Patent Publication Number: US-2022228984-A1

Title: Fluorescence generating device and digital polymerase chain reaction analysis system including the same

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This U.S. non-provisional patent application claims priority under 35 U.S.C. § 119 of Korean Patent Application Nos. 10-2021-0007997, filed on Jan. 20, 2021, and 10-2021-0056175, filed on Apr. 30, 2021, the entire contents of which are hereby incorporated by reference. 
     BACKGROUND 
     The present disclosure herein relates to an analysis system, and particularly, to a fluorescence generating device and a digital polymerase chain reaction (PCR) analysis system including the same. 
     Recently, the incidence of high-risk infectious diseases is spreading and becoming prevalent due to social culture and economic factors, and huge national, social, and economic losses are being caused by the incidence of a malignant tumor and the occurrence of various types of cancers. There is an increased need to develop techniques for rapidly and accurately reading pathogens such as high-risk viruses and bacteria. 
     SUMMARY 
     The present disclosure provides: a fluorescence generating device capable of enhancing fluorescence detection efficiency of a liquid drop for digital PCR; and a digital PCR analysis system including the same. 
     Disclosed is a fluorescence generating device. An embodiment of the inventive concept provides a fluorescence generating device including: a clad layer on a substrate; an optical waveguide disposed within the clad layer and arranged in a first direction; and a housing disposed on the optical waveguide and the clad layer, the housing having a micro fluid channel extending in a second direction crossing the first direction. Here, the optical waveguide may include: an input waveguide which is provided within one side of the clad layer and provides excitation light to a liquid drop within the micro fluid channel to generate fluorescent light; and an output waveguide provided within the other side of the clad layer, the output waveguide having an output inclined surface disposed between the micro fluid channel and the clad layer to reflect the fluorescent light. 
     In an embodiment, the input waveguide may be disposed below the micro fluid channel, the input waveguide having an input inclined surface disposed between the micro fluid channel and the clad layer to reflect the excitation light to the liquid drop within the micro fluid channel. 
     In an embodiment, the fluorescence generating device may further include a reflection layer which is disposed between the input and output inclined surfaces and the clad layer. 
     In an embodiment, the reflection layer may include: an input reflection layer below the input inclined surface; and an output reflection layer below the output inclined surface. 
     In an embodiment, the output reflection layer may include a dichroic filter. 
     In an embodiment, the fluorescence generating device may further include a fluorescent light filter which is provided within the micro fluid channel above the input inclined surface. 
     In an embodiment, the input waveguide may be connected to a side wall of the micro fluid channel. 
     In an embodiment, the fluorescent light filter may be provided at an end of the input waveguide that is in contact with the side wall of the micro fluid channel. 
     In an embodiment, the fluorescence generating device may further include an excitation light filter which is provided within the micro fluid channel above the output inclined surface. 
     In an embodiment, the optical waveguide may include a ridge-type waveguide. 
     In an embodiment of the inventive concept, a fluorescence generating device includes: a clad layer on a substrate; an input waveguide provided on one side of the clad layer, the input waveguide having an input inclined surface; an output waveguide provided on the other side of the clad layer, the output waveguide having an output inclined surface adjacent to the input inclined surface; a fluid chip disposed above the input inclined surface and the output inclined surface, the fluid chip having a micro fluid channel that accommodates oil and a liquid drop within the oil; an excitation light filter disposed within the micro fluid channel above the output inclined surface to remove excitation light provided to the liquid drop; and an fluorescent light filter disposed within the micro fluid channel adjacent to the input waveguide to remove fluorescent light discharged from the liquid drop by the excitation light. 
     In an embodiment, the input waveguide may be connected to a side wall on one side of the micro fluid channel. 
     In an embodiment, the excitation light filter and the fluorescent light filter may be disposed in an L-shape. 
     In an embodiment, the clad layer may be provided at a side wall on the other side of the micro fluid channel. 
     In an embodiment, the fluorescence generating device may further include a reflection layer provided between the input and output inclined surfaces and the clad layer. 
     In an embodiment of the inventive concept, a digital PCR analysis system includes: a light source device comprising an exciting light source configured to generate excitation light; a fluorescence generating device configured to receive the excitation light to generate fluorescent light of a liquid drop; and a detection device provided with a photo-detector configured to detect the fluorescent light. Here, the fluorescence generating device may include: a clad layer on a substrate; an optical waveguide disposed within the clad layer and arranged in a first direction; 
     and a housing disposed on the optical waveguide and the clad layer, the housing having a micro fluid channel that extends in a second direction crossing the first direction. Here, the optical waveguide may include: an input waveguide provided within one side of the clad layer, the input waveguide providing the excitation light to the liquid drop within the micro fluid channel to generate the fluorescent light; and an output waveguide provided within the other side of the clad layer, the output waveguide having an output inclined surface that is disposed between the micro fluid channel and the clad layer to reflect the fluorescent light. 
     In an embodiment, the light source device may further include a first optical transmission block provided between the exciting light source and the fluorescence generating device. The first optical transmission block may further include: a first cladding block; a first buried waveguide disposed within the first cladding block, the first buried waveguide delivering the excitation light to the fluorescence generating device; and a first dichroic mirror provided in the first buried waveguide, first dichroic mirror transmitting the excitation light and reflecting the fluorescent light. 
     In an embodiment, the detection device may further include a second optical transmission block provided between the photo-detector and the fluorescence generating device. The second optical transmission block may include: a second cladding block; a second buried waveguide disposed within the second cladding block, the second buried waveguide providing the fluorescent light to the photo-detector; and a second dichroic mirror provided in the second buried waveguide, the second dichroic mirror transmitting the fluorescent light and reflecting the excitation light. 
     In an embodiment, the light source device may further include a first lens provided between the exciting light source and the fluorescence generating device, and the detection device may further include a second lens between the fluorescence generating device and the photo-detector. 
     In an embodiment, the light source device may further include a first optical fiber between the exciting light source and the fluorescence generating device, and the detection device may further include a second optical fiber between the fluorescence generating device and the photo-detector. 
    
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
       The accompanying drawings are included to provide a further understanding of the inventive concept, and are incorporated in and constitute a part of this specification. The drawings illustrate embodiments of the inventive concept and, together with the description, serve to explain principles of the inventive concept. In the drawings: 
         FIG. 1  is a perspective view showing an example of a digital PCR analysis system according to an embodiment of the inventive concept; 
         FIG. 2  is a perspective view showing an example of a light source device of  FIG. 1 ; 
         FIG. 3  is a perspective view showing an example of a detection device of  FIG. 1 ; 
         FIG. 4  is a perspective view showing an example of a fluorescence generating device of  FIG. 1 ; 
         FIG. 5  is a cross-sectional view taken along line I-I′ of  FIG. 4 ; 
         FIG. 6  is a cross-sectional view showing another example of the fluorescence generating device of  FIG. 4 ; 
         FIG. 7  is a cross-sectional view showing another example of the fluorescence generating device of  FIG. 4 ; 
         FIG. 8  is a cross-sectional view showing another example of the fluorescence generating device of  FIG. 4 ; 
         FIG. 9  is a cross-sectional view showing another example of the fluorescence generating device of  FIG. 4 ; 
         FIG. 10  is a cross-sectional view showing an example of a digital PCR analysis system according to an embodiment of the inventive concept; and 
         FIG. 11  is a cross-sectional view showing an example of a digital PCR analysis system according to an embodiment of the inventive concept. 
     
    
    
     DETAILED DESCRIPTION 
     Hereinafter, embodiments of the inventive concept will be described in detail with reference to the accompanying drawings. Advantages and features of the present disclosure, and implementation methods thereof will be clarified through following embodiments described in detail with reference to the accompanying drawings. The present disclosure may, however, be embodied in different forms and should not be construed as 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 concept of the present disclosure to those skilled in the art. Further, the present disclosure is only defined by scopes of claims. Like reference numerals refer to like elements throughout. 
     The terms used in this specification are used only for explaining embodiments while not limiting the present disclosure. In this specification, the singular forms include the plural forms as well, unless the context clearly indicates otherwise. The meaning of ‘comprises’ and/or ‘comprising’ used in the specification does not exclude the presence or addition of one or more components, steps, operations, and/or elements other than the mentioned components, steps, operations, and/or devices. Also, in the specification, polymerase chain reaction (PCR), a droplet, and a capsule may be understood as having meanings mainly used in the field of biotechnology. Since preferred embodiments are provided below, the order of the reference numerals given in the description is not limited thereto. 
     The foregoing description is about detailed examples for practicing the inventive concept. The present disclosure includes not only the above-described embodiments but also simply changed or easily modified embodiments. In addition, the present disclosure may include techniques which may be easily modified and practiced by using the embodiments described above. 
       FIG. 1  shows an example of a digital PCR analysis system  100  according to an embodiment of the inventive concept. 
     Referring to  FIG. 1 , the digital PCR analysis system  100  according to the embodiment of the inventive concept may include a light source device  200 , a detection device  300 , and a fluorescence generating device  400 . The light source device  200  may provide excitation light  212  to a liquid drop  402  within the fluorescence generating device  400 , and may generate fluorescent light  312 . The detection device  300  may detect the fluorescent light  312  of the fluorescence generating device  400 . The fluorescence generating device  400  may be provided between the light source device  200  and the detection device  300 . The liquid drop  402  within the fluorescence generating device  400  may receive the excitation light  212  and discharge the fluorescent light  312 . The control unit (not shown) may distinguish and/or discriminate the types of DNA of the liquid drop  402  within the fluorescence generating device  400  by using a fluorescence detection signal of the detection device  300 . 
       FIG. 2  shows an example of the light source device  200  of  FIG. 1 . 
     Referring to  FIGS. 1 and 2 , the light source device  200  may include an exciting light source  210  and a first optical transmission block  220 . 
     The exciting light source  210  may generate the excitation light  212 . For example, the exciting light source  210  may include a light emitting diode. The excitation light  212  may include blue light of about 488 nm. 
     The first optical transmission block  220  may be provided between the exciting light source  210  and the fluorescence generating device  400 . The first optical transmission block  220  may transmit the excitation light  212  to the fluorescence generating device  400 . The first optical transmission block  220  may remove the fluorescent light  312  of the fluorescence generating device  400  and protect the exciting light source  210 . As one example, the first optical transmission block  220  may include a first cladding block  222 , a first buried waveguide  224 , and a first dichroic mirror  226 . 
     The first cladding block  222  may be provided between the exciting light source  210  and the fluorescence generating device  400 . The first cladding block  222  may include a silicon oxide. On the other hand, the first cladding block  222  may include a transparent polymer, but the embodiment of the inventive concept is not limited thereto. 
     The first buried waveguide  224  may be provided within the first cladding block  222 . The first buried waveguide  224  may be connected between the exciting light source  210  and the fluorescence generating device  400 . The first buried waveguide  224  may have a refractive index higher than a refractive index of the first cladding block  222 . For example, the first buried waveguide  224  may include silicon. The first buried waveguide  224  may deliver the excitation light  212  to the fluorescence generating device  400 . As one example, the first buried waveguide  224  may include a first main waveguide  223  and a first branch waveguide  225 . The first main waveguide  223  may extend from one side of the first cladding block  222  to the other side thereof. That is, the first main waveguide  223  may connect the exciting light source  210  to the fluorescence generating device  400 . The first main waveguide  223  may provide the excitation light  212  to the fluorescence generating device  400 . The first branch waveguide  225  may be branched from the first main waveguide  223 . The first branch waveguide  225  may have a direction different from a direction of the first main waveguide  223 . The first branch waveguide  225  may remove the fluorescent light  312 , which has been reflected from the first dichroic mirror  226 , by discharging the fluorescent light  312  to the outside of the first cladding block  222 . 
     The first dichroic mirror  226  may be provided within the first main waveguide  223  adjacent to the first branch waveguide  225 . The first dichroic mirror  226  may allow the excitation light  212  to be transmitted therethrough to the fluorescence generating device  400 , and reflect the fluorescent light  312  of the fluorescence generating device  400  to the first branch waveguide  225 . 
       FIG. 3  shows an example of the detection device  300  of  FIG. 1 . 
     Referring to  FIG. 3 , the detection device  300  may include a photo-detector  310  and a second optical transmission block  320 . 
     The photo-detector  310  may detect the fluorescent light  312 . For example, the photo-detector  310  may include a photo diode. On the other hand, the photo-detector  310  may include a CMOS sensor or a CCD sensor, but the embodiment of the inventive concept is not limited thereto. 
     The second optical transmission block  320  may be provided between the photo-detector  310  and the fluorescence generating device  400 . The second optical transmission block  320  may deliver the fluorescent light  312  to the photo-detector  310 . The second optical transmission block  320  may reduce noise in the fluorescent light  312  by removing the excitation light  212 . As one example, the second optical transmission block  320  may include a second cladding block  322 , a second buried waveguide  324 , and a second dichroic mirror  326 . 
     The second cladding block  322  may be provided between the photo-detector  310  and the fluorescence generating device  400 . The second cladding block  322  may include the same material as the first cladding block  222 . For example, the second cladding block  322  may include a silicon oxide or a transparent polymer. 
     The second buried waveguide  324  may be provided within the second cladding block  322 . The second buried waveguide  324  may be connected between the photo-detector  310  and the fluorescence generating device  400 . The second buried waveguide  324  may have a refractive index greater than a refractive index of the second cladding block  322 . For example, the second buried waveguide  324  may include silicon. The second buried waveguide  324  may deliver the fluorescent light  312  to the photo-detector  310 . As one example, the second buried waveguide  324  may include a second main waveguide  323  and a second branch waveguide  325 . The second main waveguide  323  may extend from one side of the second cladding block  322  to the other side thereof. The second main waveguide  323  may connect the photo-detector  310  to the fluorescence generating device  400 . The second main waveguide  323  may deliver the fluorescent light  312  to the photo-detector  310 . The second branch waveguide  325  may be branched from the second main waveguide  323 . The second branch waveguide  325  may remove the excitation light  212 , which has been reflected from the second dichroic mirror  326 , by discharging the excitation light  212  to the outside of the second cladding block  322 . 
     The second dichroic mirror  326  may be provided within the second main waveguide  323  adjacent to the second branch waveguide  325 . The second dichroic mirror  326  allows the fluorescent light  312  to be transmitted therethrough to the photo-detector  310 , and may reduce noise in the fluorescent light  312  by reflecting the excitation light  212  to the second branch waveguide  325 . 
       FIG. 4  shows an example of the fluorescence generating device  400  of  FIG. 1 .  FIG. 5  shows a view taken along line I-I′ of  FIG. 4 . 
     Referring to  FIGS. 4 and 5 , the fluorescence generating device  400  may be a channel fluorescence device. As one example, the fluorescence generating device  400  may include a substrate  410 , a clad layer  420 , an optical waveguide  430 , and a fluid chip  440 . 
     The substrate  410  may include a silicon substrate. The substrate  410  may include III-V group semiconductor substrate or printed circuit board, but the embodiment of the inventive concept is not limited thereto. 
     The clad layer  420  may be provided on the substrate  410 . The clad layer  420  may include a silicon oxide. On the other hand, the clad layer  420  may include a silicon nitride, but the embodiment of the inventive concept is not limited thereto. 
     The optical waveguide  430  may be provided within the clad layer  420 . The optical waveguide  430  may have a refractive index higher than a refractive index of the clad layer  420 . The optical waveguide  430  may be arranged in a first direction X. As one example, the optical waveguide  430  may be a ridge-type waveguide. On the other hand, the optical waveguide  430  may be a buried waveguide, but the embodiment of the inventive concept is not limited thereto. The top surface of the optical waveguide  430  may be coplanar with the top surface of the clad layer  420 . The optical waveguide  430  may include an input waveguide  432 , an output waveguide  434 , and a reflection layer  436 . 
     The input waveguide  432  may be provided within one side of the clad layer  420 . The input waveguide  432  may provide the excitation light  212  to the liquid drop  402  within the fluid chip  440 . The input waveguide  432  may have an input inclined surface  431 . The input inclined surface  431  may be provided below the liquid drop  402 . The input inclined surface  431  may be slantingly arranged between the top surface and the bottom surface of the input waveguide  432 . The top surface of the input waveguide  432  may be longer than the bottom surface thereof. The input inclined surface  431  may reflect the excitation light  212  to the liquid drop  402  within the fluid chip  440 . 
     The output waveguide  434  may be provided within the other side of the clad layer  420 . The output waveguide  434  may output the fluorescent light  312  of the liquid drop  402  to the detection device  300 . The output waveguide  434  may have an output inclined surface  433 . The output inclined surface  433  may be provided below the liquid drop  402 . The output inclined surface  433  may be slantingly arranged between the top surface and the bottom surface. The top surface of output input waveguide  434  may be longer than the bottom surface thereof. The output inclined surface  433  may reflect the fluorescent light  312  of the liquid drop  402  to the detection device  300 . 
     The reflection layer  436  may be provided between the clad layer  420  and the optical waveguide  430 . The reflection layer  436  may be provided between the input inclined surface  431  and the output inclined surface  433 . The reflection layer  436  may reflect the excitation light  212  and the fluorescent light  312 . The reflection layer  436  may include aluminum. On the other hand, the reflection layer  436  may include gold, silver, or tungsten, but the embodiment of the inventive concept is not limited thereto. As one example, the reflection layer  436  may include an input reflection layer  435  and an output reflection layer  437 . The input reflection layer  435  may be provided below the input inclined surface  431 . The input reflection layer  435  may reflect the excitation light  212 . The output reflection layer  437  may be provided below the output inclined surface  433 . The output reflection layer  437  may reflect the fluorescent light  312 . 
     The fluid chip  440  may be provided on the clad layer  420 , the input waveguide  432 , and the output waveguide  434 . The fluid chip  440  may have a micro fluid channel  442 . The micro fluid channel  442  may be arranged in a second direction Y. The micro fluid channel  442  may be provided above the input inclined surface  431  and the output inclined surface  433 . The micro fluid channel  442  may be in contact with the top surfaces of the input waveguide  432 , the output waveguide  434 , and the clad layer  420 . The micro fluid channel  442  may store and/or accommodate liquid drops  402  and an oil  404 . The liquid drops  402  and the oil  404  within the micro fluid channel  442  may flow in the second direction Y. Each of the liquid drops  402  may be provided within the oil  404 . The liquid drop  402  may be a liquid drop for PCR. The liquid drop  402  may include deoxyribonucleotide in which DNA, RNA, a primer, a medium, a DNA polymerase, a buffer solution, and phosphoric acid are coupled to each other, but the embodiment of the inventive concept is not limited thereto. The DNA may account for about 0.1% to about 1% of the liquid drop  402 . The deoxyribonucleotide, in which the RNA, the primer, the medium, the DNA polymerase, and phosphoric acid are coupled to each other, may account for about 0.9% to about 4% of the liquid drop  402 . The buffer solution may include de-ionized water and account for about 95% to about 99% of the liquid drop  402 . The liquid drop  402  may have a spherical shape within the oil  404  due to repulsive force and/or surface tension. Although not illustrated, a liquid drop forming device may provide the liquid drop  402  and the oil  404  into the micro fluid channel  442 . 
     Meanwhile, the input waveguide  432  may be separable from the output waveguide  434 . The input inclined surface  431  and the input reflection layer  435  reflect the excitation light  212  to the micro fluid channel  442 , and thus may minimize or prevent the inflow of the excitation light  212  into the output waveguide  434 . A noise in the excitation light  212  may be reduced. When the excitation light  212  is provided to the liquid drop  402 , the liquid drop  402  may absorb the excitation light  212  and generate the fluorescent light  312 . The fluorescent light  312  within the micro fluid channel  442  may be provided to the output waveguide  434  and the input waveguide  432 . The fluorescent light  312  within the output waveguide  434  may be reflected from the output inclined surface  433  and the output reflection layer  437  and then provided to the photo-detector  310 . The fluorescent light  312  within the input waveguide  432  may be removed by the input inclined surface  431 , the first main waveguide  223 , the first dichroic mirror  226 , and the first branch waveguide  225 . 
     Thus, the fluorescence generating device  400  may increase the fluorescence detection efficiency by propagating the excitation light  212  and the fluorescent light  312  through the input inclined surface  431 , the output inclined surface  433 , the input reflection layer  435 , and the output reflection layer  437  in opposite directions. 
       FIG. 6  shows another example of the fluorescence generating device  400  of  FIG. 4 . 
     Referring to  FIG. 6 , the fluorescence generating device  400  may further include a fluorescent light filter  450  and an excitation light filter  460 . 
     The fluorescent light filter  450  may be provided on an input waveguide  432 . The fluorescent light filter  450  may be provided between the input waveguide  432  and a liquid drop  402  within a micro fluid channel  442 . The fluorescent light filter  450  may include blue film or acrylic. The fluorescent light filter  450  may allow excitation light  212  having blue color to be transmitted therethrough to the input waveguide  432  and remove fluorescent light  312  having green color (a wavelength of about  520  nm). The fluorescent light filter  450  removes the fluorescent light  312  to be provided to the input waveguide  432  and may protect an exciting light source  210 . 
     The excitation light filter  460  may be provided on an output waveguide  434 . The excitation light filter  460  may be provided between the output waveguide  434  and the liquid drop  402  within the micro fluid channel  442 . The excitation light filter  460  may include green film or acrylic. The excitation light filter  460  may allow the fluorescent light  312  having green color to be transmitted therethrough to the output waveguide  434  and remove the excitation light  212  having blue color. Also, the excitation light filter  460  may include film or acrylic having fluorescent color, but the embodiment of the inventive concept is not limited thereto. 
     A substrate  410 , a clad layer  420 , an optical waveguide  430 , and a fluid chip  440  may be configured to be the same as those of  FIG. 5 . 
       FIG. 7  shows another example of the fluorescence generating device  400  of  FIG. 4 . 
     Referring to  FIG. 7 , an input waveguide  432  of the fluorescence generating device  400  may be connected to a side wall on one side of a micro fluid channel  442 . The input waveguide  432  may provide excitation light  212  to a liquid drop  402  near the side wall of the micro fluid channel  442  without the input inclined surface  431  and the input reflection layer  435  of  FIG. 5 . The liquid drop  402  may absorb the excitation light  212  and discharge fluorescent light  312 . The fluorescent light  312  may be provided to an output waveguide  434  below the micro fluid channel  442 . The output inclined surface  433  and the output reflection layer  437  may reflect the fluorescent light  312  to the photo-detector  310 . 
     A clad layer  420  may be disposed at a side wall on the other side of the micro fluid channel  442  opposite to the input waveguide  432 . The clad layer  420  may be disposed between the output waveguide  434  and a fluid chip  440 . The clad layer  420  may have a refractive index less than a refractive index of the output waveguide  434 . Fluorescent light  312  within the clad layer  420  may be provided to the output waveguide  434 . 
     A substrate  410  may be configured to be the same as that of  FIG. 5 . 
       FIG. 8  shows another example of the fluorescence generating device  400  of  FIG. 4 . 
     Referring to  FIG. 8 , a fluorescent light filter  450  and an excitation light filter  460  of a fluorescence generating device  400  may be arranged in an L-shape within a micro fluid channel  442 . 
     The fluorescent light filter  450  may be provided at a side wall on one side of the micro fluid channel  442 . An input waveguide  432  may be connected to the side wall on the one side of the micro fluid channel  442 . The fluorescent light filter  450  may be provided at an end of the input waveguide  432 . The fluorescent light filter  450  may be provided between a liquid drop  402  within the micro fluid channel  442  and the input waveguide  432 . The fluorescent light filter  450  may allow excitation light  212  to be transmitted therethrough to the liquid drop  402 , and may remove fluorescent light  312  of the liquid drop  402 . 
     The excitation light filter  460  may be provided on the bottom of the micro fluid channel  442  above an output inclined surface  433 . The excitation light filter  460  may allow the fluorescent light  312  to be transmitted therethrough into an output waveguide  434  and remove the excitation light  212 . 
     A substrate  410 , a clad layer  420 , an optical waveguide  430 , and a fluid chip  440  may be configured to be the same as those of  FIG. 7 . 
       FIG. 9  shows another example of the fluorescence generating device  400  of  FIG. 4 . 
     Referring to  FIG. 9 , an output reflection layer  437  of a fluorescence generating device  400  may allow excitation light  212  to be transmitted therethrough to an output waveguide  434  and a liquid drop  402  and may reflect fluorescent light  312  into the output waveguide  434 . The output reflection layer  437  may include a dichroic filter or a dichroic minor. A micro fluid channel  442  of a fluid chip  440  may be disposed spaced apart from an input waveguide  432  and disposed on the output waveguide  434 . Although not illustrated, an exciting light source  210  may be provided below the output reflection layer  437 . The excitation light  212  may be transmitted through the output reflection layer  437  and provided to the liquid drop  402 . The fluorescent light  312  of the liquid drop  402  may be provided into the output waveguide  434  through the output reflection layer  437  and an output inclined surface  433 . 
     A substrate  410  and a clad layer  420  may be configured to be the same as those of  FIG. 5 . 
       FIG. 10  shows an example of a digital PCR analysis system  100  according to an embodiment of the inventive concept. 
     Referring to  FIG. 10 , a light source device  200  and a detection device  300  of a digital PCR analysis system  100  may include a first lens  230  and a second lens  330 , respectively. The first lens  230  and the second lens  330  may correspond to the first optical transmission block  220  and the second optical transmission block  320  of  FIGS. 1 to 3 , respectively. 
     The first lens  230  may be provided between an exciting light source  210  and a fluorescence generating device  400 . The first lens  230  may include a convex lens. The first lens  230  may focus excitation light  212  on an input waveguide  432 . 
     The second lens  330  may be provided between the fluorescence generating device  400  and a photo-detector  310 . The second lens  330  may include a convex lens. The second lens  330  may focus fluorescent light  312  on the photo-detector  310 . 
     The fluorescence generating device  400  may be configured to be the same as that of  FIG. 5 . 
       FIG. 11  shows an example of a digital PCR analysis system  100  according to an embodiment of the inventive concept. 
     Referring to  FIG. 11 , a light source device  200  and a detection device  300  of a digital PCR analysis system  100  may include a first optical fiber  240  and a second optical fiber  340 , respectively. The first optical fiber  240  and the second optical fiber  340  may correspond to the first lens  230  and the second lens  330  of  FIG. 10 , respectively. 
     The first optical fiber  240  may be provided between an exciting light source  210  and a fluorescence generating device  400 . The first optical fiber  240  may deliver excitation light  212  to an input waveguide  432 . The first optical fiber  240  may change an optical path of the excitation light  212 . For example, the first optical fiber  240  may include a first cladding  242  and a first core  244 . The first cladding  242  may surround the first core  244 . The first core  244  may be provided within the first cladding  242 . The first core  244  may have a refractive index higher than a refractive index of the first cladding  242 . The first core  244  may deliver the excitation light  212  between the exciting light source  210  and the fluorescence generating device  400 . 
     The second optical fiber  340  may be provided between the fluorescence generating device  400  and a photo-detector  310 . The optical fiber  340  may deliver fluorescent light  312  to the photo-detector  310 . The second optical fiber  340  may change an optical path of the fluorescent light  312 . For example, the second optical fiber  340  may include a second cladding  342  and a second core  344 . The second cladding  342  may surround the second core  344 . The second core  344  may be provided within the second cladding  342 . The second core  344  may deliver the fluorescent light  312  between the fluorescence generating device  400  and the photo-detector  310 . 
     As described above, the fluorescence generating device according to the embodiment of the inventive concept increases the fluorescence detection efficiency by propagating the excitation light and the fluorescent light through the input inclined surface, the output inclined surface, the input reflection layer, and the output reflection layer in opposite directions. 
     The foregoing description is about detailed examples for practicing the inventive concept. The present disclosure includes not only the above-described embodiments but also simply changed or easily modified embodiments. In addition, the present disclosure may include techniques which may be easily modified and practiced by using the embodiments described above.