Abstract:
A microfluidic chip is disclosed herein. In an embodiment, the microfluidic chip includes a body including at least one microfluidic pathway configured to receive a fluid sample, the at least one microfluidic pathway including a coating configured to reduce fluid diffusion and seal a surface of the at least one microfluidic pathway, and a heating device located on the body and forming a heating zone within a portion of the at least one microfluidic pathway.

Description:
CROSS REFERENCE TO RELATED APPLICATION 
       [0001]    The present application is a continuation of U.S. patent application Ser. No. 14/934,794, entitled “Microfluidic Chips with Optically Transparent Glue Coating and a Method of Manufacturing Microfluidic Chips with Optically Transparent Glue Coating for a Microfluidic Device,” filed Nov. 6, 2015, which is a continuation of U.S. patent application Ser. No. 14/028,320, entitled “Microfluidic Chips with Optically Transparent Glue Coating and a Method of Manufacturing Microfluidic Chips with Optically Transparent Glue Coating for a Microfluidic Device,” filed Sep. 16, 2013, now U.S. Pat. No. 9,180,652, the entire contents of each of which is hereby incorporated by reference herein. 
     
    
     BACKGROUND OF THE DISCLOSURE 
       [0002]    Field of Disclosure 
         [0003]    The present disclosure relates generally to a method of manufacturing microfluidic chips for handling fluid samples on a microfluidic level, and, more specifically, to a method of manufacturing microfluidic chips with coating to reduce fluid diffusion and microfluidic chips with a coating to reduce fluid diffusion. The manufactured microfluidic chips can be used to perform real-time analysis, for example, polymerase chain reaction (PCR) analysis. 
         [0004]    Discussion of the Related Art 
         [0005]    Microfluidics can be used in medicine or cell biology researches and refers to the technology that relates to the flow of liquid in channels of micrometer size. At least one dimension of the channel is of the order of a micrometer or tens of micrometers to be considered as microfluidics. In particular, microfluidic devices are useful for manipulating or analyzing micro-sized fluid samples on microfluidic chips, with the fluid samples typically in extremely small volumes down to less than picoliters. 
         [0006]    When manipulating or analyzing fluid samples, fluids are pumped onto the micro-channel of microfluidic chips in doses or are continuously flowed onto the micro-channel of microfluidic chips. If the fluid sample is pumped in doses, the fluid sample stays in the micro-channel of the microfluidic chip until the fluid sample is suctioned out from the micro-channel. The fluid sample can be manipulated or analyzed while being held in the micro-channel. 
         [0007]    Alternatively, for continuous flow analysis, the fluid is pumped continuously into the micro-channel. Due to the continuous fluid pumping, the fluid sample instead flows and travels through the micro-channel and exits the micro-channel when reaches the outlet of the micro-channel. The fluid sample can be manipulated or analyzed while flowing through the micro-channel, and one can perform a biochemical reaction examination on the continuously flowing fluid sample, including treating and manipulating processes of the fluid. 
         [0008]    Presently, microfluidic chips have micro-channels molded in PolyDiMethyiSiloxane (“PDMS”). The micro-channels then are sealed when the PDMS block is bonded to a glass slide. 
         [0009]      FIGS. 1A-1D  are perspective views of manufacturing a microfluidic chip mold according to the related art. The manufacturing of a microfluidic chip according to the related art takes a channel design and duplicates the channel design onto a photomask  10 . As shown in Figure IA, a photoresist  22  is deposited onto a semiconductor wafer  20 . As shown in  FIG. 1B , the photomask  10  that reflects the channel design  12  is placed over the wafer  20 , and the wafer  20  with the mask  10  undergoes UV exposition to cure the photoresist  22 . Then, as shown in  FIG. 10 , the wafer  20  with the cured photoresist  22 ′ is developed. The ‘negative’ image of a channel according to the channel design is etched away from the semiconductor wafer  20 . As shown in  FIG. 1D , after all residual photoresist are removed, the resulting wafer becomes a mold  20 ′ that provides the channel according to the channel design  12 ′. 
         [0010]      FIG. 2  are perspective views of the steps of manufacturing a microfluidic chip according to the related art. As shown in  FIG. 2 , PDMS in liquid form  30  is poured onto the mold  20 ′. Liquid PDMS  30  may be mixed with crosslinking agent. The mold  20 ′ with liquid PDMS  30  is then placed into a furnace to harden PDMS  30 . As PDMS is hardened, the hardened PDMS block  30 ′ duplicates the micro-channel  12 ″ according to the channel design. The PDMS block  30 ′ then may be separated from the mold  20 ′. To allow injection of fluid into the micro-channel  12 ″ (which will subsequently be sealed), inlet or outlet is then made in the PDMS block  30 ′ by drilling into the PDMS block  30 ′ using a needle. Then, the face of the PDMS block  30 ′ with micro-channels and a glass slide  32  are treated with plasma. Due to the plasma treatment, the PDMS block  30 ′ and the glass slide  32  can bond with one another and close the chip. 
         [0011]    The microfluidic chip according to the related all has a micro-channel in the PDMS block. PDMS belongs to a group of polymeric organosilicon compounds that are commonly referred to as silicone, and can be deposited onto the master mold in liquid form and subsequently hardened. 
         [0012]    However, PDMS is inherently porous and due to its polymer structure, PDMS is highly permeable. Thus, diffusion of fluid sample through PDMS has been observed. Such diffusion of fluid sample does not impact a microfluidic system that pumps fluid samples in doses as significantly as a continuous flow microfluidic system. In particular, when a continuous flow microfluidic system monitors treating and manipulating of the flowing fluid in real-time analysis applications, diffusion or unaccounted loss of fluid sample can significantly impact the real-time analysis. Thus, there exists a need for reducing diffusion or loss of fluid sample in micro-channel of a microfluidic chip. 
       SUMMARY OF THE DISCLOSURE 
       [0013]    Accordingly, embodiments of the present disclosure are directed to a method of manufacturing microfluidic chips for handling fluid samples on a microfluidic level and microfluidic chips that can substantially obviate one or more of the problems due to limitations and disadvantages of the related art. 
         [0014]    An object of embodiments of the present disclosure is to provide a method of manufacturing microfluidic chips to reduce fluid diffusion in micro-channel, and microfluidic chips manufactured using the same. 
         [0015]    An object of embodiments of the present disclosure is to provide a method, of manufacturing microfluidic chips with micro-channel coating, and microfluidic chips manufactured using the same. 
         [0016]    Additional features and advantages of embodiments of the present disclosure will be set forth in the description which follows, and in part will be apparent from the description, or may be learned by practice of embodiments of the present disclosure. The objectives and other advantages of the embodiments of the present disclosure will be realized and attained by the structure particularly pointed out in the written description and claims hereof as well as the appended drawings. 
         [0017]    To achieve these and other advantages and in accordance with the purpose of embodiments of the present disclosure, as embodied and broadly described, a microfluidic chip device according to an embodiment of the present disclosure includes a substrate having a first thickness, at least one microfluidic pathway in the substrate, a coating along the microfluidic pathway, and a glass layer having a second thickness on the substrate and above the microfluidic pathway, wherein the coating contains cyanoacrylates, and the first thickness is greater than the second thickness. 
         [0018]    In accordance with another embodiment of the present disclosure, as embodied and broadly described, a microfluidic chip device includes a substrate having a first thickness, at least one microfluidic pathway in the substrate, a coating along the microfluidic pathway, and a glass layer having a second thickness on the substrate and above the microfluidic pathway, wherein the coating contains an optically transparent material, and the first thickness is greater than the second thickness. 
         [0019]    In accordance with another embodiment of the present disclosure, as embodied and broadly described, a method for manufacturing a microfluidic chip device includes etching a substrate having a first thickness for forming at least one microfluidic pathway in the substrate, coating the substrate, and bonding a glass layer having a second thickness on the substrate and above the microfluidic pathway, wherein the step of coating includes coating an optically transparent material, and the first thickness is greater than the second thickness. 
         [0020]    In accordance with another embodiment of the present disclosure, as embodied and broadly described, a microfluidic chip device includes a coating along the microfluidic pathway, wherein the coating includes cyanoacrylates, an UV curable epoxy adhesive, a gel epoxy or epoxy under trade name of EPO-TEK OG175, MasterBond EP30LV-1 or Locite 0151. 
         [0021]    In accordance with another embodiment of the present disclosure, as embodied and broadly described, a method for manufacturing a microfluidic chip device includes etching a substrate having a first thickness for forming at least one microfluidic pathway in the substrate and coating along the microfluidic pathway, wherein the coating includes coating with cyanoacrylates, an UV curable epoxy adhesive, a gel epoxy or epoxy under trade name of EPO-TEK OG1.75, MasterBond EP30LV-1 or Locite 0151. 
         [0022]    It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory and are intended to provide further explanation of embodiments of the present disclosure as claimed. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0023]    The accompanying drawings, which are included to provide a further understanding of embodiments of the present disclosure and are incorporated in and constitute a part of this specification, illustrate embodiments of the present disclosure and together with the description serve to explain the principles of embodiments of the present disclosure. 
           [0024]      FIGS. 1A-1D  are perspective views of manufacturing a microfluidic chip mold according to the related art. 
           [0025]      FIG. 2  illustrates the steps of manufacturing a microfluidic chip according to the related art. 
           [0026]      FIG. 3  is a perspective view of a microfluidic chip for a microfluidic system according to an embodiment of the present disclosure. 
           [0027]      FIG. 4  is a side view of the microfluidic chip shown in  FIG. 3 . 
           [0028]      FIG. 5  is a side view of the microfluidic chip according to another embodiment of the present disclosure. 
           [0029]      FIG. 6  is a top view of a heater for a microfluidic chip of a microfluidic system according to an embodiment of the present disclosure. 
       
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
       [0030]    Reference will now be made in detail to the preferred embodiments of the present disclosure, examples of which are illustrated in the accompanying drawings. 
         [0031]      FIG. 3  is a perspective view of a microfluidic chip for a microfluidic system according to an embodiment of the present disclosure, and  FIG. 4  is a side view of the microfluidic chip shown in  FIG. 3 . As shown in  FIGS. 3 and 4 , a microfluidic chip  100  includes a PDMS substrate  110  and a glass layer  120  on the substrate  110 . The glass layer  120  may be formed of borosilicate. As shown in the substrate  110 . For instance, the glass layer  120  may have a thickness of about 0.01 inch or less. 
         [0032]    The substrate  110  includes micro-channels  130 . The micro-channels  130  form a microfluidic pathway, and the channels allow fluid samples to be flowed through therein. The micro-channels  130  may be formed by etching the substrate  110 . 
         [0033]    After the micro-channels  130  are formed in the substrate  110  but prior to sealing micro-channels  130  with the glass layer  120 , the substrate  110  is coated with cyanoacrylates  112  to seal the surface pores of the substrate  110 . Cyanoacrylates are acylic resin and are mainly used as adhesives. However, cyanoacrylates are not used as adhesives in the micro-channels of the substrate  110 . Instead, cyanoacrylates are allowed to set to form a coating along the micro-channels  130 . 
         [0034]    When coating the substrate  110 , the amount of cyanoacrylates deposited is controlled so as not to fill the micro-channels  130  of the substrate  110 . In addition or alternatively, the micro-channels  130  are formed wider and/or deeper in the substrate  110  to account for the subsequent coating thickness of cyanoacrylates  112 . 
         [0035]    The microfluidic chip  100  further includes heaters  140   a ,  140   b  and  140   c . For example, the heaters  140   a ,  140   b  and  140   c  may be resistive heating devices, such as thin-film heaters. The heaters  140   a ,  140   b  and  140   c  may be formed by applying a thin film of conductive material directly on the glass layer  120 . For example, the heaters  140   a ,  140   b  and  140   c  may include aluminum. More specifically, the heaters  140   a ,  140   b  and  140   c  may have a thickness of about 0.001 inch or less. 
         [0036]    The microfluidic chip  100  further includes temperature sensors  150   a ,  150   b  and  150   c . For example, the temperature sensors  150   a ,  150   b  and  150   c  may be resistance temperature detectors. The temperature sensors  150   a ,  150   b  and  150   c  provide real-time temperature detection to more than one zones or portions of the microfluidic chip  100 . The real-time temperature detection is then used to control heaters  140   a ,  140   b  and  140   c , respectively. As such, the microfluidic chip  100  may have independently-temperature-controlled zones. 
         [0037]    A microprocessor (not shown) may be connected to the temperature sensors  150   a ,  150   b  and  150   c  and the heaters  140   a ,  140   b  and  140   c  to provide independently-temperature-controlled zones for the microfluidic chip  100 . For example, the microprocessor may implement a control algorithm, such as PID control to receive temperature inputs from the temperature sensors  150   a ,  150   b  and  150   c  and dynamically controls the output of the heaters  140   a ,  140   b  and  140   c.    
         [0038]    For real-time analysis, an optical sensor  160  is further included and can be placed above or below the microfluidic chip  100 . The optical sensor  160  provides real-time monitoring of the manipulation of the fluid sample in the micro-channel  130  of the microfluidic chip  100 . The same microprocessor (not shown) can also receive and control the optical sensor  160 . 
         [0039]      FIG. 5  is a side view of the microfluidic chip according to another embodiment of the present disclosure. In  FIG. 5 , a microfluidic chip  100 ′ includes a layer of cured optically transparent material  112 ′ between a substrate  110 ′ and a seal layer  120 ′. As shown in  FIG. 3 , the thickness of the seal layer  120 ′ is much smaller than the thickness of the substrate  110 ′. For instance, the seal layer  120 ′ may have a thickness of about 0.01 inch or, less. 
         [0040]    The substrate  110 ′ includes micro-channels  130 ′. The micro-channels  130 ′ form a microfluidic pathway, and the channels allow fluid samples to be flowed through therein. The micro-channels  130 ′ may be formed by etching the substrate  110 ′. 
         [0041]    After the micro-channels  130 ′ are formed in the substrate  110 ′ but prior to sealing micro-channels  130 ′ with the seal layer  120 ′, the substrate  110 ′ is coated with an optically transparent material to seal the surface of the substrate  110 ′. The optically transparent material is allowed to set or hardened to form the layer of cured optically transparent material  112 ′. An UV curable epoxy adhesive, a gel epoxy or epoxy under trade name of EPO-TEK OG175, MasterBond EP30LV-1 or Locite 0151 may be used to coat the surface of the substrate  110 ′. 
         [0042]    When coating the substrate  110 ′, the amount of the optically transparent material deposited are controlled so as not to fill the micro-channels  130 ′ of the substrate  110 ′. In addition or alternatively, the micro-channels  130 ′ are formed wider and/or deeper in the substrate  110 ′ to account for the subsequent layer of cured optically transparent material  112 ′. 
         [0043]    The microfluidic chip  100 ′ further includes heaters  140   a ′,  140   b ′ and  140   c ′. For example, the heaters  140   a ′,  140   b ′ and  140   c ′ may be resistive heating devices, such as thin-film heaters. The heaters  140   a ′,  140   b ′ and  140   c ′ may be formed by applying a thin film of conductive material directly on the seal layer  120 ′. For example, the heaters  140   a ′,  140   b ′ and  140   c ′ may include aluminum. More specifically, the heaters  140   a ′,  140   b ′ and  140   c ′ may have a thickness of about 0.001 inch or less. 
         [0044]    The microfluidic chip  100 ′ further includes temperature sensors  150   a ′, and  150   c ′. For example, the temperature sensors  150   a ′,  150   b ′ and  150   c ′ may be resistance temperature detectors. The temperature sensors  150   a ′,  150   b ′ and provide real-time temperature detection to more than one zones or portions of the microfluidic chip  100 ′. The real-time temperature detection is then used to control heaters  140   a ′,  140   b ′ and  140   c ′, respectively. As such, the microfluidic chip  100  may have independently-temperature-controlled zones. 
         [0045]    A microprocessor (not shown) may be connected to the temperature sensors  150   a ′,  150   b ′ and  150   c ′ and the heaters  140   a ′,  140   b ′ and  140   c ′ to provide independently-temperature-controlled zones for the microfluidic chip  100 ′. For example, the microprocessor may implement a control algorithm, such as PID control to receive temperature inputs from the temperature sensors  150   a ′,  150   b ′ and  150   c ′ and dynamically controls the output of the heaters  140   a ′,  140   b ′ and  140   c′.    
         [0046]    Although not shown, for real-time analysis, an optical sensor is further included and can be placed above or below the microfluidic chip  100 ′. The optical sensor provides real-time monitoring of the manipulation of the fluid sample in the micro-channel  130 ′ of the microfluidic chip  100 ′. The optical sensor may be controlled by a microprocessor. 
         [0047]      FIG. 6  is a top view of a heater for a microfluidic chip of a continuous-flow microfluidic system according to an embodiment of the present disclosure. As shown in  FIG. 6 , a thin-film heater  140  for a microfluidic chip of a microfluidic system preferably may include two electrical interface pads  142   a  and  142   b . The two electrical interface pads  142   a  and  142   b  may receive voltage and/or current. More specifically, electrical resistance or heat may be generated by the thin-film heater  140  based on V 2 /R or I 2 ×R. Such heat may provide temperature to the channels  130  or  130 ′ shown in  FIG. 4 or 5 . 
         [0048]    Preferably, the thin-film heater  140  is spread above the channels  130  or  130 ′ evenly to provide consistent heating of the channel below. The thin-film heater  140  may have a line-like shape between the two electrical interface pads  142   a  and  142   b . For example, the thin-film heater  140  may have elongated strips that are substantially parallel with one another. 
         [0049]    It will be apparent to those skilled in the art that various modifications and variations can be made in the microfluidic chip of embodiments of the present disclosure without departing from the spirit or scope of the present disclosure. Thus, it is intended that embodiments of the present disclosure cover the modifications and variations of this disclosure provided they come within the scope of the appended claims and their equivalents.