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Lipid nanoparticle and extracellular vesicle characterisation

A particle can carry the right targeting ligand and still not engage its receptor. Size, heterogeneity, and a crowded surface make that hard to see in an endpoint assay. Label-free analysis reveals how these particles actually interact with their targets in real time.
Sensitive detection at 0.1 RU RMS baseline noise
Flow from 5 to 100 µL/min, up to 300 µL/min
From 30 µL of sample per injection

Where EV and LNP researchers use label-free binding data

Label-free interaction analysis measures binding between unmodified molecules in real time. For EVs and LNPs it returns receptor engagement at the particle surface, association and dissociation rates, and specificity, with no dye or reporter added to the particle.

Targeting-ligand engagement

Confirm the particle reaches the receptor it was designed for.

Measure kon and koff at the particle surface.

receptor engagement

mRNA-LNP delivery

Characterise ionizable lipid formulations carrying nucleic acid cargo.

Compare formulations on receptor binding, alongside particle size.

ionizable lipid

EV surface markers

Profile exosome and microvesicle surface proteins.

Screen tetraspanins and other markers against one preparation.

tetraspanins

Protein corona

Follow what the particle picks up from its environment.

Measure serum protein binding, ApoE included, at the particle surface.

ApoE binding

Specificity and cross-reactivity

Separate on-target engagement from surface sticking.

Run competitive and blocking injections against control receptors.

receptor blocking

Benefits of the inQuiQ in EV and LNP analysis

01 / 04

One injection, four channels, sixteen sensors

Four independently addressable flow channels, each carrying four sensors, with the sample flowing through the channels in series.

30 µL minimumsequential flow paths
In-flow immobilisation
Spotter immobilisation

Measure engagement at the particle surface

The immobilised receptor captures the intact particle, measuring target engagement within the 100 nm sensing area at the sensor surface, not a lysate or released component.

kon, koff, KDtargeting ligand
particle engaging the receptor

Give a large particle time to reach the surface

EVs and LNPs diffuse slowly compared with a protein. Flow runs from 5 to 100 µL/min, up to 300 µL/min for low-viscosity samples, so contact time is set to the particle rather than to the instrument.

5 to 100 µL/minup to 300 µL/min
contact time set by flow rate

Confirm specific receptor engagement

Compare particle binding to an open target receptor, a blocked receptor, and control surfaces. A strong signal that drops when the receptor is blocked confirms specific engagement.

target · open
strong
target · blocked
minimal
blank surface
minimal
specificity controlscompetitive assays
target receptor:
available or blocked

How an EV binding run works

Every measurement follows the same steps, regardless of the type of particle. The ligand is immobilised on the sensor, the sample flows past, and the response is recorded through the whole injection.

Receptor immobilisation

The target receptor goes on the sensor surface first.

For lipid nanoparticle and extracellular vesicle characterisation the receptor, antibody, or surface marker is immobilised and the particle is injected over it. Density is kept low so large particles are not crowded on the surface.

  • receptor capture
  • surface marker
  • ligand density

Deactivation

Unused activated sites are switched off before the first particle sample arrives.

Lipid surfaces bind readily to unblocked chemistry. Deactivation, together with the antifouling hydrogel, keeps the sensorgram to receptor engagement rather than particle sticking.

  • deactivation
  • antifouling
  • non-specific binding

Association

The particle preparation flows across the surface and the response climbs.

In EV and LNP binding kinetics analysis the association phase gives kon for targeting-ligand engagement at the particle surface. Flow rate is lowered so slow-diffusing particles get enough contact time to reach the receptor.

  • targeting ligand
  • contact time
  • kon

Dissociation

Buffer replaces the particle sample and the response falls as the complex comes apart.

The dissociation phase gives koff, and the pair gives KD for the particle and receptor. Competitive injections with free ligand then separate specific receptor engagement from cross-reactivity.

  • koff
  • KD
  • receptor blocking
  • cross-reactivity

Regeneration

A regeneration buffer returns the sensor to baseline for the next preparation.

The receptor stays in place, so every LNP formulation or EV batch meets the same surface across a characterisation series.

  • regeneration
  • formulation series
  • automated cycling
Response (RU) Time

What the inQuiQ does for EV and LNP research

Six capabilities, one modular benchtop instrument, in a label-free workflow.

Many receptors, one particle preparation

Four channels with in-flow immobilisation, or sixteen sensors with a spotter, put target receptors, control receptors, and blanks under the same injected sample.

16 sensors (spotter required) 30 µL

Sensitive to a small surface response

Baseline noise stays low enough that engagement by a heterogeneous particle population is still readable.

0.1 RU RMS

Weak engagement through tight binding

One affinity range covers loose corona interactions and high-affinity targeting-ligand engagement.

10 pM to 10 mM

Contact time set to the particle

EVs and LNPs diffuse slowly compared with a protein, and flow rate is what decides how long they meet the surface.

5 to 100 µL/min up to 300 µL/min

Comparison across formulations

Lipid composition and ionic strength differ between formulations, and the same sensor surface carries the comparison across them.

formulation series

Modular system for an increased throughput

Simply add an autosampler, and run a long formulation or batch series unattended.

2×96 wells 2×384 wells
Explore the inQuiQ768
Start A conversation

Talk to an application scientist

Bring your particle. We will tell you honestly whether label-free is the right method for it, and how the assay would be built.

Ready to see the inQuiQ in action?

Questions researchers ask

Immobilise the target receptor and inject the LNP preparation over it. The association phase gives kon for targeting-ligand engagement, the dissociation phase gives koff, and the two give KD. Nothing is added to the particle, so the surface being measured is the one you formulated.

Spot capture antibodies against tetraspanins and other markers on one chip, then inject the vesicle preparation once. Every sensor reads the same injected sample in series, so a marker profile comes from a single run rather than one assay per marker.

Immobilise the serum protein of interest and inject the particle preparation, or run it the other way round. Real-time recording shows how quickly corona proteins associate and how long they stay, which an endpoint measurement of the settled corona cannot show.

EVs and LNPs diffuse far more slowly than a protein, so at high flow many particles pass without reaching the surface. Flow runs from 5 to 100 µL/min, up to 300 µL/min for low-viscosity samples, which lets contact time be set to the particle rather than to the instrument.

Run the injection over the target receptor, over a control receptor, and over a blank surface, then repeat with the receptor pre-blocked using free ligand. Binding that disappears when the receptor is blocked is receptor engagement; binding that stays is surface sticking.