Patent Publication Number: US-2018043360-A1

Title: Sealing device of microfluidic chip and operation method therefor

Description:
TECHNICAL FIELD 
     The present invention relates to a sealing device of a microfluidic chip and an operation method therefor, and specifically, to a sealing device of a microfluidic chip and an operation method therefor, which seals the microfluidic chip by applying heat to the microfluidic chip. 
     The present invention has been derived from a study developed under the support of a health care Research and Development project sponsored by the Korea Health Industry Development Institute (Project No: HI13C2262, Project name: Development of fully automated real-time PCR system capable of simultaneously detecting multiple channels on the basis of lap-chip, the PCR system for high-speed diagnosis of genes for onsite malaria inspection). 
     BACKGROUND ART 
     A microfluidic chip has a function of flowing fluid through a microfluidic channel and simultaneously conducting several experiment conditions. Specifically, the microfluidic channel is manufactured using a substrate of plastic, glass, silicon or the like (or a material of a chip), and after moving the fluid (e.g., a liquid sample) through the channel, the fluid may be, for example, mixed and reacts in a plurality of chambers in the microfluidic chip. Thus, the microfluidic chip is also referred to as a lab-on-a-chip in that experiments conventionally performed in a laboratory are performed in a small chip. 
     The microfluidic chip has the ability to lower costs and save time in the fields of pharmacy, biological engineering, medical science, chemistry and the like, and may also enhance accuracy, efficiency, and reliability. For example, since the amounts of expensive reagents used for culture, proliferation and differentiation of cells can be remarkably reduced compared with existing methods by using the microfluidic chip, cost can be reduced considerably. In addition, since much smaller amounts of protein samples and cell samples are used in comparison to existing methods. Also, image analysis can be made using the microfluidic chip, therefore the amounts of the used or consumed samples and analysis time of the samples can be reduced. 
     However, a problem occurs when the fluid is evaporated and lost due to the heat applied to a reaction region while a certain reaction,particularly, a polymerase chain reaction (PCR), is performed in the microfluidic chip, or the fluid is leaked from the microfluidic chip where the reaction is taking place. A sealing technique has been proposed to solve the problem wherein a valve or a sealing cap for sealing the reaction region in the microfluidic chip is used at both ends, customarily at an inlet unit and an outlet unit, of the reaction region. 
     However, a problem with such sealing technique is that a multitude of bubbles are generated due to the evaporation of the fluid in the reaction region. In relation to this,  FIG. 1  shows a PCR reaction result of a conventional PCR chip. As shown in the figure, while the reaction is progressed, the fluid is evaporated and a multitude of bubbles is generated due to the heat applied to the fluid (see  FIG. 1( a ) ). Since the bubbles make it difficult to precisely measure the inside of the reaction region, and results of the reaction are, therefore distorted due to the bubbles, there is a problem in regards to degrading the reliability (see  FIG. 1( b ) ). 
     Therefore, a sealing device of a microfluidic chip and an operation method therefor are required to solve such problems. 
     DISCLOSURE OF INVENTION 
     Technical Problem 
     The present invention has been devised to solve the problems described above. An objective of the present invention is to provide a sealing device of a microfluidic chip and an operation method therefor, wherein the seal of the microfluidic chip by applying heat through the sealing device of a microfluidic chip. 
     Technical Solution 
     According to an embodiment of the present invention, a sealing device of a microfluidic chip is provided. The sealing device may include: a support unit on which the microfluidic chip is arranged; and a heat-sealing unit for sealing an inlet unit and an outlet unit of the microfluidic chip by applying heat to the inlet unit and the outlet unit. 
     Preferably, the heat-sealing unit may seal the inlet unit and the outlet unit by melting protrusion units of the inlet unit and the outlet unit by contacting and heating the inlet unit and the outlet unit. 
     In addition, preferably, the heat-sealing unit may include: heat contact units thermally contacting with the inlet unit and the outlet unit of the microfluidic chip; heaters for heating the heat contact units; and a temperature sensor for measuring temperature of the heat contact units. 
     In addition, preferably, a chip contact region of the heat contact unit may be formed to be recessed toward the inside so that the protrusion units melted by the heat contact units may seal openings of the inlet unit and the outlet unit. 
     In addition, preferably, a release agent may be coated on the surface of the chip contact regions of the heat contact units. 
     In addition, preferably, the sealing device may further include a driving unit for moving the heat-sealing unit toward the microfluidic chip arranged on the support unit to apply heat to the inlet unit and the outlet unit of the microfluidic chip through the heat-sealing unit. 
     In addition, preferably, the heat-sealing unit may further include a chip fixing unit for preventing shake of the microfluidic chip when the heat-sealing unit is moved and thermally contacted by the driving unit. 
     In addition, preferably, the chip fixing unit may be protruded toward the support unit, and a protrusion length of the chip fixing unit may be adjusted by implementing at least a portion of the chip fixing unit using an elastic material. 
     In addition, preferably, the support unit may be recessed toward the inside to form an arrangement space of the microfluidic chip. 
     According to an embodiment of the present invention, a sealing system of a microfluidic chip is provided. The system may include a microfluidic chip and a sealing device of a microfluidic chip. 
     According to an embodiment of the present invention, an operation method of a sealing device of a microfluidic chip is provided. The method may include the steps of: providing the microfluidic chip on a support unit of the sealing device; heating a heat-sealing unit of the sealing device; moving the heated heat-sealing unit onto the microfluidic chip to melt at least a portion of an inlet unit and an outlet unit by contacting and heating the inlet unit and the outlet unit of the microfluidic chip; and sealing the microfluidic chip by hardening at least a portion of the melted inlet and outlet units. 
     According to an embodiment of the present invention, a microfluidic chip is provided. The microfluidic chip may include: an inlet unit through which a fluid flows in; a reaction region in which a certain reaction is performed on the fluid flowed in through the inlet unit; and an outlet through which the fluid flows out from the reaction region, wherein each of the inlet unit and the outlet unit includes an opening through which the fluid flows in and a protrusion unit which is defined to be protruded and located adjacent to the opening. 
     Preferably, the protrusion unit may seal the opening as it is applied with heat and melted. 
     In addition, preferably, the reaction may be a polymerase chain reaction (PCR). 
     Advantageous Effects 
     According to the present invention, a microfluidic chip can be sealed by applying heat to an inlet unit and an outlet unit of the microfluidic chip using a sealing device of a microfluidic chip, since at least a part of the inlet unit and the outlet unit is melted and hardened by the heat. 
     In addition, according to the present invention, since each of the inlet unit and the outlet unit of the microfluidic chip includes an opening through which a fluid flows in and a protrusion unit which is protruded and located adjacent to the opening, when a sealing operation is performed by the sealing device of the microfluidic chip, the inlet unit and the outlet unit of the microfluidic chip can be sealed further easily. 
     Therefore, loss of the fluid injected inside the microfluidic chip can be prevented, and at the same time, accuracy and promptness of reaction results can be improved by eliminating generation of bubbles although a certain reaction is performed on the microfluidic chip. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       To sufficiently understand the figures cited in the detailed description of the present invention, brief description of each figure is provided. 
         FIG. 1  shows a PCR reaction result of a conventional PCR chip. 
         FIG. 2  shows a microfluidic chip according to an embodiment of the present invention. 
         FIG. 3  shows a sealing device of a microfluidic chip according to an embodiment of the present invention. 
         FIG. 4  shows a heat-sealing unit according to an embodiment of the present invention. 
         FIG. 5  shows a heat-sealing unit according to an embodiment of the present invention. 
         FIG. 6  shows a heat-sealing unit according to an embodiment of the present invention. 
         FIG. 7  shows a heat-sealing unit according to an embodiment of the present invention. 
         FIG. 8  shows an operation method of a sealing device of a microfluidic chip according to an embodiment of the present invention. 
         FIGS. 9 to 11  show a sealing process of a sealing system of a microfluidic chip according to an embodiment of the present invention. 
         FIG. 12  shows an exemplary sealing result of a microfluidic chip according to an embodiment of the present invention. 
         FIG. 13  shows an exemplary reaction result of a sealed microfluidic chip according to an embodiment of the present invention. 
     
    
    
     BEST MODE FOR CARRYING OUT THE INVENTION 
     Hereinafter, embodiments according to the present invention will be described with reference to the accompanying drawings. It should be noted that in assigning reference numerals to constitutional components of each figure, although the identical components are shown in different figures, they have an identical reference numeral if possible. Further, in describing the embodiments of the present invention, specific descriptions of related well-known configurations or functions are determined to hinder understanding of the embodiments of the present invention, detailed description thereof will be omitted. In addition, although the embodiments of the present invention will be described hereinafter, the spirits of the present invention will not be limited or restricted by the embodiments and will be modified and diversely embodied by those skilled in the art. 
     Throughout the specification, when an element is referred to as being “connected to” another element, this includes a case of “indirect connection” with intervention of another element therebetween, as well as a case of “direct connection”. Throughout the specification, when an element is referred to as “including” a certain constitutional component, it means that the element does not exclude the component, but further includes the component unless otherwise specifically mentioned. In addition, in describing a constitutional component of an embodiment of the present invention, terms such as a first, a second, A, B, (a), (b) and the like may be used. These terms are used only to distinguish one component from the others, and the nature, the sequence, the order or the like of a corresponding component is not restricted by the terms. 
       FIG. 2  shows a microfluidic chip according to an embodiment of the present invention. 
     A microfluidic chip  200  is a chip operating together with a sealing device  300  of the microfluidic chip to perform sealing and may include an inlet unit  210 , a reaction region  220 , and an outlet unit  230  as shown in the figure. 
     In the microfluidic chip  200 , the fluid flowing through the inlet unit  210  performs a predetermined reaction in the reaction region  220  and may flow out through the outlet unit  230  thereafter. Here, although the reaction may be a PCR reaction, this is only an example, and various reactions may be performed according to embodiments to which the present invention is applied. 
     Each of the inlet unit  210  and the outlet unit  230  may include an opening  212  and  232  through which a fluid flows in and a protrusion unit  214  and  234  which is defined to be protruded and locatedadjacent to the opening  212  and  232 . As is described below in further detail, since heat is applied to the protrusion units  214  and  234  by the sealing device  300  of the microfluidic chip (particularly, heat contact units  322  of the sealing device  300  of the microfluidic chip), at least a part of the protrusion units  214  and  234  is melted, and at least a part of the melted protrusion units  214  and  234  moves to the openings  212  and  232  and hardened to seal the openings  212  and  232 . 
     Through the sealing accomplished like this, loss of the fluid injected inside the microfluidic chip  200 , which occurs in the reaction region  220  or before and after the reaction region  220 , and degradation of reliability of reaction results caused by generation of bubbles can be prevented. For example, if a PCR reaction is performed in the reaction region  220 , reliable CT and fluorescent signal values of the PCR can be obtained by preventing generation of bubbles, and it is not limited thereto. 
     The configuration or the structure of the microfluidic chip  200  shown in  FIG. 2  is only an example, and microfluidic chips  200  of various configurations or structures may be used according to embodiments to which the present invention is applied. In addition, the microfluidic chip  200  shown in  FIG. 2  may be utilized as various chips which require sealing, such as a biochip, a diagnosis chip, a microchip and the like. 
       FIG. 3  shows a sealing device of a microfluidic chip according to an embodiment of the present invention. 
     As shown in the figure, the sealing device  300  of the microfluidic chip may include a support unit  310  and a heat-sealing unit  320 . 
     The microfluidic chip  200  may be arranged on the support unit  310 . Since the surface of the support unit  310  is formed to be recessed toward the inside to this end, an arrangement space  312  of the microfluidic chip  200  may be provided. Although the space  312  preferably has a size corresponding to the size of the microfluidic chip  200 , it may have a variety of sizes according to embodiments. In addition, although it is shown in  FIG. 3  that the arrangement space  312  is provided as the surface of the support unit  310  is recessed, this is only an example, and various means for arranging and/or fixing the microfluidic chip  200  may be used according to embodiments to which the present invention is applied. 
     The heat-sealing unit  320  may seal the inlet unit  210  and the outlet unit  230  by applying heat to the microfluidic chip  200  arranged on the support unit  310 . More specifically, the heat-sealing unit  320  may include heat contact units  322  thermally contacting with the inlet unit  210  and the outlet unit  230  of the microfluidic chip  200 , and the protrusion units  214  and  234  of the inlet unit  210  and the outlet unit  230  may be melted by contacting and heating the inlet unit  210  and the outlet unit  230  of the microfluidic chip  200  through the heat contact units  322 . As the melted protrusion units  214  and  234  move to the openings  212  and  232  and are hardened thereafter, the openings  212  and  232  of the inlet unit  210  and the outlet unit  230  may be sealed. The hardening may be accomplished by blocking the heat applied to the microfluidic chip  200  as the heat-sealing unit  320  contacting with the microfluidic chip  200  is separated from the microfluidic chip  200  or the heat contact units  322  of the heat-sealing unit  320  is cooled down. 
     Although it is not shown in the figure, the sealing device  300  of the microfluidic chip may further include a driving unit according to embodiments. The driving unit may move the heat-sealing unit  320  toward the support unit  310 . More specifically, the driving unit may move the heat-sealing unit  320  toward the support unit  310  (or the microfluidic chip  200  on the support unit  310 ) to apply heat to the microfluidic chip  200  or separate the heat-sealing unit  320  from the support unit  310  (the microfluidic chip  200  on the support unit  310 ). 
     The configuration or the structure of the sealing device  300  of the microfluidic chip shown in  FIG. 3  is only an example, and sealing devices of a microfluidic chip of various configurations or structures may be used according to embodiments to which the present invention is applied. 
       FIG. 4  shows a heat-sealing unit according to an embodiment of the present invention. 
     As shown in the figure, the heat-sealing unit  320  may further include heaters  324  and  324 ′ for heating the heat contact units  322  and a temperature sensor  326  for measuring temperature of the heat contact units  322 . 
     That is, the heaters  324  and  324 ′ may heat the heat contact units  322 , and the heating may be performed until a predetermined temperature is measured by the temperature sensor  326 . Here, the temperature may be a temperature suitable for melting the protrusion units of the inlet unit  210  and the outlet unit  230  of the microfluidic chip  200 . After the heaters  324  and  324 ′ heat the heat contact units  322  to a predetermined temperature, the heated heat contact units  322  apply heat to the inlet unit  210  and the outlet unit  230  of the microfluidic chip  200  by contacting with the inlet unit  210  and the outlet unit  230 , and at least a portion of the inlet unit  210  and the outlet unit  230  may be melted down. 
     The configuration of the heat-sealing unit  320  shown in  FIG. 4  is only an example, and various configurations may be applied according to embodiments to which the present invention is applied. 
       FIG. 5  shows a heat-sealing unit according to an embodiment of the present invention. 
     As shown in the figure, the heat-sealing unit  320  may further include a chip fixing unit  328 . 
     The chip fixing unit  328  may be formed to be protruded from the heat-sealing unit  320  toward the support unit  310 , and the protruded chip fixing unit  328  may fix the microfluidic chip  200  to the support unit  310  by applying force to the microfluidic chip  200  arranged on the support unit  310  in a predetermined direction (e.g., in a lower direction). According to the chip fixing unit  328  like this, unstable movement of the microfluidic chip  200  can be prevented when the heat-sealing unit  320  moves and thermally contacts by the driving unit. 
     The chip fixing unit  328  is preferably formed to be protruded as much as to prevent shake of the microfluidic chip  200  without damaging the microfluidic chip  200 , and according to embodiments, the protrusion length of the chip fixing unit  328  can be adjusted by implementing at least a portion of the chip fixing unit  328  using an elastic material. For example, since the protrusion length of the chip fixing unit  328  is shortened as the elastic material contracts when a force larger than a predetermined threshold value is applied to the chip fixing unit  328 , damage of the protruded part to the microfluidic chip  200  can be prevented, and at the same time, the microfluidic chip  200  can be fixed. 
     More specifically, according to the configuration as described above, as the heat-sealing unit  320  moves to the support unit  310 , the protruded chip fixing unit  328  may eliminate shake of the microfluidic chip  200  by applying force to the microfluidic chip  200  in a predetermined direction as soon as contacting with the microfluidic chip  200  arranged on the support unit  200 . Subsequently, if a movement of the heat-sealing unit  320  continues in the lower direction, at least a portion of the chip fixing unit  328  implemented using an elastic material moves or contracts toward the inside of the heat-sealing unit  320 , and thus the protrusion length of the chip fixing unit  328  can be adjusted. Accordingly, the unstable movement of the microfluidic chip  200  can be effectively eliminated by continuously applying force to the microfluidic chip  200  without damaging the microfluidic chip  200 . In addition, according to the configuration as described above, since the chip fixing unit  328  does not need to be replaced or changed even when the dimension of the microfluidic chip  200  changes, reduction of cost and convenience of using the device can be provided. 
     The chip fixing unit  328  shown in  FIG. 5  is only an example, and various configurations of the chip fixing unit may be applied according to embodiments to which the present invention is applied. 
       FIG. 6  shows a heat-sealing unit according to an embodiment of the present invention. 
     As shown in the figure, the heat contact units  322  of the heat-sealing unit  320  may be formed to be recessed toward the inside. As is described below in further detail, according to the configuration of the heat contact units  322  formed to be recessed toward the inside, the protrusion units  214  and  234  of the microfluidic chip  200  melted by the heat contact units  322  may easily move to the openings  212  and  232  of the inlet unit  210  and the outlet unit  230 . 
     Although it is not shown in  FIG. 6 , according to embodiments, a release agent may be coated on the surface of the heat contact units  322  thermally contacting with the microfluidic chip  200 . Here, the release agent is for preventing an attachment of unnecessary materials to the heat contact units  322  by easily releasing the melted protrusion units  214  and  234  from the heat contact units  322 , and although silicon resin, paraffin, wax or the like can be used, it is not limited thereto. 
     The configuration or the structure of the heat contact units  322  shown in  FIG. 6  is only an example, and heat contact units of various configurations or structures may be used according to embodiments to which the present invention is applied. 
       FIG. 7  shows a heat-sealing unit according to an embodiment of the present invention. 
     If the heat-sealing unit  320  moves toward the support unit  310  (see  FIG. 7( a ) , the heat contact units  322  of the heat-sealing unit  320  may move at least a portion of the protrusion units  214  and  234  of the microfluidic chip  200  melted by the heat contact units  322  not to unnecessary directions (e.g., the outsides of the openings  212  and  232 ), but toward the openings  212  and  232  (particularly, toward the insides of the openings  212  and  232 ) (see  FIG. 7( b ) ). The at least a portion of the melted protrusion units  214  and  234  moved to the openings  212  and  232  is hardened thereafter and seal the openings  212  and  232 . 
     That is, according to the configuration of the heat contact unit  322  formed to be recessed toward the inside, since at least a portion of the protrusion units  214  and  234  melted by the heat contact units  322  may easily move to the openings  212  and  232 , further precise and effective sealing can be accomplished. 
       FIG. 8  shows an operation method of a sealing device of a microfluidic chip according to an embodiment of the present invention, and  FIGS. 9 to 11  show a sealing process of a sealing system of a microfluidic chip according to an embodiment of the present invention. Here, the system may include a microfluidic chip and a sealing device of the microfluidic chip. 
     First, referring to  FIG. 8 , a microfluidic chip  200  may be provided in the sealing device  300  of the microfluidic chip (step S 810 ). More specifically, step S 810  may be accomplished by arranging the microfluidic chip  200  on the support unit  310  of the sealing device  300  (particularly, in the arrangement space  312  of the microfluidic chip  200  formed in the support unit  310 ) (see  FIG. 9 ). According to embodiments, a step of further firmly fixing the microfluidic chip  200  to the support unit  310  may be additionally performed to prevent shake of the microfluidic chip  200  arranged on the support unit  310 . 
     Subsequently, the heat-sealing unit  320  of the sealing device is heated (step S 820 ), and the heated heat-sealing unit  320  may be moved (step S 830 ). That is, the heat contact unit  322  may contact and heat the inlet unit  210  and the outlet unit  230  of the microfluidic chip  200  by moving the heat-sealing unit  320  toward the microfluidic chip  200  after the heat contact unit  322  of the heat-sealing unit  320  is heated to a predetermined temperature (see  FIG. 10 ). According to the contact-heating like this, at least a portion of the inlet unit  210  and the outlet unit  230  of the microfluidic chip  200  (particularly, at least a portion of the protrusion units  214  and  234 ) may be melted and move to the openings  212  and  232 . 
     Subsequently, the microfluidic chip  200  may be sealed (step S 840 ). Step S 840  may be accomplished by sealing the inlet unit  210  and the outlet unit  230  as at least a portion of the inlet unit  210  and the outlet unit  230  of the microfluidic chip  200  (particularly, at least a portion of the protrusion units  214  and  234 ) is melted, moves to the openings  212  and  232  and is hardened. Here, although the hardening may be accomplished by separating the heat-sealing unit  320  contacting with the microfluidic chip  200  from the microfluidic chip  200  (see  FIG. 11 ), according to embodiments, the hardening may be accomplished by blocking the heat applied to the microfluidic chip  200  as the heat contact unit  322  of the heat-sealing unit  320  is cooled down. 
       FIG. 12  shows an exemplary sealing result of a microfluidic chip according to an embodiment of the present invention. 
     Referring to  FIG. 12( a ) , the inlet unit and the outlet unit of the microfluidic chip are shown. As shown in the figure, each of the inlet unit and the outlet unit may include an opening through which a fluid flows in and a protrusion unit which is defined to be protruded and located adjacent to the opening. 
     Referring to  FIG. 12( b ) , a microfluidic chip sealed by the sealing device of the microfluidic chip is shown. As shown in the figure, as heat is applied to the protrusion units by the sealing device of the microfluidic chip, at least a portion of the protrusion units is melted, and the melted protrusion units move to the openings and are hardened to seal the openings. 
       FIG. 13  shows an exemplary reaction result of a sealed microfluidic chip according to an embodiment of the present invention. 
     As shown in  FIG. 13( a ) , it can be confirmed that although a certain reaction (e.g., a PCR reaction) is performed on the microfluidic chip after sealing is accomplished on the microfluidic chip by the sealing device of the microfluidic chip, bubbles conventionally generated by evaporation of the fluid in the reaction region almost do not exist. 
     In addition, referring to  FIG. 13( b ) , since the bubbles are not generated, distortion of reaction results can be prevented, and thus reaction results having further improved reliability can be acquired. 
     Although operations are shown in the figure in a specific order, it should not be construed that these operations should be performed in the specific order shown in the figure or in a sequential order or all the operations shown in the figure should be performed to accomplish a desired result. 
     Optimum embodiments have been disclosed in the figures and the specifications as described above. Although specific terms are used herein, these are used only to describe the present invention, not to restrict the meaning or to limit the scope of the present invention disclosed in the claims. Therefore, it may be understood that those skilled in the art may make various modifications and equivalent other embodiments from the embodiments. Accordingly, the true technical protection scope of the present invention should be determined by the technical spirits of the attached claims.