Review
Nanomaterial-based biosensors and immunosensors for quantitative determination of cardiac troponins

https://doi.org/10.1016/j.jpba.2018.07.031Get rights and content

Highlights

  • Acute myocardial infraction (AMI) is one of the most common types of CVDs.

  • Cardiac troponin I and T as predominant cardiac infarction biomarkers considered as “gold standard” for diagnosis of AMI.

  • We have collected the developments in the application of biosensors for the detection of predominant cardiac troponins .

Abstract

Cardiovascular diseases (CVDs) are the most frequent mortality cause in many countries. The acute myocardial infraction (AMI) is one of the most common types of CVDs. Cardiac troponin I (cTnI) and cardiac troponin T (cTnT) as predominant cardiac infarction biomarkers considered as “gold standard” for diagnosis of acute myocardial infraction (AMI). The restrictions of traditional methods have encouraged the development of highly sensitive and specific methods for cTnI and cTnT detection. The rapid, early, reliable, and cost-effective diagnosis of CVDs not only helps with patient survival, but also save cost and time to prosperous prognosis. In recent years, the concept of biosensors has opened new horizons in high precision detection. Once combined with nanomaterials, nano-scale biosensors provide powerful analytical platforms for diagnosing of cTnI and cTnT. In this article, after a brief overview of the cardiac troponins, a classification and description of the research progresses of biosensors and immunosensors for the detection and quantitative determination of cardiac troponins based on optical and electrochemical platforms are presented.

Introduction

Cardiovascular diseases (CVDs) are a group of the heart and blood vessels disorders. Based on 2017 World Health Organization (WHO) report, CVDs are the main cause of death globally estimated that 31% of all global deaths (∼17.7 million deaths) in 2017 was related to CVDs [1]. According to new European cardiovascular disease statistics, CVDs cost nearly € 210 billion in a year [2]. Therefore, the quick, early and low cost diagnosis of CVDs not only helps with patient survival, but also save cost and time to prosperous prognosis. One of the most common types of the CVDs is acute myocardial infraction (AMI). After blockage of a coronary artery and lack of blood supply (ischemia), myocardial muscle getting damaged and leading to the AMI [3]. Because of myocardial necrosis is irreversible and 85% heart damage progresses within the first two hours after the onset of a heart attack, it seems that accurate diagnosis and instant treatment is important to increment the survival rate [3]. The main factor to establish the AMI happening is the determination of the concentration of biomarkers in the blood sample.

The most important cardiac infarction biomarkers include the following; cardiac troponin I (cTnI), cardiac troponin T (cTnT), C-reactive protein (CRP), myoglobin, lipoprotein-associated phospholipase, interleukin-6 (IL-6), interleukin-1 (IL-1), myeloperoxidase (MPO) and tumor necrosis factor alpha (TNF-α) [[4], [5], [6], [7], [8]]. Due to outstanding specificity and supreme sensitivity for acute myocardial cell damage, cTnI and cTnT preferred for diagnosis and these biomarkers considered as “gold standard” to AMI diagnosis [7,9]. After the onset of AMI, troponins levels elevate within 4 h; half-life is about 2 h and persist in the blood for 4–10 days. The normal value of cTnI is about 0.4 ng mL−1 and levels higher than 2.0 ng mL−1 indicate risk for future serious heart events [[10], [11], [12]]. Troponin T found in cardiac and skeletal muscle, whereas troponin I only found in cardiac muscle and Troponin C is selectively expressed in skeletal muscle cells [13,14]. A schematic view of troponin is shown in Fig. 1.

As routine tests, immunoenzymometric assays (ELISAs) have been used for cTnI and cTnT quantification [15]. Because of time limitation in terms of diagnosis and treatment, we need highly sensitive and low cost methods with stable characteristics and fast response time. In the last decade, special attention has been paid to biosensors, because of their high sensitivity, low cost, rapid and reliable determination [16].

Biosensor is an analytical device capable of generating specific quantitative or semi-quantitative analytical information using a biological recognition element integrated to a transducer unit [18]. Optical and electrochemical platforms are two accessible types of biosensors [19]. With notable achievements in nanoscience, especially nanoparticles (NPs) introduce unique properties for designing biosensors and immunosensors and display great potential for simple, swift and sensitive monitoring of biomarkers [20]. Biosensor can help in rapid diagnosis, providing better health care and reducing the waiting time for results dissemination which is highly stressful to the patients. A variety of methods such as colorimetric [21], chemiluminescent immunoassays [22], electrochemical [23,24], fluoro-immunoassays [25], fluorescent [26,27], chemiluminescence [15] and have been developed for the determination of cTnI and cTnT. In this review, we have collected the developments in the application of biosensors and immunosensors for the determination of predominant cardiac troponins (cTnI and cTnT); also highlighted the major clinically relevant parameters such as their detection limit/range and designing of the bioassay.

Section snippets

Electrochemical-based determination of cTnI

Typically, electrochemical biosensors are detected output of an electrode transducer generated following specific binding or catalytic reactions of surface modifier biomaterials such as aptamer, enzyme, antibody, or nucleic acids on the surface of a metal or carbon electrode [28,29]. Electrochemical techniques attracted considerable attention because of special features like simplicity, sensitivity and enable performing rapid analysis. For this reason, electrochemical biosensors are the most

Optical-based determination of cTnI

Optical biosensors are the most sensitive techniques that are based on the change in the phase, amplitude, polarization, or frequency of the input light in response to the biorecognition processes. The optical biosensor can divided into colorimetric, fluorescence, luminescence, surface plasma resonance (SPR) and fiber optics/bio-optrode based biosensors [55].

Electrochemical immunosensors for cTnT determination

Because of special characteristics such as rapid release in the bloodstream than creatine kinase (CK)-MB and also quick increase of its blood concentration in 3–4 h after onset of the AMI, cardiac troponin T is widely used as a clinical marker for myocardial damage associated with acute infarction. Due to the roles of the cTnT in cardiospecific diagnosis, prognostic risk assessment, therapeutic choices, and risk stratification, the improvement of an applied and rapid immunosensor for the cTnT

SPR-based biosensor for cTnT determination

The SPR method has been used for analytical application in immunosensors. Refractive index alteration and immobilizing antibodies in sensors led to the high sensitivity for the variation of mass on the transducer surface in this technique [89,90]. Dutra et al. designed an SPR immunosensor for the determination of human cTnT using specific binding of avidin to biotin at carboxymethyldextran-modified gold chip. Self-assembled monolayer employed for binding of biotinylated anti troponin T

Multiplexed analysis

Recently multiplexed strategies for detecting cardiac troponins garnered interest because of their ability to determine multiple analytes simultaneously in time and cost effective manner. For multiplexed label-free and ultra-sensitive determination some strategies have been adopted. One of the most frequently implemented methods is electrical/electrochemical based biosensor platforms which are capturing the biomarkers on the surface of electrode materials which transduces the biological signal

Conclusions and outlook

For successful treatment and recovery of CVDs patients, rapid diagnosis in early stage play main role in its process. In the other hand, it is critically important to develop sensitive and simple CVDs diagnostic methods which can determine principal cardiac biomarkers at very low concentrations in biological fluids. In this review, we have collected the developments in the application of biosensors for the determination of cardiac troponins (cTnI and cTnT), also highlighted in the major

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