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Apparatus for robotically performing sanger dideoxynucleotide DNA sequencing reactions using controlled pipet

Assignee: Thomas Jefferson University
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Filing: 1994-08-08
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Granted: 1995-10-03
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Expires: 2014-08-08
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Abstract

Abstract A robotic system for performing nucleic acid sequencing reactions in microtiter plate format. The robot has a robot arm and its controller, robot hands with which it can manipulate microtiter plates with lids and microtiter plates without lids and with which it can perform pipetting in the 5 to 200 microliter range, cooled storage chambers with electronically controllable doors for storage of microtiter plates, cooled storage with an electronically controllable cover for storage of nucleic acid sequencing reagents, heating blocks to incubate the reactions at appropriate temperatures above ambient temperature, storage for boxes of micropipet tips, storage for microtiter plates in which sequence reactions will be performed and software for controlling the operation of the robot during pipetting.

Inventors

  • 👤 James J. Earley
  • 👤 Gerardus C. Tromp
  • 👤 Darwin J. Prockop
  • 👤 Sisko H. Kuivaniemi

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-10 01:13
CPC Classifications
B; B01; B01L; B01L7/00; B01L7/52; B01J; B01J19/00; B01J19/0046; G; G01; G01N; G01N35/00; G01N35/0099; G01N35/02; G01N35/028; G01N35/10; G01N35/1002; B01J2219/00; B01J2219/00274; B01J2219/00277; B01J2219/00279; B01J2219/00306; B01J2219/00313; B01J2219/00315; B01J2219/00351; B01J2219/00353; B01J2219/00355; B01J2219/00364; B01J2219/00495; B01J2219/00583; B01J2219/0059; B01J2219/0068; B01J2219/00686; B01J2219/00689; B01J2219/00691; B01J2219/00695; B01J2219/00718; B01J2219/0072; B01J2219/00722; C; C40; C40B; C40B40/00; C40B40/04; C40B40/06; C40B60/00; C40B60/14; G01N2035/00346; G01N2035/00445; G01N2035/00455; G01N35/04; G01N2035/0401; G01N2035/0418; G01N2035/042; G01N2035/0425; G01N35/1009; G01N35/1011; G01N35/1065

Claims Analysis

Total Claims: 28
Claim 1
Independent Claim 233 words
A robotic system for automatically performing DNA sequencing, comprising: a robot having an arm mounted for motion in vertical and horizontal planes; a hand for said robot arm having means for pipetting a fluid from a microtiter plate well; a microtiter plate having a well formed therein, said well having a bottom, a reagent solution contained in said well; a plurality of work surfaces, each having means for supporting a microtiter plate; a plurality of reservoirs, each having means for holding a reagent; first storage means for storing microtiter plates; sensing means for generating a signal in response to said pipetting means making contact with said microtiter plate well bottom; and a programmable controller having (i) first logic means for instructing said robot to move said pipetting means toward said microtiter plate well bottom by a series of discrete incremental movements, each of said discrete incremental movements in said series being separated by a finite period of time, said series of incremental movements including a set of incremental movements in which each discrete incremental movement is successively smaller than each previous discrete incremental movement in said set, and (ii) second logic means for determining whether said pipetting means has made contact with said microtiter plate well bottom based on said signal from said sensing means during said finite period of time between each of said discrete incremental movements in said set of movements.
Claim 2
Dependent Claim 233 words
A robotic system for automatically performing DNA sequencing, comprising: a robot having an arm mounted for motion in vertical and horizontal planes; a hand for said robot arm having means for pipetting a fluid from a microtiter plate well; a microtiter plate having a well formed therein, said well having a bottom, a reagent solution contained in said well; a plurality of work surfaces, each having means for supporting a microtiter plate; a plurality of reservoirs, each having means for holding a reagent; first storage means for storing microtiter plates; sensing means for generating a signal in response to said pipetting means making contact with said microtiter plate well bottom; and a programmable controller having (i) first logic means for instructing said robot to move said pipetting means toward said microtiter plate well bottom by a series of discrete incremental movements, each of said discrete incremental movements in said series being separated by a finite period of time, said series of incremental movements including a set of incremental movements in which each discrete incremental movement is successively smaller than each previous discrete incremental movement in said set, and (ii) second logic means for determining whether said pipetting means has made contact with said microtiter plate well bottom based on said signal from said sensing means during said finite period of time between each of said discrete incremental movements in said set of movements.
Claim 3
Dependent Claim 85 words
The robotic system according to claim 1, wherein said first logic means further comprises means for instructing said robot to move said pipetting means toward said microtiter plate well bottom by at least one additional set of incremental movements, each incremental movement in any such additional sets being successively smaller than each previous incremental movement in its respective set, additional sets of incremental movements being successively performed until said second logic means has determined that said pipetting means has contacted said microtiter plate well bottom.
Claim 4
Dependent Claim 19 words
The robotic system according to claim 1, wherein said set of incremental movements comprises at least three incremental movements.
Claim 5
Dependent Claim 79 words
The robotic system according to claim 1, wherein said sensing means comprises means for sensing a force acting on said hand, and wherein said second logic means comprises: means for instructing said robot to sense an initial force acting on said hand prior to said set of incremental movements; means for determining if said force sensed differs from said initial force by more than a first predetermined value after each of said incremental movements in said set of movements.
Claim 6
Dependent Claim 68 words
The robotic system according to claim 4, wherein said first predetermined value is approximately equal to the difference in said forced sensed when said hand is hanging freely from said robot arm immediately after said hand has been moved in a downward direction and said force sensed when said hand is hanging freely from said robot arm immediately after said hand has been moved in an upward direction.
Claim 7
Dependent Claim 19 words
The robotic system according to claim 1, wherein said reagent solution contained in said well includes a non-ionic surfactant.
Claim 8
Dependent Claim 22 words
The robotic system according to claim 6, wherein said non-ionic surfactant in said reagent solution has a concentration of at least 0.02%.
Claim 9
Dependent Claim 21 words
The robotic system according to claim 6, wherein said non-ionic surfactant in said reagent solution has a concentration of about 0.02%.
Claim 10
Dependent Claim 17 words
The robotic system according to claim 1, further comprising means for holding and heating said microtiter plate.
Claim 11
Dependent Claim 26 words
The robotic system according to claim 9, wherein said pipetting means comprises a plurality of pipet tips capable of being coupled and uncoupled from said hand.
Claim 12
Dependent Claim 31 words
The robotic system according to claim 10, further comprising: means for storing said pipet tips; means for storing a plurality of empty microtiter plates; and means for heating said microtiter plate.
Claim 13
Dependent Claim 45 words
The robotic system according to claim 11, wherein said means for holding and heating said microtiter plate, said work surfaces, said reservoirs, and each of said storage means are arranged in a approximately circular array, and wherein said robot is centrally disposed within said array.
Claim 14
Dependent Claim 49 words
The robotic system according to claim 9, wherein said microtiter plate well defines a surface through which heat can flow into said well, and wherein said means for holding and heating said microtiter plate has a heat transfer surface formed therein that conforms to said microtiter plate well surface.
Claim 15
Dependent Claim 15 words
The robotic system according to claim 10, further comprising means for washing said pipet tips.
Claim 16
Dependent Claim 66 words
The robotic system according to claim 1, wherein said programmable controller has third logic means for instructing said robot to move said pipetting means away from said microtiter plate well bottom to allow aspiration of substantially all of said reagent solution from said microtiter plate well after said second logic means has determined that said pipetting means has made contact with said microtiter plate well bottom.
Claim 17
Dependent Claim 75 words
The robotic system according to claim 15, wherein said third logic means comprises means for instructing said robot to move said pipetting means in a direction away from said microtiter plate well bottom by a succession of incremental movements until said means for determining whether said pipetting means is still in contact with said microtiter plate well bottom has determined that said pipetting means is not still in contact with said microtiter plate well bottom.
Claim 18
Dependent Claim 83 words
The robotic system according to claim 15, wherein said third logic means comprises: means for instructing said robot to move said pipetting means in a direction away from said microtiter plate well bottom by a first predetermined increment; and means for determining whether said sensed has changed by more than a second predetermined pipetting means is still in contact with said microtiter plate well bottom after said pipetting means has been moved away from said plate well bottom by said first predetermined increment.
Claim 19
Dependent Claim 124 words
The robotic system according to claim 17, wherein: said first logic means further comprises means for instructing said robot to move said pipetting means toward said microtiter plate well bottom by at least one additional set of incremental movements, each incremental movement in any such additional sets being successively smaller than each previous incremental movement in its respective set, additional sets of incremental movements being performed in succession until said second logic means has determined that said pipetting means has contacted said microtiter plate well bottom; and the value of said first predetermined increment is variable, said third logic means having means for varying the magnitude of said first predetermined increment as a function of the number of said sets of incremental movements performed.
Claim 20
Dependent Claim 41 words
The robotic system according to claim 18, wherein said third logic means has means for varying the magnitude of said first predetermined increment so that said first predetermined increment increases as the number of said sets of incremental movements performed increases.
Claim 21
Dependent Claim 98 words
The robotic system according to claim 17, wherein said sensing means comprises means for sensing a force acting on said hand, and wherein said means for determining whether said pipetting means is still in contact with said microtiter plate well bottom further comprises: means for instructing said robot to sense an initial force acting on said hand prior to said movement by said first predetermined increment; and means for determining if said force sensed differs from said initial force by more than a first predetermined value after said pipetting means has been moved by said first predetermined increment.
Claim 22
Dependent Claim 68 words
The robotic system according to claim 20, wherein said first predetermined value is approximately equal to the difference in said forced sensed when said hand is hanging freely from said robot arm immediately after said hand has been moved in a downward direction and said force sensed when said hand is hanging freely from said robot arm immediately after said hand has been moved in an upward direction.
Claim 23
Dependent Claim 225 words
A robotic system for automatically performing reactions in sequence, comprising: means for containing a fluid, said fluid containing means having a bottom; a robot having means for drawing a fluid from said fluid containing means, said fluid drawing means normally spaced from said fluid containing means bottom by a distance; means for causing relative motion between said fluid containing means and said fluid drawing means; sensing means for generating a signal in response to said fluid drawing means making contact with said bottom of said fluid containing means; and a programmable controller having (i) first logic means for instructing said relative motion causing means to reduce said distance between said bottom of said fluid containing means and said fluid drawing means by a series of discrete incremental movements, each of said discrete incremental movements in said series being separated by a finite period of time, said series of discrete incremental movements including a set of discrete incremental movements in which each discrete incremental movement is successively smaller than each previous discrete incremental movement in said set, and (ii) second logic means for determining whether said fluid drawing means has made contact with said bottom of said fluid containing means based on said signal from said sensing means during said finite period of time between each of said discrete incremental movements in said set of movements.
Claim 24
Dependent Claim 225 words
A robotic system for automatically performing reactions in sequence, comprising: means for containing a fluid, said fluid containing means having a bottom; a robot having means for drawing a fluid from said fluid containing means, said fluid drawing means normally spaced from said fluid containing means bottom by a distance; means for causing relative motion between said fluid containing means and said fluid drawing means; sensing means for generating a signal in response to said fluid drawing means making contact with said bottom of said fluid containing means; and a programmable controller having (i) first logic means for instructing said relative motion causing means to reduce said distance between said bottom of said fluid containing means and said fluid drawing means by a series of discrete incremental movements, each of said discrete incremental movements in said series being separated by a finite period of time, said series of discrete incremental movements including a set of discrete incremental movements in which each discrete incremental movement is successively smaller than each previous discrete incremental movement in said set, and (ii) second logic means for determining whether said fluid drawing means has made contact with said bottom of said fluid containing means based on said signal from said sensing means during said finite period of time between each of said discrete incremental movements in said set of movements.
Claim 25
Dependent Claim 83 words
The robotic system according to claim 22, wherein said sensing means comprises means for sensing a force acting on said fluid drawing means, and wherein said second logic means comprises: means for instructing said robot to sense an initial force acting on said fluid drawing means prior to said set of incremental movements; means for determining if said force sensed differs from said initial force by more than a first predetermined value after each of said incremental movements in said set of movements.
Claim 26
Dependent Claim 68 words
The robotic system according to claim 22, wherein said programmable controller has third logic means for instructing said relative motion causing means to move said fluid drawing means in a direction away from said bottom of said fluid containing means by a first predetermined increment after said second logic means has determined that said fluid drawing means has made contact with said bottom of said fluid containing means.
Claim 27
Dependent Claim 58 words
The robotic system according to claim 24, wherein said third logic means comprises means for determining whether said fluid drawing means is still in contact with said bottom of said fluid containing means after said fluid drawing means has been moved in said direction away from said bottom of said fluid containing means by said first predetermined increment.
Claim 28
Dependent Claim 106 words
The robotic system according to claim 25, wherein said sensing means comprises means for sensing a force acting on said fluid drawing means, and wherein said means for determining whether said fluid drawing means is still in contact with said bottom of said fluid containing means further comprises: means for instructing said robot to sense an initial force acting on said fluid drawing means prior to said movement by said first predetermined increment; and means for determining if said force sensed differs from said initial force by more than a first predetermined value after said fluid drawing means has been moved by said first predetermined increment.

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USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1998-10-02 1999-04-03 1999-10-03 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 2002-10-02 2003-04-03 2003-10-03 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 2006-10-02 2007-04-03 2007-10-03 $7700.00 Window Closed / Lapsed

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