Abstract:
A microfluidic chip includes a thin biaxially-oriented polyethylene terephthalate (“BoPET”) film and a micro-channel in the BoPET film. A method for manufacturing a microfluidic chip includes coating UV epoxy on a first side of a BoPET film, placing the BoPET film on a first substrate with the first side facing the first substrate, curing the UV epoxy on the first side of the BoPET film to attach the BoPET film on the first substrate; forming at least one microfluidic pathway in the BoPET film, coating UV epoxy on a first side of a second substrate, placing the second substrate on the BoPET film with the first side of the second substrate facing a second side of the BoPET film, and curing the UV epoxy on the first side of the second substrate to attach the BoPET film to the second substrate. The microfluidic chip may be a multi-layered chip.

Description:
BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates generally to a method of manufacturing microfluidic chips for handling fluid samples on a microfluidic level, and, more specifically, to a method of continuously manufacturing microfluidic chips for handling fluid samples on a microfluidic level and microfluidic chips manufactured using the same. The manufactured microfluidic chips can be used to perform analysis, for example, polymerase chain reaction (PCR) analysis. 
     2. Discussion of the Related Art 
     Microfluidics 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. Microfluidics can be used in medicine or cell biology researches. 
     Microfluidic devices are useful for manipulating or analyzing micro-sized fluid samples, with the fluid samples typically in extremely small volumes down to less than pico liters. When manipulating or analyzing fluid samples, fluids are continuously flowed onto microfluidic chips or pumped onto microfluidic chips in doses. 
     A microfluidic chip includes at least one channel in a chip-shaped substrate. During manipulation or analysis of the fluid, the fluid is introduced into the channel. Typically, one end of the channel is an inlet through which the fluid enters, and another end of the channel is an outlet through which the fluid exits. Additionally, one or more valves can be along the channel pathway to control the movement of the fluid. For example, a microfluidic chip can include various functional units performing predetermined functions using the fluid and the valve(s) can limit or hold the fluid within a particular unit for a predetermined manner prior to the fluid being injected to another particular unit. 
     Presently, microfluidic chips have micro-channels are manufactured in batches. First, a design channel is made. Then, a mold reflecting the channel design is made. Using the mold, the channel design in imprinted in PolyDiMethyiSiloxane (“PDMS”) block, and a glass slide is bonded over the micro-channels and on the PDMS block to seal the micro-channels. Such microfluidic chip is made one at the time to replicate the channel design in the mold. 
       FIG. 1  is a flow illustration of steps for manufacturing a microfluidic chip mold according to the related art, and  FIGS. 2A-2D  are perspective views of the manufacturing of 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  FIG. 1  and  FIG. 2A , a photoresist  22  is deposited onto a semiconductor wafer  20 . As shown in  FIGS. 1 and 2B , the photomask  10  that reflects the channel design  12  is then 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  FIGS. 1 and 2C , 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  FIGS. 1 and 2D , after all residual photoresist are removed, the resulting wafer becomes a mold  20 ′ that provides the channel according to the channel design  12 ′. 
       FIG. 3  is a flow illustration of steps for manufacturing a microfluidic chip according to the related art, and  FIG. 4  reflects perspective views of the manufacturing of a microfluidic chip according to the related art. The manufacturing of a microfluidic chip according to the related art takes the mold and makes microfluidic chips in batches. 
     As shown in  FIG. 4 , the mold  20 ′ may first be clean. As shown in  FIGS. 3 and 4 , 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 shown in  FIGS. 3 and 4 , 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, as shown in  FIGS. 3 and 4 . 
     Then, as shown in  FIGS. 3 and 4 , 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, as shown in  FIGS. 3 and 4 . 
     To manufacture a microfluidic chip according to the related art involves first manufacturing a master mold and then, separately duplicating channel designs onto PDMS. The related art method would require manufacturing microfluidic chips in batches, and the output rate based on this related art method is limited by the number of master molds. Thus, there continues to exist a need for developing a method of manufacturing microfluidic chips that manufactures microfluidic chips continuously, and that is quick, simple, reliable and cost effective. 
     Therefore, what is needed is a method of manufacturing that can continuously, reliably and quickly form micro-channels in chips, so that it is more cost effective to manufacture microfluidic chips. Also needed is a method of manufacturing microfluidic chips that is more flexible in adopting different micro-channel designs and can quickly adopt a different micro-channel design in a consistently controlled manner. 
     SUMMARY OF THE INVENTION 
     Accordingly, embodiments of the invention are directed to a method of continuously 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. 
     An object of embodiments of the invention is to provide a method of manufacturing microfluidic chips that can continuously form micro-channels in chips. 
     Another object of embodiments of the invention is to provide microfluidic chips that are manufactured by using a method that can continuously form micro-channels in chips. 
     An object of embodiments of the invention is to provide a method of manufacturing microfluidic chips that can reliably and quickly form micro-channels in chips. 
     Another object of embodiments of the invention is to provide microfluidic chips manufactured using a method that can reliably and quickly form micro-channels in chips. 
     An object of embodiments of the invention is to provide a method of manufacturing microfluidic chips that can dynamically adopt micro-channel designs for microfluidic chips. 
     Another object of embodiments of the invention is to provide microfluidic chips manufactured using a method that can dynamically adopt micro-channel designs. 
     Another object of embodiments of the invention is to provide microfluidic chips having micro-channels in a thin biaxially-oriented polyethylene terephthalate (“BoPET”) film. The PET film may be Mylar or another transparent, stable, and electrical insulative film. 
     Additional features and advantages of embodiments of the invention 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 invention. The objectives and other advantages of the embodiments of the invention will be realized and attained by the structure particularly pointed out in the written description and claims hereof as well as the appended drawings. 
     To achieve these and other advantages and in accordance with the purpose of embodiments of the invention, as embodied and broadly described, a method for manufacturing a device according to an embodiment of the present invention includes coating UV epoxy on a first side of a BoPET film, placing the BoPET film on a first substrate with the first side facing the first substrate, curing the UV epoxy on the first side of the BoPET film to attach the BoPET film on the first substrate, forming at least one microfluidic pathway in the BoPET film, coating UV epoxy on a first side of a second substrate, placing the second substrate on the BoPET film with the first side of the second substrate facing a second side of the BoPET film, and curing the UV epoxy on the first side of the second substrate to attach the BoPET film to the second substrate. 
     In accordance with another embodiment of the invention, as embodied and broadly described, there is a method for manufacturing a device that includes coating UV epoxy on a first side of a BoPET film, placing the BoPET film on a first substrate with the first side facing the first substrate, curing the UV epoxy on the first side of the BoPET film to attach the BoPET film on the first substrate, forming at least one microfluidic pathway in the BoPET film, coating UV epoxy on a first side of a second substrate, placing the second substrate on the BoPET film with the first side of the second substrate facing a second side of the BoPET film, curing the UV epoxy on the first side of the second substrate to attach the BoPET film to the second substrate, coating UV epoxy on a first side of a second BoPET film, placing the second BoPET film on the second substrate with the first side of the second BoPET film facing the second substrate, curing the UV epoxy on the first side of the second BoPET film to attach the second BoPET film on the second substrate, forming at least one microfluidic pathway in the second BoPET film, coating UV epoxy on a first side of a third substrate, placing the third substrate on the second BoPET film with the first side of the second substrate facing a second side of the BoPET film, and curing the UV epoxy on the first side of the third substrate to attach the second BoPET film to the third substrate. 
     In accordance with another embodiment of the invention, as embodied and broadly described, a microfluidic chip is manufactured by using the method that includes coating UV epoxy on a first side of a BoPET film, placing the BoPET film on a first substrate with the first side facing the first substrate, curing the UV epoxy on the first side of the BoPET film to attach the BoPET film on the first substrate, forming at least one microfluidic pathway in the BoPET film, coating UV epoxy on a first side of a second substrate, placing the second substrate on the BoPET film with the first side of the second substrate facing a second side of the BoPET film, and curing the UV epoxy on the first side of the second substrate to attach the BoPET film to the second substrate. 
     In accordance with another embodiment of the invention, as embodied and broadly described, a microfluidic chip includes a first substrate, a BoPET film bonded on the first substrate, wherein a least one microfluidic pathway in the BoPET film, a second substrate bonded on the BoPET film. 
     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 invention as claimed. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The accompanying drawings, which are included to provide a further understanding of embodiments of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the principles of embodiments of the invention. 
         FIG. 1  is a flow illustration of steps for manufacturing a microfluidic chip mold according to the related art. 
         FIGS. 2A-2D  are perspective views of the manufacturing of a microfluidic chip mold according to the related art. 
         FIG. 3  is a flow illustration of steps for manufacturing a microfluidic chip according to the related art. 
         FIG. 4  reflects perspective views of the manufacturing of a microfluidic chip according to the related art. 
         FIG. 5  is a flow illustration of steps for manufacturing microfluidic chips according to an embodiment of the present invention. 
         FIGS. 6A-6F  are illustration of the manufacturing of microfluidic chips according to an embodiment of the present invention. 
         FIG. 7  illustrates a side view of the continuous manufacturing of a microfluidic chip according to an embodiment of the present invention. 
         FIG. 8  is a side view of a microfluidic chip according to an embodiment of the present invention. 
         FIG. 9  is a side view of a multi-layer microfluidic chip according to an embodiment of the present invention. 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     Reference will now be made in detail to the preferred embodiments of the invention, examples of which are illustrated in the accompanying drawings. 
       FIG. 5  is a flow illustration of steps for manufacturing microfluidic chips according to an embodiment of the present invention. As shown in  FIG. 5 , the method for manufacturing microfluidic chips includes coating a thin transparent polyester film with UV epoxy. Preferably, a thin biaxially-oriented polyethylene terephthalate (“BoPET”) film is coated with UV epoxy. BoPET film may be Mylar, Melinex or Hostaphan. Alternatively, a transparent, stable and electrical insulative polyester film with high tensile strength may be used. 
     After the polyester film is coated with UV epoxy, the film is placed on a glass slide or PET block and undergoes UV exposure to cure the epoxy. Thereby, the film is bonded on the glass slide or PET block. 
     After the film is bonded onto the glass slide or PET block, micro-channel(s) is made by ablating the film using laser beams. In addition, an inlet or an outlet is also made by further ablating through-holes into the glass slide or PET block. After the completion of ablating the film, a second glass slide or PET block is placed over the film to seal the micro-channel(s). In particular, the second glass slide or PET block is coated with UV epoxy. After the second glass slide or PET block is coated with UV epoxy, the second glass slide or PET is placed on the film with micro-channel(s) and undergoes UV exposure to cure the epoxy. Thereby, the second glass slide or PET block is bonded on the film with micro-channel(s). 
     Therefore, the method for manufacturing microfluidic chips according to an embodiment of the present invention does not involve a master mold. Further, the method for manufacturing microfluidic chips according to an embodiment of the present invention can be performed in a continuous manner. For example, each step may be performed at different stations of a manufacturing production line and a first station may only perform the step of coating UV epoxy on a thin film piece, and each thin film is then passed onto the next station after being coated by the first station. 
       FIGS. 6A-6G  are illustration of the manufacturing of microfluidic chips according to an embodiment of the present invention. As shown in  FIG. 6A , a first surface of a thin transparent polyester film  101  is coated with UV epoxy. Preferably, the thin transparent polyester film  101  is a thin biaxially-oriented polyethylene terephthalate (“BoPET”) film. BoPET film may be Mylar, Melinex or Hostaphan. Alternatively, the thin transparent polyester film  101  is a transparent, stable and electrical insulative polyester film with high tensile strength may be used. The thin transparent polyester film  101  is placed on a first glass slide or PET block  100 . The first glass slide or PET block  100  may first undergo a cleaning step (which is not shown). 
     As shown in  FIG. 6B , the first glass slide or PET block  100  and the thin transparent polyester film  101  undergo UV exposure to cure the UV epoxy. Preferably, a UV source  110  may radiate UV from a bottom side of the first glass slide or PET block  100 . Thereby, the first glass slide or PET block  100  and the thin transparent polyester film  101  are bonded together at the first surface. 
     As shown in  FIG. 6C , the thin transparent polyester film  101  is ablated to reflect a micro-channel design by using a laser beam  120 . As shown in  FIG. 6D , the laser beam  120  also may ablate through-holes in the first glass slide or PET block  100  to make an inlet or an outlet for the micro-channel(s). The laser beam  120  may be dynamically controlled by a microprocessor or an operator (not shown). In addition, the laser beam  120  may be adjusted in real-time to adjust the micro-channel design or to adopt a different micro-channel design. 
       FIG. 6E  shows a second glass slide or PET block  102  is place on the thin transparent polyester film  101 . The second glass slide or PET block  102  may first undergo a cleaning step. A first surface of the second glass slide or PET  102  is coated with UV epoxy prior to being place on the thin transparent polyester film  101 . 
     As shown in  FIG. 6F , the second glass slide or PET block  102  while being on the thin transparent polyester film  101  undergoes UV exposure to cure the UV epoxy on its first surface. Preferably, the UV source or another UV source  110  may radiate UV from an upper side of the second glass slide or PET block  102 . Thereby, the second glass slide or PET block  102  and the thin transparent polyester film  101  are bonded together at the first surface of the second glass slide or PET block  102  and the second surface of the thin transparent polyester film  101 . The second glass slide or PET block  102  seals the micro-channel in the thin transparent polyester film  101 . 
     Although not shown, the steps shown in  FIG. 6A-6F  may be repeated to form additional thin transparent films with micro-channels. For example, a second thin transparent film with a first surface coated with UV epoxy can be placed on the second glass slide or PET block  102  (shown in  FIG. 6F ). The second thin transparent film then undergoes UV exposure to cure UV epoxy and to be bonded to the second glass slide or PET block  102  (shown in  FIG. 6 ). Laser beam is then introduced to ablate the second thin transparent film to form a second micro-channel. Laser beam also can ablate through the second glass slide or PET block  102 , the first thin transparent film  101  and the first glass slide or PET block  100  (shown in  FIG. 6F ) to form an inlet and an outlet for the second micro-channel. Subsequently, a third glass slide or PET block with a first surface coated with UV epoxy can be placed on the second thin transparent polyester film. The third glass slide or PET block then undergoes UV exposure to cure UV epoxy and to bond the third glass slide or PET block to the second thin transparent polyester film. These steps can be repeated on additional thin transparent polyester films and glass slides or PET blocks to manufacture micro-channel in different thin transparent polyester films. 
       FIG. 7  illustrates a side view of the continuous manufacturing of a microfluidic chip according to an embodiment of the present invention. As shown in  FIG. 7 , a first glass slide or PET block  200  is placed in a station. A thin transparent polyester film  201  having a first surface coated with UV epoxy is place on the first glass slide or PET block  200 . A UV light source  210  radiates UV from a bottom side of the first glass slide or PET block  200 . The UV epoxy on the first surface of the thin transparent polyester film  201  is cured, thereby bonding the first glass slide or PET block  200  and the thin film transparent polyester film  201 . Then, a laser beam  220  is introduced to ablate the thin transparent polyester film  201  to form micro-channels  203 . 
     The laser beam  220  may also ablate through-holes in the first glass slide or PET block  200  to form an inlet or an outlet  204  for the micro-channels. After micro-channels are formed, a second glass slide or PET block  202  having a first surface coated with UV epoxy is placed on the thin transparent polyester film  201 . The UV light source or a second UV light source  210  radiates UV from an upper side of the second glass slide or PET block  202 . The UV epoxy on the first surface of the second glass slide or PET block  202  is cured, thereby bonding the second glass slide or PET block  202  and the thin transparent polyester film  201 . 
     As shown in  FIG. 7 , the method of manufacturing a microfluidic chip may be performed in a continuous manner. For example, the step of ablating the thin transparent polyester film  201  is performed immediately after the step of bonding the thin transparent polyester film  201  with the first glass slide or PET block  200 . 
       FIG. 8  is a side view of a microfluidic chip according to an embodiment of the present invention. As shown in  FIG. 8 , a microfluidic chip  300  includes a first glass slide or PET block  301 , a thin transparent polyester film  302 , micro-channel  303 , an inlet  304  for the micro-channel  303 , an outlet  305  for the micro-channel  303 , and a second glass slide or PET block  306 . In the microfluidic chip  300 , the micro-channel  303  is solely in the thin transparent polyester film  302 . The inlet  304  and the outlet  305  are through-holes in the first glass slide or PET block  301 . 
     Although not shown, the first glass slide or PET block  301  is bonded to the thin transparent polyester film  302  using epoxy. Similarly, the second glass slide or PET block  306  is boned to another surface of the thin transparent polyester film  302  using epoxy. The epoxy may be UV curable. 
       FIG. 9  is a side view of a multi-layer microfluidic chip according to an embodiment of the present invention. As shown in  FIG. 9 , a microfluidic chip  400  may be a multi-layer microfluidic chip. The microfluidic chip  400  includes a first glass slide or PET block  401 , a first thin transparent polyester film  402 , a first micro-channel  403 , an inlet  404  for the micro-channel  403 , an outlet  405  for the micro-channel  403 , and a second glass slide or PET block  406 . The micro-channel  403  is in the first thin transparent polyester film  402 . The inlet  404  and the outlet  405  are through-holes in the first glass slide or PET block  401 . 
     The microfluidic chip  400  further includes a second thin transparent polyester film  407  on the second glass slide or PET block  406 , and a second micro-channel  408  in the second thin transparent polyester film  407 . The microfluidic chip  400  also includes a third glass slide or PET block  409 . The inlet  404  and the outlet  405  also can be through the second glass slide or PET block  406 . Alternatively, another set of inlet and outlet (not shown) may be only for the second micro-channel  408  and are separate through-holes in the first glass slide or PET block  401 , the first thin transparent polyester film  402 , the second glass slide or PET block  406  and the second thin transparent polyester film  407 . 
     Although not shown, the first glass slide or PET block  401  is bonded to the first thin transparent polyester film  402  using epoxy. The second glass slide or PET block  406  is boned to the first thin transparent polyester film  402  and the second thin transparent polyester film  407  using epoxy. The third glass slide or PET block  409  is bonded to the second thin transparent polyester film  407  using epoxy. The epoxy may be UV curable. 
     Although two micro-channels in two polyester films are illustrated, any number of micro-channels in different layers may be implemented. The method of manufacturing microfluidic chips according to an embodiment of the present invention provides a method of continuously forming micro-channels in chips. The method of manufacturing microfluidic chips according to an embodiment of the present invention provides a method of manufacturing that can reliably and quickly form micro-channels in chips. 
     In addition, microfluidic chips according to an embodiment of the present invention includes micro-channel in a thin biaxially-oriented polyethylene terephthalate (“BoPET”) film. The PET film may be Mylar or another transparent, stable, and electrical insulative film. 
     Further, the method of manufacturing microfluidic chips according to an embodiment of the present invention employs dynamically controlled laser beam to ablate a thin transparent polyester film to provide real-time adjustment of laser beam/channel design. 
     It will be apparent to those skilled in the art that various modifications and variations can be made in the method of manufacturing microfluidic chips and the microfluidic chips of embodiments of the invention without departing from the spirit or scope of the invention. Thus, it is intended that embodiments of the invention cover the modifications and variations of this invention provided they come within the scope of the appended claims and their equivalents.