EP1341611B1 - Sample support, cover for a sample support and analysis preparation method - Google Patents

Sample support, cover for a sample support and analysis preparation method Download PDF

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Publication number
EP1341611B1
EP1341611B1 EP01997350A EP01997350A EP1341611B1 EP 1341611 B1 EP1341611 B1 EP 1341611B1 EP 01997350 A EP01997350 A EP 01997350A EP 01997350 A EP01997350 A EP 01997350A EP 1341611 B1 EP1341611 B1 EP 1341611B1
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EP
European Patent Office
Prior art keywords
sample carrier
cover
cover plate
liquid
sample
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Legal status (The legal status 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 status listed.)
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EP01997350A
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German (de)
French (fr)
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EP1341611A1 (en
Inventor
Nico Michaelsen
Martin Klumpp
Olaf Sollböhmer
Sabine KÖSTER
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Evotec OAI AG
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Evotec OAI AG
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    • 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

Definitions

  • the invention relates to a sample carrier, in particular a titer plate with a plurality of wells, can be introduced into the smallest samples. Furthermore, the invention relates to a lid for sample carrier and a method for examination preparation.
  • the smallest samples are, in particular, liquids or other samples having a volume of 0.01-50 ⁇ l, in particular 0.2-5 ⁇ l. Likewise, the samples may be cell culturing on this scale, preferably on a 1-5 ⁇ l scale.
  • the sample carriers may be chips.
  • chips usually have one or more channels, which may be, for example, capillary channels and possibly one or more liquid reservoirs.
  • it may be microfluidic chips with preferably two reservoirs, which communicate with each other via a channel are connected.
  • a fluid exchange takes place between the two reservoirs, which can be regulated by suitable valves, membranes, osmotic barriers and / or ion barriers.
  • the mixing behavior of liquids for example under the influence of electromagnetic forces can be investigated.
  • sample components can be separated from each other.
  • Known chips are made of silicon, glass, plastic or ceramic.
  • sample carriers can also be, for example, planar plates with a hydrophobic grid. Such plates are partially coated with a hydrophobic substance, so that droplets of sample liquid form in these areas, which can then be examined. Sample carriers may also be so-called SBS microtiter plate formats and the so-called Terasaki format.
  • the wells of titer plates can be produced, for example, by etching-milling or by using injection molding and laser machining.
  • a lid By providing a lid by which, for example, the pre-wells are sealed tightly in a titer plate, a corresponding sterility can be ensured and any evaporation from the wells of the titer plate can be prevented, but it can not set the desired cultivation conditions. For example, a CO 2 content between 5 - 7% for optimal cell cultivation (pH regulation of the cell culture medium) is needed, which can not be adjusted by the conventional arrangements.
  • WO 95/97196 a sample carrier is known whose individual wells can be sealed separately with the aid of a lid in order to avoid cross-contamination of adjacent wells.
  • the object of the invention is to provide a sample carrier, in particular a titer plate, a lid for a sample carrier and a method for preparation of investigations, in particular of chemical and / or biological micro samples, in which or in which, in particular, evaporation of samples is substantially avoided and at the same time optimal cultivation conditions, ie sufficient sterility and precise control of the gas exchange, in particular a precise classification of the CO 2 content for cells in sample carriers for very small samples, can be achieved.
  • the sample carrier has a receiving part for receiving small samples. If the sample carrier is a titer plate, the smallest samples are placed in wells of the titer plate. Is it the sample carrier around a chip, the smallest samples are introduced into channels or in depressions of the chip. Correspondingly, the samples are applied to the grid in a sample carrier designed as a planar plate with a hydrophobic grid, so that drops of sample material are formed.
  • the wells of a titer plate or the wells of a chip preferably have a volume of 0.01 to 50 ul. In particular, the volume is 0.2 to 5 ⁇ l.
  • the sample carrier has a lid, through which the receiving part is closed in such a way that a cavity is formed between a sample surface and the lid. The lid underside thus has a distance to the sample surface and generally also to the top of the receiving part.
  • the lid is designed in such a way that a saturated atmosphere in the cavity is essentially preserved under changing environmental conditions.
  • the lid thus has a certain vapor permeability and / or moisture absorption and / or dispensing capability.
  • the cover is designed such that it is suitable for receiving and dispensing liquid.
  • the saturated atmosphere in the cavity remains so constant under changing environmental conditions that there is a deviation of less than 5% from a saturation level. In particular, this deviation is less than 2%.
  • the cultivation conditions for z. B. provided in wells of a titer plate cells are maintained even in changing outdoor conditions.
  • the lid of the sample carrier according to the invention has a porous cover plate.
  • This is preferably made of ceramic or glass and serves as a liquid storage.
  • the resulting from the preferably stored in the porous cover plate liquid vapor phase creates in the cavity between the sample carrier and lid a saturated atmosphere, whereby the evaporation of sample liquid is prevented.
  • a gas exchange through the porous lid is possible, so that, for example, for cell cultivation, the optimal CO 2 concentration can be adjusted in the cavity.
  • the gas exchange takes place, for example, via pores not closed by wetting liquid, so that the gas can pass through the pores to the outside.
  • an indirect gas exchange by the gas, in particular CO 2 is dissolved in the liquid and ggl. out of the liquid into the cavity ausast.
  • the lid according to the invention is designed so that liquid in the form of vapor can escape from the pores of the lid material.
  • the sample carrier according to the invention is introduced into an incubator and exposed to elevated temperatures, steam escapes from the liquid-saturated pores within the lid and creates a saturated atmosphere corresponding to the temperature in the cavity between sample carrier and lid.
  • the porous cover material it is also possible that condensation on the inside of the cover is avoided because condensing Liquid is absorbed sufficiently quickly into the pores and thus a dripping down into individual wells is prevented.
  • a falsification of investigations by dripping liquid is excluded.
  • a lid maintains the required sterility over a long incubation period. This is achieved with a lid with small pore diameters (preferably 0.2-0.5 ⁇ m), which prevents germs from penetrating from the outside. Surprisingly, a sufficient sterility is given even with larger pore diameters.
  • the lid is also designed so that from the outside, no liquid can penetrate inwards.
  • the lid has a shape that can be used very well in automated inspection systems.
  • a porous cover plate has the particular advantage that the atmosphere in the cavity between the sample carrier and the lid by the choice of liquid, with which the porous plate is wetted, can be adjusted.
  • the goal is z. B., that due to a temperature increase resulting vapor pressure change in the cavity between the sample carrier and lid is achieved by evaporation of the liquid contained in the cover plate substantially, thus preventing the evaporation of the samples.
  • This is achieved inter alia by the much larger active surface of the porous cover plate compared to the surface of the sample carrier, so that the evaporation takes place very quickly on the surface of the porous plate and thus the vapor pressure in the cavity is built up in a short time.
  • a liquid is usually selected which has the same or a similar vapor pressure as the sample liquid.
  • an automatic regulation of the vapor pressure takes place in the cavity.
  • a porous film is provided instead of or in addition to the porous cover plate.
  • the porosity of the film also ensures that the saturated atmosphere in the cavity between the receiving part and the lid is substantially maintained under changing environmental conditions.
  • the cover instead of the porous cover plate has a porous film
  • a film can be used as the film, which automatically closes again. This is possible due to the small size of the holes created.
  • films in which the hole is retained since, with a small number of holes, the dimensions of the holes are so small that there is no appreciable impairment of the atmosphere in the cavity between the film and the receiving part.
  • a porous film in addition to a cover plate.
  • the film is preferably arranged between the cover plate and the receiving part. This makes it possible to ensure or adjust the sterility within the sample carrier by a suitable choice of the pore size of the film.
  • the pore size of the cover plate can then be chosen independently of the sterility requirements.
  • a cover plate can then, for example, a textile material, a sponge or other suitable for liquid storage material z. B. in the form of porous flakes or beads are used.
  • the gas permeability of the lid can be controlled by the film used.
  • the pore diameter of the porous cover plate and / or the film are preferably less than 0.5 .mu.m, in particular less than 0.2 .mu.m. As a result, the sterility can be ensured within the sample carrier. Surprisingly enough sterility is achieved even with larger pore diameters.
  • the invention further relates to a lid for a sample carrier, in particular a titer plate.
  • the lid according to the invention preferably has a porous cover plate which is wettable with a liquid for the purpose of regulating the vapor pressure.
  • the cover may be developed according to the preferred embodiments of the sample carrier described above.
  • the cover can serve for receiving electrodes which, for example, extend into individual recesses and cause the migration of sample components in an electric field.
  • the lid has sensors.
  • the moisture content in the cavity between the lid and the receiving part can be determined.
  • a renewed moistening of the lid can be carried out automatically, for example, if the moisture content is too low.
  • the sensors it is possible to arrange the sensors such that the moisture content of the cover plate itself can be determined.
  • sensors for determining substance contents in the cavity With such sensors, for example, the CO 2 content in the cavity can be determined.
  • the lid preferably has handle prisms, so that the lid can be handled automatically by a gripper arm.
  • the handle prisms and the dimensions of the sample carrier preferably correspond to the dimensions and the position of the handle prisms in the case of the sample carrier handled together with the lid. It is thus possible to handle both the lid and the receiving part of the sample carrier with the same gripping arm.
  • the sample carrier is a chip
  • the channels provided in the chip it is preferable for the channels provided in the chip to be micro- or nano-channels whose width and height are in the range from 1 ⁇ m to 1 mm.
  • electrodes can also be arranged within the channels.
  • the sample carrier according to the invention is in particular for the storage of reagents, for the storage of samples, such as cells or other sample substances, for the separation of liquid, for example by means of CE or CEC, for the manipulation of Samples, for example, by electroporation, electropermeation or hybridization and the like. be used.
  • sample carrier or the like a transparent glass plate. so that the samples can be used by fluorescence correlation spectroscopy, especially using convocal optics.
  • sample carriers and an optical tweezers for holding particles can be used.
  • the invention further comprises a method for the preparation of tests of chemical and / or biological micro samples.
  • small samples with a volume of preferably 0.2 to 5 .mu.l in wells of the sample carrier, in particular in wells of the titer plate are introduced.
  • the sample carrier is closed with a lid, which preferably has a porous cover plate.
  • the porous cover plate can be advantageously developed as described above.
  • the porous cover plate is wetted with a liquid. As a result, a vapor pressure regulation is achieved in the cavity formed between the sample top and the lid.
  • the inventive method has the advantages described above with regard to the use of a lid with a porous cover plate.
  • the lid is sterilized prior to sealing the sample carrier. This avoids that germs get into the samples when closing the sample carrier.
  • the liquid used is a PBS buffer containing at least 0.7% of sodium chloride.
  • a buffer solution is used which has substantially the same vapor pressure, like the samples contained in the wells. It is also advantageous to use a liquid having a pH of 7-8, in particular of 7.5.
  • the visible in Fig. 1 cover 10 has a porous cover plate 12 which is supported by a holding part 14.
  • a holding part 14 In the illustrated embodiment, it is a frame-shaped holding part 14 which completely surrounds the cover plate 12.
  • the cover plate 12 may be glued into the holding part 14.
  • supports 16 In order to define the position exactly, supports 16 (FIG. 2) are introduced into the holding part 14.
  • the supports 16 are L-shaped in cross-section and protrude from the frame-shaped holding part 14 inwards, so that the cover plate 12 can be inserted from above into the lid 10 and lies on the supports 16.
  • the pads 16 are preferably also frame-shaped so that they extend completely along the inner edge 18 of the holding part 14. However, individual pads 16 may be arranged distributed on the inner circumference 18 of the frame.
  • a sample carrier 20 (FIG. 2) has a frame-shaped holding part 22 with a rectangular opening. In this a receiving part 24 is arranged with recesses 26. In the wells 26, the samples are housed.
  • the receiving part 24 consists for example of plastic and has recesses 26 through openings. These are on the bottom, preferably with a glass plate 28, closed.
  • the sealing lip 30 is connected via the support 16 with the holding part 14. In the exemplary embodiment shown, this is a preferred embodiment in which the sealing lip extends completely along the inner circumference 32 of the sample carrier 20.
  • the sealing lip 30 is thus rectangular according to the opening in the frame-shaped holding part 22.
  • a cavity 38 is formed between a bottom 34 of the cover plate 12 and a top 36 of the receiving part 24, a cavity 38 is formed.
  • the cavity 38 forms due to very low evaporation of liquid from the wells 26 and due to the main evaporation of the liquid provided in the porous cover plate 12, a vapor pressure.
  • the lower part of the cavity 38 forms a recess in the sample carrier 20. In this recess engages the sealing lip 30 for fixing the position.

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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)
  • Sampling And Sample Adjustment (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Analysing Materials By The Use Of Radiation (AREA)

Abstract

A sample support comprises a receiving part (24) for very small samples, and a lid (10) for the support, a hollow chamber (38) formed between the sample surface and the lid, where the lid is formed in such a way that a saturated atmosphere remains in the hollow chamber with changing surrounding conditions. An independent claim is also included for a process for investigating chemical and/or biological samples using the sample support.

Description

Die Erfindung betrifft einen Probenträger, insbesondere eine Titerplatte mit mehreren Vertiefungen, in die Kleinstproben eingebracht werden können. Ferner betrifft die Erfindung einen Deckel für Probenträger sowie ein Verfahren zur Untersuchungsvorbereitung. Bei den Kleinstproben handelt es sich insbesondere um Flüssigkeiten oder andere Proben mit einem Volumen von 0,01-50 µl, insbesondere 0,2 - 5 µl. Ebenso kann es sich bei den Proben um Zellkultivierung in dieser Größenordnung handeln, vorzugsweise im 1-5-µl-Maßstab.The invention relates to a sample carrier, in particular a titer plate with a plurality of wells, can be introduced into the smallest samples. Furthermore, the invention relates to a lid for sample carrier and a method for examination preparation. The smallest samples are, in particular, liquids or other samples having a volume of 0.01-50 μl, in particular 0.2-5 μl. Likewise, the samples may be cell culturing on this scale, preferably on a 1-5 μl scale.

Ferner kann es sich bei den Probenträgern um Chips handeln. Chips weisen als Ausnehmungen üblicherweise eine oder mehrere Kanäle, bei denen es sich beispielsweise um Kapillarkanäle und ggf. ein oder mehrere Flüssigkeitsreservoirs handeln kann, auf. Beispielsweise kann es sich um mikrofluidische Chips mit vorzugsweise zwei Reservoirs handeln, die über einen Kanal miteinander verbunden sind. Zwischen den beiden Reservoirs findet ein Fluidaustausch statt, der durch geeignete Ventile, Membranen, osmotische Barrieren und/oder Ionensperren geregelt werden kann. Mit derartigen Chips kann beispielsweise das Mischverhalten von Flüssigkeiten, z.B. unter Einfluss elektromagnetischer Kräfte untersucht werden. Ferner können mit derartigen Chips Probenbestandteile voneinander getrennt werden. Bekannte Chips sind aus Silizium, Glas, Kunststoff oder Keramik hergestellt.Furthermore, the sample carriers may be chips. As recesses, chips usually have one or more channels, which may be, for example, capillary channels and possibly one or more liquid reservoirs. For example, it may be microfluidic chips with preferably two reservoirs, which communicate with each other via a channel are connected. A fluid exchange takes place between the two reservoirs, which can be regulated by suitable valves, membranes, osmotic barriers and / or ion barriers. With such chips, for example, the mixing behavior of liquids, for example under the influence of electromagnetic forces can be investigated. Furthermore, with such chips sample components can be separated from each other. Known chips are made of silicon, glass, plastic or ceramic.

Ferner kann es sich bei Probenträgern beispielsweise auch um planare Platten mit hydrophobem Raster handeln. Derartige Platten sind partiell mit einer hydrophoben Substanz beschichtet, so dass sich in diesen Bereichen Tröpfchen aus Probenflüssigkeit bilden, die sodann untersucht werden können. Bei Probenträgern kann es sich ferner um sogenannte SBS-Mikrotiterplattenformate und um das sogenannte Terasaki-Format handeln.Furthermore, sample carriers can also be, for example, planar plates with a hydrophobic grid. Such plates are partially coated with a hydrophobic substance, so that droplets of sample liquid form in these areas, which can then be examined. Sample carriers may also be so-called SBS microtiter plate formats and the so-called Terasaki format.

Die Vertiefungen von Titerplatten können beispielsweise durch Ätz-Fräsverfahren oder durch Verwendung von Spritzgussverfahren sowie durch Laserbearbeitung hergestellt werden.The wells of titer plates can be produced, for example, by etching-milling or by using injection molding and laser machining.

Bei der Untersuchung von Kleinstprobenmengen mittels Probenträgern besteht das Problem, dass beim Handhaben der Probenträger in Untersuchungsanlagen ein Teil der Proben verdunstet. Bei derartig kleinen Probenmengen führt auch bereits eine geringe Verdunstung zu einer kritischen Konzentrationsänderung der Kleinstprobe. Dies führt zu verfälschten und teilweise nicht mehr aussagekräftigen Untersuchungsergebnissen. Insbesondere bei der Zellkultivierung mit Hilfe von Inkubatoren reicht die vorhandene Feuchtigkeit nicht aus, um Probenflüssigkeiten im Kleinstmaßstab nachhaltig vor Verdunstung, d.h. bei längeren Inkubationszeiten, zu schützen.In the study of small sample volumes using sample carriers, there is the problem that some of the samples evaporate when handling the sample carriers in analysis facilities. With such small amounts of sample even a small evaporation leads to a critical concentration change of the smallest sample. This leads to falsified and sometimes no longer meaningful investigation results. Especially in cell cultivation with the help of incubators, the existing moisture is not sufficient to sustainably protect sample liquids on the smallest scale from evaporation, ie with longer incubation times.

Ferner besteht beim Handling von Probenträgern in Untersuchungsanlagen eine erhöhtes Sterilitätsproblem, wenn es sich um Kleinstproben handelt.Furthermore, the handling of sample carriers in examination facilities has an increased sterility problem when it comes to small samples.

Durch das Vorsehen eines Deckels, durch den beispielsweise die Vortiefungen in einer Titerplatte dicht verschlossen werden, kann eine entsprechende Sterilität zwar sichergestellt und auch jegliche Verdunstung aus den Vertiefungen der Titerplatte unterbunden werden, es lassen sich aber nicht die gewünschten Kultivierungsbedingungen einstellen. So wird z.B. ein CO2-Gehalt zwischen 5 - 7 % zur optimalen Zellkultivierung (pH-Regulation des Zellkulturmediums) benötigt, der durch die herkömmlichen Anordnungen nicht eingestellt werden kann.By providing a lid by which, for example, the pre-wells are sealed tightly in a titer plate, a corresponding sterility can be ensured and any evaporation from the wells of the titer plate can be prevented, but it can not set the desired cultivation conditions. For example, a CO 2 content between 5 - 7% for optimal cell cultivation (pH regulation of the cell culture medium) is needed, which can not be adjusted by the conventional arrangements.

Aus WO 95/97196 ist ein Probenträger bekannt, dessen einzelne Wells mit Hilfe eines Deckels gesondert abgedichtet werden können, um eine Cross-Kontamination benachbarter Wells zu vermeiden.Out WO 95/97196 a sample carrier is known whose individual wells can be sealed separately with the aid of a lid in order to avoid cross-contamination of adjacent wells.

Aufgabe der Erfindung ist es, einen Probenträger, insbesondere eine Titerplatte, einen Deckel für einen Probenträger sowie ein Verfahren zur Untersuchungsvorbereitung, insbesondere von chemischen und/ oder biologischen Kleinstproben zu schaffen, bei der oder bei dem insbesondere eine Verdunstung von Proben im Wesentlichen vermieden wird und gleichzeitig optimale Kultivierungsbedingungen, d.h. ausreichende Sterilität und genaue Steuerung des Gasaustausches, insbesondere eine genaue Einsteilung des CO2-Gehaltes für Zellen in Probenträgern für Kleinstproben, erreicht werden.The object of the invention is to provide a sample carrier, in particular a titer plate, a lid for a sample carrier and a method for preparation of investigations, in particular of chemical and / or biological micro samples, in which or in which, in particular, evaporation of samples is substantially avoided and at the same time optimal cultivation conditions, ie sufficient sterility and precise control of the gas exchange, in particular a precise classification of the CO 2 content for cells in sample carriers for very small samples, can be achieved.

Die Lösung der Aufgabe erfolgt erfindungsgemäß durch die Merkmale des Anspruchs 1, 13 oder 14.The object is achieved according to the invention by the features of claim 1, 13 or 14.

Der Probenträger weist ein Aufnahmeteil zur Aufnahme von Kleinstproben auf. Wenn es sich bei dem Probenträger um eine Titeplatte handelt, werden die Kleinstproben in Vertiefungen der Titeplatte eingebracht. Handelt es sich bei dem Probenträger um einen Chip, so werden die Kleinstproben in Kanäle oder in Vertiefungen des Chips eingebracht. Entsprechend werden die Proben bei einem als planare Platte ausgebildeten Probenträger mit einem hydrophoben Raster auf das Raster aufgebracht, so dass sich Tropfen aus Probenmaterial bilden. Die Vertiefungen einer Titerplatte oder die Vertiefungen eines Chips weisen vorzugsweise ein Volumen von 0,01 bis 50 µl auf. Insbesondere beträgt das Volumen 0,2 bis 5 µl. Ferner weist der Probenträger einen Deckel auf, durch den das Aufnahmeteil derart verschlossen ist, dass zwischen einer Probenoberfläche und dem Deckel ein Hohlraum ausgebildet ist. Die Deckelunterseite weist somit einen Abstand zu der Probenoberfläche und im Allgemeinen auch zu der Oberseite des Aufnahmeteils auf.The sample carrier has a receiving part for receiving small samples. If the sample carrier is a titer plate, the smallest samples are placed in wells of the titer plate. Is it the sample carrier around a chip, the smallest samples are introduced into channels or in depressions of the chip. Correspondingly, the samples are applied to the grid in a sample carrier designed as a planar plate with a hydrophobic grid, so that drops of sample material are formed. The wells of a titer plate or the wells of a chip preferably have a volume of 0.01 to 50 ul. In particular, the volume is 0.2 to 5 μl. Furthermore, the sample carrier has a lid, through which the receiving part is closed in such a way that a cavity is formed between a sample surface and the lid. The lid underside thus has a distance to the sample surface and generally also to the top of the receiving part.

Der Deckel ist erfindungsgemäß derart ausgebildet, dass eine gesättigte Atmosphäre in dem Hohlraum bei sich verändernden Umgebungsbedingungen im Wesentlichen erhalten bleibt. Der Deckel weist somit eine gewisse Dampfdurchlässigkeit und/ oder Feuchtigkeitsaufnahme und/ oder -abgabefähigkeit auf.According to the invention, the lid is designed in such a way that a saturated atmosphere in the cavity is essentially preserved under changing environmental conditions. The lid thus has a certain vapor permeability and / or moisture absorption and / or dispensing capability.

Erfindungsgemäß ist der Deckel derart ausgebildet, dass er zur Aufnahme und zur Abgabe von Flüssigkeit geeignet ist. Insbesondere bleibt die gesättigte Atmosphäre in dem Hohlraum bei sich ändernden Umgebungsbedingungen derart konstant, das eine Abweichung von weniger als 5 % von einem Sättigungsniveau stattfindet. Insbesondere ist diese Abweichung geringer als 2 %.According to the invention, the cover is designed such that it is suitable for receiving and dispensing liquid. In particular, the saturated atmosphere in the cavity remains so constant under changing environmental conditions that there is a deviation of less than 5% from a saturation level. In particular, this deviation is less than 2%.

Mit dem erfindungsgemäßen Probenträger können die Kultivierungsbedingungen für z. B. in Vertiefungen einer Titerplatte vorgesehene Zellen auch bei sich ändernden Außenbedingungen aufrecht erhalten werden.With the sample carrier according to the invention, the cultivation conditions for z. B. provided in wells of a titer plate cells are maintained even in changing outdoor conditions.

Der Deckel des erfindungsgemäßen Probenträgers weist eine poröse Abdeckplatte auf. Diese besteht bevorzugt aus Keramik oder Glas und dient als Flüssigkeitsspeicher. Die aus der vorzugsweise in der porösen Abdeckplatte gespeicherten Flüssigkeit entstehende Dampfphase schafft in dem Hohlraum zwischen Probenträger und Deckel eine gesättigte Atmosphäre, wodurch die Verdunstung von Probenflüssigkeit verhindert wird. Gleichzeitig ist ein Gasaustausch durch den porösen Deckel möglich, so dass z.B. für die Zellkultivierung die optimale CO2-Konzentration in dem Hohlraum eingestellt werden kann. Der Gasaustausch erfolgt beispielsweise über nicht von Benetzungsflüssigkeit verschlossene Poren, so dass das Gas durch die Poren hindurch nach außen gelangen kann. Zusätzlich oder anstatt dieses direkten Gasaustausches findet auch ein indirekter Gasaustausch statt, indem das Gas, insbesondere CO2, in der Flüssigkeit gelöst wird und ggl. aus der Flüssigkeit in den Hohlraum ausgast.The lid of the sample carrier according to the invention has a porous cover plate. This is preferably made of ceramic or glass and serves as a liquid storage. The resulting from the preferably stored in the porous cover plate liquid vapor phase creates in the cavity between the sample carrier and lid a saturated atmosphere, whereby the evaporation of sample liquid is prevented. At the same time a gas exchange through the porous lid is possible, so that, for example, for cell cultivation, the optimal CO 2 concentration can be adjusted in the cavity. The gas exchange takes place, for example, via pores not closed by wetting liquid, so that the gas can pass through the pores to the outside. In addition or instead of this direct gas exchange also takes place an indirect gas exchange by the gas, in particular CO 2 , is dissolved in the liquid and ggl. out of the liquid into the cavity ausast.

Der Deckel ist erfindungsgemäß so ausgebildet, dass Flüssigkeit in Form von Dampf aus den Poren des Deckelmaterials entweichen kann. Wird z.B. der erfindungsgemäße Probenträger in einen Inkubator eingebracht und erhöhten Temperaturen ausgesetzt, entweicht aus den flüssigkeitsgesättigten Poren innerhalb des Deckels Dampf und schafft eine entsprechend der Temperatur gesättigte Atmosphäre im Hohlraum zwischen Probenträger und Deckel. Wie vorstehend beschrieben, ist z. B. durch die nicht mit Flüssigkeit gefüllten Poren gleichzeitig ein Gasaustausch zwischen der Umgebung und dem Hohlraum zwischen Probenträger und Deckel möglich, so dass z.B. die optimale CO2-Konzentration in dem Hohlraum sehr gut eingestellt werden kann. Durch das poröse Deckelmaterial ist es weiterhin möglich, dass Kondensatbildung an der Deckelinnenseite vermieden wird, da kondensierende Flüssigkeit ausreichend schnell in die Poren aufgenommen und somit ein Hinuntertropfen in einzelne Vertiefungen verhindert wird. Auf diesem Wege wird eine Verfälschung der Untersuchungen durch hinuntertropfende Flüssigkeit ausgeschlossen. Ferner ist durch einen derartigen Deckel die erforderliche Sterilität über einen langen Inkubationszeitraum gewahrt. Dies wird mit einem Deckel mit kleinen Porendurchmessern (vorzugsweise 0,2 - 0,5 µm) erreicht, wodurch verhindert wird, dass Keime von außen eindringen können. Überraschenderweise ist auch bei größeren Porendurchmessern eine hinreichende Sterilität gegeben. Der Deckel ist weiterhin so ausgestaltet, dass von außen weiterhin keine Flüssigkeit nach innen dringen kann. Vorzugsweise weist der Deckel eine Form auf, die sehr gut in automatisierten Untersuchungssystemen verwendet werden kann.The lid according to the invention is designed so that liquid in the form of vapor can escape from the pores of the lid material. For example, if the sample carrier according to the invention is introduced into an incubator and exposed to elevated temperatures, steam escapes from the liquid-saturated pores within the lid and creates a saturated atmosphere corresponding to the temperature in the cavity between sample carrier and lid. As described above, z. B. by the non-liquid-filled pores simultaneously a gas exchange between the environment and the cavity between the sample carrier and lid possible, so that for example the optimal CO 2 concentration in the cavity can be very well adjusted. By the porous cover material, it is also possible that condensation on the inside of the cover is avoided because condensing Liquid is absorbed sufficiently quickly into the pores and thus a dripping down into individual wells is prevented. In this way, a falsification of investigations by dripping liquid is excluded. Further, such a lid maintains the required sterility over a long incubation period. This is achieved with a lid with small pore diameters (preferably 0.2-0.5 μm), which prevents germs from penetrating from the outside. Surprisingly, a sufficient sterility is given even with larger pore diameters. The lid is also designed so that from the outside, no liquid can penetrate inwards. Preferably, the lid has a shape that can be used very well in automated inspection systems.

Das Vorsehen einer porösen Abdeckplatte hat insbesondere den Vorteil, dass die Atmosphäre in dem Hohlraum zwischen Probenträger und Deckel durch die Wahl der Flüssigkeit, mit der die poröse Platte benetzt wird, eingestellt werden kann. Ziel ist es z. B., dass die sich aufgrund einer Temperaturerhöhung ergebende Dampfdruckänderung in dem Hohlraum zwischen Probenträger und Deckel im Wesentlichen durch Verdunstung der in der Abdeckplatte enthaltenen Flüssigkeit erreicht wird, um somit die Verdunstung der Proben zu verhindern. Erreicht wird dieses u. a. durch die wesentlich größere aktive Oberfläche der porösen Abdeckplatte im Vergleich zur Oberfläche des Probenträgers, so dass die Verdunstung sehr schnell an der Oberfläche der porösen Platte stattfindet und somit der Dampfdruck in dem Hohlraum in kurzer Zeit aufgebaut wird. So wird in der Regel eine Flüssigkeit gewählt, die denselben oder einen ähnlichen Dampfdruck wie die Probenflüssigkeit aufweist. Somit findet eine automatische Regulierung des Dampfdruckes in dem Hohlraum statt.The provision of a porous cover plate has the particular advantage that the atmosphere in the cavity between the sample carrier and the lid by the choice of liquid, with which the porous plate is wetted, can be adjusted. The goal is z. B., that due to a temperature increase resulting vapor pressure change in the cavity between the sample carrier and lid is achieved by evaporation of the liquid contained in the cover plate substantially, thus preventing the evaporation of the samples. This is achieved inter alia by the much larger active surface of the porous cover plate compared to the surface of the sample carrier, so that the evaporation takes place very quickly on the surface of the porous plate and thus the vapor pressure in the cavity is built up in a short time. Thus, a liquid is usually selected which has the same or a similar vapor pressure as the sample liquid. Thus, an automatic regulation of the vapor pressure takes place in the cavity.

Dies hat zur Folge, dass nur ein geringer Anteil der Probenflüssigkeit zum Füllen des Hohlraums bis zum Erreichen des Sättigungsdampfdrucks verdunstet.This has the consequence that only a small proportion of the sample liquid to fill the cavity evaporates until reaching the saturation vapor pressure.

Bei langen Inkubationszeiten ist es möglich, durch wiederholtes Benetzen der Abdeckplatte die Sterilität innerhalb des Probenträgers über lange Zeit aufrecht zu erhalten. Da die Benetzung der Abdeckplatte von außen erfolgt, muss der Deckel des Probenträgers hierzu nicht abgenommen werden.With long incubation times it is possible to maintain sterility within the sample carrier over a long time by repeatedly wetting the cover plate. Since the wetting of the cover plate is done from the outside, the lid of the sample holder must not be removed for this purpose.

Gemäß einer weiteren bevorzugten Ausführungsform der Erfindung ist anstatt oder zusätzlich zur porösen Abdeckplatte eine poröse Folie vorgesehen. Durch die Porosität der Folie wird ebenfalls erreicht, dass die gesättigte Atmosphäre in dem Hohlraum zwischen Aufnahmeteil und Deckel bei sich verändernden Umgebungsbedingungen im Wesentlichen erhalten bleibt.According to a further preferred embodiment of the invention, a porous film is provided instead of or in addition to the porous cover plate. The porosity of the film also ensures that the saturated atmosphere in the cavity between the receiving part and the lid is substantially maintained under changing environmental conditions.

Sofern der Deckel anstatt der porösen Abdeckplatte eine poröse Folie aufweist, ist es möglich, mit geeigneten Pipetten o.dgl. durch die Folie hindurchzustechen, um von dem Probenträger oder aus den Vertiefungen der Titerplatten Proben entnehmen oder diesen zuführen zu können. Als Folie kann hierbei eine Folie verwendet werden, die sich automatisch wieder verschließt. Dies ist aufgrund der geringen Größe der hervorgerufenen Löcher möglich. Ferner können auch Folien verwendet werden, bei denen das Loch erhalten bleibt, da bei einer geringen Anzahl von Löchern die Abmessungen der Löcher so gering ist, dass keine nennenswerte Beeinträchtigung der Atmosphäre in dem Hohlraum zwischen Folie und Aufnahmeteil erfolgt.If the cover instead of the porous cover plate has a porous film, it is possible with appropriate pipettes or the like. piercing through the film in order to be able to remove or supply samples from the sample carrier or from the wells of the titer plates. In this case, a film can be used as the film, which automatically closes again. This is possible due to the small size of the holes created. Furthermore, it is also possible to use films in which the hole is retained, since, with a small number of holes, the dimensions of the holes are so small that there is no appreciable impairment of the atmosphere in the cavity between the film and the receiving part.

Besonders bevorzugt ist das Vorsehen einer porösen Folie zusätzlich zu einer Abdeckplatte. Hierbei ist die Folie vorzugsweise zwischen der Abdeckplatte und dem Aufnahmeteil angeordnet. Hierdurch ist es möglich, durch geeignete Wahl der Porengröße der Folie die Sterilität innerhalb des Probenträgers zu gewährleisten oder anzupassen. Die Porengröße der Abdeckplatte kann sodann unabhängig von den Sterilitätsanforderungen gewählt werden. Als Abdeckplatte kann sodann beispielsweise ein textiles Material, ein Schwamm oder ein anderer zur Flüssigkeitsspeicherung geeigneter Stoff z. B. in Form poröser Flocken oder Kügelchen verwendet werden.Particularly preferred is the provision of a porous film in addition to a cover plate. Here, the film is preferably arranged between the cover plate and the receiving part. This makes it possible to ensure or adjust the sterility within the sample carrier by a suitable choice of the pore size of the film. The pore size of the cover plate can then be chosen independently of the sterility requirements. As a cover plate can then, for example, a textile material, a sponge or other suitable for liquid storage material z. B. in the form of porous flakes or beads are used.

Weiterhin kann die Gasdurchlässigkeit des Deckels durch die verwendete Folie gesteuert werden.Furthermore, the gas permeability of the lid can be controlled by the film used.

Die Porendurchmesser der porösen Abdeckplatte und/ oder der Folie sind vorzugsweise kleiner als 0,5 µm, insbesondere kleiner als 0,2 µm. Hierdurch kann die Sterilität innerhalb des Probenträgers sichergestellt werden. Überraschenderweise wird eine ausreichende Sterilität auch mit größeren Porendurchmessern erreicht.The pore diameter of the porous cover plate and / or the film are preferably less than 0.5 .mu.m, in particular less than 0.2 .mu.m. As a result, the sterility can be ensured within the sample carrier. Surprisingly enough sterility is achieved even with larger pore diameters.

Die Erfindung betrifft ferner einen Deckel für einen Probenträger, insbesondere eine Titerplatte. Der erfindungsgemäße Deckel weist vorzugsweise eine poröse Abdeckplatte auf, die zur Dampfdruckregulierung mit einer Flüssigkeit benetzbar ist. Der Deckel kann entsprechend den vorstehend beschriebenen bevorzugten Ausführungsformen des Probenträgers weitergebildet sein.The invention further relates to a lid for a sample carrier, in particular a titer plate. The lid according to the invention preferably has a porous cover plate which is wettable with a liquid for the purpose of regulating the vapor pressure. The cover may be developed according to the preferred embodiments of the sample carrier described above.

Ferner kann der Deckel zur Aufnahme von Elektroden dienen, die beispielsweise in einzelne Vertiefungen hineinreichen und die Wanderung von Probenbestandteilen in einem elektrischen Feld bewirken.Furthermore, the cover can serve for receiving electrodes which, for example, extend into individual recesses and cause the migration of sample components in an electric field.

Vorzugsweise weist der Deckel Sensoren auf. Mit Hilfe der Sensoren kann beispielsweise der Feuchtigkeitsgehalt in dem Hohlraum zwischen dem Deckel und dem Aufnahmeteil bestimmt werden. Durch eine entsprechende an die Sensoren angeschlossene Steuerung kann beispielsweise bei einem zu niedrigen Feuchtigkeitsgehalt automatisch eine erneute Befeuchtung des Deckels erfolgen. Ferner ist es möglich, die Sensoren derart anzuordnen, dass der Feuchtigkeitsgehalt der Abdeckplatte selbst bestimmt werden kann. Es ist ebenso vorteilhaft, Sensoren zur Bestimmung von Substanz-Anteilen in dem Hohlraum vorzusehen. Mit derartigen Sensoren kann beispielsweise der CO2-Gehalt in dem Hohlraum bestimmt werden.Preferably, the lid has sensors. With the help of the sensors, for example, the moisture content in the cavity between the lid and the receiving part can be determined. By a corresponding control connected to the sensors, a renewed moistening of the lid can be carried out automatically, for example, if the moisture content is too low. Furthermore, it is possible to arrange the sensors such that the moisture content of the cover plate itself can be determined. It is also advantageous to provide sensors for determining substance contents in the cavity. With such sensors, for example, the CO 2 content in the cavity can be determined.

Ferner weist der Deckel vorzugsweise Griffprismen auf, so dass der Deckel automatisch von einem Greifarm gehandhabt werden kann. Die Griffprismen sowie die Abmessungen des Probenträgers entsprechen vorzugsweise den Abmessungen und der Lage der Griffprismen bei dem zusammen mit dem Deckel gehandhabten Probenträger. Es ist somit möglich, sowohl den Deckel als auch das Aufnahmeteil des Probenträgers mit demselben Greifarm zu handhaben.Furthermore, the lid preferably has handle prisms, so that the lid can be handled automatically by a gripper arm. The handle prisms and the dimensions of the sample carrier preferably correspond to the dimensions and the position of the handle prisms in the case of the sample carrier handled together with the lid. It is thus possible to handle both the lid and the receiving part of the sample carrier with the same gripping arm.

Sofern es sich bei dem Probenträger um einen Chip handelt, handelt es sich vorzugsweise bei den in dem Chip vorgesehenen Kanälen um Mikro- oder Nannokanäle, deren Breite und Höhe im Bereich von 1 µm bis 1 mm liegt. Innerhalb der Kanäle können beispielsweise auch Elektroden angeordnet sein.If the sample carrier is a chip, it is preferable for the channels provided in the chip to be micro- or nano-channels whose width and height are in the range from 1 μm to 1 mm. For example, electrodes can also be arranged within the channels.

Der erfindungsgemäße Probenträger ist insbesondere zur Aufbewahrung von Reagenzien, zur Aufbewahrung von Proben, wie Zellen oder anderen Probesubstanzen, zur Trennung von Flüssigkeit, beispielsweise mittels CE oder CEC, zur Manipulation der Proben, beispielsweise durch Elektroporation, Elektropermeation oder Hybridisierung u.dgl. verwendet werden.The sample carrier according to the invention is in particular for the storage of reagents, for the storage of samples, such as cells or other sample substances, for the separation of liquid, for example by means of CE or CEC, for the manipulation of Samples, for example, by electroporation, electropermeation or hybridization and the like. be used.

Es ist ferner möglich, dass der Probenträger eine durchsichtige Glasplatte o.dgl. enthält, so dass die Proben mittels Fluoreszenz-Korrelations-Spektroskopie, insbesondere unter Verwendung von konvokalen Optiken eingesetzt werden kann. Insbesondere kann bei derartigen Probenträgern auch eine optische Pinzette zum Halten von Partikeln eingesetzt werden.It is also possible that the sample carrier or the like a transparent glass plate. so that the samples can be used by fluorescence correlation spectroscopy, especially using convocal optics. In particular, in such sample carriers and an optical tweezers for holding particles can be used.

Die Erfindung umfasst ferner ein Verfahren zur Untersuchungsvorbereitung von chemischen und/ oder biologischen Kleinstproben. Hierbei werden Kleinstproben mit einem Volumen von vorzugsweise 0,2 - 5 µl in Vertiefungen des Probenträgers, insbesondere in Vertiefungen der Titerplatte eingebracht. Anschließend wird der Probenträger mit einem Deckel, der vorzugsweise eine poröse Abdeckplatte aufweist, verschlossen. Die poröse Abdeckplatte kann wie vorstehend beschrieben vorteilhaft weitergebildet sein. Anschließend wird erfindungsgemäß die poröse Abdeckplatte mit einer Flüssigkeit benetzt. Hierdurch wird eine Dampfdruckregulierung in dem zwischen der Probenoberseite und dem Deckel ausgebildeten Hohlraum erreicht. Das erfindungsgemäße Verfahren weist die vorstehend beschriebenen Vorteile hinsichtlich der Verwendung eines Deckels mit poröser Abdeckplatte auf.The invention further comprises a method for the preparation of tests of chemical and / or biological micro samples. In this case, small samples with a volume of preferably 0.2 to 5 .mu.l in wells of the sample carrier, in particular in wells of the titer plate are introduced. Subsequently, the sample carrier is closed with a lid, which preferably has a porous cover plate. The porous cover plate can be advantageously developed as described above. Subsequently, according to the invention, the porous cover plate is wetted with a liquid. As a result, a vapor pressure regulation is achieved in the cavity formed between the sample top and the lid. The inventive method has the advantages described above with regard to the use of a lid with a porous cover plate.

Vorzugsweise wird der Deckel vor dem Verschließen des Probenträgers sterilisiert. Hierdurch ist vermieden, dass Keime beim Verschließen des Probenträgers in die Proben gelangen.Preferably, the lid is sterilized prior to sealing the sample carrier. This avoids that germs get into the samples when closing the sample carrier.

Vorzugsweise wird als Flüssigkeit ein PBS-Puffer mit mindestens 0,7 % Natriumchlorid verwendet. Vorzugsweise wird eine Pufferlösung verwendet, die im Wesentlichen denselben Dampfdruck aufweist, wie die in den Vertiefungen enthaltenen Proben. Es ist ferner vorteilhaft, eine Flüssigkeit mit einem pH-Wert von 7 - 8, insbesondere von 7,5, zu verwenden.Preferably, the liquid used is a PBS buffer containing at least 0.7% of sodium chloride. Preferably, a buffer solution is used which has substantially the same vapor pressure, like the samples contained in the wells. It is also advantageous to use a liquid having a pH of 7-8, in particular of 7.5.

Nachfolgend wird die Erfindung anhand einer bevorzugten Ausführungsform, unter Bezugnahme auf die anliegenden Zeichnungen näher erläutert.The invention will be explained in more detail below with reference to a preferred embodiment, with reference to the accompanying drawings.

Es zeigen:

Fig. 1
eine schematische Draufsicht auf einen erfindungsgemäßen Probenträger mit Deckel und
Fig. 2
einen Schnitt entlang der Linie II-II in Fig. 1.
Show it:
Fig. 1
a schematic plan view of a sample carrier according to the invention with lid and
Fig. 2
a section along the line II-II in Fig. 1st

Der in Fig. 1 sichtbare Deckel 10 weist eine poröse Abdeckplatte 12 auf, die von einem Halteteil 14 getragen ist. Bei der dargestellten Ausführungsform handelt es sich um ein rahmenförmiges Halteteil 14, das die Abdeckplatte 12 vollständig umgibt. Zur Fixierung der Abdeckplatte 12 in dem Halteteil 14 kann die Abdeckplatte 12 in das Halteteil 14 eingeklebt sein. Um die Lage genau zu definieren, sind in das Halteteil 14 Auflagen 16 (Fig. 2) eingebracht.The visible in Fig. 1 cover 10 has a porous cover plate 12 which is supported by a holding part 14. In the illustrated embodiment, it is a frame-shaped holding part 14 which completely surrounds the cover plate 12. For fixing the cover plate 12 in the holding part 14, the cover plate 12 may be glued into the holding part 14. In order to define the position exactly, supports 16 (FIG. 2) are introduced into the holding part 14.

Die Auflagen 16 sind im Querschnitt L-förmig und ragen von dem rahmenförmigen Halteteil 14 nach innen, so dass die Abdeckplatte 12 von oben in den Deckel 10 eingelegt werden kann und auf den Auflagen 16 liegt. Die Auflagen 16 sind vorzugsweise ebenfalls rahmenförmig, so dass sie vollständig entlang der inneren Kante 18 des Halteteils 14 verlaufen. Es können jedoch auch einzelne Auflagen 16 am inneren Umfang 18 des Rahmens verteilt angeordnet sein.The supports 16 are L-shaped in cross-section and protrude from the frame-shaped holding part 14 inwards, so that the cover plate 12 can be inserted from above into the lid 10 and lies on the supports 16. The pads 16 are preferably also frame-shaped so that they extend completely along the inner edge 18 of the holding part 14. However, individual pads 16 may be arranged distributed on the inner circumference 18 of the frame.

Ein Probenträger 20 (Fig. 2) weist ein rahmenförmiges Halteteil 22 mit einer rechteckigen Öffnung auf. In dieser ist ein Aufnahmeteil 24 mit Vertiefungen 26 angeordnet. In den Vertiefungen 26 sind die Proben untergebracht. Das Aufnahmeteil 24 besteht beispielsweise aus Plastik und weist als Vertiefungen 26 Durchgangsöffnungen auf. Diese sind auf der Unterseite, vorzugsweise mit einer Glasplatte 28, verschlossen.A sample carrier 20 (FIG. 2) has a frame-shaped holding part 22 with a rectangular opening. In this a receiving part 24 is arranged with recesses 26. In the wells 26, the samples are housed. The receiving part 24 consists for example of plastic and has recesses 26 through openings. These are on the bottom, preferably with a glass plate 28, closed.

Um den Deckel 10 lagegenau auf dem Probenträger 20 fixieren zu können, weist der Deckel 10 an der Abdeckplatte 12 oder dem Halteteil 14 eine in Richtung des Aufnahmeteils 24 weisende Dichtlippe 30 auf. Im dargestellten Ausführungsbeispiel ist die Dichtlippe 30 über die Auflage 16 mit dem Halteteil 14 verbunden. Es handelt sich im dargestellten Ausführungsbeispiel um eine bevorzugte Ausführungsform in der die Dichtlippe vollständig entlang des inneren Umfangs 32 des Probenträgers 20 verläuft. Die Dichtlippe 30 ist somit entsprechend der Öffnung in dem rahmenförmigen Halteteil 22 rechteckig.In order to be able to fix the cover 10 accurately positioned on the sample carrier 20, the cover 10 on the cover plate 12 or the holding part 14 in the direction of the receiving part 24 facing sealing lip 30. In the illustrated embodiment, the sealing lip 30 is connected via the support 16 with the holding part 14. In the exemplary embodiment shown, this is a preferred embodiment in which the sealing lip extends completely along the inner circumference 32 of the sample carrier 20. The sealing lip 30 is thus rectangular according to the opening in the frame-shaped holding part 22.

Zwischen einer Unterseite 34 der Abdeckplatte 12 und einer Oberseite 36 des Aufnahmeteils 24 ist ein Hohlraum 38 ausgebildet. In dem Hohlraum 38 bildet sich auf Grund sehr geringer Verdunstung von Flüssigkeit aus den Vertiefungen 26 sowie aufgrund der hauptsächlichen Verdunstung der in der porösen Abdeckplatte 12 vorgesehenen Flüssigkeit ein Dampfdruck.Between a bottom 34 of the cover plate 12 and a top 36 of the receiving part 24, a cavity 38 is formed. In the cavity 38 forms due to very low evaporation of liquid from the wells 26 and due to the main evaporation of the liquid provided in the porous cover plate 12, a vapor pressure.

Der untere Teil des Hohlraums 38 bildet eine Ausnehmung in dem Probenträger 20. In diese Ausnehmung greift die Dichtlippe 30 zur Lagefixierung ein.The lower part of the cavity 38 forms a recess in the sample carrier 20. In this recess engages the sealing lip 30 for fixing the position.

Claims (17)

  1. A sample carrier, in particular a titer plate, comprising
    a receiving element (24) provided with deepened portions (26) for receiving very small samples, and
    a cover (10) for closing said receiving element (24) such that between a sample surface and said cover (10) a cavity (38) is defined,
    characterized in that
    said cover (10) comprises a liquid-wettable porous cover plate (12) for receiving and delivering a liquid, such that a liquid-saturated atmosphere is substantially maintained in the cavity (38) at changing ambient conditions, and that a gas exchange through said porous cover plate (12) is allowed for,
    wherein said cavity (38) is defined between a lower side (34) of said cover plate (12) and an upper side (36) of said receiving element (24).
  2. The sample carrier according to claim 1, characterized in that at changing ambient conditions the saturated atmosphere deviates from a maximum saturation level by less than 5 %, in particular by less than 2 %.
  3. The sample carrier according to claim 1 or 2, characterized in that the cover (10) comprises a porous film.
  4. The sample carrier according to claim 3, characterized in that the porous film is arranged in parallel to the cover plate (12), preferably between said cover plate (12) and the receiving element (24).
  5. The sample carrier according to any one of claims 1-4, characterized in that the porous cover plate (12) and/or the film are supported by a holding element (14) surrounding said cover plate (12) in a frame-like manner.
  6. The sample carrier according to any one of claims 1-5, characterized in that at the cover (10) and/or the holding element (14) a sealing lip (30) facing towards the receiving element (24) is provided.
  7. The sample carrier according to claim 6, characterized in that the sealing lip (30) is closed in itself and preferably extends along the edge (32) of the receiving element (24).
  8. The sample carrier according to claim 6 or 7, characterized in that the receiving element (24) is surrounded by an elevated frame (22) such that a recess is defined in which the sealing lip (30) engages for position-fixing purposes.
  9. The sample carrier according to any one of claims 1-8, characterized in that the pores of the porous cover plate (12) and/or the film have a mean pore diameter of less than 0.5 µm, in particular less than 0.2 µm.
  10. The sample carrier according to any one of claims 1-9, characterized in that the cover plate (12) is made of ceramic material or glass.
  11. The sample carrier according to any one of claims 1-10, characterized in that the cover (10) comprises a sensor, in particular for determining the moisture content and/or the proportion of substance in the cavity (38).
  12. A cover for a sample carrier, in particular a titer plate, characterized by a porous cover plate (12) which is adapted to be wetted with a liquid for vapor pressure-regulating purposes.
  13. A method for preparing an analysis of very small chemical and/or biological samples, the method comprising the following steps:
    feeding said very small samples to a sample carrier, in particular placing said very small samples in deepened portions (26) of a titer plate,
    closing said sample carrier with a cover (10), wherein said cover (10) is configured such that at changing ambient conditions a saturated atmosphere is substantially maintained in the cavity (38) between said cover and a sample carrier surface, and
    wetting said cover (10) comprising a porous cover plate (12) with a liquid for atmosphere-regulating purposes.
  14. The method according to claim 13, wherein the cover (10) is sterilized prior to closing the sample carrier.
  15. The method according to claim 13 or 14, characterized in that a PBS buffer with at least 0.7 % sodium chloride is used as a liquid.
  16. The method according to any one of claims 13-15, characterized in that a liquid with a pH of 7-8, in particular 7.5, is used.
  17. The method according to any one of claims 13-16, wherein prior to or subsequent to introducing the sample, a reagent or nutrient solution is placed in the deepened portions (26).
EP01997350A 2000-11-23 2001-11-23 Sample support, cover for a sample support and analysis preparation method Expired - Lifetime EP1341611B1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10058108 2000-11-23
DE10058108A DE10058108A1 (en) 2000-11-23 2000-11-23 Sample support used for investigating very small chemical and/or biological samples, comprises a receiving part for very small samples, and a lid for the support
PCT/EP2001/013651 WO2002041993A1 (en) 2000-11-23 2001-11-23 Sample support, cover for a sample support and analysis preparation method

Publications (2)

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EP1341611A1 EP1341611A1 (en) 2003-09-10
EP1341611B1 true EP1341611B1 (en) 2007-09-26

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EP (1) EP1341611B1 (en)
AT (1) ATE374077T1 (en)
DE (2) DE10058108A1 (en)
WO (1) WO2002041993A1 (en)

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EP1341611A1 (en) 2003-09-10
WO2002041993A1 (en) 2002-05-30
DE10058108A1 (en) 2002-06-06
DE50113066D1 (en) 2007-11-08
ATE374077T1 (en) 2007-10-15

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