Abstract:
Control of fluid flow in a fluidic network is provided by controlling phase transitions of a phase-change material between a liquid phase and a non-fluid phase. The phase-change material is disposed at ports of the fluidic network where the fluidic network is in communication with an ambient. This advantageously provides control of pressure-driven flow within the fluidic network without altering properties of fluids within the fluidic network.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application claims the benefit of U.S. provisional patent application 61/861,602, filed on Aug. 2, 2013, and hereby incorporated by reference in its entirety. 
     
    
     FIELD OF THE INVENTION 
       [0002]    This invention relates to control of fluid flow in a fluidic system. 
       BACKGROUND 
       [0003]    Various approaches have been considered for controlling fluid flow in fluidic and microfluidic systems. Some of these approaches rely on the use of a phase-change material. For example, microvalves making use of a phase-change material for actuating the valves are considered in an article by Oh et al., (“A review of microvalves”, J. Micromechanical Microengineering, v16, pp. R13-R39, 2006) and in an article by Eddington et al. (“Flow control with hydrogels”, Advanced Drug Delivery Reviews v56, pp 199-210, 2004). 
         [0004]    In some cases a phase-change material is used directly as opposed to being an actuator of a valve. For example, Tsukita et al. (U.S. Pat. No. 7,204,263) consider adding a sol-gel material to fluid flowing through a microfluidic system and controlling fluid flow in the fluidic system by stimulating a sol-gel transition from fluid to gel in a channel of the fluidic system. This method induces a hydrodynamic resistance change within the channel of the fluidic network. A similar approach is considered by Chow et al. (U.S. Pat. No. 6,669,831), where a viscosity enhancer is added to an analyte in a fluidic system to provide flow control. 
         [0005]    Although direct use of a phase-change material in a fluidic system for flow control can advantageously avoid complexity related to the use of valves and actuators, it can disadvantageously alter the properties of fluids within the fluidic system. In many cases such alteration of fluid properties can undesirably interfere with proper operation of the system. For example, analytical results from a fluidic system may be undesirably altered by the addition of flow control material to the fluid being analyzed. 
         [0006]    Accordingly, it would be an advance in the art to provide direct control of fluid flow in a fluidic system with phase-change material without affecting the properties of fluid within the fluidic system. 
       SUMMARY 
       [0007]    We have found that direct control of fluid flow in a fluidic system can be provided by using phase-change material at ports (e.g., input/output nodes) of the fluidic system where it is in communication with the ambient. This is in contrast to using the phase-change material within the fluidic system as in the above-considered conventional examples. Such use of phase-change material at the ports of a fluidic system can provide flow control while advantageously not changing the properties of fluid within the fluidic system. 
         [0008]    In microfluidic devices, a typical configuration is to have fluidic channels and/or fluidic chambers connected to input/output nodes (often referred to as reservoirs). Various processes (e.g., transport, separations) can take place in the channels, while the input/output nodes usually provide a source or sink for fluid flow or ions for electromigration. Input/output nodes are distinguished from channels in that input/output nodes are nodes in the fluidic networks which are used to input or output fluids and/or chemical species. Also, analyses are typically performed in channels and chambers, and not in the input/output nodes. In such configurations, undesired small pressure differences at the input/output nodes can lead to undesirable bulk pressure-driven fluid flows in the channels. Such flows can often interfere with separations or analyses, and are therefore usually undesirable. Eliminating such pressure-driven flows by eliminating the relevant pressure differences is usually not easily achieved in practice, since unduly precise control of the pressures would be needed. 
         [0009]    The present approach is based on including a phase-change material in or at one or more of the input/output nodes. A transition of the phase-change material from a liquid phase to a non-fluid phase can be used to control fluid flow to/from the input/output nodes, thereby also controlling fluid flow within the channels. For example, in a simple system having one channel connected between two input/output nodes, having the phase-change material in one of the input/output nodes will stop pressure driven fluid flow in the channel when the phase-change material is in its non-fluid phase. Preferably, the non-fluid phase is a gel in order to avoid generating large and possibly destructive mechanical forces within the fluid system as a result of the phase change. Also, gel phases are able to provide ion buffering and can accommodate Faraday reactions between an electron and species used in the analysis (e.g., water). 
         [0010]    An important feature of this approach is that the characteristics of the channels and of fluid in the channels (e.g., hydrodynamic resistance, viscosity, electrical resistance) are not changed by the presence of the phase-change material in the input/output nodes. This advantageously ensures that separations and/or analyses in the channels are unaffected by this approach for preventing pressure driven fluid flow. Another important characteristic is that the phase change allows the material introduced into the input/output node to quickly take the shape of the input/output node region prior to phase change. This makes the process very versatile and able to accommodate to a wide variety of sizes and shapes of input/output nodes. The phase change feature also enables rapid and conformal sealing (to pressure driven flow) of the input/output nodes, even in the presence of an electrode or fluidic connection or connections to/from the input/output node. That is, the phase-change material can conform to the space between a portion of the inlet/outlet conduit (e.g., a wire for electrical current or a tube for species transport), the input/output node walls, and the inlet region of a fluidic channel or channels. Further, the process can be reversible because the phase-change material can be changed back to a liquid phase. 
         [0011]    The specific embodiment of a gel as a non-fluid material enables the use of electrical connection nodes in other ways. A gel can be easily prepared to include important chemical species; and these can be available in the fluidic input/output node. For example, for electrokinetic systems these species can include weak electrolyte and titrant species for pH buffering. The input/output nodes can also include, for example, silver ions for silver chloride type standard electrodes. Further, the use of a gel enables sieving or filtering functions to occur at the input/output node. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0012]      FIGS. 1A-B  show operation of a first embodiment of the invention. 
           [0013]      FIGS. 2A-B  show operation of a second embodiment of the invention. 
           [0014]      FIG. 3  shows a third embodiment of the invention. 
           [0015]      FIGS. 4A-C  show examples relating to embodiments of the invention. 
           [0016]      FIG. 5A  is an exemplary detector image from an experiment relating to an embodiment of the invention. 
           [0017]      FIG. 5B  shows the fluidic system for the experiment of  FIG. 5A . 
           [0018]      FIGS. 6A-B  show results relating to the experiment of  FIGS. 5A-B . 
           [0019]      FIG. 7  shows further results relating to the experiment of  FIGS. 5A-B . 
       
    
    
     DETAILED DESCRIPTION 
     A) General Principles 
       [0020]      FIGS. 1A-B  show operation of a first embodiment of the invention. In this example a microfluidic network formed by substrate  110  has flow channels  104  and  106  connected to a port  108  where the flow network is in communication with an ambient. Schematically, this communication is shown by meniscus  112  on  FIG. 1A . A dispenser  102  is configured to deliver a phase-change material to port  108 . The apparatus as a whole is configured to control a transition of the phase-change material between a liquid phase and a non-fluid phase.  FIG. 1B  shows one possible resulting configuration, where non-fluid phase  114  provides a local seal between the microfluidic network and the ambient. The example of  FIGS. 2A-B  is similar, except that the dispenser is disposed such that the resulting non-fluid phase  116  isolates channels  104  and  106  from each other in addition to providing the local seal between the microfluidic network and the ambient. The non-fluid phase of the phase-change material is preferably a gel. 
         [0021]    Practice of the invention does not depend critically on the nature of the dispenser. Any dispenser suitable for dispensing the phase-change material can be employed, such as pipettes etc. Practice of the invention also does not depend critically on the choice of phase-change material. In the specific example considered below, Pluronic® F-127 is employed, but any material capable of changing between liquid and non-fluid phases can be employed. 
         [0022]    In general, ports as considered above can be any location where fluid can enter or leave the microfluidic network. For example, input/output nodes where chemical species can enter or leave the flow network are exemplary ports. Preferably the phase-change material is disposed in one or more of the input/output nodes. 
         [0023]    Operation of such a system mainly depends on how the transition of the phase-change material between the liquid phase and the non-fluid phase is controlled. One mode of operation is to perform sample analysis in the microfluidic system where the phase-change material is in the non-fluid phase during the sample analysis procedure. This approach can advantageously reduce pressure-driven flow during the sample analysis procedure. An alternative mode of operation is to perform sample analysis in the microfluidic system where the phase-change material is in the liquid phase during the sample analysis procedure. This approach enables pressure-driven flow during the sample analysis procedure. 
         [0024]    Such control of pressure driven flow is applicable to any kind of analysis in a microfluidic network, including but not limited to: electrophoresis, isotachophoresis, chromatography, electrochromatography, enzymatic processes, chemical reactions involving one or more species in solution, chemical reactions between a species in solution and a surface-bound species, hybridization, antibody and antigen reactions, optical analyses, electrochemical sensing, and spectral analyses. 
         [0025]    Preferably the fluid in the microfluidic network is a liquid. The phase-change material can include pH buffering chemistry. The phase-change material can be dispensed in the liquid phase and subsequently transition to the non-fluid phase. Such a transition can be governed by temperature. For example, the phase-change material can be dispensed at a temperature other than ambient temperature and transition from the liquid phase to the non-fluid phase as its temperature approaches ambient temperature. Further, the phase-change material can be reversible to reverse the process and convert the non-fluid phase back to a liquid phase. Transition to a liquid phase enables subsequent pressure-driven flow control at the input/output node and/or removal or addition of the phase-change material. 
         [0026]    A phase-change material as considered above can be configured to conformally seal around a conduit inserted into the input/output node while also controlling pressure-driven flow in the microfluidic flow network.  FIG. 3  shows an example, where non-fluid phase  114  conformally seals around conduit  302  in input/output node  304 . Conduit  302  can be an electrode which enables electrical transport into and out of the microfluidic system. In this case, the phase-change material can act as an ion reservoir. Alternatively, conduit  302  can be a tube which enables species transport into and out of the microfluidic system. These approaches provide the capability of connecting a conduit to a microfluidic system through an input/output node while simultaneously preventing undesirable pressure-driven flow effects by locally sealing off the input/output node from the ambient. 
         [0027]    In some cases, multiple channels of a microfluidic network are in contact with the same input/output node.  FIG. 4A  shows an example where channels  404 ,  406 ,  408 ,  410 ,  412  and  414  are in communication with input/output node  402 . Local seals formed by the phase-change material in its non-fluid state can seal some ( 420  on  FIG. 4B ) or all ( 422  on  FIG. 4C ) of the channels 
       B) Experimental Demonstration 
       [0028]    This section describes an exemplary experimental demonstration of flow control according to the above-described principles.  FIG. 5B  shows the experimental arrangement. Here the fluidic system is basically a chip having a single channel loaded on the right with an aqueous buffer solution  504  and loaded on the left with an aqueous bead suspension  502  that is the same as solution  504  except for the addition of the beads. Here the beads are fluorescent particles of 1 um diameter. 
         [0029]    After loading suspension  502  and solution  504 , end-channel open reservoirs  506  and  510  and one mid-channel, open reservoir  508  were filled with approximately the same volume (40 μl) of aqueous buffer solution in an attempt to equalize hydrostatic pressure and minimize pressure driven flow. We here use “open reservoir” to denote an inlet or outlet connection between the ambient and the microfluidic system. Unwanted small differences in the hydrostatic pressure in these open reservoirs result in unwanted pressure-driven flows in the channels which may disturb on-chip processes including chemical and biological separations and analysis. 
         [0030]    The movement of fluorescent particles was monitored with a detector  520  disposed to image the beads in suspension  502 . Detector  520  is vertically separated from the flow channel of suspension  502 , although this vertical separation is not apparent in the top view of  FIG. 5B . For this experiment, detector  520  was a microscope (magnification: 20×, numerical aperture: 0.5) equipped with high-sensitivity CCD (16-bit Cascade 512F). The field of view spans 1/13th of the channel width.  FIG. 5A  shows an exemplary image from this detector. 
         [0031]    Particle movement was monitored before and after the open reservoir  506  content was replaced with the phase-change material (here this was 40 μl cooled, buffered, 25% Pluronic® F-127). This thermoreversible hydrogel is in a liquid state at low temperature (˜4° C.) and gels at high temperature (˜20° C.). The gelation temperature of this material is concentration dependent. Prepared in its inactivated state (that is, about 4° C.), Pluronic® F-127 can be mixed with appropriate electrolytes required for a specific application. The cooled solution is dispensed into the open reservoir. In less than 5 s, it reaches its gelation temperature, and seals the fluidic passage, thereby eliminating pressure driven flow. 
         [0032]    The velocity field was evaluated using a micron-resolution particle image velocimetry (micro-PIV). Micro-PIV tracks the motions of small groups of particles to quantify velocity fields in the channels. Our experiments showed that even small variations in hydrostatic pressure cause significant pressure driven flow. The following results were all obtained by averaging the velocity vectors determined from 100 sequential images recorded at a frequency of 5 Hz. 
         [0033]      FIG. 6A  shows the velocity vector field evaluated from an image sequence acquired when all open reservoirs contained purely aqueous buffering solution. The maximum velocity in this field of view is approximately 25 μm/s directed downward.  FIG. 6B  shows the velocity vector field evaluated from a set of images acquired  5  seconds after replacing the aqueous buffering solution in open reservoir  506  with the phase-change material as described above. The average velocity vector magnitude seen on  FIG. 6B  is less than about 1 μm/s. Note the viscosity, flow resistance, and electrical resistance inside the fluidic channels (in the chip) remain unchanged after the addition of the phase-change material to reservoir  506 . The bulk, pressure driven flow was eliminated by simply sealing the junction between the open reservoir and the fluidic passage. The residual velocities measured after addition of the phase-change material ( FIG. 6B ) are due to image noise and Brownian motion of the particles. The mobilities of particles and other analytes in the channel are not affected by the seal at the open reservoir. 
         [0034]    Replacement of the aqueous buffer solution in open reservoir  506  with the phase-change material resulted in a dramatic reduction of the pressure driven velocity.  FIG. 7  shows the reduction in the absolute velocity of particles in solution before and after addition of the phase-change material. In this experiment, the field of view of detector  520  is a small area of the channel, therefore the velocity profile looks relatively linear. In smaller channels, where the field of view spans the entire channel width, we would observe a parabolic velocity profile.