-UiO-66 material with dsDNA (ssDNA-Fc-Apt) containing HER2 aptamer as a gate switch inhibited its ability to adsorb TB molecules. This functionalized Co-UiO-66 material can catalyze hydrogen peroxide. Using hydrogen peroxide as a fuel, it breaks down to release oxygen bubbles, creating a propulsion force that drives dsDNA(ssDNA-Fc-Apt)@Co-UiO-66 target HER2 through whole blood. When the surface dsDNA (ssDNA-Fc-Apt)@Co-UiO-66 recognizes HER2, a strand displacement reaction occurs, and the ssDNA-Fc is released into solution. The HER2 aptamer is coiled because it targets HER2, and the ability to adsorb TB molecules is restored due to the exposed surface of Co-UiO-66. A certain negative voltage is applied to the ITO electrode, and due to the electrostatic attraction, the TB molecules and ssDNA-Fc are adsorbed and enriched on the surface of the electrode by electrostatic attraction, which produces two strong and oppositely changing electrochemical signals, and the electrochemical signals depend on the HER2 concentration. It can sensitively detect HER2 biomarkers in only 40 min with the detection range of 0.0001-10 ng/mL and detection limits as low as 10 fg/mL. The electrochemical microswimmer for the detection of trace disease biomarkers involves a one-step process of capture, signal change, and detection.

An ultra-sensitive dual-signal ratiometric electrochemical aptasensor based on functionalized MOFs for detection of HER2

The dual-signal radiometric sensor can effectively reduce the difference between repeated detection and achieve higher accuracy, sensitivity and repeatability detection. In this work, we constructed a simple ratiometric electrochemical aptasensor based on functionalized ZIF-67 and ZIF-90 for sensitive detection of human epidermal growth factor receptor-2 (HER2). ZIF-67@Ferrocene (Fc)/antimonate nano flakes (AMNFs) as the capture probe has a large specific surface area and good conductivity, and have a strong adsorption capacity for aptamer single-stranded deoxyribonucleic acid (ssDNA). When the biomarker - HER2 interacts with aptamer ssDNA, it is easily desorbed from its surface. At the same time, ZIF-90@ methylene blue (MB) as the signal probe realizes one-step encapsulation of MB signal, which can avoid interference from external environment. When the target-HER2 exists, it is recognized by the capture probe, which leads to the decrease of the conductivity of the electrode. Under the action of the signal probe, the conductivity of the signal is recovered and the detection signal is amplified significantly. The designed ratiometric electrochemical aptasensor showed a wide linear range (0.5–1000 pg mL−1) and a low detection limit (155 fg mL−1) for HER2. Subsequently, it was applied to actual serum samples and showed acceptable applicability. It shows great potential for clinical screening and immediate detection of cancer biomarkers.

Label-Free Plasmon-Enhanced Spectroscopic HER2 Detection for Dynamic Therapeutic Surveillance of Breast Cancer.

The expression of human epidermal growth factor receptor-2 (HER2) has important implications for pathogenesis, progression, and therapeutic efficacy of breast cancer. The detection of its variation during the treatment is crucial for therapeutic decision-making but remains a grand challenge, especially at the cellular level. Here, we develop a machine learning-driven surface-enhanced Raman spectroscopy (SERS)-integrated strategy for label-free detection of cellular HER2. Specifically, our method allows the extraction of cell-rich spectral signatures utilized for identification and classification of cancer cells with distinct HER2 expression with a high accuracy of 99.6%. By combining label-free SERS detection and machine learning-driven chemometric analysis, we are able to perform longitudinal monitoring of therapeutic efficacy at the cellular level during the treatment of HER2+ breast cancer, which aids in the subsequent decision-making and management. This work provides a promising technique capable of performing dynamic label-free spectroscopic detection for therapeutic surveillance of diseases.

An ultrasensitive dual-signal aptasensor based on functionalized Sb@ZIF-67 nanocomposites for simultaneously detect multiple biomarkers

In vitro detection of biomarkers requires ultrahigh sensitivity and accuracy. The use of a dual-signal (electrochemical and fluorescent) strategy has the ability of self-calibration and can overcome interferences seen from experimental and environmental factors influencing the experimental results, showing significant advantages in the detection of biomarkers. Here, we propose an enzyme-free and label-free dual-signal aptasensor based on functionalized Apt@antimonene quantum dot (Sb)@ methylene blue (MB)@ZIF-67/Apt@Sb@3,3′,5,5′-tetramethylbenzidine (TMB) @ZIF-67 material to simultaneously detect multiple tumour biomarkers -oestrogen receptor (ER) and human epidermal growth factor receptor-2 (HER2). The aptamer chain of HER2 and ER is adsorbed to cover the porous structure of ZIF-67 through Sb, which has the characteristics of single-chain adsorption, in which the target protein is desorbed later, further encapsulating its internal MB and TMB with good dual-signal properties. After Apt@Sb@MB@ZIF-67/Apt@Sb@TMB@ZIF-67 targeted HER2 and ER biomarkers, the aptamer chains on the Sb quantum dots were desorbed and transferred into the solution, and the MB and TMB signals were released. Negative pressure is applied to the ITO electrode to adsorb and enrich positively charged MB and TMB organic molecules for electrochemical detection, and the supernatant after centrifugation can be directly subjected to fluorescence detection. Therefore, accurate electrochemical and fluorescent dual-signal detection of HER2 and ER from tissue to serum is achieved. Notably, sensitive detection of HER2-ER biomarkers was achieved in only 30 min, with a detection range of 0–10 pg/mL and detection limits of 3.4 fg/mL and 6.9 fg/mL, respectively.

Dynamic detection of HER2 of circulating tumor cells in patients with gastric carcinoma and its clinical application.

The aim of the present study was to construct and characterize human epidermal growth factor receptor2 (HER2) lipid magnetic ball (H‑LMB) for separating circulating tumor cells (CTCs) in patients with gastric carcinoma (GC) and to compare the result of separated CTC counts with that of next‑generation sequencing (NGS) for single‑gene analysis to verify the consistency for evaluating the association between the detection results and the progress of clinical treatment, so as to facilitate early diagnosis and dynamic monitoring of GC. A lipid magnetic ball (LMB), coated with Fe3O4 nanoparticles, was synthesized by microemulsion technique and an anti‑HER2 antibody was conjugated to the surface of LMB to form H‑LMB, followed by the characterization of the prepared H‑LMB. The detection of capture efficiency of LMBs in GC cells was tested by MTT and expression of HER2 mRNA was determined by reverse transcription‑quantitative PCR. The positive detection rate of HER2 was verified by HER2‑fluorescence insitu hybridization (FISH) test on the separated CTCs from GC. Further verification was performed based on the consistency between the result of separated CTCs and that of single‑gene NGS assay of HER2, associated with the determination of clinical consistency. The constructed H‑LMB exhibited good stability and specificity. The mutation rate of HER2 by the FISH test was 14% in the blood samples of 50patients with GC and was 14% by NGS assay. The mutation rate of HER2 was 12% in H‑LMB and the positive detection rate was 85.7% compared with the results of the FISH test, indicating consistency with the clinical diagnosis and pathological examination results. In conclusion, the anti‑HER2 antibody‑modified LMB can separate CTCs with HER2 abnormal expression, which exhibits an application potential in GC diagnosis and treatment and is of great clinical significance for the diagnosis and evaluation of its therapeutic effect on GC.

Plasmonic Fiber Grating Biosensors Demodulated Through Spectral Envelopes Intersection

Gold-coated tilted fiber Bragg gratings (TFBGs) have been highly studied over the last years, mainly for biosensing purposes. They present a comb-like spectrum of narrow-band cladding mode resonances that is often demodulated by tracking the change of a selected peak. In this paper, we report a twentyfold more sensitive demodulation method based on the intersection of the upper and lower envelopes of gold-coated TFBG spectra. This method has been successfully applied in biosensing experiments towards the detection of HER2 (Human Epidermal Growth Factor Receptor-2) proteins, a relevant biomarker for breast cancer. Practical improvements have also been implemented. First, a uniform FBG has been superimposed on the TFBG to reduce the read-out wavelength span to 10 nm instead of 70 nm while keeping the temperature-compensated measurements. Second, a micro-fluidic system has been implemented to smoothly deliver the samples to the sensor. These 3 originalities make this sensing platform even more attractive for use in practical applications.

Progression of HER-2 lowly expressed breast cancer and the related anti-tumor drugs

Breast cancer is one of the common malignant tumors of women. In recent years, the incidence of breast cancer is high. Human epidermal growth factor receptor-2 (HER-2) is a tyrosine kinase receptor. Breast cancer with abnormal amplification or overexpression of HER-2 have the characteristics of strong tumor invasiveness and poor prognosis. With the advent of anti-HER-2 drugs, the survival period of patients with HER-2 positive breast cancer is gradually prolonged, and the prognosis of patients with HER-2 positive breast cancer is improved. However, the efficacy of traditional HER-2 targeted drugs on patients with low expression of HER-2 is very limited, and the treatment of breast cancer with low expression of HER-2 is still facing challenges. This article reviews the standardization process of the American Society of Clinical Oncology and the American Society of Pathologists guidelines for HER-2 detection, and puts forward the data basis and possibility of defining a new subtype of breast cancer with low expression of HER-2. The birth of a new generation of HER-2 targeting drugs makes it possible to treat patients with low expression of HER-2, which will redefine breast cancer with low expression of HER-2 and provide a new opportunity for the prognosis of patients with low expression of HER-2.

Plasmon-Enhanced Electroactivity of AuRu Nanostructures for Electroanalysis Applications.

An electrochemical sensing interface is limited by poor reproducibility and inevitable interferences present in practical applications due to the weak electrochemical signals of nanotags. This motivates the need for effective strategies to enhance the electroactivity performances of nanotags. In this contribution, a plasmon-enhanced electroactivity mechanism is proposed for AuRu-based nanostructures under illumination and applied for accurate detection of human epidermal growth factor receptor-2 (HER2). AuRu nanoparticles (NPs) harvested light energy through plasmon excitation and generated holes to participate in the electrooxidation process. The production of holes resulted in the electrooxidation signal enhancement of AuRu NPs. AuRu NPs were assembled with Au NPs using HER2 aptamers as linkers, and the plasmonic coupling between AuRu NPs and Au NPs produced an intense electromagnetic field, which further enhanced the electrooxidation signals of AuRu NPs. An AuRu-Au NP assembly-dependent electrochemical aptasensor was established for the accurate detection of HER2, and the limit of detection (LOD) was as low as 1.7 pg/mL. The plasmon-enhanced electroactivity mechanism endowed AuRu-based nanostructures with strong and noninterfering electrochemical signals for sensitive and accurate detection. This insight opens new horizons for the construction of desired electroactive nanostructures for electroanalysis applications.

Clinical significance of sHER2‑ECD and calpain‑10 expression in tumor tissues of patients with breast cancer.

Human epidermal growth factor receptor2 (HER2) is composed of an extracellular domain (ECD), a lipophilic transmembrane region and an intracellular domain (ICD). The most commonly used method to determine the status of HER2 is immunohistochemistry. However, false‑negative results are sometimes given, which causes some patients to lose the opportunity for anti‑HER2 therapy. We found that calpain‑10 may prohibit HER2‑ECD into peripheral blood resulting in a HER2‑negative result by the immunohistochemical method. We enrolled 289patients into our experiment to assess the relationship between sHER2‑ECD and calpain‑10. The results showed that there was a positive correlation between sHER2‑ECD and calpain‑10. Moreover, we also investigated the prognostic values of sHER2‑ECD and calpain‑10 in breast cancer patients. According to the follow‑up results, positive sHER2‑ECD and tissue calpain‑10 were indicative of a poor prognosis in breast cancer patients. Subsequently, we further validated the relationship between the two molecules in invitro experiments. In the invitro experiments, the level of HER2‑ECD in the culture medium was increased or decreased with a decrease or increase in calpain‑10 by transfection technology, showing an inverse association. The results indicated that sHER2‑ECD and tissue calpain‑10 levels were powerful factors to assess the status of HER2. In combination with tissue HER2 detection, the occurrence of false‑negative HER2 was reduced, providing patients with additional treatment opportunities. In conclusion, sHER2‑ECD and tissue calpain‑10 may be used as new prognostic indices for breast cancer.

PH-responsive allochroic nanoparticles for the multicolor detection of breast cancer biomarkers

Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) are the three crucial biomarkers for the clinical diagnosis of breast cancer. Sensitive and precise detection of ER, PR, and HER2 is of great significance for the diagnosis of breast cancer. Herein, through a simple solvent-induced self-assembly process, the self-carried allochroic nanoparticles were prepared by using some hydrophobic pH indicator molecules for allochroic NPs-linked immunosorbent assay (named ALISA) of ER, PR, and HER2, respectively. Meanwhile, the introduction of bovine serum albumin (BSA) and antibody (Ab) enhanced the dispersity of the self-assembled nanoparticles as signal tags. Since the ultra-high loading and high-efficiency release of pH indicators, the ALISA exhibitssatisfactory selectivity and sensitivity, which demonstrated the great potential in the early diagnosis and postoperative monitoring of breast cancers. Furthermore, the smartphone was introduced to combine with the ALISA for point-of-care testing, indicating the high feasibility in practical applications.

Dual signal amplification photoelectrochemical biosensor for highly sensitive human epidermal growth factor receptor-2 detection

Photoelectrochemical (PEC) biosensor for highly sensitive detection of breast cancer biomarker human epidermal growth factor receptor-2 (HER2) is reported utilizing a dual signal amplification strategy. The biosensor was prepared based on tungsten sulfide nanowire array on Ti mesh (WS2 NW/TM). Such WS2 NW/TM electrode can generate photoelectric signal under visible light excitation. The HER2 aptamer was wrapped onto the nanowire array surface for specific binding with HER2 molecules, and gold nanoparticles (Au NPs) that modified with glucose oxidase (GOx) and HER2 binding peptide was utilized for signal amplification. The H2O2 that generated by GOx catalyzed glucose reaction and localized surface plasmon resonance of Au NPs can both enhance the PEC current intensity of the biosensor, leading to dual signal amplification. The PEC current intensity is enhanced linearly with HER2 concentration in the 0.5–10 ng/mL range with limit of detection of 0.36 ng/mL. Such biosensor was applied for the detection of HER2 in breast cancer serum samples with detection results in good agreement with commercial ELISA results.

Aptamer based determination of the cancer biomarker HER2 by using phosphate-functionalized MnO2 nanosheets as the electrochemical probe.

The authors report a sensitive electrochemical aptamer-based assay for the cancer biomarker human epidermal growth factor receptor-2 (HER2). It is based on the use of MnO2 nanosheets that were functionalized with phosphate and a HER2 binding aptamer and serve as the electrochemical probe. The assay follows a sandwich protocol. A peptide that can specifically recognize HER2 was immobilized on a gold electrode for the capture of HER2. Then, the functionalized MnO2 nanosheets were linked to the electrode via the binding between HER2 and HER2 aptamer on the MnO2 nanosheets. The reaction of phosphate and aptamer on the MnO2 nanosheets with molybdate leads to the formation of redox-active molybdophosphate. This results in dual signal amplification. The generated electrochemical current was measured at 0.22V (vs. Ag/AgCl). The assay allows HER2 to be determined in the 0.1 to 500pg·mL-1 concentration range, and the detection limit is as low as 0.05pg·mL-1. The assay was successfully applied for the detection of HER2 in spiked human serum samples. Graphical abstract Electrochemical detection of breast cancer biomarker human epidermal growth factor receptor-2 (HER2) is reported utilizing phosphate ions and aptamer functionalized MnO2 nanosheet as probe.

A fluorescent aptasensor for the femtomolar detection of epidermal growth factor receptor-2 based on the proximity of G-rich sequences to Ag nanoclusters

Human epidermal growth factor receptor-2 (HER2) has been recognized as an important biomarker for the early diagnosis and management of breast cancer. However, there is still challenge in the clinical detection of HER2. In this work, a simple strategy for “turn on” fluorescent detection of HER2 with ultra-sensitivity and high specificity was developed. Herein, HER2-binding aptamer (HApt) and DNA2 containing G-rich sequences, templated sequences for Ag nanoclusters (AgNCs), and complementary bases at both ends were involved to achieve the double stranded DNA templated AgNCs (dsDNA-AgNCs) as a fluorescence probe for HER2 detection. In the presence of HER2, the highly specific binding of HER2 to HApt caused HApt separating from dsDNA-AgNCs, resulting in the folding of DNA2-AgNCs because of the complementary bases at both ends, which led to AgNCs’ proximity to G-rich sequences, and therefore the enhanced fluorescence intensity. By monitoring the change in fluorescence signal (ΔF), HER2 was measured, and a linear range from 8.5 fM to 225 fM with a limit of detection (LOD) 0.0904 fM was obtained. More significantly, the detection of HER2 in serum samples was achieved with high accuracy, and the breast cancer patients were successfully discriminated from healthy persons. In summary, this strategy is simple, time-saving, cost-effective, ultrasensitive, specific, universal and more applicable for the detection of HER2. Therefore, we expect this present aptasensor can be used in the clinical detection of biomakers, which lays a potential foundation for the early diagnosis of cancer.

Gold nanoparticles conjugated to bimetallic manganese(II) and iron(II) Prussian Blue analogues for aptamer-based impedimetric determination of the human epidermal growth factor receptor-2 and living MCF-7 cells.

An aptamer-based assay is described for the determination of trace levels of the cancer marker human epidermal growth factor receptor-2 (HER2) and living MCF-7 cells. The method is based on the use of a bimetallic MnFe Prussian blue analogue coupled to gold nanoparticles (MnFePBA@AuNP). Compared to pristine MnFe PBA nanocubes, the series of MnFePBA@AuNP exhibits a core-shell spherical nanostructure, and the shell thickness decreases from 99.9nm down to 49.3nm on increasing the fraction of AuNPs. The composite was placed on a gold electrode and incubated with the aptamer solution through electrostatic interaction. Then the modified electrode was employed to detect HER2 and MCF-7 cells using [Fe(CN)6]3-/4- as redox probe and displays good responses to both of them. Electrochemical impedance spectroscopy data show that the signal variation between each step during the whole procedure for the HER2 and MCF-7 cells detection can be embodied as the resistance value change between the [Fe(CN)6]3-/4- and electrode surface. The assay has a very low detection limit (0.247pg∙mL-1) and works in the 0.001-1.0ng∙mL-1 HER2 concentration range. It was also used to sense HER2 in MCF-7 cells, and this results in an assay that works within the 500-5 × 104 cell∙mL-1 cell concentration range and a 36 cell∙mL-1 detection limit. Furthermore, the aptamer-based assay is selective, acceptably reproducible, stable, and well feasible for the detection of HER2 and living MCF-7 cells in human serum. Graphical abstract Schematic of an electrochemical aptasensor based on the bimetallic MnFe Prussian blue analogue (MnFe PBA) coupling with gold nanoparticles (represented by MnFePBA@AuNPs). Itwas employed as the aptasensor for human epidermal growth factor receptor-2 (HER2), and living MCF-7 cells.