Ultrasensitive Detection Research Articles

A novel fluorescent sensor based on lanthanide-doped polyoxometalate for ultrasensitive detection of phytic acid

A novel fluorescent sensor based on lanthanide-doped polyoxometalate for ultrasensitive detection of phytic acid

A cascade X-ray energy converting approach toward radio-afterglow cancer theranostics.

Leveraging X-rays to initiate prolonged luminescence (radio-afterglow) and stimulate radiodynamic 1O2 production from optical agents provides opportunities for diagnosis and therapy at tissue depths inaccessible to light. However, X-ray-responsive organic luminescent materials are rare due to their intrinsic low X-ray conversion efficiency. Here we report a cascade X-ray energy converting approach to develop organic radio-afterglow nanoprobes (RANPs) for cancer theranostics. RANPs comprise a radiowave absorber that down-converts X-ray energy to emit radioluminescence, which is transferred to a radiosensitizer to produce singlet oxygen (1O2). 1O2 then reacts with a radio-afterglow substrate to generate an active intermediate that simultaneously decomposes to emit radio-afterglow. Through finetuning such a cascade, intraparticle radioluminescence energy transfer and the 1O2 transfer process, RANPs possess tunable wavelengths and long half-lives, and generate radio-afterglow and 1O2 at tissue depths of up to 15 cm. Moreover, we developed a biomarker-activatable nanoprobe (tRANP) that produces a tumour-specific radio-afterglow signal, leading to ultrasensitive detection and the possibility of surgical removal of diminutive tumours (1 mm3) under an X-ray dosage 20 times lower than inorganic materials. The efficient radiodynamic 1O2 generation of tRANP permits complete tumour eradication at an X-ray dosage lower than clinical radiotherapy and a drug dosage one to two orders of magnitude lower than most existing inorganic agents, leading to prolonged survival rates with minimized radiation-related adverse effects. Thus, our work reveals a generic approach to address the lack of organic radiotheranostic materials and provides molecular design towards precision cancer radiotherapy.

The fabrication of phosphotungstate@UIO-Au/reduced graphene oxidation for electrochemical ultrasensitive detection of alpha-fetoprotein.

As an early multi-purpose tumor marker of hepatocellular carcinoma, alpha-fetoprotein (AFP) plays a vital role in early diagnosis and treatment. To achieve the early and accurate determination of AFP, the POMOF was fabricated by embedding H3PW12O40 (PW12) into UIO-66-NH2, further immobilized on reduced GO (rGO) and fabricated an innovative POMOF nanocomposite (PW@UIO-Au/rGO) as an electrochemical immunosensor (ECI-sensor). The PW@UIO-Au/rGO achieved 17-fold signal enhancement owing to their synergistic effect, enabling PW@UIO-Au/rGO exhibit high oxidase-like catalytic activity, facilitating their sensing performance. Under optimal experimental conditions, the proposed PW@UIO-Au/rGO ECI-sensor presented excellent sensing performance over a wide range from 0.01 ng mL-1 to 500 ng mL-1 with ultra-low detection of 4.0 pg mL-1. Notably, sensing results in real serum samples were verified by the clinical enzyme-linked immunosorbent assay (ELISA) and electrochemiluminescence immunoassay (ECL) methods with excellent accuracy and consistency, indicating the excellent environmental tolerance of the proposed ECI-sensor. This work provided a promising strategy for designing feasible ultra-sensitive probe for sensing AFP in clinical test.

Abstract B029: Ultra-sensitive molecular residual disease detection through whole genome sequencing with single-read error correction

Abstract While whole genome sequencing (WGS) of cell-free DNA (cfDNA) holds enormous promise for detection of molecularresidual disease (MRD), its performance is limited by WGS error rate. Here we introduce AccuScan, an efficient cfDNA WGS technology that enables genome-wide error correction at single read level, achieving an error rate of 4.2 × 10-7, which is about two orders of magnitude lower than a read-centric de-noising method. Application of AccuScan to MRD demonstrated analytical sensitivity down to 10-6 circulating tumor allele fraction at 99% sample level specificity. AccuScan showed 90% landmark sensitivity (within 6 weeks after surgery) and 100% specificity for predicting relapse in colorectal cancer. It also showed 67% sensitivity and 100% specificity with esophageal cancer using samples collected within one week after surgery. When AccuScan was applied to monitor immunotherapy in melanoma patients, the circulating tumor DNA (ctDNA) levels and dynamic profiles were consistent with clinical outcomes. Overall, AccuScan provides a highly accurate WGS solution for MRD detection, empowering ctDNA detection at parts per million rangewithout requiring high sample input or personalized reagents. Citation Format: Xinxing Li, Tao Liu, Antonella Bacchiocchi, Mengxing Li, Wen Cheng, Tobias Wittkop, Fernando Mendez, Yingyu Wang, Paul Tang, George Yeung, Qianqian Yao, Marcus Bosenberg, Mario Sznol, Qin Yan, Malek Faham, Li Weng, Ruth Halaban, Hai Jin, Zhiqian Hu. Ultra-sensitive molecular residual disease detection through whole genome sequencing with single-read error correction [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B029.

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.

Enhanced long-lasting luminescence nanorods for ultrasensitive detection of SARS-CoV-2 N protein

AbstractPersistent luminescence nanomaterials can remain luminescence when the light source is turned off, which exhibits promise in biosensor and bioimaging fields since they have the ability to completely eradicate tissue autofluorescence. Although significant progress has been made in the persistent luminescence biosensing, there is still a dearth of long-afterglow detection platform with low limit of detection (LOD) and high sensitivity. Herein, Zn2GeO4:Mn, Cr persistently luminescent nanorods (PLNRs) with superior persistent luminescence and long afterglow time were developed. The addition of Cr3+ manifestly improves persistent luminescence intensity and afterglow duration through creating a deep defect trap. Then the biosensors were constructed by combining the Zn2GeO4:Mn,Cr PLNRs-antibody and Fe3O4 magnetic nanoparticles (MNPs)-antibody for nucleocapsid protein detection based on electrostatic attraction. The LOD value for nucleocapsid protein realizes as low as 39.82 ag/mL, which is much lower than the previously reported persistent luminescent-based biosensors. Accordingly, the low detection sensitivity is attributed to fluorescence resonance energy transfer. In addition, high specificity is also achieved. Therefore, the as-prepared Zn2GeO4:Mn,Cr persistently luminescent materials can act as the promising candidate in biosensors applications. This strategy provides effective guidance for the development of biosensing platforms with high sensitivity and specificity.

A novel electrochemiluminescent cytosensor using dual-target magnetic probe recognition and nanozymes-catalyzed cascade signal amplification for precise phenotypic enumeration of CTCs.

The inability of surgical biopsy to monitor the dynamic evolution of cancer cells hampers its capacity to reflect real-time tumor heterogeneity. Circulating tumor cells (CTCs), as a crucial target in liquid biopsy, offer a novel approach for accurate monitoring of tumors. However, the rarity and complex phenotype resulting from epithelial-mesenchymal transition pose challenges for conventional methods such as CellSearch and immunohistochemistry, which have insufficient ability for simultaneous phenotyping and enumeration of CTCs. The enumeration of a single phenotype CTCs is insufficient for accurately assessing disease progression. Herein, we propose a strategy to address this issue by fabricating an electrochemiluminescence cytosensor via the integration of dual-target enrichment and nanozymes-catalyzed cascade signal amplification. The graphene oxide@hollow mesoporous Prussian blue/Pt (GO@HMPB/Pt) complex, possessing a large specific surface area and exceptional catalytic activity, is employed for loading a substantial amount of luminol as the signal probe. Dual-target magnetic PPy@Fe3O4/Au-antibody/aptamer is utilized for the magnetic capture of both epithelial and interstitial CTCs. Glutathione (GSH) can disrupt theAu-S bond on aptamer by a thiol exchange reaction and selectively releases a specific subset of phenotypic CTCs, thereby facilitating the efficient capture, accurate classification, and ultrasensitive detection of CTCs in peripheral blood. Using the epithelial MCF-7 and mesenchymal Hela cells as models, the ECL cytosensor demonstrates excellent performance in identifying cells spiked into whole blood. This study presents a novel approach for early detection of metastasis, tracking tumor recurrence, and monitoring therapeutic efficacy.

A Tuneable and Easy-to-Prepare SERS Substrate Based on Ag Nanorods: A Versatile Tool for Solution and Dry-State Analyses

Surface-enhanced Raman spectroscopy is a powerful technique for the ultra-sensitive detection of organic analytes. In this paper, the preparation of SERS substrates based on silver nanorods (AgNRs) is proposed, exploiting a simple protocol which does not require complex procedures and/or sophisticated and expensive instrumentation. For this purpose, various syntheses of AgNRs were tested, and the best one for preparing the SERS active substrate proved to be the one which does not involve surfactants as nanoparticle stabilizers. The plasmonic properties of the selected substrate can be modified based on the concentration of the deposited nanoparticles, allowing for the experimentation of different excitation wavelengths. Positive results were obtained on reference solutions of three natural dyes of historical interest using both green exciting radiation (532 nm) and two near-infrared ones (785 and 850 nm; the latter is combined with the SSE™ technology for further fluorescence quenching). Furthermore, the substrates of AgNRs were found to be suitable for SERS measurements even in dry-state conditions, i.e., only exploiting the electromagnetic interaction between the nanostructured substrate and the dye molecules absorbed onto a wool fibre.

Spherical DNA Nanomotors Enable Ultrasensitive Detection of Active Enzymes in Extracellular Vesicles for Cancer Diagnosis.

Enzymes encapsulated in extracellular vesicles (EV)s hold promise as biomarkers for early cancer diagnosis. However, precise measurement of their catalytic activities within EVs remains a notable challenge. Here, we report an enzymatically triggered spherical DNA nanomotor (EDM) that enables one-pot, cascaded, and highly sensitive analysis of the activity of EV-associated or free apurinic/apyrimidinic endonuclease 1 (APE1, a key enzyme in base excision repair) across various biological samples. The EDM capitalizes on APE1-triggered activation of DNAzyme (Dz) and its autonomous cleavage of substrates to achieve nonlinear signal amplification. Using EDM, we reveal a strong correlation between APE1 activity in EVs and that of their parental cancer cells. Additionally, EV APE1 mirrors the fluctuation of cellular APE1 activity in response to chemotherapy-induced DNA damage. In a pilot clinical study (n = 63), the EDM-based assay reveals that more than 80% of active APE1 in serum samples is EV-encapsulated. Notably, EV APE1 can differentiate early prostate cancer (PCa) patients from healthy donors (HDs) with an overall accuracy of 92%, outperforming free APE1 in sera. We anticipate that EDM will become a versatile tool for quantifying EV-associated enzymes.

Spherical DNA Nanomotors Enable Ultrasensitive Detection of Active Enzymes in Extracellular Vesicles for Cancer Diagnosis

Enzymes encapsulated in extracellular vesicles (EV)s hold promise as biomarkers for early cancer diagnosis. However, precise measurement of their catalytic activities within EVs remains a notable challenge. Here, we report an enzymatically triggered spherical DNA nanomotor (EDM) that enables one‐pot, cascaded, and highly sensitive analysis of the activity of EV‐associated or free apurinic/apyrimidinic endonuclease 1 (APE1, a key enzyme in base excision repair) across various biological samples. The EDM capitalizes on APE1‐triggered activation of DNAzyme (Dz) and its autonomous cleavage of substrates to achieve nonlinear signal amplification. Using EDM, we reveal a strong correlation between APE1 activity in EVs and that of their parental cancer cells. Additionally, EV APE1 mirrors the fluctuation of cellular APE1 activity in response to chemotherapy‐induced DNA damage. In a pilot clinical study (n = 63), the EDM‐based assay reveals that more than 80% of active APE1 in serum samples is EV‐encapsulated. Notably, EV APE1 can differentiate early prostate cancer (PCa) patients from healthy donors (HDs) with an overall accuracy of 92%, outperforming free APE1 in sera. We anticipate that EDM will become a versatile tool for quantifying EV‐associated enzymes.

Single-atom ruthenium nanozyme-induced signal amplification strategy in photoelectrochemical aptasensor for ultrasensitive detection of chloramphenicol

To develop ultrasensitive and rapid antibiotics residue detection method is crucial for ensuring food safety and protecting human health. Herein, a novel photoelectrochemical (PEC) aptasensor integrated with single-atom ruthenium (Ru) nanozyme-mediated catalytic precipitation as a valuable signal amplification strategy, have been established for ultrasensitive chloramphenicol (CAP) detection. Particularly, the exceptional peroxidase-mimicking activity of single-atom Ru nanozyme is responsible for accelerating the oxidation of 4-chloro-1-naphthol (4-CN) to produce insoluble precipitate on the electrode, which in turn causes a notable reduction in the photocurrent. Whereas, when CAP is present, the aptamer is liberated away the electrode because of its potent affinity with CAP, resulting in an elevation of the photocurrent signal, enhancing the detection sensitivity. Importantly, the signal amplification strategy combines the effective photoactive material of Au nanoparticles/CdS quantum dot/TiO2 composites, a PEC aptasensor for determination of CAP with an ultralow detection limit of 4.12 pM is achieved in a self-powered mode with great selectivity and accuracy. This work proposes a novel reasonable approach utilizing high-activity single-atom nanozyme to induce signal amplification strategy for the advancement of single-atom nanozyme in ultrasensitive PEC biosensor, and further creates new avenues for ultrasensitive detection beyond antibiotics residue.

Ultrasensitive and simultaneous detection for bioactive compounds of baicalein and chrysin in traditional Chinese medicine via Bi2MoO6-MWCNTs based sensing platform

Ultrasensitive and simultaneous detection for bioactive compounds of baicalein and chrysin in traditional Chinese medicine via Bi2MoO6-MWCNTs based sensing platform

Fully Integrated Microfluidic Digital Chip for Simple and Highly Quantitative Detection of Norovirus.

The prevalence of foodborne illnesses is a significant global concern, resulting in numerous illnesses, deaths, and substantial economic losses annually. Traditional detection methods for foodborne pathogens are often slow, limited, and impractical for field use, underscoring the need for rapid, sensitive, and portable assays. Microfluidic technology has emerged as a promising solution for sample preparation, reaction, and detection on a small scale. Our study introduces a novel microfluidic digital loop-mediated isothermal amplification (LAMP) assay platform, which employs digital microfluidic chips for absolute quantitative analysis of nucleic acids. This portable chip utilizes LAMP technology to achieve ultrasensitive detection of target nucleic acids within 30 min and reduces the detection limit to 1 fM without the need for complex instrumentation. By digitizing amplification signals directly from the target sample, our platform offers simplicity, affordability, portability, and quantitative molecular readouts. This innovation represents a crucial step toward the on-site detection of foodborne pathogens, thereby enhancing food safety and mitigating disease outbreaks.

Ultra-sensitive dengue NS1 protein detection via asymmetric source-drain, heterojunction and dual-dielectric cavities in a uniform tunnel FET biosensor

In this paper, we present a unique Asymmetric Source-Drain Heterojunction Dual-Dielectric Uniform Tunnel Field Effect Transistor (A-SD-HJ-DD-UTFET) based biosensor tailored for the early detection of dengue NS1 protein during the acute phase of infection offering early diagnosis and potentially life-saving intervention. The proposed biosensor design features simplified fabrication, a narrow drain region, and a dual material control gate, enhancing specificity and sensitivity for dengue virus detection. Using a heterojunction configuration, this device optimizes electron flow for improved detection accuracy. The roles of Tunnel Gate (TG) and Auxiliary Gate (AG) are studied in terms of band energy, electric field, electrostatic potential, and other sensitivity parameters. Sentaurus TCAD tool is utilized for analyzing the characteristics of the proposed A-SD-HJ-DD-UTFET biosensor. Simulation results indicate that the designed A-SD-HJ-DD-UTFET biosensor achieves a superior Subthreshold Swing (SS) of 15.4 mV/dec and an enhanced ION/IOFF sensitivity of about 2.25 × 10¹¹ with a maximum ON and minimum OFF state currents of 2.28 × 10–4 A/μm and 1.28 × 10–16 A/μm respectively for detecting NS1 protein of dengue. Additionally, it boasts a high switch ratio in the order of 1012. The proposed biosensor outperforms conventional devices, including the state-of-the-art Junctionless (JL)-TFET biosensors. The superior electrical characteristics of the proposed A-SD-HJ-DD-UTFET biosensor make it a promising device for early detection of the dengue NS1 protein, providing a potent solution for mitigating the spread of dengue infections.

Highly Sensitive One-Pot Isothermal Assay Combining Rolling Circle Amplification and CRISPR/Cas12a for Aflatoxin B1 Detection.

Occurrences of mycotoxins in cereals are widespread throughout the world. However, the lack of efficient and ultrasensitive tests has largely impeded the identification of these substances in actual samples. Herein, a novel one-pot isothermal assay that integrates rolling-circle amplification (RCA) and CRISPR/Cas12a to detect aflatoxin B1 (AFB1) is reported. Upon addition of AFB1 to the magnetic bead functionalized with a duplex of the AFB1 aptamer and its complementary DNA (cDNA), the specific recognition of AFB1 by the aptamer causes the release of cDNA to activate the RCA reaction. Subsequently, the RCA amplicon initiates both trans-cleavage and cis-cleavage activities of the endonuclease Cas12a. The synergistic coupling of RCA and CRISPR/Cas12a enables exponential amplification of cDNA, which further promotes CRISPR/Cas12a to nonspecifically cleave the single-stranded DNA reporters with enhanced detection signals. Remarkably, the CRISPR/Cas12a-assisted one-pot isothermal assay can not only achieve ultrasensitive quantitative detection through fluorescence detection, but also achieve visual detection through a lateral flow strip, which improves accessibility to mycotoxin detection in resource-limited regions. The limit of detection was 0.016 and 0.408 ng/mL, respectively. The proposed assay successfully applies in real samples with satisfactory recoveries from 90 to 114%. This study presents a powerful and versatile method for reliable and ultrasensitive detection of mycotoxins in various applications.

Charge Modulation at the Liquid Crystal Droplet-Aqueous Interface Enables Ultrasensitive, Nonspecific Protein Detection.

Thermotropic nematic liquid crystals (LC) have been utilized to sense/detect various analytes such as polymers, surfactants, lipids, etc. However, their use for protein detection depends on pre-adsorbed molecules, co-nematogens, or biomolecular agents for specificity.This approach impedes the platform's sensitivity with a detection limit for the folded proteins generally reported in the micromolar concentration range. Here, this work provides fundamental insights into the type of molecular interactions and their modulation that can drive ultrasensitive protein detection at an LC microdroplet/aqueous interface formed without adding an auxiliary co-nematogen. Using ultraviolet (UV) light treated 4-cyano-4'-pentylbiphenyl (5CB) LC and a flow-focused microfluidic device, we prepared different populations of monodisperse and highly negatively charged microdroplets in water. Adding an aqueous solution of various model proteins(α-synuclein, α-chymotrypsin, myoglobin, or bovine serum albumin, BSA) with different secondary structures and surface charges triggers a rapid radial- to bipolar-defect transition in these microdroplets. Isothermal titration calorimetry measurement and molecular dynamic simulation studies attribute this to the dominant electrostatic force-mediated adsorption of proteins at the LC/aqueous interface.Further, bioconjugation-based variation of protein surface charge allows tuning their detection limit.These findings can provide crucial physical cues for designing responsive LC systems and establishing a foundation for developing versatile, molecularly tailored, and highly specific biomolecular detection platforms.

Bio-carbon-derived porous reduced graphene oxide photo- and electrochemical sensor for ultra-sensitive detection of testosterone hormone

Bio-carbon-derived porous reduced graphene oxide photo- and electrochemical sensor for ultra-sensitive detection of testosterone hormone

Sample-to-answer point-of-care testing platform for quantitative detection of small molecules in blood using a smartphone-and microfluidic-based nanoplasmonic biosensor

Rapid and ultrasensitive detection of small molecules is of great significance in point-of-care testing (POCT) for health management and biomarker detection for many diseases. In this study, a novel POCT device integrated with a metasurface plasmon resonance (MetaSPR) chip with diffusion film enhancement was designed and controlled by a smartphone app for small molecule ultrasensitive detection based on competitive immunoassays. In this method, the sample competes with the antigen immobilized on the chip, and labeled antibodies are pumped from the sample pad to the chip for multiplexed and sample-to-answer analysis of blood. The entire process of detection is 14.3-fold less time (210 s in total) compared to an enzyme-linked immunosorbent assay (ELISA). For this assay, the limit of detection was 0.36 ppt and 1.05 ppt for testosterone and 25-hydroxyvitamin D3, respectively, and showed 100- to 1000-fold greater sensitivity than that of ELISA. Collectively, the data suggest that this novel POCT platform, based on a MetaSPR biosensor, provides ultrasensitive, rapid, regenerable, versatile, and real-time quantitative analysis for applications in health management and early diagnosis.

“Dandelion” magnetic bead-driven CDs@CeO2 based-multifunctional nanoplatform for tri-modal ultrasensitive detection and efficient eradication of pathogenic bacteria

To address the challenge of foodborne pathogens, we have developed an ultra-sensitive tri-modal detection and effective pathogen eradication strategy utilizing a “dandelion” magnetic bead-driven cerium dioxide doped with carbon dots (CDs@CeO2) multifunctional nanoplatform. Aptamer (Apt) modification CDs@CeO2 specifically recognizes and binds to the outer membrane proteins of Salmonella typhimurium (S. typhimurium). Concurrently, mannose-functionalized dandelion-like magnetic beads selectively recognize adhesins of S. typhimurium, avoiding competition with Apt for binding sites and leveraging the strong bacterial capture capability for high-sensitivity detection. The prepared CDs@CeO2 has been demonstrated to exhibit favourable fluorescence characteristics. In the presence of H2O2, CDs@CeO2 is capable of oxidising colourless 3,3',5,5'-tetramethylbenzidine (TMB) into blue oxide, displaying exceptional photothermal properties. CDs@CeO2 have the potential to generate •OH through a Fenton-like reaction, which could directly damage cells. Notably, coupling the photosensitizer Ce6 to CDs@CeO2 and subsequent illumination generates 1O2, which synergistically eradicates bacteria with •OH. Detection limits of the fluorescence, colorimetry, and photothermal methods were 3.85 cfu/mL, 9.44 cfu/mL, and 5.00 cfu/mL, respectively. The platform successfully achieves precise detection of S. typhimurium in actual pre-prepared food samples through fluorescence, colorimetry, and photothermal tri-modal signals, and effectively kills bacteria, achieving trace detection and source control.

Visible light-activated signal amplification PEC aptasensor for ultrasensitive zearalenone detection based on double Z-type BiOI/g-C3N4@Au/Bi2S3 heterojunctions

Zearalenone (ZEN), also known as F-2 toxin, can enter the body through the food chain and accumulate, leading to DNA break and an abnormal number of chromosomes. Therefore, it is crucial to develop a facile and sensitive method for detecting ZEN. Herein, a visible light-activated signal amplification photoelectrochemical (PEC) aptasensor for ultrasensitive detection of ZEN has been successfully constructed, exploiting the synergistic effect of the Z-type BiOI/g-C3N4/Au heterojunctions, Bi2S3 as a signal enhancer, and the remarkable affinity and specificity of aptamers. The PEC properties and electron transfer mechanism of the double Z-type heterojunctions were thoroughly investigated. When the aptamers captured the ZEN molecules, Bi2S3 and cDNA departed from the electrode, resulting in a reduction in the photocurrent signal. Therefore, the concentration of ZEN can be quantitatively analyzed by measuring the change in the photocurrent response. The constructed PEC aptasensor exhibited exceptional sensitivity and selectivity for ZEN in the concentration range of 0.1 fg⋅mL−1 ––1.0 ng⋅mL−1, with a detection limit of 0.087 fg⋅mL−1 (S/N = 3). Finally, the PEC aptasensor was successfully applied to detect ZEN in actual coix seed samples, providing some guidance for the development of PEC aptasensors for practical medicine monitoring.