US5443791A — Automated molecular biology laboratory

Claim 1

Independent Claim 175 words

A liquid-handling instrument for transferring liquid from one container to another comprising: a stationary worksurface having machined registration elements for accurately locating and supporting a modular container station for holding said containers of liquid; a pipette subsystem for aspirating and dispensing liquid, said pipette subsystem comprising a pipette tip coupled to a capacitance sensor; a robotic translation subsystem for moving said pipette tip to all containers on said worksurface and into and out of said containers; a gauge block securely fastened to and accurately positioned on said worksurface relative to said registration elements, and having surfaces substantially orthogonal to directions of movement of said pipette tip by said robotic translation subsystem; and a control subsystem for automatically managing said liquid transfers; wherein said control subsystem controls said robotic translation subsystem to move said pipette tip to each of said surfaces on said gauge block wherein the pipette tip and the capacitance sensor sense the position of the machined surface of said gauge block thereby establishing a home position on said worksurface for said liquid transfers.

Claim 2

Dependent Claim 175 words

A liquid-handling instrument for transferring liquid from one container to another comprising: a stationary worksurface having machined registration elements for accurately locating and supporting a modular container station for holding said containers of liquid; a pipette subsystem for aspirating and dispensing liquid, said pipette subsystem comprising a pipette tip coupled to a capacitance sensor; a robotic translation subsystem for moving said pipette tip to all containers on said worksurface and into and out of said containers; a gauge block securely fastened to and accurately positioned on said worksurface relative to said registration elements, and having surfaces substantially orthogonal to directions of movement of said pipette tip by said robotic translation subsystem; and a control subsystem for automatically managing said liquid transfers; wherein said control subsystem controls said robotic translation subsystem to move said pipette tip to each of said surfaces on said gauge block wherein the pipette tip and the capacitance sensor sense the position of the machined surface of said gauge block thereby establishing a home position on said worksurface for said liquid transfers.

Claim 3

Dependent Claim 61 words

An instrument as in claim 1 wherein said registration elements comprise a cavity for positioning the modular container station, said cavity positioned accurately relative to said gauge block, such that a first modular station may be removed and a second modular station substituted therefor while maintaining known dimensions from containers in said stations to the known position of said gauge block.

Claim 4

Dependent Claim 74 words

An instrument as in claim 1 wherein said pipette subsystem further comprises a first syringe pump operable by said control subsystem at a first rate for aspirating and dispensing liquids with a first degree of accuracy and a second syringe pump operable by said control subsystem at a second rate for aspirating and delivering liquids with a second degree of accuracy, said first and second syringe pumps being commonly connected to said pipette tip.

Claim 5

Dependent Claim 45 words

An instrument as in claim 1 wherein said robotic translation subsystem comprises a robot having a carriage over said stationary worksurface for carrying said pipette tip, said carriage being translatable over the area of said worksurface and also translatable toward and away from said worksurface.

Claim 6

Dependent Claim 28 words

An instrument as in claim 4 wherein said robot is a cartesian robot having three directions of travel, two in a horizontal plane and the third direction vertical.

Claim 7

Dependent Claim 21 words

An instrument as in claim 5 wherein said robot has three principal drives, and said drives are powered by electric motors.

Claim 8

Dependent Claim 56 words

An instrument as in claim 1 wherein said control subsystem comprises an iconic interface having user-selectable icons for programming a protocol and for entering values for control variables, said icons representing specific steps in said protocol and arrangeable in series to determine action sequences, said icons being expandable-in-place to show other steps that an icon comprises.

Claim 9

Dependent Claim 63 words

An instrument as in claim 1 further comprising a tip washing station located on said stationary worksurface, and said tip washing station comprises; a fountain for enclosing said pipette tip during washing; and a well surrounding said fountain such that liquid flowing from said fountain flows into said well, said well having a drain disposed to communicate unwanted material to an external location.

Claim 10

Dependent Claim 32 words

An instrument as in claim 1 wherein at least one of said containers supported by said worksurface comprises closure means having a flexible duck-billed portion extending toward the interior of said container.

Claim 11

Dependent Claim 32 words

An instrument as in claim 9 wherein said container comprises an upper rim and said closure means comprises an annular cavity portion surrounding said duck-billed portion for sealing to said upper rim.

Claim 12

Dependent Claim 193 words

An automated laboratory for transferring liquids from one container to another and performing a chemistry protocol comprising: a stationary worksurface having machined registration elements are accurately locating and supporting a modular container station for holding said containers of liquid; a pipette subsystem for aspirating and dispensing liquid, said pipette subsystem comprising a pipette tip coupled to a capacitance sensor; a robotic translation subsystem for moving said pipette tip to all containers on said worksurface and into and out of said containers; a heating subsystem for heating liquids in said containers; a cooling subsystem for cooling liquids in said containers; a gauge block securely fastened to and accurately positioned on said worksurface and having surfaces substantially orthogonal to directions of movement of said pipette tip by said robotic translation subsystem; and a control subsystem for automatically managing said chemistry protocol; wherein said control subsystem controls said robotic translation subsystem to move said pipette tip to each of said surfaces on said gauge block wherein the pipette tip and the capacitance sensor sense the position of the machined surface of said gauge block thereby establishing a home position on said worksurface for said liquid transfers.

Claim 13

Dependent Claim 193 words

An automated laboratory for transferring liquids from one container to another and performing a chemistry protocol comprising: a stationary worksurface having machined registration elements are accurately locating and supporting a modular container station for holding said containers of liquid; a pipette subsystem for aspirating and dispensing liquid, said pipette subsystem comprising a pipette tip coupled to a capacitance sensor; a robotic translation subsystem for moving said pipette tip to all containers on said worksurface and into and out of said containers; a heating subsystem for heating liquids in said containers; a cooling subsystem for cooling liquids in said containers; a gauge block securely fastened to and accurately positioned on said worksurface and having surfaces substantially orthogonal to directions of movement of said pipette tip by said robotic translation subsystem; and a control subsystem for automatically managing said chemistry protocol; wherein said control subsystem controls said robotic translation subsystem to move said pipette tip to each of said surfaces on said gauge block wherein the pipette tip and the capacitance sensor sense the position of the machined surface of said gauge block thereby establishing a home position on said worksurface for said liquid transfers.

Claim 14

Dependent Claim 55 words

An automated laboratory as in claim 11 further comprising an incubation station heatable by said heating subsystem and coolable by said cooling subsystem, said incubation station having cavities coated with a chemically inert coating, and a latching lid with a sealing surface such that with said lid closed and latched, said cavities are individually sealed.

Claim 15

Dependent Claim 40 words

An automated laboratory as in claim 12 wherein said cavities each have a machined upper lip such that force exerted on said lid by latching said lid is concentrated on said machined upper lips of said cavities to facilitate sealing.

Claim 16

Dependent Claim 49 words

An automated laboratory as in claim 12 wherein said cavities are machined into a metal block, and said metal block is securely fastened to and accurately positioned on said worksurface and removable, such that a block of cavities may be removed and replaced with a new block of cavities.

Claim 17

Dependent Claim 36 words

An automated laboratory as in claim 12 wherein said cavities have a lower cylindrical portion for holding a sample and an upper conical portion to provide additional volume to hold liquid aspirated during a cleaning procedure.

Claim 18

Dependent Claim 72 words

An automated laboratory as in claim 11 further comprising a magnetic system for passing a magnetic field through containers supported by said worksurface to separate paramagnetic particles from a liquid in said containers, said magnetic system comprising a station having two rows of containers for holding liquid, and a magnetic bar supported on an elevator such that said magnetic bar may be selectively elevated and withdrawn from between said rows of containers.

Claim 19

Dependent Claim 15 words

An automated laboratory as in claim 16 wherein said magnetic bar comprises rare-earth magnetic material.

Claim 20

Dependent Claim 62 words

An automated laboratory as in claim 11 wherein said registration elements comprise a cavity for positioning the modular container station, said cavity positioned accurately relative to said gauge block, such that a first modular station may be removed and a second modular station substituted therefor while maintaining known dimensions from containers in said stations to the known position of said gauge block.

Claim 21

Dependent Claim 75 words

An automated laboratory as in claim 11 wherein said pipette subsystem further comprises a first syringe pump operable by said control subsystem at a first rate for aspirating and dispensing liquids with a first degree of accuracy and a second syringe pump operable by said control subsystem at a second rate for aspirating and delivering liquids with a second degree of accuracy, said first and second syringe pumps being commonly connected to said pipette tip.

Claim 22

Dependent Claim 46 words

An automated laboratory as in claim 11 wherein said robotic translation subsystem comprises a robot having a carriage over said stationary worksurface for carrying said pipette tip, said carriage being translatable over the area of said worksurface and also translatable toward and away from said worksurface.

Claim 23

Dependent Claim 29 words

An automated laboratory as in claim 20 wherein said robot is a cartesian robot having three directions of travel, two in a horizontal plane and the third direction vertical.

Claim 24

Dependent Claim 31 words

An automated laboratory as in claim 21 wherein said robot has three principal drives, one for each of said three directions of travel, and said drives are powered by electric motors.

Claim 25

Dependent Claim 57 words

An automated laboratory as in claim 11 wherein said control subsystem comprises an iconic interface having user-selectable icons for programming a protocol and for entering values For control variables, said icons representing specific steps in said protocol and arrangeable in series to determine action sequences, said icons being expandable-in-place to show other steps that comprise art icon.

Claim 26

Dependent Claim 62 words

An automated laboratory as in claim 11 further comprising a tip-washing station located on said stationary worksurface, and said tip-washing station comprises; a fountain for enclosing said pipette tip during washing; and a well surrounding said fountain such that liquid flowing from said fountain flows into said well, said well having a drain disposed to communicate unwanted material to an external location.

Claim 27

Dependent Claim 33 words

An automated laboratory as in claim 11 wherein at least one of said containers supported by said worksurface comprises closure means having a flexible duck-billed portion extending toward the interior of said container.

Claim 28

Dependent Claim 33 words

An automated laboratory as in claim 25 wherein said container comprises an upper rim and said closure means comprises an annular cavity portion surrounding said duck-billed portion for sealing to said upper rim.

Claim 29

Dependent Claim 22 words

An automated laboratory as in claim 11 wherein said control subsystem comprises control routines with steps for performing automated specific gene detection.

Claim 30

Dependent Claim 22 words

An automated laboratory in claim 11 wherein said control subsystem comprises control routines with steps for performing automated nucleic acid sequence detection.

Claim 31

Dependent Claim 23 words

An automated laboratory in claim 11 wherein said control subsystem comprises control routines with steps for performing automated fluorescent labelling of nucleic acids.

Claim 32

Independent Claim 301 words

A method for transferring liquid by a robotic translation system from a first container holding a first volume of liquid to a second container holding a second volume of liquid comprising steps of: aspirating a third volume of liquid from said first volume of liquid in said first container with a pipette having a pipette tip and a capacitance sensor for sensing the position of said pipette tip relative to proximate surfaces; moving said pipette tip away from said first container by action of said robotic translation system; dispensing a first droplet of liquid from said pipette tip such that said first droplet depends from said pipette tip but does not separate therefrom, said first droplet having a known droplet volume; moving said first droplet with said pipette tip by said robotic translation system until said first droplet touches the surface of said second volume of liquid, stopping translation when said capacitance sensor signals contact, and allowing said first droplet to become confluent with said second volume of liquid; withdrawing said pipette tip from said second volume of liquid; dispensing a second droplet of liquid from said pipette tip such that said second droplet of liquid depends from said pipette tip but does not separate therefrom, said second droplet having a volume equal to the volume of said first droplet; moving said second droplet with said pipette tip by said robotic translation system until said second droplet touches the surface of said second volume of liquid, stopping translation when said capacitance sensor signals contact, and allowing said second droplet to become confluent with said second volume of liquid; and repeating the steps of dispensing droplets and transferring the droplets to said second volume of liquid until a predetermined volume of liquid is dispensed and transferred to said second volume of liquid.

Claim 33

Independent Claim 301 words

A method for transferring liquid by a robotic translation system from a first container holding a first volume of liquid to a second container holding a second volume of liquid comprising steps of: aspirating a third volume of liquid from said first volume of liquid in said first container with a pipette having a pipette tip and a capacitance sensor for sensing the position of said pipette tip relative to proximate surfaces; moving said pipette tip away from said first container by action of said robotic translation system; dispensing a first droplet of liquid from said pipette tip such that said first droplet depends from said pipette tip but does not separate therefrom, said first droplet having a known droplet volume; moving said first droplet with said pipette tip by said robotic translation system until said first droplet touches the surface of said second volume of liquid, stopping translation when said capacitance sensor signals contact, and allowing said first droplet to become confluent with said second volume of liquid; withdrawing said pipette tip from said second volume of liquid; dispensing a second droplet of liquid from said pipette tip such that said second droplet of liquid depends from said pipette tip but does not separate therefrom, said second droplet having a volume equal to the volume of said first droplet; moving said second droplet with said pipette tip by said robotic translation system until said second droplet touches the surface of said second volume of liquid, stopping translation when said capacitance sensor signals contact, and allowing said second droplet to become confluent with said second volume of liquid; and repeating the steps of dispensing droplets and transferring the droplets to said second volume of liquid until a predetermined volume of liquid is dispensed and transferred to said second volume of liquid.

Claim 34

Independent Claim 122 words

A method for checking for positions of elements on a worksurface in a liquid-handling instrument having a pipette subsystem, said pipette subsystem comprising a pipette tip coupled to a capacitance sensor for sensing position of said pipette tip relative to proximate surfaces, said pipette tip movable over said worksurface by a robotic translation subsystem, said method comprising the steps of: moving said pipette tip in a pattern and at a height over said worksurface such that said pipette tip will not contact any surface if every part is in its proper place; stopping translation of said pipette tip if said pipette tip contacts any surface as signalled by said capacitance sensor; and activating a signal that a part is out of position.

Claim 35

Independent Claim 122 words

A method for checking for positions of elements on a worksurface in a liquid-handling instrument having a pipette subsystem, said pipette subsystem comprising a pipette tip coupled to a capacitance sensor for sensing position of said pipette tip relative to proximate surfaces, said pipette tip movable over said worksurface by a robotic translation subsystem, said method comprising the steps of: moving said pipette tip in a pattern and at a height over said worksurface such that said pipette tip will not contact any surface if every part is in its proper place; stopping translation of said pipette tip if said pipette tip contacts any surface as signalled by said capacitance sensor; and activating a signal that a part is out of position.

Claim 36

Independent Claim 126 words

A method for mixing liquids in a liquid handling instrument having a pipette subsystem with a pipette tip movable over a worksurface by a robotic translation subsystem, said method comprising the steps of: moving said pipette tip by said robotic translation subsystem to immerse said pipette tip in a volume of liquid in a container; aspirating liquid into said pipette ending with said pipette tip immersed in said volume of liquid in said container; dispensing said aspirated liquid into said container while moving said pipette tip in a pattern encompassing substantially the space occupied by said volume of liquid in said con ruiner; and repeating the steps of aspirating and dispensing while moving said tip in said pattern to thoroughly mix the contents in said container.

Claim 37

Independent Claim 126 words

A method for mixing liquids in a liquid handling instrument having a pipette subsystem with a pipette tip movable over a worksurface by a robotic translation subsystem, said method comprising the steps of: moving said pipette tip by said robotic translation subsystem to immerse said pipette tip in a volume of liquid in a container; aspirating liquid into said pipette ending with said pipette tip immersed in said volume of liquid in said container; dispensing said aspirated liquid into said container while moving said pipette tip in a pattern encompassing substantially the space occupied by said volume of liquid in said con ruiner; and repeating the steps of aspirating and dispensing while moving said tip in said pattern to thoroughly mix the contents in said container.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	1998-08-21	1999-02-20	1999-08-22	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	2002-08-21	2003-02-20	2003-08-22	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	2006-08-21	2007-02-20	2007-08-22	$7700.00	Window Closed / Lapsed

Automated molecular biology laboratory

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