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

Carbon nanotube (CNT) based biosensors are recognized to be a next generation building block for ultra-sensitive and ultra-fast biosensing systems. This article provides an overview on the recent expansion of research in the field of CNT-based biosensors. We start by first introducing the material structures and properties of CNTs. The basic and some new developed synthetic methods of CNTs are presented. This is followed by a collection of working principle and performance of different CNT-based biosensors. The roles and the processing methods of functionalized CNTs are summarized. After that, some of the practical applications and concerns in the field are addressed. What is more, the scientific and technological challenges in the field are discussed at the end of this review.

Carbon nanotube based biosensors

Screen-printing is one of the most promising approaches towards simple, rapid and inexpensive production of biosensors. Disposable biosensors based on screen printed electrodes (SPEs) including microelectrodes and modified electrodes have led to new possibilities in the detection and quantitation of biomolecules, pesticides, antigens, DNA, microorganisms and enzymes. SPE-based sensors are in tune with the growing need for performing rapid and accurate in-situ analyses and for the development of portable devices. This review (with 226 refs.) first gives an introduction into the topic and then is subdivided into sections (a) on DNA sensors (including methods for the detection of hybridization and damage), (b) on aptasensors (for thrombin, OTA, immunoglobulins and cancer biomarkers), (c) on immunosensors (for microorganisms, immunoglobulins, toxins, hormones, lactoferrin and biomarkers), (d) on enzymatic biosensors (for glucose, hydrogen peroxide, various pharmaceuticals, neurotransmitters, amino acids, NADH, enzyme based sensors).

Screen-printed electrodes for biosensing: a review (2008–2013)

Applications of conducting polymer composites to electrochemical sensors: A review

Recent advances in nanomaterial-based biosensors for antibiotics detection.

Human epidermal growth factor receptor 2 (HER2) and HER2-overexpressing breast cancer cells were detected using an electrochemical immunosensor combined with hydrazine and aptamer-conjugated gold nanoparticles (AuNPs). The sensor probe was fabricated by covalently immobilizing anti-HER2 onto a nanocomposite layer that was composed of self-assembled 2,5-bis(2-thienyl)-1H-pyrrole-1-(p-benzoic acid) (DPB) on AuNPs. The hydrazine-AuNP-aptamer bioconjugate, where the hydrazine reductant was directly attached onto AuNPs to avoid the nonspecific deposition of silver on the sensor surface, was designed and used to reduce silver ion for signal amplification selectively. The silver-stained target cells were visualized easily by the bare eye and an optical microscope, and the cells were quantitatively analyzed using stripping voltammetry. The parameters affecting the analytical response were optimized. The proposed sensor was capable of differentiating between HER2-positive breast cancer cells and HER2-negative cells. This method exhibited an excellent diagnosis method for the ultrasensitive detection of SK-BR-3 breast cancer cells in human serum samples with a detection limit of 26 cells/mL.

Ultrasensitive and selective electrochemical diagnosis of breast cancer based on a hydrazine-Au nanoparticle-aptamer bioconjugate.

Label-free detection of kanamycin based on the aptamer-functionalized conducting polymer/gold nanocomposite

Amplification strategy based on gold nanoparticle-decorated carbon nanotubes for neomycin immunosensors.

Simultaneous evaluation of the binding affinity of a series of aptamers toward a target molecule was investigated using an electrochemical microarray chip. The chip was modified by immobilizing seven aptamers obtained from the SELEX process and a control sequence onto gold nanoparticle-comprised conducting polymer-coated microarray electrodes. The chip was then incubated with the target molecule, kanamycin. The electrochemical response of the captured kanamycin was studied to evaluate the binding affinity of the aptamers, which showed the same trend with the fluorescence spectroscopic results. The lowest dissociation constant between a selected aptamer and kanamycin was determined to be 38.06 � 0.73 nM.

Electrochemical Evaluation of Binding Affinity for Aptamer Selection Using the Microarray Chip

An amperometric immunosensor for IgG was developed by covalently immobilizing anti-IgG on multiwall carbon nanotube-embedded conducting polymer, poly-5,2′ : 5′′,2′′-terthiophene-3′-carboxylic acid (MWCNT/pTTCA). The MWCNT/pTTCA modified electrode was characterized by SEM, EIS, and XPS. A hydrazine-labeled secondary antibody-MWCNT conjugate (Hyd-MWCNT-Ab2) was applied for detection. Hydrazine was used as a catalyst for the reduction of hydrogen peroxide, which was monitored at −0.3 V vs. Ag/AgCl. The calibration plots showed a linear range of 0.1–10 ng/mL with a detection limit of 0.084±0.004 ng/mL. The proposed immunosensor was evaluated for clinical applications in a rabbit serum sample.

Ye Zhu

Papers

Ultrasensitive and selective electrochemical diagnosis of breast cancer based on a hydrazine-Au nanoparticle-aptamer bioconjugate.

Label-free detection of kanamycin based on the aptamer-functionalized conducting polymer/gold nanocomposite

Amplification strategy based on gold nanoparticle-decorated carbon nanotubes for neomycin immunosensors.

Electrochemical Evaluation of Binding Affinity for Aptamer Selection Using the Microarray Chip

An Amperometric Immunosensor for IgG Based on Conducting Polymer and Carbon Nanotube‐Linked Hydrazine Label