Robust Luminescent Pyrene-Based Metal-Organic Framework Hydrogel as a pH-Responsive Fluorescence Emitter for Sensitive Immunoassay of Cardiac Troponin I.

Despite many luminescent advantages including outstanding absorption coefficient and high quantum yield, pyrene and its derivatives have been suffering from a dramatic aggregation-caused quenching (ACQ) effect. Although the dramatic ACQ effect of pyrene-based fluorophores has been restrained in pyrene-doped metal-organic frameworks (MOFs), the low loading of fluorescent (FL) units substantially impedes the improved luminescent behaviors. Herein, pyrene-based MOFs hydrogel was synthesized with a high loading of pyrene as the unique organic linker blocks instead of a dopant in MOFs. The gel matrix contributed to rigidifying the location of the FL emitters and achieving intensive FL emission and high luminescent stability and therefore efficiently overcoming the ACQ effect. Furthermore, the protonation of pyrene in the MOFs hydrogel remarkably decreased the luminescent intensity, which endowed the FL hydrogel with highly pH-responsive activity in the broad range (pH 4-10). Interestingly, glucose oxidase was immobilized into ZIF-8 as a highly efficient luminescent quencher, which contributed to catalyzing the form of gluconic acid and thus drastically quenching the FL signal of the MOFs hydrogel. Furthermore, the emitter-quencher pair of pyrene-based MOFs hydrogel and glucose oxidase was successfully employed to develop an ultrasensitive FL immunoassay platform for cardiac troponin I (as a model analyte). The limit of detection for cardiac troponin I was 5.2 pg/mL (3σ). The proof-of-principle study demonstrated the thrilling auxiliary effect of tailorable MOFs hydrogel on boosting the feasibility of aqueous insoluble FL chromophores for trace analysis.

Copper(II)-Tannic Acid@Cu with In Situ Grown Gold Nanoparticles as a Bifunctional Matrix for Facile Construction of Label-Free and Ultrasensitive Electrochemical cTnI Immunosensor.

Sensitive detection of cardiac troponin I (cTnI) is of great significance in the diagnosis of a fatal acute myocardial infarction. A redox-active nanocomposite of copper(II)-tannic acid@Cu (CuTA@Cu) was herein prepared on the surface of a glassy carbon electrode by electrochemical deposition of metallic copper combined with a metal stripping strategy. Then, HAuCl4 was in situ reduced to gold nanoparticles (AuNPs) by strong reductive catechol groups in the TA ligand. The AuNPs/CuTA@Cu composite was further utilized as a bifunctional matrix for the immobilization of the cTnI antibody (anti-cTnI), producing an electrochemical immunosensor. Electrochemical tests show that the immunoreaction between anti-cTnI and target cTnI can cause a significant reduction of the electrochemical signal of CuTA@Cu. It can be attributed to the insulating characteristic of the immunocomplex and its barrier effect to the electrolyte ion diffusion. From the signal changes of CuTA@Cu, cTnI can be analyzed in a wide range from 10 fg mL-1 to 10 ng mL-1, with an ultralow detection limit of 0.65 fg mL-1. The spiked recovery assays show that the immunosensor is reliable for cTnI determination in human serum samples, demonstrating its promising application in the early clinical diagnosis of myocardial infarction.

An Electrochemical Biosensor for the Detection of Pulmonary Embolism and Myocardial Infarction.

Due to the clinical similarities between pulmonary embolism (PE) and myocardial infarction (MI), physicians often encounter challenges in promptly distinguishing between them, potentially missing the critical window for the correct emergency response. This paper presents a biosensor, termed the PEMI biosensor, which is designed for the identification and quantitative detection of pulmonary embolism or myocardial infarction. The surface of the working electrode of the PEMI biosensor was modified with graphene oxide and silk fibroin to immobilize the mixture of antibodies. Linear sweep voltammetry was employed to measure the current-to-potential mapping of analytes, with the calculated curvature serving as a judgment index. Experimental results showed that the curvature exhibited a linear correlation with the concentration of antigen FVIII, and a linear inverse correlation with the concentration of antigen cTnI. Given that FVIII and cTnI coexist in humans, the upper and lower limits were determined from the curvatures of a set of normal concentrations of FVIII and cTnI. An analyte with a curvature exceeding the upper limit can be identified as pulmonary embolism, while a curvature falling below the lower limit indicates myocardial infarction. Additionally, the further the curvature deviates from the upper or lower limits, the more severe the condition. The PEMI biosensor can serve as an effective detection platform for physicians.

Controlled labelling of tracer antibodies for time-resolved fluorescence-based immunoassays.

Tracer antibodies, which are labelled with fluorescent or other type of reporter molecules, are widely employed in diagnostic immunoassays. Time-resolved fluorescence immunoassay (TRFIA), recognized as one of the most sensitive immunoassay techniques, utilizes tracers labelled with lanthanide ion (Ln) chelates. The conventional approach for conjugating isothiocyanate (ITC) Ln-chelates to antibodies involves random chemical targeting of the primary amino group of Lys residues, requiring typically overnight exposure to an elevated pH of 9-9.3 and leading to heterogeneity. Moreover, efforts to enhance the sensitivity of the assays by introducing a higher number of Ln-chelates per tracer antibody are associated with an elevated risk of targeting critical amino acid residues in the binding site, compromising the binding properties of the antibody. Herein, we report a method to precisely label recombinant antibodies with a defined number of Ln-chelates in a well-controlled manner by employing the SpyTag/SpyCatcher protein ligation technology. We demonstrate the functionality of the method with a full-length recombinant antibody (IgG) as well as an antibody fragment by producing site-specifically labelled antibodies for TRFIA for cardiac troponin I (cTnI) detection with a significant improvement in assay sensitivity compared to that with conventionally labelled tracer antibodies. Overall, our data clearly illustrates the benefits of the site-specific labelling strategy for generating high-performing tracer antibodies for TRF immunoassays.

Barbed arrow-like structure membrane with ultra-high rectification coefficient enables ultra-fast, highly-sensitive lateral-flow assay of cTnI.

Acute myocardial infarction (AMI) has become a public health disease threatening public life safety due to its high mortality. The lateral-flow assay (LFA) of a typical cardiac biomarker, troponin I (cTnI), is essential for the timely warnings of AMI. However, it is a challenge to achieve an ultra-fast and highly-sensitive assay for cTnI (hs-cTnI) using current LFA, due to the limited performance of chromatographic membranes. Here, we propose a barbed arrow-like structure membrane (BAS Mem), which enables the unidirectional, fast flow and low-residual of liquid. The liquid is rectified through the forces generated by the sidewalls of the barbed arrow-like grooves. The rectification coefficient of liquid flow on BAS Mem is 14.5 (highest to date). Using BAS Mem to replace the conventional chromatographic membrane, we prepare batches of lateral-flow strips and achieve LFA of cTnI within 240 s, with a limit of detection of 1.97 ng mL-1. The lateral-flow strips exhibit a specificity of 100%, a sensitivity of 93.3% in detecting 25 samples of suspected AMI patients. The lateral-flow strips show great performance in providing reliable results for clinical diagnosis, with the potential to provide early warnings for AMI.

Evaluation of Transducer Elements Based on Different Material Configurations for Aptamer-Based Electrochemical Biosensors.

The selection of an appropriate transducer is a key element in biosensor development. Currently, a wide variety of substrates and working electrode materials utilizing different fabrication techniques are used in the field of biosensors. In the frame of this study, the following three specific material configurations with gold-finish layers were investigated regarding their efficacy to be used as electrochemical (EC) biosensors: (I) a silicone-based sensor substrate with a layer configuration of 50 nm SiO/50 nm SiN/100 nm Au/30-50 nm WTi/140 nm SiO/bulk Si); (II) polyethylene naphthalate (PEN) with a gold inkjet-printed layer; and (III) polyethylene terephthalate (PET) with a screen-printed gold layer. Electrodes were characterized using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) to evaluate their performance as electrochemical transducers in an aptamer-based biosensor for the detection of cardiac troponin I using the redox molecule hexacyanoferrade/hexacyaniferrade (K3[Fe (CN)6]/K4[Fe (CN)6]. Baseline signals were obtained from clean electrodes after a specific cleaning procedure and after functionalization with the thiolate cardiac troponin I aptamers "Tro4" and "Tro6". With the goal of improving the PEN-based and PET-based performance, sintered PEN-based samples and PET-based samples with a carbon or silver layer under the gold were studied. The effect of a high number of immobilized aptamers will be tested in further work using the PEN-based sample. In this study, the charge-transfer resistance (Rct), anodic peak height (Ipa), cathodic peak height (Ipc) and peak separation (∆E) were determined. The PEN-based electrodes demonstrated better biosensor properties such as lower initial Rct values, a greater change in Rct after the immobilization of the Tro4 aptamer on its surface, higher Ipc and Ipa values and lower ∆E, which correlated with a higher number of immobilized aptamers compared with the other two types of samples functionalized using the same procedure.

A reagentless molecularly imprinted polymer-based electrochemical biosensor for single-step detection of troponin I in biofluids.

Reagentless molecular-imprinted polymer (MIP) electrochemical biosensors can offer the next generation of biosensing platforms for the detection of biomarkers owing to their simplicity, cost-efficacy, tunability, robustness, and accuracy. In this work, a novel combination of Prussian blue (PB), coated as an embedded redox probe on a gold working electrode (GWE), and a signal-off MIP assay has been proposed in an electrochemical format for the detection of troponin I (TnI) in biofluids. TnI is a variant exclusive to heart muscles, and its elevated level in the bloodstream is indicative of acute myocardial infarction (AMI). The proposed lab-manufactured PB/MIP electrochemical biosensor, consisting of a simple signal-off MIP assay and a PB redox probe embedded on the GWE surface, is the first of its kind that allows for reagentless, label-free, and single-step electrochemical biosensing of proteins. The preparation steps of the biosensor were fully characterized by cyclic voltammetry (CV), atomic force microscopy (AFM), and Raman spectroscopy. Finally, the performance of the optimized biosensor was investigated through the determination of various concentrations of TnI, ranging from 10 to 100 pg mL-1 within 5 min, in serum and plasma with limits of detection less than 3.6 pg mL-1, and evaluation of selectivity towards TnI using some relevant proteins that exist in biofluids with higher concentrations.

Facile, green and scalable synthesis of single-layer manganese dioxide nanosheets and its application for GSH and cTnI colorimetric detection.

Manganese dioxide (MnO2) nanosheets possess unique physical and chemical properties, making them widely applicable in various fields, such as chemistry and biomedicine. Although MnO2 nanosheets are produced using bottom-up wet chemistry synthesis methods, their scale is below the gram level and requires a long processing time, restricting their effective scale-up from laboratory to market. We report a facile, green and scalable synthesis of MnO2 nanosheets by mixing Shiranui mandarin orange juice and KMnO4 for 30 minutes. We produced more than one gram (1.095) of MnO2 nanosheets with a 0.65 nm mean thickness and a 50 nm mean lateral size. Furthermore, we established a visual colorimetric biosensing strategy based on MnO2 nanosheets for the assay of glutathione (GSH) and cardiac troponin I (cTnI), offering high sensitivity and feasibility in clinical samples. For GSH, the limit of detection was 0.08 nM, and for cTnI, it was 0.70 pg mL-1. Meanwhile, the strategy can be used for real-time analysis by applying a smartphone-enabled biosensing strategy, which can provide point-of-care testing in remote areas.

Liposome-embedded PtCu nanozymes for improved immunoassay of accurate myocardial infarction.

Herein, we developed a platinum-copper nano-enzyme-linked immunosorbent assay (NLISA) based split diagnostic platform for the ultrasensitive detection of cardiac troponin I (cTnI). The PtCu nanozyme synthesized by one-pot synthesis exhibited ultra-high peroxidase-like activity (35.17 U mg-1), which was about 4.5 times higher than that of the unmodified Pt nanozyme (8.83 U mg-1). Due to the efficient peroxidase-like activity of the copper-platinum complexed nanozyme, transduction and sequential amplification of cTnI biological signals were achieved in combination with a liposome-embedded amplification strategy. The encapsulation efficiency was calculated by introducing a liposomal bilayer model, which showed that the introduction of a single liposomal molecule could amplify the signal up to 870-fold, thus promising a high sensitivity test. Notably, the dynamic response of cTnI was in the range of 0.1-5000 pg mL-1 with an ultra-low detection limit (0.048 pg mL-1). The developed NLISA analysis system provides a new way to discover efficient and sensitive alternatives to ELISA kits, which can meet the practical needs of community healthcare testing conditions and rapid testing in hospitals.

A novel integrated lateral flow immunoassay platform for the detection of cardiac troponin I using hierarchical dendritic copper-nickel nanostructures.

Cardiac troponin I (cTnI) is a critical biomarker for the diagnosis of acute myocardial infarction (AMI). Herein, we report a novel integrated lateral flow immunoassay (LFIA) platform for highly sensitive point-of-care testing (POCT) of cTnI using hierarchical dendritic copper-nickel (HD-nanoCu-Ni) nanostructures. The electrodeposited HD-nanoCu-Ni film (∼22 µm thick) on an ITO-coated glass substrate exhibits superior capillary action and structural integrity. These properties enable efficient sample transport and antibody immobilization, making it a compelling alternative to conventional multi-component paper-based LFIA test strips, which are often plagued by structural fragility and susceptibility to moisture damage. The biofunctionalized HD-nanoCu-Ni substrates were laser-etched with lateral flow channels, including a sample loading/conjugate release zone, a test zone, and a control zone. Numerical simulations were used to further optimize the design of these channels to achieve optimal fluid flow and target capture. The HD-nanoCu-Ni LFIA device utilizes a fluorescence quenching based sandwich immunoassay format using antibody-labeled gold nanoparticles (AuNPs) as quenchers. Two different fluorescent materials, fluorescein isothiocyanate (FITC) and CdSe@ZnS quantum dots (QDs), were used as background fluorophores in the device. Upon the formation of a sandwich immunocomplex with cTnI on the HD-nanoCu-Ni device, introduced AuNPs led to the fluorescence quenching of the background fluorophores. The total assay time was approximately 15 min, demonstrating the rapid and efficient nature of the HD-nanoCu-Ni LFIA platform. For FITC, both inner filter effect (IFE) and fluorescence resonance energy transfer (FRET) contributed to the AuNP-mediated quenching. In the case of CdSe@ZnS QDs, IFE dominated the AuNP-induced quenching. Calibration curves were established based on the relationship between the fluorescence quenching intensity and cTnI concentration in human serum samples, ranging from 0.5 to 128 ng/mL. The limits of detection (LODs) were determined to be 0.27 ng/mL and 0.40 ng/mL for FITC and CdSe@ZnS QDs, respectively. A method comparison study using Passing-Bablok regression analysis on varying cTnI concentrations in human serum samples confirmed the equivalence of the HD-nanoCu-Ni LFIA platform to a commercial fluorescence cTnI LFIA assay kit, with no significant systematic or proportional bias observed.

A rapid and ultrasensitive cardiac troponin I aptasensor based on an ion-sensitive field-effect transistor with extended gate.

Acute myocardial infarction (AMI) is a life-threatening disease with a short course and a high mortality rate. However, it is still a great challenge to achieve the on-site diagnosis of this disease within minutes, meaning there is an urgent need to develop an efficient technology for realizing the rapid diagnosis and early warning of AMI in clinical emergencies. In this study, an ultrasensitive electrochemical aptasensor based on an extended-gate ion-sensitive field-effect transistor (EGISFET) was designed to achieve the quantitative assay of cardiac troponin I (cTnI), which is a highly sensitive and specific biomarker of AMI, within only 5 min. The EGISFET exhibits extremely high detection sensitivity due to its separated structure with a large sensing area and the surface-modified Prussian blue-gold nanoparticles (PB-AuNPs) composite, which serves as a signal magnifier and DNA loading platform for good electrocatalytic ability with a large specific area. Additionally, a target-induced strand-release strategy is proposed to shorten the recognition time of cTnI using a particular DNA strand. Under optimal conditions, the as-prepared aptasensor exhibits a wide linear range of 1-1000 pg/mL, an ultralow detection limit of 0.3 pg/mL, and reliable detection results in real serum samples. It is highly anticipated that this EGISFET-based aptasensor will have broad applications in the early warning and rapid diagnosis of AMI and other acute diseases in emergency treatment.

High-performance assaying cardiac troponin I using Bi-doped tin-based heterojunction in photoelectrochemical biosensing with the quencher of yolk-shell nanostructure.

Cardiac troponin I (cTnI), a protein regulating myocardial contraction, stands the premier biomarker for diagnosing acute myocardial infarction and stratifying heart disease risk. Photoelectrochemical (PEC) biosensing combines traditional PEC analysis with high bioconjugation specificity, rendering a prospective avenue for disease biomarker analysis. However, the performance of sensors often falls short due to inadequate photoelectric materials. Hence, designing heterojunctions with proper band alignment, effective transport and separation of photogenerated carriers is highly expected for PEC sensors. Meanwhile, doping as a synergistic strategy to tune the energy band edges and improve carrier transport in heterojunctions, can also enhance the sensing performance. In this work, bismuth-doped tin oxide and tin disulfide heterojunction (Bi-SnOS) was prepared via a simple one-step hydrothermal method and utilized as a highly sensitive platform. Integrating copper sulfide-coated nano-gold (Au@CuS), a yolk-shell shaped nanocomposites, as the double quenching probe, an excellent PEC biosensor was fabricated to assay cTnI via sandwich immunorecognition. Under optimal conditions, the proposed biosensor displayed a high-performance for cTnI in the range from 0.1 pg/mL to 5.0 ng/mL with a low detection limit (44.7 fg/mL, 3σ). The strong photocurrent response, high stability and suitable selectivity point out that the synergistic effect between heterojunction and doping provides a promising prospect for the design of new PEC materials.

Electrochemical and Plasmonic Detection of Myocardial Infarction Using Microfluidic Biochip Incorporated with Mesoporous Nanoscaffolds.

This paper reports a microfluidic device for the electrochemical and plasmonic detection of cardiac myoglobin (cMb) and cardiac troponin I (cTnI) with noticeable limits of detection (LoD) as low as a few picograms per milliliter (pg/mL) ranges, achieved in a short detection time. The device features two working electrodes, each with a mesoporous Ni3V2O8 nanoscaffold grafted with reduced graphene oxide (rGO) that improves the interaction of diffusing analyte molecules with the sensing surface by providing a high surface area and reaction kinetics. Electrochemical studies reveal sensitivities as high as 9.68 µA ng/mL and a LoD of 2.0 pg/mL for cTnI, and 8.98 µA ng/mL and 4.7 pg/mL for cMb. Additionally, the surface plasmon resonance (SPR) studies demonstrate a low-level LoD of 8.8 pg/mL for cMb and 7.3 pg/mL for cTnI. The dual-modality sensor enables dynamic tracking of kinetic antigen-antibody interactions during sensing, self-verification through providing signals of two modes, and reduced false readout. This study demonstrates the complementary nature of the electrochemical and SPR modes in biosensing, with the electrochemical mode being highly sensitive and the SPR mode providing superior tracking of molecular recognition behaviors. The presented sensor represents a significant innovation in cardiovascular disease management and can be applied to monitor other clinically important biomolecules.

Versatile conductometric biosensors for rapid and selective detection of inflammatory and cardiac biomarkers in saliva.

Biosensors have become promising alternatives to the conventional methods in early identification of diseases. However, translation of biosensors from lab to commercial products have challenges such as complex sensor fabrications and complicated detection, and inadequate sensitivity and selectivity. Here, we introduce simple and low-cost fabricated conductometric sensors based on high resistivity silicon wafers (HR-Si) which can be adopted to functionalise with both natural and synthetic antibodies in detecting five biomarkers including interleukin-6, C reactive protein, cardiac troponin I, brain natriuretic peptide, and N terminal-probrain natriuretic peptide. All five biomarkers show selective and rapid (10 min sample incubation and <1 min of reading time) detection in both media of phosphate buffer saline and saliva with the detection limits lower than that of reported healthy levels in saliva. This work highlights the versatility of HR-Si sensors in functionalisation of both natural and synthetic antibodies in sensitive and selective biomarker detection. As these miniaturised conductometric biosensors can be easily modified with on-demand biomaterials to detect corresponding target biomarkers, they enable a new category of compact point-of-care medical devices.

A Portable Readout System for Biomarker Detection with Aptamer-Modified CMOS ISFET Array.

Biosensors based on ion-sensitive field effect transistors (ISFETs) combined with aptamers offer a promising and convenient solution for point-of-care testing applications due to the ability for fast and label-free detection of a wide range of biomarkers. Mobile and easy-to-use readout devices for the ISFET aptasensors would contribute to further development of the field. In this paper, the development of a portable PC-controlled device for detecting aptamer-target interactions using ISFETs is described. The device assembly allows selective modification of individual ISFETs with different oligonucleotides. Ta2O5-gated ISFET structures were optimized to minimize trapped charge and capacitive attenuation. Integrated CMOS readout circuits with linear transfer function were used to minimize the distortion of the original ISFET signal. An external analog signal digitizer with constant voltage and superimposed high-frequency sine wave reference voltage capabilities was designed to increase sensitivity when reading ISFET signals. The device performance was demonstrated with the aptamer-driven detection of troponin I in both reference voltage setting modes. The sine wave reference voltage measurement method reduced the level of drift over time and enabled a lowering of the minimum detectable analyte concentration. In this mode (constant voltage 2.4 V and 10 kHz 0.1Vp-p), the device allowed the detection of troponin I with a limit of detection of 3.27 ng/mL. Discrimination of acute myocardial infarction was demonstrated with the developed device. The ISFET device provides a platform for the multiplexed detection of different biomarkers in point-of-care testing.

A sensitive electrochemical immunosensor based on high-efficiency catalytic cycle amplification strategy for detection of cardiac troponin I.

An electrochemical immunosensor based on the novel high efficiency catalytic cycle amplification strategy for the sensitive detection of cardiac troponin I (cTnI). With its variable valence metal elements and spiny yolk structure, the Cu2O/CuO@CeO2 nanohybrid exhibits high speed charge mobility and exceptional electrochemical performance. Notably, fluorite-like cubic crystal CeO2 shell would undergo redox reaction with Cu2O core, which successfully ensures the continuous recycling occurrence of "fresh" Cu (II)/Cu (I) and Ce (Ⅳ)/Ce (Ⅲ) pairs at the electrode interface. The "fresh" active sites continue to emerge constantly, resulting in a significant increase in the current signal. In light of the electrochemical characterization, the electron transfer pathway and catalytic cycle mechanism among CeO2, Cu2O and CuO were further discussed. The developed electrochemical immunosensor detected cTnI from 100 fg/mL to 100 ng/mL with a LOD of 15.85 fg/mL under optimal conditions. The analysis results indicate that the immunosensor would hold promise for broad application prospects in the biological detection for other biomarkers.

Quantitative measurement of acute myocardial infarction cardiac biomarkers by "All-in-One" immune microfluidic chip for early diagnosis of myocardial infarction.

Acute myocardial infarction (AMI) is a life-threatening condition with a narrow treatment window, necessitating rapid and accurate diagnostic methods. We present an "all-in-one" convenient and rapid immunoassay system that combines microfluidic technology with a colloidal gold immunoassay. A degassing-driven chip replaces a bulky external pump, resulting in a user-friendly and easy-to-operate immunoassay system. The chip comprises four units: an inlet reservoir, an immunoreaction channel, a waste pool, and an immunocomplex collection chamber, allowing single-channel flow for rapid and accurate AMI biomarker detection. In this study, we focused on cardiac troponin I (cTnI). With a minimal sample of just 4 µL and a total detection time of under 3 min, the chip enabled a quantitative visual analysis of cTnI concentration within a range of 0.5 âˆ¼ 60.0 ng mL-1. This all-in-one integrated microfluidic chip with colloidal gold immunoassay offers a promising solution for rapid AMI diagnosis. The system's portability, small sample requirement, and quantitative visual detection capabilities make it a valuable tool for AMI diagnostics.

Surface plasmon resonance biosensors for early troponin detection.

Acute myocardial infarction (AMI) is one of the life-threatening causes that decrease blood flow to the heart, leading to increased mortality and related complications. Recently, the measure of blood concentration of cardiac biomarkers has been suggested to overcome the limitations of electrocardiography (ECG) analyses for early diagnosis of this disease. Troponins, especially cardiac troponin I and cardiac troponin T, with high sensitivity and specificity, are considered the gold standards in myocardial diagnosis. Recently, the use of new biosensors such as surface plasmon resonance (SPR) for early detection of these biomarkers has been greatly appreciated. Due to the rapid, sensitive, real-time, and label-free detection of SPR-based biosensors, they can be applied for selective and nonspecific absorption that is intended to be used as an in situ cardiac biosensor. Here, we exclusively discussed the updated developments of these valuable predictors for the possible occurrence of AMI detected by SPR.

Visual and quantitative lateral flow immunoassay based on Au@PS SERS tags for multiplex cardiac biomarkers.

Rapid and sensitive detection of multiple biomarkers by lateral flow immunoassay (LFIA) remains challenging for signal amplification for commonly used nanotags. Herein, we report a novel LFIA strip for visual and highly sensitive analysis of two cardiac biomarkers based on functionalized gold nanoparticles @ polystyrene microsphere (Au@PS）microcavity as surface-enhanced Raman scattering (SERS) tags. Antibody-modified Au@PS was designed as a SERS label. The evanescent waves propagating along the surface of the PS microcavity and the localized surface plasmons of the gold nanoparticles were coupled to enhance the light-matter interaction synergistically for Raman signal enhancement. In this strategy, the proposed Au@PS SERS tags-based LFIA was carried out to quantify the content of the heart failure and infarct biomarkers synchronously within 15 min and get the limits of detection of 1 pg/mL and 10 pg/mL for cardiac troponin I (cTnI) and N-terminal natriuretic peptide precursor (NT-proBNP), respectively. The results demonstrated 10-20 folds more sensitivity than that of the standard colloidal gold strip and fluorescent strip for the same biomarkers. This novel quantitative LFIA shows promise as a high-sensitive and visual sensing method for relevant clinical and forensic analysis.