Abstract:
An apparatus and method for pumping microfluidic devices. An apparatus for pumping microfluidic devices includes a microfluidic pumping device, a pump. The pump includes a reservoir containing a pump fluid when in operation, a heat element situated to apply heat to the pump fluid to produce evaporated pump fluid, and a reservoir outlet sized to operably couple the pump to a microfluidic device and connected to the reservoir to provide an exit from the reservoir for the pump fluid. The evaporated pump fluid increases pressure in the reservoir, causing the pump fluid to flow out of the reservoir outlet at a rate determined by the pressure, the composition, configuration and dimensions the reservoir outlet and of a flow path, and characteristics of the pump fluid.

Description:
BACKGROUND  
       [0001]     Devices used for analytical separations continue to evolve to smaller and smaller sizes. The current device of choice for bioseparations on a small scale is the Agilent 2100A Bioanalyzer. The 2100A Bioanalyzer separates based on capillary electrophoresis. Another analytical technique of reasonable interest is “nano separations” in liquid chromatograph (LC)-mass spectrometer (MS) systems. The nano LC-MS is based on packed capillaries and specially designed pumps which split (waste) most of the mobile phase that they pump, directing a minor fraction to the column where it moves the sample through the separation column. Nano separations systems would benefit from the availability of pumps that do not waste most of the mobile phase. Additional advantages of such pumps as described below include lower cost than conventional alternatives, less waste of mobile phase solvents, and less waste solvents to dispose of, lower power consumption, easier maintenance, and more portability.  
         [0002]     In general, analytical microfluidic devices rely on either electro-driven separations in aqueous mobile phases (like the 2100A) or on externally-supplied pumped mobile phase sources (like the nano LC-MS). Most electro-driven separations are usually restricted to ionic or, at a minimum, water-soluble analytes. However, there are a large number of separations that are currently done by high-pressure LC (HPLC) that are not ionic or water soluble. In addition, nano-flow pumping has not been routinely extended to packed channels in microfluidic devices due to a number of complexities.  
         [0003]     Moreover, many samples outside the biology field are not compatible with aqueous mobile phases. Further, many samples need mobile phases with significant amounts of organic solvents in order to dissolve and separate the components of interest. The high amounts of organics can arrest, impede, or degrade electro-driven mechanisms. Accordingly, microfluidic sample preparation and analysis processes would benefit from the availability of on-board pumps that could supply organic, organic-modified aqueous, or gaseous mobile phases at rate compatible with and in a format appropriate to the microfluidic devices.  
       SUMMARY  
       [0004]     What are described are an apparatus and method for pumping microfluidic devices. An apparatus for pumping microfluidic devices includes a microfluidic pumping device, a pump. The pump includes a reservoir containing a pump fluid, a heat element situated to apply heat to the pump fluid to produce evaporated pump fluid, and a reservoir outlet sized to operably couple the pump to a microfluidic device and connected to the reservoir to provide an exit from the reservoir for the pump fluid. The evaporated pump fluid increases pressure in the reservoir, causing the pump fluid to flow out of the reservoir outlet at a rate determined by the pressure increase, the size of the reservoir outlet, the composition, configuration and dimensions of the flow path, and characteristics of the pump fluid.  
         [0005]     A system for performing microfluidic analyses includes a pump, a flow path and a microfluidic device. The pump includes a reservoir containing a pump fluid, a heat element situated to apply heat to the pump fluid to produce evaporated pump fluid, and a reservoir outlet connected to the reservoir to provide an exit from the reservoir for the pump fluid. The flow path is connected to the reservoir outlet. The microfluidic device is operably coupled to the pump via the reservoir outlet and the flow path. The evaporated pump fluid increases pressure in the reservoir, causing the pump fluid to flow out of the reservoir outlet and into the flow path towards the microfluidic device at a rate determined by the pressure increase, the size of the reservoir outlet, the composition, configuration and dimensions of the flow path, and characteristics of the pump fluid.  
         [0006]     A portable device for performing microfluidic analyses includes one or more pumps, a flow path, a microfluidic device, a plate or a chip, and a sample input. Each pump includes a reservoir containing a pump fluid, a heat element situated to apply heat to the pump fluid to produce evaporated pump fluid, and a reservoir outlet connected to the reservoir to provide an exit from the reservoir for the pump fluid. The flow path is connected to the reservoir outlet. The microfluidic device is operably coupled to the one or more pumps via the reservoir outlet and the flow path. The evaporated pump fluid increases pressure in the reservoir, causing the pump fluid to flow out of the reservoir outlet and into the flow path towards the microfluidic device at a rate determined by the pressure increase, the size of the reservoir outlet, and characteristics of the pump fluid. The pump, flow path, and microfluidic device are etched or otherwise created on the plate or the chip. The sample input is coupled to the flow path and provides a sample aliquot that is driven by the pump fluid into the microfluidic device.  
     
    
     DESCRIPTION OF THE DRAWINGS  
       [0007]      FIG. 1  is a diagram illustrating an embodiment of an apparatus for pumping microfluidic devices.  
         [0008]      FIG. 2  is a diagram illustrating an embodiment of an apparatus for pumping microfluidic devices.  
         [0009]      FIG. 3  is a diagram illustrating an embodiment of a system utilizing an apparatus for pumping microfluidic devices.  
         [0010]     FIGS.  4 A-C are diagrams illustrating systems with various microfluidic devices utilizing an apparatus for pumping microfluidic devices.  
         [0011]      FIG. 5  is a diagram illustrating a system utilizing a plurality of apparatus for pumping microfluidic devices.  
         [0012]      FIG. 6  is a diagram illustrating a system utilizing a plurality of apparatus for pumping microfluidic devices.  
         [0013]      FIG. 7  is a diagram illustrating an embodiment of a system utilizing an apparatus for pumping microfluidic devices.  
         [0014]      FIG. 8  is a diagram illustrating an embodiment of a flow injection analysis system utilizing an apparatus for pumping microfluidic devices.  
         [0015]      FIG. 9  is a diagram illustrating an embodiment of a system utilizing a plurality of apparatus for pumping microfluidic devices to provide mobile phase gradients. 
     
    
     DETAILED DESCRIPTION  
       [0016]     An apparatus and method for pumping of liquid or gas mobile phases in analytical microfluidic devices is described herein. The apparatus and method utilize controlled evaporation of liquids to pump the mobile phase. The apparatus and method take advantage of the fact that liquids evaporate at a rate proportional to the heat (watts) supplied. If the liquid is contained in a sealed vessel with one outlet and with appropriate temperature control, the rate of evaporation can be accurately controlled. Moreover, the rate of evaporation can be calculated as a function of the liquid constants, vessel constants, and the heat supplied. If the rate of evaporation is controlled, the pressure within the sealed vessel and the resulting flow to the microfluidic device can be controlled. Further, the pressure increase and the resulting flow can be calculated from the rate of evaporation. Consequently, by controlling the temperature (through the heat supplied), the resulting flow is controlled. By taking advantage of these known principles, the apparatus and method described herein achieve this control.  
         [0017]     With reference now to  FIG. 1 , illustrated is an apparatus for pumping analytical microfluidic devices, pump  10 . The pump  10  is itself a microfluidic device, a microfluidic pumping device. As shown, pump  10  includes a reservoir  12 , a reservoir outlet  13 , a heat element  14 , and a control  15 . The control  15  controls the heat element  14  and the heat supplied by the heat element  14  in any manner known to one of skill in the art. For example, the control  15  may control the temperature of the supplied heat by controlling the amount of power supplied to the heat element  14 . The heat element  14  may be a separate structure or component from the reservoir or may be integrated with the reservoir as one structure. The heat element  14  may be, e.g., a coil, plate, sleeve, or other structure suitable to provide heat to the reservoir  12  and the pump fluid  18 . The control  15  may also monitor the temperature of a pump fluid (e.g., a solvent)  18 , the flow rate of the pump fluid  18 , the amount of pump fluid  18 , and any other variable necessary for controlling and monitoring the pump  10  in manners known to one of skill in the art.  
         [0018]     The reservoir  12  contains the pump fluid  18 , and when heat element  14  has supplied and/or is supplying heat of sufficient temperature, evaporated pump fluid  16 . If the heat element  14  is supplying increasing heat of sufficient temperature, the amount of evaporated pump fluid  16  will increase. The heat migrates over time so that the evaporated pump fluid  16  stays evaporated. The evaporated pump fluid  16  will continue to expand, forcing the pump fluid  18  out of the reservoir  12 . As a result, the pump fluid  18  will flow to an analytical microfluidic device  20 .  
         [0019]     Based on the above principles, an increasing amount of evaporated pump fluid  16  results in increased pressure and, therefore, increased flow to microfluidic device  20 . If the temperature of the supplied heat is reduced to a sufficient level, the evaporated pump fluid  16  remaining in the reservoir  12  will begin to condense, resulting in decreased pressure and, therefore, decreased flow to the microfluidic device  20 . If the temperature of the supplied heat is held at a certain level, the flow will stop. If the temperature of the supplied heat is reduced sufficiently or if the heat is removed entirely, the pressure may decrease enough to create a vacuum into the reservoir  12 , reversing the flow into the reservoir  12 . A cooling element (not shown) may be added to the pump  10  to increase the temperature reduction and therefore, the rate of condensation and pressure drop, resulting in a more rapid decrease and reversal in flow.  
         [0020]     With continued reference to  FIG. 1 , the pump  10  is connected to the microfluidic device  20  via a flow path (e.g., a microfluidics channel or a small tube)  19  connected to the reservoir outlet  13 . The flow path  19  may be of any length, width, or shape necessary for a desired implementation and may include additional components along its length. Further, the pump  10  is typically sized to be of similar dimensions as separation sections of the instrumentation in which and with which the pump  10  is used. A typical microfluidic device  20  is a few centimeters by a few centimeters (e.g., 2×2 cm), with channel dimensions in the low tens of microns (e.g., 10×30 μm). Consequently, the pump  10  may be similarly scaled and integrated with the microfluidic device  20  or simply coupled to the microfluidic device  20 .  
         [0021]     If integrated with the microfluidic device  20 , the pump  10  may be etched (or otherwise formed) on the same board as the microfluidic device  20  using known etching (or other) methods. The pump  10  may be etched on a chip or plate (e.g., steel). If coupled to the microfluidic device  20 , the pump  10  may be etched on a disposable chip that is connected to the microfluidic device  20  and removed when the pump fluid  18  in the reservoir is exhausted. Similarly, the reservoir  12  alone may be etched on a disposable chip that is removed from pump  10  when the pump fluid  18  supply is exhausted. Indeed, the pump  10  may be fabricated using any know manner of fabricating micro-devices.  
         [0022]     The material chosen for the pump  10  components and the flow path  19  may be based in part on the type of pump fluid (e.g., solvent)  18  that may be used. It may be desirous to construct the components and the channel from a material that is opposite in nature from the pump fluid  18  (e.g., hydrophilic vs. hydrophobic). For example, a teflon or like material (hydrophobic) may be used. This may prevent a hydrophilic pump fluid  18  from wetting the component and channel walls, therefore decreasing resistance to the flow of the pump fluid  18  and ensuring a defined front miniscus. Likewise, in an existing pump  10 , the choice of the pump fluid  18  may be influenced by the material used for the pump components and the microfluidics channel.  
         [0023]     If the flow generated by the pump  10  is sufficient, the pump fluid  18  drives a sample  22  into and through the microfluidic device  20 . The sample  22  may be a second liquid. The pump fluid  18  is the mobile phase in this implementation. The pump fluid  18  may be non-aqueous or aqueous, although the pump fluid  18  should evaporate at low-enough temperature to be practical and have other characteristics that do not hinder its effectiveness as the mobile phase (e.g., the pump fluid  18  should be miscible with the sample  22 ). With these factors in mind, the pump  10 , therefore, enables substantial flexibility in the choice of a mobile phase.  
         [0024]     Alternatively, the pump fluid  18  may drive a piston where when it is desirable to isolate contact of the pump fluid  18  with a secondary fluid, gas, or sample substance. With reference now to  FIG. 2 , the pump  10  includes a piston  24  that is situated between the pump fluid  18  and the secondary fluid or gas  23 . The piston  24  may be a fluid with a high boiling point (i.e., sufficiently higher than the pump fluid  18  so that the piston fluid will not evaporate) that is immiscible with the pump fluid  18 . The piston fluid may also be chosen so as to avoid wetting the walls of the flow path  19 . Configured as shown in  FIG. 2 , the pump fluid  18  drives the piston  24  which in turn drives the secondary fluid or gas  23  into the microfluidic device  20 . The secondary fluid or gas may be the sample  22  or may be the mobile phase driving the sample  22 . An embodiment of an apparatus for pumping microfluidic devices is shown in which the pump fluid  18  drives a gas  23  into the microfluidic device  20 .  
         [0025]     A system in which the pump  10  is pumping fluid or gas may include a reservoir.  FIG. 3  illustrates a system utilizing an embodiment of an apparatus for pumping microfluidic devices, e.g., the embodiment shown in  FIG. 2 . As shown, the flow path  19  in the system includes a reservoir  26 . The reservoir  26  may include an amount of gas necessary for the desired analysis to be performed in the microfluidic device  20 .  
         [0026]     With reference again to  FIG. 2 , shown is an embodiment of the heat element  14 . The embodiment of the heat element  14  shown includes a heating coil wound around the reservoir  12 . A voltage supply  25  may be connected to the heating coil to provide the necessary voltage to activate and run the heating coil.  
         [0027]     With reference now to  FIGS. 4A-4C , shown are various embodiments of a system utilizing an embodiment of an apparatus for pumping microfluidic devices, e.g., the embodiment shown in  FIG. 1 . In the systems shown, the pump fluid  18  is the mobile phase driving the sample  22  into and through the microfluidic device  20 . As shown, the flow path  19  includes a sample loop  28 . The sample  22  is inserted into the mobile phase (e.g., the pump fluid  18 ) and, hence, into the flow path  19 , via the sample loop  28 .  
         [0028]     For example, the sample loop  28  may include a quantity of sample  22  and a switch (not shown) that diverts the pump fluid  18  from the flow path  19  into the sample loop  28 . When the switch is activated, the pump fluid  18  enters the sample loop  28  and drives the quantity of sample  22  in the sample loop  28  out of the sample loop  28  and into the flow path  19 . Once the sample  22  is driven out of the sample loop  28 , the switch may be deactivated and the pump fluid  18  will resume traveling through the flow path  19 , driving the inserted sample  22  into and through the microfluidic device  20 . In the meantime, the sample loop  28  may be refilled with a quantity of sample  22 .  
         [0029]     The process described in the preceding paragraph can be repeated again, as many times as necessary for multiple analyses to be performed in the microfluidic device  20 . In this manner, the system shown in  FIGS. 4A-4C  enables repeated injections of small amounts of isolated samples  22  into the microfluidics flow path. Greater instrument performance, reliability and usability can result from the greater integration of system components. By inserting the sample  22  into the mobile phase (e.g., the pump fluid  18 ), a small amount of isolated sample  22  may be efficiently provided to microfluidic device  20  for chromatographic separation.  
         [0030]     With reference again to  FIGS. 4A-4C , shown are microfluidic devices  20  with a variety of separation regions  30  and detectors  32 .  FIG. 4A  illustrates a microfluidic device  20  (i.e., a liquid chromatograph) with a serpentine separation region  30  and a connected detector  32 . The detector  32  detects the chromatographic elution of the individual components of the sample  22 , identifying the individual components and/or the amount of each.  FIG. 4B  illustrates a microfluidic device  20  (i.e., a liquid chromatograph) with a linear separation region  30  and a connected detector  32 .  FIG. 4C  illustrates a microfluidic device  20  (i.e., a liquid chromatograph) with a spiral separation region  30  and a connected detector  32 . Other microfluidic devices  20  and other separation regions  30  may be used.  
         [0031]     As discussed above, as heat is applied to the reservoir  12  by the heat element  14 , the evaporated pump fluid  16  will expand. The pump fluid  18  will be forced out of the reservoir  12  by the resulting pressure increase until no pump fluid  18  remains in the reservoir  12 . At this point, the reservoir  12  will be exhausted. The evaporated pump fluid  16  may continue to expand into the flow path  19  for some time, continuing to force the pump fluid  18  to flow to the microfluidic device  20 . The amount of continued expansion of the evaporated pump fluid  16  will be limited based on pump fluid, reservoir and other component (e.g., flow path  19 ) constants, the maximum heat supplied, and heat transfer characteristics of the evaporated pump fluid  16 . At the point which the expansion of the evaporated pump fluid  16  ceases, the flow of the pump fluid  18  will cease. For many types of analysis performed in microfluidic devices  20 , a continuous flow of the mobile phase (e.g., the pump fluid  18 ) is necessary or desirous until the analysis is complete. If the maximum expansion of the evaporated pump fluid  16  is reached or the flow of the pump fluid  18  otherwise stops before the analysis is complete, the flow will not be continuous.  
         [0032]     Moreover, evaporated pump fluid  16  may interfere with analysis performed by the microfluidic device  20 . Therefore, it may be necessary to prevent the evaporated pump fluid  16  from expanding to the point at which evaporated pump fluid  16  enters the microfluidic device  20 . It may also be desirous or necessary to prevent the evaporated pump fluid  16  from flowing beyond a certain point in the flow path  19  (in many cases the evaporated pump fluid  16  may reach its maximum expansion prior to flowing significantly into the flow path  19 , let alone the microfluidic device  20 ).  
         [0033]     With reference now to  FIG. 5 , shown is a system that addresses these issues. Specifically, the system shown enables the continuous flow of the mobile phase and may prevent evaporated pump fluid  16  from entering the microfluidic device  20  or beyond a certain point in the flow path  19 . The system includes two pumps  10 , a refill tank  34 , and a valve  36 . Additional pumps  10  may be added to the system. Further, although not shown, other components may be added to the flow path  19 , such as the gas reservoir  26  shown in  FIG. 3  or fluid reservoirs.  
         [0034]     In operation, a first pump  10  is activated and pumps the mobile phase (e.g., the pump fluid  18 ) until a certain switching point. The switching point may be, for example, when the evaporated pump fluid  16  reaches its maximum expansion, when the reservoir  12  is exhausted, when the flow of the pump fluid  18  stops, or when the evaporated pump fluid  16  reaches the valve  36 . The control  15  (not shown in  FIG. 5 ) may monitor the system and determine when the certain switching point is met. When the switching point is met, the valve  36  switches from the first pump  10  to a second pump  10 . The valve  36 , which may be controlled by the control  15 , may achieve this by closing the connection from the first pump  10  via the flow path  19  to the microfluidic device  20  and opening a connection from the second pump  10  via the flow path  19  to the microfluidic device  20 . The second pump  10  may be activated at a time sufficiently prior to the switching point so that the second pump  10  pumps pump fluid  18  into the flow path  19  as soon as the valve  36  switches to the second pump  10 . In this manner, the system maintains continuous pumping of the mobile phase.  
         [0035]     When the reservoir  12  in a pump  10  is exhausted, the exhausted reservoir  12  may be swapped with a full reservoir  12 . Alternatively, the exhausted reservoir  12  may simply be refilled. With continued reference to  FIG. 5 , the system shown enables the refilling of an exhausted reservoir  12  via pump fluid  18  stored in the refill tank  34 . The refill tank  34  is connected to the pumps  10 , and hence the reservoirs  12 , via the valve  36 . As shown, when the valve  36  closes the connection from the first pump  10  to the microfluidic device  20 , the valve  36  opens a connection from the refill tank  34  to the first pump  10 , specifically to the reservoir  12  of the first pump  10 .  
         [0036]     Simultaneously, or nearly so, the heat element  14  of the first pump  10  may be turned off and the reservoir  12  allowed to cool. A cooling element may also be activated to increase the cooling of the reservoir  12 . As discussed above, this cooling of the reservoir  12  causes the evaporated pump fluid  16  to condense, creating a vacuum in the reservoir  12  and reversing flow into the reservoir  12 . The vacuum and reversed flow draw the pump fluid  18  out of the refill tank  34  and into the reservoir  12 . As a result, the pump fluid  18  in the refill tank  34  will refill the reservoir  12  of the first pump  10 . The valve  36  may close the connection from the refill tank  34  to the first pump  10  if the reservoir  12  is filled with the pump fluid  18 . The control  15  may control the valve  36  and the refill operation.  
         [0037]     With continued reference to  FIG. 5 , other means, including gravity, may be used to cause the refill tank  34  to refill the reservoir  12  of the first pump  10 . Moreover, when the valve  36  closes the connection from the second pump  10  to the microfluidic device  20  and re-opens the connection from the first pump  10  to the microfluidic device  20 , the re-filled reservoir  12  of the first pump  10  enables the first pump  10  to maintain continuous pumping of the mobile phase, as described above. Further, when the valve  36  switches from the second pump  10  to the first pump  10 , the valve  36  opens a connection from the refill tank  34  to the second pump  10 , specifically to the reservoir  12  of the second pump  10 . As a result, the refilling process described herein can be performed with the second pump  10 .  
         [0038]     If additional pumps  10  are connected to the system, these additional pumps can provide continuous pumping and be refilled in like manners. For example, the valve  36  may sequentially switch between the pumps  10 , opening and closing connections to the microfluidic device  20  and the refill tank  34  as necessary to maintain continuous pumping and refill one pump  10  at a time. Alternatively, the valve  36  may maintain one open connection from a pump  10  to the microfluidic device  20  while opening a connection from the refill tank  34  to some or all of the remaining pumps  10  simultaneously. In this configuration, the refill tank  34  refills a plurality of pumps  10  simultaneously. Likewise, a system may comprise multiple valves  36  and/or multiple refill tanks  34  enabling still further configurations and operations as can be easily determined by one of skill in the art.  
         [0039]     With reference now to  FIG. 6 , illustrated is another system utilizing a plurality of apparatus for pumping microfluidic devices. The system comprises multiple valves  36  and a single refill tank  34 . Alternatively, the single refill tank  34  may be replaced by multiple refill tanks  34 . As shown, there are two pumps  10 , each connected to the refill tank  34  with a valve  36 . The valves  36  also connect the pumps  10  to the microfluidic device  20  via a switch  38  and the flow path  19 . The switch  38  switches between one pump  10  and the other pump  10 , connecting the pumps  10  to the microfluidic device  20 . The control  15  (not shown in  FIG. 6 ) may control the switch  38 . The switch  38  may switch between the pumps  10  based on a certain switching point as described above. The system may be configured with a plurality of additional pumps  10  connected to the switch  38  in the manner shown in  FIG. 6  (e.g., with a pump  10  connected via a valve  36  to the refill tank(s)  36  and to the switch  38 ).  
         [0040]     An advantage of the systems described herein, in addition to providing continuous pumping and easy refilling, is that such systems can be provided on a single chip or plate due to the size and characteristics of the pump  10 . Due to their nano-size, multiple pumps  10  may be etched on a chip or plate. The refill tanks  34 , valves  36  and switches  38  are similarly sized and may be similarly etched. Accordingly, the systems described enable greater miniaturization and compactness of microfluidic device systems than presently possible.  
         [0041]     As described above, the apparatus for pumping microfluidic devices may be utilized with a number of components and in different configurations. With reference now to  FIG. 7 , shown is a system including a pump  10  connected to a stream splitter  40  via a flow path  19 . The stream splitter  40  splits the mobile phase (e.g., the pump fluid  18 ) onto multiple paths, enabling the pump  10  to provide a mobile phase to multiple microfluidic devices  20  or as a means of reducing flow to a given device (flow reduction). If the pump fluid  18  is not the mobile phase, the stream splitter  40  may be placed on the flow path  19  at a location prior to where the pump fluid  18  encounters the mobile phase. The description herein is not intended to provide an exhaustive description of the various systems, configurations, and components with which the apparatus for pumping microfluidic devices may be utilized.  
         [0042]     The pumps  10  described herein are not limited to providing pump fluid  18  or the mobile phase. Likewise, the pumps  10  and systems utilizing the pumps  10  may be provided on a single chip or plate. Accordingly, the apparatus for pumping microfluidic devices may also facilitate the miniaturization of analytical techniques that are not currently miniaturized. For example, the apparatus for pumping microfluidic devices facilitates the miniaturization of the Flow Injection Analysis (FIA) technique. In FIA, a sample is mixed with a chemical reagent that reacts with a certain component(s). If there is a chemical reaction, the certain component(s) is known to be present. As is indicated by its name, FIA needs flow in order for the analysis to take place. A combination of pumps  10  could supply the reagents, diluents, gas segmentation (bubbles) and transport flow (e.g., the mobile phase) used in FIA. By using a combination of pumps  10 , complete sample handling may be accomplished on a single-chip or plate.  
         [0043]     With reference now to  FIG. 8 , illustrated is a FIA system utilizing a plurality of pumps  10 . The FIA system includes a mobile phase pump  42 , a reagent pump  44 , a sample input  46 , a mixer  48 , a mixer heater  52 , and a detector  54 . The sample input  46  may also be provided by a pump  10 . If diluents and/or gas segmentation is necessary for the FIA being performed, a diluent pump and/or gas pump may also be included. The pumps  42 - 46  may operate and be configured as described above for the pump  10 . The mobile phase pump  42  evaporates a pump fluid and provides the flow necessary for the FIA. Alternatively, the reagent may be the mobile phase. For example, the reagent may be the pump fluid  18  that is evaporated or the reagent may be separated from the pump fluid  18  by a piston  24  and driven by the pump fluid  18  as described-above. If the reagent is the mobile phase, then the mobile phase pump  42  and the reagent pump  44  may be replaced by a single pump.  
         [0044]     With reference now to  FIG. 9 , illustrated is a system utilizing a plurality of pumps  10  to form mobile phase gradients. As shown, the pumps  10  are joined by a coupling device  60  to a flow path  19 . Each pump  10  includes different effluents; accordingly, combining together effluent of the pumps  10  enables different mixtures of the mobile phases. The relative flow rates of liquids from the pumps  10  or the time-gated selection of flow from each pump dictates the composition of the mixture. By appropriately applying heat independently to the pumps  10 , e.g., via separate heat elements  14  for each pump  10 , relative flow rates may be adjusted. By using a valve or combination of valves (e.g., a proportioning valve(s)) within the coupling devices of constant flow or pressure, the relative amounts of fluids from each pump can be controlled by the relative duration of time each stream is allowed to pass to the combined flow stream. In this manner, the system shown in  FIG. 9  can provide flexibility in mobile phase composition, analogous to gradient elution separations common to traditional scale separations.  
         [0045]     The apparatus for pumping microfluidic devices may also be used for Solid Phase Extraction (SPE). A system, such as the systems shown in FIGS.  5  or  6 , may include multiple pumps  10 , each with a different solvent as the pump fluid  18 . A weak solvent in a first pump  10  may be used as a sample preparation, pumped through the microfluidic device  20  to prepare the microfluidic device  20  for the sample  22 . A moderate solvent in a second pump  10  may be used as the mobile phase for the chromatographic separation. A strong solvent in a third pump  10  may be used as a drive-off solvent to cleanse the microfluidic device  20  after the analysis is performed.  
         [0046]     The pump  10  may also be used to activate a diaphragm valve. When the pump  10  is activated and the heat element  14  provides heat, the pump  10  may supply pressure to the diaphragm valve, deforming the diaphragm until it closes an associated channel or opening. When the heat element stops providing heat, the evaporated pump fluid  16  will condense, the pressure will reduce, and the diaphragm will reform, opening the associated channel or opening.  
         [0047]     As is apparent from the description herein, the apparatus and method for pumping microfluidic devices have a significant number of advantages. These advantages may include, for example: no pulsation related to mechanical pumping; no moving parts; no pump fluid (e.g., solvent) waste due to splitting; environmentally friendly and minimal clean-up due to minimized waste; effective coupling to nano-scale devices; enhanced portability of microfluidic systems; flexibility in mobile phase composition (e.g., non-aqueous or gaseous); predictable relationships between temperature, pressure, flow and watts supplied; low cost; multiple simple construction approaches; ability to do standard LC separations on microfluidic devices; sample preparation (dilution, transfer, addition of reagents, rinsing, etc.); freedom from needing external mobile phase reservoirs; less void volume/time/delay during mobile phase ramping; and many others inherent from the above description.  
         [0048]     These advantages enable many different applications utilizing the apparatus and method for pumping microfluidic devices. For example, a small, portable, disposable FIA system may be built as described above. The FIA system illustrated in  FIG. 8  may be implemented on a single chip or plate and contained in a small box. Such a FIA system could be used for a Homeland Defense implementation. For example, the FIA system could be loaded with reagents for detecting the presence of Ricin. A small sample is collected and input into the FIA system. If the Ricin is present, the FIA system will indicate such. After being used, the FIA system is disposed. Since there is no waste, the FIA system can be disposed in an environmentally friendly and safe way.  
         [0049]     It should be noted that the illustrations provided by the Figures herein are not intended to be to scale. Moreover, the arrangement of various elements in the Figures are not intended to indicate a particular orientation (e.g., above or below) of the elements.  
         [0050]     The foregoing description provides illustration and description, but is not intended to be exhaustive or to limit the invention to the embodiments disclosed. Modifications and variations are possible consistent with the above teachings or may be acquired from practice of the embodiments disclosed. Therefore, it is noted that the scope is defined by the claims and their equivalents.