Instruments and method relating to thermal cycling

Abstract

The present invention relates to a device for thermal cycling of biological samples, a heat sink used in such a device and a method. The heat sink comprises a base plate designed to fit in a good thermal contact against a generally planar thermoelectric element included in the device, and a plurality of heat transfer elements projecting away from the base plate. According to the invention, the heat transfer elements of the heat sink and arranged in a non-parallel configuration with respect to each other for keeping the temperature of the base plate of the heat sink spatially uniform during thermal cycling.

Claims

1. A thermal cycling instrument for processing biological samples, comprising a sample holder designed to receive a plurality of biological samples, a heat sink comprising a base plate and a plurality of heat transfer elements projecting away from the base plate, a thermoelectric element sandwiched between the sample holder and the base plate of the heat sink, wherein the heat transfer elements of the heat sink are arranged in a non-parallel configuration with respect to each other such that the footprint of the elements at a distance from the base plate is larger than a footprint of the elements near an area of contact of the elements and the base plate for keeping a temperature of the base plate of the heat sink spatially uniform.

2. The instrument according to claim 1, wherein the heat transfer elements are oriented in a fan-like manner.

3. The instrument according to claim 1, wherein the base plate has a footprint essentially equal to the footprint of the sample holder.

4. The instrument according to claim 1, wherein the thermoelectric element comprises at least one peltier element thermally connected to the sample holder and the heat sink.

5. The instrument according to claim 1, wherein the heat transfer elements of the heat sink are oriented such that the heat dissipation capacity of the heat sink is spatially essentially evenly distributed across the base plate so as to minimize variations in passive heat transfer through the thermoelectric element during heating and cooling of the sample holder.

6. The instrument according to claim 5, wherein the majority of the heat transfer elements are oblique with respect to the normal of the base plate, the angle of the lateral elements being regularly larger than the angle of the inner elements.

7. The instrument according to claim 1, wherein the heat transfer elements have the form of fins or fin pins.

8. The instrument according to claim 1, wherein the heat transfer elements are planar or pleated.

9. The instrument according to claim 1, wherein the heat sink is formed of a unitary piece of metal.

10. The instrument according to claim 1, which comprises a fan for forcedly circulating air between the heat transfer elements of the heat sink.

11. The instrument according to claim 1, which is portable and adapted to be operated by batteries.

12. A method for processing biological samples, comprising subjecting a plurality of biological samples to a temperature cycling regime in a thermal cycling instrument, which comprises the steps of: providing a sample holder designed to receive a plurality of biological samples, providing a heat sink comprising a base plate and a plurality of heat transfer elements projecting away from the base plate, and providing a thermoelectric element sandwiched between the sample holder and the base plate of the heat sink, and keeping a temperature of the base plate of the heat sink spatially uniform by arranging the heat transfer elements such that a footprint of the elements at a distance from the base plate is larger than a footprint of the elements near an area of contact of the elements and the base plate.

13. The method according to claim 12, wherein the heat transfer elements are oriented in a fan-like.

14. The method according to claim 12, wherein a base plate and a sample holder are used, which have essentially equal footprints.

15. The method according to claim 12, wherein at least one peltier element thermally connected to the sample holder and the heat sink is used as the thermoelectric element.

16. The method according to claim 12, wherein a heat sink is used, where the heat transfer elements are oriented such that the heat dissipation capacity of the heat sink is spatially essentially evenly distributed across the base plate so as to minimize variations in passive heat transfer through the thermoelectric element during heating and cooling of the sample holder.

17. The method according to claim 16, wherein a heat sink is used, where the majority of the heat transfer elements are oblique with respect to the normal of the base plate, the angle of the lateral elements being regularly larger than the angle of the inner elements.

18. The method according to claim 12, wherein a heat sink having heat transfer elements in the form of fins or fin pins is used.

19. The method according to claim 12, wherein a heat sink having planar or pleated heat transfer elements is used.

20. The method according to claim 12, wherein a heat sink formed of a unitary piece of metal is used.

21. The method according to claim 12, which comprises forcedly circulating air between the heat transfer elements of the heat sink.

22. A heat sink for use in a thermal cycler having a sample holder designed to receive a plurality of biological samples, comprising a base plate designed to fit in a thermal contact against a generally planar thermoelectric element configured to be positioned between the sample holder and the base plate of the heat sink, and a plurality of heat transfer elements projecting away from the base plate, wherein the base plate has a footprint essentially equal to a footprint of a microtiter plate conforming to SBS standards, and further wherein the heat transfer elements of the heat sink are arranged in a non-parallel configuration with respect to each other such that the footprint of the elements at a distance from the base plate is larger than a footprint of the elements near an area of contact of the elements and the base plate for keeping a temperature of the base plate of the heat sink spatially uniform.

23. The heat sink according to claim 22, wherein the heat transfer elements are oriented in a fan-like manner.

24. The heat sink according to claim 22, wherein the base plate is thermally connected to a sample holder via a planar thermoelectric element.

25. The heat sink according to claim 24, wherein the thermoelectric element comprises at least one peltier element.

26. The heat sink according to claim 22, wherein the heat transfer elements are oriented such that the heat dissipation capacity of the heat sink is spatially essentially evenly distributed across the base plate.

27. The heat sink according to claim 26, wherein the majority of the heat transfer elements are oblique with respect to the normal of the base plate, the angle of the lateral elements being regularly larger than the angle of the inner elements.

28. The heat sink according to claim 22, wherein the heat transfer elements have the form of fins or fin pins.

29. The heat sink according to claim 22, wherein the heat transfer elements are planar or pleated.

30. The heat sink according to claim 22, which is formed of a unitary piece of metal.

31. A thermal cycling instrument for processing biological samples, comprising a sample holder designed to receive a plurality of biological samples, a heat sink comprising a base plate and a plurality of heat transfer elements projecting away from the base plate, a thermoelectric element sandwiched between the sample holder and the base plate of the heat sink, wherein said thermoelectric element comprises at least one peltier element thermally connected to the sample holder and heat sink, and further wherein the majority of the heat transfer elements are oblique with respect to the normal of the base plate, the angle of the lateral elements being regularly larger than the angle of the inner elements for keeping a temperature of the base plate of the heat sink spatially uniform.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1 shows a cross-sectional view of a typical core of a thermal cycler according to prior art,

(2) FIG. 2 depicts a cross-sectional view of a core of a thermal cycler according to one embodiment of the present invention,

(3) FIG. 3 shows a bottom view of a heat sink according to one embodiment of the present invention, and

(4) FIG. 4 shows a bottom view of a heat sink according to another embodiment of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

(5) The general principle of the invention is shown in FIG. 2. A sample holder 26, a peltier element 24 and heat sink 20 are stacked so as to form a core of a thermal cycler instrument. Between the parts, there is typically thermally well conducting agent applied. The heat sink comprises a base plate 21 and a plurality of heat transfer elements 22. In the embodiment shown in the figure, the heat transfer elements 22 are aligned uniformly pitched and having growing angle with respect to the normal axis of the base plate towards the lateral portions of the plate. It should be noted that non-parallel nature of the heat transfer elements in one dimension only is shown in the Figure. If fins or fin pins are used as heat transfer elements, there may or may not be a corresponding alignment also in a direction perpendicular to the image plane. A two-dimensional fin configuration is shown in FIG. 3. In the case of plates, the edges of the plates may be non-parallel, as shown in FIG. 4.

(6) Common to the embodiments described above is that the heat transfer elements are oriented in a fan-like manner such that the footprint of the elements at a distance from the base plate is larger than the footprint of the elements near the area of contact of the elements and the base plate. More generally, it can also be said that the heat transfer elements of the heat sink are preferably oriented in a non-parallel configuration such that the heat dissipation capacity of the heat sink is spatially essentially evenly distributed across the base plate so as to minimize variations in passive heat transfer through the thermoelectric element during heating and cooling of the sample holder. Non-parallelity of the protruding portions of the heat sink compensates for the limited size of the base plate (and the pettier module) and causes the temperature of the upper side of the base plate to remain at even temperature. Thus, no “hot spot” is formed in the middle portion of the base plate, such as in some prior art solutions.

(7) The spacing between the neighboring heat transfer elements is thus typically increasing when moved away from the base plate, i.e., there is a considerable angle between neighboring elements. The angle can also be non-constant in along the length of the elements. Also when viewed in the plane of the base plate, the angle may vary between different element pairs. In addition, or alternatively, the heat transfer elements may be initially non-uniformly pitched to the base plate. Both described methods have an effect on the spatial heat, dissipation capacity of the sink.

(8) The heat transfer elements can have the form of fins, fin pins, straight plates, pleated plates, or any other solid member in the form of an extended surface experiencing energy transfer by conduction within its boundaries, as well as energy-transfer with its surroundings by convection and/or radiation, used to enhance heat transfer by increasing surface area.

(9) The heat sink can be made of many different materials including aluminum, copper, silver, magnesium, silicon carbide and others, either singly or in combination. It also can be fabricated by any common method of manufacturing heat sinks, including extrusion, casting, machining, or fabrication techniques, either in entirety or in combination with simple finishing via machining. Most advantageously, the heat sink consists of a single continuous (unitary) piece. The even heat distribution is achieved solely by the proper alignment of the heat transfer elements, whereby there is typically no need for separate heat diffusion blocks, heat conductor arrangements or additional active heaters or coolers.

(10) The thermoelement used in connection with the present heat sink is preferably a pettier unit comprising one or more individual peltier modules. Multiple peltier modules may be driven in parallel without individual temperature control.

(11) The sample holder may be of any known type. Typically, it is fabricated from aluminium or comparable metal and is shaped to accommodate microtiter plates according to SBS standards (Society for Biomolecular Screening). Thus, on the top surface of the holder, there area plurality of wells arranged in a grid. The bottoms of the wells are formed to tightly fit against the outer walls of the microtiter plates so as to provide good thermal connection between the holder and the plate, in a preferred embodiment, a sample holder designed for v-bottomed (or u-bottomed) plates is used.

(12) Preferably, the footprints of the thermoelement and the base plate of the heat sink are essentially equal. Thus, no increased heat flow takes place at the lateral portions of the heat sink (cf. FIG. 1). Typically, also, the footprint of the sample holder corresponds to the areas of the heat sink and the thermoelement. Typically, the above-mentioned footprints correspond roughly to the footprint of SBS standard microtiter plates, but the beat sink according to the invention may also be manufactured to any other size or shape, depending among other things on the microtiter plate format used. Also, the exact heat transfer element configuration of the heat sink has an effect on the preferred size of the base plate.

(13) According to a preferred embodiment of the invention, a fan directed to the heat rejection zone (i.e., between the heat transfer elements) of the heat sink is used during cycling. This significantly increases the energy transfer rate from the heat sink to the ambient air.

(14) According to a further embodiment, the device according to the invention is a lightweight portable thermal cycler, possibly operated by a battery. Such a device can be used in field circumstances, i.e., where the biological samples to be analyzed are in the first place, in field circumstances, the benefits provided by the heat sink at hand, i.e., compact and simple form and low energy consumption, are emphasized.

(15) The invention may also be used in connection with other solutions for increasing thermal uniformity or efficiency of thermal cyclers, for example those referred to as prior art in this document. However, it has been found that shaping of the heat sink according to the invention is usually sufficient for practically eliminating the temperature non-uniformity caused by conventional heat sinks and thermal cyclers.

(16) Many different configurations are possible within the scope of this invention, including variations on part geometries, methods of assemblies and configurations of parts relative to each other. The description here is meant to illustrate and represent some possible embodiments of the invention.

(17) The invention in not limited to the embodiments presented above in the description and drawings, but it may vary within the full scope of the following claims. The embodiments defined in the dependent claims, and in the description above, may be freely combined.