Development of Novel Conductive Inks for Screen-Printed Electrochemical Sensors: Enhancing Rapid and Sensitive Drug Detection

Abstract

The development of screen-printed electrochemical sensors represents a rapidly expanding research field with great potential for applications in the rapid and sensitive determination of drugs in complex matrices. This work presents a review of the state-of-the-art examples of this technology, focusing on its application in real matrices such as water, pharmaceutical formulations, and biological fluids. We discuss the main materials used in developing conductive inks, highlighting their properties and influence on sensor performance. The characterization of materials and sensors is crucial to ensure the reproducibility and reliability of results. Additionally, we address the challenges associated with the application of these sensors in complex matrices, such as interferences from other components and the need for sample pretreatment. Finally, we present future perspectives for developing screen-printed electrochemical sensors, with an emphasis on new technologies and materials that can improve the sensitivity, selectivity, and stability of these devices.

1. Introduction

The pharmaceutical industry has evolved significantly, driven by the growing global demand and the complexity of human diseases. Although historical treatments often lacked scientific rigor, modern medicine offers effective solutions, even for common diseases. Over-the-counter (OTC) medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs), can be harmful when used incorrectly. Self-medication, influenced by various factors, poses significant health risks due to potential overdoses, drug interactions, and adverse effects [1].

The discovery of penicillin in 1928 revolutionized the treatment of bacterial infections. However, the indiscriminate use of antibiotics has led to the emergence of drug-resistant strains, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Staphylococcus aureus 1 (VRSA), highlighting the need for responsible use [2]. The World Health Organization (WHO) warns that the inappropriate use of antibiotics is the main factor in developing bacterial resistance, emphasizing the need for control measures to ensure the rational use of these drugs [3,4].

Given the indiscriminate use of drugs, the quantitative analysis of these substances in various matrices (biological fluids, the environment, effluents) becomes essential to monitor exposure, evaluate their therapeutic efficacy, and mitigate the risks to health and the environment [5].

The literature describes various analytical methods, such as chromatography, spectrophotometry, and electroanalytical methods, for the determination of drugs in different matrices. Among them, electroanalytical methods stand out due to their characteristics, which include a rapid response, portability, a low cost, and a lower environmental impact, being frequently used due to their practicality and efficiency [6,7,8,9]. In addition, electrodes offer a high sensitivity, selectivity, and economic viability. This article aims to discuss innovations in printed sensors by applying a screen-printing technique for drug detection. The screen-printing process, the materials used in the composition of conductive inks, and the potential applications will be highlighted.

2. Electrochemical Sensors

Electrodes are crucial elements in electrochemical analyses, allowing the investigation of charge transfer processes at interfaces. The electrochemical cell is composed of a working electrode (WE), a reference electrode (RE), and a counter electrode (CE) immersed in an electrolyte solution, which enables the quantification of analytes through electrochemical measurements [10,11,12,13,14].

The working electrode (WE), where the oxidation or reduction of the analyte occurs, must be composed of an inert material that covers the potential range of the analysis. The reference electrode (RE) maintains a constant and stable potential during measurements. The counter electrode or auxiliary electrode (CE) directs the current generated directly to the working electrode (WE), minimizing current variations during the experiment. The three-electrode system is the most widely used, as it allows analyses in more dilute support solutions and electrolytes with a higher electrical resistance. Figure 1 illustrates a system of an electrochemical cell containing three electrodes (WE, RE, and CE) immersed in an electrolyte solution [14,15,16].

Printed electrodes are devices manufactured using printing techniques, such as screen-printing and 3D printing, enabling various types of applications. Unlike conventional electrodes, these devices present a complete system on a single support, containing the working, auxiliary, and quasi-reference electrodes, as illustrated in Figure 2 [17].

These electrodes were developed as an alternative to conventional electrodes due to their numerous advantages, such as the possibility of miniaturization, a good sensitivity and selectivity, and a low cost [18,19]. They can be manufactured on a large scale and, being disposable, eliminate the need for cleaning, making the analysis process faster and more practical. In addition, they minimize the cross-contamination effects between samples, increasing the reliability of the analytical results [20].

Printed electrodes, manufactured by screen-printing, find wide applications in the electrochemical detection of drugs. The versatility of conductive inks, composed of conductive particles (graphene, carbon nanotubes, carbon black), polymeric binders, and solvents, allows the creation of customized sensors for various molecules of interest. Therefore, these devices offer portable and low-cost solutions for health monitoring, quality control, and clinical analyses [21,22,23,24,25,26,27,28,29,30].

2.1. Printing Electrodes Using the Screen-Printed Technique

Screen-printing has existed for over 2000 years, with rudimentary fabric-printing methods having been developed. In the 18th century, the technique gained popularity in Europe, especially for printing fabrics. Over the years, it has been modernized with the use of synthetic inks and polyester screens, becoming widely used for printing posters, labels, signs, bags, and electronic circuits. Today, this technique continues to evolve and is used in various applications, including the fabrication of printed electrodes and electronic devices [31].

The production of printed electrodes using screen-printing is a widely used technique in fabricating electronic devices, sensors, and biosensors. This method allows for the creation of electrodes with specific electrical properties and the customization of their geometries to meet the needs of different applications. The technique is easily applicable in any laboratory, as it does not require complex equipment, and several stages of the fabrication process can be adjusted using alternative materials for manual production [32].

The fabrication process of these devices involves several steps: substrate preparation, electrode design, conductive material deposition, drying, and curing [33]. Electrode designs are created digitally and optimized for size using software, and are then cut onto an adhesive sheet using a plotter. Conductive inks, often based on carbon materials, nanomaterials, or conductive polymers, are screen-printed onto the substrate using a squeegee to fill the stencil uniformly and achieve the desired thickness [34]. Afterward, these devices undergo a drying process that can occur at room temperature or under controlled conditions, depending on the ink composition and the desired electrode properties. The printed electrodes can also be subjected to additional treatments, such as the application of protective coatings or surface modifications, to increase the sensor’s sensitivity and selectivity [34].

Therefore, screen-printing applied to electrode production has great potential for continued advancement, driven by the increasing demand for more cost-effective, efficient, and customized devices in various sectors of technology and healthcare. Figure 3 illustrates the fabrication process of printed electrodes using the screen-printing technique.

2.2. Conductive Inks for Printing Electrodes

With the advancement of technology and the search for more sustainable solutions, conductive inks have become a promising alternative in various areas, such as printed electronics, sensors, and wearable devices [26]. Their formulations are mainly made up of three main components: conductive particles that transport the charge, a binder responsible for aggregating the particulate material, and a solvent that homogenizes and solubilizes the components (Figure 4) [28].

The most used conductive materials include metal particles, conductive polymers, and carbonaceous materials. Although metal-based conductive inks are more conductive, they are more expensive, less biocompatible, and more unstable to oxidation than carbon-based inks [27,35,36]. Conductive polymers have a good conductivity and mechanical stability, but certain polymers are sensitive to changes in environmental parameters such as temperature, humidity, and pH [37]. Carbon-based inks have excellent properties due to the characteristics of carbonaceous materials, including an excellent electrical and thermal conductivity, chemical stability, a good surface area, a reasonable cost, and easy accessibility [26,27,28,38]. The following topics will discuss the main materials used in developing conductive inks, subdivided into carbonaceous materials, binders, and solvents.

2.2.1. Carbonaceous Materials

Carbonaceous materials have been widely used in the development of conductive inks for printing electrodes. Graphite, carbon nanotubes (CNTs), and graphene have been widely used in the development of inks [39,40]. Graphite is valued for its high purity and low cost and is often used in the production of conductive inks [41]. Verma et al. (2024) produced a conductive ink based on graphite, shellac as a binding agent, and deionized water as a solvent. The proposed ink showed a good homogeneity and viscosity suitable for screen-printing. The devices manufactured with this ink exhibited an excellent electrical conductivity and good adhesion to various types of surfaces. The authors highlighted the sensitivity and reproducibility of the developed sensors, demonstrating the properties that graphite confers to the ink [42].

Carbon nanotubes (CNTs) [43] and graphene [44] are characterized by superior properties compared to other carbonaceous materials [26]. CNTs are cylindrical carbon structures with exceptional electrical and mechanical properties, such as a high electrical conductivity and a large surface area. Their structure, consisting of coiled layers of graphene, can vary from single-walled to multi-walled, which influences their properties [45]. Due to these properties, CNTs have been widely used in developing conductive inks, offering a high conductivity and flexibility. This versatility makes them suitable for fabricating various flexible and wearable electronic devices [45,46]. In this context, Park et al. (2024) used single-walled carbon nanotubes to prepare a highly conductive ink with suitable rheological properties. The ink was composed of a combination of single-walled carbon nanotubes, cellulose, and water. The results of their research showed that the developed ink exhibited a high conductivity due to the alignment of the single-walled carbon nanotubes in the cellulose fibril networks. This alignment was achieved by interfibrillar sliding, which significantly improved the electrical conductivity of the ink [47].

Another material that stands out is graphene, a two-dimensional carbon material with a hexagonal structure that has favorable physical and chemical properties such as a large surface area, an excellent electrical conductivity, a high mechanical strength, thermal conductivity, and ease of surface functionalization [48]. The use of graphene was successfully employed by Kim et al. (2021) in preparing conductive ink. The authors reported that the ink was prepared by the exfoliation process, in which a mixture of graphite and ethyl cellulose (9:1 by weight) was dispersed in terpineol/ethanol (5:5 by volume) and loaded into a fluid dynamic reactor. The intense shear and cavitation forces in the reactor enabled the rapid and efficient production of high-quality graphene ink. This ink was used to fabricate printed sodium ion sensors, demonstrating an excellent detection performance by monitoring the concentration of sodium ions in sweat in real time during exercise. In addition, the ink was found to be highly conductive, and its consistency enabled the production of screen-printed sensors with a high sensitivity, a good reproducibility and selectivity, and a fast response time [27].

Another approach to the production of conductive inks involves the combination of carbonaceous materials, which can result in improvements in analytical performance. In this sense, Poulin et al. (2021) presented the development of a conductive ink based on graphite and carbon black, resulting in a high electrical conductivity. Graphite gives materials flexibility, while carbon black contributes to forming an efficient conductive network. In addition to a high conductivity, the ink demonstrated water resistance and temperature variations, making it ideal for various applications. This combination of properties makes ink a promising alternative for manufacturing flexible electronic devices. However, for these inks to be applied to different surfaces and under different conditions, it is essential to have a component that can provide the necessary cohesion and adhesion for the conductive particles [49].

2.2.2. Binders

A binder has the function of agglomerating the particulate material, giving the ink properties such as adhesion, durability, and resistance. The selection of the most suitable binder is contingent upon the specific application and the desired characteristics of the ink, including conductivity, flexibility, and chemical resistance. A range of binder types can be employed, with each exhibiting distinctive properties [27,45].

A literature review revealed that the vast array of existing binders has made possible the development of a diverse range of ink formulations. These include cellulose acetate [50], ethyl cellulose [51], polymeric vinyl acetate [52], polyurethane [53], and others. In a study by Carvalho et al. (2021), a high-quality conductive ink was developed using graphite and cellulose acetate, dispersed in an organic solvent to produce screen-printed sensors. The role of cellulose acetate in forming a polymer matrix, agglomerating the graphite particles, and imparting a gel-like consistency to the ink was pivotal in facilitating the application and formation of a conductive surface after drying. Ultimately, the authors reported the successful development of low-cost sensors that demonstrated an excellent performance, including a wide linear range, a high sensitivity, and a low detection limit. These sensors were shown to be effective in determining levodopa (L-dopa) [54].

The versatility in the choice of binders for conductive ink production is evidenced in the literature, which presents the use of alternative binders such as stained-glass varnish [55], nail polish [56], and chitosan [57] in the production of conductive inks. These materials, in addition to being more commercially accessible, exhibit suitable properties for forming conductive films. The search for binders for conductive inks has increasingly turned to green chemistry. Materials such as shellac stand out for their biocompatible and biodegradable characteristics, making them a promising option. Henrique et al. (2021) demonstrated the potential of shellac in developing ink for printing electrochemical sensors. The authors prepared a conductive ink using shellac powder, graphite, and polyurethane solvent. The resulting sensor was effective in detecting the antibiotic sulfamethoxazole, exhibiting a wide linear range and a low detection limit. Shellac, as a natural bioadhesive polymer, contributed to the simplicity and low cost of the sensor, as well as providing desirable characteristics such as biocompatibility and biodegradability. The results obtained by the authors demonstrate the feasibility of using biodegradable binders in electrochemical sensors, paving the way for the development of more sustainable and efficient technologies [58].

2.2.3. Solvents

Another essential component for the formulation of conductive inks is the solvent. The solvent plays a fundamental role in the production of conductive inks, acting as the medium for making the mixture liquid, facilitating application, and ensuring the uniform dispersion of the components. Without the solvent, the production and application of these inks would become more complex and less efficient [27]. The selection of the solvent is crucial to ensure efficient interactions of the conductive ink components. Various organic solvents, such as acetone [59], cyclohexanone [50], mixtures of toluene and ethanol [51], and dimethylformamide [60], among others, are employed for this purpose. Although organic solvents have been traditionally used, concerns about human health and the environment have led to the exploration of green solvents as a safer and more sustainable alternative [61].

Within the context of green chemistry, which seeks to minimize the environmental impact of chemical processes, the use of water as a solvent stands out. In addition to being abundant and low-cost, water is non-flammable and non-toxic. These attributes make it a promising alternative for producing conductive inks, driving the search for more efficient and sustainable procedures [62]. In this context, Chung et al. (2024) presented a significant advancement by developing a water-based conductive ink composed of gallium, indium, and carbon nanotubes. This formulation demonstrated a high stability and compatibility with various flexible substrates, allowing the fabrication of e-textiles, which are fabrics that incorporate electronic components, such as sensors or circuits, directly into their structure. The produced e-textiles exhibited a high conductivity, flexibility, durability, and biocompatibility, combining a superior mechanical and electrical performance with comfort and safety. These promising results pave the way for new applications of water as an alternative solvent [63].

Different ink compositions can be produced using various types of materials, depending on the desired application. However, the search for more effective and environmentally friendly formulations continues, driven by the need to meet the requirements of increasingly sophisticated applications [26,27,28,63,64].

In addition to the ink composition, the other factors that can influence the electrode printing process are the viscosity and homogeneity of the ink. Viscosity is an essential characteristic of all fluids, as it determines a liquid’s resistance to flow or shear deformation. This resistance arises from cohesive intermolecular forces, which are responsible for the friction between adjacent layers of the fluid that move relative to each other. Several factors, such as the temperature and pressure, influence the viscosity, making it one of the most important properties in the performance of inks [65].

Homogeneity is related to the uniform distribution of the ink components and is an essential parameter in the manufacturing process. This uniformity ensures that the ink maintains a stable conductivity and that the films formed have a consistent thickness and quality. The lack of homogeneity can lead to ink performance failures, such as an irregular conductivity and the formation of defective areas, compromising its application in the printing of flexible sensors. Homogeneity is also crucial to ensure adhesion to the substrate and the durability of the inks after application, especially on complex and flexible surfaces.

3. Chemically Modified Printed Electrodes

The use of electrodes in electrochemical systems is limited by the performance of the electrodes due to several factors, such as the inserted medium, the composition of the electrode, and the potential applied to the surface. Therefore, the selectivity and sensitivity of conventional electrodes are often insufficient for detecting analytes of interest in complex matrices, such as biological and environmental samples. With the emergence of chemically modified electrodes (CMEs), the applications of these devices have grown considerably, becoming a valuable and reliable tool for determining various compounds, from environmental pollutants to disease biomarkers. Therefore, the ability to chemically modify electrodes has paved the way for the development of increasingly sensitive analytical devices for applications in diverse fields, such as environmental monitoring, medical diagnoses, and industrial quality control [66,67,68,69].

CMEs can be defined as electrodes that have active chemical species attached to their surface, to modify the properties of the interface between the electrode and the solution. This modification allows for control of the electrode’s reactivity and selectivity, paving the way for a wide range of applications. These electrodes can be printed; made of glassy carbon, paste, etc.; and have their surface altered by the deposition of a thin layer of conductive or semiconductor material, or by other modifications that enhance the sensor’s performance, depending on its intended use. These modifications confer new electrochemical properties to the electrode, significantly expanding its electroactive area and improving its selectivity, linear response range, catalytic properties, and stability. They can be applied in various fields such as analytical chemistry, biosensors, and electrocatalysis [70,71,72,73].

In recent years, the modification of electrode surfaces has been widely used in the manufacture of highly sensitive devices for determining various compounds. Figure 5 shows the number of articles published between 1974 and 2023 according to the Scopus and Web of Science databases, by using the term “chemically modified electrode” and focusing on the title, article summary, and keywords. The growth observed over the years may be associated with an increase in investments in research in this area and the emergence of several materials with the potential to be used in the modification of electrochemical sensors.

3.1. Materials Applied in Sensor Modifications

Various materials can be used in the chemical modification of screen-printed electrodes, among which the most used are metallic nanoparticles, carbonaceous nanomaterials, polymers, and composites. The high surface area of nanomaterials, their unique electronic properties, and their functionalization capacity allow the creation of electrochemical sensors with a greater sensitivity, selectivity, and stability. Some examples of the most used nanomaterials are carbon nanotubes, graphene, carbon black, gold, and silver nanoparticles (Figure 6). Some of the carbonaceous nanomaterials, such as those mentioned previously, have a high surface area, providing many active sites for interaction with the analyte and increasing the sensitivity of the sensors. Furthermore, the excellent electrical conductivity of these nanomaterials facilitates the transfer of electrons between the electrode and the analyte, improving the efficiency of electrochemical processes. The use of metallic nanoparticles to modify CMEs has also been shown to be advantageous because these nanoparticles, such as gold, silver, and platinum, have a high electrical conductivity, which facilitates electron transfer and increases the sensor sensitivity. Regarding conductive polymers, they present a good versatility, a low market cost, and attractive chemical and physical properties for the development of sensors, in addition to biocompatibility and a high surface area, and are commonly used to immobilize biomolecules in the manufacture of biosensors [74,75,76,77].

Shehata et al. (2020) developed a printed electrochemical sensor (SPE) modified with gold nanoparticles (AuNPs) through electrochemical deposition. This sensor was called GNMSPE and was applied in the electrochemical determination of moxifloxacin hydrochloride (Moxi). The electrochemical performance was compared with that of other sensors (carbon paste electrodes) and modified with other nanomaterials (graphene oxide, multi-walled carbon nanotubes, and silver nanoparticles, among others). The results obtained demonstrated that GNMSPE presented the best electrochemical performance, a high sensitivity, and applicability for determining Moxi in urine samples from human infants, with recoveries between 99.8% and 101.6%, in addition to the advantage of being disposable [78].

In another study conducted by Khosrokhavar et al. (2020), a printed electrochemical sensor modified with a molecularly imprinted polymer (MIP) and graphene nanosheets was developed for the detection of sertraline (STR). To perform the polymerization, precipitation was performed in the presence of sertraline hydrochloride (a template molecule) to synthesize the MIP [79]. The SPE was fabricated in the laboratory and a thin layer of the MIP/graphene suspension was incorporated under the surface of the electrodes. A comparative study was carried out on the sensor modified with the MIP/graphene and with an NIP (non-imprinted polymer)/graphene. The sensor with the MIP/graphene showed a better performance, which can be associated with the high selectivity of the MIP associated with the high conductivity and surface area of graphene nanosheets. Finally, this sensor showed a good sensitivity and was applied in tablet and human serum samples with recoveries between 97.98% and 101.33%. To ensure that the modification process of the screen-printed electrodes was effective, characterization techniques were used, as they can guarantee the quality and performance of these sensors in determining drugs. This step allows the modification process to be optimized, ensuring the reproducibility of the results and the understanding of the molecular recognition mechanisms, which are fundamental for developing sensitive sensors.

3.2. Transition Metal Materials

In addition to the previously mentioned nanomaterials, other materials composed of transition metals and abundant Earth metal oxides have gained prominence in developing electrochemical sensors. Transition metals such as iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), and manganese (Mn), and their oxide-based nanomaterials, exhibit an exceptional set of properties that make them promising candidates for various applications. The oxides of these metals can mimic the catalytic activity of noble metals, making them more accessible and sustainable alternatives for reactions of industrial interest. The high surface area and chemical nature of these metal oxides make them excellent supports for noble metal nanoparticles (gold, silver, platinum, palladium), enhancing their catalytic activity and stability [80,81].

Another relevant characteristic is the abundance of these metals on Earth, which significantly reduces the production costs of the nanomaterials, making them economically viable for large-scale applications. With appropriate surface modifications, metal oxide-based nanomaterials can exhibit biocompatibility, paving the way for applications in biomedicine and biotechnology. Beyond applications in electrochemical devices, these materials offer a wide range of catalytic properties, making them suitable for various energy conversion reactions, such as water electrolysis and CO₂ reduction reactions. Maduraiveeran et al. (2019) described in their review the recent progress and main approaches for the synthesis and application of transition metal oxide nanomaterials for various electrochemical devices. Chen et al. (2024) investigated the application of iron-based electrode material composites in electrochemical sensors for real sample detection, demonstrating the main developments around sensor applications. Finally, transition metal oxide-based nanomaterials represent a class of materials with great potential to revolutionize various areas, from catalysis and energy to biomedicine. Their unique properties, combined with their abundance and low cost, make them highly attractive materials for research and development [80,81].

4. Characterizations of Screen-Printed Electrodes

The characterization of electrodes and the materials that constitute the inks is a crucial step in developing electrochemical sensors. Through them, it is possible to obtain crucial information about electrochemical characteristics (sensor resistivity) and structural and morphological characteristics. Several studies exist in the literature that include characterization techniques to correlate the properties of the materials with the electrochemical performance of the sensor, in addition to validating the results obtained [82,83]. The most used techniques are cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, and X-ray diffraction (XRD).

4.1. Cyclic Voltammetry and Electrochemical Impedance Spectroscopy

Electrochemical characterizations are generally carried out using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) techniques. CV is an electrochemical technique that involves applying a cyclically varying potential to an electrode and measuring the resulting current. EIS, on the other hand, applies a small-amplitude alternating potential perturbation to the electrochemical system and measures the resulting alternating current response. Both techniques can provide information about the reaction mechanism, the material resistivity, the charge transfer at the electrode/electrolyte interface, the kinetics of electrochemical processes, and a material’s ability to act as an electrode in an electrochemical device. These techniques are widely used to optimize the performance of electrochemical devices [82,83,84,85,86,87,88].

In the literature, Ehsan et al. (2021) employed cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) to characterize the modification of SPEs with various biomolecules. Their results indicated that the immobilization of proteins such as protein A and antibodies can substantially impact electron transfer at the electrode/electrolyte interface. By analyzing the changes in the peak current and charge transfer resistance (Rct) values, they were able to assess the immobilization efficiency and the influence of different biomolecules on the electrochemical properties of the sensor [88].

4.2. Scanning Electron Microscopy (SEM)

SEM is an essential tool for characterizing materials used in electrochemical sensors. This technique allows high-resolution images of the surface of materials and electrodes to be obtained, revealing details about the morphology, such as the particle size, roughness, and shape. This information is crucial to understanding how the surface structure influences the interaction of the electrode with chemical species and, consequently, the sensor performance [89,90,91,92,93].

Saenchoopa et al. (2021), in addition to using CV to compare the performance of the sensors after modification with each of the compounds employed, used the SEM technique to analyze the morphology of the SPE after modification with silver/hydroxypropylmethylcellulose/chitosan/urease nanowires. The results indicated that the sensor surface became more homogeneous due to the action of the hydroxypropylmethylcellulose, chitosan, and urease solution, filling the gaps between the silver nanowires. Using these characterizations, it was possible to verify that the modification promoted an increase in the electroactive surface area, facilitating electron transfer and optimizing the sensor’s performance [93].

4.3. Transmission Electron Microscopy

Transmission electron microscopy (TEM) is essential for developing printed electrochemical sensors. By providing high-resolution images, TEM allows the detailed characterization of the microstructure and the composition of these materials. This technique enables a correlation between the morphological characteristics (grain size, porosity) and the electrochemical properties, elucidating detection mechanisms and optimizing sensor performance. Impurity identification and elemental quantification, also performed by TEM, ensure the reproducibility and reliability of the devices.

In this context, Liao et al. (2019) developed a conductive ink based on graphite, acrylic resin, and water. Through TEM, it was possible to confirm the presence of graphene with few layers in the ink. In addition, the authors were able to correlate the dispersibility of the material in the ink with its conductivity. Wang et al. (2023) also applied TEM to characterize the conductive ink developed based on carbon black and graphite (1:2), polymer resin, and water. Through the analyses, the authors were able to identify a structure similar to graphene, indicating the presence of transparent few-layer graphene [94,95].

4.4. Fourier-Transform Infrared Spectroscopy (FTIR)

FTIR is a widely used technique for the structural characterization of conductive inks and electrochemical sensors, which allows detailed information to be obtained about the chemical bonds, functional groups, and molecular structure of the analyzed compounds [94,95,96,97,98,99]. This technique has been widely used to characterize the biofunctionalization process of SPEs.

In a study conducted by Inam et al. (2022), this technique was applied to confirm the successful immobilization of each component of the aptasensor BSA-Aptamer-N(3-dimethylaminopropyl) N-ethylcarbodiimide/N-hydroxysulfosuccinimide sodium salt-11-mercaptoundecanoic acid-Ag. By analyzing the characteristic bands of each molecule, the authors showed the formation of bonds between the different components, demonstrating the effectiveness of the biofunctionalization protocol. The presence of bands corresponding to the functional groups of each molecule corroborated the formation of the proposed structure for the aptasensor. In addition to this technique, CV and EIS were employed to evaluate the effectiveness of the fabrication steps of the developed sensor. Together, these techniques contributed to providing valuable information about the aptasensor fabrication process [100].

4.5. Raman Spectroscopy

Raman spectroscopy has also been proven to be indispensable for the detailed characterization of electrochemical sensors. By interacting monochromatic light with matter, this technique provides a unique molecular vibrational profile, including detailed information about the molecular structure, interfacial interactions, and the dynamics of electrochemical processes and significantly contributing to the development of more efficient, selective, and robust sensors, with applications in several areas [101,102,103,104,105].

By applying Raman spectroscopy, Gomes et al. (2021) investigated the effects of different modifications on the surface of SPEs, showing the formation of polymer networks of polypyrrole and their composites with carbon nanotubes with conjugated C=C bonds, so that the technique allowed the different materials to be compared and the influence of the presence of polymeric materials in the film structure to be identified in devices with a molecularly printed poly(Py) matrix (MPPy) and with a non-imprinted poly(Py) matrix (NPPy) [105].

4.6. X-Ray Diffraction (DRX)

XRD is a fundamental analytical technique in the development of printed electrochemical sensors. When an X-ray beam is incident on a material, the interaction with the crystal structure generates a characteristic diffraction pattern, which allows the identification of the crystalline phases present, the calculation of the lattice parameters, and the evaluation of the degree of crystallinity. In the context of sensors, XRD is used to determine the chemical composition of materials, evaluate the purity of the substances used, analyze the crystal structure of modified electrodes, and identify the presence of secondary phases that may affect the sensor performance. In addition, XRD can be used to monitor the formation of new phases during electrode surface modification processes, providing valuable information for optimizing the manufacturing of printed electrochemical sensors.

Pradella-Filho et al. (2020) developed an ink based on graphite and stained-glass varnish, and applied XRD to the graphite powder, ink, and varnish to better understand the crystallinity of the materials. The results obtained suggest the presence of the materials in the formation of the conductive carbon ink [106].

The characterization of SPEs, especially those that are chemically modified, is an extremely important step to ensure reliability and accuracy in drug detection. By subjecting the sensors and ink components to the techniques mentioned above, it is possible to obtain fundamental information for understanding the mechanisms of interaction between the sensor and the drug, optimizing the analysis conditions, and validating the analytical method (Figure 7). In this way, the characterization of the sensors allows more accurate and reproducible results to be obtained in the determination of drugs in real samples, such as biological fluids, river water, and pharmaceutical samples, among others.

5. Applications of SPEs in the Determination of Drugs

The increasing interdependence between health and the environment, driven by the pursuit of a higher quality of life and environmental preservation, has increased the demand for precise analytical technologies. Electrochemical sensors, capable of detecting pollutants with a high sensitivity, stand out in this context. The search for new drugs and the need for faster and more accurate analytical methods drive the development of innovative sensors for detecting and quantifying drugs in various matrices [20].

In their work, Hoppe (2024) used electrosynthesis to create a molecularly imprinted polymer on a screen-printed carbon electrochemical sensor, developed for the quantitative determination of paracetamol in water samples [107]. The developed electrode demonstrated an excellent performance in the detection of paracetamol, presenting a linear detection range of 5.0 × 10⁻⁸ mol L⁻¹, indicating a high sensor sensitivity [107].

Modifying the electrode surface with synthetic materials such as molecularly imprinted polymers (MIPs) aids in constructing an electrode with an enhanced selective performance. In this context, Kim (2023) developed an electrochemical sensor modified with a molecularly imprinted polymer quantifying cortisol. Synthetic cortisol, also known as hydrocortisone, is a medication prescribed for the treatment of infections, allergies, and autoimmune diseases. The developed sensor exhibited good mechanical resistance after successive measurements, contributing to the production of MIP-modified sensors. The performance in cortisol detection was positive, presenting a detection limit of 0.036 nM [108]. The primary application of this sensor lies in the non-invasive monitoring of cortisol levels, enabling continuous real-time detection. This can be beneficial in fields such as sports medicine, medical diagnoses, and the management of stress-related conditions.

Beyond their application in water and bodily fluid samples, these sensors are also employed in food samples for the detection of drugs administered for the prevention and treatment of diseases in food-producing animals destined for human consumption [109].

Souza et al. (2022) presented the development of a printed electrochemical sensor for the detection of ciprofloxacin (CIP) in honey and milk samples. This drug is used to treat bacterial infections such as American foulbrood, caused by the bacterium Paenibacillus larvae. This disease affects bee larvae, leading to the death of the colony if not treated adequately. It is also used as a preventive and therapeutic measure in dairy cattle for the treatment of mastitis, among others. If ciprofloxacin is not managed correctly, it can contaminate bee products (honey, wax, etc.) and milk produced by dairy cattle with drug residues [104]. In this context, the researchers developed a sensor using paper as a support material, making it sustainable and easily accessible. The device was fabricated using a low-cost conductive ink made from graphite powder and nail polish. In addition, the device underwent a polishing process that exposed the active sites of the graphite, thus improving its sensitivity. The device demonstrated a good precision and reproducibility in quantifying the antibiotic, with detection limits suitable for food samples such as honey and milk. The method stood out for its simplicity and low cost, making it suitable for rapid analyses in food-production environments. The developed sensor showed a good performance with a wide linear range of 9.90–220 µmol L ⁻¹ and a detection limit of 4.96 µmol L ⁻¹ [109].

Table 1. Printed electrochemical sensors for drug determination.

Sensor Configuration	Detection Technique	Analyte	Linear Range	Detection Limit	Analyte/Sample	Ref.
COFTpTt@c-MWCNTs/SPCE	DPV	Fluoxetine	62.5–2000 ng mL−1	24.3 ng mL−1	Spiked rat serum	[110]
SPE/SiO2/ZrO2/Cdot-N	SWV	Ceftriaxone	0.0078–40.02 μmol L−1	0.2 nmol L−1	Urine and tap water	[111]
SPCE/MWCNT-COOH	SWV	Imatinib	50–912 nmol L−1	7.0 nmol L−1	Urine	[112]
CuO/SPCE	DPV	Isoniazid	4.0–200 μmol L−1	8.39 μmol L−1	Pharmaceutical formulations	[113]
MIP-Pt@g-C3N4/F-MWCNT/SPE	DPV	Tenofovir	0.005–0.69 μmol L−1	0.0030 μmol L−1	Human plasma, urine, and water	[114]
PPyNTs/ZIF-67/SPGE	DPV	Metronidazole	0.01–500 μmol L−1	0.004 μmol L−1	Pharmaceutical formulations and urine samples	[115]
Zn(II)-MOF/SPCE	DPV	Fentanyl	1–100 μmol L−1	0.3 μmol L−1	Urine and plasma	[116]
C60-rGO-NF/SPE	SWV	Metronidazole	0.25-34 µmol L−1	0.21 µmol L−1	Serum and urine	[117]
SPE	DPV	Ketamine	50–500 µmol L−1	15.0 µmol L−1	Pharmaceutical formulations and seized drugs	[118]
PL-Dy2Ce2O7/SPE	DPV	Mesalazine	0.02–145 µmol L−1	0.008 µmol L−1	Pharmaceutical formulations, human blood serum, and urine	[119]
SPE/rGO–NHS–AuNFs	DPV	Chloramphenicol	0.05–100 µmol L⁻¹	1.0 nmol L⁻¹	Blood serum, poultry feed, milk, eggs, honey, and powdered milk	[120]
SPCE	SWV	Metamizole	0.35–50 µmol L−1	0.09 µmol L−1	Human urine	[121]
MIP/SPCE	DPV	Trazodone	5–80 µmol L−1	1.6 µmol L−1	Human serum and water	[122]
ZnO/Co3O4NC/SPE	DPV	Levodopa	0.001–800.0 µmol L−1	0.81 nmol L−1	Levodopa pills and urine	[123]
SPE-CSS	SWV	Acetaminophen, hydroquinone	1.5–14.0 µmol L−1 3.0–23.0 µmol L−1	0.85 µmol L−1 2.7 µmol L−1	Tap water and tablets	[124]
NPSPCE	SWV	Ciprofloxacin	0.0005–0.03 µmol L−1	6.3 × 10−5 µmol L−1	Sewage and bodily fluids	[125]
Ce-BTC MOF/SPGE	DPV	Metronidazole	0.05–400.0 µmol L⁻¹	0.02 µmol L−1	Pharmaceutical formulations and urine	[126]
MoS2 NSs-SPE	DPV	Isoniazid	0.035–390.0 µmol L⁻¹	10.0 n mol L−1	Pharmaceutical formulations and urine	[127]
aSPCE	DPV	Ibuprofen	0.50–20.0 µmol L−1 and 20.0–500.0 µmol L−1	0.059 µmol L−1	Pharmaceutical formulations	[128]
aSPCE/SDS	DPAdSV	Paracetamol, diclofenac, tramadol	0.0149 µmol L⁻¹ 0.00021 µmol L⁻¹ 0.00171 µmol L⁻¹	14.87 nmol L−1 0.21 nmol L−1 1.71 nmol L−1	River water, serum samples, and pharmaceuticals formulations	[129]
SPCIE-TiO2 NPs	CV	Azithromycin	0.05–50 µmol L⁻¹	0.93 µmol L⁻¹	Urine and water	[130]
SPE/MNP-TA/Ab Amx	SWV	Amoxicillin	0.50–100 µmol L⁻¹	0.44 µmol L⁻¹	Milk	[131]
SPE-BDD	SWV	Dipyrone, norfloxacin	2.0–250 µmol L⁻¹ 2.0–62.5 µmol L⁻¹	0.30 µmol L⁻¹ 0.40 µmol L⁻¹	Water and organic fertilizers	[132]
CB/SPE	LSV	Chloroquine	0.5–500 µmol L−1	0.5 µmol L−1	Milk	[133]
MIP/SPCs	SWV	Irbesartan	20–220 nmol L⁻¹	0.012 µmol L⁻¹	Water	[134]
SPCE	BIA-SWAdSV	Diazepam	5–40 µmol L⁻¹	2.0 µmol L⁻¹	Pharmaceuticals and spiked alcoholic drinks	[135]
SPEs	POT	Metformin	10−5–1.0 mol L−1	4 µmol L⁻¹	Pharmaceutical formulations	[136]
CoOOH-rGO/SPCE	DVP	Clonazepam	0.1–350 µmol L⁻¹	5.6 µmol L⁻¹	Drink samples	[137]
VMSF/pSPCE	DPV	Clozapine	0.050–20 μmol L⁻¹	28 nmol L⁻¹	Human blood	[138]
Go/Fe3O4/SiO2/SPE	DPV	Clozapine	0.1–700.0 μmol L⁻¹	0.03 μmol L⁻¹	Tablets and urine	[139]

DPV: differential pulse voltammetry; SWV: square wave voltammetry; MIP: molecularly imprinted polymer; CV: cyclic voltammetry; COF_TpTt: covalent organic framework material; c-MWCNTs: carboxylated multi-walled carbon nanotubes; Cdot-Ns: nitrogen-doped carbon quantum dots; MWCNT-COOH: multi-walled carbon nanotubes modified with carboxyl groups; MOF: metal–organic framework; NF: Nafion; C60: fullerene; rGO: graphene oxide; SDS: sodium dodecyl sulfate; DPAdSV: differential pulse adsorptive stripping voltammetry; Dy: dysprosium; Ln₂Ce₂O₇: lanthanide cerate; MOF: metal–organic framework; SPCIE: screen-printed carbon ink electrode; TiO₂ NPs: tetragonal (rutile) nanostructures of TiO₂ nanoparticles; MNP: magnetic nanoparticles; LSV: linear sweep voltammetry; ePADs: electrochemical paper-based analytical devices; BIA: batch injection analysis; SWAdSV: square-wave adsorptive stripping voltammetry; SPCE: screen-printed carbon electrode; BDD: boron-doped diamond; SPEs: screen-printed electrodes; SPCs: graphite working electrode of screen-printed cells; SPE/MNP-TA/Ab Amx: screen-printed electrode, magnetic nanoparticle amino-functionalized iron oxide anti-amoxillim antibodies; CB: carbon black; POT: potentiometry; Dp: dipyrone; NF: norfloxacin; PA: paracetamol; TR: tramadol; DF: diclofenac; SWCNT: single-walled carbon nanotube; CSS: carbon spherical shells; NPSPCE: nanoporous screen-printed; PRO: propranolol; TIM: timolol; AML: amlodipine; TRI: triamterene; SPE: screen-printed electrode; SCPE: screen-printed carbon electrode; VMSF: mesoporous silica nanomembrane film.

shows other studies where printed electrodes were applied to the analytical determination of drugs.

The advances highlighted in this review underscore the significant potential of screen-printed electrochemical sensors for drug detection across diverse matrices. The versatility of screen-printing enables the fabrication of miniaturized, disposable, and cost-effective devices, making them ideal for point-of-care applications, drug production monitoring, and environmental quality control. The ability to modify conductive inks with various materials and optimize experimental conditions expands the range of detectable drugs. However, further research is needed to assess these sensors’ long-term stability and delve deeper into potential interferences from other substances present in real-world samples.

6. Perspectives and Challenges

Developing new conductive inks for screen-printed electrochemical sensors represents a promising field of research with the potential to revolutionize the area of drug detection. However, there are still some challenges to be overcome. Complex matrices such as water, biological fluids, and pharmaceutical formulations can impair analyses, so it is necessary to develop conductive inks that present a high selectivity, minimizing interference from other components. This problem can be solved by inserting new components into the ink and modifying the electrode surface. Ensuring the electrochemical and mechanical stability of conductive inks over time and in different environmental conditions is also a challenge. To this end, the choice of the ink component materials and the support on which this ink will be applied must be carefully chosen, giving preference to those materials that present a greater stability.

Ensuring the reproducibility of the manufactured sensors, both in terms of performance and manufacturing, is also a crucial factor in guaranteeing efficient analyses. Exploring new conductive materials (nanomaterials and conductive polymers) and employing surface modification techniques enable an improved sensor sensitivity and selectivity, in addition to expanding the application possibilities. Another relevant factor that can be explored in developing printed sensors is the use of machine learning algorithms to improve the interpretation of data obtained by the sensors and develop more robust analysis methods.

7. Conclusions

This review provides information on developing conductive inks to obtain screen-printed electrochemical sensors applied in drug detection. Various compositions of conductive inks are discussed, and their main properties, such as their conductivity, malleability, ease of modification, chemical stability, and high surface area, are highlighted. These sensors have been extensively modified with various materials capable of expanding the properties of SPEs, giving them a greater sensitivity, selectivity, and stability, as well as low detection and quantification limits. In the long term, screen-printed sensors are expected to revolutionize drug monitoring in various matrices, making analyses more reliable, simple, and accessible. Finally, this review presents an overview of the current scenario, focusing on developing new conductive inks for fabricating SPEs focused on drug detection.