Micro-Fluidic System Using Micro-Apertures for High Throughput Detection of Cells

A microfluidic system for isolating first target entities and second target entities from a fluid, wherein the fluid also contains a plurality of first magnetic beads capable of binding specifically to the first target entities and a plurality of second magnetic beads capable of binding specifically to the second target entities, and wherein each first target entity has a smallest effective dimension greater than a largest effective dimension of each second target entity and greater than a largest effective dimension of each of said first and second magnetic beads, the system comprising:

• (a) a body defining a reservoir;
• (b) a plate separating the reservoir into a first chamber and a second chamber, wherein the plate defines a plurality of openings therethrough, wherein each opening is sized to permit passage of the first and said second magnetic beads and the second target entities, and to prevent passage of the first target entities, wherein the body comprises a first inlet to the first chamber and a first outlet from the first chamber;
• (c) a first magnet affixed to or supported relative to an outer surface of the body and arranged so that the second chamber and the plate are situated between the magnet and the first chamber, wherein the first magnet generates at a surface of the plate facing the first chamber a magnetic force
• (i) sufficient to attract through the openings in the plate from the first chamber into the second chamber:
• at least some unbound first magnetic beads,
• at least some unbound second magnetic beads, and
• at least some of the second magnetic beads bound to the second target entities in the first chamber, and
• (ii) sufficient to attract and hold at least some of the first target entities bound to the first magnetic beads against the surface of the plate without being dislodged from the surface by fluid flowing through the first chamber;
• and
• (d) a second magnet affixed to or supported relative to an outer surface of the body and arranged so that the first chamber and the plate are situated between the second magnet and the second chamber, wherein the second magnet generates at the surface of the plate facing the first chamber a magnetic force sufficient to move towards the openings in the plate:
• at least some unbound first magnetic beads,
• at least some unbound second magnetic beads, and
• at least some second magnetic beads bound to second target entities.