From 100µL/min to 30 mL/min
Produce liposomes and lipid nanoparticles from few µL to L
Reproduce highly monodisperse nanoparticles - from 60 to 250 nm.
The lipid nanoparticle generation Pack offered by Elveflow is designed for researchers with no experience in microfluidics and/or lipid nanoparticle generation to easily produce lipid nanoparticles (LNP) using microfluidics techniques.
Thanks to our pressure-driven flow control system, a wide range of flow rates (TFR) – from µL/min to 10s of mL/min – can accommodate both low (µL) and large (L) volume production.
This versatile platform can be easily scaled up to meet your requirements from the screening to the production stage.
Lipid nanoparticle (LNP), solid lipid nanoparticles (SLN) and nanoliposomes can be synthesized using this instrument pack.
Historically, the generation of LNPs was carried out using standard bulk processes (precipitation, emulsion, solvent evaporation and sonication). However, these techniques suffer from broad size distribution and poor batch-to-batch reproducibility. This is highly problematic in clinical trials and production stages of drug development. Microfluidics is a highly promising alternative that has attracted a lot of attention for its advantages as a LNP fabrication method.
Some of these advantages include:
For more information you can read our review about nanoparticles synthesis in microfluidics.
We have conducted extensive characterisation of LNPs generated using this pack including DLS and cryoTEM measurements. Using various TFR and FRR conditions, we synthesised LNPs ranging from 60 up to 250 nm diameter.
Intensity (yellow), number (green) and volume (blue) profiles of LNPs generated using the Herringbone micromixer with a 3:1 FRR and a 4ml/min TFR.
Plot of ImageJ analysis of LNPs size generated using the Herringbone micromixer with a 3:1 FRR and a 4ml/min TFR.
Mixing the two aqueous/RNA and ethanol/lipid phases is the key step of NPs generation. In this Pack, based on microfluidics efficiency, this is done using micromixing chips. For instance, one would use a flow focusing micromixer allowing for passive nucleation of nanoparticles.
This Pack and our experts help you choosing the appropriate chip!
All our application notes
All our reviews
Ribonucleic acid (RNA) is a critical polymeric molecule for the regulation and expression of genes. RNA interference (RNAi) is a method that silences genes by using sequence-specific small interfering RNA (siRNA). Based on their mRNA counterpart nucleotide sequences siRNAs block the production of specific proteins [1-3]. To deliver siRNA for therapeutic applications, lipid nanoparticles (LNP) are the most commonly used system for in vivo applications like anti-tumor agent or polyneuropathies treatment [4-5]. The BioNTech/Pfizer’s BNT162b2 and Moderna’s mRNA-1273 vaccines also use lipid nanoparticles as vehicles for mRNA delivery into the cytoplasm of host cells that lead to the production of COVID-neutralizing antibodies [5]. Thus, lipid nanoparticle synthesis have played a critical role in the development of COVID-19 vaccines and other nanomedicines and are considered to be very promising for the development of new drug delivery systems [6].
Lipid nanoparticles can be used for other applications like using solid lipid nanoparticle (SLN) as cosmetic delivery systems [7].
The lipid nanoparticle synthesis pack includes staggered herringbone micromixers that create chaotic flows. They are the most commonly used microfluidic chips for LNP synthesis [8]. The structure generates chaotic advection which is able to induce rapid mixing at Reynolds numbers smaller than 1 [9] thus allowing a better encapsulation efficiency than bulk methods [10].
Lipid nanoparticle (LNP) formulation example
The amazing benefits of microfluidics can be applied to many Liposome and Lipid Nanoparticle applications and therefore the content of the Liposome and Lipid Nanoparticle Synthesis Pack can be adjusted to suit your specific needs!
There are a few ways to generate lipid nanoparticles in microfluidics. In any case, the most important part relies on the fast mixing of two phases (organic and aqueous). The more efficient and homogeneous the mixing is, the better the control over the size and its distribution. The following figure illustrates how the speed of mixing influences the LNPs size; a slow dilution of the ethanol phase (a) leads to large particles in comparison with a faster dilution (b).
The Herringbone ChipShop Fluidic 187
The Flow focusing ChipShop Fluidic 386
Contact our experts to know which one will be best suited to your requirements!
“The advantage of this instrument is the capability it offers to easily move the experiments anywhere you want. This feature is very convenient, especially when we encapsulate cells into droplets in cell culture platforms.”Pr. Annie Viallat, Adhesion & Inflammation Lab – CNRS UMR 6212 – INSERM UMR 600, FranceOB1 flow controller user
“I appreciate rapid setup time and the fact that we can very precisely adjust the flow rates through the user-friendly interface”Dr. Caglar Elbuken, UNAM, Bilkent University, TurkeyOB1 flow comtroller user
“I found the systems quite robust and easy to connect and use. ”Dr. Martino Chiara, DeMello's Group, ETH Zurich, Switzerland OB1 flow controller user
The Liposome and Lipid nanoparticle synthesis pack is designed to suit your application requirements.
It contains at least two pumping channels to push the two chemical solutions needed to perform the Liposome and lipid nanoparticle synthesis process inside at least one herringbone micromixer chip. Lipid nanoparticle (LNP), solid lipid nanoparticles (SLN) and nanoliposomes can be synthesized using this instrument pack.
Microfluidics chips are used in this system to induce the mixing of your two solutions at a microfluidic scale. The first liquid contains the lipids in ethanol and the second one is the aqueous solution with possibly the hydrophile load that will be encapsulated inside the newly formed LNP such as siRNA or mRNA for example (see the application tab).
Two different chip designs can be provided with this pack, depending on your requirements:
The production can be easily scaled up by increasing the volumes and flow rates, and/or parallelizing several micromixers instead of one, thus increasing the overall throughput of the system while maintaining monodispersity and yield.
The stability and the speed of the reaction directly depend on the flow rates of each fluid and their ratios in the microfluidic channel. The flow is created by the Elveflow OB1 mk3+ flow controller and the flow rates are measured and regulated thanks to flow rate sensors (MFS or BFS series) permitting a very high accuracy and stable flow control. The combination of these instruments is the fastest and most precise microfluidic flow control available on the market which guaranties the best possible LNP monodispersity and reproducibility. Furthermore, the lipid nanoparticle synthesis process can be automated thanks to the software controlling the Elveflow instruments.
Pressure-driven flow control systems are well-suited for Liposome and Lipid nanoparticle synthesis compared to peristaltic or syringe pumps as they offer the most pulsless flow and can be easily adapted for small and large volumes.
The fluidic 187 herringbone chip from microfluidic ChipShop is composed of three separate channels that are 200 µm deep and 600 µm wide. The two inlets for a single channel are 300 µm wide and the single outlet is 600 µm wide. The microfluidic chip is available in polycarbonate (PC) or Zeonor cyclo-olefin copolymer (COP) materials: these materials are optically transparent and harder than the classically used PDMS.
Herringbone micromixer, ChipShop Fluidic187
Alternatively, you can choose a flow focusing micromixer wich will allow for nanoparticle nucleation thanks to diffusion at the interface of the phases.
The microfluidic platform flexibility can be increased by adding a MUX Distribution 12:1 valve after the reservoirs that allows switching between up to 12 different solutions in an instant. This can be, for example, used to quickly change the load of the lipid nanoparticle!
A broad range of reservoirs are compatible with our OB1 flow controller, from 1.5 mL Eppendorf tubes to 100 mL bottles. It is also possible to add pumping channels on the OB1 pressure control pump to increase the number of parallel micromixer channels further.
Contact our experts to answer any questions about this lipid nanoparticle synthesis pack and how it can match your specifications!
For any help to determine what microfluidic instruments you need, you can contact us! Our experts will help you build the best microfluidic setup for your application, with our state-of-the-art microfluidic line.
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