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EP3342485B1 - Holder for reagent elements - Google Patents

Holder for reagent elements Download PDF

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Publication number
EP3342485B1
EP3342485B1 EP17150044.0A EP17150044A EP3342485B1 EP 3342485 B1 EP3342485 B1 EP 3342485B1 EP 17150044 A EP17150044 A EP 17150044A EP 3342485 B1 EP3342485 B1 EP 3342485B1
Authority
EP
European Patent Office
Prior art keywords
support
assembly according
plate
holder
support elements
Prior art date
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.)
Active
Application number
EP17150044.0A
Other languages
German (de)
French (fr)
Other versions
EP3342485A1 (en
Inventor
Lutz Weber
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Thinxxs Microtechnology GmbH
Original Assignee
Thinxxs Microtechnology GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Thinxxs Microtechnology GmbH filed Critical Thinxxs Microtechnology GmbH
Priority to EP17150044.0A priority Critical patent/EP3342485B1/en
Priority to PCT/EP2017/081543 priority patent/WO2018121961A1/en
Priority to CN201780082071.2A priority patent/CN110198784B/en
Priority to US16/475,455 priority patent/US11071984B2/en
Publication of EP3342485A1 publication Critical patent/EP3342485A1/en
Application granted granted Critical
Publication of EP3342485B1 publication Critical patent/EP3342485B1/en
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Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/52Containers specially adapted for storing or dispensing a reagent
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/52Containers specially adapted for storing or dispensing a reagent
    • B01L3/527Containers specially adapted for storing or dispensing a reagent for a plurality of reagents
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00Supporting devices; Holding devices
    • B01L9/52Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02Adapting objects or devices to another
    • B01L2200/026Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B01L2200/027Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02Adapting objects or devices to another
    • B01L2200/028Modular arrangements
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/16Reagents, handling or storing thereof
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • B01L2300/0829Multi-well plates; Microtitration plates
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/502707Containers 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 manufacture of the container or its components

Definitions

  • the invention relates to an arrangement of a multiplicity of carrier elements for a reagent which is to be introduced via the respective carrier element into a microfluidic device, in particular a flow cell, and a holder which holds the multiplicity of carrier elements, the respective carrier element being kept at least free by the holder one of the reagent-receiving areas of the support element is fixed in all spatial directions by positive locking, and the support elements are formed in a plug-like manner with only one reagent receiving area on one end face and an expansion comprising a handling area on the other end face, and the holder is a support plate with through-openings into which the Carrier elements can be used with the reagent receiving area ahead.
  • the result is a flow cell that has an outwardly opening passage for introducing a dry reagent through a carrier element.
  • the carrier element receiving the dry reagent By finally inserting the carrier element receiving the dry reagent into the passage, the dry reagent reaches the intended location within the flow cell and the carrier element closes the passage in a fluid-tight manner.
  • the above EP 2 821 138 A1 also describes a holder which holds a large number of carrier elements provided with the dry reagent for processing in the process of flow cell production.
  • the carrier plate with through openings receives plug-like carrier elements in a grid arrangement, the carrier elements having a receiving area for a reagent at one end and a handling area formed by a flange-like widening at the other end.
  • the EP 1 792 654 A1 describes carrier elements in the form of an expanding cuvette.
  • the cuvettes which are open on both sides, can be inserted into through-openings in a carrier plate, with one flange of the cuvettes abutting against the carrier plate.
  • IT MI20 112 073 A An arrangement with the features mentioned above is the IT MI20 112 073 A refer to. This results in chambers for receiving cell cultures that are inserted into through openings in a two-part mounting plate.
  • the chambers are defined in the through openings by connecting pieces protruding laterally between the plate parts and each containing a channel.
  • the invention has for its object to facilitate the manufacture of reagents containing microfluidic flow cells.
  • Such an arrangement according to the invention can advantageously be used both for processing the carrier elements, in particular for applying the dry reagent and possibly surface functionalization, and for holding the processed carrier elements ready for further processing in the manufacturing process of the flow cells.
  • the carrier elements remain fixed to the holder in every processing position.
  • An efficient process chain can be formed with the arrangement according to the invention.
  • the carrier element is fixed by the holder while keeping a further area free, in particular a handling area separated from the receiving area for the dry reagent.
  • a handling area separated from the receiving area for the dry reagent.
  • the handling area that is kept free during the processing of the carrier elements can e.g. be labeled or marked.
  • the carrier element is designed in a plug-like manner with the receiving area at one end and a handling area at the other end, the widening being formed at the other end.
  • the holder receives the carrier elements, preferably arranged in one plane and in particular in a grid arrangement.
  • the carrier element is fixed so that it can move with play.
  • there is a play of the carrier element in the holder such that the carrier element can be removed from the holder without any force after the positive connection has been released. This considerably facilitates its further processing in the context of an automated manufacturing process, if necessary.
  • the holder comprises a carrier plate with through-openings into which the carrier elements with the receiving area can be inserted, the carrier elements being fixed in each of the through-openings by the holding plate arranged behind the flanges in the insertion direction and connected to the carrier plate.
  • the holding plate preferably also has through openings which are aligned with the carrier elements inserted into the through openings in the carrier plate. At least part of the handling area remains freely accessible for processing.
  • the carrier plate is preferably connected to a frame and in particular arranged sunk into the frame.
  • the holding plate can also expediently be lowered into the frame and can preferably be connected to the frame by latching.
  • the frame preferably has dimensions such that the reagent receiving areas of the carrier elements are arranged sunk into the frame.
  • this arrangement allows holders provided with occupied support elements to be stacked in a space-saving manner without affecting the dry reagents.
  • a separate locking mechanism for fixing the carrier element in all spatial directions can be assigned to each through opening of the carrier plate, this locking mechanism being e.g. has elastic locking levers which snap in behind the widening, in particular in a paired diametrical arrangement, with a sliding bevel for unlocking.
  • the sliding bevels can be aligned with each other in such a way that all locking levers can be unlocked simultaneously with the aid of a stamping tool.
  • the carrier plate is formed in several parts from carrier plate parts. Accordingly, the frame has a number of compartments which receive the plates, for example by latching.
  • the carrier plate and the frame are formed in one piece from a deep-drawn film.
  • holder areas made of frame and carrier plates made of deep-drawn film are connected to one another to form a band, and the holding plate is designed as a continuous film band.
  • the arrangement shown comprises carrier elements 1 for a reagent which is to be introduced into a microfluidic flow cell (not shown) and a holder 2 which receives the carrier elements 1 in a flat grid arrangement.
  • carrier elements 1 and the parts of the holder 2 in particular by injection molding, come for example plastics such as PP, PMMA, PC, PS, PE and PEEK into consideration, but also glass, metal, ceramics, composite materials or combinations of different materials such as a plastic body with a local or complete glass or metal coating.
  • the carrier elements 1 are plug-shaped with a slightly conical section 3 and an expansion 4 in the form of a flange at one end.
  • a depression in the ring at the other end in the example forms a receiving area 5 for the reagent.
  • the multi-part holder 2 comprises a carrier plate 6 and a holding plate 7 which fixes the carrier elements 1 to the carrier plate 6.
  • the carrier plate 6 is connected in one piece to a frame 8, the frame 8 protruding from the carrier plate 6 on both sides of the carrier plate 6 perpendicular to the plane of the plate. That is, the carrier plate 6 is sunk into the frame 8.
  • the frame 8 has reinforcing beads and ribs distributed over its circumference.
  • Through openings 9 formed in a grid in the support plate 6 serve to receive the support elements 1, which can be inserted into the through openings 9 until the expansion 4 stops against the support plate 6.
  • the receiving area 5 protrudes from the carrier plate 6 and the carrier element 1 has less play in the through opening 9 parallel to the plane of the plate.
  • the play is preferably less than 0.1 mm, in particular 0.05 mm.
  • the receiving area 5 of the carrier elements 1 is set back with respect to a surface 21 of the frame 8 which is parallel to the plate plane.
  • the holding plate 7 forms a lock in the insertion direction behind the widening 4 of the carrier elements 1, so that the carrier elements 1 are fixed in the holder 2 in all spatial directions, apart from the slight play parallel to the plane of the plate.
  • the holding plate 7 can be snapped onto the frame 8 via elastic locking elements 11 and 12. On its side facing away from the carrier plate 6, the holding plate 7 has a stabilizing honeycomb structure 13 that avoids material accumulation. The holding plate 7 is sunk into the frame 8 in the locked state.
  • the frame 8 has a circumferentially widened end edge 14, which forms a stack seat 15, on which one in a stack according Fig. 8 adjacent arrangement with the frame surface 21 rests. How Fig. 8 shows, stack packs can be formed, in which the reagents are protected from contact by the offset of the receiving areas 5 to the surface 21.
  • the stack packages can be sealed in foil and, if necessary, vacuumed or placed under protective gas.
  • Fig. 9 shows a compared to the embodiment of Fig. 1 downsized embodiment.
  • Fig. 10 shows an embodiment with a carrier plate formed from four carrier plate parts 16, wherein the carrier plate parts 16 can be clipped into a frame 8 having cross struts 17. Likewise, four clip-on holding plate parts 18 are formed, which are congruent with the supporting plate parts 16 in the example.
  • the carrier plate parts 16 and holding plate parts 18 are, for example, metallic, possibly etched stamped parts.
  • Fig. 10 shows an empty frame compartment, a frame compartment with a carrier plate part 16, a frame compartment with an equipped carrier plate part 16 and a frame compartment with a (not visible) carrier plate part 16 and a holding plate part 18.
  • Fig. 11 shows a support plate 6 integrally connected to a frame 8 with through openings 9, with each individual through opening 9 being assigned a separate holding mechanism for a support element 1, by means of which a support plate common to all support elements 1 is unnecessary.
  • each holding mechanism has four, elastically bendable latching levers 19, which are connected in one piece to the carrier plate 6, in pairs in a diametrical arrangement, which are behind the widening 4 of the carrier element in question 1 snap in and reach behind the carrier elements 1.
  • bracket parts are not made as in the previous embodiments by injection molding or printing or from metal but only from film material.
  • the arrangement shown comprises a band in which successive holding regions 25 with frames 8 and carrier plates 6 are formed by deep drawing in the longitudinal direction of the band and through openings 9 for punching carrier elements 1 are punched into the carrier plates 6.
  • the deep-drawn tape has perforated edges 22, whereby transport means can engage in the perforation holes.
  • a holding plate holding the carrier elements 1 in the carrier plate 6 is designed continuously as a film tape 24 and is glued to the tape containing the carrier plates 6.
  • a continuous cover 23 as a band covers the recessed exposed areas of the carrier elements 1.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Description

Die Erfindung betrifft eine Anordnung aus einer Vielzahl von Trägerelementen für ein Reagenz, das über das jeweilige Trägerelement in eine mikrofluidische Einrichtung, insbesondere Flusszelle, einzubringen ist, und aus einer die Vielzahl von Trägerelementen aufnehmenden Halterung, wobei das jeweilige Trägerelement durch die Halterung unter Freihaltung wenigstens eines das Reagenz aufnehmenden Bereichs des Trägerelements in sämtlichen Raumrichtungen durch Formschluss festgelegt ist und wobei die Trägerelemente pfropfenartig mit nur einem Reagenzaufnahmebereich an einer Stirnseite und einer einen Handhabungsbereich umfassenden Aufweitung an der anderen Stirnseite ausgebildet sind und wobei die Halterung eine Trägerplatte mit Durchgangsöffnungen, in welche die Trägerelemente mit dem Reagenzaufnahmebereich voran einsetzbar sind, aufweist.The invention relates to an arrangement of a multiplicity of carrier elements for a reagent which is to be introduced via the respective carrier element into a microfluidic device, in particular a flow cell, and a holder which holds the multiplicity of carrier elements, the respective carrier element being kept at least free by the holder one of the reagent-receiving areas of the support element is fixed in all spatial directions by positive locking, and the support elements are formed in a plug-like manner with only one reagent receiving area on one end face and an expansion comprising a handling area on the other end face, and the holder is a support plate with through-openings into which the Carrier elements can be used with the reagent receiving area ahead.

Im Zuge der Herstellung Reagenzien enthaltender mikrofluidischer Flusszellen (Lab on chip) hat es sich als vorteilhaft erwiesen, die Einbringung der Reagenzien in einer späten Produktionsphase mit Hilfe gesonderter, abschließend in die Flusszelle einzubauender Trägerelemente durchzuführen. Beeinträchtigungen eingebrachter Reagenzien, z.B. durch nachträgliche Klebe- oder Schweißarbeiten, lassen sich so vermeiden.In the course of the production of microfluidic flow cells (lab on chip) containing reagents, it has proven to be advantageous to carry out the introduction of the reagents in a late production phase with the aid of separate carrier elements which are finally to be installed in the flow cell. Impairment of introduced reagents, e.g. through subsequent gluing or welding work can be avoided.

Aus der EP 2 821 138 A1 geht eine Flusszelle hervor, die zum Einbringen eines Trockenreagenz durch ein Trägerelement einen nach außen öffnenden Durchgang aufweist. Durch abschließendes Einsetzen des das Trockenreagenz aufnehmenden Trägerelements in den Durchgang gelangt das Trockenreagenz an die vorgesehene Stelle innerhalb der Flusszelle und das Trägerelement verschließt fluiddicht den Durchgang. Die obengenannte EP 2 821 138 A1 beschreibt ferner eine Halterung, welche im Prozess der Flusszellenfertigung eine Vielzahl mit dem Trockenreagenz versehener Trägerelemente zur Verarbeitung bereithält.From the EP 2 821 138 A1 the result is a flow cell that has an outwardly opening passage for introducing a dry reagent through a carrier element. By finally inserting the carrier element receiving the dry reagent into the passage, the dry reagent reaches the intended location within the flow cell and the carrier element closes the passage in a fluid-tight manner. The above EP 2 821 138 A1 also describes a holder which holds a large number of carrier elements provided with the dry reagent for processing in the process of flow cell production.

Eine Anordnung aus einer Trägerplatte und Trägerelementen geht aus der US 2016/167040 A1 hervor. Die Trägerplatte mit Durchgangsöffnungen nimmt pfropfenartige Trägerelemente in einer Rasteranordnung auf, wobei die Trägerelemente an einem Stirnende einen Aufnahmebereich für ein Reagenz und am anderen Stirnende eine durch eine flanschartige Aufweitung gebildeten Handhabungsbereich aufweisen.An arrangement of a carrier plate and carrier elements goes from the US 2016/167040 A1 forth. The carrier plate with through openings receives plug-like carrier elements in a grid arrangement, the carrier elements having a receiving area for a reagent at one end and a handling area formed by a flange-like widening at the other end.

Die EP 1 792 654 A1 beschreibt Trägerelemente in Form einer sich aufweitenden Küvette. Die beidseitig offenen Küvetten sind in Durchgangsöffnungen in einer Trägerplatte einsteckbar, wobei jeweils ein Flansch der Küvetten gegen die Trägerplatte anschlägt.The EP 1 792 654 A1 describes carrier elements in the form of an expanding cuvette. The cuvettes, which are open on both sides, can be inserted into through-openings in a carrier plate, with one flange of the cuvettes abutting against the carrier plate.

Eine Anordnung mit den eingangs erwähnten Merkmalen ist der IT MI20 112 073 A zu entnehmen. Daraus gehen in Durchgangsöffnungen einer zweiteiligen Halterungsplatte eingesetzte Kammern zur Aufnahme von Zellkulturen hervor. Die Kammern sind in den Durchgangsöffnungen durch seitlich zwischen den Plattenteilen vorstehende, jeweils einen Kanal enthaltende Anschlussstutzen festgelegt.An arrangement with the features mentioned above is the IT MI20 112 073 A refer to. This results in chambers for receiving cell cultures that are inserted into through openings in a two-part mounting plate. The chambers are defined in the through openings by connecting pieces protruding laterally between the plate parts and each containing a channel.

Der Erfindung liegt die Aufgabe zugrunde, die Fertigung Reagenzien enthaltender mikrofluidischer Flusszellen zu erleichtern.The invention has for its object to facilitate the manufacture of reagents containing microfluidic flow cells.

Diese Aufgabe wird durch eine Anordnung der eingangs erwähnten Art gelöst, die dadurch gekennzeichnet ist, dass die Aufweitung der Trägerelemente durch einen Flansch gebildet ist und die Trägerelemente in die Durchgangsöffnung bis zum Anschlag des Flansches gegen die Trägerplatte einführbar sind, wobei in der Anschlagstellung die Trägerelemente mit dem Reagenzaufnahmebereich von der Trägerplatte vorstehen, und dass an dem Flansch auf seiner der Trägerplatte abgewandten Seite eine allen Trägerelementen gemeinsame, mit der Trägerplatte verbundene Halteplatte oder ein gesonderter, jeder der Durchgangsöffnungen zugeordneter Verriegelungsmechanismus angreift.This object is achieved by an arrangement of the type mentioned at the outset, which is characterized in that the widening of the support elements is formed by a flange and the support elements can be inserted into the through opening until the flange stops against the support plate, the support elements in the stop position protrude from the carrier plate with the reagent receiving area, and that a retaining plate common to all carrier elements and connected to the carrier plate or a separate locking mechanism assigned to each of the through openings engages on the flange on its side facing away from the carrier plate.

Vorteilhaft lässt sich eine solche Anordnung nach der Erfindung sowohl zur Bearbeitung der Trägerelemente, insbesondere zur Aufbringung des Trockenreagenz und ggf. Oberflächenfunktionalisierung, als auch zur Bereithaltung der bearbeiteten Trägerelemente für die Weiterverarbeitung im Fertigungsprozess der Flusszellen nutzen. Die Trägerelemente bleiben in jeder Bearbeitungsstellung an der Halterung fixiert. Mit der erfindungsgemäßen Anordnung lässt sich eine effiziente Prozesskette bilden.Such an arrangement according to the invention can advantageously be used both for processing the carrier elements, in particular for applying the dry reagent and possibly surface functionalization, and for holding the processed carrier elements ready for further processing in the manufacturing process of the flow cells. The carrier elements remain fixed to the holder in every processing position. An efficient process chain can be formed with the arrangement according to the invention.

Erfindungsgemäß ist das Trägerelement durch die Halterung unter Freihaltung eines weiteren Bereichs festgelegt, insbesondere eines von dem Aufnahmebereich für das Trockenreagenz abgesetzten Handhabungsbereichs. So kann der freigehaltene Handhabungsbereich im Rahmen der Bearbeitung der Trägerelemente z.B. beschriftet oder markiert werden.According to the invention, the carrier element is fixed by the holder while keeping a further area free, in particular a handling area separated from the receiving area for the dry reagent. For example, the handling area that is kept free during the processing of the carrier elements can e.g. be labeled or marked.

Erfindungsgemäß ist das Trägerelement pfropfenartig mit dem Aufnahmebereich an einem Stirnende und einem Handhabungsbereich am anderen Stirnende ausgebildet, wobei an dem anderen Ende die Aufweitung gebildet ist.According to the invention, the carrier element is designed in a plug-like manner with the receiving area at one end and a handling area at the other end, the widening being formed at the other end.

Die Halterung nimmt die Trägerelemente vorzugsweise unter Anordnung in einer Ebene und insbesondere in einer Rasteranordnung auf.The holder receives the carrier elements, preferably arranged in one plane and in particular in a grid arrangement.

In einer besonders bevorzugten Ausführungsform der Erfindung ist das Trägerelement durch die Halterung spielbeweglich festgelegt. Insbesondere besteht ein Spiel des Trägerelements in der Halterung derart, dass sich das Trägerelement nach Lösung des Formschlusses aus der Halterung ohne Kraftaufwand entnehmen lässt. Dies erleichtert erheblich seine Weiterverarbeitung im Rahmen eines ggf. automatisierten Fertigungsprozesses.In a particularly preferred embodiment of the invention, the carrier element is fixed so that it can move with play. In particular, there is a play of the carrier element in the holder such that the carrier element can be removed from the holder without any force after the positive connection has been released. This considerably facilitates its further processing in the context of an automated manufacturing process, if necessary.

Erfindungsgemäß umfasst die Halterung eine Trägerplatte mit Durchgangsöffnungen, in welche die Trägerelemente mit dem Aufnahmebereich voran einsetzbar sind, wobei die Trägerelemente jeweils in den Durchgangsöffnungen durch die in Einsteckrichtung hinter den Flanschen angeordnete, mit der Trägerplatte verbundene Halteplatte festgelegt sind. Durch Verbindung mit einer solchen, allen Trägerelementen gemeinsamen Halteplatte lässt sich eine Vielzahl vorab in die Durchgangsöffnungen eingesteckter Trägerelemente in der Halterung in einem einzigen Arbeitsgang fixieren.According to the invention, the holder comprises a carrier plate with through-openings into which the carrier elements with the receiving area can be inserted, the carrier elements being fixed in each of the through-openings by the holding plate arranged behind the flanges in the insertion direction and connected to the carrier plate. By connecting such a support plate common to all support elements, a large number of support elements inserted in advance into the through openings can be fixed in the holder in a single operation.

Vorzugsweise weist auch die Halteplatte Durchgangsöffnungen auf, die zu den in die Durchgangsöffnungen in der Trägerplatte eingesetzten Trägerelementen ausgerichtet sind. So bleibt wenigstens ein Teil des Handhabungsbereichs für eine Bearbeitung frei zugänglich.The holding plate preferably also has through openings which are aligned with the carrier elements inserted into the through openings in the carrier plate. At least part of the handling area remains freely accessible for processing.

Die Trägerplatte ist vorzugsweise mit einem Rahmen verbunden und insbesondere in den Rahmen hinein eingesenkt angeordnet.The carrier plate is preferably connected to a frame and in particular arranged sunk into the frame.

Zweckmäßig ist auch die Halteplatte in den Rahmen hinein versenkbar und lässt sich vorzugsweise unter Einrastung mit dem Rahmen verbinden.The holding plate can also expediently be lowered into the frame and can preferably be connected to the frame by latching.

Der Rahmen weist vorzugsweise solche Abmessungen auf, dass die Reagenzaufnahmebereiche der Trägerelemente in den Rahmen hinein versenkt angeordnet sind. Vorteilhaft erlaubt diese Anordnung, mit belegten Trägerelementen versehene Halterungen ohne Beeinträchtigung der Trockenreagenzien platzsparend zu stapeln.The frame preferably has dimensions such that the reagent receiving areas of the carrier elements are arranged sunk into the frame. Advantageously, this arrangement allows holders provided with occupied support elements to be stacked in a space-saving manner without affecting the dry reagents.

Alternativ zu der Halteplatte kann erfindungsgemäß jeder Durchgangsöffnung der Trägerplatte ein gesonderter Verriegelungsmechanismus zur Festlegung des Trägerelements in sämtlichen Raumrichtungen zugeordnet sein, wobei dieser Verriegelungsmechanismus z.B. elastische, hinter der Aufweitung einrastende Rasthebel, insbesondere in paarweise diametraler Anordnung, mit einer Gleitschräge zur Entriegelung aufweist. Die Gleitschrägen können zueinander derart ausgerichtet sein, dass mit Hilfe eines Stempelwerkzeugs gleichzeitig eine Entriegelung aller Rasthebel erfolgen kann.As an alternative to the holding plate, according to the invention a separate locking mechanism for fixing the carrier element in all spatial directions can be assigned to each through opening of the carrier plate, this locking mechanism being e.g. has elastic locking levers which snap in behind the widening, in particular in a paired diametrical arrangement, with a sliding bevel for unlocking. The sliding bevels can be aligned with each other in such a way that all locking levers can be unlocked simultaneously with the aid of a stamping tool.

In einer weiteren Ausführungsform ist die Trägerplatte mehrteilig aus Trägerplattenteilen gebildet. Entsprechend weist der Rahmen mehrere, die Platten, z.B. unter Einrastung, aufnehmende Fächer auf.In a further embodiment, the carrier plate is formed in several parts from carrier plate parts. Accordingly, the frame has a number of compartments which receive the plates, for example by latching.

In einer Ausführungsform sind die Trägerplatte und der Rahmen einstückig aus einer tiefgezogenen Folie gebildet. Insbesondere sind Halterbereiche aus Rahmen und Trägerplatten aus tiefgezogener Folie zu einem Band miteinander verbunden und die Halteplatte als durchgehendes Folienband ausgebildet. Eine solche Anordnung ist aufrollbar und eine Vielzahl vorbereiteter, mit einem Trockenreagenz versehener Trägerelemente lässt sich, wie bei Stapelung der Anordnungen, in kompakter Form bereithalten.In one embodiment, the carrier plate and the frame are formed in one piece from a deep-drawn film. In particular, holder areas made of frame and carrier plates made of deep-drawn film are connected to one another to form a band, and the holding plate is designed as a continuous film band. Such an arrangement can be rolled up and a large number of prepared carrier elements provided with a dry reagent can be kept in a compact form, as when the arrangements are stacked.

Die Erfindung wird nachfolgend anhand von Ausführungsbeispielen und der beiliegenden, sich auf diese Ausführungsbeispiele beziehenden Zeichnungen weiter erläutert. Es zeigen:

Fig. 1
eine erfindungsgemäße Anordnung in Explosionsdarstellung in perspektivischer Ansicht,
Fig. 2
in der Anordnung von Fig. 1 verwendete Reagenzträgerelemente in verschiedenen perspektivischen Ansichten,
Fig. 3
die Anordnung von Fig. 1 in einer weiteren perspektivischen Ansicht in Explosionsdarstellung,
Fig. 4 und 5
die Anordnung von Fig. 1 im zusammengebauten Zustand in verschiedenen perspektivischen Ansichten,
Fig. 6 und 7
Details der Anordnung von Fig. 4 und 5,
Fig. 8
mehrere der Anordnungen von Fig. 4 und 5 im gestapelten Zustand,
Fig. 9 und 10
weitere Ausführungsbeispiele für eine erfindungsgemäße Anordnung in perspektivischen Ansichten,
Fig. 11
einen alternativen Haltermechanismus für Reagenzträgerelemente, und
Fig. 12 bis 15
ein drittes Ausführungsbeispiel für eine erfindungsgemäße Anordnung mit einer teilweise aus tiefgezogenem Folienmaterial hergestellten Halterung.
The invention is further explained below using exemplary embodiments and the accompanying drawings relating to these exemplary embodiments. Show it:
Fig. 1
an arrangement according to the invention in an exploded view in perspective view,
Fig. 2
in the order of Fig. 1 reagent carrier elements used in different perspective views,
Fig. 3
the arrangement of Fig. 1 in another perspective view in an exploded view,
4 and 5
the arrangement of Fig. 1 in the assembled state in different perspective views,
6 and 7
Details of the arrangement of 4 and 5 ,
Fig. 8
several of the arrangements of 4 and 5 when stacked,
9 and 10
further exemplary embodiments of an arrangement according to the invention in perspective views,
Fig. 11
an alternative holder mechanism for reagent carrier elements, and
12 to 15
a third embodiment of an arrangement according to the invention with a holder partially made of deep-drawn film material.

Eine in den Figuren 1 bis 8 dargestellte Anordnung umfasst Trägerelemente 1 für ein Reagenz, das in eine (nicht gezeigte) mikrofluidische Flusszelle einzubringen ist, und eine die Trägerelemente 1 in einer ebenen Rasteranordnung aufnehmende Halterung 2. Zur Herstellung der Trägerelemente 1 und der Teile der Halterung 2, insbesondere durch Spritzgießen, kommen z.B. Kunststoffe wie PP, PMMA, PC, PS, PE und PEEK in Betracht, darüber hinaus aber auch Glas, Metall, Keramik, Verbundwerkstoffe oder Kombinationen aus verschiedenen Materialien wie z.B. ein Kunststoffkörper mit einer lokalen oder vollständigen Glas- oder Metallbeschichtung.One in the Figures 1 to 8 The arrangement shown comprises carrier elements 1 for a reagent which is to be introduced into a microfluidic flow cell (not shown) and a holder 2 which receives the carrier elements 1 in a flat grid arrangement. For producing the carrier elements 1 and the parts of the holder 2, in particular by injection molding, come for example plastics such as PP, PMMA, PC, PS, PE and PEEK into consideration, but also glass, metal, ceramics, composite materials or combinations of different materials such as a plastic body with a local or complete glass or metal coating.

Wie insbesondere Fig. 2 erkennen lässt, sind die Trägerelemente 1 pfropfenartig mit einem leicht konischen Abschnitt 3 und einer Aufweitung 4 in Form eines Flansches an einem Stirnende ausgebildet. Eine in dem Beispiel ringförmige Einsenkung am anderen Stirnende bildet einen Aufnahmebereich 5 für das Reagenz.How in particular Fig. 2 shows, the carrier elements 1 are plug-shaped with a slightly conical section 3 and an expansion 4 in the form of a flange at one end. A depression in the ring at the other end in the example forms a receiving area 5 for the reagent.

Der mehrteilige Halter 2 umfasst eine Trägerplatte 6 und eine die Trägerelemente 1 an der Trägerplatte 6 fixierende Halteplatte 7.The multi-part holder 2 comprises a carrier plate 6 and a holding plate 7 which fixes the carrier elements 1 to the carrier plate 6.

Die Trägerplatte 6 ist in dem Beispiel einstückig mit einem Rahmen 8 verbunden, wobei der Rahmen 8 auf beiden Seiten der Trägerplatte 6 von der Trägerplatte 6 senkrecht zur Plattenebene vorsteht. Das heißt, die Trägerplatte 6 ist in den Rahmen 8 hinein versenkt.In the example, the carrier plate 6 is connected in one piece to a frame 8, the frame 8 protruding from the carrier plate 6 on both sides of the carrier plate 6 perpendicular to the plane of the plate. That is, the carrier plate 6 is sunk into the frame 8.

Wie die Figuren erkennen lassen, weist der Rahmen 8 verteilt über seinen Umfang verstärkende Sicken und Rippen auf.As can be seen from the figures, the frame 8 has reinforcing beads and ribs distributed over its circumference.

In der Trägerplatte 6 in einem Raster gebildete Durchgangsöffnungen 9 dienen der Aufnahme der Trägerelemente 1, die in die Durchgangsöffnungen 9 bis zum Anschlag der Aufweitung 4 gegen die Trägerplatte 6 einsteckbar sind. In letzterem Zustand (Fig. 4) steht der Aufnahmebereich 5 von der Trägerplatte 6 vor und das Trägerelement 1 hat in der Durchgangsöffnung 9 ein geringeres Spiel parallel zur Plattenebene. Das Spiel beträgt vorzugsweise weniger als 0,1 mm, insbesondere 0,05 mm. Der Aufnahmebereich 5 der Trägerelemente 1 ist gegenüber einer zur Plattenebene parallelen Oberfläche 21 des Rahmens 8 zurückversetzt.Through openings 9 formed in a grid in the support plate 6 serve to receive the support elements 1, which can be inserted into the through openings 9 until the expansion 4 stops against the support plate 6. In the latter state ( Fig. 4 ) the receiving area 5 protrudes from the carrier plate 6 and the carrier element 1 has less play in the through opening 9 parallel to the plane of the plate. The play is preferably less than 0.1 mm, in particular 0.05 mm. The receiving area 5 of the carrier elements 1 is set back with respect to a surface 21 of the frame 8 which is parallel to the plate plane.

Die Halteplatte 7 bildet in Einsteckrichtung hinter der Aufweitung 4 der Trägerelemente 1 eine Sperre, so dass die Trägerelemente 1 in der Halterung 2 in sämtlichen Raumrichtungen, von dem leichten Spiel parallel zur Plattenebene abgesehen, festgelegt sind.The holding plate 7 forms a lock in the insertion direction behind the widening 4 of the carrier elements 1, so that the carrier elements 1 are fixed in the holder 2 in all spatial directions, apart from the slight play parallel to the plane of the plate.

Wie insbesondere Fig. 6 und 7 erkennen lassen, weist die Halteplatte 7 zu den Durchgangsöffnungen 9 ausgerichtete Durchgangsöffnungen 10 auf, über welche das aufgeweitete Stirnende der gehalterten Trägerelemente 1, das einen Handhabungsbereich für die Trägerelemente 1 bildet, zumindest teilweise zugänglich ist.How in particular 6 and 7 can be seen, the holding plate 7 to the through openings 9 aligned through openings 10, through which the widened front end of the supported carrier elements 1, which forms a handling area for the carrier elements 1, is at least partially accessible.

Die Halteplatte 7 ist über elastische Rastelemente 11 und 12 an dem Rahmen 8 einrastbar. Auf ihrer der Trägerplatte 6 abgewandten Seite weist die Halteplatte 7 eine Materialhäufung meidende, stabilisierende Wabenstruktur 13 auf. Die Halteplatte 7 ist im eingerasteten Zustand in den Rahmen 8 hinein versenkt.The holding plate 7 can be snapped onto the frame 8 via elastic locking elements 11 and 12. On its side facing away from the carrier plate 6, the holding plate 7 has a stabilizing honeycomb structure 13 that avoids material accumulation. The holding plate 7 is sunk into the frame 8 in the locked state.

Der Rahmen 8 weist einen umlaufend aufgeweiteten Endrand 14 auf, der einen Stapelsitz 15 bildet, auf dem eine in einem Stapel gemäß Fig. 8 benachbarte Anordnung mit der Rahmenoberfläche 21 aufliegt. Wie Fig. 8 zeigt, lassen sich Stapelpakete bilden, in denen durch den Versatz der Aufnahmebereiche 5 zu der Oberfläche 21 die Reagenzien vor Berührung geschützt sind. Die Stapelpakete lassen sich in Folien einschweißen und ggf. vakuumieren oder unter Schutzgas setzen.The frame 8 has a circumferentially widened end edge 14, which forms a stack seat 15, on which one in a stack according Fig. 8 adjacent arrangement with the frame surface 21 rests. How Fig. 8 shows, stack packs can be formed, in which the reagents are protected from contact by the offset of the receiving areas 5 to the surface 21. The stack packages can be sealed in foil and, if necessary, vacuumed or placed under protective gas.

Fig. 9 zeigt eine gegenüber der Ausführungsform von Fig. 1 verkleinerte Ausführungsform. Fig. 9 shows a compared to the embodiment of Fig. 1 downsized embodiment.

Fig. 10 zeigt ein Ausführungsbeispiel mit einer aus vier Trägerplattenteilen 16 gebildeten Trägerplatte, wobei die Trägerplattenteile 16 in einen Querstreben 17 aufweisenden Rahmen 8 einclipsbar sind. Ebenso sind vier einclipsbare Halteplattenteile 18 gebildet, die in dem Beispiel zu den Trägerplattenteilen 16 deckungsgleich sind. Bei den Trägerplattenteilen 16 und Halteplattenteilen 18 handelt es sich z.B. um metallische, ggf. geätzte Stanzteile.
Fig. 10 zeigt ein leeres Rahmenfach, ein Rahmenfach mit einem Trägerplattenteil 16, ein Rahmenfach mit einem bestückten Trägerplattenteil 16 und ein Rahmenfach mit einem (nicht sichtbaren) Trägerplattenteil 16 und einem Halteplattenteil 18.
Fig. 10 shows an embodiment with a carrier plate formed from four carrier plate parts 16, wherein the carrier plate parts 16 can be clipped into a frame 8 having cross struts 17. Likewise, four clip-on holding plate parts 18 are formed, which are congruent with the supporting plate parts 16 in the example. The carrier plate parts 16 and holding plate parts 18 are, for example, metallic, possibly etched stamped parts.
Fig. 10 shows an empty frame compartment, a frame compartment with a carrier plate part 16, a frame compartment with an equipped carrier plate part 16 and a frame compartment with a (not visible) carrier plate part 16 and a holding plate part 18.

Fig. 11 zeigt eine einstückig mit einem Rahmen 8 verbundene Trägerplatte 6 mit Durchgangsöffnungen 9, wobei jeder einzelnen Durchgangsöffnung 9 ein gesonderter Haltemechanismus für ein Trägerelement 1 zugeordnet ist, durch den sich eine sämtlichen Trägerelementen 1 gemeinsame Halteplatte erübrigt. Fig. 11 shows a support plate 6 integrally connected to a frame 8 with through openings 9, with each individual through opening 9 being assigned a separate holding mechanism for a support element 1, by means of which a support plate common to all support elements 1 is unnecessary.

In dem gezeigten Beispiel weist jeder Haltemechanismus vier, einstückig mit der Trägerplatte 6 verbundene, elastisch abbiegbare Rasthebel 19 in paarweise diametraler Anordnung auf, die hinter der Aufweitung 4 des betreffenden Trägerelements 1 einrasten und das Trägerelemente 1 hintergreifen. Die einander paarweise diametral gegenüberliegenden Rasthebel 19 weisen jeweils eine Gleitschräge 20 auf, so dass durch ein Stempelwerkzeug eine gemeinsame Aufspreizung aller vier Rasthebel und dadurch Lösung der Verriegelung möglich ist.In the example shown, each holding mechanism has four, elastically bendable latching levers 19, which are connected in one piece to the carrier plate 6, in pairs in a diametrical arrangement, which are behind the widening 4 of the carrier element in question 1 snap in and reach behind the carrier elements 1. The locking levers 19, which are diametrically opposed to each other in pairs, each have a sliding bevel 20, so that a common spreading of all four locking levers and thereby releasing the locking is possible by means of a stamping tool.

Die Figuren 12 bis 15 zeigen ein Ausführungsbeispiel, dessen Halterungsteile nicht wie bei den vorangehenden Ausführungsbeispielen durch Spritzgießen oder Drucken oder aus Metall sondern allein aus Folienmaterial hergestellt sind.The Figures 12 to 15 show an embodiment, the bracket parts are not made as in the previous embodiments by injection molding or printing or from metal but only from film material.

Die gezeigte Anordnung umfasst ein Band, in dem durch Tiefziehen in Bandlängsrichtung aufeinanderfolgende Haltebereiche 25 mit Rahmen 8 und Trägerplatten 6 gebildet und Durchgangsöffnungen 9 für die Aufnahme von Trägerelementen 1 in die Trägerplatten 6 gestanzt sind. Das tiefgezogene Band weist perforierte Ränder 22 auf, wobei in die Perforationslöcher Transportmittel eingreifen können.The arrangement shown comprises a band in which successive holding regions 25 with frames 8 and carrier plates 6 are formed by deep drawing in the longitudinal direction of the band and through openings 9 for punching carrier elements 1 are punched into the carrier plates 6. The deep-drawn tape has perforated edges 22, whereby transport means can engage in the perforation holes.

Eine die Trägerelemente 1 in der Trägerplatte 6 festhaltende Halteplatte ist durchgehend als Folienband 24 ausgeführt und mit dem die Trägerplatten 6 enthaltenden Band verklebt. Eine als Band durchgehende Abdeckung 23 deckt die zurückgesetzt freiliegenden Aufnahmebereiche der Trägerelemente 1 ab.A holding plate holding the carrier elements 1 in the carrier plate 6 is designed continuously as a film tape 24 and is glued to the tape containing the carrier plates 6. A continuous cover 23 as a band covers the recessed exposed areas of the carrier elements 1.

Die in Fig. 15 komplett mit der Abdeckung 23 gezeigte Anordnung ist in ihrer Gesamtheit aufrollbar.In the Fig. 15 The arrangement shown completely with the cover 23 can be rolled up in its entirety.

Claims (13)

  1. Assembly from a multiplicity of support elements (1) for a reagent which by way of the respective support element (1) is to be incorporated in a microfluidic installation, in particular a flow cell, and from a holder (2) which receives the multiplicity of support elements (1), wherein the respective support element (1), while keeping vacant at least a region (5) of the support element (1) which receives the reagent, is secured in all spatial directions by the holder (2) by way of a form-fit,
    wherein the support elements (1) in the manner of a plug are configured having a reagent receptacle region (5) at one end side and a widening (4) which comprises a handling region at the other end side, and the holder (2) has a support plate (6) having passage openings (9) which are formed in a modular grid and in which the support elements (1) are able to be inserted with the reagent receptacle region (5) leading, and wherein
    the widening (4) of the support elements (1) is formed by a flange and the support elements (1) by way of a slightly conical portion (3) are able to be introduced into the passage openings (9) until the flange (4) stops on the support plate (6) so as to have minor play parallel to the plate plane, wherein the support elements (1) in the stop position by way of the reagent receptacle region project from the support plate (6),
    characterized in that
    a holding plate (7) which is common to all support elements (1) and is connected to the support plate (6), or a dedicated locking mechanism which is assigned to each of the passage openings (9), engages on the flange (4) on the side thereof that faces away from the support plate (6).
  2. Assembly according to Claim 1,
    characterized in that
    the support element (1), while keeping vacant a further region, in particular a region which is offset from the reagent receptacle region (5) and preferably serves for handling the support element (1), is secured by the holder (2).
  3. Assembly according to Claim 1 or 2,
    characterized in that
    the holder (2), while disposing the support elements (1) in a plane, preferably in a modular grid arrangement, is configured for receiving the support elements (1).
  4. Assembly according to one of Claims 1 to 3,
    characterized in that
    the support element (1) is secured by the holder (2) so as to be movable by way of play.
  5. Assembly according to one of Claims 1 to 4,
    characterized in that
    the holding plate (7) has passage openings (10) which are aligned with the support elements (1) inserted in the passage openings (9).
  6. Assembly according to one of Claims 1 to 5,
    characterized in that
    the support plate (6) is connected to a frame (8) and is preferably disposed so as to be sunk into the frame (8).
  7. Assembly according to Claim 6,
    characterized in that
    the holding plate (7) is able to be sunk into the frame (8) and is preferably able to be connected to the frame (8) by latching.
  8. Assembly according to Claim 6 or 7,
    characterized in that
    the reagent receptacle regions (4) of the support elements (1) are disposed so as to be sunk into the frame (8).
  9. Assembly according to one of Claims 1 to 8,
    characterized in that
    the locking mechanism has elastic latching levers (15) which are diametrically disposed in pairs and latch behind the widening and for unlocking have a sliding chamfer (20).
  10. Assembly according to one of Claims 1 to 9,
    characterized in that
    the support plate (6) is configured in multiple parts from support plate parts (16).
  11. Assembly according to one of Claims 1 to 10,
    characterized in that
    the assembly is able to be stacked.
  12. Assembly according to one of Claims 1 to 11,
    characterized in that
    the support plate (6) and the frame (8) are formed integrally from a vacuum-formed film.
  13. Assembly according to Claim 12,
    characterized in that
    holding regions (25) composed of frames (8) and the support plates (6) from vacuum-formed film are connected to one another so as to form a strip, and the holding plate is configured as a continuous film strip (24) and/or a plurality of holding regions are able to be rolled up.
EP17150044.0A 2017-01-02 2017-01-02 Holder for reagent elements Active EP3342485B1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
EP17150044.0A EP3342485B1 (en) 2017-01-02 2017-01-02 Holder for reagent elements
PCT/EP2017/081543 WO2018121961A1 (en) 2017-01-02 2017-12-05 Holder for reagent tray elements
CN201780082071.2A CN110198784B (en) 2017-01-02 2017-12-05 Supports for reagent carrier elements
US16/475,455 US11071984B2 (en) 2017-01-02 2017-12-05 Holder for reagent tray elements

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP17150044.0A EP3342485B1 (en) 2017-01-02 2017-01-02 Holder for reagent elements

Publications (2)

Publication Number Publication Date
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EP3342485B1 true EP3342485B1 (en) 2020-07-08

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CN (1) CN110198784B (en)
WO (1) WO2018121961A1 (en)

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TWI785636B (en) * 2021-06-07 2022-12-01 新加坡商克雷多生醫有限公司 Analysis cartridge
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Also Published As

Publication number Publication date
US20200023367A1 (en) 2020-01-23
WO2018121961A1 (en) 2018-07-05
CN110198784A (en) 2019-09-03
CN110198784B (en) 2021-07-20
US11071984B2 (en) 2021-07-27
EP3342485A1 (en) 2018-07-04

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