Detection Of Disease Biomarkers Research Articles

Ultrasensitive Detection of Blood-Based Alzheimer's Disease Biomarkers: A Comprehensive SERS-Immunoassay Platform Enhanced by Machine Learning.

Accurate and early disease detection is crucial for improving patient care, but traditional diagnostic methods often fail to identify diseases in their early stages, leading to delayed treatment outcomes. Early diagnosis using blood derivatives as a source for biomarkers is particularly important for managing Alzheimer's disease (AD). This study introduces a novel approach for the precise and ultrasensitive detection of multiple core AD biomarkers (Aβ40, Aβ42, p-tau, and t-tau) using surface-enhanced Raman spectroscopy (SERS) combined with machine-learning algorithms. Our method employs an antibody-immobilized aluminum SERS substrate, which offers high precision, sensitivity, and accuracy. The platform achieves an impressive detection limit in the attomolar (aM) range and spans a wide dynamic range from aM to micromolar (μM) concentrations. This ultrasensitive and specific SERS immunoassay platform shows promise for identifying mild cognitive impairment (MCI), a potential precursor to AD, from blood plasma. Machine-learning algorithms applied to the spectral data enhance the differentiation of MCI from AD and healthy controls, yielding excellent sensitivity and specificity. Our integrated SERS-machine-learning approach, with its interpretability, advances AD research and underscores the effectiveness of a cost-efficient, easy-to-prepare Al-SERS substrate for clinical AD detection.

Photothermally Active Quantum Dots in Cancer Imaging and Therapeutics: Nanotheranostics Perspective.

Cancer is becoming a global threat, as the cancerous cells manipulate themselves frequently, resulting in mutants and more abnormalities. Early-stage and real-time detection of cancer biomarkers can provide insight into designing cost-effective diagnostic and therapeutic modalities. Nanoparticle and quantum dot (QD)-based approaches have been recognized as clinically relevant methods to detect disease biomarkers at the molecular level. Over decades, as an emergent noninvasive approach, photothermal therapy has evolved to eradicate cancer. Moreover, various structures, viz., nanoparticles, clusters, quantum dots, etc., have been tested as bioimaging and photothermal agents to identify tumor cells selectively. Among them, QDs have been recognized as versatile probes. They have attracted enormous attention for imaging and therapeutic applications due to their unique colloidal stability, optical and physicochemical properties, biocompatibility, easy surface conjugation, scalable production, etc. However, a few critical concerns of QDs, viz., precise engineering for molecular imaging and sensing, selective interaction with the biological system, and their associated toxicity, restrict their potential intervention in curing cancer and are yet to be explored. According to the U.S. Food and Drug Administration (FDA), there is no specific regulation for the approval of nanomedicines. Therefore, these nanomedicines undergo the traditional drug, biological, and device approval process. However, the market survey of QDs is increasing, and their prospects in translational nanomedicine are very promising. From this perspective, we discuss the importance of QDs for imaging, sensing, and therapeutic usage pertinent to cancer, especially in its early stages. Moreover, we also discuss the rapidly growing translational view of QDs. The long-term safety studies and cellular interaction of these QDs could enhance their visibility and bring photothermally active QDs to the clinical stage and concurrently to FDA approval.

DNA Nanomaterial-Based Electrochemical Biosensors for Clinical Diagnosis.

Sensitive and quantitative detection of chemical and biological molecules for screening, diagnosis and monitoring diseases is essential to treatment planning and response monitoring. Electrochemical biosensors are fast, sensitive, and easy to miniaturize, which has led to rapid development in clinical diagnosis. Benefiting from their excellent molecular recognition ability and high programmability, DNA nanomaterials could overcome the Debye length of electrochemical biosensors by simple molecular design and are well suited as recognition elements for electrochemical biosensors. Therefore, to enhance the sensitivity and specificity of electrochemical biosensors, significant progress has been made in recent years by optimizing the DNA nanomaterials design. Here, the establishment of electrochemical sensing strategies based on DNA nanomaterials is reviewed in detail. First, the structural design of DNA nanomaterial is examined to enhance the sensitivity of electrochemical biosensors by improving recognition and overcoming Debye length. In addition, the strategies of electrical signal transduction and signal amplification based on DNA nanomaterials are reviewed, and the applications of DNA nanomaterial-based electrochemical biosensors and integrated devices in clinical diagnosis are further summarized. Finally, the main opportunities and challenges of DNA nanomaterial-based electrochemical biosensors in detecting disease biomarkers are presented in an aim to guide the design of DNA nanomaterial-based electrochemical devices with high sensitivity and specificity.

Ab Initio Molecular Dynamics Investigation of Water and Butanone Adsorption on UiO-66 with Defects.

Volatile organic compounds (VOCs) are harmful chemicals that are found in minute quantities in the atmosphere and are emitted from a variety of industrial and biological processes. They can be harmful to breathe or serve as biomarkers for disease detection. Therefore, capture and detection of VOCs is important. Here, we have examined if the Zr-based UiO-66 metal-organic framework (MOF) can be used to capture butanone─a well-known VOC. Toward that end, we have performed Born-Oppenheimer ab initio molecular dynamics (AIMD) at 300 and 500 K to probe the energetics and molecular interactions between butanone [CH3C(O)CH2CH3] and open-cage Zr-UiO-66. Such interactions were systematically interrogated using three MOF structures: defective MOF with a missing 1,4-benzene-dicarboxylate linker and two H2O; pristine MOF with two H2O; and pristine dry MOF. These structures were loaded with one and four molecules of butanone to examine the effect of concentration as well. One-molecule loading interacted favorably with the defective structure at 300 K, only. In comparison, interactions with four-molecule loading were energetically favorable for all conditions. Persistent hydrogen bonds between the O atom of butanone, H2O, and μ3-OH hydroxyl attachments at Zr nodes substantially contributed to the intermolecular interactions. At higher loadings, butanone also showed a pronounced tendency to diffuse into the adjoining cages of Zr-UiO-66. The effect of such movement on interaction energies was rationalized using simple statistical mechanics-based models of interacting and noninteracting gases. Broadly, we learn that the presence of prior moisture within the interstitial cages of Zr-UiO-66 significantly impacts the adsorption behavior of butanone.

Advances in Nanomaterial-Based Sensors for Early Disease Detection

Nanomaterial-based sensors are emerging as highly promising tools for the early detection of diseases, offering superior sensitivity, specificity, and miniaturization compared to traditional diagnostic methods. By leveraging the unique properties of nanomaterials such as gold nanoparticles, carbon nanotubes, graphene, and quantum dots, these sensors can detect disease biomarkers at much lower concentrations, enabling earlier diagnosis and intervention. This paper reviews the latest advancements in nanomaterial-based sensors, focusing on their applications in cancer, infectious diseases, and neurological disorders. Key developments include gold nanoparticle-based colorimetric sensors for cancer biomarker detection, graphene-based electrochemical sensors for prostate cancer and other malignancies, and quantum dot-based fluorescence sensors for both cancer and pathogen detection. Despite their promise, challenges remain, including issues with sensitivity, selectivity, reproducibility, biocompatibility, and scalability. Future directions for nanomaterial-based sensors involve improving their performance, developing multiplexed platforms for simultaneous detection of multiple biomarkers, and integrating these sensors into wearable or point-of-care devices. Overcoming these challenges and achieving regulatory approval will be crucial for the widespread clinical adoption of these advanced sensors, ultimately transforming healthcare by enabling more effective, rapid, and accessible early disease detection.

Optimizing Magnetic Separation and Cleaning Module in Fully Automated Chemiluminescence Immunoassay Analyzer Using a Special Arrangement of Spliced Magnets and a Three-Stage Magnetic Bead Collection Method

The magnetic separation and cleaning module, as a core component of the fully automated chemiluminescence immunoassay (CLIA) analyzer, encounters issues including high magnetic bead loss rate, long cleaning time, and poor cleaning effect. Based on a simulation analysis using COMSOL, we proposed a novel magnetic separation and cleaning module applied to a fully automated CLIA analyzer. The module adopted a method of arranging spliced rectangular magnets on opposite sides, where the same polarity faced each other, as well as a three-stage magnetic bead collection method. With the proposed method, the total cleaning process can be accomplished within 225 s; the total magnetic bead loss rate over three rounds of cleaning is 6.03%, whereas that of traditional instruments is 25.85%; the coefficient of variation (CV) of the magnetic bead loss rate is less than 0.5%; effective cleaning of free markers is achieved under various sample conditions. Compared with traditional CLIA instruments, this method comprehensively improves key performance indicators of the magnetic separation and cleaning module, providing a reference for similar modules in fully automated CLIA analyzers and positively impacting the accuracy of CLIA for the detection of disease biomarkers.

Electrografted Laser-Induced Graphene: Direct Detection of Neurodegenerative Disease Biomarker in Cerebrospinal Fluid.

There are more than 50 neurodegenerative disorders, and amyotrophic lateral sclerosis (ALS) is one of the most common disorders that poses diagnostic and treatment challenges. The poly glycine-proline (polyGP) dipeptide repeat is a toxic protein that has been recognized as a pharmacodynamic biomarker of C9orf72-associated (c9+) ALS, a subtype of ALS that originates from genetic mutation. Early detection of polyGP will help healthcare providers start timely gene therapy. Herein, we developed a label-free electrochemical immunoassay for the simple detection of polyGP in unprocessed cerebrospinal fluid (CSF) samples collected from ALS patients in the National ALS Biorepository. For the first time, an electrografted laser-induced graphene (E-LIG) electrode system was employed in a sandwich format to detect polyGP using a label-free electrochemical impedance technique. The results show that the E-LIG-modified surface exhibited high sensitivity and selectivity in buffer and CSF media with limit of detection values of 0.19 and 0.27 ng/mL, respectively. The precision of the calibration model was better in CSF than in the buffer. The E-LIG immunosensor can easily select polyGP targets in the presence of other dipeptide proteins translated from the c9 gene. Further study with CSF samples from ALS patients demonstrated that the label-free E-LIG-based immunosensor not only quantified polyGP in the complex CSF matrix but also distinguished between c9+ and non-c9- ALS patients.

Filter Membrane-Based Colorimetric Approach for Point-of-Care Detection of Biomarkers Using CRISPR-Cas12a.

CRISPR-Cas-based point-of-care testing (POCT) strategies have been widely explored for the detection of diverse biomarkers. However, these methods often require complicated operations, such as careful solution transfer steps, to achieve high sensitivity and accuracy. In this study, we combine a filter membrane-based POCT method with CRISPR-Cas12a for colorimetric detection of biomarkers. For the nucleic acid target, the trans-cleavage activity of CRISPR-Cas12a is directly triggered, cutting the single-stranded DNA linkers on glucose oxidase (GOx)-modified polymer nanoparticles. Due to the size difference between GOx and the polymer nanoparticles, GOx can be separated using a filter membrane. The filtrate containing GOx reacts with the substrate to generate a colorimetric signal. For the non-nucleic acid target, the non-nucleic acid signal is converted into a nucleic acid signal that activates CRISPR-Cas12a, resulting in a colorimetric signal. The entire operation is easy to perform, and the signal can be directly observed via the naked eye, which circumvents the use of costly instruments. The developed strategy holds great promise for accurate and accessible POCT detection of disease biomarkers in resource-limited settings.

Development and Optimization of Micro‐Nanotopographical Platforms for Surface Enhanced Raman Scattering Biomolecular Detection

AbstractTopologically designed micro‐ and nanostructured surface‐enhanced Raman scattering (SERS) substrates propel the advancements of innovative applications, including environmental and forensic point‐of‐care miniaturised devices via enhancing the localised electric fields for accurate analyte sensing. Herein, a method for designing, optimising and fabricating fine‐tuneable concentric hexagonal, triangular and rectangular SERS‐active micronano‐substrates is developed, with each unit yielding significant enhancement. Numerical simulations of the 3D near‐field electric field guided the optimal design process. While the coaxial SERS substrates consistently outperformed their solid counterparts, the hexagonal micro‐nano topologies exhibited ×21 higher signal than coaxial square arrays and a 12‐15‐fold increase over the triangle structures. Alternation of the topological designs from square to triangle lattice yielded more uniform plasmonic modes propagating along the 60°‐directions with various resonance modes playing key roles in light reflectance. This enables the engineering of platforms with tailor‐enhanced signals by changing the arrangement of micro‐nano patterned coaxial arrays. The fabricated SERS substrates are validated by detecting traumatic brain injury biomarkers, effectively yielding the characteristic fingerprint spectra of each neuro‐molecule. The straightforward development of sub‐micrometre tuneable SERS‐active architectures enables anelegant route for high‐throughput biochemical sensing, laying a platform for amplified bimolecular detection of disease biomarkers and integration in bioanalytical systems.

Ratiometric surface-enhanced Raman spectroscopy detection of 5-hydroxyindole-3-acetic acid based on Au@MIL-125@MIPs substrates

5-Hydroxyindole-3-acetic acid (5-HIAA) is a molecular marker that can be used in the early diagnosis of carcinoid tumors, and the development of sophisticated 5-HIAA assays is therefore of great importance. Surface-enhanced Raman spectroscopy (SERS) has been widely used for the rapid and sensitive detection of disease biomarkers. Insufficient specificity for tumor markers and poor spectral reproducibility are the bottlenecks in the practical use of SERS technology. In this study, based on MIL-125 surface-loaded gold nanoparticles (Au@MIL-125), a novel strategy was proposed to obtain Au@MIL-125@molecularly imprinted polymers (MIPs) as functional SERS substrates by wrapping a thin MIP shell around the Au@MIL-125 surface for selective separation followed by a 5-HIAA assay. The Raman peak intensity ratio (I865/I1078) was used to quantify 5-HIAA after a SERS spectral calibration with an embedded internal standard (i.e., 4-aminobenzenethiol) to improve the quantitative accuracy. The linear range was from 10−11 to 10−7 M, and the limit of detection (LOD) was 5.45 × 10−13 M. The method of integrating the MIPs with the metal MOF-based nanocomposites was shown to be useful in the analysis of real samples using SERS. The application of SERS for the selective and quantitative detection of analytes in real sample analysis, therefore, has great potential.

Portable multimodal platform with carbon nano-onions as colorimetric and fluorescent signal output for trypsin detection

Multimodal biosensors with independent signaling pathways can self-calibrate and improve the reliability of disease biomarker detection. Herein, a colorimetric-fluorescent dual-mode paper-based biosensor with PAN/Fe(III)–CNOs (FPCs) as core components has been developed, which information is recognized by smartphone and naked eye. Using 1-(2-pyridylazo)-2-naphthol (PAN) as a mediator, Fe(III) is enriched on the surface of carbon nano-onions (CNOs), endowing FPCs with excellent mimetic enzyme activity and photothermal conversion ability, which allows it to output amplified colorimetric signals under laser irradiation. In addition, the complexation of PAN with Fe(III) broadens its absorption spectrum, which makes FPCs more suitable to be energy acceptors to quench fluorescence of polymer dots (Pdots), resulting in the changes of output fluorescent signal. Based on the above design, a portable colorimetric-fluorescent dual-mode biosensor is proposed for trypsin detection with Pdots as fluorescence sources and FPCs as fluorescence quenchers and nanoenzymes. This work provides a convenient way for constructing portable visual multimodal biosensors, which is expected to applied in various disease diagnosis.

Carbon‐Based Biosensor in Point of Care Setting

AbstractIn medical diagnosis, detecting disease biomarkers at ultra‐low concentrations is vital. Point‐of‐care (POC) diagnostics require rapid detection, live monitoring, high sensitivity, low detection threshold, and cost‐effectiveness. Carbon‐based nanomaterials (CBNs) are promising due to their large surface‐to‐volume ratio, conductivity, biocompatibility, and stability, making them ideal for biosensors. Recent advancements in CBN applications, including biosensing, drug delivery, and cancer therapy, highlight their potential in enhancing detection sensitivity and specificity. Electrochemical sensors and biosensor platforms using carbon nanocomposites are pivotal in diagnostics. This review explores the current state and future challenges of CBN integration in POC settings, envisioning a transformative impact on healthcare diagnostics and therapeutics.

Surface-engineered vertically-aligned ZnO nanorod for sensitive non-enzymatic electrochemical monitoring of cholesterol

Developing highly sensitive and selective non-enzymatic electrochemical biosensors for disease biomarker detection has become challenging in healthcare applications. However, advances in material science are opening new avenues for creating more dependable biosensing technologies. In this context, the present work introduces a novel approach by engineering a hybrid structure of zinc oxide nanorod (ZnO NR) modified with iron oxide nanoparticle (Fe2O3 NP) on an FTO electrode. This Fe2O3 NP-ZnO NR hybrid material functions as a nanozyme, facilitating the catalysis of cholesterol and enabling the direct transfer of electrons to the fluorine-doped tin oxide (FTO) electrode, limiting the need for costly and traditional enzymes in the detection process. This innovative non-enzymatic cholesterol biosensor showcases remarkable sensitivity, registering at 642.8 μA/mMcm2 within a linear response range of up to 9.0 mM. It also exhibits a low detection limit (LOD) of ∼12.4 μM, ensuring its capability to detect minimal concentrations of cholesterol accurately. Moreover, the developed biosensor displays exceptional selectivity by effectively distinguishing cholesterol molecules from other interfering biological species, while exhibiting outstanding stability and reproducibility. Our findings indicate that the Fe2O3 NP-ZnO NR hybrid nanostructure on the FTO electrode holds promise for enhancing biosensor stability. Furthermore, the present device fabrication platform offers versatility, as it can be adapted with various enzymes or modified with different metal oxides, potentially broadening its applicability in a wide range of biomarkers detection.

A microfluidic chip with integrated plasma separation for sample-to-answer detection of multiple chronic disease biomarkers in whole blood

Point-of-care testing of multiple chronic disease biomarkers is crucial for timely intervention and management of chronic diseases. Here, a “sample-to-answer” microfluidic chip was developed for simultaneous detection of multiple chronic disease biomarkers in whole blood by integrating a plasma separation module. The whole detection process is very convenient, i.e., just add whole blood and get the results. The chip successfully achieved the simultaneous detection of total cholesterol, triglycerides, uric acid, and glucose in undiluted whole blood within 21 min, including 6 min for plasma separation and 15 min for enzymatic chromogenic reactions. Moreover, the sensitivity levels of on-chip detection of chronic disease biomarkers can also meet clinically relevant thresholds. The chip is easy to use and has significant potential to improve home self-management of chronic diseases and enhance healthcare outcomes.

Pushing the Limits of Lateral Flow Immunoassay by Digital SERS for the Ultralow Detection of SARS‐CoV‐2 Virus

Lateral flow immunoassays (LFIAs) are easy‐to‐use antigen tests that provide different signal readouts, with colorimetric readouts being the most commonly used. However, these analytical devices have relatively low sensitivity and produce semiquantitative results, limiting their diagnostic applications. Herein, we address these challenges by implementing a digital surface‐enhanced Raman spectroscopy (SERS)‐based LFIA for the accurate and ultrasensitive quantitative detection of SARS‐CoV‐2 nucleocapsid (N) protein. Compared with average SERS intensity measurements, the digital approach allowed to overcome fluctuations in Raman scattering signals, thereby increasing the analytical sensitivity of the assay. Our method exhibited a quantification range of the viral protein in nasal swabs from 0.001 to 10 pg mL−1, and a limit of detection down to 1.9 aM (0.9 fg mL−1), improving colorimetric LFIAs and conventional‐SERS‐based LFIAs by several orders of magnitude. Importantly, this approach shows an analytical sensitivity of 0.03 TCID50 mL−1, which is greater than that reported by other immunoassays. In conclusion, we successfully demonstrate the robust detection and quantification of SARS‐CoV‐2N protein in nasal swabs at ultralow concentrations. The improvement in the sensitivity of LFIA by digital SERS may pave the way to translate this technology into the diagnostic arena for the ultrasensitive detection of microbes and disease biomarkers.

(Invited) Recent Progress in Functional Nanomaterials for Biosensing and Theranostics

In this talk, I will present an overview of our pioneering research in functional nanomaterials for biosensing and theranostics. Our work primarily focuses on novel materials such as protein cages, peptoids, single-atom nanozymes, and nanoflowers, and their applications in the field of biosensing and theranostics.Building on my extensive background in developing materials and systems for biosensors, including immunosensors and microfluidic devices, we have explored the development of various smartphone-based biosensors. These biosensors are primarily based on DNA assays and immunoassays for point-of-care diagnostics, significantly enhancing the detection of disease biomarkers. Our research utilizes nanomaterials loaded with optical or electroactive signal molecules as amplification tags, dramatically improving the sensitivity in detecting disease biomarkers and food pathogens.An exciting frontier in our research is the application of nano-peptoids in cell imaging, single-particle tracking, and cancer theranostics. The unique properties of nano-peptoids, including their biocompatibility and the ability for precise control over interactions, have opened new avenues in biomedicine and healthcare. These advancements hold promise for groundbreaking applications, particularly in enhancing the efficacy and precision of cancer diagnostics and treatment.Moreover, the integration of 3D printing technology has enabled us to fabricate compact and efficient devices, a testament to our commitment to innovation in biosensor technology.Throughout this talk, we will delve into the intricate details of these innovations, discussing their implications for the future of biosensing and theranostics.

Aqueous Two-Phase Extraction of Single-Chirality Carbon Nanotubes with Functionalized ssDNA for Biomarker-Specific Antibody Conjugation

Multiplexed detection of biomarkers for cancer and chronic inflammatory diseases is necessary to improve diagnostic sensitivity and specificity. Our prior studies and that of others has used near-infrared fluorescent single-walled carbon nanotubes (SWCNT) as sensor transducers because of their sensitivity to the local environment, photostability, and emission in the tissue-transparent window. That work engineered the SWCNT surface through non-covalent interactions with short ssDNA oligonucleotides containing a functional group to which a biomarker-specific antibody was conjugated. Further, previous work by other groups has demonstrated the ability to obtain single SWCNT chiralities using the aqueous two-phase extraction (ATPE) technique with non-functionalized ssDNA sequences. Here, we have incorporated primary amine-functionalized ssDNA sequences into the ATPE separation technique to obtain individual SWCNT chiralities with functionalized ssDNA. To those primary amine-functionalized ssDNA-SWCNT complexes, we conjugated antibodies against two inflammatory cytokines. We investigated the sensitivity and specificity of these individual SWCNT chirality sensors specific to two biomarkers together in buffer and serum, finding that each chirality responds specifically only to its cognate biomarker and not the other. This is the first demonstration of single-chirality, molecularly-specific multiplexed SWCNT sensors. It forms the basis of ongoing work to obtain additional chiral species with other functional groups, as well as to develop multiplexed cytokine sensors for in vivo diagnostics.

Innovations in Biosensor Technologies for Healthcare Diagnostics and Therapeutic Drug Monitoring: Applications, Recent Progress, and Future Research Challenges.

This comprehensive review delves into the forefront of biosensor technologies and their critical roles in disease biomarker detection and therapeutic drug monitoring. It provides an in-depth analysis of various biosensor types and applications, including enzymatic sensors, immunosensors, and DNA sensors, elucidating their mechanisms and specific healthcare applications. The review highlights recent innovations such as integrating nanotechnology, developing wearable devices, and trends in miniaturisation, showcasing their transformative potential in healthcare. In addition, it addresses significant sensitivity, specificity, reproducibility, and data security challenges, proposing strategic solutions to overcome these obstacles. It is envisaged that it will inform strategic decision-making, drive technological innovation, and enhance global healthcare outcomes by synthesising multidisciplinary insights.

Electrochemiluminescence Lateral Flow Immunoassay Using Ruthenium(II) Complex‐Loaded Dendritic Mesoporous Silica Nanospheres for Highly Sensitive and Quantitative Detection of SARS‐CoV‐2 Nucleocapsid Protein

AbstractLateral flow immunoassays (LFIA) are widely used for the cost‐effective and rapid detection of diverse analytes. However, traditional LFIA suffers from difficulties in providing quantitative results and has low sensitivity. Herein, LFIA is combined with electrochemiluminescence (ECL), a leading transduction technique with high sensitivity and wide dynamic range, to achieve highly sensitive and quantitative detection of severe acute respiratory syndrome coronavirus nucleocapsid protein (SARS‐CoV‐2 N protein). Ruthenium(II)‐based complexes are synthesized and loaded into dendritic mesoporous silica nanospheres (PEI‐Ru/dSiO2), which possessed central‐radial pore channels and served as tags for ECL‐LFIA. The electrodes are fabricated on a nitrocellulose (NC) membrane, which simplifies the structure of the ECL‐LFIA. PEI‐Ru/dSiO2 is captured on the electrode surface via a sandwich immunoreaction, which enhances the ECL signal by decreasing the distance between PEI‐Ru/dSiO2 and the electrode surface. Using 2,2‐bis(hydroxymethyl)‐2,2′,2′'‐nitrilotriethanol (BIS‐TRIS) as coreactant, the ECL‐LFIA is used for detecting SARS‐CoV‐2 N protein, with a linear range of 1–104 ng mL−1 and a limit of detection (LOD) of 0.52 ng mL−1. ECL‐LFIA can also be used to detect analytes in complex matrices. These results demonstrate that the prepared ECL‐LFIA has great potential as a point‐of‐care testing platform for the rapid and quantitative detection of disease biomarkers.

Efficient CdIn2S4/MgIn2S4 heterojunction for ultrasensitive detection of lung cancer marker neuron-specific enolase

In this work, a photoelectrochemical (PEC) immunosensor was constructed for the ultrasensitive detection of lung cancer marker neuron-specific enolase (NSE) based on a microflower-like heterojunction of cadmium indium sulfide and magnesium indium sulfide (CdIn2S4/MgIn2S4, CMIS) as photoactive material. Specifically, the well-matched energy level structure and narrow energy level gradients between CdIn2S4 and MgIn2S4 could accelerate the separation of electron-hole (e−-h+) pairs in the CMIS heterojunction to enhance the photocurrent of CMIS, which was increased 5.5 and 80 times compared with that of single CdIn2S4 and MgIn2S4, respectively. Meanwhile, using CMIS as photoactive material, increasing the biocompatibility by dropping Pt NPs on the surface of CMIS to immobilize the antibody through Pt–N bond. Fe3O4-Ab2, acting as the quencher, competitively consumes electron donors and absorbs light, leading to photocurrent quenching. With the increasing of quencher, the photocurrent decreased. Hence, the developed “signal-off” PEC immunosensor realized the trace detection of NSE within the range from 1.0 fg/mL to 10 ng/mL with a low detection limit of 0.34 fg/mL. This strategy provided a new perspective for establishing ternary metal sulfide heterojunction to construct PEC immunosensor for sensitive detection of disease biomarkers.