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| ==Hand Driven Liposome Extruders== | | ==Hand Driven Liposome Extruders== |
| | [[File:Hand_Driven_Liposome_Extruders.png|thumb|250px|right|Hand Driven Liposome Extruders]] |
| The hand driven liposome extruders are capable of processing the sample volume from 0.25mL to 2.5mL, which is suitable for mini sample volume applications during the experimental phase. It is operated by simply pushing the plunger manually. | | The hand driven liposome extruders are capable of processing the sample volume from 0.25mL to 2.5mL, which is suitable for mini sample volume applications during the experimental phase. It is operated by simply pushing the plunger manually. |
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| The hand driven Nano Pore liposome extruders with cooling jacket are designed for those extrusion conditions to control the sample temperature. | | The hand driven Nano Pore liposome extruders with cooling jacket are designed for those extrusion conditions to control the sample temperature. |
| [[File:Hand_Driven_Liposome_Extruders.png|thumb|250px|right|Hand Driven Liposome Extruders]]
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| =Applications= | | ==Jacketed Liposome Extruders== |
| [[File:High Pressure Homogenizers_Interaction_applications.png|thumb|250px|right|Classification of nanotechnology applications]] | | [[File:Jacketed_Liposome_Extruders.png|thumb|250px|right|Jacketed Liposome Extruders]] |
| The high pressure homogenizer is one of the most effective pieces of equipment for preparing nanomaterial using top-down nanotechnology. The high pressure homogenizer and its interaction chamber have a wide variety of applications in the production of nanomaterial and nanotechnology. | | The jacketed liposome extruders have a wide range of processing capacities, from sample volume 2mL to 3L depending on the models. It is suitable for lab scale and pilot scale applications. It is driven by compressed nitrogen cylinder. Most of the jacketed liposome extruders are designed with jacketed barrel to achieve the temperature control of the sample. |
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| These applications include:
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| * Preparation of fat emulsion, microemulsions, liposomes, nanosuspensions, and nanoparticles in the pharmaceutical industry;
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| * Cell disruption, microcapsules, and vaccine adjuvants in biotechnology products;
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| * Homogenization and emulsification in the food and beverage industry to improve stability, taste, appearance, and encapsulation of nutrients in food products;
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| * Homogeneous dispersion of products in the cosmetics, fine chemical, and other industries to improve product functionality, increase value, and ensure process stability;
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| * Dispersion and exfoliation of conductive paste, resistance paste, graphene, carbon nanotubes, and nano-oxides.
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| =Classification= | | ==Online Liposome Extruders== |
| | [[File:Online_Liposome_Extruders.png|thumb|250px|right|Online Liposome Extruders]] |
| | Online liposome extruders are available for the processing capacity from 2mL to 20L depending on the different models. These extruders are more suitable for pilot scale applications. It is powered by a high-pressure pump unit or other production equipment. |
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| ==By energy source== | | ==Multiple Liposome Extruders System== |
| | [[File:Multiple_Liposome_Extruders_systems_with_liposome_extruding_control_panel.png|thumb|250px|right|Multiple Liposome Extruders systems with liposome extruding control panel]] |
| | The multiple liposome extruders system is able to process the volume from 1L to 200L. It features both the temperature and pressure sensors in the product line, and a control panel to control the production for liposomes. |
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| ===Electric===
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| [[File:High_Pressure_Homogenizers_electric.jpg|thumb|250px|right|Electric high pressure homogenizer with intensifier]]
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| Electric homogenizers are powered by an electric motor. This category of homogenizer can be further subdivided into two types: direct-drive and intensifier.
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| ===Direct-drive type=== | | =Track-Etched Polycarbonate Extrusion Membranes= |
| The motor drives the crankshaft to move the plunger back and forth, directly pressurizing the material. Multiple plungers in the crankshaft work together to produce constant pressure and a high flow rate; large quantities of materials are required to produce the constant pressure. To drive the crankshaft, the motor requires a multi-stage gear reduction mechanism, which makes the equipment large in size. The homogenizer with a crankshaft is suitable for large-scale production with low-pressure applications. | | [[File:Microscopic_Representation_for_Track-Etched_Polycarbonate_Membranes.png|thumb|250px|right|Microscopic Representation for Track-Etched Polycarbonate Membranes]] |
| | The operations of liposome extruders have high requirements for the extrusion membranes. The nucleus track-etched polycarbonate membranes should have uniform distributions of filter pores. In an ideal membrane, all nano pores should be of the same size. Furthermore, the extrusion membrane with vertical pore distribution is more conducive to the preparation of liposome extrusion. |
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| ===Intensifier type===
| | In general, selecting right size of the polycarbonate membranes will ensure successful extrusion. It is strongly recommended to know the initial particle size of the processing sample before the extrusion. Another factor to consider for selecting the membrane is the desired particle size for your end product. |
| In intensifier-type high pressure homogenizers, the motor drives the intensifier to pressurize the material through the interaction chamber. The intensifier system can provide higher pressure, thereby improving the performance of the homogenization process. The flow rate of the homogenizer with an intensifier is lower than it is for the homogenizer with a crankshaft, smaller amounts of materials are required, and the pressure is higher. | |
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| It can be used for laboratory applications with small amounts sample, and for production applications with high pressure. When equipped with the diamond interaction chamber, the electric high pressure homogenizer with an intensifier falls into the category of high-end homogenizers. This type is widely used in biology, pharmaceutical, and nanotechnology laboratories. The traditional intensifier is hydraulic, and the new type of electric cylinder by linear actuator is emerged with more performance.
| | For example, if the initial particle size of the sample is 1μm, and the target is to achieve the particle size below 100 nm, here are several options available: |
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| ===Hand Driven=== | | ==Extrusion Multiple Times via the Target Pore Size Membranes== |
| [[File:High_Pressure_Homogenizers_handdriven.png|thumb|250px|right|Hand-driven high pressure homogenizer]]
| | For example, the user can extrude the sample through a 100 nm polycarbonate membrane using a liposome extruder several times. |
| Hand driven homogenizers<ref>HandGenizer,[https://www.genizer.com/handgenizer-laboratory-hand-drive_p0009.html]</ref> pressurize the material by manual power. The flow rate of a hand homogenizer is small, but it is portable and easy to assemble and disassemble. It requires very small amounts of materials, making it suitable for small-scale experiments. This type of device is capable of supporting biopharmaceutical laboratories’ research and development needs. The manual high-pressure homogenizer is also called the Handgenizer.1
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| ===Air Driven===
| | But the problems that may arise are: |
| The air driven homogenizer converts the pressure of compressed gas into hydraulic pressure. Therefore, it needs the support of a nitrogen cylinder or an air compressor. This homogenizer’s gas consumption and noise levels are high, and its maximum homogenization pressure is generally low. However, since there is no separate intensifier pump structure, its volume is small, and it is suitable for sites equipped with compressed nitrogen. | | * The difficulties in extrusion process; |
| | * The large vesicles may block the surface of the polycarbonate membrane, and request a replacement of a new membrane, etc. |
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| | ==Extrusion via the Different Pore Size Membranes== |
| | This procedure is to use different pore size membranes to extrude step by step. For example, the sample is extruded through a 400nm polycarbonate membrane first, and observe the extrusion process. If it is hard to extrude the sample through the 400nm membranes, then replace a new membrane with a larger pore size, such as 800nm for extrusion 3~5 times. It can be optimized during the process. After the first-round extrusion, select a smaller pore size polycarbonate membrane, such as 100 nm or 80 nm to extrude again. 200 nm polycarbonate membranes can be used as a transition if the extrusion is difficult to go through the 100nm membranes. |
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| ==By principle and structure of the interaction chamber== | | ==High Pressure Homogenization-Extrusion Method== |
| [[File:High_Pressure_Homogenizers_principle.png|thumb|300px|right|The three-type principle of high pressure homogenization<ref>Three-Types Homogenizing Mechanism in History. [https://www.genizer.com/art/technology_a0043.html]</ref>]] | | [[File:High_Pressure_Homogenizer_combines_with_online_liposome_extruder.png|thumb|250px|right|High Pressure Homogenizer combines with online liposome extruder]] |
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| ===First Generation: Impact Type===
| | The sample can be high pressure homogenized first, and extruded through a 100nm or 80nm polycarbonate membrane after homogenization. |
| '''Cavitation nozzles:''' The main function of this nozzle is cavitation, which leads to the separation of the emulsion and thereby increases the particle size. Under the pressure of the homogenizer, the materials flow into the cavitation nozzle with a very small aperture at several times the speed of sound. Meanwhile, intense friction and collision take place between the particles and the metal valve parts. This friction reduces the service life of the equipment, and the collisions cause metallic particles to fall into the final products.
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| '''Impact valve:''' The impact valve and impact ring structure moderately reduce local wear and prolong the homogenization chamber’s service life by using tungsten alloy materials. The role of the impact valve is a combination of impact and cavitation. However, its basic principle is the collision of the material in the suspension with the structure of a high-hardness metal (such as tungsten alloy). Therefore, the impact valve still cannot solve the problem of metallic particle residue. By the first decade of the 20th century, most high pressure homogenizers have added impact valve component.
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| | =Videos= |
| | <youtube>VoxAsfb34IQ</youtube> |
| | <youtube>xxoGovXZdVA</youtube> |
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| ===Second Generation: Interaction Type===
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| [[File:High_Pressure_Homogenizers_Interaction_chamber.png|thumb|250px|right|Interaction chamber with cooling jacket]]
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| '''Y-type interaction chamber:''' The Y-type interaction chamber, regarded as one of the most powerful homogenization chambers to date, has been used by several manufacturers in the USA. In these systems, the flow stream is split into two channels that are redirected over the same plane at right angles and propelled into a single flow stream. High pressure promotes a high speed at the crossover of the two flows, which results in high shear, turbulence, and cavitation over the single outbound flow stream.
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| With the unique Y-type structure, the high-speed moving materials in the high-pressure solution collide with each other, in a process that greatly improves the service life of the chamber over those with more conventional designs. The use of diamond material prevents the formation of metal particle residue.
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| The Y-type interaction chamber is widely used in the preparation of pharmaceutical emulsions because it minimizes cavitation and produces exquisite, stable particle size and PDI (poly dispersity index) control ability. Genizer and Microfluidics Corp. are the main manufacturers of the diamond interaction chamber. At present, the Y-type diamond interaction chamber is mainly used in high-end nanotechnology, and it occupies more than 90% of the US pharmaceutical industry. Genizer’s temperature-controlled interaction chamber avoids temperature surges and enables working pressure of up to 60,000 psi.
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| Low emulsification efficiency and metallic particle residue are two problems caused by homogenization chambers designed with the impact principle. When particles collide with internal metal components during the production of pharmaceutical injections, residual inert metallic particles generate. These metallic particles may gather and form larger particles. In pharmaceutical applications, this is a problem because large particles will lead to a decrease in capillary blood flow, which in turn will cause mechanical damage to tissues in the human body, causing acute or chronic inflammation. The interaction chamber solves the problems of particle residue and demulsification. However, the chamber’s internal structure means that when the products’ concentration and viscosity are high, the chamber is more prone to cause flow blocking than impact homogenizers are.
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| ==By principle of pressurization==
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| The ultra-high pressure homogenizer needs a large thrust to push the piston in the cylinder to achieve high pressure levels. The rotating motor needs to reduce the speed, increase the torque, and convert the linear motion to obtain the linear reciprocating motion with high thrust. The principle of pressurization operates differently in direct-drive type and intensifier-type homogenizers.
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| ===Direct-drive type===
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| [[File:High_Pressure_Homogenizers_direct-drive.jpg|thumb|250px|right|Internal structure diagram of direct-drive type homogenizer]]
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| The motor drives the crankshaft to move the plunger back and forth and directly pressurize the material. Multiple sets of plungers provide constant pressure, and the flow rate is high for this type of homogenizer. However, the minimum material requirements are also high, as is the amount of residual produced.
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| The crankshaft driven by the motor needs a multi-stage gear reduction mechanism, which limits these homogenizers to only moderate efficiency and requires large unit dimensions. This homogenizer type is suitable for the food and chemical industries, as well as other applications that do not have high pressure requirements.
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| ===Intensifier type===
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| [[File:High_Pressure_Homogenizers_hydraulic_type-quad_pump.jpg|thumb|250px|right|Structural diagram of hydraulic type-quad pump with constant pressure]]
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| The intensifier-type homogenizer is the result of the development of ultra-high pressure technology in recent years. One of its mechanisms involves the motor driving the oil pump to pressurize the material through the hydraulic system. The pressure provided by the hydraulic system is higher than in direct-drive homogenizers, while the volume and the minimum material requirement is smaller. The intensifier-type homogenizer can be applied to both laboratory and production homogenizers with high pressure.
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| Hydraulic homogenizers are expensive, but the hydraulic intensifier can achieve low-frequency and high-thrust piston movement, which increases the machine’s service life and reduces its maintenance costs. Using parallel four-cylinder technology, stable pressure can be obtained without an accumulator, achieving ultra-high pressure of up to 45,000 psi.
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| In the past, most high pressure homogenizers were the direct-drive type, but this type’s disadvantage is obvious. Its service life is short, and its wearing parts need frequent maintenance, especially those pressure-bearing parts when the pressure is above 100 MPa. Hydraulic homogenizers have a high manufacturing cost, but they also offer a long service life and lower maintenance costs for wearing parts.
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| =How to select a high pressure homogenizer=
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| ==Selecting a high pressure generator==
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| [[File:High_Pressure_Homogenizers_Ceramic_piston.png|thumb|250px|right|Ceramic piston]]
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| Overall, a cylinder with an intensifier is superior to a direct-drive one.
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| Under the same flow rate, higher pressure produces lower frequency, fewer pressure fluctuations, better product quality, and greater equipment durability. At 30,000 psi, a laboratory high pressure homogenizer<ref>NanoGenizer, [https://www.genizer.com/nanogenizer_p0039.html]</ref>, can reach fluctuation levels of less than 10 Hz, as opposed to 60 Hz from a normal homogenizer.
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| High pressure piston materials can be divided into ceramics, tungsten carbide, and hardened stainless steel, with ceramics as the costliest option and hardened stainless steel as the most affordable. Quality and durability align with cost: Ceramic materials offer the highest quality, followed by hard tungsten alloy, with hardened stainless steel as a lower-quality option.
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| ==Selecting homogenization parts==
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| [[File:High_Pressure_Homogenizers_Homogenization_chamber_performance_comparison.jpg|thumb|400px|right|Homogenization chamber performance comparison]]
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| As a core component of homogenizers, homogenization chambers play a decisive role in achieving optimum results for the process. Different inner constructions of homogenization chambers lead to different results and applications.
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| When selecting a suitable homogenizer, the purchaser must consider both performance and cost. In general, the cost of the first-generation homogenization chamber is more economical, but its performance in the homogenization process is not as good as the second generation’s. The second-generation homogenization chamber produces a superior product, but when processing materials with high concentration and viscosity, it is more likely to block than first-generation machines, and its cost is higher as well. The interaction chamber with a cooling system, developed by Genizer, can be used for thermally unstable biological and pharmaceutical products.
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| ==Maximum homogenizing pressure==
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| In general, higher homogenizing pressure leads to better quality. This is because the particle size will be much smaller and more uniform if the homogenizer’s pressure is higher, which means processors produce the nanomaterial more efficiently. Higher homogenizing pressure also allows more kinds of samples to be processed. For example, emulsions usually require a homogenizing pressure of 20,000 psi to achieve a particle size of 100 nm, while suspensions usually require at least 45,000 psi to reach nanoscale.
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| It should also be noted that high temperature will affect the results of the homogenization process. The higher the pressure is, the higher the temperature will be. Because of this, 30,000 psi is the maximum pressure for high pressure homogenization without a cooling system. Due to the high temperature, the homogenization effect of more than 30,000 psi does not increase with pressure. The development of the ultra-high pressure diamond interaction chamber with a cooling system can effectively reduce the content of large particles and solve the problem of emulsion stability caused by high temperature. Therefore, machines equipped with this type of chamber can achieve pressures up to 60,000 psi.
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| ==Product uniformity==
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| Generating a uniform particle size distribution is quite important during the production process. A wide distribution of particle size from nanometer to micron not an acceptable result, especially if particles larger than 5 um are present in a pharmaceutical emulsion. USP (US Pharmacopeia) regulates the particle size distribution of pharmaceutical emulsions. Interaction chambers produce a more uniform particle size distribution than impact valve homogenizers.
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| =The future of high pressure homogenizers=
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| In 2010, the FDA announced a recall of eleven batches of clevidipine butyrate injection emulsion across the United States due to the possibility that the emulsion contained inert metallic particles<ref>Recall -- Firm Press Release. FDA.[https://www.fda.gov/media/78662/download]</ref>. Particles gathering and forming larger particles would theoretically lead to clogging in blood capillaries, causing mechanical damage to the body or other acute or chronic inflammations.
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| Therefore, it is not recommended to use the impact type of homogenization chamber in the pharmaceutical industry. These models are no longer suitable for mass production of pharmaceutical emulsion injection. The interaction mechanism is also more durable in ultra-high pressure machines when equipped with temperature control. With increasing demand for nanomaterials, which require higher pressure and higher performance in nano-dispersion, interaction chambers will be more widely used in nanotechnology fields, such as pharmaceuticals, semiconductors, and microelectronics.
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| In the past century, the homogenizer has experienced many changes, from the shift from low pressure (10,000 psi) to high (20,000 psi) and ultra-high pressure (60,000 psi); from the homogenizing valve design, to the use of interaction chambers and chambers with temperature control; from the direct-drive type to the intensifier and multi-pump constant pressure types.
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| With the development of the high thrust linear actuator system, high-thrust and low-speed linear motors will be applied in ultra-high pressure homogenizers in the future. As the pressure increases, temperature control will be a major technical challenge—and therefore, a temperature-controlled and ultra-high pressure-durable interaction chamber is a major avenue for future development.
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| =Videos=
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| <youtube>DG-KCCc8bC8</youtube>
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| <youtube>7ceRNlsDo3c</youtube>
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| <youtube>jdi8z-PWIGc</youtube>
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| <youtube>L75LnkRXNLw</youtube>
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| =References= | | =References= |
| <references /> | | <references /> |
Gene delivery liposome with phospholipid bilayers
Liposome extruders are mainly used for the liposome formulation and achieving uniform size distributions. It is an ideal instrument to generate nanoscale liposome formulations, and to prepare exosomes and artificial cell membranes. By utilizing the tracked-etched filter membranes, the liposome extruders are capable of capturing large particles, precipitation and achieving sterile filtration.
A liposome is a spherical-shaped vesicle composed of phospholipid bilayers. Phospholipid bilayers are critical components of cell membranes, with hydrophilic and hydrophobic properties. In an aqueous solution, the hydrophobic ends tend to bind to each other, and spontaneously form small spherical liposomes. The liposome extruder is designed for the preparation of liposomes. It is easy to use, and has high precision particle size control ability with narrow distributions and satisfactory repeatability. So far it has been widely used in the preparations of complex injectable products, such as paclitaxel liposomes, adriamycin liposomes, amphotericin B liposomes, doxorubicin liposomes, cytarabine liposomes, and irinotecan liposomes.
Schematic diagram depicting the liposome extrusion
Liposome extrusion technology is employing the structural and performance characteristics of liposomal phospholipid bilayers. When the operational temperature is slightly above the phase transition temperature of phospholipids, the large vesicles of liposomes will pass through polycarbonate membranes with specific pore sizes by a certain external extrusion force. The large particle size liposome or multiple compartments liposomes are rapidly repolymerized into smaller-size liposomes after being ruptured by the shear of membrane pores. Since the pore size of polycarbonate membrane is fixed (e.g., 50nm, 100nm, 200nm, 400nm, 1um, etc.), and the polycarbonate extrusion membrane features vertical and uniform nano pore distributions on the membrane surface, when the large vesicles pass through the membrane with a specific nano pore size several times, the sample is extruded to the uniform size decided by the pore.
Application
Research and Development for the liposomal drug delivery system, vaccine, gene delivery, and cosmetics. Liposome extruders are mainly used for the liposome formulation and achieving uniform size distributions. It is an ideal instrument to generate nanoscale liposome formulations, and to prepare exosomes and artificial cell membranes. By utilizing the tracked-etched filter membranes, the liposome extruders are capable of capturing large particles, precipitation and achieving sterile filtration.
Common Types of Liposome Extruders
Liposome extruders can be classified into three categories: hand driven liposome extruders, jacketed liposome extruders, and online liposome extruders. Each category is based on its different power sources.
Hand Driven Liposome Extruders
Hand Driven Liposome Extruders
The hand driven liposome extruders are capable of processing the sample volume from 0.25mL to 2.5mL, which is suitable for mini sample volume applications during the experimental phase. It is operated by simply pushing the plunger manually.
There are two types of hand driven extruders:
- extruders under ambient temperature
- extruders with jacketed option
The hand driven Nano Pore liposome extruders with cooling jacket are designed for those extrusion conditions to control the sample temperature.
Jacketed Liposome Extruders
Jacketed Liposome Extruders
The jacketed liposome extruders have a wide range of processing capacities, from sample volume 2mL to 3L depending on the models. It is suitable for lab scale and pilot scale applications. It is driven by compressed nitrogen cylinder. Most of the jacketed liposome extruders are designed with jacketed barrel to achieve the temperature control of the sample.
Online Liposome Extruders
Online Liposome Extruders
Online liposome extruders are available for the processing capacity from 2mL to 20L depending on the different models. These extruders are more suitable for pilot scale applications. It is powered by a high-pressure pump unit or other production equipment.
Multiple Liposome Extruders System
Multiple Liposome Extruders systems with liposome extruding control panel
The multiple liposome extruders system is able to process the volume from 1L to 200L. It features both the temperature and pressure sensors in the product line, and a control panel to control the production for liposomes.
Track-Etched Polycarbonate Extrusion Membranes
Microscopic Representation for Track-Etched Polycarbonate Membranes
The operations of liposome extruders have high requirements for the extrusion membranes. The nucleus track-etched polycarbonate membranes should have uniform distributions of filter pores. In an ideal membrane, all nano pores should be of the same size. Furthermore, the extrusion membrane with vertical pore distribution is more conducive to the preparation of liposome extrusion.
In general, selecting right size of the polycarbonate membranes will ensure successful extrusion. It is strongly recommended to know the initial particle size of the processing sample before the extrusion. Another factor to consider for selecting the membrane is the desired particle size for your end product.
For example, if the initial particle size of the sample is 1μm, and the target is to achieve the particle size below 100 nm, here are several options available:
Extrusion Multiple Times via the Target Pore Size Membranes
For example, the user can extrude the sample through a 100 nm polycarbonate membrane using a liposome extruder several times.
But the problems that may arise are:
- The difficulties in extrusion process;
- The large vesicles may block the surface of the polycarbonate membrane, and request a replacement of a new membrane, etc.
Extrusion via the Different Pore Size Membranes
This procedure is to use different pore size membranes to extrude step by step. For example, the sample is extruded through a 400nm polycarbonate membrane first, and observe the extrusion process. If it is hard to extrude the sample through the 400nm membranes, then replace a new membrane with a larger pore size, such as 800nm for extrusion 3~5 times. It can be optimized during the process. After the first-round extrusion, select a smaller pore size polycarbonate membrane, such as 100 nm or 80 nm to extrude again. 200 nm polycarbonate membranes can be used as a transition if the extrusion is difficult to go through the 100nm membranes.
High Pressure Homogenization-Extrusion Method
High Pressure Homogenizer combines with online liposome extruder
The sample can be high pressure homogenized first, and extruded through a 100nm or 80nm polycarbonate membrane after homogenization.
Videos
References
