A screen is many formulations run in rounds, and a result only means something when it can be set against the others. That puts the formulation method at the center of the decision, because the method is what has to make dozens of small-volume formulations and mix every one the same way so the results stay comparable across the whole set. The method a team picks decides how far limited RNA and lipid stretch, how tightly particle size and PDI hold from one formulation to the next, and how much hands-on work piles up across a full set.

Those three pressures separate methods built to scale a screen from methods built to make one formulation at a time. The four metrics below are the ones LNP teams weigh most often, from bulk mixing through microfluidic mixing on the liquid handler, and each one answers the same demands differently.

Bulk mixing combines the lipid and aqueous phases by hand or by simple stirring. It needs no dedicated equipment and sets up in minutes, which is why it is where many formulation efforts begin. The cost is in the mixing itself, which is slow and uneven, so the lipids assemble into larger particles with broader size distributions.

The problem for a screen is that this variability carries straight into the data, where a result cannot separate a real formulation difference from a mixing artifact. Bulk mixing can confirm that a composition makes particles at all, but its run-to-run variability makes it unsuitable for comparing candidates reliably across a screen.

Impinging jet mixing drives the lipid and aqueous streams together at high velocity on a pump-driven benchtop system. The force of that collision mixes the phases fast and evenly, so particle size and PDI come out far tighter than bulk mixing reaches.

An impinging jet system formulates one sample at a time and cleans its fluid path between formulations, which adds dead time to every formulation in a screen. It is built to produce a larger volume of a single formulation rather than the many small-volume formulations a screen works through, so it scales poorly as the candidate count climbs.

Benchtop microfluidic instruments mix the two phases inside a chip or cartridge under controlled flow, which produces the small, uniform particles a screen needs. It hits that quality at the small volumes a screen works through, which impinging jet mixing cannot.

Benchtop microfluidic mixing gives ground on throughput and handling. Each formulation is loaded and collected by hand, and the mixer is cleaned or swapped between formulations, so a run stays in the tens of formulations per hour. The instrument also sits outside the liquid handler, so every formulated sample transfers back by hand for dilution and characterization, which piles more steps onto an already manual set.

On-deck microfluidic mixing keeps the same controlled microfluidic mixing but moves it into a consumable that sits in a standard deck position, so the liquid handler drives each formulation through it. Particle size and PDI hold as tightly as a benchtop instrument reaches, because the mixing is controlled the same.

There is no fluid path to clean and no cartridge to swap between formulations, so a screen reaches 100+ formulations per hour. Formulation and collection stay in one method on the deck, so fewer manual transfers stand between mixing and characterization.

The table below lays out all four methods against what a screen asks of them.

The LNP Screening Array runs this on-deck microfluidic mixing on standard liquid handlers, holding particle quality while formulating at 100+ formulations per hour. Each formulation uses as little as 100 µL, so a method that scales to a full screen still conserves the limited RNA and lipid a screen runs on.

Blank SM-102 LNPs made on the LNP Screening Array measure 56 to 60 nm with PDI of 0.12 to 0.14 and under 3% Z-average CV across standard liquid handler platforms. Those figures hold the particle quality a benchtop instrument reaches at a throughput no one-at-a-time method can match.

Hold particle quality at 100+ formulations an hour on the liquid handler you already own.