Detection Of Carcinoembryonic Antigen Research Articles

All-in-one magnetic beads: Searching, capturing and simultaneous detection of dual tumor related proteins in real samples

Simultaneous assay of multiple tumor marker proteins is of great importance for accurate diagnosis of cancer because most of cancers are usually related to various tumor-related proteins. In this work, we prepared yellow-colored carbon dots (y-CDs) and blue-colored carbon dots (b-CDs) for simultaneous detection of carcinoembryonic antigen (CEA) and cancer antigen125 (CA125) based on the antifouling magnetic beads (MBs) in real samples. Two sandwich structures were constructed by MBs modified with aptamer 1(Apt1) of proteins and aptamer 2(Apt2) tagged with CDs in the presence of target proteins. After CDs were cut off and separated, the fluorescence intensities at 430 nm (b-CDs) and 550 nm (y-CDs), relating to quantities of two proteins, were measured at a single excitation wavelength, obtaining the detection limits of 0.11 ng mL−1 (CEA) and 0.57 U mL−1 (CA125) respectively. Due to the target specific searching, recognition, capturing with aptamers, magnetic separation and antifouling property of peptides, the simultaneous differentiating and assaying CEA and CA125 in human serum can be easily operated, and results reveal a good correlation with data from the electrochemiluminescent (ECL) immunoassay in hospitals, demonstrating the promising candidate for clinical diagnosis of ovarian cancer.

An electrochemical immunosensor for simultaneous detection of two lung cancer markers based on electroactive probes

A multiplex electrochemical immunosensor was developed for the simultaneous detection of two lung cancer markers, carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125), using electroactive probes. Cu-TCPP nanomaterials were synthesized by a hydrothermal method. Cu-TCPP–TB-anti-CEA and Cu-TCPP-PB-anti-CA125 immunosensor probes were prepared using toluidine blue (TB) and prussian blue (PB) as the indicators. The electrochemical immunosensor was constructed for the simultaneous detection of CEA and CA125. The linear range of CEA was 0.1–160 ng mL−1 with a low detection limit of 0.03 ng mL−1. The linear range of CA125 was 0.5–200 U mL−1 with a low detection limit of 0.05 U mL−1. Furthermore, the immunosensor was applied for the simultaneous determination of CEA and CA125 in real samples (human blood serum), with results comparable to the reference values obtained by the standard enzyme-linked immunosorbent assay. This study furthers knowledge on the construction of electrochemical immunosensors showing the simultaneous detection of two lung cancer markers.

Development of Carcinoembryonic Antigen Rapid Detection System Based on Platinum Microelectrode.

Rapid and highly sensitive detection of carcinoembryonic antigen (CEA) in blood could effectively improve the diagnostic sensitivity of colorectal cancer. In this work, a platinum microelectrode (PtμE) modified with gold nanoparticles was developed as a microsensor for the detection of CEA. As the recognition element, a CEA aptamer modified with sulfhydryl could be conjugated onto the surface of the PtμEs/Au. The quantitative analysis of the concentration of CEA [CEA] by the prepared PtμEs/Au aptasensor was carried out through square wave voltammetry. Under the optimized conditions, the PtμEs/Au aptasensor exhibits a linear response toward [CEA] in the range of 1.0 × 10–11—1.0 × 10–7 g/ml (S = 5.5 nA/dec, R 2 = 0.999), and the detection limit is 7.7 × 10–12 g/ml. The PtμEs/Au aptasensor also has good selectivity against other types of proteins existing in blood. The availability of the developed assay toward [CEA] in blood samples was investigated, and the results agreed well with those obtained through electrochemiluminescence provided by the hospital, and the volume of the blood sample for detection is only 20 μl. Herein, the proposed detection system could be used for the quantitative analysis of CEA in blood, with the advantages of high sensitivity, short time, and low cost. Moreover, the PtμEs/Au aptasensor has a potential application in clinical diagnosis.

Electrochemical stripping chemiluminescence coupled with recycling amplification strategy for sensitive detection of carcinoembryonic antigen

As a new generation of electrochemiluminescence (ECL) technology, the electrochemical stripping chemiluminescence (ESCL), which combines the advantages of chemiluminescence and stripping voltammetry, has attracted increasing attention in the biosensor field. Here, Ag nanoclusters (NCs) were prepared using DNA double strands as a template and explored to construct an ESCL aptamer sensor (aptasensor) for the detection of a carcinoembryonic antigen (CEA). During the detection process, Ag NCs and the Ag+ cations stripped out from Ag NCs were found to respectively catalyze the electrochemical reduction and oxidation of H2O2, accelerating the decomposition of H2O2 to generate reactive oxygen species (ROSs) and thus effectively enhancing the ECL intensity of luminol. Coupled with the exonuclease I-assisted recycling amplification technology, the developed ESCL aptasensor enabled the sensitive detection of CEA, exhibiting a broad linear response from 100 ag/mL to 10 ng/mL with a low detection limit of 38.86 ag/mL (S/N = 3). In addition, the aptasensor showed good performance in the determination of CEA in human serum with a relative standard deviation (RSD) below 5 %. This work provides an effective method for constructing simple, fast, and sensitive biosensors.

Generation of selenium nanoparticles under γ-Irradiation for optical sensing of Carcinoembryonic antigen

A simple and rapid analytical method is reported using selenium nanoparticles (SeNP) for the detection of carcinoembryonic antigen (CEA), a biomarker of colorectal cancer. The red coloured SeNPs were synthesized at room temperature from aqueous solution of selenourea. SeNPs were then subjected to γ-irradiation for 24 h to attain surface charge and enhanced surface activity. The detection of CEA by both gamma-irradiated and non-irradiated nanoparticles was carried out by UV visible spectroscopy. Our results showed that γ- irradiated (24 h) SeNPs were able to detect CEA with higher sensitivity (LOD 8.82 pg/mL) as compared to non-irradiated SeNPs (LOD 16.76 pg/mL). Moreover, the interference from the comorbidity-causing biomolecules like dextrose, cholesterol and bilirubin during the detection of CEA in serum medium was further checked. An increase in LOD values of control (in absence of NPs) was observed in presence of these biomolecules which may lead to erroneous determination of CEA for the patients suffering from different pathophysiological conditions like diabetes or hypercholesterolemia or hepatic disorders. However, LOD values were found to be lowered in presence of these serological variables even in their combined physiological conditions. The mechanism of detection of CEA by the nanoparticles were established by different spectroscopic methods like fluorescence and CD and theoretical docking as well.

Molybdenum blue mediated photothermal immunoassay for CEA detection based on Ag4P2O7@Ag nanocomposites

A photothermal immunoassay was built for tumor marker detection based on Ag4P2O7@Ag nanocomposites. Ag4P2O7@Ag nanomaterials were synthesized by precipitation-photoreduction reaction, and characterized by transmission electron microscope (TEM), scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray photoelectron spectra (XPS) and X-ray powder diffraction (XRD). Come about PO43− derived from Ag4P2O7@Ag under acidic conditions react with ammonium molybdate in the action of reductant generating molybdenum blue. The photothermal change is due to molybdenum blue solution depending on the concentration of carcinoembryonic antigen (CEA) in immunoassay. Under optimal conditions, there is a linear relation between ΔT and CEA concentration in the range of 1 pg mL−1–40 ng mL−1 with the detection limit of 0.33 pg mL−1. Meanwhile, the developed photothermal immunoassay displays preferable selectivity, repeatability, and stability.

Clinical value of combining serum tumor marker detection with fecal occult blood testing in diagnosing colorectal cancer.

This study aimed to investigate the value of combining the detection of serum tumor markers, namely, carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 199, CA 242, and CA 50, with fecal occult blood (FOB) testing in the diagnosis of colorectal cancer (CRC). One hundred patients with CRC who were diagnosed and treated at the First Hospital of Jiaxing, Zhejiang Province, China, between January 2019 and April 2020 were enrolled as the case group, and 200 healthy people who underwent a physical examination at the hospital during the same period were recruited as the control group. The concentrations of CEA, CA199, CA242, and CA50 in serum were measured alongside FOB indicators. Compared with the control group, the concentrations of CEA, CA199, CA242, and CA50 in the case group were significantly higher, and they were related to age, tumor differentiation, tumor stage, and other clinicopathological features (P<0.05). The diagnostic performance of the combination of four tumor markers for CRC was significantly better than when using a single marker (four-combined test: AUC (area under the curve) AUC=0.80), and the diagnostic performance was further improved after adding the fecal occult blood test test (FOBT) results (five-combined test: AUC=0.90). The combined detection of the five indexes was found to be effective for the early diagnosis of CRC (AUC=0.87). We concluded that the detection of serum tumor markers CEA, CA199, CA242, and CA50 combined with an FOBT could significantly improve the sensitivity and accuracy of a CRC diagnosis and contributed to an early diagnosis and appropriate treatment.

Prognostic value of serum carcinoembryonic antigen combined with nutritional status control score in patients with colorectal cancer*

Abstract Objective To investigate the prognostic value of serum carcinoembryonic antigen (CEA) and controlling nutritional status (CONUT) score in patients with colorectal cancer. Methods We retrospectively studied 261 patients with colorectal cancer in our hospital. The patients were divided into two groups by CONUT = 3 and CEA = 5 ng/mL, and the effects of CONUT score and CEA level on the prognosis and clinicopathological parameters were statistically analyzed. Results (1) Different CONUT scores were significantly correlated with age, tumor diameter, differentiation type, and T stage (P &lt; 0.05). The older the patient was, the larger the tumor diameter, undifferentiated tumor, and T stage were, the higher the CONUT score was. (2) Seventy-five patients died during the follow-up period, and 45 patients died of progression or recurrence of colorectal cancer. The 5-year overall survival (OS) rate of the low CONUT score group was significantly higher than that of the high CONUT score group, and the 5-year OS rate of the low CEA group was significantly higher than that of the high CEA group; the difference was statistically significant (P &lt; 0.01). (3) According to the serum CEA level and CONUT score, the 5-year survival rates of CEAlow/CONUTlow, CEAlow/CONUThigh, CEAhigh/CONUTlow, and CEAhigh/CONUThigh were 84.7%, 69%, 55.3%, and 36.1% respectively, with statistical significance (P &lt;0.01). (4) The Cox multivariate analysis showed that age, CONUT score, CEA combined with CONUT score, lymph node metastasis, and distant metastasis were independent risk factors for the prognosis of colorectal cancer patients. Conclusion: The combination of CEA detection and CONUT score can more accurately judge the prognosis of colorectal cancer patients.

Surface-Enhanced Electrochemiluminescence Imaging for Multiplexed Immunoassays of Cancer Markers in Exhaled Breath Condensates.

Recently we have demonstrated that the surface plasmon of noble metal nanoparticles can effectively enhance the ECL intensity of Ru(bpy)32+, and we named this detection principle as surface-enhanced electrochemiluminescence (SEECL-I). However, SEECL based on photomultiplier tube (PMT) detection can only detect one target at a time, which is not suitable for multiple targets detection. In this work, we combined our previous developed SEECL with a bioimaging device to develop a novel multiplexed immunassay for simultaneous and fast analysis of cancer markers. A core-shell nanocomposite consisted of gold-silicon dioxide nanoparticles doped with Ru(bpy)32+(Au@SiO2-Ru) with strong ECL emission was employed as ECL label due to the localized surface plasmon resonance (LSPR) of AuNPs, which can significantly enhance the ECL emission of Ru(bpy)32+. The ECL signals from the 4 × 4 electrode arrays were collected using the constant potential method (current-time curve method) imaging with a sCOMS camera. As a proof-of-concept application, we demonstrated the use of the proposed SEECL-I for simultaneous detection of carcinoembryonic antigen (CEA), neuron specific enolase (NSE), and squamous cell carcinoma antigen (SCC) in exhaled breath condensates (EBCs) with low detection limit (LOD) of 0.17, 0.33, and 0.33 pg/mL (S/N = 3), respectively. The results demonstrated that the proposed SEECL-I strategy can provide a high sensitivity, fast analysis, and high-throughput platform for clinical diagnosis of cancer markers in EBCs.

Highly Sensitive Detection of Carcinoembryonic Antigen via an Electrochemical Platform Fabricated by AuNPs/Streptavidin/Reduced Graphene Oxide.

Tumor markers are one of the important indicators for early cancer diagnosis. As a new analytical method, electrochemical immunosensing analysis has the advantages of high sensitivity, good selectivity, and rapid detection, which is of great significance for the detection of tumor markers. In this work, an AuNP/reduced graphene oxide (AuNP/rGO) composite was synthesized. We used it for electrochemical sensor fabrication with the assistance of the biotin–streptavidin protein (SA) system to further amplify the signal to achieve sensitive detection of carcinoembryonic antigen (CEA). In addition, AuNPs have been incorporated due to their good electrical conductivity and biocompatibility, which can accelerate electron transfer at the electrode interface and improve the loading capacity to capture antibodies. The fabricated AuNPs/SA/rGO has a large working surface area and high material utilization ratio, which improves the catalytic capacity of H2O2 reduction and effectively amplifies the current signal. The linear range of the response current signal of the sensor toward the CEA concentration is 20 fg/ml to 200 ng/ml, and the limit of detection can achieve 6.2 fg/ml. In addition, the fabricated immunosensor has good reproducibility, selectivity, and stability.

Recent Advances in Nanomaterial-based Optical Biosensors as Potential Point-of-Care Testing (PoCT) Probes in Carcinoembryonic Antigen Detection.

For the past decades, several cancer biomarkers have been exploited for rapid and accurate prognosis or diagnosis purposes. In this review, the optical biosensor is targeted for carcinoembryonic antigen (CEA) detection. The CEA level is a prominent parameter currently used in clinical cases for the prognosis of cancer-related diseases. Many nanomaterial-based biosensors are invented as alternatives for the commonly used enzyme-linked immunosorbent assays (ELISA) immunoassay method in CEA detection as the traditional approach. But they possess certain drawbacks such as tedious procedure, high technical demand, and costly. Nevertheless, the effort appears to be wasted as none of them are being actualised. Generally, the sensor function was carried out by converting bio-signals generated upon the interface of the receptor into light signals. These sensors were popular due to specific advantages such as sensitivity, being free from chemical and electromagnetic interferences, wide dynamic range, and being easy to be monitored. The features of PoC diagnostics are discussed and associated to the various applications of colorimetric-based and chemiluminescent-based biosensors. The roles of nanomaterials in each application were also summarised by comparing the modification, incubation period, lowest detection limit (LOD) and linear range of detection amount. The challenges and future perspectives were highlighted as well at the end of the review.

Ratiometric electrochemical aptasensor for the sensitive detection of carcinoembryonic antigen based on a hairpin DNA probe and exonuclease I-assisted target recycling

A novel ratiometric electrochemical aptasensor was constructed for the detection of carcinoembryonic antigen (CEA) based on a hairpin DNA (hpDNA) probe and exonuclease Ⅰ (Exo Ⅰ)-assisted target recycling amplification strategy. A thiolated methylene blue (MB)-labeled hpDNA as the internal control element was fixed on the surface of the gold nanoparticles (AuNPs)-modified gold electrode (AuE) through Au–S bonds. A ferrocene (Fc)-modified aptamer DNA (Fc-Apt) was partially hybridized with hpDNA to form a Fc-Apt/hpDNA duplex. Due to the specific recognition of Fc-Apt to CEA, the presence of CEA caused dissociation of Fc-Apt from the duplex, and further triggered the degradation process of Exo Ⅰ and recycling of CEA. Hence, the Fc tags were released from the electrode surface and the oxidation peak current of Fc (IFc) decreased while that of MB (IMB) remained stable owing to the distance between MB tags and the electrode unchanged. A linear relationship was observed between IFc/IMB and the logarithm of CEA concentration from 10 pg mL−1 to 100 ng mL−1 with a detection limit of 1.9 pg mL−1. Moreover, the developed aptasensor had been applied to detect CEA in diluted human serum with satisfactory results, indicating its great potential in practical applications.

A novel chemiluminescence biosensor based on dual aptamers bound nanoparticles with multi-site signal amplification for sensitive detection of carcinoembryonic antigen

The establishment of stable and simple detection methods for cancer markers is very necessary for the treatment of cancer. In this study, based on the fact that carcinoembryonic antigen (CEA) has dual recognized aptamers, the aptamer1 (Apt1) is connected with magnetic beads (MBs) to form MBs-Apt1. Meanwhile, using the histidine (His) as the medium, nickel hexacyanoferrate nanoparticles (Ni NPs) as the catalyst, the Ni NPs-His-aptamer2 (Apt2) has also been prepared. In the presence of CEA, the MBs-Apt1 combined with Apt2-His-Ni NPs can specifically recognize CEA and form MBs-Apt1/CEA/Apt2-His-Ni NPs classical “sandwich” structure with signal cascade amplification. Remarkably, the cubic crystal structure of Ni NPs allows it to have multiple catalytically active sites, and plentiful His with − COOH can quickly bind to amino-modified Apt2 and chelate Ni NPs to form Apt2-His-Ni NPs. In another strategy, specific recognition of streptavidin (SA)-modified gold nanoparticles (Au NPs) using streptavidin aptamer (SAA), similarly established the MBs-Apt1/CEA/Apt2-SAA-SA@Au NPs classical “sandwich” structure with signal cascade amplification of luminol. The detection limits of the two methods were 0.092 pg/mL and 0.122 pg/mL, respectively. As predicted, protein biomarkers with concentrations as low as pg/mL can be detected in a very small amount of serum. And thus, there will be a bright future in the detection of CEA and other tumor markers in the early diagnosis of cancer.

A new ratiometric electrochemical aptasensor for the sensitive detection of carcinoembryonic antigen based on exonuclease I-assisted target recycling and hybridization chain reaction amplification strategy

In this work, a novel ratiometric electrochemical aptasensor was designed on the basis of dual-amplification mechanism by using exonuclease I (Exo I)-assisted target recycling and hybridization chain reaction (HCR). The thiol-modified capture DNA (Cp-DNA) was fixed on the surface of the gold electrode (AuE) modified with gold nanoparticles (AuNPs) through Au-S bonds. The ferrocene (Fc)-labeled DNA (Fc-DNA) hybridized with Cp-DNA to form Fc-DNA/Cp-DNA duplex. The presence of carcinoembryonic antigen (CEA) led to the dissociation of Fc-DNA from Fc-DNA/Cp-DNA duplex and initiated Exo Ⅰ-assisted target recycling to digest Fc-DNA, so numerous Fc left away from the electrode surface and resulting in the “signal off” of Fc. Moreover, Cp-DNA was exposed to bind trigger DNA and initiate HCR with the presence of H1 and H2 probes, resulting in the intercalating of numerous methylene blue (MB) molecules and the “signal-on” of MB. This dual signal strategy significantly amplified the decrease of Fc signal and the increase of MB signal, achieving a linear range of 1 pg mL−1 to 100 ng mL−1 with a detection limit of 0.479 pg mL−1 (S/N = 3). Besides, the developed aptasensor exhibited high specificity, good stability and reproducibility. More importantly, the aptasensor had been applied in detection of CEA in diluted human serum and displayed satisfactory anti-interference property. By changing the corresponding aptamer sequences, the designed strategy can be employed to detect other targets, which holds promising application in clinical diagnosis.

Diagnostic value of combined detection of CA72-4, CA19-9, and carcinoembryonic antigen comparing to CA72-4 alone in gastric cancer: a systematic review and meta-analysis

BackgroundGastric cancer (GC) is one of the most common malignant tumors in humans. Carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, and CA72-4 are all serum tumor markers for diagnosis of gastric cancer. However, the results of studies reporting the diagnosis of the combined three varied. In this study, the combined diagnostic performance of these 3 serum tumor markers was systematically evaluated.MethodsPubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang data were searched for literature on serum tumor markers CEA, CA19-9, and CA72-4 in the diagnosis of gastric cancer. The inclusion criteria were designed according to the Participants, Intervention, Control, Outcomes, Study (PICOS) principles. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) scoring scale was used to assess the quality of the literature. After extracting the data, Stata 16.0 software was used for meta-analysis.ResultsA total of 10 articles were finally included, and a total of 6,574 patients participated in diagnosis, 3,077 for confirmed GC and 3,497 for non-GC respectively. Meta-analysis results showed that the diagnostic sensitivity of the combined diagnosis of the 3 tumor markers was 0.67 [95% confidence interval (CI): 0.54, 0.77], the specificity was 0.89 (95% CI: 0.82, 0.93), the positive likelihood ratio was 5.9 (95% CI: 3.5, 9.8), the negative likelihood ratio was 0.38 (95% CI: 0.27, 0.53), and the diagnostic odds ratio (DOR) was 16 (95% CI: 8, 32). The diagnostic sensitivity of CA72-4 diagnosis alone was 0.58 (95% CI: 0.40, 0.73), specificity was 0.86 (95% CI: 0.80, 0.90), the positive likelihood ratio was 4.0 (95% CI: 3.1, 5.1), the negative likelihood ratio was 0.49 (95% CI: 0.34, 0.71), and the DOR was 8 (95% CI: 5, 14). The area under the ROC curve (AUC) values of the combined three diagnosis and CA72-4 diagnosis alone were 0.87 (95% CI: 0.83, 0.89) and 0.84 (95% CI: 0.81, 0.87), respectively, the difference was statistically significant (Z=4.86, P<0.05).DiscussionThe combined use of the 3 tumor markers has higher sensitivity and specificity than single marker diagnosis in the diagnosis of gastric cancer.

Ratiometric electrochemical immunosensor triggered by an advanced oxidation process for the ultrasensitive detection of carcinoembryonic antigen

Conventional electrochemical immunosensors often achieve detection purposes through a single signal output, but its electrical signal is susceptible to external environmental interference, which seriously interferes with the sensitivity and repeatability of the sensors. In this work, a novel ratiometric electrochemical immunosensor triggered by an advanced oxidation process (AOP) was developed for the ultrasensitive detection of carcinoembryonic antigen (CEA). The sensor uses gold nanoparticle-reduced graphene oxide/methylene blue adsorbed by sodium alginate (Au-rGO/MB-SA) as matrix to immobilize primary antibody (Ab1) and Ag nanoparticles-functionalized egg yolk structure Co3O4@SiO2 (Co3O4-Ag@SiO2) as a marker to label secondary antibody (Ab2). When the detection solution contains peroxymonosulfate (PMS), the signal probe Co3O4-Ag@SiO2 activates PMS to produce SO4•−/•OH radicals to degrade MB, thus generating two independent electrochemical signals with opposite directional changes (IAg and IMB). The sensitivity of the sensor is improved due to an enhanced response magnitude on account of the processing of the dual selective responsive signals to yield a response magnitude greater than that of the signal from a single sensor. Square wave voltammetry (SWV) analysis shows that the dual signal ratio (I = IAg/IMB) has a linear relationship with the logarithm of the CEA concentration in the range of 0.01 pg/mL to 40 ng/mL, and the detection limit is as low as 3.42 fg/mL. In addition, the sensor has good selectivity and reproducibility, showing great promise for applications in bioanalysis and disease diagnosis.

Ultrasensitive photoelectrochemical immunosensor for carcinoembryonic antigen detection based on pillar[5]arene-functionalized Au nanoparticles and hollow PANI hybrid BiOBr heterojunction

In this study, an ultrasensitive and specific photoelectrochemical (PEC) immunosensor was designed for carcinoembryonic antigen (CEA) detection. Benefitting from the ascorbic acid (AA) used as an electron donor that led to a notable change in the photocurrent density, pillar[5]arene functionalized Au and Polyaniline-Bismuth oxybromide heterojunction (Au@WP5/PANI-BiOBr) displayed superior PEC performance for CEA sensing. In detail, the localized surface plasmon resonance (LSPR) of the Au NPs and host-guest complexation between WP5 and AA increased the photocurrent signal, the photogenerated holes on BiOBr accelerated the oxidation of AA, and the fast electron transfer of the hollow PANI tubes benefited an increase in the photocurrent. The antibody effectively bound with CEA when bovine serum albumin blocked the residual sites on the Au@WP5/PANI-BiOBr electrode, generating a clear decrease in photocurrent density in AA solution. Under the optimum condition, the developed PEC immunosensor exhibited a sensitive response to CEA which was linear in the range of 0.01 ng mL-1 to 50 ng mL-1 with a detection limit of 3 pg mL-1. The proposed PEC immunosensor displayed high specificity, good stability, and excellent reproducibility, paving a new way to construct sensitive and specific photoactive heterojunction materials for biomarker immunosensing.

Magnetic antifouling material based ratiometric electrochemical biosensor for the accurate detection of CEA in clinical serum

A novel ratio electrochemical biosensor based on multi-functional nanocomposite was developed. Fe3O4 was synthesized in situ on carboxyl functionalized 2D nanomaterial MXene, and then covalently bonded with [Ru(NH3)6]3+ to obtain nanocomposites MXC-Fe3O4-Ru. Fe3O4 and [Ru(NH3)6]3+ can neutralize the electronegativity of the MXene to make the nanocomposites electrically neutral. Combine with the good hydrophilicity and conductivity of MXene, the nanocomposites can be utilized to construct antifouling electrochemical biosensors without modifying with specific antifouling materials. Moreover, Fe3O4 can endow the nanocomposites with magnetism, and [Ru(NH3)6]3+ is used as an internal standard molecule. The strong magnetic MXC-Fe3O4-Ru can be easily separated and firmly modified on the magnetic gold electrode (MGE). DNA double-stranded (dsDNA) containing an ferrocene (Fc)-modified carcinoembryonic antigen (CEA) aptamer can be specifically captured to the surface of the electrode by amido bond. In the presence of CEA, CEA binds to the aptamer and leaves the electrode surface, the electrochemical signal of Fc decreases, while the electrochemical signal of [Ru(NH3)6]3+ is fixed on the electrode surface remains basically unchanged. The ratio of the electrochemical signals of Fc and [Ru(NH3)6]3+ is proportional to the CEA concentration. The linear range of the sensor is 1 pg/mL to 1 μg/mL with a detection limit of 0.62 pg/mL. With the excellent antifouling performance, good conductivity of the nanocomposite, and the application of the ratiometric strategy, the biosensor can achieve high selectivity, accuracy, and sensitivity for the detection of targets even in complex samples, such as FBS and clinical serum.

An Immunosensor Using Electroactive COF as Signal Probe for Electrochemical Detection of Carcinoembryonic Antigen.

Two kinds of two-dimensional (2D) covalent-organic frameworks (COF) were used to construct a sandwich-type electrochemical immunosensor for a proof-of-concept study. Vinyl-functionalized COFTab-Dva could be linked with Ab1 by the thiol-ene "click" reaction. Electroactive COFTFPB-Thi was modified with gold nanoparticles (AuNPs) to ensure the successful connection with Ab2 through Au-S bond. Meanwhile, electroactive COFTFPB-Thi was used to as signal probe to realize both the detection of carcinoembryonic antigen (CEA) and the amplification of detection signal. In detection process of the sandwich-type electrochemical immunosensor, glassy carbon electrode (GCE) was modified with 2D COFTab-Dva first then connected with Ab1 by the thiol-ene "click" reaction, next quantitative CEA was captured, followed by specificially capturing signal probe of Ab2/AuNPs/COFTFPB-Thi where AuNPs acted as nanocarriers of Ab2 and COFTFPB-Thi served as the signal producers. As the amount of CEA was increased, the amount of signal probe captured to the electrode was also increased, and the peak signal intensity of the redox reaction of COFTFPB-Thi was enhanced accordingly. Thus, the quantitative detection of CEA could be realized according to the peak signal intensity of electroactive COFTFPB-Thi. The electrochemical immunosensor owned wide detection range of 0.11 ng/mL-80 ng/mL, low detection limit of 0.034 ng/mL and good practicability. This study opens up a new revelation for quantitative detection of CEA using electroactive COF as enhanced signal probe.

A study on surface plasmon resonance biosensor for the detection of CEA biomarker using 2D materials graphene, Mxene and MoS2

In this work, A surface plasmon resonance (SPR) biosensor is designed for the selective detection of carcinoembryonic antigen (CEA) present in the sensing medium (PBS solution) using three kinds of 2D materials i.e. graphene, molybdenum disulfide (MoS2) and mxene. Initially we introduce a basic design of Ti-Ag-Graphene based SPR biosensor for detection of CEA. After that, include the mxene and MoS2 layer between silver and graphene layer in basic Ti-Ag-Graphene structure separately for performance enhancement and also for comparative analysis. Over the graphene layer, bovine serum albumin (BSA) is deposited for the selective attachment of CEA biomarkers present in PBS solution in all structures. We find that the performance parameters are improved by the introduction of MoS2 and mxene as sandwiched between silver and graphene layers. The proposed design shows maximum sensitivity 144.72 deg./RIU and detection accuracy 2.24 for MoS2-Graphene based structure, which is better than other reported works. A comparative study shows that the MoS2-Graphene combination shows better performance as compared to Mxene-Graphene combination. This study may prove their importance to enhancement in sensitivity of SPR biosensors by using these 2D materials.