scholarly journals Manufacturing Considerations for the Development of Lipid Nanoparticles Using Microfluidics

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1095 ◽  
Author(s):  
Carla B. Roces ◽  
Gustavo Lou ◽  
Nikita Jain ◽  
Suraj Abraham ◽  
Anitha Thomas ◽  
...  
Keyword(s):  
Flow Rate ◽  
Physicochemical Characteristics ◽  
Lipid Nanoparticles ◽  
Flow Rate Ratio ◽  
Total Flow ◽  
Total Flow Rate ◽  
Citrate Buffer ◽  
Vaccine Candidates ◽  
Wide Range ◽  
Formulation Parameters

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.

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 ◽  
...  
Keyword(s):  
Zeta Potential ◽  
Flow Rate ◽  
Size Range ◽  
Physicochemical Characteristics ◽  
Flow Rate Ratio ◽  
Total Flow ◽  
Experimental Conditions ◽  
Periodic Disturbance ◽  
Liposome Size ◽  
The Relationship

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.

Effect of CS2 Flow Rate on the Formation of Aligned Carbon Microcoils

2019 ◽  
Vol 947 ◽  
pp. 40-46
Author(s):  
Hyun Ji Kim ◽  
Sung Hoon Kim
Keyword(s):  
Flow Rate ◽  
Vapor Deposition ◽  
Rate Ratio ◽  
Chemical Vapor ◽  
Regular Structure ◽  
Flow Rate Ratio ◽  
Total Flow ◽  
Total Flow Rate ◽  
Flow Rates ◽  
Thermal Chemical Vapor Deposition

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.

scholarly journals Microfluidic Manufacture of Solid Lipid Nanoparticles: A Case Study on Tristearin-Based Systems

2020 ◽  
Vol 10 (3) ◽  
pp. 197-208 ◽  
Author(s):  
Giulia Anderluzzi ◽  
Yvonne Perrie
Keyword(s):  
Process Parameters ◽  
Flow Rate ◽  
Solid Lipid Nanoparticles ◽  
Rate Ratio ◽  
Lipid Nanoparticles ◽  
Flow Rate Ratio ◽  
Total Flow ◽  
Production Methods ◽  
Solid Lipid ◽  
Aqueous Flow

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.

scholarly journals Effects of water salinity on the foam dynamics for EOR application

2021 ◽  
Author(s):  
Svetlana Rudyk ◽  
Sami Al-Khamisi ◽  
Yahya Al-Wahaibi
Keyword(s):  
Flow Rate ◽  
Liquid Flow ◽  
Apparent Viscosity ◽  
Liquid Flow Rate ◽  
Salinity Range ◽  
Porous System ◽  
Foam Formation ◽  
Total Flow ◽  
Total Flow Rate ◽  
Foam Flow

AbstractFactors limiting foam injection for EOR application are exceptionally low rock permeability and exceedingly high salinity of the formation water. In this regard, foam formation using internal olefin sulfonate is investigated over a wide salinity range (1, 5, 8, 10, and 12% NaCl) through 10 mD limestone. The relationships between pressure drop (dP), apparent viscosity, liquid flow rate, total flow rate, salinity, foam texture, and length of foam drops at the outlet used as an indicator of viscosity are studied. Foaming is observed up to 12% NaCl, compared to a maximum of 8% NaCl in similar core-flooding experiments with 50 mD limestone and 255 mD sandstone. Thus, the salinity limit of foam formation has increased significantly due to the low permeability, which can be explained by the fact that the narrow porous system acts like a membrane with smaller holes. Compared to the increasing dP reported for highly permeable rocks, dP linearly decreases in almost the entire range of gas fraction (fg) at 1–10% NaCl. As fg increases, dP at higher total flow rate is higher at all salinities, but the magnitude of dP controls the dependence of apparent viscosity on total flow rate. Low dP is measured at 1% and 10% NaCl, and high dP is measured at 5, 8, and 12% NaCl. In the case of low dP, the apparent viscosity is higher at higher total flow rate with increasing gas fraction, but similar at two total flow rates with increasing liquid flow rate. In the case of high dP, the apparent viscosity is higher at lower total flow rate, both with an increase in the gas fraction and with an increase in the liquid flow rate. A linear correlation is found between dP or apparent viscosity and liquid flow rate, which defines it as a governing factor of foam flow and can be considered when modeling foam flow.

EXTRACTION OF MINUTE GAS BUBBLES FROM LIQUIDS FLOWING IN A SIMULATED CARDIOPULMONARY BYPASS SYSTEM BY A VENTURI-ASPIRATOR UNIT

2002 ◽  
Vol 02 (03n04) ◽  
pp. 297-312
Author(s):  
WEN-JEI YANG ◽  
AMR EID ◽  
R. ECHIGO
Keyword(s):  
Cardiopulmonary Bypass ◽  
Flow Rate ◽  
Whole Blood ◽  
Pressure Difference ◽  
Gas Bubbles ◽  
Blood Oxygenation ◽  
Straight Tube ◽  
Suction Pressure ◽  
Total Flow ◽  
Total Flow Rate

An experimental study is performed to extract minute gas bubbles from liquids flowing in a simulated cardiopulmonary bypass system using a Venturi-aspirator unit. In other words, oxygen bubbles in oxygenated blood are simulated by air bubbles in water with AP30 (about same viscosity as whole blood). This study is intended to determine the feasibility of using a Venturi aspirator unit to extract minute gas bubbles from a simulated cardiopulmonary bypass system. Testing of the Venturi-type bubble extraction is carried out using three different test sections. Two Venturis are used, and a straight tube configuration is used as a control. The two Venturis are similar, with the exception that one has a longer inlet cone which causes the entering liquid to accelerate at a slower rate. Results are obtained for effectiveness of the aspirator unit as functions of total flow rate, extraction suction, suction pressure difference, and hydraulic head. It is concluded from the study that:(i) The effectiveness of the Venturis is typically between 90 and 100 percent. It increases with an increase in suction or suction pressure difference but decreases with an increase in total flow rate.(ii) The Venturi is most suitable for extraction of minute gas bubbles, especially for use with AP30 (whole blood), which yields substantially higher effectiveness than water.(iii) It is anticipated that a Venturi-aspirator unit can be superior to other bubble separation device as the cardiopulmonary bypass system for applications in extra corporeal blood oxygenation.

LTCC 3D MICROMIXERS FOR NON-MISCIBLE FLUIDS MICROEMULSION GENERATION

2016 ◽  
Vol 2016 (CICMT) ◽  
pp. 000096-000102
Author(s):  
Houari Cobas Gomez ◽  
Bianca Oliveira Agio ◽  
Jéssica Gonçalves da Silva ◽  
Natalia Neto Pereira Cerize ◽  
Adriano Marim de Oliveira ◽  
...  
Keyword(s):  
Microfluidic Device ◽  
Flow Rate ◽  
Device Fabrication ◽  
Chaotic Advection ◽  
Drop Diameter ◽  
Production Volume ◽  
Total Flow ◽  
Total Flow Rate ◽  
Miscible Fluids ◽  
Working Region

Abstract The present work shows a ceramics microfluidic device for non-miscible fluids microemulsion generation using 3D serpentine micromixers. The technology used for device fabrication was Low Temperature Cofired Ceramics (LTCC) which allows us for complex, high temperature and pressure resistant 3D microfluidic devices. The proposed device aims to obtain microemulsion with controlled drop size, low dispersion index and high production volumes using Top-Down approach. Previous simulation work had showed 3D serpentine as one of the best structures for rapid mixing due the chaotic advection generated on every 90 deg direction change. This effect, when mixing two fluids as oil and water leads to streamlines pinching-off making possible drop generation. We have used this effect on our device. For the experimental section, it was fabricated a 3D serpentine mixer microfluidic device with working region suitable for variable total flow rate. For certain value of total flow rate, the microemulsion showed higher drop diameter and polydispersity values. In this region, no control could be done in order to obtain the same drop value with the same process parameters. Inside the working region drop diameter values repeatability was obtained. In this region our experimental results had showed a relation between drop diameter and total flow rate. As a total flow rate increase the drop diameter decrease due to a stronger chaotic advection effect. In the other hand, the polydispersity index also decreases. Microemulsions with average size lower than few micrometer or submicron were obtained. When compared with other reported devices, our device presented a production volume in the range of tens of ml/s for the same output microemulsion size.

scholarly journals The effect of increasing CO2concentration and flow rate on amine still performance in meeting gas sale specifications

2018 ◽  
Vol 67 ◽  
pp. 03006
Author(s):  
Yuswan Muharam ◽  
Hendra Kristianto
Keyword(s):  
Flow Rate ◽  
Design Flow ◽  
Equilibrium Curve ◽  
Total Flow ◽  
Total Flow Rate ◽  
Gas Well ◽  
Desorption Equilibrium ◽  
Packing Column ◽  
Design Flow Rate

The main purpose of this study is to examine the effect of increasing CO2removal and flow rate on performance of an amine still. The amine still is located in Field X in South East Sumatra at a new gas well producing gases with a rich CO2content. The still uses activated MDEA as the amine and has an IMTP 40-type packing column. Two film and desorption equilibrium curve theories were employed to analyse the amine still design conditions. Design equations were utilized to find the slope of the equilibrium curve. A slope of the equilibrium curve of 45° in the amine still is obtained in this study. The maximum liquid CO2composition of the amine still feedstock (xo) which can be separated to produce lean amine according to the specification design flow rate is 0.0307. The total flow rate of CO2-rich amine at xo= 0.029 is 761,157.6 kg/hour; the total flow rate of CO2-rich amine atxo= 0.0295 is 628,861.1 kg/hour; the total flow rate of CO2- rich amine at xo= 0.03 is 513,962.6 kg/hour; and the total flow rate of CO2-rich amine at xo= 0.0305 is 409,575.3 kg/hour.

Numerical Analysis for the Assessment of Factors Influencing the Breakdown of Swirl Flow in a Cylinder Driven by a Rotating End Wall

2020 ◽  
Vol 143 (2) ◽  
Author(s):  
M. Sreejith ◽  
S. Anil Lal ◽  
Abhijith S. Pai
Keyword(s):  
Reynolds Number ◽  
Flow Rate ◽  
Momentum Flux ◽  
Vortex Breakdown ◽  
Axial Flow ◽  
Swirl Flow ◽  
Total Flow ◽  
Total Flow Rate ◽  
Stream Tube ◽  
Axial Vortex

Abstract Finite element solution for the classical problem of swirl flow in a cylinder with a rotating lid has been used to study the characteristic features of the stream-tube and identify the factors contributing to axial vortex breakdown. An increase of rotational Reynolds number has been found to result in (i) a decrease of total flow rate; (ii) an increase of flow rate through the boundary layer over the stationary walls; (iii) an increase of the throat area of the stream-tube, with the upstream axial vortex flow in some cases having a deficit in momentum flux needed to overcome the pressure and viscous forces; and (iv) an increase of distance for the axial flow to sustain deceleration in the diverging passage. Based on the analysis, it is hypothesized that “flow with particles in axial vortex motion having a deficit of momentum flux for axial flow when subjecting to a fluctuating radial force undergoes axial vortex breakdown.” This explanation has been able to justify the disappearance of vortex breakdown at larger Re of laminar regime and the absence of vortex breakdown in small aspect ratio cylinders. We report novel results pertaining to total flow rate and its distribution within the vessel. The momentum flux of axial vortex, a main determinant of bubble breakdown, is found to be governed by the total flow rate, distribution of flow through the boundary layers, and the Reynolds number. The proposed hypothesis has been verified by analyzing two cases, one involving a passive and the other involving an active mechanism for regulating the axial momentum.

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