Thin channel split flow process and apparatus for particle fractionation

An apparatus for separating small particles into desired fractions consisting of a separation cell or channel comprising:

• a. a channel system formed between two sets of opposing walls, the end set of walls comprising an inlet end wall and an outlet end wall, and the thickness of the channel being very thin compared to the other two dimensions and being less than 5 millimeter and the length of the channel being not more about than 20 centimeters,
• b. an inlet means for introducing a fluid stream containing the particles to be separated at the inlet end of the channel so as to constitute a substream entering the channel,
• c. at least one other inlet means for introducing an additional substream having different composition at the inlet end of the channel,
• d. at least one means at the outlet end of the channel for splitting the substreams into at least two substreams and permitting separate recovery of the said substreams,
• e. means for removing the split substreams at the outlet means at the outlet end of the channel,
• f. and means for effecting one or more transverse driving forces or gradients having a component perpendicular to the plane of the flow stream in the channel.

A continuous process for fractinating small particles as small as polypeptides and no larger than biological cells contained in a fluid stream comprising:

• a. continuously introducing two or more fluid substreams of different composition into the inlet end of a thin enclosed channel having an inlet end possessing at least two inlet means and an outlet end possessing at least two outlet means and having a thickness which is very thin compared to the other two dimensions and is less than 5 millimeter, and has a length of not more than about 20 centimeters, and bringing the substream into contact with adjacent substreams so as to collectively form a series of thin laminae flowing parallel to one another within the channel and in contact with one another over a sufficient length of channel to allow a desired level of mass transport between and through the laminae without substantial hydrodynamic mixing between the laminae,
• b. continuously introducing the fluid medium containing the particles to be separated by means of one of said inlet means into one or more of the fluid substreams and varying the fluid composition of the non-particle containing substreams as needed to realize separation,
• c. employing one or more means along the length of the channel to split the stream as it passes along the channel causing one or more of the obtained substreams to enter the following section of channel as a new substream for that section, causing other substreams to exit the channel for collection, discarding or to enter another separation channel, and to introduce new substream into the channel from outside the channel,
• d. at the outlet end of the channel splitting the collective channel stream into another set of substreams so as to permit separate recovery of at least two of the substreams at separate outlet means at the outlet end of the channel,
• e. adjusting the flow rates at the inlet end as well as at the outlet end so as to obtain the desired separation,
• f. continuously removing all of the substreams being separated at at least two separate outlet means at the outlet end of the channel,
• g. during the separation process subjecting the channel to one or more transverse driving forces or gradients having a component perpendicular to the plane of the flow stream in the channel, and being selected from the group consisting of gravitation, centrifugation, electrical, dielectrical forces, cross-flow forces, temperature gradients, density gradients and concentration gradients, and combinations thereof.

An apparatus for separating small particles into desired fractions consisting of a separation cell or channel comprising:

• a. a channel system formed between two sets of opposing walls, the end set of walls comprising an inlet end wall and an outlet end wall, and the thickness of the channel being very thin compared to the other two dimensions and being less than 5 millimeter and the length of the channel being not more than 20 centimeters,
• b. an inlet means for introducing a fluid stream containing the particles to be separated at the inlet end of the channel so as to constitute a substream entering the channel,
• c. at least one other inlet means for introducing an additional substream having different composition at the inlet end of the channel,
• d. one or more means present along the length of the channel to split the stream as it passes along the channel causing one or more of the obtained substreams to enter the following section of channel as a new substream for that section, causing other substreams to exit the channel for collection, discarding or to enter another separation channel, and to introduce new substreams into the channel from outside the channel,
• e. at least one mean at the outlet end of the channel for splitting the substreams into at least two substreams and permitting separate recovery of the said substreams,
• f. means for removing the split substreams at the outlet means at the outlet end of the channel,
• g. and means for effecting one or more transverse driving forces or gradients having a component perpendicular to the plane of the flow stream in the channel.