WO2000029109A1 - Sample holder for serial analysis of liquid samples - Google Patents

Sample holder for serial analysis of liquid samples Download PDF

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Publication number
WO2000029109A1
WO2000029109A1 PCT/EP1999/007281 EP9907281W WO0029109A1 WO 2000029109 A1 WO2000029109 A1 WO 2000029109A1 EP 9907281 W EP9907281 W EP 9907281W WO 0029109 A1 WO0029109 A1 WO 0029109A1
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WO
WIPO (PCT)
Prior art keywords
sample carrier
carrier according
substrate part
sample
measuring chambers
Prior art date
Application number
PCT/EP1999/007281
Other languages
German (de)
French (fr)
Inventor
Hermann Leistner
Dieter Schimkat
Gerhard Hotz
Heiner KÖHLER
Original Assignee
Stratec Biomedical Systems Ag
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Publication date
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Publication of WO2000029109A1 publication Critical patent/WO2000029109A1/en

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Classifications

    • 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
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0605—Metering of fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/04—Closures and closing means
    • B01L2300/041—Connecting closures to device or container
    • B01L2300/044—Connecting closures to device or container pierceable, e.g. films, membranes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0803—Disc shape
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0864—Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0409—Moving fluids with specific forces or mechanical means specific forces centrifugal forces
    • 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
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • 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
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502738—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by integrated valves

Definitions

  • the invention relates to a sample carrier for carrying out series analyzes on liquid samples with a substrate part which has a multiplicity of cavities for receiving liquid samples and optionally reagents.
  • sample analyzes In immunological diagnostics, gene analysis, microbiology, environmental analysis, clinical chemistry and other areas, it is often necessary to carry out a large number of sample analyzes automatically, using optical measurement methods such as photometry or luminometry in particular.
  • optical measurement methods such as photometry or luminometry in particular.
  • microtiter or microtest plates as sample carriers, in which a large number of samples can be placed in cavities or cells arranged in a matrix. It is usually necessary to align the individual cavities sequentially by means of a positioning device with respect to a measuring or processing station.
  • devices have already been developed that enable parallel processing through a large number of addition and measuring stations. However, the expenditure on equipment for this is considerable, especially if uniform sample processing is to be ensured.
  • the object of the invention is to develop a sample carrier of the type mentioned at the outset in such a way that a time and space-optimized process and measurement sequence with the possibility of simplified automation is ensured. Extensive miniaturization should also be made possible, in particular for processing small amounts of samples.
  • the invention is based on the idea of simultaneously distributing a liquid from a central feed chamber into a multiplicity of radially surrounding measuring chambers or reaction chambers. Accordingly, it is proposed according to the invention that the cavities are arranged as measuring chambers in an annular zone of the substrate part at an angular distance from one another, that in a central region of the substrate part a feed chamber to which a liquid sample is applied is arranged concentrically with the ring zone, and that the feed chamber with the Measuring chambers communicated via a connecting channel. This allows a test liquid to be easily divided into many
  • the substrate part is formed by a circular-cylindrical substrate disk, that the feed chamber and the measuring chambers are arranged coaxially to the central axis of the substrate disk, and that the connecting channels in the substrate disk extend radially. It is also advantageous if the measuring chambers are arranged symmetrically distributed with respect to the central axis of the substrate wafer.
  • the feed chamber is advantageously formed by a central recess in the substrate part which is designed as a cylindrical blind hole. To completely fill the measuring chambers, it should be ensured that the volume of the feed chamber is greater than or equal to the total volume of the measuring chambers.
  • the feed chamber, the connecting channels and the measuring chambers are open at the edges as recesses on a planar surface of the substrate part, and if at least the connecting channels and the measuring chambers are covered in a liquid-tight manner by a cover element on the planar surface which is firmly connected to the substrate part.
  • a cover element is formed by a flat material which forms a piercing membrane for sample injection in the area of the feed chamber.
  • the cover element it is advantageous for the cover element to be formed by a cover plate, which in the region of the feed chamber preferably faces the opening of the Feed chamber has widening breakthrough for sample application.
  • the substrate part has an engagement part which can be positively connected to a rotary drive for rotation about its central axis.
  • the sample liquid can thus be distributed in a metered manner under the influence of centrifugal force, and the measuring chambers can be positioned in a simple manner with only one degree of freedom.
  • the engagement part is formed by a toothed ring region toothed on the circumferential side or by an axial gear wheel extension of the substrate part.
  • the engagement part is formed by a recess designed for the engagement of a rotary driver.
  • the connecting channels have a mouth opening which widens towards the measuring chamber and preferably opens into the upper region thereof.
  • the measuring chambers are connected to an associated additional chamber via an additional channel.
  • the cover plate on its broad side facing away from the substrate part, separates an optionally sector-wise te ring recess, which opens into the additional chambers via an axial opening.
  • a controllable flow through the measuring chambers can be made possible in that the measuring chambers each have an outlet channel, which is preferably siphon-like and opens out on a lateral surface of the substrate part.
  • the substrate part advantageously consists of plastic, glass or a semiconductor material as a molded part.
  • FIG. 1 shows a disk-shaped sample carrier for performing series analyzes in a first embodiment with the cover part removed in an axial plan view;
  • Fig. 2 is a partially sectioned side view of the closed sample holder along the line 2-2 of Fig. 1;
  • FIG. 3 shows a further exemplary embodiment of a sample carrier with the cover plate shown partially broken off in plan view
  • FIG. 4 shows an axial section of the sample carrier along the section line 4 - 4 of FIG. 3; 5 and 6 show the sample carrier according to FIG. 3 equipped with a gear extension in a side view and an end view from below;
  • FIG. 7 shows a further exemplary embodiment of a sample carrier in a partial plan view with the cover part removed.
  • FIG. 8 shows an embodiment of a sample carrier with a recess designed for the engagement of a rotary driver in accordance with the illustration according to FIG. 6.
  • the sample carriers shown in the drawing are formed by a disk-shaped molded part or substrate part 10, which on its planar upper side 12 is firmly connected or can be connected to a cover element 14, 14 '.
  • the substrate part 10 is provided in an axial central region 16 with a feed chamber or central recess 18, which can be acted upon as a cylindrical blind hole via a feed opening on the top 12 of the substrate part with a liquid sample.
  • the substrate part 10 has a peripheral ring zone 20
  • the measuring chambers 22 have a clear cross section elongated in the radial direction and are open at the edges as recesses on the upper side of the substrate part 12.
  • the feed chamber 18 is connected to the measuring chambers 22 via a connecting channel 26.
  • the connecting channels 26 run as recesses on the upper side 12 of the substrate part 10 starting from the feed chamber 18 in a straight line in the radial direction and have an opening 28 which widens towards the respective measuring chamber 22.
  • the cover element 14 for the liquid-tight covering of the feed chamber 18 as well as the measuring chambers 22 and connecting channels 26 is formed by a flat material or foil material 30, which is integrally connected flat to the top 12 of the substrate part 10 and in the opening area of the feed chamber 18 forms a piercing membrane for injecting a liquid sample.
  • the measuring chambers 22 are each connected to an associated additional chamber 34 via an additional channel 32.
  • the additional chambers 34 are arranged between the connecting channels 26 in a space-saving manner. On the one hand, they enable the air displaced when the liquid enters the measuring chambers 22 to be taken through or on the other hand, and on the other hand allow the measuring chambers 22 to be additionally charged with a washing liquid, for example, in the manner described below.
  • a disk-shaped cover plate 14 ' is provided as a cover element to close the recesses 22, 26, 32, 34. This has an opening 36, which widens conically towards the opening of the feed chamber 18, for the sample applicators.
  • the cover plate 14 is provided on its broad side 38 facing away from the substrate part 10 with an annular recess 40, which opens into an additional chamber 34 located below it via an axial opening 42 in each case.
  • a liquid can be distributed into the additional chambers 34 and from there into the measuring chambers 22 by acting on the annular recess 40.
  • the ring recess 40 it is also possible for the ring recess 40 to be separated in sectors for separate liquid distribution.
  • the connecting channels 26 and, if appropriate, the additional channels 32 are designed as capillary tubes.
  • the substrate part 10 has an engagement part which can be positively connected to a rotary drive (not shown) for rotation about its central axis 24. In this way, a liquid from the feed chamber 14 under centrifugal force, which can be adjusted via the rotational speed, can be conveyed into the measuring chambers 22 in a defined manner.
  • the engagement part can be formed by an axially toothed wheel extension 44 of the substrate part 10 that is toothed on the circumference.
  • the extension 44 can also serve to receive a bottom section of the feed chamber 18 (FIG. 4).
  • FIG. form has the substrate part 10 instead of a gear extension on an axially stepped bottom portion 46 which is provided with a transverse recess 48 for the engagement of a rotary driver, not shown.
  • the outlet channel 50 can be designed siphon-like or S-shaped in order to allow a liquid passage only when a certain centrifugal force is exceeded.
  • the substrate part 10 and the cover plate 14 ' it is expedient if they are designed as one-piece molded parts, in particular injection molded plastic parts.
  • a transparent material with the desired optical properties can be used for optical measurements, glass or quartz also being suitable.
  • the measuring chambers can, for example, have a volume of less than 100 microliters, with sufficient filling ensuring that the volume of the feed chamber is greater than or equal to the total volume of the measuring chambers.
  • Another advantageous variant can consist in that one or several antechambers are arranged for a gradual reaction process.

Abstract

The invention relates to a sample holder used for carrying out serial analysis of liquid samples and comprising a substrate part (10) having a plurality of recesses (22) for receiving liquid samples and optionally reagents. The aim of the invention is to optimise process and measuring conduct. For that purpose, the recesses are placed at an angular distance from each other in an annular area (20) of said substrate part (10) and are in the form of measuring chambers (22). In addition, a distribution chamber (18) which can be fed with liquid samples is concentrically placed with the annular area (20) within a central area (16) of the substrate part (10). Said distribution chamber (18) is in communication with the measuring chambers (22) through a respective connecting channel (26).

Description

PROBENTRÄGER FÜR REIHENANALYSEN AN FLÜSSIGPROBENSAMPLE CARRIER FOR SERIES ANALYSIS ON LIQUID SAMPLES
Beschreibungdescription
Die Erfindung betrifft einen Probenträger zur Durchführung von Reihenanalysen an Flüssigproben mit einem Substratteil, das eine Vielzahl von Kavitäten zur Aufnahme von Flüssigproben und gegebenenfalls Reagenzien aufweist .The invention relates to a sample carrier for carrying out series analyzes on liquid samples with a substrate part which has a multiplicity of cavities for receiving liquid samples and optionally reagents.
In der immunologischen Diagnostik, Genanalyse, Mikrobiologie, Umweltanalytik, klinischen Chemie und weiteren Bereichen ist es häufig erforderlich, eine Vielzahl von Probenanalysen automatisch durchzuführen, wobei vor allem optische Meßverfahren wie Photometrie oder auch Luminome- trie zum Einsatz kommen. Zu diesem Zweck ist es bekannt, sogenannte Mikrotiter- bzw. Mikrotestplatten als Probenträger einzusetzen, bei denen in matrixartig angeordneten Kavitäten bzw. Näpfchen eine Vielzahl von Proben vorge- legt werden können. Dabei ist es in der Regel erforderlich, die einzelnen Kavitäten sequentiell mittels einer Positioniervorrichtung bezüglich einer Meß- oder Verarbeitungsstation auszurichten. Alternativ wurden bereits Geräte entwickelt, die durch eine Vielzahl von Zugabe- und Meßstationen eine Parallelverarbeitung ermöglichen. Der apparative Aufwand hierfür ist jedoch beträchtlich, insbesondere wenn eine einheitliche Probenverarbeitung sichergestellt sein soll. Außerdem sind einer gewünschten Miniaturisierung durch die dann erschwerte Handhabung der Mikrotiterplatten Grenzen gesetzt. Ausgehen hiervon liegt der Erfindung die Aufgabe zugrunde, einen Probenträger der eingangs genannten Art dahingehend zu entwickeln, daß ein zeitlich und räumlich optimierter Prozeß- und Meßablauf mit der Möglichkeit zur vereinfachten Automatisierung gewährleistet ist. Weiter soll insbesondere zur Verarbeitung kleiner Probenmengen eine weitgehende Miniaturisierung ermöglicht werden.In immunological diagnostics, gene analysis, microbiology, environmental analysis, clinical chemistry and other areas, it is often necessary to carry out a large number of sample analyzes automatically, using optical measurement methods such as photometry or luminometry in particular. For this purpose it is known to use so-called microtiter or microtest plates as sample carriers, in which a large number of samples can be placed in cavities or cells arranged in a matrix. It is usually necessary to align the individual cavities sequentially by means of a positioning device with respect to a measuring or processing station. Alternatively, devices have already been developed that enable parallel processing through a large number of addition and measuring stations. However, the expenditure on equipment for this is considerable, especially if uniform sample processing is to be ensured. In addition, a desired miniaturization is limited by the then difficult handling of the microtiter plates. Proceeding from this, the object of the invention is to develop a sample carrier of the type mentioned at the outset in such a way that a time and space-optimized process and measurement sequence with the possibility of simplified automation is ensured. Extensive miniaturization should also be made possible, in particular for processing small amounts of samples.
Zur Lösung dieser Aufgabe wird die im Patentanspruch 1 angegebene Merkmalskombination vorgeschlagen. Vorteilhafte Ausgestaltungen und Weiterbildungen der Erfindung ergeben sich aus den abhängigen Ansprüchen.To achieve this object, the combination of features specified in claim 1 is proposed. Advantageous refinements and developments of the invention result from the dependent claims.
Die Erfindung geht von dem Gedanken aus, eine Flüssigkeit aus einer zentralen Aufgabekammer simultan in eine Vielzahl von radial umgebenden Meßkammern bzw. Reaktionskammern zu verteilen. Dementsprechend wird nach der Erfindung vorgeschlagen, daß die Kavitäten als Meßkammern in einer Ringzone des Substratteils im Winkelabstand vonein- ander angeordnet sind, daß in einem Zentralbereich des Substratteils eine mit einer Flüssigprobe beaufschlagbare Aufgabekammer konzentrisch mit der Ringzone angeordnet ist, und daß die Aufgabekammer mit den Meßkammern über jeweils einen Verbindungskanal kommuniziert. Damit läßt sich eine Testflussigkeit auf einfache Weise in vieleThe invention is based on the idea of simultaneously distributing a liquid from a central feed chamber into a multiplicity of radially surrounding measuring chambers or reaction chambers. Accordingly, it is proposed according to the invention that the cavities are arranged as measuring chambers in an annular zone of the substrate part at an angular distance from one another, that in a central region of the substrate part a feed chamber to which a liquid sample is applied is arranged concentrically with the ring zone, and that the feed chamber with the Measuring chambers communicated via a connecting channel. This allows a test liquid to be easily divided into many
Meßkammern eindosieren. Durch die ringförmige Meßkammeranordnung wird ein paralleler Prozeßablauf ermöglicht. Zugleich wird die Positionierung bezüglich einer Verarbeitungsstelle auch bei miniaturisierter Ausbildung auf- grund einer möglichen Drehbewegung vereinfacht. In baulich vorteilhafter Ausgestaltung ist es vorgesehen, daß das Substratteil durch eine kreiszylindrische Substratscheibe gebildet ist, daß die Aufgabekammer und die Meßkammern koaxial zu der Zentralachse der Substrat- scheibe angeordnet sind, und daß die Verbindungskanäle in der Substratscheibe sich radial erstrecken. Dabei ist es weiter günstig, wenn die Meßkammern bezüglich der Zentralachse der Substratscheibe symmetrisch verteilt angeordnet sind.Add the measuring chambers. A parallel process sequence is made possible by the annular measuring chamber arrangement. At the same time, the positioning with respect to a processing point is simplified even with a miniaturized design due to a possible rotary movement. In a structurally advantageous embodiment, it is provided that the substrate part is formed by a circular-cylindrical substrate disk, that the feed chamber and the measuring chambers are arranged coaxially to the central axis of the substrate disk, and that the connecting channels in the substrate disk extend radially. It is also advantageous if the measuring chambers are arranged symmetrically distributed with respect to the central axis of the substrate wafer.
Vorteilhafterweise ist die Aufgabekammer durch eine als zylindrisches Sackloch ausgebildete Zentralausnehmung des Substratteils gebildet. Dabei sollte zur vollständigen Befüllung der Meßkammern sichergestellt sein, daß das Vo- lumen der Aufgabekammer größer oder gleich dem Gesamtvolumen der Meßkammern ist .The feed chamber is advantageously formed by a central recess in the substrate part which is designed as a cylindrical blind hole. To completely fill the measuring chambers, it should be ensured that the volume of the feed chamber is greater than or equal to the total volume of the measuring chambers.
In herstellungstechnischer Hinsicht ist es von Vorteil, wenn die Aufgabekammer, die Verbindungskanäle und die Meßkammern als Ausnehmungen an einer Planarflache des Substratteils randoffen sind, und wenn zumindest die Verbindungskanäle und die Meßkammern durch ein mit dem Substratteil fest verbundenes Abdeckelement an der Planarflache flüssigkeitsdicht abgedeckt sind. Dies kann dadurch erfolgen, daß das Abdeckelement durch ein Flachmaterial gebildet ist, welches im Bereich der Aufgabekammer eine Durchstechmembran zur Probeninjektion bildet. Alternativ ist es vorteilhaft, das Abdeckelement durch eine Deckelplatte gebildet ist, welche im Bereich der Aufgabekammer einen vorzugsweise sich zu der Öffnung der Aufgabekammer hin erweiternden Durchbruch zur Probenaufgabe aufweist.From a manufacturing point of view, it is advantageous if the feed chamber, the connecting channels and the measuring chambers are open at the edges as recesses on a planar surface of the substrate part, and if at least the connecting channels and the measuring chambers are covered in a liquid-tight manner by a cover element on the planar surface which is firmly connected to the substrate part. This can be done in that the cover element is formed by a flat material which forms a piercing membrane for sample injection in the area of the feed chamber. Alternatively, it is advantageous for the cover element to be formed by a cover plate, which in the region of the feed chamber preferably faces the opening of the Feed chamber has widening breakthrough for sample application.
Gemäß einer besonders bevorzugten Ausgestaltung der Er- findung weist das Substratteil zur Rotation um seine Zentralachse eine formschlüssig mit einem Drehantrieb verbindbare Eingriffspartie auf. Damit läßt sich die Probenflüssigkeit unter Fliehkrafteinwirkung dosiert verteilen, und die Meßkammern können auf einfache Weise mit nur ei- nem Freiheitsgrad positioniert werden. Eine vorteilhafte Ausführung sieht vor, daß die Eingriffspartie durch einen umfangsseitig gezahnten Zahnringbereich oder axialen Zahnradfortsatz des Substratteils gebildet ist. Alternativ kommt es auch in Betracht, daß die Eingriffspartie durch eine für den Eingriff eines Drehmitnehmers ausgebildete Ausnehmung gebildet ist .According to a particularly preferred embodiment of the invention, the substrate part has an engagement part which can be positively connected to a rotary drive for rotation about its central axis. The sample liquid can thus be distributed in a metered manner under the influence of centrifugal force, and the measuring chambers can be positioned in a simple manner with only one degree of freedom. An advantageous embodiment provides that the engagement part is formed by a toothed ring region toothed on the circumferential side or by an axial gear wheel extension of the substrate part. Alternatively, it is also contemplated that the engagement part is formed by a recess designed for the engagement of a rotary driver.
Ein selbsttätiger Transport der Probenflüssigkeit unter Kapillarwirkung kann dadurch erreicht werden, daß die Verbindungskanäle als Kapillarröhren ausgebildet sind.Automatic transport of the sample liquid under capillary action can be achieved in that the connecting channels are designed as capillary tubes.
Für eine optimale Probenverteilung in den Meßkammern ist es günstig, wenn die Verbindungskanäle eine sich zu der Meßkammer hin erweiternde, vorzugsweise in deren oberen Bereich mündende Mündungsδffnung aufweisen.For optimal sample distribution in the measuring chambers, it is expedient if the connecting channels have a mouth opening which widens towards the measuring chamber and preferably opens into the upper region thereof.
Um komplexere Reaktionsabläufe steuern zu können, wird vorgeschlagen, daß die Meßkammern über einen Zusatzkanal mit jeweils einer zugeordneten Zusatzkammer verbunden sind. In diesem Zusammenhang ist es weiter günstig, wenn die Deckelplatte an ihrer von dem Substratteil abgewandten Breitseite eine gegebenenfalls sektorweise abgetrenn- te Ringausnehmung aufweist, welche über jeweils einen Axialdurchbruch in die Zusatzkammern mündet.In order to be able to control more complex reaction sequences, it is proposed that the measuring chambers are connected to an associated additional chamber via an additional channel. In this context, it is further advantageous if the cover plate, on its broad side facing away from the substrate part, separates an optionally sector-wise te ring recess, which opens into the additional chambers via an axial opening.
Eine steuerbarer Durchfluß durch die Meßkammern kann da- durch ermöglicht werden, daß die Meßkammern jeweils einen vorzugsweise siphonartig ausgebildeten, an einer Mantelfläche des Substratteils mündenden Auslaßkanal aufweisen.A controllable flow through the measuring chambers can be made possible in that the measuring chambers each have an outlet channel, which is preferably siphon-like and opens out on a lateral surface of the substrate part.
Vorteilhafterweise besteht das Substratteil als Formteil aus Kunststoff, Glas oder einem Halbleitermaterial.The substrate part advantageously consists of plastic, glass or a semiconductor material as a molded part.
Im folgenden wird die Erfindung anhand der in der Zeichnung in schematischer Weise dargestellten Ausführungsbeispiele näher erläutert . Es zeigenThe invention is explained in more detail below on the basis of the exemplary embodiments shown schematically in the drawing. Show it
Fig. 1 einen scheibenförmigen Probenträger zur Durchführung von Reihenanalysen in einer ersten Aus- führungsform bei abgenommenem Abdeckteil in axialer Draufsicht;1 shows a disk-shaped sample carrier for performing series analyzes in a first embodiment with the cover part removed in an axial plan view;
Fig. 2 eine teilweise geschnittene Seitenansicht des geschlossenen Probenträgers entsprechend der Linie 2 - 2 der Fig. 1 ;Fig. 2 is a partially sectioned side view of the closed sample holder along the line 2-2 of Fig. 1;
Fig. 3 ein weiteres Ausführungsbeispiel eines Probenträgers mit teilweise abgebrochen dargestellter Abdeckplatte in der Draufsicht;3 shows a further exemplary embodiment of a sample carrier with the cover plate shown partially broken off in plan view;
Fig. 4 einen Axialschnitt des Probenträgers entlang der Schnittlinie 4 - 4 der Fig. 3; Fig. 5 und Fig. 6 den mit einem Zahnradfortsatz ausgestatteten Probenträger nach Fig. 3 in einer Seitenansicht und einer Stirnseitenansicht von unten;FIG. 4 shows an axial section of the sample carrier along the section line 4 - 4 of FIG. 3; 5 and 6 show the sample carrier according to FIG. 3 equipped with a gear extension in a side view and an end view from below;
Fig. 7 ein weiteres Ausführungsbeispiel eines Probenträgers in einer ausschnittsweisen Draufsicht bei abgenommenem Abdeckteil ; und7 shows a further exemplary embodiment of a sample carrier in a partial plan view with the cover part removed; and
Fig. 8 eine Ausführungsform eines Probenträgers mit einer für den Eingriff eines Drehmitnehmers ausgebildeten Ausnehmung entsprechend der Darstellung nach Fig. 6.8 shows an embodiment of a sample carrier with a recess designed for the engagement of a rotary driver in accordance with the illustration according to FIG. 6.
Die in der Zeichnung dargestellten Probenträger sind durch ein scheibenförmiges Formteil bzw. Substratteil 10 gebildet, das an seiner planaren Oberseite 12 fest mit einem Abdeckelement 14 , 14 ' verbunden oder verbindbar ist. Das Substratteil 10 ist in einem axialen Zentralbereich 16 mit einer Aufgabekammer bzw. Zentralausnehmung 18 versehen, die als zylindrisches Sackloch über eine Aufgabeöffnung an der Oberseite 12 des Substratteils mit einer Flüssigprobe beaufschlagbar ist. Weiterhin weist das Substratteil 10 in einer peripheren Ringzone 20 eineThe sample carriers shown in the drawing are formed by a disk-shaped molded part or substrate part 10, which on its planar upper side 12 is firmly connected or can be connected to a cover element 14, 14 '. The substrate part 10 is provided in an axial central region 16 with a feed chamber or central recess 18, which can be acted upon as a cylindrical blind hole via a feed opening on the top 12 of the substrate part with a liquid sample. Furthermore, the substrate part 10 has a peripheral ring zone 20
Vielzahl von Kavitäten bzw. Meßkammern 22 auf, die in gleichem Winkelabstand voneinander bezüglich seiner Zentralachse 24 symmetrisch verteilt angeordnet sind. Die Meßkammern 22 weisen einen in radialer Richtung oval- langgestreckten lichten Querschnitt auf und sind als Ausnehmungen an der Substratteil-Oberseite 12 randoffen. Zur Verteilung der Flüssigprobe ist die Aufgabekammer 18 mit den Meßkammern 22 über jeweils einen Verbindungskanal 26 verbunden. Die Verbindungskanäle 26 verlaufen als Vertiefungen an der Oberseite 12 des Substratteils 10 ausgehend von der Aufgabekammer 18 geradlinig in radialer Richtung und weisen eine zu der jeweiligen Meßkammer 22 hin sich erweiternde Mündungsδffnung 28 auf.A plurality of cavities or measuring chambers 22, which are arranged symmetrically distributed at the same angular distance from one another with respect to its central axis 24. The measuring chambers 22 have a clear cross section elongated in the radial direction and are open at the edges as recesses on the upper side of the substrate part 12. to Distribution of the liquid sample, the feed chamber 18 is connected to the measuring chambers 22 via a connecting channel 26. The connecting channels 26 run as recesses on the upper side 12 of the substrate part 10 starting from the feed chamber 18 in a straight line in the radial direction and have an opening 28 which widens towards the respective measuring chamber 22.
Die vorstehend beschriebenen Merkmale sind bei allen in der Zeichnung dargestellten Ausführungsbeispielen verwirklicht, wobei funktionsgleiche Elemente mit denselben Bezugszeichen versehen sind. Bei der Ausführungsform nach Fig. 2 ist das Abdeckelement 14 zur flüssigkeitsdichten Abdeckung der Aufgabekammer 18 sowie der Meßkammern 22 und Verbindungskanäle 26 durch ein Flachmaterial bzw. Folienmaterial 30 gebildet, welches stoffschlüssig flächig mit der Oberseite 12 des Substratteils 10 verbunden ist und im Öffnungsbereich der Aufgabekammer 18 eine Durchstechmembran zur Injektion einer Flüssigprobe bildet.The features described above are implemented in all of the exemplary embodiments shown in the drawing, elements with the same function being provided with the same reference symbols. In the embodiment according to FIG. 2, the cover element 14 for the liquid-tight covering of the feed chamber 18 as well as the measuring chambers 22 and connecting channels 26 is formed by a flat material or foil material 30, which is integrally connected flat to the top 12 of the substrate part 10 and in the opening area of the feed chamber 18 forms a piercing membrane for injecting a liquid sample.
Bei der in Fig. 3 und 4 gezeigten Ausführungsform sind die Meßkammern 22 über jeweils einen Zusatzkanal 32 mit einer zugeordneten Zusatzkammer 34 verbunden. Die Zusatzkammern 34 sind in raumsparender Weise zwischen den Ver- bindungskanälen 26 angeordnet. Sie ermöglichen einerseits die Aufnahme bzw. Durchleitung der beim Flüssigkeitseintritt aus den Meßkammern 22 verdrängten Luft und erlauben andererseits eine zusätzliche Beaufschlagung der Meßkammern 22 beispielsweise mit einer Waschflüssigkeit in der nachstehend beschriebenen Weise. Zum Verschluß der Ausnehmungen 22, 26, 32, 34 ist eine scheibenförmige Deckelplatte 14' als Abdeckelement vorgesehen. Diese weist einen zu der Öffnung der Aufgabekammer 18 hin sich konisch erweiternden Durchbruch 36 zur Pro- benaufgäbe auf . Weiterhin ist die Deckelplatte 14 ' an ihrer von dem Substratteil 10 abgewandten Breitseite 38 mit einer Ringausnehmung 40 versehen, welche über jeweils einen Axialdurchbruch 42 in eine darunterliegende Zusatz- kammer 34 mündet. Auf diese Weise kann eine Flüssigkeit durch Beaufschlagung der Ringausnehmung 40 in die Zusatzkammern 34 und von dort in die Meßkammern 22 verteilt werden. Grundsätzlich ist es auch möglich, daß die Ringausnehmung 40 zur getrennten Flüssigkeitsverteilung sektorweise abgetrennt ist.In the embodiment shown in FIGS. 3 and 4, the measuring chambers 22 are each connected to an associated additional chamber 34 via an additional channel 32. The additional chambers 34 are arranged between the connecting channels 26 in a space-saving manner. On the one hand, they enable the air displaced when the liquid enters the measuring chambers 22 to be taken through or on the other hand, and on the other hand allow the measuring chambers 22 to be additionally charged with a washing liquid, for example, in the manner described below. A disk-shaped cover plate 14 'is provided as a cover element to close the recesses 22, 26, 32, 34. This has an opening 36, which widens conically towards the opening of the feed chamber 18, for the sample applicators. Furthermore, the cover plate 14 'is provided on its broad side 38 facing away from the substrate part 10 with an annular recess 40, which opens into an additional chamber 34 located below it via an axial opening 42 in each case. In this way, a liquid can be distributed into the additional chambers 34 and from there into the measuring chambers 22 by acting on the annular recess 40. In principle, it is also possible for the ring recess 40 to be separated in sectors for separate liquid distribution.
Zum selbsttätigen Transport der Flüssigprobe bzw. von Testflüssigkeiten kann es vorgesehen sein, daß die Verbindungskanäle 26 und gegebenenfalls die Zusatzkanäle 32 als Kapillarrδhren ausgebildet sind. Eine weitere Mδg- lichkeit besteht darin, daß das Substratteil 10 zur Rotation um seine Zentralachse 24 eine formschlüssig mit einem nicht gezeigten Drehantrieb verbindbare Eingriffspartie aufweist . Auf diese Weise kann eine Flüssigkeit aus der Aufgabekammer 14 unter Fliehkrafteinwirkung, welche über die Drehzahl einstellbar ist, definiert in die Meßkammern 22 gefördert werden. Wie in Fig. 5 und 6 gezeigt, kann die Eingriffspartie durch einen umfangsseitig gezahnten axialen Zahnradfortsatz 44 des Substratteils 10 gebildet sein. Der Fortsatz 44 kann zugleich dazu dienen, einen bodenseitigen Abschnitt der Aufgabekammer 18 aufzunehmen (Fig. 4) . Bei der in Fig. 8 gezeigten Ausführungs- form weist das Substratteil 10 anstelle eines Zahnradfortsatzes einen axial abgestuften Bodenabschnitt 46 auf, welcher mit einer Querausnehmung 48 für den Eingriff eines nicht gezeigten Drehmitnehmers versehen ist.For the automatic transport of the liquid sample or test liquids, it can be provided that the connecting channels 26 and, if appropriate, the additional channels 32 are designed as capillary tubes. A further possibility is that the substrate part 10 has an engagement part which can be positively connected to a rotary drive (not shown) for rotation about its central axis 24. In this way, a liquid from the feed chamber 14 under centrifugal force, which can be adjusted via the rotational speed, can be conveyed into the measuring chambers 22 in a defined manner. As shown in FIGS. 5 and 6, the engagement part can be formed by an axially toothed wheel extension 44 of the substrate part 10 that is toothed on the circumference. The extension 44 can also serve to receive a bottom section of the feed chamber 18 (FIG. 4). In the embodiment shown in FIG. form has the substrate part 10 instead of a gear extension on an axially stepped bottom portion 46 which is provided with a transverse recess 48 for the engagement of a rotary driver, not shown.
Zur Durchleitung von Flüssigkeiten durch die Meßkammern 22 können diese mit einem Auslaßkanal 50 verbunden sein, welcher an der Mantelfläche 52 des Substratteils 10 mündet. Der Auslaßkanal 50 kann dabei siphonartig bzw. S- förmig ausgebildet sein, um so einen Flüssigkeitsdurchlaß erst bei Überschreiten einer gewissen Fliehkraft zu erlauben. Grundsätzlich ist es auch möglich, die Substrat- Scheibe 10 mit einem Strichcode zur Probenkennzeichnung zu versehen, welcher bei einer Drehung des Substratteils 10 einfach abtastbar ist.For the passage of liquids through the measuring chambers 22, these can be connected to an outlet channel 50 which opens onto the lateral surface 52 of the substrate part 10. The outlet channel 50 can be designed siphon-like or S-shaped in order to allow a liquid passage only when a certain centrifugal force is exceeded. In principle, it is also possible to provide the substrate wafer 10 with a bar code for sample identification, which can be easily scanned when the substrate part 10 is rotated.
Zur Herstellung des Substratteils 10 und der Abdeckplatte 14' ist es zweckmäßig, wenn diese als einstückige Formteile, insbesondere Spritzgußformteile aus Kunststoff ausgebildet sind. Für optische Messungen kann ein transparentes Material mit den gewünschten optischen Eigenschaften verwendet werden, wobei auch Glas bzw. Quarz in Frage kommt. Grundsätzlich ist es auch möglich, die Meßkammern 22 und Zusatzkammern 34 an ihren Wandungen mit Reagenzien zu beschichten oder dort Meßelemente anzubringen. Die Meßkammern können beispielsweise ein Volumen von weniger als 100 Mikrolitern aufweisen, wobei zur ausreichenden Befüllung sichergestellt sein sollte, daß das Volumen der Aufgabekammer größer oder gleich dem Gesamtvo- lumen der Meßkammern ist. Eine weitere vorteilhafte Variante kann darin bestehen, daß den Meßkammern eine oder mehrere Vorkammern für einen stufenweisen Reaktionsablauf vorgeordnet sind. Zur weiteren Miniaturisierung ist es auch denkbar, das Substratteil als eine Art von Miniaturlabor durch Ätzen einer Halbleiterstruktur zu ferti- gen. To produce the substrate part 10 and the cover plate 14 ', it is expedient if they are designed as one-piece molded parts, in particular injection molded plastic parts. A transparent material with the desired optical properties can be used for optical measurements, glass or quartz also being suitable. In principle, it is also possible to coat the measuring chambers 22 and additional chambers 34 with reagents on their walls or to attach measuring elements there. The measuring chambers can, for example, have a volume of less than 100 microliters, with sufficient filling ensuring that the volume of the feed chamber is greater than or equal to the total volume of the measuring chambers. Another advantageous variant can consist in that one or several antechambers are arranged for a gradual reaction process. For further miniaturization, it is also conceivable to manufacture the substrate part as a type of miniature laboratory by etching a semiconductor structure.

Claims

Patentansprüche claims
1. Probenträger zur Durchführung von Reihenanalysen mit einem eine Vielzahl von Kavitäten (22) zur Aufnahme von Flüssigproben und gegebenenfalls Reagenzien aufweisenden Substratteil (10) , dadurch gekennzeichnet, daß die Kavitäten als Meßkammern (22) in einer Ringzone (20) des Substratteils (10) im Winkelabstand voneinander angeordnet sind, daß in einem Zentralbe- reich (16) des Substratteils (10) eine mit einer Flüssigprobe beaufschlagbare Aufgabekammer (18) konzentrisch mit der Ringzone (20) angeordnet ist, und daß die Aufgabekammer (18) mit den Meßkammern (22) über jeweils einen Verbindungskanal (26) kommuni- ziert.1. Sample carrier for performing series analyzes with a plurality of cavities (22) for receiving liquid samples and possibly reagents having substrate part (10), characterized in that the cavities as measuring chambers (22) in an annular zone (20) of the substrate part (10 ) are arranged at an angular distance from one another, that in a central area (16) of the substrate part (10) a feed chamber (18) to which a liquid sample can be applied is arranged concentrically with the ring zone (20), and that the feed chamber (18) with the measuring chambers (22) communicates via a connecting channel (26).
2. Probenträger nach Anspruch 1, dadurch gekennzeichnet, daß das Substratteil durch eine kreiszylindrische Substratscheibe (10) gebildet ist, daß die Au gabe- kammer (18) und die Meßkammern (22) koaxial zu der Zentralachse (24) der Substratscheibe angeordnet sind, und daß die Verbindungskanäle (26) in der Substratscheibe sich radial erstrecken.2. Sample carrier according to claim 1, characterized in that the substrate part is formed by a circular cylindrical substrate disc (10), that the Au delivery chamber (18) and the measuring chambers (22) are arranged coaxially to the central axis (24) of the substrate disc, and that the connecting channels (26) in the substrate disk extend radially.
3. Probenträger nach Anspruch 2, dadurch gekennzeichnet, daß die Meßkammern (22) bezüglich der Zentralachse (24) der Substratscheibe (10) symmetrisch verteilt angeordnet sind.3. Sample holder according to claim 2, characterized in that the measuring chambers (22) with respect to the central axis (24) of the substrate disc (10) are arranged symmetrically distributed.
4. Probenträger nach einem der Ansprüche 1 bis 3, dadurch gekennzeichnet, daß die Aufgabekammer durch ei- ne als zylindrisches Sackloch ausgebildete Zentral- ausnehmung (18) des Substratteils (10) gebildet ist.4. Sample carrier according to one of claims 1 to 3, characterized in that the feed chamber by egg ne formed as a cylindrical blind hole central recess (18) of the substrate part (10).
5. Probenträger nach einem der Ansprüche 1 bis 4, da- durch gekennzeichnet, daß das Volumen der Aufgabekammer (18) größer oder gleich dem Gesamtvolumen der Meßkammern (22) ist.5. Sample carrier according to one of claims 1 to 4, characterized in that the volume of the feed chamber (18) is greater than or equal to the total volume of the measuring chambers (22).
6. Probenträger nach einem der Ansprüche 1 bis 5, da- durch gekennzeichnet, daß die Aufgabekammer (18) , die6. Sample carrier according to one of claims 1 to 5, characterized in that the feed chamber (18), the
Verbindungskanäle (26) und die Meßkammern (22) als Ausnehmungen an einer Planarflache (12) des Substratteils (10) randoffen sind, und daß zumindest die Verbindungskanäle (26) und die Meßkammern (22) durch ein mit dem Substratteil (10) fest verbundenes oder verbindbares Abdeckelement (14,14') an der Planarflache flüssigkeitsdicht abgedeckt sind.Connecting channels (26) and the measuring chambers (22) as recesses on a planar surface (12) of the substrate part (10) are open to the edge, and that at least the connecting channels (26) and the measuring chambers (22) by a firmly connected to the substrate part (10) or connectable cover element (14, 14 ') are covered liquid-tight on the planar surface.
7. Probenträger nach Anspruch 6, dadurch gekennzeichnet, daß das Abdeckelement durch ein Flachmaterial (14) gebildet ist, welches im Bereich der Aufgabekammer (18) eine Durchstechmembran zur Probeninjektion bildet.7. Sample carrier according to claim 6, characterized in that the cover element is formed by a flat material (14) which forms a piercing membrane for sample injection in the region of the feed chamber (18).
8. Probenträger nach Anspruch 6, dadurch gekennzeichnet, daß das Abdeckelement durch eine Deckelplatte (14') gebildet ist, welche im Bereich der Aufgabekammer (18) einen vorzugsweise sich zu der Öffnung der Aufgabekammer (18) hin erweiternden Durchbruch (36) zur Probenaufgabe aufweist. 8. Sample holder according to claim 6, characterized in that the cover element is formed by a cover plate (14 '), which in the area of the feed chamber (18) preferably to the opening of the feed chamber (18) towards opening (36) for sample application having.
9. Probenträger nach einem der Ansprüche 1 bis 8, dadurch gekennzeichnet, daß das Substratteil (10) zur Rotation um seine Zentralachse (24) eine formschlüssig mit einem Drehantrieb verbindbare Eingriffspartie (44,48) aufweist.9. Sample carrier according to one of claims 1 to 8, characterized in that the substrate part (10) for rotation about its central axis (24) has a form-fittingly connectable with a rotary drive engagement part (44,48).
10. Probenträger nach Anspruch 9, dadurch gekennzeichnet, daß die Eingriffspartie durch einen umfangsseitig gezahnten Zahnringbereich oder axialen Zahnradfortsatz (44) des Substratteils (10) gebildet ist.10. Sample carrier according to claim 9, characterized in that the engagement part is formed by a toothed ring region or toothed gear extension (44) of the substrate part (10).
11. Probenträger nach Anspruch 9, dadurch gekennzeichnet, daß die Eingriffspartie durch eine für den Eingriff eines Drehmitnehmers ausgebildete Ausnehmung (48) ge- bildet ist.11. Sample carrier according to claim 9, characterized in that the engagement part is formed by a recess (48) designed for the engagement of a rotary driver.
12. Probenträger nach einem der Ansprüche 1 bis 11, dadurch gekennzeichnet, daß die Verbindungskanäle (26) zum Transport der Flüssigprobe unter Kapillarwirkung als Kapillarröhren ausgebildet sind.12. Sample carrier according to one of claims 1 to 11, characterized in that the connecting channels (26) for transporting the liquid sample under capillary action are designed as capillary tubes.
13. Probenträger nach einem der Ansprüche 1 bis 12, dadurch gekennzeichnet, daß die Verbindungskanäle (26) eine sich zu der jeweiligen Meßkammer (22) hin erwei- ternde, vorzugsweise in deren oberen Bereich mündende Mündungsöffnung (28) aufweisen.13. Sample carrier according to one of claims 1 to 12, characterized in that the connecting channels (26) have an opening (28) which widens towards the respective measuring chamber (22) and preferably opens into the upper region thereof.
14. Probenträger nach einem der Ansprüche 1 bis 13, dadurch gekennzeichnet, daß die Meßkammern (22) über einen Zusatzkanal (32) mit jeweils einer zugeordneten Zusatzkammer (34) verbunden sind. 14. Sample carrier according to one of claims 1 to 13, characterized in that the measuring chambers (22) via an additional channel (32) are each connected to an associated additional chamber (34).
15. Probenträger nach einem der Ansprüche 8 bis 14, dadurch gekennzeichnet, daß die Deckelplatte (14') an ihrer von dem Substratteil (10) abgewandten Breitsei- te (38) eine gegebenenfalls sektorweise abgetrennte Ringausnehmung (40) aufweist, welche über jeweils einen Axialdurchbruch (42) in die Zusatzkammern (34) mündet .15. Sample carrier according to one of claims 8 to 14, characterized in that the cover plate (14 ') on its broad side (38) facing away from the substrate part (10) has an optionally sector-wise separated ring recess (40), each having one Axial opening (42) opens into the additional chambers (34).
16. Probenträger nach einem der Ansprüche 1 bis 15, dadurch gekennzeichnet, daß die Meßkammern (22) jeweils einen vorzugsweise siphonartig ausgebildeten, an einer Mantelfläche des Substratteils (10) mündenden Auslaßkanal (50) aufweisen.16. Sample carrier according to one of claims 1 to 15, characterized in that the measuring chambers (22) each have a preferably siphon-like, on a lateral surface of the substrate part (10) opening outlet channel (50).
17. Probenträger nach einem der Ansprüche 1 bis 16, dadurch gekennzeichnet, daß das Substratteil (10) als Formteil aus Kunststoff, Glas oder einem Halbleitermaterial besteht . 17. Sample carrier according to one of claims 1 to 16, characterized in that the substrate part (10) as a molded part consists of plastic, glass or a semiconductor material.
PCT/EP1999/007281 1998-11-17 1999-10-01 Sample holder for serial analysis of liquid samples WO2000029109A1 (en)

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DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
122 Ep: pct application non-entry in european phase