"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.

Development of a sticker sealed microfluidic device for in situ analytical measurements using synchrotron radiation.

Shedding synchrotron light on microfluidic systems, exploring several contrasts in situ/operando at the nanoscale, like X-ray fluorescence, diffraction, luminescence, and absorption, has the potential to reveal new properties and functionalities of materials across diverse areas, such as green energy, photonics, and nanomedicine. In this work, we present the micro-fabrication and characterization of a multifunctional polyester/glass sealed microfluidic device well-suited to combine with analytical X-ray techniques. The device consists of smooth microchannels patterned on glass, where three gold electrodes are deposited into the channels to serve in situ electrochemistry analysis or standard electrical measurements. It has been efficiently sealed through an ultraviolet-sensitive sticker-like layer based on a polyester film, and The burst pressure determined by pumping water through the microchannel(up to 0.22 MPa). Overall, the device has demonstrated exquisite chemical resistance to organic solvents, and its efficiency in the presence of biological samples (proteins) is remarkable. The device potentialities, and its high transparency to X-rays, have been demonstrated by taking advantage of the X-ray nanoprobe Carnaúba/Sirius/LNLS, by obtaining 2D X-ray nanofluorescence maps on the microchannel filled with water and after an electrochemical nucleation reaction. To wrap up, the microfluidic device characterized here has the potential to be employed in standard laboratory experiments as well as in in situ and in vivo analytical experiments using a wide electromagnetic window, from infrared to X-rays, which could serve experiments in many branches of science.

Salivary diagnostics on paper microfluidic devices and their use as wearable sensors for glucose monitoring.

Microfluidic paper-based devices (µPADs) and wearable devices have been highly studied to be used as diagnostic tools due to their advantages such as simplicity and ability to provide instrument-free fast results. Diseases such as periodontitis and diabetes mellitus can potentially be detected through these devices by the detection of important biomarkers. This study describes the development of µPADs through craft cutter printing for glucose and nitrite salivary diagnostics. In addition, the use of µPADs integrated into a mouthguard as a wearable sensor for glucose monitoring is also presented. µPADs were designed to contain two detection zones for glucose and nitrite assays and a sampling zone interconnected by microfluidic channels. Initially, the analytical performance of the proposed µPADs was investigated and it provided linear behavior (r2 ≥ 0.994) in the concentration ranges between 0 to 2.0 mmol L-1 and 0 to 400 µmol L-1 for glucose and nitrite, respectively. Under the optimized conditions, the limits of detection achieved for glucose and nitrite were 27 µmol L-1 and 7 µmol L-1, respectively. Human saliva samples were collected from healthy individuals and patients previously diagnosed with periodontitis or diabetes and then analyzed on the proposed µPADs. The results found using µPADs revealed higher glucose concentration values in saliva collected from patients diagnosed with diabetes mellitus and greater nitrite concentrations in saliva collected from patients diagnosed with periodontitis, as expected. The results obtained on µPADs did not differ statistically from those measured by spectrophotometry. With the aim of developing paper-based wearable sensors, µPADs were integrated, for the first time, into a silicone mouthguard using a 3D-printed holder. The proof of concept was successfully demonstrated through the monitoring of the glucose concentration in saliva after the ingestion of chocolate. According to the results reported herein, paper-based microfluidic devices offer great potential for salivary diagnostics, making their integration into a silicone mouthguard possible, generating simple, low-cost, instrument-free, and powerful wearable sensors.

Photochemical Deposition of Silver Nanoparticles on Clays and Exploring Their Antibacterial Activity.

Photochemical method was used to synthesize silver nanoparticles (AgNPs) in the presence of citrate or clay (SWy-1, SYn-1, and Laponite B) as stabilizers and Lucirin TPO as photoinitiator. During the photochemical synthesis, an appearance of the plasmon absorption band was seen around 400 nm, indicating the formation of AgNPs. X-ray diffraction results suggested that AgNPs prepared in SWy-1 were adsorbed into interlamellar space, and moreover, showed some clay exfoliation. In the case of SYn-1, AgNPs was not intercalated. For the AgNP/Lap B sample, the formation of an exfoliated structure occurred. Transmission electron microscopy revealed the spherical shape of AgNPs for all samples. The particle sizes obtained for AgNP/SWy-1, AgNP/SYn-1, and AgNP/Lap B were 2.6, 5.1, and 3.8 nm, respectively. AgNPs adsorbed on SYn-1 reveal nonuniform size and aggregation of some particles. However, AgNP/SWy-1 and AgNP/Lap B samples are more uniform and have diameters smaller than those prepared with SYn-1. This behavior is due to the ability to exfoliate these clays. The antibacterial activities of pure clays, AgNP/citrate, and AgNP/clays were investigated against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). AgNPs in the presence of clays (AgNPs/SYn-1 and AgNPs/SWy-1) showed a lower survival index percentage compared to those obtained for pure clays and AgNPs. The AgNP/SWy-1 sample showed good antibacterial activity against both tested species and the lowest survival index of 3.9 and 4.3 against E. coli and S. aureus, respectively. AgNPs are located in the interlayer region of the SWy-1, which has acid sites. These acidic sites may contribute to the release of Ag(+) ions from the surface of AgNPs. On the other hand, Laponite B and AgNP/Lap B samples did not demonstrate any bactericidal activity.

Short-term treatment with cabergoline can lead to tumor shrinkage in patients with nonfunctioning pituitary adenomas.

This study was carried out to evaluate the effectiveness of cabergoline in the treatment of nonfunctioning pituitary adenomas (NFPA), in a short-term follow-up period. Nineteen patients (10 men and 9 women) followed at the University Hospital of Brasilia and harboring nonfunctioning pituitary macroadenomas were enrolled in the study. Eleven patients were previously submitted to transsphenoidal surgery, and in 8 patients no previous treatment had been instituted. Their response to the use of cabergoline (2 mg/week) by 6 months was evaluated. Significant tumor shrinkage (above 25 % from baseline tumor volume) was observed in 6 (31.6 %) of the 19 patients, and no adverse effects were observed during treatment. In 9 patients (47.4 %), a reduction in tumor volume of at least 10 % was noted, whereas tumor growth was observed in four patients (increase above 25 % was only observed in one patient). Cabergoline (2 mg/week) can lead to significant tumor shrinkage in NFPA in a considerable number of patients, and this effect can be observed early (6 months after starting medication). Thus, this therapeutic strategy may be a low cost and safe alternative for treatment of NFPA in patients with remnant or recurrent tumor after transsphenoidal surgery or in those not operated by contraindications or refusal to surgical procedure.