Sensitive Detection Of Carcinoembryonic Antigen Research Articles

Hydrangea-like TiO2/Bi2MoO6 porous nanoflowers triggering highly sensitive electrochemical immunosensing to tumor marker.

Rapid and sensitive detection of carcinoembryonic antigen (CEA) is of great significance for cancer patients. Here, molybdenum (Mo) was doped into bismuth oxide (Bi2O3) by one-pot hydrothermal method forming porous tremella Bi2MoO6 nanocomposites with a larger specific surface area than the spherical structure. Then, a new kind of hydrangea-like TiO2/Bi2MoO6 porous nanoflowers (NFs) was prepared by doping titanium into Bi2MoO6, where titanium dioxide (TiO2) grew in situ on the surface of Bi2MoO6 nanoparticles (NPs). The hydrangea-like structure provides larger specific surface area, higher electron transfer ability and biocompatibility as well as more active sites conducive to the attachment of anti-carcinoembryonic antigen (anti-CEA) to TiO2/Bi2MoO6 NFs. A novel label-free electrochemical immunosensor was then constructed for the quantitative detection of CEA using TiO2/Bi2MoO6 NFs as sensing platform, showing a good linear relationship with CEA in the concentration range 1.0pg/mL ~ 1.0mg/mL and a detection limit of 0.125pg/mL (S/N = 3). The results achieved with the designed immunosensor are comparable with many existing immunosensors used for the detection of CEA in real samples.

Functionalized gold nanoparticle enhanced nanorod hyperbolic metamaterial biosensor for highly sensitive detection of carcinoembryonic antigen

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-Ab2) 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-Ab2 nanocomposites-based NHMM (AuNP/Ab2-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/Ab2-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.

Dual-potential ratiometric electrochemiluminescence based on single emitter and single coreactant for the sensitive detection of carcinoembryonic antigen

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 (H2O2) with a mild potential range from −0.1 to 0.6 V. Luminol could produce a strong cathodic ECL (Ec) induced by hydroxyl radicals (HO‧) from the reduction of H2O2, and a relatively weak anodic ECL (Ea). After the ferrocene modified CEA aptamer (Apt-Fc) was attached, Fc could promote Ea by catalyzing the oxidation of H2O2, and reduce Ec 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 Ea and the rise of Ec. So, the ratio of Ec to Ea (Ec/Ea) 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.

Improving CEA detection Sensitivity: Carboxyfluorescein-Loaded liposomes in aptamer sandwich assay

This study aimed to develop an effective method for highly sensitive detection of carcinoembryonic antigen (CEA), a tumor biomarker, using an aptasensor sandwich assay based on a liposome loaded with carboxyfluorescein. In this approach, liposomes loaded with carboxyfluorescein (CF) were anchored with a cholesterol-labeled anti-CEA aptamer (Apt1-Lip) using a post-insertion technique. Furthermore, the successful insertion of the aptamer into the liposome outer layer was confirmed through UV absorption, PAGE electrophoresis, dynamic light scattering (DLS), and zeta potential measurements. Additionally, a secondary aptamer was conjugated with magnetic beads via biotin-streptavidin interactions and used as a capture probe (MBs/Apt2). Aptamer-decorated liposomes successfully bound to the CEA antigen in the presence of the target, leading to the formation of a sandwich assay when combined with MBs/Apt2. The specific binding signal was further increased by dissolving the lipid nanospheres with Triton X-100. This liposome-based aptasensor demonstrated a detection limit of 35.48 pg/mL over a wide linear range from 0.1 ng/mL to 100 ng/mL, with high specificity and sensitivity at CEA. Additionally, the proposed approach exhibited notable promise for on-site testing in early clinical diagnosis, as it showed excellent selectivity, satisfactory reproducibility, and good recovery in CEA detection from human serum samples.

A novel split-type photoelectrochemical biosensor based on liposome-induced in situ formation of Bi2S3@BiOI/Ag2S heterojunction for the sensitive detection of CEA

A novel split-type photoelectrochemical (PEC) biosensor was constructed for the sensitive detection of carcinoembryonic antigen (CEA) based on the Ag+-liposome (ALL) signal amplification strategy and Bi2S3@BiOI heterojunction as the substrate material. The split-type sensing mode effectively avoids the complex fixation of biomolecules on the electrode surface and preserves the activity of biomolecules. The sandwich complex was formed between CEA and aptamer-anchored streptavidin-functionalized magnetic beads (SMB-Apt) and ALL-labeled aptamer (ALL-Apt). After the methanol was added, a large amount of Ag+ was released from the liposome. The released Ag+ was transferred to the Bi2S3@BiOI modified electrode surface for incubation and then soaked in Na2S solution to form a narrow band gap photosensitive material Ag2S on the electrode surface. Bi2S3@BiOI/Ag2S ternary heterojunction in situ was formed due to the band gap matching relationship between Ag2S and the Bi2S3@BiOI heterojunction, which effectively expanded the light absorption range and enhanced the photocurrent signal. Under the optimal experimental conditions, the constructed PEC sensing platform exhibited good analytical performance for CEA with a linear range of 0.005 ∼ 50 ng mL−1 and a detection limit of 1.21 pg mL−1. Additionally, the PEC sensor had good selectivity, reproducibility, and stability, which provided a new research idea for the detection of clinical tumor biomarkers.

2D Z-scheme ZnIn2S4/g-C3N4 heterojunction based on photoelectrochemical immunosensor with enhanced carrier separation for sensitive detection of CEA

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 ZnIn2S4/g-C3N4 heterojunction as a photosensitive material and BiVO4 as a photoquencher was designed for the sensitive detection of carcinoembryonic antigen (CEA). Firstly, the 2D ZnIn2S4/g-C3N4 structure provided a multitude of activated sites which facilitated the loading of the capture antibody (Ab1). 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, BiVO4 with large spatial potential resistance was introduced for the first time to realize signal amplification. BiVO4 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.

Development Pt/CoFe2O4/NC for efficient hydrogen evolution and sensitive detection of CEA

In this study, we designed a Pt/CoFe2O4/NC composite material as an excellent electrocatalyst for hydrogen evolution reaction (HER) and used the HER signal to construct an electrochemical immunosensor for carcinoembryonic antigen (CEA) detection. Remarkably, Pt/CoFe2O4/NC demonstrated superior HER performance compared to alternative Pt-based materials. It exhibited a low overpotential of only 42 mV and a Tafel slope of 253 mV dec−1 in acidic medium. Furthermore, due to the excellent conductivity, large surface area, and superior HER performance of Pt/CoFe2O4/NC, it was used as secondary antibody (Ab2) label to achieve signal amplification in the electrochemical immunosensor. The results showed that this immunosensor possessed high selectivity and sensitivity. The linear detection range is 1.0 × 10−4–5.0 ng mL−1, and the detection limit is 0.0134 pg mL−1. It has potential applications in the clinical analysis field.

Early Detection of Carcinoembryonic Antigen Using Hollow Nanospheres Improves the Outcome of Pediatric Solid Tumors

A sandwich electrochemical immunosensor was developed for sensitive detection of carcinoembryonic antigen (CEA) using hollow nanospheres composite material loaded with gold nanoparticles as the signal tag and gold triangular nanoplate as the substrate material. Samples obtained from pediatric solid tumor tissue and their blood samples were used to detect CEA using this nanoparticle. The hollow nanospheres constructed in this study, provided abundant reaction sites and high catalytic activity, while the loading of Au NPs enhances conductivity and biocompatibility. The immunosensor has good analytical ability in detecting CEA in the mass concentration range of 1 pg/mL to 50 ng/mL, with a low detection limit (LOD) of 0.37 pg/mL. This novel method provides a valuable tool for rapid clinical detection of CEA in the context of pediatric solid tumors.

Labeled free electrochemiluminescence aptamer platform based on one-step cathodic electrochemical growth of 2D/3D Ru-BTC-MOFs nanoparticles to detect carcinoembryonic antigen

[Ru(dcbpy)3]2+ functionalized 2D/3D hybrid metal–organic frameworks (Ru-BTC-MOFs), which performed good ECL performance, were synthesized by on one-step cathodic electrodeposition with Zn(NO3)2 as metal ion source, Ru(dcbpy)3Cl2) (tri(4,4-dicarboxybipyridine) ruthenium chloride) and H3BTC (1,3,5-phenyl tricarboxylic acid) as organic ligand. The effect of electrodeposition voltage, electrodeposition time, H3BTC and [Ru(dcbpy)3]Cl2 concentration on the morphology and ECL performance of Ru-BTC-MOFs were investigated in detail. An ECL biosensor platform for sensitive detection of carcinoembryonic antigen (CEA) was constructed by further modified AuNPs and aptamer on the Ru-BTC-MOFs/GCE. The specifically recognition and adsorption of CEA would hinder the electron transfer between Ru-BTC-MOFs and trinpropylamine (TPA) as the co-reactive agent, resulting in decreasing the ECL intensity. Under the optimal experimental conditions, the ECL intensity and logarithm of CEA concentration showed a good linear relationship in the concentration range of 10.0 fg/mL to 10.0 ng/mL, and the detection limit was 5.56 fg/mL. The proposed sensor performed acceptable reproducibility, repeatability, anti-interference ability and stability, and it would be expected to have broad application prospects in clinical trials.

Ultrathin mesoporous BiOCl nanosheets-mediated liposomes for photoelectrochemical immunoassay with in-situ signal amplification

Designing new biochemical sensors and achieving selectivity and high-sensitivity analysis is one of main research directions for immunoassays. Herein, a liposome-amplification photoelectrochemical (PEC) immunoassay was developed using ultrathin mesoporous bismuth chloride oxide nanosheets (BiOCl MSCN) for the highly selective and sensitive detection of carcinoembryonic antigen (CEA). Based on good photocurrent response of BiOCl MSCN toward dopamine, a liposome-conjugated secondary antibody loaded with dopamine was added for specific recognition in the presence of CEA. After the lysis treatment, the liberated dopamine was injected into the three-electrode electrolytic cell to enhance the photocurrent of BiOCl MSCN. Under the optimized conditions, the constructed liposome-mediated PEC immunoassay showed high sensitivity against CEA, with a dynamic response in the linear range of 0.05 ng mL−1 to 100 ng mL−1 and a detection limit of 35 pg mL−1. The present study proposes a new approach to the liposome-mediated PEC immunoassay constructed on ultrathin mesoporous BiOCl nanosheets, which can be used to target further the study of the sensing mechanism.

Difunctional Magnetic Nanoparticles Employed in Immunochromatographic Assay for Rapid and Quantitative Detection of Carcinoembryonic Antigen.

Immunochromatographic assay (ICA) plays an important role in in vitro diagnostics because of its simpleness, convenience, fastness, sensitivity, accuracy, and low cost. The employment of magnetic nanoparticles (MNPs), possessing both excellent optical properties and magnetic separation functions, can effectively promote the performances of ICA. In this study, an ICA based on MNPs (MNP-ICA) has been successfully developed for the sensitive detection of carcinoembryonic antigen (CEA). The magnetic probes were prepared by covalently conjugating carboxylated MNPs with the specific monoclonal antibody against CEA, which were not only employed to enrich and extract CEA from serum samples under an external magnetic field but also used as a signal output with its inherent optical property. Under the optimal parameters, the limit of detection (LOD) for qualitative detection with naked eyes was 1.0 ng/mL, and the quantitative detection could be realized with the help of a portable optical reader, indicating that the ratio of optical signal intensity correlated well with CEA concentration ranging from 1.0 ng/mL to 64.0 ng/mL (R2 = 0.9997). Additionally, method comparison demonstrated that the magnetic probes were beneficial for sensitivity improvement due to the matrix effect reduction after magnetic separation, and the MNP-ICA is eight times higher sensitive than ICA based on colloidal gold nanoparticles. The developed MNP-ICA will provide sensitive, convenient, and efficient technical support for biomarkers rapid screening in cancer diagnosis and prognosis.

An electrochemiluminescence immunosensor based on functionalized metal organic layers as emitters for sensitive detection of carcinoembryonic antigen

The concentration of carcinoembryonic antigen (CEA) is an important indicator for clinical monitoring and diagnosis of tumor. Early sensitive detection of CEA is significant for cancer diagnosis and therapy. In this study, a sensitive electrochemiluminescence (ECL) immunosensor was fabricated based on functionalized metal organic layers (MOLs) for the determination of CEA. In this immunosensor, Au nanoparticles (AuNPs) were grown on ultrathin two-dimensional MOLs via in situ reduction. AuNPs not only can accelerate the electron transfer but also can be used as the labels to conjugate with antibody. The as-prepared AuNPs@Ir-Zr-MOL nanocomposite showed high ECL efficiency and can be used as an ECL emitter owing to the great ECL property of Ir-Zr-MOL. The ECL intensity of AuNPs@Ir-Zr-MOL decreased linearly with the logarithm of CEA concentration in the range from 1.00 pg mL−1 to 100 ng mL−1. And the detection limit was 0.200 pg mL−1 (S/N = 3). What’s more, the as-prepared immunosensor worked well in human blood samples, showing its potential for real analysis.

Two-dimensional substrate assisted SERS immunosensor for accurate detection of carcinoembryonic antigen

Accurate and sensitive detection of carcinoembryonic antigen (CEA) is essential for the detection of various diseases in healthcare and the medical field. Currently, due to the high false negative rate of CEA assay in clinical setting and its use as a common indicator for early cancer screening, a novel CEA detection method with high sensitivity, increased specificity and the lower cost has become a clinical challenge. Here, a facile sandwich type immunosensor based on surface-enhanced Raman scattering (SERS) was presented including 4-mercaptobenzonitrile (4MBN) labeled gold core-silver shell nanoparticles (Au@4MBN@Ag NPs) as SERS tag and 4-mercaptophenylboronic acid (4-MPBA) functionalized two-dimensional (2D) silver nanoparticle film (Ag FM) as SERS capture substrate for CEA detection. A linearity of 10-9-10-14M was observed with high sensitivity and excellent selectivity for the detection of CEA. Additionally, the spiking experiment yielded 105.33–127.00% recovery with variation coefficients below 10% demonstrating high assay accuracy and precision. The immunosensor we proposed here is a promising approach to quantify CEA in liquid biopsy samples with high sensitivity, which could be further developed for early cancer screening.

Immobilization-free electrochemical homogeneous aptasensor for highly sensitive detection of carcinoembryonic antigen by dual amplification strategy

Electrochemical aptasensor has been widely studied, while its practical application is limited by the unavoidable variations of aptamer loading densities and low signal amplification efficiency. To overcome these restrictions, an immobilization-free and label-free electrochemical homogeneous aptasensor was constructed for carcinoembryonic antigen (CEA) assay by combining RecJf exonuclease-mediated target cycling strategy and rolling circle amplification technology. In this system, the pre-immobilization of aptamers or other relevant signal elements on the electrode substrate is no longer necessary, thus the electrochemical homogeneous aptasensor shows good versatility on different transducers. Moreover, the whole recognition and signal amplification process are activated instantaneously by a non-professional operation of the solution mixture. This strategy can not only increase the stability (95.1% after 30 days of storage) and reproducibility (2.12% among five independent electrodes), but also further improve the sensitivity (detection limit of fg mL−1 level) due to the free target recognition and dual signal amplification in the homogeneous solution phase. The proposed immobilization-free electrochemical homogeneous aptasensors on different electrode substrates both achieve satisfactory results in actual sample tests, which has the potential for commercial applications and the establishment of other target platforms in the future.

Homogeneous Electrochemical Aptamer Sensor Based on Two-Dimensional Nanocomposite Probe and Nanochannel Modified Electrode for Sensitive Detection of Carcinoembryonic Antigen.

A rapid and convenient homogeneous aptamer sensor with high sensitivity is highly desirable for the electrochemical detection of tumor biomarkers. In this work, a homogeneous electrochemical aptamer sensor is demonstrated based on a two-dimensional (2D) nanocomposite probe and nanochannel modified electrode, which can realize sensitive detection of carcinoembryonic antigen (CEA). Using π-π stacking and electrostatic interaction, CEA aptamer (Apt) and cationic redox probe (hexaammineruthenium(III), Ru(NH3)63+) are co-loaded on graphite oxide (GO), leading to a 2D nanocomposite probe (Ru(NH3)63+/Apt@GO). Vertically ordered mesoporous silica-nanochannel film (VMSF) is easily grown on the supporting indium tin oxide (ITO) electrode (VMSF/ITO) using the electrochemical assisted self-assembly (EASA) method within 10 s. The ultrasmall nanochannels of VMSF exhibits electrostatic enrichment towards Ru(NH3)63+ and size exclusion towards 2D material. When CEA is added in the Ru(NH3)63+/Apt@GO solution, DNA aptamer recognizes and binds to CEA and Ru(NH3)63+ releases to the solution, which can be enriched and detected by VMSF/ITO electrodes. Based on this mechanism, CEA can be an electrochemical detection ranging from 60 fg/mL to 100 ng/mL with a limit of detection (LOD) of 14 fg/mL. Detection of CEA in human serum is also realized. The constructed homogeneous detection system does not require the fixation of a recognitive aptamer on the electrode surface or magnetic separation before detection, demonstrating potential applications in rapid, convenient and sensitive electrochemical sensing of tumor biomarkers.

Gold nanoparticles modified reduced graphene oxide nanosheets based dual-quencher for highly sensitive detection of carcinoembryonic antigen

In the current scenario, the dominance of cancer is becoming a disastrous threat to mankind. Therefore, an advanced analytical approach is desired as the need of the hour for early diagnosis to curb the menace of cancer. In this context, the present work reports the development of nano surface energy transfer (NSET) based fluorescent immunosensor for carcinoembryonic antigen (CEA) detection utilizing protein functionalized graphene quantum dots (anti-CEA/amine-GQDs) and a nanocomposite of nanostructured gold and reduced graphene oxide (AuNPs@rGO) as energy donor-acceptor pair, respectively. The obtained AuNPs@rGO nanocomposite has been characterized by different advanced analytical techniques. The functionality of the biosensor depends on quenching the fluorescence of anti-CEA/amine-GQDs donor species by AuNPs@rGO acceptor species, followed by the gradual recovery of GQDs' fluorescence after CEA addition. The efficient energy transfer kinetics have been envisaged by utilizing the AuNPs@rGO nanocomposite as a dual-quencher nanoprobe that revealed improved energy transfer and quenching efficiency (∼62 %, 88 %) compared to AuNPs (∼43 %, 81 %) as a single quencher. Further, the developed biosensing platform successfully detected CEA biomarker with notable biosensing parameters, including a wider linear detection range (0.001–500 ng mL−1), fast response time (24 min), and a significantly low detection limit (0.35 pg mL−1).

Ultrasensitive detection of carcinoembryonic antigen based on exonuclease Ⅲ-assisted recycling and hybridization chain reaction strategies

In this work, we developed a novel ratiometric electrochemical aptasensor for the sensitive detection of carcinoembryonic antigen (CEA). Upon the addition of CEA, the specific binding between CEA and hairpin probe 1 (HP1) could trigger the Exo Ⅲ cleavage reaction and release large amounts of single stranded DNA (S1), which then hybridized with thiolated ferrocene-labeled hairpin probe 3 (Fc-HP3) on the electrode surface. Exo Ⅲ then cyclically digested the resulting duplexes to generate Fc-HP3 fragments on the electrode, accompanying the Fc molecules far away from the electrode surface and the Fc oxidation peak current signal (IFc) decreased. The HCR process was triggered by the Fc-HP3 fragment as an initiator, producing many long DNA sequences for electroactive probe methylene blue (MB) intercalation; thus, the MB oxidation peak current signal (IMB) increased. The IMB/IFc ratio was proportional to the logarithm value of CEA concentration from 100 fg mL−1 to 50 ng mL−1, with a lower detection limit of 30.5 fg mL−1. Furthermore, the aptasensor exhibited good selectivity and stability, with satisfactory reproducibility. Additionally, the developed aptasensor effectively measured CEA in real serum samples, verifying its practical application in biological samples.

Ag/MoO3–Pd-mediated gasochromic reaction: An efficient dual-mode photoelectrochemical and photothermal immunoassay

Herein, we presented a dual-readout gasochromic immunosensing platform for accurate and sensitive detection of carcinoembryonic antigen (CEA) based on Ag-doped/Pd nanoparticles loaded MoO3 nanorods (Ag/MoO3–Pd). Initially, the presence of analyte CEA would prompt the formation of sandwich-type immunoreaction, accompanied by the introduction of Pt NPs labeled on detection antibody. Upon the addition of NH3BH3, the product hydrogen (H2) will interact with Ag/MoO3–Pd as a bridge between the sensing interface and the biological assembly platform. Both photocurrent and temperature signals can serve as readouts due to the significantly increased PEC performance and enhanced photothermal conversion capability of H–Ag/MoO3–Pd (the product of Ag/MoO3–Pd react with H2) compared to Ag/MoO3–Pd. In addition, the DFT results show that the band gap of Ag/MoO3–Pd becomes narrower after the reaction with H2, thus improving the utilization of light, which theoretically explains the internal mechanism of gas sensing reaction. Under optimal conditions, the designed immunosensing platform showed good sensitivity for CEA detection with the limit of detection (LOD) of 26 pg mL−1 (photoelectrochemical mode) and 98 pg mL−1 (photothermal mode). This work not only presents the possible reaction mechanism of Ag/MoO3–Pd and H2, but also creatively applicate it in photothermal biosensors that give a new path for devising dual-readout immunosensor.

Metal–Organic Framework-Mediated Bioorthogonal Reaction to Immobilize Bacteria for Ultrasensitive Fluorescence Counting Immunoassays

Ultrasensitive quantification of protein biomarkers has significant implications in disease diagnosis. Herein, we report a fluorescent bacteria counting immunoassay (FBCIA) strategy for protein biomarker detection based on a cascade signal conversion and amplification strategy including the copper metal-organic framework (Cu-MOF)-mediated Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) for fluorescent bacteria immobilization that converted the concentration of target protein to countable bacterial number and the further self-proliferation of bacteria to amplify the detectable bacterial number. The developed low-background and enzyme-free cascade methodology achieved highly sensitive detection of carcinoembryonic antigen (CEA) and prostate-specific antigen (PSA) with detection limits down to 0.8 pg/mL and 64.5 fg/mL, respectively. On top of that, we also developed a smartphone device for visualizing individual bacteria and point-of-care counting of the resulting bacteria for the detection of clinical samples. The good consistency between FBCIA and clinical enzyme-linked immunosorbent assay (ELISA) validated the high reliability and promising potential of our developed platform in clinical applications.

PEC/Colorimetric Dual-Mode Lab-on-Paper Device via BiVO4/FeOOH Nanocomposite In Situ Modification on Paper Fibers for Sensitive CEA Detection.

A dual-mode lab-on-paper device based on BiVO4/FeOOH nanocomposites as an efficient generating photoelectrochemical (PEC)/colorimetric signal reporter has been successfully constructed by integration of the lab-on-paper sensing platform and PEC/colorimetric detection technologies for sensitive detection of carcinoembryonic antigen (CEA). Concretely, the BiVO4/FeOOH nanocomposites were in situ synthesized onto the paper-working electrode (PWE) through hydrothermal synthesis of the BiVO4 layer on cellulose fibers (paper-based BiVO4) which were initially modified by Au nanoparticles for improving the conductivity of three dimensional PWE, and then the photo-electrodeposition of FeOOH onto the paper-based BiVO4 to construct the paper-based BiVO4/FeOOH for the portable dual-mode lab-on-paper device. The obtained nanocomposites with an FeOOH needle-like structure deposited on the BiVO4 layer exhibits enhanced PEC response activity due to its effective separation of the electron-hole pair which could further accelerate the PEC conversion efficiency during the sensing process. With the introduction of CEA targets onto the surface of nanocomposite-modified PWE assisted by the interaction with the CEA antibody from a specific recognition property, a signal-off PEC signal state with a remarkable photocurrent response decreasing trend can be achieved, realizing the quantitative detection of CEA with the PEC signal readout mode. By means of a smart origami paper folding, the colorimetric signal readout is achieved by catalyzing 3,3',5,5'-tetramethylbenzidine (TMB) to generate blue oxidized TMB in the presence of H2O2 due to the satisfied enzyme-like catalytic activity of the needle-like structure, FeOOH, thereby achieving the dual-mode signal readout system for the proposed lab-on-paper device. Under the optimal conditions, the PEC and colorimetric signals measurement were effectively carried out, and the corresponding linear ranges were 0.001-200 ng·mL-1 and 0.5-100 ng·mL-1 separately, with the limit of detection of 0.0008 and 0.013 ng·mL-1 for each dual-mode. The prepared lab-on-paper device also presented a successful application in serum samples for the detection of CEA, providing a potential pathway for the sensitive detection of target biomarkers in clinical application.