A full-face mask for protection against respiratory infections.

BACKGROUND: Aerosols and droplets are the transmission routes of many respiratory infectious diseases. The COVID-19 management guidance recommends against the use of nebulized inhalation therapy directly in the emergency room or in an ambulance to prevent possible viral transmission. The three-dimensional printing method was used to develop an aerosol inhalation treatment mask that can potentially prevent aerosol dispersion. We conducted this utility validation study to understand the practicability of this new nebulizer mask system. RESULTS: The fit test confirmed that the filter can efficiently remove small particles. The different locations of the mask had an excellent fit with a high pressure making a proper face seal usability. The full-face mask appeared to optimize filtration with pressure and is an example of materials that perform well for improvised respiratory protection using this design. The filtering effect test confirmed that the contamination of designated locations could be protected when using the mask with filters. As in the clinical safety test, a total of 18 participants (10 [55.6%] females; aged 33.1 ± 0.6 years) were included in the final analysis. There were no significant changes in SPO2, EtCO2, HR, SBP, DBP, and RR at the beginning, 20th, 40th, or 60th minutes of the test (all p >.05). The discomfort of wearing a mask increased slightly after time but remained within the tolerable range. The vision clarity score did not significantly change during the test. The mask also passed the breathability test. CONCLUSION: The results of our study showed that this mask performed adequately in the fit test, the filtering test, and the clinical safety test. The application of a full-face mask with antiviral properties, together with the newly designed shape of a respirator that respects the natural curves of a human face, will facilitate the production of personal protective equipment with a highly efficient filtration system. METHODS: We conducted three independent tests in this validation study: (1) a fit test to calculate the particle number concentration and its association with potential leakage; (2) a filtering effect test to verify the mask's ability to contain aerosol spread; and (3) a clinical safety test to examine the clinical safety, comfortableness, and visual clarity of the mask.

A Parametric Study for Tensile Properties of Silicone Rubber Specimen Using the Bowden-Type Silicone Printer.

Silicone printing can enable a lot more accessibility and customizability towards utilizing silicone in different applications, including medicine for its biocompatibility. However, challenges existed for printing in specific geometries due to the lack of guidelines and studies on the mechanical properties. To support the understanding of printing three-dimensional silicone structure having different infill patterns and gel-like material, this paper conducted a parametric study for the specimens printed using a Bowden-type silicone printer and measurements of the tensile properties. Four printing parameters of print speed, infill density, flow rate, and infill pattern, are categorized following the Taguchi L9 method, and arranged into the four-parameter-three-level orthogonal array. The signal-to-noise (S/N) ratio was calculated based on the principle of the-larger-the-better, and analysis of variance (ANOVA) was also obtained. Tensile performance was further discussed with the characterization of internal structure, using the cross-sections of the printed specimens. It was found that the change of flow rate is the most significant to the tensile stress; and for the tensile strain, infill pattern was found to be the most significant parameter. The Line infill pattern consistently presented the highest tensile stress. Agglomeration can be seen inside the printed structure, hence optimal printing parameters play an important role for complicated geometry, while ensuring the flow rate and infill density do not exceed a reasonable value. This study would serve as the guideline for printing three-dimensional silicone structures.

A novel DNA aptamer targeting lung cancer stem cells exerts a therapeutic effect by binding and neutralizing Annexin A2.

Cancer remains one of the leading causes of death worldwide. Cancer stem cells (CSCs) are the underlying reason for tumor recurrence, progression, and therapeutic resistance. Aptamers are synthetic single-stranded oligonucleotides that can specifically bind to various molecular targets. Here, we aim to develop an effective aptamer-based biomarker and therapeutic tool that targets CSCs for cancer therapy. We perform whole-cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX) to screen DNA aptamers that specifically bound to lung CSCs, modeled by E-cadherin-silenced A549 cells. We develop a CSC-specific aptamer (AP-9R) specifically recognizing lung CSCs with high affinity and identify Annexin A2, a Ca2+-dependent membrane-binding protein, as its target. Annexin A2 expression was upregulated in lung CSCs and involved in cancer stemness. The expression of Annexin A2 was associated with signatures of stemness and metastasis, as well as poor clinical outcomes, in lung cancer in silico. Moreover, AP-9R decreased Annexin A2 expression and suppressed CSC properties in CSCs in vitro and in vivo. The present findings suggest that Annexin A2 is a CSC marker and regulator, and the CSC-specific aptamer AP-9R has potential theranostic applications for lung cancer.

Paper-Based Microfluidics Perform Mixing Effects by Utilizing Planar Constricted-Expanded Structures to Enhance Chaotic Advection.

This study aimed to design and fabricate planar constricted-expanded structures that are integrated into paper-based channels in order to enhance their chaotic advection and improve their mixing performance. Chromatography papers were used to print paper-based microfluidics using a solid-wax printer. Three different constricted-expanded structures-i.e., zigzag, crossed, and curved channels-were designed in order to evaluate their mixing performance in comparison with that of straight channels. A numerical simulation was performed in order to investigate the mixing mechanism, and to examine the ways in which the planar constricted-expanded structures affected the flow patterns. The experimental and numerical results indicated that the proposed structures can successfully mix confluents. The experimental results revealed that the mixing indices (σ) rose from the initial 20.1% (unmixed) to 34.5%, 84.3%, 87.3%, and 92.4% for the straight, zigzag, curved, and cross-shaped channels, respectively. In addition, the numerical calculations showed a reasonable agreement with the experimental results, with a variation in the range of 1.0-11.0%. In future, we hope that the proposed passive paper-based mixers will be a crucial component in the application of paper-based microfluidic devices.

Preconcentration of diluted mixed-species samples following separation and collection in a micro-nanofluidic device.

A microfluidic device consisting of a nanoscale Nafion membrane and a polydimethylsiloxane microchannel is proposed for the preconcentration of diluted multi-mixed species samples then following separation and collection. When an electric field is applied across the microchip, an accumulation of the mixed-species sample occurs at the junction between the microchannel and the membrane by means of ion concentration polarization effect. A separation of the sample then takes place due to the difference in the electrophoretic mobilities of the sample components. Finally, the component of interest is guided to a collection reservoir by manipulating the external potential configuration and is trapped in place by means of a magnetically actuated valve. The preconcentration performance of the proposed device is evaluated in both straight and convergent microchannels using a fluorescein isothiocyanate labeled bovine serum albumin (FITC-BSA) sample. It is shown that a preconcentration factor of 40 times can be achieved using a straight microchannel. By contrast, the preconcentration factor increases to 50 times when using a convergent channel. The practical feasibility of the proposed device is demonstrated by performing the preconcentration, separation, and collection of a mixed FITC-BSA and Tetramethylrhodamine sample.

Preconcentration and Separation of Mixed-Species Samples Near a Nano-Junction in a Convergent Microchannel.

A fluidic microchip incorporating a convergent microchannel and a Nafion-nanoporous membrane is proposed for the preconcentration and separation of multi-species samples on a single platform. In the device, sample preconcentration is achieved by means of the ion concentration polarization effect induced at the micro/nano interface under the application of an external electric field, while species separation is achieved by exploiting the different electrophoretic mobilities of the sample components. The experimental results show that the device is capable of detecting C-reactive protein (CRP) with an initial concentration as low as 9.50 × 10(-6) mg/L given a sufficient preconcentration time and driving voltage. In addition, it is shown that a mixed-species sample consisting of three negatively-charged components (bovine serum albumin (BSA), tetramethylrhodamine(TAMRA) isothiocyanate-Dextran and fluorescent polymer beads) can be separated and preconcentrated within 20 min given a driving voltage of 100 V across 1 cm microchannel in length. In general, the present results confirm the feasibility of the device for the immunoassay or detection of various multi-species samples under low concentration in the biochemical and biomedical fields. The novel device can therefore improve the detection limit of traditional medical facilities.

Cancer cell-specific oligopeptides selected by an integrated microfluidic system from a phage display library for ovarian cancer diagnosis.

Ovarian cancer is one of the leading causes of female mortality worldwide. Unfortunately, there are currently few high-specificity candidate oligopeptide targeting agents that can be used for early diagnosis of this cancer. It has been suggested that cancer-specific oligopeptides could be screened from a phage display library. However, conventional methods are tedious, labor-intensive, and time consuming. Therefore, a novel, integrated microfluidic system was developed to automate the entire screening process for ovarian cancer cell-specific oligopeptides. An oligopeptide screened with microfluidic chip-based technique was demonstrated to have high affinity to ovarian cancer cells and demonstrated relatively low binding to other cancer cells, indicating a high specificity. Furthermore, the developed method consumed relatively low volumes of samples and reagents; only 70 µL of reactant was used within the whole experimental process. Each panning process was also significantly shortened to only 7.5 hours. Therefore, the screened oligopeptide could be used to isolate ovarian cancer cells in a rapid manner, thus greatly expediting the diagnosis and its application as oligopeptide targeting agent for theranostics of this cancer.

Colored wax-printed timers for two-dimensional and three-dimensional assays on paper-based devices.

Microfluidic paper-based analytical devices (µPADs) are widely used for performing diagnostic assays. However, in many assays, time-delay valves are required to improve the sensitivity and specificity of the results. Accordingly, this study presents a simple, low-cost method for realizing time-delay valves using a color wax printing process. In the proposed approach, the time-delay effect is controlled through a careful selection of both the color and the saturation of the wax content. The validity of the proposed method is demonstrated by performing nitrite and oxalate assays using both a simple two-dimensional µPAD and a three-dimensional µPAD incorporating a colored wax-printed timer. The experimental results confirm that the flow time can be controlled through an appropriate selection of the color and the wax content. In addition, it is shown that nitrite and oxalate assays can be performed simultaneously on a single device. In general, the results presented in this study show that the proposed µPADs provide a feasible low-cost alternative to conventional methods for performing diagnostic assays.

Screening of aptamers on microfluidic systems for clinical applications.

The use of microfluidic systems for screening of aptamers and their biomedical applications are reviewed in this paper. Aptamers with different nucleic acid sequences have been extensively studied and the results demonstrated a strong binding affinity to target molecules such that they can be used as promising candidate biomarkers for diagnosis and therapeutics. Recently, the aptamer screening protocol has been conducted with microfluidic-based devices. Furthermore, aptamer affinity screening by a microfluidic-based method has demonstrated remarkable advantages over competing traditional methods. In this paper, we first reviewed microfluidic systems which demonstrated efficient and rapid screening of a specific aptamer. Then, the clinical applications of screened aptamers, also performed by microfluidic systems, are further reviewed. These automated microfluidic systems can provide advantages over their conventional counterparts including more compactness, faster analysis, less sample/reagent consumption and automation. An aptamer-based compact microfluidic system for diagnosis may even lead to a point-of-care device. The use of microfluidic systems for aptamer screening and diagnosis is expected to continue growing in the near future and may make a substantial impact on biomedical applications.

A suction-type microfluidic immunosensing chip for rapid detection of the dengue virus.

The enzyme-linked immunosorbent assay (ELISA) is widely used in medical diagnostics. In order to reduce the diagnosis time and to lower the consumption of sample/reagents in an ELISA assay, a suction-type, automatic, pneumatically-driven microfluidic chip has been designed and fabricated in this study. The microfluidic chip integrates a multi-functional micro-transport/mixing unit, for transporting metering and mixing of samples and reagents in order to automatically perform the entire ELISA protocol. A new surface modification has been adopted which allows for a high processing capacity. The detection sensitivity for the dengue virus is found to be 10(1) PFU/ml, which is much better than a conventional ELISA assay (10(3) PFU/ml). The entire assay time is only 30 min, which is much faster than with 96-well microtiter plates (4 h). The consumed sample and reagent volume is only 12 µl, which is less than a conventional assay (100 µl). The development of this microfluidic chip may be promising for other immunosensing applications.

Biomedical microdevices synthesis of iron oxide nanoparticles using a microfluidic system.

The preparation of nanoparticles is essential in the application of many nanotechnologies and various preparation methods have been explored in the previous decades. Among them, iron oxide nanoparticles have been widely investigated in applications ranging from bio-imaging to bio-sensing due to their unique magnetic properties. Recently, microfluidic systems have been utilized for synthesis of nanoparticles, which have the advantages of automation, well-controlled reactions, and a high particle uniformity. In this study, a new microfluidic system capable of mixing, transporting and reacting was developed for the synthesis of iron oxide nanoparticles. It allowed for a rapid and efficient approach to accelerate and automate the synthesis of the iron oxide nanoparticles as compared with traditional methods. The microfluidic system uses micro-electro-mechanical-system technologies to integrate a new double-loop micromixer, two micropumps, and a microvalve on a single chip. When compared with large-scale synthesis systems with commonly-observed particle aggregation issues, successful synthesis of dispersed and uniform iron oxide nanoparticles has been observed within a shorter period of time (15 min). It was found that the size distribution of these iron oxide nanoparticles is superior to that of the large-scale systems without requiring any extra additives or heating. The size distribution had a variation of 16%. This is much lower than a comparable large-scale system (34%). The development of this microfluidic system is promising for the synthesis of nanoparticles for many future biomedical applications.

Development and characterization of an all-solid-state potentiometric biosensor array microfluidic device for multiple ion analysis.

A microfluidic device with an all-solid-state potentiometric biosensor array was developed using microfabrication technology. The sensor array included a pH indicator, and potassium and calcium ion-selective microelectrodes. The pH indicator was an iridium oxide thin film modified platinum microelectrode and the iridium oxide was deposited by an electrochemical method. The potassium and calcium ion-selective microelectrodes were platinum coated with silicon rubber based ion-selective membranes with respectively potassium (valinomycin) and calcium (ETH 1001) ionophores. The detection system was integrated with a micro-pneumatic pump which can continuously drive fluids into the microchannel through sensors at flow rates ranging from 52.4 microl min(-1) to 7.67 microl min(-1). The sensor array microfluidic device showed near-Nernstian responses with slopes of 62.62 mV +/- 2.5 mV pH(-1), 53.76 mV +/- 3 mV -log[K+](-1) and 25.77 mV +/- 2 mV -log[Ca2+](-1) at 25 degrees C +/- 5 degrees C, and a linear response within the pH range of 2-10, with potassium and calcium concentrations between 0.1 M and 10(-6) M. In this study the device provided a convenient way to measure the concentration of hydrogen, potassium and calcium ions, which are important physiological parameters.