A lipid nanoparticle (LNP) carries nucleic acid cargo, such as mRNA or siRNA, inside a particle built from four lipids. An ionizable lipid binds the cargo during mixing and helps release it inside the cell, while a helper lipid, cholesterol, and a PEG-lipid give the particle its structure and stability.

Small changes to any of these components can shift particle size, cargo loading, and delivery in ways that are hard to predict, so teams make many candidate formulations and test them side by side. Each screen answers one of two questions, depending on whether the carrier or the cargo is under study.

Both types of screens end in a shortlist of formulations backed by enough data to justify further testing.

A screen's design space is the set of components a team changes from one formulation to the next. Many screens change one or two components at a time and hold the rest steady, so a difference in results can be traced to a specific change. Design-of-experiments (DoE) screens vary several components together to map how they interact.

The mixing method needs to stay constant as well, because when mixing changes between formulations, differences in the particles can reflect how each sample was made instead of what it contains.

A screen runs in rounds, and each round moves through the same stages, from choosing what to make to choosing what advances.

The shortlist feeds the design of the next round, so the time one pass takes decides how many rounds fit in a program. Formulation often runs on a separate instrument between two liquid handler steps, which makes it the step where time and manual handling add up fastest.

Each measurement in a screen answers a specific question about the formulation. Size, PDI, and encapsulation efficiency are typically measured on every formulation, while structural methods and cell-based assays are usually reserved for the formulations that pass because they take more time and material.

A promising result earns a repeat preparation before it advances, because a single formulation can't show whether the result reproduces.

Everything a screen compares depends on the formulation step. Size and PDI can only separate candidates when mixing is fast and identical for every formulation, and a round only moves quickly when formulation runs without manual steps between input prep and processing.

The table below compares common formulation methods on how well each one controls the particles and how much setup and hands-on work it adds to every formulation.

Pipette mixing is the easiest to start but gives up particle control, and a benchtop instrument controls the particles but adds manual loading and recovery to every formulation. On-deck microfluidic formulation controls the particles with no manual steps between formulations, so every sample is made the same way and moves straight into processing.

The LNP Screening Array brings microfluidic formulation onto your liquid handler. Each formulation is generated in seconds and collected on deck, ready for processing in the same method.

For a step-by-step view of the process, see How the LNP Screening Array Works.

Evaluations run in your lab with your own lipids and cargo. Our applications team helps you with the first run and runs DLS with you during the visit.