Artificial Samples Research Articles

Optical method supported by machine learning for urinary tract infection detection and urosepsis risk assessment.

The study presents an optical method supported by machine learning for discriminating urinary tract infections from an infection capable of causing urosepsis. The method comprises spectra of spectroscopy measurement of artificial urine samples with bacteria from solid cultures of clinical E. coli strains. To provide a reliable classification of results assistance of 27 algorithms was tested. We proved that is possible to obtain up to 97% accuracy of the measurement method with the use of use of machine learning. The method was validated on urine samples from 241 patients. The advantages of the proposed solution are the simplicity of the sensor, mobility, versatility, and low cost of the test.

Disposable and Sensitive Electrochemical Determination of Molnupiravir at a Pencil Graphite Electrode (PGE) by Differential Pulse Voltammetry (DPV)

This study describes the sensitive voltammetric determination of the COVID-19 drug, molnupiravir, at a pencil graphite electrode (PGE) which is easily available, inexpensive, disposable, and highly electrochemically active. For comparison purposes, cyclic and differential pulse voltammetric responses of molnupiravir were compared at the carbon paste electrode (CPE) and glassy carbon electrode (GCE). The results show that the oxidation potential of molnupiravir shifts to a more negative direction and the peak current of molnupiravir increases significantly with the PGE compared to the CPE and GCE. The PGE demonstrates remarkable electrocatalysis upon the oxidation of molnupiravir. The detection limit and linear range for molnupiravir were determined to be 7.2 nM and 25 to 1000 nM by differential pulse voltammetry. In addition, the selectivity of PGE is high for molnupiravir. The applicability of the sensor was examined by the analysis of pharmaceutical and artificial blood samples. This low-cost and practical sensor was demonstrated to determine molnupiravir with good accuracy and precision.

Dual-Analyte Sensing with a Molecularly Imprinted Polymer Based on Enhancement-Mode Organic Electrochemical Transistors.

Novel enhancement-mode organic electrochemical transistors (OECTs) have been prepared by poly(3, 4-ethylenedioxythiophene)-poly(styrenesulfonate) de-doped polyethylenimine on the multi-walled carbon nanotube-modified viscose yarn. The fabricated devices exhibit low power consumption with a high transconductance of 6.7 mS, rapid response time < 2 s, and excellent cyclic stability. In addition, the device has washing durability and bending and long-term stability suitable for wearable applications. Biosensors based on enhancement-mode OECTs for the selective detection of adrenaline and uric acid (UA) are developed by using molecularly imprinted polymer (MIP)-functionalized gate electrodes. The detection limits of adrenaline and UA analysis are as low as 1 pM, with the linear ranges of 0.5 pM to 10 μM and 1 pM to 1 mM, respectively. Moreover, the sensor based on enhancement-mode transistors can efficiently amplify the current signals according to the modulation of the gate voltage. The MIP-modified biosensor has high selectivity in the presence of interferents and desirable reproducibility. Additionally, due to the wearable nature of the developed biosensor, this sensing tool has the capability of being integrated with fabrics. Therefore, it has successfully been applied in textiles for the determination of adrenaline and UA in artificial urine samples. The excellent recoveries and rsds are 90.22-109.05% and 3.97-6.94%, respectively. Ultimately, these sensitive, low-power, wearable, and dual-analyte sensors help to develop non-laboratory tools for early disease diagnosis and clinical research.

Nickel Oxy-Hydroxy/Multi-Wall Carbon Nanotubes Film Coupled with a 3D-Printed Device as a Nonenzymatic Glucose Sensor.

A rapid and simple method for the amperometric determination of glucose using a nanocomposite film of nickel oxyhydroxide and multi-walled carbon nanotube (MWCNTs) was evaluated. The NiHCF)/MWCNT electrode film was fabricated using the liquid-liquid interface method, and it was used as a precursor for the electrochemical synthesis of nickel oxy-hydroxy (Ni(OH)2/NiOOH/MWCNT). The interaction between nickel oxy-hydroxy and the MWCNTs provided a film that is stable over the electrode surface, with high surface area and excellent conductivity. The nanocomposite presented an excellent electrocatalytic activity for the oxidation of glucose in an alkaline medium. The sensitivity of the sensor was found to be 0.0561 μA μmol L-1, and a linear range from 0.1 to 150 μmol L-1 was obtained, with a good limit of detection (0.030 μmol L-1). The electrode exhibits a fast response (150 injections h-1) and a sensitive catalytic performance, which may be due to the high conductivity of MWCNT and the increased active surface area of the electrode. Additionally, a minimal difference in the slopes for ascending (0.0561 µA µmol L-1) and descending (0.0531 µA µmol L-1) was observed. Moreover, the sensor was applied to the detection of glucose in artificial plasma blood samples, achieving values of 89 to 98% of recovery.

Supramolecular cyclization induced emission enhancement in a pillar[5]arene probe for discrimination of spermine

Early diagnosis and treatment of cancer requires the development of tools that are both sensitive and selective in detecting spermine. In this study, we presented a "supramolecular cyclization-induced emission enhancement" strategy for the sensitive and selective detection of spermine. A new pillar[5]arene probe (P1) demonstrated excellent solution/solid dual-state emission properties, and the addition of certain spermine (Spm) resulted in fluorescence enhancement due to the synergy of multiple weak interactions that restricted the free motion of P1 in the P1⊃Spm complex. This mechanism was further confirmed by time-resolved spectroscopy, DFT calculations, and IGM analysis. With its low limit of detection and high selectivity, P1 is a promising tool for measuring spermine in artificial urine samples.

Effect of Magnesium Chloride in Supporting Electrolyte for Enhancing Sensitive and Selective Electrochemical Sensor: An Approach for Anti-Rheumatic Sulfasalazine Detection

In this work, an electroanalytical evaluation for voltammetric sensing of the anti-rheumatic sulfasalazine (SSZ) at an unmodified screen-printed graphene electrode (SPGE) is demonstrated. By using the differential pulse (DPV) technique, the SSZ produced a well-defined peak of around −0.3 V (vs Ag AgCl−1) in Britton-Robinson (BR) buffer pH 4. Supporting electrolytes, pH, and salts all significantly impact SSZ reduction. Therefore, their impact on the working solutions was assessed. We discovered that using a mixture of Britton–Robinson (BR) buffer with pH 4 and MgCl2 as a supporting electrolyte can enhance SSZ sensitivity by approximately 1.7 times while simultaneously increasing detection selectivity. Under optimal conditions, the proposed assay demonstrated the ultrasensitive determination of SSZ with a broad linear detection range from 0.01 to 100 μM and a low detection limit of 4.7 nM (S/N = 3). To demonstrate the impact of the proposed method, the sensor has been successfully applied for the quantitative determination of SSZ in pharmaceutical, urine, and artificial serum sample. Therefore, this approach could offer simplicity, and rapidity, and serve as an alternative to the SSZ detection in practical applications.

New fluorescent probe for sensing of mefenamic acid in aqueous medium: An integrated experimental and theoretical analysis

Abnormal levels of mefenamic acid (MFA) in living organisms can result in hepatic necrosis, liver, and gastrointestinal diseases. Therefore, development of accurate and effective method for detection of MFA is of great significance for the protection of public health. Herein, we designed a stilbene based sensor ECO for the sensitive and selective detection of mefenamic acid by employing fluorescence spectroscopy for the first time. The developed sensor ECO displayed fluorescence turn-off response towards MFA based on PET (photoinduced electron transfer) and hydrogen bonding. The sensing mechanism of MFA was investigated through 1H NMR titration experiment and density functional theory (DFT) calculations. The presence of non-covalent interaction was confirmed through spectroscopic analysis and was further supported by non-covalent interaction (NCI) analysis and Bader’s quantum theory of atoms in molecules (QTAIM) analysis. Additionally, the sensor ECO coated test strips were fabricated for on-site detection of mefenamic acid. Furthermore, the practical applicability of sensor ECO to detect MFA was also explored in human blood and artificial urine samples.

Chemical structure and thermal maturation of the vitrinite-like maceral in the Lower Paleozoic shales: Insights from Raman spectroscopy of artificial pyrolysis residues

Vitrinite-like macerals (VLM) are ubiquitous in many pre-Devonian marine shales. The thermal maturity of these sediments, which are devoid of classical vitrinite, has been commonly evaluated using the reflectance of VLM as a substitute for vitrinite reflectance, but the molecular structure of VLM itself has seldom been examined. In this study, the immature VLM-rich Cambrian Alum shales from Scandinavia were selected and pyrolyzed at 300–550 ℃ to acquire a series of artificial pyrolysis samples with different ranks. The molecular structures and thermal evolution of VLM in natural and artificial shales were investigated by Raman spectroscopy. These Raman spectra and optical properties were compared with those of vitrinite, graptolite, and solid bitumen. The Raman spectra of VLM in natural samples of variable thermal maturities and immature samples altered by pyrolysis were generally comparable. The reduction of WD (D band position) and FWHM-G (full width at half maximum of the G band) and the increase of WG (G band position) and AD/AG (area ratio) in VLM spectra, which parallels the increasing thermal maturity of the samples, indicated an increased degree of aromatic conjugation and more structurally ordered carbon moieties. The increase in wavenumber difference between the D and G bands positions in Raman spectra (Raman band separation, RBS) demonstrated the gradual removal of oxygen-containing functional groups, the loss of aliphatic side chains, and the increased degree of aromatic ring condensation. In this way, with progressing maturity, the molecular structure of VLM gradually evolved from heterocyclic aromatic compounds and amorphous carbon structures at low maturity levels to structurally better-ordered, larger, aromatic fused-ring units characteristic of post-to-over mature samples. These molecular structures and their changes associated with thermal maturation were similar to those known from classical vitrinite. Aside from its reflectance, the thermal maturity of VLM-rich sediments could be assessed by Raman spectroscopy, notably through the RBS parameter of VLM Raman spectra, which closely correlated with VLM random reflectance throughout the reflectance interval between 0.5% and 5.5%.

Selection of DNA aptamer recognizing CD44 for high-efficiency capture of circulating tumor cells

Cancer stem cells play critical roles in cancer progression, cancer invasion and metastasis, and cancer recurrence. CD44 is known as a specific surface marker of cancer stem cells, which has been well-studied in cancer invasion and metastasis. Herein, we successfully selected the DNA aptamers for recognizing CD44+ cells using Cell-SELEX strategy, in which the engineered CD44 overexpression cells were used as target cells for selection. The optimized aptamer candidate C24S showed high binding affinity with the Kd value of 14.54 nM and good specificity. Then, the aptamer C24S was employed to prepare the functional aptamer-magnetic nanoparticles (C24S-MNPs) for CTC capture. To investigate the capture efficiency and sensitivity of C24S-MNPs, series of cell capture tests were performed using artificial samples with 10–200 of HeLa cells spiked into 1 mL PBS or PBMCs isolated from 1 mL peripheral blood, obtaining an efficiency of 95% and 90%, respectively. More importantly, we finally explored the facility of C24S-MNPs for CTC detection in blood samples from clinical cancer patients, indicating a potential and feasible strategy for cancer diagnostic technology in clinical applications.

Backstress Influence on the Formation Stress Field in Hydraulic Fracturing Experiments

This work presents an analysis of data obtained through unique laboratory experiments on hydraulic fracturing. In the experiments, sufficiently large artificial samples were used to model a reservoir. Thus, it was possible to simulate several wells simultaneously, given that hydraulic fracture was initiated in one of them. In addition, the setup construction provided a true triaxial stress–strain state. The setup allowed us to investigate parameters that are difficult to access in real conditions. The data processing based on six laboratory experiments on hydraulic fracturing showed discrepancies between the values of the minimum stresses calculated from the fracture closure pressure and the actual values known based on the experimental conditions. There was also a discrepancy between the theoretical values of the fracture breakdown pressure and those obtained through the experiments. This paper examines phenomena such as backstress as the main reasons for this discrepancy. Backstress is stress acting on the walls of a fracture or well and is caused by the filtered hydraulic fracturing fluid. The authors demonstrated that by taking into account this phenomenon, one can significantly reduce the differences between calculated and experimental values. Therefore, the authors call for the careful use of the standard theory when determining the stress state in real fields.

Application of toroidal magnet excitation and hall sensor array in magnetic leakage field detection of rail surface defect

To detect rail top surface defects, NdFeB toroidal permanent magnets were firstly used to excite the rail detection area, and the magnetic excitation direction was perpendicular to the rail direction. So that, the magnetic circuit can be analyzed, and the model was verified by finite element simulation. Secondly, the artificial rectangular defect samples were machined on the top surface of the rail, and the magnetic field data acquisition system was developed and equipped on the inspection vehicle. With that, a linear array which consisted of three-dimensional hall sensors was designed to detect the magnetic leakage field signal from the defect samples. Finally, the features of the leakage field signal in each dimension were extracted. And then, the length, width, and depth of the defects were predicted using BP neural network algorithm. The results indicate that the method can improve the excitation efficiency, and the average absolute errors of prediction for defect length, width, and depth were 1.43 mm, 1.01 mm, and 0.63 mm respectively.

Development of Optical-Based Molecularly Imprinted Nanosensors for Adenosine Detection.

Adenosine nucleoside is an important molecule in human physiology. The levels of adenosine nucleoside in urine and plasma are directly or indirectly related to diseases such as neurodegenerative diseases and cancer. In the present study, adenosine-imprinted and non-imprinted poly(2-hydroxyethyl methacrylate-methacrylic acid) (poly(HEMA-MAA)) surface plasmon resonance (SPR) nanosensors were prepared for the determination of adenosine nucleoside. First, MAA/adenosine pre-polymerization complexes were prepared at different molar ratios using adenosine as a template molecule and methacrylic acid (MAA) as a monomer, and SPR nanosensor surfaces were optimized by determining the highest imprinting factor of the chip surfaces. The surfaces of adenosine-imprinted and non-imprinted SPR nanosensors were characterized by using atomic force microscopy, ellipsometry, and contact angle measurements. Kinetic analyses were made with different concentrations in the range of 0.5-400.0 nM for the detection range with a pH 7.4 phosphate buffer solution. The limit of detection in adenosine aqueous solutions, artificial plasma, and artificial urine was determined to be 0.018, 0.015, and 0.013 nM, respectively. In the selectivity analysis of the developed nanosensors, the selectivity of adenosine SPR nanosensors in solutions at different concentrations was determined by using guanosine and cytidine nucleosides. The relative selectivity coefficients of adenosine-imprinted SPR nanosensors for adenosine/cytidine and adenosine/guanosine are 3.836 and 3.427, respectively. Since adenosine-imprinted SPR nanosensors are intended to be used in medical analysis and research, adenosine analysis has also been studied in artificial urine and artificial plasma samples.

A Novel SPR Immunosensor Based on Dual Signal Amplification Strategy for Detection of SARS-CoV-2 Nucleocapsid Protein

Since the global outbreak of coronavirus disease 2019 (COVID-19), it has spread rapidly around the world. The nucleocapsid (N) protein is one of the most abundant SARS-CoV-2 proteins. Therefore, a sensitive and effective detection method for SARS-CoV-2 N protein is the focus of research. Here, we developed a surface plasmon resonance (SPR) biosensor based on the dual signal-amplification strategy of Au@Ag@Au nanoparticles (NPs) and graphene oxide (GO). Additionally, a sandwich immunoassay was utilized to sensitively and efficiently detect SARS-CoV-2 N protein. On the one hand, Au@Ag@Au NPs have a high refractive index and the capability to electromagnetically couple with the plasma waves propagating on the surface of gold film, which are harnessed for amplifying the SPR response signal. On the other hand, GO, which has the large specific surface area and the abundant oxygen-containing functional groups, could provide unique light absorption bands that can enhance plasmonic coupling to further amplify the SPR response signal. The proposed biosensor could efficiently detect SARS-CoV-2 N protein for 15 min and the detection limit for SARS-CoV-2 N protein was 0.083 ng/mL, with a linear range of 0.1 ng/mL~1000 ng/mL. This novel method can meet the analytical requirements of artificial saliva simulated samples, and the developed biosensor had a good anti-interference capability.

Stress Sensitivity of Proppant-Containing Fractures and Its Influence on Gas Well Productivity

Formation pressure gradually decreases with fracturing fluid flowback and gas production. Due to the stress sensitivity of the fractures, the permeability of the artificial fractures after fracturing becomes lower, which significantly affects gas well productivity. This paper focuses on two questions: (1) the stress sensitivity of proppant-containing fractures with different roughness and (2) tight gas well productivity considering stress sensitivity. Two types of artificial fracture samples, smooth and rough, are prepared and filled with different proppant concentrations. Then, the changing confining pressure method is used to quantify sample stress sensitivity. On this basis, the productivity equation for the fractured well with finite conductivity that considers fracture and matrix stress sensitivity is derived, and the influence of stress sensitivity on productivity is discussed. The results show that proppant concentration and fracture surface roughness will significantly affect fracture permeability and stress sensitivity; with increasing proppant concentration, fracture permeability increases, stress sensitivity decreases, and well productivity increases; under the same proppant concentration, the stress sensitivity is lower and the gas production is higher for smooth fracture; and when the artificial fracture changes from no proppant to proppant, the productivity of the fracturing well is improved the most.

Highly Selective, Single-Tube Colorimetric Assay for Detection of Multiple Mutations in the Epidermal Growth Factor Receptor Gene

Many closed-tube methods are designed to detect DNA biomarkers. However, the utility of biomarkers such as a DNA mutation related to personalized medicine is limited as the operation of expensive detection instruments requires well-trained technicians. Therefore, we developed a simple and cheap colorimetric assay based on aggregation of silica-gold nanoparticle-modified probes, with linking probes, to detect mutations. This method consists of target amplification, sequence identification, and aggregation of the silica-gold nanoparticle-modified probes. All reactions are controlled by one individual and proceed sequentially, in a single tube, with no manual intervention. Approximately 10 copies of target DNA were detected with this assay, using 12 hot-spot mutations in exon 19 of EGFR gene as the example. In artificial samples, 0.1% mutant DNA can be distinguished from wild-type genomic DNA. The technology was tested on 104 clinical samples, which included 29 samples that were positive for an exon 19 deletion. The data were consistent with amplification refractory mutation system PCR, with the exception of one weakly positive sample, which was confirmed to be positive by digital PCR. The limit of detection of this colorimetric assay was verified to be better than that of amplification refractory mutation system PCR, and it provides a tool to discriminate multiple mutations in EGFR gene in clinical samples.

The effects of clay mineralogy and crack properties on elastic properties of dry and water-saturated transversely isotropic rocks

The causes of the intrinsic elastic anisotropy of shales are very complicated, and clay mineralogy and crack properties are critical for rock-physics models and geomechanics applications in shales, but they are still poorly understood. Further, it is difficult to directly measure the elastic properties of single-crystal clays due to their small particle size. To reduce the multiparametric influence factors caused by complex components in natural shales, two sets of artificial rocks with different clay minerals are fabricated, and their porosity, permeability, and ultrasonic velocities are measured under different pressure conditions. The results suggest that clay mineralogy can significantly affect physical and elastic properties and their pressure sensitivity, and the permeabilities of the sample composed of kaolinite are much higher than those of the sample composed of smectite due to the larger particle size of kaolinite compared with smectite. Further, the type of clay can cause a difference in “intrinsic” velocity and anisotropy. The microcrack can enhance the velocity anisotropy on the basis of intrinsic anisotropy, and crack properties such as maximum dip angle and normal-to-tangential compliance ratio are obtained by a theoretical model, which is also affected by clay type, causing the difference in the pressure sensitivity of elastic properties. Water has a significant influence on the elastic properties and anisotropy of artificial clay samples, which can reduce the S-wave velocity and increase the P-wave velocity driven by multiple competing factors. Water reduces the velocity anisotropy because the presence of water narrows the difference between the velocity parallel and perpendicular to the axis of symmetry. The normal-to-tangential compliance ratio of cracks is also affected by water as a stiffer fluid can reduce the normal compliance of cracks at the grain scale.

Cell-on-a-Chip Based Detection of Propranolol Hydrochloride Using Ag@CDs Nanocomposites

Herein, Ag@CDs nanocomposites were utilized for the detection of Propranolol hydrochloride (PPH). Structural characterization of the nanocomposites was performed using UV–vis. Spectroscopy, Dynamic light scattering, Zeta potential, and Contact angle measurements. Electrochemical analysis of the prepared electrode Ag@CDs/ITO was done using Electrochemical impedance spectroscopy and Cyclic voltammetry. Three electrodes were fabricated on same ITO substrate through selective etching of ITO followed by deposition of different materials on each electrode. To the best of our knowledge, miniaturization of the bulky electrochemical measurement setup has not been reported yet. Moreover, the proposed setup was able to give good limit of detection of 0.38 μM and exhibited linear response in the range of 5–45 μM PPH. Also, the sensor was functional in artificial urine samples showing 81%–102% recoveries. The excellent stability, repeatability, and reproducibility of the proposed sensor validate its application in real sample analysis.

Development of Fe3O4/reduced graphene oxide nanocomposite-based dispersive solid-phase extraction for the quantification of five steroid hormones.

Aim: An accurate and sensitive analytical method was proposed to detect some steroid hormones in biological samples. Materials & methods: An Fe3O4/reduced graphene oxide nanocomposite-based dispersive solid-phase extraction was developed for the effective and simple preconcentration of steroid hormones from human serum samples. Results & conclusion: The nanocomposite was firstly used as adsorbent to simultaneously extract the selected hormones. Limit of detection values for the selected hormones were calculated between 5.5 and 39.2ng/kg (mass based). An artificial serum sample was used to test the applicability and accuracy of the developed method; percentage recovery results obtained from two different spiked concentrations were found to be in the range of 80.5-99.9%.

Hybrid Nanomaterial of Graphene Oxide Quantum Dots with Multi-Walled Carbon Nanotubes for Simultaneous Voltammetric Determination of Four DNA Bases.

In this proof-of-concept study, a novel hybrid nanomaterial-based electrochemical sensor was developed for the simultaneous detection of four DNA bases. For the modification of the working electrode surface, graphene oxide quantum dots (GOQDs) were synthesized using a solvothermal method. GOQDs were then used for the preparation of a hybrid nanomaterial with multi-walled carbon nanotubes (GOQD-MWCNT) using a solvothermal technique for the first time. Transmission electron microscopy (TEM) was used to characterize the GOQDs-MWCNTs. A glassy carbon electrode (GCE) was modified with the GOQDs-MWCNTs using Nafion™ to prepare a GOQD-MWCNT/GCE for the simultaneous determination of four DNA bases in phosphate buffer solution (PBS, pH 7.0) using differential pulse voltammetry (DPV). The calibration plots were linear up to 50, 50, 500, and 500 µM with a limit of detection at 0.44, 0.2, 1.6, and 5.6 µM for guanine (G), adenine (A), thymine (T) and cytosine (C), respectively. The hybrid-modified sensor was used for the determination of G, A, T, and C spiked in the artificial saliva samples with the recovery values ranging from 95.9 to 106.8%. This novel hybrid-modified electrochemical sensor provides a promising platform for the future development of a device for cost-effective and efficient simultaneous detection of DNA bases in real biological and environmental samples.

Catalytic Modification of Porous Two-Dimensional Ni-MOFs on Portable Electrochemical Paper-Based Sensors for Glucose and Hydrogen Peroxide Detection.

Rapid and accurate detection of changes in glucose (Glu) and hydrogen peroxide (H2O2) concentrations is essential for the predictive diagnosis of diseases. Electrochemical biosensors exhibiting high sensitivity, reliable selectivity, and rapid response provide an advantageous and promising solution. A porous two-dimensional conductive metal-organic framework (cMOF), Ni-HHTP (HHTP = 2,3,6,7,10,11-hexahydroxytriphenylene), was prepared by using a one-pot method. Subsequently, it was employed to construct enzyme-free paper-based electrochemical sensors by applying mass-producing screen-printing and inkjet-printing techniques. These sensors effectively determined Glu and H2O2 concentrations, achieving low limits of detection of 1.30 μM and 2.13 μM, and high sensitivities of 5573.21 μA μM-1 cm-2 and 179.85 μA μM-1 cm-2, respectively. More importantly, the Ni-HHTP-based electrochemical sensors showed an ability to analyze real biological samples by successfully distinguishing human serum from artificial sweat samples. This work provides a new perspective for the use of cMOFs in the field of enzyme-free electrochemical sensing, highlighting their potential for future applications in the design and development of new multifunctional and high-performance flexible electronic sensors.