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.

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.

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.

Dielectrophoresis Multipath Focusing of Microparticles through Perforated Electrodes in Microfluidic Channels.

This paper presents focusing of microparticles in multiple paths within the direction of the flow using dielectrophoresis. The focusing of microparticles is realized through partially perforated electrodes within the microchannel. A continuous electrode on the top surface of the microchannel is considered, while the bottom side is made of a circular meshed perforated electrode. For the mathematical model of this microfluidic channel, inertia, buoyancy, drag and dielectrophoretic forces are brought up in the motion equation of the microparticles. The dielectrophoretic force is accounted for through a finite element discretization taking into account the perforated 3D geometry within the microchannel. An ordinary differential equation is solved to track the trajectories of the microparticles. For the case of continuous electrodes using the same mathematical model, the numerical simulation shows a very good agreement with the experiments, and this confirms the validation of focusing of microparticles within the proposed perforated electrode microchannel. Microparticles of silicon dioxide and polystyrene are used for this analysis. Their initial positions and radius, the Reynolds number, and the radius of the pore in perforated electrodes mainly conduct microparticles trajectories. Moreover, the radius of the pore of perforated electrode is the dominant factor in the steady state levitation height.

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.

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.

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.