Electrical sensing zone (ESZ) / microfluidic resistive pulse sensing (MRPS)
Electrical Sensing Zone (ESZ), also known as (microfluidic) resistive pulse sensing ((M)RPS), is a non-light-based technique for sizing and counting of particles in the nm- and µm-size range.
ESZ/MRPS works by applying an electrical field between opposite sides of an orifice. Particles suspended in a conductive electrolyte solution are aspirated through the orifice and, upon passage, increase the electrical resistance proportional to the volume of their non-conductive part (Coulter principle). Size determination is based on calibration with spherical sizing-standards and provides therefore an equivalent spherical diameter of the analyzed particles. Depending on the system and set-up, particles from about 50 nm up to 1 mm can be measured.
On the one hand, ESZ/MRPS is used as an early research tool in combination with nanoparticle tracking analysis [NTA] and dynamic light scattering [DLS]. The largest benefit when measuring in this low size range is the need for very low sample volumes of only a few µL. On the other hand, ESZ/MRPS is used as an orthogonal technique to validate results from light-based particle characterization techniques in the nanometer and visible size range, such as flow imaging microscopy [FIM] and light obscuration [LO]. The need for large sample volumes in the upper size range restricts the technique’s application during formulation development and stability studies. ESZ/MRPS additionally requires a minimum sample conductivity, which in some instances requires the addition of electrolytes.
ESZ/MRPS is suitable for the analysis of protein aggregates and particles, as well as colloidal systems, such as virus-like particles and polymers.
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Grabarek AD, Weinbuch D, Jiskoot W, Hawe A., Critical Evaluation of Microfluidic Resistive Pulse Sensing for Quantification and Sizing of Nanometer- and Micrometer-Sized Particles in Biopharmaceutical Products, J Pharm Sci. 2019 Jan