Filtration is generally a mechanical or physical operation used to separate a substance (e.g., a particle, a molecule, a precipitate, a solid) from a fluid (i.e., a liquid or a gas) by interposing a medium through which only the fluid can pass. Substances that are larger than a specified filter “cut-off” are retained by the filter and smaller substances pass through the filter with the filtrate.
Fluids flow through a filter due to a difference in pressure—i.e., fluid flows from the high pressure side to the low pressure side of the filter, leaving some material behind on the filter. Gravity provides one way to achieve a pressure difference. In other applications, a pressure filter is used, which requires the application of force to cause liquid to flow through the filter. For example, pressure in the form of compressed air on the feed side (or a vacuum on the filtrate side) may be applied to achieve the filtration. Alternatively, the liquid may flow through the filter by the force exerted by a pump or a piston (e.g., a syringe).
In some applications, a centrifuge is used to apply an inertial force (a “centrifugal force”) on the solution or suspension and push it through the filter. Such filters are typically called “spin filters” because they are designed to be spun in the buckets or sample slots of a centrifuge. A conventional spin filter is generally constructed as a tube having an open top end and a filter means on the bottom end opposite the top end. The tubular filter body is made from a non-permeable material (e.g., plastic) that will contain the fluid to be filtered. The typically disc-shaped filter is attached to one end of the tubular filter body and made from a porous or permeable material that is suitable for the filtration task or application. In use, the spin filter is positioned in the centrifuge with the long axis of the tubular body generally aligned along a radius of the centrifuge rotor with the filter end farther away from the point of rotation than the top end. As such, when the rotor is spun, the “centrifugal force” pulls the solution or suspension through the filter and thus achieves the filtration.
The spin filter is generally adapted to fit within the upper portion of a standard centrifuge holder, e.g., a centrifuge tube or a centrifuge cup. The usage of spin filters for separation is largely dictated by the type of filters attached to or laid on top of the bottom end of the spin filter. Examples of filters currently used with commercially available spin filters are ion exchange membranes to separate proteins on the basis of their charges from low molecular weight contaminants (e.g., salts, detergents, etc.); membranes with pore sizes in the micrometer or nanometer ranges for removing particles, concentrating proteins, for buffer exchange, reducing or removing salts or other low molecular weight contaminants. Affinity membranes, on the other hand, are used to capture specific proteins.
This conventional design is adaptable to the volumes and sizes of various types of samples requiring filtration. For example, microcentrifuge spin filters are often used for separations on the scale of approximately a milliliter (see, e.g., U.S. Pat. Nos. 4,683,058 and 6,221,655). Larger spin filters are available for processing samples on the scale of tens to hundreds of milliliters. Different commercial manufacturers have adopted the concept and are selling variations of the spin filters either as a stand-alone unit or as a component of an assay kit.
For many applications, the conventional design is problematic. In particular, the material collected on the filter can accumulate to form a barrier to subsequent fluid flow, thus clogging the filter. The filter at the bottom end of the tubular body is the only permeable exit for the filtrate and consequently, when clogged, the filtration cannot proceed. Remedying the problem to allow the filtration to continue can prolong processing time and result in sample loss. Accordingly, there remains a need for a spin filter that can be used to filter problematic samples without clogging the filter.