Electrochemical Paper-based Devices Research Articles

Laser‐scribed graphene toward scalable fabrication of electrochemical paper-based devices for lidocaine detection in forensic and pharmaceutical samples

Lidocaine (LID), a tertiary amine drug, is widely used as a local anesthetic for topical anesthesia and also presents antiarrhythmic and analgesic properties. Given its use can induce a temporary loss of sensory, motor, and autonomic function, it has been associated with criminal instances of drug-facilitated sexual assault. Herein, we manufactured an electrochemical paper-based analytical device (ePAD) using the laser-scribed graphene (LSG) technique for LID detection in pharmaceutical and forensic applications. The paper-based devices were characterized by scanning electron microscopy (SEM) and Raman spectroscopy, confirming the porosity and graphene-derived nature of the LSG material. In addition, to enhance the electrocatalytic properties, the LSG electrode was modified with a nanocomposite based on the mixture of multi-walled carbon nanotubes (MWCNT) and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS). Electrochemical characterizations of the non-modified and MWCNT/PEDOT:PSS-modified electrodes by impedance spectroscopy (EIS), cyclic voltammetry (CV), and differential pulse voltammetry (DPV), revealed the enhancement of the electrochemical properties of the modified electrode, providing higher detectability for LID detection. An analytical curve was built using DPV technique and exhibited a linear response in the concentration range of 31 to 248 µmol L−1 LID. The limits of detection (LOD) and quantification (LOQ) of the method were 0.72 µmol L−1 and 2.39 µmol L−1, respectively. The manufacturing reproducibility of the method was assessed by testing 8 sensors from different batches and provided a relative standard deviation (RSD) of 4.92 % (n = 8). The developed sensor was applied to LID determination in a commercial anesthetic sample and, as proof of the applicability of potential use in crime scenes of drug-facilitating crimes, we analyzed spiked LID in alcoholic drinks (vodka and tequila samples). The recovery percentages ranged from 79 % to 109 %, highlighting the practical use of our portable method for in-field analysis. In addition, four seized cocaine samples containing LID were successfully analyzed to demonstrate the potential use as a LID screening tool in street drug samples.

A selective dual-signal electrochemical paper-based device using imprinted sensors for voltammetric and impedance analysis of 4-NQO and carcinoembryonic antigen (CEA)

BackgroundCarcinoembryonic Antigen (CEA) and 4-nitroquinoline-N-oxide (4-NQO) are cancer markers that play a crucial role in tumor risk assessment and early cancer diagnosis. Therefore, it is in demand to develop a fast, accurate, simple, and cost-effective method to detect these cancer markers for quick and early stage-cancer diagnosis and treatment. ResultsHerein, we report a dual signaling approach for direct and indirect signal transduction of cancer biomarker binding on molecularly imprinted-electrodes integrated on an ePAD, enabling sensitive and selective quantitative analysis of 4-NQO and CEA. Multiple test zones on a single device based on artificial recognition sites using core-shell Cu-MOF@MIP were developed to create a selective “Dual-signal-ePAD”. An effective and facile imprinting method on a Cu-MOF surface based on the synthesized of 4-VPBA/MAA/TRIM polymer. It resulted in a novel MIP useable as a high-performance sensing tool for the ultrasensitive and specific quantification of the target cancer biomarkers. Multiple tests consisted of voltammetric analysis of 4-NQO via oxidation of the analyte on a WE1, and impedance analysis of CEA via the molecular interaction with the imprinted WE2. SignificanceThe proposed device provides enhanced electrochemical signal amplification due to its high conductivity, electrocatalytic activity, and the target-specific recognition sites for accurate determination of 4-NQO and CEA targets. The Dual-signal-ePAD exhibits good voltammetric and EIS response, oxidation currents of 4-NQO at −0.06 V and RCT of CEA, resulting in high selectivity and sensitivity with a linear response range covering the concentration range of clinical interest for both analytes. Dual-signal ePAD is a good candidate for clinical screening and POCT.

Electrocatalytic efficiency of carbon nitride supported gold nanoparticle based sensor for iodide and cysteine detection

Extensive investigations are being conducted on gold nanoparticles focusing on their applications in biosensors, laser phototherapy, targeted drug delivery and bioimaging utilizing advanced detection techniques. In this work, an electrochemical sensor was developed based on graphite carbon nitride supported gold nanoparticles. Carbon nitride supported gold nanoparticles (Au–CN) was synthesized by applying a deposition-precipitation route followed by a chemical reduction technique. The composite system was characterized by X-ray diffraction and X-ray photo electron spectroscopy methods. Electron microscopy analysis confirmed the formation of gold nanoparticles within the size range of 5–15 nm on the carbon nitride support. Carbon nitride supported gold based sensor was employed for the electrochemical detection of iodide ion and l-cysteine. The limit of detection and sensitivity of the sensor was attained 8.9 μM and 0.96 μAμM⁻1cm⁻2, respectively, for iodide ion, while 0.48 μM and 5.8 μAμM⁻1cm⁻2, respectively, was achieved for the recognition of cysteine. Furthermore, a paper-based electrochemical device was developed using the Au–CN hybrid system that exhibited promising results in detecting iodide ions, highlighting its potential for economic and portable device applications.

Flexible electrochemical paper-based device for detection of breast cancer-derived exosome using nickel nanofoam 3D nanocomposite

Flexible electrochemical paper-based device for detection of breast cancer-derived exosome using nickel nanofoam 3D nanocomposite

Paper-based screen-printed electrode to detect miRNA-652 associated to triple-negative breast cancer

Triple-negative breast cancer (TNBC) is one of the most aggressive and lethal types of BC, affecting mostly young women and its diagnosis is difficult and requires invasive methods, such as tissue biopsy which is painful and expensive. However, nowadays liquid biopsy is emerging as a great tool for determining blood-circulating species associated to cancer and to its early diagnosis and prognosis. Among the species, the relevance of microRNAs (miRNAs) has been highlighted as promising biomarker, and miRNA-652 has been associated with TNBC as it promotes the growth and migration of cancer cells. In this work we designed and characterized a paper-based electrochemical device capable of recognizing and quantifying miRNA-652, as future tool for liquid biopsy in TNBC. The device consists of an AuNP-modified office paper-based screen-printed electrode customized with an anti-miRNA probe for the selective recognition of miRNA-652. All the experimental parameters have been carefully evaluated, and the platform allowed to detect miRNA-652 in standard solution and human serum down to 0.4 nM, with a satisfactory repeatability of about 6 and 3 % respectively. The selectivity presence of other miRNA sequences was satisfactory demonstrated. In addition, we demonstrated the effectiveness of pre-concentration of miRNA by coupling the office paper-based electrode with an external disk made by chromatographic paper: the detection limit has been improved of 10-fold without the use of complex/expensive procedures. The presented manuscript represents an important step towards the development of a non-invasive, sensitive and TNBC-specific diagnostic platform that could improve patients' prognosis and quality of life, ulteriorly improved with pre-concentering properties of frugal supports as the external chromatographic paper-based ones.

Paper-based electrochemical device for early detection of integrin αvβ6 expressing tumors

Despite progress in the prevention and diagnosis of cancer, current technologies for tumor detection present several limitations including invasiveness, toxicity, inaccuracy, lengthy testing duration and high cost. Therefore, innovative diagnostic techniques that integrate knowledge from biology, oncology, medicinal and analytical chemistry are now quickly emerging in the attempt to address these issues. Following this approach, here we developed a paper-based electrochemical device for detecting cancer-derived Small Extracellular Vesicles (S-EVs) in fluids. S-EVs were obtained from cancer cell lines known to express, at a different level, the αvβ6 integrin receptor, a well-established hallmark of numerous epithelial cancer types. The resulting biosensor turned out to recognize αvβ6-containing S-EVs down to a limit of 0.7*103 S-EVs/mL with a linear range up to 105 S-EVs /mL, and a relative standard deviation of 11%, thus it may represent a novel opportunity for αvβ6 expressing cancers detection.

Microfluidic paper-based analysis device applying black phosphorus nanosheets@MWCNTs-COOH: A portable and efficient strategy for detection of β-Lactoglobulin in dairy products

This study prepared a novel, portable and cost-effective microfluidic paper-based electrochemical analysis device (μ-PAD) using black phosphorus nanosheets@carboxylated multi-walled carbon nanotubes (BPNSs@MWCNTs-COOH) nanocomposites for β-lactoglobulin (β-LG) detection. At the appreciate ratio, the synthesized BPNSs@MWCNTs-COOH was demonstrated to not only serve as a high-quality substrate for the specific aptamer immobilization, but also improve the electron transfer capability of the sensing interface. The μ-PADs, utilizing BPNSs@MWCNTs-COOH and aptamer recognition, exhibited a wider detection range (10–1000 ng mL−1) and lower detection limit (LOD: 0.12 ng mL−1) for β-LG, and demonstrated enhanced specificity, satisfactory anti-interference ability and stability. When applied to the β-LG determination in dairy samples, the μ-PAD yielded β-LG concentrations highly correlated with those obtained using the HPLC method (R2: 0.9982). These results emphasized the reliable performance of the developed μ-PADs in β-LG allergen quantification, highlighting their potential as an efficient platform for the rapid screening of β-LG allergens.

Integrated Ink Printing Paper Based Self-Powered Electrochemical Multimodal Biosensing (IFP-Multi ) with ChatGPT-Bioelectronic Interface for Personalized Healthcare Management.

Personalized healthcare management is an emerging field that requires the development of environment-friendly, integrated, and electrochemical multimodal devices. In this study, the concept of integrated paper-based biosensors (IFP-Multi ) for personalized healthcare management is introduced. By leveraging ink printing technology and a ChatGPT-bioelectronic interface, these biosensors offer ultrahigh areal-specific capacitance (74633 mF cm-2 ), excellent mechanical properties, and multifunctional sensing and humidity power generation capabilities. Moreimportantly, the IFP-Multi devices have the potential to simulate deaf-mute vocalization and can be integrated into wearable sensors to detect muscle contractions and bending motions. Moreover, they also enable monitoring of physiological signals from various body parts, such as the throat, nape, elbow, wrist, and knee, and successfully record sharp and repeatable signals generated by muscle contractions. In addition, the IFP-Multi devices demonstrate self-powered handwriting sensing and moisture power generation for sweat-sensing applications. As a proof-of-concept, a GPT 3.5 model-based fine-tuning and prediction pipeline that utilizes recorded physiological signals through IFP-Multi is showcased, enabling artificial intelligence with multimodal sensing capabilities for personalized healthcare management. This work presents a promising and ecofriendly approach to developing paper-based electrochemical multimodal devices, paving the way for a new era of healthcare advancements.

Development of Electrochemical Paper-Based Devices for Field Assays

The birth of the modern field of paper-based analytical devices (PADs) was marked by the pioneering work by the Whitesides’ group which demonstrated that it was possible to perform complex manipulation of liquids within hydrophilic paper channels delimited by hydrophobic barriers [1]. The key features of paper as a platform are: a) flexibility; b) low thickness and lightness; c) absorbency; d) high surface-to-volume ratio; e) hydrophilicity and capillary action; f) chemical and biological inertness; g) disposability and biodegradability, and; h) low cost and wide availability. Among the various detection modes that are compatible with PADs, electrochemical detection is very attractive since electrochemical transducers can be readily and rapidly patterned on paper using various approaches. Combined with low-cost and portable instrumentation, electrochemical PADs (ePADs) are well suited to on-site assays and point-of-care testing and relevant applications have been developed in various fields such as clinical diagnostics, environmental monitoring and food quality control [2-4].The methods of patterning of the hydrophobic barriers and of depositing the electrodes are critical in the fabrication of ePADs and several approaches have been proposed in the literature [2-4]. Τhe aim of this work was the development of different approaches for the fabrication of ePADs. For this purpose, hydrophobic barriers were delimited using: x-y plotting with commercial hydrophobic marker pens, wax printing and thermal printing. Electrodes were deposited on the PADs using x-y plotting with commercial writing pencils and conductive inks formulated in-house and screen-printing. Different fabrication parameters were optimized including the selection of the paper substrate, the conditions for the formation of the hydrophobic barriers and the electrode deposition parameters. Applicability of the ePADs was demonstrated for different applications for on-site assays including the enzymatic amperometric detection of glucose, the determination of trace metals by stripping analysis and the voltammetric detection of organic compounds.

Graphene Pseudoreference Electrode for the Development of a Practical Paper-Based Electrochemical Heavy Metal Sensor.

Paper-based electrochemical devices (PEDs) have emerged as versatile platforms that bridge analytical chemistry and materials science, demonstrating advantages of portability, cost-effectiveness, and environmental sustainability. This study investigates the integration of a graphene pseudoreference electrode (GPRE) into a PED, and it exhibits potential advantages over the traditional Ag/AgCl pseudoreference electrode (PRE). In addition, the electrochemical properties and stability of GPRE are compared with those of the traditional Ag/AgCl PRE. The results demonstrate that GPRE exhibits a stable and reproducible potential during electrochemical measurement throughout 180 days, demonstrating its suitability as an alternative to an expensive metal PRE. Furthermore, a GPRE-incorporated paper-based device is designed and evaluated for use in the electrochemical detection of cadmium (Cd) and lead (Pb) using an in situ bismuth-modified electrode. The GPRE-incorporated PED exhibited good analytical performance, with a low limit of detection of 0.69 and 5.77 ng mL-1 and electrochemical sensitivities of 70.16 and 38.34 μA·mL·μg-1·cm-2 for Cd(II) and Pb(II), respectively. More than 99.9% accuracy of the sensor was obtained for both ions with respect to conventional inductively coupled plasma-mass spectrometry. The results highlight the effectiveness and suitability of the GPRE-incorporated PED as a sensor for various applications, such as environmental monitoring, food quality control, and medical diagnostics.

A novel paper-based electrochemical device modified with Ni-doped TiO2 nanocrystals-decorated graphene oxide for ascorbic acid detection

This study presents the development of a novel paper-based electrochemical device modified with pure and nickel-doped TiO2 nanocrystals and graphene oxide to enhance its ability to detect ascorbic acid (AA). The use of nanomaterials in the fabrication of the sensor provides a high surface area-to-volume ratio, leading to an increase in the sensitivity and selectivity of the device. The nanomaterials were synthesized, and a combination with the best properties was selected for detecting AA. The morphological, structural, and electrical properties of the nanomaterials in the paper device were investigated using scanning electron microscopy (SEM), Raman spectroscopy (Raman), and cyclic voltammetry (CV), respectively. The sensor's performance was evaluated through various experiments, including cyclic voltammetry, to measure its sensitivity and selectivity in detecting AA. The results indicate that adding Ni-doped TiO2 nanocrystals improves the sensor's sensitivity while incorporating graphene oxide enhances its selectivity. Furthermore, the sensor's performance was compared to that of other commonly used sensors, and it was found to be highly sensitive and selective. Therefore, this paper-based electrochemical sensor, modified with nanomaterials, shows great potential for detecting AA and other applications, such as environmental monitoring and medical diagnostics, due to its high sensitivity and selectivity, low cost, and ease of use.

Paper as smart support for bioreceptor immobilization in electrochemical paper-based devices

The use of paper as a smart support in the field of electrochemical sensors has been largely improved over the last 15 years, driven by its outstanding features such as foldability and porosity, which enable the design of reagent and equipment-free multi-analysis devices. Furthermore, the easy surface engineering of paper has been used to immobilize different bioreceptors, through physical adsorption, covalent bonding, and electrochemical polymerization, boosting the fine customization of the analytical performances of paper-based biosensors. In this review, we focused on the strategies to engineer the surface of the paper for the immobilization of (bio)recognition elements (eg., enzymes, antibodies, DNA, molecularly imprinted polymers) with the overriding goal to develop accurate and reliable paper-based electrochemical biosensors. Furthermore, we highlighted how to take advantage of paper for designing smart configurations by integrating different analytical processes in an eco-designed analytical tool, starting from the immobilization of the (bio)receptor and the reagents, through a designed sample flow along the device, until the analyte detection.

µPED based electrode modified with nanocomposite for the detection of proline: An abiotic stress biomarker in plant

Plants when exposed to stressful conditions, accumulates array of metabolites. Among them proline plays significant and beneficial role as osmolyte, metal chelator and as anti-oxidative defense and regulator molecule. Thus the proline content is one of the potent bio-marker for the early detection of abiotic stress in plant. In this work a microfluidic paper-based electrochemical device (µPED) modified with copper oxide nanoparticles (CuO) decorated reduced graphene oxide (rGO) nanocomposite is utilized to develop disposable system for the detection of proline. Wax and screen printings were utilized to create microfluidic chambers and electrode pattern on paper device, respectively. Portable potentiostat was used for measuring the current in response from the addition of proline. The proposed sensor exhibits excellent electrochemical performance with broad linear responses over a proline concentration ranging from 0.1 mM to 7.5 mM (R2 =0.99) and showed lower detection limit of 0.05 mM at 0.4 V vs. pseudo Ag/AgCl. Excellent electrochemical performance may be attributed to presence of electroactive rGO and catalytic activity towards proline is due to the coordination between proline and copper (II) oxide nanoparticles. These results demonstrate that the proposed paper-based electrochemical sensor can be utilized in disposable and portable way to detect proline content in the abiotic-stressed plants and has potential to be applied in on-site application.

3D-printed holder for drawing highly reproducible pencil-on-paper electrochemical devices.

Pencil drawing is one of the simplest and most cost-effective ways of fabricating miniaturized electrodes on a paper substrate. However, it is limited by the lack of reproducibility regarding the electrode drawing process. A 3D-printed pencil holder (3DPH) is proposed here for simple, reproducible, and low-cost hand-drawn fabrication of paper-based electrochemical devices. 3DPH was designed to keep pressure and angulation of the graphite mine constant on the paper substrate using a micromechanical pencil regardless of the user/operator. This approach significantly improved the reproducibility and cost of making reliable pencil-drawn electrodes. The results showed high reproducibility and accuracy of the 3DPH-assisted electrodes prepared by 4 different operators in terms of sheet resistance and electrochemical behavior. Cyclic voltammetric (CV) curves in the presence of [Fe(CN)6]3-/4- redox probe showed only 3.9% variation for the anodic peak currents of different electrodes prepared by different operators when compared with electrodes prepared without the 3D-printed support. SEM analyses revealed a more uniform graphite deposition/design of the electrodes prepared with 3DPH, which corroborates the results obtained by CV. As a proof of concept, 3DPH-assisted pencil-drawn graphite electrodes were employed for dopamine detection in synthetic saliva, showing a proportional increase in anodic peak current at 0.12 V vs. carbon pRE with increasing dopamine (DA) concentration, with a detection limit of 0.39μmol L-1. Moreover recoverywas in the range93-104% of DA (4-7% RSD) in synthetic saliva for three different concentrations, demonstrating the reliability of the approach. Finally, we believe this approach can make pencil-drawn technology more robust, accessible, reliable, and inexpensive for real on-site applications, especially in hard-to-reach locations or research centers with little investment.

Paper-based electrochemical biosensors for the diagnosis of viral diseases.

Paper-based electrochemical analytical devices (ePADs) have gained significant interest as promising analytical units in recent years because they can be fabricated in simple ways, are low-cost, portable, and disposable platforms that can be applied in various fields. In this sense, paper-based electrochemical biosensors are attractive analytical devices since they can promote diagnose several diseases and potentially allow decentralized analysis. Electrochemical biosensors are versatile, as the measured signal can be improved by usingmainly molecular technologies andnanomaterials to attach biomolecules, resulting in an increase in their sensitivity and selectivity. Additionally, they can be implementedin microfluidic devices that drive and control the flow without external pumping and store reagents, and improve the mass transport of analytes, increasing sensor sensitivity. In this review, we focus on the recent developments in electrochemical paper-based devices for viruses' detection, including COVID-19, Dengue, Zika, Hepatitis, Ebola, AIDS, and Influenza, among others, which have caused impacts on people's health, especially in places with scarce resources. Also, we discuss the advantages and disadvantages of the main electrode's fabrication methods, device designs, and biomolecule immobilization strategies. Finally, the perspectives and challenges that need to be overcome to further advance paper-based electrochemical biosensors' applications are critically presented.

Laser-induced fabrication of gold nanoparticles onto paper substrates and their application on paper-based electroanalytical devices

A fast approach for synthesizing gold nanoparticles over electrochemical paper-based devices is reported. The device was fabricated by paper laser pyrolysis carbonization followed by in situ laser synthesis of AuNPs.

A paper chromatographic-based electrochemical analytical device for the separation and simultaneous detection of carbofuran and carbaryl pesticides

We developed an electrochemical paper-based device (ePAD) for the online separation and simultaneous determination of structurally similar carbofuran (CBF) and carbaryl (CBR). Our device combined paper chromatography and an electrochemical sensor as a single system for increasing the selectivity to simultaneous detection of the two pesticides. During the simultaneous detection of CBF and CBR, the separation of the two carbamate compounds depends on the differences between the movements of the substances on the chromatographic paper in the moving phase flow. The isolated pesticides were electrochemically measured using an amperometric method. Under optimal conditions, which include the effect of the mobile phase, separation channel, and the applied potential, the proposed device provides a linear range for the simultaneous determination of CBF and CBR from 0.1 to 2.0 and 0.5–7.5 mg L−1, with the limits of detection at 0.06 and 0.40 mg L−1, respectively. Furthermore, we successfully used the developed device to determine CBF and CBR in water, cucumber, and cabbage samples. The obtained results correspond to results obtained from a standard method. This developed ePAD is low-cost and uses a low sample volume (2 µL). Moreover, it is disposable, portable, and a promising tool for the on-site quantification of pesticides in actual samples.

Flexible Paper-Based Immunosensor for the Detection of Specific Cancer-Derived Exosomes

This study aims at an electrochemical paper-based device for the selective and sensitive detection of exosomes as an economic and flexible platform. Using a laser cutter, a three-electrode platform was patterned on a hydrophobic paper, and then synthetic carbon and silver ink were screen-printed on the paper. Anti-human CD9 antibody was covalently attached to the surface of a carbon ink electrode enriched with graphene oxide aerogel/CoFe2O4@chitosan nanocomposite. The immobilization, incubation and binding time of the capture antibody were investigated as effective parameters. Under optimum conditions, the differential pulse voltammetry (DPV) was used to establish a calibration plot that covered 500 to 5 × 106 exosoms μl−1 with a detection limit of 100 exosome μl−1. This method was implemented successfully for the detection of exosomes in a serum sample. As the results show, the fabricated biosensor is capable of detecting exosomes for the early diagnosis of cancers.

Binary Cooperative Thermal Treatment of Cellulose and MoS2 for the Preparation of Sustainable Paper-Based Electrochemical Devices for Hydrogen Evolution

Binary Cooperative Thermal Treatment of Cellulose and MoS₂ for the Preparation of Sustainable Paper-Based Electrochemical Devices for Hydrogen Evolution

Paper-based electrochemical immunosensor device via Ni-Co MOF nanosheet as a peroxidase mimic for the label-free detection of alpha-fetoprotein

The quantitative detection of tumor biomarkers (TMs) is of great importance in clinical cancer diagnosis and curative effect evaluation. Conventional TM detection methods require bulky equipment and well-trained personnel, resulting in high complexity and cost for diagnostics. To resolve these issues, a paper-based electrochemical immunosensor device coupled with a Ni-Co metal-organic framework (Ni-Co MOF) as a peroxidase mimic was constructed for the label-free detection of alpha-fetoprotein (AFP). First, aminated Ni-Co MOF nanosheets were synthesized by a facile solvothermal method, and then carbon nanotubes and streptavidin-functionalized Ni-Co MOF were successively modified onto a graphene nanosheet-printed polyethylene terephthalate (GNP) electrode. The Ni-Co MOF provided a large specific surface area for capturing the biotin-antibody of AFP efficiently. Afterward, a prepared three-electrode system was assembled with patterned paper to fabricate a highly integrated paper-based electrochemical immunosensor for AFP. Due to the remarkable peroxidase-like activity of the Ni-Co MOF, it was found to amplify the electrode signal obviously. After the formation of the immune complex, the catalytic activity of the MOF was greatly inhibited and led to a reduced current signal, and the highly sensitive and selective detection of AFP with a linear range of 1–200 ng/mL and a detection limit of 0.3 ng/mL was realized. The integrated paper-based immunosensor based on a Ni-Co MOF peroxidase mimic shows great application potential in the personalized point-of-care diagnosis of disease.