CONTAINER FOR DIAGNOSTIC ASSAYS

Abstract

A container or consumable like a reaction tube for use in diagnostic assays. The present disclosure provides a system for fluid handling and transport, comprising a plate with at least one cavity for receiving a fluid which is surrounded by a rim, and a separate cover comprising a centrally arranged surface as a sealing element which is surrounded by a rim, wherein the plate or the cover comprise at least one snap-fit mechanism for connecting at least two plates, at least two covers or a plate and a cover, wherein the snap-fit mechanism extends upwards or downwards from the surrounding rim of the plate or the cover, and wherein the rim of the plate or cover which is to be connected is configured for accommodating the snap-fit mechanism of an upper or lower plate or cover in a retaining element arranged at the rim.

Claims

1. A system for fluid handling and transport, comprising: a plate with at least one cavity for receiving a fluid which is surrounded by a rim, and a separate cover comprising a centrally arranged surface as a sealing element which is surrounded by a rim, wherein the plate or the cover comprise at least one snap-fit mechanism for connecting at least two plates, at least two covers or a plate and a cover, wherein the snap-fit mechanism extends upwards or downwards from the surrounding rim of the plate or the cover, and wherein the rim of the plate or cover which is to be connected is configured for accommodating the snap-fit mechanism of an upper or lower plate or cover in a retaining element arranged at the rim.

2. The system of claim 1, wherein the centrally arranged surface is surrounded by a frame holding a sealing foil.

3. The system of claim 1, wherein the sealing foil is configured to be permanently connected to the upper ends of the cavities' openings by heat sealing, or wherein the sealing foil is configured to be permanently connected to the upper ends of the cavities' openings by an adhesive.

4. The system of claim 1, wherein the centrally arranged surface is a rigid plate configured to be permanently pressed onto the upper ends of the cavities' openings by the engagement of the at least one snap-fit mechanism in the retaining element.

5. The system of claim 1, wherein the centrally arranged surface is made of a translucent material and/or comprises a translucent window configured to allow light transmission.

6. The system of claim 1, wherein the centrally arranged surface comprises at least one downwards projecting protrusion which accommodates form-fit into the opening of a cavity.

7. The system of claim 1, wherein the walls of the cavities are made of a white material for increasing light reflection inside the cavity and preventing light refraction out of the cavity; or a black material for reducing background light reflection.

8. The system of claim 1, wherein upper ends of the cavities are surrounded by a collar extending over the surface surrounding the openings of the plate.

9. The system of claim 8, wherein the collar is made of a material configured to melt with the centrally arranged surface of the cover during heat sealing.

10. The system of claim 9, wherein the collar is a sealing ring.

11. The system of claim 1, wherein the plate comprises four cavities arranged two by two.

12. The system of claim 1, wherein the plate and its surrounding rim have a quadratic shape.

13. The system of claim 1, wherein the at least one snap-fit mechanism is a hook extending upwards or downwards from the rim of the cover or the plate.

14. The system of claim 1, comprising a plate and a cover with sealing element with four snap-fit mechanisms on two opposing sides.

15. A method of using for fluid handling and transport, comprising providing a plate with at least one cavity comprising a fluid which is surrounded by a rim, and attaching a separate cover comprising a centrally arranged surface as a sealing element which is surrounded by a rim, wherein the plate or the cover comprise at least one snap-fit mechanism for connecting the and the cover, wherein the snap-fit mechanism extends upwards or downwards from the surrounding rim of the plate or the cover, and wherein the rim of the plate or cover which is to be connected is configured for accommodating the snap-fit mechanism of an upper or lower plate or cover in a retaining element arranged at the rim, and applying the connected plate and cover in PCR applications.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0041] The invention 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 stacks of consumables.

[0043] FIGS. 2A and 2B show a well plate in a perspective from above and below.

[0044] FIG. 3 shows a sectional view through a consumable with liquids in the cavities.

[0045] FIG. 4 shows a sectional view of cavities which are placed into an element for heating and cooling of the liquids.

[0046] FIGS. 5A-5C show in FIG. 5A the left part a sealing element, in FIG. 5B a sealing element connected to a plate with fluids and in FIG. 5C a heating element for sealing the sealing element permanently to the plate.

[0047] FIGS. 6A-6B show in FIG. 6A a comparison between light refraction in a well, made of clear material (left) and white material (right) and it FIG. 6B a comparison between light detection in clear cavities (upper row) and white cavities (lower row).

[0048] FIGS. 7A-7B show an embodiment of the cover with sealing element which has a central surface which comprises at least one plug.

[0049] FIGS. 8A-8B show a stack of two plates with downwards projecting snap-fit mechanisms.

DETAILED DESCRIPTION

[0050] The technical problem is solved by the present invention.

[0051] The present disclosure provides a system comprising a consumable in terms of a device intended for single use which represents an attractive trade-off for potential customers between throughput, processing flexibility and overall costs. The system according to the present disclosure reduces the waste volume and further the number of unused process cavities of a consumable in an automated analyser system.

[0052] The system of the present disclosure represents a very compact and stackable consumable which may be used for polymerase chain reaction (PCR) besides other applications with detachable retaining features. Only a small space is required during storage and transport of the product because the consumable and its cover can be stacked which reduces the required space.

[0053] The system provides a high loading and storage capacity to an automated analyser system like a diagnostic instrument for instance. The risk of consumable, instrument, or sample contamination during manual handling by the user is minimized and automated handling inside the analyser is optimised.

[0054] A heat sealing or plastic welding is intended for obtaining air-tight sealed reaction cavities. The consumable according to the present disclosure comprises a system with a plate with at least one cavity for receiving a fluid like a liquid and cover for sealing said at least one cavity is optimised with respect to its performance in terms of allowing fast cycling, fluorescence measurement, and avoiding condensation during PCR for instance. Handling of the consumables is also optimized regarding stackability, automated transfer capabilities etc.

[0055] The product design is optimized for machine handling, not only in the context of a laboratory environment but also with respect to manufacturing of the consumables comprising plate and cover for reducing costs.

[0056] The product and consumable design focusses on a quick, easy, and reliable handling as well as self-explanatory usability.

[0057] A consumable according to the present disclosure may be used in the field of molecular diagnostics, more specific in PCR applications, e.g., real-time PCR and quantitative PCR. The primary function of the system or the consumable, respectively, encompasses the holding and sealing of the added liquids like samples and reagents during nucleic acid (NA) amplification for instance. The consumable is intended exclusively for single use only. It is designed for the usage in automated analytical systems in a lab environment in a clinic or privately owned labs, in line with in-vitro diagnostic (IVD) analysis.

[0058] The usage of a consumable in a fully automated analyser system includes loading, storage, separation, transportation, pipetting, sealing, centrifugation, thermal cycling, fluorescence measurement and disposal. An explanatory workflow considering operator, instrument and consumable may contain the following steps: [0059] a. System checks consumable resources on board; [0060] b. System requests reloading; [0061] c. Lab technician puts on gloves (if not yet done); [0062] d. Open cardboard box and remove plastic bag with consumables batches; [0063] e. Remove batches/stacks from plastic bag; [0064] f. Scan or type in consumable ID for traceability; [0065] g. Place stacks in the according (separated) loading interface of the analytical system; [0066] h. System checks/monitors stack loading (message to operator in case of failure); [0067] i. System allows/releases stack insertion; [0068] j. Analyzer stores and distributes loaded stacks; [0069] k. Demand-based separation, supply and transfer of plate; [0070] l. Pipetting (and optional mixing) of sample and reagent to plate; [0071] m. Demand-based separation, supply and transfer of sealing element; [0072] n. Assembly of plate and sealing element (attach sealing on top of plate); [0073] o. Heat sealing of filled plate; [0074] p. Transfer of sealed consumable to centrifuge; [0075] q. Centrifugation of reaction sample within consumable; [0076] r. Transfer of consumable to thermal cycler (including cycler closing); [0077] s. Thermal cycling of reaction sample according to selected thermal profile/assay; [0078] t. Fluorescence measurement of reaction sample during or after thermal cycling; [0079] u. Open cycler and discard/transfer processed consumable into solid waste; and [0080] v. Operator removes solid waste from system (if requested by the system).

[0081] A consumable 1 according to the present invention comprises a plate 5 and a cover with a sealing element 8. Important aspects for the design and shape of a consumable relate to its optimization it for machine automation and stacking. FIG. 1 shows stacks of plates 15 and stacks of cover with sealing elements 18. Therefore, each plate 5 and each cover with sealing element 8 provide a specific rim 25, 28 configured for accommodating a snap-fit mechanism 10. The detachable snap-fit mechanism 10 keeps stackable parts together but allows the needs-based separation of stack portions or single elements.

[0082] The snap-fit mechanism 10 comprises in an embodiment a hook which extends from the upper surface of rims 25, 28 and the lower surface of rims 25, 28 is configured to accommodate the hook so that the rim may comprise a retaining element, which can be an edge that is formed at the bottom side of the respective rim into which the hook of a lower plate snaps in (comp. FIG. 1). The hook may also extend downwards so that it accommodates from an upper plate or cover into the rim of a lower partner (FIGS. 8A and 8B).

[0083] It is to be noted that a single snap-fit mechanism within the meaning of the present disclosure is sufficient for connecting two plates, two cover or a plate to a cover. An embodiment with a hook extending upwards or downwards from a rim of a plate will accommodate in the retaining element of the cover's or plate's rim which surrounds the cover so that the force which connects the parts will be applied to the complete surrounding rim. Providing more than one snap-fit mechanism may be used to achieve a more equal distribution of the connecting forces resulting from the connection between snap-fit mechanism, e.g., a hook, and the retaining element of an above arranged rim.

[0084] Plates 5 and cover with sealing elements 8 are stacked separately depending on their type (FIG. 1). Consumable stacks ensure a dense packaging as well as a compact storage inside and outside of an analyzer. Each component of a system according to the instant disclosure may in an embodiment also provide a four-fold symmetric design which allows the handling of the consumable 1 independent from its orientation with respect to a symmetry plane. This reduces the overall manipulation effort, because no alignment or orientation steps are necessary, facilitates loading, positioning, separation, transport as well as other processes during handling of the consumable 1 and increases the reliability of the complete system.

[0085] FIGS. 2A and 2B shows a plate 5 in a perspective from above (FIG. 2A) and below (FIG. 2B). The plate provides four separate cavities 6 which are surrounded by a structure which can be regarded to be a supporting rim 25.

[0086] The cavities 6 of a consumable or plate 5 are intended to receive a liquid 55 which may comprise extracted nucleic acids, enzymes, primers, beads etc. during PCR setup and PCR for instance (comp. FIG. 3). All liquids 55 will be pipetted from above through a cavity's opening 16.

[0087] To ensure a fast energy transfer between the surfaces of the cycler's heating and cooling device and the liquids 55 which are located inside a cavity 6, the free-standing conical cavities may have thin walls and will be in direct contact to the surfaces of the thermal treatment unit 50 which is responsible for heating and cooling (comp. FIG. 4). The conical cavities 6 ensure a proper seating in the thermal interface and facilitate consumable handling and insertion.

[0088] All plate cavities 6 can be closed by the cover with sealing element 8 (FIG. 5A) which ensures contamination-free handling of the liquids and avoids evaporation of the pipetted liquids along thermal cycling for example. A two-stage sealing process may comprises the capping (FIG. 5B) and plastic welding indicated by the arrow in the block (comp. FIG. 5C). Following filling of a liquid in the cavities of a consumable and optionally mixing of the liquids using a pipettor, the cover with sealing element 8 will be attached to the plate automatically (FIG. 5B) and held in place by the snap-fit mechanism 10 for stacking.

[0089] In the next step, both components will be joined permanently. One way for achieving the permeant sealing is heat sealing resulting in an air-tight connection between the sealing element of the cover and the upper opening of the cavities 6, respectively (comp. FIG. 5C). The sealing element is formed by a central surface, wherein this term is used synonymously with centrally arranged surface, because the central surface is surrounded by a rim and thus arranged centrally with respect to the rim, as can be taken from the figures. The plate may provide a collar 30 (comp. FIG. 2A) like welding edges or rips surrounding each well's opening, wherein the collar will melt down for creating a material bonding between plate and sealing element. A heater applies from above the required energy for melting through the (thin) sealing element, like a foil, and applies additional pressure to join sealing element 8 and collar 30 surrounding the cavities' openings 16.

[0090] An alternative solution is to use a two-component cover with sealing element 8, comprising a frame for holding a sealing foil. The sealing foil can be either an adhesive or a heat-sealing foil. The sealing foil can be fixed above or underneath of the frame.

[0091] The sealing element can be made of a clear a highly light transmissive (translucent) material and it may comprise a measurement window for fluorescence excitation and detection. The sealing element is designed to support the light transmission through the areas (cover) above the well's opening. The (well) plates are made of white or opaque material, respectively, in order to enhance light emission towards the cover. The use of white plastics improves the sensitivity and consistency of qPCR data by preventing fluorescence refraction out of the well. With refraction being minimized, more signals will be reflected to the detector, increasing the signal-to-noise ratio. In addition, the white walls of a well will minimize variation across technical replicates by preventing transmission of fluorescence signals to the thermal cycler interface where it can be absorbed or inconsistently reflected.

[0092] FIG. 6A shows schematically the differences between using clear well walls (left part, left well) and white well walls (left part, right well). The signal refraction (indicated by arrows) is minimized when the wells are made of a white material so that there is no absorption of fluorescence by the thermal block but an improved reflection towards the upper opening for signal detection. With wells made of a clear material there will occur signal refraction because the light may be reflected by the inner surface of the thermo block instead of the inner surface of the well.

[0093] FIG. 6B shows in comparison the signal detection of identical fluorescein dilutions in water, wherein the upper row shows the results obtained using wells made of a clear and translucent plastic and the lower row shows the results using wells made of white plastic in qPCRs. Obviously, using a white material for the consumable's wells results in an improved light signal detection.

[0094] FIGS. 7A-7B shows an embodiment of the cover with sealing element 8 which has a centrally arranged surface 7 which comprises at least one plug 60 in terms of a downwards projecting protrusion which form-fits into the respective opening of a cavity 6 from a plate 5 as can be taken from FIG. 7A. FIG. 7B indicates the location of plug 60 in the centrally arranged surface 7. It is also within the scope of the present disclosure that plug 60 is made of a material suitable to melt under heat with the upper part of the opening or a collar, if present.

[0095] FIGS. 8A-8B show in its left part a stack 15 of two plates 5 with cavities 6. FIG. 8A shows a sectional view through the stack 15 of two plates 5. The plates 5 comprise downwards projecting snap-fit mechanisms 10 so that such a snap fit mechanism of the upper plate engages in a retaining rim 25 of a lower plate for connecting both plates 5.

[0096] The advantages of the present disclosure can be summarized as follows: [0097] allowing a needs-based consumption and processing of consumables and wells with a minimized plastic waste; [0098] compact and stackable consumable design for improved storage and usability; [0099] low space consumption (at shipping, storage, inside instrument etc.) due to dense packaging of components; [0100] symmetric design for decreased handling and orientation effort; [0101] minimizing contamination risk by a design allowing to provide the consumable and the cover in stacks; [0102] a compact and symmetric cycler block and thermal interface design: [0103] Equal thermal conditions for each well; [0104] Improved homogeneity and well-to-well-consistency; [0105] Lower energy consumption (low thermal masses); [0106] air-tight sealing of plate wells via heat sealing or welding; and [0107] design supports and improves fluorescence measurement.

[0108] Alternative approaches to realize or to circumvent the disclosure may relate to: [0109] Sealing of the plate via foil or thin plate; [0110] Sealing of plate via blister (thermoformed part); [0111] Well plate with integrated sealing (e.g., sealing caps on flexible arms); [0112] Well plate made of transparent material to also allow measurement from below; [0113] Well plate made of black material for influencing the optical performance; [0114] Mixed stacks (plate and sealing) compared to single-origin; [0115] Different number of cavities (e.g., 3×3, 4×2 or 4×4); [0116] Consumable parts without retaining and snap features; [0117] Consumables stored on common tray or carrier (mixed or single-origin); [0118] Welding features replaced by other well sealing elements: [0119] Flexible sealing elements (e.g., similar to O-ring), element is an integrated part or separate component, sealing effect is achieved by compressing the sealing element, compression force applied by external/peripheral devices (e.g., movable cycler lid); [0120] Matching conical interfaces at plate and cap; and [0121] Individual plug/stopper sealing elements at cap; [0122] Thermal conductive material for consumable components to support cycling; and [0123] Two-part sealing cap consisting of frame and foil.

[0124] 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

[0125] 1 consumable [0126] 5 plate [0127] 6 cavity [0128] 8 cover with sealing element [0129] 7 centrally arranged surface [0130] 10 snap-fit mechanism [0131] 15 stack of plates [0132] 16 opening [0133] 18 stack of cover with sealing elements [0134] 25 retaining rim of plate [0135] 28 retaining rim of sealing element [0136] 30 collar [0137] 50 thermal treatment unit [0138] 55 liquid [0139] 60 plug