Abstract:
A microfluidic device having a coating on a surface which surface properties can be altered by applying an external stimulus. Such a surface change may be used to guide or direct fluid on these surfaces, thus controlling flow in the microfluidic system.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS  
         [0001]    This patent application claims benefit from U.S. Provisional Application Serial No. 60/233,396, filed Sep. 18, 2000, which application is incorporated herein by reference.  
         BACKGROUND OF THE INVENTION  
         [0002]    1. Field of the Invention  
           [0003]    This invention relates generally to microfluidic devices and, in particular, to devices having a coating on surfaces within said devices, where the properties of the coating may be altered by applying an external stimulus such as voltage or light to affect fluid flow within said devices.  
           [0004]    2. Description of the Prior Art  
           [0005]    Microfluidic devices have recently become popular for performing analytical testing. Using tools developed by the semiconductor industry to miniaturize electronics, it has become possible to fabricate intricate fluid systems which can be inexpensively mass produced. Systems have been developed to perform a variety of analytical techniques for the acquisition of information in many fields, such as the medical field.  
           [0006]    Microfluidic technology can be used to deliver a variety of in vitro diagnostic applications at the point of care, including blood cell counting and characterization, and calibration-free assays directly in whole blood. There are also other applications for this technology, including food safety, industrial process control, and environmental monitoring. The reduction in size and ease of use of these systems allows the devices to be deployed closer to the patient, where quick results facilitate better patient care management, thus lowering healthcare costs and minimizing inconvenience. In addition, this technology has potential applications in drug discovery, synthetic chemistry, and genetic research.  
           [0007]    Microfluidic devices may be constructed in a multi-layer laminated structure where each layer has channels and structures fabricated from a laminate material to form microscale voids or channels where fluids flow. A microscale channel is generally defined as a fluid passage which has at least one internal cross-sectional dimension that is less than 1 mm and typically between about 0.1 μm and about 500 μm. The control and pumping of fluids through these channels is affected by either external pressurized fluid forced into the laminate, or by structures located within the laminate.  
           [0008]    Control of fluid movement within microfluidic channels is usually accomplished by the use of mechanical valves. An example of such a valve is taught in U.S. Patent Application No. 09/677,250, entitled “Valve for Use In Microfluidic Structures”, filed Oct. 2, 2000, and is assigned to the assignee of the present invention. This application describes a valve manufactured from a flexible material which allows one-way flow through microfluidic channels for directing fluids through a microfabricated analysis cartridge. This type of valve, however, is often difficult to fabricate due to its extremely small dimensions.  
           [0009]    It has also been proposed to use passive or nonmechanical means to control fluid movement in microfluidic channels. U.S. Pat. No. 6,193,471 is directed to a process and system for introducing menisci, arresting the movement of menisci at defined locations within the system, and for removing menisci from capillary volumes of a liquid sample, as well as delivering precise small volumes of liquid samples to a point of use.  
           [0010]    U.S. Pat. No. 6,130,098, which issued on Oct. 10, 2000, is directed to microscale devices using flow-directing means including a surface tension gradient mechanism in which discrete droplets are differentially heated and propelled through etched channels. Electronic components are fabricated on the same substrate material, allowing sensors and controlling circuitry to be incorporated in the same device.  
           [0011]    Physical surface features of fluid containing solids are known to affect the behavior of fluids moving through microfluidic channels. For example, U.S. Pat. No. 6,143,248 describes a device having means for controlling pressures necessary for flow comprising textures in the surface material, such as concentric rings around the exit post, as such textures have increased resistance to flow along the surface relative to a smooth surface. It also teaches that the precise shape of a capillary orifice affects the applied pressures at which microvalves permit fluid flow.  
           [0012]    U.S. Pat. No. 6,056,860uses surface modifications to effect movement of entities through a medium in electrophoretic applications, as various means have been developed for the surface modification of materials employed in these applications. Surface modification techniques include physical or chemical alteration of the material surface, such as etching, chemical modification, and coating a new material over the existing surface (radiation grafting, vapor deposition, or solvent coating). In this patent, an electrophoretic layer is used to move entities through a medium under the influence of an applied electric field.  
           [0013]    U.S. Pat. No. 6,238,538 teaches a microfluidic device using electroosmotic fluid control systems which generally require channels having surfaces with sufficient zeta potentials to propagate an acceptable level of electroosmotic mobility within the channels. Surface modification of the polymeric substrates used in these devices may take on a variety of different forms, including coating those surfaces with an appropriately charged material, derivatizing molecules present on the surface to yield charged groups on that surface, or coupling charged compounds to the surface.  
           [0014]    The properties of some surfaces can be changed by applying an external stimulus such as voltage or light. Examples are photosensitive materials that break down into their components, or molecules that reverse their orientation upon being exposed to a certain trigger voltage. As a result of such surface changes, for example, a surface can change from being hydrophilic to hydrophobic. This change can be reversible or irreversible.  
           [0015]    Such a surface change can be used to guide or divert fluid flow on these surfaces, or, if the surfaces are part of a channel system, can control flow in microfluidic system. An example for such a surface coating is a photoresist, a UV curable adhesive, a photographic paper, a liquid crystal layer, etc.  
         SUMMARY OF THE INVENTION  
         [0016]    It is therefore an object of the present invention to provide a microfluidic device having channels in which the surface properties may be altered using an external stimulus.  
           [0017]    It is a further object of the present invention to provide a microfluidic device in which flow patterns within channels of the device can be established by use of the external stimulus.  
           [0018]    It is a still further object of the present invention to provide a device in which changes in the surface properties of the channels of the device can be reversibly accomplished.  
       
    
    
       [0019]    These and other objects of the present invention will be more readily apparent in the description and drawings that follow.  
       BRIEF DESCRIPTION OF THE DRAWINGS  
       [0020]    [0020]FIG. 1 is a cross-section view of a channel employing the principles of the present invention; and  
         [0021]    [0021]FIG. 2 is a representation of a microfluidic cartridge embodying the present invention. 
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT  
       [0022]    [0022]FIG. 1 is a representation of a sheet having the properties of the present invention. Referring now to FIG. 1, there is shown a sheet  10  which is supported by a substrate  12 . Sheet  10  may comprise a channel within a microfluidic device. On the upper surface of sheet  10  a surface coating  14  is deposited. A fluid  16  flows across coating  14  on sheet  10 . Substrate  12  may be composed of plastic or a similar material.  
         [0023]    A series of electrodes  20  are embedded within sheet  10  in FIG. 1. When a voltage is applied to electrodes  20 , properties of surface coating  14  are changed, as is shown at  24  in FIG. 1. This property change causes an interruption in the flow of fluid  16  across sheet  10  and coating  14 , as is seen at  26 .  
         [0024]    In the present embodiment, surface coating  14  is changed from hydrophilic to hydrophobic upon the application of an electric charge to electrodes  20 . Several isolated drops of fluid l 6  can be seen at  16   a  between electrodes  20  in FIG. 1. By removing the electrical charge from electrodes  20 , surface coating  14  will return to its hydrophilic state, allowing fluid  16  to resume its flow across sheet  10 . It is also possible to use magnetic fields or sonic radiation to change the state of coating  14 .  
         [0025]    An example of electric field sensitive polymers is the complex of polyethyloxazoline and poly (methacrylic acid), which changes from a solid state to solution after an electric current is applied.  
         [0026]    Temperature can be used to control the surface hydrophilicity of a microfluidic device. An example for this application is polymerized N-isopropylacrylamide, which shows a lower critical solution temperature (LCST) of 32° C. in the aqueous environment. The surface after coating is hydrophilic when the temperature is below 32° C. Upon heating to above 32° C., the surface becomes hydrophobic.  
         [0027]    Photosensitive polymers can also switch between hydrophobic and hydrophilic states, depending on the light source. For example, copolymers of N,N-dimethyl acrylamide and 4-phenylazophenyl acrylate turn hydrophilic and dissolve in aqueous solution upon ultraviolet (UV) light (350 nm) irradiation, while copolymers of N,N-dimethyl acrylamide and N-4-phenylazophenyl acrylamide turn hydrophobic and precipitate upon UV light irradiation.  
         [0028]    In addition, pH sensitive polymers such as polyacrylic acid can ionize reversibly at an inherent pH range and affect the polarity of the polymer. At pH 7, polyacrylic acid is hydrated and hydrophilic. When pH drops below 4, the polymer contracts and becomes hydrophobic.  
         [0029]    Chemical coatings for modification of the surface chemistry of a microlfuidic device may be derived from one or more of the following to create multi-sensitivity surfaces: N-isopropylacrylamide, N-acetylacrylamide, N-acetylmethacrylamide, acrylic acid, propylacrylic acid, N,N-dimethyl acrylamide, 4-phenylazophenyl acrylate, N-4-phenylazophenyl acrylamide, ethyloxazoline, and methacrylic acid, acryl-L-amino acid amide, N-acryloyl pyrrolidine, N-acryloyl piperdline, hydroxypropyl acrylate, methylcellulose, ethylene oxide and vinyl methyl ether.  
         [0030]    The surface coatings may be applied via plasma deposition. The monomers may be vaporized into the plasma reactor and deposited directly onto the desired surface areas of a microfluidic device. Alternatively, specific areas of a microfluidic device surface can be activated with argon plasma, coated with the desired chemicals dissolved in solvent, and further plasma treated with argon plasma to achieve the desired surface chemistry. Desired surface chemistry may also be achieved via absorption, surface grafting, and covalent or ionic chemical derivatization of specific polymers, which initially display abilities to switch between hydrophobic and hydrophilic states upon external stimuli. By applying a mask on the sheet of a microfluidic device, desired surface areas of the sheet can be chemically modified.  
         [0031]    [0031]FIG. 2 shows a microfluidic cartridge which uses an embodiment of the present invention. Referring now to FIG. 2, there is shown a microfluidic cartridge, generally indicated at  40 . Cartridge  40  is used to separate small molecules from a blood sample. Cartridge  40  contains an inlet  42  for receiving a blood sample. Inlet  42  is connected to an inlet channel  44  which is coupled to an H-Filter device  46 . The H-Filter structure is described in detail in U.S. Pat. No. 5,932,100, the disclosure of which is hereby incorporated by reference.  
         [0032]    H-Filter  46  is formed by a pair of inlet channels  48 ,  50 , a main channel  52 , and a pair of outlet channels  54 ,  56 . A buffer inlet  58  is coupled to channel  50  at the end opposite H-Filter  46 , while a sample collector port  60  is coupled to channel  56  at the end opposite H-Filter  46 . A waste port  62  is coupled to channel  54  at the end opposite H-Filter  46 . Finally, a section of hydrophobic responsive coating  60  is located at the junction between inlet channel  44  and H-Filter  46 .  
         [0033]    The operation of microfluidic cartridge  40  will now be described. A sample of blood is introduced to cartridge  40  at inlet  42 . The sample is drawn into inlet channel  42  until it reaches coated section  60 , where it stops due to surface tension within channel  42 . An external energy control source is then applied to cartridge  40  and section  60  in the form of light, electric field, temperature, pH, or the like, which changes the hydrophobic surface on section  60  to a hydrophilic surface, which allows the blood sample within inlet channel  44  to enter H-Filter  46 .  
         [0034]    H-Filter  46  acts to separate small molecules from the blood sample using the process described in U.S. Pat. No. 5,932,100. The separated molecules enter sample collector port  60  via channel  56 , while the rest of the fluid collects in waste port  62  via channel  54 . The external force is again applied to cartridge  40  in order to reverse the property of surface coating  60  to the hydrophobic state to halt the blood flow from channel  44 .  
         [0035]    While the present invention has been shown and described in terms of several preferred embodiments thereof, it will be understood that this invention is not limited to these particular embodiments and that many changes and modifications may be made without departing from the true spirit and scope of the invention as defined in the appended claims.