Publications
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2-dimensional materials-based electrical/optical platforms for smart on-off diagnostics applications
Kou J., Nguyen E.P., Merkoçi A., Guo Z. 2D Materials; 7 (3, 032001) 2020. 10.1088/2053-1583/ab896a. IF: 7.140
The concept of two-dimensional (2D) materials was first proposed after the first successful separation of graphene, a monoatomic layered material. 2D materials are referred to materials in which electrons can only move freely on the nanoscale in two dimensions, and have expanded to also include the transition metal dichalcogenides (TMDs), black phosphorus (BP) and hexagonal boron nitride (hBN). Different 2D materials have unique electrical or optical characteristics due to the special properties of the crystal structure, and are widely used as field-effect transistors and optoelectronic devices. Moreover, based on the electrochemical and fluorescence quenching properties, many researchers have developed and fabricated light-switching and current-switching sensors for various medical diagnostics. In this paper, we summarize the characteristics of 2D materials and introduce their photoelectric properties, and review the recent applications of 2D materials based switching sensors for the diagnosis of various diseases. © 2020 IOP Publishing Ltd.
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Chitin Nanofiber Paper toward Optical (Bio)sensing Applications
Naghdi T., Golmohammadi H., Yousefi H., Hosseinifard M., Kostiv U., Horák D., Merkoçi A. ACS Applied Materials and Interfaces; 12 (13): 15538 - 15552. 2020. 10.1021/acsami.9b23487. IF: 8.758
Because of numerous inherent and unrivaled features of nanofibers made of chitin, the second most plentiful natural-based polymer (after cellulose), including affordability, abundant nature, biodegradability, biocompatibility, commercial availability, flexibility, transparency, and extraordinary mechanical and physicochemical properties, chitin nanofibers (ChNFs) are being applied as one of the most appealing bionanomaterials in a myriad of fields. Herein, we exploited the beneficial properties offered by the ChNF paper to fabricate transparent, efficient, biocompatible, flexible, and miniaturized optical sensing bioplatforms via embedding/immobilizing various plasmonic nanoparticles (silver and gold nanoparticles), photoluminescent nanoparticles (CdTe quantum dots, carbon dots, and NaYF4:Yb3+@Er3+&SiO2 upconversion nanoparticles) along with colorimetric reagents (curcumin, dithizone, etc.) in the 3D nanonetwork scaffold of the ChNF paper. Several configurations, including 2D multi-wall and 2D cuvette patterns with hydrophobic barriers/walls and hydrophilic test zones/channels, were easily printed using laser printing technology or punched as spot patterns on the dried ChNF paper-based nanocomposites to fabricate the (bio)sensing platforms. A variety of (bio)chemicals as model analytes were used to confirm the efficiency and applicability of the fabricated ChNF paper-based sensing bioplatforms. The developed (bio)sensors were also coupled with smartphone technology to take the advantages of smartphone-based monitoring/sensing devices along with the Internet of Nano Things (IoNT)/the Internet of Medical Things (IoMT) concepts for easy-to-use sensing applications. Building upon the unrivaled and inherent features of ChNF as a very promising bionanomaterial, we foresee that the ChNF paper-based sensing bioplatforms will emerge new opportunities for the development of innovative strategies to fabricate cost-effective, simple, smart, transparent, biodegradable, miniaturized, flexible, portable, and easy-to-use (bio)sensing/monitoring devices. Copyright © 2020 American Chemical Society.
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Editorial note - Professor Turner's retirement
Gu M.B., Li C., Merkoçi A., the new editorial team of Biosensors and Bioelectronics, Co-Editors in chief Biosensors and Bioelectronics; 150 (111913) 2020. 10.1016/j.bios.2019.111913. IF: 10.257
[No abstract available]
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Experimental Comparison in Sensing Breast Cancer Mutations by Signal on and Signal off Paper-Based Electroanalytical Strips
Cinti S., Cinotti G., Parolo C., Nguyen E.P., Caratelli V., Moscone D., Arduini F., Merkoci A. Analytical Chemistry; 92 (2): 1674 - 1679. 2020. 10.1021/acs.analchem.9b02560. IF: 6.785
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. © 2019 American Chemical Society.
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Graphene-based biosensors
Merkoi A. 2D Materials; 7 (4, 040401) 2020. 10.1088/2053-1583/aba3bf. IF: 7.140
[No abstract available]
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Highly Loaded Mildly Edge-Oxidized Graphene Nanosheet Dispersions for Large-Scale Inkjet Printing of Electrochemical Sensors
Nagar B., Jović M., Bassetto V.C., Zhu Y., Pick H., Gómez-Romero P., Merkoçi A., Girault H.H., Lesch A. ChemElectroChem; 7 (2): 460 - 468. 2020. 10.1002/celc.201901697. IF: 4.154
Inkjet printing of electrochemical sensors using a highly loaded mildly edge-oxidized graphene nanosheet (EOGN) ink is presented. An ink with 30 mg/mL EOGNs is formulated in a mixture of N-methyl pyrrolidone and propylene glycol with only 30 min of sonication. The absence of additives, such as polymeric stabilizers or surfactants, circumvents reduced electrochemical activity of coated particles and avoids harsh post-printing conditions for additive removal. A single light pulse from a xenon flash lamp dries the printed EGON film within a fraction of a second and creates a compact electrode surface. An accurate coverage with only 30.4 μg of EOGNs per printed layer and cm2 is achieved. The EOGN films adhere well to flexible polyimide substrates in aqueous solution. Electrochemical measurements were performed using cyclic voltammetry and differential pulse voltammetry. An all inkjet-printed three-electrode living bacterial cell detector is prepared with EOGN working and counter electrodes and silver-based quasi-reference electrode. The presence of E. coli in liquid samples is recorded with four electroactive metabolic activity indicators. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Inkjet-printed electrochemically reduced graphene oxide microelectrode as a platform for HT-2 mycotoxin immunoenzymatic biosensing
Kudr J., Zhao L., Nguyen E.P., Arola H., Nevanen T.K., Adam V., Zitka O., Merkoçi A. Biosensors and Bioelectronics; 156 (112109) 2020. 10.1016/j.bios.2020.112109. IF: 10.257
The design and application of an inkjet-printed electrochemically reduced graphene oxide microelectrode for HT-2 mycotoxin immunoenzymatic biosensing is reported. A water-based graphene oxide ink was first formulated and single-drop line working microelectrodes were inkjet-printed onto poly(ethylene 2,6-naphthalate) substrates, with dimensions of 78 μm in width and 30 nm in height after solvent evaporation. The printed graphene oxide microelectrodes were electrochemically reduced and characterized by Raman and X-ray photoelectron spectroscopies in addition to microscopies. Through optimization of the electrochemical reduction parameters, differential pulse voltammetry were performed to examine the sensing of 1-naphthol (1-N), where it was revealed that reduction times had significant effects on electrode performance. The developed microelectrodes were then used as an immunoenzymatic biosensor for the detection of HT-2 mycotoxin based on carbodiimide linking of the microelectrode surface and HT-2 toxin antigen binding fragment of antibody (anti-HT2 (10) Fab). The HT-2 toxin and anti-HT2 (10) Fab reaction was reported by anti-HT2 immune complex single-chain variable fragment of antibody fused with alkaline phosphatase (anti-IC-HT2 scFv-ALP) which is able to produce an electroactive reporter – 1-N. The biosensor showed detection limit of 1.6 ng ∙ mL−1 and a linear dynamic range of 6.3 – 100.0 ng ∙ mL−1 within a 5 min incubation with 1-naphthyl phosphate (1-NP) substrate. © 2020 Elsevier B.V.
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Lab in a Tube: Point-of-Care Detection of Escherichia coli
Amin N., Torralba A.S., Álvarez-Diduk R., Afkhami A., Merkoçi A. Analytical Chemistry; 92 (6): 4209 - 4216. 2020. 10.1021/acs.analchem.9b04369. IF: 6.785
Significant levels of infectious diseases caused by pathogenic bacteria are nowadays a worldwide matter, carrying considerable public health care challenges and huge economic concerns. Because of the rapid transmission of these biothreat agents and the outbreak of diseases, a rapid detection of pathogens in early stages is crucial, particularly in low-resources settings. To this aim, we developed for the first time a new sensing approach carried out in a single step for Escherichia coli O157:H7 detection. The detection principle is based on Förster resonance energy transfer using gold nanoclusters as a signal reporter and gold nanoparticles conjugated with antibodies as a quencher. The sensing platform includes an ultraviolet-light-emitting diode to provide the proper excitation and consists of a microtube containing two pieces of fiber glass; one of them is embedded with label-free gold nanoclusters and the other one with gold nanoparticles conjugated with antibodies. Upon the addition of the sample containing bacteria, the florescence of gold nanoclusters is recovered. The assay was evaluated by the naked eye (on/off) and quantitatively with use of a smartphone camera. The biosensor proved to be highly specific and sensitive, achieving a limit of detection as low as 4.0 cfu mL-1. Additionally, recoveries of 110% and 95% were obtained when the platforms in spiked river and tap water, respectively, were evaluated. Copyright © 2020 American Chemical Society.
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Lateral flow assay modified with time-delay wax barriers as a sensitivity and signal enhancement strategy
Sena-Torralba A., Ngo D.B., Parolo C., Hu L., Álvarez-Diduk R., Bergua J.F., Rosati G., Surareungchai W., Merkoçi A. Biosensors and Bioelectronics; 168 (112559) 2020. 10.1016/j.bios.2020.112559. IF: 10.257
The ease of use, low cost and quick operation of lateral flow assays (LFA) have made them some of the most common point of care biosensors in a variety of fields. However, their generally low sensitivity has limited their use for more challenging applications, where the detection of low analytic concentrations is required. Here we propose the use of soluble wax barriers to selectively and temporarily accumulate the target and label nanoparticles on top of the test line (TL). This extended internal incubation step promotes the formation of the immune-complex, generating a 51.7-fold sensitivity enhancement, considering the limit of quantification, and up to 96% signal enhancement compared to the conventional LFA for Human IgG (H-IgG) detection. © 2020 Elsevier B.V.
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Nano-lantern on paper for smartphone-based ATP detection
Calabretta M.M., Álvarez-Diduk R., Michelini E., Roda A., Merkoçi A. Biosensors and Bioelectronics; 150 (111902) 2020. 10.1016/j.bios.2019.111902. IF: 10.257
ATP-driven bioluminescence relying on the D-luciferin-luciferase reaction is widely employed for several biosensing applications where bacterial ATP detection allows to verify microbial contamination for hygiene monitoring in hospitals, food processing and in general for cell viability studies. Several ATP kit assays are already commercially available but an user-friendly ATP biosensor characterized by low-cost, portability, and adequate sensitivity would be highly valuable for rapid and facile on site screening. Thanks to an innovative freeze-drying procedure, we developed a user-friendly, ready-to-use and stable ATP sensing paper biosensor that can be combined with smartphone detection. The ATP sensing paper includes a lyophilized “nano-lantern” with reaction components being rapidly reconstituted by 10 μL sample addition, enabling detection of 10−14 mol of ATP within 10 min. We analysed urinary microbial ATP as a biomarker of urinary tract infection (UTI), confirming the capability of the ATP sensing paper to detect the threshold for positivity corresponding to 105 colony-forming units of bacteria per mL of urine. © 2019 Elsevier B.V.
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Nanomaterials for Nanotheranostics: Tuning Their Properties According to Disease Needs
Wong X.Y., Sena-Torralba A., Álvarez-Diduk R., Muthoosamy K., Merkoçi A. ACS Nano; 14 (3): 2585 - 2627. 2020. 10.1021/acsnano.9b08133. IF: 14.588
Nanotheranostics is one of the biggest scientific breakthroughs in nanomedicine. Most of the currently available diagnosis and therapies are invasive, time-consuming, and associated with severe toxic side effects. Nanotheranostics, on the other hand, has the potential to bridge this gap by harnessing the capabilities of nanotechnology and nanomaterials for combined therapeutics and diagnostics with markedly enhanced efficacy. However, nanomaterial applications in nanotheranostics are still in its infancy. This is due to the fact that each disease has a particular microenvironment with well-defined characteristics, which promotes deeper selection criteria of nanomaterials to meet the disease needs. In this review, we have outlined how nanomaterials are designed and tailored for nanotheranostics of cancer and other diseases such as neurodegenerative, autoimmune (particularly on rheumatoid arthritis), and cardiovascular diseases. The penetrability and retention of a nanomaterial in the biological system, the therapeutic strategy used, and the imaging mode selected are some of the aspects discussed for each disease. The specific properties of the nanomaterials in terms of feasibility, physicochemical challenges, progress in clinical trials, its toxicity, and their future application on translational medicine are addressed. Our review meticulously and critically examines the applications of nanotheranostics with various nanomaterials, including graphene, across several diseases, offering a broader perspective of this emerging field. © 2020 American Chemical Society.
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Organic-based field effect transistors for protein detection fabricated by inkjet-printing
Martínez-Domingo C., Conti S., de la Escosura-Muñiz A., Terés L., Merkoçi A., Ramon E. Organic Electronics; 84 (105794) 2020. 10.1016/j.orgel.2020.105794. IF: 3.310
Biosensors based on Organic Field-Effect Transistors (OFETs) have attracted increasing attention due to the possibility of rapid, label-free, and inexpensive detection. Among all the different possibilities, inkjet-printed top-gate organic Field Effect Transistors-Based Biosensors (BioFETs) using a polymeric gate insulator have been seldom reported. In this work, a systematic investigation in terms of topographical and electrical characterization was carried out in order to find the optimal fabrication process for obtaining a reliable polymer insulator. Previous studies have demonstrated that the best electrical performance arises from the use of the perfluoropolymer Cytop™[12,13,14]. Consequently, a simple immobilization protocol was used to ensure the proper attachment of a model biomolecule onto the Cytop's hydrophobic surface whilst keeping its remarkable insulating properties with gate current in the range of dozens of pico-amperes. The top-gate inkjet-printed BioFETs presented in this study operate at threshold voltages in the range of 1–2 V and show durability even when exposed to oxygen plasma, wet amine functionalization treatments, and aqueous media. As a preliminary application, the inkjet-printed top-gate BioFETs is used for monitoring an immunoreaction by measuring changes in the drain current, paving the way for further use of this device in the immunosensing field. © 2020 Elsevier B.V.
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Recent advancement in biomedical applications on the surface of two-dimensional materials: From biosensing to tissue engineering
Nguyen E.P., De Carvalho Castro Silva C., Merkoçi A. Nanoscale; 12 (37): 19043 - 19067. 2020. 10.1039/d0nr05287f. IF: 6.895
As biosensors and biomedical devices have become increasingly important to everyday diagnostics and monitoring, there are tremendous, and constant efforts towards developing and improving the reliability and versatility of such technology. As they offer high surface area-to-volume ratios and a diverse range of properties, from electronic to optical, two dimensional (2D) materials have proven to be very promising candidates for biological applications and technologies. Due to the dimensionality, 2D materials facilitate many interfacial phenomena that have shown to significantly improve the performance of biosensors, while recent advances in synthesis techniques and surface engineering methods also enable the realization of future biomedical devices. This short review aims to highlight the influence of 2D material surfaces and the properties that arise due to their 2D structure. Using recent (within the last few years) examples of biosensors and biomedical applications, we emphasize the important role of 2D materials in advancing developments and research for biosensing and healthcare. © The Royal Society of Chemistry.
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Selective stamping of laser scribed rGO nanofilms: From sensing to multiple applications
Giacomelli C., Álvarez-Diduk R., Testolin A., Merkoçi A. 2D Materials; 7 (2, 024006) 2020. 10.1088/2053-1583/ab68a7. IF: 7.140
A rapid low-cost technology to produce highly conductive laser-scribed reduced-graphene oxide (rGO) thin films on flexible substrates is developed. Isolated rGO films, up to 30 nm thick and with a conductivity of 102 S m-1 are produced at room temperature in a three-step process: filtering the graphene oxide (GO) solution through nitrocellulose membranes, reduction of GO surface using a DVD-burner laser and solvent-free transfer of the resulting rGO pattern onto new substrates via pressure-based mechanism. The loss of density in the reduced part produces an increase in the thickness enabling the transfer of rGO only. The rGO is characterized with several analytical techniques, and its reduction degree, thickness, morphology, electrochemical and electromechanical properties are investigated and optimized. The validation of the technology is tested using a wide variety of substrates, and its applicability as a sensing platform for dopamine detection and back electrode in an electroluminescent lamp is demonstrated, opening the venue for a plethora of other new applications. © 2020 IOP Publishing Ltd.
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Toward Nanotechnology-Enabled Approaches against the COVID-19 Pandemic
Weiss C., Carriere M., Fusco L., Fusco L., Capua I., Regla-Nava J.A., Pasquali M., Pasquali M., Pasquali M., Scott J.A., Vitale F., Vitale F., Unal M.A., Mattevi C., Bedognetti D., Merkoçi A., Merkoçi A., Tasciotti E., Tasciotti E., Yilmazer A., Yilmazer A., Gogotsi Y., Stellacci F., Delogu L.G. ACS Nano; 14 (6): 6383 - 6406. 2020. 10.1021/acsnano.0c03697. IF: 14.588
The COVID-19 outbreak has fueled a global demand for effective diagnosis and treatment as well as mitigation of the spread of infection, all through large-scale approaches such as specific alternative antiviral methods and classical disinfection protocols. Based on an abundance of engineered materials identifiable by their useful physicochemical properties through versatile chemical functionalization, nanotechnology offers a number of approaches to cope with this emergency. Here, through a multidisciplinary Perspective encompassing diverse fields such as virology, biology, medicine, engineering, chemistry, materials science, and computational science, we outline how nanotechnology-based strategies can support the fight against COVID-19, as well as infectious diseases in general, including future pandemics. Considering what we know so far about the life cycle of the virus, we envision key steps where nanotechnology could counter the disease. First, nanoparticles (NPs) can offer alternative methods to classical disinfection protocols used in healthcare settings, thanks to their intrinsic antipathogenic properties and/or their ability to inactivate viruses, bacteria, fungi, or yeasts either photothermally or via photocatalysis-induced reactive oxygen species (ROS) generation. Nanotechnology tools to inactivate SARS-CoV-2 in patients could also be explored. In this case, nanomaterials could be used to deliver drugs to the pulmonary system to inhibit interaction between angiotensin-converting enzyme 2 (ACE2) receptors and viral S protein. Moreover, the concept of "nanoimmunity by design"can help us to design materials for immune modulation, either stimulating or suppressing the immune response, which would find applications in the context of vaccine development for SARS-CoV-2 or in counteracting the cytokine storm, respectively. In addition to disease prevention and therapeutic potential, nanotechnology has important roles in diagnostics, with potential to support the development of simple, fast, and cost-effective nanotechnology-based assays to monitor the presence of SARS-CoV-2 and related biomarkers. In summary, nanotechnology is critical in counteracting COVID-19 and will be vital when preparing for future pandemics. © 2020 American Chemical Society.
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Tutorial: design and fabrication of nanoparticle-based lateral-flow immunoassays
Parolo C., Sena-Torralba A., Bergua J.F., Calucho E., Fuentes-Chust C., Hu L., Rivas L., Álvarez-Diduk R., Nguyen E.P., Cinti S., Quesada-González D., Merkoçi A. Nature Protocols; 15 (12): 3788 - 3816. 2020. 10.1038/s41596-020-0357-x. IF: 10.419
Lateral-flow assays (LFAs) are quick, simple and cheap assays to analyze various samples at the point of care or in the field, making them one of the most widespread biosensors currently available. They have been successfully employed for the detection of a myriad of different targets (ranging from atoms up to whole cells) in all type of samples (including water, blood, foodstuff and environmental samples). Their operation relies on the capillary flow of the sample throughout a series of sequential pads, each with different functionalities aiming to generate a signal to indicate the absence/presence (and, in some cases, the concentration) of the analyte of interest. To have a user-friendly operation, their development requires the optimization of multiple, interconnected parameters that may overwhelm new developers. In this tutorial, we provide the readers with: (i) the basic knowledge to understand the principles governing an LFA and to take informed decisions during lateral flow strip design and fabrication, (ii) a roadmap for optimal LFA development independent of the specific application, (iii) a step-by-step example procedure for the assembly and operation of an LF strip for the detection of human IgG and (iv) an extensive troubleshooting section addressing the most frequent issues in designing, assembling and using LFAs. By changing only the receptors, the provided example procedure can easily be adapted for cost-efficient detection of a broad variety of targets. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.
