The Coulter Principle is the reference method for studying particle size and dynamics, which is based on measurable variations in electrical impedance that is produced by non-conductive particles in an electrolyte solution. Today it is also used as limit test for particulate matter in parenteral solutions of large volumes.
Since Coulter patented a method to count and size particles suspended in a conducting solution in 1953, the Coulter principle has become extensively used for that purpose. Although the technique was initially used to count and size red blood cells, today it forms the basis of several different particle counting instruments manufactured by a number of firms around the world.
General characterization of the Coulter principle
The Coulter principle is based on the fact that the placement of objects in an electric field modifies the flow of a current in that field. A small opening or aperture that is positioned between electrodes represents the sensing zone where suspended particles pass through, and their volume is measured by using electrical impedance.
Since electrical current is confined within the limits of the aperture, particles disarrange a volume of conductive liquid equal to their size as they are pulled through by vacuum. This in turn generates measurable pulses that can be further analyzed with advanced equipment.
The result is simultaneous analysis of particle size and concentration in high resolution, which separates this principle from the measurements of light scattering that do not yield concentration information. To be more precise, light scattering techniques provide measurement of whole particle population, whereas the Coulter principle provides particle-by-particle analysis.
A wide array of particle counting instruments based on the Coulter principle are being commercially produced and used in a variety of settings. These instruments range from small counters employed for red and white cell counts in small hospital settings, to the multi-parameter microprocessor controlled instruments with fully automatic dilution of samples and printing of results.
Blood cell counters operate on the principle of conductivity change, which occurs every time a cell passes through an orifice. The resulting series of voltage pulses (of magnitude proportional to the particle volume) are electronically amplified, scaled and displayed on a suitable display.
The instrument based on the Coulter principle works most adequately when the average diameter of the particles ranges between 2 to 40% of the diameter of the measuring hole. Therefore the upper limit of measurement is imposed by the increasing size of the particles.
The Coulter counters usually come with an oscilloscope monitor to display the pulse information that has passed through the amplifier, and acts as a visible check on the counting process, indicating any malfunctions (such as a blocked orifice) immediately.
Beckman Coulter analyzers
An American company Beckman Coulter has introduced the Coulter Principle in a wide array of instruments that range from those for simple cell counting purposes, to large and automated clinical analyzers that can be employed for the analysis of whole blood.
For example, analyzers such as UniCel DxH 800 or LH 750 can count platelets as particles between 2 and 25 femtoliters in volume. It gives the curve with a range of 0-70 femtoliters, which is used to derive platelet count and other parameters for industrial and research purposes.
In conclusion, the Coulter principle is still regarded as the original technology for particle characterization, and Beckman Coulter’s instruments are powerful and user-friendly devices for particle counting. The Z series is intended for basic cell counting, whereas the Multisizer series offers digital pulse analysis and expanded size ranges.
- Khandpur RS. Handbook of Biomedical Instrumentation, Second Edition. Tata McGraw-Hill Education, 2003; pp. 444-464.
- Berge LI, Feder J, Jøssang T. A New Perspective on Particle Sizing by the Coulter Principle: Single Particle Dynamics. In: Stanley-Wood N, Lines RW. Particle Size Analysis. Royal Society of Chemistry, 1992; pp. 374-383.