LNP clean-up & concentration

The problem

After lipid nanoparticles (LNP) are formed, organic solvents like ethanol need to be removed quickly to maintain drug encapsulation and LNP integrity. Dialysis is often used but takes longer and requires a secondary concentration step to reduce the sample volume.

The right tools for the job

Unagi is the first benchtop buffer exchange platform that brings together all the painful, hands-on steps it takes to clean up, concentrate and exchange LNPs, without compromising integrity. Unagi uses ultrafiltration/diafiltration (UF/DF) to exchange 1 to 8 samples from a starting volume of 0.5 to 8 mL. Unagi keeps careful track of sample volumes during a run with ultrasonic volume measurement, filters samples down and knows the exact volume to add to each sample. It repeats this until each sample hits the target percent exchange and/or LNP concentration.
The secret sauce
Unagi uses a consumable called the Una. Each Una holds 0.5 to 8 mL of sample and Unagi handles 1-8 sample per run. They use regenerated cellulose membranes with 10, 30, and 100 kDa molecular weight cutoffs to make sure your samples stay put, don’t get absorbed, and the liquid passes right through — with ≥96% recovery.
Big Tuna is a fully automated buffer exchange system that scales up the throughput using the same modified ultrafiltration/diafiltration (UF/DF) technology to quickly clean up, concentrate and exchange LNPs. Big Tuna monitors the sample volumes during the run, adds back the filtered volume and gets your samples to the right percent exchange and concentration every time. The organic solvents that LNPs typically start in flow rapidly and Big Tuna has the ability to make the right adjustment, so wells won’t run dry.

Big Tuna uses a plate-based consumable called the Unfilter. All Unfilters use a regenerated cellulose membrane that reduces non-specific binding. They come in 2 formats, 24-well (0.45 – 8 mL) or 96-well (100 – 450 µL). The Unfilter 96 is available with molecular weight cutoffs of 3, 10, 30, and 100 kDa. The Unfilter 24 has 10, 30, and 100 kDa MWCOs. The 24- well, 100 kDa Unfilter is best for processing high volume LNP samples at fast rates.


The proof

Unagi’s buffer exchange and concentration parameters can be optimized to achieve high sample recovery with minimal change to sample integrity. You won’t have to sacrifice sample quality, like size change or encapsulation efficiency, in your LNP sample preps to save hands on time.
Unagi table_2

Big Tuna is really good at nanoparticle concentration and clean-up while also maintaining payload encapsulation. A typical nanoparticle concentration and cleanup run can be set up in under 30 minutes and can be finished in as little as 90 minutes.

LNP clean up & concentrate table


Buffer exchange and concentration are two of the most annoying things you have to do before you can work with your sample, even for just a handful. It takes forever, you physically have to be there and just when you think it’s done, you’re tweaking it again, even for a handful of samples. Unagi is the first completely hands-free benchtop buffer exchange solution that’s made to take this not-so-fun task off your plate — so you can be anywhere else instead of tied to your bench.

Big Tuna front_crop

Big Tuna

Buffer exchange and nanoparticle concentration are the time consuming, hands-on chores you have to deal with before all the things you really want to do. Big Tuna automates exchange to formulate, concentrate and clean up proteins or gene therapy vectors like AAVs, LNPs, and VLPs — with just 30 mins of setup time. Skip the slow and manual ways of prepping samples to free yourself up for other critical work.

Want more info?

Want to learn more about how Unagi or Big Tuna can help you prep your lipid nanoparticles?