Tunable Resistive Pulse Sensing (TRPS) technology enables accurate measurements of nanoparticle properties suspended in electrolytes, as opposed to the estimates provided by light scattering techniques. A scientific measurement must be quantifiable and reproducible, delivering as a minimum:
/01 The concentration of particles in the fluid as a number of particles per unit volume of fluid, across a specified detectable particle size range.
/02 An accurate size distribution of these particles plotted as a histogram of concentration v particle diameter (or volume). TRPS is the only technology that delivers these fundamental requirements, and in addition can measure the surface charge of individual nanoparticles. See the technology comparison section for details of where competing technologies are failing.
Figure 1.
Tunable Resistive Pulse Sensing (TRPS), Nanoparticle Tracking Analysis (NTA) and Multi-angle Dynamic Light Scattering (MADLS) measurements of quadrimodal sample C (CPN100/CPN150/CPN200/CPN240 at 25/25/25/25). TRPS, NTA and MADLS measurements were averaged over 3 runs. TRPS identifies all four sub populations clearly. NTA was able to identify that multiple sub populations were present. MADLS was not about to identify any sub populations.
How Does Tunable Resistive Pulse Sensing Work?
The impedance of a nanopore in an electrolyte fluid cell is sampled 50,000 times per second. Sample particles are driven through the nanopore by applying a combination of pressure and voltage, and each particle causes a resistive pulse or “blockade” signal that is detected and measured by the application software.
01
Blockade magnitude is directly proportional to the volume of each particle.
02
Frequency of blockades is directly proportional to the sample concentration.
03
Measured against calibration particles of known size, concentration and surface charge.
Magnitude, duration and frequency values are converted into respective particle properties by calibration with particles of known size, concentration and surface charge.
What is “Tunable” and Why?
Nanoparticle suspensions are complex systems. Characterising them fully requires an optimised setup and measurements of each sample under more than one condition.
The Stretch “S” of the nanopore can be adjusted to optimise the nanopore size to the particle size range at hand.
The applied Pressure “P” can be tuned to adjust or even reverse the fluid flow through the nanopore – allowing adjustment of both blockade frequency and duration. Measurements at more than one pressure are required to calculate particle concentration, and very fine pressure control is needed for single particle charge analysis.5, 6
The applied Voltage “V” can be tuned to attract particles of different surface charge or polarity through the nanopore, and optimise the signal to noise ratio of the system. Measurements at more than one voltage are required to calibrate single particle charge values.
Why is TRPS Inherently Accurate?
Tunable Resistive Pulse Sensing (TRPS) guarantees highly accurate measurement of physicochemical properties of nanoparticles, such as concentration, size and surface charge. TRPS accuracy is predominantly based on its standardised calibration process with NIST traceable standards, the precise control of convective flow and electrokinetic forces via pressure and voltage actuation, and its single particle nature. Particles are counted on a particle by particle basis, without the use of any averaging algorithms, enabling highly accurate concentration measurements. Particle diameters are calculated from resistive pulse heights. These are proportional to particle volume as opposed to particle diameter, resulting in increased accuracy of particle diameter when compared with optical based methods. Particle size accuracy is further optimised by tuning the pore to the particulates at hand. The high accuracy in particle surface charge measurements is guaranteed through the combined effect of high electric fields within the pore and precise control of convection, electroosmosis and electrophoresis.
The Exoid: Successor of the qNano Gold
The Exoid is Izon’s Tunable Resistive Pulse Sensing (TRPS) system. Unlike with the qNano Gold, where parameters were adjusted manually, pressure, voltage and pore stretch are adjusted directly from your Exoid-connected device. Significant hardware improvements reduce noise levels significantly over the qNano, meaning that smaller particles can be measured more reliably. The Exoid also has a clean user interface which provides guidance throughout the setup and measurement process.