Inside TAMARA LNP Nano Lipid Particle Synthesis System

TAMARA is an integrated microfluidic nanoparticle preparation system jointly developed by Inside Therapeutics (InsideTx) and Elveflow in France. It focuses on plug and play, zero sample loss, and high reproducibility, and is specifically designed for the research, development, and small-scale production of biomedical nanocarriers such as liposomes and RNA-LNP (lipid nanoparticles).

1、 Core positioning and purpose

• 全称： TAMARA Plug-and-Play Nanoparticle Formulation System

• Core applications: preparation of liposomes, RNA-LNP (mRNA/siRNA/circRNA delivery), polymer nanoparticles (PLGA), solid lipid nanoparticles (SLN), etc.

Application scenarios: vaccine development, gene therapy, drug delivery, personalized tumor vaccines, CRISPR gene editing delivery, and other preclinical research.

Core advantages: seamless transition from 0.2mL screening to 30mL in vivo experimental scale, zero head and tail loss, encapsulation rate>98% PDI<0.2、 Minimalist operation.

2、 Working principle (microfluidic nanoprecipitation method)

Using pressure driven microfluidic rapid mixing technology to precisely control the self-assembly process of nanoparticles:

1. Two phase preparation

Organic phase: Lipid mixture (ionizable lipids, PEG lipids, phospholipids, Cholesterol) dissolved in ethanol.

Water phase: A buffer solution containing RNA (mRNA/siRNA) or other hydrophilic drugs.

2. Microfluidic mixing

Dual phase precise mixing in dedicated microfluidic chips (with built-in herringbone/baffle chaotic mixer).

By regulating TFR (total flow rate) and FRR (flow rate ratio), controlling the mixing rate, triggering lipid nanoparticle precipitation and self-assembly, uniform nanoparticles are formed.

3. Zero loss collection

The flow path design eliminates head and tail loss, and 100% of the active substance is encapsulated, especially suitable for trace precious samples (such as RNA).

3、 System composition and key parameters

1. Hardware composition

Host: Integrated pressure controller, flow sensor, touch screen operation interface, plug and play, no need for professional microfluidic knowledge.

Microfluidic chip (reusable):

Herringbone mixer: suitable for small particle sizes (~20-100nm), high PDI control, and mainstream RNA-LNP preparation.

Baffle mixer: suitable for large particle size (~100-200nm) and wide particle size range preparation.

Sample reservoir (reusable): Suitable for volumes ranging from 0.2mL to 30mL, reducing consumable costs.

2. Core performance parameters

• Volume range: 0.2mL (screening) 30mL (in vivo), seamless scale up.

Particle size control: adjustable from 20-200nm, with reproducibility of ± 5nm.

• Dispersion (PDI):<0.2 (highly monodisperse).

Encapsulation rate (EE%):>98% (RNA/drug).

• Processing speed:<2 minutes/batch, up to 20 formula screenings per hour.

• Loss rate: 0% (flow path design).

• Difficulty of operation:new userFriendly, touch screen preset parameters, one click operation.

4、 Comparison with traditional methods/competitors

1. Pain points of traditional methods (extrusion/high-pressure homogenization/ultrasound)

Wide particle size distribution (PDI>0.3), large batch differences, low encapsulation efficiency (<80%), high sample loss (>30%), and difficulty in micro screening.

2. TAMARA vs self-developed microfluidic system (such as Elveflow LNP Pack)

TAMARA: Integrated, plug and play Zero loss、 Minimalist operation, reproducibility, and repeatable chips; Disadvantage: Low automation customization.

• Self developed system: highly customizable and compatible with automation; Disadvantages: Complex construction, steep learning curve, high loss (starting from~300 μ L), and reproducibility dependent operations.

5、 Typical application cases

Preparation of mRNA vaccine LNP: such as Moderna style mRNA LNP (ionizable lipid/PEG/phospholipid/Cholesterol), particle size~80nm, PDI<0.15, encapsulation efficiency>98%.

SiRNA drug delivery: such as Onpattro ® Patisiran class siRNA LNP, efficient encapsulation and liver targeting.

Personalized tumor vaccine: Rapid screening of tumor neoantigen mRNA LNP formula to accelerate the development of immunotherapy.

CRISPR-Cas9 delivery: Preparation of Cas9/sgRNA LNP for in vivo gene editing, replacing viral vectors.

VI. Summary

TAMARA is currently an easy-to-use and efficient integrated microfluidic nanoparticle preparation platform on the market, which solves the core pain points of traditional methods and greatly reduces the threshold for RNA-LNP/liposome development. It is a golden tool for preclinical research in the fields of vaccines, gene therapy, and drug delivery.