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WO1997014041A1 - Poste de lavage de bancs de reactions - Google Patents

Poste de lavage de bancs de reactions Download PDF

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Publication number
WO1997014041A1
WO1997014041A1 PCT/US1996/016099 US9616099W WO9714041A1 WO 1997014041 A1 WO1997014041 A1 WO 1997014041A1 US 9616099 W US9616099 W US 9616099W WO 9714041 A1 WO9714041 A1 WO 9714041A1
Authority
WO
WIPO (PCT)
Prior art keywords
reaction block
reaction
array
station
wash station
Prior art date
Application number
PCT/US1996/016099
Other languages
English (en)
Other versions
WO1997014041A9 (fr
Inventor
Romaine R. Maiefski
John Cargill
Original Assignee
Ontogen Corporation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ontogen Corporation filed Critical Ontogen Corporation
Priority to AU73958/96A priority Critical patent/AU7395896A/en
Publication of WO1997014041A1 publication Critical patent/WO1997014041A1/fr
Publication of WO1997014041A9 publication Critical patent/WO1997014041A9/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/04—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers
    • C07K1/045—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers using devices to improve synthesis, e.g. reactors, special vessels
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L13/00—Cleaning or rinsing apparatus
    • B01L13/02—Cleaning or rinsing apparatus for receptacle or instruments
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • B01L3/50853—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates with covers or lids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00279—Features relating to reactor vessels
    • B01J2219/00281—Individual reactor vessels
    • B01J2219/00286—Reactor vessels with top and bottom openings
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00279—Features relating to reactor vessels
    • B01J2219/00306—Reactor vessels in a multiple arrangement
    • B01J2219/00308—Reactor vessels in a multiple arrangement interchangeably mounted in racks or blocks
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00279—Features relating to reactor vessels
    • B01J2219/00306—Reactor vessels in a multiple arrangement
    • B01J2219/00308—Reactor vessels in a multiple arrangement interchangeably mounted in racks or blocks
    • B01J2219/0031—Reactor vessels in a multiple arrangement interchangeably mounted in racks or blocks the racks or blocks being mounted in stacked arrangements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00279—Features relating to reactor vessels
    • B01J2219/00306—Reactor vessels in a multiple arrangement
    • B01J2219/00313—Reactor vessels in a multiple arrangement the reactor vessels being formed by arrays of wells in blocks
    • B01J2219/00315—Microtiter plates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00279—Features relating to reactor vessels
    • B01J2219/00331—Details of the reactor vessels
    • B01J2219/00333—Closures attached to the reactor vessels
    • B01J2219/00335—Septa
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B01J2219/00373—Hollow needles
    • B01J2219/00376—Hollow needles in multiple or parallel arrangements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00479—Means for mixing reactants or products in the reaction vessels
    • B01J2219/00484—Means for mixing reactants or products in the reaction vessels by shaking, vibrating or oscillating of the reaction vessels
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00495—Means for heating or cooling the reaction vessels
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/0054—Means for coding or tagging the apparatus or the reagents
    • B01J2219/00542—Alphanumeric characters
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/0054—Means for coding or tagging the apparatus or the reagents
    • B01J2219/00547—Bar codes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/0068—Means for controlling the apparatus of the process
    • B01J2219/00686—Automatic
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/0068—Means for controlling the apparatus of the process
    • B01J2219/00686—Automatic
    • B01J2219/00691—Automatic using robots
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0829—Multi-well plates; Microtitration plates
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
    • C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B70/00—Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1065—Multiple transfer devices

Definitions

  • the present invention relates generally to methods and _ apparatus for the generation of chemical libraries of known
  • composition and more particularly to reaction block wash stations.
  • 1 _ molecules is a fundamental issue in the study of biological and other chemistry-based systems. Structure-function relationships are important in understanding, for example, the function of enzymes, cellular communication, and cellular control and feedback mechanisms. Certain macromolecules are known to interact and bind to other molecules having a specific three-dimensional spatial and electronic distribution. Any macromolecuie having such specificity can be considered a receptor, whether the macromolecuie is an enzyme, a protein, a glycoprotein, an antibody, an oligonucleotide sequence of DNA,
  • ligands The various molecules to which receptors bind are known as ligands.
  • an automated combinatorial chemical library synthesizer is the Model 396 MPS fully automated multiple peptide synthesizer, manufactured by Advanced ChemTech, Inc. ("ACT") of Louisville, KY.
  • ACT Advanced ChemTech, Inc.
  • Another example of an automated combinatorial chemical library- synthesizer is described in application serial no. 08/422,809, entitled “METHODS AND APPARATUS FOR THE GENERATION OF CHEMICAL LIBRARIES,” filed April 17, 1995, assigned to the assignee of the present invention and incorporated herein by reference.
  • each growing polymer chain usually contains the same number of monomers at the end of each
  • the process of combinatorial synthesis not only requires the introduction of a series of reagents including the desired monomers, but also requires washing, deblocking, capping, oxidation and other steps as well. These steps must be performed regardless of the sequence in which the various monomers are introduced into the reaction chambers.
  • the preferred embodiments meet these needs by providing a multiple pipetting needle wash station which can introduce an appropriate reagent or solvent into all reaction chambers of a 5 reaction block simultaneously.
  • the wash station may also include a vortexing docking station which provides for secure registration of the reaction blocks, and provides for introduction of gases and liquids into the reaction blocks .
  • An 1 - inert atmosphere in the reaction block can be maintained by a top and (optional) bottom seal.
  • Figure 1 is a plan view of a pipetting work station.
  • Figure 2 is an isometric view of a reaction block and its associated hardware according to a preferred embodiment.
  • Figure 3 is a top view of the reaction block shown in Figure 2.
  • Figure 4 is a side cross-sectional view of the reaction - - block shown in Figure 2.
  • Figure 5 is a side cross-sectional view of the reaction block shown in Figure 2 including a removable bottom seal.
  • Figure 6 is a side cross-sectional view of the reaction block shown in Figure 2 including a microtiter plate.
  • Figure 7 is a bottom view of the reaction block shown in Figure 2.
  • Figure 8 is a bottom plan view of the reaction block shown in Figure 2.
  • Figure 9 is a top view of a docking station according to _- a preferred embodiment.
  • Figure 10 is a cross sectional view of a connector in the docking station shown in Figure 9, inserted into a port in the reaction block shown in Figure 2.
  • Figure 11 is a cross sectional view of a connector in __ the docking station shown in Figure 9, inserted into a port having an open valve in the reaction block shown in Figure 2.
  • Figure 12 is a cross sectional view of a connector in the docking station shown in Figure 9, inserted into a port having a closed valve in the reaction block shown in Figure 2.
  • Figure 13 is a plan view of a reaction block wash station according to a preferred embodiment.
  • Figure 14 is a top cross sectional view of the reaction block wash station shown in Figure 13.
  • Figure 15 is a cross sectional view showing a portion of a needle array including a needle manifold assembly as used in the reaction block wash station shown in Figure 13.
  • - Figure 16 is a side view of the reaction block wash station shown in Figure 13, showing the needle arrays above the arrays of rinse tubes.
  • Figure 17 is a side view of the reaction block wash station shown in Figure 13, showing the needle arrays above , _ the reaction blocks.
  • Figure i ⁇ is a front view of the reaction block wash station shown in Figure 13, showing a portion of a needle array inserted into a reaction block.
  • Figure 19 is a front view of the reaction block wash -_ station shown in Figure 13, showing a portion of a needle array inserted into a rinse tube array.
  • Figure 20 is a schematic diagram showing some of the wiring and plumbing connections used in the reaction block wash station shown in Figure 13.
  • Figure 1 is a plan view showing a portion of an automated pipetting work station 250 as may be used in a preferred
  • Automated pipetting work station 250 may be a TECAN 5032 automated pipetting work station with one or more pipetting arms 252.
  • Pipetting arm 252 attaches to needle assembly 20, which may be a coaxial needle assembly of the type disclosed in application serial no. 08/423,142 entitled
  • Coaxial needle assembly 20 includes a needle 22, a gas inlet port 30, and may also include an electrical connection 31.
  • Work station 250 may also include pipetting needle rinse stations 70, which may be of the type disclosed in application
  • a locking reagent container rack 90 holds several containers 44 of reagents sealed from the outside air with _ septum seals 46.
  • Rack 90 is preferably placed on the left J * .5 side of work station deck 254.
  • On the right side of work station deck 254 is a docking station 300 for receiving two reaction blocks 140.
  • Each reaction block 140 contains an array of 48 reaction chambers 110 (see, e.g., Figure 2) .
  • a _ standard 96 well microtiter plate 302 may be mounted below reaction block 140 if product is to be removed from reaction chambers 110.
  • Reaction block 140 (and its associated hardware) according to a preferred embodiment is shown.
  • Reaction block 140 is preferably machined out of 6061 aluminum (which is easily machinable and has good corrosion resistance) and then anodized for additional corrosion protection.
  • Reaction block 140 could be
  • reaction block 140 could be machined or molded from any suitable metal, engineering plastics, filled plastics, crystalline plastics, ceramics, machinable ceramics, or any other material that can withstand the temperature, pressure,
  • reaction block 140 5 and chemical environment to which reaction block 140 will be exposed. If non-metallic materials are used, product reaction could be enhanced by the application of microwaves. If materials transparent to ultraviolet (UV) light are used, product could be cleaved from the synthesis support using UV light, and without the application of an acid or base.
  • UV ultraviolet
  • reaction block 140 is preferably fitted with _ two pins 178 to facilitate handling by a robotic gripper (not shown) .
  • Each side of reaction block 140 is preferably fitted with one pin 180 to facilitate securing reaction block 140 onto docking station 300.
  • Robotic manipulation of reaction block 140 makes automation of the entire synthesis process
  • reaction block 140 could be introduced into reaction chambers 110 when reaction block 140 is locked onto docking station 300 of pipetting work station 250. Reaction block 140 could then be moved to a separate docking station 300, reaction block wash station 400 (see Figures 13 - 20) ,
  • reaction blocks capable of mating directly with a 96 well microtiter plate are
  • the 48 reaction chamber 110 (and drain tube 138) positions of a first type of (or "A") block are offset from the 48 reaction chamber and drain tube positions of a second type of (or "B") block such that a type "A” and a type "B” block can fill every position in a standard 96 well microtiter plate.
  • Reaction block 140 may be color coded for ease of identification, may have identification numbers 320 machined
  • Top portion 142 of reaction block 140 is shown.
  • Top portion 142 preferably has an array of circular openings 144 arranged in a staggered grid.
  • reaction block 140 has 48 circular openings 144. Openings 144 also preferably include a keying notch 145 (see Figure 2) which cooperates with a keying protrusion (not shown) on reaction chamber 110 and requires reaction chamber 110 to be in a predetermined orientation when inserted into opening 144.
  • the 48 openings 144 are divided into four chambers 14 A through 146D of twelve openings 144 each.
  • the chambers 146A- D are separated from each other by a plurality of raised beads 148, which are preferably machined into top portion 142.
  • Top portion 142 also includes four gas inlet ports 150A through 150D. Gas flows from gas inlet ports 150A-D, into
  • chambers 146A and 146C can be pressurized, without pressurizing chambers 146B and 146D.
  • reaction chambers 110 When reaction chambers 110 are inserted and locked into place in openings 144, the top portions 120 of reaction chambers 110 are in approximately the same plane as the tops
  • septum 153 is preferably manufactured from 1/10" thermoplastic rubber (TPR) sheet. Septum 153 is
  • a septum retainer plate 155 which is preferably fastened with six captive screw-type fasteners 156 which attach to openings 157. Fasteners 156 pass through openings 159 in septum 153, and screw into machined fastener openings 158.
  • -_ Reaction block 140 may be sealed from underneath with a bottom seal 220.
  • An o-ring or quad ring 221 (see Figure 5) may be used to ensure a gas-tight seal.
  • Bottom seal 220 may include a one-way valve 222 to allow pressure regulation. Bottom seal 220 is preferably fitted to reaction block 140
  • __with screw-type fasteners 224 As can be seen in Figure 2, fasteners 224 pass through openings 226 in plate 155, through openings 228 in septum 153, through openings 230 in reaction block 140, and into openings 232 in bottom seal 220. Bottom seal 220 permits a desired atmosphere or pressure to be maintained within reaction block 140, allowing reaction block 140 to be moved from location to location (such as to a _ separate reaction block wash station 400, to a shaker table, heating or cooling chamber, or any other location or device useful in the synthesis or collection of material) without loss of such atmosphere or pressure. This can be especially useful in chemistries requiring long periods of time for reactions to
  • septum retainer plate 155 is machined from 6061 aluminum and anodized.
  • . _ plate 155 could also be machined or molded from engineering plastics, ceramics, or any other material that can withstand the temperature, pressure, and chemical environment to which retainer plate 155 will be exposed.
  • Plate 155 is also preferably machined with 48 openings
  • Chambers 146 A through D include recessed waste basins
  • reaction block 140 is shown. Reaction chambers 110 are held in place by machined annular steps 170 (which define openings 171) , and machined annular beads 172. S-shaped trap tube 136 and drain tube 138 are held in place by a friction fit against walls 174 and openings 176 (See Figures 7 and 8) .
  • Steps 177 are machined into the bottom of reaction block 140 to allow reaction block 140 to mate directly with a standard 96-well microtiter plate 302 (see, e.g., Figures 1 and 6) . Steps 177 also allow mating and sealing with bottom seal 220 (see Figures 2 and 5) .
  • reaction block 140 The underside of reaction block 140 includes a generally planar surface 190 which includes a plurality of openings 171 and 176, discussed above.
  • Openings 176 include a relatively larger portion 192, which accommodates drain tube 138, and a relatively smaller portion 194, which accommodates s-shaped trap tube 136.
  • reaction block 140 also includes four gas ports 196A through 196D located on bottom surface 198. Ports 196A-D connect to gas inlet ports 150A-D (See Figure 3) , respectively, through machined tunnels (not shown) in reaction block 140.
  • bottom surface 198 Also included on bottom surface 198 is a gas inlet port 200 which connects to a gas outlet port 201 via a machined tunnel (not shown) . This allows pressure on the underside of reaction block 140 to be independently controlled when it is sealed by bottom seal 220 (see Figures 2 and 5) .
  • Bottom surface 198 also includes two gas or liquid ports 202A and 202B.
  • the interior of reaction block 140 is preferably machined to include passages (not shown) in which heating or cooling gas or liquid can flow if desired. Gas or liquid can enter port 202A and exit through port 202B, or vice
  • reaction block 140 is made of material having high thermal stability or thermal mass such as 6061 aluminum, this arrangement allows reaction block 140 to be quickly and efficiently heated or cooled for chemistries that require such heating or cooling.
  • Ports 196A-D, 200 and 202 may also serve as guide pin holes to position reaction block 140 properly on docking station 300 (see, e.g., Figures i ⁇ g anc j 13) .
  • a bar magnet 204 may be mounted flush with surface 198. Bar magnet 204 serves to activate magnetic reed
  • -_ switch 314 mounted in docking station 300 (see Figure 9) .
  • one or more reed switches can be used to prevent the operation of work station 250 or reaction block wash station 400 (see Figures 13 - 20) unless one or more reaction blocks 140 are properly in place.
  • Docking station 300 preferably includes two stations, 306A and 306B, for receiving reaction blocks 140 of Type "A” and Type “B", respectively, as discussed above. As is known to those skilled in the art, docking station 300 may also be fitted with the
  • Docking station 300 also preferably includes three _ locking linkages 304 for locking onto pins 180 on reaction blocks 140.
  • Each station 306 includes gas outlet connectors 308A through 308D which connect to ports 196A through 196D, respectively in reaction block 140 (see Figure 7) .
  • Each station 306 also includes two coolant or heating fluid (i.e.,
  • FIG. 1 shows fluid lines 320A and 320B attached to connectors 310A and 310B, respectively. Although not shown in Figures 1, 9, and 13, controllable fluid lines attach to each connector shown in docking station 300. Connectors 310A and 310B connect to
  • a gas outlet connector 312 which connects to gas inlet port 200 of reaction block 140 is also included in each station 306.
  • stations 306A and 306B each include a magnetic
  • Station 306A and more specifically the placement of connectors 312, 310A, and 310B, is arranged such that only an A-type reaction block 140 can be fully inserted and locked into position.
  • station 306B and more specifically the placement of port 312, is arranged such that only a B-type reaction block 140 can be fully inserted and locked into position.
  • FIG 10 a cross sectional view of a connector 308A inserted into port 196A of reaction block 140 is shown. Although only the interface between connector 308A and 196A will be discussed, it will be understood that similar interfaces are preferably included in other connections between reaction block 140 and docking station 300.
  • connector 308A is inserted into port 196A. In this fashion, connector 308A acts as a guide pin to ensure proper alignment of reaction block 140 with station 306A.
  • a gas-tight seal between connector 308A and port 196A is preferably provided by quad ring 330.
  • a quad ring is preferred over a standard o-ring because a quad ring has less tendency to adhere to surfaces when connector 308A is removed from port 196A.
  • port 196A an alternative embodiment of port 196A is shown.
  • a normally closed valve such as schraeder valve 360 may be placed in port 196A.
  • Schraeder valve 360 may be replaced with a bi-directional
  • connector 308A is inserted into port 196A and engages pin 362 of schraeder valve 360.
  • Connector 308A also forms a seal against quad ring 330. Gas flows out of opening 364 and through schraeder valve 360.
  • reaction block 140 moves downward, creating a gas-tight seal. Again, this allows reaction block 140 to be moved from place to place while maintaining a desired atmosphere.
  • Pipetting work station 250 (see Figure 1) and reaction block wash station 400 (see Figure 13) are preferably
  • Wash station 400 includes a docking station 300 of the type discussed above in part with respect to Figures 1 and 9. Docking station 300 is _ preferably adapted to receive a type A reaction block 140A and a type B reaction 140B. Docking station 300 is mounted on platform 402, along with a first array of 404A of rinse tubes and a second array 404B of rinse tubes.
  • Wash station 400 also includes an assembly 406 which . preferably includes an array 408A of 48 non-coring luer lock needles and a second array 408B of 48 non-coring luer lock needles (see, e.g., Figure 16) .
  • Assembly 406 is slidably mounted to wash station 400 along slot 410 in wall 412, and may also be slidably mounted in a slot (not shown) in wall
  • Assembly 406 (and thus arrays 408A and 408B) is movable along the X axis so that arrays 408A and 408B may be positioned over reaction blocks 140A and 140B or over rinse tube arrays 404A and 404B.
  • Arrays 408A and 408B are also movable up and down along the Z axis so that they may be raised
  • the motion of assembly 406 and needle arrays 408A and 408B may be achieved using any means known to those skilled in the art.
  • needle arrays 408A and 408B are preferably moved up and down along the Z axis through the use
  • Assembly 406 is preferably moved side to side along the X axis using an air pressure or hydraulic cylinder 451 (see Figure 20) .
  • Cylinder 451 is preferably a band cylinder of the type manufactured by the Tol-o-Matic Corporation of Minneapolis,
  • a band cylinder is preferred because it can provide a large linear motion relative to its overall length.
  • assembly 406 could be moved along the X axis by a stepper motor or a servo controlled motor.
  • a stepper motor or a servo controlled motor would require a much more complex
  • a hardware interlock including a "light curtain" which passes around the periphery of platform 402 can be used.
  • a light curtain operates in a manor well known to those skilled in the art.
  • a light source 416 generates a light beam 418 which is reflected
  • Reflected light beam 418 is then detected by a detector 422. If the light curtain is interrupted, the wash station ceases to function until reset by the operator. This reset operation is preferably performed when the operator presses a reset button (not shown) .
  • the hardware interlock may also include a manually operated emergency stop button (not shown) , which also causes the wash station to cease functioning until reset by the
  • Wash station 400 preferably also includes four servo motor controlled pumps 424 and eight solenoid valves 425 (see Figure 20) to deliver metered amounts of one of four solvents
  • Needle arrays 408A and 408B can be individually controlled. This function will be discussed further below.
  • the solvent reservoirs are preferably stainless steel
  • __ tanks (not shown) which are pressurized with helium.
  • Undesirable gasses dissolved in the solvents are removed by sparging the solvents with helium gas. After the undesirable gasses have been vented, the solvents remain pressurized with helium, preferably to a pressure of about 5 psig. This
  • each distribution _ manifold 432 includes 48 non-coring luer lock needles 426. Needles 426 are attached to luer connectors 428 which are mounted in wall 430. Needles 426 receive fluid (i.e., either liquid or gas) from distribution manifold 432 via tubes 434. Distribution manifold 432 includes a cavity 436 which is communication with each tube 434. In a preferred embodiment, each distribution _ manifold 432 includes four solvent inlet ports 438 (only two are shown in Figure 13) which are in communication with cavity 436 via one way valves 440. Inlet ports 438 are driven by pumps 424 (see Figure 14) .
  • Each distribution manifold 432 preferably also includes a . - nitrogen inlet line 442, which is in communication with cavity 436 via one way valve 444. This allows nitrogen to pass through or purge needles 426 if desired.
  • Figure 16 is a partial side view of wash station 400 showing assembly 406 and needle arrays 408A and 408B .-positioned over rinse tube arrays 404A and 404B. Needles 426 in needle arrays 408A and 408B may be washed by lowering the needles 426 along the Z axis into rinse tubes 446 of rinse tube arrays 404A and 404B. Rinse tubes 446 are preferably closed at the bottom and have an open lip at the top. When -- cleaning solution is pumped through needles 426, the solution flows into rinse tubes 446 and then out the top of rinse tubes 446 into a waste receptacle (not shown) .
  • Figure 17 is a side view of wash station 400 showing assembly 406 and needle arrays 408A and 408B positioned over _ -. __> reaction blocks 104A and 104B.
  • needle assemblies 408A and 408B are lowered along the Z axis until the needles 426 enter the reaction chambers within reaction blocks 1 0A and 140B. At that time, the desired solvent may
  • Needle arrays 408A and 408B are then removed from reaction blocks 140A and 140B.
  • docking station 300 can be made to
  • reaction blocks 140A and 140B to be agitated, if that is desired for the particular reaction step being performed.
  • the needle arrays 408A and 408B must be at a sufficient elevation before the reaction blocks 140 are vortexed to prevent bending of the needles.
  • a hardware interlock (not shown) may be used to prevent vortexing while the needles are within the reaction _ blocks.
  • Figure 18 is a front view of wash station 400 showing needle array 408B inserted into reaction block 140B, as discussed above.
  • Figure 19 is a front view of wash station 400 showing
  • Figure 20 is a wiring and plumbing schematic of wash station 400 according to a preferred embodiment. As discussed above, four solvent pumps 424 and eight solenoid valves 425
  • Nitrogen line 442 feeds manifold assemblies 432.
  • Nitrogen lines 452A and 452B feed stations 306A and 306B.
  • Programmable shaker motor 448 is used when docking station 300 acts as a vortexing shaker table.
  • Z axis motor 450 is used to move needle arrays 408A
  • Cylinder 451 is used to move needle arrays 408A and 408B along the X axis .
  • Wash station 400 is preferably computer controlled. In a preferred embodiment, the operator will be able to program "wash profiles" for various purposes. Each wash profile can
  • a synthesis support such as solid phase resin is deposited onto each frit 124 in reaction chambers 110.
  • Reaction block 140 is then assembled as shown in Figure 2.
  • Bottom seal 220 may be mounted if reaction block 140 must be moved from place to place while maintaining a desired atmosphere or pressure.
  • Reaction block 140 may then be manually or robotically inserted into station 306A of docking station 300 on work station 250 (see Figure 1) . At this point, microtiter plate 302 is not located in station 306A. Locking linkages 304
  • a type "B" reaction block may be simultaneously mounted in station 306B.
  • Pipetting work station 250 then operates under computer control to deliver the chosen combination of reagents into . reaction chambers 110.
  • pipetting needle 22 (as controlled by pipetting arm 252) is used to transfer reagents from septum 46 sealed containers 44 into septum 253 sealed reaction chambers 110.
  • the interior and exterior of pipetting needle 22 may be cleaned as necessary in rinse stations 70.
  • reaction block 140 is mounted in station
  • reaction block 140 may be heated or cooled, pressurized with inert gas, or vortexed as described above.
  • reaction block 140 For reactions that take a considerable amount of time or that require common reagents, reaction block 140 may be
  • _ _ be cleaved from the synthesis supports using the appropriate reagents. These reagents may be applied at work station 250, or they may be applied robotically at some other location such as wash station 400. If bottom seal 220 had been mounted, it is then removed, and a microtiter plate 302 is then inserted beneath reaction block 140 in station 306A. Reaction chambers
  • Microtiter plate 302 is then moved to station 306B, and inserted beneath a type "B" reaction block 140. Product is then deposited into the alternate empty wells of microtiter plate 302 as discussed above. Again, this process allows 0 product to be deposited directly into the wells of a standard microtiter plate, without requiring an intermediate step.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Clinical Laboratory Science (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Hematology (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)

Abstract

La présente invention concerne un poste de lavage (400) de bancs de réactions. Un bloc d'aiguilles de pipettage (408A, 408B) permet d'introduire en une seule opération un réactif ou un solvant approprié dans l'ensemble des chambres de réactions d'un tel banc de réactions (140A, 140B). Le poste de lavage (400) peut également comporter un bloc d'accueil (300) générateur de vortex, assurant le calage précis des bancs de réactions (140A, 140B) et assurant l'introduction de gaz et de liquides dans les bancs de réactions (140A, 140B). Ce poste de lavage (400) de bancs de réactions peut être piloté par un ordinateur.
PCT/US1996/016099 1995-10-13 1996-10-07 Poste de lavage de bancs de reactions WO1997014041A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU73958/96A AU7395896A (en) 1995-10-13 1996-10-07 Reaction block wash station

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US54298195A 1995-10-13 1995-10-13
US08/542,981 1995-10-13

Publications (2)

Publication Number Publication Date
WO1997014041A1 true WO1997014041A1 (fr) 1997-04-17
WO1997014041A9 WO1997014041A9 (fr) 1997-10-16

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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998040159A2 (fr) * 1997-03-10 1998-09-17 Trega Biosciences, Inc. Procede et dispositif de synthese chimique combinatoire
US5976470A (en) * 1998-05-29 1999-11-02 Ontogen Corporation Sample wash station assembly
US6126904A (en) * 1997-03-07 2000-10-03 Argonaut Technologies, Inc. Apparatus and methods for the preparation of chemical compounds
US6395235B1 (en) 1998-08-21 2002-05-28 Argonaut Technologies, Inc. Devices and methods for accessing reaction vessels
EP1681570A3 (fr) * 2003-06-19 2006-08-02 Abbott Laboratories Appareil et procédé de manipulation de fluides pour analyse
US7115234B2 (en) 1998-12-04 2006-10-03 Symyx Technologies, Inc. Parallel semi-continuous or continuous reactor system
US7815866B2 (en) 2003-06-19 2010-10-19 Abbott Laboratories, Inc. Apparatus and method for handling fluids for analysis
EP2687856A3 (fr) * 2012-07-20 2015-05-06 Medicatec Inc. Dispositif de rinçage de microplaque
WO2019109020A1 (fr) 2017-11-30 2019-06-06 Leica Biosystems Imaging, Inc. Rideau de lumière de sécurité pour désactiver une rotation de carrousel

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US4931402A (en) * 1986-03-06 1990-06-05 Tecan Ag Analytische Instrumente Photometric analysis equipment
US4952518A (en) * 1984-10-01 1990-08-28 Cetus Corporation Automated assay machine and assay tray
US5114681A (en) * 1990-03-09 1992-05-19 Biomedical Research And Development Laboratories, Inc. Superfusion apparatus
US5306510A (en) * 1988-01-14 1994-04-26 Cyberlab, Inc. Automated pipetting system

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US4952518A (en) * 1984-10-01 1990-08-28 Cetus Corporation Automated assay machine and assay tray
US4830832A (en) * 1985-12-17 1989-05-16 Hamilton Bonaduz Ag Pipette and pipetting apparatus
US4931402A (en) * 1986-03-06 1990-06-05 Tecan Ag Analytische Instrumente Photometric analysis equipment
US5306510A (en) * 1988-01-14 1994-04-26 Cyberlab, Inc. Automated pipetting system
US5114681A (en) * 1990-03-09 1992-05-19 Biomedical Research And Development Laboratories, Inc. Superfusion apparatus

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6126904A (en) * 1997-03-07 2000-10-03 Argonaut Technologies, Inc. Apparatus and methods for the preparation of chemical compounds
WO1998040159A2 (fr) * 1997-03-10 1998-09-17 Trega Biosciences, Inc. Procede et dispositif de synthese chimique combinatoire
WO1998040159A3 (fr) * 1997-03-10 1999-01-07 Trega Biosciences Inc Procede et dispositif de synthese chimique combinatoire
US6045755A (en) * 1997-03-10 2000-04-04 Trega Biosciences,, Inc. Apparatus and method for combinatorial chemistry synthesis
US5976470A (en) * 1998-05-29 1999-11-02 Ontogen Corporation Sample wash station assembly
US6416718B1 (en) 1998-05-29 2002-07-09 Ontogen Corporation Sample wash station assembly
US6395235B1 (en) 1998-08-21 2002-05-28 Argonaut Technologies, Inc. Devices and methods for accessing reaction vessels
US7115234B2 (en) 1998-12-04 2006-10-03 Symyx Technologies, Inc. Parallel semi-continuous or continuous reactor system
EP1681570A3 (fr) * 2003-06-19 2006-08-02 Abbott Laboratories Appareil et procédé de manipulation de fluides pour analyse
US7815866B2 (en) 2003-06-19 2010-10-19 Abbott Laboratories, Inc. Apparatus and method for handling fluids for analysis
US8357543B2 (en) 2003-06-19 2013-01-22 Abbott Laboratories Apparatus and method for handling fluids for analysis
US8409528B2 (en) 2003-06-19 2013-04-02 Abbott Laboratories Apparatus and method for handling fluids for analysis
EP2687856A3 (fr) * 2012-07-20 2015-05-06 Medicatec Inc. Dispositif de rinçage de microplaque
US9517497B2 (en) 2012-07-20 2016-12-13 Medicatec Inc. Rinsing device for microplate
WO2019109020A1 (fr) 2017-11-30 2019-06-06 Leica Biosystems Imaging, Inc. Rideau de lumière de sécurité pour désactiver une rotation de carrousel
CN111279199A (zh) * 2017-11-30 2020-06-12 徕卡生物系统成像股份有限公司 用于禁用转盘旋转的安全光幕
EP3625570A4 (fr) * 2017-11-30 2021-06-09 Leica Biosystems Imaging, Inc. Rideau de lumière de sécurité pour désactiver une rotation de carrousel
US11519925B2 (en) 2017-11-30 2022-12-06 Leica Biosystems Imaging, Inc. Safety light curtain to disable carousel rotation
CN111279199B (zh) * 2017-11-30 2023-12-12 徕卡生物系统成像股份有限公司 用于禁用转盘旋转的安全光幕

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