Abstract:
Multi-valve autoregulatory microfluidic devices and methods are described. The described devices and methods offer improved performance and new means of tuning autoregulatory effects in microfluidic devices.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
       [0001]    The present application claims priority to U.S. Prov. App. No. 61/201,889 filed on Dec. 16, 2008, which is incorporated herein by reference in its entirety. The present application is also related to U.S. Pat. App. No. 2007/0119510 which is incorporated herein by reference in its entirety. 
     
    
     STATEMENT OF GOVERNMENT GRANT 
       [0002]    The U.S. Government has certain rights in this invention pursuant to Grant No. W911NF-07-1-0277 awarded by ARO—US Army Robert Morris Acquisition Center, Grant No. HR0011-04-1-0032 awarded by DARPA and Grant No(s). HG002644 and 1K99007151 awarded by National Institutes of Health. 
     
    
     FIELD 
       [0003]    The present disclosure relates to microfluidic devices. In particular, it relates to multi-valve microfluidic devices and methods. 
       BACKGROUND 
       [0004]    Microfluidic autoregulator devices are shown in US Pat. App. No. 2007/0119510 A1 as mentioned above. For the sake of clarity and ease of read, some aspects of that disclosure are summarized in this section. 
         [0005]      FIG. 1  shows a top view of a current source ( 100 ). Fluid flows from an origin ( 110 ) to a sink ( 120 ) along a flow channel ( 130 ). The current source ( 100 ) is referenced as a “detour” current source in view of a dead-end detour ( 145 ) provided from a detour split ( 135 ) into a detour channel ( 140 ) and through a via ( 150 ) ending at a valve ( 160 ). It is noted from  FIG. 1  that the valve ( 160 ) (shown in white) is located in a different plane than the rest of the current source ( 100 ) (shown in gray) and a connection between the valve ( 160 ) and the rest of the current source ( 100 ) is made through the via ( 150 ). The valve ( 160 ) has a function of controlling the throughput of the current source ( 100 ). 
         [0006]    When viscous laminar flow is established into the flow channel ( 130 ), e.g. by applying pressure at the origin ( 110 ) and allowing the fluid to leave at the sink ( 120 ), Poiseuille&#39;s law establishes that static pressure will decrease from the origin ( 110 ) to the sink ( 120 ) down the flow channel ( 130 ). Simultaneously, there is no flow in the dead-end detour channel ( 140 ), so a static pressure there is constant and the same as the one at the detour split ( 135 ). As a result, a pressure difference is generated across the valve ( 160 ) and therefore the valve ( 160 ) constricts the flow channel ( 130 ). Thus an overall fluidic resistance of the flow channel ( 130 ) increases with applied pressure between the origin ( 110 ) and the sink ( 120 ). The result is a non-linear device. 
         [0007]      FIG. 2  shows a current source ( 200 ) in a “loop” configuration. Differently from the embodiment of  FIG. 1 , the current source ( 200 ) is not using a detour. The flow channel ( 230 ) passes through a valve ( 260 ), forming a loop ( 235 ) to the sink ( 220 ) through a via ( 250 ) and a channel ( 240 ). It is noted from  FIG. 2  that the channel ( 240 ) and the sink ( 220 ) (shown in gray) are located in a separate plane from that of the rest of the current source ( 200 ) (shown in white). 
         [0008]    In a similar way as described above in reference to  FIG. 1 , when fluid flows into the current source ( 200 ) by applying a pressure at an origin ( 210 ), a pressure difference across the valve ( 260 ) based on the Poiseuille&#39;s law results in a channel constriction. Hence, overall device resistance to flow from the origin ( 210 ) to the sink ( 220 ) increases as applied pressure increases resulting in a non-linear behavior of the current source ( 200 ). 
         [0009]    Referring to the representation of  FIG. 1 , the current source ( 100 ) comprises a multi-layer chip (not shown in this view) and can be constructed in two different configurations, “pushdown” (in which the valve ( 160 ) is fabricated above the main channel ( 130 ) and a valve membrane (not shown in this view) deflects downward to constrict the main channel( 130 )), or “pushup” (in which the valve ( 160 ) is fabricated below the main channel ( 130 ) and the valve membrane deflects upward to constrict the main channel ( 130 )). In the same way, referring to  FIG. 2 , a relative position of valve ( 260 ) and main channel ( 240 ) determines and allows for “pushdown” and “pushup” configurations to be executed with the loop current source ( 200 ). Therefore, four types of autoregulatory architectures are possible: pushdown detour, pushup detour, pushdown loop, and pushup loop. 
         [0010]    Further referring to  FIG. 1 , by varying various dimensions the current source ( 100 ), throughput can be controlled. As an example, by changing a detour ratio L 1 /L, the current source ( 100 ) throughput saturation level can be modified. As another example, varying the valve width W results in different throughput saturation levels. The larger is the valve width W, the lower is the throughput saturation level, while lowering saturation is important in building autoregulators of superior performance and quality. However, increasing the valve ( 160 ) width while maintaining the same thickness of membrane results in a flabby structure which may cause manufacturing issues. As an example, a flabby membrane can sag downward by gravity and get stuck in a lower channel during fabrication. This defect is usually irreversible in view of the material curing during a manufacturing process. Such effects pose challenges in manufacturing current sources with lower saturation points. 
       SUMMARY 
       [0011]    A solution to the problem illustrated in the background section is to construct architectures with a series of valves connected to a same detour channel and acting on a same flow channel. Such architectures lower the saturation point of a current source as they result in larger increases of resistance for the same increase in pressure. This solution is further described in the following sections of the present disclosure. Additionally, the presented architectures can be used as a novel tool to tune autoregulatory properties of current sources and their derivative compound devices. 
         [0012]    According to a first aspect, a method of controlling a microfluidic device throughput is provided, comprising: providing an origin of a fluid; providing a sink of the fluid; providing a flow channel containing the fluid; the flow channel coupling the origin and the sink; applying a pressure difference between the origin and the sink; and constricting the flow channel at a plurality of points on the flow channel by applying forces to the plurality of the points on the flow channel, wherein the forces are dependent on a throughput of the fluid. 
         [0013]    According to a second aspect, a multi-valve current source is provided, comprising: an origin of a fluid; a sink for the fluid; a flow channel coupling the origin and the sink; a plurality of valves communicated to the flow channel to selectively control flow of the fluid therethrough; and means dependent on flow through the flow channel for creating pressure differentials across the plurality of valves to at least partially activate the plurality of valves to control flow of fluid through the flow channel. 
         [0014]    Further aspects of the present disclosure are shown in the descriptions, drawings and claims of the present application. 
     
    
     
       BRIEF DESCRIPTION OF FIGURES 
         [0015]      FIG. 1  shows a top view of a prior art “detour” microfluidic current source. 
           [0016]      FIG. 2  shows a top view of a prior art “loop” microfluidic current source. 
           [0017]      FIGS. 3A-B  shows top views of detour multi-valve current sources. 
           [0018]      FIGS. 4A-B  shows top views of loop multi-valve current sources. 
       
    
    
     DETAILED DESCRIPTION 
       [0019]    Herein, multi-valve microfluidic devices and methods are described. 
         [0020]      FIGS. 3A-B  show top views of detour multi-valve current sources ( 300 A,  300 B) in respective pushdown and pushup configurations, in accordance with embodiments of the present disclosure. Throughout the present application, a current source is defined as a microfluidic device wherein the fluid throughput is substantially constant over a range of applied pressures. Sections shown in lighter color are located in a lower layer (not shown in this view) and the ones in darker color are located in an upper layer (not shown in this view). The sections in the lower layer are coupled with the ones in the upper layer through vias ( 350 ). Referring to  FIG. 1A , according to an embodiment of the disclosure, the detour multi-valve current sources ( 300 A,  300 B) have each three valves ( 360 ) denoted by letters A, B, and C. Moreover, each of the detour multi-valve current sources ( 300 A,  300 B) comprises an origin ( 310 ), a sink ( 320 ), a flow channel ( 330 ) and a detour channel ( 340 ) split from the flow channel ( 330 ) at a detour split ( 335 ). 
         [0021]    Referring to  FIGS. 3A-B , fluid flows from the origin ( 310 ) to the sink ( 320 ) by applying pressure to the origin ( 310 ). In a detour configuration, the static pressure inside the detour channel ( 340 ) is constant and the same as the one at the detour split ( 335 ). In other words, a side of the valve ( 360 ) connected to the detour channel ( 340 ) experiences the same static pressure as the detour split ( 335 ). At the same time, the pressures in the flow channel ( 330 ) on an other side of valves ( 360 ) A, B, and C are lower than the static pressure at the detour split ( 335 ) according to Poiseuille&#39;s law. As such, the valves ( 360 ) experience a pressure difference and therefore, constrict the flow channel ( 330 ). As each valve ( 360 ) has an independent contribution to an overall channel resistance, individual valve resistances add up. As a consequence, a larger increase in resistance as a function of applied pressure is achieved compared to a scenario wherein only one valve is used. In other words, at the same applied pressure, a multi-valve device offers a larger resistance than a single-valve device does, resulting in an accordingly lowered saturation throughput. 
         [0022]    Further referring to  FIGS. 3A-B , the person skilled in the art will understand that further embodiments utilizing any number of valves ( 360 ) can be envisaged. The person skilled in the art will also appreciate that a new lever of throughput control is achieved by changing the number of valves ( 360 ), in contrast with the ones described in reference to the embodiment of  FIG. 1 . Referring to  FIGS. 3A-B , according to an embodiment of the disclosure, varying a detour ratio L 1 /L can control a throughput of the detour multi-valve current sources ( 300 A,  300 B). According to further embodiments of the present disclosure, varying individual valve widths W 1 , W 2  and W 3  is also used to tune the throughput of the detour multi-valve current sources ( 300 A,  300 B). Additionally, since a detour length is measured from the common detour split ( 335 ) to the location of a respective valve down the main channel, multi-valve devices technically have their valves situated at different detour lengths, e.g. L 1 , L 2 , L 3  as shown in  FIGS. 3A-B . A combination of the detour lengths L 1 , L 2 , and L 3  with the flow channel ( 330 ) length L establishes different detour ratios (L 1 /L, L 2 /L, L 3 /L) and thus different saturation characteristics. Since these lengths are independently tunable, an increased flexibility in engineering operational parameters of autoregulatory devices can be achieved. In yet another embodiment of the present disclosure, the valves ( 360 ) are asymmetric having membranes with non-uniform width and/or thickness. Such embodiment provides an additional lever of control on autoregulatory behavior of the multi-valve current sources ( 300 A,  300 B). 
         [0023]      FIGS. 4A-B  show top views of loop multi-valve current sources ( 400 A,  400 B) in respective pushdown and pushup configurations, in accordance with further embodiments of the present disclosure. Sections shown in lighter color are located in a lower layer and the ones in darker color are located in an upper layer. The sections in the lower layer are coupled with the ones in the upper layer through vias ( 450 ). The embodiments shown in  FIGS. 4A-B , function according to the same principle as described above in reference to the embodiment of  FIGS. 2-3 . Three valves ( 460 ) A, B, and C are shown in  FIGS. 4A-B . According to embodiments of the present disclosure, in the same way as described regarding the embodiments of  FIGS. 3A-B , by varying individual widths W 1 , W 2  and W 3  of the valves ( 460 ), the loop multi-valve current source ( 400 ) throughput is controlled. Finally, the multi-valve loop current source ( 400 A,  400 B) in  FIGS. 4A-B  can be tuned by varying a location of the valves ( 460 ) along the flow channel ( 430 ). For example, moving a valve closer to an origin ( 410 ) will increase the pressure difference at the valve as a percentage of the total applied pressure (in analogy with an electrical potentiometer), leading to saturation at lower total applied pressure. 
         [0024]    The embodiments presented with reference to  FIGS. 3A-B  and  FIGS. 4A-B  are exemplary embodiments described in the context of a multi-layer fabrication approach. The person skilled in the art will understand that the described multi-valve architectures can also be built using other fabrication methods, such as single-layer fabrication. Furthermore, the multi-valve methods and concepts as described in the present disclosure are immediately applicable to microfluidic channels acting upon themselves to produce regulatory features and fabricated using any manufacturing approach. 
         [0025]    The present disclosure has shown microfluidic control devices and related methods. While the microfluidic control devices and related methods have been described by means of specific embodiments and applications thereof, it is understood that numerous modifications and variations could be made thereto by those skilled in the art without departing from the spirit and scope of the disclosure. It is therefore to be understood that within the scope of the claims, the disclosure may be practiced otherwise than as specifically described herein.