Effect Of Pore Size Research Articles

Enhancing Osteogenic Potential in Bone Tissue Engineering: Optimizing Pore Size in Alginate–Gelatin Composite Hydrogels

Bone tissue engineering relies on crucial scaffolds for tissue formation and stem cell differentiation. A composite scaffold of alginate‐gelatin effectively supports these processes. This study aims to design a porous alginate‐gelatin hydrogel and assess pore size effects on cell behavior, focusing on morphology, adhesion, and proliferation in distinct osteogenic environments. Hydrogels are prepared using various alginate‐gelatin concentrations: 4% alginate and 6% gelatin (4A6G) or 3% alginate and 5% gelatin (3A5G), cross‐linked with 2% CaCl2. Pore size optimization employs simple freezing and thawing cycles. Scanning electron microscopy reveals varying pore sizes: 340 µm ± 30 µm for 4A6G and 635 µm ± 25 µm for 3A5G. Stiffness measurements indicate significant differences: ≈26.3 kPa ± 0.6 KPa for 4A6G and 21.6 kPa ± 0.2 KPa for 3A5G. Cell interaction studies demonstrate higher adhesion and proliferation rates in larger‐pored hydrogels. Evaluation of bone tissue formation, including RT‐PCR, ALP activity, and ARS staining, reveal superior osteogenic potential in the 3A5G hydrogel compared to 4A6G. In conclusion, the 3A5G hydrogel (3% alginate and 5% gelatin) holds promise for bone tissue regeneration due to its biodegradability and favorable bone‐forming properties.

Doped Porous Carbon Spheres with Controllable Vesicle Structure: Preparation and the Effects of Pore Size on Electromagnetic Wave Absorption Properties.

This work reports on the preparation of uniform vesicle-structural carbon spheres doped with heteroatoms of N, P, and S, with the pore sizes strictly controlled by the hard templates of monodisperse submicron SiO2 spheres. The uniformly doped vesicular carbon microspheres are obtained in three steps: Stöber hydrolysis for the SiO2; in situ polymerization for the immobilization; and alkaline etching after carbonization. The size of the vesicles can be easily adjusted by regulating the particle size of the submicron SiO2 spheres, which has a significant effect on its electromagnetic wave (EMW) absorption performance. Compared with microspheres with pore sizes of 180 and 480nm, when the vesicle aperture is 327nm, with only 5.5wt.% filling load and 1.9mm thickness, the material shows the best EMW absorption behavior with the effective absorption bandwidth (EAB) covers the entire Ku band (6.32GHz) and the minimum reflection loss (RLmin) of -36.10dB, suggesting the optimized pore size of the microspheres can significantly improve the overall impedance matching of the material and achieve broadband wave absorption. This work paves the way for the enhancement of EMW absorption properties of porous material by optimizing the pore size of uniform apertures while maintaining their composition.

Effects of Copper Foam Wall/Obstacles on the Deflagration-to-Detonation Transition

To investigate the process of deflagration-to-detonation transition (DDT) of the copper foam wall in the pulse detonation engine, detonation combustion experiments were carried out using ethylene and oxygen-enriched air (oxygen concentration: 40%) as fuel and oxidant. The effects of copper foam pore size, thickness, installation length, and structure on the flame acceleration were studied experimentally, as were the effects of blockage ratio and mixture equivalence ratio. The results show that among the four pore sizes selected, the 10 PPI case produces the fastest flame development on the porous flat wall. For conditions with successful detonation, the 10 PPI case reduces the DDT distance and time by 34.97 and 42.57%, respectively, compared with the 40 PPI case. Regarding the installation length of copper foam, it is found that copper foam with a large pore size (10 PPI) and a short installation length achieves stable detonation. The general structure of copper foam was also analyzed, including the porous flat wall, porous obstacle, and solid obstacle with the same installation length. These three structures effectively accelerate the initiation of detonation. Particularly, porous obstacles show more pronounced effects on flame acceleration than the commonly used solid obstacles. These results are instructive for optimizing the short-distance ignition ability of pulsed detonation engines.

Porous Hydrogels for Immunomodulatory Applications.

Cancer immunotherapy relies on the insight that the immune system can be used to defend against malignant cells. The aim of cancer immunotherapy is to utilize, modulate, activate, and train the immune system to amplify antitumor T-cell immunity. In parallel, the immune system response to damaged tissue is also crucial in determining the success or failure of an implant. Due to their extracellular matrix mimetics and tunable chemical or physical performance, hydrogels are promising platforms for building immunomodulatory microenvironments for realizing cancer therapy and tissue regeneration. However, submicron or nanosized pore structures within hydrogels are not favorable for modulating immune cell function, such as cell invasion, migration, and immunophenotype. In contrast, hydrogels with a porous structure not only allow for nutrient transportation and metabolite discharge but also offer more space for realizing cell function. In this review, the design strategies and influencing factors of porous hydrogels for cancer therapy and tissue regeneration are first discussed. Second, the immunomodulatory effects and therapeutic outcomes of different porous hydrogels for cancer immunotherapy and tissue regeneration are highlighted. Beyond that, this review highlights the effects of pore size on immune function and potential signal transduction. Finally, the remaining challenges and perspectives of immunomodulatory porous hydrogels are discussed.

Predicting the compressive strength of tight sandstone based on the low field NMR and pseudo-triaxial compression measurements

The compressive strength is very important for petroleum and other engineering studies. However, the effect of pore size and fluid distribution on the rock’s strength is not fully understood. We developed comprehensive research to study the controlling factors of the compressive strength based on low field nuclear magnetic resonance (NMR) measurements and pseudo-triaxial compression test for tight sandstones. The relationship between the compressive strength and the NMR obtained parameters are investigated completely, aiming for a better estimation of the compressive strength using the NMR data. The result shows that the rock’s strength is strongly controlled by the pore size distribution and the fluid existing state. Generally, the compressive strength is negatively correlated with the average transversal relaxation time, the movable water saturation, and the porosity, but positively correlated with the irreducible water saturation. The result reveals that the rock with larger pore radius and higher percentage of movable fluid is easier to reach the failure state. Further, the precision of the empirical model by multiple regression of the geometric mean of the relaxation time and the porosity is greatly improved compared with the model established by the brittle minerals, which is potentially to be use for geophysical prospecting when the NMR logging data is available.

Separation of Perfluorooctanoic Acid from Water Using Meso- and Macroporous Syndiotactic Polystyrene Gels.

Per- and polyfluoroalkyl substances are an emerging class of contaminants that are environmentally persistent, bioaccumulative, and noxious to human health. Among these, perfluorooctanoic acid (PFOA) molecules are widely found in ground and surface water sources. A novel high surface area, meso- and macroporous syndiotactic polystyrene (sPS) wet gel is used in this work as the adsorbent of PFOA molecules from water at environmentally relevant PFOA concentrations (≤1 μg/L) and cleanse water to below the U.S. EPA's 2023 health advisory limit of 4 parts per trillion (ppt). The sigmoidal shape of the PFOA adsorption isotherm indicates a two-step adsorption mechanism attributed to the strong affinity of PFOA molecules for the sPS surface and molecular aggregation at solid-liquid interfaces or within the pores of the sPS wet gel. The adsorption kinetics and the effects of sPS wet gel porosity, pore size, and pore volume on the removal efficiency are reported. The adsorption kinetics is seen to be strongly dependent on pore size and pore volume.

The influence of activated carbon fiber paper structure on adsorption performance of cyclohexane

Activated carbon fibers paper (ACFP), made through wet-laid technology, had exhibited promising adsorption performance compared with granular and powdered activated carbon. This study prepared activated carbon fibers papers with different fibrous structures and investigated the dynamic adsorption performance of thin-layered ACFP against cyclohexane gas. The effects of inter-fiber pore size, dilution degree of activated carbon fibers, and porosity of the paper sheet on the adsorption performance were explored. The Bed Depth Service Time (BDST) model was employed for fitting and calculation, and the Flowdict module in Geodict software was used to analyze the flow field within the paper sheet. The results indicated that the inter-fiber pore size variation of ACFP had no significant effect on its adsorption breakthrough curve against cyclohexane gas. However, as the dilution degree of activated carbon fibers in the ACFP increased, the breakthrough time prolonged, and the adsorption utilization efficiency of activated carbon fibers continuously improved. Furthermore, decrease of ACFP porosity significantly impaired the adsorption performance. When the porosity decreased from 95.4 % to 91.4 %, the breakthrough adsorption capacity decreased from 134 mg/g to 95 mg/g, and the critical bed thickness increased from 0.029 cm to 0.044 cm.

Separation of milk fat using silicon carbide support ceramic membranes with different pore sizes

The effect of pore size and type of material on the separation of fat from raw milk using hydrophilic silicon carbide (SiC) support ceramic membranes has not previously been reported in literature. The separation performance of the fat globules (MFGs) showed 98% for SiC 0.5 μm, 92% for SiC 1.4 μm, 90% fat for ZrO2-SiC 0.06 μm, while the permeate had a fat % ranging from 0.1 to 0.6% (w/w). The MFGs were kept highly intact with well distributed proteins and phospholipids in the MFG membrane. The total filtration time at 50 °C to reach maximum VCR was 134 min for ZrO2 (VCR 3), 148 min for SiC 0.5 μm and 16 min for SiC 1.4 μm (VCR4). Further, all membranes showed a fully recoverable water permeability indicating no irreversible fouling. Industrial relevanceMicrofiltration may be an alternative process to fat separation from raw milk. In this study, for the first time was demonstrated that effective milk fat separation, and retentate and permeate streams with variable characteristics, in terms of composition and integrity of the milk fat globules can be obtained by using silicon carbide support membranes with different sizes and materials. The results obtained, provide new insights for industrial use of membrane technology to separate milk.

Facial Skin Rejuvenation Using Poly- dl -Lactic Acid Injected With a Laser-Generated Needle-Free Microjet Injector.

A laser-induced needle-free microjet injector was developed for rapid, high-speed drug delivery of microliters into the skin. This study evaluated the clinical rejuvenation effect of repeated dermal injections of the collagen simulator poly- dl -lactic acid (PDLA) using a laser-induced needle-free microjet injector. Five PDLA injection sessions using a laser-induced needle-free microjet injector were conducted in patients concerned about aging skin. Facial uplifting, darkness, redness, roughness, pore size, subjective satisfaction, and side effects were evaluated before each session and 4 weeks after treatment completion. Histological evaluation was also performed with immunohistochemical staining of collagen and elastic fibers. The clinical results of 27 female patients were evaluated. The treatment resulted in a noticeable skin surface uplifting (0.711 ± 0.42 mm) and significant improvements in darkness ( p = .013), redness ( p = .009), and roughness ( p = .036), with no significant difference in the pore size ( p = .770). Patients were reported being satisfied with the overall therapeutic effects, despite mild and tolerable adverse effects. Histological findings revealed growth and thickening of collagen and elastic fibers, with marked increase in collagen I and III levels. Repeated dermal injections of PDLA using a laser-induced microjet injector offer excellent drug delivery, achieving high efficacy in skin rejuvenation, patient satisfaction, and safety.

Molecular simulations of hydrogen diffusion in underground porous media: Implications for storage under varying pressure, confinement, and surface chemistry conditions

Assessing the feasibility of porous formations for hydrogen geo-storage demands a comprehensive understanding of hydrogen (H2) transport behavior in porous media at subsurface conditions. In this study, we employ molecular dynamics simulations to evaluate the effects of pressure (20–500 atm), pore size (2–20 nm), and surface composition on H2 diffusion and interactions within organic and inorganic slit pores. Our analysis of H2 density profiles and interaction energies reveals a distinct preference for H2 molecules to adsorb more readily onto graphene surfaces than kaolinite surfaces. However, self-diffusion results demonstrate that H2 molecules interact relatively weakly with both substrate types. Further insights are provided by velocity autocorrelation functions, emphasizing the occurrence of wall-mediated collisions as H2 molecules diffuse along the pore surfaces, particularly within kaolinite. This highlights the significance of surface roughness in mitigating H2 loss via diffusion in subsurface nanopores, given the small molecular size of H2 and its limited interactions with both organic and inorganic materials. Furthermore, the results demonstrate that self-diffusion coefficients in both pore types increase with pore size and decrease with pressure. Notably, surface composition plays a critical role in low-pressure environments, with self-diffusion coefficients beginning to converge beyond a pressure of 100 atm. Self-diffusion coefficients also become less sensitive to slit aperture beyond a pressure of 50 atm. In high-pressure environments, hydrogen transport is governed by thermal collisions between gas molecules, leading to negligible property variations between pore types. These findings hold significance in the investigation of efficient H2 storage within porous media and caprock formations.

Immunomodulatory potential of rapamycin-loaded mesoporous silica nanoparticles: pore size-dependent drug loading, release, and in vitro cellular responses

Rapamycin is a potent immunosuppressive drug that has been recently proposed for a wide range of applications beyond its current clinical use. For some of these proposed applications, encapsulation in nanoparticles is key to ensure therapeutic efficacy and safety. In this work, we evaluate the effect of pore size on mesoporous silica nanoparticles (MSN) as rapamycin nanocarriers. The successful preparation of MSN with 4 different pore sizes was confirmed by dynamic light scattering, zeta potential, transmission electron microscopy and N2 adsorption. In these materials, rapamycin loading was pore size-dependent, with smaller pore MSN exhibiting greater loading capacity. Release studies showed sustained drug release from all MSN types, with larger pore MSN presenting faster release kinetics. In vitro experiments using the murine dendritic cell (DC) line model DC2.4 showed that pore size influenced the biological performance of MSN. MSN with smaller pore sizes presented larger nanoparticle uptake by DC2.4 cells, but were also associated with slightly larger cytotoxicity. Further evaluation of DC2.4 cells incubated with rapamycin-loaded MSN also demonstrated a significant effect of MSN pore size on their immunological response. Notably, the combination of rapamycin-loaded MSN with an inflammatory stimulus (lipopolysaccharide, LPS) led to changes in the expression of DC activation markers (CD40 and CD83) and in the production of the proinflammatory cytokine TNF-α compared to LPS-treated DC without nanoparticles. Smaller-pored MSN induced more substantial reductions in CD40 expression while eliciting increased CD83 expression, indicating potential immunomodulatory effects. These findings highlight the critical role of MSN pore size in modulating rapamycin loading, release kinetics, cellular uptake, and subsequent immunomodulatory responses.Graphical abstract

Removal of turbidity in low-alcohol Chinese baijiu by coalescence separation

Chinese Baijiu has always been preferred by the majority of alcoholic drink lovers with its rich aroma. With the popularity of drinking culture and mental health, low-alcohol Baijiu has achieved increasing attention. This paper innovatively adopts the coalescence method of separating emulsion to solve the turbidity problem in the process of degrading Baijiu. Firstly, the characteristics of feasible materials for turbidity removal via coalescence were explored. Three materials with different pore size, chemical composition, and wetting behavior, namely polyether sulfone (PES), glass fiber (GF) and polyvinylidene fluoride (PVDF), were characterized. Secondly, the emulsion structure and composition of the diluted Chinese Baijiu were analyzed. Finally, the selected porous materials were conducted to separate the precipitates in the degraded Baijiu for a clear Baijiu. The results found that both PVDF with excellent affinity to esters under alcohol solution and PES with small pore size exhibited efficient turbidity removal efficiency. Furthermore, the effect of pore size ranging from 0.1 to 5 μm of the PVDF coalescing material on the turbidity removal was investigated. However, the small pore size resulted in great pressure drop and followed the screening mechanism which contributed to high energy consumption and membrane fouling issue. The large pore size PVDF materials with average pore size of 1.6–4.0 μm achieved high flux of 5.30 × 104 L/(m2·h) with 90∼100% turbidity removal for 39% alcohol content-Baijiu via coalescence. The quality after coalescence removal of turbid was good indicating the coalescence removal method is a Chinese Baijiu turbidity removal potential technology.

Molecular Simulation of Competitive Adsorption of Hydrogen and Methane: Analysis of Hydrogen Storage Feasibility in Depleted Shale Gas Reservoirs

Summary As a clean energy carrier, hydrogen (H2) is considered an indispensable part of the energy transition roadmap. To meet increasing energy demand, extremely large storage capacities are required. Previous studies have focused on underground H2 storage in conventional depleted gas reservoirs, salt caverns, and saline aquifers. The increasing number of depleted shale gas reservoirs may be good candidates for H2 storage. In this work, we analyze the potential of H2 storage in depleted gas reservoirs using Monte Carlo (MC) simulations. The competitive adsorption of a methane-hydrogen (C1-H2) system under nanoscale conditions is investigated, including the effects of pore size, temperature, pressure, boundary material, and fluid composition. Our results show that C1 is preferentially adsorbed in a C1-H2 system. C1 forms the adsorption layer near the boundary surface, while H2 molecules are freely distributed in the pore. The fluid distribution indicates that H2 can be easily produced during H2 recovery processes, which contributes to H2 storage in depleted shale gas reservoirs. In addition, the effect of water on C1-H2 competitive adsorption is analyzed. The strong interactions between water and boundary atoms force C1 molecules away from the adsorbed region. This work provides a foundation for hydrogen storage in depleted shale gas reservoirs at a molecular level.

Nanobubbles produced by nanopores to probe gas-liquid mass transfer characteristics

HypothesisThis study tested the hypothesis of how the nanopore size of membranes and how the surface charge of nanobubbles responds to its pinch-off from the nanopore. This study also tested the hypothesis that nanobubbles that remain in solution after production may increase the dissolved oxygen content in water. ExperimentsThe effect of membrane pore size, hydrodynamic conditions (gas and liquid flow rates), and physicochemical parameters (pH and temperature) on volumetric mass transfer coefficient (kLa) for oxygen nanobubbles formed by the nanopore diffusion technique was investigated. This study experimentally determined the kLa by carefully removing the dissolved oxygen by nitrogen purging from nanobubble suspension to examine the sole contribution of nanobubble dissolution in water to the reaeration. ResultsScaling estimates indicate that the nanobubble pinch-off radius and nanopore radius have a power-law correlation and that nanobubble size declines with the nanopore size. This is in line with our experimental results. The surface charge of nanobubbles delays its pinch-off at the gas-liquid interface. Nanobubbles offered 3-4 times higher kLa than microbubbles. Standard oxygen transfer efficiency in water was found to be 78%, significantly higher than that in microbubbles. However, dissolving stable nanobubbles in water does not considerably increase dissolved oxygen levels.

The effect of porous silicon thickness and pore size on the electrical properties of TiO2/PS heterojunctions

Heterojunctions made by depositing Titanium dioxide (TiO2) on porous silicon using the sol-gel method were electrically characterized. It was found that charge transfer mechanisms are dependent on the porosity and layer thickness, as well as the pore size. For the case of devices fabricated in mesoporous matrix, the current-potential curve appears like a Schottky ohmic contact, associated with the predominance of the tunneling charge transfer mechanism, depicting a reduction in current intensity as the meso-PS thickness increases. This behavior was related to the increase of TiO2 into the pores, which in turn leads to the hole concentration decrease from around 1020 to 1012 cm−3 because the compensation effect, as revealed by the Mott-Schottky analysis, while the impedance analysis shows that this reduction in holes is traduced as increase of the resistance associated with each interface. In the case of the devices yielded in macroporous layers, it was found that devices with thinner layers behaves as hole-blocking device or even as ohmic contact, depending on the amount of interface states. In addition, in hole blocking devices, the presence of at least two diodes with opposite behavior is marked.

Enhancing manganese removal through pre-deposition of powdered activated carbon-manganese oxide (PAC-MnOx) film on gravity-driven ceramic membrane: The impact of biofilm integrity and fluid dynamics

Manganese is widely distributed in the natural environment, and its presence in drinking water poses a risk to human health. In this study, an integrated pre-deposited powdered activated carbon (PAC) and manganese oxide (MnOx) bio-functional layer of inorganic origin was coupled with gravity-driven ceramic membrane (GDCM) reactor. The study aims to investigate the effects of the membrane pore size and functional layer integrity on the Mn2+ removal and flux. The results reveal that the average Mn2+ removal efficiency of the large pore size membranes (300 kDa and 0.45 μm) was lower (75 % – 78 %) compared to those with smaller pores (15 kDa and 50 kDa) (87 % – 88 %) during long-term operation. Such differences are attributed to a period of manganese leakage before the PAC-MnOx matured in large-pore membrane units and a longer residence time in small-pore membranes. The functional layer leaded to reversible fouling, which was more prominent in membranes with larger pores (contributing to 93 % of total resistance) than those with smaller ones (ranging from 51.7 % to 61.9 %). Although the damaged functional layer resulted in occasional high Mn2+ concentrations in the effluent, it did not significantly impact long-term flux development. Optical coherence tomography (OCT), in conjunction with COMSOL analysis, non-destructively evaluate biofilm formation process and indicate a homogeneous flow field and mass transfer in the “dual layers” (active film layer and ceramic membrane layer) of the GDCM. The presence of manganese-oxidizing bacteria (Hyphomicrobium, Reyranella, and Pseudomonas) in the GDCM reactor was verified using confocal laser scanning microscopy (CLSM) and high-throughput sequencing. Additional material characterization revealed that a portion of the PAC-MnOx exhibited characteristics of birnessite, with autocatalytic oxidation of Mn2+, and that Mn (III) and Mn (IV) were the primary species in MnOx, which exhibited excellent catalytic oxidation and adsorption capabilities for Mn (II), respectively. Overall, the developed PAC-MnOx GDCM system shows great promise in efficiently removing manganese and producing water of desired quality, thereby holding potential in applications across several sectors of advanced water treatment processes.

Evaluation of size-exclusion chromatography, multi-angle light scattering detection and mass photometry for the characterization of mRNA

The recent approval of messenger ribonucleic acid (mRNA) as vaccine to combat the COVID-19 pandemic has been a scientific turning point. Today, the applicability of mRNA is being demonstrated beyond infectious diseases, for example in cancer immunotherapy, protein replacement therapy and gene editing. mRNA is produced by in vitro transcription (IVT) from a linear DNA template and modified at the 3′ and 5′ ends to improve translational efficiency and stability. Co-existing impurities such as RNA fragments and double-stranded RNA (dsRNA), amongst others, can drastically impact mRNA quality and efficacy. In this study, size-exclusion chromatography (SEC) is evaluated for the characterization of IVT-mRNA. The effect of mobile phase composition (ionic strength and organic modifier), pH, column temperature and pore size (300 Å, 1000 Å, and 2000 Å) on the separation performance and structural integrity of IVT-mRNA varying in size is described. Non-replicating, self-amplifying (saRNA), temperature degraded, and ribonuclease (RNase) digested mRNA, the latter to characterize the 3′ poly(A) tail, were included in the study. Beyond ultraviolet (UV) detection, refractive index (RI) and multi-angle light scattering (MALS) detection were implemented to accurately determine molecular weight (MW) of mRNA. Finally, mass photometry is introduced as a complementary methodology to study mRNA under native conditions.

Rationally designed nanotrap structures for efficient separation of rare earth elements over a single step

Extracting rare earth elements (REEs) from wastewater is essential for the growth and an eco-friendly sustainable economy. However, it is a daunting challenge to separate individual rare earth elements by their subtle differences. To overcome this difficulty, we report a unique REE nanotrap that features dense uncoordinated carboxyl groups and triazole N atoms in a two-fold interpenetrated metal-organic framework (named NCU-1). Notably, the synergistic effect of suitable pore sizes and REE nanotraps in NCU-1 is highly responsive to the size variation of rare-earth ions and shows high selectivity toward light REE. As a proof of concept, Pr/Lu and Nd/Er are used as binary models, which give a high separation factor of SFPr/Lu = 796 and SFNd/Er = 273, demonstrating highly efficient separation over a single step. This ability achieves efficient and selective extraction and separation of REEs from mine tailings, establishing this platform as an important advance for sustainable obtaining high-purity REEs.

Encapsulation of mRNA in lipid nanoparticles by membrane micromixing

Messenger RNA encapsulated in lipid nanoparticles (mRNA-LNPs) are successfully used worldwide for vaccination against COVID-19. mRNA-LNPs are manufactured by mixing an ethanolic phase (containing an ionizable lipid, a phospholipid, a PEGylated lipid and cholesterol) and an aqueous phase (citrate buffer at pH 4.5 containing mRNA). The characteristics of the mRNA-LNPs obtained (size, internal structure, mRNA functional delivery in vivo, etc) depend on several parameters and among them are the mixing conditions of the ethanolic and aqueous phases. While the impact of these parameters is well-recognized for small scale preparations (some microliters), their effect at a larger scale is less well-known. The purpose of this study is to investigate the production of some hundreds of millilitres of mRNA-LNP suspension using a ceramic membrane (SPG Technology) as a new mixing device. Summarily, in this technique, the ethanolic phase permeates through the membrane pores and mixes with the aqueous phase flowing in a small annular pipe between the tubular membrane and an inside rod. First, empty LNPs were prepared to determine the effect of membrane pore size, flow rate, and the ratio between the ethanolic and aqueous phase volumes. The experimental conditions tested did not change the characteristics of the LNPs obtained. Second, mRNA-LNPs were prepared and the suspensions obtained were then submitted to buffer exchange/concentration/ sterile filtration dialysis. The resulting mRNA-LNPs had a particle size of 103 ± 5 nm, a polydispersity index of 0.15 ± 0.005, and encapsulation efficiency of 96 ± 0.0 %. mRNA-LNPs with similar characteristics were obtained using ethanol ratios of 1/4 (20 % ethanol in the final preparation) and 1/6 (14 % ethanol). Overall, membrane micromixing using a ceramic membrane was shown to be a suitable technology for the preparation of mRNA-LNP suspensions.

Effect of inner diameter, filter length, and pore size on hollow fiber filter fouling during perfusion cell culture.

As the need for higher volumetric productivity in biomanufacturing grows, biopharmaceutical companies are increasingly investing in a perfusion cell culture process, most commonly one that uses a hollow fiber filter as the cell retention device. A current challenge with using hollow fiber filters is fouling of the membrane, which reduces product sieving and can increase transmembrane pressure (TMP) past process limitations. In this work, the impact of hollow fiber filter geometries on product sieving and hydraulic membrane resistance profiles is evaluated in a tangential flow filtration (TFF) perfusion system. The hollow fibers tested had lengths ranging from 19.8 to 41.5 cm, inner diameters (IDs) ranging from 1.0 to 2.6 mm, and pore sizes of 0.2 or 0.65 μm. The results showed that the shortest hollow fibers experienced higher product sieving while larger IDs contributed to both higher product sieving and lower hydraulic membrane resistances, illustrating the impact of filter geometry on process performance. The results also showed 0.2 μm pore size filters maintain higher product sieving, but also higher membrane resistances compared to 0.65 μm pore size filters. This study highlights the need for optimized hollow fiber filter geometries to maximize use of the membrane area, which in turn can reduce production costs and increase scalability of the perfusion process.