Patent Publication Number: US-2015086443-A1

Title: Microfluidic chips with micro-to-macro seal and a method of manufacturing microfluidic chips with micro-to-macro seal

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 microfluidic chips with micro-to-macro seal and a method of manufacturing microfluidic chips with micro-to-macro seal. 
     2. Discussion of the Related Art 
     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 pico liters. 
     When manipulating or analyzing fluid samples, fluids are pumped onto the micro-channel of microfluidic chips. Presently, microfluidic chips have micro channels etched or molded in a PolyDiMethyiSiloxane (“PDMS”), silicon or glass chip. The micro-channel then is sealed when the chip is bonded to a glass slide. 
       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  FIG. 1A , 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 .  FIG. 1C  shows the wafer  20  with the cured photoresist  22 ′ being 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 ′. 
       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  14  or outlet  15  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 treated glass slide  32 ′ can bond with one another and close the chip. 
     The resulting microfluidic chip according to the related art therefore has an open surface. The inlet and outlet openings are on the open surface of the microfluidic chip. Particles or contaminants may get into the micro-channel through the open surface and impact subsequent fluid sample analysis. Thus, there exists a need for preventing particles or contaminants entering into micro-channels of microfluidic chips. 
     SUMMARY OF THE INVENTION 
     Accordingly, embodiments of the invention 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. 
     An object of embodiments of the invention is to provide a method of manufacturing microfluidic chips with micro-to-macro seal, and microfluidic chips manufactured using the same. 
     An object of embodiments of the invention is to provide a method of manufacturing microfluidic chips with no open surface, and microfluidic chips manufactured using the same. 
     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 microfluidic chip device according to an embodiment of the present invention includes a substrate having a thickness, at least one microfluidic pathway in the substrate, and a PDMS layer on the substrate and above the microfluidic pathway, wherein the PDMS layer provides a seal above the microfluidic pathway 
     In accordance with another embodiment of the invention, as embodied and broadly described, a microfluidic chip device includes a substrate having a thickness, at least one microfluidic pathway in the substrate, and a rubber layer on the substrate and above the microfluidic pathway, wherein the rubber layer provides a seal above the microfluidic pathway. 
     In accordance with another embodiment of the invention, as embodied and broadly described, a method for manufacturing a microfluidic chip device includes spinning a substrate having a first thickness and at least one microfluidic pathway in the substrate, depositing a layer of liquid PDMS onto the substrate, and hardening the PDMS layer. 
     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 herein constituting 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. 
         FIGS. 1A-1D  are perspective views of manufacturing a microfluidic chip mold according to the related art. 
         FIG. 2  illustrates the steps of manufacturing a microfluidic chip according to the related art. 
         FIG. 3  is a flow chart illustrating the steps of manufacturing of a microfluidic chip for a microfluidic system according to an embodiment of the present invention. 
         FIG. 4  is a perspective view of the microfluidic chip according to an embodiment of the present invention. 
         FIG. 5  is a side view of the microfluidic chip shown in  FIG. 4 . 
         FIG. 6  is a side view of the microfluidic chip according to another embodiment of the present invention. 
         FIG. 7  is another side view of the microfluidic chip shown in  FIG. 6 . 
         FIG. 8  illustrates an application of the microfluidic chip shown in  FIG. 7 . 
         FIG. 9  is a side view of the microfluidic chip according to another 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. 3  is a flow chart illustrating the steps of manufacturing of a microfluidic chip for a microfluidic system according to an embodiment of the present invention. As shown in  FIG. 3 , at least one micro-channel is formed in a chip. The chip may be PDMS, silicon or glass chip. A master mold may be used to form micro-channels in PDMS chips, and a series of photolithography with photomasks may be used to form micro-channels in silicon or glass chip. The chip with micro-channel has an open surface, which is a surface of the chip that has at least the inlet and outlet openings. 
     While the chip is spun, liquid PDMS or a rubber material is poured over the open surface of the chip. Once a thin uniform layer of liquid PDMS or the rubber material is formed, then, the thin layer of liquid PDMS or the rubber material is hardened. For example, the chip may be baked or exposed to UV to cure the thin layer of liquid PDMS. 
     The hardened thin layer of PDMS or rubber forms a seal to the open surface. The microfluidic chip then can be transported without an open surface. Immediately prior to application, a needle or another piping can pierce through the thin hardened thin layer of PDMS or rubber to gain access to the micro-channel of the chip. Further, due to the elasticity and small thickness of the PDMS layer, the PDMS layer squeezes around the needle or piping to create a seal around the needle or piping. 
     Therefore, the hardened thin layer of PDMS or rubber provides seals to the microfluidic chip during transportation or prior to application, as well as during application. During application and after being pierced, the hardened thin layer of PDMS or rubber seals around the needles and continue to prevent particles or contaminants entering the micro-channel. 
       FIG. 4  is a perspective view of the microfluidic chip according to an embodiment of the present invention, and  FIG. 5  is a side view of the microfluidic chip shown in  FIG. 4 . The microfluidic chip  1  includes a substrate  30 , a micro-channel  12 ″ in the substrate  30 ′, and an inlet  14  and an outlet  15  in the substrate  30 ′. The micro-channel  12 ″ is formed in a first surface of the substrate  30 ′ and sealed with a glass side  32 ′. The inlet  14  and the outlet  15  are formed on an opposing surface of the substrate  30 ′ and into the substrate  30 ′. The inlet  14  and the outlet  15  are connected to the micro-channel  12 ″. The inlet  14  may be at one end of the micro-channel  12 ″, and the outlet  15  may be at another end of the micro-channel  12 ″. 
     The microfluidic chip I further includes a seal layer  34  over the openings of the inlet  14  and the outlet  15 . The seal layer  34  may be a hardened PDMS layer or a rubber layer. The seal layer  34  may be formed by first pouring liquid PDMS while spinning the substrate  30 ′ to create a thin layer of liquid PDMS and hardening the thin layer of liquid PDMS. Alternatively, a rubber material may be used instead of liquid PDMS. 
     As shown in  FIG. 5 , the thickness of the seal layer  34  is smaller than the thickness of the substrate  30 ′ and the thickness of the glass slide  32 ′. The thickness of the seal layer  34  is small enough to allow a needle or a piping to subsequently pierce through the seal layer  34 . The seal layer  34  provides sealing the interconnect between larger macro piping and the micro-channel  12 ″. With the seal layer  34 , fluid can be pumped into the microfluidic chip  1  for processing without concern for the fluid leaking despite high pressure required to pump or drive the fluid into the micro-channel  12 ″. 
       FIG. 6  is a side view of the microfluidic chip according to another embodiment of the present invention. In  FIG. 6 , a microfluidic chip  100  includes a substrate  130 , a micro-channel  112  in the substrate  130 , and an inlet  114  and an outlet  115  in the substrate  130 . The micro-channel  112  is formed in the middle of the substrate  130 . The inlet  114  and the outlet  115  are formed on an opposing surface of the substrate  130  and into the substrate  130 . The inlet  114  and the outlet  115  are connected to the micro-channel  112 . The inlet  114  may be at one end of the micro-channel  112 , and the outlet  115  may be at another end of the micro-channel  112 . 
     The microfluidic chip  100  further includes a seal layer  134  over the openings of the inlet  114  and the outlet  115 . The seal layer  134  may be a hardened PDMS layer or a rubber layer. The seal layer  134  may be formed by first pouring liquid PDMS while spinning the substrate  130  to create a thin layer of liquid PDMS and hardening the thin layer of liquid PDMS. Alternatively, a rubber material may be used instead of liquid PDMS. 
     The thickness of the seal layer  134  is smaller than the thickness of the substrate  130 . In particular, the thickness of the seal layer  134  is small enough to allow a needle or a piping to subsequently pierce through the seal layer  134 . The seal layer  134  provides sealing the interconnect between larger macro piping and the micro-channel  112 . With the seal layer  134 , fluid can be pumped into the microfluidic chip  100  for processing without concern for the fluid leaking despite high pressure required to pump or drive the fluid into the micro-channel  112 . 
       FIG. 7  is another side view of the microfluidic chip shown in  FIG. 6 , and  FIG. 8  illustrates an application of the microfluidic chip shown in  FIG. 7 . As shown in  FIG. 7 , the seal layer  134  seals the inlet  114  and the micro-channel  112  from exterior environment. The seal  134  prevents particles or contaminants entering the micro-channel  112 . 
     As shown in  FIG. 8 , a needle or a piping  150  can subsequently pierce through the seal layer  134  to set up pumping of fluid sample into the micro-channel  112 . Despite being pierced through, the seal layer  134  squeezes around the needle or piping  150 , thereby creating a seal around the needle or piping  150 . As a result, fluid can be pumped into the microfluidic chip  100  for processing without concern for the fluid leaking despite high pressure required to pump or drive the fluid into the micro-channel  112 . 
       FIG. 9  is a side view of the microfluidic chip according to another embodiment of the present invention. In  FIG. 9 , a microfluidic chip  200  includes a substrate  230 , a micro-channel  212  in the substrate  230 , and an inlet  214  and an outlet  215  in the substrate  230 . The substrate  230  is on a bottom slide  232 . The bottom slide  232  can provide enforcement structure for the microfluidic chip  200 . 
     The micro-channel  212  is formed in the middle of the substrate  230 . The inlet  214  and the outlet  215  are formed on an opposing surface of the substrate  230  and into the substrate  230 . The inlet  214  and the outlet  215  are connected to the micro-channel  212 . The inlet  214  may be at one end of the micro-channel  212 , and the outlet  215  may be at another end of the micro-channel  212 . A top slide  234  is over the substrate  230 , and the inlet  214  and the outlet  215  are through the top slide  234 . The top slide  234  can provide enforcement structure for the microfluidic chip  200 . 
     The microfluidic chip  200  further includes a seal layer  234  over the openings of the inlet  214  and the outlet  215 . The seal layer  234  may be a. hardened PDMS layer or a rubber layer. The seal layer  234  may be formed by first pouring liquid PDMS while spinning the substrate  230  to create a thin layer of liquid PDMS and hardening the thin layer of liquid PDMS. Alternatively, a rubber material may be used instead of liquid PDMS. 
     The thickness of the seal layer  234  is smaller than the thickness of the substrate  230 . In particular, the thickness of the seal layer  234  is small enough to allow a needle or a piping to subsequently pierce through the seal layer  234 . The seal layer  234  provides sealing the interconnect between larger macro piping and the micro-channel  212 . With the seal layer  234 , fluid can be pumped into the microfluidic chip  200  for processing without concern for the fluid leaking despite high pressure required to pump or drive the fluid into the micro-channel  212 . 
     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 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.