EP2446967A1

EP2446967A1 - System for processing and/or analyzing liquid samples, sealing arrangement and method for heat-sealing a microplate

Info

Publication number: EP2446967A1
Application number: EP10189647A
Authority: EP
Inventors: Thomas Schlaubitz; Pius Studer
Original assignee: F Hoffmann La Roche AG; Roche Diagnostics GmbH
Current assignee: F Hoffmann La Roche AG; Roche Diagnostics GmbH
Priority date: 2010-11-02
Filing date: 2010-11-02
Publication date: 2012-05-02

Abstract

The present invention pertains to a system for processing involving pipetting and/or analyzing liquid samples comprising a sealing arrangement for heat-sealing a microplate (28) having an upper face provided with a plurality of open-top wells (5), comprising a pressing element (8) provided with a pressing face for pressing a thermally fixable sealing cover (9) for sealing said wells on said microplate and a plurality of heat releasing sections (12) located in a manner to release heat to said microplate-pressed sealing cover except for foil regions covering openings of said wells. It further relates to a method for heat-sealing a microplate provided with a plurality of wells, comprising the following steps of: disposing a thermally fixable sealing cover over said wells; pressing said sealing cover on said microplate by means of a pressing element; and releasing heat to said sealing cover except for regions covering openings of said wells so as to thermally fix said sealing cover to said microplate.

Description

TECHNICAL FIELD

The present invention is in the field of clinical analysis and medical diagnostics and more particularly relates to a system for processing and/or analyzing liquid samples comprising a sealing arrangement for heat-sealing a microplate. It further relates to a sealing arrangement and a method for heat-sealing a microplate.

BACKGROUND OF THE INVENTION

In daily routine, commercially available instruments enable a large number of liquid samples to be processed and/or analyzed simultaneously. Usually, integrally molded plastic disposables provided with plural open-top wells sized to receive the liquid samples are used for performing the various processing and analysis steps, respectively. Such disposables are commonly known as "microplates".
It has been found advantageous to air-tightly seal the wells containing the samples. One reason is the necessity to avoid evaporation so as to ensure the integrity of the samples to thereby obtain a good reproducibility of test results especially in the case of small sample volumes. Another reason is to prevent spilling of the contents of the wells during transport of the microplate from one location to another. A yet another reason is to prevent cross contamination of the samples so as to provide a generally sterile and controlled environment under which reactions can be carried out.
In practical use, it is convenient to use transparent plastic foils which allow for an optical detection of reaction products even during progress of the reactions. For instance, a transparent foil provided with an adhesive backing is positioned over the microplate and pressed on the upper face, e.g., by means of a pressure roll rolling back and forth to obtain uniform adhesion to the microplate. However, adhesive foils often cause problems as to an air-tight sealing of the wells. Otherwise, the adhesive material can eventually influence the outcome of the sample analysis.
Better results can usually be obtained by thermally fusible foils. In practical use, the foil is pressed on the upper face of the microplate and heated, e.g., by means of a heated stamp to ensure a close adhesive fit with full contact to the microplate.
In light of the foregoing, it is an object of the invention to provide an improved system for processing and/or analyzing liquid samples comprising an arrangement for the automated heat-sealing of microplates. These and further objects are met by a system for processing and/or analyzing liquid samples, a sealing arrangement and a method for heat-sealing a microplate according to the independent claims. Preferred embodiments of the invention are given by the features of the dependent claims.

SUMMARY OF THE INVENTION

As used herein, the term "heat releasing sections" relates to individual elements for releasing heat which can be actively or passively heated and, e.g., can be configured as separate components or, in the more strict sense of the term, as portions or parts of one structural entity.
According to a first aspect of the invention, a new system for processing liquid samples involving pipetting of said samples and/or for analyzing liquid samples is proposed. The system comprises a sealing arrangement for the automated heat-sealing of a microplate involving the use of a thermally fixable sealing cover for sealing the wells. In some embodiments, the sealing arrangement can be manually operated for heat-sealing the microplate. In some embodiments, the sealing arrangement is automatically operated for heat-sealing the microplate. As usual, the microplate has an upper face forming a plurality of open-top retention regions or wells sized to receive liquid samples such as reaction mixtures. By heating the thermally fixable sealing cover, adherence of the sealing cover to the microplate can be induced so as to air-tightly seal the wells.
As used herein, the term "sealing cover" generally refers to laminar objects which can be used for air-tightly heat-sealing the wells. In some embodiments, the sealing cover is a thermally fusible sealing cover which can be fused to adhere to the microplate during solidification such as a sealing foil. In some alternative embodiments, the sealing cover is provided with an adhesive material which can be thermally activated. Such adhesive materials are well-known to those of skill in the art and, e.g., are described in US-patent No. 7037580 . In some embodiments, the sealing cover is configured as transparent sealing cover enabling optical detection of substances contained in the wells. Generally, the sealing cover can be planar or non-planar, flat or non-flat and, especially, can be structured in various ways, e.g., to comprise functional components such as optical lenses. Examples for materials which can be used for sealing covers are plastic materials such as polypropylene (PP) and polyethylene (PE) and laminates, e.g., made of aluminium (Al) and polypropylene (PP).
The system of the invention can be used for processing liquid samples wherein processing of the liquid samples involves pipetting of the samples by means of one or more pipettors. Stated more particularly, in some embodiments, the samples are subject to pipetting operations prior to heat-sealing the wells of the microplate, e.g., to pipette the samples into the wells and/or to add fluids and/or remove to aliquots of the samples contained in the wells. In some embodiments, the samples contained in the wells are subject to pipetting operations after heat-sealing wells, e.g., to add fluids to the samples contained in the wells and/or to remove aliquots therefrom.
Additionally or alternatively, the system of the invention can be used for analyzing liquid samples contained in the heat-sealed wells by means of one or more analytical compartments for performing tests and assays related to various immunochemical and/or clinical-chemical analysis items. In some embodiments, the system is adapted to thermally treat reaction mixtures contained in the heat-sealed wells to be put through a series of temperature excursions, e.g., for performing the PCR (polymerase chain reaction) or any other reaction of the nucleic acid amplification type. Specifically, transparent sealing covers enable quantitative real-time PCR by optically detecting the reaction products obtained during progress of the reactions.
According to the invention, the sealing arrangement of the system for processing and/or analyzing liquid samples comprises a pressing element provided with a pressing face for pressing the thermally fixable sealing cover on the upper face of the microplate. In some embodiments the pressing element can be moved to be brought in and out of direct (physical) contact with the sealing cover for pressing the sealing cover on the microplate.
The sealing arrangement further comprises a plurality of heat releasing sections arranged in a manner to release heat to the microplate-pressed sealing cover except for sealing cover regions covering openings of the wells. In some embodiments, the pressing element is provided with the heat releasing sections so that heat can be released to the sealing cover when operating the pressing element for pressing the sealing cover on the microplate. Specifically, the sealing arrangement is adapted to position the pressing element with respect to the microplate in a manner to enable the heat releasing sections to release heat to the sealing cover except for regions covering openings of the wells. In some embodiments, the sealing cover is provided with the heat releasing sections so that heat can be released to the sealing cover when operating the pressing element for pressing the sealing cover on the microplate. Specifically, the sealing arrangement is adapted to position the sealing cover with respect to the microplate in a manner to enable the heat releasing sections to release heat to the sealing cover except for regions covering openings of the wells. In some embodiments, the microplate is provided with the heat releasing sections so that heat can be released to the sealing cover except for regions covering the openings of the wells when operating the pressing element for pressing the sealing cover on the microplate.
Accordingly, the sealing arrangement of the invention advantageously enables the sealing cover to be locally heated to thereby induce adherence to the microplate wherein the liquid samples contained in the wells are subject to a reduced heat input. Specifically in the case of performing the PCR or any other reaction of the nucleic acid amplification type, especially in the case of small sample volumes, an inadvertent start of the amplification reaction caused by heat-sealing the microplate can advantageously be avoided. Hence, unspecific nucleic acid amplification prior to thermally cycling the liquid samples can be prevented so as to improve the reliability and reproducibility of the test results.
In some embodiments, the system of the invention includes a source for generating electromagnetic radiation wherein the heat releasing sections are being adapted for absorbing the electromagnetic radiation to be passively heated for releasing heat to the sealing cover. In some embodiments, the heat releasing sections are made of carbon black which, e.g., can be applied to the pressing element or sealing cover or microplate by using conventional printing technology such as screen printing or laser printing. In some embodiments, the source is adapted to generate infrared radiation. Accordingly, the heat releasing sections can be readily heated by illuminating with the electromagnetic radiation.
In some embodiments in which the sealing arrangement includes a source for generating electromagnetic radiation, the sealing arrangement is provided with a plurality of reflective sections for reflecting the electromagnetic radiation, wherein the reflective sections are located in a manner to shield the openings of the wells from the electromagnetic radiation. Accordingly, heat input to the samples contained in the wells can advantageously be further reduced.
In some embodiments of the system, the heat releasing sections are thermally isolated in a manner to reduce heat transfer to the ambient other than the sealing cover. Accordingly, heat input to the arrangement for heat-sealing the sealing cover can advantageously be reduced for improving the efficiency in heat-sealing the microplate.
In some embodiments of the system, the heat releasing sections are electrically conductive structures adapted for generating Ohmic heat for releasing heat to the sealing cover. Accordingly, the heat releasing sections can be actively heated by supplying electric current. In some embodiments, the heating sections are formed by a meshed structure interconnecting the heating sections.
In some embodiments of the system, the pressing face of the pressing element has first and second zones, wherein the first zones are located in a manner to be brought in opposite relationship to first regions of the sealing cover covering the openings of the wells and the second zones are located in a manner to be brought in opposite relationship to second regions of the sealing cover covering microplate portions other than the openings of the wells. Furthermore, the first and second zones have one or more of the following characteristics:

the second zones have a darker colour than the first zones;
the first zones have a lower thermal conductivity than the second zones;
the first zones are not in contact with the microplate-pressed sealing cover, while the second zones are in contact with the microplate-pressed sealing cover.

By these characteristics, a favourable synergistic effect with respect to a low heat input to the liquid samples and low heat loss in the sealing arrangement for heat-sealing the microplate can advantageously be obtained.
According to a second aspect, the invention relates to a sealing arrangement for the automated heat-sealing of a microplate involving the use of a thermally fixable sealing cover for sealing the wells. The sealing arrangement comprises a pressing element provided with a pressing face for pressing a thermally fixable sealing cover on the microplate for sealing the wells and a plurality of heat releasing sections located in a manner to release heat to the microplate-pressed sealing cover except for sealing cover regions covering openings of the wells. The sealing arrangement can be configured according to the various embodiments as above-detailed in connection with the system of the invention.
According to a third aspect of the invention, a new method for automatically heat-sealing a microplate provided with a plurality of open-top wells for receiving liquid samples is proposed. The method of the invention comprises a step of disposing a thermally fixable sealing cover over the wells, a step of pressing the sealing cover on the microplate by means of a pressing element and a step of releasing heat to the sealing cover except for regions covering the wells so as to thermally fix the sealing cover to the microplate.
In some embodiments of the method of the invention, heat releasing sections of the pressing element are actively or passively heated for releasing heat to the sealing cover for thermally fixing the sealing cover to the microplate. Typically, such embodiments comprise a step of positioning the pressing element with respect to the microplate in a manner to enable the heat releasing sections to release heat to the sealing cover except for regions covering the wells of the microplate.
In some embodiments of the method of the invention, heat releasing sections of the sealing cover are actively or passively heated for releasing heat to the sealing cover for thermally fixing the sealing cover to the microplate. Typically, such embodiments comprise a step of positioning the sealing cover with respect to the microplate in a manner to enable the heat releasing sections to release heat to the sealing cover except for regions covering the wells of the microplate.
In some embodiments of the method of the invention, heat releasing sections of the microplate are actively or passively heated for releasing heat to the sealing cover for thermally fixing the sealing cover to the microplate.
In some embodiments of the method of the invention, the heat releasing sections are illuminated by electromagnetic radiation absorbed by the heat releasing sections to be passively heated for releasing heat to the sealing cover for thermally fixing the sealing cover to the microplate.
In some embodiments of the method of the invention, in which the heat releasing sections are illuminated by electromagnetic radiation, the openings of the wells are shielded from the electromagnetic radiation.
In some embodiments of the method of the invention, the heat releasing sections are actively heated by supplying electric current passing through the heat releasing sections for generating Ohmic heat.

BRIEF DESCRIPTION OF THE DRAWINGS

Other and further objects, features and advantages of the invention will appear more fully from the following description. The accompanying drawings, together with the general description given above and the detailed description given below, serve to explain the principles of the invention.

FIG. 1 is a schematic sectional view of a first exemplary system including a sealing arrangement according to the invention;
FIG. 2 is a schematic sectional view of a second exemplary sealing arrangement of the invention;
FIG. 3 is a schematic sectional view of a third exemplary sealing arrangement of the invention;
FIG. 4 is a schematic sectional view of a fourth exemplary sealing arrangement of the invention;
FIG. 5 is a schematic sectional view of a fifth exemplary sealing arrangement of the invention;
FIG. 6 is a schematic sectional view of a sixth exemplary sealing arrangement of the invention.

DETAILED DESCRIPTION OF THE INVENTION

By way of illustration, specific exemplary embodiments in which the invention may be practiced now are described. In this regard, terminology with respect to orientations and directions such as "horizontal", "vertical", "upper", "lower" is used with reference to the orientation of the figures being described. Because components described can be positioned in a number of different orientations, this terminology is used for the purpose of illustration only and is in no way limiting.
First, reference is made to FIG. 1 illustrating a first exemplary system for processing and/or analyzing liquid samples generally referred to at reference numeral 1. The system 1 comprises a sealing arrangement generally referred to at reference numeral 2 for heat-sealing a microplate 28. As schematically illustrated in FIG. 1, the system 1 comprises one or more analytical compartments 29 which can be related to various immunochemical and/or clinical analysis items for analyzing liquid samples contained in wells 5 of the microplate 28. The system 1, e.g., can be adapted for performing the PCR, in particular real-time PCR, or any reaction of the nucleic acid amplification type and optically detecting the reaction products obtained. The system 1 further comprises one or more pipettors 30 for pipetting liquid samples and/or other fluids prior to and/or after heat-sealing the wells 5 of the microplate 28.
The sealing arrangement 2 includes a support 3 for supporting the microplate 28 in horizontal position. As schematically illustrated by the double-headed horizontal arrow, in some embodiments, the support 3 is slidably mounted to a base (not illustrated) enabling a repetitive, bidirectional movement between an operative position for heat-sealing the microplate 2 and an inoperative position for loading/unloading the microplate 2 to/from the support 3 like a tray. Since such sliding mechanism is well-known to those of skill in the art, it need not be further elucidated herein.
An upper microplate face 4 forms a plurality of open-top wells 5 for receiving liquid samples. The wells 5 can, e.g., be regularly arranged with respect to each other forming a two-dimensional array of columns and rows intersecting each other at right angles. As is further illustrated, in some embodiments, a plurality of circular rims 13, each of which surrounding an opening 14 of one well 5, projects from the microplate plate face 4. In some embodiments, the microplate 28 is an integrally molded plastic disposable intended for single use only.
With continued reference to FIG. 1, in some embodiments, the support 3 is provided with a plurality of helical compression springs 6 arranged in correspondence to the wells 5 for accommodating the wells 5. Specifically, in some embodiments, the pressure springs 6 are in an upright position relative to an upper support face 7 so that the microplate 28 can be vertically moved against the elastic force of the compression springs 6. Otherwise, by inserting the wells 5 into the compression springs 6, the microplate 28 is horizontally secured. In some alternative embodiments, the support 3 is equipped with one or more resilient means other than compression springs 6 such as an elastic gum or rubber for elastically supporting the microplate 28.
As further illustrated, in some embodiments, the sealing arrangement 1 comprises a pressing element 8 provided with a rigid pressing plate 26 and having a lower pressing face 19 for pressing a sealing foil 9 on the upper microplate face 4. For instance, the pressing plate 26 can be made of aluminium and have a thickness of about 10 mm. It is to be appreciated that other rigid materials and/or thicknesses can be envisaged according to the specific demands of the user.
With continued reference to FIG. 1, in some embodiments, the pressing element 8 is provided with a supporting layer 10 fixed to a lower plate face 11 of the pressing plate 26 for supporting a plurality of electrically conductive heat releasing sections 12. The supporting layer 10 can, e.g., be made of an electrically isolating material having a low thermal capacity such as ceramics or plastics. Specifically, in some embodiments, the supporting layer 10 is made of polyimide having a layer thickness of about 0.5 mm. It, however, is to be appreciated that other materials and/or layer thicknesses can be envisaged according to the specific demands of the user.
In the sealing arrangement 2 of FIG. 1, the heat releasing sections 12 are electrically conductive structures configured to generate Ohmic heat. Specifically, in some embodiments, the heat releasing sections 12 are connected to connecting line 27 for supplying electric current. The heat releasing sections 12 can, e.g. be embedded in a carrier layer (not illustrated) made of isolating material such as plastics enabling the heat releasing sections 12 to be readily fixed to the supporting layer 10.
In some embodiments, an isolating layer (not illustrated) made of thermally isolating material is sandwiched in-between the pressing plate 26 and the supporting layer 10 so as to inhibit heat transfer from the heat releasing sections 12 to the pressing plate 26. The isolating layer can, e.g., be made of polytetrafluoroethylene (PTFE) commonly known as Teflon and, e.g., have a layer thickness in the range of from 3 to 5 mm. Those of skill in the art will appreciate that any other material and/or layer thicknesses can be envisaged according to the specific demands of the user.
As schematically illustrated in FIG. 1 by the vertical double-headed arrow, in some embodiments, the pressing element 8 can be vertically moved so as to press the thermally fixable sealing foil 9 on the upper microplate face 4 and to bring the heat releasing sections 12 in and out of (direct) physical contact with the sealing foil 9. Since such moving mechanism is well-known to those of skill in the art, it need not be further elucidated herein. Accordingly, the sealing foil 9 can be pressed on the microplate 2 while heated by the heat releasing sections 12, the pressing element 8 thereby acting against the elastic forces of the helical compression springs 6. Due to the resilient forces of the helical compression springs 6, a homogeneous pressure force can be exerted on the microplate 2, e.g., for levelling at a pre-defined height. Otherwise, in case of a slightly non-even microplate 2, the microplate 2 can be planarized so that a close fit of the sealing foil 9 can be ensured.
In the sealing arrangement 1, the heat releasing sections 12 are located in such a manner that heat can exclusively be released to second foil regions 16 where the microplate-pressed sealing foil 9 is in contact with the circular rims 13 projecting from the upper microplate face 4. Otherwise, heat cannot be released to first foil regions 15 covering the openings 14 of the wells 5. In some embodiments, the heat releasing sections 12 are configured as conductive rings, e.g., formed by a mesh-like structure to exclusively contact the second foil regions 16 of the sealing foil 9. The sealing arrangement 1 is adapted to bring the pressing element 8 in a position with respect to the microplate 28 so that the heat releasing sections 12 are in opposite relationship with respect to the circular rims 13. This can, e.g. be reached by placing the microplate 28 in an appropriate horizontal position below the pressing element 8 and vertically moving the pressing element 8 towards the microplate 28. As illustrated in FIG. 1, in some embodiments, the heating sections 12 protrude from the lower plate face 11. In some alternative embodiments, the heating sections 12 are integrated in the pressing plate 26, e.g., located adjacent the lower plate face 11, resulting in a planar pressing face 19.
With continued reference to FIG. 1, the pressing face 19 of the pressing element 8 has first and second zones 23, 24, the first zones 23 being located in a manner to be brought in opposite relationship to the first foil regions 15 covering the openings 14 of the wells 5, the second zones 24 being located in a manner to be brought in opposite relationship to the second foil regions 16 covering microplate portions other than the openings 14 of the wells 5. Hence, the second zones 24 relate to the heat releasing sections 12. In some embodiments, the first zones 23 have a lower thermal conductivity than the second zones 25 so that heat transfer to the samples contained in the wells 5 can be further reduced. In some embodiments, the first zones 23 are not in contact with the microplate-pressed sealing cover 9, while the second zones 24 are in contact with the microplate-pressed sealing cover so that heat transfer to the samples contained in the wells 5 can be further reduced. In some embodiments, the second zones 24 have a darker colour than the first zones 23 so that heat transfer to the samples contained in the wells 5 by means of radiation can be reduced.
In practical use, the following scenario can, e.g., be performed. Those of skill will appreciate that other scenarios can also be performed according to the specific demands of the user.
Starting with horizontally moving the support 3 in inoperative position, the microplate 28 containing liquid samples such as reaction mixtures is put on the support 3. The pipettor 30 can be used to transfer liquid samples to the wells 5 of the microplate 28 prior to putting the microplate 28 on the support 3. The support 3, together with the microplate 2, is horizontally moved into operative position where the microplate 2 is kept ready for heat-sealing. In some embodiments, the thermally fixable sealing foil 9 is placed over the microplate 2 in sealing position. In some other embodiments, the sealing foil 9 is placed over the microplate 2 prior to transporting the microplate 2 into sealing position. In operative position, in some embodiments, the microplate 28 is in a position that the heat releasing sections 12 can be brought in contact with the second foil regions 16 by vertically moving the pressing element 8. The pressing element 8 then is vertically moved towards the microplate 2 until the sealing foil 9 is pressed on the upper microplate face 4. In this situation, the heat releasing sections 12 are in thermal communication with the sealing foil 9. When applying electric current to the heat releasing sections 12, the heat releasing sections 12 generate Ohmic heat released to the second foil regions 16, e.g., for fusing the sealing foil 9, to cause adherence of the sealing foil 9 to the microplate 28 to air-tightly seal the wells 5. When fusing the sealing foil 9, in some embodiments, pressing action of the pressing element 8 is not stopped before the sealing foil 9 is in a fully solidified state. Alternatively, in operative position, the microplate 28 can be in a position that the heat releasing sections 12 can be brought in contact with the second foil regions 16 by moving the pressing element 8 in a manner to perform a combined vertical and horizontal movement.
In some embodiments, the pressing element 8 is then moved upwards, followed by moving the support 3 into the inoperative position so that the heat-sealed microplate 2 can be removed from the support 3 for further processing, e.g. thermal cycling, of the reaction mixtures contained therein.
Alternatively, in some embodiments, the microplate 28 can be brought in contact with the second foil regions 16 by moving the microplate 28 in a manner to perform a vertical movement or a combined vertical and horizontal movement, the pressing element 8 counteracting the movement of the microplate 28.
In some embodiments, the sealing arrangement 2 of the system 1 is manually operated for sealing the microplate 28. In some embodiments, the sealing arrangement 2 is automatically operated under control of controller 31 for heat-sealing the microplate 28.
Reference is now made to FIG. 2 illustrating a second exemplary sealing arrangement 2 of the system 1 according to the invention. In order to avoid unnecessary repetitions, only differences with respect to the first exemplary sealing arrangement 2 of FIG. 1 are explained and, otherwise, reference is made to the explanations made in connection therewith.
Accordingly, the sealing arrangement 2 includes a transparent pressing element 8, in particular a transparent pressing plate 26, at least transparent for electromagnetic radiation 17 generated by radiation source 18 and directed towards the pressing element 8. In some embodiments, the source 18 is configured to generate infrared light having a wavelength longer than that of visible light but shorter than that of microwaves. The wavelength of infrared light typically is in a range of from 700 nm to 1 mm. In some embodiments, the source 18 is located right above the pressing element 8. In some embodiments, the source 18 is operatively coupled to light-guiding elements such as prisms, mirrors and the like for directing the radiation 17 towards the pressing element 8.
On the lower plate face 11, the pressing plate 26 of the pressing element 8 is provided with a plurality of heat releasing sections 12 configured to absorb the electromagnetic radiation 17 generated by the source 18. Stated more particularly, the heat releasing sections 12 are made of material which can passively be heated by the electromagnetic radiation 17 so as to release heat to the sealing foil 9. In some embodiments, the heat releasing sections 12 are made of carbon black. Those of skill in the art will appreciate that other materials adapted for heating by the electromagnetic radiation 17 can also be used. The heat releasing sections 12 can, e.g., be applied to the lower plate face by using a conventional printing technology such as screen or laser printing. Accordingly, contrary to the heat releasing sections 12 of the first exemplary sealing arrangement 2 of FIG. 1 which can be actively heated by supplying electric current for generating Ohmic heat, the heat releasing sections 12 of the second exemplary arrangement 1 of FIG. 2 can be passively heated by illumination with electromagnetic radiation 17.
Similar to the sealing arrangement 1 of FIG. 1, in the sealing arrangement 1 of FIG. 2, the heat releasing sections 12 are located in a manner that heat can exclusively be released to the second foil regions 16. Otherwise, heat cannot be released to the first foil regions 16 covering the openings 14 of the wells 5, provided the pressing element 8 is appropriately positioned with respect to the circular rims 13 of the microplate 28. Specifically, the heat releasing sections 12 can, e.g., be configured as rings to exclusively contact the sealing foil 9 in the second foil regions 16 where the microplate-pressed sealing foil 9 is in contact with the circular rims 13 projecting from the upper microplate face 4.
With continued reference to FIG. 2, in some embodiments, the pressing plate 26 is provided with a plurality of reflective sections 20 arranged at an upper plate face 25 of the pressing plate 26. Stated more particularly, the reflective sections 20 are configured to reflect the electromagnetic radiation 17 generated by the source 18 and are located in a manner to shield the openings 14 of the wells 5 from the electromagnetic radiation 17. Accordingly, the radiation 17 can exclusively enter the pressing element 8 in regions in-between the reflective sections 20 to illuminate the heat releasing sections 12 arranged at the lower plate face 11. Hence, on the one hand, liquid samples contained in the wells 5 are subject to a further reduced heat impact, and, on the other hand, heat input to the pressing plate 26 can be reduced.
Reference is now made to FIG. 3 illustrating a third exemplary sealing arrangement 2 according to the invention which is a variant of the sealing arrangement 1 of FIG. 2. In order to avoid unnecessary repetitions, only differences with respect to the second exemplary sealing arrangement 2 of FIG. 2 are explained and, otherwise, reference is made to the explanations made in connection therewith.
Accordingly, instead of using dedicated heat releasing sections 12 configured to absorb the electromagnetic radiation 17, the pressing plate 26 is made of material configured to absorb the electromagnetic radiation 17 generated by the source 18. Furthermore, on the upper plate face 25, the pressing plate 26 is provided with the reflective sections 20. Accordingly, combining the passively heated pressing plate 26 with the reflective sections 20 on the upper plate face 25 thereof, heat can exclusively enter the pressing element 8 in plate regions 21 in-between the reflective sections 20 to illuminate and thereby heat the pressing plate 26. Hence, heat can exclusively be released to the sealing foil 9 by the illuminated plate regions 21 or heat releasing sections 12 of the pressing plate 26 of the pressing plate 26, which are arranged in opposite relationship to the second foil portions 16.
Reference is now made to FIG. 4 illustrating a fourth exemplary sealing arrangement 2 according to the invention which is another variant of the sealing arrangement of FIG. 2. In order to avoid unnecessary repetitions, only differences with respect to the second exemplary sealing arrangement 2 of FIG. 2 are explained and, otherwise, reference is made to the explanations made in connection therewith.
Accordingly, on the lower plate face 11, the pressing plate 26 is provided with a plurality of recesses 22 located in-between the heat releasing sections 12. Stated more particularly, each of the recesses 22 is arranged in opposite relationship to one first foil region 15 so that conductive heat transfer to the first foil regions 15 can advantageously be reduced. In some embodiments, the recesses 22 have a darker colour than the heat releasing sections 12 so that heat released by radiation to the openings 14 of the wells 5 can be reduced. In some embodiments, the recesses 22 have a lower thermal conductivity than the heat releasing sections 12 so that heat input to the samples contained in the wells 5 is further reduced.
Reference is now made to FIG. 5 illustrating a fifth exemplary sealing arrangement 2 according to the invention which is another variant of the sealing arrangement of FIG. 2. In order to avoid unnecessary repetitions, only differences with respect to the second exemplary sealing arrangement 2 of FIG. 2 are explained and, otherwise, reference is made to the explanations made in connection therewith.
Accordingly, instead of the pressing element 8, the sealing foil 9 is provided with the heat releasing sections 12 which can be illuminated by the electromagnetic radiation 17 passing the transparent pressing element 8. As illustrated, in some embodiments, the heat releasing sections 12 are arranged at an upper surface of the sealing foil 9 and can, e.g., be applied by a conventional printing technology such as screen or laser printing. The heat releasing sections 12 are arranged in a manner to exclusively release heat to the second foil regions 16 of the sealing foil 9 for thermally fixing it to the microplate 28. Otherwise, heat is not released to the first foil regions 15 covering the openings 14 of the wells 5 provided that the sealing foil 9 is appropriately positioned with respect to the circular rims 13 of the microplate 28. As illustrated, in some embodiments, the pressing plate 26 is provided with reflective sections 20 arranged in a manner to reflect the radiation 17 in-between the heat releasing sections 12 of the sealing foil 9.
Reference is now made to FIG. 6 illustrating a sixth exemplary sealing arrangement 2 according to the invention which is a variant of the sealing arrangement of FIG. 1. In order to avoid unnecessary repetitions, only differences with respect to the second exemplary sealing arrangement 2 of FIG. 1 are explained and, otherwise, reference is made to the explanations made in connection therewith.
Accordingly, in some embodiments, instead of using helical compression springs 6, the sealing arrangement 2 comprises a rigid support 3 for supporting the microplate 28 provided with plural hollows 32 for accommodating the wells 5 of the microplate 28. Due to the rigid support 3 counteracting the pressing force of the pressing element 8, pressure force can readily be applied to the microplate 28, e.g., to planarized a non-planar microplate 28.
From the former description of the various exemplary sealing arrangements 2 of the system 1 of the present invention it becomes apparent that, due to the fact that the sealing foil 9 is exclusively heated in the second foil regions 16, the liquid samples contained in the wells 5 are subject to a strongly reduced heat input compared to the conventional case of heating the whole sealing foil. Hence, temperature-induced effects influencing the integrity (stability) of the liquid samples contained in the wells 5 can advantageously be avoided. In particular, in case reaction mixtures for the PCR or any other reaction of the nucleic acid amplification type are contained in the wells 5, unspecific amplification of nucleic acids caused by heat-sealing the microplate 28 can advantageously be prevented.
Furthermore, since there is only a comparably small heat input required for heat-sealing the microplate 28 and in light of the fact that heat loss within the arrangement 2 can be reduced, power efficiency in heat-sealing the microplate 28 can be improved. Otherwise, the heating sections 12 can quickly be heated and cooled to thereby reduce the time needed for heat-sealing the microplate 28. In the case of using a thermally fusible sealing foil 9, due to enabling a quick cooling of the sealing foil 9, pressing of the sealing foil 9 on the microplate 28 can be stopped after having the sealing foil 9 solidified thus enabling a simple and cost-effective structure of the sealing foil 9. Stated more particularly, contrary to the conventional case, the sealing foil 9 not necessarily has to include a laminated structure consisting of several individual layers including a fusible layer, an adhesive layer and a separating layer so as to not cause a poorly adhering or even damaged sealing foil 9 when removing the heat releasing sections 12. Accordingly, the sealing foil 9 can be produced in a highly cost-effective manner. Otherwise, optical transparency of the sealing foil 9 can be improved.
With respect to the first and sixth exemplary sealing arrangement 2 of FIGS. 1 and 6, by the virtue of the fact that not only heat is exclusively released to the second foil regions 16, but that also one or more of the following characteristics:

the supporting layer 10 and optionally the pressing plate 26 have a low thermal capacity,
heat transfer to the pressing plate 26 is inhibited by the isolating layer,
the second zones have a darker colour than the first zones, are realized, a favourable combined effect with respect to low heat input to the liquid samples and low heat loss within the sealing arrangement 2 for heat-sealing the microplate 28 can advantageously be obtained.

With respect to the second to fifth exemplary sealing arrangements 1 of FIGS. 2 to 5, by the virtue of the fact that not only heat is exclusively released to the second foil regions 16, but that also one or more of the following characteristics:

radiation 17 is reflected by the reflective sections 20,
the pressing plate 26 has a low thermal capacity,
the heat releasing sections 12 are thermally isolated from the ambient except for the sealing foil 9,
the pressing plate 26 is provided with recesses 22 opposite to the first foil regions 15,
the second zones have a darker colour than the first zones, are realized, a favourable combined effect with respect to low heat input to the liquid samples and low heat loss within the sealing arrangement 2 for heat-sealing the microplate 28 can advantageously be obtained.

Obviously many further modifications and variations of the present invention are possible in light of the above description. It is therefore to be understood, that within the scope of appended claims, the invention may be practiced otherwise than as specifically devised.

Reference list

1: System
2: Sealing arrangement
3: Support
4: Microplate face
5: Well
6: Compression spring
7: Support face
8: Pressing element
9: Sealing foil
10: Supporting layer
11: Lower plate face
12: Heat releasing section
13: Rim
14: Opening
15: First foil region
16: Second foil region
17: Radiation
18: Source
19: Pressing face
20: Reflective section
21: Plate region
22: Recess
23: First zone
24: Second zone
25: Upper plate face
26: Pressing plate
27: Connecting line
28: Microplate
29: Analytical compartment
30: Pipettor
31: Controller

Claims

A system (1) for processing involving pipetting and/or analyzing liquid samples comprising a sealing arrangement (2) for heat-sealing a microplate (28) having an upper face (4) provided with a plurality of open-top wells (5), said arrangement (2) comprising:
a pressing element (8) provided with a pressing face (19) for pressing a thermally fixable sealing cover (9) on said microplate (28) for sealing said wells (5),

a plurality of heat releasing sections (12) located in a manner to release heat to said microplate (28)-pressed sealing cover (9) except for sealing cover regions (15) covering openings (14) of said wells (5).
The system (1) according to claim 1, further including a source (18) for generating electromagnetic radiation (17), said heat releasing sections (12) being adapted for absorbing said electromagnetic radiation (17) for releasing heat to said sealing cover (9).
The system (1) according to claim 2, wherein said pressing element (8) is provided with a plurality of reflective sections (20) being adapted for reflecting said electromagnetic radiation (17), said reflective sections (20) being located in a manner to shield said openings (14) of said wells (4) from said electromagnetic radiation (17).
The system (1) according to any one of the preceding claims 1 to 3, wherein said heat releasing sections (12) are thermally isolated in a manner to reduce heat transfer to the ambient other than said sealing cover (9).
The system (1) according to claim 1, wherein said heat releasing sections (12) are adapted for generating Ohmic heat for releasing heat to said sealing cover (9).
The system (1) according to any one of the preceding claims 1 to 5, wherein said pressing element (8) is provided with said heat releasing sections (12).
The system (1) according to any one of the preceding claims 1 to 5, wherein said sealing cover (9) is provided with said heat releasing sections (12).
The system (1) according to any one of the preceding claims 1 to 7, wherein said pressing face (19) of said pressing element (8) has first and second zones (23, 24), said first zones (23) being located in a manner to be brought in opposite relationship to first regions (15) of said sealing cover (9) covering said openings (14) of said wells (5), said second zones (24) being located in a manner to be brought in opposite relationship to second regions (16) of said sealing cover (9) covering microplate portions (13) other than said openings (14) of said wells (5), said first and second zones (23, 24) having one or more of the following characteristics:
- said second zones (24) have a darker colour than said first zones (23);

- said first zones (23) have a lower thermal conductivity than said second zones (25);

- said first zones (23) are not in contact with said microplate (2)-pressed sealing cover (9), while said second zones (24) are in contact with said microplate (28)-pressed sealing cover (9).
A sealing arrangement (2) for heat-sealing a microplate (28) having an upper face (4) provided with a plurality of open-top wells (5), comprising:
a pressing element (8) provided with a pressing face (19) for pressing a thermally fixable sealing cover (9) on said microplate (28) for sealing said wells (5),

a plurality of heat releasing sections (12) located in a manner to release heat to said microplate (28)-pressed sealing cover (9) except for sealing cover regions (15) covering openings (14) of said wells (5).
A method for heat-sealing a microplate (28) provided with a plurality of wells (2), comprising the following steps of:
disposing a thermally fixable sealing cover (9) over said wells (5);

pressing said sealing cover (9) on said microplate (28) by means of a pressing element (8);

releasing heat to said sealing cover (9) except for regions (15) covering openings (14) of said wells (5) so as to thermally fix said sealing cover (9) to said microplate (28).
The method according to claim 10, wherein heat releasing sections (12) of said sealing cover (9) are heated for releasing heat to said sealing cover (9) for thermally fixing said sealing cover (9) to said microplate (28).
The method according to claim 10, wherein heat releasing sections (12) of said pressing element (8) are heated for releasing heat to said sealing cover (9) for thermally fixing said sealing cover (9) to said microplate (28).
The method according to claims 11 or 12, in which said heat releasing sections (12) are illuminated by electromagnetic radiation (17) absorbed by said heat releasing sections (12) for releasing heat for thermally fixing said sealing cover (9) to said microplate (28).
The method according to claim 13, in which said openings (14) of said wells (5) are shielded from said electromagnetic radiation (17).
The method according to claims 11 or 12, in which said heat releasing sections (12) are heated by electric current passing through said heat releasing sections (12) for generating Ohmic heat.