US20020007093A1 - Method for screening multiple reactants and catalyst systems using incremental flow reactor methodology - Google Patents
Method for screening multiple reactants and catalyst systems using incremental flow reactor methodology Download PDFInfo
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- US20020007093A1 US20020007093A1 US09/728,751 US72875100A US2002007093A1 US 20020007093 A1 US20020007093 A1 US 20020007093A1 US 72875100 A US72875100 A US 72875100A US 2002007093 A1 US2002007093 A1 US 2002007093A1
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- B01J4/00—Feed or outlet devices; Feed or outlet control devices
- B01J4/02—Feed or outlet devices; Feed or outlet control devices for feeding measured, i.e. prescribed quantities of reagents
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- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0006—Controlling or regulating processes
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- 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
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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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- 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
- B01J2219/00283—Reactor vessels with top opening
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- 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
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- 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
- B01J2219/00364—Pipettes
- B01J2219/00367—Pipettes capillary
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- 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
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- 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
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- B01J2219/00277—Apparatus
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- B01J2219/00414—Means for dispensing and evacuation of reagents using suction
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- 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
- B01J2219/00481—Means for mixing reactants or products in the reaction vessels by the use of moving stirrers within the reaction vessels
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- 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
- B01J2219/00497—Features relating to the solid phase supports
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- 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
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00596—Solid-phase processes
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- 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
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- 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
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- 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
- B01J2219/00718—Type of compounds synthesised
- B01J2219/0072—Organic compounds
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- 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
Definitions
- the present invention is generally directed to a method for the rapid screening of chemicals, catalysts, reactants, process conditions and the like. More specifically, the present invention is directed to the use of Incremental Flow Reactor (IFR) methodology on large arrays of miniaturized reactor vessels to identify potential reactants and catalyst systems for the bulk chemical industry.
- IFR Incremental Flow Reactor
- the present invention is directed to the use of IFR methodology on large arrays of miniaturized reactor vessels to produce chemical reactions that emulate those carried out in production-scale, continuous flow or continuous stirred tank reactors.
- IFR high throughput combinatorial screening of chemicals, catalysts, reactants, and associated process conditions is achieved.
- liquid and solid handling robotic equipment to implement the IFR on numerous reactor arrays is also described.
- the method includes the steps of providing a large array of reactor vessels and reactants; loading each reactor vessel with at least one reactant; and allowing the reactions to proceed for a predetermined time interval.
- a volume increment is withdrawn from each of the reactor vessels and a volume increment of at least one reactant is added to each reactor vessel in the array. The steps of volume increment withdrawal and addition are repeated after successive time intervals until the reactions reach a substantially steady state.
- volume increment withdrawal can take place before, after, or contemporaneously with the volume increment addition.
- FIG. 1 is a graphical representation of concentration gradients of various reactions
- FIG. 2 illustrates the IFR method as applied to a single reaction vial
- FIG. 3 is a graphical representation of the relationship among various reaction conditions
- FIG. 4 is a graphical representation of a reaction kinetics model comparing a continuous stirred tank reactor with an incremental flow reactor
- FIG. 6 illustrates the IFR method as applied to a 96-well micro-titre plate using an 8-probe liquid handling robot.
- the present invention is directed to the use of IFR on large arrays of miniature reactor vessels for the rapid combinatorial screening of chemicals, catalysts, reactants, and associated process conditions. Rapid combinatorial screening requires that a large number of reactions or catalyst systems be tested in parallel.
- the method of the present invention produces chemical reactions that emulate those carried out in production-scale, continuous flow or continuous stirred tank reactors, and provides useful information that may be dependent on flow rate and configuration (e.g., reaction yield; selectivity; and other reaction characteristics or process variables).
- flow rate and configuration e.g., reaction yield; selectivity; and other reaction characteristics or process variables.
- increments of liquid or solid flow are delivered to and removed from the arrays of reactor vessels at predetermined time intervals to mimic the continuous flow of reactor influents and effluents.
- the method is particularly useful for studying the formation of bisphenol A from phenol and acetone.
- substantially steady state refers to a point where the reaction effectively emulates a reaction of interest, such as those carried out in production-scale, continuous flow or continuous stirred tank reactors.
- reaction data are dependent on flow rate, residence time, or similar parameters. Utilizing the present method, these parameters can be manipulated in order to obtain useful data on a micro scale.
- the volume increment withdrawal can take place before, after, or contemporaneously with the volume increment addition.
- the preferred order will depend on the discrete circumstances of a given application. For example, when working with micro amounts, it may be preferable to add a volume increment before withdrawal in order to maintain favorable reaction conditions within the reaction vessel.
- the time increments are selected such that the withdrawals are made before the reactants present in the reactor vessels have had a chance to completely react, thereby ensuring substantially continuous reactivity within the reactor vessel.
- Each volume increment that is added contains at least one of the reactants.
- reactant means any substance that affects the reaction in any capacity, including catalysts, promoters, and the like.
- the relative amounts of each reactant in the volume increments can be determined based on the differential depletion, exhaustion, or inactivation of each species during the course of the reaction. It is also contemplated that multiple additions of various reactants and reactant combinations can be made. In one embodiment, the total volume of the multiple additions is equivalent to the volume increment withdrawn.
- volume increments that are withdrawn can be handled in a number of ways. For example, each volume increment withdrawn from the reactor vessel can be analyzed individually for properties of interest. Selected volume increments can be analyzed, while the non-analyzed volume increments are discarded. Alternatively, withdrawn volume increments can be pooled to provide cumulative data for the entire course of the reaction or for selected time periods of interest.
- automated liquid or solid robotic equipment is used to deliver and remove the volume increments from a large array of reactor vessels. Desired space velocity and reactor residence times can be obtained by controlling the size of the volume increments withdrawn and added and the size of the time intervals between volume increment additions. Unless otherwise noted, time intervals denote the period of time between successive volume additions.
- ⁇ t time interval
- ⁇ V volume increment
- V tot total liquid volume in the reaction vessel.
- ⁇ t and ⁇ V values The selection of optimal ⁇ t and ⁇ V values will depend on several factors, including reaction kinetics and the capabilities of the liquid-handling equipment. As shown in FIG. 1, a faster reaction will generally exhibit larger concentration gradients within a given time interval than a slower reaction. Preferably, for a given reaction system, the ⁇ t and ⁇ V values should be chosen to minimize the within-increment concentration gradients without placing excessive demands on liquid handling equipment.
- Volume sub-increments are then withdrawn at appropriate subintervals within the time interval, such that the sum of the volume sub-increments is equivalent to the sample volume increment. Analysis of the withdrawn sub-increments provides desired concentration gradient data. The reactions are allowed to continue until sub-interval concentration gradient information is again desired, at which point the steps for obtaining such information can be repeated.
- volume increment withdrawals are effected by inserting a probe to a predetermined level in the reactor vessels and withdrawing reactor fluid until no further fluid can be withdrawn.
- the probe acts as a liquid level controller, thereby ensuring that the liquid level in the reactor vessels will be the same at the end of each time interval.
- This embodiment reduces or eliminates the possibility of cumulative volume error related to the accuracy of incremental volume withdrawals and also compensates for error related to the accuracy of incremental volume additions. For example, if a slightly larger than desired volume increment is added at the beginning of a time interval, a similarly larger volume increment will be withdrawn at the end of that time interval since the volume increment removal is based on a liquid level control mechanism. Conversely, a smaller than desired volume increment addition would be compensated for by a smaller volume increment removal.
- the dihydric phenol 2,2-bis(p-hydroxyphenyl)propane (commonly referred to as “bisphenol-A”, “BPA” or “pp-BPA”) is commercially prepared by condensing 2 moles of phenol with a mole of acetone in the presence of an acid catalyst.
- the phenol is typically provided in molar excess of the stoichiometric requirement.
- Optional reaction promoters such as free mercaptans, can be added to aid the reaction.
- Common acid catalysts for the production of BPA include acidic ion exchange resins, such as sulfonic acid, substituted polystyrene, and the like.
- each vial or reaction well is loaded with the appropriate mixture of phenol:acetone feed 12 .
- the feed can contain optional promoter(s) and catalyst(s).
- Each vial is provided with resin beads 16 and an optional stir bar 18 .
- reaction is allowed to proceed in batch mode for one time interval, ⁇ t.
- a probe (not shown) withdraws one liquid volume increment, ⁇ V, of reaction mixture 14 from the vial (reactor effluent).
- the withdrawn volume increment is replaced with an equal volume increment, ⁇ V, of fresh feed 12 .
- Cycle time, ⁇ t is defined as the time period between successive volume increment additions. The incremental withdrawal and addition of reactants is continued until the reaction reaches a substantially steady state, and screening data are collected.
- the values of the time intervals and volume increments can be selected to obtain a desired space velocity.
- the relationship between the time intervals and volume increments is as follows:
- ⁇ t time interval
- ⁇ V volume increment
- ⁇ density of liquid feed
- R amount of resin
- FIG. 4 is a comparison of the IFR method and a traditional continuous stirred tank reactor (CSTR).
- CSTR continuous stirred tank reactor
- the IFR method was used on many arrays of miniaturized reactor vessels using liquid handling robotic equipment such as the Gilson Multiprobe 215 Liquid Handler (Middleton, Wis.). Experimental data was generated using the IFR methodology on two systems: 1) a single-probe liquid handling robot to operate a one-dimensional array of 12 IFRs (1 column ⁇ 12 rows); and 2) an 8-probe liquid-handling robot to operate a two-dimensional array of 96 IFRs (8 columns ⁇ 12 rows).
- the transfer lines are flexible tubes connecting the individual syringe pump heads to the liquid-handling probes. These lines contain a “system fluid.”
- a motor-driven syringe pulls a desired volume of system fluid through the transfer line which, therefore, draws the same volume of sample fluid into the probe.
- the motor-driven syringe pushes the desired volume of system fluid out through the transfer line, thereby displacing the sample fluid from the probe.
- the transfer lines must be kept warn (60° C.) in order to prevent “freezing” of the sample fluids in the probe.
- the transfer lines are, therefore, sheathed in an electrically-heated wrapping.
- Heat-traced rinse station to prevent freezing of phenol-containing rinsates.
- the probes can be rinsed with system fluid by lowering the 8 probes into a rinse station and flushing with system fluid.
- the system fluid is pumped out through the probes and then flushed out of the rinse station to a drain line.
- the rinse station is electrically heated to prevent freezing of phenol-containing rinsates.
- Heat-traced drain line to prevent freezing of phenol-containing rinsates in the line leading from the rinse station to the waste collection reservoir.
- 1 ⁇ 4′′ copper tubing was used for the drain line.
- the tubing was wrapped with commercially-available heat tape (electrical) to keep it warm.
- heating blocks were custom-built to keep the chemicals warm during the experiments.
- the heating blocks were mounted on the liquid-handling robot's deck. Each is described individually as follows:
- a) Heating block for stock solutions Stock solutions (containing reactants such as phenol, acetone, and promoter) were stored in 48-well deep-well micro-titre plates. These solutions were the “feeds” to the 96 reaction vials. The 48-well plates were clamped within an aluminum frame and bolted to an aluminum base. The base was heated with electrical cartridge heaters. Power to the electrical heaters was regulated by a temperature controller based on feedback from a thermocouple mounted in the aluminum base.
- a single-probe Gilson 215 liquid-handling robot was used to implement the IFR methodology on a limited number of reactor vessels, for example, a one-dimensional array of 12 IFRs.
- the robotic probe sequentially addressed each reactor in the array until the entire array was addressed.
- the robotic probe then returned to the first reactor in the array and repeated the process.
- the IFR methodology was implemented in several different ways.
- the robotic probe removed a liquid volume increment from the first reactor, and then immediately delivered an increment of fresh feed to the first reactor. This process was then repeated for the second reactor, then the third, and so on, until all reactors in the array had been addressed. The robotic probe then returned to the first reactor and repeated the process. In this manner, a single “time interval” of the IFR method was carried out each time the robotic probe cycled through the array of reactor vessels.
- the robotic probe removed a liquid volume increment from the first reactor, then removed a liquid volume increment from the second reactor, and so on, until liquid volume increments had been removed from all reactors in the array. Then, the robotic probe delivered an increment of fresh feed to the first reactor, then delivered an increment of fresh feed to the second reactor, and so on, until all reactors in the array had been addressed. In this manner, the robotic probe cycled through the array of reactor vessels twice in order to carry out a single “time interval” of the IFR method.
- IFR methodology can also be implemented as described in U.S. patent application Ser. No. 09/443,640, the reference being hereby incorporated by reference.
- large volume additions followed by sequential removals of smaller volume increments can be used to obtain reaction kinetic data at various points throughout the course of the reaction.
- two additions of different reactants can be followed by removal of single or multiple volume increments.
- single or multiple additions of multiple reactants can be followed by removal of single or multiple volume increments.
- the single-probe approach is not limited to the specific examples described herein.
- the IFR method can be applied to either one-dimensional or small two-dimensional arrays.
- the number of reactors that can be addressed with a single-probe robot is limited by the ability of the robot to deliver and remove liquid volume increments to all the reactors in the array at the desired time intervals.
- An eight-probe liquid-handling robot was used to conveniently implement the IFR methodology on a 96-reactor (8 ⁇ 12) array.
- the eight robotic probes aligned directly with the first row of eight reactors as shown in FIG. 5.
- the eight probes simultaneously addressed the eight reactors in the first row, and then moved on to the second row, and so on, until all rows in the array had been addressed.
- Any variation of the IFR methodology discussed above can also be implemented using the eight-probe liquid-handling robot.
- any type of liquid-handling robot which is fitted with any number of probes or tips can also be used to implement the IFR methodology on an array of reactor vessels.
- any robotic liquid-handling device which utilizes an array of probes or pipette tips that is geometrically identical to the array of miniature reactor vessels can be used to simultaneously implement the IFR methodology on all of the reactor vessels in the array.
- a commercially-available robotic liquid handling device equipped with 96 tips in a standard 8 ⁇ 12 array can be used to simultaneously address a 96-reactor array as shown in FIG. 6. Liquid volume increments can be simultaneously removed from all 96 reactors, and then liquid volume increments of fresh feed is simultaneously added to all 96 reactors.
- the IFR methodology may be applied to any type or geometric configuration of miniature reactor arrays. This includes: 1) micro-titre plates of any size, including 48 wells (8 ⁇ 6 array), 96 wells (8 ⁇ 12 array), 384 wells (15 ⁇ 24 array), 1536 wells (32 ⁇ 48 array), or any other number of wells; and 2) any array of glass (or metal or plastic or any other material) vials, tubes, bottles, cups, or any other suitable container.
- FIG. 6 illustrated the IFR method as applied to a 96-well micro-titre plate using an 8-probe liquid-handling robot. The robot simultaneously addresses 8 reaction wells in a single row, then moves to the next row, etc.
- the micro-titre plate has overall exterior dimensions of 31 ⁇ 4′′ ⁇ 5′′ ⁇ 23 ⁇ 4′′. Each well is capable of holding ⁇ 2 mL of liquid volume.
- each reaction well contained 50 mg of resin beads and 200 ⁇ L of phenol:acetone; the volume increments of fresh feed/sample were 30 ⁇ L.
- the system reservoir was topped-off with an appropriate solvent, which was either maintained at room temperature or heated using a heating mantle. 96 empty well microtitre plates were placed at the appropriate position on the liquid-handling robot's deck. These plates were used for sample collection.
- the probes were dipped into the first phenol reservoir to rinse the system fluid (and other contaminants) off the outside of the probes. The probes were then moved to the second phenol reservoir and a small volume of phenol was simultaneously loaded into each probe. The probes were pulled out of the phenol reservoir and an air gap was put into each probe. The probes were then moved to the stock block, and a (30 ⁇ L) aliquot of fresh feed was pulled into each probe. It should be noted that at this point, each probe was in a different well of the stock block, so different stock solutions can be loaded into the different probes.
- the probes were then moved to the first row of the reactor array, and the (30 ⁇ L) aliquots of fresh feed were delivered to the reactor wells.
- the probes were then moved to the rinse station, and a volume (250 ⁇ L) of system fluid was expressed through the probes to rinse out the phenol and feed solutions.
- the first step of the new cycle involved rinsing each probe in the first phenol reservoir to remove any system fluid and contaminants from the outside of the probe.
- the probes were then moved to the second phenol reservoir and a small volume of phenol was simultaneously loaded into each probe.
- the probes were pulled out of the phenol reservoir and an air gap was put into each probe.
- the probes were then moved to the first row of 8 reaction wells, and set at a pre-determined height above well bottom.
- the robot was then programmed to attempt to remove more than 30 ⁇ l (about 45 ⁇ L). This step serves as a level control and corrects for systematic differences between aspiration and dispensing volumes.
- sample plates were removed from the liquid-handler's deck and prepared for gas chromatographic analysis.
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Application Number | Priority Date | Filing Date | Title |
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US09/728,751 US20020007093A1 (en) | 1999-05-07 | 2000-12-04 | Method for screening multiple reactants and catalyst systems using incremental flow reactor methodology |
US10/233,720 US6693220B2 (en) | 1999-05-07 | 2002-09-04 | Method for screening multiple reactants and catalyst systems using incremental flow reactor methodology |
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US13306199P | 1999-05-07 | 1999-05-07 | |
US44364099A | 1999-11-18 | 1999-11-18 | |
US09/728,751 US20020007093A1 (en) | 1999-05-07 | 2000-12-04 | Method for screening multiple reactants and catalyst systems using incremental flow reactor methodology |
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US10/233,720 Continuation-In-Part US6693220B2 (en) | 1999-05-07 | 2002-09-04 | Method for screening multiple reactants and catalyst systems using incremental flow reactor methodology |
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EP (1) | EP1189691A1 (de) |
JP (1) | JP2002543962A (de) |
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US20030219363A1 (en) * | 2002-05-17 | 2003-11-27 | Kobylecki Ryszard J. | Examining chemical reactions |
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US9137745B2 (en) * | 2007-10-12 | 2015-09-15 | Qualcomm Incorporated | System and method to locate femto cells with passive assistance from a macro cellular wireless network |
IT201600092675A1 (it) * | 2016-09-14 | 2018-03-14 | Acel S R L | Impianto di produzione di monoclorammina per trattamento di fluidi |
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NZ215788A (en) * | 1985-04-12 | 1988-04-29 | Weston George Ltd | Continuous ethanol production by bacterial fermentation |
US5262575A (en) * | 1992-08-04 | 1993-11-16 | The Dow Chemical Company | Production of allylic chlorides |
DE69616232T2 (de) * | 1995-09-29 | 2002-06-27 | Gen Electric | Verfahren zur Herstellung von Bisphenol-Verbindungen mit gleichzeitiger Entwässerung |
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2000
- 2000-04-14 AU AU42403/00A patent/AU4240300A/en not_active Abandoned
- 2000-04-14 EP EP00922174A patent/EP1189691A1/de not_active Withdrawn
- 2000-04-14 JP JP2000616914A patent/JP2002543962A/ja not_active Withdrawn
- 2000-04-14 WO PCT/US2000/009988 patent/WO2000067895A1/en not_active Application Discontinuation
- 2000-12-04 US US09/728,751 patent/US20020007093A1/en not_active Abandoned
-
2002
- 2002-06-26 US US10/180,870 patent/US6710212B2/en not_active Expired - Fee Related
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20030219363A1 (en) * | 2002-05-17 | 2003-11-27 | Kobylecki Ryszard J. | Examining chemical reactions |
Also Published As
Publication number | Publication date |
---|---|
EP1189691A1 (de) | 2002-03-27 |
WO2000067895A1 (en) | 2000-11-16 |
US20030045758A1 (en) | 2003-03-06 |
US6710212B2 (en) | 2004-03-23 |
JP2002543962A (ja) | 2002-12-24 |
AU4240300A (en) | 2000-11-21 |
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