Liquid handlers can automate plate-based steps of an LNP screen process, such as dilution, RiboGreen assay preparation, and dynamic light scattering (DLS) plate preparation, because each one comes down to accurate volume transfers between plates.

Formulation is harder to automate because consistent LNP synthesis requires rapid, controlled mixing that pipetting alone does not deliver. Until recently, automating formulation meant buying a dedicated benchtop instrument or accepting the limits of pipette mixing.

Benchtop formulation systems brought controlled microfluidic mixing to LNP screening, but on an instrument separate from the liquid handler. Single-sample instruments such as the NanoAssemblr Ignite produce about 10 formulations per hour, with an operator loading inputs and collecting each sample by hand. Automated benchtop systems such as Unchained Labs Sunscreen reach 15 to 20 formulations per hour but must clean the mixing path between formulations.

Both run as separate instruments, so formulated samples are collected by hand before dilution and characterization.

Some labs formulate on the deck with pipette mixing, using the liquid handler’s own tips to combine the lipid and aqueous phases in a well. Formulation then stays inside the automated method, with no transfer to a separate instrument.

A 2026 ACS Nano study on automated LNP library generation identifies pipette mixing on liquid handlers as a source of batch-to-batch variability in LNP size. Labs have had to choose between formulating quickly on the deck and controlling particle formation on a benchtop instrument. Pipette Mixing vs. Microfluidic Mixing for LNP Screening examines that tradeoff in detail.

On-deck microfluidic formulation resolves that tradeoff by placing a microfluidic consumable in a standard deck position, which gives the liquid handler controlled mixing without a separate instrument. The liquid handler dispenses the lipid and aqueous phases through the consumable with its own pipette tips, and each formulation collects on deck.

Each formulation takes seconds, and the liquid handler moves straight to the next formulation with no cleaning or cartridge change. Throughput rises from 10 to 20 formulations per hour on leading benchtop systems to 100+ formulations per hour on the liquid handler. Speed is one of several criteria for an automated formulation workflow, alongside particle quality and keeping samples on deck for the next step.

Faster formulation lets each screening round include more lipids, molar ratios, and replicates without adding operator time between formulations, so the scope of a higher-throughput screening workflow is set by the lipid library rather than instrument capacity.

A lipid library that once had to be split across several rounds can now be screened with full replicates in one, so every lipid is compared within the same round.

The LNP Screening Array brings microfluidic formulation onto standard liquid handlers, with automation protocols configured for air-displacement, positive-displacement, and pressure-controlled pipetting. Each LNP Screening Array holds eight independent micromixers in an SLAS microplate format and occupies one standard deck position.

Running multiple LNP Screening Arrays in one method brings a screen to 100+ formulations per hour. Each formulation collects on deck, and dilution and assay preparation can be added to the same method.

Tell us which liquid handler you run and what your next screen needs, and we will show you how formulation fits into the method you already use.