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Tumor markers should be measured regularly and accurately to prevent, diagnose, and monitor cancers efficiently. We aimed to characterize the pre-analytical factors effecting on the analytical performance of point-of-care test (POCT) platform Ichroma TM II (Boditech Med Inc., Gangwon-do, Korea) for alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and prostate specific antigen (PSA) and evaluate their consequences in clinical practice. Based on comprehensive evaluation for the analytical performance of Ichroma TM II including precision, linearity, and method comparison performed according to CLSI guidelines, pre-analytical factors of sample types and conditions were extensively analyzed. A total of five sample types [serum, plasma (PL) and whole blood (WB) from EDTA tube, PL and WB from sodium heparin tube] from 40 patients were used for comparing among specimen types. Additionally, stability was assessed up to 21 h at room temperature, refrigerated for 8 days, and frozen for 16 weeks by using 4 levels of pooled patient samples which were measured in triplicate. Precision, linearity and correlation with central laboratory analyzers observed in all three tumor markers were within acceptable criteria. However, variable degrees of percent deviations were observed according to sample type and storage conditions. Only EDTA PL samples presented clinically acceptable percentage biases for all three tumor markers when stored at room temperature or refrigerated condition. Positive bias of CEA and PSA in storage duration until 16 weeks were observed when stored in frozen condition. While Ichroma TM II showed an adequate analytical performance as a POCT platform with simple operating procedures for the measurement of tumor markers, clinical laboratories should be aware of stability issues when different types of blood specimens are practically utilized., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Organic-inorganic hybrid nanocomposites (OIHN), with tailored surface chemistry, offer ultra-sensitive architecture capable of detecting ultra-low concentrations of target analytes with precision. In the present work, a novel nano-biosensor was fabricated, acquainting dynamic synergy of reduced graphene oxide (rGO) decorated hexagonal boron nitride nanosheets (hBNNS) for detection of carcinoembryonic antigen (CEA). Extensive spectroscopic and microscopic analyses confirmed the successful hydrothermal synthesis of cross-linked rGO-hBNNS nanocomposite. Uniform micro-electrodes of rGO-hBNNS onto pre-hydrolyzed ITO were obtained via electrophoretic deposition (EPD) technique at low DC potential (15 V). Optimization of antibody incubation time, pH of supporting electrolyte, and immunoelectrode preparation was thoroughly investigated to enhance nano-biosensing efficacy. rGO-modified hBNNS demonstrated 29% boost in electrochemical performance over bare hBNNS, signifying remarkable electro-catalytic activity of nano-biosensor. The presence of multifunctional groups on the interface facilitated stable crosslinking chemistry, increased immobilization density, and enabled site-specific anchoring of Anti-CEA, resulting in improved binding affinity. The nano-biosensor demonstrated a remarkably low limit of detection of 5.47 pg/mL (R 2  = 0.99963), indicating exceptional sensitivity and accuracy in detecting CEA concentrations from 0 to 50 ng/mL. The clinical evaluation confirmed its exceptional shelf life, minimal cross-reactivity, and robust recovery rates in human serum samples, thereby unraveling the potential for early, highly sensitive, and reliable CEA detection., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

In this study, a quartz crystal microbalance (QCM) aptasensor for carcinoembryonic antigen (CEA), a well-known biomarker for various cancer types, was reported, utilizing two different aptamers. To achieve this, a nanofilm of 4-mercaptophenyl was electrochemically attached to gold-coated QCM crystal surfaces via the reduction of 4-mercaptobenzenediazonium salt (4 MB-DAT) using cyclic voltammetry. Subsequently, gold nanoparticles (AuNP) were affixed to this structure, and then aptamers (antiCEA1 and antiCEA2) modified with SH-functional ends bound to AuNPs completed the modification. The analytical performance of the CEA sensor was evaluated through simultaneous QCM measurements employing CEA solutions ranging from 0.1 ng/mL to 25 ng/mL. The detection limit (LOD) for CEA was determined to be 102 pg/mL for antiCEA1 and 108 pg/mL for antiCEA2 aptamers. Interday and intraday precision and accuracy tests yielded maximum results of 4.3 and + 3.8, respectively, for both aptasensors, as measured by relative standard deviation (RSD%) and relative error (RE%). The kinetic data of the aptasensors resulted in affinity values (K D ) of 0.43 ± 0.14 nM for antiCEA1 and 0.75 ± 0.42 nM for antiCEA2. These values were lower than the reported values of 3.9 nM and 37.8 nM for both aptamers, respectively. The selectivity of the aptasensor was evaluated by measuring the signal changes caused by alpha-fetoprotein (AFP), cancer antigen (CA-125), and vascular endothelial growth factor (VEGF-165) individually and together at a concentration of 500 ng/mL, resulting in a maximum 4.1 % change, which was comparable to precision and accuracy values reported in the literature. After confirming the selectivity of the aptamers, recovery experiments were conducted using spiked commercial serum samples to simulate real samples, and the lowest recovery value obtained was 95.4 %. It was determined that two different aptasensors could be successfully used for the QCM-based detection of CEA in this study., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

In this work, flower-like ZnO nanoparticles (ZnONPs) were synthesized using zinc nitrate (Zn(NO 3 ) 2 6H 2 O) as a precursor with KOH. The morphology of the ZnONPs was controlled by varying the synthesis temperature at 50, 75 and 95 °C. The morphology and structure of ZnONPs were characterized using Scanning Electron Microscopy, and X-Ray Diffraction and Brunauer-Emmett Teller analysis. ZnONPs were successfully synthesized by a simple chemical precipitation method. A synthesis temperature of 75 °C produced the most suitable flower-like ZnONPs, which were combined with graphene nanoplatelets to develop a label-free electrochemical immunosensor for the detection of the colon cancer biomarker carcinoembryonic antigen in human serum. Under optimum conditions, the developed immunosensor showed a linear range of 0.5-10.0 ng mL -1 with a limit of detection of 0.44 ng mL -1 . The label-free electrochemical immunosensor exhibited good selectivity, reproducibility, and repeatability, and recoveries were excellent. The immunosensor is used with a Near-Field Communication potentiostat connected to a smartphone to facilitate point-of-care cancer detection in low-resource locations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A label-free optical sandwich immunoassay sensor, utilizing weak value amplification and total internal reflection, was devised for real-time, high-sensitivity analysis and detection of low-concentration targets. 3D printed channels and sodium chloride solution were employed to ensure reproducibility, reliability, and stability of the measurements for calibration. The sandwich structure demonstrated enhanced responsiveness in the proposed optical biosensor through a comparative analysis of the direct assay and sandwich assay for detecting alpha-fetoprotein (AFP) at the same concentration. By optimizing the binding sequences of the coating antibody, target, and detection antibody in the sandwich method, a more suitable sandwich sensing approach based on weak value amplification was achieved. With this approach, the limit of detection (LOD) of 6.29 ng/mL (pM level) for AFP in PBS solution was achieved. AFP testing and regeneration experiments in human serum have proved the feasibility of our methods in detecting complex samples and the reusability of sensing chips. Additionally, the method demonstrated excellent selectivity for unpaired antigens. The efficacy of this methodology was evaluated by simultaneously detecting AFP, carcinoembryonic antigen (CEA), and CA15-3 on a singular sensor chip. In conclusion, the label-free sandwich immunoassay sensing scheme holds promise for advancing the proposed optical sensors based on weak value amplification in early diagnosis and prevention applications. Compared to other biomarker detection methods, it will be easier to promote in practical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

A novel signal amplification strategy was developed by combining near-infrared light with MoS 2 /CuO/Au nanocomposite for building a colorimetric immunoassay. First, MoS 2 /CuO/Au nanocomposite was synthesized by precipitation and photoreduction methods and characterized by scanning electron microscopy (SEM) and X-ray powder diffraction (XRD). MoS 2 /CuO/Au nanocomposite has oxidase-like activity and can oxidize TMB to form a blue product (TMBox). Further, the catalytic oxidation of TMB was accelerated under near-infrared (NIR) laser radiation. The sandwich-type colorimetric immunoassay was constructed using MoS 2 /CuO/Au nanocomposite. Under the enhancement of near-infrared light, carcinoembryonic antigen (CEA) was sensitively detected in the range 0.1 to 40 ng/mL with the limit of detection of 0.03 ng/mL. Moreover, the immunosensor has excellent selectivity and anti-interference, good repeatability, and stability., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

An intense cathodic electrochemiluminescence (ECL) is reported from a polarized glassy carbon electrode (GCE) in peroxydisulfate solution. After the polarization in 1 M Na 2 SO 4 at the potential of - 3.7 V for 3 s, carbon nanosheets (C-NSs) were in situ grown on the surface of the GCE. Measured in 100 mM K 2 S 2 O 8 solution, the ECL intensity of the GCE/C-NSs is 112-fold that of a bare GCE. The ECL spectrum revealed that the true ECL luminophore in the GCE/C-NSs-peroxydisulfate system is O 2 /S 2 O 8 2- which is promoted by C-NSs. When Cu 2+ was electrochemically enriched and reduced to Cu(0) on the catalytic sites of C-NSs, the ECL from GCE/C-NSs/Cu in K 2 S 2 O 8 solution was decreased with increasing logarithmic concentration of Cu 2+ in the range from 10 pM to 1 μM, with a limit of detection (LOD) of 3 pM. An immunoanalysis method is proposed via a biometallization strategy using CuS nanoparticles as the tags and carcinoembryonic antigen (CEA) as the model analyte. After the immune recognition in the microplate, the CuS tags in the immunocomplex were dissolved and the resultant Cu 2+ was electrochemically enriched and reduced on the catalytic sites of C-NSs, quenching the ECL intensity of GCE/C-NSs-O 2 /S 2 O 8 2- system. The proposed ECL immunoanalysis method was used to quantify CEA in actual serum samples with an LOD of 1.0 fg mL -1 , possessing the advantages of simple electrode modification, high sensitivity and good reproducibility., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

BRCA1 gene and carcinoembryonic antigen (CEA) are important markers of breast cancer, so accurate detection of them is significant for early detection and diagnosis of breast cancer. In this study, a potential-resolved ratio electrochemiluminescence (ECL) biosensor using perylene diimide (PDI)-metal-organic framework and DNA nanoflowers (NFs)-CdS quantum dots (QDs) was constructed for detection of BRCA1 and CEA. Specifically, PDI-MOF and CdS QDs can generate potential-resolved intense ECL signals only using one coreactant, so the detection procedure can be effectively simplified. PDI-MOF was first attached to the electrode by graphene oxide, and the dopamine (DA) probe was linked to quench the ECL signal by DNA hybridization. In the presence of target BRCA1, it can form a bipedal DNA walker, so the quenching molecules (DA) were detached from the electrode via the walker amplification process aided by Mg 2+ , so that the PDI signal at -0.25 V was restored for the BRCA1 assay. Moreover, CdS QDs@DNA NFs as amplified signal probes were formed by self-assembly, and the target CEA-amplified product introduced the CdS QDs@DNA NFs to the electrode, so the QD ECL signal at -1.42 V was enhanced, while the ECL signal of PDI is unchanged; thus, CEA detection was achieved by the ratio value between them. Therefore, the detection accuracy is guaranteed by detection of two cancer markers and a ratio value. This biosensor has a great contribution to the development of new ECL materials and a novel ECL technique for fast and efficient multitarget assays, showing great significance for the early monitoring and diagnosis of breast cancer.

Hyperbolic metamaterial (HMM) biosensors based on metals have superior performance in comparison with conventional plasmonic biosensors in the detection of low concentrations of molecules. In this study, a nanorod HMM (NHMM) biosensor based on refractive index changes for carcinoembryonic antigen (CEA) detection is developed using secondary antibody modified gold nanoparticle (AuNP-Ab 2 ) nanocomposites as signal amplification element for the first time. Numerical analysis based on finite element method is conducted to simulate the perturbation of the electric field of bulk plasmon polariton (BPP) supported by a NHMM in the presence of a AuNP. The simulation reveals an enhancement of the localized electric field, which arises from the resonant coupling of BPP to the localized surface plasmon resonance supported by AuNPs and is beneficial for the detection of changes of the refractive index. Furthermore, the AuNP-Ab 2 nanocomposites-based NHMM (AuNP/Ab 2 -NHMM) biosensor enables CEA detection in the visible and near-infrared regions simultaneously. The highly sensitive detection of CEA with a wide linear range of 1-500 ng/mL is achieved in the near-infrared region. The detectable concentration of the AuNP/Ab 2 -NHMM biosensor has a 50-fold decrease in comparison with a NHMM biosensor. A low detection limit of 0.25 ng/mL (1.25 pM) is estimated when considering a noise level of 0.05 nm as the minimum detectable wavelength shift. The proposed method achieves high sensitivity and good reproducibility for CEA detection, which makes it a novel and viable approach for biomedical research and early clinical diagnostics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The distinction between lung adenocarcinoma-associated malignant pleural effusion (MPE) and tuberculous pleural effusion (TPE) continues to pose a challenge. This study sought to assess the supplementary value of tumor markers in enabling a differential diagnosis., Methods: Data concerning tumor markers, which included carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), cancer antigen 153 (CA153), cancer antigen 724 (CA724), neuron-specific enolase (NSE), cytokeratin19 fragment (Cyfra21-1), and squamous cell carcinoma antigen (SCCA), in both serum and pleural effusion samples, were retrospectively compiled from lung adenocarcinoma-associated MPE and TPE patients. A comparative analysis of tumor marker concentrations between the two groups was performed to assess diagnostic utility, followed by a multiple logistic regression to control for confounding variables., Results: While gender, serum CA125 and SCCA, and pleural effusion SCCA manifested comparability between the groups, distinctions were noted in patient age and the concentration of other tumor markers in serum and pleural effusion, which were notably elevated in the MPE group. Multiple logistic regression demonstrated a positive association between the risk of lung adenocarcinoma-associated MPE and levels of CEA and CA153 in serum and pleural effusion, as well as Cyfra21-1 in serum (P < 0.05). The odds ratio for CEA surpassed that of CA153 and Cyfra21-1., Conclusions: CEA and CA153 in serum and pleural effusion, and Cyfra21-1 in serum emerge as biomarkers possessing supplementary diagnostic value in distinguishing lung adenocarcinoma-associated MPE from TPE. The diagnostic efficacy of CEA is superior to CA153 and Cyfra21-1. Conversely, the utility of CA125, CA724, NSE, and SCCA appears constrained., Competing Interests: Declaration of Competing Interests The author has no financial or other conflicts of interest to disclose., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Considering that cancer has become the second leading cause of death in humans, it is essential to develop an analytical approach that can sensitively detect tumor markers for early detection. We report an attenuated photoelectrochemical (PEC) immunoassay based on the organic-inorganic heterojunction 10MIL-88B(FeV)/ZnIn 2 S 4 (10M88B(FeV)/ZIS) as a photoactive material for monitoring carcinoembryonic antigen (CEA). The 10M88B(FeV)/ZIS heterojunctions have excellent light-harvesting properties and high electrical conductivity, which are attributed to the advantages of both organic and inorganic semiconductors, namely, remarkable photogenerated carrier separation efficiency and long photogenerated carrier lifetime. Horseradish peroxidase (HRP) in the presence of H 2 O 2 can catalyze 3,3'-diaminofenamide (DAB) producing brown precipitates (oxDAB), which is then loaded onto the 10M88B(FeV)/ZIS heterojunction to reduce the photocurrent and enable the quantitative detection of CEA. Under optimal conditions, the photocurrent values of the PEC biosensor are linearly related to the logarithm of the CEA concentrations, ranging from 0.01 ng mL -1 to 100 ng mL -1 with a detection limit (LOD) of 4.0 pg mL -1 . Notably, the accuracy of the PEC biosensor is in agreement with that of the human CEA enzyme-linked immunosorbent assay (ELISA) kit., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The rise of two-dimensional (2D) materials has provided a confined geometry and yielded methods for guiding electrons at the nanoscale level. 2D material-enabled electronic devices can interact and transduce the subtle charge perturbation and permit significant advancement in molecule discrimination technology with high accuracy, sensitivity, and specificity, leaving a significant impact on disease diagnosis and health monitoring. However, high-performance biosensors with scalable fabrication ability and simple protocols have yet to be fully realized due to the challenges in wafer-scale 2D film synthesis and integration with electronics. Here, we propose a molybdenum oxide (MoO x )-interdigitated electrode (IDE)-based label-free biosensing chip, which stands out for its wafer-scale dimension, tunability, ease of integration and compatibility with the complementary metal-oxide-semiconductor (CMOS) fabrication. The device surface is biofunctionalized with monoclonal anti-carcinoembryonic antigen antibodies (anti-CEA) via the linkage agent (3-aminopropyl)triethoxysilane (APTES) for carcinoembryonic antigen (CEA) detection and is characterized step-by-step to reveal the working mechanism. A wide range and real-time response of the CEA concentration from 0.1 to 100 ng mL -1 and a low limit of detection (LOD) of 0.015 ng mL -1 were achieved, meeting the clinical requirements for cancer diagnosis and prognosis in serum. The MoO x -IDE biosensor also demonstrates strong surface affinity towards molecules and high selectivity using L-cysteine (L-Cys), glycine (Gly), glucose (Glu), bovine serum albumin (BSA), and immunoglobulin G (IgG). This study showcases a simple, scalable, and low-cost strategy to create a nanoelectronic biosensing platform to achieve high-performance cancer biomarker discrimination capabilities.

A colorimetric immunoassay was built for determination of carcinoembryonic antigen (CEA) based on papain-based colorimetric catalytic sensing system through the use of glucose oxidase (GOx). In the presence of GOx, glucose was catalytically oxidized to produce H 2 O 2 . Through the assistance of papain (as a peroxide mimetic enzyme), the signal came from the oxidative color development of 3,3',5,5'-tetramethylbenzidine (TMB, from colorless to blue) catalyzed by the generated H 2 O 2 . Herein, a sandwich-type immunoassay was built based on GOx as labels. As the concentration of CEA increased, more GOx-labeled antibodies specifically associate with target, which leaded to more H 2 O 2 generation. Immediately following this, more TMB were oxidized with the addition of papain. Accordingly, the absorbance increased further. As a result, the concentration of CEA is positively correlated with the change in absorbance of the solution. Under optimal conditions, the CEA concentration was linear in the range of 0.05-20.0 ng/mL, and the limit of detection (LOD) reached 37 pg/mL. The papain-based colorimetric immunoassay also exhibited satisfactory repeatability, stability, and selectivity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Electrochemical biosensors have emerged as powerful tools for the ultrasensitive detection of lung cancer biomarkers like carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and alpha fetoprotein (AFP). This review comprehensively discusses the progress and potential of nanocomposite-based electrochemical biosensors for early lung cancer diagnosis and prognosis. By integrating nanomaterials like graphene, metal nanoparticles, and conducting polymers, these sensors have achieved clinically relevant detection limits in the fg/mL to pg/mL range. We highlight the key role of nanomaterial functionalization in enhancing sensitivity, specificity, and antifouling properties. This review also examines challenges related to reproducibility and clinical translation, emphasizing the need for standardization of fabrication protocols and robust validation studies. With the rapid growth in understanding lung cancer biomarkers and innovations in sensor design, nanocomposite electrochemical biosensors hold immense potential for point-of-care lung cancer screening and personalized therapy guidance. Realizing this goal will require strategic collaboration among material scientists, engineers, and clinicians to address technical and practical hurdles. Overall, this work provides valuable insight for developing next-generation smart diagnostic devices to combat the high mortality of lung cancer.

Background: Fine-needle aspiration (FNA) diagnosis of pancreatic serous cystadenoma (SCA) remains challenging. This retrospective study aimed to evaluate the roles of cyst fluid ancillary testing and combined fine-needle biopsy (FNB) in improving the diagnostic yield., Methods: The authors retrospectively reviewed cytology cases that were histologically confirmed SCAs. Clinical features and FNA cyst fluid biochemical and molecular analysis results along FNB findings were reviewed., Results: The study cohort included 31 cases from 13 male and 18 female patients with a mean age of 65. The original cytologic diagnoses were nondiagnostic (n = 6, 19%), negative for malignant cells/cyst contents (n = 7, 23%), atypical cells (n = 3, 10%), nonmucinous cyst (n = 11, 35%), and serous cystadenoma (n = 4, 13%). Cyst fluid carcinoembryonic antigen (CEA) analysis was performed in 17 cases, all of which showed a low CEA level (<192 ng/mL). All 14 cases with molecular testing showed a wild-type KRAS. Inhibin immunohistochemistry was retrospectively performed on the FNA cell blocks, inhibin was positive in six of seven cases tested. In 15 cases with concurrent FNA and FNB biopsies, the diagnosis of SCA was seen in only one FNA case (7%) but 13 FNB cases (87%)., Conclusions: This study suggests that FNA diagnosis of SCA remains challenging even with ancillary testing including cyst fluid CEA level and KRAS mutation analysis. Adjunct inhibin immunostaining may help improve the cytologic diagnosis of selective SCA cases. FNB appears superior to FNA for a definite diagnosis of SCA., (© 2024 American Cancer Society.)

Dual-potential ratiometric electrochemiluminescence (ECL) is in favor of resistance to environmental interference. However, two kinds of emitters or coreactants, and a wide scan potential range (>2 V) are mandatory. This work developed a new dual-potential ratiometric ECL sensor for detection of carcinoembryonic antigen (CEA) using single emitter (luminol) and single coreactant (H 2 O 2 ) with a mild potential range from -0.1 to 0.6 V. Luminol could produce a strong cathodic ECL (E c ) induced by hydroxyl radicals (HO‧) from the reduction of H 2 O 2 , and a relatively weak anodic ECL (E a ). After the ferrocene modified CEA aptamer (Apt-Fc) was attached, Fc could promote E a by catalyzing the oxidation of H 2 O 2 , and reduce E c by consuming HO‧. With the cycling amplification of the exonuclease I, CEA could substantially reduce the amount of Apt-Fc, resulting in the decrease of E a and the rise of E c . So, the ratio of E c to E a (E c /E a ) was used as the detection signal, realizing the sensitive determination of CEA from 0.1 pg mL -1 to 10 ng mL -1 with a LOD of 41.85 fg mL -1  (S/N = 3). The developed sensor demonstrated excellent specificity, stability and reproducibility, with satisfactory results in practical detection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

In this work, a highly sensitive lung cancer biomarkers detection probe was developed based on Ag and MXene co-functionalized magnetic microspheres. By using carboxyl magnetic microspheres as carrier, MXene was coated repeatedly by Poly (allylamine hydrochloride) (PAH) as interlayer adhesive, and silver particles grown on the surface of MXene in situ can efficiently improve the sensitivity of the probe. The detection of neuron specific enolase (NSE) is mainly through the formation of a specific complex between NSE antigen and antibody, and the release of antibody labeled with amino carbon quantum dots (CQDs) from the surface of Ag nanoparticles (AgNPs), so that the fluorescence is restored and "OFF-ON" is formed. The biosensor exhibits excellently wide linear range (0.0001-1500 ng/mL) and the limit of detection (LOD) is up to 0.03 pg/mL, which is superior to most tumor marker probes based on fluorescence mechanism. Furthermore, we constructed dual detection strategy for NSE and carcinoembryonic antigen (CEA) simultaneously., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Early detection of cancer markers is critical for cancer diagnosis and cancer therapy since these markers may indicate cancer risk, incidence, and disease prognosis. Carcinoembryonic antigen (CEA) is a type of non-specific and broad-spectrum cancer biomarker commonly utilized for early cancer diagnosis. Moreover, it serves as an essential tool to assess the efficacy of cancer treatment and monitor tumor recurrence as well as metastasis, thus garnering significant attention for precise and sensitive CEA detection. In recent years, photoelectrochemical (PEC) techniques have emerged as prominent methods in CEA detection due to the advantages of PEC, such as simple equipment requirements, cost-effectiveness, high sensitivity, low interference from background signals, and easy of instrument miniaturization. Different signal amplification methods have been reported in PEC sensors for CEA analysis. Based on these, this article reviews PEC sensors based on various signal amplification strategies for detection of CEA during the last five years. The advantages and drawbacks of these sensors were discussed, as well as future challenges., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Carcinoembryonic Antigen (CEA), an acidic glycoprotein with human embryonic antigen properties, is found on the surface of cancer cells that have differentiated from endodermal cells. This paper presents a label-free electrochemical immunoassay for the dual amplification detection of CEA using gold nanoparticles loaded with polypyrrole polydopamine (Au/PPy-PDA) and polymerized polycaprolactone (Ng-PCL) prepared by ring-opening polymerization (ROP). First, the composite Au/PPy-PDA was adhered to the electrode surface. Then, gold nanoparticles form a Au-S bond with the sulfhydryl group in Apt1 to secure it on the electrode surface. Subsequently, the non-specific binding sites on the electrodes surface are closed by bovine serum albumin (BSA). Next, CEA is dropped onto the electrode surface, which is immobilized by antigen-antibody specific recognition, and the carboxyl-functionalized Apt2 forms a "sandwich structure" of antibody-antigen-antibody by specific recognition. Polymeric Ng-PCL is adhered to the electrode surface, leading to an increase in the electrochemical impedance signal, resulting in a complete chain of signal analysis. Finally, the response signal is detected by electrochemical impedance spectroscopy (EIS). Under optimal experimental conditions, the method has the advantages of high sensitivity and wide linear range (1 pg mL -1 ∼100 ng mL -1 ), and the lower limit of detection (LOD) is 0.234 pg mL -1 . And it has the same high sensitivity, selectivity and interference resistance for the real samples detection. Thus, it provides a new way of thinking about biomedical and clinical diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study explores the principles of resonance energy transfer and adsorption modulation using composites of Cu 2 S-MPA/NGODs. These composites can efficiently control the quenching process of electrochemiluminescence (ECL). Mercaptopropionic acid (MPA) was added during the synthesis of Cu 2 S-MPA to enhance its attachment to nitrogen-doped graphene quantum dots (NGODs). The UV absorption peaks of NGODs coincided with the emission peaks of luminol ECL, enabling resonance energy transfer and enhancing the quenching capability of Cu 2 S-MPA. Meanwhile, there is another quenching strategy. When the readily reducible Cu + ions underwent partial reduction to Cu when they were bound to NGODs. This weakened the electrocatalytic effect on reactive oxygen species (ROS) and had a detrimental impact on electron transfer. Under optimal conditions, the immunosensor ECL intensity decreased linearly with the logarithm of carcinoembryonic antigen (CEA) concentration in the range of 0.00001-40 ng/mL, with a detection limit of 0.269 fg/mL. The sensor was effectively utilized for the identification of CEA in actual serum samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A smartphone-based electrochemical aptasensing platform was developed for the point-of-care testing (POCT) of carcinoembryonic antigen (CEA) based on the ferrocene (Fc) and PdPt@PCN-224 dual-signal labeled strategy. The prepared PdPt@PCN-224 nanocomposite showed a strong catalytic property for the reduction of H 2 O 2 . Phosphate group-labeled aptamer could capture PdPt@PCN-224 by Zr-O-P bonds to form PdPt@PCN-224-P-Apt. Therefore, a dual signal labeled probe was formed by the hybridization between Fc-DNA and PdPt@PCN-224-P-Apt. The presence of CEA forced PdPt@PCN-224-P-Apt to leave the electrode surface due to the specific affinity, leading to the decrease of the reduction current of H 2 O 2 . At the same time, the Fc-DNA strand changed to hairpin structure, which made Fc closer to the electrode and resulted in the increase of the oxidation current of Fc. Thus, CEA can be accurately determined through both signals: the decrease of H 2 O 2 reduction current and the increase of Fc oxidation current, which could avoid the false positive signal. Under the optimal conditions, the prepared aptasensor exhibited a wide linear range from 1 pg·mL -1 to 100 ng·mL -1 and low detection limits of 0.98 pg·mL -1 and 0.27 pg·mL -1 with Fc and PdPt@PCN-224 as signal labels, respectively. The aptasensor developed in this study has successfully demonstrated its capability to detect CEA in real human serum samples. These findings suggest that the proposed sensing platform will hold great potential for clinical tumor diagnosis and monitoring., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Early diagnosis of cancer can be achieved by detecting associated biomarkers before the appearance of symptoms. Herein, we have developed an electrochemical immunosensor of ionic liquid tailored to molybdenum trioxide-reduced graphene oxide (MoO 3 -rGO-IL) nanocomposite to detect carcinoembryonic antigen (CEA), a cancer biomarker. The MoO 3 -rGO-IL nanocomposite has been synthesized in situ via the hydrothermal method. The functionalization of 1-butyl-3-methylimidazolium tetrafluoroborate IL with MoO 3 -rGO synergistically improves the electrochemical and surface properties of the nanocomposite. The characterization studies revealed that the MoO 3 -rGO-IL nanocomposite is a highly appropriate material for the construction of immunosensors. The material exhibits exceptional electrical conductivity, surface properties, stability, and a large electrochemical effective surface area (13.77×10 -2  cm 2 ) making it ideal for fabricating immunosensors. The quantitative outcome showed that the developed immunosensor (BSA/anti-CEA/MoO 3 -rGO-IL/GCE) possesses excellent sensitivity, broad linearity from 25 fg mL -1 to 100 ng mL -1 , and a low detection limit of 1.19 fg mL -1 . Moreover, the remarkable selectivity, repeatability, and efficiency of detecting CEA in serum specimens demonstrated the feasibility of the immunosensor. Thus, the projected electrochemical immunosensor can potentially be utilized for the quantification of CEA in clinical specimens., (© 2024 Wiley-VCH GmbH.)

Breast cancer poses the significance of early diagnosis and treatment. Here, we developed an innovative photoelectrochemical (PEC) immunosensor characterized by high-level dual photocurrent signals and exceptional sensitivity. The PEC sensor, denoted as MIL&Ag 2 S, was constructed by incorporating Ag 2 S into a metal-organic framework of MIL-101(Cr). This composite not only enhanced electron-hole separation and conductivity but also yielded robust and stable dual photocurrent signals. Through the implementation of signal switching, we achieved the combined detection of cancer antigen 15-3 (CA15-3) and carcinoembryonic antigen (CEA) with outstanding stability, reproducibility, and specificity. The results revealed a linear range for CEA detection spanning 0.01-32 ng/mL, with a remarkably low detection limit of 0.0023 ng/mL. Similarly, for CA15-3 detection, the linear range extended from 0.1 to 320 U/mL, with a low detection limit of 0.014 U/mL. The proposed strategy introduces new avenues for the development of highly efficient, cost-effective, and user-friendly PEC sensors. Furthermore, it holds promising prospects for early clinical diagnosis, contributing to potential breakthroughs in medical detection and ultimately improving patient outcomes.

Simultaneous sensitive and precise determination of multibiomarkers is of great significance for improving detection efficiency, reducing diagnosis and treatment expenses, and elevating survival rates. However, the development of simple and portable biosensors for simultaneous determination of multiplexed targets in biological fluids still faces challenges. Herein, a unique and versatile immobilization-free dual-target electrochemical biosensing platform, which combines distinguishable magnetic signal reporters with buoyancy-magnetism separation, was designed and constructed for simultaneous detection of carcinoembryonic (CEA) and α-fetoprotein (AFP) in intricate biological fluids. To construct such distinguishable magnetic signal reporters with signal transduction, amplification, and output, secondary antibodies of CEA and AFP were respectively functionalized on methylene blue (MB) and 6-(ferrocenyl)hexanethiol (FeC) modified Fe 3 O 4 @Au magnetic nanocomposites. Meanwhile, a multifunctional flotation probe with dual target recognition, capture, and isolation capability was prepared by conjugating primary antibodies (Ab 1 -CEA, Ab 1 -AFP) to hollow buoyant microspheres. The target antigens of CEA and AFP can trigger a flotation-mediated sandwich-type immunoreaction and capture a certain amount of the distinguishable magnetic signal reporter, which enables the conversion of the target CEA and AFP quantities to the signal of the potential-resolved MB and FeC. Thus, the MB and FeC currents of magnetically adsorbed distinguishable magnetic reporters can be used to determine the CEA and AFP targets simultaneously and precisely. Accordingly, the proposed strategy exhibited a delightful linear response for CEA and AFP in the range of 100 fg·mL -1 -100 ng·mL -1 with detection limits of 33.34 and 17.02 fg·mL -1 ( S / N = 3), respectively. Meanwhile, no significant nonspecific adsorption and cross-talk were observed. The biosensing platform has shown satisfactory performance in the determination of real clinical samples. More importantly, the proposed approach can be conveniently extended to universal detection just by simply substituting biorecognition events. Thus, this work opens up a new promising perspective for dual and even multiple targets and offers promising potential applications in clinical diagnosis.

Pressure and temperature, as common physical parameters, are important for monitoring human health. In contrast, single-mode monitoring is prone to causing experimental errors. Herein, we innovatively designed a dual-mode flexible sensing platform based on a platinum/zinc-meso-tetrakis(4-carboxyphenyl)porphyrin (Pt/Zn-TCPP) nanozyme for the quantitative monitoring of carcinoembryonic antigen (CEA) in biological fluids with pressure and temperature readouts. The Pt/Zn-TCPP nanozyme with catalytic and photothermal efficiencies was synthesized by means of integrating photosensitizers into porous materials. The flexible sensing system after the antigen-antibody reaction recognized the pressure using a flexible skin-like pressure sensor with a digital multimeter readout, whereas the temperature was acquired via the photoheat conversion system of the Pt/Zn-TCPP nanozyme under 808 nm near-infrared (NIR) irradiation using a portable NIR imaging camera on a smartphone. Meanwhile, the dual-mode flexible sensing system was carried out on a homemade three-dimensional (3D)-printed device. Results revealed that the developed dual-mode immunosensing platform could exhibit good pressure and temperature responses within the dynamic range of 0.5-100 ng mL -1 CEA with the detection limits of 0.24 and 0.13 ng mL -1 , respectively. In addition, the pressure and temperature were sensed simultaneously without crosstalk interference. Importantly, the dual-mode flexible immunosensing system can effectively avoid false alarms during the measurement, thus providing great potential for simple and low-cost development for point-of-care testing.

An optical fiber sensing probe using a composite sensitive film of polyacrylonitrile (PAN) nanofiber membrane and gold nanomembrane is presented for the detection of a carcinoembryonic antigen (CEA), a biomarker associated with colorectal cancer and other diseases. The probe is based on a tilted fiber Bragg grating (TFBG) with a surface plasmon resonance (SPR) gold nanomembrane and a functionalized polyacrylonitrile (PAN) PAN nanofiber coating that selectively binds to CEA molecules. The performance of the probe is evaluated by measuring the spectral shift of the TFBG resonances as a function of CEA concentration in buffer. The probe exhibits a sensitivity of 0.46 dB/(µg/ml), a low limit of detection of 505.4 ng/mL in buffer, and a good selectivity and reproducibility. The proposed probe offers a simple, cost-effective, and a novel method for CEA detection that can be potentially applied for clinical diagnosis and monitoring of CEA-related diseases.

Background: Distinguishing mucinous (M) pancreatic cystic neoplasms (PCNs) from non-mucinous (NM) is challenging but crucial. Low intracystic glucose level has shown diagnostic tool promise, however further investigation is needed to understand metabolic processes., Aims: To compare the diagnostic accuracy of intracystic glucose and CEA levels in a large cohort and explore lactate levels as potential marker., Methods: PCNs≥15 mm which underwent EUS-fine needle aspiration were prospectively enrolled. Glucose, CEA and lactate levels were measured. Diagnostic accuracy for M-PCN diagnosis was evaluated using surgical/cytology reports or multidisciplinary evaluations., Results: 169 PCNs were included (64 % M-PCNs). Median intracystic glucose was significantly lower in M-PCNs (1 mg/dL) compared to NM-PCNs (101 mg/dL); mean intracystic CEA was significantly higher in M-PCNs (152.5 ng/mL) compared to NM-PCNs (0.3 ng/mL). ROC curve analysis revealed best glucose cut-off ≤58 mg/dL (accuracy 93.5 %) and CEA cut-off >2.5 ng/mL (accuracy 90.5 %) for M-PCNs. Intracystic lactates were significantly lower in M-PCNs correlating directly with glucose. Single glucose dosage evidenced best diagnostic accuracy respect markers combination., Conclusion: Intracystic glucose demonstrated high diagnostic utility for M-PCNs differentiation, surpassing CEA. Lactate levels correlated with glucose, suggesting their uptake by M-PCNs cells. These findings contribute to a better metabolic landscape understanding glucose use as diagnostic marker., Competing Interests: Conflict of interest None., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Squamoid eccrine ductal carcinoma (SEDC) is a cutaneous adnexal malignancy that is histologically challenging to distinguish from squamous cell carcinoma. We report three cases of this rare entity and review the present literature regarding clinical, histological, and immunohistochemical features. Patients presented with a single nodule or plaque lesion on their back and temple. The shave biopsies for Patient A and C were interpreted as SEDC. Patient B's initial shave biopsy was interpreted as probable surface of squamous cell carcinoma, and subsequent excision revealed SEDC. Ductal differentiation was confirmed by positive expression of epithelial membrane antigen and carcinoembryonic antigen immunostains in all three patients. Review of the 67 previously reported cases emphasizes the importance of diagnosing SEDC accurately and promptly given its potential for distant metastasis and mortality. Perineural or lymphatic invasion is associated with higher rate of recurrence or metastasis. There should be high pathologic suspicion for SEDC in an elderly patient presenting with a palpable lesion, even if located outside of the head and neck area, particularly when there is suggestion of ductal differentiation in a sample of a squamous neoplasm.

Background and Aims: Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is essential for the classification of pancreatic cystic lesions (PCLs). Recently, intracystic glucose has been suggested as an alternative to carcinoembryonic antigen (CEA) level as a predictor of mucinous cystic lesions (M-PCLs). This study aims to evaluate the diagnostic performance of intra-cystic glucose in distinguishing between M-PCLs and non M-PCLs (NM-PCLs) and to analyze the possibility of on-site glucose measurement with a standard glucometer., Methods: Patients with PCLs submitted to EUS-FNA with simultaneous intracystic glucose measurement between 2017 and 2022 were included. The diagnostic performance of glucose versus CEA for the differentiation between M-PCLs and NM-PCLs was compared to a final diagnosis based on the analysis of surgical specimen, intracystic biopsy or, if this data was unavailable, multidisciplinary evaluation. A cut-off of <50 mg/dL was used for the diagnosis of MCLs. Additionally, the agreement between on-site glucose determination with a standard glucometer and laboratory glucose measurement was assessed., Results: Mucinous lesions accounted for 56% of all PCLs. The median values of glucose and CEA for M-PCLs were 18 mg/dL and 286 ng/mL, respectively. Intracystic glucose had a sensitivity and specificity of 93.2% and 76.5%, respectively, for the diagnosis of MCLs (versus 55.6% and 87.5%, respectively, for CEA). The area under the curve was 0.870 for on-site glucose (versus 0.806 for CEA). An excellent correlation was observed between on-site and laboratory glucose measurement (ρ=0.919)., Conclusions: The measurement of intracystic glucose showed superior performance compared with CEA in distinguishing between M-PCLs and NM-PCLs, with excellent correlation between on-site and conventional lab glucose measurement. Thus, on-site intracystic glucose appears to be an excellent biomarker for the characterization of PCLs due to its low cost, high availability, and the need for a minimal cyst fluid volume for its determination.

Most clinical doctors rely on high-risk factors recommended by guidelines to decide whether to undergo adjuvant chemotherapy for stage II colon cancer. However, these high-risk factors do not include postoperative carcinoembryonic antigen (CEA). This study aims to explore the elevation of postoperative CEA as a risk factor, in addition to other high-risk factors, to guide adjuvant chemotherapy for patients with stage II colon cancer. A retrospective analysis was conducted on stage II colon cancer patients who underwent curative surgery at Yunnan Cancer Hospital and The Sixth Affiliated Hospital of Sun Yat-Sen University from April 2008 to January 2019. Patients were classified into three groups based on high-risk factors recommended by guidelines and postoperative CEA levels: low-risk with normal postoperative CEA, low-risk with elevated postoperative CEA and high-risk. COX regression analysis was used to identify independent prognostic factors affecting patients' recurrence free survival (RFS). The Kaplan-Meier method was used to create the patients' RFS curve. The restricted cubic spline (RCS) curve was used to assess the correlation between postoperative CEA and RFS on a continuous scale. Among 761 patients, there were 444 males (62.01%), with a median [IQR] age of 58.0 (18.0-88.0) years. A group of 425 high-risk patients had a 3-year RFS of 82.2% (95% CI 78.5-86.1%), while a group of 291 low-risk patients had a 3-year RFS of 89.7% (95% CI 86.1-93.5%). There was a statistically significant difference between the two groups (HR 1.83; 95% CI 1.22-2.74; P = 0.0067). Among them, the 3-year RFS of 261 low-risk patients with normal postoperative CEA was 93.6% (95% CI 90.5-96.8%), while the 3-year RFS of 30 low-risk patients with elevated postoperative CEA was 57.3% (95% CI 41.8-71.4%). There was a significant difference compared to the 3-year RFS of 425 high-risk patients (overall log-rank P < 0.0001). The multivariate analysis adjusted by the COX proportional hazards model showed that low-risk patients with elevated postoperative CEA patients (HR 14.95, 95% CI 4.51-49.63, P < 0.0001) was independently associated with a 3-year RFS. The restricted cubic spline model showed that in stage II colon cancer patients with tumor diameter > 1.955 ng/mL, the risk of postoperative recurrence increased with increasing postoperative CEA levels. Patients with elevated postoperative CEA levels have a significantly increased risk of recurrence. They should be included as high-risk factors to guide adjuvant chemotherapy for stage II colon cancer., (© 2024. The Author(s).)

A label-free electrochemical immunosensor utilising nitrogen-rich mesoporous carbon (MNC) as the substrate material was developed for the sensitive quantification of carcinoembryonic antigen (CEA). The synergic interactions between MNC and AbCEA also eliminated the need for coupling agents such as EDC/NHS. The novel immunosensor demonstrated a wide detection range from 500 fM (9.04 pg mL -1 ) to 50 nM (1 μg mL -1 ) and a low detection limit (LOD) of 500 fM. Moreover, the immunosensor showed sensitivities of 12.27 mA nM -1 cm -2 and 0.066 mA nM -1 cm -2 for detecting CEA in the linear ranges 10 pM to 1 nM and 2 nM to 50 nM, respectively, while maintaining long-term storage stability of 6 weeks. Analysis of real serum sample analysis yielded highly accurate results with recovery rates ranging from 99.3% to 103.7%. Furthermore, the developed paper-based screen-printed electrode exhibited a similar detection range, suggesting its potential for use in point-of-care detection devices in future applications.

Objective: Elevated pancreatic cyst fluid carcinoembryonic antigen (CEA) has been routinely used to classify mucinous cysts. This study incorporates original data that established the CEA ≥192 ng/mL threshold with over 20 years of additional data and reassesses the diagnostic performance of CEA for differentiating mucinous from non-mucinous cysts., Design: 1169 pancreatic cysts (1999-2021) with CEA results were identified. 394 cases had histological confirmation as the diagnostic standard. Additionally, 237 cysts without histological confirmation demonstrated KRAS , GNAS , or RNF43 mutations by molecular testing and were combined with the histologically confirmed cysts for separate analysis on a total cohort of 631 cysts., Results: Median CEA was significantly higher in mucinous cysts (323.9 ng/mL, n=314) versus non-mucinous cysts (204.6 ng/mL, n=80) (p<0.001). Receiver operating characteristic curve analysis demonstrated an optimal CEA cut-off of 20 ng/mL (area under the curve: 80%), though the specificity was lower than desired (sensitivity 89%, specificity 64%). At the previously established threshold of 192 ng/mL, sensitivity and specificity were 56% and 78%, respectively. To achieve a specificity of 85% as originally reported, a CEA threshold of 250 ng/mL was needed; the 13 false positive cases at this threshold included 4 benign simple cysts, 2 squamoid cysts, 1 serous cystadenoma, 1 lymphoepithelial cyst and 5 more uncommon entities. All results remained similar within the total cohort after including additional cases with KRAS/GNAS/RNF43 mutations only., Conclusion: Cyst fluid CEA continues to be a useful test in the diagnosis of mucinous pancreatic cysts but does not appear as specific as previously reported. Raising the CEA threshold to 250 ng/mL to maintain specificity for differentiating mucinous from non-mucinous cysts may be considered., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Semiconducting materials based on photoelectrochemical (PEC) sensors have been widely utilized for detection. Meanwhile, the sensitivity of the PEC sensor was limited by low-efficiency carrier separation. Thus, a novel sandwich-type PEC bioimmunosensing based on 2D Z-scheme ZnIn 2 S 4 /g-C 3 N 4 heterojunction as a photosensitive material and BiVO 4 as a photoquencher was designed for the sensitive detection of carcinoembryonic antigen (CEA). Firstly, the 2D ZnIn 2 S 4 /g-C 3 N 4 structure provided a multitude of activated sites which facilitated the loading of the capture antibody (Ab 1 ). Secondly, the Z-scheme heterojunction had a high redox capacity while promoting the rapid separation and migration of photogenerated electron-hole pairs (e - /h + ). Thus it was able to consume more electron donors to a certain extent, resulting in a higher initial photocurrent. In addition, BiVO 4 with large spatial potential resistance was introduced for the first time to realize signal amplification. BiVO 4 could not only compete with substrate materials for electron donors, but also effectively prevent electron donors from contacting the substrate, further reducing the photocurrent signal. Under optimized conditions, the sensor had a favorable detection range (0.0001-100 ng/mL) to CEA and a low detection limit of 0.03 pg/mL. With high specificity, excellent stability, and remarkable reproducibility, this sensor provided a new perspective for constructing accurate and convenient PEC immunosensor for bioanalysis and early disease diagnosisdisease diagnosis., Competing Interests: Declaration of competing interest The authors acknowledge that there are no known competing financial interests or personal relationships that might influence the work reported here., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Gastric cancer is the fifth most common malignant tumor worldwide. Many attempts have been made over the years to investigate the relationship between tumor markers and the risk of recurrence. This study aims to explore the predictive value of tumor markers measured in peritoneal washing during staging laparoscopy, regarding peritoneal carcinomatosis and mortality within 1 year., Methods: Patients with locally advanced gastric cancer, staged as at least usT2anyNM0 were submitted to staging laparoscopy in a Portuguese single center. CA 19.9, CEA, CA 125, and CA 72.4 were measured in the peritoneal washing after being harvested during staging laparoscopy., Results: Thirty-eight patients were enrolled. After 1 year, 20 patients did not recur (52.5%), 11 (28.9%) developed carcinomatosis, and 7 (18.4%) had distant metastasis. Mortality reached 23.7% (n = 9). A statistically significant prediction of carcinomatosis was obtained for CA 125 (cutoff: 107.6 U/mL (p = 0.019)) and CEA (cutoff: 2.0 ng/mL (p = 0.020)) with 87.5% and 75% sensitivity, respectively. Prediction of mortality was significant for CA 125 (cutoff: 103.8 U/mL (p = 0.044)) and CA 125 + CEA (p = 0.030). CEA and CA 125 had NPVs of 87.9% and 93.1% regarding PC, respectively. NPVs of 88.9% and 89.2% were met concerning mortality, for the same tumor markers., Conclusion: Performing the peritoneal liquid harvest during staging laparoscopy makes this analysis cost effective, reproducible, and does not add further morbidity. CA 125 and CEA, individually and in association, are good predictors of progression of disease and mortality within a year of staging laparoscopy in GC patients., (© 2023. The Author(s).)

This work reports the development of a novel microfluidic biosensor using a graphene field-effect transistor (GFET) design for the parallel label-free analysis of multiple biomarkers. Overcoming the persistent challenge of constructing μm 2 -sized FET sensitive interfaces that incorporate multiple receptors, we implement a split-float-gate structure that enables the manipulation of multiplexed biochemical functionalization using microfluidic channels. Immunoaffinity biosensing experiments are conducted using the mixture samples containing three liver cancer biomarkers, carcinoembryonic antigen (CEA), α-fetoprotein (AFP), and parathyroid hormone (PTH). The results demonstrate the capability of our label-free biochip to quantitatively detect multiple target biomarkers simultaneously by observing the kinetics in 10 minutes, with the detection limit levels in the nanomolar range. This microfluidic biosensor provides a valuable analytical tool for rapid multi-target biosensing, which can be potentially utilized for domiciliary tests of cancer screening and prognosis, obviating the need for sophisticated instruments and professional operations in hospitals.

Introduction: To decide treatment of hepatic cysts diagnosis between simple hepatic cyst (SHC) and cystic mucinous neoplasm (CMN). Radiological features are not patognomonic. Some studies have suggested the utility of intracystic tumor markers., Methods: Retrospective analysis of our prospective database including patients treated due to symptomatic SHC from 2003 to 2021. The aim of the study was to evaluate the results of treatment of symptomatic SHC and the usefulness of the determination of intracystic "carcinoembryonic antigen" (CEA) and "carbohydrate antigen" CA 19.9., Results: 50 patients diagnosed and treated for symptomatic SHC were included. In 15 patients the first treatment was percutaneous drainage. In 35 patients the first treatment was laparoscopic fenestration. Four patients were diagnosed of premalignant or malignant liver cystic lesions (MCN, IPMN, lymphoma B); three of them required surgery after initial fenestration and pathological diagnosis. Median CEA and CA 19-9 were 196 μg/L and 227.321 U/mL respectively. Patients with malignant or premalignant pathology did not have higher levels of intracystic tumor markers. Positive predictive value was 0% for both markers, and negative predictive value was 89% and 91% respectively., Conclusion: Values of intracystic tumor markers CEA and CA 19-9 do not allow distinguishing simple cysts from cystic liver neoplasms. The most effective treatment for symptomatic simple liver cysts is surgical fenestration. The pathological analysis of the wall of the cysts enables the correct diagnosis, allowing to indicate a surgical reintervention in cases of hepatic cyst neoplasia., (Copyright © 2023. Published by Elsevier España, S.L.U.)

As the most well-known analytical tool, the thermometer has been extended to the field of biological analysis based on the photothermal effect. Herein, isoniazide modified Ag nanoparticles were prepared as nanolabels to build an immunoassay. The nanoparticles were characterized by transmission electron microscope (TEM), dynamic laser scattering (DLS), X-ray powder diffraction (XRD), and Fourier transform infrared (FT-IR). When the target protein was present, the sandwich immunoassay was developed and the photothermal reaction was triggered by isoniazide modified Ag nanoparticles. As a reducing agent, isoniazide is used to transform phosphomolybdic acid hydrate into molybdenum blue solution. And molybdenum blue had good photothermal stability and high photothermal conversion efficiency. The temperature variation of molybdenum blue solution showed a positive correlation with the concentration of carcinoembryonic antigen (CEA). Thus, the target protein of CEA was quantitative detection by thermometer. The linear response range is 0.1 ng mL -1 to 40 ng mL -1 , and the detection limit is 0.08 ng mL -1 . Moreover, the proposed protocol had satisfactory selectivity, accuracy, and reproducibility., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In this research, a novel biosensing platform is described based on graphene nano-sheets decorated with Ag nano-particles (GNSs@Ag NPs). The designed electrochemical aptasensor was employed to determine carcinoembryonic antigen (CEA), an important cancer biomarker. Inherently, aptasensing interfaces provide high sensitivity for CEA tumor marker because of the high specific surface area and excellent conductivity of the prepared GNSs@Ag NPs composite. The established assay demonstrated a wide linear range from 0.001 pg/mL to 10 pg/mL with a correlation coefficient of 0.9958 and low detection limit (DL) of 0.5 fg/mL based on S/N = 3 protocol. The derived biosensor illustrated acceptable selectivity towards common interfering species including HER2, VEGF, IgG, MUC1 and CFP10. In addition, the aptsensor showed good reproducibility and fast response time. The applicability of the suggested strategy in human serum samples was also examined and compared to the commercial enzyme-linked immunosorbent assay (ELISA). Based on the experimental data, it was found that the discussed sensing platform can be exerted in the monitoring of CEA in different cancers for early diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Misidentification errors in tumor marker tests can lead to serious diagnostic and treatment errors. This study aims to develop a method for detecting these errors using a machine learning (ML)-based delta check approach, overcoming limitations of conventional methods., Methods: We analyzed five tumor marker test results: alpha-fetoprotein (AFP), cancer antigen 19-9 (CA19-9), cancer antigen 125 (CA125), carcinoembryonic antigen (CEA), and prostate-specific antigen (PSA). A total of 246,261 records were used in the analysis. Of these, 179,929 records were used for model training and 66,332 records for performance evaluation. We developed a misidentification error detection model based on the random forest (RF) and deep neural network (DNN) methods. We performed an in silico simulation with 1 % random sample shuffling. The performance of the developed models was evaluated and compared to conventional delta check methods such as delta percent change (DPC), absolute DPC (absDPC), and reference change values (RCV)., Results: The DNN model outperformed the RF, DPC, absDPC, and RCV methods in detecting sample misidentification errors. It achieved balanced accuracies of 0.828, 0.842, 0.792, 0.818, and 0.833 for AFP, CA19-9, CA125, CEA, and PSA, respectively. Although the RF method performed better than DPC and absDPC, it showed similar or lower performance compared to RCV., Conclusions: Our research results demonstrate that an ML-based delta check method can more effectively detect sample misidentification errors compared to conventional delta check methods. In particular, the DNN model demonstrated superior and stable detection performance compared to the RF, DPC, absDPC, and RCV methods., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

The current study has focused on electrochemical immunosensing of carcinoembryonic antigen (CEA) employing an immobilized antibody on a thionine, chitosan, or graphene oxide nanocomposite modified glassy carbon electrode (anti-CEA/THi-CS-GO/GCE) as an indicator of cancer monitoring. THi-CS-GO nanocomposites were made using ultrasonication, and analyses of their morphology and crystal structure using SEM, FTIR, and XRD showed that thionine and chitosan molecules were intercalated with stacking interactions with both the top and bottom of GO nanosheets. Electrochemical experiments revealed anti-CEA, THi-CS-GO/GCE to have exceptional sensitivity and selectivity towards CEA compounds. The detection limit value was established to be 0.8 pg/mL when it was discovered that variations in the decrease peak current were directly proportional to the logarithm concentration of CEA over a wide range from 10-3 to 104 ng/mL. Results of testing the immunosensor's application capability for detecting CEA in a sample of human serum show that ELISA and DPV results are very congruent. The produced immunosensor demonstrated adequate immunosensor precision in determining CEA in prepared genuine samples of human serum and clinical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In order to detect carcinoembryonic antigen (CEA) as a tumor marker in lung cancer for early cancer diagnosis, this study aimed to develop a label-free electrochemical immunosensor based on the immobilization of an Anti-CEA antibody on a metal-organic framework (MOF)-graphene oxide nanocomposite modified glassy carbon electrode (Anti-CEA/Ag-MOF/GO/GCE). Ag-MOF/GO nanocomposite was prepared on the GCE surface using the ultrasonic irradiation method, and Anti-CEA antibody was subsequently immobilized on the surface. Analysis of the crystal structure and morphology of the modified electrode using FE-SEM and XRD revealed that the correct combination of GO nanosheets and Ag-MOF nanoparticles produced a high surface area to trap the antibodies. Electrochemical tests utilizing the CV and DPV methods revealed that the immunosensor's sensitivity, stability, and selectivity were improved by Anti-CEA/Ag-MOF/GO/GCE. Results showed that, with a detection limit of 0.005 ng/mL, the change in the reduction peak current was inversely correlated with the logarithm concentration of CEA in the range of 10-3 to 5000 ng/mL. The suggested CEA immunosensor's applicability in a human serum sample was investigated, and findings of analytical studies via standard addition technique for both ELISA and DPV assays revealed that significant agreement existed between the outcomes of the two assays. Additionally, the recoveries ranged from 99.00% to 99.25%, and all relative standard deviations (RSDs) for the sample detections were below 5.01%, indicating satisfactory accuracy in results measured with the proposed CEA immunosensor, indicating that the prepared CEA immunosensor in this study can be used in clinical applications and human fluids., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Colorectal cancer is still a major global health concern, and early detection and accurate biomarker analyses are critical to its successful management. This paper describes the design and testing of a new biosensor based on a graphene oxide (GO) nanocomposite for the exact measurement of carcinoembryonic antigen (CEA), a well-known biomarker for colorectal cancer. The current study attempted to create a highly sensitive immunosensor for sensitive measurement of CEA based on a polypropylene-imine-dendrimer (PPI) and GO nanocomposite on GCE (PPI/GO/GCE). The PPI/GO nanocomposite served as an appropriate biocompatible nanostructure with a large surface area for immobilizing carcinoembryonic antigen (anti-CEA) and bovine serum albumin (BSA) molecules (BSA/anti-CEA/PPI/GO/GCE), thereby promoting the selectivity of electrochemical immunosensors, according to structural and electrochemical studies. Results showed that the BSA/anti-CEA/PPI/GO/GCE as a selective, sensitive, and stable immunosensor revealed a wide linear response from 0.001 to 2000 ng/mL, and a limit of detection of 0.3 pg/mL, which indicated comparable or better performance towards the CEA immunosensors in recent reports in the literature. This was due to the synergetic effect of the GO nanosheets and PPI with porous structure and more conductivity. Analytical results showed values of RSD (4.49%-5.04%) and recovery (90.00%-99.98%) are suitable for effective and accurate practical assessments in CEA in clinical samples. The capacity of the BSA/anti-CEA/PPI/GO/GCE to determine CEA in human blood was studied., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cation exchange (CE) is a burgeoning method for controlled crystal synthesis; however, its applications in bioanalysis are still in their infancy. Herein, we explored the transformation of ZnIn 2 S 4 in properties after the CE reaction with Cu 2+ ions; furthermore, the discrepancy was employed to design a dual-readout detection system of photothermal and polarity-switchable photoelectrochemical (PEC) immunoassays to realize reliable detection of carcinoembryonic antigen (CEA). In the presence of CEA, the CuO nanoparticles (CuO NPs) employed as dual-signal response probes would bond to the microplates and be acidolyzed by HCl to release Cu 2+ , which could replace Zn 2+ and In 3+ via the CE reaction. After the CE reaction is completed, the photocurrent would switch from a weak anodic photocurrent to a cathode one by using a 635 nm laser as a signal amplifier, while the photothermal signal would be enhanced with 808 nm laser illumination. On the basis of the polarity-switchable PEC strategy, CEA could be accurately detected from 0.1 to 50 ng mL -1 with a limit of detection (LOD) of 48 pg mL -1 (S/N = 3). Moreover, the photothermal assay for CEA detection possesses a linear range from 0.5 to 100 ng mL -1 with a LOD of 0.21 ng mL -1 . In addition, the designed sensing platform only relies on devices with portability that are permitted for point-of-care detection.

Background: Mucinous pancreatic cysts harbor the potential to progress to highly lethal pancreatic ductal adenocarcinoma (PDAC). Since these precursor cysts require cancer surveillance or surgical resection, they need to be reliably distinguished from harmless pancreatic cysts. Current clinical and radiographic assessment is imperfect and the value of cyst fluid analysis for differential diagnosis is unclear. Therefore, we set out to investigate the value of cyst fluid biomarkers in distinguishing pancreatic cysts., Methods: We performed a systematic review of the current literature to identify articles that evaluated the diagnostic performance of clinically relevant and promising candidate cyst fluid biomarkers, with a particular emphasis on DNA-based biomarkers. Meta-analysis was performed for biomarkers targeted at identifying cyst type and presence of high-grade dysplasia or PDAC., Results: Data from a total of 42 studies was analyzed. Mutations in KRAS and/or GNAS allowed identification of mucinous cysts with a sensitivity of 79% and specificity of 98%. This exceeded the performance of the traditional biomarker carcinoembryonic antigen (CEA; sensitivity 58%, specificity 87%). Mutations in VHL were specific for serous cystadenomas (SCAs; sensitivity 56%, specificity 99%) and help to exclude mucinous cysts. Mutations in CDKN2A, PIK3CA, SMAD4, and TP53 each had high specificities of 97%, 97%, 98%, and 95%, respectively, to identify high-grade dysplasia or PDAC in mucinous cysts., Conclusions: Cyst fluid analysis can be a valuable tool in the characterization of pancreatic cysts, with relevant clinical implications. Our results support the use of DNA-based cyst fluid biomarkers in the multidisciplinary diagnostic work-up of pancreatic cysts., (Copyright © 2023 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

The detection of carcinoembryonic antigen (CEA) has profound implications in cancer diagnostics and therapeutic monitoring. In this work, we developed a colorimetric immunoassay for the detection of CEA. This assay involves the utilization of zinc(II)-based coordination polymers (ZnCPs) as a host for integrating glucose oxidase (GOx) and anti-carcinoembryonic antigen antibody (anti-CEA), which results in the formation of a detection antibody (anti-CEA/GOx@ZnCPs). The adaptable inclusion properties of ZnCPs enable the preservation of the original catalytic behavior of GOx and antigen capture ability of anti-CEA. Consequently, the anti-CEA/GOx@ZnCPs can act as a detection antibody to facilitate the development of an immunoassay. The combination of anti-CEA/GOx@ZnCPs in the immunoassay triggers a cascade reaction involving GOx and MnO 2 nanosheets, leading to the generation of an amplified colorimetric signal through self-supplying oxygen. This colorimetric immunoassay exhibits a linear response ranging from 2 to 180 ng mL -1 CEA and has a detection limit of 50 pg mL -1 . The practicality of this colorimetric immunoassay in biological matrices was demonstrated by the successful determination of CEA in serum samples with good recovery and precision. We believe that this study will pave the way to rationally design multifunctional CP-based composites for a wide range of applications in bioanalysis.

In this research, gold nanoparticle (GNPs)-modified metal-organic framework/reduced graphene oxide (MOF(801)/rGO) hybrid was employed to design a new aptasensor for carcinoembryonic antigen (CEA) quantification in biological sample. The sensing ability of the electrode for CEA biomarker was examined with electrochemical impedance spectroscopy (EIS) and cyclic voltammetry procedures. Besides, CEA was electrochemically quantified by the EIS method. With respect to the high surface-to-volume ratio of MOF(801) and the good electron transfer ability of rGO, the proposed sensor displayed notable sensitivity and reliability in the CEA analysis. The derived electrode showed an appreciable detection limit of 0.8 pg L -1 using EIS protocol. In addition, the present aptasensor revealed diverse advantages including anti-interference property, wide linear range (0.0025-0.25 ng L -1 ), convenience and high efficiency toward CEA quantification. More importantly, the performance of the suggested assay remains unchanged in analysis of CEA in body fluids. The established assay demonstrates that the suggested biosensor is a promising device in clinical diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

An enzyme-catalyzed high-performing reaction with in-situ amplified photocurrent was innovatively designed for the quantitative screening of carcinoembryonic antigen (CEA) in biological fluids by coupling with carbon-functionalized inorganic photoanode. A split-type photoelectrochemical (PEC) immunoassay was initially executed with horseradish peroxidase (HRP)-labeled secondary antibody on the capture antibody-coated microtiter. Then, the photocurrent of carbon-functionalized inorganic photoanode were improved through enzymatic insoluble product. Experimental results revealed that introduction of the outer carbon layer on the inorganic photoactive materials caused the amplifying photocurrent because of the improving light harvesting and separation of photo-generated e - /h + pairs. Under optimum conditions, the split-type photoelectrochemical immunosensing platform displayed good photocurrent responses within the dynamic range of 0.01 - 80 ng mL -1 CEA, and allowed the detection of CEA as low as a concentration of 3.6 pg mL -1 at the 3S blank level. The strong attachment of antibodies onto nano label and high-performing photoanode resulted in a good repeatability and intermediate precision down to 9.83%. No significant differences at the 0.05 significance level were encountered in the analysis of six human serum specimens between the developed PEC immunoassay and the commercially available CEA ELISA kits., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Histopathological molecular testing of tissue sections is an essential step in tumor diagnosis; however, the commonly used immunohistochemical methods have problems such as low specificity and the subjective bias of the observer. Here, we report an electrochemiluminescence (ECL) imaging method to detect a membrane carcinoembryonic antigen (CEA) at the single tissue sections of cancer patients. By permeabilizing the tissue attached to a glassy carbon electrode, Ru(bpy) 3 2+ tagged at the membrane CEA of the tissue could electrochemically react with TPrA in solution to emit ECL that has near-zero background and an extremely high signal-to-background ratio. Using the established ECL method, the expression differences and distribution characteristics of the CEA protein in the carcinoma and paracancerous tissues of pancreatic ductal carcinoma (PDAC) and lung adenocarcinoma (LUAD) patients are investigated. The images reveal that CEA proteins are mostly distributed in the acini and surrounding areas both in PDAC and LUAD tissues. Therefore, the presented approach could be able to provide a new molecular recognition method for the diagnosis of adenocarcinoma and other tumors.

Accurate quantitative analysis of tumor markers in a wide linear range has important practical significance towards complex clinical samples in cancer identification and monitoring of tumor development stages, but remains challenging. Herein, three-layer dumbbell-like upconversion nanoparticles NaErF 4 :Tm@NaYF 4 @NaNdF 4 (labeled as UCNPs) combined with G-quadruplex (G 4 ) DNAzyme are reported for tri-modal sensing of carcinoembryonic antigen (CEA) in a wide range using upconversion luminescence (UCL), photothermal and catalysis signal readouts. Initially, dumbbell-like UCNPs were controlled synthesized by a three-dimensional epitaxial growth strategy through tuning the concentration of Nd precursors. After surface functionalization, G 4 zyme-UCNPs-cDNA/Apt-MB was subsequently fabricated by biotin-streptavidin interaction and DNA hybridization. Quantitative detection of CEA was achieved by competitive interaction and magnetic separation, and the intensities of tri-modal signals (light, heat and catalysis-based chrominance) of dissociative probes are linearly related to the concentration of CEA. The results showed that the tri-modal sensing method exhibited a wide linear range (0.005-2000 ng/mL) and low limit of detection (LOD) across three models: the luminescence model (0.005-50 ng/mL, LOD = 0.910 pg/mL), the catalysis model (10-1000 ng/mL, LOD = 0.387 ng/mL), and the temperature model (50-2000 ng/mL, LOD = 1.114 ng/mL). These findings suggest that the tri-modal sensing platform is suitable for use in the analysis of a wide range of complex and diverse clinical samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In this paper, a novel donor-acceptor pair was creatively proposed based on the principle of electrochemiluminescence resonance energy transfer (ECL-RET): luminol immobilized on polyethyleneimine (PEI)-functionalized manganese-based single-atom nanozymes (Mn SANE/PEI-luminol, donor) and a PtCu-grafted hollow metal polydopamine framework (PtCu/h-MPF, acceptor). A quenched ECL immunosensor was constructed for the ultrasensitive analysis of carcinoembryonic antigen (CEA). Mn SANE, as an efficient novel coreaction accelerator with the outstanding performance of significantly activating H 2 O 2 to produce large amounts of ROS, was further modified by the coreactant PEI, which efficiently immobilized luminol to form a self-enhanced emitter. As a result, the electron transport distance was effectively shortened, the energy loss was reduced, and luminol achieved a high ECL efficiency. More importantly, PtCu-grafted h-MPF (PtCu/h-MPF) was proposed as a novel quencher. The UV-vis spectra of PtCu/h-MPF partially overlap with the ECL spectra of Mn SANE/PEI-luminol, which can effectively trigger the ECL-RET behavior between the donor and the acceptor. The multiple quenching effect on Mn SANE/PEI-luminol was achieved, which significantly improved the sensitivity of the immunosensor. The prepared immunosensor exhibited good linearity in the concentration range of 10 -5 to 80 ng/mL. The results indicate that this work provides a new method for the early detection of CEA in clinical diagnosis.