Technology
Precision nanocapsules delivered at industrial scale
We design, develop and manufacture next generation high-throughput microfluidic devices tailored to production of Liposomes, Dendromers and PLGA nanoparticles.
Our microfluidic devices enable:
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Low stress mixing (no seer, chemical or heat stress) allowing us to work with fragile compounds (such as proteins and mRNA)
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Precision control over nanocapsule size and size distribution (CV as low as 1%)
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Highly efficient and consistent loading of individual nanocapsules
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Lot-to-Lot reproducibility
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Scalability
Purpose designed microfluidic devices
Liposomes, Dendrimers and PLGA nanoparticles are produced using a process of nanoprecipitation.
This is a complicated process where the nanocapsules are assembled from the bottom-up in several distinct stages, all of which are reversible:
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Nucleation
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Fast growth – formation of initial seeds and particles
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Slow growth – formation of larger particles
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Quenching in the final form
Each of these stages will have an effect the properties of nanocapsules. Final size of the particles is dependent on the balance between nucleation stages and growth stages. Particle uniformity (monodispersed) is determined by growth histories of all particles that ideally have to be identical. Efficiency of encapsulation and ability to encapsulate fragile ingredient (e.g. proteins or mRNA) is dependent on low seer mixing, which in turn has to be balanced with the requirement for fast diffusion rates needed to initiate particle nucleation.
SMALL Bio Microfluidic devices are designed such that each stage of the nanocapsule formation takes place in a dedicated zone of the chip.
ZONE 1
Mixing
The architecture is designed to enable rapid, sub millisecond, mixing times and thus enable instantaneous nucleation of nanocapsules. At the same time, the mixing is low sheer, enabling work with fragile compounds such as proteins and mRNA.
ZONE 2
Fast Growth
The architecture is designed to enable fast diffusion of nanocapsule materials towards the initial nuclei formed in Zone 1. In this zone the working solutions are settled to prevent unwanted chaotic mixing.
ZONE 3
Slow Growth
In this zone the working solution mixing is slowed down even further to enable steady sate diffusion of nanocapsule components, surfactants and other surface-active groups to the nanocapsules formed in Zone 2.
ZONE 4
Residence Time
This part of the microfluidic device is designed to enable sufficient residence time for nanocapsule formation to complete fully. By the end of the residence time zone the nanocapsules are fully formed, stable and ready for post processing.
ZONE 5
Post Processing
This zone is used to introduce additional functionality to the nanocapsules or undertake any additional post processing e.g. undertaking additional chemical processing, substituting a surfactant or placing additional functional coating on the surface of the particles.
ZONE 3
FAST MIXING
SLOW PARTICLE GROWTH
FAST PARTICLE GROWTH
RESIDENCE TIME
LIMIT
POST PROCESSING
ZONE 1
ZONE 2
ZONE 4
ZONE 5
This enables:
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Ability to work with fragile materials such as proteins and mRNA
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High material quality (particle uniformity)
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High process reproducibility
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High encapsulation efficiency
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Scalability
Scalability to industrial volumes of production
Today, Liposomes, Dendromers and PLGA nanoparticles are produced at industrial scale using large-scale batch reactors. These techniques are outdated, ineffective and wasteful leading to polydisperse materials with high batch-to-batch variation and poor encapsulation efficiencies. These materials perform poorly in target applications and require substantial purification steps.
By contrast, Microfluidic approaches result in highly uniform (monodisperse), lot-to-lot consistent nanocapsules that are able to encapsulate materials with high degree of efficiency. These techniques however are limited to laboratory scale and deliver materials at scale sufficient only for R&D purposes.
SMALL Bio bridges the gap between industrial scale of production and precision manufacturing of modern nanocapsules. Our Microfluidic devices are packaged very efficiently into large industrial units that enable throughputs up to 1 tone per day.
