Abstract:
A valve for use in connection with microfluidic devices includes a safety feature such that flow is controlled even in the case of a loss of power, thus having applications in critical applications such as the precise delivery of drugs overtime. The valve may be used in connection with multiple tubes delivering drugs, and may be used with a pump, such as an electrochemical pump, to provide the force to move the fluids containing drugs for delivery. In certain applications, more than one medicine may be delivered and metered independently using a single pump with multiple reservoirs and valves.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application claims the benefit of U.S. provisional patent application No. 62/037,474, filed on Aug. 14, 2014, and entitled “Multifunctional Microvalves.” Such application is incorporated herein by reference in its entirety. 
     
    
     BACKGROUND 
       [0002]    The field of the invention is valves for microfluidic applications, and in particular to the use of such microvalves for safe and controlled delivery of fluids from a reservoir. 
         [0003]    Fluidic microvalves can be constructed from shape-memory alloys. For example, U.S. Pat. No. 7,260,932 teaches a fluid control pinch valve using shape memory alloy that receives a current to open or close the pinch valve. Similarly, U.S. Pat. No. 6,843,465 teaches a shape-memory wire actuated control valve, in which the shape-memory wire is connected to an electrical platform and mechanically coupled to a transfer mechanism. The actuator is actuated by conducting electrical current through the shape-memory wire causing the wire to contract and thereby actuating the transfer mechanism, which is operably coupled to the fluid control valve such that actuating and de-actuating the transfer mechanism opens and closes the valve. U.S. Pat. No. 6,742,761 teaches a poppet valve that is used for opening and closing a miniature latching valve by means of an actuator mechanism that includes a shape-memory alloy wire. The change in shape of the shape-memory alloy wire causes the poppet to either move toward or away from the valve seat, thereby either closing or opening the valve. U.S. Pat. No. 6,840,257 teaches a proportional valve using a shape-memory alloy actuator, with a shutter axially movable from and towards a valve seat under the control of a shape-memory alloy actuating member. 
         [0004]    Valves are a critical component of microfluidic systems. Miniaturized valves can be used in combination with miniaturized pumps to deliver pulsed and/or constant flow of microliter or nanoliter volumes of solution (or less). The valves themselves must be small and use little power to activate. Additional power can be saved by using a latching valve that does not require power to remain in any one state. Latching valves are not designed in a normally open or normally closed state; rather they can rest in either state. In drug delivery and other applications, latching valves are an important safety feature when properly configured as they prevent a direct flow path from a large reservoir to a patient in the case of a system failure. 
       BRIEF SUMMARY 
       [0005]    The present invention relates generally to a valve and systems for using valves for controlled delivery of fluid and to provide a failsafe whereby the state of the valve is maintained despite a loss of power or other failure. This provides, in certain embodiments, certain advantages in applications such as the precise delivery of medicines to a patient over time. In certain embodiments, the valve may be used in connection with multiple tubes delivering drugs, and may be used with a pump, such as an electrochemical pump, to move the fluids containing drugs for delivery. In certain applications, more than one medicine may be delivered and metered independently using a single pump with multiple reservoirs and valves. 
         [0006]    These and other features, objects and advantages of the disclosed subject matter will become better understood from a consideration of the following detailed description, drawings, and claims directed to the invention. This brief summary and the following detailed description and drawings are exemplary only, and are intended to provide further explanation of various implementations without limiting the scope of the invention as set forth in the claims. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0007]      FIG. 1  is a schematic diagram of a single sliding latching nitinol valve in the open (a) and closed (b) position (based on prior art U.S. Pat. No. 7,260,932 B1). 
           [0008]      FIG. 2  is a graph showing fluid flow through a fluid sensor as the single sliding latching nitinol valve of  FIG. 1  opens and closes. 
           [0009]      FIG. 3  is a schematic diagram of a dual sliding latching nitinol valve in the inlet open/outlet closed (a) and outlet open/inlet closed (b) position. 
           [0010]      FIG. 4  is a schematic diagram of a dual pivot latching nitinol valve. 
           [0011]      FIG. 5  is a graph showing fluid flow through the dual pivot latching valve of  FIG. 4 . 
           [0012]      FIG. 6  is a graph showing results of a syringe pump coupled with the dual pivot latching valve of  FIG. 4  and delivering it to a pressurized reservoir at 2 psi. 
           [0013]      FIG. 7  shows one dual latching valve used to control fluid flow from a reciprocating pump. 
           [0014]      FIG. 8  shows two dual latching valves with a two-sided reciprocating electrochemical pump, showing the two steps in drug delivery. 
           [0015]      FIG. 9  shows two dual latching valves with two-sided reciprocating electrochemical pump to deliver controlled amounts of two different drugs to a patient. 
       
    
    
     DETAILED DESCRIPTION 
       [0016]    Referring now to  FIG. 1  (based on prior art U.S. Pat. No. 7,260,932 B1), a single sliding latching nitinol valve is shown in the open ( FIG. 1( a ) ) and closed ( FIG. 1( b ) ) positions. Tube  115  is located in an open receiving area between valve arm  109  and valve seat  121  which is in a fixed position. To close the valve, nitinol wire  101  attached to valve arm  109  is activated by associated circuit  103  to pull valve arm  109 , which thereby pinches tube  115  closed, as shown in  FIG. 1( b ) . A resilient member such as spring  106  on latch arm  112  pushes the latch arm  112  so that it interferes with the return of valve arm  109 , causing tube  115  to remain pinched and closed without any additional power requirement. To open the valve, current is applied to circuit  104 , which activates nitinol wire  102  attached to latch arm  112 . Spring  105  forces valve arm  109  to its open position, where it interferes with the return path of latch arm  112  so that the valve remains open without any additional power. In this way, a single sliding valve may be employed using shape-memory alloy wire that stays in a desired position for an indefinite period of time without the addition of external power, until the valve is moved from the closed to open position, or the open to closed position. The valve is not dependent upon the presence of electrical power once set in either position. In a drug delivery device comprising a reciprocating pump, two of these valves may be used, one as an inlet valve and one as an outlet valve. In this case, there are no restrictions on whether either valve is open or closed so that at any point in time both valves could be open, both valves could be closed or one could be open while the other was closed. If both valves are open due to a system failure then there would be an open path from the reservoir to the delivery site, which could have devastating consequences in drug delivery applications. 
         [0017]    The graph of  FIG. 2  shows experimental results from the opening and closing of the valve shown in  FIG. 1 . As can be seen from  FIG. 2 , flow through tube  115  is quickly and effectively opened and closed by the operation of the valve. 
         [0018]      FIG. 3  shows the inventive step beyond the valve of  FIG. 1  in which two sections of a single fluid path (or two separate fluid paths),  305  and  307 , cannot both be in an open position at the same time. In the configuration of  FIG. 3( a ) , tube  305  is open while tube  307  is pinched closed. In the configuration of  FIG. 3( b ) , tube  305  is pinched closed while tube  307  is open. The dual sliding latching nitinol valve of  FIG. 3  is designed so that both valves close during switching states and it is mechanically impossible for both tubes  305  and  307  to be open at the same time, thereby always preventing an unintended flow of fluid through the system in the case of a failure. 
         [0019]    To move from the configuration of  FIG. 3( a )  to the configuration of  FIG. 3( b ) , nitinol wire  101  attached to inlet valve arm  301  is activated by running current through associated circuit  103 . This causes valve arm  301  to move up, pinching inlet tube  305  and allowing spring  106  to force outlet valve arm  302  to a position where outlet tube  307  is open and inlet valve arm  301  is prevented from returning to its original position. To return to the configuration of  FIG. 3( a ) , nitinol wire  102  attached to outlet valve arm  302  is activated by running a current through associated circuit  104 . This causes outlet valve arm  302  to move to the right as shown in the figure, thereby pinching outlet tube  307  closed and allowing spring  105  to force inlet valve arm  301  to a position where inlet tube  305  is open and outlet valve arm  302  is prevented from returning to its open position. It may be seen that during each transition, there is a brief period during which both inlet tube  305  and outlet tube  307  are both closed; however, there is no time when both inlet tube  305  and outlet tube  307  are open, as this operation is mechanically prevented. This arrangement prevents flow in the case of a failure, such as is vitally important when the valve is used for the delivery of medication from a reservoir to a patient. 
         [0020]      FIG. 4  depicts a variation on this design using a dual pivot latching nitinol valve. The figure shows the position of outlet tube  409  pinched closed by outlet valve arm  404 . To change the valve position, nitinol wire  101  attached to inlet arm  401  is activated to move inlet arm  401  to pinch inlet tube  405 . During this time, spring  407  forces outlet arm  404  to move so that outlet tube  409  is open (inlet tube  405  is closed) and outlet arm  404  prevents inlet arm  401  from returning to its normal position. Later activation of nitinol wire  102  attached to outlet arm  404  returns the valve to the open position (inlet tube  405  is open and outlet tube  409  is closed) as shown in  FIG. 4 . As with the arrangement depicted in  FIG. 3 , it may be seen that at no time in the process are both tubes  405  and  409  open. Such operation is mechanically prevented by the design of the valve, thereby providing a safety mechanism in the case of valve failure. The use of a pivot arm allows for a mechanical advantage to be used to reduce the length of nitinol wires  101  and  102  required to switch valve positions. The result is thus a smaller and more energy efficient valve. 
         [0021]    Although various embodiments of the invention have been described herein with reference to particular applications related to the delivery of fluids and in particular drugs, it will be apparent that the invention is not so limited. In addition, the dual valve safety mechanism can be realized with a ratcheting action, or an appropriately shaped cam, for example. Furthermore, any actuation mechanism can be used to switch valve states of coupled valves including solenoid, magnetic, pneumatic or hydraulic controls, stepping motor, or manual operation. In addition, the preceding description has focused on two-dimensional layouts of the sliding or pivoting members, however, it can be extended to acting members which are arranged in a non-planar manner. Larger or smaller embodiments of a dual latching valve could be used for safety-enhanced flow control at any scale. 
         [0022]    The graph of  FIG. 5  shows normalized results from the opening and closing of the dual pivot latching nitinol valve of  FIG. 4 . As can be seen from  FIG. 5 , like in  FIG. 2 , flow through each of outlet tube  409  and inlet tube  405  is efficiently switched by the valve. However,  FIG. 5  also shows that the opening of either one of the valves always directly corresponds with the closing of the other. In this graph the y-axis shows no flow at 0 and flow at 1. The x-axis shows the cycles of alternately switching the two valve arms between open and closed. There is no time when fluid is flowing through both of the valves because at no time are both outlet tube  409  and inlet tube  405  open, thereby preventing flow through both simultaneously. 
         [0023]    The graph of  FIG. 6  shows experimental results of using a syringe pump as a fluid displacement source with the dual pivot latching valve of  FIG. 4 . Fluid is removed from a balance to provide a weight reading and delivered to a reservoir held at a pressure of 2 psi. As can be seen from  FIG. 6 , fluid is delivered from the balance in a stair-step fashion, with fluid removal from the balance alternating with a period when the valve is closed and fluid is being delivered to an off-balance reservoir, in a relatively even delivery over time. This data also shows that there is no backflow onto the balance from the pressurized reservoir, illustrating that there is never a time when both valves arms are open. 
         [0024]      FIG. 7  shows an application of a dual latching valve as described herein with an electrochemical pump or “ePump”  725 . Electrochemical pumps suitable for use with the invention are taught, for example, in U.S. Pat. Nos. 7,718,047, 8,343,324, and 8,187,441, which are incorporated by reference herein. In this embodiment a dual latching valve is used for controlled dosing of a fluid, such as a drug to patient  821 . In the first step, the inlet valve arm is open (the outlet valve is closed) and the ePump is used to draw a dose of fluid along flow path  705  into chamber  706 . In the second step, the outlet valve is open (the inlet valve is closed) and the ePump is used to push fluid from chamber  706  into the patient  821 . Please note that at no time is there an open path from the reservoir to the patient, an important safety feature in drug delivery. 
         [0025]      FIG. 8  shows an application of a two-sided ePump  825  used in combination with two dual-latching valves to generate near-continuous controlled dosing of a fluid, such as a drug, to a patient  821 . The two-sided ePump  825  has two chambers  806  and  816 . As the pump action draws fluid into the top chamber  806 , it expels fluid from the bottom chamber  816 . Conversely, as fluid is drawn into bottom chamber  816 , it is expelled from top chamber  806 . As can be seen in  FIG. 8 , there are two distinct fluid paths that run from the reservoir  801  to patient  821 :  805 - 806 - 807  and  815 - 816 - 817 . Flow through each path is controlled by a dual latching valve. The upper dual latching valve has inlet valve arm  401  and outlet valve arm  404  which control flow through path  805 - 806 - 807 . Just as described in  FIG. 4 , when inlet valve  401  is open, then outlet valve  404  must be closed. And, when outlet valve  404  is open, then inlet valve  401  must be closed. This important control and safety feature allows only the delivery of a metered dose (the volume of chamber  806 ) of fluid to be delivered and prevents the possibility of an open channel running from reservoir  801  to the patient. The same organization of inlet valve  411  and outlet valve  414  controls fluid movement along path  815 - 816 - 817 . 
         [0026]    Alternatively, by arranging the inlet line  805  and outlet line  817  to both run through valve arm  401  and the outlet line  807  and inlet line  815  to both run through valve arm  404 , then only one dual latching valve is needed to provide flow from reservoir  801  to the patient  821 . In this arrangement as well, at no time is there an open fluid flow path from the reservoir to the patient. 
         [0027]    The following steps describe how a metered dose of fluid is delivered in a near continuous fashion from reservoir  801  to the patient. In this case, the system has already been primed so that both fluid paths are full of fluid. In step ( 1 ), inlet valve  401  and outlet valve  414  are open and outlet valve  404  and inlet valve  411  are closed. When the ePump  825  is activated, it first pulls fluid from the drug reservoir  801  through flow path  805  and into chamber  806  where it is stored. Simultaneously, ePump  825  expels fluid stored in chamber  816  through path  817  and into the patient. In step ( 2 ), the valves are reversed such that output valve  404  and input valve  411  are open and input valve  401  and output valve  414  are closed. In this case, the pump draws fluid from the reservoir  801  through flow path  815  and into chamber  816  where it is stored. Simultaneously, the metered volume of fluid stored in chamber  806  (from step  1 ) is expelled through flow path  807  into the patient. Repeating of Steps  1  and  2  will result in near continuous (or intermittent) and safe delivery of controlled doses of fluid (in this case, a drug) to the patient. 
         [0028]      FIG. 9  shows a variation of the arrangement in  FIG. 8  wherein two different drugs may be dispensed to a patient  821  from two different reservoirs  901  and  902 . Using the steps described in  FIG. 8 , drug A in reservoir  901  would be delivered in alternation with drug B in reservoir  902 . However, it may be desirable to deliver more doses of drug A and fewer doses of drug B. For example, insulin and glucagon as may be used in conjunction for treatment of diabetes, but insulin may need to be dispensed in more volume and or more frequently (or alternatively less) than glucagon. The following steps would allow differential and controlled delivery of two drugs using only one dual-sided ePump and two dual-latching valves. For example, nine doses of drug A in reservoir  901  are needed before a single dose of drug B in reservoir  902  is delivered to the patient. Starting with a fully primed system with both fluid paths  805 - 806 - 807  and  815 - 816 - 817  filled with the respective fluids: drug A and drug B. In Step  1 , inlet valves  401  and  411  are both open and outlet valves  404  and  414  are both closed. The first action of ePump  825  draws a metered amount of fluid from reservoir A into chamber  806  where it is stored. Simultaneously, fluid is expelled from chamber  816  through the only open path: back into reservoir  902 . In Step  2 , the top dual-latching valve switches positions such that inlet valve  401  is closed and outlet valve  404  is open. This means that the second action of ePump  825  expels the fluid stored in reservoir  806  out through path  807  and into the patient  821 . Repeating Steps  1  and  2  results in only fluid from reservoir  901  (drug A) being delivered to the patient, while the fluid from reservoir  902  (drug B) is cycled back and forth between reservoir  902  and chamber  816 , this cycling back and forth potentially having a mixing or stirring effect on the contents of the reservoir. Once it is desired to deliver fluid from reservoir  902  to the patient  821  then the bottom dual-latching valve will switch positions such that inlet valve  411  is closed and outlet valve  414  is open so that the fluid stored in chamber  816  is expelled to the patient  821 . Opposite protocol to the above would cause repeated delivery of fluid from reservoir B to be delivered to the patient and for fluid from reservoir A to be cycled back and forth between reservoir  901  and chamber  806 . By selectively operating the two dual-latching valves, each drug can be selectively pumped back into its originating reservoir or to the patient as needed. 
         [0029]    Although various embodiments of the invention has been described herein with reference to particular applications related to the delivery of fluids and in particular drugs, it will be apparent that the invention is not so limited, and instead will find application in other fields where the precise delivery of fluids is desired in a fail-safe manner. Furthermore, although certain embodiments of the invention have been described for use in connection with an ePump, it will be apparent that the invention is not so limited, and that other types of pumps could be used in connection with the valves of the invention as described herein. In addition, although nitinol has been used as the shape-memory alloy in certain embodiments described herein, it will be understood that other shape-memory alloys or materials or actuation methods could be substituted therefor within the scope of the invention. 
         [0030]    Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any systems and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention, a limited number of the exemplary systems and materials are described herein. It will be apparent to those skilled in the art that many more modifications are possible without departing from the invent concepts herein. All terms used herein should be interpreted in the broadest possible manner consistent with the context. Any ranges expressed herein are intended to include all particular values within the stated range, as well as all sub-ranges that fall within the stated range. 
         [0031]    The present invention has been described with reference to the foregoing specific implementations. These implementations are intended to be exemplary only, and not limiting to the full scope of the present invention. Many variations and modifications are possible in view of the above teachings. The invention is intended to be limited only as set forth in the appended claims.