Detection Of Tumor Biomarkers Research Articles

Dual-signal biosensor based on G-quadruplex/hemin DNAzyme and zinc-doped molybdenum disulfide quantum dots for ultrasensitive detection of tumor biomarker

Herein, a dual-mode fluorometric and colorimetric biosensor for Pax-5a gene was developed based on zinc-doped molybdenum disulfide quantum dots (Zn-MoS2 QDs) by coupling exonuclease-assisted recycling amplification and peroxidase-mimic DNAzyme. In the presence of Pax-5a gene, the exonuclease III can cleave the duplexes formed by Pax-5a gene and the hairpin DNA (HP), releasing the output DNA (oDNA). G-rich DNA and magnetic beads (MBs) labeled with capture DNA (cDNA) can hybridize with oDNA to form the MBs-cDNA/oDNA/G-rich DNA sandwich complex. The remaining G-rich DNA in the supernatant through magnetic separation could bind hemin to produce G-quadruplex/hemin peroxidase-mimicking DNAzyme, which catalyzed the oxidization of 3,3'-diaminobenzidine (DAB) by H2O2. The generated brown oxidation product (oxDAB) had a distinct absorption peak at 464 nm and could quench the fluorescence of Zn-MoS2 QDs at 406 nm. The high peroxidase activity of DNAzyme, recycling amplification strategy and magnetic separation technique led to excellent sensitivity and specificity of this detection platform. The detection limits of Pax-5a gene by fluorometric and colorimetric methods were 0.52 pM and 1.12 pM, respectively. Furthermore, this sensing system was successfully applied to Pax-5a gene determination in human serum samples, which had promising potential in biochemical analysis and clinical diagnosis.

Solid-phase electrochemiluminescence immunosensing platform based on bipolar nanochannel array film for sensitive detection of carbohydrate antigen 125.

Development of simple solid-phase electrochemiluminescence (ECL) immunosensor with convenient fabrication for high-performance detection of tumor biomarkers is crucial. Herein, a solid-phase ECL immunoassay was constructed based on a bipolar silica nanochannel film (bp-SNA) modified electrode for highly sensitive detection of carbohydrate antigen 125 (CA 125). Inexpensive and readily available indium tin oxide (ITO) electrode was used as the supporting electrode for the growth of bp-SNA. bp-SNA consists of a bilayer SNA film with different functional groups and charge properties, including negatively charged inner layer SNA (n-SNA) and positively charged outer layer SNA (p-SNA). The nanochannels of bp-SNA were used for the immobilization of ECL emitter tris(bipyridine)ruthenium(II), while the outer surface was utilized for constructing the immunorecognition interface. Due to the dual electrostatic interaction composed of electrostatic attraction from n-SNA and electrostatic repulsion from p-SNA, ECL emitter could be stably confined within bp-SNA, providing stable and high ECL signals to the modified electrode. After amino groups on the outer surface of bp-SNA were derivatized with aldehyde groups, recognition antibodies could be covalently immobilized, and an immunosensor was obtained after blocking nonspecific sites. When CA 125 binds to the antibodies on the recognition interface, the formed complex reduces the diffusion of the co-reactant tripropylamine (TPrA) to the supporting electrode, decreasing the ECL signal. Based on this mechanism, the constructed immunosensor can achieve sensitive ECL detection of CA 125. The linear detection range is from 0.01 to 100U/mL, with a detection limit of 4.7mU/mL. CA 125 detection in serum is also achieved. The construction immunosensor has advantages including simple and convenient fabrication, high stability of the immobilized emitter, and high selectivity, making it suitable for CA 125 detection.

Enhanced Electrochemiluminescence of Luminol and-Dissolved Oxygen by Nanochannel-Confined Au Nanomaterials for Sensitive Immunoassay of Carcinoembryonic Antigen.

Simple development of an electrochemiluminescence (ECL) immunosensor for convenient detection of tumor biomarker is of great significance for early cancer diagnosis, treatment evaluation, and improving patient survival rates and quality of life. In this work, an immunosensor is demonstrated based on an enhanced ECL signal boosted by nanochannel-confined Au nanomaterial, which enables sensitive detection of the tumor biomarker-carcinoembryonic antigen (CEA). Vertically-ordered mesoporous silica film (VMSF) with a nanochannel array and amine groups was rapidly grown on a simple and low-cost indium tin oxide (ITO) electrode using the electrochemically assisted self-assembly (EASA) method. Au nanomaterials were confined in situ on the VMSF through electrodeposition, which catalyzed both the conversion of dissolved oxygen (O2) to reactive oxygen species (ROS) and the oxidation of a luminol emitter and improved the electrode active surface. The ECL signal was enhanced fivefold after Au nanomaterial deposition. The recognitive interface was fabricated by covalent immobilization of the CEA antibody on the outer surface of the VMSF, followed with the blocking of non-specific binding sites. In the presence of CEA, the formed immunocomplex reduced the diffusion of the luminol emitter, resulting in the reduction of the ECL signal. Based on this mechanism, the constructed immunosensor was able to provide sensitive detection of CEA ranging from 1 pg·mL-1 to 100 ng·mL-1 with a low limit of detection (LOD, 0.37 pg·mL-1, S/N = 3). The developed immunosensor exhibited high selectivity and good stability. ECL determination of CEA in fetal bovine serum was achieved.

A Smartphone-Mediated "All-In-One" Biosensing Chip for Visual and Value-Assisted Detection.

A smartphone-mediated self-powered biosensor is fabricated for miRNA-141 detection based on the CRISPR/Cas12a cross-cutting technique and a highly efficient nanozyme. As a novel nanozyme and a signal-amplified coreaction accelerator, the AuPtPd@GDY nanozyme exhibits an excellent ability to catalyze cascade color reactions and high conductivity to enhance the electrochemical signal for miRNA-141 assays. After CRISPR/Cas12a cross-cutting of S2-glucose oxidase (S2-GOD), the electrochemical signal is weakened, and miRNA-141 is detected by monitoring the decrease in the signal. On the other hand, a cascade reaction among glucose, H2O2, and TMB is catalyzed by GOD and AuPtPd@GDY, respectively, resulting in a color change of the solution, which senses miRNA-141. The self-powered biosensor enables value-assisted and visual detection of miRNA-141 with limits of detection of 3.1 and 15 aM, respectively. Based on the dual-modal self-powered sensing system, a smartphone-mediated "all-in-one" biosensing chip is designed to achieve the real-time and intelligent monitoring of miRNA-141. This work provides a new approach to design multifunctional biosensors to realize the visualization and portable detection of tumor biomarkers.

CRISPR/Cas12a cleavage triggered nanoflower for fluorescence-free and target amplification-free biosensing of ctDNA in the terahertz frequencies.

The detection of tumor biomarkers in liquid biopsies requires high sensitivity and low-cost biosensing strategies. However, few traditional techniques can satisfy the requirements of target amplification-free and fluorescence-free at the same time. In this study, we have proposed a novel strategy for ctDNA detection with the combination of terahertz spectroscopy and the CRISPR/Cas12 system. The CRISPR/Cas12a system is activated by the target ctDNA, resulting in a series of reactions leading to the formation of an Au-Fe complex. This complex is easily extracted with magnets and when dropped onto the terahertz metamaterial sensor, it can enhance the frequency shift, providing sensitive and selective sensing of the target ctDNA. Results show that the proposed terahertz biosensor exhibits a relatively low detection limit of 0.8 fM and a good selectivity over interference species. This detection limit is improved by three orders of magnitude compared with traditional biosensing methods using terahertz waves. Furthermore, a ctDNA concentration of 100 fM has been successfully detected in bovine serum (corresponding to 50 fM in the final reaction system) without amplification.

3D Printed Nanosensors for Cancer Diagnosis: Advances and Future Perspective.

Cancer is the leading cause of mortality worldwide, requiring continuous advancements in diagnosis and treatment. Traditional methods often lack sensitivity and specificity, leading to the need for new methods. 3D printing has emerged as a transformative tool in cancer diagnosis, offering the potential for precise and customizable nanosensors. These advancements are critical in cancer research, aiming to improve early detection and monitoring of tumors. In current times, the usage of the 3D printing technique has been more prevalent as a flexible medium for the production of accurate and adaptable nanosensors characterized by exceptional sensitivity and specificity. The study aims to enhance early cancer diagnosis and prognosis by developing advanced 3D-printed nanosensors using 3D printing technology. The research explores various 3D printing techniques, design strategies, and functionalization strategies for cancer-specific biomarkers. The integration of these nanosensors with detection modalities like fluorescence, electrochemical, and surface-enhanced Raman spectroscopy is also evaluated. The study explores the use of inkjet printing, stereolithography, and fused deposition modeling to create nanostructures with enhanced performance. It also discusses the design and functionalization methods for targeting cancer indicators. The integration of 3D-printed nanosensors with multiple detection modalities, including fluorescence, electrochemical, and surface-enhanced Raman spectroscopy, enables rapid and reliable cancer diagnosis. The results show improved sensitivity and specificity for cancer biomarkers, enabling early detection of tumor indicators and circulating cells. The study highlights the potential of 3D-printed nanosensors to transform cancer diagnosis by enabling highly sensitive and specific detection of tumor biomarkers. It signifies a pivotal step forward in cancer diagnostics, showcasing the capacity of 3D printing technology to produce advanced nanosensors that can significantly improve early cancer detection and patient outcomes.

Cascade signal amplifying strategy for ultrasensitive detection of tumor biomarker by DNAzyme cleaving mediated HCR

Tumor biomarkers are a kind of important biomolecules for aiding cancer diagnosis and assessing tumor efficacy, among which alpha-fetoprotein (AFP) is a crucial tumor biomarker for the early diagnosis of hepatocellular carcinoma. In this study, a novel cascade signal amplifying strategy was designed for the ultrasensitive detection of AFP by DNAzyme cleaving-mediated hybridization chain reaction (HCR). The primary antibody was immobilized on the Au nanoparticles modified glassy carbon electrode, which subsequently captured AFP and the secondary antibody. Then, streptavidin was combined with the biotin-modified secondary antibody and Cu2+-specific DNAzyme. When Cu2+ was present, the substrate strand of the DNAzyme would cleave and produce an ssDNA end. Finally, HCR was triggered to form long double-stranded DNA on the electrode, which would greatly inhibit the charge transfer at the electrode/solution interface. Therefore, the DNAzyme cleaving-mediated HCR strategy can be applied as cascade signal amplification for the ultrasensitive electrochemical determination of tumor biomarker AFP. Under optimal conditions, the immunosensor exhibits a broad linear range of 0.001−100 ng·mL−1 (R2 = 0.990) and a low detection limit of 15.8 fg·mL−1. The proposed sensor displays high sensitivity and selectivity for AFP detection, which can be employed as a universal sensing platform in clinical diagnostics.

Nanochannel-confined platinum nanostructure for enhancement of luminol-dissolved oxygen electrochemiluminescence coupled with gated aptasensor for sensitive detection of carcinoembryonic antigen

Rapid and precise detection of tumor biomarkers in serum is of great significance for early diagnosis, treatment assessment, and recurrence monitoring of cancers. The fabrication of user-friendly electrochemiluminescence (ECL) aptasensors with effective signal amplification is highly desirable. In this study, an ECL aptasensor was developed with luminol-based ternary ECL platform using dissolved oxygen as endogenous co-reactant and nanochannel-confined platinum nanoparticles (PtNPs) as co-reactant promoter, which can realize highly sensitive detection of the tumor biomarker, carcinoembryonic antigen (CEA). On the cost-effective indium tin oxide (ITO) electrode, amino-modified vertically-ordered mesoporous silica film (NH2-VMSF) was easily grown to form high-density nanochannel array with ultrasmall nanochannels. PtNPs were then in-situ synthesized within the nanochannels via electrodeposition. Ternary ECL system was successfully fabricated as confined PtNPs can catalyze the electroreduction of dissolved oxygen at negative potentials as well as electrochemical oxidation of luminol, enhancing the ECL signal of luminol. The recognitive aptamer (Apt) was covalently immobilized on the outer surface of NH2-VMSF, resulting in the fabrication of an aptasensor. In presence of CEA, a decreased ECL signal was obtained as the formed complex on the recognition interface hindered the diffusion of ECL emitter to the supporting electrode. Based on this signal turn-off mode, sensitive detection of CEA was achieved ranged from 10 fg mL−1 to 100 ng mL−1, with a low detection limit (DL, 0.4 fg mL−1). The aptasensor displayed high selectivity and good reproducibility. The nanochannel-based aptasensor and ternary ECL system demonstrates great potential in convenient and sensitive detection of cancer biomarker.

A multifunctional N-GO/PtCo nanocomposite bridged carbon fiber interface for the electrochemical aptasensing of CA15-3 oncomarker

The development of integrated analytical devices is crucial for advancing next-generation point-of-care platforms. Herein, we describe a facile synthesis of a strongly catalytic and durable Nitrogen-doped graphene oxide decorated platinum cobalt (NGO-PtCo) nanocomposite that is conjugated with target-specific DNA aptamer (i-e. MUC1) and grown on carbon fiber. Benefitting from the combined features of the high electrochemical surface area of N-doped GO, high capacitance and stabilization by Co, and high kinetic performance by Pt, a robust, multifunctional, and flexible nanotransducer surface was created. The designed platform was applied for the specific detection of a blood-based oncomarker, CA15-3. The electrochemical characterization proved that nanosurface provides a highly conductive and proficient immobilization support with a strong bio-affinity towards MUC1 aptamer. The specific interaction between CA15-3 and the aptamer alters the surface properties of the aptasensor and the electroactive signal probe generated a remarkable increase in signal intensity. The sensor exhibited a wide dynamic range of 5.0 × 10−2 -200 U mL−1, a low limit of detection (LOD) of 4.1 × 10−2 U mL−1, and good reproducibility. The analysis of spiked serum samples revealed outstanding recoveries of up to 100.03 %, by the proposed aptasensor. The aptasensor design opens new revelations in the reliable detection of tumor biomarkers for timely cancer diagnosis.

Click-response-driven high-speed and ultrasensitive electrochemical sensing interface: Addressing its accuracy challenge

For electrochemical sensors, maintaining accuracy while achieving sensitive detection is of paramount importance. The fixation of the signal substance as one of the main steps in the construction process of a sensor has a significant impact on the accuracy. Currently, physical and chemical methods are the primary approaches for the fixation of the signal substance, which have the following issues. The accuracy of a sensor may be affected by the instability resulting from the physical immobilization of the signal substance and the chemical immobilization process is typically time-consuming. To overcome these obstacles, the ultra-sensitive electrochemical sensing interface is constructed by click reaction to achieve accurate and rapid detection of tumor biomarkers. After the formation of immune-sandwich structure in a test tube, a large amount of ethynylferrocene (EFc) molecules in the Zeolitic imidazolate frameworks (ZIF-8) immunoprobe are released under acidic conditions, followed by covalently linking to the substrate within 6 minutes through a click reaction. Under optimal conditions, the electrochemical sensor had an ultralow detection limit of 32.90 fg mL−1 for the model analyte (CEA) with a wide detection range from 100 fg mL−1 to 100 ng mL−1. This work provides a new perspective for designing electrochemical sensors with excellent performance.

Dynamically controllable hot spots in DNA-derived hydrogel scaffold SERS substrate for exosome recognition using DNA self-assembly amplification

In the context of surface-enhanced Raman scattering (SERS) applications, an effective active substrate is supposed to exhibit a high enhancement factor, long-term stability, and excellent repeatability, as well as allow target molecules to enter the hot spot area with adequate quantity and affinity. The electromagnetic field in hot spots can be drastically amplified and results in an extraordinary large signal enhancement. However, uncontrolled formation of hot spots has hampered the realization of this intention. Here, we reported an innovative SERS active substrate, named as DNA-derived dynamic hydrogel scaffold (DDHS), which is endowed with the robust electromagnetic enhancement and exceptional target affinity. Based on this integrated microfluidic chip, rationally designed DNA oligonucleotides were introduced to recognize exosome indicator-CD63, which achieved a limit of 2.63 particles μL−1. Taken together, we believed that the proposed strategy would be possible to accelerate SERS applied to trace detection of tumor biomarkers, thus offering a promising route toward screening test and early diagnostic of cancerdiseases.

Enhancing electrochemical detection through machine learning-driven prediction for canine mammary tumor biomarker with green silver nanoparticles

This study developed an innovative biosensor strategy for the sensitive and selective detection of canine mammary tumor biomarkers, cancer antigen 15–3 (CA 15–3) and mucin 1 (MUC-1), integrating green silver nanoparticles (GAgNPs) with machine learning (ML) algorithms to achieve high diagnostic accuracy and potential for noninvasive early detection. The GAgNPs-enhanced electrochemical biosensor demonstrated selective detection of CA 15–3 in serum and MUC-1 in tissue homogenates, with limits of detection (LODs) of 0.07 and 0.11 U mL−1, respectively. The nanoscale dimensions of the GAgNPs endowed them with electrochemically active surface areas, facilitating sensitive biomarker detection. Experimental studies targeted CA 15–3 and MUC-1 biomarkers in clinical samples, and the biosensor exhibited ease of use and good selectivity. Furthermore, ML algorithms were employed to analyze the electrochemical data and predict biomarker concentrations, enhancing the diagnostic accuracy. The Random Forest algorithm achieved 98% accuracy in tumor presence prediction, while an Artificial Neural Network attained 76% accuracy in CA 15–3-based tumor grade classification. The integration of ML techniques with the GAgNPs-based biosensor offers a promising approach for noninvasive, accurate, and early detection of canine mammary tumors, potentially revolutionizing veterinary diagnostics. This multilayered strategy, combining eco-friendly nanomaterials, electrochemical sensing, and ML algorithms, holds significant potential for advancing both biomedical research and clinical practice in the field of canine mammary tumor diagnostics.Graphical

Recent Advancements in the Application of Circulating Tumor DNA as Biomarkers for Early Detection of Cancers.

Early detection of cancer is vital for increasing patient survivability chances. The three major techniques used to diagnose cancers are instrumental examination, tissue biopsy, and tumor biomarker detection. Circulating tumor DNA (ctDNA) has gained much attention in recent years due to advantages over traditional technology, such as high sensitivity, high specificity, and noninvasive nature. Through the mechanism of apoptosis, necrosis, and circulating exosome release in tumor cells, ctDNA can spread throughout the circulatory system and carry modifications such as methylations, mutations, gene rearrangements, and microsatellite instability. Traditional gene-detection technology struggles to achieve real-time, low-cost, and portable ctDNA measurement, whereas electrochemical biosensors offer low cost, high specificity alongside sensitivity, and portability for the detection of ctDNA. Therefore, this review focuses on describing the recent advancements in ctDNA biomarkers for various cancer types and biosensor developments for real-time, noninvasive, and rapid ctDNA detection. Further in the review, ctDNA sensors are also discussed in regards to their selections of probes for receptors based on the electrode surface recognition elements.

Multiplexed electrochemical nucleic acid sensor based on visible light-mediated metal-free thiol-yne click reaction for simultaneous detection of different nucleic acid targets

Simultaneous detection of multiple tumor biomarkers with a simple and low-cost assay is crucial for early cancer detection and diagnosis. Herein, we presented a low-cost and simple assay for multiplexed detection of tumor biomarkers using a spatially separated electrodes strategy. The sensor is fabricated based on a metal-free thiol-yne click reaction, which is mediated by visible light, on commercially available indium tin oxide (ITO) electrodes. Four biomarkers, including p53 DNA, Brca2 DNA, K-ras DNA, and MicroRNA-204 RNA, were used as model analytes, and the corresponding oligonucleotide probes were modified on the desired electrode units sequentially with 530 nm irradiation light in the presence of photosensitizer Eosin Y. By this visible light-mediated coupling reaction, oligonucleotide probe densities of up to 9.2 ± 0.7 × 1010 molecules/cm2 were readily obtained on the ITO electrode surface. The proposed multiplexed E-NA sensor could detect four different nucleic acid targets concurrently without crosstalk among adjacent electrodes and was also successfully applied for detecting targets in a 20% fetal calf serum sample. The detection limits for p53 DNA, Brca2 DNA, K-ras DNA, and MicroRNA-204 RNA were 0.72 nM, 0.97 nM, 2.15 nM, and 1.73 nM, respectively. The developed approach not only has a great potential for developing cost-effective biosensors on affordable substrates for nucleic acid target detection, but also be easily extended to detect other targets by modifying the specific oligonucleotide probes anchored on the electrode.

Tumor biomarkers for diagnosis, prognosis and targeted therapy.

Tumor biomarkers, the substances which are produced by tumors or the body's responses to tumors during tumorigenesis and progression, have been demonstrated to possess critical and encouraging value in screening and early diagnosis, prognosis prediction, recurrence detection, and therapeutic efficacy monitoring of cancers. Over the past decades, continuous progress has been made in exploring and discovering novel, sensitive, specific, and accurate tumor biomarkers, which has significantly promoted personalized medicine and improved the outcomes of cancer patients, especially advances in molecular biology technologies developed for the detection of tumor biomarkers. Herein, we summarize the discovery and development of tumor biomarkers, including the history of tumor biomarkers, the conventional and innovative technologies used for biomarker discovery and detection, the classification of tumor biomarkers based on tissue origins, and the application of tumor biomarkers in clinical cancer management. In particular, we highlight the recent advancements in biomarker-based anticancer-targeted therapies which are emerging as breakthroughs and promising cancer therapeutic strategies. We also discuss limitations and challenges that need to be addressed and provide insights and perspectives to turn challenges into opportunities in this field. Collectively, the discovery and application of multiple tumor biomarkers emphasized in this review may provide guidance on improved precision medicine, broaden horizons in future research directions, and expedite the clinical classification of cancer patients according to their molecular biomarkers rather than organs of origin.

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.

New Perspectives on the Role of Liquid Biopsy in Bladder Cancer: Applicability to Precision Medicine.

Bladder cancer (BC) is one of the most common tumors in the world. Cystoscopy and tissue biopsy are the standard methods in screening and early diagnosis of suspicious bladder lesions. However, they are invasive procedures that may cause pain and infectious complications. Considering the limitations of both procedures, and the recurrence and resistance to BC treatment, it is necessary to develop a new non-invasive methodology for early diagnosis and multiple evaluations in patients under follow-up for bladder cancer. In recent years, liquid biopsy has proven to be a very useful diagnostic tool for the detection of tumor biomarkers. This non-invasive technique makes it possible to analyze single tumor components released into the peripheral circulation and to monitor tumor progression. Numerous biomarkers are being studied and interesting clinical applications for these in BC are being presented, with promising results in early diagnosis, detection of microscopic disease, and prediction of recurrence and response to treatment.

Sensitive Electrochemical Detection of Carcinoembryonic Antigen Based on Biofunctionalized Nanochannel Modified Carbonaceous Electrode.

The convenient construction of carbon-based electrochemical immunosensors with high performance is highly desirable for the efficient detection of tumor biomarkers. In this work, an electrochemical immunosensor was fabricated by integrating a biofunctionalized mesoporous silica nanochannel film with a carbon-based electrode, which can enable the sensitive determination of carcinoembryonic antigen (CEA) in serum. The commonly used carbonaceous electrode, glassy carbon electrode (GCE), was employed as the supporting electrode and was pre-treated through electrochemical polarization to achieve the stable binding of a vertically ordered mesoporous silica film with amino groups (NH2-VMSF) without the use of any adhesive layer. To fabricate the immunorecognition interface, antibodies were covalently immobilized after the amino groups on the outer surface of NH2-VMSF was derivatized to aldehyde groups. The presence of amino sites within the high-density nanochannels of NH2-VMSF can facilitate the migration of negatively charged redox probes (Fe(CN)63-/4-) to the supporting electrode through electrostatic adsorption, leading to the generation of electrochemical signals. In the presence of CEA, the formation of immunocomplexes on the recognitive interface can reduce the electrochemical signal of Fe(CN)63-/4- on the supporting electrode. Based on this principle, the sensitive electrochemical detection of CEA was achieved. CEA can be determined to range from 0.01 ng mL-1 to 100 ng mL-1 with a limit of detection of 6.3 pg mL-1. The fabricated immunosensor exhibited high selectivity, and the detection of CEA in fetal bovine serum was achieved.

Smartphone-assisted self-powered dual-mode biosensor designed on binary 3D DNA Walkers mediated CRISPR/Cas12a system

Malignant tumors are significant diseases that pose a threat to human life and health. The advancement of highly sensitive and specific methods is of excellent significance. This study proposes a novel detection platform that employs a smartphone-assisted self-powered sensing system with binary 3D DNA Walkers mediated CRISPR/Cas12a system and ultra-thin 2D graphdiyne for ultrasensitive dual-mode detection of breast cancer biomarker microRNA-let-7a. The binary 3D DNA Walkers possess high efficiency in movement and multifunctional characteristics. When combined with the CRISPR/Cas12a system, they can retain the advantages of 3D DNA Walker while releasing a large of trigger strands complementary to CRISPR RNA, thereby greatly enhancing the sensitivity of the sensor. In addition, capacitors are also integrated into the sensing system to further amplify the detection signal, resulting in a 20.7-fold increase in sensitivity of the method. Additionally, the adoption of an electrochemical/colorimetric dual-mode detection strategy significantly enhances the accuracy of the new approach. The newly developed detection method exhibits a linear range of 0.0001–10000 pM with a detection limit of 8.11 aM (S/N = 3). This work offers a reliable portable sensor for sensitive and accurate detection of tumor biomarkers, enabling remote disease sensing and on-site monitoring applications.

A Novel Label-Free Electrochemical Immunosensor for the Detection of Thyroid Transcription Factor 1 Using Ribbon-like Tungsten Disulfide-Reduced Graphene Oxide Nanohybrids and Gold Nanoparticles.

Thyroid transcription factor 1 (TTF1) is an important cancer-related biomarker for clinical diagnosis, especially for carcinomas of lung and thyroid origin. Herein, a novel label-free electrochemical immunosensor was prepared for TTF1 detection based on nanohybrids of ribbon-like tungsten disulfide-reduced graphene oxide (WS2-rGO) and gold nanoparticles (AuNPs). The proposed immunosensor employed H2O2 as the electrochemical probe because of the excellent peroxidase-like activity of ribbon-like WS2-rGO. The introduction of AuNPs not only enhanced the electrocatalytic activity of the immunosensor, but also provided immobilization sites for binding TTF1 antibodies. The electrochemical signals can be greatly amplified due to their excellent electrochemical performance, which realized the sensitive determination of TTF1 with a wide linear range of 0.025-50 ng mL-1 and a lower detection limit of 0.016 ng mL-1 (S/N = 3). Moreover, the immunosensor exhibited high selectivity, good reproducibility, and robust stability, as well as the ability to detect TTF1 in human serum with satisfactory results. These observed properties of the immunosensor enhance its potential practicability in clinical applications. This method can also be used for the detection of other tumor biomarkers by using the corresponding antigen-antibody complex.