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

Micromachines ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 235 ◽  
Author(s):  
Rubén R. López ◽  
Ixchel Ocampo ◽  
Luz-María Sánchez ◽  
Anas Alazzam ◽  
Karl-F. Bergeron ◽  
...  

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.

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1095 ◽  
Author(s):  
Carla B. Roces ◽  
Gustavo Lou ◽  
Nikita Jain ◽  
Suraj Abraham ◽  
Anitha Thomas ◽  
...  

In the recent of years, the use of lipid nanoparticles (LNPs) for RNA delivery has gained considerable attention, with a large number in the clinical pipeline as vaccine candidates or to treat a wide range of diseases. Microfluidics offers considerable advantages for their manufacture due to its scalability, reproducibility and fast preparation. Thus, in this study, we have evaluated operating and formulation parameters to be considered when developing LNPs. Among them, the flow rate ratio (FRR) and the total flow rate (TFR) have been shown to significantly influence the physicochemical characteristics of the produced particles. In particular, increasing the TFR or increasing the FRR decreased the particle size. The amino lipid choice (cationic—DOTAP and DDAB; ionisable—MC3), buffer choice (citrate buffer pH 6 or TRIS pH 7.4) and type of nucleic acid payload (PolyA, ssDNA or mRNA) have also been shown to have an impact on the characteristics of these LNPs. LNPs were shown to have a high (>90%) loading in all cases and were below 100 nm with a low polydispersity index (≤0.25). The results within this paper could be used as a guide for the development and scalable manufacture of LNP systems using microfluidics.


2019 ◽  
Vol 947 ◽  
pp. 40-46
Author(s):  
Hyun Ji Kim ◽  
Sung Hoon Kim

The formation of aligned carbon microcoils could be achieved using C2H2 as a source gas and CS2 as an incorporated additive gas under thermal chemical vapor deposition system. To elucidate the ratio of C2H2/CS2 for the formation of the aligned carbon microcoils, the CS2 flow rate was first manipulated under the identical C2H2 flow rate (500sccm) condition. The formation and the alignment of carbon microcoils could be only achieved under the ratio of C2H2/CS2 = 33.3 condition, namely the flow rates of CS2 = 15sccm and C2H2= 500sccm. The total flow rate of the used gases was varied under the identical C2H2/CS2 flow rate ratio (33.3) condition. The C2H2 flow rate was manipulated under the identical CS2 flow rate (15sccm) condition. It was found that the formation and the alignment of carbon microcoils could be only achieved under the condition of 15sccm of CS2 flow rate in the range of 200 ~ 500sccm of C2H2 flow rate, regardless of the flow rate ratio of C2H2/CS2 and the total flow rate. The crystal structure of the well-aligned CMCs reveals the increase in the (002) peak in XRD spectrum for the aligned carbon microcoils, indicating the existence of the more regular structure in the aligned carbon microcoils. Based on these results, the cause for the formation of the aligned carbon microcoils only in the case of the CS2 flow rate = 15sccm with the imaginary pictures for the flow rate ratio of C2H2/CS2 just above the substrate were proposed.


2021 ◽  
Vol 4 (1) ◽  
pp. 42
Author(s):  
Ixchel Ocampo ◽  
Rubén R. Lopéz ◽  
Vahée Nerguizian ◽  
Ion Stiharu ◽  
Sergio Camacho León

Artificial Neural Networks (ANN) and Data analysis are powerful tools used for supporting decision-making. They have been employed in diverse fields and one of them is nanotechnology used, for example, in predicting particles size. Liposomes are nanoparticles used in different biomedical applications that can be produced in Dean Forces-based Periodic Disturbance Micromixers (PDM). In this work, ANN and data analysis techniques are used to build a liposome size prediction model by using the most relevant variables in a PDM, i.e., Flow Rate Radio (FRR) and Total Flow Rate (TFR). The ANN was designed in MATLAB and fed data from 60 experiments, which were 70% training, 15% validation and 15% testing. For data analysis, regression analysis was used. The model was evaluated; it showed 98.147% of regression number for training and 97.247% in total data compared with 78.89% regression number obtained by data analysis. These results demonstrate that liposomes’ size can be better predicted by ANN with just FRR and TFR as inputs, compared with data analysis techniques when the temperature, solvents, and concentrations are kept constant.


Micromachines ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1046
Author(s):  
Shuyan Deng ◽  
Yukun Zeng ◽  
Mingying Li ◽  
Cuixiang Liang

To help in the efficient design of fluid flow in electroosmotic pumps, electroosmotic flow of non-Newtonian fluid through porous polymer membrane at high zeta potentials is studied by mainly evaluating the total flow rate at different physical parameters. Non-Newtonian fluid is represented by the power-law model and the porous polymer membrane is considered as arrays of straight cylindrical pores. The electroosmotic flow of non-Newtonian fluid through a single pore is studied by solving the complete Poisson–Boltzmann equation and the modified Cauchy momentum equation. Then assuming the pore size distribution on porous polymer membrane obeys Gaussian distribution, the performance of electroosmotic pump operating non-Newtonian fluid is evaluated by computing the total flow rate of electroosmotic flow through porous polymer membrane as a function of flow behavior index, geometric parameters of porous membrane, electrolyte concentration, applied voltage, and zeta potential. It is found that enhancing zeta potential and bulk concentration rather than the applied voltage can also significantly improve the total flow rate in porous polymer membrane, especially in the case of shear thinning fluid.


2010 ◽  
Vol 62 (9) ◽  
pp. 2021-2027
Author(s):  
Huang Ting-lin ◽  
Zhang Gang ◽  
Guo Ning ◽  
He Wen-jie ◽  
Han Hong-da ◽  
...  

Pelleting flocculation blanket (PFB) process has been successfully applied to high turbidity suspensions for high efficient solid/liquid separation. In this paper, by using the PFB process, a dynamic experimental study was carried out on concentrating ferric flocs sludge with a scale of 1.3–5.4 m3/h. The pilot experiment aimed to optimize the conditioning system and determine the operational parameters. Under the raw sludge concentrations of 103–1,154 mg/L, the system could achieve ideal conditioning effect with polyacrylamide (PAM) dosages of 0.3–2.7 mg/L, agitation speed of 10 rpm, and water up-flow rates of 18–48 m/h. Under the experimental conditions, the increase of polymer dosage would improve effluent turbidity and pellets settling behaviour, the moderate up-flow rate had no marked effect on treatment results, while too large surface loading could worsen effluent turbidity. The experimental results also revealed that there existed an approximately linear relationship between the raw sludge concentration and optimum PAM dosage, that is, the optimum dosage of PAM increased synchronously as the raw sludge concentration increased. While the relationship between the raw sludge concentration and maximum up-flow rate reflected another linear dependence, namely, the maximum up-flow rate would decreased linearly as the raw sludge concentration increased.


2011 ◽  
Vol 403-408 ◽  
pp. 20-23
Author(s):  
Ming Bo Yang ◽  
Hui Li ◽  
Wei Zhang ◽  
Tao Zhou

In the paper, the effects of the holding time and temperature on Sr content of the Mg-Sr master alloys produced by the metallothermic reduction of SrO into magnesium melt were investigated. The results preliminarily indicated that effects of the holding time and temperature on the Sr content of the Mg-Sr master alloys produced by the metallothermic reduction of SrO into magnesium melt were relatively obvious. For a given experimental conditions: magnesium melt of ~10 kg and powder flow rate to carrier gas flow rate ratio of 20 g SrO/min / 15 L Ar/min, with the increasing of holding time from 30min to 150 min at 800 °C or holding temperature from 700°C to 850 °C for 90 min, the Sr content of the Mg-Sr master alloy increased gradually. Obviously, the long holding time or high holding temperature was beneficial to produce Mg-Sr master alloys with high Sr content by the metallothermic reduction of SrO into magnesium melt.


2020 ◽  
Vol 10 (3) ◽  
pp. 197-208 ◽  
Author(s):  
Giulia Anderluzzi ◽  
Yvonne Perrie

Background: Solid lipid nanoparticles are lipid-based carriers that can be used for a range of drugs and biomolecules. However, most production methods currently used do not offer easy translation from laboratory preparation to scale-independent production. Objectives: Within this study, we have investigated the use of microfluidics to produce solid lipid nanoparticles and investigated their protein loading capability. In the development of this process, we have investigated and identified the critical process parameters that impact on the product attributes of the solid lipid nanoparticles. Method: Solid lipid nanoparticles based on Tristearin and 1,2-Distearoyl-phosphatidylethanolaminemethyl- polyethyleneglycol conjugate-2000 were formulated using the NanoAssemblr® Benchtop system. The flow rate ratio, total flow rate and initial protein concentration were investigated as process parameters and the particle size, PDI, zeta potential, drug loading and drug release were measured as product attributes. Results: Our results demonstrate the suitability of microfluidics as a production method for solid lipid nanoparticles containing protein. In terms of key process parameters to consider, both the solvent to aqueous flow rate ratio and the total flow rate were shown to have a notable impact on particle size. Protein loading capacity was influenced by the solvent to aqueous flow rate ratio but was similar across all flow rates tested. Conclusion: Within this study, we outline a rapid and easy protocol for the scale-independent production of solid lipid nanoparticles. This process can support the rapid translation of production methods from bench to clinic.


Micromachines ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1164
Author(s):  
Ixchel Ocampo ◽  
Rubén R. López ◽  
Sergio Camacho-León ◽  
Vahé Nerguizian ◽  
Ion Stiharu

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.


Author(s):  
A.M. Zetty Akhtar ◽  
M.M. Rahman ◽  
K. Kadirgama ◽  
M.A. Maleque

This paper presents the findings of the stability, thermal conductivity and viscosity of CNTs (doped with 10 wt% graphene)- TiO2 hybrid nanofluids under various concentrations. While the usage of cutting fluid in machining operation is necessary for removing the heat generated at the cutting zone, the excessive use of it could lead to environmental and health issue to the operators. Therefore, the minimum quantity lubrication (MQL) to replace the conventional flooding was introduced. The MQL method minimises the usage of cutting fluid as a step to achieve a cleaner environment and sustainable machining. However, the low thermal conductivity of the base fluid in the MQL system caused the insufficient removal of heat generated in the cutting zone. Addition of nanoparticles to the base fluid was then introduced to enhance the performance of cutting fluids. The ethylene glycol used as the base fluid, titanium dioxide (TiO2) and carbon nanotubes (CNTs) nanoparticle mixed to produce nanofluids with concentrations of 0.02 to 0.1 wt.% with an interval of 0.02 wt%. The mixing ratio of TiO2: CNTs was 90:10 and ratio of SDBS (surfactant): CNTs was 10:1. The stability of nanofluid checked using observation method and zeta potential analysis. The thermal conductivity and viscosity of suspension were measured at a temperature range between 30˚C to 70˚C (with increment of 10˚C) to determine the relationship between concentration and temperature on nanofluid’s thermal physical properties. Based on the results obtained, zeta potential value for nanofluid range from -50 to -70 mV indicates a good stability of the suspension. Thermal conductivity of nanofluid increases as an increase of temperature and enhancement ratio is within the range of 1.51 to 4.53 compared to the base fluid. Meanwhile, the viscosity of nanofluid shows decrements with an increase of the temperature remarks significant advantage in pumping power. The developed nanofluid in this study found to be stable with enhanced thermal conductivity and decrease in viscosity, which at once make it possible to be use as nanolubricant in machining operation.


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