Abstract:
A network of microfluidic channels may include at least three loops interconnected at a junction. Each of the loops may include a fluid channel having a length extending from the junction to a second end; and a fluid actuator along the fluid channel and located at a first distance from junction along the length of the fluid channel and at a second distance less than the first distance from the second end. Activation of the fluid actuator of selected ones of the at least three loops may selectively produce net fluid flow in different directions about the loops. In one implementation, a fluid channel having a fluid actuator may have a bridging portion that extends over another fluid channel.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
       [0001]    The present application is a continuation application that claims priority from co-pending U.S. patent application Ser. No. 13/698,064 filed on Nov. 15, 2012 by Kornilovich et al. and entitled MICROFLUIDIC SYSTEMS AND NETWORKS, the full disclosure of which is hereby incorporated by reference. 
     
    
     BACKGROUND 
       [0002]    Microfluidics is an increasingly important technology that applies across a variety of disciplines including engineering, physics, chemistry, microtechnology and biotechnology. Microfluidics involves the study of small volumes of fluid and how to manipulate, control and use such small volumes of fluid in various microfluidic systems and devices such as microfluidic chips. For example, microfluidic biochips (referred to as “lab-on-chip”) are used in the field of molecular biology to integrate assay operations for purposes such as analyzing enzymes and DNA, detecting biochemical toxins and pathogens, diagnosing diseases, etc. 
         [0003]    The beneficial use of many microfluidic systems depends in part on the ability to properly introduce fluids into microfluidic devices and to control the flow of fluids through the devices. In general, an inability to manage fluid introduction and flow in microfluidic devices on a micrometer scale limits their application outside of a laboratory setting where their usefulness in environmental and medical analysis is especially valuable. Prior methods of introducing and controlling fluid in microfluidic devices have included the use of external equipment and various types of pumps that are not micrometer in scale. These prior solutions have disadvantages related, for example, to their large size, their lack of versatility, and their complexity, all of which can limit the functionality of the microfluidic systems implementing such microfluidic devices. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0004]    The present embodiments will now be described, by way of example, with reference to the accompanying drawings, in which: 
           [0005]      FIG. 1  shows a microfluidic system suitable for incorporating microfluidic devices, networks and inertial pumps, according to an embodiment; 
           [0006]      FIG. 2  shows examples of closed, unidirectional, one-dimensional fluidic networks with integrated inertial pumps, according to some embodiments; 
           [0007]      FIG. 3  shows examples of closed, bidirectional, one-dimensional fluidic networks with integrated inertial pumps, according to some embodiments; 
           [0008]      FIG. 4  shows an example of an open, bidirectional, one-dimensional fluidic network with an integrated inertial pump, according to an embodiment; 
           [0009]      FIG. 5  shows an example of a closed, two-dimensional fluidic network illustrating fluid flow patterns generated by different pump activation regimes through selective activation of single fluid pump actuators, according to an embodiment; 
           [0010]      FIG. 6  shows an example of a closed, two-dimensional fluidic network illustrating fluid flow patterns generated by different pump activation regimes through selective activation of two fluid pump actuators, according to an embodiment; 
           [0011]      FIG. 7  shows an example of a closed, two-dimensional fluidic network illustrating fluid flow patterns generated by different pump activation regimes through selective activation of three fluid pump actuators, according to an embodiment; 
           [0012]      FIG. 8  shows a top down view and corresponding cross-sectional view of an example of an open, bidirectional, three-dimensional fluidic network, according to an embodiment; 
           [0013]      FIG. 9  shows examples of fluidic networks incorporating both fluid pump actuators and active elements, according to some embodiments; 
           [0014]      FIG. 10  shows a side view of an example fluidic network channel with an integrated fluid pump actuator in different stages of operation, according to an embodiment; 
           [0015]      FIG. 11  shows the active fluid actuator at the operating stages from  FIG. 10 , according to an embodiment; 
           [0016]      FIGS. 12, 13 and 14  show the active fluid actuator at the operating stages from  FIG. 10 , including net fluid flow direction arrows, according to some embodiments; 
           [0017]      FIGS. 15, 16 and 17  show example displacement pulse waveforms, according to some embodiments; and 
           [0018]      FIG. 18  shows a side view of an example fluidic network channel with an integrated fluid pump actuator in different stages of operation, according to an embodiment. 
       
    
    
     DETAILED DESCRIPTION 
     Overview of Problem and Solution 
       [0019]    As noted above, previous methods of managing fluid in microfluidic devices include the use of external equipment and pump mechanisms that are not micrometer in scale. These solutions have disadvantages that can limit the range of applications for microfluidic systems. For example, external syringes and pneumatic pumps are sometimes used to inject fluids and generate fluid flow within microfluidic devices. However, the external syringes and pneumatic pumps are bulky, difficult to handle and program, and have unreliable connections. These types of pumps are also limited in versatility by the number of external fluidic connections the microfluidic device/chip can accommodate. 
         [0020]    Another type of pump is a capillary pump that works on the principle of a fluid filling a set of thin capillaries. As such, the pump provides only a single-pass capability. Since the pump is completely passive, the flow of fluid is “hardwired” into the design and cannot be reprogrammed. Electrophoretic pumps can also be used, but require specialized coating, complex three-dimensional geometries and high operating voltages. All these properties limit the applicability of this type of pump. Additional pump types include peristaltic and rotary pumps. However, these pumps have moving parts and are difficult to miniaturize. 
         [0021]    Embodiments of the present disclosure improve on prior solutions for fluid management in microfluidic systems and devices, generally through improved microfluidic devices that enable complex and versatile microfluidic networks having integrated inertial pumps with fluid actuators. The disclosed microfluidic networks may have one-dimensional, two-dimensional, and/or three-dimensional topologies, and can therefore be of considerable complexity. Each fluidic channel edge within a network can contain one, more than one, or no fluid actuator. Fluid actuators integrated within microfluidic network channels at asymmetric locations can generate both unidirectional and bidirectional fluid flow through the channels. Selective activation of multiple fluid actuators located asymmetrically toward the ends of multiple microfluidic channels in a network enables the generation of arbitrary and/or directionally-controlled fluid flow patterns within the network. In addition, temporal control over the mechanical operation or motion of a fluid actuator enables directional control of fluid flow through a fluidic network channel. Thus, in some embodiments precise control over the forward and reverse strokes (i.e., compressive and tensile fluid displacements) of a single fluid actuator can provide bidirectional fluid flow within a network channel and generate arbitrary and/or directionally-controlled fluid flow patterns within the network. 
         [0022]    The fluid actuators can be driven by a variety of actuator mechanisms such as thermal bubble resistor actuators, piezo membrane actuators, electrostatic (MEMS) membrane actuators, mechanical/impact driven membrane actuators, voice coil actuators, magneto-strictive drive actuators, and so on. The fluid actuators can be integrated into microfluidic systems using conventional microfabrication processes. This enables complex microfluidic devices having arbitrary pressure and flow distributions. The microfluidic devices may also include various integrated active elements such as resistive heaters, Peltier coolers, physical, chemical and biological sensors, light sources, and combinations thereof. The microfluidic devices may or may not be connected to external fluid reservoirs. Advantages of the disclosed microfluidic devices and networks generally include a reduced amount of equipment needed to operate microfluidic systems, which increases mobility and widens the range of potential applications. 
         [0023]    In one example embodiment, a microfluidic system includes a fluidic channel coupled at both ends to a reservoir. A fluid actuator is located asymmetrically within the channel creating a long and short side of the channel that have non-equal inertial properties. The fluid actuator is to generate a wave that propagates toward both ends of the channel and produces a unidirectional net fluid flow through the channel. A controller can selectively activate the fluid actuator to control the unidirectional net fluid flow through the channel. In one implementation, the fluid actuator is a first fluid actuator located toward a first end of the channel, and a second fluid actuator is located asymmetrically within the channel toward a second end of the channel. The controller can activate the first fluid actuator to cause net fluid flow through the channel in a first direction from the first end to the second end, and can activate the second fluid actuator to cause net fluid flow through the channel in a second direction from the second end to the first end. 
         [0024]    In another example embodiment, a microfluidic system includes a network of microfluidic channels having first and second ends. The channel ends are coupled variously to one another at end-channel intersections. At least one channel is a pump channel having a short side and a long side distinguished by a fluid actuator located asymmetrically between opposite ends of the pump channel. The fluid actuator is to generate a wave propagating toward the opposite ends of the pump channel that produces a unidirectional net fluid flow through the pump channel. In one implementation, a second fluid actuator integrated within the channel is located asymmetrically toward a second end of the pump channel, and a controller can selectively activate the first and second fluid actuators to generate bidirectional fluid flow through the network. In another implementation, additional fluid actuators are located asymmetrically toward first and second ends of multiple microfluidic channels and a controller can selectively activate the fluid actuators to induce directionally-controlled fluid flow patterns throughout the network. 
         [0025]    In another embodiment, a microfluidic network includes microfluidic channels in a first plane to facilitate two-dimensional fluid flow through the network within the first plane. A microfluidic channel in the first plane extends into a second plane to cross over and avoid intersection with another microfluidic channel in the first plane, which facilitates three-dimensional fluid flow through the network within the first and second planes. An active element is integrated within at least one microfluidic channel. Fluid actuators are integrated asymmetrically within at least one microfluidic channel, and a controller can selectively activate the fluid actuators to induce directionally-controlled fluid flow patterns within the network. 
         [0026]    In another example embodiment, a method of generating net fluid flow in a microfluidic network includes generating compressive and tensile fluid displacements that are temporally asymmetric in duration. The displacements are generated using a fluid actuator that is integrated asymmetrically within a microfluidic channel. 
         [0027]    In another example embodiment, a microfluidic system includes a microfluidic network. A fluid actuator is integrated at an asymmetric location within a channel of the network to generate compressive and tensile fluid displacements of different durations within the channel. A controller regulates fluid flow direction through the channel by controlling the compressive and tensile fluid displacement durations of the fluid actuator. 
         [0028]    In another example embodiment, a method of controlling fluid flow in a microfluidic network includes generating asymmetric fluid displacements in a microfluidic channel with a fluid actuator located asymmetrically within the channel. 
       Illustrative Embodiments 
       [0029]      FIG. 1  illustrates a microfluidic system  100  suitable for incorporating microfluidic devices, networks and inertial pumps as disclosed herein, according to an embodiment of the disclosure. The microfluidic system  100  can be, for example, an assay system, a microelectronics cooling system, a nucleic acid amplification system such as a polymerase chain reaction (PCR) system, or any system that involves the use, manipulation and/or control of small volumes of fluid. Microfluidic system  100  typically implements a microfluidic device  102  such as a microfluidic chip (e.g., a “lab-on-a-chip”) to enable a wide range of microfluidic applications. A microfluidic device  102  generally includes one or more fluidic networks  103  having channels with inertial pumps for circulating fluid throughout the network. In general, the structures and components of a microfluidic device  102  can be fabricated using conventional integrated circuit microfabrication techniques such as electroforming, laser ablation, anisotropic etching, sputtering, dry etching, photolithography, casting, molding, stamping, machining, spin coating and laminating. A microfluidic system  100  may also include an external fluid reservoir  104  to supply and/or circulate fluid to microfluidic device  102 . Microfluidic system  100  also includes an electronic controller  106  and a power supply  108  to provide power to microfluidic device  102 , the electronic controller  106 , and other electrical components that may be part of system  100 . 
         [0030]    Electronic controller  106  typically includes a processor, firmware, software, one or more memory components including volatile and non-volatile memory components, and other electronics for communicating with and controlling microfluidic device  102  and fluid reservoir  104 . Accordingly, electronic controller  106  is programmable and typically includes one or more software modules stored in memory and executable to control microfluidic device  102 . Such modules may include, for example, a fluid actuator selection, timing and frequency module  110 , and a fluid actuator asymmetric operation module  112 , as shown in  FIG. 1 . 
         [0031]    Electronic controller  106  may also receive data  114  from a host system, such as a computer, and temporarily store the data  114  in a memory. Typically, data  114  is sent to microfluidic system  100  along an electronic, infrared, optical, or other information transfer path. Data  114  represents, for example, executable instructions and/or parameters for use alone or in conjunction with other executable instructions in software/firmware modules stored on electronic controller  106  to control fluid flow within microfluidic device  102 . Various software and data  114  executable on programmable controller  106  enable selective activation of fluid actuators integrated within network channels of a microfluidic device  102 , as well as precise control over the timing, frequency and duration of compressive and tensile displacements of such activation. Readily modifiable (i.e., programmable) control over the fluid actuators allows for an abundance of fluid flow patterns available on-the-fly for a given microfluidic device  102 . 
         [0032]      FIG. 2  shows examples of closed, unidirectional, one-dimensional (i.e., linear) fluidic networks  103  (A, B, C, D) having integrated inertial pumps  200  suitable for implementing within a microfluidic device  102 , according to embodiments of the disclosure. As used in this document: A “closed” network means a network that has no connections with an external fluid reservoir; A “unidirectional” network means a network that generates fluid flow in only one direction; and, A one-dimensional network means a linear network. An inertial pump  200  generally includes a pump channel  206  with an integrated fluid actuator  202  disposed asymmetrically toward one end of the pump channel  206 . Note that in some embodiments as discussed below, a network channel  204  itself serves as a pump channel  206 . The example inertial pumps  200  of  FIG. 2  each have a fluid pump actuator  202  to move fluid through the pump channel  206  between network channels  204  ( 1  and  2 ). In this example, each network channel  204  serves as a fluid reservoir at each end of pump channel  206 . Although the networks  103  (A, B, C, D) are one-dimensional (i.e., linear) with fluid to flow from one end to the other end, the dashed lines shown at the ends of the network channels  204  ( 1  and  2 ) are intended to indicate that in some embodiments the network channels  204  may extend farther as part of a larger network  103  that has additional dimensions (i.e., two and three dimensions) where the network channels  204  intersect with other network channels as part of such a larger network  103 . Examples of such larger networks are discussed below. 
         [0033]    The four inertial pumps  200  shown in networks A, B, C and D, of  FIG. 2  each contain a single integrated fluid pump actuator  202  located asymmetrically within the pump channels  206  toward one end of the pump channel  206 . The fluid actuators  202  in the pumps  200  of networks A and C are passive, or not activated, as indicated by the Legend provided in  FIG. 2 . Therefore, there is no net fluid flow through the pump channels  206  between network channels  1  and  2  ( 204 ). However, the fluid actuators  202  in the pumps  200  of networks B and D are active, which generates net fluid flow through the pump channels  206  between network channels  1  and  2  ( 204 ). 
         [0034]    A fluidic diodicity (i.e., unidirectional flow of fluid) is achieved in active inertial pumps  200  of networks B and D through the asymmetric location of the fluid actuators  202  within the pump channels  206 . When the width of the inertial pump channel  206  is smaller than the width of the network channels  204  it is connecting (e.g., network channels  1  and  2 ), the driving power of the inertial pump  200  is primarily determined by the properties of the pump channel  206  (i.e., the width of the pump channel and the asymmetry of the fluid actuator  202  within the pump channel). The exact location of a fluid actuator  202  within the pump channel  206  may vary somewhat, but in any case will be asymmetric with respect to the length of the pump channel  206 . Thus, the fluid actuator  202  will be located to one side of the center point of the pump channel  206 . With respect to a given fluid actuator  202 , its asymmetric placement creates a short side of the pump channel  206  and a long side of the pump channel  206 . Thus, the asymmetric location of the active fluid actuator  202  in inertial pump  200  of network B nearer to the wider network channel  2  ( 204 ) is the basis for the fluidic diodicity within the pump channel  206  which causes the net fluid flow from network channel  2  to network channel  1  (i.e., from right to left). Likewise, the location of the active fluid actuator  202  in pump  200  of network D at the short side of the pump channel  206  causes the net fluid flow from network channel  1  to network channel  2  (i.e., from left to right). The asymmetric location of the fluid actuator  202  within the pump channel  206  creates an inertial mechanism that drives fluidic diodicity (net fluid flow) within the pump channel  206 . The fluid actuator  202  generates a wave propagating within the pump channel  206  that pushes fluid in two opposite directions along the pump channel  206 . When the fluid actuator  202  is located asymmetrically within the pump channel  206 , there is a net fluid flow through the pump channel  206 . The more massive part of the fluid (contained, typically, in the longer side of the pump channel  206 ) has larger mechanical inertia at the end of a forward fluid actuator pump stroke. Therefore, this body of fluid reverses direction more slowly than the liquid in the shorter side of the channel. The fluid in the shorter side of the channel has more time to pick up the mechanical momentum during the reverse fluid actuator pump stroke. Thus, at the end of the reverse stroke the fluid in the shorter side of the channel has larger mechanical momentum than the fluid in the longer side of the channel. As a result, the net flow is typically in the direction from the shorter side to the longer side of the pump channel  206 . Since the net flow is a consequence of non-equal inertial properties of two fluidic elements (i.e., the short and long sides of the channel), this type of micropump is called an inertial pump. 
         [0035]      FIG. 3  shows examples of closed, bidirectional, one-dimensional (i.e., linear) fluidic networks  103  (A, B) having integrated inertial pumps  200  suitable for implementing within a microfluidic device  102  such as discussed above with reference to  FIG. 2 , according to embodiments of the disclosure. Instead of one fluid pump actuator  202 , the example inertial pumps  200  of  FIG. 3  have two fluid pump actuators  202  to move fluid through and between network channels  204 . The two fluid actuators  202  are located asymmetrically toward opposite sides of each pump channel  206 . Having a fluid actuator  202  at each side of the pump channel  206  enables the generation of net fluid flow through the channel  206  in either direction depending on which fluid actuator  202  is active. Thus, in inertial pump  200  of network A of  FIG. 3 , the active fluid actuator  202  is located asymmetrically toward the right side of the pump channel  206  near network channel  2 , and the net fluid flow generated is from the right side of the pump channel  206  (the short side) to the left side (the long side), which moves fluid from network channel  2  toward network channel  1 . Similarly, in inertial pump  200  of network B, the active fluid actuator  202  is located asymmetrically toward the left side of the pump channel  206  near network channel  1 , and the net fluid flow generated is from the left side of the pump channel  206  (again, the short side) to the right side (the long side), which moves fluid from network channel  1  toward network channel  2 . 
         [0036]    As noted above, controller  106  is programmable to control a microfluidic device  102  in a variety of ways. As an example, with respect to the inertial pumps  200  of  FIG. 2  which each have a single integrated fluid pump actuator  202 , the module  110  (i.e., the fluid actuator selection, timing and frequency module  110 ) in controller  106  enables the selective activation of any number of actuators  202  in any number of pump channels  206  throughout a network  103 . Thus, although the networks A, B, C, and D, are one-dimensional, having inertial pumps  200  with only one fluid actuator  202 , in different embodiments they may be part of larger networks where selective activation of other actuators  202  in other interconnecting network channels  204  can enable control over the direction of fluid flow throughout a larger network  103 . Module  110  also enables control over the timing and frequency of activation of the fluid actuators  202  to manage when net fluid flow is generated and the rate of fluid flow. With respect to the inertial pumps  200  of  FIG. 3 , which have two fluid actuators  202  located asymmetrically toward opposite sides of each pump channel  206 , the module  110  on controller  106  enables selective activation of the two actuators within a single pump channel  206  in addition to selective activation of any number of actuators in any number of other pump channels throughout a larger network  103 . The ability to selectively activate fluid actuators in this manner enables control over the direction of fluid flow within individual network channels  204 , as well as throughout an entire expanded network  103 . 
         [0037]      FIG. 4  shows an example of an open, bidirectional, one-dimensional fluidic network  103  having an integrated inertial pump  200  suitable for implementing within a microfluidic device  102 , according to an embodiment of the disclosure. As used in this document, an “open” network is a network that connects to at least one external fluid reservoir such as reservoir  400 . When connecting with a fluid reservoir  400 , in the same manner as connecting with network channels  204 , if the width of the inertial pump  200  is smaller than the width of the fluid reservoir  400  it is connecting to, the driving power of the inertial pump  200  is primarily determined by the properties of the pump channel  206  (i.e., the width of the pump channel and the asymmetry of the fluid actuator  202  within the pump channel). Thus, in this example, while one end of the pump channel  206  connects to an external fluid reservoir  400  and the other end of the pump channel  206  connects to a network channel  204  (Channel  1 ), both the reservoir  400  and the network channel  204  serve as fluid reservoirs with respect to the driving power of the inertial pump  200 . In other implementations of such an “open” network  103 , both ends of the pump channel  206  can readily be connected to external fluid reservoirs  400 . The asymmetric location of the fluid actuator  202  in pump  200  of network  103  at the short side of the pump channel  206  near the wider fluid reservoir  400  is the basis for fluidic diodicity within the pump channel  206  which causes a net fluid flow from the fluid reservoir  400  to network channel  1  (i.e., from right to left). Note that one reservoir  400  can be connected to a network  103  by more than one pump channel  206 , or to one or more network channels  204  with or without any inertial pumps. In general, reservoirs may facilitate a variety of fluidic applications by providing storage and access to various fluids such as biological samples to be analyzed, waste collectors, containers of DNA building blocks and so on. 
         [0038]    Networks  103  within a microfluidic device  102  may have one-dimensional, two-dimensional, or three-dimensional topologies, as noted above. For example, the networks  103  in  FIGS. 2 and 3  discussed above are shown as linear, or one-dimensional networks  103 . However, the network channels  204  within these networks are also discussed in terms of potentially being connected to other network channels as part of larger networks  103 .  FIGS. 5-7  show examples of such larger networks  103 , demonstrating two-dimensional network topologies. 
         [0039]      FIG. 5  shows an example of a closed, two-dimensional fluidic network  103  illustrating fluid flow patterns (A, B, C, D) generated by different pump activation regimes through selective activation of singular fluid pump actuators  202  within the network  103 , according to an embodiment of the disclosure. The two-dimensional network  103  has four fluid pump actuators  202  and eight network channels (or edges) separated by five vertices or channel intersections (referenced as  1 ,  2 ,  3 ,  4 ,  5 ). In this embodiment, inertial pumps include fluid pump actuators  202  integrated into network channels  204 . Therefore, separate pump channels as discussed above in previous networks are not shown. The network channels  204  themselves serve as pump channels for the fluid pump actuators  202 . The narrower widths of the network channels  204  connected at the wider channel intersections (vertices  1 ,  2 ,  3 ,  4 ,  5 ) enables the driving power of the inertial pump, which is based on the asymmetric placement of the fluid actuators  202  within the narrower widths of the network channels  204 . 
         [0040]    Referring to network  103  of  FIG. 5  exhibiting fluid flow pattern A, the active fluid actuator  202  (see the Legend in  FIG. 5  identifying the active fluid actuator) generates net fluid flow in a direction from vertex  3  to vertex  5 , as indicated by the net flow direction arrow. At vertex  5  the flow of fluid divides and follows different directions through network channels extending from vertex  5  to vertices  1 ,  2  and  4 . Thereafter, the fluid flows back to vertex  3  from vertices  1 ,  2  and  4 , as indicated by the net flow direction arrows. Thus, the selective activation of the single fluid pump actuator  202  near vertex  3  as shown in flow pattern A results in a particular directional flow of fluid throughout the network. 
         [0041]    By contrast, the selective activations of other individual fluid pump actuators  202  as shown in flow patterns B, C and D, result in entirely different directional fluid flows through the network  103 . For example, referring to network  103  of  FIG. 5  exhibiting fluid flow pattern B, the active fluid actuator  202  generates net fluid flow in a direction from vertex  1  to vertex  5 , as indicated by the net flow direction arrow. At vertex  5  the flow of fluid divides and follows different directions through network channels extending from vertex  5  to vertices  2 ,  3  and  4 . Thereafter, the fluid flows back to vertex  1  from vertices  2 ,  3  and  4 , as indicated by the net flow direction arrows. Different directional fluid flows apply similarly to the flow patterns C and D. Accordingly, a programmable controller  106  in a microfluidic system  100  can readily adjust fluid flow patterns within a particular network  103  of a microfluidic device  102  through the selective activation of a single fluid pump actuator  202  within the network. 
         [0042]      FIG. 6  shows an example of a closed, two-dimensional fluidic network  103  illustrating fluid flow patterns (E, F, G, H, I, J) generated by different pump activation regimes through selective activation of two fluid pump actuators  202  simultaneously within the network  103 , according to an embodiment of the disclosure. The two-dimensional network  103  is the same as shown in  FIG. 5 , and has four fluid pump actuators  202  with eight network channels (or edges) separated by five vertices or channel intersections (referenced as  1 ,  2 ,  3 ,  4 ,  5 ). The selective activation of two fluid pump actuators  202  simultaneously as shown in the fluid flow patterns (E, F, G, H, I, J) results in particular directional fluid flows through the network  103  that vary for each pattern. 
         [0043]    Referring to network  103  of  FIG. 6  exhibiting fluid flow pattern E, for example, the active fluid actuators  202  generate net fluid flow in directions from vertices  2  and  3  to vertex  5 , as indicated by the net flow direction arrows. At vertex  5  the flow of fluid divides and follows different directions through network channels extending from vertex  5  to vertices  1  and  4 . Thereafter, the fluid flows back to vertices  2  and  3  from vertices  1  and  4 , as indicated by the net flow direction arrows. Note that there is no net fluid flow in network channels between vertices  1  and  4 , and vertices  2  and  3 . Thus, the selective activation of two fluid pump actuators  202  near vertices  2  and  3  simultaneously as shown in the fluid flow pattern E results in particular directional flow of fluid throughout the network. For each of the other fluid flow patterns shown in  FIG. 6 , different directional fluid flows are generated as indicated by the net flow direction arrows in each pattern. Thus, a programmable controller  106  in a microfluidic system  100  can readily adjust fluid flow patterns within a particular network  103  of a microfluidic device  102  through the selective activation of a two fluid pump actuators  202  simultaneously within the network. 
         [0044]      FIG. 7  shows an example of a closed, two-dimensional fluidic network  103  illustrating fluid flow patterns (K, L, M, N) generated by different pump activation regimes through selective activation of three fluid pump actuators  202  simultaneously within the network  103 , according to an embodiment of the disclosure. The two-dimensional network  103  is the same as shown in  FIG. 5 , and has four fluid pump actuators  202  with eight network channels (or edges) separated by five vertices or channel intersections (referenced as  1 ,  2 ,  3 ,  4 ,  5 ). The selective activation of three fluid pump actuators  202  simultaneously as shown in the fluid flow patterns (K, L, M, N) results in particular directional fluid flows through the network  103  that vary for each pattern. 
         [0045]    Referring to network  103  of  FIG. 7  exhibiting fluid flow pattern K, for example, the active fluid actuators  202  generate net fluid flow in directions from vertices  1 ,  2  and  3 , through vertex  5 , and on to vertex  4 , as indicated by the net flow direction arrows. At vertex  4  the flow of fluid divides and follows different directions through network channels extending from vertex  4  to vertices  1  and  3 . Fluid reaching vertices  1  and  3  divides again and flows in different directions to vertices  5  and  2 , as indicated by the net flow direction arrows. Thus, the selective activation of three of the four fluid pump actuators  202  near vertices  1 ,  2  and  3 , simultaneously, as shown in the fluid flow pattern K results in particular directional flow of fluid throughout the network  103 . For each of the other fluid flow patterns shown in  FIG. 7 , different directional fluid flows are generated as indicated by the net flow direction arrows in each pattern. The various fluid flow patterns can be implemented in the network of a microfluidic device  102  through selective activation of fluid actuators  202  by a programmable controller  106 . 
         [0046]    As noted above, networks  103  within a microfluidic device  102  may have one-dimensional, two-dimensional, or three-dimensional topologies.  FIG. 8  shows a top down view and corresponding cross-sectional view of an example of an open, bidirectional, three-dimensional fluidic network  103 , according to an embodiment of the disclosure. The open fluidic network  103  is connected to a fluidic reservoir  400  and facilitates fluid flow in three dimensions with a fluid channel crossing over another fluid channel. Such networks can be fabricated, for example, using conventional microfabrication techniques and a multilayer SU8 technology such as wet film spin coating and/or dry film lamination. SU8 is a transparent photoimageable polymer material commonly used as a photoresist mask for fabrication of semiconductor devices. As shown in  FIG. 8 , for example, the fluidic reservoir  400  and network channels  1 ,  2  and  3 , can be fabricated in a first SU8 layer. A second SU8 layer  802  can then be used to route fluidic channels over other channels to avoid unwanted channel intersections within the network. Such three-dimensional topologies enable complex and versatile microfluidic networks having integrated inertial pumps within microfluidic devices. 
         [0047]    The usefulness of microfluidic devices  102  is enhanced significantly by the integration of various active and passive elements used for analysis, detection, heating, and so on. Examples of such integrated elements include resistive heaters, Peltier coolers, physical, chemical and biological sensors, light sources, and combinations thereof.  FIG. 9  shows examples of several fluidic networks  103  incorporating both fluid pump actuators  202  and active elements  900 . Each of the fluidic networks discussed herein is suitable for incorporating such integrated elements  900  in addition to fluid pump actuators that provide a variety of fluid flow patterns within the networks. 
         [0048]    Although specific fluidic networks have been illustrated and discussed, the microfluidic devices  102  and systems contemplated herein can implement many other fluidic networks having a wide variety of layouts in one, two, and three dimensions, that include a multiplicity of configurations of integrated fluid pump actuators and other active and passive elements. 
         [0049]    As previously noted, the pumping effect of a fluidic pump actuator  202  depends on an asymmetric placement of the actuator within a fluidic channel (e.g., within a pump channel  206 ) whose width is narrower than the width of the reservoir or other channel (such as a network channel  204 ) from which fluid is being pumped. (Again, a pump channel may itself be a network channel that pumps fluid, for example, between wider fluid reservoirs). The asymmetric placement of the fluid actuator  202  to one side of the center point of a fluidic channel establishes a short side of the channel and a long side of the channel, and a unidirectional fluid flow can be achieved in the direction from the short side (i.e., where the fluid actuator is located) to the long side of the channel. A fluid pump actuator placed symmetrically within a fluidic channel (i.e., at the center of the channel) will generate zero net flow. Thus, the asymmetric placement of the fluid actuator  202  within the fluidic network channel is one condition that needs to be met in order to achieve a pumping effect that can generate a net fluid flow through the channel. 
         [0050]    However, in addition to the asymmetric placement of the fluid actuator  202  within the fluidic channel, another component of the pumping effect of the fluid actuator is its manner of operation. Specifically, to achieve the pumping effect and a net fluid flow through the channel, the fluid actuator should also operate asymmetrically with respect to its displacement of fluid within the channel. During operation, a fluid actuator in a fluidic channel deflects, first in one direction and then the other (such as with a flexible membrane or a piston stroke), to cause fluid displacements within the channel. As noted above, a fluid actuator  202  generates a wave propagating in the fluidic channel that pushes fluid in two opposite directions along the channel. If the operation of the fluid actuator is such that its deflections displace fluid in both directions with the same speed, then the fluid actuator will generate zero net fluid flow in the channel. To generate net fluid flow, the operation of the fluid actuator should be configured so that its deflections, or fluid displacements, are not symmetric. Therefore, asymmetric operation of the fluid actuator with respect to the timing of its deflection strokes, or fluid displacements, is a second condition that needs to be met in order to achieve a pumping effect that can generate a net fluid flow through the channel. 
         [0051]      FIG. 10  shows a side view of an example fluidic network channel  1000  with an integrated fluid pump actuator  1002  in different stages of operation, according to an embodiment of the disclosure. Fluidic reservoirs  1004  are connected at each end of the channel  1000 . The integrated fluid actuator  1002  is asymmetrically placed at the short side of the channel near an input to a fluidic reservoir  1004 , satisfying the first condition needed to create a pumping effect that can generate a net fluid flow through the channel. The second condition that needs to be satisfied to create a pump effect is an asymmetric operation of the fluid actuator  1002 , as noted above. The fluid actuator  1002  is generally described herein as being a piezoelectric membrane whose up and down deflections (sometimes referred to as piston strokes) within the fluidic channel generate fluid displacements that can be specifically controlled. However, a variety of other devices can be used to implement the fluid actuator including, for example, a resistive heater to generate a vapor bubble, an electrostatic (MEMS) membrane, a mechanical/impact driven membrane, a voice coil, a magneto-strictive drive, and so on. 
         [0052]    At operating stage A shown in  FIG. 10 , the fluid actuator  1002  is in a resting position and is passive, so there is no net fluid flow through the channel  1000 . At operating stage B, the fluid actuator  1002  is active and the membrane is deflected upward into the fluidic channel  1000 . This upward deflection, or forward stroke, causes a compressive displacement of fluid within the channel  1000  as the membrane pushes the fluid outward. At operating stage C, the fluid actuator  1002  is active and the membrane is beginning to deflect downward to return to its original resting position. This downward deflection, or reverse stroke, of the membrane causes a tensile displacement of fluid within the channel  1000  as it pulls the fluid downward. An upward and downward deflection is one deflection cycle. A net fluid flow is generated through the channel  1000  if there is temporal asymmetry between the upward deflection (i.e., the compressive displacement) and the downward deflection in repeating deflection cycles. Since temporal asymmetry and net fluid flow direction are discussed below with reference to  FIGS. 11-14 ,  FIG. 10  includes question marks inserted between opposite net flow direction arrows for the operating stages B and C. These question marks are intended to indicate that the temporal asymmetry between the compressive and tensile displacements has not been specified and therefore the direction of flow, if any, is not yet known. 
         [0053]      FIG. 11  shows the active fluid actuator  1002  at the operating stages B and C from  FIG. 10 , along with time markers “t 1 ” and “t 2 ” to help illustrate temporal asymmetry between compressive and tensile displacements generated by the fluid actuator  1002 , according to an embodiment of the disclosure. The time t 1  is the time it takes for the fluid actuator membrane to deflect upward, generating a compressive fluid displacement. The time t 2  is the time it takes for the fluid actuator membrane to deflect downward, or back to its original position, generating a tensile fluid displacement. Asymmetric operation of the fluid actuator  1002  occurs if the t 1  duration of the compressive displacement (upward membrane deflection) is greater or lesser than (i.e., not the same as) the t 2  duration of the tensile displacement (downward membrane deflection). Such asymmetric fluid actuator operation over repeating deflection cycles generates a net fluid flow within the channel  1000 . However, if the t 1  and t 2  compressive and tensile displacements are equal, or symmetric, there will be little or no net fluid flow through the channel  1000 , regardless of the asymmetric placement of the fluid actuator  1002  within the channel  1000 . 
         [0054]      FIGS. 12, 13 and 14  show the active fluid actuator  1002  at the operating stages B and C from  FIG. 10 , including net fluid flow direction arrows that indicate which direction fluid flows through the channel  1000 , if at all, according to embodiments of the disclosure. The direction of the net fluid flow depends on the compressive and tensile displacement durations (t 1  and t 2 ) from the actuator.  FIGS. 15, 16 and 17  show example displacement pulse waveforms whose durations correspond respectively with the displacement durations t 1  and t 2  of  FIGS. 12, 13 and 14 . For various fluid pump actuators the compressive displacement and tensile displacement times, t 1  and t 2 , can be precisely controlled by a controller  106 , for example, executing instructions such as from module  112  (the fluid actuator asymmetric operation module  112 ) within a microfluidic system  100 . 
         [0055]    Referring to  FIG. 12 , the compressive displacement duration, t 1 , is greater than the tensile displacement duration, t 2 , so there is a net fluid flow in a direction from the short side of the channel  1000  (i.e., the side where the actuator is located) to the long side of the channel. The difference between the compressive and tensile displacement durations, t 1  and t 2 , can be seen in  FIG. 15  which shows a corresponding example displacement pulse waveform that might be generated by the fluid actuator with a compressive displacement duration of t 1  and a tensile displacement duration of t 2 . The waveform of  FIG. 15  indicates a displacement pulse/cycle on the order of 1 pico-liter (pl) with the compressive displacement duration, t 1 , of approximately 0.5 microseconds (ms) and the tensile displacement duration, t 2 , of approximately 9.5 ms. The values provided for the fluid displacement amount and displacement durations are only examples and not intended as limitations in any respect. 
         [0056]    In  FIG. 13 , the compressive displacement duration, t 1 , is greater than the tensile displacement duration, t 2 , so there is a net fluid flow in the direction from the long side of the channel  1000  to the short side of the channel. The difference between the compressive and tensile displacement durations, t 1  and t 2 , can be seen in  FIG. 16  which shows a corresponding example displacement pulse waveform that might be generated by the fluid actuator with a compressive displacement duration of t 1  and a tensile displacement duration of t 2 . The waveform of  FIG. 16  indicates a displacement pulse/cycle on the order of 1 pico-liter (pl) with the compressive displacement duration, t 1 , of approximately 9.5 microseconds (ms) and the tensile displacement duration, t 2 , of approximately 0.5 ms. 
         [0057]    In  FIG. 14 , the compressive displacement duration, t 1 , is equal to the tensile displacement duration, t 2 , so there is little or no net fluid flow through the channel  1000 . The equal compressive and tensile displacement durations of t 1  and t 2 , can be seen in  FIG. 17  which shows a corresponding example displacement pulse waveform that might be generated by the fluid actuator with a compressive displacement duration of t 1  and a tensile displacement duration of t 2 . The waveform of  FIG. 17  indicates a displacement pulse/cycle on the order of 1 pico-liter (pl) with the compressive displacement duration, t 1 , of approximately 5.0 microseconds (ms) and the tensile displacement duration, t 2 , of approximately 5.0 ms. 
         [0058]    Note that in  FIG. 14 , although there is asymmetric location of the fluid actuator  1002  within the channel  1000  (satisfying one condition for achieving the pump effect), there is still little or no net fluid flow through the channel  1000  because the fluid actuator operation is not asymmetric (the second condition for achieving the pump effect is not satisfied). Likewise, if the location of the fluid actuator was symmetric (i.e., located at the center of the channel), and the operation of the actuator was asymmetric, there would still be little or no net fluid flow through the channel because both of the pump effect conditions would not be satisfied. 
         [0059]    From the above examples and discussion of  FIGS. 10-17 , it is significant to note the interaction between the pump effect condition of asymmetric location of the fluid actuator and the pump effect condition of asymmetric operation of the fluid actuator. That is, if the asymmetric location and the asymmetric operation of the fluid actuator work in the same direction, the fluid pump actuator will demonstrate a high efficiency pumping effect. However, if the asymmetric location and the asymmetric operation of the fluid actuator work against one another, the asymmetric operation of the fluid actuator reverses the net flow vector caused by the asymmetric location of the fluid actuator, and the net flow is from the long side of the channel to the short side of the channel  1000 . 
         [0060]    In addition, from the above examples and discussion of  FIGS. 10-17 , it can now be better appreciated that the fluid pump actuator  202  discussed above with respect to the microfluidic networks  103  of  FIGS. 2-8  is assumed to be an actuator device whose compressive displacement is greater that its tensile displacement. An example of such an actuator is a resistive heating element that heats the fluid and causes displacement by an explosion of supercritical vapor. Such an event has an explosive asymmetry whose expansion phase (i.e., compressive displacement) is faster than its collapse phase (i.e., tensile compression). The asymmetry of this event cannot be controlled in the same manner as the asymmetry of deflection caused by a piezoelectric membrane actuator, for example. 
         [0061]      FIG. 18  shows a side view of an example fluidic network channel  1000  with an integrated fluid pump actuator  1002  in different stages of operation, according to an embodiment of the disclosure. This embodiment is similar to that shown and discussed regarding  FIG. 10  above, except that the deflections of the fluid actuator membrane are shown working differently to create compressive and tensile displacements within the channel  1000 . At operating stage A shown in  FIG. 18 , the fluid actuator  1002  is in a resting position and is passive, so there is no net fluid flow through the channel  1000 . At operating stage B, the fluid actuator  1002  is active and the membrane is deflected downward and outside of the fluidic channel  1000 . This downward deflection of the membrane causes a tensile displacement of fluid within the channel  1000 , as it pulls the fluid downward. At operating stage C, the fluid actuator  1002  is active and the membrane is beginning to deflect upward to return to its original resting position. This upward deflection causes a compressive displacement of fluid within the channel  1000 , as the membrane pushes the fluid upward into the channel. A net fluid flow is generated through the channel  1000  if there is temporal asymmetry between the compressive displacement and the tensile displacement. The direction of a net fluid flow is dependent upon the durations of the compressive and tensile displacements, in the same manner as discussed above.