System and methods for cell selection

A method for performing on a cell-by-cell basis the operation of observing or measuring a living cell at two different times, comprising the steps of:

• (a) providing a carrier defining first and second outer surfaces and comprising an ordered array of holes therethrough, the positions on the carrier of the holes being identifiable and the holes being sized to contain individual living cells therewithin in that the holes have (i) a first cross section at the first outer surface of the carrier of such dimensions that the living cell can pass through the first cross section without suffering substantial damage, (ii) a second cross section at a level spaced from the first outer surface of such dimensions that the living cell cannot pass through the second cross section, and (iii) a height between the first outer surface and the level of the second cross section such that either the entire living cell or substantially the entire living cell is contained within the hole so that the living cell is not washed out of the hole by the passage of a fluid across the first outer surface of the carrier;
• (b) applying a fluid containing living cells to the first outer surface of the carrier;
• (c) applying a force to the living cells to move the living cells into the holes;
• (d) observing or measuring at a first time a property of an individual living cell located at one of the holes of the carrier;
• and
• (e) observing or measuring at a second time a property of the same individual living cell which was observed or measured in step (d), the cell being located at the same hole of the carrier as in step (d).

A method for placing individual living cells at identifiable addresses within the holes of a carrier comprising the steps of:

• (a) providing:
• a carrier defining first and second outer surfaces and comprising an ordered array of holes therethrough, the holes being sized to contain individual living cells therewithin in that the holes have (i) a first cross section at the first outer surface of the carrier of such dimensions that the living cell can pass through the first cross section without suffering substantial damage, (ii) a second cross section at a level spaced from the first outer surface of such dimensions that the living cell cannot pass through the second cross section, and (iii) a height between the first outer surface and the level of the second cross section such that either the entire living cell or substantially the entire living cell is contained within the hole so that the living cell is not washed out of the hole by the passage of a fluid across the first outer surface of the carrier;
• and
• means for holding the carrier so that the individual addresses of the holes in the carrier are identifiable by means of a set of x and y coordinates;
• (b) applying a fluid containing living cells to the first outer surface of the carrier;
• and
• (c) applying a force to the living cells to move the living cells into the holes.

Apparatus for performing on a cell-by-cell basis one or more of the operations of (i) observing or measuring a property of a living cell, (ii) moving a living cell, or (iii) killing a living cell, comprising:

• (a) a carrier defining first and second outer surfaces and comprising an ordered array of holes therethrough, the positions on the carrier of the holes being identifiable and the holes being sized to contain individual living cells therewithin in that the holes have (i) a first cross section at the first outer surface of the carrier of such dimensions that the living cell can pass through the first cross section without suffering substantial damage, (ii) a second cross section at a level spaced from the first outer surface of such dimensions that the living cell cannot pass through the second cross section, and (iii) a height between the first outer surface and the level of the second cross section such that either the entire living cell or substantially the entire living cell is contained within the hole so that the living cell is not washed out of the hole by the passage of a fluid across the first outer surface of the carrier;
• (b) means for applying a fluid containing living cells to the first outer surface of the carrier;
• (c) means for applying a force to the living cells to move the living cells into the holes;
• and
• (d) means for performing on an individual living cell located in one of the holes in the carrier one or more of the operations of (i) observing or measuring a property of the living cell, (ii) moving the living cell, or (iii) killing the living cell.

Apparatus for selecting particular living cells from among other living cells comprising:

• (a) a carrier defining first and second outer surfaces and comprising an ordered array of holes therethrough, the addresses on the carrier of the holes being identifiable by means of a set of x and y coordinates, the holes being sized to contain individual living cells therewithin in that the holes have (i) a first cross section at the first outer surface of the carrier of such dimensions that the living cell can pass through the first cross section without suffering substantial damage, (ii) a second cross section at a level spaced from the first outer surface of such dimensions that the living cell cannot pass through the second cross section, and (iii) a height between the first outer surface and the level of the second cross section such that either the entire living cell or substantially the entire living cell is contained within the hole so that the living cell is not washed out of the hole by the passage of a fluid across the first outer surface of the carrier;
• (b) means for applying a fluid containing living cells to the first outer surface of the carrier;
• (c) means for applying a force to the living cells to move the living cells into the holes;
• (d) means for observing or measuring one or more properties of the living cells while the cells are in the holes;
• and
• (e) means associated with the means for observing or measuring for recording the addresses on the carrier of particular living cells based on the results of observing or measuring the one or more properties.