CONSUMABLE FOR SAMPLE PROCESSING IN AUTOMATED ANALYSER

Abstract

A consumable which is a device intended for single use comprising a cavity for receiving a liquid. The disclosure provides a consumable for use in an automated analyser system for performing biochemical assays, comprising a rim surrounding at least one cavity for receiving a fluid, wherein the at least one cavity is connected via a flexible bridge to the rim; and a cover foil that is arranged on top of the consumable and above the openings of the at least one cavity, wherein the cover foil comprises holes which are configured to be arranged in an open position above the openings of all cavities, wherein the cover foil is connected rotatable at and around a centrally arranged hole.

Claims

1. A consumable for use in an automated analyser system for performing biochemical assays, comprising a rim surrounding at least one cavity for receiving a fluid, wherein the at least one cavity is connected via a flexible bridge to the rim; and a cover foil that is arranged on top of the consumable and above the opening of the at least one cavity, wherein the cover foil comprises holes which are configured to be arranged in an open position above the openings of all cavities, wherein the cover foil is connected rotatable at and around a centrally arranged hole with the consumable.

2. The consumable of claim 1, wherein the at least one cavity is made of a white or translucent material.

3. The consumable of claim 1, wherein the cover foil is made of a translucent material.

4. The consumable of claim 1, wherein the at least one cavity is made of a thermally conductive material.

5. The consumable of claim 1, wherein the centrally arranged hole is configured to accommodate a gripper for taking up the consumable with an alignment cone.

6. The consumable of claim 1, wherein the flexible bridge is configured to allow a horizontal and/or vertical movement of the at least one cavity.

7. The consumable of claim 1, wherein the cover foil has additional holes configured to accommodate spikes of a rotation gripper for rotating the cover foil from an open position to a closed position where the cover foils closes the opening of the at least one cavity.

8. The consumable of claim 1, wherein the upper end of the cavities' openings comprise a raised border made of a heat meltable material.

9. The consumable of claim 1, wherein the foil is made of a heat meltable material, is coated with an adhesive or glue on the surface directed towards the at least one cavity's openings.

10. The consumable of claim 1, wherein the rim comprises a snap-in feature comprising a retaining element at the bottom side of the rim and a hook arranged above the retaining element and thus above the rim.

11. A system for performing biochemical assays, comprising: at least one consumable according to claim 1; and an automated analyser system with an element providing recesses configured to receive the cavities of the at least one consumable.

12. The system of claim 11, comprising glass fibres which are arranged above each cavity for introducing light into the respective cavity.

13. The system of claim 11, comprising a rotation gripper with spikes which are configured to accommodate into additional holes of the cover foil for rotating the cover foil from an open position to a closed position and vice versa.

14. The system of claim 11, comprising a member for sealing the cover foil onto the consumable.

15. The system of claim 11, comprising a gripper for moving a consumable, wherein the gripper comprises an interface pin which is arranged centrally in a strip-off-shell.

16. The system of claim 15, wherein the interface pin comprises a rotation lock.

17. The system of claim 16, herein the rotation lock comprises flattened longitudinal surfaces on the interface pin.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0041] The disclosure will be described based on figures. It will be understood that the embodiments and aspects of the disclosure described in the figures are only examples and do not limit the protective scope of the claims in any way. The disclosure is defined by the claims and their equivalents. It will be understood that features of one aspect or embodiment of the disclosure can be combined with a feature of a different aspect or aspects of other embodiments of the disclosure, in which:

[0042] FIG. 1 shows a consumable according to the disclosure.

[0043] FIG. 2 shows schematically the bridges for connecting each consumable with the rim.

[0044] FIGS. 3A-3B show in FIG. 3A a consumable with open cavities and in FIG. 3B a device for rotating the foil to close the cavities.

[0045] FIG. 4 shows a stack of consumables.

[0046] FIG. 5 shows in a sectional view two stacked consumables.

[0047] FIGS. 6A-6B show a gripper for handling a consumable.

[0048] FIG. 7 shows the interface pin in more detail.

[0049] FIG. 8 shows an exemplary setup for supply and preparation of the specific PCR consumables.

[0050] FIG. 9 shows an alternative sample preparation process.

[0051] FIGS. 10A-10C show an alternative embodiment of a circular consumable with closable cavities which is stackable.

[0052] FIGS. 11A-11C show a cruciform embodiment of a consumable.

[0053] FIGS. 12A-12B show an embodiment of a consumable with an additional frame.

[0054] FIGS. 13A-13B show a multi cavity consumable which has an integrated cover foil.

[0055] FIGS. 14A-14B show alternative designs for a bridge allowing the connected cavities to move for tolerance compensation.

[0056] FIG. 15A-15B show an embodiment with self destacking feature.

[0057] FIGS. 16A-16C show alternative designs for tolerance compensation of cavities.

[0058] FIG. 17 shows an embodiment of a process using a consumable shown in FIG. 13.

[0059] FIGS. 18A-18B shows a consumable that can be loaded and stored into the system without a cover foil or lid.

[0060] FIG. 19 shows exemplary a process requiring a translatory movement instead of a rotary movement.

[0061] FIGS. 20A-20B show a consumable with a slidable foil.

[0062] FIG. 21 depicts a process for the consumable shown in FIGS. 20A-20B with a slidable cover foil.

DETAILED DESCRIPTION

[0063] The technical problem is solved by the independent claims. The dependent claims cover further specific embodiments of the disclosure.

[0064] The term consumable refers within the present disclosure to a device which provides cavities, receptacles or recesses for receiving a fluid which can be a liquid patient sample for instance. The term fluid refers to a liquid which can be a patient sample that comprises solids. A patient sample may be liquids like whole blood, urine, lymph or saliva.

[0065] The present disclosure comprises a disposable consumable with multiple reaction cavities. Such a consumable is intended for single use only for performing an analytical assay like a PCR. It is obvious for a person having ordinary skill in the art that the consumable according to the present disclosure may also be used for other assays and is thus not limited to its use in PCR.

[0066] The consumable according to the present disclosure comprises an integrated sealing element, which can be heat sealed or welded to obtain air-tight sealed reaction cavities. The consumable is furthermore stackable for minimizing the required space. The sealing element can be closed and subsequently sealed with a heat-sealing device for obtaining the air-tight sealed cavities. It is an advantage of a consumable according to the present disclosure that no other elements than the consumables with its already connected parts must be handled.

[0067] A relevant feature of the present disclosure relates to the integrated heat-sealing element that allows stacking of the consumable as well as sealing of multiple cavities. This sealing element safeguards further processing and avoids evaporation of the liquids in the cavity as well as contamination of said liquids.

[0068] The present disclosure provides a new consumable design and sample preparation process prior to performing an assay like a PCR. The consumables according to the instant disclosure is stackable and relate to a multi-cavity consumable with preferably four cavities. It is obvious that consumable with a different number of cavities for receiving a liquid also within the scope of the present disclosure.

[0069] As already mentioned, the consumables provide an integrated sealing element which is a foil thin sheet of a material that is suitable heat-sealing or welding to cover the cavity inside the instrument while offering the possibility to open the cavities before heat sealing or welding for adding a liquid to a cavity. The cavities will be air-tight sealed when the respective liquid or multiple liquids have been filled into a cavity.

[0070] The consumables according to the present disclosure further comprises structural elements enabling handling of the consumable with a simple gripper. The structural element is a circular hole for accommodating a gripper.

[0071] It is further intended that the cover or seal of the cavities is made of a translucent material for enabling fluorescence measurement at least through a window made of a translucent material in the cover or seal. It is also within the scope of the present disclosure to use a translucent and thin sealing element allowing to measure fluorescence. The walls of the cavity may also be made of a translucent material or alternatively of a white material for enhancing emitted fluorescence, respectively for reflecting optical signals resulting from emitted fluorescence.

[0072] The consumables 2 for assay preparation according to the present disclosure comprises an integrated and rotatable cover which is a cover foil 5 or can be a plate (comp. FIG. 1). The cover foil 5 may be made of a transparent or translucent material or can be made in another embodiment of a solid or rigid material. The consumable 2 has on its outside a surrounding stable rim 15 for handling, stacking and unstacking of consumables 2. The cover foil 5 has holes 17 which are arranged in an open position above the openings of cavities 7 so that a liquid may be added to a cavity. The foil has further holes 19 for rotating the foil. In an embodiment of the consumable, the cavities are made of a white material and will be covered with a clear (translucent) foil to support fluorescence measurement. An alternative design for the consumable is a cavity with a frosted surface and clear wells. An alternative material can be a thermally conductive plastic or a material compound comprising a metal and plastic foil (e.g. blister packaging).

[0073] The consumable 2 further provides a centrally arranged hole 11 for taking up the tip of a gripper so that the consumable can be moved (comp. FIG. 1).

[0074] Each of the separate cavities 7 is fixed through a bridge 8 to the rim 15 (comp. FIG. 1, FIG. 2). The cavities 7 can be moved in a limited degree, because the bridges 8 allows for a limited movement which is indicated by the arrows in FIG. 2. A design for each of the four cavities as shown in the embodiments in FIG. 1 and FIG. 2 provides and guarantees a tolerance compensation in x-, y-, and also in z-direction.

[0075] The tolerance compensation is in particular required for use of the consumable with cavities in a thermocycler because it is necessary that the consumable fits exactly in the thermo unit, respectively the cavities providing the surfaces for transferring thermal changes to the cavities of the consumable. Appropriate heat transfer can only be guaranteed if the side walls of the cavities are in tight contact with the surfaces of the heating and cooling element.

[0076] Light can be introduced into the cavities through a first light guiding fiber 80 arranged above each cavity and emitted fluorescent light can be absorbed by a second light guiding fiber 80. Due to the thin foil and the consumable design, it is possible to bring the glass fibers as close as possible to the fluid surface to get the best readout (comp. FIGS. 11A-11C).

[0077] The cover foil 5 can be rotated and thus allows for closing all cavities simultaneously. FIG. 3A shows a consumable with holes 17 arranged above the openings of cavities 7 so that the cavities are open and may receive a liquid. FIG. 3B shows a rotation gripper 18 that engaged with spikes 12 into openings 19 of the cover foil 5 for rotating it so that all cavities are closed. Following rotation and closing of the cavities 7, the cover foil 5 has to be sealed (e.g., by heat) onto the upper end of the cavities openings 7 which may be surrounded by a raised border 9 so that this raised border can be configured to melt during heating of cover foil 5 for obtaining an airtight sealing of the cavities.

[0078] FIG. 4 shows a stack 22 of consumable 2 with cover foil 5 according to the present disclosure which is stackable. FIG. 5 shows in a sectional view exemplary two stacked consumables 2 with cover foil 5. Rim 15 has a snap-in feature comprising a retaining element 16 which can be formed like an edge at the bottom side of the rim 15 and a hook 14 extending from the upper side of rim 15 so that the hook 14 of a lower consumable snaps into the retaining element 16 of the above arranged consumable.

[0079] The consumables can be handled via a gripper 25 comprising an interface pin 27 for engaging into hole 11 and a strip-off-shell 29 for setting down or placing down the consumable 2 with cover foil 5 (comp. FIGS. 6A-6B). The interface pin 27 can plug into the hole 11 for the gripper 25. The tip of interface pin 27 can be formed conically (comp. FIG. 6B) and acts as an alignment cone for centrally arranging the interface pin 27 in the consumable 2 for achieving a form fit connection between interface pin 27 and consumable 2. The picked-up consumable 2 can be transported inside the automated analyser system, loaded or unloaded from the automated analyser system. To eject the consumable 2 at its final destination, the protruding interface pin 27 can be moved upwards into the strip-off shell 29 in order to strip-off the consumable 2 (FIG. 6B).

[0080] The interface pin 27 provides a rotation lock to avoid an unintentional twisting, turning, or rotating of the consumable during handling. The anti-rotation function of the interface pin 27 is realized by three or more flattened longitudinal surfaces 28 which are arranged at the outer circumference of the interface pin 27 (comp. FIG. 7). During the vertical downwards movement of the gripper the interface pin 27 enters the centrally arranged hole 11 of the consumable which circumference is indicated by the dotted line in FIG. 7 and deforms the centered hole 11 for generating form fitting connection avoiding any rotational movements of the consumable around interface pin 27.

[0081] Different steps are necessary for the whole sample preparation process like a PCR. FIG. 8 shows an exemplary setup for supply and preparation of the consumables 2 for a PCR. A consumable 2 is separated from a stack of consumables 22 and loaded onto a circular shaped processing unit 51. After loading of consumable 2, the disc shaped processing unit 51 turns by one position so that an empty position for loading of the next consumable is rotated next to the stack of consumables 22 and the loaded consumable 2 is rotated to a pipetting position so that a pipette 60 can fill the respective cavities with a liquid. The disc shaped processing unit 51 is moved by a further position so that the consumable 2 with liquid filled cavities reaches a closing position. Rotation gripper 18 engages with spikes 12 into openings 19 of the cover foil 5 for rotating it so that all cavities are closed after rotation of the cover foil 5. Processing unit 51 rotates again by one position so that the consumable with closed cavities is positioned below a heating element 20 which is pressed onto cover foil 5 for sealing the foil 5 with the upper end of the openings by applying heat and optionally pressure to cover foil 5. The disc shaped processing unit 51 rotates again by one position and consumable 2 is positioned below a gripper 25 which engages into the centrally arranged hole for removing the consumable 2 from the processing unit 51. The empty place in the processing unit 51 is then moved before the stack of consumables 22 so that the process can restart with another consumable 2 which is separated from the stack of consumables 22. It is also possible that this circular preparation process may employ a centrifuge. Thus, bubbles in liquids will be removed by centrifuging from the cavities of the consumables after pipetting the liquid into the cavities. Such a configuration will save a transfer step to a separate centrifuge and the consumables can directly be transported back to the circular shaped processing unit 51 for further processing as described above.

[0082] FIG. 9 shows an alternative sample preparation process. This embodiment represents an individual preparation process in contrast to the one depicted in FIG. 8. In a loading unit 69 the consumables 2 are loaded in stacks 22 and then provided individually, respectively single consumables separated from a stack. The individual consumables 2 will be transferred into a pipetting and sealing unit 70 with different processing lines. The processing lines comprise different processing stations such as a loading and pipetting unit 71, a foil turning unit 72 and a sealing unit 73 for each consumable. The consumable is in this case able to pass through the various processing stations independent from other consumables. Additionally, this embodiment comprises a linear movement instead of a rotational movement.

[0083] The advantages of the disclosure can be summarized as follows: [0084] The stackable consumable requires less space during transport and provision to an automated analyser. [0085] Stacking of the consumable reduces the risk of a contamination of the cavities prior to receiving a liquid. [0086] The multi-cavity consumable results in lower test costs for small batch sizes. [0087] Integrated sealing foil makes additional devices for loading, separation and handling of consumable caps redundant. [0088] A heat sealing process results in air tight closed cavities. [0089] Heat sealing allows for a fully automatic sealing process inside an automated analyser system. [0090] No separate device for handling of sealing material required. [0091] Consumable can be handled with a simple gripper. [0092] The rotating sealing (foil) enables to close all cavities in parallel. [0093] Tolerance compensation enables a precise fitting of the cavities inside the thermal cycler device. [0094] Fluorescence measurements can directly be performed inside the cavities.

[0095] Alternative designs of a multi cavity consumable 2 and a cover 6 for sealing are shown in FIGS. 10A-10C and FIGS. 11A-11C. Both designs may have a stackable cover 66 and a stackable consumable 22 (FIG. 10A), wherein a cover 6 can close the cavities 7 of a consumable 2 (FIG. 10B) but is not rotatable on the consumable. The tightness for closing of the cavities will be generated by applying a force from the top onto the cover and thus onto the sealing surface. In both alternatives, the cover 6 or a cover foil 5 (not shown) is not part of the consumable itself and must therefore be handled separately. The designs shown in FIGS. 10A-10C and FIGS. 11A-11C do not belong to the present disclosure.

[0096] FIGS. 11A-11C show an embodiment comprising a light guiding fiber 80 for detecting light emission resulting from reactions inside the cavity.

[0097] Another design of a multi-well consumable is shown in FIGS. 12A-12B. The cover foil 5 is heat sealed between a frame 40 and a base plate 45 of the consumable 2 comprising the cavities 7 to ensure the best possible optical transparence. The frame 40 with the cover foil 5 can be snapped onto the multi cavity consumable 2.

[0098] FIGS. 13A-13B show a multi cavity consumable 2 which has an integrated cover foil 5 like the consumables belonging to the disclosure as described above. The cover foil 5 can also rotate for opening (FIG. 13A) or closing (FIG. 13B) the cavities of a consumable. A consumable 2 according to FIGS. 13A-13B has large handling features 50 for gripping and transporting with another gripper design. The cover foil 5 rotates around the centrally arranged handling feature 50.

[0099] There are also other designs conceivable for obtaining a tolerance compensation between the cavities of a consumable and a rim or supporting frame. FIGS. 14A-14B show alternative designs for a bridge 8 allowing the connected cavities 7 to move for tolerance compensation. The bridges 8 are a kind of part of the rim. The consumable is stackable as can be taken from FIG. 14B.

[0100] FIGS. 15A-15B show an alternative design of a consumable 2 with bridges 8 connecting cavities 7 to a rim or frame. The consumable 2 has a handling features 50 for a gripper (not shown) which differs from the embodiment shown in FIG. 1. In this alternative embodiment are the snap-fit features for stacking of consumables located at the inner hole 11 comprising a ring 46 below base plate 45 which snaps into a collar 47 located above the base plate 45, wherein both, ring 46 for snap fit and collar 47 surround the centrally arranged hole 11 on the upper or lower end of the hole, respectively. A gripper with rotation lock (not shown) simultaneously grips the upper consumable 2 of a stack of consumables and spreads the clipping feature to release the upper consumable 2.

[0101] FIGS. 16A-16C show further designs for tolerance compensation of the cavities 7 of a consumable 2 with different embodiments for bridges 8.

[0102] There are also other methods conceivable for sealing a consumable with a cover foil without thermo sealing, comprising: [0103] using a foil with microencapsulated glue that will activated via force; [0104] ultrasonic welding; [0105] laser welding; [0106] heat impulse welding; [0107] wedge welding; [0108] convection welding; [0109] resistance welding; [0110] high frequency welding; [0111] induction welding.

[0112] The processing of a consumables 2 with a rotatable cover foil 5 is similar to the processing of a consumables of the present disclosure as shown in FIG. 8. The difference is the rotation of the cover foil 5 via a frictional connection and the different gripper 18 that will be used as can be seen in the right part of FIG. 17. Such a consumable 2 is shown in more detail in FIGS. 13A-13B. In a first step, the consumable 2 is separated from the stack 22 and loaded onto a circular shaped processing unit 51 which rotates by one position to a pipetting position where pipette 60 fills liquids in cavities 7. Processing unit 51 is rotated by a further position so that the consumable 2 reaches a rotating position where cover foil 5 is rotated via a gripper 18 which rotates cover foil 5 by frictional forces so that the openings of a cavity are closed by the tongues of cover foil 5. The next position is used for heat sealing of the cover foil 5 by a heating element 20 to the openings of the cavities. The final position is used for removing the sealed consumable by a removal gripper 90 which engages with the centrally arranged gripping element 50.

[0113] FIGS. 18A-18B show a consumable 2, which may be used for PCR for instance, that can be loaded and stored into the system without a cover foil 5 (FIG. 18A). Within the rectangular design of the consumable's embodiment shown in FIGS. 18A-18B, there are four cavities 7 located. For tolerance compensation, they are connected to the frame 40 by bridges 8.

[0114] A difference resulting from the consumable design shown in FIGS. 18A-18B is that consumable 2 and cover foil 5 (FIG. 18B) need to be handled separately inside the instrument (comp. FIG. 19). A stack of consumables 22 is loaded into a supply 21. Separation wheels 86 which can be gear wheels are moving consumables 2 downwards and separate them so that a single consumable 2 can be moved onto processing unit 51. In the next step, pipette 60 applies liquids to the cavities and a fitting piece of cover foil is cut from roll 85 providing the foil. In addition to cutting the cover foil from roll 85, the foil may be stamped in a circular shape and holes may also be stamped. The following steps are similar to the ones described above for a consumable according to the disclosure. An advantage of the embodiment shown in FIG. 18 and FIG. 19 is that the cover foil 5 can be provided from a roll 85.

[0115] FIGS. 20A-20B show an embodiment of a consumable 2 which is not belonging to the disclosure with slidable cover foil 5. Cavities 7 of such a consumable 2 can be closed for example with a pipetting system and a disposable tip (not shown) before heat sealing. It is advantageous to use a disposable tip for avoiding contamination of the consumable.

[0116] FIG. 21 depicts a process for the consumable 2 shown in FIGS. 20A-20B with a slidable cover foil 5 in more detail. The consumables 2 are provided in stacks 22 and may be grouped in eight stacks with ten consumables each so that a rack with the eight stacks may comprise in total 80 consumables 2. A removal gripper 90 is picking a single consumable 2 from a stack 22 and transfers it into a processing unit 51 where a pipette 60 adds a liquid to cavities 7 and slides cover foil 5 for closing the cavities. In a next step heating element 20 seals the cavities by heating cover foil 5. In a next step the consumable 2 is removed from the processing unit 51.

[0117] The foregoing description of the preferred embodiment of the disclosure has been presented for purposes of illustration and description. It is not intended to be exhaustive or to limit the disclosure to the precise form disclosed, and modifications and variations are possible in light of the above teachings or may be acquired from practice of the disclosure. The embodiment was chosen and described in order to explain the principles of the disclosure and its practical application to enable one skilled in the art to utilize the disclosure in various embodiments as are suited to the particular use contemplated. It is intended that the scope of the disclosure be defined by the claims appended hereto, and their equivalents. The entirety of each of the aforementioned documents is incorporated by reference herein.

REFERENCE NUMERALS

[0118] 2 consumable [0119] 5 cover foil [0120] 6 cover [0121] 7 cavity [0122] 8 bridge [0123] 9 border [0124] 11 hole for gripper [0125] 12 spikes [0126] 14 hook [0127] 15 rim [0128] 16 retaining element [0129] 17 hole [0130] 18 rotation gripper [0131] 19 opening cover foil [0132] 20 heating element [0133] 21 supply [0134] 22 stack of consumables [0135] 25 gripper [0136] 27 interface pin [0137] 28 longitudinal surfaces [0138] 29 strip-off shell [0139] 40 frame [0140] 45 base plate [0141] 46 ring [0142] 47 collar [0143] 50 handling feature [0144] 51 processing unit [0145] 60 pipette [0146] 66 stackable cover [0147] 69 loading unit [0148] 70 pipetting and sealing unit [0149] 71 pipetting unit [0150] 72 turning unit [0151] 73 sealing unit [0152] 80 light guiding fiber [0153] 85 roll [0154] 86 separation wheel [0155] 90 removal gripper