Liposome Production Pack

[O-MIX-LIPO-PCK]

Complete system for producing liposomes reproducibly over the size range from 40 nm to 150 nm

Liposomes are nano-spherical lipid vesicles. These structures hold promise for delivering therapeutic agents due to their biocompatibility, and ability to encapsulate various types of drugs and nucleic acids. Microfluidics revolutionizes liposome production by providing precise control over mixing organic and water phases on-chip. This enables reproducible outcomes in liposomal size, polydispersity, morphology, and lamellarity, ensuring high-quality lipid-based nanoparticles.

The Fluigent Liposome Production Pack is a reliable and complete system for long-term production, with the ability to vary the particle size over the range from 40 to 150 nm. This includes Fluigent’s LineUP microfluidic pumps and Little Things Factory (GmbH)'s staggered herringbone mixer, a reusable glass microfluidic chip.

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Main benefits

Cost effective
Reusable glass herringbone mixer
Easy to use
Ready-to-use system with complete protocol
Versatile
Adjustable liposome size
High precision
< 0.2 PdI

Features of the Pack

Complete System

Provides all the components needed to start generating liposomes with high monodispersity and stability.

Engineered Solution

Designed with right pressure controllers, microfluidic chip, and accessories to give you the greatest possible flexibility in terms of particle size and generation rate.

Dedicated Protocol

A complete method is provided to assist you in setting up and starting your experiments.

Customization

We can adapt the package to meet your needs (particle size, generation rate).

Related applications

Why use microfluidics for liposome synthesis?

The physical characteristics of liposomes (size, polydispersity index (PDI), lamellarity) depend not only on the lipid composition but also on the method of preparation. Traditional methods like thin-film hydration and extrusion have been commonly used, though they come with limitations. These can be time-consuming processes with high batch-to-batch variation, making them less suitable in drug development. The emergence of microfluidics in the last decade has advanced the field by offering a more efficient and precise approach to liposome synthesis. These include control of fluid dynamics, high control of flow ratios, contributing to uniform size, minimal variation, and reproducibility of the size of the liposomes generated.⁶

Manufacturing Method	Advantages	Disadvantages
Film hydration	– Established method – Understood method	– High consumption of organic solvents – High PDI – Lack of reproducibility Need for additional downsizing step – Difficulties in scaling-up
Solvent injection	– Simple and fast – Scale-up possibility	– Exposure to organic solvent – High PDI – Stability problems
Extrusion	– Uniform and homogenous formulation	– Possible clogging of the membrane pores – Difficulties in scale-up
Microfluidics	– High encapsulation rate – Control of the liposome size – Homogeneous size distribution – Ability to control temperature	– Highly dependent on the instrument – May require some expertise for manufacturing microfluidic chip

Microfluidics staggered herringbone mixer for liposome production: Efficient, sustainable, and cost-effective

The Little Things Factory (GmbH) staggered herringbone mixer includes an Inlet, mixing section, and outlet. The inlets of the device are shaped in a flow-focusing design, which permits instant visualization and easy control of the aqueous and lipid phases before mixing. After, the mixing section is formed by 30 half-cycles including 6 herringbone structures each.

The herringbone structures induce rotational flow, causing the two phases to wrap around each other with alternating orientations between each half-cycle. This process results in a flow profile characterized by a decreasing diffusion length between the streams. This facilitates rapid mixing and promotes the lipids to self-assemble into liposomes. By tuning the lipid concentration, flow rate ratio, and total flow rate, the size and monodispersity of the liposomes are efficiently controlled.⁷

Manufactured in glass, the chip can be easily connected to the microfluidic setup with standard 1/4-28 UNF threaded ports. The chip can be cleaned and reused.

Liposome generation set-up

Figure 1: Liposome production set-up.

flow ez microfluidic flow and pressure controller

Microfluidic flow controller

Bidirectional Microfluidic Flow Sensor

Real-Time Control & Lab Automation Software

Case Study: How to produce drug-loaded liposomes for ovarian cancer treatment studies

See our case study, based on the paper published in Scientific Reports (2024) from the Ca’Foscari University of Venice. This describes the production of amiodarone-loaded liposomes with precise control over size and drug content obtained using the Flow EZ and the glass herringbone mixer.

Figure 2: TEM image of the obtained liposomes for FRR 3:1 (at TFR = 1 mL/min, the flow rate was 750 µL/min for the aqueous phase and 250 µL/min for the organic phase).⁸

Figure 3: Liposome internalization by cells.⁸

Specifications

LineUp Flow EZ pressure controller (7000 mbar) x2

LineUp LINK Module (software control) x1

FLOW UNIT XL (x2)

P-CAP series 15 mL (x2)

P-CAP series 50 mL (x1)

OxyGEN Software

Digital High-speed Opto Microscope (optional)

Staggered herringbone mixer chip

Microfluidic Chip Specifications

Herringbone micromixer chip	Little Things Factory – T29
Material	Borofloat®33
Dimension	75 x 25 x 2 ± 0.3 mm
Total volume	3.0 µL
Mixer volume	0.47 µL
Mixer length	28.7 mm
Channel depth	0.08 – 0.11 mm
Channel width	0.1 – 0.5 mm

Liposome Production

Lipid phase	Lipids in organic solvent (depending on the application). In the User Guide, absolute ethanol, lipids (40 mg/mL), and Dimethyldioctadecylammonium (DDAB – 10mg/mL) were used.
Aqueous phase	Phosphate-buffered saline (PBS) (pH 7.2)
Particle size range*	40 nm to 150 nm
Polydispersity*	From 10% to 20%

* Depending on FRR (download the Liposome production pack User Guide for more information).

OxyGEN

Control in real-time, protocol automation, data record and export

ver. 2.2.0.0 or more recent

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Software Development Kit

Custom software application

ver. 22.2.0.0 or more recent

See the offer

Imaging

OptoViewer Software

	Batch Method	Fluigent microfluidic method
Particle size distribution	Low	High
Reproducibility	Low	High
Live particle size control	No	Precise
Range of particle size	Limited size range	Wide size range
Continuous (in line) production	No	Yes

Liposome Production Pack