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Metabolic rare diseases present a serious clinical manifestation causing several problems such as mental retardation, liver damage, hepatocarcinoma and even death without a diagnosis in the first days of life. Additionally, there is not any final treatment for these diseases but a dietary restriction, so patients have to control their biomarkers level during their whole life. Current methods for diagnosis and monitoring are tedious, very time-consuming, not portable and need high amount of sample, so they are not suitable for a point-of-care (POC) application. In this sense, electrochemistry presents the required characteristics to be used as POC for metabolic rare diseases. Specifically, this review explores the current methods for amino acids and carbohydrates sensing as biomarkers of metabolic rare diseases using electrochemical (bio)-sensing approaches, especially those based on nanomaterials in both, off and on-chip detection, as well as their suitability in metabolic rare diseases diagnosis and monitoring using clinical samples.

We report on a wearable tear bioelectronic platform, integrating a microfluidic electrochemical detector into an eyeglasses nose-bridge pad, for non-invasive monitoring of key tear biomarkers. The alcohol-oxidase (AOx) biosensing fluidic system allowed real-time tear collection and direct alcohol measurements in stimulated tears, leading to the first wearable platform for tear alcohol monitoring. Placed outside the eye region this fully wearable tear-sensing platform addresses drawbacks of sensor systems involving direct contact with the eye as the contact lenses platform. Integrating the wireless electronic circuitry into the eyeglasses frame thus yielded a fully portable, convenient-to-use fashionable sensing device. The tear alcohol sensing concept was demonstrated for monitoring of alcohol intake in human subjects over multiple drinking courses, displaying good correlation to parallel BAC measurements. We also demonstrate for the first time the ability to monitor tear glucose outside the eye and the utility of wearable devices for monitoring vitamin nutrients in connection to enzymatic flow detector and rapid voltammetric scanning, respectively. These developments pave the way to build an effective eyeglasses system capable of chemical tear analysis.

Here, the on-line coupling of millimeter size motors (m-motors) and chronoamperometry for real time bio-sensing of branched-chain amino acids ( l -b-AAs) in maple syrup urine disease (MSUD) clinical samples is proposed. Marangoni effect for controlled mixing and delivery of active enzyme for substrate digestion and subsequent electrochemical sensing is conveniently explored. To this end, an integrated cell device, which includes reservoirs for motors movement and electrochemical detection, was fabricated. l -amino acid oxidase (LAO)-loaded m-motors just by capillarity without any coating chemistry are used for the enantiomers selective recognition, and then the hydrogen peroxide released from enzymatic reaction is electrochemically monitored at −0.20 V using copper microwires as exclusive transducers. The inherent enzyme m-motor features – “self-micro mixing” and the continuous release of fresh and free enzyme-, not only avoided the use of external stirring or the enzymatic physical adsorption or chemical bonding to the electrode; but a dramatic decreasing of analysis times (just 200 s vs. 25 min without motors, yielding only a 70% of the m-motor signal). In addition, an excellent accuracy (Er l -b-AAs determination in clinical samples from patients previously diagnosed by a reference center was also obtained. We envision future opportunities for this approach to be a potential point of care (POC) testing device, because of its rapid response, simplicity, selectivity and sensitivity; becoming into another step facing towards the challenges of rare disease diagnostics.

In this work, we present the combination of Carbon Black (CB) and electrodeposited Prussian Blue (PB) covered with a Nafion layer on Screen-Printed electrodes (CB/PB-SPE) used for non-enzymatic H2O2 sensing in Neuroblastoma cell line SH-SY5Y. These cells were challenged with 6-hidroxidopamine (6-OHDA) for modelling Parkinson’s disease. The electrodes surface was investigated using Scanning Electron Microscopy (SEM) and electrochemically characterized, in terms of electroactivity and stability. Electrochemical sensing of H2O2 was carried out at very low potentials (−50 mV), with a LOD of 0.01 μM and linear range between 0.2 and 1000 μM, allowing interference-free detection of H2O2 in the selected cell culture. The H2O2 concentration was successfully monitored in an experimental model of Parkinson’s disease. These results pave the way to a method for the continuous monitoring of H2O2 in culture medium for future studies of the role of H2O2 in Parkinson’s disease.

Alpha-1-acid glycoprotein (AGP) or Orosomucoid is a serum glycoprotein which belongs to the group of acute phase proteins. It is a potential biomarker for inflammatory bowel diseases. In this sense, there is a need for developing fast and cheap analytical methods for diagnosis, prognosis and follow-up of these diseases. In this work, we propose a simple and cheap electrochemical method for total AGP determination using disposable carbon screen-printed electrodes (SPE) and using a selective acidic precipitation of the rest of proteins. This method avoids the use of biological components, decreasing dramatically the analysis cost. Firstly, AGP is labeled with an electrochemical tag (osmium (VI) complex) and then the total amount of AGP is quantified by adsorptive transfer stripping square wave voltammetry. The method optimized showed a good linear correlation (r = 0.9992) and limit of detection of 1.6mgl-1. The methodology was successfully applied to quantify AGP in a commercial serum sample. This methodology could be useful in clinical diagnosis because of AGP levels increase two or three times when inflammatory processes happen. Moreover, the inherent advantages of SPE technology (low sample consumption, low cost and point of care testing) make this methodology very attractive in this field.

Point of cares (POCs) recent efforts have been the development of easy-to-use miniaturized devices with high analytical performance meeting the patients needs. Here, we propose a simple electroanalytical device based on filtered multi-walled carbon nanotubes (MW-FEs) for a rapid detection and monitoring of L-tyrosine (L-Tyr) in relevant clinical samples. The MW-FE fabrication relies on the simply filtration of a homogeneous dispersion of the MWs on the Teflon filter, which becomes the scaffold for the nanomaterial assembling without the need of any high external pressure, energy or growing chemistry. Then, Teflon filter is cut and pasted with the desirable size and shape, being the transduction carried out exclusively on the nanomaterial, since the Teflon filter is a non-conductive substrate. Using just 50 μL of sample and in less than 1 min, this approach allows L-Tyr sensing and monitoring in clinically diagnosed tyorosinemia plasma and blood samples. Excellent analytical performance on the MW-FEs was achieved (r ≥ 0.9995 in the range 25–750 μM with a LOD of 8 μM and quantitative recoveries ranging from 93 to 97%) despite the extreme simplicity of the device even operating in complex clinical samples. Furthermore, this approach opens novel possibilities for rapid screening and further monitoring of this rare disease in the point of care and for clinical decentralized analysis.

A systematic study for correlating the chemical structure of phenolic compounds with their capacity to form gold nanoparticles was carried out. Two groups of phenolic compounds were selected: one group with a substituent with different size at ortho position respect to hydroxyl group (phenol, o-cresol, 2-ethylphenol, 2-isopropylphenol, 2-tert-butylphenol and 2-methoxyphenol); and the second group consists of phenolic compounds with the same substituent (methyl) at different positions respect to hydroxyl group (o-cresol, m-cresol and p-cresol). In addition to the characteristic gold nanoparticles (AuNPs) formation band at 550 nm obtained for all the structures of phenolic compounds studied, ortho-alkyl substituted yielded selectively a metastable band at 400 nm, due to gold nanoclusters (AuNCs) formation. We hypothesized that these specific phenolic compounds can temporally stabilize AuNCs with number of Au atoms ranging from 3 to 41. This new band was proposed for rapid screening of these phenolics with promising results, paving the way to new and more selective colorimetric assay for phenolic compounds determination.

Janus micromotors are self-propelled micro and nanoscale devices that combine different properties within a single entity. Material aspects are key factors influencing the locomotion and application of Janus micromotors. This timely review will provide a comprehensive overview of different materials and fabrication methods used for its preparation. Emerging applications of Janus swimmers for environmental water treatment, drug delivery, biodetoxification and analytical sensing will be also described. Prospects of this rapidly developing field will be given in the conclusions.

Carbon black nanoparticles (CBNPs) press imprinted films are proposed for class-selective electrochemical detection of ortho-diphenols (o-diphenols) and mono-phenols (m-phenols) antioxidants. In order to optimize the sensor construction, different surface immobilizations of CBNPs electroactive films on a PMMA support were assayed by using different amounts of CBNPs dispersions. The best sensor in terms of selectivity, sensitivity and stability was obtained when 30 mL of a CBNPs dispersion (0.50 mg/100 mL in 1,2-dichloroethane) were transferred onto PMMA substrates applying a pressure of 4.6 ton. The electrodes were characterized by Electrochemical Impedance Spectroscopy (EIS) and Cyclic Voltammetry (CV) to explore their electrical properties. The effective transfer of CBNPs on the PMMA support and the CBNPs film conductivity have been evaluated by Atomic Force Microscopy (AFM) confirming that the carbon black film is effectively imprinted on the polymer surface and that retains its good conductivity. X-ray Photoelectron Spectroscopy (XPS) and Raman spectroscopy have been employed to investigate the CBNPs composition and the CBNPs electrode surface, respectively. CBNPs electrodes exclusively supported the o-diphenols and m-phenols sensing, at low detection potentials (+0.100 and +0.560 V, respectively) and with negligible surface fouling (peak intensity RSDs, E and LV acknowledge financial support from the Spanish Ministry of Economy and Competitiveness (CTQ2014-58643-R and BIO2016-79618-R, respectively), and the NANOAVANSENS program (S2013/MIT-3029) from the Community of Madrid. The Authors acknowledge the financial contribution of the Italian Ministry of Foreign Affairs for the Project “Materiali nanostrutturati per sistemi (bio)chimici sensibili ai pesticidi”. This research has also been financed by the “Spanish Ministry of Economy and Competitiveness (MINECO) under projects MAT2016-80394-R (FJP), MAT2014-54231-C4-1-P (LV).

Laccase-based poly(3,4-ethylenedioxythiophene)-polypyrrole/Pt (PEDOT-PPy-COOH/Pt) micromotors were electrosynthesized, characterized and applied for the decolorization of azo dyes widely used in the textile industry and found in textile wastewater. These laccase-based micromotors, due to their self-propulsion capabilities, were successfully used for the degradation of dyes by the improved activity of the on-the-fly immobilized laccase enzyme compared to that of the free enzyme. The Pt layer of the micromotor produced O2 by breaking down H2O2 and enabled the micromotor to move, while the carboxyl groups in the pyrrole units were used for the binding of laccase enzyme effectively, using the EDC/NHS coupling reaction. Enzyme stability studies were carried out, showing improved stability of the on-board immobilized enzyme at different pH and temperature conditions without a significant loss in affinity to the substrate. The overall dye removal capacity of the laccase-functionalized micromotors was demonstrated using dyes with 76–94% of decolorization efficiencies in comparison with those found using the free enzyme approach with lower decolorization efficiencies of about 34–55%.

Here, two class-enzyme motors are properly designed allowing the rapid dispersion of the class-enzyme D-amino acid oxidase (DAO) and L-amino acid oxidase (LAO) for selective “on the fly” biodetection of D and L-amino acids (AAs), respectively. The efficient movement together with the continuous release of fresh class-enzyme leads to a greatly accelerated enzymatic reaction processes without the need of external stirring or chemical and physical attachment of the enzyme. Ultra-fast detection (

In this work, a bi-enzymatic biosensor allowed the total content of D-amino acids (DAAs) determination in highly relevant matrices involving bacteria. The strategy is based on the unique coimmobili ...

A low-cost scalable xurography cleanroom-free approach is proposed for the development of disposable electrochemical microfluidic devices (EMDs). Microband carbon electrodes as narrow as 300 μm and microchannels as small as 250 × 75 μm (width x height) were thermally laminated at the bottom of the microchannels without further post-processing. Microband carbon electrodes exhibited a well-defined behavior in agreement to a Levich-like equation that led to a finely reaction control. In less than 1 h, about 50 EMDs can be produced (

Self-propelled artificial milli, micro and nanomotors offer considerable promise to solve analytical challenges. Herein we will review recent advances in the use of these vanguard analytical tools for real-time in situ analyte (bio-)sensing and isolation. We will describe first the shape-design, fabrication pathways and propulsion mechanism of the most relevant milli, micro and nanomotors. Next, the main relevant analytical (bio) sensing and isolation applications will be discussed towards selected and relevant works. We will also discuss future outlook and main challenges of this new exciting area of analytical nano science and nanotechnology.

In food producing and developing countries having a reliable and inexpensive tool for the analysis of agricultural commodities is essential. This article describes a reliable disposable electrochemical magnetoimmunosensor for monitoring of coffee samples for Ochratoxin A contamination. The electrochemical detection performed on carbon screen-printed electrodes (CSPEs) used magnetic beads as antibody immobilization support and enzyme horseradish peroxidase as tracer. A remarkable limit of detection of 0.32 μg L −1 , well below of the legislative requirements, demonstrated the suitability of the proposed immunosensor as a screening tool for the analysis of Ochratoxin A in coffee samples. A simultaneous simplified Ochratoxin A calibration and coffee sample analysis strategy allowed the accurate determination of the mycotoxin with recoveries of 90% reducing the long times used in conventional calibration. This strategy enhanced the analytical merits of immunosensor approach towards truly disposable tools for screening of Ochratoxin A in coffee samples and opens novel avenues for food-safety monitoring.

Herein we describe an "OFF-ON" Janus micromotor approach for the fast (5 min) and sensitive determination (limit of detection, 120 pM) of Escherichia coli O111:B4 lipopolysaccharide (LPS) associated with sepsis shock in microliter samples. The OFF-ON strategy relies on the loading of a specifically designed rhodamine-labeled affinity peptide into WS2-Pt-Fe2O3 polycaprolactone Janus micromotors. Specific attachment of the peptide with the WS2 via electrostatic and hydrophobic interactions results in fluorescent quenching, which is subsequently recovered by the detachment of the probe in the presence of the target LPS. Peptide loading into the micromotor structure increases the overall stability for over 2 months without any change in its properties and excellent analytical performance. No fluorescence recovery is observed in the presence of LPS with a similar structure, illustrating the high selectivity of the protocol, along with quantitative recoveries in human serum and bacteria cultures. The method was validated against the gold standard Limulus Amoebocyte lysate assay in real bacteria culture containing naturally occurring LPS, with similar recoveries in both cases. The micromotors hold great potential to carry out analytical measurements in real-time with small amounts of sample and reagents, allowing for fast detection of deadly toxins with high clinical relevance.

Graphdiyne (GDY) micromotors have been synthesized by direct electrochemical deposition, avoiding harsh conditions or sophisticated equipment. GDY is directly electrodeposited in a membrane template by cyclic voltammetry, followed by the deposition of diverse inner catalytic layers (Pt/Ni, MnO2, or Pd/Cu) conferring the micromotors with structural stability to avoid nanoscale deformation. The best performance in terms of catalytic activity is observed for Pt-based micromotors, with up to 4-fold speed increase on average. In addition, compared with similarly prepared graphene oxide (GO) micromotors, a 2-fold speed enhancement is observed both in water and complex samples (saliva, blood serum, milk, and wine). The combination of the unique GDY properties with the moving capabilities of micromotors is also illustrated in the micromotor navigation against fluid flows in microfluidic channels. Practical applications are illustrated in fluorescent assay experiments for bacteria toxins detection and for the capture of a fluorescent probe, also used as model environmental pollutant. The template electrodeposition route holds great potential for the preparation of a myriad of GDY micromotors for diverse applications.