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An economical, rapid, and ultrasensitive detection of biomolecules in clinical settings is very crucial, particularly for the early detection of Cardiac Troponin I (cTnI), which is the gold standard biomarker for Acute Myocardial Infarction (AMI). Electrochemiluminescence (ECL) has risen in prominence as an important technique for in vitro diagnosis and detection by virtue of its high sensitivity reaching a femtomolar level. This study introduces an economically feasible nanoplatform for ECL immunosensing, consisting of a gold nanoparticle (AuNP) with Ru(bpy) 3 2+ and tripropylamine (TPA) system, which is a potential ECL luminophore and coreactant system. AuNPs serve the role of an ECL signal enhancer as well as the carrier of antibody, which enables the creation of a label-free immunosensor for antigen-antibody interactions. The prepared immunosensor detected cTnI with a detection limit (LOD) of 0.03 ng/mL. This potential immunosensor provides appreciable results in the detection of cTnI from spiked real serum analysis, which shows its potential application in low-resource clinical settings.

Acute myocardial infarction (AMI) is one of the leading causes of human mortality worldwide. In the early stages of AMI, the patient's electrocardiogram (ECG) may not change, so the fast, sensitive, and accurate detection of the specific biomarker of cardiac troponin I (cTnI) is of great importance in the early diagnosis of AMI. In this work, for the first time, electrostatic nanoaggregates of negatively charged Au nanoparticles and positively charged trisbipyridine ruthenium(II) ions (i.e., (-)AuNPs|[Ru(bpy) 3 ] 2+ ENAs) as novel and signal-amplifying surface-enhanced Raman scattering (SERS) tags were synthesized in an easy and rapid (<3 min) way and applied in the highly sensitive, rapid detection of cTnI in human serum by being combined with an immunochromatographic test strip (ICTS). The synthesized (-)AuNPs|[Ru(bpy) 3 ] 2+ ENAs exhibited strong SERS activity due to the multiple Raman-active units (three bpy ligands) carried by each [Ru(bpy) 3 ] 2+ complex ion and abundant hotspots in each SERS tag. The developed (-)AuNPs|[Ru(bpy) 3 ] 2+ ENAs-based SERS-ICTS has been validated to be applicable in detection of cTnI in human serum with excellent sensing performances, such as fast testing (5 min) and a low detection limit (60 pg/mL). It is envisioned that the developed (-)AuNPs|[Ru(bpy) 3 ] 2+ ENAs-based SERS-ICTS sensor may have promising applications in point of care testing of various biomarkers in clinic. Additionally, this work may inspire the finding and the application of new types of Raman reporter molecules based on high valent metal-multi ligand coordination compounds like [Ru(bpy) 3 ] 2+ .

Cardiac troponin I (cTnI) is the most resorted biomarker for the detection of cardiovascular disease (CVD). The means of rapid quantification of cTnI levels in the blood can substantially minimize the risk of acute myocardial infarction and heart failure. A sensor for the non-enzymatic evaluation of cardiac troponin-I has been developed using fluorescent iron nanoclusters via a one-pot synthesis employing (BSA) as the template and reducing agent, and hydrogen peroxide as the additive. The fluorescence of Iron Nanocluster is quenched with graphene oxide (GO) via fluorescence resonance energy transfer (FRET) between conjugate iron nanoclusters and graphene oxide. The sensor shows a low detection limit of 0.011 ng/mL. The benefits of utilizing a non-enzymatic probe for detecting cardiac troponin I is that it avoids the need for enzymes and hence is economical, stable, and less impacted by environmental conditions such as temperature and pH. Non-enzymatic probes are more useful for clinical use since they are more stable and have a longer shelf life. The developed non-enzymatic probes are also highly selective and sensitive to the target analyte, making them suitable for the direct detection of cardiac troponin I in actual biological samples., (© 2024 Wiley-VCH GmbH.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Pneumonia often causes myocardial damage. This study sought to understand how early myocardial injury affects severe pneumonia patients' prognoses. This multi-center prospective cohort study from March 2020 to October 2023 comprised severe pneumonia patients. Binary logistic regression analysis examined how myocardial damage affects cardiac complications and acute renal injury (AKI). We used Spearman correlation analysis to examine the relationship between troponin I levels and the vasoactive inotropic score (VIS) in shock patients with myocardial injury. We used the Kaplan-Meier survival curve to evaluate the impact of myocardial injury on 30-day and 1-year survival rates. Mediation investigations examined how AKI and cardiac complications mediate myocardial injury and death. This study included 363 severe pneumonia patients, of whom 204 (56.2%) developed myocardial damage, 132 (36.4%) had cardiac problems, and 146 (40.2%) had AKI. Myocardial damage independently elevated the incidence of cardiac complications (OR = 2.548, 95% CI = 1.404-4.303, P = 0.002) and AKI (OR = 1.946, 95% CI = 1.177-3.219, P = 0.009). There was a positive link between troponin I and VIS in myocardial injury and shock patients (r = 0.43, P < 0.001). COX regression found myocardial injury to be a death risk (HR = 1.472, 95% CI = 1.043-2.077, P = 0.028). Adjusted Kaplan-Meier survival analysis showed significantly decreased short-term and long-term survival rates with myocardial injury (log-rank test P < 0.05). The mediation study showed that cardiac complications and AKI mediated myocardial injury and death by 19.30% and 17.18%, respectively. Early myocardial injury in severe pneumonia patients raises the likelihood of cardiac problems, AKI, and refractory shock, reducing short- and long-term survival., Competing Interests: Declarations. Conflict of interest: All authors declare no conflict of interest relevant to the contents of the present manuscript. Ethical approval and consent to participate: This study was approved by the Ethics Committee of Changzhou No. 2 People’s Hospital (approval no: [2020] KY020-01). All patients received informed consent prior to the study. This study strictly followed the Declaration of Helsinki. Participants’ confidentiality was strictly observed throughout the study using the anonymous unique serial number for each subject and restricting data only to the investigators. Consent for publication: Not applicable. Human and animal rights: This article does not contain any studies with human participants or animals performed by any of the authors. Informed consent: None., (© 2024. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Monitoring biomarkers secreted by cardiomyocytes is critical to evaluate anticancer drug-induced myocardial injury (MI). Cardiac troponin I (cTnI) is considered the gold standard biomarker for MI. Herein, an electrochemical aptasensor is engineered for cTnI detection based on lanthanide europium metal-organic frameworks (Eu-MOFs) and a hybridization chain reaction-directed DNAzyme strategy. Three types of Eu-MOF morphologies were easily synthesized by changing the solvent, and the Eu-MOF modulated by mixing the solvent of dimethylformamide and H 2 O (D-Eu-MOF) exhibited the best performance compared to other morphologies of the Eu-MOFs. Multifunctional nanoprobes were constructed from D-Eu-MOF@Pt loaded with natural horseradish peroxidase and combined with an aptamer-initiated nuclear acid hybridization chain reaction to form G-quadruplex/hemin DNAzymes for signal amplification. A novel capture probe is constructed on the basis of DNA nanotetrahedrons modified on screen-printed gold electrodes to enhance the capture of the target and multifunctional nanoprobes for signal amplification. It exhibits a detection limit of 0.17 pg mL -1 and a linear range from 0.5 pg mL -1 to 15 ng mL -1 . The practicality of the platform is evaluated by measuring cTnI in real samples and secreted by cardiomyocytes after drug treatment, which provides great potential in drug-induced MI evaluation for clinical application.

Fluorescence anisotropy (FA) is a versatile and efficient platform for developing biosensors that rely on the rate of rotations of fluorescence molecular entities in biochemical systems. However, by virtue of its intricate complexity, FA is a neglected and less explored area for developing biosensors. Herein, we experimented with the possibility of developing a fluorescence anisotropic probe to detect cardiac troponin I (cTnI), the gold standard biomarker for acute myocardial infarction, via target-specific monoclonal antibody-conjugated gold nanoclusters. The successful detection of cTnI antigen in clinically relevant concentration with a low detection limit of 0.91 ng mL -1 was achieved. The specific molecular interaction between the cTnI antigen and its monoclonal antibody tagged at the surface of gold nanoclusters has restricted the free rotation of gold nanoclusters and increased the FA value. This incremental increase in FA can be correlated to the concentration of cTnI antigen in the sample, thereby achieving the quantitative linear detection of cTnI.

Successful integration of point-of-care testing (POCT) into clinical settings requires improved assay sensitivity and precision to match laboratory standards. Here, we show how innovations in amplified biosensing, imaging, and data processing, coupled with deep learning, can help improve POCT. To demonstrate the performance of our approach, we present a rapid and cost-effective paper-based high-sensitivity vertical flow assay (hs-VFA) for quantitative measurement of cardiac troponin I (cTnI), a biomarker widely used for measuring acute cardiac damage and assessing cardiovascular risk. The hs-VFA includes a colorimetric paper-based sensor, a portable reader with time-lapse imaging, and computational algorithms for digital assay validation and outlier detection. Operating at the level of a rapid at-home test, the hs-VFA enabled the accurate quantification of cTnI using 50 μL of serum within 15 min per test and achieved a detection limit of 0.2 pg/mL, enabled by gold ion amplification chemistry and time-lapse imaging. It also achieved high precision with a coefficient of variation of <7% and a very large dynamic range, covering cTnI concentrations over 6 orders of magnitude, up to 100 ng/mL, satisfying clinical requirements. In blinded testing, this computational hs-VFA platform accurately quantified cTnI levels in patient samples and showed a strong correlation with the ground truth values obtained by a benchtop clinical analyzer. This nanoparticle amplification-based computational hs-VFA platform can democratize access to high-sensitivity point-of-care diagnostics and provide a cost-effective alternative to laboratory-based biomarker testing.

Multiplexed flow cytometry, known for its powerful high-throughput identification capability, is widely applied across various biomedical and clinical fields. However, classical flow cytometry relies on multichannel lasers and detectors, which are significant in cost and size, limiting their application in miniaturized assays. Herein, we developed an acoustic streaming-based flow cytometry technique that focuses on multisized microbeads flowing sheathlessly. This method enables the discrimination of particle types and the quantification of target protein concentrations using only a single detector. Microbeads of different sizes exhibit distinct behaviors in the continuous acoustic streaming tunnel, leading to an increased velocity difference during their transition under the laser spot. Consequently, a size detection method based on "velocity stretching" has been established. A multiplex assay of three proteins: cardiac troponin I, creatine kinase-MB and myoglobin, in acute myocardial infarction is performed to validate the feasibility and evaluate the performance of the system. This new multiplexed flow cytometry strategy is expected to enable low-cost and onsite detection of multiple biomarkers.

The rising demand for point-of-care testing (POCT) in disease diagnosis has made LFIA sensors based on dendritic metal thin film (HD-nanometal) and background fluorescence technology essential for rapid and accurate disease marker detection, thanks to their integrated design, high sensitivity, and cost-effectiveness. However, their unique 3D nanostructures cause significant fluorescence variation, challenging traditional image processing methods in segmenting weak fluorescence regions. This paper develops a deep learning method to efficiently segment target regions in HD-nanometal LFIA sensor images, improving quantitative detection accuracy. We propose an improved UNet++ network with attention and residual modules, accurately segmenting varying fluorescence intensities, especially weak ones. We evaluated the method using IoU and Dice coefficients, comparing it with UNet, Deeplabv3, and UNet++. We used an HD-nanoCu-Ni LFIA sensor for cardiac troponin I (cTnI) as a case study to validate the method's practicality. The proposed method achieved a 96.3% IoU, outperforming other networks. The R 2 between characteristic quantity and cTnI concentration reached 0.994, confirming the method's accuracy and reliability. This enhances POCT accuracy and provides a reference for future fluorescence immunochromatography expansion.

Herein, a direct in situ alkaline phosphatase (ALP)-labeled luminescent nanoimmunoassay platform was constructed using Mn 2+ -triggered aggregation-induced emission transformation of levodopa fluorescent copolymer (LFC) nanoparticles. Using cardiac troponin I (cTn I) as the model antigen, the proposed nanoimmunosensor has been applied to detect cTn I in clinical samples with satisfactory results.

Fluorescent lateral flow immunoassays (FLFIA) is a well-established rapid detection technique for quantitative analysis. However, achieving accurate analysis of biomarkers at the pg mL -1 level using FLFIA still poses challenges. Herein, an ultrasensitive FLFIA platform is reported utilizing a kiwi-type magneto-fluorescent silica nanohybrid (designated as MFS) that serves as both a target-enrichment substrate and an optical signal enhancement label. The spatially-layered architecture comprises a Fe 3 O 4 core, an endocarp-fibers like dendritic mesoporous silica, seed-like quantum dots, and a kiwi-flesh like silica matrix. The MFS demonstrates heightened fluorescence brightness, swift magnetic response, excellent size uniformity, and dispersibility in water. Through liquid-phase capturing and fluorescence-enhanced signal amplification, as well as magnetic-enrichment sample amplification and magnetic-separation noise reduction, the MFS-based FLFIA is successfully applied to the detection of cardiac troponin I that achieved a limit of detection at 8.4 pg mL -1 , tens of times lower than those of previously published fluorescent and colorimetric lateral flow immunoassays. This work offers insights into the strategic design of magneto-fluorescent synergetic signal amplification on LFIA platform and underscores their prospects in high-sensitive rapid and on-site diagnosis of biomarkers., (© 2024 Wiley‐VCH GmbH.)

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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Madhu Bhaskaran reports financial support was provided by Australian Research Council. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

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 Cu 2 O/CuO@CeO 2 nanohybrid exhibits high speed charge mobility and exceptional electrochemical performance. Notably, fluorite-like cubic crystal CeO 2 shell would undergo redox reaction with Cu 2 O 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 CeO 2 , Cu 2 O 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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.

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Air pollution and traffic noise are detrimental to cardiovascular health. However, the effects of different sources of these exposures on cardiovascular biomarkers remain unclear. We explored the associations of long-term exposure to source-specific air pollution (vehicular exhausts and residential woodsmoke) at low concentrations and road-traffic noise with systemic inflammation and cardiovascular disease biomarkers., Material and Methods: Modeled outdoor exposure to fine particulate matter (aerodynamic diameter ≤2.5 μm; PM 2.5 ) from vehicular exhausts and residential woodsmoke, nitrogen dioxide (NO 2 ) from road traffic, and road-traffic noise were linked to the home addresses of the participants (Finnish residents aged 25-74) in the FINRISK study 1997-2012. The participants were located in the cities of Helsinki, Vantaa, and the region of Turku, Finland. The outcomes were high-sensitivity C-reactive protein (CRP), a biomarker for systemic inflammation, and cardiovascular disease biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin I. We performed cross-sectional analyses with linear and additive models and adjusted for potential confounders., Results: We found no association between PM 2.5 from vehicular exhausts (% CRP difference for 1 μg/m 3 increase in PM 2.5 : -0.9, 95% confidence interval, CI: -7.2, 5.8), or from residential woodsmoke (% difference: -8.1, 95% CI: -21.7, 7.9) and CRP (N = 4147). Road-traffic noise >70 dB tended to be positively associated with CRP (% CRP difference versus noise reference category of ≤45 dB: 18.3, 95% CI: -0.5, 40.6), but the association lacked significance and robustness (N = 7142). Otherwise, we found no association between road-traffic noise and CRP, nor between NO 2 from road traffic and NT-proBNP (N = 1907) or troponin I (N = 1951)., Conclusion: Long-term exposures to source-specific, fairly low-level air pollution from vehicular exhausts and residential woodsmoke, or road-traffic noise were not associated with systemic inflammation and cardiovascular disease biomarkers in this urban area., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Tanja Zeller has patent #397 WO2022043229A1 licensed to a computing device to estimate the probability of myocardial infarction. Tanja Zeller is shareholder of the ART.EMIS GmbH Hamburg. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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, HAuCl 4 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.

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.

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., (© 2024. The Author(s).)

Electrochemical immunosensors have gained considerable attention in detecting human disease markers due to their excellent specificity, high sensitivity, and facile operation. Herein, a rational-designed sandwich-type electrochemical immunosensor is constructed for the sensitive detection of cardiac troponin I (cTnI) using nitrogen-doped carbon nanotubes loaded with gold nanoparticles (Au NPs/N-CNTs) as substrate and highly active mesoporous palladium-nitrogen nanocubes (meso-PdN NCs) as secondary antibody markers. Benefitting from its large specific surface area (638.04 m 2 g -1 ) and high nitrogen content, novel polydopamine (PDA)/ halloysite nanotubes (HNTs) hybrid derived one-dimensional (1D) N-CNTs can provide more binding sites for the in-situ growth of Au NPs to connect Ab 1 . Furthermore, as an ideal substrate material, Au NPs/N-CNTs exhibit finely tuned mesoporous structures and outstanding conductivity, which facilitate the mass and electron transfer during the electrocatalysis process. Besides, highly concave surfaces and crystalline mesopores of meso-PdN NCs expose more surfaces and crevices, providing abundant reactive sites for H 2 O 2 reduction. Remarkably, the as-obtained immunosensor presented a wide linear range (from 10 fg mL -1 to 100 ng mL -1 ) and an excellent low detection limit (9.85 fg mL -1 ). This study may offer new insights into the precise fabrication of efficient electrochemical immunosensors for various clinical diagnosis applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Manganese dioxide (MnO 2 ) nanosheets possess unique physical and chemical properties, making them widely applicable in various fields, such as chemistry and biomedicine. Although MnO 2 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 MnO 2 nanosheets by mixing Shiranui mandarin orange juice and KMnO 4 for 30 minutes. We produced more than one gram (1.095) of MnO 2 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 MnO 2 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.

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.

Lateral flow immunoassays (LFIAs) are an essential and widely used point-of-care test for medical diagnoses. However, commercial LFIAs still have low sensitivity and specificity. Therefore, we developed an automatic ultrasensitive dual-color enhanced LFIA (DCE-LFIA) by applying an enzyme-induced tyramide signal amplification method to a double-antibody sandwich LFIA for antigen detection. The DCE-LFIA first specifically captured horseradish peroxidase (HRP)-labeled colored microspheres at the Test line, and then deposited a large amount of tyramide-modified signals under the catalytic action of HRP to achieve the color superposition. A limit of detection (LOD) of 3.9 pg/mL and a naked-eye cut-off limit of 7.8 pg/mL were achieved for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein. Additionally, in the inactivated virus detections, LOD equivalent to chemiluminescence (0.018 TCID 50 /mL) was obtained, and it had excellent specificity under the interference of other respiratory viruses. High sensitivity has also been achieved for detection of influenza A, influenza B, cardiac troponin I, and human chorionic gonadotrophin using this DCE-LFIA, suggesting the assay is universally applicable. To ensure the convenience and stability in practical applications, we created an automatic device. It provides a new practical option for point-of-care test immunoassays, especially ultra trace detection and at-home testing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

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 (I pa ), cathodic peak height (I pc ) 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 I pc and I pa 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.

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 ∼ 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., (© 2024. The Author(s).)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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 Ni 3 V 2 O 8 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.

Objectives: This study performed an analytical validation study of the Mindray high-sensitivity cardiac troponin I (hs-cTnI) assay addressing limit of blank (LoB), limit of detection (LoD), precision, linearity, analytical specificity and sex-specific 99th percentile upper reference limits., Methods: LoB, LoD, precision, linearity and analytical specificity were studied according to Clinical and Laboratory Standards Institute. We used one reagent lot and one CL1200i analyzer. Skeletal troponin I and T, cardiac troponin T, troponin C, actin, tropomyosin, myosin light chain, myoglobin and creatine kinase (CK-MB) were studied for cross-reactivity. Interference with biotin was examined. Lithium heparin samples (one freeze thaw cycle) from healthy males and females were measured to determine the 99th percentiles by using the non-parametric method. Analyses were performed before and after excluding subjects with clinical conditions and/or increased surrogate biomarkers., Results: The Mindray hs-cTnI assay met criteria to be considered as a hs-cTn assay. LoB and LoD was <0.1 ng/L and 0.1 ng/L, respectively. Repeatability had a coefficient of variation 1.2-3.8 %, and within-laboratory imprecision 1.7-5.0 %. The measuring interval ranged from 1.1 to 28,180 ng/L. The analytical specificity was clinically acceptable for the interferents studied. After exclusions, the 99th percentile URLs obtained were 10 ng/L overall, 5 ng/L for females and 12 ng/L for males., Conclusions: Analytical observations of the Mindray hs-cTnI assay demonstrated excellent LoB, LoD, precision, linearity and analytical specificity, that were in alignment with the manufacturer's claims and regulatory guidelines for hs-cTnI. The assay is suitable for clinical investigation for patient-oriented studies., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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. Ta 2 O 5 -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.

Objectives: About 10 million individuals in USA presented annually in the emergency department (ED) with chest pain or with signs and symptoms of acute coronary syndrome (ACS). The advent of point of care (POC) devices, able to measure high sensitivity troponin, are a very interesting tool in the ED setting for its rapid turnaround time (<10 min)., Methods: The present study evaluates the diagnostic performance of the Atellica VTLi (Siemens) in real life setting using the clinical data derived from integrated diagnoses of emergency room staff and cardiologist and in comparison with standard laboratory hs-cTnT assay (Cobas 8000, Elecsys, Roche). 966 patients admitted to the emergency department of "G. Mazzini Hospital" in Teramo, Italy, from July 27, 2022, through June 09, 2023, were enrolled., Results: The diagnostic performance of POC hs-cTnI was evaluated. An appropriate POC hs-cTnI threshold values <4 ng/L supplied a sensitivity and an NPV of 100 % (95 % CI: 99.5-100) in order to achieve rapid rule out for MI through a single measurement at patient presentation in the ED. Furthermore, a derivation POC hs-cTnI concentration >54 ng/L provided a specificity of 97.2 % (95 % CI: 95.9-98.1) and a PPV of 43.5 % (95 % CI: 40.3-46.7) for ruling in MI., Conclusions: This platform showed comparable diagnostic performance for myocardial infarction to the central laboratory. Our data suggest the possible use of the Atellica VTLi hs-cTnI POC assay either in emergency department of urban medical centre, either in rural hospital for triage and patient management., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Efficient and robust electrochemiluminescence (ECL) emitters are crucial for enhancing the ECL immunosensor sensitivity. This study introduces a novel ECL emitter, CoBIM/Cys, featuring a hierarchical core-shell structure. The core of the structure is created through the swift coordination between the sulfhydryl and carboxyl groups of l-cysteine (l-Cys) and cobalt ions (Co 2+ ), while the shell is constructed by sequentially coordinating benzimidazole (BIM) with Co 2+ . This design yields a greater specific surface area and a more intricate porous structure compared to CoBIM, markedly enhancing mass transfer and luminophore accessibility. Moreover, the l-Cys and Co 2+ core introduces Co-S and Co-O catalytic sites, which improve the catalytic decomposition of H 2 O 2 , leading to an increased production of hydroperoxyl radicals (OOH • ). This mechanism substantially amplifies the ECL performance. Leveraging the competitive interaction between isoluminol and BIM for OOH • during ECL emission, we developed a ratiometric immunosensor for cardiac troponin I (cTnI) detection. This immunosensor demonstrates a remarkably broad detection range (1 pg mL -1 to 10 ng mL -1 ), a low detection limit (0.4 pg mL -1 ), and exceptional reproducibility and specificity.

Objectives: The current study was designed to evaluate the analytical performance of the new Mindray highly sensitive cardiac troponin I (hs-cTnI) chemiluminescent immunoassay on Mindray CL-1200i, as a thorough validation of novel hs-cTnI methods is required before introduction into clinical practice., Methods: The evaluation of the analytical performance of this hs-cTnI immunoassay encompassed the calculation of the limit of blank (LOB), limit of detection (LOD), functional sensitivity, imprecision, linearity, 99th percentile upper reference limit (URL) and concordance with another previously validated hs-cTnI chemiluminescent immunoassay., Results: The LOB and LOD were 0.32 and 0.35 ng/L, whilst the functional sensitivity (expressed as cTnI value with <10 % imprecision), was 0.35 ng/L. The linearity was excellent throughout a wide range of clinically measurable values (r=1.00 between 0.8 and 9,726.9 ng/mL). The intra-assay, inter-assay and total imprecision were 1.1-1.3 %, 5.5-8.1 % and 5.6-8.2 %, respectively. The 99th percentile URL calculated using residual plasma from 246 ostensibly healthy blood donors was 9.2 ng/L (4.3 ng/L in women vs. 12.3 ng/L in men). The Spearman's correlation between Mindray hs-cTnI and Access hs-TnI was 0.97, with mean bias of 7.2 % (95 % CI, 2.6-11.9 %)., Conclusions: Although we failed to confirm the very optimistic analytical characteristics previously reported for this method, our evaluation of the novel Mindray hs-cTnI immunoassay on CL-1200i demonstrated that the overall performance is comparable to that of other commercially available hs-cTnI techniques, making it a viable alternative to other methods., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Troponin I as a particular and major biomarker of cardiac failure is released to blood demonstrating hurt of myocardial cells. Unfortunately, troponin I detection in the first hours of acute myocardial infarction usually faces with most negligence. Therefore, developments of point of care devices such as lateral flow strips are highly required for timely diagnosis and prognosis. Lateral flow assays are low-cost paper-based detection platforms relying on specific diagnostic agents such as aptamers and antibodies for a rapid, selective, quantitative and semi-quantitative detection of the analyte in a complex mixture. Moreover, lateral flow assay devices are portable, and their simplicity of use eliminates the need for experts or any complicated equipment to operate and interpret the test results. Additionally, by coupling the lateral flow assay technology with nanotechnology, for labeling and signal amplification, many breakthroughs in the field of diagnostics have been achieved. The present study reviews the use of lateral flow assays in early stage, quantitative, and sensitive detection of cardiac troponin I and mainly focuses on the structure of each type of developed lateral flow assays. Finally, this review summarized the improvements, detection time, and limit of detection of each study as well as the advantages and disadvantages.

Cardiac troponin I (cTnI), a gold biomarker for the diagnosis of acute myocardial infarction (AMI), plays a vital role in the early diagnosis, treatment and prognosis analysis of AMI. In this paper, an electrochemical biosensor for the highly sensitive determination of cTnI was fabricated based on the dual signal amplification strategy of electron transfer atom transfer radical polymerization (ARGET ATRP) and ring-opening polymerization (ROP) for the first time. Briefly, the thiolate cTnI-aptamer 1, which was bonded to the electrode via Au-S bonds, specifically captured cTnI to the electrode surface. Then, cTnI-aptamer 2 (Apt2) was successfully introduced to the electrode surface to form Apt-cTnI-Apt sandwich structure. Subsequently, the initiator BIBB was connected to Apt2 through bromination reaction, and then the resulting ATRP polymer was employed as a macromolecular initiator for the succeeding reaction. Next, the monomers, α-amino acid-N-carboxylic acid anhydride ferrocene derivatives (NCA-Fc), used for the ROP reaction produced numerous electroactive polymers on the electrode surface. The dual action of ARGET ATRP and ROP significantly improved sensitivity of cTnI biosensor assay, the prepared biosensor displayed a wide linear detection range from 100 fg mL -1 to 100 ng mL -1 , with a detection limit of 32.24 fg mL -1 . The method exhibited favorable selectivity, simple operation and excellent stability. Furthermore, the biosensor still rendered satisfactory analytical performance in the detection of clinical serum samples, indicating the application potential in clinical diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Dilated cardiomyopathy (DCM) is common in Great Danes (GDs) but screening for this condition can be challenging. We hypothesised that cardiac troponin-I (cTnI) concentration is elevated in GDs with DCM and/or ventricular arrhythmias (VAs), and is associated with reduced survival time in GDs., Animals: One hundred and twenty-four client-owned GDs assigned echocardiographically as normal (n = 53), equivocal (n = 37), preclinical DCM (n = 21), or clinical DCM (n = 13)., Materials and Methods: A retrospective epidemiological study. Echocardiographic diagnosis, VAs, and contemporaneous cTnI concentrations were recorded. Diagnostic accuracy and cTnI cut-offs were determined with receiver operating characteristic analyses. Effects of the cTnI concentration and disease status on survival and cause of death were explored., Results: Median cTnI was greater in clinical DCM (0.6 ng/mL [25th-75th percentiles: 0.41-1.71 ng/mL]) and GDs with VAs (0.5 ng/mL [0.27-0.80 ng/mL], P<0.001). Elevated cTnI detected these dogs with good accuracy (area under the curve: 0.78-0.85; cut-offs 0.199-0.34 ng/mL). Thirty-eight GDs (30.6%) suffered a cardiac death (CD); GDs suffering CD (0.25 ng/mL [0.21-0.53 ng/mL]) and specifically sudden cardiac death (SCD) (0.51 ng/mL [0.23-0.72 ng/mL]) had higher cTnI than GDs dying of other causes (0.20 ng/mL [0.14-0.35 ng/mL]; P<0.001). Elevated cTnI (>0.199 ng/mL) was associated with shorter long-term survival (1.25 years) and increased risk of SCD. Great Danes with VAs had shorter survival times (0.97 years)., Conclusions: A cardiac troponin-I concentration is a useful adjunctive screening tool. Elevated cTnI is a negative prognostic indicator., Competing Interests: Conflict of Interest Statement The authors do not have any conflicts of interest to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Cardiac troponin I (cTnI) is considered as the gold standard for the diagnosis of acute myocardial infarction (AMI) because of its excellent specificity and sensitivity. Herein, a novel aptasensor based on the dual signal amplification strategy of Polyethyleneimine functionalized Graphene oxide (GO) and ring-opening polymerization (ROP) for the first time was successfully constructed to achieve high sensitivity detection of cTnI. Briefly, cTnI-aptamer 1 (Apt1) was immobilized on the surface of gold electrode by self-assembly of Au-S bonds to specifically capture cTnI. After specific recognition of cTnI, Apt2 coated PEI-functionalized GO composites acted as macroinitiators for the subsequent ROP reaction. Next, α-amino acid-N-carboxylic acid anhydride ferrocene derivatives (NCA-Fc), the monomer for ROP reaction, was added to the electrode surface. The combined application of PEI-functionalized GO and NCA-Fc better achieves the high sensitivity and signal amplification of the aptasensor. Under optimal conditions, the aptasensor exhibited a wide linear range of 10 fg mL -1 to 10 ng mL -1 and the limit of detection was 3.78 fg mL -1 . Moreover, this method displayed the advantages of good selectivity, simple operation and excellent stability. Meanwhile, the aptasensor had good accuracy and applicability even in real serum samples analysis, demonstrating its considerable application potential in biomedical assays., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Galectin-3, a biomarker of inflammation and fibrosis, can be associated with renal and myocardial damage and dysfunction in patients with acute heart failure (AHF)., Methods and Results: We retrospectively analyzed 790 patients with AHF who were enrolled in the AKINESIS study. During hospitalization, patients with galectin-3 elevation (> 25.9 ng/mL) on admission more commonly had acute kidney injury (assessed by KDIGO criteria), renal tubular damage (peak urine neutrophil gelatinase-associated lipocalin [uNGAL] > 150 ng/dL) and myocardial injury (≥ 20% increase in the peak high-sensitivity cardiac troponin I [hs-cTnI] values compared to admission). They less commonly had ≥ 30% reduction in B-type natriuretic peptide from admission to last measured value. In multivariable linear regression analysis, galectin-3 was negatively associated with estimated glomerular filtration rate and positively associated with uNGAL and hs-cTnI. Higher galectin-3 was associated with renal replacement therapy, inotrope use and mortality during hospitalization. In univariable Cox regression analysis, higher galectin-3 was associated with increased risk for the composite of death or rehospitalization due to HF and death alone at 1 year. After multivariable adjustment, higher galectin-3 levels were associated only with death., Conclusions: In patients with AHF, higher galectin-3 values were associated with renal dysfunction, renal tubular damage and myocardial injury, and they predicted worse outcomes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Considering the fact that acute myocardial infarction has shown a trend towards younger age and has become a major health problem, it is necessary to develop rapid screening devices to meet the needs of community health care. Herein, we developed an artificial neural network-assisted solar-powered photoelectrochemical (SP-PEC) sensing platform for rapid screening of cardiac troponin I (cTnI) protein in the prognosis of patients with acute myocardial infarction (AMI) by integrating a self-powered photoelectric signal output system with low-cost screen-printed paper electrodes functionalized with ultrathin Bi 2 O 2 S (BOS) nanosheets. An integrated solar-powered PEC immunoassay with micro-electro-mechanical system (MEMS) was constructed without an excitation light source. The quantification of cTnI protein was obtained by the electrical signal changes caused by the electro-oxidation process of H 2 O 2 , generated by the classical split immune reaction, on the electrode surface. The test electrodes were developed as dual working electrodes, one for target cTnI testing and the other for evaluating light intensity, to reduce the temporal inconsistency of sunlight. The photoelectrodes were discovered to exhibit satisfactory negative response to target concentrations in the dynamic range of 2.0 pg mL -1 -10 ng mL -1 since being regressed in an improved artificial neural network (ANN) model using the pooled dataset of target signals affected by the light source. The difference of hot electron and hole transfer behavior in different thickness of nano-materials was determined by finite element analysis (FEA), which provided a theoretical basis for the development of efficient PEC sensors. This work presents a unique perspective for the design of a revolutionary low-cost bioassay platform by inventively illuminating the PEC biosensor's component process without the use of light., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This work reports the construction of a novel nanostructured immunosensor for detection of the troponin I biomarker (cTnI). Anti-troponin I antibody was anchored on the modified graphite electrode with reduced graphene oxide and polytyramine for detection of troponin I in serum samples. The performance of the electro-immunosensor was evaluated by differential pulse voltammetry. The immunosensor presented a wide work range, from 4 ng mL -1 to 4 pg mL -1 , whose detection limit (4 pg mL -1 ) is significantly lower than the basal level in human serum, and maintained 100% of response after 30 days of storage. Moreover, the immunosensor showed good selectivity for detection of cTnI in real sample containing interfering substances and specificity of response to cTnI in the serum of healthy and sick patients, and demonstrated the possibility of reuse for two consecutive analyses, in addition to using a simplified and inexpensive platform when compared to other devices, demonstrating them excellent potential for application in diagnosis in the early stages of acute myocardial infarction., (© 2022 John Wiley & Sons Ltd.)

The cardiac troponin I (cTnI) detection is increasingly significant given its promising value in the clinical acute myocardial infarction diagnosis. Here a sensitive sandwich-type cTnI electrochemical aptasensor was developed by using zirconium-carbon loaded with Au (Au/Zr-C) as electrode-modified material and snowflake-like PtCuNi catalyst as label material. The Au/Zr-C was prepared from a carbonation process and a reduction step. The PtCuNi was synthesized by a one-pot hydrothermal reaction. On the one hand, due to its many merits of large effective area, rich pores, high degree of graphitization, the assistance of Au, the Au/Zr-C exhibited remarkable electronic conductivity but low catalytical capacity, thus improving the electrochemical property but lowing the background signal of electrode. On the other hand, because of its accessible active sites of the special snowflake-like structure and the synergy of three elements, the PtCuNi catalyst presented excellent catalytic activity and improved stability compared to binary alloy. The recognition reactions were achieved by stepwise incubation of aptamer 1, cTnI, and aptamer 2-PtCuNi (denoted as Apt2-label) on the Au/Zr-C-modified electrode. The electrocatalytic signals of the immobilized Apt2-label towards the H 2 O 2 reduction were recorded in all tests for cTnI analysis. Consequently, this cTnI aptasensor exhibited excellent performance involving a wide linear range of 100 ng mL -1 to 0.01 pg mL -1 with a detection limit of 1.24 × 10 -3  pg mL -1 (S/N = 3), good selectivity, satisfying reproducibility, outstanding stability, and good recovery., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Coronavirus disease 2019 (COVID-19) is still challenging health care systems worldwide. Over time, it has become clear that respiratory disease is not the only important entity as critically ill patients are also more prone to develop complications, such as acute cardiac injury. Despite extensive research, the mainstay of treatment still relies on supportive care and targeted therapy of these complications. The development of a prognostic model which helps clinicians to diverge patients to an appropriate level of care is thus crucial. As a result, several prognostic markers have been studied in the past few months. Among them are the cardiac biomarkers, especially cardiac troponins T/I and brain natriuretic peptide, which seem to have important prognostic values as several reports have confirmed their strong association with adverse clinical outcomes and death. The use of these biomarkers as part of a prognostic tool could potentially result in more precise risk stratification of COVID-19 patients and divergence to an adequate level of care. However, several caveats persist causing international guidelines to still recommend in favour of a more conservative approach to cardiac biomarker testing for prognostic purposes.

We present the development of novel tetrapolar EIS biosensor for the detect of troponin. Troponin has considerable diagnostic power and provide invaluable prognostic information for risk stratification. of acute coronary syndromes. Clinical Relevance- A feasibility study was undertaken to assess the diagnostic performance of serial cardiac troponin measurements which is excellent as these structural proteins are unique to the heart and thus sensitive and specific of damage to the myocardium. clinical molecular diagnostics and home healthcare. Troponin's biosensors would provide point-of-care and rapid decision making for the early detection of CS. Clinically relevant window of cTnI testing, concentrations from 10pM to 0.1μM were achieved.

Surface engineering of upconverting nanoparticles (UCNPs) is crucial for their bioanalytical applications. Here, an antibody specific to cardiac troponin I (cTnI), an important biomarker for acute myocardial infection, was covalently immobilized on the surface of UCNPs to prepare a label for the detection of cTnI biomarker in an upconversion-linked immunoassay (ULISA). Core-shell UCNPs (NaYF 4 :Yb,Tm@NaYF 4 ) were first coated with poly(methyl vinyl ether-alt-maleic acid) (PMVEMA) and then conjugated to antibodies. The morphology (size and uniformity), hydrodynamic diameter, chemical composition, and amount of coating on the of UCNPs, as well as their upconversion luminescence, colloidal stability, and leaching of Y 3+ ions into the surrounding media, were determined. The developed ULISA allowed reaching a limit of detection (LOD) of 0.13 ng/ml and 0.25 ng/ml of cTnI in plasma and serum, respectively, which represents 12- and 2-fold improvement to conventional enzyme-linked immunosorbent based on the same immunoreagents., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The estimation of accurate post mortem interval (PMI) is a crucial question in forensic medicine. Several approaches have been used to determine the PMI including physical, metabolic, autolytic, entomological, physiochemical and biochemical methods over time. For estimation of PMI, RNA degradation after death is reported to be an important tool. This study aimed to analyse the pattern of gene expression by serial estimation of cardiac specific cardiac troponin I (cTnI) gene and autophagy gene HMGB1 for determining PMI at room temperature by using housekeeping gene GAPDH. Right ventricular heart tissue weighing 10 g was collected and harvested from 17 medico-legal autopsies. The tissue was homogenized in phosphate-buffered saline (PBS) on ice. Further, homogenate of cardiac tissue was analysed by quantitative Real time polymerase chain reaction (qRtPCR) for gene amplification and gene expression of cTnI, HMGB1 gene and GAPDH, at different time intervals (0,6,12 h) at room temperature. The result revealed ∆Ct value of cTnI gene of the cardiac muscle showing almost equal degradation at equal time interval correlated with PMI within 0-12 h at room temperature, and the ∆Ct value of HMGB1 degraded to half in every subsequent 6-hour interval at room temperature. In conclusion, the estimation of PMI by analysis of serial estimation of gene expression is a decent new tool in forensic medicine. The study shows an equal degradation of cTnI gene at equal time interval and HMGB1 degrades to half at six-hour interval. Therefore, these can be useful for estimation for PMI., (Copyright © 2022 Elsevier B.V. All rights reserved.)