Abstract:
A polymerase chain reaction (“PCR”) apparatus includes a PCR chip holder which accommodates and supports a PCR chip, a housing which supports ends of the PCR chip holder, a temperature control element which moves perpendicularly with respect to the PCR chip holder in a space between the housing and the PCR chip holder in the housing, and an elastic unit which elastically biases the temperature control element toward the PCR chip holder, between the temperature control element and the housing. The temperature control element includes a top surface which is selectively contacted to a bottom surface of the PCR chip.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application claims priority to Korean Patent Application No. 10-2010-0084184, filed on Aug. 30, 2010, and all the benefits accruing therefrom under 35 U.S.C. §119, the disclosure of which is incorporated herein in its entirety by reference. 
       BACKGROUND 
       [0002]    1. Field 
         [0003]    Provided are polymerase chain reaction (“PCR”) apparatuses, and more particularly, a PCR apparatus including a unit for providing a close contact between a PCR chip and a thermal control element. 
         [0004]    2. Description of the Related Art 
         [0005]    Polymerase chain reaction (“PCR”) technology for amplifying a certain region of deoxyribonucleic acid (“DNA”) or ribonucleic acid (“RNA”) in a reaction container is widely used not only in fields of genetic engineering and life science, but also in medical fields for diagnosing diseases. In order to efficiently perform PCR, it is essential to quickly and accurately adjust a temperature of a gene sample to be amplified, to a target temperature. 
         [0006]    A PCR apparatus includes a thermal control element for heating and cooling a sample solution in a reaction chamber of a PCR chip in which PCR occurs. The PCR chip can be heated and cooled by the thermal control element in the form of conduction and, in order to efficiently transfer thermal energy between the PCR chip and the thermal control element, both of the PCR chip and the thermal control element should be closely contacted with each other. 
         [0007]    When the PCR chip and the thermal control element are closely contacted with each other, the PCR chip or a contact part of the thermal control element may be damaged due to strong contact pressure. Specifically, if the PCR chip or the contact part of the thermal control element is composed of silicon which has high thermal diffusivity but is easily deformed to be broken, the PCR chip or the thermal control element may be damaged more severely. Accordingly, a unit for suitably adjusting contact pressure between the PCR chip and the thermal control element is required. 
       SUMMARY 
       [0008]    Provided are polymerase chain reaction (“PCR”) apparatuses for suitably adjusting contact pressure between a PCR chip and a thermal control element. 
         [0009]    Embodiments will be set forth in part in the description which follows and, in part, will be apparent from the description, or may be learned by practice of the illustrated embodiments. 
         [0010]    Provided is a PCR apparatus including a PCR chip holder which fixes and supports a PCR chip, a housing which supports both ends of the PCR chip holder, a temperature control element which selectively contacts a bottom surface of the PCR chip and moves perpendicularly to the bottom of the housing, and an elastic unit which elastically biases the temperature control element away from the bottom of the housing. 
         [0011]    In an embodiment, the PCR chip holder may be attachable to and/or detachable from the housing. 
         [0012]    In an embodiment, the PCR apparatus may further include a fixing unit in the housing, and the PCR chip holder is selectively fixed to the housing. 
         [0013]    In an embodiment, the fixing unit may include a groove at each of facing sides of the housing, a elastic element held on a bottom of the groove of the housing, and a ball which is connected to the elastic element and selectively moves towards and away from a bottom of the groove of the housing by an elastic force of the elastic element. The PCR chip holder includes a concave groove at each of the opposing ends, and the ball of the fixing unit is in the concave groove when the opposing ends of the PCR chip holder are attached to the housing. 
         [0014]    In an embodiment, the temperature control element may further include a printed circuit board (“PCB”) facing the bottom of the housing and parallel to the contact part of the temperature control element, and a supporting member connected to both the contact part and the PCB. The supporting member maintains a predetermined interval between the contact part of the temperature control element and the PCB in the housing. 
         [0015]    In an embodiment, the PCR apparatus may further include a stopper which overlaps the supporting member of the temperature control element, so as to limit a distance that the temperature control element moves away from the bottom of the housing, in the housing. 
         [0016]    In an embodiment, the elastic unit may be an elastic spring. 
         [0017]    In an embodiment, the contact part of the temperature control element may include silicon, and may include a heater, such as patterned line of metal, on a surface of the contact part of the temperature control element. 
         [0018]    In an embodiment, the contact part of the temperature control element may be a Peltier element. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0019]    These and/or other aspects will become apparent and more readily appreciated from the following description of the embodiments, taken in conjunction with the accompanying drawings of which: 
           [0020]      FIG. 1  is a cross-sectional view of an embodiment of a polymerase chain reaction (“PCR”) chip according to the present invention; 
           [0021]      FIG. 2  is a plan view of an embodiment of a PCR apparatus according to the present invention; 
           [0022]      FIG. 3  is a cross-sectional view taken along line III-III′ of  FIG. 2 ; 
           [0023]      FIG. 4  is a cross-sectional view taken along line IV-IV′ of  FIG. 2 ; 
           [0024]      FIG. 5  is a diagram for describing operation of the PCR apparatus according to the present invention; and 
           [0025]      FIG. 6  is a cross-sectional view of another embodiment a PCR apparatus according to the present invention. 
       
    
    
     DETAILED DESCRIPTION 
       [0026]    Reference will now be made in detail to embodiments, examples of which are illustrated in the accompanying drawings. In the drawings, the thicknesses of layers and regions are exaggerated for clarity, and like reference numerals refer to the like elements throughout. In this regard, the present embodiments may have different forms and should not be construed as being limited to the descriptions set forth herein. Accordingly, the embodiments are merely described below, by referring to the figures, to explain aspects of the present description. In the drawings, the size and relative sizes of layers and regions may be exaggerated for clarity. 
         [0027]    It will be understood that when an element or layer is referred to as being “on” or “connected to” another element or layer, the element or layer can be directly on or connected to another element or layer or intervening elements or layers. In contrast, when an element is referred to as being “directly on” or “directly connected to” another element or layer, there are no intervening elements or layers present. Like numbers refer to like elements throughout. As used herein, the term “and/or” includes any and all combinations of one or more of the associated listed items. 
         [0028]    It will be understood that, although the terms first, second, third, etc., may be used herein to describe various elements, components, regions, layers and/or sections, these elements, components, regions, layers and/or sections should not be limited by these terms. These terms are only used to distinguish one element, component, region, layer or section from another region, layer or section. Thus, a first element, component, region, layer or section discussed below could be termed a second element, component, region, layer or section without departing from the teachings of the invention. 
         [0029]    Spatially relative terms, such as “lower,” “upper” and the like, may be used herein for ease of description to describe the relationship of one element or feature to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation, in addition to the orientation depicted in the figures. For example, if the device in the figures is turned over, elements described as “lower” relative to other elements or features would then be oriented “upper” relative to the other elements or features. Thus, the exemplary term “lower” can encompass both an orientation of above and below. The device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly. 
         [0030]    The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the singular forms “a,” “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and/or “comprising,” when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. 
         [0031]    Embodiments of the invention are described herein with reference to cross-section illustrations that are schematic illustrations of idealized embodiments (and intermediate structures) of the invention. As such, variations from the shapes of the illustrations as a result, for example, of manufacturing techniques and/or tolerances, are to be expected. Thus, embodiments of the invention should not be construed as limited to the particular shapes of regions illustrated herein but are to include deviations in shapes that result, for example, from manufacturing. 
         [0032]    Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein. 
         [0033]    All methods described herein can be performed in a suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., “such as”), is intended merely to better illustrate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention as used herein. 
         [0034]    Hereinafter, the invention will be described in detail with reference to the accompanying drawings. 
         [0035]      FIG. 1  is a cross-sectional view of an embodiment of a polymerase chain reaction (“PCR”) chip  10  according to the present invention. Referring to  FIG. 1 , a lower substrate  20  may include a material having high thermal conductivity, such as silicon, and an upper substrate  30  may include a transparent material, such as glass or plastic. A chamber  22  in which PCR is to occur, may be in the lower substrate  20 . The chamber  22  may extend from an upper surface or upper plane of the lower substrate  20 , partially through a thickness of the lower substrate  20  and to an interior of the lower substrate  20 . 
         [0036]    The upper substrate  30  includes an inlet  31  and a first microchannel  33  through which a liquid is injected into the chamber  22 , and a second microchannel  34  and an outlet  32  through which a reactant is discharged from the chamber  22  and to an outside of the PCR chip  10 . In  FIG. 1 , only one chamber  22  is illustrated in the lower substrate  20 , but the present invention is not limited to the one chamber  22 . In an alternative embodiment, for example, a plurality of chambers  22  may be in one PCR chip  10 . Where there is a plurality of chambers  22 , the one PCR chip  10  may include a first microchannel, an inlet, a second microchannel and an outlet for each of the chambers. 
         [0037]    The inlet  31  and the first microchannel  33  are in fluid communication with each other, and the second microchannel  34  and the outlet  32  are in fluid communication with each other. A continuous fluid channel may be respectively formed by the inlet  31  and the first microchannel  33 , and by the second microchannel  34  and the outlet  32 . The continuous fluid channel may extend from an upper surface or upper plane of the upper substrate  30 , and completely through a thickness of the upper substrate  30 , as illustrated in  FIG. 1 . 
         [0038]      FIG. 2  is a plan view of an embodiment of a PCR apparatus  100  according to the present invention,  FIG. 3  is a cross-sectional view taken along line III-III′ of  FIG. 2 , and  FIG. 4  is a cross-sectional view taken along line IV-IV′ of  FIG. 2 . 
         [0039]    Referring to  FIGS. 2 through 4 , the PCR apparatus  100  includes a housing  110 , a temperature control element  120  supported within the housing  110  through an elastic unit  140 , and a PCR chip holder  130  whose two ends are supported by a side of the housing  110 . The elastic unit  140  may be an elastic spring. The PCR apparatus  100  may include a single elastic unit  140 , or a plurality of elastic units  140 . The elastic unit  140  is between the temperature control element  120  and the bottom of the housing  110 . 
         [0040]    The housing  110  may include a bottom portion at the bottom of the housing  110 , a pair of first sidewalls facing each other and extending from the bottom portion, and a pair of second sidewalls different from the first sidewalls, facing each other and extended from the bottom portion. A top of the housing  110  facing the bottom of the housing  110  may be substantially open, such that an inside of the housing  110  is accessible from an outside of the housing  110 . 
         [0041]    The PCR chip holder  130  fixes and supports the PCR chip  10  within the housing  110 . The PCR chip holder  130  enables easy handling of the PCR chip  10 , and stable contact between the PCR chip  10  and the temperature control element  120 . The PCR chip holder  130  may be attached to and removed from the second sidewalls of the housing  110 . 
         [0042]    The temperature control element  120  may move up and down with respect to a bottom of the housing  110 . In other words, a bottom of the temperature control element  120  is connected to and movable with respect to the bottom of the housing  110  through the elastic unit  140 . The temperature control element  120  is elastically biased by the elastic unit  140  to be positioned away from the bottom of the housing  110 , as illustrated in  FIG. 3 . 
         [0043]    The housing  110  may include a plastic material. A stopper  114  for limiting a distance that the temperature control element  120  may travel in a direction away from the bottom of the housing  110  may be on a top portion of the housing  110 . A portion of the stopper  114  overlaps a portion of the temperature control element  120 , such that the temperature control element  120  is movable between the bottom of the housing  110  and a lower surface of the stopper  114 . 
         [0044]    The temperature control element  120  includes a supporting member  121 , and a contact part  122  and a printed circuit board (“PCB”)  124  that are connected to the supporting member  121 . The contact part  122  and the PCB  124  are disposed in parallel to each other while being on the supporting member  121 . The elastic unit  140  is connected to a bottom of the supporting member  121 . The supporting member  121  may include two column elements, and each column element may respectively face the first sidewalls of the housing  110 . As shown in  FIG. 3 , each of the two column elements of the supporting member  121  may be connected to each other by the PCB  124  and the contact part  122 . The contact part  122  includes a silicon plate (not shown) having good thermal conductivity, and a heater, such as patterned line of metal (not shown) at a bottom of the silicon plate. The silicon plate directly contacts the PCR chip  10 . 
         [0045]    Wiring (not shown) for supplying power to the heater of the contact part  122  is on the PCB  124 . The heater of the contact part  122  and the PCB  124  are electrically connected to each other by wiring  126  in the supporting member  121 . A portion of the wiring  126  may be completely within each of the column elements, as indicated by the dotted outline shown in  FIG. 3 . Alternatively, an entire of the wiring  126  may be completely within only one of the column elements. The wiring  126  may include wiring for supplying a current to the heater of the contact part  122 , and/or wiring connected to a temperature sensor (not shown) attached to the contact part  122  in order to measure temperature of the contact part  122 . In embodiments, the temperature sensor may include, but is not limited to, at least one of a resistance temperature detector (“RTD”), a thermocouple, and a thermistor. 
         [0046]    The PCR apparatus  100  may further include a fan  128 . For convenience, the fan  128  is included in the housing  110 , but the fan  128  may be disposed outside the housing  110 . The fan  128  and the contact part  122  operate as a temperature control member of the PCR chip  10 . 
         [0047]    A fixing unit  150  is placed at the side of the housing  110  so as to fix the PCR chip holder  130  to a position at which the PCR chip  10  contacts the contact part  122 , in the housing  110 . An embodiment of the fixing unit  150  according to the invention is shown in  FIGS. 2 and 4 . The fixing unit  150  may include at least one concave groove  151  recessed into each of opposing ends of the PCR chip holder  130 , a groove  152  in the housing  110  and a ball spring mechanism which protrudes into the groove  152  in the housing  110 , to fix a position of the PCR chip holder  130  with respect to the housing  110 . The groove  152  is disposed recessed into both of opposing sides of the housing  110 , and may be aligned with the concave groove  151  of the PCR chip holder  130 . The ball spring mechanism includes a spring  153  including a first end attached on a bottom of the groove  152  at a first side wall of the housing  110 , and a ball  154  connected to a second end of the spring  153  opposing the first end. A first area of the ball  154  is connected to the second end of the spring  153 , and a second area of the ball  154  opposing the first area, is in and connected to the concave groove  151  in the PCR chip holder  130 . The PCR chip holder  130  may be fixed to the sidewall of the housing  110 , by the ball spring mechanism. 
         [0048]      FIG. 5  is a diagram for describing operations of an embodiment of a PCR apparatus according to the present invention. Operations of the PCR apparatus  100  will now be described with reference to  FIGS. 1 through 5 . 
         [0049]      FIG. 5  shows a state where the PCR chip holder  130  is not installed in the PCR apparatus  100 . The temperature control element  120  is elastically biased upward in a direction away from the bottom of the housing  110  by the elastic unit  140 . A vertical position of the temperature control element  120  is limited by the stopper  114 , as shown by the supporting member  121  in contact with the lower surface of the stopper  114 . 
         [0050]    From the state in  FIG. 5 ,  FIGS. 3 and 4  show the operation of fixing the PCR chip holder  130  to the housing  110 . The PCR chip holder  130  including the PCR chip  10  is initially placed between two first opposing sidewalls of the housing  110  on the contact part  122 , in such a way that the concave groove  151  of the PCR chip holder  130  including the PCR chip  10  is placed at a location along two second opposing sidewalls different from the first opposing sidewalls and corresponding to the ball spring mechanism of the housing  110 . 
         [0051]    Then, the PCR chip holder  130  is pushed downward towards the bottom of the housing  110 . With the concave groove  151  of the PCR chip holder  151  aligned with the ball spring mechanism along the two second opposing walls, when the PCR chip holder  130  is moved downward, the ball  154  enters the concave groove  151 . When the concave groove  151  of the PCR chip holder  151  aligns with the groove  152  of the housing  110 , the ball spring mechanism is fully released between the concave groove  151  and the groove  152 , as the ball  154  contacts portions of the concave groove  151 . Accordingly, the position of the PCR chip holder  130  is fixed relative to the housing  110  by the fixing unit  150 . When the position of the PCR chip holder  130  is fixed relative to the housing  110  by the fixing unit  150 , a lower surface of the PCR chip  10  on the PCR chip holder  130 , contacts an upper surface of the contact part  122 , as shown n  FIG. 4 . 
         [0052]    Since an elastic force is applied to the temperature control element  120  in the direction away from the bottom of the housing by the elastic unit  140 , and since the position of the PCR chip holder  130  is fixed by the fixing unit  150 , the contact part  122  of the temperature control element  120  contacts the lower substrate  20  of the PCR chip  10  by the elastic force from the elastic unit  140 . 
         [0053]    Additionally, since the elastic unit  140  biases the temperature control member  120  in a direction away from the bottom portion of the housing  110 , the lower surface of the PCR chip  10  contacts the upper surface of the contact part  122  solely by attaching and fixing the PCR chip holder  130  to the housing  110 . 
         [0054]    When the contact part  122  is in contact with the PCR chip  10 , the contact part  122  is heated by supplying a current to the heater through the wiring  126 . The temperature of the contact part  122  of the temperature control element  120  is maintained at a desired temperature by measuring the temperature of the contact part  122  through the wiring  126 , and controlling the temperature of the contact part  122 . 
         [0055]    According to the PCR apparatus  100 , when the PCR chip  10  and the contact part  122  closely contact each other, thermal energy transfers more rapidly between the contact part  122  and the PCR chip  10 . Also, since the contact part  122  directly contacts the PCR chip  10  with predetermined pressure based on a predetermined elastic force from the elastic unit  140 , damage to the PCR chip  10  and the contact part  122  are reduced or effectively prevented, even when the PCR chip  10  and the contact part  122  include a fragile material such as silicon. 
         [0056]    In releasing the ball spring mechanism of the housing  110 , such as by moving the ball  154  towards the bottom of the groove  152 , the PCR chip holder  130  may be moved upward and away from the bottom of the housing  110 , and may be removed from the PCR apparatus  100 , thereby returning the PCR apparatus  100  to the state shown in  FIG. 5 . When the PCR chip holder  130  is removed from the PCR apparatus  100 , a new PCR chip  10  may be mounted onto the PCR chip holder  130 , and the PCR chip holder including the new PCR chip  10  may be reinserted into the PCR apparatus  100  as shown in  FIGS. 3 and 4  discussed above. That is, the PCR chip holder  130  is removably disposed (e.g., both attachable to and detachable from the housing  110 ) with respect to the PCR apparatus  100 . 
         [0057]      FIG. 6  is a cross-sectional view of another embodiment of PCR apparatus according to the present invention. Like reference numerals denote like elements in drawings, and thus details thereof are not repeated. 
         [0058]    Referring to  FIG. 6 , a PCR apparatus  200  includes a Peltier element  222  instead of the contact part  122  of the PCR apparatus  100  in  FIGS. 2-5 . In the Peltier element  222 , a plurality of pairs of p-columns and n-columns are arranged in series between two plates, and a direct current (“DC”) voltage is applied to lead electrodes at ends of the plurality of pairs of p-columns and n-columns. A voltage may be applied to the lead electrodes through the wiring  126  in the supporting members  121  of the temperature control element  120 . The plate of the Peltier element  222  contacting the PCR chip  10  heats up or cools down the PCR chip  10  based on the supplied voltage. 
         [0059]    In an embodiment, the fan  128  and the Peltier element  222  may be attached to each other, while disposing a heat sink (not shown) therebetween. The Peltier element  222  and the fan  128  together operate as a temperature control member. Since the Peltier element  222  is well known to one ordinarily skilled in the art, detailed descriptions thereof are omitted. 
         [0060]    An embodiment of the present invention also provides a method of controlling a temperature of a sample solution in a PCR chip, with reference to the PCR apparatus  100  in  FIGS. 2-5 . The method may also be applied to the PCR apparatus  200  in  FIG. 6 . 
         [0061]    The method includes mounting the PCR chip  10  to the PCR chip holder  130 , attaching the PCR chip holder  130  to both of facing sidewalls of the housing  100  of the PCR apparatus  100 , contacting the temperature control element  120  in the housing of the PCR apparatus  100  to a lower surface of the PCR chip  10 , and adjusting the temperature of the temperature control element  120 , such that the temperature of the sample solution in the PCR chip  10  is controlled. To contact the temperature control element  120  to the lower surface of the PCR chip  10 , the temperature control element  120  is biased in a first direction towards the PCR chip holder  130 , while the PCR reaction chip holder  130  is simultaneously moved in a second direction opposite to the first direction during the attaching of the PCR chip holder  130  to the housing  110 . 
         [0062]    It should be understood that the embodiments described herein should be considered in a descriptive sense only and not for purposes of limitation. Descriptions of features or aspects within each embodiment should typically be considered as available for other similar features or aspects in other embodiments.