Recently, there has been increasing interest in electrochemical printed sensors for a wide range of applications such as biomedical, pharmaceutical, food safety, and environmental fields. A major challenge is to obtain selective, sensitive, and reliable sensing platforms that can meet the stringent performance requirements of these application areas. Two-dimensional (2D) nanomaterials advances have accelerated the performance of electrochemical sensors towards more practical approaches. This review discusses the recent development of electrochemical printed sensors, with emphasis on the integration of non-carbon 2D materials as sensing platforms. A brief introduction to printed electrochemical sensors and electrochemical technique analysis are presented in the first section of this review. Subsequently, sensor surface functionalization and modification techniques including drop-casting, electrodeposition, and printing of functional ink are discussed. In the next section, we review recent insights into novel fabrication methodologies, electrochemical techniques, and sensors' performances of the most used transition metal dichalcogenides materials (such as MoS2, MoSe2, and WS2), MXenes, and hexagonal boron-nitride (hBN). Finally, the challenges that are faced by electrochemical printed sensors are highlighted in the conclusion. This review is not only useful to provide insights for researchers that are currently working in the related area, but also instructive to the ones new to this field.
Spermine (SPM) is considered a biomarker for prostate cancer and detecting it becomes highly challenging due to its electro- and optical-inactive nature. SPM has a tendency to interact with groups such as phosphates and sulfides to form macrocyclic arrangements known as nuclear aggregates of polyamines. Using this tendency, an electrochemical sensor has been developed using a polysulfide (PS) modified Au electrode (PS@Au electrode). PS has been synthesized from elemental sulfur by hydrothermal method and characterized using UV-Vis, fluorescence, FTIR, SEM, and XPS analyses. The PS@Au electrode was employed for electrochemical sensing of SPM. In the presence of SPM, a decrease in gold oxide reduction current was noted which is proportional to the concentration of SPM. The decrease in gold oxide reduction (0.5 V) current was attributed to the complexing nature of SPM-PS at the electrode interface. The reason for the decrease in current has been substantiated using XRF, XPS, and spectroelectrochemical studies. Under the optimized conditions, the PS@Au electrode exhibited a linear range of 1.55-250 µM with LOD of 0.511 ± 0.02 µM (3σ). The electrochemical strategy for SPM sensing exhibited better selectivity even in the presence of possible interferents. The selectivity stems from the selective interaction of SPM with PS on the Au electrode surface; the tested amino acids, and other molecules do not complex with PS and hence they could not interfere. The PS@Au electrode has been subjected to the determination of SPM in artificial urine samples and exhibited outstanding performance in the synthetic sample.
The penicillin derivative amoxicillin (AMX) plays an important role in treating various types of infections caused by bacteria. However, excessive use of AMX may have negative health effects. Therefore, it is of utmost importance to detect and quantify the AMX in pharmaceutical drugs, biological fluids, and environmental samples with high sensitivity. Therefore, this review article provides valuable and up-to-date information on nanostructured material-based optical and electrochemical sensors to detect AMX in various biological and chemical samples. The role of using different nanostructured materials on the performance of important optical sensors such as colorimetric sensors, fluorescence sensors, surface-enhanced Raman scattering sensors, chemiluminescence/electroluminescence sensors, optical immunosensors, optical fibre-based sensors, and several important electrochemical sensors based on different electrode types have been discussed. Moreover, nanocomposites, polymer, and MXenes-based electrochemical sensors have also been discussed, in which such materials are being used to further enhance the sensitivity of these sensors. Furthermore, nanocomposite-based photo-electrochemical sensors and the market availability of biosensors including AMX have also been discussed briefly. Finally, the conclusion, challenges, and future perspectives of the above-mentioned sensing techniques for AMX detection are presented.
Lung cancer remains the leading cause of cancer-related death. In addition to chest X-rays and computerised tomography, the detection of cancer biomarkers serves as an emerging diagnostic tool for lung cancer. This review explores biomarkers including the rat sarcoma gene, the tumour protein 53 gene, the epidermal growth factor receptor, the neuron-specific enolase, the cytokeratin-19 fragment 21-1 and carcinoembryonic antigen as potential indicators of lung cancer. Biosensors, which utilise various transduction techniques, present a promising solution for the detection of lung cancer biomarkers. Therefore, this review also explores the working principles and recent implementations of transducers in the detection of lung cancer biomarkers. The transducing techniques explored include optical techniques, electrochemical techniques and mass-based techniques for detecting biomarkers and cancer-related volatile organic compounds. Graphene has outstanding properties in terms of charge transfer, surface area, thermal conductivity and optical characteristics, on top of allowing easy incorporation of other nanomaterials. Exploiting the collective merits of both graphene and biosensor is an emerging trend, as evidenced by the growing number of studies on graphene-based biosensors for the detection of lung cancer biomarkers. This work provides a comprehensive review of these studies, including information on modification schemes, nanomaterials, amplification strategies, real sample applications, and sensor performance. The paper concludes with a discussion of the challenges and future outlook of lung cancer biosensors, including scalable graphene synthesis, multi-biomarker detection, portability, miniaturisation, financial support, and commercialisation.
An electrochemical method for detecting the presence of zinc (Zn2+) ions in drinking water was developed using functionalized multi-walled carbon nanotubes (f-MWCNTs) and chitosan (CS). Numerous cylinder-shaped graphene molecules make up f-MWCNTs, which have a high mechanical and electrical conductivity. CS benefits from nanomaterials include biocompatibility, biodegradability, and low toxicity, which are excellent in capacity absorption of metal ions. Dangerous levels of metal ions such as zinc are currently present in drinking water as a result of human and natural activity. Zinc toxicity is associated with a variety of disorders, including Alzheimer's, Parkinson's, diabetes, and cancer. This study incorporated f-MWCNTs and CS with Prussian blue (PB) immobilised on a gold electrode (AuE). Several parameters, including as buffers, pH, scan rate, redox indicator, accumulation time, and volume, were optimised using the cyclic voltammetry (CV) method. According to the CV method, the optimal parameters were phosphate buffered saline (0.1 M, pH 2), 5 mM Prussian blue, 200 mVs-1 scan rate, and 5 s accumulation time. Under ideal circumstances, the differential pulse voltammetry (DPV) method was used to determine the Zn2+ ions concentration range of 0.2-7.0 ppm. The limit of detection (LOD) was 2.60 × 10-7 mol L-1 with a correlation coefficient of R2 = 0.9777. The recovery rate of the developed sensor (f-MWCNTs/CS/PB/AuE) ranged from 95.78 to 98.96%. The developed sensor showed a variety of advantages for detecting Zn2+ in drinking water, including a quick setup process, quick detection, high sensitivity, and mobility. This study developed the essential sensor for monitoring Zn2+ levels in drinking water in the future.
Heavy metal pollution has gained global attention due to its high toxicity and non-biodegradability, even at a low level of exposure. Therefore, the development of a disposable electrode that is sensitive, simple, portable, rapid, and cost-effective as the sensor platform in electrochemical heavy metal detection is vital. Disposable electrodes have been modified with nanomaterials so that excellent electrochemical properties can be obtained. This review highlights the recent progress in the development of numerous types of disposable electrodes modified with nanomaterials for electrochemical heavy metal detection. The disposable electrodes made from carbon-based, glass-based, and paper-based electrodes are reviewed. In particular, the analytical performance, fabrication technique, and integration design of disposable electrodes modified with metal (such as gold, tin and bismuth), carbon (such as carbon nanotube and graphene), and metal oxide (such as iron oxide and zinc oxide) nanomaterials are summarized. In addition, the role of the nanomaterials in improving the electrochemical performance of the modified disposable electrodes is discussed. Finally, the current challenges and future prospect of the disposable electrode modified with nanomaterials are summarized.
Aptamers are single stranded DNA or RNA oligonucleotides that have high affinity and specificity towards a wide range of target molecules. Aptamers have low molecular weight, amenable to chemical modifications and exhibit stability undeterred by repetitive denaturation and renaturation. Owing to these indispensable advantages, aptamers have been implemented as molecular recognition element as alternative to antibodies in various assays for diagnostics. By amalgamating with a number of methods that can provide information on the aptamer-target complex formation, aptamers have become the elemental tool for numerous biosensor developments. In this review, administration of aptamers in applications involving assays of fluorescence, electrochemistry, nano-label and nano-constructs are discussed. Although detection strategies are different for various aptamer-based assays, the core of the design strategies is similar towards reporting the presence of specific target binding to the corresponding aptamers. It is prognosticated that aptamers will find even broader applications with the development of new methods of transducing aptamer target binding.
The sensing responses in aqueous solution of an open-gated pH sensor fabricated on an AlGaN/GaN high-electron-mobility-transistor (HEMT) structure are investigated. Under air-exposed ambient conditions, the open-gated undoped AlGaN/GaN HEMT only shows the presence of a linear current region. This seems to show that very low Fermi level pinning by surface states exists in the undoped AlGaN/GaN sample. In aqueous solution, typical current-voltage (I-V) characteristics with reasonably good gate controllability are observed, showing that the potential of the AlGaN surface at the open-gated area is effectively controlled via aqueous solution by the Ag/AgCl gate electrode. The open-gated undoped AlGaN/GaN HEMT structure is capable of distinguishing pH level in aqueous electrolytes and exhibits linear sensitivity, where high sensitivity of 1.9 mA/pH or 3.88 mA/mm/pH at drain-source voltage, V(DS) = 5 V is obtained. Due to the large leakage current where it increases with the negative gate voltage, Nernstian like sensitivity cannot be determined as commonly reported in the literature. This large leakage current may be caused by the technical factors rather than any characteristics of the devices. Surprisingly, although there are some imperfections in the device preparation and measurement, the fabricated devices work very well in distinguishing the pH levels. Suppression of current leakage by improving the device preparation is likely needed to improve the device performance. The fabricated device is expected to be suitable for pH sensing applications.
Reduction of graphene oxide becomes an alternative way to produce a scalable graphene and the resulting nanomaterial namely reduced graphene oxide (rGO) has been utilized in a wide range of potential applications. In this article, the level of green reduction strategies, especially the solution-based reduction methods are overviewed based on recent progression, to get insights towards biomedical applications. The degrees of gaining tips with the solution-based green reduction methods, conditions, complexity and the resulting rGO characteristics have been elucidated comparatively. Moreover, the application of greenly produced rGO in electrochemical biosensors has been elucidated as well as their electrical performance in term of linear range and limit of detections for various healthcare biological analytes. In addition, the characterization scheme for graphene-based materials and the analyses on the reduction especially for the solution-based green reduction methods are outlined for the future endeavours.
Different parts of a plant (seeds, fruits, flower, leaves, stem, and roots) contain numerous biologically active compounds called "phytoconstituents" that consist of phenolics, minerals, amino acids, and vitamins. The conventional techniques applied to extract these phytoconstituents have several drawbacks including poor performance, low yields, more solvent use, long processing time, and thermally degrading by-products. In contrast, modern and advanced extraction nonthermal technologies such as pulsed electric field (PEF) assist in easier and efficient identification, characterization, and analysis of bioactive ingredients. Other advantages of PEF include cost-efficacy, less time, and solvent consumption with improved yields. This review covers the applications of PEF to obtain bioactive components, essential oils, proteins, pectin, and other important materials from various parts of the plant. Numerous studies compiled in the current evaluation concluded PEF as the best solution to extract phytoconstituents used in the food and pharmaceutical industries. PEF-assisted extraction leads to a higher yield, utilizes less solvents and energy, and it saves a lot of time compared to traditional extraction methods. PEF extraction design should be safe and efficient enough to prevent the degradation of phytoconstituents and oils.
In this work, analysis of ion transport parameters of polymer blend electrolytes incorporated with magnesium trifluoromethanesulfonate (Mg(CF3SO3)2) was carried out by employing the Trukhan model. A solution cast technique was used to obtain the polymer blend electrolytes composed of chitosan (CS) and poly (2-ethyl-2-oxazoline) (POZ). From X-ray diffraction (XRD) patterns, improvement in amorphous phase for the blend samples has been observed in comparison to the pure state of CS. From impedance plot, bulk resistance (Rb) was found to decrease with increasing temperature. Based on direct current (DC) conductivity (σdc) patterns, considerations on the ion transport models of Arrhenius and Vogel-Tammann-Fulcher (VTF) were given. Analysis of the dielectric properties was carried out at different temperatures and the obtained results were linked to the ion transport mechanism. It is demonstrated in the real part of electrical modulus that chitosan-salt systems are extremely capacitive. The asymmetric peak of the imaginary part (Mi) of electric modulus indicated that there is non-Debye type of relaxation for ions. From frequency dependence of dielectric loss (ε″) and the imaginary part (Mi) of electric modulus, suitable coupling among polymer segmental and ionic motions was identified. Two techniques were used to analyze the viscoelastic relaxation dynamic of ions. The Trukhan model was used to determine the diffusion coefficient (D) by using the frequency related to peak frequencies and loss tangent maximum heights (tanδmax). The Einstein-Nernst equation was applied to determine the carrier number density (n) and mobility. The ion transport parameters, such as D, n and mobility (μ), at room temperature, were found to be 4 × 10-5 cm2/s, 3.4 × 1015 cm-3, and 1.2 × 10-4 cm2/Vs, respectively. Finally, it was shown that an increase in temperature can also cause these parameters to increase.
Two-phase micro-electrodriven membrane extraction (EME) procedure for the pre-concentration of selected non-steroidal anti-inflammatory drugs (NSAIDs) in aquatic matrices was investigated. Agarose film was used as interface between donor and acceptor phase in EME which allowed for selective extraction of the analytes prior to high performance liquid chromatography-ultraviolet detection. Charged analytes were transported from basic aqueous sample solution through agarose film into 1-octanol as an acceptor phase at 9 V potential. Response surface methodology in conjunction with the central composite design showed good correlations between extraction time and applied voltage (R2 > 0.9358). Under optimized extraction conditions, the method showed good linearity in the concentration range of 0.5-500 μg L-1 with coefficients of determination, r2≥ 0.9942 and good limits of detection (0.14-0.42 μg L-1) and limits of quantification (0.52-1.21 μg L-1). The results also showed high enrichment factors (62-86) and good relative recoveries (72-114%) with acceptable reproducibilities (RSDs ≤ 7.5% n = 3). The method was successfully applied to the determination of NSAIDs from tap water and river water samples. The proposed method proved to be rapid, simple and requires low voltage and minute amounts of organic solvent, thus environmentally friendly.
In this work, we proposed a biosensor for trypsin proteolytic activity assay using immobilization of model peptides on screen-printed electrodes (SPE) modified with gold nanoparticles (AuNPs) prepared by electrosynthetic method. Sensing of proteolytic activity was based on electrochemical oxidation of tyrosine residues of peptides. We designed peptides containing N-terminal cysteine residue for immobilization on an SPE, modified with gold nanoparticles, trypsin-specific cleavage site and tyrosine residue as a redox label. The peptides were immobilized on SPE by formation of chemical bonds between mercapto groups of the N-terminal cysteine residues and AuNPs. After the incubation with trypsin, time-dependent cleavage of the immobilized peptides was observed by decline in tyrosine electrochemical oxidation signal. The kinetic parameters of trypsin, such as the catalytic constant (kcat), the Michaelis constant (KM) and the catalytic efficiency (kcat/KM), toward the CGGGRYR peptide were determined as 0.33 ± 0.01 min-1, 198 ± 24 nM and 0.0016 min-1 nM-1, respectively. Using the developed biosensor, we demonstrated the possibility of analysis of trypsin specificity toward the peptides with amino acid residues disrupting proteolysis. Further, we designed the peptides with proline or glutamic acid residues after the cleavage site (CGGRPYR and CGGREYR), and trypsin had reduced activity toward both of them according to the existing knowledge of the enzyme specificity. The developed biosensor system allows one to perform a comparative analysis of the protease steady-state kinetic parameters and specificity toward model peptides with different amino acid sequences.
The design and development of eco-friendly fabrication of cost-effective electrochemical nonenzymatic biosensors with enhanced sensitivity and selectivity are one of the emerging area in nanomaterial and analytical chemistry. In this aspect, we developed a facile fabrication of tertiary nanocomposite material based on cobalt and polymelamine/nitrogen-doped graphitic porous carbon nanohybrid composite (Co-PM-NDGPC/SPE) for the application as a nonenzymatic electrochemical sensor to quantify glucose in human blood samples. Co-PM-NDGPC/SPE nanocomposite electrode fabrication was achieved using a single-step electrodeposition method under cyclic voltammetry (CV) technique under 1 M NH4Cl solution at 20 constitutive CV cycles (sweep rate 20 mV/s). Notably, the fabricated nonenzymatic electroactive nanocomposite material exhibited excellent electrocatalytic sensing towards the quantification of glucose in 0.1 M NaOH over a wide concentration range from 0.03 to 1.071 mM with a sensitive limit of detection 7.8 μM. Moreover, the Co-PM-NDGPC nanocomposite electrode with low charge transfer resistance (Rct∼81 Ω) and high ionic diffusion indicates excellent stability, reproducibility, and high sensitivity. The fabricated nanocomposite materials exhibit a commendable sensing response toward glucose molecules present in the blood serum samples recommends its usage in real-time applications.
Myocardial infarction (MI) is highly related to cardiac arrest leading to death and organ damage. Radiological techniques and electrocardiography have been used as preliminary tests to diagnose MI; however, these techniques are not sensitive enough for early-stage detection. A blood biomarker-based diagnosis is an immediate solution, and due to the high correlation of troponin with MI, it has been considered to be a gold-standard biomarker. In the present research, the cardiac biomarker troponin I (cTnI) was detected on an interdigitated electrode sensor with various surface interfaces. To detect cTnI, a capture aptamer-conjugated gold nanoparticle probe and detection antibody probe were utilized and compared through an alternating sandwich pattern. The surface metal oxide morphology of the developed sensor was proven by microscopic assessments. The limit of detection with the aptamer-gold-cTnI-antibody sandwich pattern was 100 aM, while it was 1 fM with antibody-gold-cTnI-aptamer, representing 10-fold differences. Further, the high performance of the sensor was confirmed by selective cTnI determination in serum, exhibiting superior nonfouling. These methods of determination provide options for generating novel assays for diagnosing MI.
Genosensor-based electrodes mediated with nanoparticles (NPs) have tremendously developed in medical diagnosis. Herein, we report a facile, rapid, low cost and highly sensitive biosensing strategy for early detection of HPV 18 using gold-nanoparticles (AuNPs) deposited on micro-IDEs. This study represents surface charge transduction of micro-interdigitated electrodes (micro-IDE) alumina insulated with silica, independent and mini genosensor modified with colloidal gold NPs (AuNPs), and determination of gene hybridization for early detection of cervical cancer. The surface of AuNPs deposited micro-IDE functionalized with optimized 3-aminopropyl-triethoxysilane (APTES) followed by hybridization with deoxyribonucleic acid (DNA) virus to develop DNA genosensor. The results of ssDNA hybridization with the ssDNA target of human papillomavirus (HPV) 18 have affirmed that micro-IDE functionalized with colloidal AuNPs resulted in the lowest detection at 0.529 aM. Based on coefficient regression, micro-IDE functionalized with AuNPs produces better results in the sensitivity test (R2 = 0.99793) than unfunctionalized micro-IDE.
In view of the presence of pathogenic Vibrio cholerae (V. cholerae) bacteria in environmental waters, including drinking water, which may pose a potential health risk to humans, an ultrasensitive electrochemical DNA biosensor for rapid detection of V. cholerae DNA in the environmental sample was developed. Silica nanospheres were functionalized with 3-aminopropyltriethoxysilane (APTS) for effective immobilization of the capture probe, and gold nanoparticles were used for acceleration of electron transfer to the electrode surface. The aminated capture probe was immobilized onto the Si-Au nanocomposite-modified carbon screen printed electrode (Si-Au-SPE) via an imine covalent bond with glutaraldehyde (GA), which served as the bifunctional cross-linking agent. The targeted DNA sequence of V. cholerae was monitored via a sandwich DNA hybridization strategy with a pair of DNA probes, which included the capture probe and reporter probe that flanked the complementary DNA (cDNA), and evaluated by differential pulse voltammetry (DPV) in the presence of an anthraquninone redox label. Under optimum sandwich hybridization conditions, the voltammetric genosensor could detect the targeted V. cholerae gene from 1.0 × 10-17-1.0 × 10-7 M cDNA with a limit of detection (LOD) of 1.25 × 10-18 M (i.e., 1.1513 × 10-13 µg/µL) and long-term stability of the DNA biosensor up to 55 days. The electrochemical DNA biosensor was capable of giving a reproducible DPV signal with a relative standard deviation (RSD) of <5.0% (n = 5). Satisfactory recoveries of V. cholerae cDNA concentration from different bacterial strains, river water, and cabbage samples were obtained between 96.5% and 101.6% with the proposed DNA sandwich biosensing procedure. The V. cholerae DNA concentrations determined by the sandwich-type electrochemical genosensor in the environmental samples were correlated to the number of bacterial colonies obtained from standard microbiological procedures (bacterial colony count reference method).
We have developed a DNA sensor that can be finalized to detect a specific target on demand. The electrode surface was modified with 2,7-diamino-1,8-naphthyridine (DANP), a small molecule with nanomolar affinity for the cytosine bulge structure. The electrode was immersed in a solution of synthetic probe-DNA that had a cytosine bulge structure at one end and a complementary sequence to the target DNA at the other end. The strong binding between the cytosine bulge and DANP anchored the probe DNAs to the electrode surface, and the electrode became ready for target DNA sensing. The complementary sequence portion of the probe DNA can be changed as requested, allowing for the detection of a wide variety of targets. Electrochemical impedance spectroscopy (EIS) with the modified electrode detected target DNAs with a high sensitivity. The charge transfer resistance (Rct) extracted from EIS showed a logarithmic relationship with the concentration of target DNA. The limit of detection (LoD) was less than 0.01 μM. By this method, highly sensitive DNA sensors for various target sequences could be easily produced.
Coronavirus disease 2019 (COVID-19) is a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diagnosis of COVID-19 depends on quantitative reverse transcription PCR (qRT-PCR), which is time-consuming and requires expensive instrumentation. Here, we report an ultrasensitive electrochemical biosensor based on isothermal rolling circle amplification (RCA) for rapid detection of SARS-CoV-2. The assay involves the hybridization of the RCA amplicons with probes that were functionalized with redox active labels that are detectable by an electrochemical biosensor. The one-step sandwich hybridization assay could detect as low as 1 copy/μL of N and S genes, in less than 2 h. Sensor evaluation with 106 clinical samples, including 41 SARS-CoV-2 positive and 9 samples positive for other respiratory viruses, gave a 100% concordance result with qRT-PCR, with complete correlation between the biosensor current signals and quantitation cycle (Cq) values. In summary, this biosensor could be used as an on-site, real-time diagnostic test for COVID-19.
The current study has focused on electrochemical immunosensing of carcinoembryonic antigen (CEA) employing an immobilized antibody on a thionine, chitosan, or graphene oxide nanocomposite modified glassy carbon electrode (anti-CEA/THi-CS-GO/GCE) as an indicator of cancer monitoring. THi-CS-GO nanocomposites were made using ultrasonication, and analyses of their morphology and crystal structure using SEM, FTIR, and XRD showed that thionine and chitosan molecules were intercalated with stacking interactions with both the top and bottom of GO nanosheets. Electrochemical experiments revealed anti-CEA, THi-CS-GO/GCE to have exceptional sensitivity and selectivity towards CEA compounds. The detection limit value was established to be 0.8 pg/mL when it was discovered that variations in the decrease peak current were directly proportional to the logarithm concentration of CEA over a wide range from 10-3 to 104 ng/mL. Results of testing the immunosensor's application capability for detecting CEA in a sample of human serum show that ELISA and DPV results are very congruent. The produced immunosensor demonstrated adequate immunosensor precision in determining CEA in prepared genuine samples of human serum and clinical applications.