Patent Description:
Biochemical reaction devices, such as polymerase chain reaction (PCR) devices, must undergo loops of three reaction steps, including denaturation, annealing, and extension, when performing nucleic acid amplification reactions. Each reaction step has a preset optimal reaction temperature. For example, the denaturation reaction is generally set between about <NUM> and <NUM>, the annealing reaction is set between about <NUM> to <NUM> depending on the different primers, and the extension reaction is set at a temperature of about <NUM> suitable for the polymerase reaction. The aforementioned reaction temperatures are closely correlated to the results of nucleic acid amplification, especially in the annealing reaction stage. If it is used to detect a target nucleic acid, the positive or negative determination is further affected by the reaction conditions. Therefore, accurate control of the reaction temperature is one of the important requirements of the device.

In regard to the use of the heating mechanism in the polymerase chain reaction device, the reaction tubes containing the reaction solution are respectively placed into a heating module provided with a plurality of holes, thereby achieving the purpose of controlling the temperature of the reaction tubes through a heat conduction by the contact between an inner wall of the heating module and the reaction tubes. However, since the numerous types and specifications of the reaction tube will cause uneven or insufficient contact between the outer wall of the reaction tube and the hole of the heating module, this may result in the uneven temperature of the solution in the reaction tube or the solution may fail to reach the preset temperature, thereby lowering efficiency of the reaction or yield of the amplified product. When the reaction tubes are used to detect a specific target nucleic acid sequence, the accuracy of the detection result is also affected.

In order to solve the above problem, mineral oil may be added to the hole to fill the gap between the reaction tube and the hole to improve heat transfer efficiency. However, the addition of mineral oil may easily cause sample contamination and cause mechanical cleaning and maintenance difficulties. More importantly, the mineral oil will also absorb and dissipate heat. After adding different volumes of mineral oil to the holes, there is also often a difference between the actual temperature and the preset temperature among the holes or even in the whole heating module. In addition, the heating module is bulky and thus requires a longer time to heat and dissipate heat, and therefore the required overall reaction time increases.

<CIT>discloses a device for processing a biological sample that includes a processing unit having at least one opening to receive a sample vessel and a plurality of processing stations positioned along the opening. The processing stations each have a compression member adapted to compress the sample vessel within the opening and thereby move the sample within the sample vessel among the processing stations. An energy transfer element can be coupled to one or more of the processing stations for transferring thermal energy to the sample at a processing station. However, <CIT>only provides a stationary member that can indirectly transfer heat to the sample vessel clamped by the compression member, and thus a heating efficiency needs to be improved.

The present invention provides a heating mechanism for a biochemical reaction device capable of conveniently placing a reaction container to be heated therein and capable of easily limiting the reaction container in a position. According to the heating mechanism of the present invention, the reaction container can be easily held and fixed in the heating mechanism by applying a thrust thereto but without deliberately adjusting the placement position of the reaction container, and then can be heated by heat conduction due to the clamping by the heat-conducting blocks thereon.

The present invention also provides a heating mechanism capable of precisely regulating the temperature of a biochemical reaction. According to the heating mechanism of the present invention, the heat-conducting blocks can be in close and direct contact with the reaction container for heat conduction, so that the solution in the reaction container can assuredly reach the preset temperature. As such, the heating conditions of the respective reaction containers are consistent with each other, so that the reaction can be more efficiently performed with fast heat transfer, and the reproducibility and accuracy of the reaction result can also be improved.

The present invention also provides a heating mechanism that can reduce the volume of a biochemical reaction device. According to the small and compact heating mechanism of the present invention, the same objective of the heat conduction can be achieved, but the required volume and space for the overall device can be reduced. Also, because of the compact size, it is more convenient in maintenance and replacement.

The present invention also provides a heating mechanism for a biochemical reaction device capable of shortening the reaction time. According to the small and compact heating mechanism of the present invention, the heating time and the heat dissipation time can be shortened, so that the time required for the overall reaction is greatly shortened, and thus the reaction efficiency can be improved.

The present invention provides a heating mechanism for a biochemical reaction device, comprising: a heat-conducting body, the heat-conducting body comprising: at least one accommodating groove each comprising a chamber and an opening communicating with the chamber; a clamping hole, in communication with the opening and for insertion of a reaction tube; at least one heat-conducting block, movably disposed in the chamber and having one end connected to an elastic element and another opposite end provided with an abutting portion, the elastic element enabling the abutting portion of the heat-conducting block to protrude from the opening and locate in the clamping hole; and a temperature control element, the temperature control element being connected to the heat-conducting body for heating and regulating a temperature of the heat-conducting block, characterised in that the abutting portion of the heat-conducting block is spherical.

In an embodiment of the present invention, the heating mechanism of the biochemical reaction device further comprises a reaction container, and the reaction container may further be provided with a heat-conducting element. When the reaction container is inserted into the heat-conducting body through the clamping hole, the reaction container is pressed by the abutting portion of the heat-conducting block reaction hole so that the reaction container is clamped therein and the heat-conducting element is in contact with the heat-conducting block to conduct heat energy.

In the heating mechanism of the biochemical reaction device according to an embodiment of the present invention, the accommodating groove is provided in plurality, and the openings provided in the accommodating grooves are distributed in a circumferential range of the clamping hole by about <NUM>°, preferably a circumferential range of the clamping hole by about <NUM>°, for one-sided heating the reaction tube. The accommodating grooves and the openings thereof may also be equally spaced apart in a circumference of the clamping hole to uniformly heat an outer edge of the reaction tube.

In the heating mechanism of the biochemical reaction device according to an embodiment of the present invention, the temperature control element is laid on and connected to a surface of the heat-conducting body, and the temperature control element is provided with a first through-hole, the first through-hole is in communication with the clamping hole.

In the heating mechanism of the biochemical reaction device according to an embodiment of the present invention, the abutting portion of the heat-conducting block is spherical, and thus the heat conducting block may be a shape of an ellipsoid, a sphere, a semi-ellipsoid or a hemisphere.

In the heating mechanism of the biochemical reaction device according to an embodiment of the present invention, the heat-conducting body is further provided with a recessed groove on the accommodating groove, and a limiting member is disposed in the recessed groove. The limiting member is provided with a second through-hole, and the second through-hole is in communication with a first through-hole of the temperature control element, and the clamping hole.

Since the reaction container for biochemical reaction can be easily placed in the clamping hole of the heat-conducting body of the present invention and clamped by the heat-conducting block, on the one hand, the reaction container can be fixed, and on the other hand, the direct contact between the reaction container and each heat-conducting block can be ensured. This avoids the disadvantage of the failure of contact between the outer edge of the reaction container and the heat-conducting block due to an offset placement of the reaction container. Therefore, not only the portion where the reaction container is in contact with the heat-conducting block can be heated uniformly, but also the consistency of the conditions of the heating reaction each time can be ensured, so that the biochemical reaction is reproducible and the reaction result is more accurate. In addition, since the reaction container is disposed in an insertion and clamping manner in the heating mechanism of the present invention, it is not necessary to provide a heating element or a heating module with a shape corresponding to that of the reaction container. Therefore, the reaction container or the heating device can be manufactured with a more widely allowable tolerance range, thereby reducing the manufacturing cost. On the other hand, because of the assured contact between the reaction container and the heat-conducting block, the heat energy can be quickly and precisely transferred to the reaction container. Therefore, the solution in the reaction tube can react accurately at the preset temperature, thereby further improving the reaction efficiency and the reaction accuracy.

The embodiments of the present invention are further described below, and the following examples are set forth to illustrate the present invention, and are not intended to limit the scope of the present invention. Those skilled in the art can make various changes and modifications without departing from the spirit and scope of the present invention. Therefore, the protection scope of the present invention shall be defined by the appended claims.

Referring to <FIG> is an exploded schematic view of a heating mechanism according to an embodiment of the present invention. The heating mechanism of the biochemical reaction device of the present invention comprises a heat-conducting body <NUM> and a temperature control element <NUM>, and the temperature control element <NUM> is connected to the heat-conducting body <NUM> for heat conducting and regulating the temperature change of the heat-conducting body <NUM>. For the convenience of assembling, the heat-conducting body <NUM> may be formed with a recessed groove <NUM>, and a limiting member <NUM> is disposed therein, so that related elements of the heat-conducting body <NUM> are limited therein. A clamping hole <NUM> provided in the heat-conducting body <NUM>, a first through-hole <NUM> provided in the temperature control element <NUM> and a second through-hole <NUM> provided in the limiting member <NUM> are in communication with one another, so that a reaction container <NUM> (see <FIG>) is clamped herein after inserting. The shape, length and outer diameter of the reaction container may be, but not limited to, designed according to the volume of the reaction solution and the shape of the corresponding heating mechanism. Optionally, the reaction container may be a tubular container, such as the reaction tube <NUM> of the embodiment. The tubular container may be, but not limited to, a circular tube or a polygonal tube.

Referring to <FIG> is a schematic view of a heat-conducting body in the heating mechanism according to an embodiment of the present invention. The structural shape of the heat-conducting body <NUM> is not particularly limited, and may be adjusted according to the requirements of the device, the size of the reaction tube, and the temperature control element. The clamping hole <NUM> of the heat-conducting body <NUM> is provided for insertion of the reaction tube <NUM>. The clamping hole <NUM> may be a through-hole or a blind hole, as long as the reaction tube <NUM> can enter and be clamped therein. In addition, at least one accommodating groove <NUM> is disposed in the heat-conducting body <NUM>, and each accommodating groove <NUM> includes a chamber <NUM> in which a heat-conducting block <NUM> is disposed, and the chamber <NUM> is extended to communicate with an opening <NUM>, and the opening <NUM> is connected to the clamping hole <NUM>.

Referring to <FIG> and <FIG> is a top view of the heat-conducting body in the heating mechanism according to an embodiment of the present invention. The heat-conducting block <NUM> is disposed in the chamber <NUM> in a movable manner and one end of the heat-conducting block <NUM> is connected to an elastic member <NUM>. The heat-conducting block <NUM> is pushed by an elastic force of the elastic member <NUM> towards against the opening <NUM>. As such, an abutting portion <NUM> of the heat-conducting block <NUM> is exposed to protrude from the opening <NUM> and is located in the clamping hole <NUM>. Therefore, the opening <NUM> is sized to expose the abutting portion <NUM>, but the heat-conducting block <NUM> as a whole is still located in the chamber <NUM>.

Referring to <FIG> is a schematic view of the heat-conducting body after assembling a limiting member in the heating mechanism according to an embodiment of the present invention. Furthermore, for the convenience of assembling, the limiting member <NUM> can be installed in the recessed groove <NUM> of the heat-conducting body <NUM>, and thus the heat-conducting block <NUM> and the like can be limited in the heat-conducting body <NUM>. Therefore, the structure of the limiting member <NUM> is not particularly limited or does not necessarily have to be installed. After the limiting member <NUM> is installed, the second through-hole <NUM> must also be provided to communicate with the clamping hole <NUM>, so that the reaction tube <NUM> can pass and then be placed therein, and the abutting portion <NUM> of the heat-conducting block <NUM> is still exposed in the clamping hole <NUM>, so that the reaction tube <NUM> can be in contact with the abutting portion <NUM> when inserted into the clamping hole <NUM>, and thus be clamped by the action of the elastic force.

Referring to <FIG>, <FIG> and <FIG>, <FIG> is a schematic view of the heating mechanism ready for insertion of the reaction tube according to an embodiment of the present invention; <FIG> is a cross-sectional view of the heating mechanism without inserting the reaction tube according to an embodiment of the present invention; and <FIG> is a cross-sectional view of the heating mechanism after inserting the reaction tube according to an embodiment of the present invention. The temperature control element <NUM> is provided to regulate the temperature of the heat-conducting block <NUM>, and the arrangement position and manner thereof are not particularly restricted, and may be provided, but not limited to, on a part or all of an upper surface of the heat-conductive body <NUM> (the surface facing the insertion direction of the reaction tube <NUM>), a part or all of side surfaces of the heat-conductive body <NUM>, or a part or all of a lower surface of the heat-conductive body <NUM> (the surface opposite to the upper surface). In the present embodiment, the temperature control element <NUM> is laid in shape matching on and connected to the upper surface of the heat-conducting body <NUM>, and then the heat energy generated by the heating wire (not shown) disposed thereon is first transferred to the heat-conducting body <NUM>, and then transferred to the heat-conducting block <NUM> for heating. In performing the heating, the reaction tube <NUM> passes the first through-hole <NUM> of the temperature control unit <NUM> and the second through-hole <NUM> of the limiting member <NUM> and enters the clamping hole <NUM> of the heat-conducting body <NUM>. When the reaction tube <NUM> enters the clamping hole <NUM>, since the abutting portions <NUM> of the heat-conducting blocks <NUM> protrude therein, and the inner diameter defined by the abutting portions <NUM> is smaller than the outer diameter of the tubular body <NUM> of the reaction tube <NUM>, the reaction tube <NUM> will experience a hindrance of the clamping, and after a small force is applied, the outer wall of the front end of the tubular body <NUM> can push the abutting portion <NUM> of the heat-conducting block <NUM> towards the inside of the chamber <NUM> to overcome the action of the elastic force by an oblique component force through a surface of the heat-conducting block <NUM>. At this moment, the front end of the tubular body <NUM> can overcome the hindrance of the abutting portion <NUM> of the heat-conducting block <NUM> to pass through therebetween. After that, the tubular body <NUM> is clamped between the abutting portions <NUM>/ the heat-conducting blocks <NUM>. Thereafter, the subsequent reactions can be performed.

In order to further make the heat transfer more rapid and uniform, the tubular body <NUM> of the reaction tube <NUM> may be provided with a heat-conducting element <NUM>. The heat conducting element <NUM> may be disposed in a region configuration, a single side configuration or a circumferential configuration on the tubular body <NUM> according to the arrangement of the heat-conducting blocks <NUM>. In the embodiment, the heat-conducting element <NUM> is disposed in a circumferential configuration. Furthermore, the material of the heat-conducting element <NUM> is not particularly limited, but preferably has a higher heat transfer coefficient. It should be noted that in the case where the reaction tube <NUM> is provided with the heat-conducting element <NUM>, after the reaction tube <NUM> is inserted, the position of the heat-conducting element <NUM> should be corresponding to the position of the abutting portion <NUM>, so that a heat can be transferred therebetween.

It should be noted that the number and position of the accommodating grooves <NUM> are not particularly limited. It can be with only a single accommodating groove <NUM> and only an opening <NUM>. Therefore, when the reaction tube <NUM> is inserted and clamped by the heat-conducting block <NUM>, one-sided heating is performed. This heating way can be applied to, for example, a device for a convectional PCR. If a plurality of accommodating grooves <NUM> are provided, the accommodating grooves <NUM> may be disposed in a circumferential range of the arranging hole <NUM> by about <NUM> degrees to allow the openings <NUM> to face an outer edge of one side of the reaction tube <NUM> so that the plurality of heat-conducting blocks <NUM> performs one-sided heating. Alternatively, the accommodating grooves <NUM> / openings <NUM> may be equally spaced apart in the circumference of the clamping hole <NUM> to perform heating evenly on the circumference of the outer edge of the reaction tube <NUM>. This can also be applied to a general PCR reaction device.

Referring to <FIG> is a schematic view of a bottom portion of the heat-conducting body in the heating mechanism according to an embodiment of the present invention. In order to allow the heat-conducting body <NUM> to dissipate heat rapidly after heating, a heat dissipation hole <NUM> communicating with the accommodating groove <NUM> may be provided. The position of the heat dissipation hole <NUM> is not particularly limited. In the present embodiment, the heat dissipation hole <NUM> is disposed at a bottom of the heat-conducting body <NUM>, that is, a bottom of the accommodating groove <NUM>, and the number of the heat dissipation holes may be determined, but not limited, according to the size of the structure or the range of the reaction temperature.

Refer to <FIG>, which show various embodiments and designs of the abutting portion of the heat-conducting block. The purpose of the heat-conducting block <NUM> is to clamp the reaction tube <NUM> and to transfer heat. Therefore, the front end of the tubular body <NUM> can be smoothly passed through the abutting portions <NUM> and clamped between the abutting portions <NUM>/ the heat-conducting blocks <NUM> as the reaction tube <NUM> is inserted. According to the invention the abutting portion <NUM> has a spherical surface. In the embodiment of <FIG> the heat-conducting block <NUM> is a sphere, but may alternatively be an ellipsoidal, semi-ellipsoidal or hemispherical structure (not shown) and further directly connected to the elastic member <NUM>. The heat-conducting block 13A shown in <FIG> has an abutting portion 131A with a hemispherical/semi-ellipsoidal structure according to the invention. In alternative structures which are not according to the invention, the heat-conducting block 13B as shown in <FIG> has an abutting portion 131B with an arc-shaped structure, and the heat-conducting block 13C shown in <FIG> has an abutting portion 131C with a sloped surface structure for the insertion of the reaction tube. The heat-conducting block is sleeve-connected to the elastic member <NUM> through a columnar extension structure. Herein, the elastic member <NUM> can be, but not limited to, a spring.

Claim 1:
A heating mechanism for a biochemical reaction device, comprising:
a heat-conducting body (<NUM>), the heat-conducting body (<NUM>) comprising:
at least one accommodating groove (<NUM>) each comprising a chamber (<NUM>) and an opening (<NUM>) communicating with the chamber (<NUM>); and
a clamping hole (<NUM>), in communication with the opening (<NUM>) and for insertion of a reaction tube (<NUM>);
at least one heat-conducting block (<NUM>), movably disposed in the chamber (<NUM>) and having one end connected to an elastic element (<NUM>) and another opposite end provided with an abutting portion (<NUM>), the elastic element (<NUM>) enabling the abutting portion (<NUM>) of the heat-conducting block (<NUM>) to protrude from the opening (<NUM>) and locate in the clamping hole (<NUM>); and
a temperature control element, being connected to the heat-conducting body (<NUM>) for heating and regulating a temperature of the heat-conducting block (<NUM>);
characterised in that the abutting portion (<NUM>) of the heat-conducting block is spherical.