Massively parallel fluid dispensing systems and methods

A method of simultaneously producing multiple fluid mixtures in multiple multiwell plates, the method comprising:

• (a) providing a fluid dispensing system that comprises an array of fluid dispensers, wherein the array comprises at least two fluid dispensers that are spaced at least a sufficient distance apart to simultaneously dispense a fluid into a well of a first multiwell plate and a corresponding well of a second multiwell plate when both plates are placed beneath the array of fluid dispensers;
• (b) sequentially positioning each well of the multiple multiwell plates underneath each of the fluid dispensers;
• and
• (c) dispensing selected volumes of fluid from selected fluid dispensers into selected wells of the multiple multiwell plates when the selected fluid dispensers are positioned above the selected wells, thereby simultaneously producing the multiple fluid mixtures in multiple multiwell plates.

An apparatus for preparing fluid mixtures in a plurality of multiwell vessels, each of the multi-well vessels having a plurality of wells, the apparatus comprising:

• a multi-well vessel moving apparatus configured to receive and move the plurality of multi-well vessels in a first direction;
• a plurality of tubes, each tube configured to dispense a fluid into individual wells of the multi-well vessels, where the tubes have a footprint in the column direction, where each of the multi-well vessels has a footprint in the column direction, where the footprint of the tubes in the column direction is longer than the footprint of any single one of the multi-well vessels in the column direction;
• a tube mover configured to move the plurality of tubes in a second direction;
• and
• a controller communicating with the vessel moving apparatus, the plurality of tubes and the tube mover, the controller programmed to selectively move the multi-well vessels and the tube mover and dispense fluid into individual wells of the multi-well vessels.

An apparatus for preparing fluid mixtures, comprising:

• a vessel receiving area constructed to hold a plurality of vessels, with each vessel configured to hold a fluid mixture;
• a plurality of dispensers, each dispenser configured to dispense a determined quantity of a fluid into one of the vessels;
• where the dispensers have a footprint in the column direction, where each of the multi-well vessels has a footprint in the column direction, where the footprint of the dispensers in the column direction is longer than the footprint of any single one of the multi-well vessels in the column direction;
• a mover configured to position a selected one of the dispensers directly above a selected one of the vessels;
• and
• a controller communicating with the mover and the dispensers, the controller configured to control the positioning of the mover and to control the dispensing of the fluid.

A system for preparing mother liquors in multi-well sample plates for a protein crystallization screen, the mother liquor being a mixture of stock liquids, the system comprising:

• a plurality of fluid dispensers arranged in an array, at least two of the fluid dispensers dispensing different stock liquids, where the fluid dispensers have a footprint in the column direction, where each of the multi-well vessels has a footprint in the column direction, where the footprint of the fluid dispensers in the column direction is longer than the footprint of any single one of the multi-well vessels in the column direction;
• a drive mechanism constructed to position fluid dispensers in the array directly over wells in the sample plates, the sample plates having sample wells arranged in rows and columns;
• and a processor performing the steps of:
• receiving instruction on the formulation of each mother liquor in each sample well, the formulation being a combination of the stock liquids;
• calculating the quantity of each stock liquid to be dispensed into each sample well;
• moving the fluid dispenser array to a new row position;
• directing the drive mechanism to position the fluid dispenser array directly above a new column of sample wells;
• identifying which positioned fluid dispensers have a stock liquid required for the formulation in the sample well associated with each positioned fluid dispenser;
• dispensing, with the identified fluid dispensers, the calculated quantity of stock liquid into each respective sample well;
• and
• repeating the moving, directing, identifying, and dispensing steps until all instructed formulations are complete.

A system for efficiently preparing mother liquors in a plurality of multi-well sample plates for a protein crystallization screen, the plurality of sample plates arranged with corresponding columns aligned, the system comprising:

• a plate arranging area configured to receive the plurality of sample plates;
• a plurality of fluid containers, each fluid container holding a stock solution;
• a plurality of fluid dispensers arranged in an array, each fluid dispenser being in fluid communication with an associated one of the fluid containers, where the fluid dispensers have a footprint in the column direction, where each of the multi-well vessels has a footprint in the column direction, where the footprint of the fluid dispensers in the column direction is longer than the footprint of each of the multi-well vessels in the column direction;
• a drive mechanism constructed to sequentially position the fluid dispensers in the array directly over each column of wells in the sample plates;
• a dispensing mechanism associated with each fluid dispenser;
• and a fluid controller communicating to the dispensing mechanism;
• wherein the fluid controller directs the dispensing mechanisms to deliver a quantity of each associated mother liquor into each sample well in a column before the drive mechanism moves the fluid dispenser array to a next column.

A method for automatically preparing a mixture in a well of multiwell holder, said method comprising the steps of:

• moving the multi-well holder so that at least one of the wells is positioned below a fluid dispensing device, where each of the fluid dispensing devices have a footprint in the column direction, where each of a plurality of multi-well holders has a footprint in the column direction, where the footprint of the fluid dispensing devices in the column direction is longer than the footprint of any single one of the multi-well holders in the column direction;
• dispensing fluid from the fluid dispensing device into the well;
• and
• repeatedly moving the multi-well holders so that the well is positioned below a next fluid dispensing device and dispensing fluid from the next fluid dispensing device into the well until a predetermined mixture is prepared.

A method of preparing mother liquors in multi-well sample plates, each of the multi-well sample plates having an array of sample wells organized in rows and columns, with a predetermined number of sample wells in a column, the method comprising:

• positioning the sample plates end to end so that corresponding columns of adjacent sample plates align;
• arranging a plurality of fluid dispensers into a generally linear array of fluid dispensers arranged in a column direction, where each of the fluid dispensers have a footprint in the column direction, where each of the sample plates has a footprint in the column direction, where the footprint of the fluid dispensers in the column direction is longer than the footprint of any single one of sample plates in the column direction;
• positioning at least some of the fluid dispensers in the array of fluid dispensers with reference to a first column of sample wells;
• dispensing a predetermined volume of a material into selected sample wells in the first column from at least some of the fluid dispensers;
• moving the array of fluid dispensers in a row direction so that at least some fluid dispensers in the array of fluid dispensers are positioned with reference to a second column of sample wells;
• and
• dispensing a predetermined volume of a material into selected sample wells in the second column from at least some of the fluid dispensers.