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In the last few decades, nanomaterials have made great advances in the biosensor field, thanks to their ability to enhance several key issues of biosensing analytical tools, namely, sensitivity, selectivity, robustness, and reproducibility. The recent trend of sustainability has boosted the progress of novel and eco-designed electrochemical paper-based devices to detect easily the target analyte(s) with high sensitivity in complex matrices. The huge attention given by the scientific community and industrial sectors to paper-based devices is ascribed to the numerous advantages of these cost-effective analytical tools, including the absence of external equipment for solution flow, thanks to the capillary force of paper, the fabrication of reagent-free devices, because of the loading of reagents on the paper, and the easy multistep analyses by using the origami approach. Besides these features, herein we highlight the multifarious aspects of the nanomaterials such as (i) the significant enlargement of the electroactive surface area as well as the area available for the desired chemical interactions, (ii) the capability of anchoring biorecognition elements on the electrode surface on the paper matrix, (iii) the improvement of the conductivity of the cellulose matrix, (iv) the functionality of photoelectrochemical properties within the cellulose matrix, and (v) the improvement of electrochemical capabilities of conductive inks commonly used for electrode printing on the paper support, for the development of a new generation of paper-based electrochemical biosensors applied in the biomedical field. The state of the art over the last ten years has been analyzed highlighting the various functionalities that arise from the integration of nanomaterials with paper-based electrochemical biosensors for the detection of biomarkers.

The use of paper as a multifunctional material in electrochemical sensing has been intensively explored over the last decade. The combination among different kinds of paper as well as their coupling with different electrochemical cell configurations have been demonstrated, disclosing innovative sensing performances and features that are still to be fully investigated. This ongoing research has found applications in a variety of fields, including the biomedical, agri-food, security, and environmental ones, thanks to the high versatility and adaptability of the paper material. In this review, we report a critical and comparative analysis of electrochemical devices based on paper published within 2010–2021 and applied for the detection of pollutants of environmental interest in fresh water, seawater, and other real environmental matrices. Several paper types, from common office paper to Whatman filter paper with different filtering grades, were proved to be useful in this field. In detail, the multifarious roles played by the paper are discussed, highlighting how the paper can be a suitable material for electrochemical sensing while being capable of simplifying the measurement of complex real matrices or realizing programmable origami-like structures. Among the most important pollutants, a special focus is dedicated to the emerging pollutants. Furthermore, the unique advantages achieved by the paper have been analyzed and highlighted, reporting the future perspectives regarding the use of this surprising material.

The recent global events of COVID-19 in 2020 have alerted the world to the risk of viruses and their impacts on human health, including their impacts in the social and economic sectors. Rapid tests are urgently required to enable antigen detection and thus to facilitate rapid and simple evaluations of contagious individuals, with the overriding goal to delimitate spread of the virus among the population. Many efforts have been achieved in recent months through the realization of novel diagnostic tools for rapid, affordable, and accurate analysis, thereby enabling prompt responses to the pandemic infection. This review reports the latest results on electrochemical and optical biosensors realized for the specific detection of SARS-CoV-2 antigens, thus providing an overview of the available diagnostics tested and marketed for SARS-CoV-2 antigens as well as their pros and cons.

Botulinum neurotoxins (BoNTs) produced by soil bacterium Clostridium botulinum are cause of botulism and listed as biohazard agents, thus rapid screening assays are needed for taking the correct countermeasures in a timely fashion. The gold standard method relies on the mouse lethality assay with a lengthy analysis time, i.e., 2–5 days, hindering the prompt management of food safety and medical diagnosis. Herein, we propose the first paper-based antibody-free sensor for reliable and rapid detection of BoNT/A and BoNT/C, exploiting their cleavage capability toward a synthetic peptide able to mimic the natural substrate SNAP-25. The peptide is labelled with the electroactive molecule methylene blue and immobilized on the paper-based electrode modified with gold nanoparticles. Because BoNT/A and BoNT/C can cleave the peptide with the removal of methylene blue from electrode surface, the presence of these neurotoxins in the sample leads to a signal decrease proportional to BoNT amount. The biosensor developed with the selected peptide and combined with smartphone assisted potentiostat is able to detect both BoNT/A and BoNT/C with a linearity up to 1 nM and a detection limit equal to 10 pM. The applicability of this biosensor was evaluated with spiked samples of orange juice, obtaining recovery values equal to 104 ± 6% and 98 ± 9% for 1 nM and 0.5 nM of BoNT/A, respectively.

In the last 10 years, paper-based electrochemical biosensors have gathered attention from the scientific community for their unique advantages and sustainability vision. The use of papers in the design the electrochemical biosensors confers to these analytical tools several interesting features such as the management of the solution flow without external equipment, the fabrication of reagent-free devices exploiting the porosity of the paper to store the reagents, and the unprecedented capability to detect the target analyte in gas phase without any sampling system. Furthermore, cost-effective fabrication using printing technologies, including wax and screen-printing, combined with the use of this eco-friendly substrate and the possibility of reducing waste management after measuring by the incineration of the sensor, designate these type of sensors as eco-designed analytical tools. Additionally, the foldability feature of the paper has been recently exploited to design and fabricate 3D multifarious biosensors, which are able to detect different target analytes by using enzymes, antibodies, DNA, molecularly imprinted polymers, and cells as biocomponents. Interestingly, the 3D structure has recently boosted the self-powered paper-based biosensors, opening new frontiers in origami devices. This review aims to give an overview of the current state origami paper-based biosensors, pointing out how the foldability of the paper allows for the development of sensitive, selective, and easy-to-use smart and sustainable analytical devices.

In the overall scenario of precision medicine, we propose a novel paper-based lab-on-a-chip to deliver a cost-effective and easy to use sensing tool for customized administration of drugs in Alzheimer’s disease. Among several drugs, we designed the device for evaluating the efficacy of compounds (e.g. physostigmine, rivastigmine, donepezil) which are able to inhibit in a reversible way the cholinesterase enzyme. Because cholinesterase activity is peculiar to each patient, the administration of customized amount of the drug can improve the treatment efficacy and the quality of patient life, avoiding side effects due to the overdosage. In detail, we exploited Vivid™ Plasma Separation membrane to threat the whole blood sample, filter paper to load the reagents needed for the measurement, and office paper to print electrodes able to measure the butyrylcholinesterase activity, delivering a reagent free analytical tool. The calibration curve of butyrylcholinesterase obtained in blood sample provided linearity between 2 and 12 U/mL, with sensitivity of 0.050 ± 0.004 μA mL/U. The physostigmine, rivastigmine, and donepezil inhibition activities toward the butyrylcholinesterase enzyme were also measured in blood sample with linearity up to respectively 0.5 μM, 25 μM, 30 μM, and detection limits of 0.009 μM, 0.4 μM, 0.3 μM. These results demonstrate the capability of paper-based origami sensors as point of care devices to customize the drug administration in Alzheimer’s disease.

Pancreatic ductal adenocarcinoma is the predominant neoplastic disease of the pancreas and it represents the fourth most frequent cause of death in cancer-related disease, with only 8% of survivors after 5-year to the diagnosis. The main issues of this type of cancer rely on fast progress (i.e. 14 months from T1 to a T4 stage), nonspecific symptoms with delay in diagnosis, and the absence of effective screening strategies. To address the lack of early diagnosis, we report a cost-effective paper-based biosensor for the detection of miRNA-492, which is recognised as a biomarker for pancreatic ductal adenocarcinoma. To design a miniaturised, sensitive, and robust paper-based platform, an electrochemical sensor was screen-printed on office paper previously wax-patterned via wax-printing technique. The paper-based sensor was then engineered with a novel and highly specific peptide nucleic acid (PNA) as the recognition element. The formation of PNA/miRNA-492 adduct was evaluated by monitoring the interaction between the positively charged ruthenium (III) hexamine with uncharged PNA and/or negatively charged PNA/miRNA-492 duplex by differential pulse voltammetry. The paper-based biosensor provided a linear range up to 100 nM, with a LOD of 6 nM. Excellent selectivity towards one- and two-base mismatches (1MM, 2MM) or scrambled (SCR) sequences was highlighted and the applicability for biomedical analyses was demonstrated, measuring miRNA-492 in undiluted serum samples.

Altres ajuts: the ICN2 is funded by the CERCA Programme/Generalitat de Catalunya. The development of paper-based electroanalytical strips as powerful diagnostic tools has gained a lot of attention within the sensor community. In particular, the detection of nucleic acids in complex matrices represents a trending topic, especially when focused toward the development of emerging technologies, such as liquid biopsy. DNA-based biosensors have been largely applied in this direction, and currently, there are two main approaches based on target/probe hybridization reported in the literature, namely Signal ON and Signal OFF. In this technical note, the two approaches are evaluated in combination with paper-based electrodes, using a single strand DNA relative to H1047R (A3140G) missense mutation in exon 20 in breast cancer as the model target. A detailed comparison among the analytical performances, detection protocol, and cost associated with the two systems is provided, highlighting the advantages and drawbacks depending on the application. The present work is aimed to a wide audience, particularly for those in the field of point-of-care, and it is intended to provide the know-how to manage with the design and development stages, and to optimize the platform for the sensing of nucleic acids using a paper-based detection method.

In the last decades, there is a growing search for analytical strategies to ensure clinical analysis without the need of laboratory set-up and skilled personnel. Indeed, user-friendly and low-cost devices are highly valued in the era of sustainability for their capability to be applied in low-resource contexts, such as developing countries. To address this issue, herein we report a 96-well paper-based and laboratory setup-free optical platform for the detection of butyrylcholinesterase enzyme (BChE) activity in human serum. We used chromatographic paper to realize a novel analytical tool exploiting its porous structure for reagentless synthesize Prussian Blue Nanoparticles (the sensing element), as well to load all the reagents required for the measurement. The principle of BChE activity detection relies on the reaction between the enzymatic product thiocholine and Prussian Blue, giving the Prussian White with subsequently Prussian Blue's fading, detected by a common office scanner supported by ImageJ software. Using this novel paper-based optical platform, BChE activity was linearly detected in the 2–15 U/mL range with a detection limit down to 0.8 U/mL. The accuracy was successfully demonstrated by recovery study with spiked serum and by comparing the data with the gold standard method.

Herein, we propose the first three-dimensional origami paper-based device for the detection of several classes of pesticides by combining different enzyme-inhibition biosensors. This device was developed by integrating two different office paper-based screen-printed electrodes and multiple filter paper-based pads to load enzymes and enzymatic substrates. The versatile analysis of different pesticides was carried by folding and unfolding the filter paper-based structure, without any addition of reagents and any sample treatment (i.e. dilution, filtration, pH adjustment). The paper-based platform was employed to detect paraoxon, 2,4-dichlorophenoxyacetic acid, and atrazine by exploiting the capability of these different types of pesticides (i.e. organophosphorus insecticides, phenoxy-acid herbicides, and triazine herbicide) to inhibit butyrylcholinesterase, alkaline phosphatase, and tyrosinase, respectively. The degree of inhibition correlating to the quantity of pesticides was evaluated by chronoamperometrically monitoring the enzymatic activity in the absence and in the presence of pesticides by using a portable potentiostat. To improve the sensitivity, the paper-based electrodes were modified with carbon black alone in the case of platforms for 2,4-dichlorophenoxyacetic acid and atrazine detection, or decorated with Prussian blue nanoparticles for the detection of paraoxon. The paper-based device was applied for the detection of paraoxon, 2,4-dichlorophenoxyacetic acid, and atrazine at ppb level in both standard solutions and river water sample. The accuracy of this origami multiple paper-based electrochemical biosensor was evaluated in river water by recovery studies, obtaining satisfactory values (e.g. for paraoxon 90 ± 1% and 88 ± 2%, for 10 and 20 ppb, respectively). The proposed three-dimensional origami paper device allows for rapid, cost-effective and accurate pesticide detection in surface water as a result of combining filter and office papers, screen-printing, wax-printing and nanomaterial technology.

From the first investigations on peptide nucleic acids (PNA), peculiar features have been described as intrinsic of the singular chemical nature of these biomolecules. Relevant applications in the development of biosensors occurred in the last decades, exploiting them as bioreceptors. Their outstanding chemical and thermal stability as well as highly sensitive towards both complementary and non-complementary sequences, promoted them in the Olympus of biocomponents for applications in diagnostics. The intent of this review (85 ref) is to describe the last trends on the astonishing PNA technology in the biosensing field, in the view of the positive contamination with vanguard technologies including rational design and nanotechnology. In particular, electrochemical and optical biosensors exploiting PNA were reported from the literature, as well as nanostructured and paper-based biosensors for the design of microfluidics and lab-on-chip tools. (C) 2020 Elsevier B.V. All rights reserved.