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Paper-Based Analytical Device for Sensitive Colorimetric Determination of Sulfonamides in Pharmaceutical Samples
Abstract
Sulfa drugs are frequently used to treat infections, particularly in antibiotic resistant people. There are several techniques available to determine sulfa drugs, however, they are laborious operation, reagent consumption, expensive, and need specialized types of equipment. Here, a new, very simple and inexpensive paper-based analytical device described for the determination of five sulfa drugs: sulfacetamide, sulfadiazine, sulfamerazine, sulfamethoxazole, and sulfathiazole in pharmaceutical preparations. The method is a one-step reaction, based on the colorimetric reaction between acid-hydrolyzed sulfa drugs and 4-dimethylaminobenzaldehyde. Using a smartphone, the RGB value of color intensity was used as an analytical signal. The paper-based device displayed linear ranges of 0.10-5.00 µg mL-1, linear correlations ranging from 0.9903 to 0.9972, limits of detection 0.0030 to 0.0082 µg mL-1, and RSD of ≤0.258 under optimal conditions. The suggested approach was applied for determining five sulfa drugs in pharmaceutical formulations. This approach is appropriate for pharmaceutical applications since it is inexpensive, simple to utilize, sensitive, and selective.
... MA and EMA are determined by analytical methods including atomic absorption spectrometry [12], high performance liquid chromatographic method [13][14][15], gas chromatography-mass spectrometric method [16], UV-Visible spectrophotometric methods [17][18][19], chemiluminescence [20], liquid chromatography-mass spectrometry [21], and electrochemical methods [22][23][24]. Because of its intrinsic simplicity, inexpensive, and widespread availability in quality control laboratories, spectrophotometric method is perhaps the most practical analytical technique for routine examination [25][26][27]. ...
It is important for flavor additives to maintain adequate thermal stability under high temperature conditions. Since many excellent fragrances are organic and have relatively small molecular weights, they lack thermal stability. As a result, a rapid and accurate method has been developed for simultaneous determination of maltol and ethyl maltol by reaction with iron(III) in sulfuric acid solution. This reaction was the basis for an indirect spectrophotometric method, which followed the development of the pink ferroin product (?max = 520 nm). It appears that ethyl maltol and maltol follow Beer's law at concentrations of 0.5–20.0 mg/L according to the optimized method. According to the alternative standard method, the LOD values for maltol and ethyl maltol are 0.2 mg/L and 0.3 mg/L, respectively. Commercial food samples were successfully analyzed using the proposed methods. A study was conducted to determine how different storage conditions affected the concentrations of maltol and ethyl maltol. High temperature and sunlight lead to decomposition of these two flavor enhancer concentrations more than 10%.
Smartphone-derived colorimetric tools have the potential to revolutionize food safety control by enabling citizens to carry out monitoring assays. To realize this, it is of paramount significance to recognize recent study efforts and figure out important technology gaps in terms of food security. Driven by international connectivity and the extensive distribution of smartphones, along with their built-in probes and powerful computing abilities, smartphone-based sensors have shown
enormous potential as cost-effective and portable diagnostic scaffolds for point-of-need tests.
Meantime, the colorimetric technique is of particular notice because of its benefits of rapidity, simplicity, and high universality. In this study, we tried to outline various colorimetric platforms using smartphone technology, elucidate their principles, and explore their applications in detecting target analytes (pesticide residues, antibiotic residues, metal ions, pathogenic bacteria, toxins, and mycotoxins) considering their sensitivity and multiplexing capability. Challenges and desired future perspectives for cost-effective, accurate, reliable, and multi-functions smartphone-based colorimetric tools have also been debated.
Molecular imprinting technology (MIT) produces artificial binding sites with precise complementarity to substrates and thereby is capable of exquisite molecular recognition. Over five decades of evolution, it was predicted that the resulting host imprinted materials would overtake natural receptors for research and application purposes, but in practice, this has not yet been realized due to the unsustainability of their life cycles (i.e., precursors, creation, use, recycling, and end‐of‐life). To address this issue, greenificated molecularly imprinted polymers (GMIPs) are a new class of plastic antibodies that have approached sustainability by following one or more of the greenification principles, while also demonstrating more far‐reaching applications compared to their natural counterparts. In this review, we survey the most recent developments in the delicate design and advanced application of GMIPs in six fast‐growing and emerging fields, namely biomedicine/therapy, catalysis, energy harvesting/storage, nanoparticle detection, gas sensing/adsorption, and environmental remediation. In addition, we highlight their distinct features, and discuss the optimal means to utilize these features for attaining incredibly far‐reaching applications. Importantly, the obscure technical challenges of the greenificated MIT are revealed, and conceivable solutions are offered. Lastly, several perspectives on future research directions are proposed. This article is protected by copyright. All rights reserved
Gold nanoparticle–catalyzed chemiluminescence (CL) of luminol is an attractive alternative to strategies relying on enzymes, as their aggregation leads to significantly enhanced CL signals. Consequently, analytes disturbing such aggregation will lead to an easy-to-quantify weakening of the signal. Based on this concept, a homogeneous aptamer-based assay for the detection of sulfadimethoxine (SDM) has been developed as a microfluidic CL flow-injection platform. Here, the efficient mixing of gold nanoparticles, aptamers, and analyte in short channel distances is of utmost importance, and two-dimensional (2D) and three-dimensional (3D) mixer designs made via Xurography were investigated. In the end, since 2D designs could not provide sufficient mixing, a laminated 3D 5-layer microfluidic mixer was developed and optimized with respect to mixing capability and observation by the charge-coupled device (CCD) camera. Furthermore, the performance of standard luminol and its more hydrophilic derivative m-carboxy luminol was studied identifying the hydrophilic derivative to provide tenfold more signal enhancement and reliable results. Finally, the novel detection platform was used for the specific detection of SDM via its aptamer and yielded a stunning dynamic range over 5 orders of magnitude (0.01–1000 ng/ml) and a limit of detection of 4 pg/ml. This new detection concept not only outperforms other methods for SDM detection, but can be suggested as a new flow-injection strategy for aptamer-based rapid and cost-efficient analysis in environmental monitoring and food safety.
Graphical abstract
Advances in revolutionary technologies pose new challenges for human life; in response to them, global responsibility is pushing modern technologies toward greener pathways. Molecular imprinting technology (MIT) is a multidisciplinary mimic technology simulating the specific binding principle of enzymes to substrates or antigens to antibodies; along with its rapid progress and wide applications, MIT faces the challenge of complying with green sustainable development requirements. With the identification of environmental risks associated with unsustainable MIT, a new aspect of MIT, termed green MIT, has emerged and developed. However, so far, no clear definition has been provided to appraise green MIT. Herein, the implementation process of green chemistry in MIT is demonstrated and a mnemonic device in the form of an acronym, GREENIFICATION, is proposed to present the green MIT principles. The entire greenificated imprinting process is surveyed, including element choice, polymerization implementation, energy input, imprinting strategies, waste treatment, and recovery, as well as the impacts of these processes on operator health and the environment. Moreover, assistance of upgraded instrumentation in deploying greener goals is considered. Finally, future perspectives are presented to provide a more complete picture of the greenificated MIT road map and to pave the way for further development.
Background
Sulfonamides ( sulfa drugs ) and the metals like mercury, copper, and silver bear antimicrobial properties. The discovery of broad-spectrum antibiotics such as penicillins, cephalosporins, and fluoroquinolones has reduced their use. However, in some instances these drugs are the first-line treatment. The metal-based sulfonamide (e.g., silver sulfadiazine) is considered as first choice treatment in post-burn therapy while the use of silver nanoparticle-cephalexin conjugate to cure Escherichia coli infection explains the synergistic effect of sulfa drugs and their metal conjugates. With growing interest in metal-based sulfonamides and the Schiff base chemistry, it was decided to synthesize sulfonamide Schiff base metal complexes as antioxidant and antimicrobial agent.
Results
The Fe (III), Ru (III), Co (II), Ni (II), Cu (II), Pd (II), Zn (II), Cd (II), and Hg (II) metal complexes of 4-((thiophen-2-ylmethylene)-amino)-benzenesulfonamide (TMABS) were prepared and studied for thermal stability, geometry, and other electronic properties. The ligand TMABS (Schiff base) and its metal complexes were screened in-vitro for 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and antimicrobial properties against Gram-positive (+ve) Bacillus subtilis (MTCC-441), Staphylococcus aureus (MTCC 7443), Gram-negative (-ve) Escherichia coli (MTCC 40), Salmonella typhi (MTCC 3231), and fungal strains Aspergillus niger (MTCC-1344) and Penicillium rubrum by agar well diffusion method. Results summarized in Tables 3, 4, and 5 represent the inhibitory concentration (IC 50 ) in micromole (μM). The zone of inhibition (ZI) in millimeter (mm) represents antimicrobial properties of TMABS and its metal complexes.
Conclusions
The synthesized sulfanilamide Schiff base (TMABS) behaved as a neutral and bidentate ligand coordinating with metal ions through its azomethine nitrogen and thiophene sulfur to give complexes with coordination number of 4 and 6 (Fig. 3). The nucleophilic addition of sulfanilamide amino group (–NH 2 ) group to carbonyl carbon (>C=O) of benzaldehyde gave sulfanilamide Schiff base (imine) (Fig. 2). All the metal complexes were colored and stable at room temperature. With IC 50 of 9.5 ± 0.1 and 10.0 ± 0.7 μM, the Co, Cu, and Pd complexes appeared better antioxidant than the ligand TMABS (155.3±0.1 μM). The zone of inhibition (ZI) of Hg (28 mm) and Ru complexes (20 mm) were similar to the ligand TMABS (20 mm) against Aspergillus niger (MTCC-1344) as in Figs. 4, 5, and 6. None of the synthesized derivatives had shown better antimicrobial properties than the standard streptomycin sulfate and fluconazole.
Sulfonamide (or sulphonamide) functional group chemistry (SN) forms the basis of several groups of drug. In vivo sulfonamides exhibit a range of pharmacological activities, such as anti-carbonic anhydrase and anti-t dihydropteroate synthetase allowing them to play a role in treating a diverse range of disease states such as diuresis, hypoglycemia, thyroiditis, inflammation, and glaucoma. Sulfamethazine (SMZ) is a commonly used sulphonamide drug in veterinary medicine that acts as an antibacterial compound to treat livestock diseases such as gastrointestinal and respiratory tract infections. Sulfadiazine (SDZ) is another frequently employed sulphonamide drug that is used in combination with the anti-malarial drug pyrimethamine to treat toxoplasmosis in warm-blooded animals. This study explores the research findings and the work behaviours of SN (SMZ and SDZ) drugs. The areas covered include SN drug structure, SN drug antibacterial activity, SN drug toxicity, and SN environmental toxicity.
Sulfonamides are antimicrobial drugs which are widely used in human and veterinary medicine but pose a potential risk as emerging pollutants when present even at low concentrations in soil or water. Therefore, the development of analytical tools for sulfonamide monitoring is needed. Electrochemical methods have been commonly reported for sulfonamide detection. Here are reported recent developments related to the use of electrochemical detection of sulfonamides from 2006 to 2016. A discussion of sulfonamide detection is provided for pharmaceutical formulations, biological fluids, food, and environmental samples. In addition to the developed electrochemical methods, a brief review of sulfonamide sample preparation is also included.
KEYWORDS: electrochemical sensors, environmental monitoring, food, pharmaceutical formulation, sulfonamides
The authors have developed a sensitive spectrophotometric method for determination of sulfonamide derivatives such as sulfanilamide (SAA), sulfadiazine (SDZ), sulfacetamide (SCT) sulfamethoxazole (SMX), sulfamerazine (SMR), sulfadimethoxine (SDX), sulfamethiazole (SMT) and Sulfathiazole (STZ). This method is based on the Bratton-Marshall reaction, which involves the diazotization of sulfonamides with sodium nitrite under acidic conditions, followed by coupling with N-(1-naphtyl) ethylenediamine dihydrochloride (NED) to form a pink colored compound. Therefore, the Bratton-Marshall method was modified by optimizing the reaction conditions, which allows us to determine a low concentration range of sulfonamides compared to the reported methods. The limits of detection and quantification obtained were 0.019–0.05 and 0.06–0.16 μg mL− 1, respectively. In comparison with other reported methods using different coupling agents, the proposed method was found to be the most simple and sensitive for sulfonamides determination. In this paper, the modified method was successfully employed for the determination of sulfonamides in drinking water, seawater and pharmaceutical and veterinary formulations.
The purpose of this work is to optimize and develop a simple method for extraction and concentration of sulfonamides present as residues in seawater and their quantification with the recommended spectrophotometric method. Solid phase extraction (SPE) of sulfonamides from seawater samples was evaluated using Oasis HLB cartridges (3 mL, 540 mg). The recovery efficiency was investigated in the sulfonamides concentration range comprised between 0.19 and 126 ng mL− 1. The ease of use of this extraction method makes it very useful for routine laboratory work.
Keywords: Sulfonamides; Spectrophotometric method; Drug analysis; Seawater; Solid phase extraction; Pre-concentration
A simple and sensitive flow injection chemiluminescence method was proposed for the determination
of acetylsalicylic acid (aspirin) in pharmaceutical formulations. The method was based on inhibition effect
of acetylsalicylic acid on the chemiluminescence reaction of luminol–hydrogen peroxide and potassium
hexacyanoferrate. Different experiment parameters affecting the chemiluminescence intensity were
carefully studied and incorporated into the procedure. The detection limit was 0.5 μg/mL of acetylsalicylic
acid, and chemiluminescence emission intensity was correlated with the drug concentration in the range
2.5-125 μg/mL with correlation coefficient of 0.9985 and analytical frequency of 75 determinations per
hour. The results obtained for the assay of pharmaceutical formulations were compared well with those
obtained by the official method in British Pharmacopoeia and demonstrated good accuracy and precision.
A rapid and sensitive spectrophotometric method is proposed for the determination of sulfamethoxazole and sulfadiazine. This method is based on the diazotization of sulfonamide with sodium nitrite and a coupling reaction of the diazo-compound with thymol. The optimum reaction conditions and other analytical parameters were evaluated. The linear ranges for the determination of sulfamethoxazole and sulfadiazine are 1-10 μg mL -1 and 1-7 μg mL -1 and their detection limits are 0.008 μg mL -1 and 0.007 μg mL -1 respectively. There was no interference from commonly utilized tablet excipients. The method has been used to determine sulfamethoxazole and sulfadiazine in pharmaceuticals preparation without separation.
A new simple and sensitive spectrophotometric procedure for the determination of sulfacetamide sodium (I), sulfadiazine (II), sulfadimidine (III) and sulfathiazole (IV) is based on the reaction of the drug with acetylacetone-formaldehyde reagent to give a yellow product having max at 400 nm. Optimization of the reaction conditions has been investigated. A linear correlation was obtained between absorbance at max and the concentration. The Beer's law limits of I, II, III and IV are 4–80, 4–72, 4–60 and 4–80 g/ml, respectively. For more accurate results, Ringbom optimum concentration ranges were evaluated to be 6–76, 8–66, 6–56 and 8–75 g/ml for I, II, III and IV, respectively. The molar absorptivities and Sandell sensitivities for all sulfa drugs under consideration were evaluated. Relative standard deviations of 0.98, 1.07, 0.86 and 0.79% were obtained for I, II, III and IV, respectively. The method has been compared to the official method and found to be simple, accurate (t-test) and reproducible (F-test). The developed procedures were applied for bulk sulfa drugs and some of their dosage forms without interferences from additive and common prescribed drugs.
A new, simple and sensitive spectrophotometric method for the determination of some sulfonamide drugs has been developed. The method is based on the diazotization of sulfacetamide, sulfadiazine, sulfaguanidine, sulfamerazine, sulfamethazine, sulfamethoxazole, and their coupling with 8-hydroxyquinoline in alkaline media to yield red coloured products with absorption maxima at 500 nm. Beer's law is obeyed from 0.1-7.0 microg mL-1. The limits of quantification and limits of detection were 0.11-0.18 and 0.03-0.05 microg mL-1, respectively. Intraday precision (RSD 0.1-0.5%) and accuracy (recovery 97.3--100.8%) of the developed method were evaluated. No interference was observed from common adjuvants. The method has been successfully applied to the assay of sulpha drug in pharmaceutical formulations.
Smartphone-based devices show the capability to be the main biomedical diagnosis device, enabling persons to perform for self-screening tests. In the healthcare, smartphone-based devices are reforming patient care and management. However, there are some important issues relating to the reliability of the fabricated probes which must be improved to be utilized as the main detection probes. This review discussed the applications smartphone-based lateral flow assay (LFA) devices in the detection of biomolecules, focusing on the analytical performance and probe signal transducing techniques. Also, this review discloses the technology gaps of the smartphone-based LFA system such as the need to fabricate more sensitive light image lens and better interface to transduce the signal intensity to the digits in the completed whole blood media to obtain reliable results. Addressing the benefits and limitations motivates investors to prioritize the development of potent smartphone-LFAs for personalized medicine.
Food safety and contamination issues associated with food hygiene, pesticides, bacteria, chemical additives, and heavy metals are of utmost importance owing to their direct effect on human and even animal health. So, the advance of proper diagnostic tools that are rapid, reliable, sensitive, and efficient devices are needed to meet the extensive request for legislative action on early detection and control of increasing food contaminations. Microfluidic probes coupled with miniaturized portable diagnosis tools are well-suited for rapid test probes, which meaningfully minimize the analysis time and decrease the sample/reagent consumption without relying on operators and laboratories. Smartphone-assisted microfluidic sensors are appropriate for Point-of-Care testing (POCT) diagnosis due to their high data transferability and computational capability, making them quickly emerging as a promising alternative for classical laboratory devices. In this review, we outlined the smartphone functionalities that can be realized in the microfluidic system and described the determination methods employed in smartphone-assisted microfluidic sensors, comprising electrochemical, fluorescent, chemilumines-cent, and colorimetric detecting. We hope that this study can explore appropriate monitoring approaches for chemical pollutants and accelerate the transfer of smartphone-assisted microfluidic sensors technology from the lab into the field.
It is still challenging to sensitively detect protein biomarkers via surface-enhanced Raman scattering (SERS) technique owing to their low Raman activity. SERS tag-based immunoassay is usually applied; however, it is laborious and needs specific antibodies. Herein, an ultrasensitive and universal “Raman indicator” sensing strategy is proposed for protein biomarkers, with the aid of a glass capillary-based molecularly imprinted SERS sensor. The sensor consists of an inner SERS substrate layer for signal enhancement and an outer mussel-inspired polydopamine imprinted layer as a recognition element. Imprinted cavities have two missions: first, selectively capturing the target protein, and second, the only passageway of Raman indicator to access SERS substrate. Specific protein recognition means filling imprinted cavities and blocking Raman indicator flow. Thus, the quantity of captured protein can be reflected by the signal decrease of ultra-Raman active indicator molecule. The capillary sensor exhibited specific and reproducible detection at the level down to 4.1 × 10⁻³ μg L⁻¹, for trypsin enzyme in as-received biological samples without sample preparation. The generality of the mechanism is confirmed by using three different protein models. This platform provides a facile, fast and general route for sensitive SERS detection of Raman inactive biomacromolecules, which offers great promising utility for in situ and fast point-of-care practical bioassay.
On-site monitoring of some specific health-related problems is continuously increasing and become a prime aspect of the scientific community. Herein, we have developed a user-friendly colorimetric sensor for rapid and unaided eye detection of glucose using a novel nanozyme ([email protected]) synthesized by decorating CuO nanoparticles over a reduced graphene oxide sheet(rGO) using an ultrasonication method. [email protected] nanocomposites displayed amplified intrinsic peroxidase mimetic property and catalyzes the oxidation of the chromogenic substrate, 3, 3’, 5, 5’-tetramethylbenzidine (TMB) with the existence of electron acceptor H2O2 to produce blue coloured charge transfer product. The developed sensor has shown good selectivity with a lower detection limit of 7.0 to 8.0 μM in a linear range from 1 to 10 mM (R² = 0.98-0.99). The accuracy of the as-proposed sensor is investigated with the standard addition method (recovery 99–102%) and validated with a commercially available Glucometer. The proposed novel colorimetric sensor has good potential for the sensitive and selective determination of glucose in the buffer as well as in human blood samples. In addition, a modest, economic, portable, and smartphone-assisted digital image colorimetry (DIC) method is proposed for glucose sensing using RGB software analysis. This work opens a new prospect in clinical diagnosis.
A simple and mild method for the separation of sulfonamide residues based on a condensation reaction with O-phthalaldehyde solution (OPA) as labeling reagent with capillary electrophoresis has been developed. A 58.5 cm × 50 μm i.d. (50 cm effective length) untreated fused-silica capillary was used. To optimize the separation conditions, the background electrolyte concentration, pH, column temperature, voltage and other factors were evaluated. The optimal separation conditions were as follows: 20 mmol L⁻¹ borate buffer; pH 9.1; column temperature 20 °C; separation voltage 18 kV, pressure 50 mbar and injection time 8 s. Under the optimal conditions, 10 kinds of sulfonamide derivatives could be well-separated within 8 min, and the linear ranges were 0.35–100 μg kg⁻¹. The detection limit (at a signal-to-noise ratio of 3) was in the range of 0.12–0.25 μg kg⁻¹, and the quantification limit (at a signal-to-noise ratio of 10) was in the range of 0.35–0.70 μg kg⁻¹. The sulfonamide residues from cultured sea cucumber samples were determined under the optimal conditions with satisfactory results.
Disposable electrochemical paper-based analytical devices were developed from a conductive ink using graphite powder, automotive varnish and magnetite nanoparticles. The addition of magnetite nanoparticles in the conductive ink improved the sensitivity of the analytical devices. The devices were applied in the quantification of vitamins B2 (VB2) and B6 (VB6) in commercial dietary supplements. The characterization of the analytical devices was carried out by microscopy and electrochemical techniques. Square wave voltammetry (SWV) was used to study the electrochemical behavior of the vitamins and the experimental parameters were optimized (pH, supporting electrolyte and SWV parameters). The calibration plot for VB2 (−484 mV vs. graphite) was obtained in Britton-Robinson buffer (pH 2.0) in the range of 2.0 to 20.0 μmol L⁻¹ with a detection limit of 0.25 µmol L⁻¹. Similarly, for the VB6 (+675 mV vs. graphite), the calibration plot was obtained in McIlvaine buffer (pH 4.0) in the range of 0.2 to 2.0 mmol L⁻¹ with a detection limit of 29.5 µmol L⁻¹. The analytical devices were employed to determine VB2 and VB6 levels in B-complex supplements (capsules and sublingual liquid) and the results were compared with those provided by fluorescence spectrometry. The statistical analysis showed no considerable difference in terms of the precision and accuracy of the data obtained by both methods.
Combating environmental pollution constantly requires new affinity tools to selectively recognize and sensitively detect them. Molecularly imprinted polymers (MIPs) are plastic antibodies that have exhibited great potential as recognition units in optical sensing platforms to monitor wide varieties of environmental pollutants, including ionic species, organic compounds, gases, and even manufactured nanoparticles. The construction, sensing strategies, and applications of molecular-imprinting-based optical sensors (MI-OSs) have been discussed in recent reviews, thus we deliberately set them aside. This Perspective elaborates on unanswered questions and main approaches being taken to address the challenges of MI-OS technologies, which have been less considered until now. Specifically, we highlight obscure technical aspects of MI-OS fabrication and validation that impact their practical applications and importantly offer conceivable solutions to related problems to bridge the research gap.
Background
Synthetic chemical pesticides play a significant role in increasing the overall yield and productivity of agricultural foods by controlling and eradicating pests, insects, and numerous plant-related diseases. The over-spraying of pesticides onto crops has escalated pesticide contamination of food products and water bodies, as well as disturbing ecological and environmental systems. In this regard, developing simple, low-cost, and rapid-sensing strategies and portable devices for the precise, efficient, rapid, and on-site detection of pesticide residues in agricultural fields is indeed necessary and urgently required for the wellbeing and safety of mankind and other species.
Scope and approach
In this review, we make a comprehensive study of the up-to-date state-of-the-art research progress on the on-site sensing strategies and portable devices for the detection of pesticide residues in agricultural foods using paper-, liquid-, and gel-based optical-sensing techniques. Moreover, we delineate the detailed on-site detection mechanism and sensing behavior of the aforementioned strategies and discuss the challenges and future perspectives associated with the development of optical techniques.
Key findings and conclusions
Recent scientific and technological studies on optical sensors such as fluorescence sensors, target-responsive hydrogels, chemiluminescence assay, tube enzyme-linked immunosorbent assay, enzymatic fiber-optic biosensor, phosphorescence, lateral flow immunoassay, double-signal fluorescence strategy, wearable glove-based sensors, and paper-based sensors have made novel advancements and brought scientific insight for the on-site detection of pesticide residues in agricultural foods. This review provides significant insights and future perspectives that might serve as the basis for the fabrication of novel optical sensors with applicability in various fields.
The presence of copper ions in sugarcane spirits is harmful due to the high toxicity to humans and its maximum allowed concentration is defined as 5 mg L⁻¹, according to the Brazilian agency of agricultural e food (ANVISA). In order to monitor the product quality, the recommended analytical method for quantification of Cu(II) employs Flame Atomic Absorption Spectroscopy (FAAS) providing accurate and sensitive results, although the instrument bulkiness makes the method less attractive for routine and screening analysis. In this study, we have described a simple analytical method for the determination of Cu(II) based on the colorimetric reaction between Cu(II) and diethyldithiocarbamate (DDTC) performed onto a paper-based spot test. The yellow-brownish product was formed and the measurement of the analytical signal was performed directly on the paper-based device with no needing of previous extraction steps. Digital images were obtained using an ordinary flatbed scanner and parameters derived from the RGB color space were used for quantification. Under optimized conditions, a linear relation (R²>0,99) from 3 to 25 mg L⁻¹ of Cu(II) was obtained using 20 µL of the sample solution and 40 µL of the reagent. The developed paper-based analytical device was therefore applied for copper quantification in sugarcane spirits. It represents an interesting alternative for a fast, simple, portable, and low-cost method for evaluating sugarcane spirit quality according to the current legislation.
In the overall scenario of precision medicine, we propose a novel paper-based lab-on-a-chip to deliver a cost-effective and easy to use sensing tool for customized administration of drugs in Alzheimer’s disease. Among several drugs, we designed the device for evaluating the efficacy of compounds (e.g. physostigmine, rivastigmine, donepezil) which are able to inhibit in a reversible way the cholinesterase enzyme. Because cholinesterase activity is peculiar to each patient, the administration of customized amount of the drug can improve the treatment efficacy and the quality of patient life, avoiding side effects due to the overdosage. In detail, we exploited Vivid™ Plasma Separation membrane to threat the whole blood sample, filter paper to load the reagents needed for the measurement, and office paper to print electrodes able to measure the butyrylcholinesterase activity, delivering a reagent free analytical tool. The calibration curve of butyrylcholinesterase obtained in blood sample provided linearity between 2 and 12 U/mL, with sensitivity of 0.050 ± 0.004 μA mL/U. The physostigmine, rivastigmine, and donepezil inhibition activities toward the butyrylcholinesterase enzyme were also measured in blood sample with linearity up to respectively 0.5 μM, 25 μM, 30 μM, and detection limits of 0.009 μM, 0.4 μM, 0.3 μM. These results demonstrate the capability of paper-based origami sensors as point of care devices to customize the drug administration in Alzheimer’s disease.
pH of fluids is an important indicator in biomedical and environmental studies. Conventional pH analysis techniques are often either instrumentation-intensive, expensive or qualitative in nature. Microfluidics based analytical devices have emerged as powerful alternative to overcome some of the existing limitations. These devices are characterized by low reagent and sample volumes, controlled flow, cost-effectiveness and portability. In this work, we report a microfluidic paper-based lab-on-a-chip pH sensing platform that incorporates passive fluid flow of samples. The colorimetric pH detection is integrated with mobile phone based image acquisition, followed by digital image processing and analysis for quantitative interpretation of data. The images are analyzed using image processing algorithms and color space. Regression analysis of data acquired from digital image analysis was used to evaluate the mathematical model for estimation of pH. The insights gained by this work would prove useful in development and deployment of portable and miniaturized sensors.
A hapten of sulfabenzamide was first synthesized to generate a monoclonal antibody that simultaneously recognized 32 sulfonamides. The computational simulation showed that the 3D conformation, molecular bend angle, molecular volume, electronic charge of core structure of these drugs all showed influences on the antibody binding. The antibody was combined with a heterologous enzyme-labeled hapten to develop a direct competitive chemiluminescence enzyme linked immunosorbent assay for determination of the 32 sulfonamides in chicken muscle sample. The CRs of the optimized method for these drugs were in the range of 7.3%-1778%, and the IC50 values were in the range of 0.038-11.2 ng/g. The limits of detection for detection of these drugs in chicken were in the range of 0.03-26 ng/g. Their recoveries from the standards fortified blank chicken samples were in the range of 60.8%-97.1%. Therefore, this method could be used as a useful tool for routine screening sulfonamides residues in meat.
A well-designed yolk-shell Fe3O4@graphitic carbon (YS-Fe3O4@GC) submicroboxes with a tunable internal cavity were constructed by one-step pyrolysis strategy followed by partially etching, in which the Fe3O4 magnetic core was well confined in compartment of GC submicroboxes. The suitable internal cavity, graphitic carbon shell and large specific surface area, play great roles in improving mass transfer of analytes. Compared to its core-shell structure, the YS-Fe3O4@GC submicroboxes as dispersive magnetic solid-phase extraction (d-MSPE) materials exhibited superior enrichment performance for sulfonamides (SAs). Thus, it was applied to sensitive/simultaneous detection of trace SAs in milk and meat samples, combing with high performance liquid chromatography (HPLC). Under optimized conditions, limits of detection (LODs, 0.11-0.25 μg L-1 for milk and 0.46-2.24 μg kg-1 for meat) and recoveries (77.2-118.0%) were obtained. This work not only offers a facile strategy for the tunable fabrication of yolk-shell architecture, but also successfully affords its exploration as d-MSPE materials.
Most of the on-site approaches for inferring of the post-mortem interval are still based on observative data from the direct body inspection, whereas, objective and quantitative analyses, such as potassium in the vitreous humor, are require laboratory instrumentation and skilled personnel. The present paper presents a simple and low cost analytical method suitable for use at the crime scene for inferring the time since death. The method uses a microfluidic paper-based device (μPAD) for the determination of ammonium in the vitreous humor (VH) based on the selective interaction between the ammonium and the Nessler's reagent. The color change was measured in terms of "RGB distance" by using a simple and free smartphone application. The optimized device showed a limit of detection of 0.4 mmol L-1, with between days precision less than 9.3% expressed as relative standard deviation, and accuracy between days from 94.5% to 104.5%. The selectivity of the Nessler's reaction was tested towards the main vitreous humor compounds, and no significant interferences were found. This paper-based analytical device was successfully used for the determination of ammonium ion in VH samples from forensic autopsies. The results obtained with the proposed method, although for a limited number of cases (n = 25), showed a close correlation with the data obtained with an instrumental analysis based on capillary electrophoresis. Moreover, in order to make the evaluation of results as simple as possible, a direct correlation between the color intensity, expressed as RGB distance, and the post-mortem interval was studied and a significant correlation was found (R2 > 0.78). In conclusion, the present preliminary study showes that the proposed device could be an additional tool to the traditional methods for a more accurate, although still presumptive, estimation of the time of death directly at the crime scene.
This work describes the development of a paper-based platform for highly sensitive detection of diclofenac. The quantification of this anti-inflammatory drug is of importance in clinical (e.g. quality and therapeutic control) and environmental (e.g. emerging contaminant determination) areas. The easy-to-handle platform here described consists of a carbon-ink paper-based working electrode and two metallic wires, provided by a gold-plated standard connector, as reference and counter electrodes. The porous paper matrix enables the preconcentration of the sample, decoupling sample and detection solutions. Thus, relatively large sample volumes can be used, which significantly improves the sensitivity of the method. A wide dynamic range of four orders of magnitude, between 0.10 and 100 μM, was obtained for diclofenac determination. Due to the predominance of adsorption at the lowest concentrations, there were two linear concentration ranges: one comprised between 0.10 and 5.0 μM (with a slope of 0.85 μA μM ⁻¹ ) and the other between 5.0 and 100 μM (with a slope of 0.48 μA μM ⁻¹ ). A limit of detection of 70 nM was achieved with this simple device that provided accurate results with an RSD of ca. 5%. The platform was applied for diclofenac quantification in spiked tap water samples. The versatility of this design enabled the fabrication of a multiplexed platform containing eight electrochemical cells that work independently. The low cost, small size and simplicity of the device allow on-site analysis, which is very useful for environmental monitoring.
We report the colorimetric detection of dopamine (DA) on microfluidic paper-based analytical devices (μPADs) using an oxidation-reduction method. Here, dopamine reacts with ferric chloride forming reduced Fe²⁺ that subsequently reacts with phenanthroline to form the red tris(1,10-phenanthroline)iron(II) complex. The devices were fabricated by wax printing and changes in color intensity were recorded using a common cell phone. Subsequent analysis using Photoshop software, yielded a limit of detection (LOD) for DA of 0.37 μmol/L with a linear range of 0.527–4.75 μmol/L and relative standard deviation of 0.11% (inter-day) and 0.15% (intra-day) for n = 15 paper chips. The effects of detection conditions have been investigated and are discussed. Cow serum samples and human blood serum and plasma samples were detected. The work, herein, demonstrates the potential of this method as a low cost and rapid colorimetric technique to detect DA in real samples.
This review reports on recent advances in state-of-the-art detection methods for microfluidic paper-based analytical devices (μPADs). The review commences by describing the materials, fabrication methods and driving mechanisms employed in μPADs. The review then explores the main detection methods and applications of μPADs proposed over the past five years. The discussions focus on seven detection technologies, namely (1) colorimetric detection, (2) fluorescent detection, (3) electrochemical detection and photoelectrochemical detection, (4) chemiluminescent detection, (5) electrochemiluminescent detection, (6) nanoparticle-based detection, and (7) spectrometry detection. Overall, the review provides a useful insight into recent advances in the μPAD detection field and serves as a useful source of reference for further research and innovation in the field.
An office paper-based colorimetric device is proposed as a portable, rapid, and low-cost sensor for forensic applications aiming to detect phenacetin used as adulterant in illicit seized materials such as cocaine. The proposed method uses white office paper as the substrate and wax printing technology to fabricate the detection zones. Based on the optimum conditions, a linear analytical curve was obtained for phenacetin concentrations ranging from 0 to 64.52 µg mL‒1, and the straight line was in accordance with the following equation: (Magenta percentage color) = 1.19 + 0.458 (CPhe/µg mL‒1), R² = 0.990. The limit of detection was calculated as 3.5 µg mL‒1 (3σ/slope). The accuracy of the proposed method was evaluated using real seized cocaine samples and the spike-recovery procedure.
Paper-based microfluidic analytical devices (μPADs) are becoming valuable tools in analytical area due to their attractive passive movements of analyte without any external forces due to capillary phenomenon. Techniques used to design microfluidic patterns are cost-effective, less sample requirement, environmentally benign and rapid analysis. The application of μPADs with intricate fabrication methods have emerged over a decade in several fields such as diagnostics, biological, food safety, environmental analysis, electrochemical and colorimetric detections. The present review addresses colorimetric detection of metal ions and nitrites from various sources using a simple filter paper (Whatman®) as μPADs, since filter paper is white in colour, possibility of liquid transport through capillary action and high surface area offers high detection efficiency. Due to its importance as an analytical tool, an attempt has been made here to critically discuss the present scenario and future prospects of this technique.
A spectrophotometric method for the determination of Sulfamethaxazole (SMX) in
bulk drug and in solid dosage was developed. The method was based on the
condensation reaction between primary aromatic amine group present in drug with
aromatic aldehyde, vanillin, to produce a yellow color. The resulting Schiff’s base
shown maximum absorption at 372nm. The reaction product is stable. The reaction
was carried out in acetic acid and in 0.1M perchloric acid medium. The Beer’s law
was obeyed in the ranges 1.5–40 mg/L with the acceptable correlation coefficient r =
0.9993. The detection limit and limit of detection were 0.19 and 0.24 mg/L of SMX,
respectively. The method was successfully applied to the determination of this
compound in pharmaceutical formulation.
Paper-based devices are a leading alternative among the main analytical tools for point-of-care testing, due to their portability, low-cost, and ease-of-use. Colorimetric readouts are the most common method of detection in these microfluidic devices, enabling qualitative, semi-quantitative and fully quantitative analysis of multiple analytes. There are manifold ways to obtain a colorimetric output in such devices, including nanoparticles, dyes, redox and pH indicators, and each has unique drawbacks and benefits. There are also multiple variables that impact the analysis of colorimetric reactions in microfluidic paper-based systems, including color homogeneity, image capture methods, and the data handling itself. Here, we present a critical review of recent developments and challenges of colorimetric detection on microfluidic paper-based analytical devices (µPADs), and present thoughts and insights towards future perspectives in the area to improve the use of colorimetric readouts in conjunction with µPADs.
Herein, we have developed a simple, sensitive and paper-based colorimetric sensor for the selective detection of Chromium (Ⅵ) ions (Cr (VI)). Silanization- titanium dioxide modified filter paper (STCP) was used to trap bovine serum albumin capped gold nanoparticles (BSA-Au NPs), leading to the fabrication of BSA-Au NPs decorated membrane (BSA-Au NPs/STCP). The BSA-Au NPs/STCP operated on the principle that BSA-Au NPs anchored on the STCP were gradually etched by Cr (VI) as the leaching process of gold in the presence of hydrobromic acid (HBr) and hence induced a visible color change. Under optimum conditions, the paper-based colorimetric sensor showed clear color change after reaction with Cr (VI) as well as with favorable selectivity to a variety of possible interfering counterparts. The amount-dependent colorimetric response was linearly correlated with the Cr (VI) concentrations ranging from 0.5 µM to 50.0 µM with a detection limit down to 280 nM. Moreover, the developed cost-effective colorimetric sensor has been successfully applied to real environmental samples which demonstrated the potential for field applications.
The analysis of veterinary drugs in organic fertilizers is crucial for an assessment of potential risks to soil microbial communities and human health. We develop a robust and sensitive method to quantitatively determine 19 veterinary drugs (amantadine, sulfonamides and fluoroquinolones) in organic fertilizers. The method involved a simple solid-liquid extraction step using the combination of acetonitrile and McIlvaine buffer as extraction solvent, followed by cleanup with a solid-phase extraction cartridge containing polymeric mixed-mode anion-exchange sorbents. Ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was used to separate and detect target analytes. We particularly focused on the optimization of sample clean-up step: different diluents and dilution factors were tested. The developed method was validated in terms of linearity, recovery, precision, sensitivity and specificity. The recoveries of all the drugs ranged from 70.9% to 112.7% at three concentration levels, with the intra-day and inter-day relative standard deviation lower than 15.7%. The limits of quantification were between 1.0 and 10.0μg/kg for all the drugs. Matrix effect was minimized by matrix-matched calibration curves. The analytical method was successfully applied for the survey of veterinary drugs contamination in 20 compost samples. The results indicated that fluoroquinolones had higher incidence rate and mean concentration levels ranging from 31.9 to 308.7μg/kg compared with other drugs. We expect the method will provide the basis for risk assessment of veterinary drugs in organic fertilizers.
Rapid, simple and sensitive kinetic spectrophotometric methods for the determination of some sulfa drugs namely Sulfacetamide Na, sulfadimidine and Sulfanilamide have been developed. The method based on oxidation of each of studied drugs with alkaline potassium permanganate. The reaction is followed spectrophotometrically by measuring the rate of change of absorbance at 526 nm & 610nm. The rate constant and fixed time methods are utilized for construction of calibration graphs to determine the concentration of the studied drugs. The results are validated statistically and checked through recovery studies. The method has been successfully applied for the determination of the studied sulfa drugs in commercial dosage forms.
The present work describes the construction and application of a simple, low cost and sensitive microfluidic paper-based device with electrochemical detection for the detection of paracetamol and 4-aminophenol. The separation channels of a width of 2.0 mm were created on paper using a wax printing process to define the regions of the device. A baseline separation level of the analytes can be obtained in 0.1 mol L(-1) acetate buffer solution at pH 4.5 and by injecting 500 nL of the standard solutions at 12 mm from the working electrode. The electrochemical detection system was created at the end of the channels through a process known as sputtering. The previously separated analytes were detected at the end of the hydrophilic separation channel by applying a potential of 400 mV vs. pseudo Au on the working electrode. Experimental variables such as type of paper (cation exchanger and n1), pH, sample volume, applied potential and distance of sample injection were evaluated and, under the conditions of higher response, it was possible to obtain detection limits of 25.0 and 10.0 μmol L(-1) for paracetamol and 4-aminophenol, respectively.
Detection of sulfonamide compounds in a mixture of standards at a poly(3-methylthiophene) coated on glassy carbon (GC) electrode is reported. The polymer, poly(3-methylthiophene), was electrochemically synthesized at a GC rotating disk-working electrode versus Ag/AgCl using cyclic voltammetry (+0.5 to +2.0 V). Square wave voltammetry (SQWV) with cathodic reduction (0 to -4.0 V) was used for the detection of seven sulfonamide compounds in a mixture. The working concentration ranges (curvilinear) established for different compounds in Britton-Robinson (BR) buffer (pH 6.26), were: 5.0x10(-6)-3.2x10(-3) M sulfamerazine, 5.0x10(-6)-3.2x10(-3) M sulfadiazine, 7.5x10(-7)-3.2x10(-4) M sulfasalazine, 9.0x10(-7)-5.0x10(-4) M sulfamethazine, 6.5x10(-8)-3.5.0x10(-5) M sulfamethoxazole, 9.7x10(-8)-5.0x10(-5) M sulfathiazole, and 9.0x10(-8)-3.2x10(-5) M 5-sulfaminouracil. Detection limits were calculated as: 3.9x10(-6) M for sulfamerazine; 4.0x10(-6) M sulfadiazine; 2.5x10(-7) M sulfasalazine; 3.7x10(-7) M sulfamethazine; 4.0x10(-8) M sulfamethoxazole; 6.4x10(-8) M sulfathiazole and 6.0x10(-9) M 5-sulfaminouracil. The data suggests a potential application of the poly(3-methylthiophene) (P3MT) electrode for determination of sulfonamides in veterinary and other applications.
A simple spectrophotometric method for the determination of 15 sulphonamides in bulk and in dosage forms is described. The method is based on the interaction of p-benzoquinone with sulphonamides in 0.1 M hydrochloric acid. The resulting chromophore is measured at 500 nm. The effects of different variables on colour development were established. Beer's law was obeyed in a concentration range of 10-50 micrograms ml-1. Results from the analysis of different sulphonamide tablets and ophthalmic solutions marketed locally were in good agreement with that of a reference method. Correlations between A1cm(1%) and certain physical parameters such as pKa values, characteristic volume Vx, and molecular connectivity indices 1X and 1Xv were determined by linear regression equations. A poor correlation was found between A1cm(1%) and bulkiness parameters but a highly significant negative correlation was obtained with apparent pKa values.
A rapid, selective and simple spectrophotometric method for the determination of sulfa-drugs is described. The method is based on the formation of violet colored azo product by the diazotization of sulfonamides, viz. sulfathiazole (SFT), sulfadiazine (SFD), sulfacetamide (SFA), sulfamethoxazole (SFMx), sulfamerazine (SFMr), sulfaguanidine (SFG) and sulfadimidine (SFDd) followed by a coupling reaction with iminodibenzyl in alcohol medium. Absorbance of the resulting violet azo product is measured at 570-580 nm and is stable for 24 h at 27 degrees C. Beer's law is obeyed in the concentration range of 0.05-6.0 microg ml(-1) at the wavelength of maximum absorption. The method is successfully employed for the determination of sulfonamides in various pharmaceutical preparations and common excipients used as additives in pharmaceuticals do not interfere in the proposed method. The method offers the advantages of simplicity, rapidity and sensitivity without the need for extraction or heating. A reaction mechanism is proposed for the formation of the violet azo product.
A sensitive, rapid, and simple spectrophotometric method is described for the determination of sulfa drugs. The method is based on the formation of a red-colored product by the diazotization of sulfonamides such as sulfathiazole (SFT), sulfadiazine (SFD), sulfacetamide (SFA), sulfamethoxazole (SFMx), sulfamerazine (SFMr), sulfaguanidine (SFG), and sulfamethazine (SFMt), followed by complexation with dopamine in the presence of molybdate ions in (1 + 1) H2SO4 medium. Absorbance of the resulting red product is measured at 490-510 nm, and the product is stable for 2 days at 27 degrees C. Beer's law is obeyed in the concentration range of 0.04-8.0 microg/mL at the wavelength of maximum absorption. The method was used successfully for the determination of some sulfonamides in tablets and eye drops. Common excipients used as additives in pharmaceuticals do not interfere in the proposed method. The method offers the advantages of simplicity, rapidity, and sensitivity without the need for extraction or heating. The limits of detection and quantitation were calculated for SFT, SFD, SFA, SFMx, SFMr, SFG, and SFMt.
The sulfonamides constitute an important class of drugs, with several types of pharmacological agents possessing antibacterial, anticarbonic anhydrase, diuretic, hypoglycemic, and antithyroid activity among others. A large number of structurally novel sulfonamide derivatives have ultimately been reported to show substantial protease inhibitory properties. Of particular interest are some metalloprotease inhibitors belonging to this class, which by inhibiting several matrix metalloproteases (MMPs) show interesting antitumor properties. Some of these compounds are currently being evaluated in clinical trials. The large number of sulfonamide MMP inhibitors ultimately reported also lead to the design of effective tumor necrosis factor-alpha converting enzyme (TACE) inhibitors, potentially useful in the treatment of inflammatory states of various types. Since both MMPs and TACE contribute synergistically to the pathophysiology of many diseases, such as arthritis, bacterial meningitis, tumor invasion; the dual inhibition of these enzymes emerged as an interesting target for the drug design of anticancer/antiinflammatory drugs, and many such sulfonamide derivatives were recently reported. Human neutrophyl elastase (HNE) inhibitors of the sulfonamide type may also be useful in the treatment of inflammatory conditions, such as emphysema, cystic fibrosis, chronic bronchitis, ischemia reperfusion injury, and acute respiratory distress syndrome. Inhibition of some cysteine proteases, such as several caspase and cathepsin isozymes, may lead to the development of pharmacological agents effective for the management of several diseases, such as rheumatoid arthritis, inflammatory bowel disease, brain damage, and stroke. Another research line that progressed much in the last time regards different sulfonamides with remarkable antiviral activity. Some clinically used HIV protease inhibitors (such as amprenavir) possess sulfonamide moieties in their molecules, which are critical for the potency of these drugs, as shown by means of X-ray crystallography, whereas a very large number of other derivatives are constantly being synthesized and evaluated in order to obtain compounds with lower toxicity or augmented activity against viruses resistant to the such first generation drugs. Other viral proteases, such as those isolated from several types of herpes viruses may be inhibited by sulfonamide derivatives, leading thus to more effective classes of antiviral drugs.
This manuscript reports the usefulness of the determination of sulphathiazole (ST) using photochemically induced fluorescence (RTPF) and RTPF coupling with first derivative (D1-RTPF), and the determination of sulphanilamide (SAN) by meaning first derivative of the emission spectrum. By irradiating 5 min, with intense UV radiation, sulphathiazole, in ethanol:water 20:80 (v/v) solutions at pH 4.5-5.0, show fluorescence emission at 342 nm (lambdaex=251 nm). Under these conditions, a linear relation, fluorescence intensity-ST concentration, was found between 0.23 and 3.00 microg mL(-1) of ST. The method was applied for determining ST in a pharmaceutical drug. ST was also determined in honey by using the D1-RTPF signal, applying the standard addition method, and measuring at 324.8 nm. Under the same experimental conditions of pH and solvent, a fluorimetric method for determining SAN in presence of ST is proposed. Calibration graphs for SAN determination were established using the amplitude of the first derivative of the emission spectrum measured at 324.4 nm, as the analytical signal. This method has been applied to determining SAN in a pharmaceutical formulation.
An analytical HPLC method for the simultaneous determination of eight sulfonamides in swine wastewater was developed. The samples were collected from three states in Malaysia. Sample clean up was carried out by employing solid-phase extraction using a 60 mg Oasis HLB (Waters) cartridge with 3 ml reservoir. The HPLC column used was Supelcosil C18 (250 mm x 4.6mm I.D.) and elution was carried out using gradient mode. The mobile phases used were acetonitrile and 0.5% acetic acid in purified water. Antibiotics were detected using UV absorbance at 272 nm. Recoveries obtained for sulphanilamide ranged from 31.9+/-5.1% to 36.2+/-1.0%, while recoveries for other sulfa drugs studied were from 91.9+/-5.0% to 106.0+/-1.1%. The limit of quantitation (LOQ) for sulfamerazine, sulfamethazine and sulfamethoxypyridazine was 7.5 ng/L, while the LOQ for the other studied antibiotics was 5.0 ng/L. The method was used to analyse sulfonamides in wastewater collected from selected Malaysian swine facilities.
(Chemical Equation Presented) By the book: A method for patterning paper with photoresist to create well-defined, millimeter-sized channels comprising hydrophilic paper bounded by hydrophobic polymer is described. This type of patterned paper is a prototype of a class of low-cost, portable, and technically simple platforms for running multiplexed bioassays with microliter volumes of a single biological sample.
Cambios en el área de la salud e impactos para la psicología
- Silva