Rapid progress in identifying biomarkers that are hallmarks of disease has increased demand for high-performance detection technologies. Implementation of electrochemical methods in clinical analysis may provide an effective answer to the growing need for rapid, specific, inexpensive, and fully automated means of biomarker analysis. This Review summarizes advances from the past 5 years in the development of electrochemical sensors for clinically relevant biomolecules, including small molecules, nucleic acids, and proteins. Various sensing strategies are assessed according to their potential for reaching relevant limits of sensitivity, specificity, and degrees of multiplexing. Furthermore, we address the remaining challenges and opportunities to integrate electrochemical sensing platforms into point-of-care solutions.

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Electrochemical Methods for the Analysis of Clinically Relevant Biomolecules

Synthesis and Applications of Boronic Acid-Containing Polymers: From Materials to Medicine.

The cardiovascular disease (CVD) is considered as a major threat to global health. Therefore, there is a growing demand for a range of portable, rapid and low cost biosensing devices for the detection of CVD. Biosensors can play an important role in the early diagnosis of CVD without having to rely on hospital visits where expensive and time-consuming laboratory tests are recommended. Over the last decade, many biosensors have been developed to detect a wide range of cardiac marker to reduce the costs for healthcare. One of the major challenges is to find a way of predicting the risk that an individual can suffer from CVD. There has been considerable interest in finding diagnostic and prognostic biomarkers that can be detected in blood and predict CVD risk. Of these, C-reactive protein (CRP) is the best known biomarker followed by cardiac troponin I or T (cTnI/T), myoglobin, lipoprotein-associated phospholipase A(2), interlukin-6 (IL-6), interlukin-1 (IL-1), low-density lipoprotein (LDL), myeloperoxidase (MPO) and tumor necrosis factor alpha (TNF-α) has been used to predict cardiovascular events. This review provides an overview of the available biosensor platforms for the detection of various CVD markers and considerations of future prospects for the technology are addressed.

/pdf/biosensors-for-cardiac-biomarkers-detection-a-review-4qnv27zln9.pdf

Biosensors for cardiac biomarkers detection: A review

Surface plasmon resonance (SPR)-based biosensors are very powerful tools for the study of biomolecular interactions, chemical detection and immunoassays. This paper reviews the performance of various SPR structures and detection schemes focusing on propagating surface plasmons generated in planar structures. Some aspects of their surface functionalization, the key element which imparts biofunctionality to these structures and hence transforming them into biosensors, will also be discussed accordingly. The ultimate performance of SPR-based biosensors will thus be determined by both their inherent optical performance and suitable surface functionalization.

Surface plasmon resonance-based biosensors: From the development of different SPR structures to novel surface functionalization strategies

In this review, we wish to show that in the recent years a
significant progress was done in the EC analysis of practically
all proteins, based on electroactivity of amino acid (aa)
residues in proteins. Also electrochemistry of polysaccharides,
oligosaccharides and glycoproteins greatly advanced in creating
important steps for its larger application in the glycoprotein
research. In recent decades, a great effort was devoted to the
discovery and application of biomarkers for analysis of
different diseases, including cancer. In the following
paragraphs, special attention will be paid (i) to intrinsic
electroactivity of peptides and proteins, including the
sensitivity to changes in protein 3D structures, as well as to
recent advances in EC investigations of DNA-protein
interactions, (ii) to intrinsic electroactivity of glycans and
polysaccharides, advances in EC detection of
lectin-glycoprotein interactions and to introduction of
electroactive labels to polysaccharides and glycans and finally
(iii) to EC detection of protein biomarkers, based
predominantly on application of antibodies in immunoassays,
nucleic acid and peptide aptamers for construction of
aptasensors, and lectin biosensors for detection of
glycoprotein biomarkers.

Electrochemistry of Nonconjugated Proteins and Glycoproteins. Toward Sensors for Biomedicine and Glycomics

A fluoro-microbead guiding chip for simple and quantifiable immunoassay of cardiac troponin I (cTnI).

We studied electrochemical detection of glycated hemoglobin (HbA1c) using boronic acid-modified electrodes. Boronic acid is known to form covalent bonds between its diol group and cis-diol group of the carbohydrate chain. Therefore, to detect HbA1c, boronic acid was functionalized on the chemically modified electrode surface using poly(amidoamine) G4 dendrimer as an interface material. HbA1c was biospecifically attached to the chip surface through the cis-diol interaction between peripheral glucose from HbA1c and functionalized boronic acid. To confirm the HbA1c binding to the boronic acid layer, periodate-treated glucose oxidase (GOx) was backfilled to the remaining amine groups of dendrimer on the electrode surface and quantified electrochemically. A sensitive decrement of the current was achieved with increasing percentile concentration from 2.5% to 15% HbA1c per total hemoglobin. This method has potential not only to determine HbA1c concentration but also to determine the concentrations of a variety of glycoproteins that contain peripheral sugar groups.

Boronic acid-modified thin film interface for specific binding of glycated hemoglobin (HbA1c) and electrochemical biosensing

We investigated the electrochemical detection of aspartate transaminase (AST) and alanine transaminase (ALT) by using a multienzyme-modified electrode surface. Determination of the activities of transaminases in human serum is clinically significant because their concentrations and ratios indicate the presence of hepatic diseases or myocardial dysfunction. For electrochemical detection of AST and ALT, enzymes that participate in the reaction mechanism of AST and ALT, such as pyruvate oxidase (POX) and oxaloacetate decarboxylase, were immobilized on an electrode surface by using an amine-reactive self-assembled monolayer and a homobifunctional cross-linker. In the presence of suitable substrates such as L-aspartate (L-alanine) and α-ketoglutarate, AST and ALT generate pyruvate as an enzymatic end product. To determine the activities of AST and ALT, electroanalyses of pyruvate were conducted using a POX and ferrocenemethanol electron shuttle. Anodically generated oxidative currents from multienzyme-mediated reactions were correlated to AST and ALT levels in human plasma. On the basis of the electrochemical analysis, we obtained calibration results for AST and ALT concentrations from 7.5 to 720 units/L in human plasma-based samples, covering the required clinical detection range.

Multienzyme-modified biosensing surface for the electrochemical analysis of aspartate transaminase and alanine transaminase in human plasma.

Chip-based cartilage oligomeric matrix protein detection in serum and synovial fluid for osteoarthritis diagnosis

Bioelectrocatalytic detection of glycated hemoglobin (HbA1c) based on the competitive binding of target and signaling glycoproteins to a boronate-modified surface.

Seung Yeon Song

Papers

A fluoro-microbead guiding chip for simple and quantifiable immunoassay of cardiac troponin I (cTnI).

Boronic acid-modified thin film interface for specific binding of glycated hemoglobin (HbA1c) and electrochemical biosensing

Multienzyme-modified biosensing surface for the electrochemical analysis of aspartate transaminase and alanine transaminase in human plasma.

Chip-based cartilage oligomeric matrix protein detection in serum and synovial fluid for osteoarthritis diagnosis

Bioelectrocatalytic detection of glycated hemoglobin (HbA1c) based on the competitive binding of target and signaling glycoproteins to a boronate-modified surface.