Method for replicating DNA, rotary device and system for DNA replication

Abstract

The DNA replication method of the present invention involves rotating a sample carrier (4) having at least one cavity (20) containing a sample liquid containing DNA around a rotation axis (14) using a rotating device (2), heating the cavity (20) to a high temperature only on the heat input side (26) lying in the rotation plane using a heating device (30), generating convection of the sample liquid within the cavity (20) by heating, with a substantial flow portion directed perpendicular to the rotation plane, and the circulation period of the liquid particles along the convection flow path being set by the rotation speed of the sample carrier.

Description

Technical Field

[0001] The present invention relates to a method for replicating DNA, and preferably, a rotating device configured and provided for performing the method. Furthermore, the present invention relates to a system for DNA replication.

Background Art

[0002] DNA (deoxyribonucleic acid) is frequently analyzed for scientific genetic material analysis, paternity testing, etc., or for the detection of existing diseases or the search for pathogens. For this purpose, it is necessary to replicate a specific site of DNA (optionally also RNA) contained therein from a sample such as a mucosal tissue or a blood sample. When detecting or analyzing RNA in a sample (such as virus detection), this is first transcribed into DNA by so-called "reverse transcription" and then replicated.

[0003] To replicate DNA, usually, a so-called polymerase chain reaction (abbreviated as PCR) is used in a liquid reaction mixture. DNA usually has a double helix structure consisting of two complementary single-stranded DNAs. In PCR, first, the temperature of the liquid reaction mixture is raised to usually between 90 and 96 °C to separate the DNA into two single strands ("denaturation step").

[0004] Subsequently, the temperature is lowered again ("annealing step", usually in the range of 50 to 70 °C), and so-called primer molecules are specifically attached to the single strand. Primer molecules are complementary short DNA strands that bind to single-stranded DNA at determined positions. The primer serves as a starting point for an enzyme called a so-called polymerase, which fills in basic components (dNTPs) complementary to the existing single-stranded DNA sequence in a so-called extension step. In this process, double-stranded DNA is formed again starting from the primer molecule. Extension is usually carried out at the same temperature as the annealing step or at a slightly higher temperature, usually between 65 and 75 °C. After extension, the temperature is raised again for the denaturation step.

[0005] Circulating the temperature in the liquid reaction mixture in a temperature range of two to three steps in this way is called PCR thermal cycling, and is usually repeated 30 cycles and 50 cycles. In each cycle, a specific DNA region is replicated. Generally, the thermal cycling of the liquid reaction mixture is converted by controlling the external temperature in the reaction vessel. The reaction vessel is arranged, for example, in a thermoblock, in which the PCR thermal cycle is converted by heating and cooling a solid that is in thermal contact with the reaction vessel, and at this time, heat is supplied to and removed from the liquid. Alternatively, the heating and cooling concept for the conversion of the PCR thermal cycle is the temperature control of a fluid (especially air and water) flowing around the reaction vessel, and also a concept based on radiation by heat supply using, for example, ultraviolet irradiation or laser irradiation.

[0006] In the conventional polymerase chain reaction, the processing period is in the range of about several minutes, and thus it takes a relatively long time. Summary of the Invention Problems to be Solved by the Invention

[0007] The problem of the present invention is to accelerate the polymerase chain reaction. Means for Solving the Problems

[0008] According to the present invention, this problem is solved by a method for replicating DNA having the features of claim 1. Further, according to the present invention, this problem is solved by a rotating device having the features of claim 9. Further, according to the present invention, this problem is solved by a system having the features of claim 13. Further advantageous and in part inventive embodiments and further forms of the present invention are described in the dependent claims and the following description.

[0009] The method according to the present invention is useful for DNA replication. According to this method, preferably, first, a sample carrier having at least one cavity for accommodating a sample solution is filled with a sample solution containing DNA so that the sample solution is accommodated in the cavity. Subsequently, the sample carrier is rotated about a rotation axis by a rotating device. At this time, the cavity, preferably the sample carrier, is heated to a high temperature value only on the heat input side lying in the rotation plane (i.e., particularly parallel to the rotation plane) by a heating device. Preferably, heating is not performed on the side opposite to the heat input side. By this heating, convection of the sample solution occurs in the cavity. This convection has a substantial flow portion in a direction (at least mainly) perpendicular to the rotation plane, i.e., from the heat input side to the opposite side of the sample carrier (hereinafter referred to as the "heat release side") and / or vice versa. Preferably, the convection is generated substantially annularly at that time. At this time, the first flow portion extends particularly substantially parallel to the heat input side, the second flow portion extends from the heat input side to the heat release side, the third flow portion extends parallel to the heat release side, and the fourth flow portion returns to the heat input side again (from the heat release side). Thereby, the sample solution is preferably induced to return to the denaturation zone via a denaturation zone (particularly having a high temperature value), a so-called annealing zone (also referred to as a primer hybridization zone), and an extension zone. Further, the circulation period of the liquid particles of the sample solution along the flow path of the convection is set (particularly "controlled") by the number of rotations of the rotation of the sample carrier.

[0010] In particular, the circulation period of the liquid particles is further affected by other parameters such as the shape of the cavity, the viscosity of the sample solution, the density of the sample solution, and the temperature gradient generated. However, the number of rotations is a parameter that can be changed relatively easily and quickly (similarly generally regarding the shape).

[0011] By the one-sided heating of the above-described cavity, in other words, a temperature gradient (therefore in a direction decreasing from the heat input side to the heat release side) is preferably applied to the sample solution in the cavity perpendicular to the dominant force, particularly the centrifugal force generated from the rotation.

[0012] As used herein and hereinafter, the term "substantial flow portion" is understood to mean, in particular, that this flow portion has a non-negligible proportion of the volume of the sample liquid flowing within the convection. That is, this flow portion is not simply a locally occurring, in some cases temporarily limited, partial flow that occurs by chance. For example, the proportion of such a vertical flow portion is up to about one-fourth of the total flow rate. In particular, the fluid communication between the denaturation zone and the annealing zone required for the polymerase chain reaction is carried out through these flow portions or flow sections mainly perpendicular to the rotation plane. "Mainly perpendicular" is understood to mean, in particular, that these flow sections are exactly or at least approximately (for example, under an inclination of up to 30 degrees) perpendicular to the rotation plane.

[0013] Preferably, alongside the above four flow sections, there are portions that flow laterally with respect to them due to centrifugal force and / or Coriolis force. This preferably further promotes the mixing of the sample liquid, thereby enabling as uniform a mixing as possible of the reaction partners (i.e., the DNA to be replicated, primer molecules, and "chain components").

[0014] As used herein and hereinafter, the term "cycle period" is understood to mean the period (time) required for (particularly minute) liquid particles to flow back to the denaturation zone via the denaturation zone, annealing zone (also referred to as the primer hybridization zone), and extension zone. The cycle period can be set in the range of 0.1 second to 20 seconds depending on the number of rotations (and thus the rotation speed). Inside the cavity corresponding to the reaction chamber of the sample carrier, the average flow velocity can be set on the order of up to 22 mm / s.

[0015] With such a short cycle period and / or high flow velocity, a particularly high-speed polymerase chain reaction becomes possible, thereby advantageously saving processing time.

[0016] In a preferred variant of the method, the cavity is cooled on the heat release side opposite the heat input side to a lower temperature value compared to the high temperature value on the heat input side. Thereby, advantageously, the temperature of the annealing zone (and the elongation zone) can be adjusted, and in particular, it is possible to prevent the sample liquid from being further heated in the region of the annealing zone.

[0017] In a preferred variant of the method, for heating, a constant temperature value is applied to the heat input side by a heating device. If necessary, similarly, for cooling, a constant temperature value is likewise applied to the heat release side. Thereby, in a conventional polymerase chain reaction, it is possible to omit the (overall) relatively long (conventional cyclic) heating and cooling steps during DNA replication. Furthermore, the execution of the polymerase chain reaction is simplified because only the control of the target value (high temperature value or low temperature value) is required and a "ramp function" is unnecessary. Also, the heating device can have a simple structure, and if necessary, a rotating device can also have a simple structure.

[0018] Preferably, the temperature value of the heating device is set to 80 to 110 °C, particularly 90 to 100 °C, whereby a temperature value above the melting temperature of DNA is set in the denaturation zone. In particular, a temperature value of about 10 to 60, preferably about 40 °C is applied to the heat release side, whereby a temperature value of 50 to 70, particularly about 60 °C is set in the annealing or elongation zone (which are preferably arranged within the same region on the heat release side).

[0019] Preferably, a cooling air flow is used for cooling the cavity. The cooling air flow can be generated by relatively simple means, such as a type of processor fan, a (for example, cooling) fan, etc.

[0020] More preferably, heating is performed by a heating device disposed on the heat input side and covering at least the bottom surface of the cavity. That is, the heating device used preferably has a planar heating element. In that case, the surface area of the heating device preferably covers an area larger than the bottom area of the cavity, preferably several times the area. Thereby, advantageously, a plurality of cavities (a plurality of the same sample carriers or a plurality of sample carriers) can be heated simultaneously, thereby improving the throughput. Preferably, the heating device is integrated with the sample holder of the rotating device that supports the sample carrier.

[0021] As a preferred variant of the method, convection in the cavity is induced by a flow resistor belonging to the cavity. Thereby, the flow velocity and / or the pressure can be locally changed.

[0022] In a preferred variant of the method, the portion of the flow path from the heat input side to the heat release side runs specifically only along the side portion of the cavity facing the rotation axis, and the portion of the flow path from the heat release side to the heat input side runs specifically only along the side portion of the cavity on the side opposite to the rotation axis. Convection is induced by the above flow resistor. Preferably, the flow resistor is selected and set as follows. That is, the flow resistor is selected and set such that at least twice the flow resistance acts on the sample liquid in the region between the heat input side and the heat release side compared to the regions (i.e., specifically the denaturation zone, as well as the annealing and extension zones) belonging to the heat input side and the heat release side (i.e., high temperature or low temperature). Optionally, the flow resistor is selected and set such that a larger volume portion of the cavity is assigned to the lower temperature region, thereby allowing the sample liquid to stay longer in this lower temperature region than in the higher temperature region. Therefore, by this control, the residence time of the liquid particles, preferably the extension time, in each region is advantageously set.

[0023] In a preferred embodiment, the cavity has a substantially cuboid shape. The flow resistor is preferably formed by a type of beam or transverse web and divides the cavity into at least one flow path each from the heat input side to the heat release side, particularly on the radially inner and outer sides of the cavity. Through these two flow paths, the high-temperature volume part and the low-temperature volume part of the cavity (each belonging to the heat input side and the heat release side) are fluidly coupled to each other. Optionally, each of the two flow paths is further subdivided into divided paths by webs.

[0024] In a further preferred variant of the method, for the influence (control) on convection, the structure of the sample carrier in the vicinity of the cavity can be appropriately selected. The shape, wall thickness, and / or material of the sample carrier are appropriately selected in order to influence the heat release on the heat input side of the heating device and, as an option, on the heat release side (to the cooling device), particularly in order to set the resulting thermal conductivity. A relatively thick wall made of plastic, such as polycarbonate or polymethyl methacrylate, results in a relatively low thermal conductivity. The addition of a thermally conductive filler (such as carbon black, ceramic, etc.) improves the thermal conductivity in the case of the same wall thickness.

[0025] In a further preferred variant of the method, a sample carrier having a plurality of cavities is used for the parallel replication of DNA. Thereby, advantageously, the throughput can be improved, and thereby the amount of DNA to be replicated can be increased. In this case, additionally or alternatively, different primers and / or probes can also be assigned to different cavities that are already "dry" (i.e., before being filled with the sample solution). This enables the parallel detection of different target DNA fragments in the respectively assigned cavities.

[0026] Optionally, the above method is used in the context of multi-stage replication for the first replication stage ("preliminary stage") and / or the second replication stage (main replication). Optionally, the sample carriers have different cavities for each stage. Thereby, the samples assigned to each stage can be replicated simultaneously (with "transfer" to the cavities of the next higher stage).

[0027] The rotating device according to the invention is configured and provided for use in DNA replication, in particular in the context of the method described above. For this purpose, the rotating device comprises a processing chamber and a sample holder arranged in the processing chamber.

[0028] This sample holder is configured and provided for holding at least one sample carrier of the above type. This sample carrier thus has at least one (of the above type) cavity for accommodating a sample liquid containing DNA. Furthermore, the rotating device comprises a rotation drive device by which, in the intended operation, the sample holder rotates about the (above) axis of rotation. Furthermore, the rotating device comprises the above heating device by which, during the intended operation, at least the heat input side of the cavity of the sample carrier lying in the plane of rotation of the sample holder is heated to a high temperature value. Furthermore, the rotating device comprises a controller that is coupled to the rotation drive device and the heating device in a control-technical manner and is configured to carry out the above-described method for DNA replication, in particular automatically and optionally in cooperation with a laboratory operator.

[0029] The rotating device and the method described above share the above-described advantages and, in particular, the material features described in the context of the method as required.

[0030] Within the scope of the present invention, the controller (also referred to as the "control unit" as an option) can be formed as a non-programmable electronic circuit. However, preferably, the controller is formed by a microcontroller in which the functions for executing the method according to the present invention are implemented in the form of software modules. Optionally, this microcontroller and / or software module is realized within the scope of an individual control computer.

[0031] Preferably, the sample holder is a plate (also: disk or plate) of a type that can fix the sample carrier for executing the method. For fixing, the sample holder optionally has a clamping device (for example, of the type of a clamp, clamping jaws, etc.).

[0032] In a preferred embodiment, the heating device has a Peltier element. Alternatively, the heating device has a resistive heating element, a ceramic heater, etc. Also, optionally, a heater based on radiation, for example an infrared heater, is used. Preferably, the heating device extends planar, whereby it can cover a plurality of cavities of one or more sample carriers.

[0033] In this case, particularly preferably, the heating device is integrated into the sample holder and at least embedded within the sample holder (for example, inserted into a recess of appropriate dimensions in the sample holder). Thereby, a compact form becomes possible.

[0034] In a preferred embodiment, the rotation device comprises the above-described cooling device for cooling the cavities on the heat release side opposite to the heat input side to a low temperature value.

[0035] In a preferred variant, the cooling device is formed by a (cooler) fan. By means of this fan, in the intended operation, preferably, the processing chamber is circulated by the cooling air. In this case, preferably, the fan is also used for cooling the rotation drive device. Optionally, the fan is arranged in the processing chamber such that the flow is directed towards the heat dissipation side of the sample carrier. This can be advantageous if the outflow of air from the sample carrier due to centrifugal force, which results from the rotation of the sample carrier, is not sufficient for cooling. Alternatively, the cooling device can be formed by a cooling plate arranged on the sample carrier on its heat dissipation side. This cooling plate preferably has Peltier elements used for cooling.

[0036] Optionally, the above-mentioned fan also has a cooling function, for example, of the type of a refrigerator, an air conditioner, etc. In this case, the rotation device can advantageously be operated even in a relatively warm environment. Alternatively, only the ambient air is blown into the processing chamber by the fan. In this case, optionally, the temperature of the processing chamber is controlled by controlling the rotation speed of the fan using a temperature sensor.

[0037] The heat input side is understood here and hereinafter to mean, in particular, the side of the sample carrier, preferably its lower side, and thus the lower side of each cavity. This lower side is located above the sample holder and thus above the heating device during the intended operation. Correspondingly, the heat dissipation side means, in particular, the upper side of the sample holder. Furthermore, the terms heat input side and heat dissipation side can be assigned to the corresponding sides of the partial volume provided in the sample carrier in the processing chamber.

[0038] In a further preferred embodiment, the rotation device also comprises a fluorescence detector for detecting sufficient replication of DNA. For this purpose, preferably, a dye (initially particularly inactive) is added to the sample solution, and the fluorescence of the dye increases, for example, with an increase in the number of replicated DNA strands (and thereby a decrease in the number of free reaction partners). Thereby, the fluorescence in the cavity represents the degree of conversion achieved.

[0039] The present invention further relates to a system for DNA replication. This system includes the above-described rotating device and at least one of the above-described sample carriers.

[0040] The conjunction "and / or" is herein and hereinafter understood to mean, in particular, that the features connected by this conjunction can be formed together or, alternatively, can be formed with respect to one another.

[0041] Hereinafter, embodiments of the present invention will be described in more detail with reference to the drawings.

Brief Description of the Drawings

[0042]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Modes for Carrying Out the Invention

[0043] In all the figures, corresponding parts are always denoted by the same reference numerals.

[0044] FIG. 1 shows a system 1 for DNA replication. This system 1 includes a rotating device 2 and a sample carrier 4. Using this system 1, the DNA replication method described in detail below with reference to FIG. 6 is carried out.

[0045] The rotating device 2 includes a housing 6 that encloses the internal space of the housing, and this internal space of the housing is hereinafter referred to as the "processing chamber 8". Further, the rotating device 2 includes a sample holder 10. On this holder, the sample carrier 4 is held during the execution of the method (i.e., in the intended operation). The sample holder 10 is rotatable about the rotation axis 14 by a rotation driving device 12. Therefore, the sample holder 10 is a turntable. Further, the rotating device 2 includes a fan 16 as a cooling device, and by this fan 16, a cooling air flow passes through the processing chamber 8 during the intended operation. Further, the rotating device 2 includes a fluorescence detector 18.

[0046] The sample carrier 4 has at least one cavity 20 (see Figure 2) for accommodating a sample solution containing DNA. In a preferred embodiment, the sample carrier 4 has a plurality of these cavities 20. The cavity 20 has a cuboid shape with exemplary dimensions of about 5×3×1.2 mm 3 and is defined by a bottom wall 22 and a top wall 24 with respect to the lower side (hereinafter: "heat input side 26") and the upper side (hereinafter: "heat release side 28"), respectively, and is defined by side walls with respect to other sides not shown in more detail. The walls of the sample carrier 4 are formed of plastic, specifically cycloolefin copolymer (COC). In the intended operation, the sample carrier 4 is placed on the sample holder 10 by the heat input side 26.

[0047] The rotating device 2 includes a heating device 30. This heating device has a Peltier element that extends planar on the upper side of the sample holder 10 facing the heat input side 26, and optionally has a plurality of Peltier elements arranged adjacent to each other for flat heat radiation. The heating device 30 is integrated with the sample holder 10. In an embodiment not shown in more detail, an aluminum plate is arranged between the Peltier element and the sample holder 10 for uniformizing the temperature distribution.

[0048] A controller of the rotating device 2 (not shown in more detail) is provided to control the rotation driving device 12, the heating device 30, and the fan 16.

[0049] For DNA replication, in the first method step S1 (see FIG. 6), a sample carrier 4 and a sample solution containing DNA are prepared. The sample solution contains, in addition to the DNA to be replicated, primer molecules, components for forming new DNA strands, and polymerase. In the second method step S2, the sample solution is filled into the cavity 20.

[0050] In the third method step S3, the heating device 30 on the heat input side 26 keeps the sample carrier 4 constantly at a high temperature value of about 95°C. In parallel with this, the rotation driving device 12 rotationally drives the sample holder 10 about the rotation axis 14, whereby each cavity 20 rotates about the rotation axis 14. A cooling air flow (preferably 40°C) is blown onto the sample carrier 4 by the fan 16, whereby the heat release side 28 of the sample carrier is always kept at this low temperature value.

[0051] By heating the bottom side and cooling the lid side, a warm region 32 and a cold region 34 are formed inside the cavity 20 (shown by dashed lines), thereby forming a temperature gradient extending parallel to the rotation axis 14. In the cold region 34, the sample solution has a temperature value of about 60°C. In the warm region 32, the temperature value of the sample solution is equal to or higher than the melting temperature of DNA, specifically 90°C or higher.

[0052] Due to the density difference caused by the temperature of the sample solution, buoyancy-induced convection occurs by heating the bottom side and cooling the lid side. This convection is basically ring-shaped (i.e., approximately elliptical, see the semi-circular arrows in FIG. 2) and is directed by a flow component substantially perpendicular to the rotation plane of the sample holder 10. However, due to the centrifugal force of rotation (right direction in FIG. 2) and the Coriolis force existing due to rotation, (homogeneous) mixing of the sample solution also occurs in a direction transverse to the basic flow path of the convection. At that time, the speed of the convection increases as the rotation speed increases.

[0053] In the convection range, the sample liquid passes through the warm region 32 (substantially parallel to the rotating surface), and within the warm region, DNA denaturation occurs due to temperature. For this reason, the warm region 32 is also referred to as the "denaturation zone". After flowing substantially perpendicular to the rotating surface towards the heat release side 28, the sample liquid passes through the cold region 34 (again substantially parallel to the rotating surface), and within it, primer hybridization and subsequent DNA strand elongation take place. Therefore, the cold region 34 is also referred to as the annealing ring zone or the elongation zone. The sample liquid that has passed through the cold region 34 flows back into the warm region 32 (substantially perpendicular to the rotating surface).

[0054] Method step S3 is maintained until it is determined by the fluorescence detector 18 that the conversion of components intended for replication, etc. is sufficiently high. For this purpose, specifically, a threshold comparison is made between the detected fluorescence value and a predetermined threshold for sufficiently high conversion (for example, one determined empirically). When this threshold is exceeded, in the fourth method step S4, the rotation of the sample holder 10 and the heating by the heating device 30 are stopped, and the sample liquid is taken out from each cavity 20.

[0055] Alternatively, method step S3 is terminated after a predetermined time has elapsed. By the time-dependent change in fluorescence, at that time, optionally, the concentration of DNA contained in the original sample is assessed.

[0056] In particular, method steps S1 to S3 can also be carried out at least partially simultaneously with each other. In particular, the sample holder 10 does not need to be stationary during the filling of the cavity 20. Similarly, the heating device 30 can also already heat the heat input side 26.

[0057] Figures 3 and 4 show alternative embodiments of the sample carrier 4 having a modified structure of each cavity 20. Inside the cavity 20, a beam-shaped or cuboid-shaped flow resistor 36 extending parallel to the rotation surface within the cavity 20 is arranged. The flow resistor 36 is arranged so as to leave a first flow path 38 on the inner side in the radial direction (towards the rotation axis 14) and a flow path 40 on the outer side in the radial direction, and a convection flow path extends through these flow paths. Thereby, the flow resistor 36 separates the warm region 32 and the cold region 34 except for the flow paths 38 and 40.

[0058] In the illustrated embodiment, the flow paths 38 and 40 have the same flow path cross section. Also, the warm region 32 and the cold region 34 have the same dimensions.

[0059] In one embodiment of the option (not shown in more detail), the flow resistor 36 is arranged so that a larger volume portion of the cavity 20 is assigned to the cold region 34 rather than the warm region 32. Thereby, a longer extension period (residence period in the cold region 34, that is, the extension zone) can be obtained.

[0060] As a further option, the flow paths 38 and 40 have different flow path cross sections.

[0061] Figure 5 shows a further embodiment of the cavity 20. In this case, the flow resistor 36 is subdivided into divided paths 44 for each flow path 38 or 40 by further webs 42. At that time, on the other hand, the divided paths 44 assigned to the flow paths 38 or 40 may have different cross sections.

[0062] Note that the subject of the present invention is not limited to the above-described embodiments. Rather, further embodiments of the present invention can be derived by those skilled in the art from the above description. In particular, the individual features of the present invention and the modified embodiments described by various embodiments can also be combined in other ways.

Description of Reference Numerals

[0063] 1 System 2 Rotating device 4 Sample carrier 6 Housing 8 Processing chamber 10 Sample holder 12 Rotation drive device 14 Rotation axis 16 Fan 18 Fluorescence detector 20 Cavity 22 Bottom wall 24 Top wall 26 Heat input side 28 Heat dissipation side 30 Heating device 32 Region 34 Region 36 Flow resistor 38 Flow path 40 Flow path 42 Web 44 Divided path S1 Method step S2 Method step S3 Method step S4 Method step S5 Method step

Claims

1. A method for replicating DNA using polymerase chain reaction, comprising: rotating a sample carrier (4) having at least one rectangular parallelepiped-shaped cavity (20) containing a sample solution containing DNA about a rotation axis (14) by a rotating device (2); heating the cavity (20) to a high temperature value only on a heat input side (26) lying in the rotation plane by a heating device (30); generating convection of the sample solution within the cavity (20) by heating, the convection having a substantial flow portion directed perpendicular to the rotation plane; cooling the cavity (20) to a lower temperature value on a heat release side (28) opposite to the heat input side (26) of the sample carrier (4) as compared with the heat input side (26); A method for replicating DNA, wherein a circulation period of liquid particles along a flow path of the convection is set by a rotation speed of rotation of the sample carrier.

2. The method according to claim 1, wherein a constant temperature value is applied to the heat input side (26) for heating, and a constant temperature value is applied to the heat release side (28) for cooling as necessary.

3. The method according to claim 1 or 2, wherein cooling of the cavity is performed by a cooling air flow.

4. The method according to any one of claims 1 to 3, wherein the heating is performed by the heating device (30) disposed on the heat input side (26) and covering at least a bottom surface of the cavity (20), and in particular, the heating device (30) is integrated with a sample holder (10) of the rotating device (2) that supports the sample carrier (4).

5. The method according to any one of claims 1 to 4, wherein the convection within the cavity (20) is induced by a flow resistor (36) belonging to the cavity (20).

6. The method according to claim 5, wherein a portion of the flow path from the heat input side (26) toward the heat release side (28) opposite to the heat input side (26) runs along a side portion of the cavity (20) facing the rotation axis (14), and a portion of the flow path from the heat release side (28) toward the heat input side (26) runs along a side portion of the cavity (20) on the side opposite to the rotation axis (14), and the convection is induced by the flow resistance body (36).

7. The method according to any one of claims 1 to 6, wherein a sample carrier (4) having a plurality of cavities (20) is used for parallel replication of DNA.

8. A rotary device (2) for DNA replication using polymerase chain reaction, comprising: a processing chamber (8); a sample holder (10) disposed in the processing chamber (8) for holding at least one sample carrier (4) having at least one rectangular parallelepiped-shaped cavity (20) for accommodating a sample solution containing DNA; a rotation driving device (12) for rotating the sample holder (10) about a rotation axis (14) in an intended operation; a heating device (30) for heating the heat input side (26) of the cavity (20) lying in the rotation plane of the sample holder (10) to a high temperature value in an intended operation; a cooling device (16) for cooling the heat input side (26) of the cavity (20) and a heat release side (28) located on the side opposite to the cavity (20) to a low temperature value; a controller that is coupled to the rotation driving device (12) and the heating device (30) in a control technical manner and is configured to execute the DNA replication method according to any one of claims 1 to 7; and a rotary device (2) for DNA replication.

9. The rotary device (2) according to claim 8, wherein the heating device (30) includes a Peltier element and / or is integrated with the sample holder (10).

10. The cooling device according to claim 9, wherein the rotating device (2) includes a fan (16) that causes cooling air to flow through the processing chamber (8).

11. A system (1) for DNA replication, comprising the rotating device (2) according to any one of claims 8 to 10, and a sample carrier (4).

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