Resistive pulse sensing (RPS) is the generic, non-commercial term given for the well-developed technology used to detect, and measure the size of, individual particles in fluid. First invented by Wallace H. Coulter in 1953, the RPS technique is the basic principle behind the Coulter Principle, which is a trademark term. Resistive pulse sensing is also known as the electrical zone sensing technique, reflecting its fundamentally electrical nature, which distinguishes it from other particle sizing technologies such as the optically-based dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). An international standard has been developed for the use of the resistive pulse sensing technique by the International Organization for Standardization.
Construction and operation. The basic design principle underlying resistive pulse sensing is shown in Fig. 1. Individual particles, suspended in a conductive fluid, flow one-at-a-time through a constriction. The fluids most commonly used are water containing some amount of dissolved salts, sufficient to carry an electrical current. The salinity levels of seawater or of a wide range of concentrations of phosphate-buffered saline are easily sufficient for this purpose, with electrical conductivity in the mS-S range and salt concentrations of order 1 percent. Typical tap water often contains sufficient dissolved minerals to conduct sufficiently for this application as well.
Electrical contact is made with the fluid using metal electrodes, in the best case using platinum or other low electrode potential metals, as are found in electrochemical cell constructions. Biasing the electrodes with an electrical potential of order 1 volt will cause an electrical current to flow through the fluid. If properly designed, the electrical resistance of the constriction will dominate in the total electrical resistance of the circuit. Particles that flow through the constriction while the electrical current is being monitored will cause an obscuration of that current, resulting in an increase in the voltage drop between the two electrodes. In other words, the particle causes a change in the electrical resistance of the constriction. The change in the electrical resistance as a particle passes through a constriction is shown schematically in Fig. 2.
Theory of operation. The quantitative relationship between the measured change in electrical resistance and the size of the particle that caused that change was worked out by De Blois and Bean in 1970. De Blois and Bean found the very simple result that the resistance change is proportional to the ratio of particle volume to the effective volume of the constriction: , where is a factor that depends on the detailed geometry of the constriction and the electrical conductivity of the working fluid.
Hence, by monitoring the electrical resistance as indicated by changes in the voltage drop across the constriction, one can count particles, as each increase in resistance indicates passage of a particle through the constriction, and one can measure the size of that particle, as the magnitude of the resistance change during the particle passage is proportional to that particle's volume. As one can usually calculate the volumetric flow rate of fluid through the constriction, controlled externally by setting the pressure difference across the constriction, one can then calculate the concentration of particles. With a large enough number of particle transients to provide adequate statistical significance, the concentration as a function of particle size, also known as the concentration spectral density, with units of per volume fluid per volume particle, can be calculated.