This discussion of methods for the differential isolation and separation of cells, and subcellular components would not be complete without a description of the use of centrifugation for harvesting large quantities of particulate material from large-volume suspensions.
The technique is generally known as continuous-flow centrifugation.
The most common application of continuous-flow centrifugation is the harvesting of bacteria, algae, protozoa, and other cells grown in multi-liter cultures as a preliminary to chemical, physiological, or morphological analysis.
However, the technique is also frequently employed:
(1) To collect cell-free culture media prior to the isolation and assay of cellular excretion products such as enzymes, vitamins, and hormones;
(2) To separate blood;
(3) To remove the larger subcellular components such as nuclei, chloroplasts, and mitochondria from large volumes of tissue homogenates; and
(4) To collect precipitates from large volumes of aqueous suspensions.
During continuous-flow centrifugation, the suspension of particles is introduced into the spinning centrifuge rotor as a continuous, uninterrupted stream. As the suspension passes through the rotor, particles are sedimented out of the stream and are trapped and concentrated within specific rotor chambers, while the clarified supernatant leaves the rotor and is collected separately.
Continuous-flow centrifuge rotors thereby eliminate the need for a series of batch separations when very large volumes of particle suspensions must be processed. When processing is completed, the rotor is simply decelerated and opened, and the trapped cells or particles removed.
Although cells or other particles present in multi- liter volumes can be harvested using conventional rotors, that approach is far less efficient. Even the largest conventional rotors generally accommodate only a few liters of suspension, so that a succession of spins is necessary when larger volumes of material must be handled.
Equally important, the increased size and weight of these rotors restricts their maximum operating speeds and may necessitate extended centrifugation time to ensure total particle “cleanout.” Because at any instant continuous-flow rotors contain only a small fraction of the total volume of material to be centrifuged, they may be quite small. Thus, in addition to eliminating the need for successive runs, continuous-flow rotors can be operated at much higher speeds (hence greater RCF), providing more rapid and efficient particle cleanout.
The RCF experienced by the particles as they enter the collection chambers of the rotor depends on rotor speed and causes the particles to sediment at specific rates. If the rate of particle sedimentation is greater than the rate at which the surrounding liquid moves toward a centripetal exit port in the chamber, then the particles become trapped in the rotor.
However, if the sedimentation rate is less than the rate of centripetal flow, the particles are carried toward the exit ports and out of the rotor. Usually, flow rate and rotor speed are selected to provide maximum cleanout of the particle suspension.
However, for heterogeneous populations of particles, the flow rate and rotor speed can often be adjusted so that a differential fractionation of the particles is achieved, that is, depending on their sizes, shapes, and densities, some particles will be trapped in the rotor, while others are conducted out of the rotor with the supernatant.