Electrochemical Aptasensors for Parkinson's Disease Biomarkers Detection.

BACKGROUND: Biomarkers are characteristic molecules that can serve as indicators of biological process status or condition; here, they are being studied with special relevance to Parkinson's Disease (PD). This disease is a chronic neurodegenerative disorder very difficult to study given the site of pathology and due to a clinical phenotype that fluctuates over time. Currently, there is no definitive diagnostic test for Parkinson's Disease; thus, clinicians hope that the detection of crucial biomarkers will help in the symptomatic and presymptomatic diagnostics and provide surrogate endpoints to demonstrate the clinical efficacy of new treatments. METHODS: Electrochemical aptasensors are excellent analytical tools that are used in the detection of PD biomarkers, as they are portable, easy to use, and perform real-time analysis. RESULTS: In this review, we discuss the most important clinical biomarkers for PD, highlighting their physiological role and function in the disease. Herein, we review, for the first time, innovative aptasensors for the detection of current potential PD biomarkers based on electrochemical techniques and discuss future alternatives, including ideal analytical platforms for point-of-care diagnostics. CONCLUSION: These new tools will be critical not only in the discovery of sensitive, specific, and reliable biomarkers of preclinical PD, but also in the development of tests that can assist in the early detection and differential diagnosis of parkinsonian disorders and in monitoring disease progression. Various methods for fixing aptamers onto the sensor surfaces, enabling quantitative and specific PD biomarker detection present in synthetic and clinical samples, will also be discussed.

Design Strategies for Electrochemical Aptasensors for Cancer Diagnostic Devices.

Improved outcomes for many types of cancer achieved during recent years is due, among other factors, to the earlier detection of tumours and the greater availability of screening tests. With this, non-invasive, fast and accurate diagnostic devices for cancer diagnosis strongly improve the quality of healthcare by delivering screening results in the most cost-effective and safe way. Biosensors for cancer diagnostics exploiting aptamers offer several important advantages over traditional antibodies-based assays, such as the in-vitro aptamer production, their inexpensive and easy chemical synthesis and modification, and excellent thermal stability. On the other hand, electrochemical biosensing approaches allow sensitive, accurate and inexpensive way of sensing, due to the rapid detection with lower costs, smaller equipment size and lower power requirements. This review presents an up-to-date assessment of the recent design strategies and analytical performance of the electrochemical aptamer-based biosensors for cancer diagnosis and their future perspectives in cancer diagnostics.

Recent Advancements in Electrochemical Biosensors for Alzheimer's Disease Biomarkers Detection.

BACKGROUND: It is estimated that the average time between the diagnosis of Alzheimer's disease (AD) and the patient's death is 5-9 years. Therefore, both the initial phase of the disease and the preclinical state can be included in the critical period in disease diagnosis. Accordingly, huge progress has recently been observed in biomarker research to identify risk factors for dementia in older people with normal cognitive functions and mild cognitive impairments. METHODS: Electrochemical biosensors are excellent analytical tools that are used in the detection of AD biomarkers as they are easy to use, portable, and can do analysis in real time. RESULTS: This review presents the analytical techniques currently used to determine AD biomarkers in terms of their advantages and disadvantages; the most important clinical biomarkers of AD and their role in the disease. All recently used biorecognition molecules in electrochemical biosensor development, i.e., receptor protein, antibodies, aptamers and nucleic acids, are summarized for the first time. Novel electrochemical biosensors for AD biomarker detection, as ideal analytical platforms for point-of-care diagnostics, are also reviewed. CONCLUSION: The article focuses on various strategies of biosensor chemical surface modifications to immobilize biorecognition molecules, enabling specific, quantitative AD biomarker detection in synthetic and clinical samples. In addition, this is the first review that presents innovative single-platform systems for simultaneous detection of multiple biomarkers and other important AD-associated biological species based on electrochemical techniques. The importance of these platforms in disease diagnosis is discussed.

Highly sensitive electrochemical biosensor based on redox - active monolayer for detection of anti-hemagglutinin antibodies against swine-origin influenza virus H1N1 in sera of vaccinated mice.

BACKGROUND: In this work, we report an electrochemical biosensor for the detection of anti-hemagglutinin antibodies against the swine virus H1N1 present in mice sera immunized with mixture of His6-H1 HA in monomeric and oligomeric form. The oriented immobilization of the recombinant His-tagged hemagglutinin (His6-H1 HA) consists of: (i) formation of a mixed layer of 4-mercaptobutanol (MBT) and the thiol derivative of dipyrromethene (DPM); (ii) complexation of Cu (II) by DPM; (iii) immobilization of His6-H1 HA via coordination bonds between Cu (II) sites from DPM-Cu (II) complex and imidazole nitrogen atoms of a histidine tag; (iv) filling free spaces with bovine serum albumin. The interactions between recombinant His6- H1 HA covalently attached to the electrode surface and the anti-hemagglutinin H1 antibodies present in mice sera were explored with Osteryoung square-wave voltammetry. RESULTS: This analytical device was able to detect the antibodies present in vaccinated mice sera diluted from 1 × 109 to 1 × 108 fold. CONCLUSIONS: The unprecedented sensitivity of described biosensor is much better than widely use ELISA test and other analytical methods for determination of antibodies against the influenza A viruses. It has been proved that redox active DPM-Cu (II) monolayer is a universal platform suitable for stable and oriented immobilization of any His-tagged sensing elements. Thus, this universal layer could be a base of numerous analytical devices suitable for detection of antibodies against different viruses.

Electrochemical Biosensor for the Detection of Glycated Albumin.

BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia. The process of AD can begin 20 years before any symptom of cognitive loss. Thus, the development of systems for early diagnosis and prevention is very important. The mechanism of AD is still under debate. Nevertheless, higher levels of glycated albumin in cerebrospinal fluid and plasma are observed in AD patients. Therefore, glycated albumin could be a biomarker of AD development. METHODS: Electrochemical biosensor for direct determination of glycated albumin was based on thiol derivative of pentetic acid (DTPA) complex with Cu(II) created on gold electrode surface. His-tagged domains of Receptors for Advanced Glycation End Products (RAGE) were applied as analytical active element for glycated albumin recognition. The binding of glycated albumin by His6- RAGE domains was monitored using Osteryoung square - wave voltammetry. RESULTS: Electrodes modified with His6 - RAGE VC1 natural domain generated decrease of Cu(II) redox currents in the presence of glycated albumin. Human albumin, Aß 1-40 and S100B protein caused negligible influence on biosensors responses towards glycated albumin. The detection limits were: 2.3 pM, 1.1 pM, 2.9 pM and 3.1 pM in the presence of: buffer, buffer + albumin, buffer + S100B, buffer + Aß1-40 , respectively. CONCLUSION: The presented electrochemical biosensor was successfully applied for the determination of glycated albumin. Considering analytical parameters such as good selectivity and sensitivity in pM range, biosensor could be recommended as an analytical tool for medical samples analysis.

Voltammetric detection of S100B protein using His-tagged receptor domains for advanced glycation end products (RAGE) immobilized onto a gold electrode surface.

In this work we report on an electrochemical biosensor for the determination of the S100B protein. The His-tagged VC1 domains of Receptors for Advanced Glycation End (RAGE) products used as analytically active molecules were covalently immobilized on a monolayer of a thiol derivative of pentetic acid (DPTA) complex with Cu(II) deposited on a gold electrode surface. The recognition processes between the RAGE VC1 domain and the S100B protein results in changes in the redox activity of the DPTA-Cu(II) centres which were measured by Osteryoung square-wave voltammetry (OSWV). In order to verify whether the observed analytical signal originates from the recognition process between the His6-RAGE VC1 domains and the S100B protein, the electrode modified with the His6-RAGE C2 and His6-RAGE VC1 deleted domains which have no ability to bind S100B peptides were applied. The proposed biosensor was quite sensitive, with a detection limit of 0.52 pM recorded in the buffer solution. The presence of diluted human plasma and 10 nM Aß(1-40) have no influence on the biosensor performance.

Oriented immobilization of His-tagged protein on a redox active thiol derivative of DPTA-Cu(II) layer deposited on a gold electrode--the base of electrochemical biosensors.

This paper concerns the development of an electrochemical biosensor for the determination of Aß(16-23') and A(ß1-40) peptides. The His-tagged V and VC1 domains of Receptor for Advanced Glycation end Products (RAGE) immobilized on a gold electrode surface were used as analytically active molecules. The immobilization of His6-RAGE domains consists of: (i) formation of a mixed layer of N-acetylcysteamine (NAC) and the thiol derivative of pentetic acid (DPTA); (ii) complexation of Cu(II) by DPTA; (iii) oriented immobilization of His6-RAGE domains via coordination bonds between Cu(II) sites from DPTA-Cu(II) complex and imidazole nitrogen atoms of a histidine tag. Each modification step was controlled by cyclic voltammetry (CV), Osteryoung square-wave voltammetry (OSWV), and atomic force microscopy (AFM). The applicability of the proposed biosensor was tested in the presence of human plasma, which had no influence on its performance. The detection limits for Aß(1-40) determination were 1.06 nM and 0.80 nM, in the presence of buffer and human plasma, respectively. These values reach the concentration level of Aß(1-40) which is relevant for determination of its soluble form in human plasma, as well as in brain. This indicates the promising future application of biosensor presented for early diagnosis of neurodegenerative diseases.