Abstract:
An ultra-low voltage microfluidic device for manipulating droplets of liquid by inducing Marangoni stress therein includes a plurality of smart-polymer electrodes having films of smart polymer exposed at their surfaces. The surface of the smart polymer becomes hydrophobic or hydrophilic in response to different electromagnetic potentials. The smart polymer is reversibly oxidized by applying an electrical potential such that the smart polymer acquires a positive electrical charge. The oxidized smart polymer is reduced by applying an electrical potential such that it loses its positive electrical charge. The smart polymer is doped with a chemical compound having a negatively-charged end and a long-chain hydrophobic tail. The smart polymer is a polypyrrole and the dopant is a dodecylbenzene sulfonate. The microfluidic device includes a plurality of individually-addressable control electrodes, each of which is electrically-connected with smart-polymer electrodes. Droplets are transported, cut, or mixed by selectively applying electrical potential to individual electrodes.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    The present application claims benefit of U.S. Provisional Patent Application No. 61/470,157, filed on Mar. 31, 2011, which is incorporated by reference herein in its entirety. 
     
    
     STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH 
       [0002]    Not applicable. 
       FIELD OF THE INVENTION 
       [0003]    The present invention relates to a microfluidic system for the manipulation of liquid droplets, and, more particularly, to a digital microfluidic system for the ultra-low voltage manipulation of liquid droplets for microfluidic applications. 
       BACKGROUND OF THE INVENTION 
       [0004]    Digital microfluidic systems have been developed in the past decade to generate and manipulate discrete droplets of liquids for biomedical applications. By manipulating liquids at a droplet scale, these systems can handle samples and reagents with lower cost and shorter time for analysis by using smaller devices. At the microscale, droplet behavior is dominated by surface forces (e.g., surface tension or Laplace pressure) rather than body forces (e.g., gravity) due to high surface area-to-volume ratios. For example, droplet manipulation has been demonstrated on individual addressable control electrodes using the electrowetting-on-dielectric effect (“EWOD”) to generate net electromechanical force. An example of such droplet manipulation is described in the journal article by Sung Kwon Cho, Hyejin Moon, and Chang-Jim Kim, titled Creating, Transporting, Cutting, and Merging Liquid Droplets by Electrowetting-Based Actuation for Digital Microfluidic Circuits, published in the Journal of Microelectromechanical Systems, Vol. 12, No. 1, February 2003 (hereinafter, the “Cho et al. Article”), which is incorporated herein by reference in its entirety. 
         [0005]    Electrostatic actuation schemes such as those described in the Cho et al. Article typically require relatively high driving voltages (e.g., 15-80 V) to manipulate liquid droplets. Such high voltage requirements have been major obstacles for clinical applications that demand portability and rapid diagnosis, and where lower voltages are desirable to promote efficient EWOD applications. In addition, the high electric fields used to achieve the electrowetting effect can cause electrolysis of the working fluid in lab-on-a-chip applications. Even using high-κ dielectric materials and conductors such as indium tin oxide (“ITO”), driving voltages in the range of tens of volts are still required to effect the manipulation of fluid droplets. Therefore, it would be desirable to have lab-on-a-chip devices that are operable at, for example, the voltages which can be obtained from commercial-standard 1.5 V AA batteries. 
       SUMMARY OF THE INVENTION 
       [0006]    In one aspect, the present invention provides ultra-low voltage microfluidic devices for manipulating droplets of liquid using voltages having a magnitude of about 1 V or less. The microfluidic device includes a patterned substrate having a plurality of smart-polymer electrodes, each of which has a film of smart polymer exposed at its surface. In some embodiments, the smart-polymer electrodes are proximate one another and separated by electrical insulators. In some embodiments, the smart polymer is made so that its surface will become hydrophobic or hydrophilic in response to different electromagnetic potentials applied to the smart-polymer film. In some such embodiments, the smart polymer is reversibly oxidized by applying an electrical potential such that the smart polymer acquires a positive electrical charge. In some such embodiments, the oxidized smart polymer is reduced by applying a different electrical potential such that it loses its positive electrical charge. In some such embodiments, the smart polymer is doped with an amphiphilic chemical compound having a negatively-charged end and a long-chain hydrophobic tail. In some such embodiments, the smart polymer is a polypyrrole and the dopant is a dodecylbenzene sulfonate. 
         [0007]    In some embodiments, the microfluidic device includes a plurality of individually-addressable electrically-conductive control electrodes, each of which is in electrical communication with at least one of the smart-polymer electrodes. In such embodiments, the control electrodes are arranged such that applying an electrical potential to a control electrode causes the electrical potential to be applied to the smart-polymer film. In some such embodiments, the control electrode is substantially coextensive with the smart-film, and separated from other control electrodes by an insulator. 
         [0008]    In some embodiments, the microfluidic device includes means for selectively and individually applying electrical potentials to the control electrodes. In some such embodiments, the means includes a voltage source, electrical connectors to the control electrodes, and switching means for selectively connecting the voltage source to the electrical connectors, and thus to the control electrodes. 
         [0009]    In another aspect, the present invention provides methods for manipulating droplets by inducing Marangoni stress in the individual droplets using microfluidic devices of the same general type described above. In some embodiments, the method includes the steps of placing a droplet on a surface of a smart-polymer film, then applying an electrical potential to the smart-polymer film to create a surface tension gradient across the contact line between the droplet and the smart polymer film, thus inducing Marangoni stress in the droplet. By manipulating the electrical potential, and thus the Marangoni stress, the droplet can be transported along adjacent smart-polymer films. By selectively and sequentially applying electrical potentials to the smart-polymer electrodes, droplets may be transported, cut into smaller droplets, or mixed with each other. In some such embodiments of the method, applying the electrical potential oxidizes the smart polymer, such that it acquires a positive charge. In some such embodiments, a dopant in the polymer, having a negatively-charged end and a long-chain hydrocarbon tail, orients such that the hydrocarbon tail is directed to the surface of the smart-polymer film, causing the surface to become hydrophobic. In some such embodiments, a second electrical potential reduces the oxidized smart-polymer, such that it loses its positive charge. Such a change in the state of the smart polymer causes the dopant to orient itself with the negatively-charged end near the surface of the smart-polymer film, causing the surface to become hydrophilic. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0010]    For a more complete understanding of the present invention, reference is made to the following detailed description of an exemplary embodiment considered in conjunction with the accompanying drawings, in which: 
           [0011]      FIG. 1  is a schematic diagram of an actuation device for droplet manipulation via Marangoni stress according to an embodiment of the present invention, in which a polymer surface is initially set in an oxidized state; 
           [0012]      FIG. 2  is a schematic diagram of the actuation device of  FIG. 1 , wherein a reductive potential is applied to an electrode, thereby inducing Marangoni stress on a droplet; 
           [0013]      FIG. 3  is a schematic diagram illustrating charge neutralization of an electrically-oxidized dodecylbenzene sulfonate-doped polypyrrole film (PPy(DBS)); 
           [0014]      FIG. 4  is a schematic diagram of the effect of electrical reduction of a PPy(DBS) film on a water droplet on a surface of the film; 
           [0015]      FIG. 5  is a schematic diagram of the effect of electrical oxidation of the PPy(DBS) film of  FIG. 4  on the water droplet of  FIG. 4 ; 
           [0016]      FIG. 6  is a schematic diagram of the effect of electrical reduction of a PPy(DBS) film on a dichloromethane droplet on a surface of the film; 
           [0017]      FIG. 7  is a schematic diagram of the effect of electrical oxidation of the PPy(DBS) film of  FIG. 6  on the dichloromethane droplet of  FIG. 6 ; 
           [0018]      FIG. 8  is a schematic diagram illustrating the effect of electrical reduction of a PPy(DBS) film on surface tension gradient and Marangoni stress relative to a dichloromethane droplet; 
           [0019]      FIG. 9  is a schematic diagram illustrating the effect of electrical oxidation of a PPy(DBS) film on Marangoni stress relative to a dichloromethane droplet; 
           [0020]      FIG. 10  is a schematic drawing of an ultra-low-voltage digital microfluidic system based on a tunable electrochemical reaction of PPy(DBS); 
           [0021]      FIG. 11  is a schematic drawing of a liquid lens having an electrical potential applied thereto, such that the liquid lens is in a first state; and 
           [0022]      FIG. 12  is a schematic drawing of a liquid lens having no electrical potential applied thereto, such that the liquid lens is in a second state. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0023]    The Marangoni effect is the mass transfer along an interface between two fluids (e.g., an electrolytic bath and a droplet of immiscible liquid within the bath) due to a surface tension gradient. Since a liquid with high surface tension pulls more strongly on the surrounding liquid than one with a low surface tension, the presence of a gradient in surface tension causes the liquid to move away from a region of low surface tension to a region of high surface tension. The induced force at the liquid-liquid interface is the so-called Marangoni stress. 
         [0024]    The present invention provides a microfluidic system that enables the operation of microfluidic devices at low voltages, such as those which can be provided by commercial-standard 1.5 V batteries, using the Marangoni effect to induce Marangoni stress between adjacent electrodes comprising a smart polymer. Certain embodiments of the present invention can be substituted for those employing the existing electrowetting-on-dielectric (EDOW) technique, as well as for other conventional microfluidic systems. Such embodiments of the present invention provide controlled manipulation of liquid droplets by inducing Marangoni stress through local reduction of the smart polymer. In contrast, prior art devices, such those described in the Cho et al. Article (see Background of the Invention, above) use polymers, such as Teflon®, that are difficult to reduce locally, or may not be reduced at all at the low voltages employed in embodiments of the present invention. 
         [0025]    For the purpose of the present disclosure, a “smart polymer” is a high-performance polymer that reversibly changes its properties according to its environment. For example, polypyrrole (PPy), which is the exemplary smart polymer discussed herein, is sensitive to an electrical field and can respond in various ways, such as by reversibly oxidizing or by altering its color, volume and/or surface wettability. 
         [0026]    The exemplary PPy electrodes discussed herein are doped with dodecylbenzenesulfonate (DBS) to form a PPy(DBS) complex, which may be locally-reduced at low voltages to change the surface energy of the electrodes. In an embodiment of the present invention, PPy can be formed by oxidation of a pyrrole monomer at a suitable anode within an electrolyte environment, where DBS is the electrolyte. Upon application of a positive potential, an insoluble, electrically-conducting polymer material (i.e., PPy(DBS)) is deposited at the anode. Since the PPy is oxidized, the DBS anions in the electrolyte are incorporated into the film to maintain charge neutrality. Thus, the PPy is “doped” with DBS. In other embodiments of the present invention, other amphiphilic compounds having hydrocarbon tails may be used in place of DBS. In embodiments where the smart polymer acquires a negative charge, a dopant having a positively-charged end may be used in place of a dopant having a negatively-charged end. 
         [0027]    The tunable wetting of PPy(DBS) in embodiments of the present invention permits liquid droplet manipulation at very low voltages (e.g., in a range of about −0.9V to 0.6V). The surface energy of PPy(DBS) is changed via re-orientation of DBS in PPy(DBS) through the application of reductive electrical potentials. When a reductive potential is applied to a first electrode made of a smart polymer that is adjacent to a second electrode of the smart polymer upon which a liquid droplet resides, a dissimilar surface state is created between the first and second electrodes to induce a surface tension gradient (i.e., Marangoni stress). The electrically-triggered surface tension gradient is utilized to manipulate liquid droplets. The actuation mechanism utilized to manipulate liquid droplets is described in detail hereinbelow: 
         [0028]    Hereinafter, the exemplary electrodes comprising smart polymer will be referred to as PPy(DBS) electrodes to distinguish them from other types of electrodes that may be included in the device. For example, in microfluidic devices made and operated according to embodiments of the present invention, the PPy(DBS) electrodes are in electrical communication with other electrodes that transmit electrical force from the voltage source to the PPy(DBS) electrodes. Such other electrodes are referred to hereinafter as addressable control electrodes. 
         [0029]      FIGS. 1 and 2  provide schematic illustrations of an actuation mechanism  10  constructed in accordance with an embodiment of the present invention. A PPy(DBS) patterned substrate  12  comprising the PPy(DBS) electrodes  14 ,  16  is contained within an electrolyte solution  18  to manipulate a droplet  20  of dichloromethane (DCM). The mechanism  10  further comprises addressable control electrodes  22 ,  24 , made of electrically-conductive materials such as gold or platinum, on a substrate  26  made of an electrically-insulating material such as silicon dioxide. Each addressable control electrode  22 ,  24  is in contact with one of the PPy(DBS) electrodes  14 ,  16 . Electrical insulators, such as electrical insulator  28 , extend from the substrate  26  to insulate adjacent addressable control electrodes  22 ,  24  from each other and adjacent PPy(DBS) electrodes  14 ,  16  from each other. Two voltage sources  30 ,  32  are provided: an oxidizing voltage source  30 , which provides a positive potential, and a reducing voltage source  32 , which provides a negative potential, both potentials being relative to a reference electrode  34  in contact with the electrolyte  18 . A switching mechanism  36  and electrical connectors  38 ,  40  are also provided, being arranged such that the voltage sources  30 ,  32  may be selectively applied to the individual control electrodes  24 ,  26 , and thus to the respective PPy(DBS) electrodes  14 ,  16 . 
         [0030]      FIG. 1  depicts a positive potential being applied to the actuation mechanism  19  to oxidize the surfaces  42 ,  44  of the PPy(DBS) electrodes  14 ,  16 .  FIG. 2  depicts a negative potential being applied to one PPy(DBS) electrode (i.e., PPy(DBS) electrode  16 ) to create localized reduction of a portion  45  of the PPy(DBS) electrode surface  44  to induce Marangoni stress. The creation of such stress moves the contact line  46  of the DCM droplet  20 , which in turn moves the DCM droplet  20  in a direction indicated by the arrows. 
       Intrinsic Wetting Property of Reduced and Oxidized PPy(DBS) 
       [0031]    Referring to  FIGS. 3-5 , the surface states of PPy(DBS) are bi-directionally ‘tuned’ from hydrophilic to hydrophobic via re-orientation of its surfactant dopant molecules, DBS. More particularly, with specific reference to  FIG. 3 , when an oxidative potential is applied to PPy(DBS)  48 , sodium (Na + ) ions are repelled from the PPy(DBS) surface  50  into the adjacent electrolyte solution (not shown) for charge neutralization, leaving behind immobilized DBS −  anions  52 . Likewise, Na +  ions enter into the PPy(DBS)  48  for charge neutralization upon reduction. As shown in  FIG. 3 , the oxidized zone  54  of the PPy(DBS)  48  encroaches on the reduced zone  56  as oxidation proceeds, with charge neutralization occurring simultaneously. 
         [0032]    Referring to  FIG. 4 , when PPy(DBS) is in its reduced state  58 , the oxidized PPy chains  60  do not carry a positive charge. DBS −  anions  62  in the reduced PPy(DBS)  58  are oriented with their hydrophobic tails  64  in the reduced PPy(DBS)  58  and the polar, electrically-negative sulfonate groups  66  at the surface  68  of the reduced PPy(DBS)  58 , rendering the surface  68  of the reduced PPy(DBS) hydrophilic and attractive to the water droplet  70  shown. 
         [0033]    Referring to  FIG. 5 , with PPy(DBS) in its oxidized state  74 , DBS −  anions  62  are coupled with PPy chains  60  via electrostatic attraction between the oxidized, electrically positive PPy chains  60  and the polar, electrically-negative sulfonate groups  66  of the DBS anions  62 , allowing their hydrophobic tails  64  to thrust away from the PPy chains  60 . Since the strongly hydrophilic polar sulfonate groups  66  are attracted to the PPy chains  60  and the hydrophobic hydrocarbon tails  64  are directed outward to the surface  76  of the oxidized PPy(DBS)  74 , the surface  76  becomes hydrophobic, decreasing the area of contact between the water droplet  70  and the surface  76 . This would cause the contact angle (not indicated) of the water droplet  70  to increase relative to the contact angle (not indicated) of the water droplet  70  when the PPy(DBS) is in its reduced state  58  (see  FIG. 4 ). 
         [0034]    Referring to  FIGS. 6 and 7 , a droplet  78  of a non-polar liquid such as dichloromethane (DCM) shows opposite wetting states to those of water. With the PPy(DBS) in its reduced state  58  (see  FIG. 6 ), the DCM droplet  78  has a smaller area in contact with the hydrophilic surface  68  of the reduced PPy(DBS)  58  than the DCM droplet  78  would have with the hydrophobic surface  76  of the oxidized PPy(DBS)  74  (see  FIG. 7 ). Thus, the DCM droplet  78  would have a greater contact angle (not shown) on the surface  68  of the reduced PPy(DBS)  58  relative to the lower contact angle (note shown) on the surface  76  of the oxidized PPy(DBS)  74 . The contact angle of the DCM droplet  78  experimentally measured on the surface  68  of the reduced PPy(DBS)  58  and the surface  76  of the oxidized PPy(DBS)  74  were measured as θ red ˜133° and θ oxi ˜107°, respectively, within 0.1 M NaNO 3  aqueous solution. 
       Theory of Droplet Actuation Upon Continuous Reduction and Oxidation Reactions 
       [0035]    In contrast to the separate measurement of the intrinsic wetting states of DCM droplets for each of the above redox states  58 ,  74 , “continuous” electrochemical tuning is performed by applying a square pulse potential to the PPy(DBS) substrate to instigate DCM droplet behavior. Without being bound by theory, droplet actuation according to embodiments of the present invention is believed to proceed as described hereinbelow. 
         [0036]    Referring to  FIG. 8 , when a PPy(DBS) substrate  80  is reduced, the portion  82  of the substrate  80  underneath the DCM droplet  84  remains in the oxidized state  74 , while the remainder of the substrate  80  is in the reduced state  58 . The contact line  88  (i.e., the outermost limit of contact between the DCM droplet  84  and the surface  90  of the PPy(DBS) substrate  80 ) moves outward (see contact line  89  and arrows (M) indicating its direction of movement) due to Marangoni stress and the DCM droplet  84  is flattened to a disk-like shape  92  (indicated by a dashed line). Since DBS −  anions  94  are relatively immobilized, the charge neutralization during PPy(DBS) redox is dominated by the transportation of cations (Na + ) in electrolyte  96 . For complete reduction of PPy(DBS) film  80 , sodium ions (Na + ) in the electrolyte  96  need to transport into PPy(DBS)  80  for charge neutralization. 
         [0037]    Continuing to refer to  FIG. 8 , no such ion is available at the ‘contact zone’  82  (i.e., portion  82  of the substrate  80  that is covered by the DCM droplet  84 ) when the reductive potential is applied. The blockage of the PPy(DBS) reduction at the contact zone  82  creates heterogeneous surface states (or localized reduction), across the droplet contact line  88 . The surface tension gradient created across the contact line  88  upon a localized reduction of the PPy(DBS)  80  thereby induces Marangoni stress. The Marangoni stress causes the liquid in the DCM droplet  84  to move away from a region of low surface tension (i.e., contact zone  82 ) towards a region of high surface tension (i.e., regions  98 ,  100 ), and the DCM droplet  84  indicated in  FIG. 8  as DCM droplet  102 . 
         [0038]    It should be noted that PPy(DBS) changes color upon reduction and oxidation, providing further evidence of the above theory. A thin PPy(DBS) film (&lt;1 μm) on a gold substrate has a brown color in the reduced state while it is dim/dark in the oxidized state. During reduction of a PPy(DBS) film (not shown) having a DCM droplet thereupon, the PPy(DBS) film was observed to change color across the contact line. This indicated that the circular area of PPy(DBS) underneath the DCM droplet was in the oxidized state while the PPy(DBS) outside of the contact line was in the reduced state. Since reduced PPy(DBS) possesses higher surface energy, this observation of color change clearly illustrated the surface tension gradient across the contact line. 
         [0039]    Referring to  FIG. 9 , the Marangoni stress vanishes when the PPy(DBS) film  80  is oxidized, rendering the surface  90  hydrophobic. The DCM droplet  102  reverts to its spherical shape, indicated in  FIG. 9  as DCM droplet  84  (indicated in  FIG. 9  by a dashed line), by an internal Laplace pressure gradient to minimize its surface energy. 
         [0040]    It should be noted that the present invention can have numerous modifications and variations. For instance, smart polymer-based droplet manipulation can benefit any device designed to utilize digital microfluidics techniques at ultra-low voltages. Besides the exemplary applications described hereinbelow, smart polymer-based droplet manipulation provides the potential for many novel device applications involving tunable wetting properties. 
       Lab-on-a-Chip Device 
       [0041]    Referring to  FIG. 10 , digital microfluidics using PPy(DBS) electrodes enables extremely flexible “lab-on-a-chip” devices that can be configured in software to execute virtually any assay protocol. For example, a lab-on-a-chip device  104  according to an embodiment of the present invention may comprise a series of actuation mechanisms similar to those discussed above with respect to  FIGS. 1 and 2 . A PPy(DBS) patterned substrate  106  comprises a plurality of PPy(DBS) electrodes  108 , indicated by squares in  FIG. 10 , mounted on an electrically-insulating substrate  110  and contained within an electrolyte solution (not shown). The device  104  further comprises electrically-conductive addressable control electrodes (not shown) underlying the PPy(DBS) electrodes  108 , between the PPy(DBS) electrodes  108  and the substrate  110 . Electrical insulators, such as electrical insulators  112 , extend from the substrate  110  to insulate adjacent control electrodes (note shown) from each other and adjacent PPy(DBS) electrodes  108  from each other. Power to operate the device  104  may be provided by a 1.5 V direct current source  114  (for example, a commercial AA battery), using switching mechanisms (not shown) and electrical connectors (not shown) in arrangements such as those discussed with respect to  FIGS. 1 and 2 , to selectively provide oxidizing and reducing voltages to individual PPy(DBS) electrodes  108 . 
         [0042]    Continuing to refer to  FIG. 10 , the specimen droplet  116  and reagent droplet  118  can be cut to form smaller specimen droplets  120  and reagent droplets  122 , to merge the smaller droplets  120 ,  122  to form mixed droplets  124 , and to transport mixed droplets  124  to a detection site  126  for testing. These operations are performed by selectively applying oxidative or reductive voltages to successive PPy(DBS) electrodes  108 . The droplet manipulation using conventional EWOD typically requires about 15-80V to manipulate liquid droplets. The present invention can manipulate droplets at ultra-low voltages (i.e., from about −0.9V to about 0.6V), thereby enabling the fabrication of practical and portable microfluidic devices. Cutting, merging, and transporting the droplets  116 ,  118 ,  120 ,  122 ,  124  can be performed using the same general techniques described in the Cho et al. Article, which discusses them in the context of conventional EWOD. Thus, the electrically-triggered Marangoni stress and local reduction of a smart polymer can be utilized in any digital microfluidic systems where low voltage input is required. 
       Liquid Lens for Autofocus 
       [0043]    Referring to  FIGS. 11 and 12 , certain conventional liquid lens manipulation techniques are based on the electrowetting phenomenon. A conventional liquid lens  128  may include an oil layer  130  and a water layer  132  confined between two transparent windows  134 ,  136  and in contact with thin insulating layers  138 ,  140  over metal substrates  142 ,  144 . The voltage applied to the substrate modifies the contact angle α of the liquid drop. Referring to  FIG. 11 , the applied voltage moves the water/oil interface  146  along the insulating layers  138 ,  140  to control the curvature of the interface  146 , and thus the focal length (not shown) of the lens  128 , such that, for example, light rays (represented by arrows  148 ) converge toward the optical axis  150  (shown as a dashed line). Referring to  FIG. 12 , the variation of voltage leads to a change of curvature of the liquid-liquid interface  146  and the focal length (not shown) of the lens  128 , such that, for example, the light rays  148  diverge about the optical axis  150 . The present invention can be efficiently utilized for the same application. A PPy(DBS) film (not shown) can be substituted for the insulating layers  138 ,  140  so that contact angle α of the organic fluid (i.e., the oil layer  130 ) can be tuned upon reduction or oxidation of the PPy(DBS). An aqueous electrolyte solution (not shown) would be substituted for the water layer  132  to act as the ion provider for the PPy(DBS). An advantage of utilizing the present invention is that the required actuation voltage in this application may be reduced from about 20V to less than 1V. 
         [0044]    It will be understood that the embodiment described herein is merely exemplary and that a person skilled in the art may make many variations and modifications without departing from the spirit and scope of the invention. For instance, all such variations and modifications are intended to be included within the scope of the invention, as described in the claims presented below.