Improved sensitivity in paper-based microfluidic analytical devices using a pH-responsive valve for nitrate analysis.

This paper presents an innovative application of chitosan material to be used as pH-responsive valves for the precise control of lateral flow in microfluidic paper-based analytical devices (µPADs). The fabrication of µPADs involved wax printing, while pH-responsive valves were created using a solution of chitosan in acetic acid. The valve-forming solution was applied, and ready when dry; by exposure to acidic solutions, the valve opens. Remarkably, the valves exhibited excellent compatibility with alkaline, neutral, and acidic solutions with a pH higher than 4. The valve opening process had no impact on the flow rate and colorimetric analysis. The potential of chitosan valves used for flow control was demonstrated for µPADs employed for nitrate determination. Valves were used to increase the conversion time of nitrate to nitrite, which was further analyzed using the Griess reaction. The µPAD showed a linear response in the concentration range of 10-100 µmol L-1, with a detection limit of 5.4 µmol L-1. As a proof of concept, the assay was successfully applied to detect nitrate levels in water samples from artificial lakes of recreational parks. For analyses that require controlled kinetics and involve multiple sequential steps, the use of chitosan pH-responsive valves in µPADs is extremely valuable. This breakthrough holds great potential for the development of simple and high-impact microfluidic platforms that can cater to a wide range of analytical chemistry applications.

Office paper and laser printing: a versatile and affordable approach for fabricating paper-based analytical devices with multimodal detection capabilities.

Multiple protocols have been reported to fabricate paper-based analytical devices (PADs). However, some of these techniques must be revised because of the instrumentation required. This paper describes a versatile and globally affordable method to fabricate PADs using office paper as a substrate and a laser printing technique to define hydrophobic barriers on paper surfaces. To demonstrate the feasibility of the alternatives proposed in this study, the fabrication of devices for three types of detection commonly associated with using PADs was demonstrated: colorimetric detection, electrochemical detection, and mass spectrometry associated with a paper-spray ionization (PSI-MS) technique. Besides that, an evaluation of the type of paper used and chemical modifications required on the substrate surface are also presented in this report. Overall, the developed protocol was suitable for using office paper as a substrate, and the laser printing technique as an efficient fabrication method when using this substrate is accessible at a resource-limited point-of-need. Target analytes were used as a proof of concept for these detection techniques. Colorimetric detection was carried out for acetaminophen, iron, nitrate, and nitrite with limits of detection of 0.04 µg, 4.5 mg mL-1, 2.7 µmol L-1, and 6.8 µmol L-1, respectively. A limit of detection of 0.048 fg mL-1 was obtained for the electrochemical analysis of prostate-specific antigen. Colorimetric and electrochemical devices revealed satisfactory performance when office paper with a grammage of 90 g m-2 was employed. Methyldopa analysis was also carried out using PSI-MS, which showed a good response in the same paper weight and behavior compared to chromatographic paper.

Distance-based detection of paracetamol in microfluidic paper-based analytical devices for forensic application.

Whisky adulteration is a prevalent practice driven by the high cost of these beverages. Counterfeiters commonly dilute whisky with less expensive alcoholic beverages, water, food additives, drugs or pharmaceuticals. Paracetamol (PAR), an analgesic drug that mitigates hangovers and headaches, is commonly used to adulterate whisky. Currently, the primary method for quantifying PAR levels is high-performance liquid chromatography, but this technique is both time consuming and usually generates more residues. In this context, the utilization of miniaturized and portable analytical devices becomes imperative for conducting point-of-care/need analyses. These devices offer several advantages, including portability, user-friendliness, low cost, and minimal material wastage. This study proposes the selective distance-based PAR quantification on whisky samples using a paper-based microfluidic analytical device (µPAD). Colorimetric detection on paper-based platforms offers great benefits such as affordability, portability, and the ability to detect PAR without complicated instrumentation. The optimal detection conditions were achieved by introducing 5 µL of a mixture containing 7.5 mmol L-1 of Fe(III) and K3[Fe(CN)6] into the detection zone, along with 12 µL of whisky samples into the sample zone. The method exhibited linear behavior within the concentration range from 15 to 120 mg L-1, with a determination coefficient of 0.998. PAR was quantified in adulterated samples. The results obtained with the paper-based devices were compared with a referenced method, and no significant differences were observed at a confidence level of 95%. The µPAD allowed to determine ca. 1 drop of pharmaceutical medicine PAR of 200 mg mL-1 in 1 L of solution, demonstrating excellent sensitivity. This method offers cost-effective and rapid analysis, reducing the consumption of samples, reagents, and wastes. Consequently, it could be considered a viable and portable alternative for analyzing beverages at criminal scenes, customs, and police operations, thereby enhancing the field of forensics.

Controlled Release and Cell Viability of Ketoconazole Incorporated in PEG 4000 Derivatives.

In recent years, polymeric materials have been gaining prominence in studies of controlled release systems to obtain improvements in drug administration. These systems present several advantages compared with conventional release systems, such as constant maintenance in the blood concentration of a given drug, greater bioavailability, reduction of adverse effects, and fewer dosages required, thus providing a higher patient compliance to treatment. Given the above, the present work aimed to synthesize polymeric matrices derived from polyethylene glycol (PEG) capable of promoting the controlled release of the drug ketoconazole in order to minimize its adverse effects. PEG 4000 is a widely used polymer due to its excellent properties such as hydrophilicity, biocompatibility, and non-toxic effects. In this work, PEG 4000 and derivatives were incorporated with ketoconazole. The morphology of polymeric films was observed by AFM and showed changes on the film organization after drug incorporation. In SEM, it was possible to notice spheres that formed in some incorporated polymers. The zeta potential of PEG 4000 and its derivatives was determined and suggested that the microparticle surfaces showed a low electrostatic charge. Regarding the controlled release, all the incorporated polymers obtained a controlled release profile at pH 7.3. The release kinetics of ketoconazole in the samples of PEG 4000 and its derivatives followed first order for PEG 4000 HYDR INCORP and Higuchi for the other samples. Cytotoxicity was determined and PEG 4000 and its derivatives were not cytotoxic.

"Do it yourself" protocol to fabricate dual-detection paper-based analytical device for salivary biomarker analysis.

This paper describes the design and construction of dual microfluidic paper-based analytical devices (dual-µPADs) as a lab-on-paper platform involving a "do-it-yourself" fabrication protocol. The device comprises a colorimetric and electrochemical module to obtain a dual-mode signal readout sensing strategy. A 3D pen polymeric resin was used to prepare graphite carbon-based electrodes and hydrophobic barriers on paper substrates. The proposed carbon-based ink was employed to manufacture electrodes on paper based on a stencil-printing approach, which were further characterized by electrochemical and morphological analyses. The analytical performance of the dual-µPADs was simultaneously evaluated for lactate, pH, nitrite, and salivary amylase (sAA) analysis. To demonstrate the proof-of-concept, saliva samples collected from both healthy individuals and those with periodontitis were successfully tested to demonstrate the feasibility of the proposed devices. Samples collected from individuals previously diagnosed with periodontitis showed high levels of nitrite and sAA (> 94 µmol L-1 and > 610 U mL-1) in comparison with healthy individuals (≤ 16 µmol L-1 and 545 U mL-1). Moreover, periodontitis saliva resulted in acid solution and almost null lactate levels. Notably, this protocol supplies a simple way to manufacture dual-µPADs, a versatile platform for sensitive detecting of biomarkers in saliva playing a crucial role towards the point-of-care diagnosis of periodontal disease.

Silicone glue-based graphite ink incorporated on paper platform as an affordable approach to construct stable electrochemical sensors.

This study describes the development of electrochemical paper-based analytical devices (ePADs) using carbon-based paste combining silicone glue and graphite powder. The ePADs were manufactured using the screen-printing technique, which consisted of depositing the conductive ink on a screencast on the paper surface. In addition, an alternative electrical connector was designed and 3D-printed to make the detection method cheaper, portable and reproducible. The morphological, structural, and electrochemical properties of the conductive material developed were investigated through scanning electron microscopy (SEM), Raman spectroscopy, electrochemical impedance spectroscopy (EIS), and cyclic voltammetry (CV) measurements. The ePADs combined with the alternative connector revealed high repeatability, reproducibility, and stable responses considering a well-known redox probe ([Fe(CN)6]4-/3-). In addition, the proposed ePAD provided a linear response for standard solutions of ascorbic acid (AA) in the concentration range between 0.1 and 2.0 mmol L-1. The achieved limit of detection was 4.0 µmol L-1. As proof of applicability, the ePADs were evaluated for AA analysis in synthetic biofluids (blood plasma and urine), vitamin C tablets, and food (gelatine and orange juice) samples. The analytical parameters of the proposed device were compared with other reports in the literature and exhibited similar or even superior performance, highlighting its feasibility for sensing applications.

Simultaneous analysis of multiple adulterants in milk using microfluidic paper-based analytical devices.

This study reports the simultaneous colorimetric detection of urea, H2O2, and pH in milk samples using microfluidic paper-based analytical devices (µPADs) fabricated through a craft cutter printer. Paper-based devices were designed to contain three detection zones interconnected to a sampling zone by microfluidic channels. Colorimetric analysis was performed using images digitalized through an office scanner. The volumes of chromogenic and sample solutions were optimized, and the best colorimetric performance was achieved by adding 0.5 and 10 µL into detection and sampling zones, respectively. Simultaneous assays were then carried out, and the recorded responses revealed a linear behavior in the concentration ranges from 0-30.0 mmol L-1, 0-10.0 mmol L-1 and 6.0-9.0 for urea, H2O2 and pH, respectively. The limit of detection values obtained for urea and H2O2 were 2.4 mmol L-1 and 0.1 mmol L-1, respectively. For pH measurements, colorimetric assay allowed the monitoring of solution pH with a resolution of 0.25 units. The use of µPADs to detect target adulterants exhibited suitable reproducibility (RSD ≤ 6.0%), accuracy (91-102%) and no cross-reaction occurrence. When compared to reference techniques, colorimetric assays did not reveal a significant difference at a confidence level of 95%. As a proof-of-concept, the feasibility of the proposed approach was successfully demonstrated through the analysis of potential adulterants in sixteen milk samples, which were tested without any pretreatment requirement. Based on the achievements, µPADs in conjunction with colorimetric measurements emerge as a powerful tool for rapid screening of potential adulterants in milk.

Preparation of glass-ionomer cement containing ethanolic Brazilian pepper extract (Schinus terebinthifolius Raddi) fruits: chemical and biological assays.

Plants may contain beneficial or potentially dangerous substances to humans. This study aimed to prepare and evaluate a new drug delivery system based on a glass-ionomer-Brazilian pepper extract composite, to check for its activity against pathogenic microorganisms of the oral cavity, along with its in vitro biocompatibility. The ethanolic Brazilian pepper extract (BPE), the glass-ionomer cement (GIC) and the composite GIC-BPE were characterized by scanning electron microscopy, attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), and thermal analysis. The BPE compounds were identified by UPLC-QTOF-MS/MS. The release profile of flavonoids and the mechanical properties of the GIC-BPE composite were assessed. The flavonoids were released through a linear mechanism governing the diffusion for the first 48 h, as evidenced by the Mt/M∞ relatively to [Formula: see text], at a diffusion coefficient of 1.406 × 10-6 cm2 s-1. The ATR-FTIR analysis indicated that a chemical bond between the GIC and BPE components may have occurred, but the compressive strength of GIC-BPE does not differ significantly from that of this glass-ionomer. The GIC-BPE sample revealed an ample bacterial activity at non-cytotoxic concentrations for the human fibroblast MRC-5 cells. These results suggest that the prepared composite may represent an alternative agent for endodontic treatment.