Detection Of CA125 Research Articles

A Dual-Ion Synergistic Catalysis Utilizing Zn2+-Regulated CdSySe1-y ECL Immunosensor Employed for the Ultrasensitive CA19-9 Detection.

Carbohydrate antigen 19-9 is a well-known malignancy biomarker, and its sensitive detection is particularly crucial in the diagnosis and assessment of pancreatic cancer. In this study, an ultrasensitive CA19-9 immunosensor was constructed using the Zn2+-regulated CdSySe1-y (Zn-CdSySe1-y) nanospheres (NSs) as the electrochemiluminescence (ECL) emitter and FeCoS2 nano octahedrons (NOs) as a coreactant enhancer. The microstructure of ternary transition metal chalcogenide CdSySe1-y was precisely tuned by Zn2+ doping to avoid aggregation and thus enable stable and efficient cathodic ECL responses. The bimetallic sulfide FeCoS2 was synthesized using a metal organic framework (MOF) as the template by ion permeation. It was able to catalyze the coreactant efficiently due to the synergistic effect of the Fe2+ and Co2+. The immunosensor exhibited low detection limit (7.6 × 10-5 U mL-1) in the wide linear range of 0.0001-100 U mL-1, offering a sensitive CA19-9 detection method.

B-357 Siemens CA 72-4: an assay for measurement of Tumor Associated Glycoprotein (TAG) 72

Abstract Background The tumor associated glycoprotein (TAG) 72, also known as CA 72-4 is a mucin protein of high molecular weight. CA 72-4 is found on the surface of many cancer cells, including stomach (gastric), ovary, breast, colon and pancreatic cells. CA 72-4 is currently one of the primary markers for the diagnosis of gastric cancer and monitoring the course and efficacy of gastric cancer. In ovarian cancer, it has a higher sensitivity for mucin- type ovarian cancer, and its combination with CA125 for detection can significantly improve the clinical sensitivity. In colorectal cancer, CA 72-4 combined with CEA detection was also found to significantly improve the sensitivity of the initial diagnosis. An assay for CA 72-4 on Siemens Atellica IM (Siemens CA 72-4) is being developed and analytical performance is being presented. Methods The Siemens CA 72-4 assay (in development) is a one-step chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of CA 72-4 in human serum and plasma. The specimen is incubated with paramagnetic microparticles coated with the monoclonal antibody (mAb) B72.3 and acridinium-labeled mAb CC49 conjugate on the Siemens Atellica IM® System. After incubation and washing, Acid and Base reagents are added. The resulting relative light units (RLUs) are directly proportional to the amount of CA 72-4 in the sample allowing for the quantitative determination of CA 72-4 in the specimen. Results The following performance were determined using 3 unique lots of reagents and calibrators with the calibration range for the assay being 0.00 to 200.00 U/mL. The limit of blank (LoB), limit of detection (LoD), and limit of quantitation at 20% CV (LoQ) were determined and met the goal of ≤ 1.00 U/mL. Linearity according to CLSI EP06 Ed2 was demonstrated for a range of 1.00 through 200.00 U/mL. A Precision study of 2 controls and 5 panels spanning the range of the assay demonstrated a total %CV ≤ 6% for samples ≥ 5.00 U/mL and ≤ 0.25 SD for samples <5.00 U/mL. In the sample tube type study, a matrix comparison of 23 matched serum and plasma samples were evaluated. Passing-Bablock slopes of < 8% and r > 0.99 were observed when evaluating samples within the measurement range for plasma (LiHep, LiHep separator, K2EDTA and K3EDTA) tubes and serum separator tubes (SST) compared to the Red Top serum samples. Five endogenous substances were evaluated for interference in the CA 72-4 assay. The average percent difference between test and control samples for all endogenous interferents was < 10%. Percent difference in the presence of 28 potentially interfering drugs was ≤ 4.0%. Conclusions The Siemens CA 72-4 assay currently in development is a sensitive and precise assay for the quantitative determination of CA 72-4 in human serum and plasma.

Self-assembled prussian blue nanoparticles on MXene quantum dots modified AuNPs for sensitive and reproducible biosensing of ovarian specific antigen (CA-125)

In this study, a practical approach has been developed to detect ovarian specific antigen (CA-125) with high sensitivity and specificity. The method utilizes enhanced differential pulse voltammogram signals of a self-assembled prussian blue nanoparticles (PB) decorated on MXene Quantum dots (QDs) supported by electrodeposited Au nanoparticles modified glassy carbon electrode (AuNP/PB/MXene QD/GCE). The fabrication procedure was completed by casting an optimized value of streptavidin and CA-125 antibody on the transducing platform. The improved electrochemical characteristics of the MXene QD/PB/AuNPs modification were ascribed to the combined impacts of MXene QD, PB, and AuNPs. The integration of MXene QD-PB composite within the modified layer contributed to enhanced mechanical strength. Additionally, the inclusion of gold nanoparticles (AuNPs) notably enhanced conductivity and promoted the attachment of anti-CA-125 onto the modified glassy carbon electrode (GCE), consequently improving sensitivity. Several analytical methods, such as energy-dispersive X-ray spectroscopy (EDS) and field emission scanning electron microscopy (FE-SEM) were utilized to investigate the structural, elemental composition and morphological characteristics. The functionality of the newly created immunosensor was evaluated using electrochemical impedance spectroscopy, differential pulse voltammetry and cyclic voltammetry to evaluate the synergistic effects. By employing this highly efficient analysis strategy, the measurement of CA-125 with differential pulse voltammetry (DPV) results a remarkable sensitivity with a detection limit of 0.57 pU.mL−1 and a wide linear range of 1 pU.mL−1 to 0.12 nU.mL−1 (R2 = 0.9824). Comparable results were obtained by analyzing serum samples from ovarian cancer patients at various stages. This study offers a significant insight into the advancement of immunosensor techniques for fabricating electrochemical transducers for the clinical detection of CA-125.

Reduced graphene oxide based ultrasensitive resistive sensor for detection of CA125

Early-stage detection of any cancer significantly improves the survival rates by enabling clinicians to design simpler and more effective treatment options, leading to a cure or remission. Early diagnosis of ovarian cancer, the leading cause of gynaecological cancer related mortalities, relies heavily on accurate detection of the serum biomarker CA125. This work presents a simple rGO/monoclonal antibody (mAB)/bovine serum albumin (BSA) based 2-port resistive sensor for CA125. The binding of mAB on rGO was confirmed by atomic force microscopy which showed increase in thickness of the device from 1.4 nm to approximately 40–60 nm after the mAB anchored on the device. FESEM further confirmed the morphologies of rGO, rGO/mAB, and rGO/mAB/CA125. The sensor exhibited impressive response ranging from 1.28% to 113.4% for 1 pg/mL to 300 ng/mL CA125. Notably, the rGO/mAB/BSA sensor displayed high selectivity towards CA125 and a readout circuit was designed, assembled, and tested with the sensors to get a portable device for detecting CA125. The developed sensors were tested with 9 clinical samples and were found to be determining the CA125 concentration accurately.

Metal-Organic framework incorporated luminescent PTCA combined with novel co-reactant accelerator for ultra-sensitive electrochemiluminescence detection of CA19-9

Polycyclic aromatic hydrocarbons (PAHs) are commonly used as electrochemiluminescence (ECL) luminophores. However, PAHs are limited by the aggregation-caused quenching (ACQ) effect, which reduces ECL emission. Therefore, developing an ECL system from PAHs with efficient luminescence is a significant challenge. In this work, a two-ligand strategy was proposed to assemble 3, 4, 9, 10-perylenetetracarboxylic acid (PTCA) into zeolitic imidazole framework-8 (ZIF-8). The ACQ effect of PTCA was inhibited by participating in the formation of metal–organic frameworks (MOFs) and a luminescent ZIF-8-PTC (Z8P) composite was obtained. Satisfactorily, conceptual experiments demonstrated that the significantly higher ECL efficiency of Z8P was achieved compared with PTCA monomers and aggregates. On the sensing substrate, a novel co-reactant accelerator (Au@MFNC) was used to achieve continuous catalysis of the persulfate (K2S2O8) with the Prussian blue analogues (PBAs) as a template under the efficient synergistic effect of MoS2. Through the reversible transformation of the transition metal valence states, a sufficient amount of sulfate radicals (SO4•−), again amplifying the ECL signal of Pd@Z8P. Under ideal conditions, the constructed dual-MOFs ECL immunosensor had a wide response range (1 × 10−4 − 1 × 102 U/mL) and a low limit of detection (LOD) (6 × 10−5 U/mL), which provided an alternative method for CA19-9 ultrasensitive detection, and broadened a new idea for the development of high-performance luminescent MOFs.

Atomically Co-dispersed nitrogen-doped carbon for sensitive electrochemical immunoassay of breast cancer biomarker CA15-3.

The development of an ultrasensitive and precise measurement of a breast cancer biomarker (cancer antigen 15-3; CA15-3) in complex human serum is essential for the early diagnosis of cancer in groups of healthy populations and the treatment of patients. However, currently available testing technologies suffer from insufficient sensitivity toward CA15-3, which severely limits early large-scale screening of breast cancer patients. We report a versatile electrochemical immunoassay method based on atomically cobalt-dispersed nitrogen-doped carbon (Co-NC)-modified disposable screen-printed carbon electrode (SPCE) with alkaline phosphatase (ALP) and its metabolite, ascorbic acid 2-phosphate (AAP), as the electrochemical labeling and redox signaling unit for sensitive detection of low-abundance CA15-3. During electrochemical detection by differential pulse voltammetry (DPV), it was found that the Co-NC-SPCE electrode did not have a current signal response to the AAP substrate; however, it had an extremely favorable response current to ascorbic acid (AA). Based on the above principle, the target CA15-3-triggered immunoassay enriched ALP-catalyzed AAP produces a large amount of AA, resulting in a significant change in the system current signal, thereby realizing the highly sensitive detection of CA15-3. Under the optimal AAP substrate concentration and ALP catalysis time, the Co-NC-SPCE-based electrochemical immunoassay demonstrated a good DPV current for CA15-3 in the assay interval of 1.0 mU/mL to 10,000 mU/mL, with a calculated limit of detection of 0.38 mU/mL. Since Co-NC-SPCE has an excellent DPV current response to AA and employs split-type scheme, the constructed electrochemical immunoassay has the merits of high preciseness and anti-interference, and its clinical diagnostic results are comparable to those of commercial kits.

A novel electrochemiluminescence immunosensor: BiOBr/Bi2WO6 heterojunction for ultrasensitive detection of CA19-9

Bi2WO6, an environmentally friendly material with certain electrochemiluminescence (ECL) properties, has been used as a novel ECL luminescent material. In the present work, bismuth tungstate (Bi2WO6) was composited with bismuth bromide (BiOBr) to form a S-type heterojunction with a flower like morphology where the Bi2WO6 core was wrapped with BiOBr outer shell. The interface of the heterojunction is closely contacted, which can promote electron transfer, improve conduction and enhance ECL emission to a certain extent. The BiOBr/Bi2WO6 (BBW) heterojunction with K2S2O8 as a co-reactant demonstrates cathodic ECL emission at 550–800 nm in the potential range of −1.8–0 V. Cu2O@Ag with a special sea urchins morphology was introduced into the system to catalyze the reduction of S2O82− to generate more SO4•−, which further enhances the ECL emission. The ECL immunosensor constructed with the heterojunction for CA19–9 detection exhibits a robust linear relationship in the concentration range from 0.1 mU·mL−1 to 100 U·mL−1 and detection limit as low as 87.6 μU·mL−1. The immunosensor successfully detected CA19–9 in serum, showing great application potential in the clinical practice.

Evaluation of the value of combined detection of tumor markers CA724, carcinoembryonic antigen, CA242, and CA19-9 in gastric cancer.

Gastric cancer is a global health concern that poses a significant threat to human well-being. To detecting serum changes in carcinoembryonic antigen (CEA), carbohydrate antigens (CA) 724, CA242, and CA19-9 expression among patients with gastric cancer. Eighty patients diagnosed with gastric cancer between January 2020 and January 2023 were included in the observation group, while 80 patients with benign gastric diseases were included in the control group. Both groups were tested for tumor markers (CA724, CEA, CA242, and CA19-9]. Tumor marker indicators (CA724, CEA, CA242, and CA19-9) were compared between the two groups, assessing positive rates of tumor markers across various stages in the observation group. Additionally, single and combined detection of various tumor markers were examined. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value observed for the combined detection of CA724, CEA, CA242, and CA19-9 were higher than those of CA724, CEA, CA242, and CA19-9 individually. Therefore, the combined detection of CA724, CEA, CA242, and CA19-9 has a high diagnostic accuracy and could reduce the occurrence of missed or misdiagnosed cases, facilitating the early diagnosis and treatment of patients. CA724, CEA, CA242, and CA19-9 serum levels in gastric cancer patients significantly surpassed those in non-gastric cancer patients (P < 0.05). Their combined detection can improve the diagnostic accuracy for gastric cancer, warranting clinical promotion.

Electrochemical sensor for rapid diagnosis and early-stage detection of pancreatic cancer using Er-GQDs decorated MoS2 nanoflowers

In this study, for the first time, the erbium-doped graphene quantum dots (Er-GQDs) were decorated onto a three-dimensional MoS2 nanoflower (EGM) for electrochemically sensitive and selective detection of carbohydrate antigen, CA 19-9, in phosphate buffer saline (PBS) and biological fluids. The MoS2 nanoflowers (MoS2 NF) were hydrothermally prepared at 200 °C for 24 h, and then 2–8 nm of Er-GQDs were uniformly deposited onto 200 nm MoS2 NF. The MoS2 NF has a high electric conductivity for electrochemical performance, whereas Er-GQDs act as an effective anchor with anti-CA19-9 antibodies (CA19-9 Ab) for ultra-selectivity to CA19-9 antigen. The SPE||EGM/Ab immunosensor has substantial benefits by providing a long-lasting, ultra-sensitive, and highly selective platform for CA19-9 antigen detection. The dynamic ranges in PBS, human serum, and saliva are 5 × 10−5–250, 5 × 10−4–250, and 3 × 10−4–250 U mL−1, respectively, with limits of detection (LODs) of (0.18–2.95) × 10−4 U mL−1. Furthermore, the SPE||EGM/Ab immunosensor can detect CA19-9 in human serum with a recovery of 97–108 %. The non-invasive detection of CA19-9 in saliva is stably sensitive before and after 1 h of breakfast. Moreover, the SPE||EGM/Ab immunosensor has excellent selectivity toward CA19-9 over the other 17 interferences. Results elaborate that the SPE||EGM/Ab immunosensor is a promising electrochemical biosensing probe for detecting CA19-9 in human serum and saliva for clinical diagnosis and prognosis of pancreatic cancer in the early stage.

A novel photoelectrochemical biosensing platform utilizing dual Type-II Bi2O3/CdLa2S4/Bi2S3 ternary heterojunctions as signal transduction materials and Cu2O nanosphere as a sensitizer for CA15-3 detection

Sensitive detection of CA15-3 is important for postoperative monitoring and early diagnosis of breast cancer. In this work, a photoelectrochemical (PEC) biosensing platform was constructed of CA15-3 by using Bi2O3/CdLa2S4/Bi2S3 ternary type-II heterojunction as the photoactive transduction material for sensitive detection, and the raspberry-shaped Cu2O nanospheres were exploited as the signal sensitizing tags. On one hand, the use of Bi2S3 as a sensitizer can effectively enhance the visible light excitation of the substrate material. On the other hand, Bi2S3 and Bi2O3/CdLa2S4 have the ability to create dual type-II heterojunctions with matched energy levels, which significantly enhances the separation and migration efficiency of the photogenerated carriers and effectively suppresses the recombination of the e-/h+ pairs. Raspberry-like semiconducting Cu2O nanospheres can mediate the PEC process of the heterojunctions. An immunosensor was developed combining the signal transduction capacity of ternary heterojunction and the signal sensitizing effect of Cu2O nanospheres. The proposed PEC immunosensor showed good selectivity and stability for detecting CA15-3 (0.001 ∼ 100 U/mL) with a detection limit of 0.0003 U/mL (S/N = 3). The constructed PEC immunosensor had potential applications in the clinical detection of CA15-3, and was expected to play a great role in the early diagnosis of breast cancer in the future. Moreover, in the design engineering of photoactive materials, the improvement of visible excitation and the enhancement of carrier separation efficiency have been realized simultaneously using a single material, which provides new ideas for the design of photoactive materials.

One-Step Electrochemical Sensing of CA-125 Using Onion Oil-Based Novel Organohydrogels as the Matrices.

To reduce the high mortality rates caused by ovarian cancer, creating high-sensitivity, quick, basic, and inexpensive methods for following cancer antigen 125 (CA-125) levels in blood tests is of extraordinary significance. CA-125 is known as the exclusive glycoprotein employed in clinical examinations to monitor and diagnose ovarian cancer and detect its relapses as a tumor marker. Elevated concentrations of this antigen are linked to the occurrence of ovarian cancer. Herein, we designed organohydrogels (ONOHs) for identifying the level of CA-125 antigen at fast and high sensitivity with electrochemical strategies in a serum medium. The ONOH structures are synthesized with glycerol, agar, and glutaraldehyde and at distinct ratios of onion oil, and then, the ONOHs are characterized with Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM). Electrochemical measurements are performed by cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS) in the absence and presence of CA-125 on the designed ONOHs. For the prepared ONOH-3 electrode, two distinct linear ranges are determined as 0.41-8.3 and 8.3-249.0 U/mL. The limit of quantitation and limit of detection values are calculated as 2.415 and 0.805 μU/mL, respectively, (S/N = 3). These results prove that the developed electrode material has high sensitivity, stability, and selectivity for the detection of the CA-125 antigen. In addition, this study can be reasonable for the practical detection of CA125 in serum, permitting early cancer diagnostics and convenient treatment.

Ratiometric electrochemical immunosensor for the detection of CA199 based on the ratios of NiCo@Fc-MWCNTs-LDH and 3D-rGOF@Ag/Au complexes

Carbohydrate antigen 199 (CA199) is the most sensitive marker reported for pancreatic cancer, and it is a difficult task to develop a highly sensitive assay for CA199. During the experiment, a ratiometric electrochemical immunosensor for quantitative analysis of CA199 was prepared for NiCo@Fc-MWCNTs-LDH as the electrode sensing surface and 3D-rGOF@Ag/Au as the label of Ab2. NiCo@Fc-MWCNTs-LDH not only provide the required signal for the immunosensor, but also have a layered structure to obtain a large specific surface area, which can provide more sites for the placement of biological molecules. rGOF has the advantages of large specific surface area and high porosity, which can adsorb Ag electrochemical probe through redox reaction. The modification of gold nanoparticles can not only enhance the electrical conductivity of nano-composites, but also immobilize more biomolecules to improve the sensitivity of electrochemical sensors. With the beefing up of CA199 concentration, the oxidation peak current of Ag increases and the oxidation peak current of Fc-COOH decreases. The ratio (y = IAg/IFc-COOH) of two different signals was linear with the logarithm of CA199 concentration in a certain value range. Under optimal conditions, the immunosensor showed excellent performance in the concentration range of 0.0001 U/mL to 10 U/mL, and the detection limit was 5.55 × 10−4 U/mL. The strategy could clearly discriminate between matched and mismatched targets, demonstrating high specifificity. This approach further detects CA199 in human plasma to differentiate pancreatic cancer patients from healthy individuals with high accuracy. This method also provided a new idea for the ultrasensitive quantitative detection of other biomarkers.

Exclusive Core-Janus Satellite Assembly Based on Au-Ag Janus Self-Aligned Distributions with Abundant Hotspots for Ultrasensitive Detection of CA19-9.

The development of surface-enhanced Raman scattering (SERS) probes with high sensitivity and stability is imminent to improve the accuracy of cancer diagnosis. Here, an exclusive core-Janus satellite (CJS) assembly was constructed by a hierarchical assembly strategy in which the Au-Ag Janus satellite is vertically self-aligned on the core surface. In the process, a silica shell template was ingeniously employed to asymmetrically mask the presatellites for the in situ formation of the Janus structure, and a series of Janus satellites with different morphologies were developed by regulating the encapsulated area of the presatellites. The ordered-oriented arrangement of Au-Ag Janus and unique heterojunction morphology permit CJS assemblies, featuring two types of plasmonic nanogaps, including intrananocrevices for individual Janus and internanogaps between neighboring Janus, thereby multiplying the "hotspots" compared to conventional core-monotonous satellites, which contributes to superior SERS activity. As anticipated, the enhancement factor of CJS assemblies was as high as 3.8 × 108. Moreover, it is intriguing that the directional distribution and head physically immobilized by Janus provided uniform and stable SERS signals. The SERS probe based on the CJS assembly for the detection of carbohydrate antigen 19-9 resulted in an ultrahigh sensitivity with a limit of detection of 3.7 × 10-5 IU·mL-1, which is nearly 10 times lower than other SERS probes, and a wide detection range of 3 × 10-5 to 1 × 104 IU·mL-1. The CJS assembly with excellent SERS performance is promising to advance further development of the early diagnosis of pancreatic cancer.

Double-Amplified Electrochemiluminescence Immunoassay Sensor for Highly Sensitive Detection of CA19-9 Using a Ternary Semiconductor CdSSe.

In this paper, an electrochemiluminescence (ECL) immunosensor for ultrasensitive detection of CA19-9 was constructed using ternary compound CdSSe nanoparticles as ECL emitter. The immunosensor employs Cu2S and gold-doped diindium trioxide (Au-In2O3) nanocubes as coreaction accelerators to achieve a double-amplification strategy. In general, a hexagonal maple leaf-shaped Cu2S with a large surface area was selected as the template, and the in situ growth of CdSSe on its surface was achieved using a hydrothermal method. The presence of Cu2S not only inhibited the aggregation of CdSSe nanoparticles to reduce their surface energy but also acted as an ECL cathode coreaction promoter, facilitating the generation of SO4•-. Consequently, the ECL intensity of CdSSe was significantly enhanced, and the reduction potential was significantly lower. In addition, the template method was employed to synthesize Au-In2O3 nanocubes, which offers the advantage of directly connecting materials with antibodies, resulting in a more stable construction of the immunosensor. Furthermore, In2O3 serves as a coreaction promoter, enabling the amplification strategy for ECL intensity of CdSSe, thus contributing to the enhanced sensitivity and performance of the immunosensor. The constructed immunosensor exhibited a wide linear range (100 μU mL-1 to 100 U mL-1) and a low detection limit of 80 μU mL-1, demonstrating its high potential and practical value for sensitive detection of CA19-9.

Low fouling electrochemical sensing interfaces based on Bovine serum albumin hydrogel for the detection of protein biomarkers in human serum

The development of electrochemical biosensor capable of detecting specific biomarkers in real complex biological samples remains a challenge significantly relevant to a range of disease diagnostic applications. Herein an antifouling electrochemical biosensor suitable for biomarker detection in human serum was constructed based on protein hydrogels. A typical protein bovine serum albumin (BSA) was crosslinked with glutaraldehyde to form a hydrogel, which was freeze-dried and re-swollen to exhibit excellent antifouling capability. The rheological testing revealed that the prepared BSA hydrogel possessed good elasticity with a critical strain value of about 600 %, which is important for the construction of stable hydrogel-based biosensors. Following the immobilization of CA125 antibodies onto the BSA hydrogel modified electrode, an electrochemical biosensor for the detection of CA125 was constructed, with a linear range of 0.1 ∼ 1000 U mL−1 and a limit of detection of 0.026 U mL−1. Owing to the unique properties of the BSA hydrogel, the biosensor exhibited good stability and excellent antifouling performances, and it was able to detect CA125 in human serum with acceptable accuracy. The strategy of constructing low fouling biosensors based on hydrogels prepared from BSA with biocompatibility and widespread availability represented a very promising advance along the road to develop biosensing devices with robust operation in complex biological fluids.

Confined growth of Ag nanogap shells emitting stable Raman label signals for SERS liquid biopsy of pancreatic cancer

To develop a reliable surface-enhanced Raman scattering (SERS) immunoassay as a new liquid biopsy modality, SERS nanoprobes emitting strong and stable signals are necessary. However, Ag nanoparticles used as SERS nanoprobes are prone to rapid fading of SERS signals by oxidation. This has driven the development of a new strategy for Ag-based SERS nanoprobes emitting stable and strong SERS signals over time. Herein, Ag nanogap shells entrapping Raman labels are created in the confined pores of mesoporous silica nanoparticles (AgNSM) through a rapid single-step reaction for SERS liquid biopsy. Each AgNSM nanoprobe possesses multiple nanogaps of 1.58 nm to entrap Raman labels, allowing superior long-term SERS signal stability and large enhancement of 1.5 × 106. AgNSM nanoprobes conjugated with an antibody specific for carbohydrate antigen (CA)19-9 are employed in the SERS sandwich immunoassay including antibody-conjugated magnetic nanoparticles for CA19-9 detection, showing a two orders of magnitude lower limit of detection (0.025 U mL−1) than an enzyme-linked immunosorbent assay (0.3 U mL−1). The AgNSM nanoprobe immunoassay accurately quantifies CA19-9 levels from clinical serum samples of early and advanced pancreatic cancer. AgNSM nanoprobes with stable SERS signals provide a new route to SERS liquid biopsy for effective detection of blood biomarkers.

Combination of serum CST1 and HE4 for early diagnosis of endometrial cancer

Purpose Optimal serological biomarkers have been absent for the early diagnosis of endometrial cancer, to date. In this study, we aimed to define the diagnostic performances of individual and combined detection of serum cysteine protease inhibitor 1 (CST1) with traditional tumor markers, including glycated antigen 125 (CA125) and human epididymis protein 4 (HE4), in patients with early-stage endometrial cancer (EC). Methods The performances of individual and combined detection of serum CST1, HE4, and CA125 were evaluated by enzyme-linked immunosorbent assay (ELISA) and chemiluminescent immunoassay, respectively. A training data set of 67 patients with early EC, 67 patients with endometrial benign lesion (EBL), and 67 healthy controls (HC) was used to develop a predictive model for early EC diagnosis, which was validated by an independent validation data set. Results In the training data set, serum CST1 and HE4 levels in the early EC group were significantly higher than in EBL/HC groups (P &lt; 0.05), while there was no significant difference of serum CA125 level between the early EC and EBL/HC groups (P &gt; 0.05). Serum CST1 and HE4 exhibited areas under the curve (AUC) of 0.715 with 31.3% sensitivity at 90.3% specificity, and 0.706 with 23.9% sensitivity at 95.5% specificity, respectively. Combined detection of serum CST1 and HE4 exhibited an AUC of 0.788 with 49.3% sensitivity at 92.5% specificity. The combination of serum CST1 and HE4 showed promise in diagnosis. Conclusion CST1 is a prospective serological biomarker for early EC diagnosis, and the combination of CST1 and HE4 contributes to the further improvement in the diagnosis of patients with early-stage EC.

Electrostatic Nanocage-Confined Probe for Electrochemical Detection of CA19-9 in Human Serum.

Prompt and accurate detection of CA19-9 in human serum has great clinical significance for the early diagnosis and disease monitoring of cancer. Herein, we develop a convenient and antifouling electrochemical sensor for CA19-9 determination by immobilization of both an electrochemical redox probe [methylene blue (MB)] and immunorecognition element (CA19-9 antibody) on an electrostatic nanocage consisting of bipolar silica nanochannel array (bp-SNA). bp-SNA is composed of a negatively charged inner layer (n-SNA) and positively charged outer layer (p-SNA), which could be stably prepared on indium tin oxide (ITO) in several seconds using a two-step electrochemically assisted self-assembly approach and display asymmetric surface charges for confinement and enrichment of cationic MB into the inner n-SNA layer through electrostatic interaction. Modification of the CA19-9 antibody on the top surface of bp-SNA confers the sensing interface with specific recognition capacity. An antibody-antigen complex formed at the as-prepared immunosensor causes the decreased electrochemical signals of MB, achieving sensitive determination of CA19-9 with a wider linear dynamic range from 10 μU/mL to 50 U/mL and a low detection limit (3 μU/mL). Furthermore, accurate and feasible analysis of the CA19-9 amount in human serum samples by our proposed probe-integrated electrochemical immunosensor is realized.

Aptasensor for ovarian cancer biomarker detection using nanostructured gold electrodes.

The development of an electrochemical aptasensor for the detection of CA125 as an ovarian cancer biomarker using gold nanostructures (GNs) modified electrodes is reported. The GNs were deposited on the surface of fluorine-doped tin oxide electrodes using a simple electrochemical method and the effects of pH and surfactant concentration on the topography and electrochemical properties of the resulting GNs modified electrodes were investigated. The electrodes were characterized using field-emission scanning electron microscopy and X-ray diffraction, cyclic voltammetry, and electrochemical impedance spectroscopy. The best electrode, in terms of the uniformity of the deposited GNs and the increase in electroactive surface area, was used for development of an aptasensor for CA125 tumor marker detection in human serum. Signal amplification was done by using aptamer-conjugated gold nanorods resulting in the detection limit of 2.6 U/ml and a linear range of 10 to 800 U/ml. The results showed that without the need for expensive antibodies, the developed aptasensor could specifically measure the clinically relevant concentrations of the tumor marker in human serum.

Simultaneous detection of CA-125 and mesothelin by gold nanoparticles in surface plasmon resonance

The early-stage diagnosis and monitoring of disease evolution is still one of the most challenging tasks in the field of cancer research. Several research have been driven toward the discovery of new cancer biomarkers as well as to the development of biosensors able to detect these biomarkers with high specificity and sensitivity. Many types of cancer have been detected at an advanced stage and, in particular, epithelial ovarian cancer (EOC) has a high incidence of diagnosis in the metastatic stage. This cancer is considered as the most aggressive type of gynecological cancer with a 5-year survival and until now, no specific biomarkers have been identified. Nevertheless, some studies have indicated that mesothelin, a protein overexpressed by tumour cells in the ovary, interacts with the CA-125 biomarker present in the blood system accelerating the metastatic process. Therefore, the simultaneous presence of CA-125 and mesothelin in the blood during the evolution of EOC could be used to diagnose this disease before the metastasis. Therefore, with this motivation, this work aimed at the development of a biosensor capable of simultaneously detecting mesothelin and CA-125 at low concentrations. A biosensor based on the surface plasmon resonance imaging (SPRi) technique was developed and gold nanoparticles (AuNPs) were used in order to enhance the sensitivity. The study analysed successive injections of the biomarkers CA-125 and mesothelin, both in solution (analytical range of 9–120 nM). The limits of detection were obtained for CA-125 and mesothelin, being of 3.03 nM and 13.62 nM, respectively. The biosensor detected mesothelin at a concentration close to the cutoff point for EOC (3 nM) and was able to detect the biomarker CA-125 at 9 nM. Furthermore, the biosensor interacted preferentially and simultaneously with the biomarkers CA-125 and mesothelin incubated in fetal bovine serum. Finally, the use of AuNPs increased the sensor signal for CA-125 detection compared to its direct detection and showed greater selectivity for both biomarkers. Therefore, the biosensor has important characteristics that allow testing with real samples. In a future project, it could be applied in the research of diagnosis and prognosis of EOC.