Real-time monitoring and actuation of a hybrid siphon valve for hematocrit-independent plasma separation from whole blood.

Centrifugal microfluidics have emerged as a pivotal area of research spanning multiple domains, including medicine and chemistry. Among passive valving strategies, siphon valves have gained prominence due to their inherent simplicity and self-reliance, eliminating the need for external equipment. However, achieving optimal valve performance mandates supplementary elements like surface adjustments or pneumatic pressure. These introduce intricacies such as time-dependent behavior and augmented spatial demands. This research introduces inventive design and manufacturing methodologies to amplify siphon valve functionality. Our proposed innovation situates the siphon microchannel on the external surface of the primary chamber, linked via an inlet. The crux of novelty lies in the adaptable material selection for the microchannel's upper or lower surfaces, allowing the integration of hydrophilic materials such as glass or super hydrophilic coverslips, ensuring a leakage-free operation. Our approach offers a streamlined concept and manufacturing process, ensures consistent time-independent functionality, and accommodates the integration of multiple siphon valves within a solitary chamber, tailored for specific applications. Experimental evaluations validate a robust alignment between acquired data and analytical outcomes based on a modified equation. A customized disc is engineered, featuring four siphon valves meticulously calibrated for hematocrit (HCT) levels spanning from 20% to 50% at 10% intervals. Harnessing these valves yields a substantial surge in plasma separation efficiency, scaling up to 75%. Notably, this performance eclipses traditional single-valve reliant microfluidic methodologies, achieving a purity level exceeding 99% in plasma separation. These findings underscore the auspicious practical applicability of our proposed technique in plasma separation, fostering heightened platelet concentration, and expediting blood sample analysis.

A New Strategy for Achieving Shape Memory Effects in 4D Printed Two-Layer Composite Structures.

In this study, a new strategy and design for achieving a shape memory effect (SME) and 4D printed two-layer composite structures is unveiled, thanks to fused deposition modeling (FDM) biomaterial printing of commercial filaments, which do not have an SME. We used ABS and PCL as two well-known thermoplastics, and TPU as elastomer filaments that were printed in a two-layer structure. The thermoplastic layer plays the role of constraint for the elastomeric layer. A rubber-to-glass transition of the thermoplastic layer acts as a switching phenomenon that provides the capability of stabilizing the temporary shape, as well as storing the deformation stress for the subsequent recovery of the permanent shape by phase changing the thermoplastic layer in the opposite direction. The results show that ABS-TPU had fixity and recovery ratios above 90%. The PCL-TPU composite structure also demonstrated complete recovery, but its fixity was 77.42%. The difference in the SME of the two composite structures is related to the transition for each thermoplastic and programming temperature. Additionally, in the early cycles, the shape-memory performance decreased, and in the fourth and fifth cycles, it almost stabilized. The scanning electron microscopy (SEM) photographs illustrated superior interfacial bonding and part integrity in the case of multi-material 3D printing.

Multiphysics modeling and experiments on ultrasound-triggered drug delivery from silk fibroin hydrogel for Wilms tumor.

In this study, silk fibroin hydrogel is employed as a carrier for vincristine and ultrasound as a method to accelerate the drug release. The Acoustic, deformation, swelling, and diffusion fields are coupled in a multi-physics model to optimize the drug delivery. A transient acoustic structure model and a chemically controlled mechanism are implemented, while a coupled model of deformation and diffusion takes the impact of mechanical forces into account. An evaluation of the model is made through experiments. To monitor the drug release rate over 40 days following injection of silk hydrogel syringes containing vincristine, they were triggered by ultrasound in some selected time intervals. Drug release rates were determined using different power intensities and induction times. Computed simulation results and laboratory experiments revealed that ultrasound could cause a significant improvement in drug release rate, with an increase of up to 10 times over a release without ultrasound stimulation. By increasing the ultrasound power and induction time up to their peak value, the drug release rate rises and drops then. Predictions of the drug release rate by the model were in good agreement with those observed in experiments. This makes the model a valuable tool for potential predictions. Results showed that the ultrasound triggers the increased cell death rates, but the Wilms tumor cells were resistant to higher concentrations of released drugs.

Computational analysis of vincristine loaded silk fibroin hydrogel for sustained drug delivery applications: Multiphysics modeling and experiments.

In this paper, silk fibroin hydrogel is used as a drug carrier for vincristine. To optimize drug delivery, a multi-physics model is proposed that couples the deformation and diffusion fields. We applied inverse analysis and general continuum mechanics to define material parameters and mechanical properties. To examine the mass transport and chemical behavior, an affinity-based diffusion and degradation of a drug-loaded polymer matrix is employed. Some experiments are carried out to examine the capability of the presented model. After preparing the vincristine loaded silk hydrogel syringes, they were injected into PBS and enzyme solutions to monitor the drug release rate for 40 days. Obtained results from the computational simulation and laboratory tests showed that the silk fibroin hydrogel was deswelled after about 40 days in enzyme solution. Degradation led to faster and higher doses of vincristine drug release in comparison to the case of PBS solution. Results revealed that more than 80% of the drug was released in the first 5 days in the enzyme solution, but in PBS solution only 10% of the drug was released during 40 days. The model predictions of deswelling behavior and drug release rate were in good agreement with those of experimental results. Therefore, it can be employed as a reliable tool for further predictions.

A Microfabrication Method of PCL Scaffolds for Tissue Engineering by Simultaneous Two PDMS Molds Replication.

Not very far away, "tissue engineering" will become one of the most important branches of medical science for curing many types of diseases. This branch needs the cooperation of a wide range of sciences like medicine, chemistry, cellular biology, and genetic and mechanical engineering. Different parameters affect the final produced tissue, but the most important one is the quality and biocompatibility of the scaffold with the desired tissue which can provide the functionality of "native ECM" as well. The quality of the scaffold is directly dependent on its materials, design, and method of fabrication. As to the design and fabrication, there are two main categories: (a) random microporosity such as phase separation, electrospinning, and fused deposition modeling (3D printing) and (b) designed microporosity mostly achievable by stereo lithography and soft lithography. The method of fabrication implemented in this research is a novel method in soft lithography employing a type of "replica molding" with one pair of polydimethylsiloxane (PDMS) molds in contrast to traditional replica molding with just one single mold. In this operation, the solution of polycaprolactone in chloroform is initially prepared, and one droplet of the solution is placed between the molds while a preset pressure is applied to maintain the molds tightly together during the solidification of the polymer layer and vaporization of the solvent. Thus, a perfect warp and woof pattern is created. In this research, it has been approved that this is a feasible method for creating complex patterns and simple straight fiber patterns with different spacings and pore sizes. Cell attachment and migration was studied to find the optimum pore size. It was shown that the small pore size improves the cells' adhesion while reducing cell migration capability within the scaffold.

Ultrasound induced strain cytoskeleton rearrangement: An experimental and simulation study.

Cytoskeleton and specially actin filaments are responsible for mechanical modulation of cellular behavior. These structures could be fluidized in response to transient mechanical cues. Ultrasound devices have been widely used in medicine which their generated ultrasonic waves could disrupt/fluidize actin filaments in cytoskeleton and thus could affect cellular organization. Present research aims at revealing the mechanism of fluidization caused by ultrasound induced strains. First, a numerical simulation was performed to reveal the effect of oscillating ultrasonic pressure on induced deformation in the cell with respect to different cell geometries and exposure conditions. The model revealed that higher pressure and frequencies induce higher levels of strain in the cell. The results also showed that spread cells are more exposed to cytomechanical remodeling due to higher level of ultrasound induced deformations but also the effect of harmonic excitation decreases with spreading. Furthermore, strain values found to be less in the nucleus comparing the value in the cytoplasm, but still these strains can affect the behavior of the cell through mechanotransduction mechanisms. Then, different experimental ultrasound protocols were used to evaluate their effects on cell viability and actin cytoskeleton distribution. Results of Live/Dead assay indicated that high pressure and duration of the exposure had negative effects on the viability of C2C12 cells, while the viability ratio still remained above 85%. In addition, actin fluorescent staining showed that high levels of filament disruption could occur with increasing the pressure. The results of this study shed light on cellular response to mechanical stimuli applied by ultrasonic waves.

Surface acoustic waves induced micropatterning of cells in gelatin methacryloyl (GelMA) hydrogels.

Acoustic force patterning is an emerging technology that provides a platform to control the spatial location of cells in a rapid, accurate, yet contactless manner. However, very few studies have been reported on the usage of acoustic force patterning for the rapid arrangement of biological objects, such as cells, in a three-dimensional (3D) environment. In this study, we report on a bio-acoustic force patterning technique, which uses surface acoustic waves (SAWs) for the rapid arrangement of cells within an extracellular matrix-based hydrogel such as gelatin methacryloyl (GelMA). A proof-of-principle was achieved through both simulations and experiments based on the in-house fabricated piezoelectric SAW transducers, which enabled us to explore the effects of various parameters on the performance of the built construct. The SAWs were applied in a fashion that generated standing SAWs (SSAWs) on the substrate, the energy of which subsequently was transferred into the gel, creating a rapid, and contactless alignment of the cells (<10 s, based on the experimental conditions). Following ultraviolet radiation induced photo-crosslinking of the cell encapsulated GelMA pre-polymer solution, the patterned cardiac cells readily spread after alignment in the GelMA hydrogel and demonstrated beating activity in 5-7 days. The described acoustic force assembly method can be utilized not only to control the spatial distribution of the cells inside a 3D construct, but can also preserve the viability and functionality of the patterned cells (e.g. beating rates of cardiac cells). This platform can be potentially employed in a diverse range of applications, whether it is for tissue engineering, in vitro cell studies, or creating 3D biomimetic tissue structures.

Acoustic Manipulation of Bio-Particles at High Frequencies: An Analytical and Simulation Approach.

Manipulation of micro and nano particles in microfluidic devices with high resolution is a challenge especially in bioengineering applications where bio-particles (BPs) are separated or patterned. While acoustic forces have been used to control the position of BPs, its theoretical aspects need further investigation particularly for high-resolution manipulation where the wavelength and particle size are comparable. In this study, we used a finite element method (FEM) to amend analytical calculations of acoustic radiation force (ARF) arising from an imposed standing ultrasound field. First, an acoustic solid interaction (ASI) approach was implemented to calculate the ARF exerted on BPs and resultant deformation induced to them. The results were then used to derive a revised expression for the ARF beyond the small particle assumption. The expression was further assessed in numerical simulations of one- and multi-directional standing acoustic waves (SAWs). Furthermore, a particle tracing scheme was used to investigate the effect of actual ARF on separation and patterning applications under experimentally-relevant conditions. The results demonstrated a significant mismatch between the actual force and previous analytical predictions especially for high frequencies of manipulation. This deviation found to be not only because of the shifted ARF values but also due to the variation in force maps in multidirectional wave propagation. Findings of this work can tackle the simulation limitations for spatiotemporal control of BPs using a high resolution acoustic actuation.

Efficient three-phase reconstruction of heterogeneous material from 2D cross-sections via phase-recovery algorithm.

Digital reconstruction of a complex heterogeneous media from the limited statistical information, mostly provided by different imaging techniques, is the key to the successful computational analysis of this important class of materials. In this study, a novel approach is presented for three-dimensional (3D) reconstruction of a three-phase microstructure from its statistical information provided by two-dimensional (2D) cross-sections. In this three-step method, first two-point correlation functions (TPCFs) are extracted from the cross-section(s) using a spectral method suitable for the three-phase media. In the next step, 3D TPCFs are approximated for all vectors in a representative volume element (RVE). Finally, the 3D microstructure is realized from the full-set TPCFs obtained in the previous step, using a modified phase-recovery algorithm. The method is generally applicable to any complex three-phase media, here illustrated for an SOFC anode microstructure. The capabilities and shortcomings of the method are then investigated by performing a qualitative comparison between example cross-sections obtained computationally and their experimental equivalents. Finally, it is shown that the method almost conserves key microstructural properties of the media including tortuosity, percolation and three-phase boundary length (TPBL).