Integral biomolecule preparation device

Claim 2

A self-contained biomolecule preparation device for automatically preparing biomolecules such as nucleic acid from samples such as cell samples, comprising: a plurality of samples tubes contained in a rotor for holding chemical compounds in liquid or solid form; a plurality of pipet tips to withdraw and dispense controlled amounts of fluid contained in said plurality of sample tubes; a centrifuge, containing the rotor, for spinning said plurality of samples tubes in said rotor at predetermined times; a pipet tip rack, separate from the centrifuge and the rotor, for holding said plurality of pipet tips, each of said tips associated with and substantially parallel to one of said sample tubes in the rotor of said centrifuge; means for maintaining a predetermined relationship between the pipet tips in said tip rack and the sample tubes in the rotor; a pipet arm assembly, proximate said pipet tip rack and the rotor of said centrifuge, including a pipet tip handling mandrel, driven to move in two dimensions by a motorized mechanism, for selectively removing pipet tips from said pipet tip rack, inserting them into the sample tubes in the rotor of said centrifuge, and returning the selected pipet tip back to the tip rack for further use, said arm assembly responsive to said means for maintaining so that the pipet tip selected for removal remains associated with the sample tube in which the pipet tip is to be inserted; a plurality of reagent reservoirs, proximate said sample tubes, for holding biomolecule preparation reagents; reagent adding means for selectively adding controlled amounts of the reagents from said reservoirs to said sample tubes at predetermined times; mixing means for mixing the sample tube contents at predetermined times; fluid withdrawal means for withdrawing fluid from a sample tube into an inserted pipet tip at predetermined times; and process control means for controlling the operation, including the integrated sequence of operations, of said centrifuge, said pipet arm, said reagent adding means, said mixing means and said fluid withdrawal means.

Claim 3

The biomolecule preparation device of claim 1 in which said mixing means includes means for agitating the rotor.

Claim 4

The biomolecule preparation device of claim 1 in which said mixing means includes means for passing air through the pipet tip inserted in the sample tube to bubble air in the fluid.

Claim 5

The biomolecule preparation device of claim 1 in which said pipet arm assembly includes a stepper motor for controllably inserting said pipeting end into the pipet tips.

Claim 6

The biomolecule preparation device of claim 1 further including centrifuge rotor control means for controlling the speed and duration of rotation of the rotor of said centrifuge.

Claim 7

The biomolecule preparation device of claim 1 in which said process control means includes a system of operating software for prompting the user to select process commands and variables to automatically produce DNA from cell samples.

Claim 8

The biomolecule preparation device of claim 1 further including tip stripping means containing a stripping structure proximate each pipet tip position in said pipet tip rack for stripping a pipet tip from said pipet arm assembly.

Claim 9

The biomolecule preparation device of claim 1 in which said mixing means further includes means for repeatedly drawing fluid in and Out of the pipet tip inserted into a sample tube.

Claim 10

The biomolecule preparation device of claim 8 in which said mixing means further includes means for controlling the fluid flow rate.

Claim 11

The biomolecule preparation device of claim 1 further including reagent volume determining means for determining the reagent volume in said reagent reservoirs.

Claim 12

The biomolecule preparation device of claim 10 in which said reagent volume determining means includes means for supplying a known volume of gas at a known pressure to said reservoir.

Claim 13

The biomolecule preparation device of claim 10 in which said reagent volume determining means includes a liquid level sensor.

Claim 14

The biomolecule preparation device of claim 1 in which said pipet arm assembly includes a passive insertion control means for controlling the depth of insertion of the pipet tip into the sample tube.

Claim 15

The biomolecule preparation device of claim 13 further including liquid level determining means for determining the liquid level height in the sample tube.

Claim 16

The biomolecule preparation device of claim 14 in which said insertion control means is responsive to said liquid level determining means for placing the pipet tip at a desired position in relation to the tube liquid surface.

Claim 17

The biomolecule preparation device of claim 1 in which said reagent adding means includes a reagent delivery orifice for delivering reagents at a predetermined flow rate.

Claim 18

The biomolecule preparation device of claim 16 in which said reagent adding means further includes reagent pressure control means for controlling the reagent pressure for delivering reagent through said orifice at a controllable rate.

Claim 19

The biomolecule preparation device of claim 17 further including means for establishing the reagent delivery period to control the volume of reagent added.

Claim 20

The biomolecule preparation device of claim 1 in which said reagent adding means includes a liquid delivery conduit from said reservoirs leading to proximate the rotor of said centrifuge.

Claim 21

The biomolecule preparation device of claim 19 in which said reagent adding means further includes reagent sensing means for sensing the presence of reagent proximate the end of said delivery conduit.

Claim 22

The biomolecule preparation device of claim 20 in which said reagent sensing means includes means for determining a change in light intensity transmitted through said conduit.

Claim 23

The biomolecule preparation device of claim 19 in which said delivery conduit further includes a bubble trap to allow air bubbles entrapped in the reagent to escape.

Claim 24

The biomolecule preparation device of claim 22 further including means for withdrawing reagent from said conduit after reagent delivery to prevent reagent spillage.

Claim 25

The biomolecule preparation device of claim 1 in which said means for maintaining includes position control means for controlling the relative positions of the rotor of said centrifuge and said pipet tip rack.

Claim 26

The biomolecule preparation device of claim 24 in which said position control means includes means for determining the position of the pipet tip rack.

Claim 27

The biomolecule preparation device of claim 25 in which said position control means further includes means, responsive to said means for determining, for rotating said pipet tip rack.

Claim 28

The biomolecule preparation device of claim 26 in which said means for rotating includes a stepper motor for indexing said pipet tip rack.

Claim 29

The biomolecule preparation device of claim 24 in which said position control means includes means for determining the position of the rotor.

Claim 30

The biomolecule preparation device of claim 28 in which said position control means further includes means, responsive to said means for determining, for rotating the rotor.

Claim 31

The biomolecule preparation device of claim 29 in which said means for rotating includes a motor for spinning or indexing said rotor.

Claim 32

The biomolecule preparation device of claim 29 in which said reagent adding means includes at least one reagent dispensing opening fixed in relation to the rotor to allow positioning of a selected sample tube below a selected dispensing opening.

Claim 33

The biomolecule preparation device of claim 29 in which said means for rotating includes a detent position for each rotor sample tube location.

Claim 34

The biomolecule preparation device of claim 32 in which said means for rotating includes a brushless DC motor.

Claim 35

The biomolecule preparation device of claim 24 in which said means for maintaining includes means for aligning a selected pipet tip with a selected sample tube.

Claim 36

The biomolecule preparation device of claim 34 further including means for moving said pipet arm in two axes, in and out of said rotor and pipet tip rack, and between said rotor and pipet tip rack.

Claim 37

The biomolecule preparation device of claim 35 in which said means for moving includes at least one stepper motor for controllably positioning the pipeting end.

Claim 38

The biomolecule preparation device of claim 36 in which said means for moving further includes means for sensing a predetermined position of said stepper motor.

Claim 39

The biomolecule preparation device of claim 1 in which said fluid withdrawal means includes an air cylinder operably connected to said pipet arm pipeting end.

Claim 40

The biomolecule preparation device of claim 38 in which said air cylinder includes a movable piston for varying the volume of said air cylinder.

Claim 41

The biomolecule preparation device of claim 39 further including piston control means for controllably moving said piston.

Claim 42

The biomolecule preparation device of claim 40 in which said piston control means includes a stepper motor.

Claim 43

The biomolecule preparation device of claim 42 further including piston sensing means for sensing a predetermined position of said piston.

Claim 44

A biomolecule preparation device for automatically preparing biomolecules such as nucleic acid from a sample such as a cell sample, comprising: a plurality of sample tubes contained in as indexing sample tube rotor for holding chemical compounds in liquid or solid form; a plurality of pipet tips to withdraw and dispense controlled amounts of fluid contained in said plurality of sample tubes; a variable speed centrifuge, with an indexing sample tube rotor, for spinning said sample tubes at predetermined times; tube position determining means for determining the position of the tube rotor with respect to the centrifuge to locate each sample tube in the rotor; an indexing pipet tip rack, separate from the centrifuge and the tube rotor, for holding at least one said pipet tip for each sample tube; said pipet tip rack holding said pipet tip substantially parrallel to said sample tube; means for determining the position of the tip rack with respect to the centrifuge to locate each pipet tip in relation to a respective sample tube; a pipet arm, proximate said indexing pipet tip rack and the rotor of said centrifuge, having a pipeting end; first arm displacing means for displacing said pipeting end in a first direction coaxially into a pipet tip to engage the tip associated with said respective sample tube; second arm displacing means for displacing said pipeting end in a second direction coaxially with the engaged pipet tip to withdraw the tip from said tip indexing tip rack; tip insertion means for inserting the engaged pipet tip into said respective sample tube at predetermined times; mixing means for mixing the tube contents by both repeatedly withdrawing at least part of the sample tube contents into the engaged pipet tip and dispensing the withdrawn tube contents back into the tube at predetermined times; a plurality of reagent reservoirs, proximate said indexing sample tube rotor, for holding biomolecule preparation reagents; a reagent dispensing orifice proximate said indexing sample tube rotor; reagent dispensing means for dispensing under pressure reagent from at least one of said reservoirs through said orifice into the sample tube at a rate controlled by the orifice size and the dispensing pressure at predetermined times; and reagent dispensing time means for establishing the reagent dispense time to control the volume of dispensed reagent.

Claim 45

A biomolecule preparation device for automatically preparing biomolecules such as nucleic acid from a sample such as a cell sample, comprising: a plurality of sample tubes contained in as indexing sample tube rotor for holding chemical compounds in liquid or solid form; a plurality of pipet tips to withdraw and dispense controlled amounts of fluid contained in said plurality of sample tubes; a variable speed centrifuge, with an indexing sample tube rotor, for spinning said sample tubes at predetermined times; tube position determining means for determining the position of the tube rotor with respect to the centrifuge to locate each sample tube in the rotor; an indexing pipet tip rack, separate from the centrifuge and the tube rotor, for holding at least one said pipet tip for each sample tube; said pipet tip rack holding said pipet tip substantially parrallel to said sample tube; means for determining the position of the tip rack with respect to the centrifuge to locate each pipet tip in relation to a respective sample tube; a pipet arm, proximate said indexing pipet tip rack and the rotor of said centrifuge, having a pipeting end; first arm displacing means for displacing said pipeting end in a first direction coaxially into a pipet tip to engage the tip associated with said respective sample tube; second arm displacing means for displacing said pipeting end in a second direction coaxially with the engaged pipet tip to withdraw the tip from said tip indexing tip rack; tip insertion means for inserting the engaged pipet tip into said respective sample tube at predetermined times; mixing means for mixing the tube contents by both repeatedly withdrawing at least part of the sample tube contents into the engaged pipet tip and dispensing the withdrawn tube contents back into the tube at predetermined times; a plurality of reagent reservoirs, proximate said indexing sample tube rotor, for holding biomolecule preparation reagents; a reagent dispensing orifice proximate said indexing sample tube rotor; reagent dispensing means for dispensing under pressure reagent from at least one of said reservoirs through said orifice into the sample tube at a rate controlled by the orifice size and the dispensing pressure at predetermined times; and reagent dispensing time means for establishing the reagent dispense time to control the volume of dispensed reagent.