Paper-based microfluidic devices (μPADs) are capable of achieving rapid quantitative measurements of a variety of analytes inexpensively. μPADs rely on patterning hydrophilic-hydrophobic regions on a ...sheet of paper in order to create capillary channels within impermeable fluidic brakes on the paper. Here, we present a novel, highly flexible and low-cost fabrication method using a desktop digital craft plotter/cutter and technical drawing pens with tip size of 0.5 mm. The pens were used with either commercial black permanent ink for drawing fluidic brakes, or with specialty in-house formulated aqueous inks. With the permanent marker ink it was possible to create barriers on paper rapidly and in a variety of designs in a highly flexible manner. For instance, a design featuring eight reservoirs can be produced within 10 s for each μPAD with a consistent line width of brakes (%RSD < 1.5). Further, we investigated the optimal viscosity range of in-house formulated inks controlled with additions of poly(ethylene glycol). The viscosity was measured by capillary electrophoresis and the optimal viscosity was in the range of ∼3–6 mPa s. A functional test of these μPADs was conducted by the screening of antioxidant activity. Colorimetric measurements of flavonoid, phenolic compounds and DPPH free radical scavenging activity were carried out on μPADs. The results can be detected by the naked eye and simply quantified by using a camera phone and image analysis software. The fabrication method using technical drawing pens provides flexibility in the use of in-house formulated inks, short fabrication time, simplicity and low cost.
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•A desktop digital craft plotter/cutter and technical drawing pens create a variety of μPAD designs rapidly.•The technical drawing pens can be used with commercial black permanent ink or specialty in-house formulated aqueous ink.•Two or more solutions can be printed without any paper repositioning in the plotter.•A functional test evaluating antioxidant activity of beverages is demonstrated.
Charantin is a mixture of β-sitosterol and stigmastadienol glucosides, which effectively lowers high blood glucose. Novel molecularly imprinted polymers coated magnetic nanoparticles (Fe
O
@MIPs) and ...filter paper (paper@MIPs) were synthesized by sol-gel polymerization to selectively extract charantin. β-sitosterol glucoside was selected as a template for imprinting a specific recognition owing to its larger molecular surface area than that of 5,25-stigmastadienol glucoside. Factorial designs were used to examine the effects of the types of porogenic solvents and cross-linkers on the extraction efficiency and imprinting factor before investigating other factors (for example, amounts of template and coated MIPs, and types of substrates for MIP immobilization). Compared to traditional liquid-liquid extraction, the optimal Fe
O
@MIP-based dispersive micro-solid phase extraction and paper@MIP extraction provided excellent extraction efficiency (87.5 ± 2.1% and 85.0 ± 2.9%, respectively) and selectivity. Charantin was well separated, and a new unidentified sterol glucoside was observed using the developed high-performance liquid chromatography with diode-array detection (Rs ≥ 2.0,
> 16,400). The developed methods were successfully utilized to extract and quantify charantin from
fruit powder and herbal products. Moreover, these methods are rapid (<10 min), inexpensive, simple, reproducible, and environmentally friendly.
Carbamazepine is an antiepileptic drug with a narrow therapeutic index, which requires an efficient method for blood level monitoring. Finger-prick dried blood spot (DBS) collection is an alternative ...microsampling technique, which is less invasive than conventional venipuncture. Paper-based molecularly imprinted-interpenetrating polymer networks (MI-IPN) were developed as blood collection devices, which allowed for selective on-spot microextraction of carbamazepine from DBS. A hybrid of homogeneous polystyrene and silica gel polymer was synthesized and coated on a Whatman
®
Grade 1 filter paper. Proteins and other interferences in the blood samples were eliminated by using the MI-IPN collection devices, and the resulting DBS extracts were suitable for direct injection into the capillary electrophoretic instrument. The lower limit of quantitation of 4 μg/mL in capillary blood was achieved by the sweeping-micellar electrokinetic chromatography method using a KCl-containing matrix, which was sufficient for the therapeutic drug monitoring purposes. Method accuracies were in the range of 88.4 ± 4.5% to 94.5 ± 2.7% with RSD values ≤ 5.1%. The developed paper-based MI-IPN provided superior extraction efficiencies (92.2 ± 2.5%) in comparison with commercially available DBS collection cards, i.e., Whatman
®
903 protein saver card (59.8 ± 2.8%) and GenCollect™ 2.0 card (47.2 ± 1.4%). The paper-based MI-IPN devices for DBS collection and on-spot extraction were characterized by simple fabrication, low costs, disposability, and reduction in sample preparation steps, and their further developments might open new perspectives in clinical applications, such as in therapeutic drug monitoring.
Graphical abstract
•Novel microchip electrophoresis (ME) technology including modes and detectors are reviewed.•Recent biomedical applications of ME during 2010 to date are presented.•Advantages and limitations of ME ...are addressed.
Many separation methods have been developed for biomedical analysis, including chromatographic (e.g. high performance liquid chromatography (HPLC) and gas chromatography (GC)) and electrophoretic methods (e.g. gel electrophoresis and capillary electrophoresis (CE)). Among these techniques, CE provides advantages in terms of high separation efficiency, simplicity, low sample and solvent volume consumption, short analysis time and applicability to a wide range of biomedically important substances. Microchip electrophoresis (ME) is a miniaturized platform of CE and is now considered as a simpler and more convenient alternative, which has demonstrated potential in analytical chemistry. High-throughput, cost-effective and portable analysis systems can be developed using ME. The current review describes different separation modes and detectors that have been employed in ME to analyze various classes of biomedical analytes (e.g. pharmaceuticals and related substances, nucleic acids, amino acids, peptides, proteins, antibodies and antigens, carbohydrates, cells, cell components and lysates). Recent applications (during 2010–2014) in these areas are presented in tables and some significant findings are highlighted.
This work presents an affordable distance-based microfluidic paper-based device (μPAD), using polydiacetylene (PDA) liposome as a chromogenic substance with a smartphone-based photo editor, for rapid ...and in-field analysis of quaternary ammonium compounds (QACs) (e.g., didecyldimethylammonium chloride (DDAC), benzyldimethyltetradecyl ammonium chloride (BAC), and cetylpyridinium chloride (CPC)). In-field analysis of these compounds is important to ensure their antimicrobial activity and user safety since they are widely utilized as disinfectants in households and hospitals. The μPAD featured a thermometer-like shape consisting of a sample reservoir and a microchannel as the detection zone, which was pre-deposited with PDA liposome. The color change from blue to red appeared in the presence of QACs and the color bar lengths were proportional to the QAC concentrations. Reactions of QACs with the PDA required a specific pH range (from pH 4.0 to 10.0) and a readout time of 7 min. Analytical performance characteristics of the device were tested with DDAC, BAC, and CPC showing acceptable specificity, accuracy (96.1–109.4%), and precision (%RSDs ≤ 9.3%). Limits of detection and quantitation were in the ranges of 20 to 80 and 70 to 250 μM, respectively. Feasibility of the newly developed device was demonstrated for in-field analysis of QACs in fumigation solution providing comparable results with those obtained from a colorimetric assay (
P
> 0.05). The proposed device shows potentials for further applications of other analytes since it offers speed, simplicity, and affordability for in-field analysis, especially in remote areas where expertise, resources, and infrastructures are limited.
Graphical abstract
•The review focuses on the integration of microneedles with optical sensors.•Advantages and limitations of microneedles for microsampling action are covered.•Microneedles are fabricated using various ...methods chosen by type, geometry, and material.•Microneedles-based optical sensing show potential for transdermal diagnostics.•The future perspectives cover ways of enhancing selectivity and sensitivity.
Interstitial fluid is a readily accessible source of biomarkers for various diseases, providing a less invasive and more convenient option than traditional blood or tissue sampling methods. Microneedle-based point-of-care testing devices have gained significant interest due to their potential for direct detection of target analytes in ISF, accomplished through minimally invasive penetration of the stratum corneum. Thus, microneedle-based devices can be considered as adhesive tools for diagnostic sensing and therapeutic drug administration. Microneedle-based colorimetric and fluorescence sensing has the potential to revolutionize disease diagnosis and monitoring, offering a rapid, highly sensitive, specific, and cost-effective alternative to traditional methods. These devices enable the detection of low levels of biomarkers in the collected fluid, which is particularly important in situations requiring prompt diagnosis and treatment. This review covers the types of microneedles and their fabrication methods, the detection principles of microneedle-based colorimetric and fluorescence sensing, as well as their key applications, advantages, and limitations. Additionally, the review explores ways to overcome current limitations and improve the performance, as well as future perspectives for the development of microneedle-based devices.
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Microneedles (MNs) have shown a great potential for the microsampling of dermal interstitial fluid (ISF) in a minimally invasive manner for point-of-care testing (POCT). The swelling properties of ...hydrogel-forming microneedles (MNs) allow for passive extraction of ISF. Surface response approaches, including Box-Behnken design (BBD), central composite design (CCD), and optimal discrete design, were employed for the optimization of hydrogel film by studying the effects of independent variables (i.e., the amount of hyaluronic acid, Gantrez
S-97, and pectin) on the swelling property. The optimal discrete model was selected to predict the appropriate variables, due to the good fit of the experimental data and the model validity. The analysis of variance (ANOVA) of the model demonstrated
-value < 0.0001, R
= 0.9923, adjusted R
= 0.9894, and predicted R
= 0.9831. Finally, the predicted film formulation containing 2.75%
/
hyaluronic acid, 1.321%
/
Gantrez
S-97, and 1.246%
/
pectin was used for further fabrication of MNs (525.4 ± 3.8 µm height and 157.4 ± 2.0 µm base width), which possessed 1508.2 ± 66.2% swelling, with 124.6 ± 7.4 µL of collection volume, and could withstand thumb pressure. Moreover, almost 50% of MNs achieved a skin insertion depth of approx. 400 µm, with 71.8 ± 3.2% to 78.3 ± 2.6% recoveries. The developed MNs show a promising prospect in microsample collection, which would be beneficial for POCT.
The antifungal drug miconazole nitrate has a low solubility in water, leading to reduced therapeutic efficacy. To address this limitation, miconazole-loaded microemulsions were developed and assessed ...for topical skin delivery, prepared through spontaneous emulsification with oleic acid and water. The surfactant phase included a mixture of polyoxyethylene sorbitan monooleate (PSM) and various cosurfactants (ethanol, 2-(2-ethoxyethoxy) ethanol, or 2-propanol). The optimal miconazole-loaded microemulsion containing PSM and ethanol at a ratio of 1:1 showed a mean cumulative drug permeation of 87.6 ± 5.8 μg/cm
across pig skin. The formulation exhibited higher cumulative permeation, permeation flux, and drug deposition than conventional cream and significantly increased the in vitro inhibition of
compared with cream (
< 0.05). Over the course of a 3-month study conducted at a temperature of 30 ± 2 °C, the microemulsion exhibited favorable physicochemical stability. This outcome signifies its potential suitability as a carrier for effectively administering miconazole through topical administration. Additionally, a non-destructive technique employing near-infrared spectroscopy coupled with a partial least-squares regression (PLSR) model was developed to quantitatively analyze microemulsions containing miconazole nitrate. This approach eliminates the need for sample preparation. The optimal PLSR model was derived by utilizing orthogonal signal correction pretreated data with one latent factor. This model exhibited a remarkable R
value of 0.9919 and a root mean square error of calibration of 0.0488. Consequently, this methodology holds potential for effectively monitoring the quantity of miconazole nitrate in various formulations, including both conventional and innovative ones.
Adamantane drugs (e.g., memantine, rimantadine, and amantadine) consist of a core tricyclodecane with different substituents. Memantine is used for treatment of Alzheimer’s disease, while rimantadine ...and amantadine are recommended for influenza A infection. Additionally, amantadine is clinically used for Parkinson’s disease. Analysis of adamantine drugs by optical detection requires some derivatization due to the lack of chromophores or fluorophores in their structures. This procedure is performed to enhance their detectability, but it can be time- and labor-intensive. This work focuses on developments of a simple and fast technique for the analysis of these drugs in a microplate platform. Derivatization was achieved in 50 mM borate buffer (pH 11.0) using a stoichiometric ratio between the analyte and fluorescamine (as a derivatizing reagent) of 1:10 and a reaction time of 10 min. The fluorescent derivatives were determined in a 96-well microplate using excitation and emission wavelengths at 385 and 485 nm, respectively. The method showed good linearity (
r
2
> 0.968), repeatability (RSDs of < 2.6%), and accuracy (% recovery 96.2–101.1 with RSD < 4.5%) with acceptable limits of detection (< 3 µM) and quantitation (< 10 µM). The method was successfully applied for the determination of the drugs in pharmaceutical formulations.
Graphic abstract
Turmeric consumption is continually increasing worldwide. Curcuminoids are major active constituents in turmeric and are associated with numerous health benefits. A combination of spectroscopic ...methods and chemometrics shows the suitability of turmeric for food quality control due to advantages such as speed, versatility, portability, and no need for sample preparation. Five calibration models to quantify curcuminoids in turmeric were proposed using benchtop and portable devices. The most remarkable results showed that Raman and NIR calibration models present an excellent performance reporting RMSEP of 0.44% w/w and 0.41% w/w, respectively. In addition, the five proposed methods (FT-IR, Raman, and NIR) were compared in terms of precision and accuracy. The results showed that benchtop and portable methods were in good agreement and that there are no significant differences between them. This study aims to foster the use of portable devices for food quality control in situ by demonstrating their suitability for the purpose.
