contact@elveflow.com+33(0).184.163.807+1(414)-406-4343 Elveflow is an Elvesys brand, an international microfluidics innovation center with high level researchers dedicated to microfluidics and organ-on-a-chip.
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From Laboratory Immunoassays to Integrated Microfluidic Immunosensors: A Revolutionary Leap in Diagnostic Technology
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The photolithography mask is an important tool in soft photolithography processes, we explain here how they are made
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Together, we’ve combined our cutting-edge microfluidic flow control capabilities and Inside Therapeutics’ deep formulation expertise to bring you TAMARA, the most advanced microfluidic-based nanoparticle manufacturing system on the market. Introducing TAMARA: Microfluidic Precision for Nanoparticle and RNA-LNP Synthesis TAMARA is based on a bottom-up microfluidic formulation approach to precisely control nanoparticle formulation conditions. The goal was simple: combine the best of microfluidics with user-friendly operation so researchers can focus entirely on drug development, not microfluidic technicalities. That’s exactly what TAMARA delivers: by embedding Elveflow’s high-performance pressure-driven flow control technology within an intuitive platform, TAMARA makes optimal formulation conditions easily accessible, without needing to be a microfluidic expert. With its near instant response time and zero sample loss, TAMARA eliminates common issues that limit regular microfluidic systems such as head and tail losses. Its broad volume range supports the full drug development pipeline from screening to preclinical studies. Its integrated microfluidic device is both reusable and affordable, making it an ideal tool for screening development and meeting quality requirements. Why use Microfluidics for Lipid Nanoparticle Synthesis? Traditionally, nanoparticle formulation relied on top-down techniques such as extrusion, high-pressure homogenization, or sonication. While effective at scale, these techniques often suffer from broad particle size distribution and poor batch-to-batch reproducibility. In contrast, bottom-up approaches, especially nanoprecipitation via microfluidics, offer enhanced control over formulation conditions. Microfluidics is particularly promising for RNA-loaded lipid nanoparticles (RNA-LNPs) due to:
The Lipid Nanoparticle Synthesis Pack includes all the parts needed to easily synthesize your lipid nanoparticles with high monodispersity, production rate and reproducibility for the optimal encapsulation of your mRNA or siRNA molecules.
Microfluidics presents tremendous advantages to overcome the issues encountered with common Liposome bulk preparation. Being characterised by laminar flow conditions and diffusive mass transfer, microfluidics allows for the production of liposomes with excellent control over size and lamellarity. In addition, it enables in situ monitoring of lipid nanoparticles formation process, continuous production and straighforward scale up.
Based on our high accuracy OB1 flow controller, this solution reduces lipid nanoparticle synthesis time and allow to work at small and large volumes (µL to L) while optimizing reagent consumption.
For several years, we have worked hand-in-hand with Inside Therapeutics (InsideTx) to deliver advanced microfluidic solutions for nanoparticles and RNA-LNP formulation. Together, we’ve combined our cutting-edge microfluidic flow control capabilities and Inside Therapeutics’ deep formulation expertise to bring you TAMARA, the most advanced microfluidic-based nanoparticle manufacturing system on the market.
TAMARA is based on a bottom-up microfluidic formulation approach to precisely control nanoparticle formulation conditions. The goal was simple: combine the best of microfluidics with user-friendly operation so researchers can focus entirely on drug development, not microfluidic technicalities.
That’s exactly what TAMARA delivers: by embedding Elveflow’s high-performance pressure-driven flow control technology within an intuitive platform, TAMARA makes optimal formulation conditions easily accessible, without needing to be a microfluidic expert.
With its near instant response time and zero sample loss, TAMARA eliminates common issues that limit regular microfluidic systems such as head and tail losses. Its broad volume range supports the full drug development pipeline from screening to preclinical studies.
Its integrated microfluidic device is both reusable and affordable, making it an ideal tool for screening development and meeting quality requirements.
Traditionally, nanoparticle formulation relied on top-down techniques such as extrusion, high-pressure homogenization, or sonication. While effective at scale, these techniques often suffer from broad particle size distribution and poor batch-to-batch reproducibility.
In contrast, bottom-up approaches, especially nanoprecipitation via microfluidics, offer enhanced control over formulation conditions. Microfluidics is particularly promising for RNA-loaded lipid nanoparticles (RNA-LNPs) due to:
Overview of the nanoparticle and RNA-LNP formulation methods
More info: RNA-LNP manufacturing methods by InsideTx.
Typical RNA-LNP composition used in the mRNA-LNP covid vaccine (Moderna formulation)
RNA-LNPs are formed by rapid mixing of two phases:
When mixed, lipids self-assemble into nanoparticles due to solubility changes. Microfluidics enables precise control of this process, improving reproducibility and reducing waste.
Note: Downstream steps such as solvent removal or sterilization are typically performed post-synthesis and are not part of TAMARA’s integrated process.
Thanks to their flexibility, RNA-LNP can be used for a wide range of vaccines and therapeutics applications
RNA-LNP technology is widely used to develop vaccines that generate strong immune responses against infectious diseases. By delivering mRNA encoding a disease-specific antigen , (viral or bacterial protein) the immune system is trained to recognize and combat the actual pathogen.
This approach showed its potential with the COVID-19 mRNA vaccine but can also be used for other infectious diseases such as Malaria, HIV… While mRNA is the most common payload, other RNA types like self-amplifying RNA (saRNA) and circular RNA (circRNA) are also being explored to enhance efficacy and stability.
By delivering tumor-specific RNA sequences that encode neoantigens, RNA-LNPs can prime the immune system to recognize and eliminate cancer cells . This personalized approach is tailored to the unique mutation profile of each patient’s tumor, opening the door to highly targeted immunotherapies.
RNA-LNPs are increasingly used to deliver therapeutic RNA into cells to treat genetic disorders. This includes two key therapeutic strategies:
mRNA-Based and siRNA Therapies
These approaches are designed for transient protein expression or temporary gene silencing , making them ideal for conditions where short-term therapeutic effects are sufficient. A prominent example is in vivo CAR-T therapy in oncology, where mRNA-LNPs deliver genetic instructions for chimeric antigen receptor (CAR) expression directly in the patient’s T cells. In this context, gene delivery remains a critical challenge, primarily due to the liver tropism of lipid nanoparticles. Overcoming this barrier often involves surface functionalization of lipid nanoparticles to improve targeting specificity.
Another example is Onpattro® (patisiran) by Alnylam, a siRNA-LNP based therapy that targets and silences the mRNA responsible for producing abnormal transthyretin (TTR) protein in hereditary transthyretin-mediated amyloidosis (hATTR).
LNPs are also used to deliver CRIPSR-CAS9 components for permanent gene correction, offering a safer, non-viral alternative to traditional RNA delivery methods such as electroporation or lentivirus. This approach holds promises for treating monogenic diseases at their root cause. Additionally, RNA-LNPs can be adapted to deliver antisense oligonucleotides and other gene-silencing tools to precisely regulate gene expression.
Check out our recent review to know more about CRISPR-CAS9 and its relationship with microfluidics !
This list is not exhaustive. As this field is very active, there are many other applications.
RNA-LNP therapeutics and vaccines have revolutionized modern medicine, yet several key challenges remain before their full potential can be realized. Beyond achieving therapeutic efficacy, enhancing stability, immunogenicity, and extra hepatic delivery are central to advancing next-generation RNA therapeutics. Current efforts focus on three major areas:
1.Targeted Delivery and Biodistribution Control One of the most pressing challenges is improving biodistribution , where and how the LNPs travel and accumulate in the body. Current LNPs show a strong liver tropism , which is not always ideal for vaccines or non-hepatic diseases. Improved biodistribution enhances therapeutic efficacy and safety, especially in systemic applications and repeated dosing scenarios. Improved targeting can be achieved using two different approaches, passive and active targeting:
For more information on this topic, see the detailed review of RNA-LNP active and passive targeting techniques from InsideTx.
2.Mitigating PEG Immunogenicity and Improving Repeat Dosing PEGylation is commonly used to prolong LNP circulation time, but it also poses risks. Anti-PEG antibodies can develop, reducing efficacy upon re-administration and increasing the risk of hypersensitivity reactions. Alternatives such as PEG substitutes , biodegradable polymers , or zwitterionic coatings are under investigation to preserve stealth properties while minimizing immune responses.
3.RNA-LNP vaccine stability The cold chain requirement for mRNA vaccines is a major barrier to global distribution. In a first step, adjusting the lipid mix can significantly enhance the thermal and chemical stability of RNA-LNPs. This involves screening large libraries of lipid combinations, an area where microfluidics excels , thanks to its ability to test hundreds of compositions using minimal sample volumes. Other approaches such as lyophilization , or freeze-drying, can stabilize RNA-LNPs for storage at room or refrigerator temperatures. However, maintaining nanoparticle structure and RNA integrity during rehydration is complex.
From oncology to immunity and rare disease treatment, RNA-LNPs are transforming what’s possible in drug development. Whatever your application, the Elveflow and InsideTx teams are here to help, feel free to reach out to us to discuss your project.
Nanoparticle size is one of the most critical characteristics, influencing biodistribution , cellular uptake , and overall therapeutic performance . The size of the LNPs is primarily governed by the mixing speed between the solvent and aqueous phase triggering the LNP formation. Faster microfluidic mixing leads to smaller particles, while slower mixing results in larger ones, as illustrated in the below graph.
Influence of mixing speed and conditions on RNA-LNP size
To achieve precise and tunable size control, microfluidic devices typically incorporate efficient microfluidic mixing structures, such as baffle and herringbone micromixer , two of the most popular microfluidic chaotic mixers. These micromixers allow users to control nanoparticle size by simply tuning the TFR ( Total Flow Rate , or sum of the aqueous and solvent flow rates ), making size optimization intuitive and repeatable.
Furthermore, FRR (Flow Rate Ratio, or the ratio of the aqueous flow rate over the solvent flow rate) can also be tuned to further control the nanoparticle characteristics.
Illustration and image under a microscope of a baffle and a herringbone microfluidic mixers used for RNA-LNP formulation.
In practice, the graph below illustrates the impact of the formulation conditions on nanoparticle characteristics. It can be noticed that both the lipid composition and the formulation parameters (here the TFR) greatly impact the nanoparticle size, reinforcing the importance of the high level of control offered by microfluidics.
Influence of TFR and composition on LNP size and PDI in a Herringbone microfluidic mixer
While size is critical, other formulation parameters, such as lipid ratios , ionizable lipid choice, and process conditions, have a direct impact on other Critical Quality Attributes (CQAs) like encapsulation efficiency, morphology , and in vivo performance . This complexity underscores the importance of screening a wide range of formulation conditions, particularly during early phase development. This is precisely where microfluidics excels , enabling the efficient production and testing of numerous RNA-LNP formulations at ultra-low volumes, accelerating development while minimizing the use of expensive RNA material.
One of the greatest strengths of microfluidic systems is their adaptability. The same microfluidic platform can be used to produce a wide array of nanoparticle types, from liposomes to complex RNA-LNP formulations, across a broad range of working volumes. This flexibility makes microfluidics ideal not only for screening and optimization but also for producing material for preclinical animal studies.
In practice, microfluidic formulation systems can be deployed in two main ways: homemade system, such as the LNP pack, a custom system including the OB1 pressure controller and flow sensors from Elveflow, and more integrated platform, such as TAMARA from Inside Terapeutics:
Liposome and Lipid Nanoparticle Synthesis Pack related videos
Liposome and Lipid nanoparticle synthesis 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 hydrophilic 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: Flow focusing chips for smooth control of your low volumes/flow rates Staggered herringbone which induces a chaotic mixing for larger volumes/flow rates. 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) allowing 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 guarantees 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 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 hydrophilic 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) allowing 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 guarantees 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.
Configure your microfluidics lipid nanoparticle production 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!
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!
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