Abstract:
There is provided a biochip including: a first substrate having a first surface in which a plurality of grooves are provided to accommodate at least one type of culture medium therein, and including a first electrode which is connected to the plurality of grooves; and a second substrate having a first surface in which a plurality of biomaterial fixing parts are provided to attach at least one type of biomaterial thereto, and including a second electrode which is connected to the plurality of biomaterial fixing parts. The biochip can rapidly and precisely measure a reaction of the biomaterial.

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
       [0001]    This application claims the priority and benefit of Korean Patent Application No. 10-2014-0122535 filed on Sep. 16, 2014, with the Korean Intellectual Property Office, the disclosure of which is incorporated herein by reference. 
       BACKGROUND 
       [0002]    The present disclosure relates to a biochip configured to measure the degree of biomaterial culturing. 
         [0003]    A biochip is used to culture biomaterials or to measure reactions of such biomaterials with drugs. 
         [0004]    The reaction measurement of the biomaterials is performed by a method of observing the biochip with the naked eye or by a method of scanning the biochip using a digital image processing device. The former method has difficulty in measuring a fine reaction of the biomaterials, while the latter method have difficulties in performing such measurements in real time as well as increased costs due to equipment required for the device. 
         [0005]    Therefore, the development of a biochip capable of precisely measuring reactions of the biomaterials with drugs in real time has been demanded. 
         [0006]    As related art, there is provided Patent Document 1. 
       RELATED ART DOCUMENT 
       [0007]    (Patent Document 1) KR2012-138082 A 
       SUMMARY 
       [0008]    An aspect of the present disclosure may provide a biochip configured to precisely and rapidly measure reactions of biomaterials, and a device for measuring the biochip. 
         [0009]    According to an aspect of the present disclosure, a biochip may include an electrode unit configured to measure electrical resistance of a biomaterial. 
         [0010]    According to another aspect of the present disclosure, a device for measuring a biochip may include an measuring unit configured to measure a reaction state of a biomaterial using electrical resistance characteristics of the biomaterial cultured in the biochip. 
     
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
         [0011]    The above and other aspects, features and advantages of the present disclosure will be more clearly understood from the following detailed description taken in conjunction with the accompanying drawings, in which: 
           [0012]      FIG. 1  is an exploded perspective view of a biochip according to an exemplary embodiment in the present disclosure; 
           [0013]      FIG. 2  is a bottom perspective view of the biochip illustrated in  FIG. 1 ; 
           [0014]      FIG. 3  is an assembled perspective view of the biochip illustrated in  FIG. 1 ; 
           [0015]      FIG. 4  is a cross-sectional view of the biochip illustrated in  FIG. 3 , taken along line A-A; 
           [0016]      FIG. 5  is an exploded perspective view of biochip according to another exemplary embodiment in the present disclosure; 
           [0017]      FIG. 6  is a bottom perspective view of the biochip illustrated in  FIG. 5 ; 
           [0018]      FIG. 7  is an assembled perspective view of the biochip illustrated in  FIG. 5 ; 
           [0019]      FIG. 8  is a cross-sectional view of the biochip illustrated in  FIG. 7 , taken along line B-B; 
           [0020]      FIG. 9  is an exploded perspective view of a biochip according to another exemplary embodiment in the present disclosure; 
           [0021]      FIG. 10  is a bottom view of a first substrate illustrated in  FIG. 9 ; 
           [0022]      FIG. 11  is an assembled perspective view of the biochip illustrated in  FIG. 9 ; 
           [0023]      FIG. 12  is a cross-sectional view of the biochip illustrated in  FIG. 11 , taken along line C-C; 
           [0024]      FIG. 13  is a cross-sectional view of the biochip illustrated in  FIG. 11 , taken along line D-D; 
           [0025]      FIG. 14  is an exploded perspective view of a biochip according to another exemplary embodiment in the present disclosure; 
           [0026]      FIG. 15  is a bottom view of a first substrate illustrated in  FIG. 14 ; 
           [0027]      FIG. 16  is an assembled perspective view of the biochip illustrated in  FIG. 14 ; 
           [0028]      FIG. 17  is a cross-sectional view of the biochip illustrated in  FIG. 16 , taken along line E-E; 
           [0029]      FIG. 18  is a cross-sectional view of the biochip illustrated in  FIG. 16 , taken along line F-F; and 
           [0030]      FIG. 19  is a configuration diagram a device for measuring a biochip according to an exemplary embodiment in the present disclosure. 
       
    
    
     DETAILED DESCRIPTION 
       [0031]    Exemplary embodiments of the present disclosure will now be described in detail with reference to the accompanying drawings. 
         [0032]    The disclosure may, however, be embodied in many different forms and should not be construed as being limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the disclosure to those skilled in the art. 
         [0033]    In the drawings, the shapes and dimensions of elements may be exaggerated for clarity, and the same reference numerals will be used throughout to designate the same or like elements. 
         [0034]    Further, the term “biomaterial” as used in the present specification may include cells, proteins, DNA, RNA, and the like, of animals and plants, including human beings. Further, “biomaterial” may also refer to pathogens, pathogenic cells, and the like, generated from animals and plants. 
         [0035]    A biochip according to an exemplary embodiment will be described with reference to  FIG. 1 . 
         [0036]    A biochip  10  may include a first substrate  100  and a second substrate  200 . For example, the biochip  10  may include the first substrate  100  in which at least one type of culture medium is stored, and the second substrate  200  to which at least one type of biomaterial is attached. The biochip  10  may include a first electrode  120  and a second electrode  220 . For example, the biochip  10  may include the first electrode  120  formed on the first substrate  100 , and the second electrode  220  formed on the second substrate  200 . 
         [0037]    The first substrate  100  may be formed in a thin plate form. For example, the first substrate  100  may be formed in a rectangular form having a predetermined thickness. The first substrate  100  may be formed of a material having excellent chemical resistance and corrosion resistance. For example, the first substrate  100  may be formed of a material such as plastic, glass, silicon, or the like. 
         [0038]    The first substrate  100  may have a plurality of grooves  110  formed therein. For example, the plurality of grooves  110  for accommodating the culture medium may be formed in a first surface of the first substrate  100 . The first substrate  100  may be coated with a plurality of materials. For example, the grooves  110  may be coated with a hydrophilic material, and portions other than the grooves  110  may be coated with a hydrophobic material. 
         [0039]    The first substrate  100  may have the first electrode  120  formed thereon. For example, the groove  110  of the first substrate  100  may have a first internal electrode  130  formed therein, wherein the first internal electrode  130  is a part of the first electrode  120 . The first internal electrode  130  may be extended from the groove  110  to a second surface of the first substrate  100 . 
         [0040]    The second substrate  200  may be formed in a thin plate form, similar to the first substrate  100 . For example, the second substrate  200  may be formed in a rectangular form having a very thin thickness. The second substrate  200  may be formed of a material having excellent chemical resistance and corrosion resistance. For example, the second substrate  200  may be formed of a material such as plastic, glass, silicon, or the like. 
         [0041]    The second substrate  200  may be coated with a plurality of materials. For example, a portion of the second substrate  200  may be coated with a hydrophobic material, and other portions may be coated with a hydrophilic material (a description thereof will be provided below with reference to  FIG. 2 ). 
         [0042]    The second substrate  200  may have the second electrode  220  formed thereon. For example, the second substrate  200  may have a second external electrode  240  formed on the first surface thereof, wherein the second external electrode  240  is a part of the second electrode  220 . The second external electrode  240  may be formed on the first surface of the second substrate  200  to be wide and may be extended in a length direction (a direction of a Y axis based on  FIG. 1 ) of the second substrate  200  to be long. 
         [0043]    A bottom shape of the biochip will be described with reference to  FIG. 2 . 
         [0044]    The biochip  10  may have a plurality of electrodes  120  and  220  formed thereon. For example, the first substrate  100  may have the first electrode  120  formed thereon and the second substrate  200  may have the second electrode  220  formed thereon. 
         [0045]    The first electrode  120  may be formed in the groove  110  of the first substrate  100  and on the second surface of the first substrate  100 . For example, the first internal electrode  130  of the first electrode  120  may be formed in each of the grooves  110  as described above, and the first external electrode  140  of the first electrode  120  may be formed on the second surface of the first substrate  100 . The first external electrode  140  may be formed to be connected to a plurality of first internal electrodes  130 . For example, the first external electrode  140  may be formed to be wide to be connected all of the first internal electrodes  130  that are extended from the groove  110  to the first surface of the first substrate  100 . 
         [0046]    The second electrode  220  may be each formed on the first surface and the second surface of the second substrate  200 . For example, the second internal electrode  230  of the second electrode  220  may be formed to be long from the second surface of the second substrate  200  to the first surface thereof, and the second external electrode  240  of the second electrode  220  may be formed on the first surface of the second substrate  200  to be wide. The second external electrode  240  may be formed to be connected to a plurality of second internal electrodes  230 . For example, the second external electrode  240  may be formed to be wide to be connected all of the second internal electrodes  230  that are extended to the first surface of the second substrate  200 . 
         [0047]    The second surface of the second substrate  200  may be partitioned into a plurality of regions. For example, the second surface of the second substrate  200  may be partitioned into a region to which the biomaterial is attached (for reference, corresponding to a biomaterial fixing part described in the claims) and other regions. Here, the latter may be a first region  204  which is coated with the hydrophobic material, and the former is a second region  206  which is coated with the hydrophilic material. 
         [0048]    An assembled shape of the biochip will be described with reference to  FIG. 3 . 
         [0049]    The biochip  10  may be formed in a shape in which the first substrate  100  and the second substrate  200  are assembled with each other. For example, the biochip  10  may be formed by the first surface of the first substrate  100  and the second surface of the second substrate  200  that are assembled with each other to be in contact with each other. 
         [0050]    The biochip  10  formed as described above may be used for the culture of the biomaterials or a drug reaction experiment of the biomaterials. 
         [0051]    A shape of a cross section of the biochip taken along line A-A will be described with reference to  FIG. 4 . 
         [0052]    The biochip  10  may be formed in the assembled form of the first substrate  100  and the second substrate  200  as described above. 
         [0053]    The first substrate  100  may be disposed below the biochip  10  and may accommodate a culture medium or a drug  40 . For example, the groove  110  of the first substrate  100  may accommodate the culture medium or the drug  40 . The first substrate  100  may include the first electrode  120  that transmits or senses an electrical signal which is necessary for the experiment of the biomaterials. For example, the first internal electrodes  130  that are extended in one direction (a direction of a Z axis based on  FIG. 4 ) to be long may be each formed in the grooves  110  of the first substrate  100 , and one first external electrode  140  that is connected to the plurality of first internal electrodes  130  may be formed on a lower surface of the first substrate  100 . 
         [0054]    The second substrate  200  may be disposed over the biochip  10  and may accommodate a biomaterial  50 . For example, the biomaterial  50  may be attached to the second substrate  200 . For reference, the attachment of the biomaterial  50  may be performed by a separate fixing material. The second substrate  200  may include the second electrode  220  that transmits or senses an electrical signal which is necessary for the experiment of the biomaterials. For example, the second internal electrodes  230  that are extended in one direction (a direction of a Z axis based on  FIG. 4 ) from a region to which the biomaterial  50  is attached to be long may be each formed on the second surface of the second substrate  200 , and one second external electrode  240  that is connected to the plurality of second internal electrodes  230  may be formed on an upper surface of the second substrate  200 . 
         [0055]    The biochip  10  configured as described above may measure electrical characteristics (e.g., electrical resistance, impedance, and the like) of the biomaterial  50  through the first electrode  120  and the second electrode  220 . Further, the biochip  10  may measure a culture state or a drug reaction state of the biomaterial  50  through the measured electrical characteristics values. 
         [0056]    Hereinafter, another exemplary embodiment in the biochip will be described. For reference, in the description of another exemplary embodiment in the bio chip, the same components as those of an exemplary embodiment described above will be denoted by the same reference numerals as those of an exemplary embodiment described above and a description thereof will be omitted. 
         [0057]    A biochip according to another exemplary embodiment will be described with reference to  FIGS. 5 and 6 . 
         [0058]    The biochip  10  according to the present exemplary embodiment may be distinguished from an exemplary embodiment described above in a shape of the second substrate  200 . 
         [0059]    The second substrate  200  may have a plurality of protrusions  202  formed thereon. For example, the plurality of protrusions  202  may be formed on the second surface of the second substrate  200 . The second internal electrode  230  may be formed in each of the protrusions  202  (see  FIG. 6 ). The protrusion  202  formed as described above may provide the second region  206  to which the biomaterial is attached. 
         [0060]    The second substrate  200  may have two or more interval maintaining members  208  formed thereon. For example, four interval maintaining members  208  may be formed on the second surface of the second substrate  200 . The interval maintaining members  208  formed as described above may maintain an interval between the first surface of the first substrate  100  and the second surface of the second substrate  200  to be constant. 
         [0061]    An assemble shape and a cross-section shape of the biochip will be described with reference to  FIGS. 7 and 8 . 
         [0062]    The biochip  10  may be formed by the assembly of the first substrate  100  and the second substrate  200 . For example, the biochip  10  may have a configuration in which the protrusion  202  of the second substrate  200  is assembled with the groove  110  of the first substrate  100  to substantially face each other. Here, the protrusion  202  may be partially inserted into the groove  110 . However, the protrusion  202  is not necessarily inserted into the groove  110 . For example, an end portion of the protrusion  202  may also be positioned to be higher than the upper surface of the groove  110 . 
         [0063]    The first substrate  100  and the second substrate  200  may be partially in contact with each other by the interval maintaining member  208 . For example, the first substrate  100  and the second substrate  200  may be assembled with each other so as not in contact with any portion except for the interval maintaining member  208 . Since the above-mentioned assembled structure significantly reduces a friction area between the first substrate  100  and the second substrate  200 , it may easily perform an assembly and a separation between the first substrate  100  and the second substrate  200 . 
         [0064]    A biochip according to another exemplary embodiment will be described with reference to  FIGS. 9 and 10 . 
         [0065]    The biochip  10  according to the present exemplary embodiment may be distinguished from an exemplary embodiment described above in formed shapes of the electrodes  120  and  220 . 
         [0066]    The first electrode  120  may include a plurality of first internal electrodes  130  and a plurality of first external electrodes  140  ( 142 ,  144 , and  146 ). For example, the plurality of first internal electrodes  130  may be formed in each of the grooves  110 , and the plurality of first external electrodes  140  ( 142 ,  144 , and  146 ) may be formed on the second surface of the first substrate  100  (see  FIG. 10 ). The first internal electrode  130  may be formed along a thickness direction (a direction of a Z axis based on  FIG. 9 ) of the first substrate  100 . For example, the first internal electrode  130  may be formed from a bottom surface of the groove  110  to the second surface of the first substrate  100  to be long. The first external electrodes  140  ( 142 ,  144 , and  146 ) may be formed along a length direction (a direction of a Y axis based on  FIG. 9 ) of the first substrate  100  to be long. For example, the respective first external electrodes  140  ( 142 ,  144 , and  146 ) may be formed to be parallel to each other along the direction of the Y axis to be able to be connected the first internal electrodes  130  having the same number as that of the first external electrodes. 
         [0067]    The second electrode  220  may include a plurality of second internal electrodes  230  and a plurality of second external electrodes  240  ( 242 ,  244 , and  246 ). For example, the plurality of second internal electrodes  230  may be formed on the second surface of the second substrate, and the plurality of second external electrodes  240  ( 242 ,  244 , and  246 ) may be formed on the first surface of the second substrate  200 . The second internal electrode  230  may be formed along a thickness direction (a direction of a Z axis based on  FIG. 9 ) of the second substrate  200 . For example, the second internal electrode  230  may be formed from the second surface of the second substrate to the first surface of the second substrate  200  to be long. The second external electrodes  240  ( 242 ,  244 , and  246 ) may be formed along a length direction (a direction of a Y axis based on  FIG. 9 ) of the second substrate  200  to be long. For example, the respective second external electrodes  240  ( 242 ,  244 , and  246 ) may be formed to be parallel to each other along the direction of the Y axis to be able to be connected the second internal electrodes  230  having the same number as that of the second external electrodes. 
         [0068]    The biochip configured as described above may have a structure in which the plurality of internal electrodes  130  and  230  are partitioned by three external electrodes  140  and  240 . 
         [0069]    An assemble shape and a cross-section shape of the biochip will be described with reference to  FIG. 11 through 13 . 
         [0070]    The biochip  10  may be formed by assembling the first substrate  100  having the plurality of first external electrodes  140  ( 142 ,  144 , and  146 ) and the second substrate  200  having the plurality of second external electrodes  240  ( 242 ,  244 , and  246 ). For example, the biochip  10  may be formed by assembling the first substrate  100  having three first external electrodes  140  ( 142 ,  144 , and  146 ) and the second substrate  200  having the second external electrodes  240  ( 242 ,  244 , and  246 ) having the same number as the first external electrodes. The first external electrodes  140  ( 142 ,  144 , and  146 ) and the second external electrodes  240  ( 242 ,  244 , and  246 ) may be formed to be in parallel to each other. For example, the first external electrodes  140  ( 142 ,  144 , and  146 ) may be formed along a length direction (a direction of a Y axis based on  FIG. 11 ) of the first substrate  100  to be long, and the second external electrodes  240  ( 242 ,  244 , and  246 ) may be formed along a length direction (a direction of a Y axis based on  FIG. 11 ) of the second substrate  200  to be long. 
         [0071]    The biochip  10  formed as described above may be used to simultaneously experiment a plurality of biomaterials or drugs. For example, the biochip  10  may measure a first type of biomaterial  50  and drug  40  using the first external electrode  142  and the second external electrode  242 , may measure a second type of biomaterial  50  and drug  40  using the first external electrode  144  and the second external electrode  244 , and may measure a third type of biomaterial  50  and drug  40  using the first external electrode  146  and the second external electrode  246 . 
         [0072]    Therefore, an effort involved in separately performing experiments for various biomaterials and various drug reactions may be saved. 
         [0073]    Meanwhile, although the present exemplary embodiment describes a case in which the plurality of external electrodes  140  and  240  are extended along the length direction (the direction of Y axis based on  FIG. 11 ) of the substrates  100  and  200 , the plurality of external electrodes  140  and  240  may be extended along a width direction (a direction of an X axis based on  FIG. 11 ) of the substrates  100  and  200 , as needed. In this case, experiments for more various biomaterials and drug reactions may be performed using the biochip  10 . 
         [0074]    A biochip according to another exemplary embodiment will be described with reference to  FIGS. 14 and 15 . 
         [0075]    The biochip  10  according to the present exemplary embodiment may be distinguished from an exemplary embodiment described above in formed shapes of the external electrodes  140  and  240 . For example, the first external electrode  140  and the second external electrode  240  may be formed to correspond to the grooves  110  of the first substrate  100  as illustrated in  FIGS. 14 and 15 . Further, the first external electrode  140  and the second external electrode  240  may be formed to have the same number as that of grooves  110  of the first substrate  100  as illustrated in  FIGS. 14 and 15 . 
         [0076]    An assemble shape and a cross-section shape of the biochip will be described with reference to  FIG. 16 through 18 . 
         [0077]    The biochip  10  may be configured to separately measure the biomaterials cultured in the plurality of grooves  110 . For example, the first electrode  120  and the second electrode  220  are each separated from each other with respect to the length direction (the direction of the Y axis) and the width direction (the direction of the X axis) of the substrates  100  and  200  (see  FIGS. 17 and 18 ). 
         [0078]    Therefore, the biochip  10  according to the present exemplary embodiment may simultaneously measure the reaction experiments of the biomaterials for different culture mediums or drugs by attaching the same type of biomaterial onto the second substrate  200  and storing different types of culture mediums or drugs in the grooves  110  of the first substrate  100 . Further, the biochip  10  according to the present exemplary embodiment may simultaneously measure the reaction experiments of various biomaterials for the same type of culture medium or drug by attaching different types of biomaterials onto the second substrate  200  and storing the same type of culture medium or drug in the grooves  110  of the first substrate  100 . 
         [0079]      FIG. 19  is a configuration diagram a device for measuring a biochip according to an exemplary embodiment in the present disclosure. 
         [0080]    A device  30  for measuring a biochip may include one of the bio chips  10  according to various exemplary embodiments described above and a measuring unit  20 . 
         [0081]    The measuring unit  20  may be connected to the external electrodes  140  and  240  of the substrates  100  and  200 . The measuring unit  20  may measure a culture state of the biomaterial or a reaction state of the biomaterial and the drug. For example, the measuring unit  20  may measure electrical characteristics of the biomaterial and the culture medium using the external electrodes  140  and  240 , and consequently, may measure the culture state of the biomaterial or the reaction state of the biomaterial and the drug. To this end, the measuring unit  20  may include a memory element in which basis information on the biomaterial, the culture medium, the drug, and the like of an experiment target is stored. Further, the measuring unit  20  may include a computing element capable of determining the culture state of the biomaterial or the reaction state of the biomaterial and the drug by comparing the basic information with measured information. 
         [0082]    The device for measuring the biochip configured as described above may rapidly and precisely measure a state of the cultured biomaterial using the biochip. 
         [0083]    Hereinafter, a principle and a method for measuring the biomaterial using the device for measuring the biochip will be described. 
         [0084]    The device  30  for measuring the biochip may measure the state of the biomaterial using impedance of the biomaterial. 
         [0085]    For example, in the case in which the first internal electrode  120  and the second internal electrode  220  are supplied with an alternating current, since cells configuring the biomaterial are charged with charges, the biomaterial may have impedance. Then, the device  30  for measuring the biochip may indirectly determine the state of the biomaterial by measuring the impedance of the biomaterial. For example, since the cell having an intact cell membrane and a membrane potential acts as a capacitor to accumulate the charges in the cell, it may have a high impedance value, but since the cell having a cell membrane which is not intact and having a degraded function of mitochondria does not smoothly generate energy for maintaining a cell membrane potential, which causes a decrease in a capacitive phenomenon, it may have a low impedance value. 
         [0086]    Therefore, in the case in which the impedance value of the biomaterial measured by the device  30  for measuring the biochip is high, it may be determined that the number of cells configuring the biomaterial is large, and in the case in which the impedance value of the biomaterial is low, it may be determined that the number of cells configuring the biomaterial is small. That is, the device  30  for measuring the biochip may directly or indirectly determine a state of a bio cell membrane, whether or not energy of the cell is generated, and the like, using the impedance difference described above. 
         [0087]    Further, the device  30  for measuring the biochip may measure a cell state of the biomaterial by varying a frequency of a current. For example, the device  30  for measuring the biochip may determine the state of the biomaterial through a change in the frequency over time after applying a predetermined voltage or alternating current to the biomaterial. 
         [0088]    As set forth above, according to exemplary embodiments of the present disclosure, the reaction of the biomaterials may be rapidly and precisely measured. 
         [0089]    While exemplary embodiments have been shown and described above, it will be apparent to those skilled in the art that modifications and variations could be made without departing from the scope of the present invention as defined by the appended claims.