Microfluidic Preparation Research Articles

Fabrication of apigenin and adenosine-loaded nanoparticles against doxorubicin-induced myocardial infarction by reducing inflammation and oxidative stress.

The study's goals are to fabricate PLGA nanoparticles (PNPs) loaded with apigenin (AP) and adenosine (AD) using a microfluidic preparation method to a standard emulsification method and investigate the possible heart-protective effects of AP-AD PNPs made using the emulsification method. Compared to microfluidics, the emulsification method fabricated small-size nanoparticles, which are better at encapsulating drugs, retaining more drugs, and having a low viscosity for the myocardial infarction (MI) injection. TheMI model was developed using SD rats injected under the skin with 85mg/kg doxorubicin (DOX) for 2 days. The metabolic results showed that our AP-AD PNPs accelerated the blood flow in rats with MI, which increased the amounts of AP and AD in the circulatory system. This led to significant improvements in the cardiac index and lower amounts of AST, LDH, and CK in the blood. A histopathological study using Hematoxylin&eosin, and TUNEL staining showed that cardiac function had improved and apoptosis had decreased. Moreover, tests that checked the amounts of IL-6, TNF-α, NO, GSH, MDA, and SOD showed that AP-AD PNPs may help treat MI by reducing oxidative stress and inflammation, making it a potentially useful therapeutic approach.

Usage of Machine Learning Techniques to Classify and Predict the Performance of Force Sensing Resistors

Recently, there has been a huge increase in the different ways to manufacture polymer-based sensors. Methods like additive manufacturing, microfluidic preparation, and brush painting are just a few examples of new approaches designed to improve sensor features like self-healing, higher sensitivity, reduced drift over time, and lower hysteresis. That being said, we believe there is still a lot of potential to boost the performance of current sensors by applying modeling, classification, and machine learning techniques. With this approach, final sensor users may benefit from inexpensive computational methods instead of dealing with the already mentioned manufacturing routes. In this study, a total of 96 specimens of two commercial brands of Force Sensing Resistors (FSRs) were characterized under the error metrics of drift and hysteresis; the characterization was performed at multiple input voltages in a tailored test bench. It was found that the output voltage at null force (Vo_null) of a given specimen is inversely correlated with its drift error, and, consequently, it is possible to predict the sensor’s performance by performing inexpensive electrical measurements on the sensor before deploying it to the final application. Hysteresis error was also studied in regard to Vo_null readings; nonetheless, a relationship between Vo_null and hysteresis was not found. However, a classification rule base on k-means clustering method was implemented; the clustering allowed us to distinguish in advance between sensors with high and low hysteresis by relying solely on Vo_null readings; the method was successfully implemented on Peratech SP200 sensors, but it could be applied to Interlink FSR402 sensors. With the aim of providing a comprehensive insight of the experimental data, the theoretical foundations of FSRs are also presented and correlated with the introduced modeling/classification techniques.

Formation of flake-like DAAF crystals with tunable size realized on a microfluidic platform for binder-free initiator explosives

Flake-like energetic crystal has a great potential to achieve initiator explosive with high reactivity, low initiation threshold, high safety, and facile post-processing, but it has been limited for 3,3′-diamino-4,4′-azoxyfurazan (DAAF) by the difficulties in controlling crystal morphology. Here reported is a microfluidic preparation of flake-like DAAF crystals (f-DAAF) with tunable size by combined effect of the adding of facet-controlling agent (nigrosin alcohol soluble) and tuning of the external crystallization conditions. The results show that the crystal system of f-DAAF belong to monoclinic system, the (−201) facet is the largest exposed face. The f-DAAF possess high crystallinity, tunable flake aspect ratio from 6.15 to 66.8 and specific surface area from 2.57 to 5.67 m2·g−1. Molecular dynamics simulations were performed to investigate the selective interactions between the two molecules (facet-controlling agent and solvent) and different crystal faces of DAAF in a real experiment environment. Combined with the experimental results, a possible growth mechanism of the flake-like morphology was discussed. It is found that the f-DAAF not only possess lower impact sensitivity itself, but also can reduce the impact sensitivity of other explosives with high impact sensitivity. The electric explosion derived flyer initiation experiments show that the initiation sensitivity of f-DAAF is much lower than that of raw DAAF in micron size, and comparable to that of ultrafine DAAF. This work demonstrates the promising application potential of f-DAAF as high-performance initiator explosives with low initiation threshold and high safety, and also provides an effective way for their preparation.

A temperature-responsive dual-hormone foam nanoengine improves rectal absorptivity of insulin-pramlintide for diabetes treatment.

Despite the therapeutic benefits of insulin-pramlintide dual-hormone therapy in diabetes, its application potential has been limited due to a lack of efficient delivery routes. Here, we developed a temperature-responsive dual-hormone foam nanoengine (HormFoam) and combined it with a customized spraying device to further construct an in situ foam-generating system for improving the rectal bioavailability of dual-hormone therapy. To support rapid clinical translation, a continuous microfluidic preparation for HormFoam was proposed, including the power unit of perfluorocarbon nanodroplets and the pharmaceutical components Pluronic F127-functionalized liposomal insulin and pramlintide. We found that HormFoam could consistently generate foams to drive drugs forward after rectal administration, which enhanced intestinal distribution and mucosa absorption, leading to systemic codelivery of insulin-pramlintide. HormFoam reproduced the physiology of endocrine pancreas for glycemic control and induced body weight loss while reversing metabolic disorders in diabetic mice with good biosafety. Therefore, HormFoam represents a state-of-the-art dual-hormone regimen with the potential to address unmet needs in diabetes management.

Hydrophilic phycocyanin encapsulation in PLGA nanoparticles using benchtop microfluidic device

Phycocyanin (PC), a sensitive hydrophilic protein with significant biological functions, is prone to denaturation in harsh environmental conditions. Here, we employ a microfluidic-assisted nanoprecipitation approach using poly lactic-co-glycolic acid (PLGA) as a protective coating material to shield PC from such conditions. Despite the complexity of microfluidic device preparation and the challenge of encapsulating water-like protein with high association efficiency, our study demonstrates the successful generation of nanosized PC-loaded particles using a 1-mm-width microfluidic device. Optimal device parameters, including a 90˚ intersecting angle, a 3-cm-length outlet channel, and a total flow rate of 396 µLmin−1, yielded particles approximately 200 nm in size with an association efficiency (AE) of around 80 %. Notably, DMSO proved to be an effective organic solvent for preserving PC. Interestingly, surfactants typically employed for stability and biocompatibility in microfluidic techniques, were found to be unnecessary in this system, potentially altering the secondary structure of PC, as indicated by circular dichroism (CD) spectra. Overall, this research confirms the feasibility of producing nanosized particles with monodisperse spherical morphology using a benchtop microfluidic device. Moreover, the enhanced association efficiency of hydrophilic protein in PLGA holds significant promise for encapsulating non-hydrophobic proteins.

Microfluidic preparation and optimization of (Kollicoat ® IR-b-PCL) polymersome for co-delivery of Nisin-Curcumin in breast cancer application

This work aimed to develop amphiphilic nanocarriers such as polymersome based diblock copolymer of Kollicoat ® IR −block-poly(ε-caprolactone) (Kollicoat ® IR-b-PCL) for potential co-delivery of Nisin (Ni) and Curcumin (CUR) for treatment of breast cancer. To generate multi-layered nanocarriers of uniform size and morphology, microfluidics was used as a new technology. In order to characterise and optimize polymersome, design of experiments (Design-Expert) software with three levels full factorial design (3-FFD) method was used. Finally, the optimized polymersome was produced with a spherical morphology, small particle size (dH < 200 nm), uniform size distribution (PDI < 0.2), and high drug loading efficiency (Ni 78 % and CUR 93 %). Furthermore, the maximum release of Ni and CUR was found to be roughly 60 % and 80 % in PBS, respectively. Cytotoxicity assays showed a slight cytotoxicity of Ni and CUR −loaded polymersome (N- Ni /CUR) towards normal cells while demonstrating inhibitory activity against cancer cells compared to the free drugs. Also, the apoptosis assays and cellular uptake confirmed the obtained results from cytotoxic analysis. In general, this study demonstrated a microfluidic approach for preparation and optimization of polymersome for co-delivery of two drugs into cancer cells.

Finger-operated pumping platform for microfluidic preparation of nanoparticles

Finger-operated pumping platform for microfluidic preparation of nanoparticles

Process optimization for microfluidic preparation of liposomes using food-grade components

This study explores the potential for optimizing a sustainable manufacturing process that maintains the essential characteristics of conventional liposomes using food-grade solvents and components. The focus was comparing the physicochemical, morphological, and interfacial properties of liposomes produced with these food-grade ingredients to those made by conventional methods. It was found that there was no significant difference in particle size (195.87 ± 1.40 nm) and ζ-potential (−45.13 ± 0.65 mV) between liposomes made from food-grade and conventional materials. The manufacturing process for liposomes, utilizing food-grade solvents and components, was optimized through the application of Plackett-Burman design and response surface methodology. This approach helped identify key parameters (soy lecithin, β-sitosterol, W/O ratio) and their optimal values (3.17 g, 0.25 g, 1:2.59). These findings suggest that it is possible to enhance the use of liposomes as an effective and safe delivery system in the food industry, adhering to the strict guidelines set by regulatory agencies.

Microfluidic preparation of surfactant-free ultrafine DAAF with tunable particle size for insensitive initiator explosives

High purity and ultrafine DAAF (u-DAAF) is an emerging insensitive charge in initiators. Although there are many ways to obtain u-DAAF, developing a preparation method with stable operation, accurate control, good quality consistency, equipment miniaturization, and minimum manpower is an inevitable requirement to adapt to the current social technology development trend. Here reported is the microfluidic preparation of u-DAAF with tunable particle size by a passive swirling microreactor. Under the guidance of recrystallization growth kinetics and mixing behavior of fluids in the swirling microreactor, the key parameters (liquid flow rate, explosive concentration and crystallization temperature) were screened and optimized through screening experiments. Under the condition that no surfactant is added and only experimental parameters are controlled, the particle size of recrystallized DAAF can be adjusted from 98 nm to 785 nm, and the corresponding specific surface area is 8.45 m2·g−1 to 1.33 m2·g−1. In addition, the preparation method has good batch stability, high yield (90.8%–92.6%) and high purity (99.0%–99.4%), indicating a high practical application potential. Electric explosion derived flyer initiation tests demonstrate that the u-DAAF shows an initiation sensitivity much lower than that of the raw DAAF, and comparable to that of the refined DAAF by conventional spraying crystallization method. This study provides an efficient method to fabricate u-DAAF with narrow particle size distribution and high reproducibility as well as a theoretical reference for fabrication of other ultrafine explosives.

Microfluidic preparation of monodisperse PLGA-PEG/PLGA microspheres with controllable morphology for drug release.

Monodisperse biodegradable polymer microspheres show broad applications in drug delivery and other fields. In this study, we developed an effective method that combines microfluidics with interfacial instability to prepare monodispersed poly(lactic-co-glycolic acid)-b-polyethylene glycol (PLGA-PEG)/poly(lactic-co-glycolic acid) (PLGA) microspheres with tailored surface morphology. By adjusting the mass ratio of PLGA-PEG to PLGA, the concentration of stabilizers and the type of PLGA, we generated microspheres with various unique folded morphologies, such as "fishtail-like", "lace-like" and "sponge-like" porous structures. Additionally, we demonstrated that risperidone-loaded PLGA-PEG/PLGA microspheres with these folded morphologies significantly enhanced drug release, particularly in the initial stage, by exhibiting a logarithmic release profile. This feature could potentially address the issue of delayed release commonly observed in sustained-release formulations. This study presents a straightforward yet effective approach to construct precisely engineered microspheres offering enhanced control over drug release dynamics.

Microfluidic Preparation of pH-Responsive Microsphere Fibers and Their Controlled Drug Release Properties.

In this study, a capillary microfluidic device was constructed, and sodium alginate solution and a pH-sensitive hydrophobic polymer (p(BMA-co-DAMA-co-MMA)) solution were introduced into the device for the preparation of hydrogel fibers loaded with polymer microspheres. The structure of the microsphere fiber, including the size and spacing of the microspheres, could be controlled by flow rate, and the microspheres were able to degrade and release cargo responding to acidic pH conditions. By modification with carboxymethylcellulose (CMC), alginate hydrogel exhibited enhanced pH sensitivity (shrunk in acidic while swollen in basic condition). This led to an impact on the diffusion rate of the molecules released from the inner microspheres. The microsphere fiber showed dramatic and negligible degradation and drug release in tumor cell (i.e., A431 and A549 cells) and normal cell environments, respectively. These results indicated that the microsphere fiber prepared in this study showed selective drug release in acidic environments, such as tumor and inflammation sites, which could be applied as a smart surgical dressing with normal tissue protective properties.

#353 : Microfluidic Preparation of Spermatozoa: A Potential Approach in Assisted Reproductive Technology

Background and Aims: While density gradient centrifugation (DGC) is a conventional method in sperm preparation, this method can induce reactive oxygen species (ROS) which cause sperm dysfunction, sperm DNA damage, a recent advancement in sperm processing using microfluidic system is believed to reduce damage and to select the good quality sperm. The aim of this study was to evaluate the effectiveness of sperm preparation between DGC method and microfluidic system. Method: 30 semen samples were separated into 2 equal small samples, each sample was processed by DGC methods (control) and microfluidic (intervention) respectively. Pre- and post processing parameters was evaluated according to WHO-2010 and the DNA fragmentation index (DFI) was determined by flow cytometry technique. Results: The result showed that DFI values from the microfluidic preparation (0.67 ± 0.53%) was significantly lower than that of the DCG group (1.18 ± 13.73%). In particular, for semen samples with high DFI (&gt;15%), the microfluidic system showed a noticeable reduction in DFI compared to the results from the DGC method. The progressive motile sperm recovery rate was higher in the intervention group (39.75 ± 19.20 vs 32.14 ± 18.14). Our data also showed that the vitality and mobility of sperm in the microfluidic group was higher than those of the DGC group (97.9 ± 2.21 vs 96.56 ± 4.11%, 96.36 ± 2.60 vs 95.06 ± 2.35%, respectively). However, there was no difference in sperm progressive motility and sperm morphology between two groups. Conclusions: There were significant improvement in sperm DFI and progressive motility in the microfluidic system. With this result, microfluidic system is a potential approach to reduce DNA fragmentation for ICSI procedures.

Induced-charge electroosmosis flow of viscoelastic fluids under different voltage arrangements

Efficient mixing of chemical analysis reagents with laboratory samples at a microscale is a key issue in numerous biomedical and chemical analyses but hardly to implement due to the limited of the low diffusivity in laminar flow. Induced-charge electroosmosis flow, as an innovative mixing method, has been proved to be effective and simple in rapid mixing attributes to its mechanism of vortex generation. This work aims to propose a new strategy for chaotic induced-charge electroosmosis flow based on different voltage arrangements to improve the mixing of viscoelastic fluids. The Phan–Thien–Tanner constitutive model is applied to characterize the flow behavior of viscoelastic fluid in a microfluidic preparation mixer. The direct numerical simulation method is used to solve the fully coupled Navier–Stokes and Poisson–Nernst–Planck equations for a polarizable cylinder in a two-dimensional cavity filled with electrolyte solution. The impact of Weissenberg number (Wi), Debye parameter, voltage strength on the velocity, net charge density, and potential profiles is investigated. The simulation results indicate that a greater Wi leads to the decrease in the maximum velocity, and a large voltage strength can heighten the net charge density and potential, thus improve the peak velocity. Moreover, the classical theoretical prediction that the maximum velocity is proportional to the square of the applied voltage has been authenticated.

PLGA nanoparticles enhanced cardio-protection of scutellarin and paeoniflorin against isoproterenol-induced myocardial ischemia in rats

This study aims to examine the impact of the microfluidic preparation process on the quality of poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) co-delivered with scutellarin (SCU) and paeoniflorin (PAE) in comparison to a conventional emulsification method and to evaluatethe potential cardio-protective effect of SCU-PAE PLGA NPs produced through emulsification method. As compared with microfluidics, the nanoparticles prepared by emulsification method exhibited a smaller size, higher encapsulation efficiency, higher drug loading and lower viscosity for injection. Subsequently, a rat myocardial ischemia (MI) was established using male Sprague-Dawley (SD) rats (250 ± 20 g) subcutaneously injected with 85 mg/kg isoproterenol (ISO) for two consecutive days. The pharmacokinetic findings demonstrated that our SCU-PAE PLGA NPs exhibited prolonged blood circulation time in MI rats, leading to increased levels of SCU and PAE in the heart. This resulted in significant improvements in electrocardiogram and cardiac index, as well as reduced serum levels of CK, LDH, AST. Histopathological analysis using H&E and TUNEL staining provided further evidence of improved cardiac function and decreased apoptosis. Additionally, experiments measuring SOD, MDA, GSH, NO, TNF-α and IL-6 levels indicated that SCU-PAE PLGA NPs may effectively treat MI through oxidative stress and inflammatory pathways, thereby establishing it as a promising therapeutic intervention.

Microfluidic preparation of thin film composite hollow fiber membrane modules for water nanofiltration: Up-scaling, reproducibility and MOF based layers

BackgroundThe commercialization of thin film composite (TFC) hollow fiber (HF) membranes remains challenging owing to issues associated with membrane manufacturing. MethodsTFC membranes were synthesized by microfluidic interfacial polymerization of polyamide (PA) on polysulfone hollow fiber (HF) membrane modules. A total of 33 HF membrane modules were prepared with different number of HFs (from 1 to 25) and different lengths (from 10 to 50 cm). They were evaluated in a nanofiltration operation in terms of water permeance and rose Bengal (RB) and MgSO4 rejections. Significant findingsAmong the 33 modules, 73% showed RB rejections higher than 95%, while 36% of the modules reached rejections above 99%. During the membrane synthesis, different parameters, such as PA monomer concentration, residence time and reaction time, were studied. As a result, the amount of monomer was reduced by ca. 80%. The versatility of microfluidics allowed incorporating hydrophilic metal-organic framework (MOF) ZIF-93 to produce HF modules with PA/MOF bilayered membranes (a continuous layer of MOF between the support and the PA film) which led to an important enhancement of the water permeance from 1.3 (bare PA membrane) to 5.3 L·m−2·h−1·bar−1 (PA/ZIF-93 HF membrane), maintaining RB rejection above 95%.

An investigation on microfluidic preparation of aluminum phosphate adjuvant

An investigation on microfluidic preparation of aluminum phosphate adjuvant

Microfluidic controllable preparation of iodine-131-labeled microspheres for radioembolization therapy of liver tumors.

Transcatheter arterial radioembolization (TARE) is of great significance for the treatment of advanced hepatocellular carcinoma (HCC). However, the existing radioembolic microspheres still have problems such as non-degradability, non-uniform size, and inability to directly monitor in vivo, which hinders the development of TARE. In this paper, a novel radioembolic agent, 131 I-labeled methacrylated gelatin microspheres (131 I-GMs), is prepared for the treatment of HCC. Water-in-oil (W/O) emulsion templates are prepared by a simple one-step microfluidic method to obtain methacrylated gelatin microspheres (GMs) after UV irradiation. A series of GMs with uniform and controllable size are obtained by adjusting the flow rate of each fluid. Both air-dried and freeze-dried GMs can quickly restore their original shape and size, and still have good monodispersity, elasticity and biocompatibility. The radiolabeling experiments show that 131 I can efficiently bind to GMs by chloramine-T method, and the obtained 131 I-GMs have good radioactive stability in vitro. The results of in vivo TARE treatment in rats show that 131 I-GMs can be well retained in the hepatic artery and have a good inhibitory effect on the progression of liver cancer, showing the potential for the treatment of HCC. This article is protected by copyright. All rights reserved.

P-782 The influence of microfluidic preparation of spermatozoa for ICSI (intracytoplasmic sperm injection) in an unselected IVF population on fertilization rate, embryo-quality and pregnancy rate

Abstract Study question Does the microfluidic technique as a new preparation option for sperm in ICSI during IVF have a better outcome in fertilization, blastocysts and pregnancy rate? Summary answer The patients that had the sperm preparation for ICSI with the microfluidic sperm selection had similar results as with the gradient centrifugation selection. What is known already Semen analysis is a poor predictor of the fertilization potential of spermatozoa and a male factor may contribute to poor outcomes of IVF procedure despite a normal semen analysis. Traditionally, sperm processing is accomplished by density gradient centrifugation or swim-up methods but this have been shown in some studies to increase reactive oxygen species and induce sperm DNA fragmentation. The microfluidic sperm selection (ZyMot- ICSI) is based on the selection of the spermatozoa with the lowest DNA fragmentation rate but studies do not prove better clinical outcomes after this method. Study design, size, duration This is a prospective randomized study carried out in a university level fertility clinic in Oradea, Romania from January 2022 to December 2022, including 239 patients in total. The patients that underwent IVF-ICSI procedures for various indications were randomized in two groups: the control group swim-up technique was used for sperm selection for ICSI during IVF and the study group with the ZyMot-ICSI (microfluidic sperm selection technique) was used. Participants/materials, setting, methods We conducted a prospective trial comparing 119 couples that were allocated to the classic swim-up technique (control group) and 120 couples that were allocated with the microfluidic technique was used (study group) in our university level clinic to go through IVF. Inclusion criteria were couples with known infertility requiring IVF and willing to participate in the study. Exclusion criteria were: severe oligoasthenospermia (concentration &amp;lt; 5x10^6 spermatozoa/ml or motility &amp;lt;10%), oocyte or sperm donation. Main results and the role of chance The statistical analysis showed that there is no significant difference between the fertilization rate (study vs control p = 0.37 with absolute difference -1.182, 95% CI (-7.2, 5.4)) or blastocyst rate (study vs control p = 0.88 with absolute difference -0.5 95% (-6.5, 6)) nor is there a difference in clinical pregnancy. Even if microfluidic preparation of spermatozoa did not seem to improve the results it may be utilized more broadly for standard IVF, intrauterine insemination and could also improve workflow, decrease intervention by laboratory personal and provide more consistent incubation conditions. Limitations, reasons for caution The population studied was inclusive with unselected IVF indications and did not attempt to isolate male factor infertility cases or patients with a history of elevated sperm DNA fragmentation. Wider implications of the findings Microfluidic sperm preparation performs similarly to density gradient centrifugation in sperm preparation for IVF in an unselected population. Trial registration number Not applicable

Nanohybrids Composed of Tannic Acid Cross-Linked by Metal Ions Obtained by a Microfluidic Technique

Naturally occurring compounds, such as tannic acid (TA), are perfect for constructing nanohybrids (NHs) with metal ions due to their anticarcinogenic, antimicrobial, and antioxidant properties. To date, the batch methods are the ones in which such NHs were constructed; however, those methods possess many drawbacks, such as low reproducibility or size variations. To overcome this limitation, microfluidic preparation is proposed for NHs construction composed of TA and iron (III). The spherical particles with a size between 70 and 150 nm and antimicrobial properties can be easily fabricated in a controlled manner.

Programmed release of hydrogel microspheres via regulating the immune microenvironment to promotes bone repair

Bone tissue repair is influenced by the synergistic interaction between acute immune microenvironment and osteogenesis. In this study will be independently by film dispersion method and static loading shell polymers and resveratrol liposome preparation CS - Res @ Lipo (CRL) and microfluidic technology preparation of HAMA@HepMA hydrogel microspheres (MS) by condensation reaction of chemical grafting, and then the non-covalent binding site of the MS microsphere was used to skillfully bind BMP-2, construct procedural release of hydrogel microspheres (CRL @ BMP - 2 @ MS). CRL@BMP-2@MS inhibit the acute immune peak by rapidly releasing Res, in addition, the sustained liberation of BMP-2 synchronizes osteoimmunity and osteogenesis, thereby accelerating bone repair. The results showed that Res was released with an increased cumulative rate of 72.4 ± 3.6% in the first 24 h, TNF-α and IL-1β levels were significantly decreased by 4.27 times and 3.65 times as compared to the control group, respectively. Furthermore, continuous release of approximately 40.26 ± 6.8% of BMP-2 occurred within the first 72 h, CRL@BMP-2@MS microspheres significantly increased osteogenic activity compared with the control group by 2.98 and 2.82 times, respectively. In conclusion, the programmed CRL@BMP-2@MS constructed in this study can realize the programmed synergistic linkage of immunity and osteogenesis, dynamically regulate bone repair, and the treatment of clinical bone repair will be based on a new strategy for diagnosis and treatment.