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What is RPS?
Resistive Pulse Sensing (RPS), also known as the Coulter principle, is currently the only particle characterization method based on electrical detection. In a constant-current circuit, when particles suspended in an electrolyte pass through a small aperture, a transient change in current occurs between the electrodes on either side of the pore, generating a resistive pulse. The amplitude of the pulse is proportional to the particle size, while the number of pulses corresponds to the particle concentration.
What is zeta potential and how does NanoCoulter measure it?
Zeta potential reflects the surface charge of particles and is a key indicator of colloidal stability—the higher the absolute value, the more stable the system.
Most instruments measure Zeta potential via electrophoresis. Optical methods like DLS and NTA use light scattering (ELS) to get an average value for the entire sample.
NanoCoulter™ uses electrical sensing to measure Zeta potential at the single-particle level, offering unmatched resolution. It tracks each particle’s migration through a nanopore under an electric field to calculate its individual Zeta potential and links it to particle size. This allows for more precise and detailed particle-level analysis than any bulk optical method.
Why Choose RPS Over DLS/NTA?
NanoCoulter™ is a single-particle analysis system based on Resistive Pulse Sensing (RPS), an electrical detection method. Unlike DLS and NTA, which rely on optical principles, RPS detects the electrical pulse generated as each particle passes through a nanopore, providing direct measurements of particle size and Zeta potential. It offers higher accuracy, sensitivity, and consistency with electron microscopy results.
RPS is also recommended by the International Society for Extracellular Vesicles (ISEV) for EV analysis and by regulatory bodies like CDE and NIFDC for LNPs and viral vectors.
DLS uses a fitting algorithm based on the assumption that all particles are identical spheres, producing an average size from a normal distribution. It is only suitable for monodisperse samples with uniform sizes. For polydisperse biological samples such as EVs, liposomes, or viruses, DLS results are often inaccurate and inconsistent with EM. Also, DLS cannot measure concentration, which is a major limitation.
NTA also relies on light scattering, and its size results are widely known to be biased larger. While it can estimate concentration, its usable concentration range is narrow, requiring users to fine-tune each sample’s dilution before reliable results can be obtained—making it time-consuming and impractical for routine use.
In contrast, NanoCoulter™ analyzes each particle individually, making it ideal for polydisperse biological samples containing a mix of particle sizes. It also features the widest linear detection range for concentration (10⁸–10¹⁰ particles/mL), with excellent linearity (R² > 0.999)—a level of precision unmatched by other platforms.
Why does the device have two channels? Can they measure simultaneously?
The two channels correspond to different detection ranges. Since RPS has a defined limit of detection (LOD), it’s important to select the appropriate range based on your sample.
Channel A is for smaller particles (50–250 nm), ideal for common biological samples like extracellular vesicles (EVs), LNPs, lentiviruses, and adenoviruses.
Channel B covers larger particles (120–2000 nm), suitable for detecting aggregates, large vesicles, or particulate impurities.
The two channels operate independently—only one channel is active per measurement. You simply choose the appropriate chip and port (A or B) depending on the expected particle size of your sample.
Will irregularly shaped particles—such as rod-shaped ones—affect the measurement if they pass through the nanopore at different angles or positions?
No, it won’t affect the measurement. Like optical methods, RPS reports the equivalent spherical diameter for non-spherical particles.
In principle, RPS can detect signal variations caused by shape differences, but since market demand for shape analysis is limited, this feature has not been developed commercially.
RPS calculates particle size based purely on the volume displaced during translocation, so the angle or orientation at which a particle passes through the pore does not affect the result.
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