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DLS vs. MRPS: Why electrical sensing outperforms light scattering for biological nanoparticles.
Dynamic Light Scattering has been the default nanoparticle characterization tool for decades. For many applications, it’s adequate. But for biological nanoparticles, like lipid nanoparticles, extracellular vesicles, & viruses, DLS’s fundamental reliance on light scattering creates blind spots that can cost you critical information about your formulation.
The comparison on this page draws on peer-reviewed data from a Johns Hopkins University study published in the Journal of Extracellular Vesicles (Arab et al., 2021) that compared four orthogonal single-particle platforms — MRPS, NTA, nanoFCM, and SP-IRIS — across both synthetic and biological EV samples.
The limitation
DLS sees light. MRPS measures particles.
Dynamic Light Scattering infers particle size from fluctuations in scattered light caused by Brownian motion. It is a bulk, ensemble technique — it collects signals from millions of particles simultaneously and reports a single averaged distribution. This approach has three fundamental weaknesses for biological nanoparticle work.
Head-to-head
DLS vs. MRPS: a direct comparison
| DLS Dynamic Light Scattering |
MRPS Spectradyne |
|---|
View plain text data table
| Attribute | DLS | MRPS (Spectradyne) |
|---|---|---|
| Measurement principle | Optical — light scattering ensemble average | Electrical — direct single-particle measurement |
| Single-particle measurement | No — ensemble average across millions of particles | Yes — every particle measured individually |
| Polydisperse sample resolution | Poor — single broadened peak, D&sup6; bias toward large particles | High — multiple populations resolved simultaneously |
| Absolute concentration | No — complex conversion from scattering intensity, requires assumptions | Yes — particle count divided by measured sample volume |
| Refractive index dependence | High — must be known or assumed; biological particles vary widely | None — electrical sensing is independent of optical properties |
| Calibration required | Yes — reference standard before each new cuvette | No — no calibration, alignment, or cleaning required |
| Sample volume required | 50–1,500 µL depending on cuvette | Only 3 µL required |
| Sizing accuracy vs CryoTEM | Poor — biased distribution, overestimates mean size | Excellent — validated in near-perfect agreement with CryoTEM for LNPs |
Why it matters
Where DLS falls short for biological samples
Biological nanoparticles present particular challenges for DLS because they are inherently heterogeneous, polydisperse, and have low refractive index contrast in aqueous media. These properties amplify all three of DLS’s core limitations simultaneously.
Validated against CryoTEM for LNP sizing
In a collaboration with NanoImaging Services, Spectradyne analyzed a lipid nanoparticle sample using both MRPS and CryoTEM \u2014 one of the most highly trusted nanoparticle characterization methods available. Both measurements yielded high-resolution particle size distributions in near-perfect agreement. DLS on the same sample failed to distinguish between three different LNP formulations entirely.
Read the CryoTEM validation application note →See it for yourself
Ready to see what MRPS reveals about your sample?
Send us your LNP, EV, or other nanoparticle sample and we’ll run a free measurement on our instruments. You’ll receive a full size distribution and concentration report \u2014 so you can see exactly what MRPS can tell you that DLS cannot.
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