Advancements in Hybrid Cellulose-Based Films: Innovations and Applications in 2D Nano-Delivery Systems.

This review paper delves into the realm of hybrid cellulose-based materials and their applications in 2D nano-delivery systems. Cellulose, recognized for its biocompatibility, versatility, and renewability, serves as the core matrix for these nanomaterials. The paper offers a comprehensive overview of the latest advancements in the creation, analysis, and application of these materials, emphasizing their significance in nanotechnology and biomedical domains. It further illuminates the integration of nanomaterials and advanced synthesis techniques that have significantly improved the mechanical, chemical, and biological properties of hybrid cellulose-based materials.

SiCNFe Ceramics as Soft Magnetic Material for MEMS Magnetic Devices: A Mössbauer Study.

Polymer-derived SiCNFe ceramics is a prospective material that can be used as soft magnets in MEMS magnetic applications. The optimal synthesis process and low-cost appropriate microfabrication should be developed for best result. Homogeneous and uniform magnetic material is required for developing such MEMS devices. Therefore, the knowledge of exact composition of SiCNFe ceramics is very important for the microfabrication of magnetic MEMS devices. The Mössbauer spectrum of SiCN ceramics, doped with Fe (III) ions, and annealed at 1100 °C, was investigated at room temperature to accurately establish the phase composition of Fe-containing magnetic nanoparticles, which were formed in this material at pyrolysis and which determine their magnetic properties. The analysis of Mössbauer data shows the formation of several Fe-containing magnetic nanoparticles in SiCN/Fe ceramics, such as α-Fe, FexSiyCz, traces of Fe-N and paramagnetic Fe3+ with octahedral oxygen environment. The presence of iron nitride and paramagnetic Fe3+ ions shows that the pyrolysis process was not completed in SiCNFe ceramics annealed at 1100 °C. These new observations confirm the formation of different Fe-containing nanoparticles with complex composition in SiCNFe ceramic composite.

A review on microfluidic-assisted nanoparticle synthesis, and their applications using multiscale simulation methods.

Recent years have witnessed an increased interest in the development of nanoparticles (NPs) owing to their potential use in a wide variety of biomedical applications, including drug delivery, imaging agents, gene therapy, and vaccines, where recently, lipid nanoparticle mRNA-based vaccines were developed to prevent SARS-CoV-2 causing COVID-19. NPs typically fall into two broad categories: organic and inorganic. Organic NPs mainly include lipid-based and polymer-based nanoparticles, such as liposomes, solid lipid nanoparticles, polymersomes, dendrimers, and polymer micelles. Gold and silver NPs, iron oxide NPs, quantum dots, and carbon and silica-based nanomaterials make up the bulk of the inorganic NPs. These NPs are prepared using a variety of top-down and bottom-up approaches. Microfluidics provide an attractive synthesis alternative and is advantageous compared to the conventional bulk methods. The microfluidic mixing-based production methods offer better control in achieving the desired size, morphology, shape, size distribution, and surface properties of the synthesized NPs. The technology also exhibits excellent process repeatability, fast handling, less sample usage, and yields greater encapsulation efficiencies. In this article, we provide a comprehensive review of the microfluidic-based passive and active mixing techniques for NP synthesis, and their latest developments. Additionally, a summary of microfluidic devices used for NP production is presented. Nonetheless, despite significant advancements in the experimental procedures, complete details of a nanoparticle-based system cannot be deduced from the experiments alone, and thus, multiscale computer simulations are utilized to perform systematic investigations. The work also details the most common multiscale simulation methods and their advancements in unveiling critical mechanisms involved in nanoparticle synthesis and the interaction of nanoparticles with other entities, especially in biomedical and therapeutic systems. Finally, an analysis is provided on the challenges in microfluidics related to nanoparticle synthesis and applications, and the future perspectives, such as large-scale NP synthesis, and hybrid formulations and devices.

Advancement in Biosensor Technologies of 2D MaterialIntegrated with Cellulose-Physical Properties.

This review paper provides an in-depth analysis of recent advancements in integrating two-dimensional (2D) materials with cellulose to enhance biosensing technology. The incorporation of 2D materials such as graphene and transition metal dichalcogenides, along with nanocellulose, improves the sensitivity, stability, and flexibility of biosensors. Practical applications of these advanced biosensors are explored in fields like medical diagnostics and environmental monitoring. This innovative approach is driving research opportunities and expanding the possibilities for diverse applications in this rapidly evolving field.

Optimizing Biodegradable Starch-Based Composite Films Formulation for Wound-Dressing Applications.

This paper utilizes response surface methodology (RSM) design-based analyses to optimize starch-based wound dressings that were characterized based on weight loss (WL%), swelling index (SI%), and mechanical strength (TS). The wound-dressing materials were prepared by employing a modified casting method, using various concentrations of starch (0.5-2 w/w%), polyvinyl alcohol (PVA) (0.5-2 weight%), citric acid (1.5-4 weight%), and glycerol (1.5-4 weight%) to yield wound-dressing films with appropriate combinations of in vitro degradation, swelling index, and tensile strength. As a result of the response surface method-based analysis, the swelling index, in vitro degradation, and tensile strength were linearly related to variations in the formulation of organic components. Based on our experimental investigations, the optimized film (formulation: 1 weight% PVA, 2 weight% starch, 1.5 weight% citric acid, and 1.5 weight% glycerol) exhibited an outstanding swelling index (343.52%), suitable in vitro degradation (53.22%), and excellent tensile strength (8.82 MPa). The response surface plots for the dependent variables, swelling index (SI%), weight loss (WL%), and mechanical strength (TS), showed that in all dual relations, the PVA-starch combination significantly affected all dependent variables; however, the PVA-citric acid interaction showed the most excellent effect on the swelling index. As a result, every component of the resulting film had a lesser amount of all ingredients to achieve better properties at a lower material cost. Starch-based/PVA films have been identified in this paper as optimal and more affordable wound-dressing films.

Preparation and Characterization of Eco-Friendly Transparent Antibacterial Starch/Polyvinyl Alcohol Materials for Use as Wound-Dressing.

In this study, eco-friendly and transparent starch-based/polyvinyl alcohol/citric acid composite films are evaluated for their efficacy as wound dressing materials. The starch/polyvinyl alcohol (PVA) materials with added citric acid (0.46-1.83 wt%) and glycerol were made and handled based on the modified casting method. This new formulation decreases the amount of PVA used in the conventional preparation method. Citric acid ensures an appropriate antibacterial environment for wound-dressing materials. The mechanical, chemical, and surface morphological properties of such films were assessed and analyzed by tensile strength tests, UV-Vis spectrometry, swelling index, and scanning electron microscopy (SEM). Furthermore, the water vapor transmission (WVT) quantity was measured for an ideal wound-healing process to investigate an optimal moisture environment around the wound bed. Moreover, the pH level of the dressings was measured to examine the possibility of bacterial growth around these starch-based films. Additionally, the films' in-vitro antibacterial activities were studied against the two most common Gram-positive and Gram-negative bacteria (Escherichia coli and Staphylococcus aureus). The new starch-based dressings demonstrated suitable degradation, antibacterial activity, fluid absorption, and adequate mechanical strength, representing wound-dressing materials' vital features.

Comparative Evaluation of Artificial Neural Networks and Data Analysis in Predicting Liposome Size in a Periodic Disturbance Micromixer.

Artificial neural networks (ANN) and data analysis (DA) are powerful tools for supporting decision-making. They are employed in diverse fields, and one of them is nanotechnology; for example, in predicting silver nanoparticles size. To our knowledge, we are the first to use ANN to predict liposome size (LZ). Liposomes are lipid nanoparticles used in different biomedical applications that can be produced in Dean-Forces-based microdevices such as the Periodic Disturbance Micromixer (PDM). In this work, ANN and DA techniques are used to build a LZ prediction model by using the most relevant variables in a PDM, the Flow Rate Radio (FRR), and the Total Flow Rate (TFR), and the temperature, solvents, and concentrations were kept constant. The ANN was designed in MATLAB and fed data from 60 experiments with 70% training, 15% validation, and 15% testing. For DA, a regression analysis was used. The model was evaluated; it showed a 0.98147 correlation coefficient for training and 0.97247 in total data compared with 0.882 obtained by DA.

Numerical and Experimental Validation of Mixing Efficiency in Periodic Disturbance Mixers.

The shape and dimensions of a micromixer are key elements in the mixing process. Accurately quantifying the mixing efficiency enables the evaluation of the performance of a micromixer and the selection of the most suitable one for specific applications. In this paper, two methods are investigated to evaluate the mixing efficiency: a numerical model and an experimental model with a software image processing technique. Using two methods to calculate the mixing efficiency, in addition to corroborating the results and increasing their reliability, creates various possible approaches that can be selected depending on the circumstances, resources, amount of data to be processed and processing time. Image processing is an easy-to-implement tool, is applicable to different programming languages, is flexible, and provides a quick response that allows the calculation of the mixing efficiency using a process of filtering of images and quantifying the intensity of the color, which is associated with the percentage of mixing. The results showed high similarity between the two methods, with a difference ranging between 0 and 6% in all the evaluated points.

Parametric Study of the Factors Influencing Liposome Physicochemical Characteristics in a Periodic Disturbance Mixer.

Liposomes encapsulate different substances ranging from drugs to genes. Control over the average size and size distribution of these nanoparticles is vital for biomedical applications since these characteristics determine to a high degree where liposomes will accumulate in the human body. Micromixers enable the continuous flow synthesis of liposomes, improving size control and reproducibility. Recently, Dean flow dynamics-based micromixers, such as the periodic disturbance mixer (PDM), have been shown to produce controlled-size liposomes in a scalable and reproducible way. However, contrary to micromixers based on molecular diffusion or chaotic advection, their production factors and their influence over liposome properties have not yet been addressed thoroughly. In this work, we present a comprehensive parametric study of the effects of flow conditions and molecular changing factors such as concentration, lipid type, and temperature on the physicochemical characteristics of liposomes. Numerical models and confocal images are used to quantitatively and qualitatively evaluate mixing performance under different liposome production conditions and their relationship with vesicle properties. The total flow rate (TFR) and, to a lesser extent, the flow rate ratio (FRR) control the liposome size and size distribution. Effects on liposome size are also observed by changing the molecular factors. Moreover, the liposome ζ potential is independent of the factors studied here. The micromixer presented in this work enables the production of liposomes as small as 24 nm, with monodispersed to low or close to low polydispersed liposome populations as well as a production rate as high as 41 mg/h.

The effect of different organic solvents in liposome properties produced in a periodic disturbance mixer: Transcutol®, a potential organic solvent replacement.

Liposomes are versatile particles used in the biomedical field as drug delivery systems (DDS). Liposome production using micromixers have shown to yield nanoparticles for DDS in a single step with a controllable size by changing flow conditions. Nonetheless, other factors such as the organic solvent, play a crucial role in the liposome formation process. Furthermore, drug solubility and toxicity are pivotal when deciding which organic solvent to choose. In this work, liposomes were produced in a periodic disturbance mixer (PDM). We investigated three conventional organic solvents: ethanol, methanol, and isopropanol as well as Transcutol®. We assessed the organic solvent influence on liposome characteristics (size, size distribution and zeta potential). Among the four organic solvents, Transcutol® yielded the smallest liposomes, which ranged from 80 nm to 160 nm. Moreover, a more in-depth investigation showed that Transcutol® produced smaller or similar-sized particles under different temperature and lipid concentration conditions, compared with ethanol. Furthermore, we proved that particles zeta potential was not influenced by the organic solvent, production temperature, or lipid concentration. This work results show that Transcutol® could replace the conventional alcohol-based solvents and can potentially avoid filtration steps due to its low toxicity. Therefore, the present approach is appealing for DDS development.

Surface Response Based Modeling of Liposome Characteristics in a Periodic Disturbance Mixer.

Liposomes nanoparticles (LNPs) are vesicles that encapsulate drugs, genes, and imaging labels for advanced delivery applications. Control and tuning liposome physicochemical characteristics such as size, size distribution, and zeta potential are crucial for their functionality. Liposome production using micromixers has shown better control over liposome characteristics compared with classical approaches. In this work, we used our own designed and fabricated Periodic Disturbance Micromixer (PDM). We used Design of Experiments (DoE) and Response Surface Methodology (RSM) to statistically model the relationship between the Total Flow Rate (TFR) and Flow Rate Ratio (FRR) and the resulting liposomes physicochemical characteristics. TFR and FRR effectively control liposome size in the range from 52 nm to 200 nm. In contrast, no significant effect was observed for the TFR on the liposomes Polydispersity Index (PDI); conversely, FRR around 2.6 was found to be a threshold between highly monodisperse and low polydispersed populations. Moreover, it was shown that the zeta potential is independent of TFR and FRR. The developed model presented on the paper enables to pre-establish the experimental conditions under which LNPs would likely be produced within a specified size range. Hence, the model utility was demonstrated by showing that LNPs were produced under such conditions.

Fabrication of Porous Gold Film Using Graphene Oxide as a Sacrificial Layer.

An original and simple fabrication process to produce thin porous metal films on selected substrates is reported. The fabrication process includes the deposition of a thin layer of gold on a substrate, spin coating of a graphene oxide dispersion, etching the gold film through the graphene oxide layer, and removing the graphene oxide layer. The porosity of the thin gold film is controlled by varying the etching time, the thickness of the gold film, and the concentration of the graphene oxide dispersion. Images by scanning electron and metallurgical microscopes show a continuous gold film with random porosity formed on the substrate with a porosity size ranging between hundreds of nanometers to tens of micrometers. This general approach enables the fabrication of porous metal films using conventional microfabrication techniques. The proposed process is implemented to fabricate electrodes with patterned porosity that are used in a microfluidic system to manipulate living cells under dielectrophoresis. Porous electrodes are found to enhance the magnitude and spatial distribution of the dielectrophoretic force.

The effect of dielectrophoresis on living cells: crossover frequencies and deregulation in gene expression.

This article documents the effect of dielectrophoresis on living cells. Given the longer duration procedures performed on microfluidic platforms, the influence of electric fields of high intensity may be of interest in manipulations other than dielectrophoresis. The crossover frequencies of several cell lines were experimentally determined using a microfluidic device. The crossover frequencies are investigated at different medium conductivities for red blood cells, white blood cells-Jurkat, 92.1 and OCM melanoma, and MDA-MB-231 breast cancer cell lines. The effect of dielectrophoresis on the cells at the gene level was also investigated by studying the alteration in gene expressions using microarray analysis. The alterations in genes due to the manipulation of cells at 10 kHz and 100 kHz with a sinusoidal 10 V peak signal for 60 minutes are explored. The two frequencies correspond to negative and positive dielectrophoresis, respectively. The cell line MDA-MB-231 is used as a model for studying the genes in this work. The dielectrophoresis was found to alter genes related to apoptosis, rRNA transcription, cellular respiration, energy production, cellular transcriptional activity, and other cellular functions.

A Novel Physical Sensing Principle for Liquid Characterization Using Paper-Based Hygro-Mechanical Systems (PB-HMS).

In recent years paper-based microfluidic systems have emerged as versatile tools for developing sensors in different areas. In this work; we report a novel physical sensing principle for the characterization of liquids using a paper-based hygro-mechanical system (PB-HMS). The PB-HMS is formed by the interaction of liquid droplets and paper-based mini-structures such as cantilever beams. The proposed principle takes advantage of the hygroscopic properties of paper to produce hygro-mechanical motion. The dynamic response of the PB-HMS reveals information about the tested liquid that can be applied to characterize certain properties of liquids. A suggested method to characterize liquids by means of the proposed principle is introduced. The experimental results show the feasibility of such a method. It is expected that the proposed principle may be applied to sense properties of liquids in different applications where both disposability and portability are of extreme importance.

Model-based analysis of a dielectrophoretic microfluidic device for field-flow fractionation.

We present the development of a dynamic model for predicting the trajectory of microparticles in microfluidic devices, employing dielectrophoresis, for Hyperlayer field-flow fractionation. The electrode configuration is such that multiple finite-sized electrodes are located on the top and bottom walls of the microchannel; the electrodes on the walls are aligned with each other. The electric potential inside the microchannel is described using the Laplace equation while the microparticles' trajectory is described using equations based on Newton's second law. All equations are solved using finite difference method. The equations of motion account for forces including inertia, buoyancy, drag, gravity, virtual mass, and dielectrophoresis. The model is used for parametric study; the geometric parameters analyzed include microparticle radius, microchannel depth, and electrode/spacing lengths while volumetric flow rate and actuation voltage are the two operating parameters considered in the study. The trajectory of microparticles is composed of transient and steady state phases; the trajectory is influenced by all parameters. Microparticle radius and volumetric flow rate, above the threshold, do not influence the steady state levitation height; microparticle levitation is not possible below the threshold of the volumetric flow rate. Microchannel depth, electrode/spacing lengths, and actuation voltage influence the steady-state levitation height.

Impact of single-walled carbon nanotubes on the embryo: a brief review.

Carbon nanotubes (CNTs) are considered one of the most interesting materials in the 21st century due to their unique physiochemical characteristics and applicability to various industrial products and medical applications. However, in the last few years, questions have been raised regarding the potential toxicity of CNTs to humans and the environment; it is believed that the physiochemical characteristics of these materials are key determinants of CNT interaction with living cells and hence determine their toxicity in humans and other organisms as well as their embryos. Thus, several recent studies, including ours, pointed out that CNTs have cytotoxic effects on human and animal cells, which occur via the alteration of key regulator genes of cell proliferation, apoptosis, survival, cell-cell adhesion, and angiogenesis. Meanwhile, few investigations revealed that CNTs could also be harmful to the normal development of the embryo. In this review, we will discuss the toxic role of single-walled CNTs in the embryo, which was recently explored by several groups including ours.

Significant toxic role for single-walled carbon nanotubes during normal embryogenesis.

In order to investigate the effect of SWCNTs in the embryo, we examined the outcome of SWCNTs in avian embryo at an early stage of development. We found that SWCNTs-treatment inhibits the angiogenesis of the chorioallantoic membrane (CAM) and in the chicken embryo. Moreover, we showed that SWCNTs can harm the normal development of the embryo since all SWCNTs-exposed embryos are smaller in comparison with their matched controls. We also found that the majority of SWCNTs-exposed embryos die before 12days of incubation. Macroscopic examination did not reveal any anomalies in these embryos. However, RT-PCR analysis of eleven genes, which are important regulators of cell proliferation, apoptosis, survival and angiogenesis, shows that these genes are deregulated in brain and liver tissues from SWCNTs-treated embryos in comparison with their matched controls. This study suggests that SWCNTs could have a very toxic effect on the normal development of the embryo. FROM THE CLINICAL EDITOR: In this study, a significant toxicity of single-walled carbon nanotubes was observed during normal embryogenesis: the nanotubes inhibited the angiogenesis of the chorioallantoic membrane (CAM) in chicken embryos. All exposed embryos died before 12 days of incubation, suggesting a severe effect.

A new concept to measure cell proliferation using Fourier transform infrared spectroscopy.

In our laboratory, we recently developed a new technique to measure cell proliferation that is based on infrared spectro-photometry and the density of cell culture medium. The fluid exchange between intra and extra cellular environments is the key to our method. Using this technique, we found that cell proliferation assessment may be performed much faster than presently existing methods, using two separate pieces of equipment (a cell culture incubator and an interferometer). We confirmed the viability of our method using five different cell lines, breast cancer cells (BT20), mouse normal embryonic fibroblast (NEF) as well as those expressing E6/E7 onco-proteins of human papillomavirus (HPV) type 16, and a human cervical cancer cell line (HeLa). Based on our findings, we propose the design of a mini-incubator allowing cell culture as well as infrared spectra collection of the culture medium, as an accessory to the FTIR work bench, which would become a promising arrangement for continuous cell proliferation monitoring. Moreover, the use of the collected culture medium will be highly efficient in terms of reducing both experimental time and cost.

Optimization of Q-factor of AFM cantilevers using genetic algorithms.

Micro cantilever beams have been intensively used in sensing applications including to scanning profiles and surfaces where there resolution and imaging speed are critical. Force resolution is related to the Q-factor. When the micro-cantilever operates in air with small separation gaps, the Q-factor is even more reduced due to the squeeze-film damping effect. Thus, the optimization of the configuration of an AFM micro-cantilever is presented in this work with the objective of improving its Q-factor. To accomplish this task, we propose the inclusion of holes as breathing chimneys in the initial design to reduce the squeeze-film damping effect. The evaluation of the Q-factor was carried out using finite element model, which is implemented to work together with the squeeze-film damping model. The methodology applied in the optimization process was genetic algorithms, which considers as constraints the maximum allowable stress, fundamental frequency and spring constant with respect to the initial design. The results show that the optimum design, which includes holes with an optimal location, increases the Q-factor almost five times compared to the initial design.

Analytical solutions and validation of electric field and dielectrophoretic force in a bio-microfluidic channel.

In a microbiological device, cell or particle manipulation and characterization require the use of electric field on different electrodes in several configurations and shapes. To efficiently design microelectrodes within a microfluidic channel for dielectrophoresis focusing, manipulation and characterization of cells, the designer will seek the exact distribution of the electric potential, electric field and hence dielectrophoresis force exerted on the cell within the microdevice. In this paper we describe the approach attaining the analytical solution of the dielectrophoretic force expression within a microchannel with parallel facing same size electrodes present on the two faces of channel substrates, with opposite voltages on the pair electrodes. Simple Fourier series mathematical expressions are derived for electric potential, electric field and dielectric force between two distant finite-size electrodes. Excellent agreement is found by comparing the analytical results calculated using MATLAB™ with numerical ones obtained by Comsol. This analytical result can help the designer to perform simple design parametric analysis. Bio-microdevices are also designed and fabricated to illustrate the theoretical solution results with the experimental data. Experiments with red blood cells show the dielectrophoretic force contour plots of the analytical data matched to the experimental results.