Electrochemical detection in complex biofluids is a long-standing challenge as electrode biofouling hampers its sensing performance and commercial translation. To overcome this drawback, pyrolyzed ...paper as porous electrode coupled with the drop casting of an off-the-shelf polysorbate, that is, Tween 20 (T20), is described here by taking advantage of the
formation of a hydrophilic nanocoating (2 nm layer of T20). The latter prevents biofouling while providing the capillarity of samples through paper pores, leveraging redox reactions across both only partially fouled and fresh electrodic surfaces with increasing detection areas. The nanometric thickness of this blocking layer is also essential by not significantly impairing the electron-transfer kinetics. These phenomena behave synergistically to enhance the sensibility that further increases over long-term exposures (4 h) in biological fluids. While the state-of-the-art antibiofouling strategies compromise the sensibility, this approach leads to peak currents that are up to 12.5-fold higher than the original currents after 1 h exposure to unprocessed human plasma. Label-free impedimetric immunoassays through modular bioconjugation by directly anchoring spike protein on gold nanoparticles are also allowed, as demonstrated for the COVID-19 screening of patient sera. The scalability and simplicity of the platform combined with its unique ability to operate in biofluids with enhanced sensibility provide the generation of promising biosensing technologies toward real-world applications in point-of-care diagnostics, mass testing, and in-home monitoring of chronic diseases.
This technical note describes a new microfluidic sensor that combines low-cost (USD $0.97) with rapid fabrication and user-friendly, fast, sensitive, and accurate quantification of a breast cancer ...biomarker. The electrodes consisted of cost-effective bare stainless-steel capillaries, whose mass production is already well-established. These capillaries were used as received, without any surface modification. Microfluidic chips containing electrical double-layer capillary capacitors (μEDLC) were obtained by a cleanroom-free prototyping that allows the fabrication of dozens to hundreds of chips in 1 h. This sensor provided the successful quantification of CA 15-3, a biomarker protein for breast cancer, in serum samples from cancer patients. Antibody-anchored magnetic beads were utilized for immunocapture of the marker, and then, water was added to dilute the protein. Next, the CA 15-3 detection (<2 min) was made without using redox probes, antibody on electrode (sandwich immunoassay), or signal amplification strategies. In addition, the capacitance tests eliminated external pumping systems and precise volumetric sampling steps, as well as presented low sample volume (5 μL) and high sensitivity using bare capillaries in a new design for double-layer capacitors. The achieved limit-of-detection (92.0 μU mL
) is lower than that of most methods reported in the literature for CA 15-3, which are based on nanostructured electrodes. The data shown in this technical note support the potential of the μEDLC toward breast cancer diagnosis even at early stages. We believe that accurate analyses using a simple sample pretreatment such as magnetic field-assisted immunocapture and cost-effective bare electrodes can be extended to quantify other cancer biomarkers and even biomolecules by changing the biorecognition element.
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•Commercial stainless-steel capillaries into a scalable microfluidic chip acted as multidimensional double-layer parallel capacitors.•Fundamentals related to multidimensional ...responses were studied from capacitance, microscopy, and spectroscopy analyses.•Oxidized multi-walled carbon nanotubes were used as bulk probe to further improve the sensor repeatability and recognition ability.•In addition to recognizing mineral water and lake samples, our platform was used to monitor the salinity of offshore petroleum exploratory well.•Using supervised machine learning, the platform assured simultaneous quantification of the individual content of heavy metal ions in mixtures.
While multidimensional sensors are powerful platforms towards multitarget analyses, the successive synthesis/fabrication of multiple probes and measurements to each one of these units still damage the device miniaturization, scalability, cost, consumption of samples, operational simplicity, precision, and analysis time. Herein, we describe an electrochemical sensing array that affords the discrimination of metal ions from a single ready-to-use probe and experiment. The sensing probe consisted of commercial stainless-steel capillaries, which defined a microfluidic circuit and acted as electric double-layer parallel capacitors into devices prototyped by a fast, cleanroom-free, and green technique. The probes assured differential responses due to heterogeneous interactions with samples and multichannel capacitance outputs. In addition, we address an effective strategy to further improve the repeatability and recognition ability of the sensor by using oxidized multi-walled carbon nanotubes as a single bulk probe. The nanotubes provided differential electrostatic adsorptions of ions, then increasing the variance of the capacitance responses. The approach was successfully applied in the identification of samples of mineral water, lake, and petroleum according to the presence of metal ions. Using supervised machine learning tasks, the sensor assured reproducible, sensitive, and accurate classification of dozens of lake samples spiked with multiple heavy metals in accordance with their safe limits. Remarkably, simultaneous quantification of the individual concentration of these ions was also possible from universal impedimetric assays by treating the data through multi-output regression. The sensor will be of significance for advanced discriminations from a single ordinary probe and measurement in a direct mode using scalable chips.
Extracellular vesicles (EVs) are a frontier class of circulating biomarkers for the diagnosis and prognosis of different diseases. These lipid structures afford various biomarkers such as the ...concentrations of the EVs (
) themselves and carried proteins (
). However, simple, high-throughput, and accurate determination of these targets remains a key challenge. Herein, we address the simultaneous monitoring of
and
from a single impedance spectrum without using recognizing elements by combining a multidimensional sensor and machine learning models. This multidetermination is essential for diagnostic accuracy because of the heterogeneous composition of EVs and their molecular cargoes both within the tumor itself and among patients. Pencil HB cores acting as electric double-layer capacitors were integrated into a scalable microfluidic device, whereas supervised models provided accurate predictions, even from a small number of training samples. User-friendly measurements were performed with sample-to-answer data processing on a smartphone. This new platform further showed the highest throughput when compared with the techniques described in the literature to quantify EVs biomarkers. Our results shed light on a method with the ability to determine multiple EVs biomarkers in a simple and fast way, providing a promising platform to translate biofluid-based diagnostics into clinical workflows.
