Limits of time-based separation methods

Time-based separation methods such as: - High Performance Liquid Chromatography (HPLC) - size exclusion chromatography - Flow induced dispersion analysis

that induce a different circulation time to separate particles (or molecules) has a sever problem with scalability.

Separation columns/fibers, etc. are designed for specific volumes of sample, that ensure the output will be sufficiently separated for it to be useful. If one would change the sample volume, the entire system would not work.

For example, SEC columns do not control the percolation time, since they act by gravity. If the sample volume would be too large, there wouldn't be enough interactions between sample and column to induce a full separation before coming out.

On the other hand, if columns are over-specified, the sample would need to be diluted in order to fill the entire column.

These methods are very handy because of their simplicity, but they will always lack the ability of scaling that spatial-based separation methods offer.