WO2001090721A1 - Procede et dispositif pour reguler l'echange de matiere entre un echantillon et l'atmosphere entourant l'echantillon - Google Patents

Procede et dispositif pour reguler l'echange de matiere entre un echantillon et l'atmosphere entourant l'echantillon Download PDF

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Publication number
WO2001090721A1
WO2001090721A1 PCT/EP2001/005903 EP0105903W WO0190721A1 WO 2001090721 A1 WO2001090721 A1 WO 2001090721A1 EP 0105903 W EP0105903 W EP 0105903W WO 0190721 A1 WO0190721 A1 WO 0190721A1
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WIPO (PCT)
Prior art keywords
sample
substance
atmosphere
determined
volume
Prior art date
Application number
PCT/EP2001/005903
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German (de)
English (en)
Inventor
Ralph Müller
Original Assignee
Basf-Lynx Bioscience Ag
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 Basf-Lynx Bioscience Ag filed Critical Basf-Lynx Bioscience Ag
Priority to AU2001283821A priority Critical patent/AU2001283821A1/en
Publication of WO2001090721A1 publication Critical patent/WO2001090721A1/fr

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • G01N1/4077—Concentrating samples by other techniques involving separation of suspended solids
    • 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
    • B01L3/50851—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 specially adapted for heating or cooling samples
    • 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
    • G01N2035/00346—Heating or cooling arrangements
    • G01N2035/00455—Controlling humidity in analyser
    • 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
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/028—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having reaction cells in the form of microtitration plates

Definitions

  • So-called genome expression profile analyzes are carried out to elucidate the molecular effects of potential drugs. An attempt is made to determine the genes actually expressed in a cell, since the associated proteins influence the development of the cell. One way to determine the proteins actually present is to determine the mRNA synthesized in the cell, since the proteins are formed from them.
  • isolated cells are disrupted.
  • the mRNA is isolated from the cells by suitable purification steps. Then it is usually translated into cDNA using the reverse transcriptase. This is usually amplified using linear PCR.
  • the cDNA is usually labeled radioactively or with dyes.
  • the cDNA obtained in this way is then z.
  • the wells are small wells with a volume per well of, for example, 20 ⁇ l.
  • Each well contains a known, specially synthesized DNA fragment.
  • the construction of a complete DNA array takes a few hours to a few days and is usually carried out in a closed chamber.
  • the pipetted DNA fragments are then immobilized on the slide, be it by a covalent crosslinking reaction or by simple adsorption.
  • the sample to be examined is then placed on the slide or the DNA array.
  • the sample contains radioactive or DNA-labeled DNA or RNA molecules.
  • the hybridization is awaited in a special hybridization chamber at a suitable temperature. Unhybridized DNA or RNA from the sample to be examined ⁇ is removed by rinsing. Hybridized DNA or RNA molecules are detected in a reader. Difficulties are encountered in the rapid evaporation of the solvents from the small volumes of the wells, which leads to a shift in concentration and thus a change in reaction conditions. During the pipetting process, some of the solvent can evaporate completely. DNA arrays with well-defined properties cannot be built in this way.
  • evaporation can be counteracted by cooling the microplate or nanotiter plate.
  • a low temperature of the microplate or nanotiter plate leads to condensation on the microplate or nanotiter plate. This causes liquid to enter the wells and the concentration of the solutions in the wells changes.
  • the reaction conditions for the construction of the DNA arrays change in an uncontrolled manner. With stronger condensation, it can even overflow Wells come, which means that the solutions in the individual wells sometimes mix. A DNA array can no longer be reliably built under these conditions.
  • WO 99/39829 describes a method for solving these problems by cooling the sample to the dew point of the vapor of the solvent in the surrounding atmosphere. Then there is hardly any evaporation or condensation.
  • the object of the invention is to control the mass transfer between a sample and the atmosphere surrounding the sample.
  • the sample can be a solution, e.g. B. DNA molecules in an aqueous buffer solution. It can also be any other solution.
  • the sample can be a solid, e.g. B. ice or PVC, the substance can exchange with the environment via sublimation.
  • the sample can also be a solid with particles distributed therein. H. dissolved substances and with its associated vapor pressure.
  • the substance that is exchanged is usually a solvent, such as water, aqueous buffer solution, alcohol or the like, with the associated vapor pressure.
  • a solvent such as water, aqueous buffer solution, alcohol or the like
  • evaporation There is a continuous exchange between the sample and the substance or its vapor by means of evaporation and condensation.
  • the concentration of steam in the surrounding atmosphere i.e. the partial pressure of the steam can be at most equal to the saturated steam pressure at the respective temperature. If the partial pressure exceeds the saturation vapor pressure, the excess is removed by condensation. This can occur, for example, on the sample if the temperature of the sample is so low that the saturation vapor pressure associated with the low sample temperature is below the instantaneous partial pressure of the vapor in the warmer atmosphere surrounding the sample. In such a situation, condensation occurs on the sample.
  • the temperature of the sample and the partial pressure of the steam above the sample are decisive for the question of whether evaporation or condensation occurs on the sample.
  • the temperature of the sample must be based on the dew point of the steam in the atmosphere surrounding the sample.
  • the dew point of the steam is the temperature at which the partial pressure of the steam is equal to the saturation steam pressure. If the temperature of the sample is above the dew point, effective evaporation occurs; if it is below this, condensation occurs.
  • the dew point can e.g. B. can be determined with a dew point hygrometer.
  • the dew point of the steam can also be determined by measuring the temperature of the surrounding atmosphere and the vapor pressure of the substance in the surrounding atmosphere. The dew point can be calculated from these two variables.
  • the vapor pressure can also be measured as a relative vapor pressure, for example as a relative humidity, ie as a percentage of the saturation vapor pressure.
  • the relative humidity can be measured, for example, with a hygrometer or other relative or absolute humidity sensors.
  • the (absolute) saturation vapor pressure of the substance in the atmosphere results from the temperature.
  • the partial pressure of the vapor results from the saturation vapor pressure of the substance and the relative vapor pressure. From this in turn, the dew point is obtained via suitable reference values. This can, for. B. are at 8 ° C.
  • the solvent vapor is decisive for determining the vapor pressure in the surrounding atmosphere.
  • the volume of the sample and / or the concentration of the dissolved substance and / or the amount of the substance dissolved in the sample is determined directly or indirectly.
  • weight loss can be determined. If parts of the sample are not taken, this can usually only be attributed to evaporation. In such a case, the temperature of the sample is above the dew point. If weight gain is observed, usually only condensation can take place. The temperature of the sample is then below the dew point.
  • the determination of volume, weight or concentration thus offers a further possibility of determining the dew point, namely as the temperature at which the volume, weight or concentration does not change. In this way, regulation around the dew point and mass transfer control is easily possible.
  • the various options for determining the dew point can be combined.
  • z. B. the temperature of the sample can be regulated in such a way that z. B. does not change the volume or weight of the sample. This results alternately in a mini male evaporation and minimal condensation, which cancel each other out in total.
  • a small sample of e.g. B. 20 ⁇ l in a well of a microtiter plate or a sample of less than one microliter in a nanotiter plate can be kept in the open atmosphere for at least three to four days by means of the method according to the invention; the concentrations of the substances in the sample remain constant during this time. Constant and reproducible conditions of the solutions in the wells are obtained over a long period of time. This also results in precisely defined quantities, e.g. B. the DNA fragments on a DNA array. A large DNA array can therefore be built up over several days under precisely defined conditions. These advantages are achieved with the simplest technical means. Disturbances in the environmental conditions, e.g. B. can be quickly compensated by opening the reaction chamber or the entire automation system.
  • the chamber in which the microplate or nanotiter plate is located is ventilated by a fan.
  • a targeted, slight evaporation can be set to concentrate the sample. To do this, the temperature of the sample is set slightly above the dew point.
  • the partial pressure of the steam should be below the saturation pressure, otherwise there would be no evaporation. comes because the surrounding atmosphere could no longer absorb any more steam.
  • Targeted condensation can also be brought about by adjusting the temperature of the sample below the dew point.
  • the temperature of the atmosphere based on the dew point of the vapor of the substance or the vapor pressure of the substance in the surrounding atmosphere can be adjusted based on the saturation vapor pressure.
  • the vapor pressure over the sample can be easily adjusted using an evaporator. In the simplest case, this is a hot plate under an open solvent container.
  • the method according to the invention can also be used to bring about a precisely defined entry of different solvents by building up the associated vapor pressures over the sample.
  • the method according to the invention is thus also able to pump, for. B. micropumps or piezoelectric pipetting heads on the technical basis of inkjet heads to replace.
  • the latter can dose about 100 pl.
  • the condensation control according to the invention by setting low partial pressures, small surfaces and short interaction times, almost any small amounts of solvent can be introduced or deposited on solid surfaces.
  • Wells can be filled with small amounts of solvents, concentrations can be changed and mixtures can be created.
  • mixed vapors with defined partial pressures can be produced.
  • various solvents such. B. can be provided in different wells of a micro- or nanotiter plate, or different solvents are evaporated in succession.
  • Reliable temporary storage of samples, in particular liquid samples or solutions, in open vessels, for example after completion of a reaction or a reaction sequence such as the PCR reaction can also be achieved with the method according to the invention.
  • the method according to the invention can also be used for coating substrates.
  • An alternative way of introducing liquid into the sample is to apply a mist of liquid to the sample.
  • the mist consists of small droplets, which are deposited on the surface of the sample and thereby introduce the liquid from the mist into the sample., - Furthermore, a mist increases the vapor pressure, since the vapor pressure is increased over the strongly curved surfaces of small droplets , In this way, for example, the mass, the volume or the concentration of the sample can be controlled and kept approximately constant.
  • the sample can also be diluted with a mist.
  • the temperature of the sample can be adjusted to the dew point of the solvent in the surrounding atmosphere.
  • Such a mist can be generated with an ultrasonic or piezo nebulizer, for example.
  • the mist can also be formed from a solvent with a substance dissolved in it. This means that a substance can also be added to the sample.
  • the substance can be, for example, a mononucleotide that is required for the synthesis of DNA. It is also possible with this method to introduce chemical components into the sample volume for example, a next reaction step can be triggered.
  • control variable is the volume of the sample and / or the concentration of the dissolved substance and / or the amount of the substance dissolved in the sample.
  • Controlled variables can be determined directly or indirectly in various ways.
  • any indirect measurement variable for the above-mentioned control variables volume, concentration and quantity is sufficient as a control variable. In principle, it is sufficient, e.g. B. only observe the weight of the sample.
  • the volume of the sample can be determined in different ways, e.g. B. by an optical measurement or by a capacitive or inductive measurement and by a vibration measurement.
  • the concentration of the dissolved substance can also. be determined by an optical measurement - for example an absorption or fluorescence measurement.
  • An electrical measurement for example a measurement of the impedance or the dielectric constant of the sample, is also conceivable for determining the concentration of the dissolved substance or the amount of the substance dissolved in the sample.
  • the device for carrying out the method according to the invention has a negative shape with depressions for the wells of the microplate or nanotiter plate for fast and precise control of the temperature of a microplate or nanotiter plate.
  • This form can e.g. B. made of aluminum or copper.
  • the mold itself is tempered by a temperature control device. It can be flushed with tempered, double-distilled water from a cryostat, or it can be cooled by a Peltier element or a combination of the two. Due to the close contact between the wells and the negative mold, the temperature of the sample can be controlled quickly and precisely. Further advantageous developments of the invention are characterized in the subclaims.
  • Fig. 1 is a schematic representation of a device for controlling the mass transfer between a sample and the atmosphere surrounding the sample.
  • FIG. 1 shows a microtiter plate 10 with wells 12, which is arranged on a copper negative mold 14 with depressions 15 for the wells 12. Above the microtiter plate 10 there is a pipetting robot 16, which applies solutions from the wells 12 of the microtiter plate 10 to a slide,... 18. In this way, a DNA array is built up on the slide 18.
  • a humidity and temperature sensor 20 In the atmosphere above the microtiter plate 10 there is a humidity and temperature sensor 20, which is connected to a microcontroller 22.
  • the microcontroller 22 calculates the dew point from the humidity and temperature data.
  • the microcontroller 22 also regulates the temperature of the microtiter plate 10 via a cryostat 24, with which it communicates via a line 26.
  • the cryostat 24 tempers the negative mold 14 with chilled water. The water is transported via an inlet 28 and a reflux 30 between the cryostat 24 and the negative mold 14.
  • the temperature of the microtiter plate 10 is also measured by a sensor 32.
  • the measurement signal is fed to the microcontroller 22 via a line 34.
  • the weight of the microtiter plate - together with the negative mold 14 - is monitored with a balance 36.
  • the Signals of the scale are also routed to the microcontroller 22 via a line (not shown).
  • the microcontroller 22 uses the balance 36 to observe whether changes in the weight of the microtiter plate 10 occur. If the weight decreases for no apparent reason (for example, removal of solution from the wells 12 of the microtiter plate 10), evaporation occurs. The microtiter plate is therefore too warm. Accordingly, the microcontroller 22 sends a signal to the cryostat 24 to lower the temperature of the microtiter plate.
  • the microcontroller 22 checks whether the temperature of the microtiter plate 10 is above the dew point. If this is the case, the microcontroller 22 sends a suitable control signal via the line 26 to the cryostat 24, which then lowers the temperature of the water accordingly in order to bring the microtiter plate 10 to the dew point.
  • the volume of the sample can in principle be determined by a relative measurement.
  • the wells 12 are filled in a spotting or pipetting step, which specifies a volume that is known with sufficient accuracy. The aim is then to maintain this predetermined volume, possibly less a desired discharge.
  • the volume of the liquid in a well 12 is preferably determined by an optical reflection measurement.
  • the deflection of a laser beam which is dependent on the fill heights of the respective well 12, is measured via a position-sensitive 4-quadrant diode.
  • a height resolution of approximately 10 nm can thus be achieved.
  • the volume can also be determined optically via the imaging properties of a lenticular, transparent liquid drop if this is used to image a plurality of lines. In the event of a change in the lumen of the drop there is an offset of the lines, from which the volume can be determined if the refractive index is known.
  • the volume can also be determined by various electrical measurements.
  • a capacitive measurement of the volume - with a known dielectric constant - the sample volume is brought into the electrical field of a capacitor.
  • the capacitance of the capacitor is then determined.
  • the volume can be used to infer the volume of the sample. For this purpose, for example, a spot can be placed on an electrically conductive surface as the sample volume.
  • a counter electrode is then aligned parallel to the conductive surface and brought up to it.
  • the weight of the sample or microtiter plate 10 can be measured with a precision balance with an accuracy of less than
  • Weight measurement can also be used to control the amount of a discharge by determining the difference between the weight before and after the discharge.
  • a mass determination by means of a vibration measurement is also possible. To do this, the sample is positioned on the surface of a body. The mass of the sample can then be determined by shifting the surface oscillation frequency.
  • the concentration of charged species in the solution can e.g. B. determine by an impedance measurement.
  • the impedance can be determined ion-selectively by varying the frequency of an applied AC voltage. The concentration of the individual ions results from the ion-selective impedance.
  • chromophores are present, their concentration can be determined by an absorption measurement. If fluorophores are also present, the concentration can be determined via a fluorescence measurement, preferably via a laser-induced fluorescence (LIF) measurement. Fluorophores can also be used to determine the volume. For this purpose, a fluorophore is artificially added to the volume. The sample as a whole is excited to fluoresce. Your brightness is determined. The volume can be inferred from the brightness using a calibration curve.
  • LIF laser-induced fluorescence
  • a nebulizer is used to refill the wells 12 when weight loss is detected.
  • a nebulizer alternatively also in an inkjet or piezo dispenser - droplets with volumes from a few picoliters to several nanoliters are generated.
  • the fog can be generated by excitation of a piezo actuator with low or high frequencies.
  • Liquid jets are broken down into quantifiable droplets in a highly reproducible manner.
  • the number of droplets can be precisely determined in the so-called single-shot mode, in which individual droplets are dispensed in a well-defined manner.
  • droplets can be generated thermally using the so-called bubble jet process.
  • the nebuliser is preferably set up in the immediate vicinity of the substance to be controlled, in particular when other areas are to be separated from the mist, which can be achieved by suitable barriers.
  • the nebulizer can also be placed further away from the microtiter plate 10 if the mist is to be distributed homogeneously over different samples.
  • the mist droplets can perform different tasks:
  • the droplets from the mist can be introduced into wells 12 or onto existing liquid droplets or particles. These can be present in various media, for example in solid or gel-like matrices or bound to surfaces or in the gas phase. In any case, the existing droplets are mixed with the droplets from the mist.
  • the droplets present can contain solutions, such as DNA in an aqueous buffer solution.
  • the fog can introduce new reaction partners to the existing solution. These can be, for example, nucleotides or DNA, RNA or PNA fragments of different lengths. It can also be amino acids, peptides and the whole variety of proteins, such as enzymes, etc. Accordingly, the solvents that make up the mist droplets must be varied accordingly: from water to aqueous solutions to polar or amphiphilic solvents.
  • the method according to the invention is not restricted to use on microplates or nanotiter plates. It can be used for samples of any shape. reference numeral
  • Microtiter plate corrugated copper negative form wells pipetting robot microscope slide humidity and temperature sensor microcontroller cryostat communication line inlet return flow temperature sensor communication line scale

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

L'invention concerne un procédé pouvant être mis en oeuvre pour tous les échantillons ou chambres de réaction ouverts. Il sert en particulier à conditionner des plaques de microtitration ou de nanotitration comportant une pluralité de puits de faible dimension, lors de la constitution de réseaux d'ADN. L'atmosphère entourant la plaque de microtitration ou de nanotitration contient de la vapeur d'eau, et les puits renferment des solutions aqueuses. Un échange permanent d'eau s'effectue par condensation et évaporation entre l'atmosphère et les solutions. Afin d'éviter qu'un de ces processus ne prenne le dessus, la température de l'échantillon est régulée de sorte que le poids de l'échantillon, par exemple, reste constant. La plaque de microtitration ou de nanotitration comportant les solutions dans les puits peut être maintenue plusieurs dans cet atmosphère ouverte, sans qu'une variation des concentrations de matières ne se produise dans les puits.
PCT/EP2001/005903 2000-05-24 2001-05-22 Procede et dispositif pour reguler l'echange de matiere entre un echantillon et l'atmosphere entourant l'echantillon WO2001090721A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2001283821A AU2001283821A1 (en) 2000-05-24 2001-05-22 Method and device for controlling the exchange of substances between a sample and the surrounding atmosphere thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10025809.3 2000-05-24
DE2000125809 DE10025809A1 (de) 2000-05-24 2000-05-24 Verfahren und Vorrichtung zum Steuern des Stoffaustauschs zwischen einer Probe und der die Probe umgebenden Atmosphäre

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Publication Number Publication Date
WO2001090721A1 true WO2001090721A1 (fr) 2001-11-29

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PCT/EP2001/005903 WO2001090721A1 (fr) 2000-05-24 2001-05-22 Procede et dispositif pour reguler l'echange de matiere entre un echantillon et l'atmosphere entourant l'echantillon

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AU (1) AU2001283821A1 (fr)
DE (1) DE10025809A1 (fr)
WO (1) WO2001090721A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008035074A2 (fr) * 2006-09-19 2008-03-27 Bg Research Ltd. Améliorations à un appareil de réaction
WO2008111035A2 (fr) * 2007-03-13 2008-09-18 Provost Fellows And Scholars Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth Near Dublin Substance et dispositif
CH711362A1 (de) * 2015-07-29 2017-01-31 Sias Ag Steuergerät für relative Feuchtigkeit.

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111893031B (zh) * 2020-08-12 2022-03-22 山东省农业科学院农业质量标准与检测技术研究所 一种半固体样品微生物检测用取样装置

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5587321A (en) * 1995-07-31 1996-12-24 University Of Kansas Moated tissue culture plate
US5851492A (en) * 1997-09-30 1998-12-22 Blattner; Frederick R. Microtiter plate sealing system
DE19739120A1 (de) * 1997-09-06 1999-03-11 Univ Schiller Jena Verfahren zur Bestimmung der Antioxidanzkapazität von Proben
US5908776A (en) * 1998-04-06 1999-06-01 Pharmacopeia, Inc. Cell culture chamber for multiple well plates
WO1999039829A1 (fr) * 1998-02-04 1999-08-12 Merck & Co., Inc. Puits virtuels destines a etre utilises dans des criblages a haut rendement

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3720189C1 (de) * 1987-06-16 1988-12-29 Endress Hauser Gmbh Co Taupunkt-Sensor

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5587321A (en) * 1995-07-31 1996-12-24 University Of Kansas Moated tissue culture plate
DE19739120A1 (de) * 1997-09-06 1999-03-11 Univ Schiller Jena Verfahren zur Bestimmung der Antioxidanzkapazität von Proben
US5851492A (en) * 1997-09-30 1998-12-22 Blattner; Frederick R. Microtiter plate sealing system
WO1999039829A1 (fr) * 1998-02-04 1999-08-12 Merck & Co., Inc. Puits virtuels destines a etre utilises dans des criblages a haut rendement
US5908776A (en) * 1998-04-06 1999-06-01 Pharmacopeia, Inc. Cell culture chamber for multiple well plates

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008035074A2 (fr) * 2006-09-19 2008-03-27 Bg Research Ltd. Améliorations à un appareil de réaction
WO2008035074A3 (fr) * 2006-09-19 2008-09-18 Bg Res Ltd Améliorations à un appareil de réaction
WO2008111035A2 (fr) * 2007-03-13 2008-09-18 Provost Fellows And Scholars Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth Near Dublin Substance et dispositif
WO2008111035A3 (fr) * 2007-03-13 2008-11-06 Trinity College Dublin Substance et dispositif
US8337785B2 (en) 2007-03-13 2012-12-25 The Provost, Fellows And Scholars Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth, Near Dublin Substance and a device
CH711362A1 (de) * 2015-07-29 2017-01-31 Sias Ag Steuergerät für relative Feuchtigkeit.

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AU2001283821A1 (en) 2001-12-03
DE10025809A1 (de) 2001-11-29

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