Abstract:
Provided is an apparatus for performing a chemical reaction using a microchip having at least one micro-channel. The device, which is a semiautomatic operating device for a microchip on which at least one micro-channel with a reagent inlet is formed, includes: a base which accommodates the microchip; a slider with injection inlets corresponding to the reagent inlets that reciprocally move parallel to the base; and a slider moving unit which selectively moves the slider to a first location at which the microchip is opened, after the injection inlet of the slider and the reagent inlet are aligned, and to a second location where the microchip is sealed by a bottom surface of the slider covering the reagent inlet.

Description:
This application claims the priority of Korean Patent Application No. 10-2005-0025974, filed on Mar. 9, 2005 in the Korean Intellectual Property Office, the disclosure of which is incorporated herein in its entirety by reference. 
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates to a semiautomatic operating device for a microchip having at least one micro-channel capable of making the performance of biochemical reaction experiments using the microchip easier. 
     2. Description of the Related Art 
     Conventional micro-channels and microchips including chambers in which a biochemical reaction can occur are well known. An example of a microchip is a polymerase chain reaction (PCR) chip in which a micro-channel and a reaction chamber are formed. In conventional microchips, injection equipment such as a pipette is used to inject reaction reagents directly into a reagent inlet of the microchip. However, when a multi-channel PCR chip having a plurality of reaction chambers is used, such a manual operation can cause a large error due to confusing channels of the PCR or shaking of the hands. 
     In addition, the microchip must be sealed after a PCR reagent is injected so that the PCR reagent is not lost by, for example, evaporation while a PCR is performed. An example of a conventional method of sealing the microchip is adhering an optical tape to the reagent inlet and outlet of the PCR chip. In this case, a conventional reaction experiment using the microchip is inconvenient since the PCR reagent must be manually injected and the reagent inlet and outlet sealed using a separately prepared sealing material such as tape. 
     Therefore, a semiautomatic operating device for a microchip in which a reaction solution can be simply and accurately injected and a reagent inlet and outlet can be easily sealed after injecting the reaction solution by a simple manipulation of the device regardless of the level of the skill of a user is required. 
     SUMMARY OF THE INVENTION 
     The present invention provides a microchip unit which opens a reagent inlet of a micro-channel, guides a pipette tip that injects a reaction solution into the reagent inlet, and includes a slider which seals the reagent inlet and an outlet of the micro-channel after the injection, and a semiautomatic operating device for the microchip unit which can slide the slider to an injection location or a sealing location through a simple manipulation. 
     According to an aspect of the present invention, there is provided a semiautomatic operating device for a microchip on which at least one micro-channel with a reagent inlet is formed. The semiautomatic operating device includes: a base which accommodates the microchip; a slider with injection inlets corresponding to the reagent inlets that reciprocally move parallel to the base; and a slider moving unit which selectively moves the slider to a first location at which the microchip is opened, after the injection inlet of the slider and the reagent inlet are aligned, and to a second location where the microchip is sealed by a bottom surface of the slider covering the reagent inlet. 
     Hereinafter, the base accommodating the microchip and a portion including the slider will be referred as a “microchip unit” for convenience. The microchip unit is disclosed in more detail in Korean Patent Application No. 2004-0079957 filed by the present applicant prior to the filing of the present application, and the present invention provides the microchip unit and the semiautomatic operating device for a microchip, which accurately moves the slider of the microchip to the first and second locations through a simple manipulation. 
     The term “microchip” used throughout the specification includes a micro-channel and a chamber that is connected to the micro-channel and can be opened and closed from the micro-channel. The microchip can perform various chemical reactions in the chamber using a small amount of a reaction solution. Such a microchip is well known to those skilled in the prior art related to the present invention. An example of the microchip is a PCR chip in which a micro-channel and a reaction chamber that can be connected to the micro-channel are formed. 
     The PCR chip used in the present invention as an example of the microchip is well known to those skilled in the prior art related to the present invention. Generally, a “PCR chip” refers to a device including a micro-channel and a micro chamber in which a micro PCR can be performed. The PCR chip may be a single PCR chip having a single channel and chamber, or a multi-channel PCR chip having a plurality of channels and chambers. 
     Throughout the specification, “PCR,” an acronym for a polymerase chain reaction, is a process in which a target nucleotide is amplified from a pair of primers specifically binded to the target nucleotide using the polymerase. In PCR, an enzyme related polymerization, a primer, a template, and a solution including other subsidiary elements (a.k.a. “PCR mixture”) are injected into a chamber. Then, the contents of the chamber are maintained at an annealing temperature at which the primer and the template are annealed, a polymerizating temperature at which polymerization occurs by the polymerase, and a denaturizing temperature at which the polymerized double strands are denatured into single strands for a predetermined periods of time. A target nucleotide is amplified by repeating the temperature cycle mentioned above. PCR is also known as thermal cycling reaction. The PCR chip used in the present invention may represent every sort of PCR chips ever known in the art. 
     According to the present invention, an accommodating unit for accommodating the microchip and slider guides which allow the sliders to slide parallel to the base are formed on the base. Any fixing element may fix the base and the microchip. The slider guides on the base and the sliders may be connected by grooves in the shape of horizontal straight lines and protrusions in the shape of horizontal straight lines corresponding to the grooves so that the sliders can slide. 
     According to the present invention, the sliders have injection inlets corresponding to each of the reagent inlets of the microchip. The bottom surfaces of the sliders adjacent to the injection inlets are formed to be able to open or close the reagent inlets. The sliders may include a pressurizing sealing element to maintain inside the microchip airtight while the reagent inlets are closed. The sliders cannot slide perpendicular to the base by being guided by the slider guides of the base, they can slide between first and second locations in a parallel direction to the base. 
     The first location is where the injection inlets are aligned with each of the reagent inlets of the microchip to open the microchip. The second location is where the pressurizing sealing element seals the reagent inlets and outlets of the microchip to close the microchip. The pressurizing sealing element may be made of any material having elasticity and little reaction, and is not limited to a specific material. However, the pressurizing sealing element may be made of rubber or PDMS, and may be made of PDMS. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The above and other features and advantages of the present invention will become more apparent by describing in detail exemplary embodiments thereof with reference to the attached drawings in which: 
         FIG. 1  is a perspective view of a polymerase chain reaction (PCR) chip unit including two sliders disposed at a first location according to an embodiment of the present invention; 
         FIG. 2  is a perspective view of the PCR chip unit of  FIG. 1  when the sliders are disposed in a second location; 
         FIG. 3  is an exploded perspective view of the PCR chip unit illustrated in  FIGS. 1 and 2 ; 
         FIG. 4  is a cross-section of the slider in  FIG. 3  taken along the line  4 - 4 ′; 
         FIG. 5  is a cross-section of the PCR chip unit in  FIG. 1  taken along the line  5 - 5 ′ when a PCR reagent is injected into the PCR chip unit using a pipette and the slider is disposed in the first location; 
         FIG. 6  is a cross-section of the PCR chip unit in  FIG. 2  taken along the line  6 - 6 ′ when the slider is disposed in the second location; 
         FIGS. 7A and 7B  are plan views of a semiautomatic operating device for a microchip according to an embodiment of the present invention; 
         FIGS. 8A and 8B  are plan views of a semiautomatic operating device for a microchip according to another embodiment of the present invention; 
         FIGS. 9A and 9B  are plan views of a semiautomatic operating device for a microchip according to another embodiment of the present invention; and 
         FIGS. 10A and 10B  are plan views a semiautomatic operating device for a microchip with a vertical interceptor structure according to an embodiment of the present invention. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The present invention will now be described more fully with reference to the accompanying drawings, in which exemplary embodiments of the invention are shown. Like reference numerals in the drawings denote like elements. 
       FIG. 1  is a perspective view of a polymerase chain reaction (PCR) chip unit including two sliders  100  disposed at a first location according to an embodiment of the present invention. Referring to  FIG. 1 , a micro-channel  220  and a micro chamber  230  are formed on a PCR chip  200 , and thus PCR can be performed by a heat supplying element. The PCR chip  200  is accommodated on a base  300  on which slider guides  310  are formed. Injection inlets  110  are formed on the sliders  100 , and the sliders  100  are guided by the slider guides  310  to slide parallel to the PCR chip  200  and the base  300 . The injection inlets  110  are aligned with reagent inlets  210  (see  FIG. 3 ) of the PCR chip  200  when the sliders  100  are disposed at the first location. As a result, a PCR reagent can be injected into the micro-channel  220  and the chamber  230  of the PCR chip  200  via the injection inlet  110  using an injection device such as a pipette. As an example, in  FIG. 1 , the sliders  100  have grooves in the shape of horizontal straight lines on both sides thereof and the slider guides  310  have protrusions in the shape of horizontal straight lines corresponding to the grooves formed on the slider  100 , and the sliders  100  and the slider guides  310  are coupled to each other by meshing. The sliding guides  310  may have any other structures as long as the sliders  100  are fixed in the vertical direction and enables the slider  100  to slide in the horizontal direction. 
       FIG. 2  is a perspective view of the PCR chip unit of  FIG. 1  when the two sliders  100  are disposed in a second location. When the sliders  100  are located at the first location in  FIG. 1  and slide in directions indicated by arrows illustrated in  FIG. 1  by applying a force to the sliders  100 , the sliders  100  move to the second location illustrated in  FIG. 2 . By sliding the sliders  100  from the first location to the second location, pressurizing sealing elements  120  (see  FIG. 4 ) formed on bottom surfaces of the sliders  100  seal the reagent inlets  210  and outlets of the PCR chip  200 . The reagent inlets  210  sealed in this way experience pressure in the vertical direction, and are thus sealed by the pressurizing sealing elements  120 . Consequently, leakage of a PCR reaction solution during a PCR reaction is prevented. 
       FIG. 3  is an exploded perspective view of the PCR chip unit illustrated in  FIGS. 1 and 2 . Referring to  FIG. 3 , the PCR chip is composed of the two sliders  100 , the multi-channel PCR chip  200 , and the base  300 . The multi-channel PCR chip  200  is horizontally fixed to a PCR chip accommodating unit  330  of the base  300  on which the sliders guides  310  are formed. The PCR chip  200  comprises the reagent inlets  210  and outlets into which a PCR mixture or a reaction product is injected or output, the micro-channels  220 , and the chambers  230 , and these components are connected to one another. The sliders  100  are installed on the slider guides  310  after the PCR chip  200  is fixed to the base  300 . The sliders  100  are fixed in the vertical direction and are guided to slide in the horizontal direction from the first location to the second location and vice versa. 
       FIG. 4  is a cross-section of the slider  100  in  FIG. 3  taken along the line  4 - 4 ′. Referring to  FIG. 4 , the injection inlet  110  is formed in the slider  100 , and a lower portion of the injection inlet  110  is aligned with the reagent inlet  210  of the PCR chip  200  when the slider  100  is at the first location, thereby allowing the PCR reagent to freely flow into the reagent inlet  210 . Therefore, when the slider  100  is disposed in the first location, the PCR reagent can be injected into the channels  220  and the chambers  230  of the PCR chip  200  by injecting the PCR reagent into the injection inlet  110  using an injection device such as a pipette. The pressurizing sealing element  120  such as a PDMS or rubber may be formed on the bottom surface of the slider  100 . The pressurizing sealing element  120  may protrude from the bottom surface of the slider  100  so that a predetermined pressure can be applied to the reagent inlets  210  and outlets in a downward direction. 
       FIG. 5  is a cross-section of the PCR chip unit in  FIG. 1  taken along the line  5 - 5 ′ when the PCR reagent is injected into the PCR chip unit using a pipette  400  and the slider  100  is disposed in the first location, which is an injection location. As illustrated in  FIG. 5 , the PCR reagent is injected from the pipette  400  into the reagent inlet  210  of the PCR chip  200  through the injection inlet  110 . The injected PCR reagent travels to the chamber  230  via the channel  220 . At this time, the pressurizing sealing element  120  on the bottom surface of the slider  100  is not in contact with the reagent inlet  210 . 
       FIG. 6  is a cross-section of the PCR chip unit in  FIG. 2  taken along the line  6 - 6 ′ when the slider  100  is disposed at the second location. As illustrated in  FIG. 6 , by sliding the slider  100  in the horizontal direction after the PCR reagent is injected, the pressurizing sealing element  120  on the bottom surface of the slider  100  comes in contact with the reagent inlet  210  of the PCR chip  200 , thereby sealing the reagent inlet  210 . The pressurizing sealing element  120  applies a predetermined pressure in the downward direction such that the pressurizing sealing element  120  is coupled to the PCR chip unit, thereby preventing leakage of the PCR reagent from the reagent inlet  210  during PCR. The pressurizing sealing element  120  can apply a pressure in the downward direction because the pressurizing sealing element  120  is protruded from the bottom surface of the slider  100 , which can be explicitly seen when the slider  100  is not coupled to the PCR chip unit. 
       FIGS. 7A and 7B  are plan views of a semiautomatic operating device for a microchip according to an embodiment of the present invention. The semiautomatic operating device includes a shuttle  420  which moves parallel to the base  300  after receiving an external force (e.g., pushing or pulling force exerted by a finger) in the direction indicated by an arrow in  FIG. 7 . A portion  421  of the shuttle  420  is connected to the slider  100  and transmits the external force back and forth to the slider  100 . The slider  100  receives the force from the shuttle  420  and reciprocally slides with respect to the base  300  and a microchip (not shown). 
     The semiautomatic operating device includes a stopper  304  formed as a single body with the base  300  as a first location limiting element which stops the slider  100  from sliding after the slider  100  reaches a first location P 1  while sliding in the direction indicated in  FIG. 7A . The shuttle  420  slides from top to bottom in  FIG. 7A  together with the slider  100 . Here, when the slider  100  reaches the first location P 1 , the stopper  304  limits further sliding of the shuttle  420 . At the first location P 1 , the injection inlet  110  of the slider  100  is aligned with the reagent inlet  210  and guides the pipette  400 , which injects the PCR reagent, as illustrated in  FIG. 5 . 
     The semiautomatic operating device includes second location limiting elements  320  and  422  which stop the slider  100  sliding from the first location P 1  after injecting the PCR reagent when the slider  100  reaches a second location P 2 . The second location limiting element can be an elastic stopper which includes an elastic protrusion  320  formed on the base  300  and a groove  422  formed on one side of the shuttle  420  at a location corresponding to the elastic protrusion  320 . In  FIG. 7B , the shuttle  420  slides from bottom to top together with the slider  100 . Here, when the slider  100  reaches the second location P 2 , the elastic protrusion  320  enters the groove  422 , thereby limiting the sliding of the shuttle  420 . At the second location P 2 , the pressurizing sealing element  120  of the slider  100  covers and pressurizes the reagent inlet  210  and outlet of the microchip, thereby sealing the reagent inlet  210  and outlet, as illustrated in  FIG. 6 . 
     Here, the elastic protrusion  320  is forced into a recess in the base  300  when the slider  100  is at the first location P 1 , and is restored to its original shape and inserted into the groove  422  when the slider  100  is at the second location P 2 . The location of the elastic protrusion  320  relative to the groove  422  does not change until an external force large enough to retransform the elastic protrusion  320  is applied to the shuttle  420 . Therefore, the elastic protrusion  320  and the groove  422  need not be limited as illustrated in  FIGS. 7A and 7B . An elastic medium providing a recovery force may be a coil spring, a leaf spring, an elastomer, etc. In addition, the first location limiting element may also be an elastic protrusion and a groove corresponding to the elastic protrusion. 
       FIGS. 8A and 8B  are plan views of a semiautomatic operating device for a microchip according to another embodiment of the present invention. The semiautomatic operating device is installed on one side of the base  300 , and includes a rotatable handle  430  connected to a bolt  431  and rotational/linear motion transmitting units  431  and  442  which convert rotation motion of the rotatable handle  430  into linear motion and transmits the linear motion to one end of a shuttle  440 . The structure of the rotational/linear motion transmitting unit is limited only to converting the rotation motion at the rotation handle  430  into the linear motion of the shuttle  440 , and may be a screw coupling structure, a cylindrical cam structure, a worm gear, or a rack gear. 
     The semiautomatic operating device according to the present embodiment includes the bolt  431  formed on one end of the rotatable handle  430  and the shuttle  440  having an internal screw  442  formed on one end thereof corresponding to the bolt  431 . The location of the slider  100  is fixed at a first location P 1  or a second location P 2  by limiting the sliding of the shuttle  440  in the same manner as in the previous embodiment, except that first and second location limiting elements can directly limit the rotation of the rotatable handle  430  in the present embodiment. 
     When providing an automatic operating device, the rotatable handle  430  can be rotated by a motor, and of course, the displacement of the shuttle  440  can be limited by a position control motor. 
       FIGS. 9A and 9B  are plan views of a semiautomatic operating device for a microchip according to another embodiment of the present invention. The semiautomatic operating device includes a first moving unit  400 , which moves the slider  100  to a first location P 1  by pushing the slider  100  in one direction, and a second moving unit  500 , which moves the slider  100  from the first location P 1  to a second location P 2  by pushing the slider  100  in another direction. 
     Here, the first moving unit includes a first interceptor  410  that is pressed until the slider  100 , pushed by one end  411  of the first interceptor  410 , reaches the first location P 1 . The second moving unit includes a second interceptor  520  which is pressed to a predetermined location at a right angle to the direction in which the first interceptor  410  is pressed and a dependent element  550  which moves at a right angle to the direction in which the second interceptor  520  is pressed, indicated by an arrow in  FIG. 9B . To obtain this motion, an inclined surface  521  of the second interceptor  520  contacting an inclined surface  551  of the dependent element  550  exerts a force on the inclined surface  551  to move the slider  100  when the second interceptor  520  is pressed. When the second interceptor  520  reaches the predetermined location, the slider  100  reaches the second location P 2 . 
     The mechanism of moving the slider  100  using the second interceptor  520  is not limited to that described above. Any cam structure that fixes the slider  100  at the second location P 2  by converting the maximum displacement to which the second interceptor  520  is pressed to movement of the slider  100  at a right angle to the displacement is sufficient. 
     The movement range of the first and second interceptors  410  and  520  can be limited by first and second stoppers  304  and  305  formed on the base  300  as a single body. 
       FIGS. 10A and 10B  are plan views a semiautomatic operating device of a microchip with a vertical interceptor structure according to an embodiment of the present invention. The semiautomatic operating device includes a base  300 , which has an accommodating unit for accommodating the microchip on which a plurality of micro-channels with reagent inlets  210  are formed, and a pair of sliders  100  and  100 ′ that have injection inlets  110  corresponding to each of the reagent inlets  210  and perform reciprocal movement parallel to the base  300  to open and close the reagent inlets  210 . 
     In addition, the semiautomatic operating device includes a pair of first interceptors  410  and  410 ′ to move the pair of sliders  100  and  100 ′ to a first location through a single symmetrical operation and a pair of second interceptors  510  and  510 ′ to move the pair of sliders  100  and  100 ′ from the first location to a second location through a single symmetrical operation. 
     The first interceptors  410  and  410 ′ face each other and are symmetrically pressed to a predetermined maximum location. As a result, the sliders  100  and  100 ′ can be moved to the first location. The second interceptors  510  and  510 ′ are disposed at right angles to the first interceptors  410  and  410 ′. The second interceptors  510  and  510  move the sliders  100  and  100 ′ to a second location when pressed to the maximum displacement via a predetermined mechanism. In the predetermined mechanism, front ends of the second interceptors  510  and  510 ′ are respectively connected to a pair of inclined elements  540  and  540 ′ via a pair of connecting loads  530  and  530 ′, and the displacement of the second interceptors  510  and  510 ′ is converted into the displacement of the inclined elements  540  and  540 ′ at right angles to the direction to which the second interceptors  510  and  510 ′ are pressed. 
     For example, the mechanism may be composed of the pair of inclined elements  540  and  540 ′ and the pair of connecting loads  530  and  530 ′. Surfaces  542  and  542 ′ of the inclined elements  540  and  540 ′ respectively correspond to surfaces of the sliders  100  and  100 ′ facing each other, and surfaces  541  and  541 ′ of the inclined element  540  opposite the surfaces  542  and  542 ′ are respectively inclined with respect to the surfaces  542  and  542 ′. The surfaces  541  and  541 ′ face each other between the sliders  100  and  100 ′. First ends of the connecting loads  530  and  530 ′ are rotatably connected to the inclined elements  540  and  540 ′, respectively, and second ends of the connecting loads  530  and  530 ′ are rotatably connected to the second interceptors  510  and  510 ′, respectively, thereby transmitting the force form the first and second interceptors  510  and  510 ′ to the inclined elements  540  and  540 ′. 
     The mechanism through which the sliders  100  and  100 ′ are moved using the second interceptors  510  and  510 ′ is not limited to that described above. Any mechanism which moves the sliders  100  and  100 ′ to the second location P 2  by converting the displacement of the second interceptors  510  and  510 ′ into displacement of the sliders  100  and  100 ′ at a right angle to the direction in which the second interceptors  510  and  510 ′ are pressed can be used. 
     According to the present invention, a semiautomatic operating device for a microchip provides a microchip unit including a slider which guides a pipette for injecting a reaction solution into a reagent inlet of a micro-channel and seals the reagent inlet and outlet of the micro-channel after the reaction solution is injected. Also, regardless of a user&#39;s dexterity, the slider can be fixed to a position for an injection mode or a sealing mode through a simple operation of the semiautomatic operation device. 
     In addition, as described above, by using the semiautomatic operation device which can simply and accurately operate the microchip unit, possibilities of failure due to manual operation are eliminated and the microchip can be further miniaturized and integrated. 
     While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it will be understood by those of ordinary skill in the art that various changes in form and details may be made therein without departing from the spirit and scope of the present invention as defined by the following claims.