Patent Publication Number: US-6905479-B1

Title: Pumping cartridge having an integrated filter and method for filtering a fluid with the cartridge

Description:
FIELD OF THE INVENTION 
   The present invention relates generally to systems and methods for metering and pumping fluids. In particular, in some embodiments, the invention relates to pumping cartridges for use with pump drive systems, which cartridges include filter elements disposed therein. 
   BACKGROUND OF THE INVENTION 
   A wide variety of applications in industrial and medical fields require fluid metering and pumping systems able to deliver precisely measured quantities of fluids at accurate flow rates to various destinations. In the medical field especially, precise and accurate fluid delivery is critical for many medical treatment protocols. Medical infusion and fluid-handling systems for use in the pumping or metering fluids to and/or from the body of a patient typically require a high degree of precision and accuracy in measuring and controlling fluid flow rates and volumes. For example, when pumping medicaments or other agents to the body of a patient, an infusion flow rate which is too low may prove ineffectual, while an infusion flow rate which is too high may prove detrimental or toxic to the patient. 
   Pumping and fluid metering systems for use in medical applications, for example in pumping fluids to and/or from the body of a patient, are known in the art. Many of such prior art systems comprise peristaltic or similar type pumping systems. Such prior art systems typically deliver fluid by compressing and/or collapsing a flexible tube or other flexible component containing the fluid to be pumped. While such known systems are sometimes adequate for certain applications, precise and accurate flow rates in such systems can be difficult to measure and control due to factors such as distortion of the walls of collapsible tubing or components of the systems, changes in relative heights of the patient and fluid supply, changes in fluid supply line or delivery line resistance, and other factors. 
   Another shortcoming of such prior art systems is that it is often difficult to determine and maintain accurate volumetric flow rates in real time during operation of the infusion system. Typically, many such prior art systems utilize volume and flow rate measurement techniques that are cumbersome and difficult to implement and cannot be performed in real time as the system is operating. Some approaches which have been used in such prior art systems for measuring volumes and flow rates include optical drop counting, the weighing of chambers containing infusion liquids, and other approaches. 
   Many such prior art infusion systems also employ valving systems which comprise clamps, or other pinching devices, which open and close a line by pinching or collapsing the walls of tubing. Such valving arrangements can have several shortcomings for applications involving medical infusion including difficulties in obtaining a fluid-tight seal and distortion of the walls of the tubing, which can lead to undesirable fluid leakage and/or irregular flow rates. 
   In addition, many typical prior art infusion systems, such as those described above, are constrained to fairly simple fluid handling tasks, such as providing a single or, in some cases, several individual flow paths between one or more fluid sources and a patient. Such prior art systems are not well suited for performing complex, multi-functional fluid handling and pumping tasks and often do not have sufficient operating flexibility to be used for a wide variety of fluid handling applications, without significant rearranging or retooling of the components of the system. 
   Also, for medical infusion applications involving the pumping or metering of fluids to the body of a patient, it is important to detect air present in a line pumping fluid to the body of a patient and to prevent such air from entering the body of the patient. Typically, prior art infusion systems employed for such applications detect the presence of air in the system by relying only on external air detection components, for example ultrasonic detectors, which are typically downstream of a pump and immediately upstream of the patient. Also, for such systems, once air has been detected in the line, purging the air from the line before it reaches the patient may require manual intervention and, in some cases, disconnection of lines within the system. 
   For pumping and infusion systems utilized for pumping fluids to the body of a patient, it is also typically desirable to pass fluids through a filter or screen prior to their entering the body of the patient in order to remove any insoluble clumps, or aggregates of material therefrom that may be detrimental to the patient if infused into the body. Such filters are especially important when pumping blood or blood components to the body of a patient; in which case, the filters serve primarily as blood clot filters to remove clots or aggregated cells from the blood or blood components. Prior art infusion systems used for such applications can include blood clot/particulate filters outside the pumping component of the system, installed on the line providing infused fluid to the patient. Such assembly requires additional setup time and attention from an operator of the system and often results in another potential location of fluid leakage or site of contamination within the system. 
   While the above mentioned and other prior art pumping and fluid handling systems represent, in some instances, useful tools in the art of fluid handling and pumping there remains a need in the art to: (a) provide pumping and fluid metering systems which have an improved ability to control and measure volumes and flow rates; (b) provide improved valving systems; (c) provide increased flexibility for multiple uses; and (d) include air detection capability and integrated fluid filtration. Certain embodiments of the present invention address one or more of the above needs. 
   SUMMARY OF THE INVENTION 
   Certain embodiments of the present invention provide a series of pumping systems, methods for operating the systems, and components of the systems. These embodiments include, in one aspect, a series of systems for measuring the volume of a volumetric chamber, detecting the presence of a gas in a pump chamber, and/or pumping a liquid with a pump chamber. Some embodiments of the present invention include a series of methods for pumping a liquid at a desired average flow rate with a pumping cartridge of a pumping system. Some embodiments of the present invention provide a series of pumping cartridges and pump chambers, and methods for operating such cartridges and chambers. 
   According to one embodiment of the present invention, a method and corresponding system for detecting the presence of a gas in a pump chamber is disclosed. The pump chamber may be an isolatable pump chamber. According to this embodiment, the method includes the steps of: isolating the pump chamber; determining a first measured parameter related to the volume of the pump chamber with at least a first force supplied to a surface of the pump chamber; determining a second measured parameter related to the volume of the pump chamber with at least a second force applied to the surface of the pump chamber; and then comparing the first measured parameter and the second measured parameter. 
   In another embodiment, a method for detecting the presence of a gas in a pump chamber is disclosed, where the pump chamber is coupled to or contained within a control chamber. In this embodiment, the method comprises: supplying a measurement gas to the control chamber at a first measured pressure; changing the pressure of the measurement gas in the control chamber to a second measured pressure; supplying a measurement gas to the control chamber at a third measured pressure; changing the pressure of the measurement gas in the control chamber to a fourth measured pressure; and determining the presence of a gas in the pump chamber based at least in part on the measured pressures. 
   In yet another embodiment, a method for detecting the presence of gas in a pump chamber is disclosed, where the pump chamber is coupled to or contained within a control chamber. The method comprises determining a first measured parameter related to the volume of the pump chamber and/or the control chamber with a fluid supplied to the control chamber at a first pressure, determining a second measured parameter related to the volume of the pump chamber and/or the control chamber with a fluid supplied to the control chamber at a second pressure, and comparing the first measured parameter and the second measured parameter. 
   In yet another embodiment, a method for detecting the presence of gas in a pump chamber is disclosed, where the pump chamber is at least partially comprised of a movable surface. The method comprises determining a first measured parameter related to a volume of the pump chamber with at least a first force applied to the movable surface, where the first force creates a first level of stress in the movable surface. The method further comprises determining a second measured parameter related to a volume of the pump chamber with at least a second force applied to the movable surface, where the second force creates a second level of stress in the movable surface. The method further comprises comparing the first measured parameter and the second measured parameter. 
   In another embodiment, a method for detecting the presence of a gas in a pump chamber is disclosed, where the pump chamber is at least partially comprised of a movable surface and is coupled to or contained within a control chamber. The method comprises: supplying a measurement gas to the control chamber at a first measured pressure, where the first measured pressure creates a first difference in pressure between the pump chamber and the control chamber; supplying a measurement gas to the control chamber at a second measured pressure, where the second measured pressure creates a second difference in pressure between the pump chamber and the control chamber; and determining the presence of a gas in the pump chamber based at least in part on the measured pressures. 
   In another embodiment, a system for detecting the presence of a gas in an isolatable pump chamber is disclosed. In this embodiment, the system includes a force applicator that is constructed and arranged to apply a force to a surface of the pump chamber at at least a first level of force and a second level of force. The system further includes a comparer configured to determined the presence of a gas in the pump chamber based at least in part on a first measured parameter related to the volume of the pump chamber at a first condition, and a second measured parameter related to the volume of the pump chamber at a second condition. 
   In another embodiment, a system for detecting the presence of a gas in a pump chamber is disclosed. The system in this embodiment includes a control chamber that is coupled to or contains the pump chamber, a flexible membrane comprising at least a portion of the pump chamber, and at least one pressure measuring component able to measure a pressure in the control chamber. The system further includes a fluid supply system in fluid communication with the control chamber that is able to supply a fluid to the control chamber at at least a first and a second predetermined pressure, where the fluid pressure in the control chamber is measured with the pressure measuring component. The system in this embodiment also includes a comparer configured to determine the presence of a gas in the pump chamber based on a first measured parameter related to a volume of the control chamber at at least the first pressure and a second measured parameter related to the volume of a control chamber at at least the second pressure. 
   In yet another embodiment, a system for detecting the presence of a gas in a pump chamber is disclosed. The system in this embodiment includes a control chamber that is coupled to or contains the pump chamber, a pressure supply to pressurize the control chamber at at least a first pressure and a second pressure, and a comparer that is configured to determine the presence of gas in the pump chamber based at least in part on a first measured parameter related to a volume of the pump chamber and/or control chamber at a first condition, and a second measured parameter related to a volume of a pump chamber and/or control chamber at a second condition. 
   In another embodiment, a system for detecting the presence of a gas in a pump chamber is disclosed. The system in this embodiment comprises force applicator means for supplying a force to the surface of the pump chamber at a first level of force and a second level of force, and processor means for determining the presence of a gas in the pump chamber based at least in part on a first measured parameter related to the volume of the pump chamber at a first condition and a second measured parameter related to the volume of the pump chamber at a second condition. 
   In another embodiment, a pump chamber is disclosed. The pump chamber in this embodiment includes a wall and a movable surface comprising at least a portion of the wall. The pump chamber further includes at least one spacer positioned within the pump chamber to inhibit gas from being pumped through the pump chamber. 
   In yet another embodiment, a pump chamber including a wall and a flexible membrane disposed over at least a portion of the wall is disclosed. The pump chamber in this embodiment further includes at least one spacer positioned within the pump chamber to assist air to rise in the pump chamber. 
   In yet another embodiment, a pump chamber comprising a volumetric container is disclosed. The pump chamber in this embodiment includes a flexible membrane comprising at least a portion of a wall of the container, with at least one spacer positioned within the container to inhibit contact between internal surfaces of the container. 
   In another embodiment, a pump chamber is disclosed. The pump chamber is this embodiment comprises a first movable wall of the pump chamber, a second wall of the pump chamber, and at least one elongate spacer attached to the second wall and projecting towards the first movable wall. 
   In another embodiment, a method of pumping of fluid is disclosed. The method involves providing a pump chamber, which includes a flexible membrane, and preventing any gas contained within the pump chamber from being pumped from the pump chamber by providing at least one spacer element within the pump chamber. The spacer element in this embodiment prevents the flexible membrane from contacting an internal surface of the pump chamber during pumping. 
   In another aspect, a series of pumping systems is disclosed. In one embodiment, the system is for pumping a liquid with a pump chamber. The system in this embodiment includes at least one fluid source, containing a fluid at a first pressure, where the source is able to be placed in fluid communication with a control chamber that is coupled to the pump chamber when the system is in operation. The system in this embodiment further includes a variable sized orifice valve able to be placed in fluid communication with the fluid source and the control chamber. The system may also include a processor which controls the variable sized orifice valve to selectively allow the control chamber to be pressurized with a fluid from the fluid source to a desired pressure. In this embodiment, the processor also controls the pressure within the control chamber during filling of the pump chamber with a liquid or during discharge of a liquid ftom the pump chamber by selectively changing the size of an orifice within the variable sized orifice valve. 
   In another embodiment, a method for pumping a liquid using a pump chamber is disclosed. The method comprises: providing a first fluid source that supplies a fluid at a first pressure in fluid communication with an inlet of a variable sized orifice valve; providing a control chamber that is coupled to the pump chamber, where the control chamber is in fluid communication with an outlet of the variable sized orifice valve; selectively changing a size of an orifice within the variable sized orifice valve in order to pressurize the control chamber with the fluid to a desired pressure; and maintaining the desired pressure in the control chamber by selectively changing the size of the orifice. 
   In another embodiment, a system for measuring the volume of a volumetric chamber is disclosed. The system includes a reference chamber, a first fluid source supplying fluid at a first pressure, and a second fluid source supplying fluid at a second pressure. The system in this embodiment also includes a switch valve having a first and second inlet and an outlet. The first inlet of the switch valve is connected in fluid communication with the first fluid source, and the second inlet of the switch valve is connected in fluid communication with the second fluid source. The outlet of the switch valve is connected in fluid communication with at least one line able to be placed in fluid communication with the reference chamber and the volumetric chamber. The switch valve has a first position that provides fluid communication between the first fluid source and the reference chamber and volumetric chamber, and has a second position that provides fluid communication between the second fluid source and the reference chamber and volumetric chamber. The system may also include a processor which controls the switch valve to selectively allow the reference chamber and/or the volumetric chamber to be pressurized to a selected pressure with a fluid from either the first fluid source or the second fluid source. The processor also determines a volume of the volumetric chamber based at least in part on the selected pressure. 
   In another embodiment, a method for measuring a volume of a volumetric chamber is disclosed. The method comprises providing a first fluid source to supply fluid at a first pressure, a second fluid source to supply fluid at a second pressure, and a switch-valve having a first inlet, a second inlet, and an outlet, where the first inlet is connected in fluid communication with the first fluid source, the second inlet is connected in fluid communication with the second fluid source, and the outlet is connected in fluid communication with at least one line that is able to be placed in fluid communication with the volumetric chamber. The method further comprises positioning the switch valve to allow the volumetric chamber to be pressurized with the fluid from the first fluid source, determining a first pressure of the volumetric chamber, and determining a volume of the volumetric chamber based at least in part on the first pressure. 
   In yet another embodiment, a system for pumping a liquid with a pump chamber is disclosed. The system in this embodiment includes a first fluid source supplying fluid at a first pressure, and a second fluid source supplying fluid at a second pressure. The system in this embodiment also includes a switch valve having a first and a second inlet and an outlet. The first inlet is connected in fluid communication with the first fluid source, and the second inlet is connected in fluid communication with the second fluid source. The outlet of the switch valve is connected in fluid communication with at least one line able to be placed in fluid communication with a control chamber that is coupled to the pump chamber when the system is in operation. The switch valve has a first position that provides fluid communication between the first fluid source and the control chamber, and has a second position that provides fluid communication between the second fluid source and the control chamber. 
   In another embodiment, a method for pumping a liquid with a pump chamber is disclosed. The method comprises providing a first fluid source to supply fluid at a first pressure, a second fluid source to supply fluid at a second pressure, and a switch-valve having a first inlet, a second inlet, and an outlet, where the first inlet is connected in fluid communication with the first fluid source, the second inlet is connected in fluid communication with the second fluid source, and the outlet is connected in fluid communication with at least one line able to be placed in fluid communication with a control chamber to be coupled to a pump chamber when the system is in operation. The method further comprises positioning the switch-valve to provide fluid communication between the first fluid source and the control chamber so as to at least partially fill the pump chamber with a liquid, and positioning the switch-valve to provide fluid communication between the second fluid source and the control chamber for dispensing the liquid from the pump chamber. 
   In yet another aspect, a series of methods and systems for pumping a liquid at a desired average flow rate with a pumping cartridge is disclosed. In one embodiment, the method involves pumping a liquid at a desired average flow rate with a pumping cartridge, where the cartridge includes at least one pump chamber, at least a portion of which pump chamber includes a movable surface. The method of this embodiment involves: at least partially filling the pump chamber with a liquid; isolating the pump chamber; applying a force to the movable surface and regulating the flow of liquid from the pump chamber while maintaining the force on the surface. 
   In another embodiment, a method for pumping a liquid at a desired average flow rate with a pumping cartridge that includes at least one pump chamber, at least a portion of which pump chamber comprises a movable surface is disclosed. The method of this embodiment involves: closing a valve positioned on an outlet line of the pump chamber; at least partially filling the pump chamber with a liquid; closing a valve positioned on the inlet line of the pump chamber thereby isolating the pump chamber; and, while maintaining the inlet valve in a closed position, applying a force to the movable surface and opening the outlet valve for predetermined periods at predetermined intervals while maintaining the force on the movable surface. The predetermined time periods and intervals may be selected to yield a desired average flow rate. 
   In yet another embodiment, a fluid metering system is disclosed. The system of this embodiment comprises a reusable component that is constructed and arranged for operative association with a removable pumping cartridge by coupling to the pumping cartridge. The pumping cartridge of this embodiment includes at least one pump chamber and has an outlet line having an outlet valve therein. The fluid metering system in this embodiment includes a processor that is configured to control pulsing of the outlet valve to achieve a desired flow rate. 
   In yet another embodiment, a fluid metering system including a reusable component that is constructed and arranged for operative association with a removable pumping cartridge is disclosed. The pumping cartridge includes at least one pump chamber having an inlet line having a first valve therein and an outlet line having a second valve therein. The pump chamber is at least partially formed from a movable surface. The system further includes valve actuating means for operating the first valve and the second valve, and pump chamber actuating means for applying a force to the movable surface. The system further includes control means for controlling the valve actuating means and pump chamber actuating means to deliver fluid at a desired flow rate from the pump chamber by closing the first valve, applying a force to the movable surface, and pulsing the second valve. 
   In another embodiment, a series of pumping cartridges is disclosed. In one embodiment, the pumping cartridge includes a first liquid flow path, a second liquid flow path, and a bypass valve in fluid communication with the first liquid flow path and the second liquid flow path. The bypass valve is constructed and arranged to selectively permit liquid flow through the first liquid flow path or the second liquid flow path, or to prevent liquid flow through both the first liquid flow path and the second liquid flow path. 
   In another embodiment, a pumping cartridge including a first component and at least one membrane disposed on the first component is disclosed. The first component and the membrane define a bypass valving chamber. The bypass valving chamber in this embodiment includes three ports, two of which ports are occludable by the membrane. The pumping cartridge in this embodiment further includes a first fluid flow path entering the bypass valving chamber through a first port and exiting the bypass valving chamber through a third occludable port. The pumping cartridge in this embodiment further includes a second fluid flow path entering the bypass valving chamber through a second occludable port and exiting the bypass valving chamber through the first port. 
   In yet another embodiment, a reusable system is disclosed that is constructed and arranged for operative association with a removable pumping cartridge, where the pumping cartridge provides at least two fluid flow paths therein and includes a bypass valving chamber in fluid communication with a first fluid flow path and a second fluid flow path. The system in this embodiment includes a pump housing component that is constructed and arranged to couple to the pumping cartridge, and a valve actuator to actuate the bypass valving chamber. The valve actuator in this embodiment is disposed within the pump housing adjacent to and in operative association with the bypass valving chamber, when the pumping cartridge is coupled to the pump housing. 
   In yet another embodiment, a reusable system is disclosed that is constructed and arranged for operative association with a removable pumping cartridge, where the pumping cartridge provides at least two liquid flow paths therein and includes a first component, with at least one membrane disposed on the first component. The first component and the membrane define a bypass valving chamber. The reusable system in this embodiment includes a pump housing component that is constructed and arranged for operative association with the pumping cartridge by coupling to the pumping cartridge. The reusable system in this embodiment also includes a valve actuator to actuate the bypass valving chamber, which actuator is disposed adjacent to and in operative association with the bypass valving chamber when the pumping cartridge is coupled to the pump housing. The system may further include a force applicator forming at least a part of the valve actuator, where the force applicator is constructed and arranged to alternatively: apply a force to at least a portion of the membrane to restrict liquid flow through a first liquid flow path through the bypass valving chamber; apply a force to at least a portion of the membrane to restrict liquid flow through a second liquid flow path through the bypass valving chamber; and apply a force to at least a portion of the membrane to restrict liquid flow through both the first and the second liquid flow paths. 
   In another embodiment, a method for directing flow in a pumping cartridge is disclosed, where the pumping cartridge includes a bypass valving chamber having three ports therein and two liquid flow paths therethrough. At least a portion of the bypass valving chamber in this embodiment is formed from a membrane. The method in this embodiment comprises occluding a first port disposed in the bypass valving chamber with the membrane to restrict the flow of liquid through the bypass valving chamber along a first flow path, or occluding a second port disposed in the bypass valving chamber with the membrane to restrict the flow of liquid through the bypass valving chamber along a second flow path, and/or occluding both the first and second ports disposed in the bypass valving chamber with the membrane to restrict the flow of liquid along both the first and second flow paths. 
   In yet another aspect, pumping cartridges including filter elements and methods for filtering fluids are disclosed. In one embodiment, a removable pumping cartridge that is constructed and arranged for operative association with the reusable component is provided, the cartridge including at least one pump chamber, at least one valving chamber, and at least one fluid flow path constructed and positioned within the cartridge to provide fluid communication between the pump chamber and a body of a patient when pumping a fluid thereto. The cartridge in this embodiment further includes at least one filter element in fluid communication with the fluid flow path. 
   In another embodiment, a method for filtering a liquid supplied to the vasculature of a patient is disclosed. The method in this embodiment includes supplying a liquid to a pump chamber disposed in a removable pumping cartridge, where the pumping cartridge is constructed and arranged for operative association with a reusable component. The method further involves pumping the liquid to the patient through a filter element disposed in the pumping cartridge. 
   In yet another aspect, occluders for occluding collapsible tubing, and methods for occluding collapsible tubing using such occluders are disclosed. In one embodiment, an occluder for occluding at least one collapsible tube is disclosed. The occluder in this embodiment comprises an occluding member and a force actuator that is constructed and positioned to bend the occluding member. 
   In another embodiment, a method for occluding at least one collapsible tube is disclosed. The method comprises applying a force to bend the occluding member in order to open the collapsible tube to enable fluid to flow therethrough, and releasing the force in order to relax the occluding member and occlude the collapsible tube. 
   Each of the above disclosed inventions and embodiments may be useful and applied separately and independently, or may be applied in combination. Description of one aspect of the inventions are not intended to be limiting with respect to other aspects of the inventions. 
   Other advantages, novel features, and objects of the invention will become apparent from the following detailed description of the invention when considered in conjunction with the accompanying drawings, which are schematic and are not intended to be drawn to scale. In the figures, identical or substantially similar components that are illustrated in various figures may be represented by a single numeral. For purposes of clarity, not every component is labeled in every, figure, nor is every component of each embodiment of the invention shown where illustration is not necessary to allow those of ordinary skill in the art to understand the invention. 

   
     BRIEF DESCRIPTION OF THE DRAWINGS 
       FIG. 1  is a schematic illustration of a pumping system according to one embodiment of the invention; 
       FIG. 2  is a schematic illustration of a fluid pump according to one embodiment of the invention; 
       FIG. 3   a  is a flow chart illustrating a series of steps in a pumping cycle according to one embodiment of the invention; 
       FIG. 3   b  is a flow chart illustrating a series of substeps of the pumping cycle of  FIG. 3   a  for performing volume calculation and air detection; 
       FIG. 3   c  is a flow chart illustrating a series of substeps of the pumping cycle of  FIG. 3   a  for detecting the presence of a gas in a pump chamber; 
       FIG. 4  is a schematic illustration of the pump of  FIG. 1  at a first condition of fluid pressure in the control chamber; 
       FIG. 5  is a schematic illustration of a pumping system according to one embodiment of the invention; 
       FIG. 6   a  is a flow chart illustrating a series of steps in a pumping cycle according to one embodiment of the invention; 
       FIG. 6   b  is a flow chart illustrating a series of substeps of the pumping cycle of  FIG. 6   a  for performing volume calculation and air detection; 
       FIG. 6   c  is a flow chart illustrating a series of substeps of the pumping cycle of  FIG. 6   a  for detecting the presence of a gas in a pump chamber; 
       FIG. 7  is a schematic illustration of a pumping system according to one embodiment of the invention; 
       FIG. 8  is a schematic illustration of a pumping system according to one embodiment of the invention; 
       FIG. 9   a  is a flow chart illustrating a series of steps in a pumping cycle according to one embodiment of the invention; 
       FIG. 9   b  is a flow chart illustrating a series of substeps of the pumping cycle of  FIG. 9   a  for performing volume calculation and air detection; 
       FIG. 9   c  is a flow chart illustrating a series of substeps of the pumping cycle of  FIG. 9   a  for detecting the presence of a gas in a pump chamber; 
       FIG. 10  is a partially-cutaway cross-sectional illustration of a removable pumping cartridge and pump housing component according to one embodiment of the invention; 
       FIG. 11   a  is a schematic illustration of a pumping cartridge according to one embodiment of the invention; 
       FIG. 11   b  is a cross-sectional illustration of the pumping cartridge of  FIG. 11   a;    
       FIG. 11   c  is a partially-cutaway cross-sectional illustration of a valve provided by the pumping cartridge of  FIG. 11   a;    
       FIG. 11   d  is a partially-cutaway cross-sectional illustration of the valve of  FIG. 1I  c, according to an alternative embodiment of the invention; 
       FIG. 11   e  is a partially-cutaway cross-sectional illustration of a bypass valving chamber of the pumping cartridge of  FIG. 11   a;    
       FIG. 11   f  is a partially-cutaway cross-sectional illustration of the bypass valving chamber of  FIG. 11   e , according to an alternative embodiment of the invention; 
       FIG. 12   a  is a schematic illustration of an occluder mechanism in an open position, according to one embodiment of the invention; 
       FIG. 12   b  is a schematic illustration of the occluder mechanism of  FIG. 12   a  in a closed position; 
       FIG. 12   c  is a schematic illustration of an occluder mechanism in an open position, according to one embodiment of the invention; 
       FIG. 12   d  is a schematic illustration of the occluder mechanism of  FIG. 12   c  in a closed position; 
       FIG. 12   e  is a schematic illustration of an occluder mechanism utilizing a spring plate, in an open position, according to one embodiment of the invention; 
       FIG. 12   f  is a schematic illustration of the occluder mechanism of  FIG. 12   e  in a closed position; and 
       FIG. 13  is a schematic illustration of a flow diagram illustrating the overall system architecture and control configuration for a pumping system, according to one embodiment of the invention. 
   

   DETAILED DESCRIPTION 
   Certain embodiments of the present invention relate to a series of methods and systems useful in fluid pumping applications. Some embodiments of these methods and systems are especially useful for applications involving the pumping of liquids to and from the body of a patient during a medical treatment or procedure. The need for pumping liquids to and from the body of a patient arises in a wide variety of medical treatments and procedures including, for example, hemodialysis for the treatment of kidney failure, plasmapheresis for separating blood cells from plasma, general infusion of intervenous fluids and/or medicaments, and a wide variety of additional treatments and procedures apparent to those of ordinary skill in the art. The methods and systems of the current invention may be advantageously utilized for any of the above-mentioned liquid pumping applications, or any other fluid pumping application, including various industrial applications, as apparent to those of ordinary skill in the art. 
   Certain embodiments of the present invention relate to pumping systems and methods for operating the pumping systems for pumping liquids with a pump chamber. The term “pump” or “pumping” as used herein refers to the forcing, controlling or metering of the flow of a fluid through a line either by metering a flow of a fluid that is moving under the influence of a pre-existing pressure drop within the line, or by forcing a fluid through a line by increasing the pressure of the fluid within the line. Many embodiments, as described in more detail below, involve systems where the pressure of the fluid being pumped is increased (e.g., increased cyclically) by using a pump chamber and a source of mechanical force acting on one or more external surfaces of the pump chamber. 
   A “chamber” as used herein, for example in the context of a pump chamber, refers to a volumetric container having a constant or variable internal volume, which is able to contain a fluid. A “fluid” as used herein can refer to a material that is either a liquid or gas. 
   The methods and systems provided in some embodiments of the present invention, in preferred embodiments, include pumping systems with pump chambers having at least one moveable surface. A “moveable surface” as used herein in this context refers to a surface of a chamber that can be displaced by a force applied thereto, so as to change an internal volume of the chamber. A non-limiting list of pumping systems that employ pump chambers including at least one moveable surface include: diaphragm pumps, piston pumps, peristaltic pumps, flexible bulb pumps, collapsible bag pumps, and a wide variety of other pump configurations, as apparent to those of ordinary skill in the art. 
   Preferred embodiments of the invention involve pumping systems including a pump chamber which comprises an isolatable chamber. An “isolatable chamber” as used herein refers to a volumetric chamber or container for holding a fluid, which can isolate the fluid from fluid communication with fluids outside of the isolatable chamber (e.g., by sealing or closing inlets and outlets to the chamber). The term “fluid communication” as used herein refers to two chambers, or other components or regions containing a fluid, where the chambers, components, or regions are connected together (e.g., by a line, pipe, or tubing) so that a fluid can flow between the two chambers, components, or regions. Therefore, two chambers which are in “fluid communication” can, for example, be connected together by a line between the two chambers, such that a fluid can flow freely between the two chambers. For embodiments involving an isolatable chamber, for example an isolatable pump chamber, lines connecting the isolatable chamber to other chambers or regions of the pumping system may include at least one valve (or other device) therein which may be closed, or occluded, in order to block fluid communication between the chambers. 
   The term “valve” as used herein refers to a component of a pumping system disposed in, or adjacent to, a fluid line or fluid flow path within the system, which component is able to block the flow of a fluid therethrough. Valves, which may be utilized in various aspects of the invention, include, but are not limited to, ball valves, gate valves, needle valves, globe valves, solenoid-activated valves, mechanisms or components for applying an external force to a fluid flow path so as to block or occlude the flow path (for example, by pinching or collapsing a length of flexible tubing), and others, as would be apparent to those of ordinary skill in the art. Two or more chambers or regions of a pumping system which are connected together by a fluid flow path including one or more valves therein are able to be placed in fluid communication. “Able to be placed in fluid communication” as used herein refers to components, regions, or chambers within a pumping system, which components, regions, or chambers are either connected in unrestricted fluid communication or have at least one valve therebetween that can be selectively opened to place the components, regions, or chambers in fluid communication. Components, regions, or chambers connected together by a fluid flow path that includes no valves or obstructions therein are said to be in “unrestricted fluid communication” as used herein. The term “fluid communication” generally includes both unrestricted fluid communication and able to be placed in fluid communication. 
   In many pumping applications, e.g., pumping liquids to the body of a patient, it is critical to prevent gases, such as air, which may find their way into a pump chamber of the system from being pumped out (e.g., pumped into the body of the patient). Certain embodiments of the present invention include methods and systems for detecting the presence of a gas in an isolatable pump chamber. Such methods and systems may utilize pump chambers having at least one moveable surface, where, in some embodiments the moveable surface is a flexible membrane, which, in some such embodiments is elastic. The term “membrane” as used herein refers to a movable surface which comprises at least a portion of a wall of a pump chamber. The term “flexible membrane” as used herein refers to a moveable surface having at least a portion that is movable by bending and/or stretching when a force is applied thereto. A flexible membrane which is “elastic” or an “elastic membrane” as used herein refers to a flexible membrane that provides a resistance to bending and/or stretching by an applied force, which resistance is proportional to an amount of the displacement/stretching of the membrane from an equilibrium configuration without such force applied. A force applied to an elastic membrane that displaces the membrane from a relaxed equilibrium condition will tend to create a stress in the membrane which resists further displacement and creates a restoring force tending to return the membrane to its relaxed equilibrium condition. An “equilibrium condition” as used herein for elastic membranes or other movable surfaces refers to the configuration of the membrane/surface at a condition where there are no applied forces tending to move or displace the membrane/surface from a stationary position. A “relaxed equilibrium condition” as used herein refers to an equilibrium condition wherein a stress within a membrane/surface is at a minimum level allowed by the configuration of the pump chamber. For example, for a pump chamber including an elastic membrane as a portion thereof, a relaxed equilibrium condition could be the configuration of the membrane at its minimum level of strain (stretching) when forces on both sides of the membrane are essentially balanced and equal. 
   In one embodiment, a method for detecting the presence of a gas in an isolatable pump chamber having at least one moveable surface is used. The method involves isolating the pump chamber, which is at least partially filled with a liquid being pumped, for example by closing an inlet and an outlet valve in fluid communication with the pump chamber. The method of this embodiment further involves determining a measured parameter related to the volume of the pump chamber with a predetermined level of force is applied to a moveable surface of the pump chamber. The method further involves determining the measured parameter related to the volume of the pump chamber again, except this time with a different level of force applied to the moveable surface of the pump chamber. The method involves comparing the measured parameters determined at each condition of the pump chamber described, and detecting the presence of a gas within the pump chamber based on the values of the measured parameters. 
   This embodiment utilizes, at least in part, the compressibility of any gas within the pump chamber, as contrasted with the essentially incompressible nature of the liquid within the pump chamber, as a means for determining the presence of a gas. The presence of such gas in the pump chamber permits the movable surface to be able to undergo a displacement in response to an applied force thereto owing to the compressibility of the gas in the pump chamber. In some embodiments, the method can involve the determination of a measured parameter related to the volume of the pump chamber determined with at least two substantially differing levels of force applied to a moveable surface of the pump chamber. For example, a first determination of the measured parameter related to the volume of the pump chamber at a first condition can be made with a positive force applied to the moveable surface of the pump chamber, such force tending to decrease the volume of the pump chamber, and a second determination at a second condition can be made with a negative (or lesser) force to the moveable surface of the pump chamber, which force tending to increase the volume of the pump chamber. If the pump chamber is essentially completely filled with a liquid, because the liquid will be essentially incompressible, the measured parameter related to the volume of the pump chamber measured with the pump chamber at a first condition (e.g., with the positive force applied to the moveable surface of the pump chamber) will be nearly identical to the value of the measured parameter related to the is volume of the pump chamber measured with the pump chamber at the second condition (e.g., with a negative force applied to the moveable surface of the pump chamber). In contrast, if the pump chamber also contains a quantity of a gas, such as air, because the air is compressible, the measured parameter related to the volume of the pump chamber measured at the first condition can differ from the value of the measured parameter measured with the pump chamber at the second condition by an amount proportional to the quantity of gas within the pump chamber. In short, when a gas is present within the pump chamber, the volume of the pump chamber measured utilizing a positive force applied to a moveable surface thereof can be measurably different than the volume of the pump chamber determined utilizing a negative force applied to a moveable surface thereof. By comparing the measured parameters related to the volume of the pump chamber determined at the first and second conditions above, it can be determined whether there is any gas present within the pump chamber and in some embodiments, roughly, the relative amount of such gas. 
   A “measured parameter related to a volume” as used herein refers either to a measure of the volume itself or to a measured parameter determined by the system that can be converted to the volume by arithmetic or mathematical transformations utilizing one or more additional parameters that are either constant conversion factors or variables which are not functions of the volume (e.g., unit conversion factors, calibration constants, curve-fit parameters, etc.). In other words, in some embodiments of the invention, the volume of the pump chamber itself need not be determined, but rather parameters from which the volume could be determined, which parameters are typically proportional to the volume, may be determined and compared. Depending on the embodiment, as discussed in more detail below, such measured parameters can include, for example, pressures and combinations of pressures, products of pressures and volumes of components of the pumping system, acoustical signals, temperatures, combinations of temperatures and pressures, values of linear displacement, etc. as apparent to those of ordinary skill in the art. A “condition” as used above in the context of the determination of a measured parameter related to the volume of a chamber, refers herein to a particular state of a pump chamber, or other chamber in which a measured parameter is being determined, which state is associated with at least one measurable parameter related to the volume of the chamber with a particular level of force or range of forces being applied to an external surface of the chamber during the volume measurement procedure. 
   As would be readily apparent to those of ordinary skill in the art from the disclosure provided herein, the method for determining the presence of a gas in a pump chamber may be utilized and find application in a wide variety of pumping systems known in the art, such pumping systems including a force applicator for applying a variable, or selectable, force and/or range of forces to a moveable surface of the pump chamber. A “force applicator” as used herein in this context refers to a component of a pumping system that is able to apply a force to an external surface of a chamber within the system. Force applicators in pumping systems which may be utilized according to the invention include, but are not limited to: moveable surfaces in contact with the external surface of the pump chamber (e.g. pistons, push rods, plungers, etc.), pressurized fluids in contact with the external surface of the pump chamber, magnetic or electrostatic fields that are able to exert a force on the external surface of the pump chamber, and many others. 
   Pumping systems utilizing the inventive methods for determining the presence of a gas in a pump chamber also preferably include a mechanism for determining a measured parameter related to the volume of the pump chamber with different levels of force or ranges of forces being applied to a moveable external surface of the pump chamber. For example, a pumping system which includes a moveable surface in contact with the external surface of the pump chamber can include a motor and linear actuator for moving the surface in contact with the pump chamber, so as to create a variable force on the surface of the pump chamber, and can further include a detector for measuring a linear displacement or position of the moveable surface, which linear displacement or position can act as the measured parameter related to the volume of the pump chamber. Similarly, systems which utilize a magnetic or electrostatic field that is able to exert a force on the external surface of the pump chamber can include detectors or measuring devices to determine either field strengths and/or displacements of the external surface of the pump chamber, which measurements can constitute a measured parameter related to the volume of the pump chamber. Other systems, and measurable parameters for determining the volume of the pump chamber for alternative systems may also be used. 
   One preferred embodiment of a pumping system able to employ the inventive method for detecting the presence of a gas in a pump chamber utilizes pressurized fluids in contact with a moveable, or flexible, surface of the pump chamber in order to apply a force to the surface. Preferred pumping systems according to the invention utilize fluid sources for providing a measuring fluid at different and selectable pressures, which fluid can be brought into contact with a moveable or flexible external surface of a pump chamber. As will be discussed in more detail below, some preferred embodiments of pumping systems utilizing measurement fluids for applying forces to moveable surfaces of pump chambers employ pump chambers having a moveable surface comprised, at least in part, by an elastic flexible membrane. The term “fluid source(s)” as used herein refers to one or more components of a pumping system that alone, or in combination, are able to supply or withdraw a quantity of fluid to another component, or components, of the pumping system with which they are, or are able to be placed, in fluid communication. As discussed below, examples include, but are not limited to, pumps, compressors, pressurized or evacuated tanks, and combinations thereof. 
   As discussed in more detail below, the fluids supplied by the fluid sources included in certain embodiments of pumping systems useful for practicing the invention provide a measurement gas, most preferably air, but in other embodiments, can also provide one or more liquids. Such fluids, which are provided by the fluid supply components of certain embodiments of the pumping systems according to the invention are hereinafter collectively referred to as “measurement fluids.” “Measurement fluids” (e.g., measurement gases or measurements liquids) as used herein refer to fluids which are used to determine a volume, or a measured parameter related to a volume of a volumetric container within the pumping system, for example a pump chamber, or for other purposes within the pumping system, which, preferably, are not in fluid communication with a fluid being pumped or metered by a pump chamber of the system. The measurement fluid sources utilized by certain preferred embodiments of pumping systems according to the invention can comprise one or more components of a measurement fluid supply system that are constructed and arranged to pressurize one or more components of the pumping system. “Constructed and arranged to pressurize” a component, as used herein, refers to a system containing the necessary sources of fluid, together with the associated components (e.g., plumbing and pneumatic or other connections), which are necessary to enable the system to change the pressure of a fluid contained within the component. 
   One embodiment of a pumping system that utilizes a measurement gas for actuating a pump chamber to pump a liquid therethrough and for detecting the presence of a gas in the pump chamber is shown schematically in FIG.  1 . Pumping system  100  includes a fluid supply system  102  containing a fixed quantity of a measurement gas and a mechanism for changing the volume of the measurement gas within the system. 
   Pumping system  100  includes a pump  104  comprising a substantially rigid container  106  that includes a pump chamber  108  and a control chamber  110  disposed therein. Pump chamber  108  and control chamber  110  are fluidically isolated (i.e., not able to be placed in fluid communication) from each other by a flexible membrane  112 , disposed between the two chambers, such that pump chamber  108  is coupled to control chamber  110  and in operative association therewith. Such a membrane may (as just one example) be constructed of medical grade polyvinyl chloride. 
   “Substantially rigid” as used herein refers to a material, or a component constructed therefrom, that does not flex or move substantially under the application of forces applied by the pumping system. A “control chamber” as used herein refers to a chamber of a pumping system that is coupled to, or contains, a volumetric chamber, for example a pump chamber, for the purpose of exerting a force on the volumetric chamber and, in preferred embodiments, for determining a measured parameter related to the volume of the volumetric container. The term “coupled to” as used in this context with respect to chambers or other components of the pumping system, refers to the chambers or components being attached to, or interconnected with, another component of the pumping system, such that the other component is able to exert a force on an external surface of the chamber or component to which it is coupled. 
   Liquid to be pumped by pump system  100  enters pump chamber  108  via inlet line  114  including an inlet valve  116  therein. Liquid can be pumped from pump chamber  108  to a desired downstream destination through outlet line  118  including an outlet valve  120  therein. 
   Control chamber  110  includes a pressure measuring component  122  therein for determining the pressure of the measurement gas within the control chamber. A “pressure measuring component” as used herein refers to a device that is able to convert a fluid pressure into a measurable signal or parameter. Pressure measuring components that may be useful in this embodiment include but are not limited to: transducers; pressure gauges; manometers; piezoresistive elements; and others as apparent to those of ordinary skill in the art. 
   Preferred embodiments of control chamber  110  of pumping system  100  also include a vent line  124  including a vent valve  126  therein. Control chamber  110  is connected in fluid communication with a variable volume cylinder  128  via a measurement gas inlet line  130 . Variable volume cylinder  128  which includes a piston  132  therein which is moved and actuated by motor  133  for compressing, or expanding the volume of the measurement gas contained within the system. 
   Pumping system  100  also preferably contains a processor  134  which is in electrical communication with the various valves, pressure transducers, motors, etc. of the system and is preferably configured to control such components according to a desired operating sequence or protocol. Reference to a processor being “configured” to perform certain tasks herein refers to such processor containing appropriate circuitry, programming, computer memory, electrical connections, and the like to perform a specified task. The processor may be implemented as a standard microprocessor with appropriate software, custom designed hardware, or any combination thereof. As discussed in more detail below, processor  134 , in addition to including control circuitry for operating various components of the system, also preferably includes a comparer that is configured to determine a measured parameter related to the volume of pump chamber  108  and to detect the presence of any gas contained within pump chamber  108  during operation of pump  104 . A “comparer” as used herein refers to a processor (e.g., with appropriate programming) or circuit or component thereof that is able to compare the values of two or more measured parameters or other parameters derived therefrom. 
   In embodiments where passing gas through the system is problematic, pump chamber  108  is oriented in an essentially vertical configuration during operation such that inlet line  114  is disposed above outlet line  118 . The above-described orientation is advantageous for preventing any gas which may be present in pump chamber  108  during operation from being pumped from the pump chamber to a downstream destination through outlet line  118 . Instead, any gas contained within pump chamber  108  will tend to rise towards the top of the pump chamber, for example the region adjacent to inlet port  136 , and will be detected by the system, as described in more detail below, before being pumped from the pump chamber. 
   In some embodiments, pump chamber  108  includes the novel inclusion of a plurality of spacers  138  included therein. The spacers  138  function to prevent flexible membrane  112  from contacting an inner surface  140  of the pump chamber when the liquid contained within pump chamber  108  is being pumped through outlet line  118 . During the pump stroke, the maximum displacement of flexible membrane  112  which is permitted by spacers  138  is shown in  FIG. 1  by dashed line  142 . It can be seen that even with flexible membrane  112  at its maximum displacement into pump chamber  108 , as defined by dashed line  142 , spacers  138  create a dead space  144  to contain any gas which may be present in pump chamber  108 , thus inhibiting the gas from being pumped through the pump chamber. Spacers  138 , in combination with the vertical orientation of pump chamber  108 , also serve to assist any gas present in pump chamber  108  to rise to the top of the pump chamber so that it may more easily be purged from the pump chamber, as described in more detail below. 
   Pump chamber  108  of pumping system  100  is essentially defined by a substantially rigid wall  145  (e.g., made of a rigid plastic such as a polyacrylate) having a flexible membrane  112  disposed over the wall, thus forming a volumetric chamber. An alternative embodiment for providing a pump chamber and a control chamber is shown in FIG.  2 . Pump  152  of pumping system  150  includes a pump chamber  154  which comprises an essentially flexible container  156  disposed within a substantially rigid enclosure  158  having an interior volume surrounding pump chamber  154  which comprises a control chamber  160 . In other embodiments (not shown), the pump chamber may be differently configured or disposed within the control chamber and may include substantially rigid, but moveable surfaces, as opposed to the flexible surfaces of pumping systems  100  and  150  described above. 
   One embodiment of a method for operating the pumping system  100  shown in  FIG. 1  for pumping a liquid with pump chamber  108 , and for detecting the presence of a gas in pump chamber  108 , is shown in detail in the flow charts of  FIGS. 3   a - 3   c.    
   Referring to  FIG. 3   a , an exemplary pump cycle utilizing pumping system  100  will be described. The pump cycle illustrated utilizes changes in displacement of the piston to change the pressure of a measurement fluid within the system in order to apply selected forces to membrane  112  for pumping and air detection. The embodiment illustrated also utilizes an equation of state (e.g. the ideal gas law) in determining pump chamber volumes from measured or known values of pressure and volume. 
   For embodiments employing a protocol for detecting air/gas where pump and/or control chamber volumes are determined, at least in part, from measured pressures by utilizing an equation of state describing the pressure-volume behavior of a measurement gas, the pump chamber preferably includes a movable surface which comprises an elastic membrane. The restoring force of the elastic membrane, when stretched or displaced from a relaxed equilibrium condition, enables the pressure on each side of the membrane (i.e. in the pump chamber and control chamber) to be different, where the degree of difference in the pressures, and the resistance to further displacement/stretching (stress/elastic energy stored in the membrane), is a function of the degree of stretch or displacement from the relaxed equilibrium condition of the membrane. In such embodiments, it is also preferred that the measurement gas pressures applied to the elastic membrane during the determination of pump/control chamber volumes at the first and second conditions of applied force for detecting air/gas in the pump chamber discussed above, tend to stretch the elastic membrane (if air/gas is present in the pump chamber), from its equilibrium configuration before the pressure is applied, by a different extent for each condition, so that the stress in the membrane and its resistance to further displacement in response to a given level of applied pressure will be different for the first and second condition (or in other words, the force/displacement response of the elastic membrane for the first and second conditions will be asymmetrical). In such embodiments, the difference in the pressure in the control chamber versus the pressure in the pump chamber, at an equilibrium condition, will be different for the first condition of applied pressure versus the second condition of applied pressure. In such embodiments, without being tied to any particular physical mechanism, it is believed that the different level of stress and strain of the elastic membrane during measurements of pump/control volume determined at the first and second conditions above create, at least in part, deviations in the pressure-volume behavior of the measurement gas from that predicted for each condition by the equation of state, which deviations can create and/or enhance a difference in the volume of the pump/control chamber determined for each condition by using the equation of state. 
   In some embodiments, one way to achieve or enhance such asymmetry in the response of the elastic membrane to the applied measurement gas pressures utilized during volume determinations for gas detection is to perform the volume determination steps when the pump chamber flexible elastic membrane has already been stretched, from the configuration it has at a relaxed equilibrium condition, with essentially equal fluid pressures on each side of the membrane, before the application of pressurized measurement gas to the membrane for the purpose of volume measurement. This can be accomplished, for example, by performing the volume determinations related to air/gas detection after filling the pump chamber with sufficient liquid so that the elastic membrane is at least somewhat stretched, and preferably substantially stretched, by displacement of the membrane in the direction of the control chamber, and by using a positive measurement gas pressure during volume measurement at the first condition and a negative measurement gas pressure during volume measurement at the second condition (or vis versa). Such a condition of displacement of elastic membrane  112  for pump  104  is illustrated in  FIG. 4 , which shows pump chamber  108  after filling with a liquid  220  to be pumped and immediately before volumetric measurements performed (as described below) for detecting the presence of a gas  222  in the pump chamber. In alternative embodiments the desired asymmetry in the response of the elastic membrane during volume determinations involved in air/gas detection could also be achieved by utilizing levels of measurement gas pressures applied to the elastic membrane for volumetric determinations performed at the first and second conditions of measurement that are selected to impart a different, and preferably substantially different degree of elastic stretch to the membrane. While preferred embodiments of pump chambers for use when utilizing an equation of state based procedure for calculating pump/control chamber volumes include a moveable surface at least partially comprised of an elastic membrane, in alternative embodiments, non-elastic movable surfaces could potentially be used so long as the measurement fluid pressures applied to the surface during volume measurement at the first condition and second condition create a different levels of stress in the surface and different differences in the equilibrium pressures within the control and pump chamber. Such embodiments could, for example, utilize a non-elastic movable surface or flacid membrane, where measurement fluid pressures applied during the first condition of volume determination tend to move the surface/membrane (if a gas is present in the pump chamber) to its maximum allowed displacement so that the surface is no longer free to move in response to the applied force, a stress is created in the surface/membrane, and a pressure difference exists between the pump and control chambers. Measurement of volume at a second condition for such embodiments could apply a different measurement fluid pressure to the surface, which pressure tends to move the surface/membrane (if a gas is present in the pump chamber) to reduce or substantially eliminate the stress within the surface/membrane so that at equilibrium, the difference in pressure in the pump and control chambers is reduced or essentially eliminated. 
   Referring again to the protocol of  FIG. 3 , initially, it will be assumed that pump chamber  108  has been emptied, and that elastic membrane  112  is extending into pump chamber  108  at its maximum allowable displacement defined by line  142 . Piston  132  is assumed to be at its far left position of travel (shown as position  1  in FIG.  1 ). Referring to  FIG. 3   a , step  1  ( 170 ) involves initializing the system so that all valves are closed and piston  132  and flexible membrane  112  are in the positions described above. 
   Step  2  ( 172 ) involves filling the pump chamber  108  with a liquid to be pumped. The step involves first opening inlet valve  116 , then actuating motor  133  so as to move piston  132  to position  3  shown in  FIG. 1 , thereby increasing the volume of pump chamber  108  by an amount defined as ΔV. Then, inlet valve  116  is closed in order to isolate pump chamber  108 . 
   Step  3  ( 174 ) of the exemplary pumping cycle involves a series of sub-steps for determining the volume of control chamber  110  and/or pump chamber  108  and for detecting the presence of any gas contained within pump chamber  108 . Step  3  ( 174 ) is described in greater detail in  FIG. 3   b.    
   Referring again to  FIG. 3   a , step  4  ( 208 ) of the pumping cycle involves delivering the liquid contained in pump chamber  108 . First, outlet valve  120  is opened. Motor  134  is then actuated to move piston  132  from position  3  to position  1 , thereby delivering a volume of fluid ΔV. Outlet valve  120  is then closed in order to isolate pump chamber  108 . In some embodiments, where the accuracy of determining the volume delivered by pump chamber  108  is critical, the volume of pump chamber  108  after step  4  ( 208 ) may be determined (e.g., by repeating substeps  1 - 4  ( 176 ,  178 ,  180 ,  182 ) of the volume calculation and air detection subcycle of  FIG. 3   b  described below). In which case, the volume delivered for the above described pump stroke can be determined by taking a difference in the volume of pump chamber  108  determined in step  3  ( 174 ) and in step  5  ( 210 ). Finally, if multiple pump strokes are desired, the entire pump cycle of  FIG. 3   a  may be repeated. 
   Referring to  FIGS. 3   b - 3   c , one embodiment of a volume calculation and gas detection method, shown at step  3  ( 174 ) of  FIG. 3   a , is shown. Substep  1  ( 176 ) of subcycle  174  involves measuring the pressure P 1  of the measurement gas in control chamber  110  with pressure transducer  122  and recording or storing the pressure with processor  134 . In substep  2  ( 178 ) piston  132  is moved from position  3  to position  1  thereby reducing the volume of the measurement gas contained within the system by ΔV. In substep  3  ( 180 ) the pressure of the measurement gas in control chamber  110  is measured again and recorded as P 2 . It will be appreciated that P 2  will be greater than P 1  due to the compression of measurement gas within the system. The volume of fluid contained in pump chamber  108  is then determined in substep  4  ( 182 ), with the pump chamber at this first condition, using an appropriate equation of state for the measurement fluid being utilized. In the case of a measurement gas, such as air, for systems utilizing pumping pressures which are relatively low (typical pumping pressures utilized by pumping systems according to the invention range from abut −14 psig to about 15 psig) the ideal gas law can be employed. Recognizing that no measurement gas was added to or removed from the system, and utilizing the ideal gas law combined with conservation of mass, the volume of fluid contained in pump chamber  108  is determined by: 
               V   F     =       V   T     -         P   2     ⁢   Δ   ⁢           ⁢   V         P   2     -     P   1                   (   1   )             
 
Equation 1 assumes that any temperatures changes or differences caused by changing the volume of measurement gas are minimal and that the system is essentially isothermal. It will be appreciated that for systems where temperature changes may be significant, the temperature dependence of the measurement fluid, as defined by the equation of state being used, may be incorporated into the volume calculation of substep  4  ( 182 ) in a straightforward fashion, as apparent to those of ordinary skill in the art. V F  in equation 1 refers to the internal volume of pump chamber  108  and V T  refers to the known total volume of the system including pump chamber  108 , control chamber  110 , and the volumes contained within measurement fluid inlet line  130  and cylinder  128 .
 
   The remaining substeps of the volume calculation subcycle  174  involve redetermining the volume of the pump chamber  108  at a different condition and comparing the volumes determined at the first and second conditions. In substep  5  ( 184 ) of  FIG. 3   b , control chamber vent valve  126  is opened to equilibrate the pressure in control chamber  110  with the surrounding atmosphere. Vent valve  126  is then closed. A new pressure P 1  is measured with transducer  122  in control chamber  110  in substep  6  ( 186 ). In substep  7  ( 188 ) piston  132  is moved from position  1  to position  3  thereby increasing the volume of measurement gas within the system by ΔV. In substep  8  ( 190 ) the new pressure P 2  in control chamber  110 , which pressure will be below atmospheric pressure, is measured and recorded. In substep  9  ( 200 ) the volume of pump chamber  108  V F  is calculated as described above in substep  4  ( 182 ). Substep  10  ( 202 ) involves determining the difference between V F  determined in substep  4  ( 182 ) and V F  determined in substep  9  ( 200 ) and taking an absolute value of the difference. In substep  11  ( 204 ), shown in  FIG. 3   c , the above difference is compared to a predetermined limit that is proportional to a maximum allowable quantity of air or other gas which can be present in pump chamber  108  during operation. The predetermined limit is typically determined empirically, as discussed below, and chosen such that air volume exceeding dead space  144  volume will also exceed the predetermined limit. If the difference exceeds the predetermined limit the processor  134  will create an alarm condition and initiate an air purge, as described in more detail below. 
   If the difference in measured volumes is less than the allowable limit ( 204 ), the system will proceed to pump the liquid contained in pump chamber  108 . In substep  12  ( 206 ) the system opens control chamber vent valve  126  in order to equilibrate the pressure in control chamber  110  and the surrounding atmosphere, and then closes vent valve  126 . Pumping system  100  is now in condition to deliver the liquid contained in pump chamber  108 . 
   As described above, the measured volumes at the two different conditions can be compared to detect the presence of gas in the pump chamber. If the presence of a gas is detected in the pump chamber and is of sufficient quantity to cause the system to set off an alarm, as described above in substep  11  ( 204 )  FIG. 3   c , instead of proceeding to deliver the fluid to a desired downstream destination as described above, the pumping system  100  will instead initiate an air purge. During the air purge, instead of outlet valve  120  being opened while fluid is being pumped from pump chamber  108 , inlet valve  116  is opened, and the fluid, including any gas in the pump chamber, is pumped from the pump chamber through inlet line  114  to a safe purge destination. 
   It should be appreciated that while the above described example of a pump stroke cycle for pumping system  100  was described as being filly controlled, and regulated by a processor, the method could equivalently be performed under manual operator control without utilizing such a processor or by using any other mechanism to control the operation. In addition, while the above described methods involve an essentially ideal gas as a measuring fluid, other embodiments of the invention may utilize non-ideal measurement gases, or liquids as measurement fluids. When such alternative measurement fluids are used, the ideal gas law may no longer be an appropriate equation of state to utilize for determining volumetric measurements but instead an equation of state appropriate for the measurement fluid being used may be utilized. In addition, as discussed earlier, a variety of other techniques for measuring the volume contained in a volumetric container can be used to determine a measured parameter related to the volume of a pump chamber having a movable surface or flexible membrane at a first and second condition of applied force, such alternative means of volumetric measurement being apparent based on the disclosure herein and are within the scope of the present invention. In addition, also as discussed previously, the skilled practitioner will envision many alternative mechanisms for applying a variable level of force to a moveable wall, for example flexible elastic membrane  112 , or other movable wall configuration, of a pump chamber, which can be substituted for the pressurized gas pump drive system  230  described in FIG.  1 . It should also be emphasized that the particular steps described as part of the exemplary pump cycle methods described herein may be performed in a different sequence, and certain steps may be substituted or eliminated, without effecting the overall performance of the methods. For example, when detecting the presence of a gas in the pump chamber, instead of applying a positive pressure to the flexible membrane of the pump chamber to calculate a first volume followed by applying a negative pressure to the flexible membrane of the pump chamber to calculate a second volume, these steps could easily be interchanged or both pressures may be positive or negative, so long as they differ by a sufficient amount to enable the detection of gas in the pump chamber. 
     FIG. 5  shows a pumping system  300  utilizing an alternative pump drive system  302  including a measurement fluid supply system  304  which is a constant volume system. Fluid supply  304  is able to apply a force to flexible membrane  112  of pump chamber  108  by changing the quantity of a measurement gas contained within constant volume fluid supply system  304 . Pump drive system  302  of pumping system  300  includes a control chamber  110  which is connected via measurement gas inlet line  306  to a reference chamber  308  having a known volume. Measurement gas is supplied to reference chamber  308  and control chamber  110  via pump  312 . Pumping system  300  also includes a processor  324 , similar to that described previously for pumping system  100  shown in  FIG. 1 , which is configured to control the operation of the various components of the system and perform determinations of measured parameters related to the volume of pump chamber  108 , as described in more detail below. 
   An exemplary embodiment of a pump stroke cycle, including the detection of a gas in pump chamber  108  utilizing the ideal gas law in determining pump chamber volumes, which can be utilized for operating pumping system  300  is described in  FIGS. 6   a - 6   c . Referring to  FIG. 6   a , initially, it is assumed that pump chamber  108  has been emptied and flexible membrane  112 , preferably an elastic membrane as previously discussed in the context of system  100  of  FIG. 1 , is displaced into pump chamber  108  as described previously with regard to  FIG. 3   a . In addition, in the initial state of the system in step  1  ( 350 ) it is assumed that all valves of the system are closed. Step  2  ( 352 ) of the method involves filling pump chamber  108  with a liquid through inlet line  114  and inlet valve  116 . The step involves first opening valve  314  located on line  310  between reference chamber  308  and pump compressor  312 , and operating pump  312  to create a desired negative pressure in reference chamber  308 , as measured by pressure transducer  316 . Next, valve  318  on line  306  and inlet valve  116  are opened. The operation of pump  312  can be discontinued when pump chamber  108  has filled with liquid to a desired extent. In step  3  ( 354 ) of the method, pump chamber  108  and control chamber  110  are isolated by closing inlet valve  116  and valve  318 . 
   Step  4  ( 356 ) comprises a volume calculation and air detection subcycle described below in more detail with reference to  FIG. 6   b . The liquid contained in pump chamber  108  is delivered through outlet line  118  in step  5  ( 374 ). Step  5  ( 374 ) involves opening valve  314 , operating pump  312  to create a desired positive pressure in reference chamber  308 , opening valves  318  and outlet valve  120 , and allowing the liquid contained in pump chamber  108  to flow through outlet line  118  until a desired quantity of liquid has been delivered. At which point, in step  6  ( 376 ), outlet valve  120  is closed, so as to isolate pump chamber  108 , and valve  318  is closed to isolate control chamber  110 . In step  7  ( 378 ) the final volume of pump chamber  108  is determined (e.g., by re-performing substeps  1 - 6  of  FIG. 6   b  described below and calculating a final volume V F2 ). The volume delivered by pump chamber  108  during the pump stroke is calculated in step  8  ( 380 ) by taking a difference between the pump chamber volume V F1  determined in step  4  ( 356 ) and the pump chamber volume V F2  determined in step  7  ( 378 ). For embodiments involving delivery of liquids via multiple pump stroke cycles, the steps described in  FIG. 6   a  can be repeated. 
     FIG. 6   b  shows one embodiment of a method for determining gas volume in the method of  FIG. 6   a  step  4  ( 356 ). Substep  1  ( 358 ) comprises an optional step whereby the pressure in control chamber  110  is equilibrated to the atmosphere by opening an optional vent valve  320  located on optional vent line  322  connected to control chamber  110 . After equilibration with the atmosphere, vent valve  320  is closed. In substep  2  ( 360 ) pressure P C1  in control chamber  110  is measured with pressure transducer  122  and stored by processor  324 . In substep  3  ( 362 ), pump  312  is operated so as to increase the pressure P R  in reference chamber  308  to a value P R1  that is greater than P C1  and also greater than atmospheric pressure. After such pressure in reference chamber  308  is obtained, the operation of pump  312  is discontinued, valve  314  is closed, and pressure P R1  in reference chamber  308  is measured with pressure transducer  316  and stored by processor  324 . 
   Substep  4  ( 364 ) involves allowing a quantity of measurement gas to be exchanged between control chamber  110  and reference chamber  308 . This can be accomplished by opening and, optionally, closing valve  318 . If desired, valve  318  may be opened for a sufficient time to allow the pressure in control chamber  110  and reference chamber  308  to equilibrate to a common value. For embodiments where the pressures in control chamber  110  and reference chamber  308  are allowed to equilibrate in substep  4 , the system can compare the pressure signals obtained from pressure transducer  122  and pressure transducer  316  and can create an alarm condition indicating a system fault if the pressures do not essentially agree. 
   In substep  5  ( 366 ) the system determines pressure P C2  in control chamber  110  and P R2  in reference chamber  308  and records the pressures (P C2  and P R2  should be essentially the same if the pressures in control chamber  110  and reference chamber  308  were allowed to equilibrate in substep  4  above). 
   In substep  6  ( 368 ) the volume of the control chamber  110 , (which also includes the volume of line  306  up to valve  318  and line  322  up to valve  320 ) is determined at this first set of conditions of measurement (or “first condition” as used herein) from the known volume of reference chamber  308  and the pressures determined above utilizing the ideal gas law equation of state and conservation of mass for the measurement gas exchanged during substep  4  ( 364 ) above. As described for the previous embodiment, equations of state other than the ideal gas law may be used for measurement fluids which do not simulate ideal gas behavior. Also, as before, the system is assumed to be isothermal, specifically, the temperature in reference chamber  308  is assumed to be equal to the temperature in control chamber  110  during pressurization and gas exchange. The volume of the control chamber described above V C  is determined by: 
               V   C     =         (       P   R1     -     P   R2       )     ⁢     V   R         (       P   C2     -     P   C1       )               (   2   )             
 
where V R  is the known volume of reference chamber  308 . The volume of fluid in pump chamber  108  may be explicitly determined, if desired, by subtracting V C  from V T , which is the known total volume of pump chamber  108  and control chamber  110 .
 
   In substep  7  ( 370 ) and substep  8  ( 372 ) the presence of any gas contained in pump chamber  108  is determined. In substep  7  ( 370 ), substeps  1 - 6  ( 358 ,  360 ,  362 ,  364 ,  366 ,  368 ) described above are repeated, except that in substep  2 , pump  312  is operated so as to decrease the pressure in reference chamber  308  to a value lower than that of the pressure in control chamber  110  and atmospheric pressure. In substep  8  ( 372 ) the processor determines the difference between the volume of pump chamber  108  determined in substep  7  ( 370 ) (i.e. the volume determined at the second set of measurement conditions or “second condition” as used herein) and the volume of pump chamber  108  determined in substep  6  ( 368 ). 
   As shown in  FIG. 6   c , the value of the difference in the calculated volumes is compared to a predetermined threshold limit (step  390 ), and if the value exceeds the limit processor  324  creates an alarm condition and initiates an air purge (step  392 ), similar to that described previously. If the system fails to detect any gas in pump chamber  108  (i.e., the difference in the measure volumes is below the threshold limit) the system will proceed to deliver liquid contained in pump chamber  108 , as described in more detail in  FIG. 6   a.    
   An alternative embodiment to the pump system  300  shown in  FIG. 5 , which also utilizes a pump drive system including a fluid supply system having a constant known volume, is shown in  FIG. 7. A  pumping system  400  having a pump drive system  402  including a fluid supply system  404  including a reference chamber  406  having a known volume. As opposed to system  300  shown in  FIG. 5 , where the measurement gas was supplied to reference chamber  308  by a pump  312 , in pumping system  400 , measurement gas is supplied to reference chamber  406  via a positive pressure storage tank  408  and a negative pressure storage tank  410 . Positive pressure storage tank  408  is connected to reference chamber  406  via line  412  containing a valve  414  therein. Negative pressure tank  410  is connected to reference chamber  406  via line  416  containing a valve  418  therein. In preferred embodiments, positive pressure tank  408  and negative pressure tank  410  each include pressure transducers  420  and  422  for continuously monitoring the pressure of a measurement gas contained therein. As illustrated in the figure, fluid supply system  404  of pumping system  400  is a completely closed system wherein measurement gas is contained within the system without additional quantities of measurement gas being added to or removed from the system during the pump cycle. However, in alternative embodiments, the system can include one or more lines for fluid communication with the environment for venting or other purposes. In one such alternative embodiment, instead of pump  424  creating a pressure difference between tanks  408  and  410  by pumping measurement gas from tank  410  to  408 , the pump could pump air from the surroundings to tank  408  and could pump air from tank  410  to the surroundings to create the pressure difference. 
   Before the beginning of a pump cycle which utilizes pumping system  400 , a pressure differential between positive tank  408  and negative tank  410  is established by opening valves  421  and  423  and operating pump  424  to move measurement gas from negative tank  410  to positive tank  408 . The pump cycle and volume measurement cycle utilizing system  400  is similar to that described for system  300  of  FIG. 5 , except that in order to create a positive pressure of measurement gas in reference chamber  406  and control chamber  110  and in order to create a different (in this example, negative) pressure in reference chamber  406  and control chamber  110  the chambers are placed in fluid communication with positive tank  408  and negative tank  410  respectively, instead of establishing the pressures by utilizing a pump. 
   Pumping system  400  enables a more constant and controllable pressure to be applied to control chamber  110  during the filling and emptying of pump chamber  108 , as compared to pump system  300  shown in FIG.  5 . Preferably, positive tank  408  and negative tank  410  have internal volumes that are substantially greater than the internal volume of reference chamber  406  and control chamber  110 . In preferred embodiments, positive tank  408  and negative tank  410  have volumes that are sufficiently greater than those of reference chamber  406  and control chamber  110  so that the pressure of measurement gas in tanks  408  and  410  remain essentially constant throughout the pump cycle. Typically, tanks  408  and  410  will be at least 10 times larger, and are preferably at least 20 times larger in volume than reference chambers  406  and control chamber  110 . In general, for pumping systems utilizing a control chamber and a reference chamber (for example the systems shown in FIG.  5  and FIG.  7  and described below in  FIG. 8 ) the control chamber preferably has a volume similar to or on the same order of magnitude as the volume of the pump chamber, and the reference chamber has a volume that is from about 1-10 times that of the control chamber. 
   It should be appreciated that the particular ways in which the various tanks, valves, pumps, and chambers of the various pumping systems described herein are arranged, configured, and interconnected can be varied considerably without changing the overall performance or operation of the pump drive system. A variety of alternative configurations for the pumping systems described herein have been previously described in U.S. Pat. Nos. 4,778,451, 4,808,161, 4,826,482, 4,976,162, 5,088,515, and 5,178,182, each of which is commonly owned and which are incorporated herein by reference in its entirety. 
   A preferred arrangement of components for providing a pump drive system according to the invention is shown in FIG.  8 . Pumping system  500  includes a pump  104  including a pump chamber  108  separated from a control chamber  110  by a flexible membrane  112  disposed therebetween, similar to that described previously. Pumping system  500  includes a pump drive system  502  including a fluid supply system  504  connected in fluid communication with control chamber  110 . Pump drive system  502  includes a processor  506  configured for controlling the various components of the system for pumping a liquid with pump chamber  108 , and including a comparer for determining the presence of a gas in pump chamber  108  from measured parameters related to the volume of pump chamber  108 , as described previously. Fluid supply system  504  includes a positive pressure source comprising a positive pressure tank  508  with a measurement gas having a positive pressure contained therein. Positive pressure tank  508  includes a pressure transducer  510  configured to measure the pressure of the measurement gas and send a signal to processor  506 . Fluid supply system  504  also includes a negative pressure source comprising a negative pressure tank  512  having a measurement gas at a negative pressure contained therein. Negative pressure tank  512  includes a pressure transducer  514  for measuring the pressure of a measurement gas contained therein. 
   Fluid supply system  504  also contains a pump  516  positioned and configured to pump measurement gas from negative tank  512  through line  518 , valve  520 , valve  522  and line  524  to positive pressure tank  508 , so as to establish a pressure difference between the measurement gas contained in positive pressure tank  508  and negative pressure tank  512 . Positive pressure tank  508  has an outlet line  526  and negative pressure tank  512  has an outlet line  528 , each of which lines are in fluid communication with a switch valve  530 . The outlet of switch valve  530  is able to be placed in fluid communication with both control chamber  110  and reference chamber  532  of the system. Switch valve  530  is preferably a solenoid-operated three-way type valve which is controlled by processor  506  so that in a first position, positive pressure tank  508  is placed in fluid communication with control chamber  110  and/or reference chamber  532 , and in a second position negative pressure tank  512  is placed in fluid communication with control chamber  110  and/or reference chamber  532 . 
   Outlet line  534  from switch valve  530  includes a variable-sized orifice valve  536  therein, which valve comprises, in preferred embodiments, a valve having an orifice for fluid flow therethrough, where the size of the orifice is selectively adjustable over an essentially continuous range of values in order to control a flow rate of fluid therethrough. The size of the orifice in variable size orifice valve  536  is controlled, in preferred embodiments, by processor  506  in order to selectively vary the pressure of the measurement gas downstream of variable size orifice valve  536 . Variable size orifice valves for use in the invention are known in the art and have been utilized for other purposes. Such valves are available, for example, from Parker Hannifin Corp., Pneutronics Division. 
   One embodiment of the present invention involves the novel incorporation of such a variable size orifice valve in a fluid supply system for measuring the volume of a volumetric chamber and, in some embodiments, for providing a pressurized fluid in contact with the moveable surface of a pump chamber. 
   The outlet of variable size orifice valve  536  is in fluid communication with measurement fluid inlet line  538 , which provides measurement gas to control chamber  110 . The outlet of variable size orifice valve  536  is also in fluid communication with valve  540  on inlet line  542  of reference chamber  532 . Reference chamber  532 , in preferred embodiments, also includes a vent line  544  through which measurement gas can be vented to the atmosphere by opening valve  546 . 
   Reference chamber  532  also includes a pressure transducer  548  in fluid communication therewith, which measures the pressure of a measurement gas in the reference chamber. 
   One embodiment of a method for operating pumping system  500  is shown in  FIGS. 9   a - 9   c . The preferred pump stroke cycle includes steps for filling and dispensing a liquid from pump chamber  108 , as well as steps for determining the volume of a volumetric container using the ideal gas law equation of state and conservation of mass, so as to determine a volume of liquid pumped and to detect the presence of any gas in pump chamber  108 . As above, it is assumed initially that pump chamber  108  has been emptied of liquid and that flexible membrane  112 , preferably an elastic membrane when, as here, pump chamber volumes are determined using the ideal gas law or other equation of state (as previously discussed), is extending to the maximum permissible extent allowed by spacers  138  into pump chamber  108 . Step  1  ( 600 ) involves initializing the system. The initialization of the system involves opening valves  520  and  522  and operating pump  516  to create a desired pressure of measurement gas in positive pressure tank  508  and negative pressure tank  512 , followed by discontinuing the operation of pump  516  and closing valves  520  and  522 . It is also assumed as an initial condition that all valves of the system are closed and that switch valve  530  is positioned so that its outlet is in fluid communication with positive pressure tank  508 . 
   Step  2  ( 602 ) involves filling pump chamber  108  with liquid through inlet line  114  and inlet valve  116 . First, switch valve  530  is positioned to select negative pressure tank  512 . Next, inlet valve  116  is opened and variable size orifice valve  536  is opened until pump chamber  108  has filled with liquid. In preferred embodiments, variable size orifice valve  536  is also selectively controlled during filling so as to provide an essentially constant negative pressure in control chamber  110 , as described in more detail below. As will also be described in more detail below, the ability to vary the pressure in control chamber  110  via control of variable size orifice valve  536  enables system  500  to detect when flexible membrane  112  is distended into control chamber  110  to its maximum permissible extent indicating that pump chamber  108  is completely full of liquid. Thus, in preferred embodiments, system  500  can detect when pump  104  has reached the end of a stroke, either in the filling or emptying of pump chamber  108 . This end of stroke detection method of preferred embodiments for operating pump system  500  is described in more detail below. 
   In step  3  ( 604 ) pump chamber  108  and control chamber  110  are isolated by closing inlet valve  116  and variable size orifice valve  536  respectively. Step  4  ( 606 ) comprises a subcycle which determines the volume of the volumetric container comprising pump chamber  108  and/or the volumetric container comprising control chamber  110 , and determines the presence of any gas in pump chamber  108  utilizing the determined volumes. The various substeps of step  4  ( 606 ) are outlined in detail in  FIGS. 9   b  and  9   c.    
   Referring to  FIG. 9   b , substep  1  ( 608 ), which is optional, involves equilibrating the pressure in control chamber  110  and reference chamber  532  with the atmosphere by opening valve  540  and valve  546  in order to vent the control chamber and the reference chamber through vent line  544 . Substep  2  ( 610 ) involves positioning switch valve  530  to select positive pressure supply tank  508 , and opening variable size orifice valve  536  in order to pressurize control chamber  110 . In some embodiments, variable size orifice valve  536  can be opened for a sufficient period of time so that the pressure of measurement gas in positive pressure supply tank  508  in control chamber  110  is allowed to equilibrate. In such embodiments, the pressure measured by transducer  122  on control chamber  110  should be essentially the same as that measured with pressure transducer  510  on the positive pressure tank. If these pressures do not agree, processor  506  can be configured to indicate that there is a system fault and can shut down operation of the system. After pressurizing control chamber  110 , variable size orifice valve  536  is closed and the measured pressure P C1  in control chamber  110  is recorded. In substep  3  ( 612 ) the pressure P R1  in reference chamber  532 , as measured with pressure transducer  548  (which will be different from that in control chamber  110 ) is stored by processor  506 . 
   Substep  4  ( 614 ) involves allowing for measurement gas exchange between control chamber  110  and reference chamber  532 . The gas exchange is enabled by opening and, optionally, closing valve  540 . In some embodiments, valve  540  may be opened for a sufficient period of time to equilibrate the pressures in reference chamber  532  and control chamber  110  to essentially the same value. For such embodiments, it should be appreciated that pressure transducer  122  in fluid communication with control chamber  110  is optional since the measurement gas pressures in control chamber  110  can be determined, for various steps of the method, with pressure transducers  548 ,  510 , or  514 . In substep  5  ( 616 ), after allowing gas exchange, pressure P C2  and P R2  in control chamber  110  and reference chamber  532  respectively are measured and stored by processor  506 . The volume V C  of the control chamber and, optionally, the volume V F  of pump chamber  108  at this first condition can be calculated from the known volume V R  of reference chamber  532  and the above-measured pressures utilizing the ideal gas equation of state and conservation of mass, as described previously, from equation 2 shown previously. 
   In order to detect the presence of any gas in pump chamber  108 , in substep  7  ( 620 ), substeps  1 - 6  ( 608 ,  610 ,  612 ,  614 ,  616 ,  618 ) are repeated as described above except that in substep  2  ( 610 ) switch valve  530  is positioned to select negative pressure supply tank  512 . In substep  8  ( 622 ) processor  506  determines an absolute value of the difference between volume measurements determined in substep  7  ( 620 ) (i.e. at the second condition) and substep  6  ( 618 ) above and, as shown in  FIG. 9   c , compares this difference to a predetermined permissible limit and creates an alarm condition and initiates an air purge from pump chamber  108 , in a manner substantially similar to that previously described, if the value exceeds the limit. If the value does not exceed the predetermined limit, the system proceeds to deliver the liquid in pump chamber  108 , as described in  FIG. 9   a , steps  5 - 7 . 
   Referring again to  FIG. 9   a , in step  5  ( 624 ), liquid is delivered from pump chamber  108  by, optionally, opening valves  546  and  540  to vent control chamber  110 , followed by closing valves  540  and  546 , positioning switch valve  530  to select positive pressure tank  508 , and opening outlet valve  120  on outlet line  118  of pump chamber  108  while opening and controlling the orifice size of variable size orifice valve  536  to yield a desired pressure in control chamber  110  for pumping the liquid from the pump chamber. In preferred embodiments, variable size orifice valve  536  is controlled by processor  506  to maintain the pumping pressure in control chamber  110  at a desired value during the pump chamber emptying stroke. In such embodiments, processor  506  preferably includes a controller, for example a PID closed loop control system, which allows the processor to selectively change the size of the orifice within the variable size orifice valve  536  based, at least in part, on a difference between a pressure measured within control chamber  110  by transducer  122 , and a desired predetermined pumping pressure. As discussed above in the context of filling pump chamber  108 , pumping system  500  also preferably includes a method for controlling variable size orifice valve  536  so that the system is able to determine when flexible membrane  112  has stopped moving into pump chamber  108  indicating that liquid flowing from pump chamber  108  has stopped. This end of stroke detection method is described in more detail below. After a desired quantity of fluid has been delivered from pump chamber  108  or after an end of stroke condition has been determined as discussed above, outlet valve  120  downstream of pump chamber  108  is closed and, optionally, variable size orifice valve  536  is closed in order to isolate the pump chamber and control chamber. 
   Step  6  ( 626 ) of the pump cycle involves repeating the volume calculation routine by re-performing substeps  1 - 6  ( 608 ,  610 ,  612 ,  614 ,  616 ,  618 ) shown in  FIG. 9   b  to calculate a final volume V F2  of pump chamber  108  after delivery of the liquid. Finally, in step  7  ( 628 ) the volume delivered by pump  104  during the pump cycle ΔV can be determined by taking a difference in the pump chamber or control chamber volume determined after filling pump chamber  108  (determined in step  4 ) and the volume determined after pumping the liquid from pump chamber  108  (determined in step  6 ). If desired, a new pump cycle can be initiated by repeating the steps outlined in  FIG. 9   a.    
   The flow rate of the liquid delivered from the pump chamber for each pump stroke will be a function of the force applied to the flexible membrane of the pump chamber during the filling steps and delivery steps discussed above, and a function of the upstream and downstream liquid pressures in fluid communication with the pump chamber inlet line and outlet line respectively during filling and delivery. Typically, the forces applied to the flexible membrane, for example due to the pressure of the measurement gas in the control chamber, during the filling and delivery steps are chosen to yield a desired liquid flow rate for a given pump stroke cycle. For applications where the pumping system is being utilized to pump a liquid to the body of a patient, the fill and delivery pressures are preferably chosen to be compatible with acceptable pressures for infusion of liquid to a patient. Typically, for delivery of liquids to the vasculature of a patient, the maximum measurement gas pressure in the pumping system will not exceed about 8 psig and the minimum measurement gas pressure in the pumping system will not exceed about −8 psig. 
   When liquid delivery involves performing a multiple number of pump stroke cycles, as described above, over a period of time, in addition to determining a liquid flow rate for a given stroke, preferred pumping systems will include a processor that also is configured to determine an average pump flow rate over the entire period of operation. An average pump flow rate or average liquid flow rate is defined as the volume of liquid dispensed by the pump during multiple pump stroke cycles divided by the total time elapsed during the cycles. For applications involving multiple pump stroke cycles, in addition to controlling liquid flow rate via selection and control of the force applied to the pump chamber membrane, the system can also control the average liquid flow rate by selectively varying the length of a dwell period that can be inserted between individual pump stroke cycles prior to filling and/or delivering liquids from the pump chamber. The pumping systems according to the invention can also be configured to deliver a desired total liquid volume during operation, as well as to deliver a desired liquid flow rate as described above. 
   The predetermined limit to which the differences in measured volumes, or measured parameters related to volumes, of the pump chamber are compared for determining when the amount of gas in the pump chamber has exceeded an acceptable value can be determined in a variety of ways. The predetermined value may be chosen, for example, to be reflect the difference in volumes determined for an amount of gas present in the pump chamber that is equal to or somewhat less than the volume of the dead space in the pump chamber created by spacers, discussed above, therein. For applications where preventing air from being pumped from the pump chamber is critical, for example, when pumping liquid to the body of a patient, the predetermined threshold limit may be chosen to be less than that discussed above for safety reasons. In some embodiments, a predetermined limit can be determined by injecting a maximum permissible quantity of gas into the pump chamber, the remainder of which is filled with a liquid, and determining with the pumping system the difference in measured volume of the pump chamber at a first condition of applied force/pressures to the flexible membrane and a second condition of applied force/pressures to the flexible membrane, as described in detail in the above embodiments. 
   As discussed above in the context of  FIGS. 8 and 9 , a preferred pump drive system according to the invention includes a variable size orifice valve which can be controlled by the processor of the system in order to more precisely control the pressure of measurement gas applied to the control chamber during filling and dispensing of liquid from the pump chamber. 
   As discussed above, for such embodiments preferred systems will also include an end of stroke detection procedure to determine when liquid has stopped flowing into the pump chamber and when liquid has stopped flowing out of the pump chamber during filling and delivery strokes respectively. This end of stroke detection methodology is described in detail in commonly owned copending application Ser. No. 09/108,528, which is hereby incorporated by reference in its entirety. Briefly, in preferred embodiments, pump drive system  502  of  FIG. 8  continuously monitors and controls the pressure of measurement gas in control chamber  110  during filling and dispensing of liquid from pump chamber  108 . The system can detect the end of stroke as follows. During the filling or delivery step, processor  506  controls variable size orifice valve  536  so that the pressure of measurement gas in control chamber  110  has an average value essentially equal to the desired delivery or fill pressure and, in addition, includes a cyclically varying, low-amplitude variation in the pressure that is superimposed thereupon. For example, for a fill or delivery pressure in the range of a few psig, the variable component superimposed can have an amplitude that differs from the average target pressure by, for example, +/− about 0.05 psig, varying at a frequency of, for example, about 1 Hz. While the pump chamber  108  is filling or emptying, flexible membrane  112  will be in motion, and the system will detect the cyclical variations in pressure discussed above. However, at the end of a stroke, when the membrane is essentially no longer free to move in at least one direction and when liquid flow into or out of the pump chamber has essentially stopped, the pressure in control chamber  110  will no longer be able to be cyclically varied as described above. The system can detect this condition by continuously monitoring the pressure signal, for example, from transducer  122  on control chamber  110 , differentiating the pressure signal with respect to time, taking an absolute value of the differentiated signal, and comparing the absolute value of the differentiated pressure signal to a minimum threshold value. At the end of the stroke, when the pressure in control chamber  110  is no longer cyclically varying, a derivative of the pressure with respect to time will approach zero and, therefore, by comparing the time derivative to a minimum threshold value, the system can determine when flexible membrane  112  has reached the end of its stroke, and can then discontinue filling or dispensing. In preferred embodiments, before comparing to the threshold value, the absolute value of the derivative of the pressure signal with respect to time is first subjected to a low pass filter in order to smooth the signal and derive a more stable value therefore. 
   Preferred pumping systems according to the invention are also able to detect a line blockage or occlusion in the inlet or outlet line of pump chamber  108  during operation, and are able to create an alarm condition and, in some embodiments, shut down the pumping cycle, when such blockage or occlusion is detected. Such a no-flow condition is detected by the system by comparing the volume of liquid delivered during the pump delivery stroke and the volume of liquid filling the pump chamber during the pump chamber filling stroke and comparing the volume, determined as described above, to the known minimum and maximum volumes for the pump chamber respectively. The system can then determine if the volume of liquid delivered by the pump chamber or the volume of liquid entering the pump chamber differs significantly from the volumes expected for a full stroke. If so, the system can create an alarm condition indicating a no/low flow condition or occlusion in the line exists. The no/low flow condition threshold value can be set based on the needs of the various applications of the inventive pumping systems and can be, in some embodiments, about one half of the maximum stroke volume of the pump chamber. 
   Certain embodiments provide an alternative way of operating a pump chamber for delivering a liquid therefrom, which is useful for generally, and especially useful when delivering very small quantities of liquid, liquid at very low average flow rates, and where precise measurement is needed. The basic steps of an example embodiment of this method include filling the pump chamber with a liquid, isolating the pump chamber, applying a force to the flexible membrane or moveable surface of the pump chamber, and regulating the flow of liquid from the pump chamber while maintaining the force on the membrane or surface. For example, in the context of pumping system  500  shown in  FIG. 8 , the method may involve first filling pump chamber  108  with a liquid as described previously with respect to  FIG. 9 , closing inlet valve  116  and taking an initial volume measurement of the pump chamber, placing control chamber  110  in fluid communication with the positive pressure tank  508  and controlling the pressure in control chamber  10  at a desired value utilizing variable size orifice valve  536 , and then selectively actuating outlet valve  120  on the outlet line  118  of the pump chamber  108  to open and close the valve for predetermined time periods at predetermined intervals while maintaining the desired delivery pressure in control chamber  110 . Volume measurements of pump chamber  108  can be performed either after each pulse (opening and subsequent closing) of outlet valve  120 , or, alternatively, can be performed after a series of pulses of the outlet valve over a measured cumulative time interval. In this fashion, the volume delivered per pulse or the average liquid flow rate over a series of pulses can be determined, and the system can be configured to adjust the length of the time periods during which outlet valve  120  is opened and to adjust the time intervals between the pulsed openings of outlet valve  120  in order to achieve a desired predetermined average liquid flow rate. While the pulsed delivery mode of delivering a liquid from a pump chamber has been described in the context of  FIG. 8 , any of the other systems previously described (and other systems, as well) can also be used to perform a pulsed delivery of liquid from a pump chamber. 
   For certain embodiments of pumping systems, it is preferred that the systems be comprised of two separable components, one component being reusable and including the pump drive system, and the other component being removable from the reusable component. Such systems may be particularly useful for medical applications for pumping fluids to and/or from the body of a patient. In many embodiments, the reusable component may be disposable and designed for a single use. 
   The removable/disposable portion of the system may include the pump chamber and the pump chamber inlet and outlet lines, including the valves therein, and the other components which are in contact with the liquid being pumped with the pumping system. The removable/disposable component of such a system is referred to herein as the “pumping cartridge,” which pumping cartridge can be configured and designed with a plurality of pump chambers, flow paths, valves, etc., specifically designed for a particular application. An exemplary pumping cartridge for use in one particular medical application is described in more detail below. 
   For example, considering the example pumping systems previously discussed, pumping system  100  shown in  FIG. 1  may comprise a reusable pumping system component  230  coupled to a disposable pumping cartridge  231 , including the disposable pump chamber  108 , inlet line  114 , inlet valve  116 , outlet line  118 , and outlet valve  120 . For pumping system  300  shown previously in  FIG. 5 , the reusable component may comprise reusable system  302 , which would be coupled in operative association with a pumping cartridge  305 , when the pumping system is in operation. Similarly, pumping system  400  of  FIG. 7  would comprise a reusable component  402  coupled to pumping cartridge  403 , and pumping system  500  shown in  FIG. 8  would include reusable component  502  coupled to a pumping cartridge  503 . 
   For embodiments involving removable/disposable pumping cartridges and reusable pump drive systems, the pumping cartridge and the reusable component are constructed and arranged to be couplable to each other. “Constructed and arranged to be couplable” as used herein indicates that the separable components are shaped and sized to be attachable to and/or mateable with each other so that the two components can be joined together in an operative association. Those of ordinary skill in the art would understand and envision a variety of ways to construct and arrange pumping cartridges and components of reusable systems to be couplable in operative association. A variety of such systems which may be employed in the present invention have been described previously in commonly owned U.S. Pat. Nos. 4,808,161, 4,976,162, 5,088,515, and 5,178,182. 
   Typically, the pumping cartridge and reusable component will be coupled together with an interface therebetween, where the reusable component adjacent to the interface will have a series of depressions formed in a surface of the interface, which depressions are sized and positioned to mate with similar depressions in the pumping cartridge, when the pumping cartridge and the reusable component are coupled together, so that upon coupling, the depressions in the pumping cartridge and the reusable components together form the various chambers utilized by the pumping system. Also, when coupled together, the pumping cartridge and the reusable component preferably interact at an interface therebetween such that the interface creates a fluid impermeable/fluid-tight seal between the components, so that the measurement fluid contained by the reusable component and the liquid present in the pumping cartridge are not in fluid communication with each other during operation of the system. Those of ordinary skill in the art would readily envision a variety of means and mechanisms for coupling together the pumping cartridges and reusable components to achieve the above requirements. For example, the components may be held together in operative association by clips, bolts, screws, clamps, other fasteners, etc., or the reusable component may include slots, channels, doors, or other components as part of a housing for holding the pumping cartridge in operative association with the reusable component. Such techniques for coupling together disposable/reusable pumping cartridges and reusable pump drive systems are well known in the art, and any such systems are potentially useful in the context of the present invention. 
     FIG. 10  shows a preferred embodiment of the interface between pumping cartridge  503  and reusable pump drive system  502  of pumping system  500  shown previously in FIG.  8 .  FIG. 10  is a cut-a-way view showing only the portion of reusable component  502  which mates with and is in contact with pumping cartridge  503  when the components are coupled together in operative association. Such portion of the reusable component will hereinafter be referred to as the “pump housing component.” Also shown in  FIG. 10  is a preferred arrangement for providing valves in fluid communication with the liquid flow paths of the pumping cartridge, which valves are described in more detail below. 
   Pump housing component  700  includes a door  702  and a mating block  704  the surface of which forms an interface when pumping cartridge  503  is coupled to pump housing component  700 . Mating block  704  has a generally planar surface in contact with the pumping cartridge having a variety of depressions  706 ,  708 ,  710  therein which mate with complementary depressions contained within pumping cartridge  503  for forming various chambers of the pumping system when the components are coupled together. For example, depression  706  in mating block  704  is coupled to depression  712  in pumping cartridge  503  thus forming a pump chamber  108  in pumping cartridge  503  and an adjacent control chamber  110  in mating block  704 , when the components are coupled together. 
   As will be described in more detail below, pumping cartridge  503  comprises a substantially rigid component  714  covered, on at least one side thereof, by a flexible membrane, which in preferred embodiments is an elastic membrane. In a preferred embodiment shown, mating block  704  is also covered by a flexible membrane  716  which is in contact with flexible membrane  112  covering pumping cartridge  503 , when the components are coupled together. Flexible membrane  716  is an optional component which provides an additional layer of safeguarding against potential leakage of fluids between pumping cartridge  503  and the reusable component thus preventing contamination of the reusable component by the liquids in the pumping cartridge. 
   Upon coupling, a fluid-tight seal should be made between the flexible membranes and the surfaces of mating block  704  and pumping cartridge rigid component  714  forming the various chambers. In order to obtain such a seal, there should be some degree of compression between pumping cartridge  503  and mating block  704  when the components are coupled together. In addition, seals  718  may be provided around the periphery of the depression within mating block  704 , which seals are positioned adjacent to the periphery of complementary depressions in pumping cartridge  503  in order to create additional compression of the flexible membranes for forming a leak-tight seal. Alternatively, such seals could be provided around the perimeter of the depressions in pumping cartridge  503  in addition to, or instead of, mating block  704 . Such seals may be provided by a variety of materials, as apparent to those of ordinary skill in the art, for example, properly sized rubber or elastomer O-rings can be used which fit into complementary grooves within mating block  704  or, alternatively, are affixed to the mating block by adhesives, etc. 
   As discussed above, pumping cartridge  503 , in the embodiment shown, includes a substantially rigid component  714  that is preferably constructed of a substantially rigid medical grade material, such as rigid plastic or metal. In preferred embodiments, substantially rigid component  714  is constructed from a biocompatible medical grade polyacrylate plastic. As will be described in more detail below, substantially rigid component  714  is molded into a generally planar shape having a variety of depressions and grooves or channels therein forming, when coupled to the reusable component, the various chambers and flow paths provided by the pumping cartridge. 
   In some embodiments, the substantially rigid component of the pumping cartridge can include a first side, which mates with the mating block, which first side contains various depressions and channels therein for forming flow paths and chambers within the pumping cartridge upon coupling to the reusable component. This first side of such pumping cartridges is covered with a flexible, an preferably elastic membrane, which can be bonded to the first side of the substantially rigid component at the periphery thereof and/or at other locations on the first side. Alternatively, instead of being a single continuous sheet, the flexible membrane may comprise a plurality of individual membranes which are bonded to the substantially rigid component only in regions comprising chambers, or other components, in operative association with the reusable component. 
     FIG. 10  shows such an embodiment of a pumping cartridge  503  which has a first side  720 , facing mating block  704 , and a second side  722 , facing door  702  of pump housing component  700 , each of which sides is covered by a flexible membrane. First side  720  of pumping cartridge  503 , as shown, includes depressions  712 ,  724 , and  726  and is covered by flexible membrane  112 . The second side  722  of pump cartridge  503  includes a variety of channels  728 ,  730  formed therein, which channels are covered by flexible membrane  732 , which is disposed on the second side  722  of pump cartridge  503 , the combination of which channels and flexible membrane provide fluid-tight liquid flow paths within pumping cartridge  503 , upon coupling to the reusable component. 
   The flexible membranes for use in pumping cartridge  503  and, in some embodiments, mating block  704 , can be comprised of a variety of flexible materials known in the art, such as flexible plastics, rubber, etc. Preferably, the material comprising the flexible membranes used for the pumping cartridge is an elastic material that is biocompatible and designed for medical use, when used for applications where the pumping cartridge is used for pumping liquid to and from the body of a patient. The material comprising the flexible membranes should also be selected based on its ability to form a fluid-tight seal with the substantially rigid component  714  of pumping cartridge  503  and with mating block  704  of the reusable component. In a preferred embodiment, where rigid component  714  of pumping cartridge  503  is formed of a clear acrylic plastic, elastic membrane  112  is comprised of polyvinyl chloride sheeting, which is about 0.014 in thick and which is hermetically sealed to the first side  720  of rigid component  714  of pumping cartridge  503 . Since the elasticity of membrane  712  disposed on the second side  722  of pumping cartridge  503  does not substantially contribute to its performance, it is not necessarily preferred to use an elastic material for membrane  712 . However, for convenience and ease of fabrication, membrane  712  can be comprised of the same material as membrane  112 , and can be hermetically sealed the second side  722  of rigid component  714  of pumping cartridge  503  in a similar fashion as membrane  112 . 
   In the embodiment illustrated, door  702  is hinged to the body of the reusable component and can be opened or closed by an operator of the system, either manually, or in some embodiments, under computer control of the processor controlling the system, so that pumping cartridge  503  can be properly inserted and mated with mating block  704 . Preferably, pumping cartridge  503 , mating block  704 , and door  702  are shaped and configured so that pumping cartridge  503  can only mate with the reusable component in the proper orientation for operative association. In preferred embodiments, door  702  latches to the reusable component when closed. In some embodiments, the pumping system may include detectors and circuitry for determining the position of the door and is configured to allow operation of the system only when pumping cartridge  503  has been properly installed and door  702  has been properly closed. Also, in preferred embodiments, the pumping system is configured to prevent the door from being opened during operation of the system, so that the fluid-tight seal that is formed between pumping cartridge  503  and the reusable system is not compromised while the system is in operation. Door  702  also, in preferred embodiments, includes an inflatable piston bladder  734  having an inlet line  736  which is in fluid communication with a fluid supply of the pumping system when the system is in operation. Also, in preferred embodiments, adjacent to piston bladder  734  and pumping cartridge  503  is an essentially planar piston surface  738 . After inserting pumping cartridge  503  and closing door  702 , but before operating pumping cartridge  503 , the system supplies pressurized fluid to piston bladder  734  to create a compressive force against pumping cartridge  503  so as to create fluid-tight seals within the system, as described previously. 
   As discussed above, pumping cartridge  503  and reusable component  502 , as shown in  FIG. 10 , together provide a unique means of operating the valves within pumping cartridge  503 . Inlet valve  116  and outlet valve  120  include valving chambers  740  and  742  which are formed from the combination of depressions  724  and  726  within rigid component  714  and flexible membrane  112 . Each valving chamber includes at least one occludable port  744 ,  746  and at least one other port  748 ,  750 . In the embodiment shown, ports  748 ,  750  are not occludable by flexible membrane  112 . In other embodiments, ports  748  and  750  may be occludable and similar in construction to occludable ports  744  and  746 . As shown, ports  744  and  750  comprise holes within rigid component  714  of pumping cartridge  503  allowing fluid communication between liquid flow paths  114  and  118  present on the second side  722  of pumping cartridge  503  and valving chambers  740  and  742  located on the first side  720  of pumping cartridge  503 . Occludable ports  744  and  746  also provide fluid communication between the valving chambers and liquid flow paths within the pumping cartridge. Occludable ports  744  and  746  are constructed so that holes through which a liquid flows are located on members  749  that protrude from the base of the depression forming the valving chambers. In preferred embodiments, protruding members  749  have a truncated conical shape, wherein ports  744  and  746  comprise holes in the truncated apex of the conical protruding members. 
   Mated to valving chambers  740  and  742 , when the pumping cartridge is in operative association with the reusable component, are valve actuating chambers  752  and  754  formed from depressions  708  and  710  within mating block  704 . In order to close the valves to restrict or block flow therethrough, pumping system  500  includes valve actuators (provided in this embodiment by the valve actuating chambers as shown) configured to selectively and controllably apply a force to flexible membrane  112  tending to force the flexible membrane against an adjacent occludable port, thus occluding the port. Inlet valve  116  is shown in such a closed configuration. To open a valve, the pumping system can release the positive force applied to flexible membrane  112  and, in some embodiments, can apply a negative force to flexible membrane  112  tending to move the membrane into the valve actuating chamber. Outlet valve  120  is shown in  FIG. 10  in such an open configuration. Pumping system  500  is configured as shown to open and close the valves within pumping cartridge  503  by selectively applying a measurement gas to the valve actuating chambers at a pressure sufficient to occlude the occludable ports contained within the valving chambers. Such pressure will exceed the pressure of any liquid contained in the valving chamber. 
   Gas inlet lines  756  and  758  supplying valve actuating chambers  752  and  754  are connected so that they are able to be placed in fluid communication with a pressurized measurement gas supply source(s) contained in pumping system  500 . It should be understood that in other embodiments not shown, pumping system  500  may include valve actuators using alternative means as a force applicator for applying a force to flexible membrane  112  in order to occlude occludable ports  744  and  746 . In alternative embodiments, the system may include a valve actuator that includes a force applicator comprising, for example, a mechanically actuated piston, rod, surface, etc., or some other force applicator using an electrical or magnetic component, disposed adjacent to the flexible membrane. In preferred embodiments, as shown, the system comprises a valve actuator comprising a valve actuating chamber, where the force applicator for applying a force to the flexible membrane comprises a pressurized gas or other fluid. 
   As with other particular features described above, this valve and mechanism for operating the valve is particularly advantageous. Use of such valves are not, however, required in all embodiments of the present invention and, in the context of a system design, any other valve and valve actuator may be used. 
   Also shown in  FIG. 10  is a preferred mechanism for providing a pressure measuring component for determining the pressure in control chamber  110 , which may be used in some (but not all) embodiments of the present invention. Pumping system  500  as shown in  FIG. 10  is configured so that pressure transducers are resident on a circuit board contained within processor  506  (not shown in FIG.  10 ), which transducers are connected in fluid communication with various chambers and components in the system via tubing or channels. For example, pressure transducer  122  (not shown) for measuring the pressure in control chamber  110  is connected in fluid communication with control chamber  110  via line  760  and port  762  in fluid communication with control chamber  110 . 
   Preferably, after mating pumping cartridge  503  to the reusable component and before commencement of operation, pumping system  500  is configured to perform a variety of integrity tests on pumping cartridge  503  to assure the proper operation of the pumping system. In such embodiments, pumping system  500  includes an inlet and outlet tube occluder (not shown) for blocking the flow of fluid to and from pumping cartridge  503  and for isolating the chambers and flow paths of pumping cartridge  503 . After coupling pumping cartridge  503  to the reusable component but before priming pumping cartridge  503  with liquid, a dry pumping cartridge integrity test can be performed. The test involves opening the inlet and outlet line occluding means so that pumping cartridge  503  is not isolated from the surroundings and supplying all of the control chambers and valve actuating chambers in the system with a measurement gas at a predetermined positive or negative pressure. The system then continuously monitors the measurement gas pressure within the various chambers of the reusable component over a predetermined period of time. If the change in pressure exceeds a maximum allowable predetermined limit, the system will indicate a fault condition and terminate operation. This dry pumping cartridge integrity test is useful for detecting holes or other leaks within flexible membrane  112 . The dry pumping cartridge integrity test integrity test briefly described above is discussed in more detail in commonly owned copending application Ser. No. 09/193,337 incorporated by reference herein in its entirety. 
   After performing the dry pumping cartridge integrity test above, but before operation, a wet pumping cartridge integrity test can also be performed. The test involves first priming all of the chambers and flow paths of pumping cartridge  503  with liquid and then performing the following two tests. First, the integrity of the valves within the pumping cartridge is tested by applying positive pressure to valve actuating chambers  752  and  754  to close valves  116  and  120  within the pumping cartridge, and then applying the maximum system measurement gas pressure to the control chamber  110  coupled to the pump chamber  108 . The system is configured to measure the volume of the pump chamber  108  within the pumping cartridge, as described previously, before the application of pressure, and again after the pressure has been applied to the pump chamber for a predetermined period of time. The system then determines the difference between the measured volumes and creates an alarm condition if the difference exceeds an acceptable predetermined limit. The second test involves determining the fluid tightness of the various fluid flow paths in chambers within pumping cartridge  503 . This test is designed to prevent the system from operating when a cartridge has been manufactured so that there may be leakage between flow paths and undesirable mixing of liquids within the pumping cartridge. The test is performed in a similar fashion as that described immediately above except that the valves within pumping cartridge  503  are maintained in an open configuration with the inlet and outlet line occlusion means being actuated by the system to isolate the pumping cartridge from its surroundings. As before, a maximum measurement gas pressure is applied to the control chamber of the reusable component, and the volume contained in the pump chamber is determined before and after application of pressure. Again, the system is configured to create an alarm condition and discontinue operation if the differences in measured volume exceed an allowable predetermined limit. It should be understood that while the various integrity tests and preferred modes of operating a pumping cartridge have been described in the context of system  500  and pumping cartridge  503  illustrated in  FIG. 10 , the methods and tests can also be applied and employed for other configurations of the pumping cartridge and reusable system. 
     FIGS. 11   a - 11   f  show various views and features of one particular embodiment of a multi-functional pumping cartridge according to the invention which includes a plurality of pump chambers, valving chambers, and fluid flow paths therein. The pumping cartridge shown in  FIGS. 11   a - 11   f  is similar in construction to pumping cartridge  503  shown in  FIG. 10 , in that the pumping cartridge includes a substantially rigid component with various depressions and channels/grooves therein covered on each side with a flexible membrane that is hermetically sealed thereto.  FIG. 11   a  is an en face view of the first side of pumping cartridge  800 , which first side is coupled to and in contact with an interface of a mating block on a complementary reusable system when the pumping cartridge is in operation. As discussed below, except for the particular arrangement and number of components, pumping cartridge  800  is similar in overall design to that described previously in the context pumping cartridge  503  of FIG.  10 . 
   Pumping cartridge  800  includes a plurality of inlet and outlet lines  802 ,  804 ,  806 ,  808 ,  810 ,  812 ,  814 ,  816 ,  818 , and  820  for connecting the various flow paths of the pumping cartridge in fluid communication with lines external to the pumping cartridge. In one preferred embodiment, pumping cartridge  800  is utilized for pumping blood from the body of a patient, treating the blood, or components thereof, and returning treated blood and other fluids to the body of the patient. For such embodiments, pumping cartridge  800  is preferably disposable and designed for a single use, and is also preferably biocompatible and sterilizable so that it may be provided to the user as part of a sterile, single-use package. 
   As shown in  FIG. 11   a , pumping cartridge  800  includes two large pump chambers  822  and  824  and a third smaller pump chamber  826 . Pumping cartridge  800  also includes a plurality of valving chambers  827 ,  828 ,  829 ,  830 ,  832 ,  834 ,  836 ,  838 ,  840 ,  842 ,  846 ,  848 ,  850 ,  852 ,  854 ,  856 , and  858  for controlling and directing the flow of liquid through the various liquid flow paths and pump chambers provided within pumping cartridge  800 . The construction of each of the pump chambers and valving chambers above is similar to that shown previously for pumping cartridge  503  shown in FIG.  10 . Pumping cartridge  800  also includes the novel inclusion of a bypass valve provided by a bypass valving chamber  860  and an integrated filter element  862 , the function and structure of which components are explained in more detail below. 
   In operation, pumping cartridge  800  is coupled in operative association with a complimentary mating block of a reusable component having depressions and pneumatic (in appropriate embodiments) connections therein for actuating the various pump chambers and valving chambers of the pumping cartridge in a similar fashion as that previously described. The reusable component also preferably includes an occluder  864  included therein, disposed adjacent to tubing in fluid communication with the various inlet/outlet ports of the pumping cartridge, for occluding the various inlet and outlet lines in fluid communication with the pumping cartridge when performing various integrity tests as described previously and/or for other purposes where it is desirable to fluidically isolate the pumping cartridge. In preferred embodiments, the occluder is constructed as described below and is configured to occlude the tubing unless a force is applied to the occluder, for example by supplying a pressurized fluid to a bladder tending to move the occluder to unocclude the various tubing. In such embodiments, in a fail safe condition (e.g. during a power failure) the occluder will be configured to occlude the tubing, thus preventing undesirable liquid flow to and/or from a source or destination (especially when such source or destination is the body of a patient. 
   As described below, the reusable system that is constructed and arranged for operative association with pumping cartridge  800  will also include various processors (or a single processor configured to perform multiple functions, or other suitable hardware or software mechanisms) to selectively control and operate the various components of pumping cartridge  800  for performing various user designated pumping applications. It will be understood by those of ordinary skill in the art that pumping cartridge  800  can be used for an extremely wide variety of potential pumping and fluid metering applications depending on the manner in which the various components contained therein are operated and controlled. Each of such uses and applications are deemed to be within the scope of the present invention. 
   The flow paths within pumping cartridge  800  which are comprised of channels formed on the first side of the pumping cartridge (the side facing the viewer), for example flow path  866 , are shown as solid lines. Flow paths that are formed from channels disposed on the second (opposite) side of pumping cartridge  800 , for example flow path  872 , are shown in  FIG. 11   a  by dashed lines. As can be seen in  FIG. 11   a , in the embodiment shown, filter element  862  is also disposed on the second side of pumping cartridge  800 . As will be described in more detail below, a preferred function of filter element  862  is to filter fluids being pumped from pumping cartridge  800  to the body of a patient to remove any blood clots or aggregated material therefrom. 
   The structure of pumping cartridge  800  can be seen more clearly from the cross-sectional view of  FIG. 11   b . Pumping cartridge  800  includes a substantially rigid component  876  having a series of depressions and channels therein forming the various chambers and flow paths of the pumping cartridge. Pumping cartridge  800  has a first side  890 , which is disposed against a mating block of the reusable component in operation, and a second side  892 , which is disposed against the door of the pump housing component when in operation. First side  890  is covered by flexible membrane  112  hermetically sealed around the periphery of rigid component  876 . Second side  892  is similarly covered by flexible membrane  732 . Clearly visible are liquid flow paths  866  and  874 , both of which are disposed on first side  890  of pumping cartridge  800  and liquid flow paths  864  and  872  disposed on second side  892  of pumping cartridge  800 . Pump chambers  822  and  824  are formed from curved depressions  894  and  896  in first side  890  of rigid component  876 . Clearly visible are spacers  868  which comprise elongated protuberances having bases  898  attached within the pump chambers to rigid component  876  and ends  900  extending into pump chambers  822  and  824  toward flexible membrane  112 . As previously described, these spacers prevent contact of flexible membrane  112  with the base of depressions  894  and  896  in rigid component  876  during pumping and provide a dead space which inhibits pumping of gas from the pump chambers during operation. In this embodiment, the spacers are small, evenly spaced bumps located on a wall of the pump chamber. The size, shape and positions of the spacers can be changed and still serve the purpose of reducing risk of passing gas through the pump chamber. 
   Referring to  FIG. 11   b , filter element  862  includes a filter  882  disposed on second side  892  of rigid component  876 . Filter  882  is preferably substantially planar and is disposed adjacent to second side  892 , spaced apart therefrom by spacers  870 , so that the filter and the region of second side  892  to which it is attached are essentially coplanar. During operation of the pumping cartridge for pumping liquid to a patient, fluid to be pumped to the patient is directed along flow path  874  to the inlet port  904  of filter element  862  (see  FIG. 11   a ) into space  906  separating filter  882  from second side  892 , through filter  882 , and out of filter element  862  through occludable port  980  (see  FIG. 11   a ). In order to prevent fluid from bypassing filter  882  within filter element  862 , filter element  862  should be sealed to second side  892  of rigid component  876  along its periphery in a fluid-tight fashion. Also, for embodiments where filter element  862  is functioning as a blood clot filter, filter  882  preferably has pores therein which are larger in diameter than the diameter of a typical human blood cell, but which are small enough to remove a substantial fraction of clotted blood or aggregated blood cells that may be present in a liquid pumped therethrough. In preferred embodiments, filter  882  comprises a polyester screen, in one embodiment having pore sizes of about 200 μm with about a 43% open area. 
     FIG. 11   c  is a cross-sectional view of outlet valving chamber  830 . Outlet valve  830  has a structure which is representative of the valving chambers provided in pumping cartridge  800 . The structure of valving chamber  830  is substantially similar to the structure of the valving chambers in pumping cartridge  503  shown in  FIG. 10  previously. Valving chamber  830  is formed in first side  890  of rigid component  876  of pumping cartridge  800  and includes one occludable port  920  in fluid communication with liquid flow path  922  on second side  892  of the pumping cartridge and a non-occludable port  924  in fluid communication with outlet line  926 .  FIG. 11   d  shows an essentially equivalent valving chamber for an alternative embodiment of a pumping cartridge having an essentially rigid component  932  covered on only a single side by a flexible membrane. Analogous components of the alternative valve embodiment of  FIG. 11   d  are given the same figure labels as in  FIG. 11   c  for comparison. 
   Referring again to  FIG. 11   a , the function of bypass valving chamber  860  and filter element  862 , as well as the flexibility of operation of pumping cartridge  800 , will be explained in the context of a particular embodiment involving an application utilizing pumping cartridge  800  that includes removing blood from the body of a patient, pumping the blood to various selectable destinations with pumping cartridge  800 , and returning treated blood or other fluids to the body of a patient. As will be described in detail below, it is desirable, in such an embodiment, to pump fluids which are being returned to the body of a patient through filter element  862  to remove any clots or aggregates therefrom, and to bypass filter element  862  when withdrawing blood from a patient with pumping cartridge  800 . When in operation, pumping cartridge  800  is preferably coupled to a reusable component such that pumping cartridge  800  is oriented essentially vertically with the various inlet and outlet lines pointing up. As illustrated, inlet/outlet port  816  is in fluid communication with a syringe or shunt  950  inserted into the vasculature of a patient. Blood withdrawn from the patient and fluid returned to the patient flows through inlet/outlet  816  and along liquid flow path  872  within pumping cartridge  800 . Liquid flow path  872  is in fluid communication with bypass valving chamber  860  via a first port  952 . Also in the illustrated embodiment, inlet valve  832  of small pump chamber  826  is in fluid communication with a supply of anticoagulant  980 , and outlet valve  830  of pump chamber  826  is in fluid communication with the syringe/shunt  950  inserted into the body of a patient. In this configuration, small pump chamber  826  can be utilized as an anticoagulant delivery pump for pumping an anticoagulant to an injection site of a patient in order to keep the injection site from blocking and in order to provide anticoagulant to blood removed from the patient. 
   As explained in greater detail below, the function of bypass valving chamber  860  is to selectively permit liquid flow along a first liquid flow path bypassing filter element  862 , or alternatively, to block flow along the first fluid flow path and direct flow along a second liquid flow path, which second liquid flow path directs the liquid so that it flows through filter element  862 . Also, as discussed below, valving chamber  860  also permits liquid flow along both liquid flow paths above to be simultaneously blocked if desired. For the present embodiment where blood is being removed from a patient and, subsequently, liquids are being returned to a patient, the first liquid flow path described above will be selected by the system, by utilizing bypass valving chamber  860 , when removing blood from the patient, and the second liquid flow path described above will be selected by the system, utilizing bypass valving chamber  860 , when liquids are being pumped from the pumping cartridge to the patient. 
   Bypass valving chamber  860  is comprised of two adjacent subchambers  970 ,  972  separated by a partition  974  therebetween, which has an aperture therethrough permitting unrestricted fluid communications between the two subchambers. “Subchamber(s)” as used herein refers to regions of a chamber within a pumping cartridge, which region includes an internal partition, that are adjacent and are separated one from the other by the internal partition, where the internal partition allows unrestricted fluid communication between the regions. 
   The structure of bypass valving chamber  860  is shown in greater detail in the cross-sectional view of  FIG. 11   e . Referring to  FIG. 11   e , partition  974  separates the bypass valving chamber into subchambers  970  and  972  and is in fluid-tight contact with flexible membrane  112  when the pumping cartridge is coupled to a reusable component. When coupled with a reusable component, subchamber  970  and subchamber  972  can each be coupled adjacent to and in operative association with a separate and independently controllable valve actuating chamber in the reusable component, which is each disposed adjacent to the subchamber. The valve actuating chambers can be independently operated to selectively occlude and open occludable port  980  in subchamber  970  and occludable port  982  in subchamber  972 . 
   Also shown in  FIG. 11   e , for the purposes of illustrating the function of bypassing valving chamber  860 , is a schematic representation of a second liquid flow path through the bypass valving chamber where the liquid is forced through filter element  862 . Referring to both  FIGS. 11   a  and  11   e  together, consider a first step in a pumping method using the pumping cartridge during which blood is withdrawn from the patient by filling pump chamber  822  and/or  824 . During this step, as discussed above, it is desirable to flow blood from the patient through bypass valving chamber  860  along a first liquid flow path which bypasses filter element  862 . This can be accomplished by occluding occludable port  980  in subchamber  970  while leaving occludable port  982  in subchamber  972  non-occluded. In such a situation, blood will flow from the patient, along liquid flow path  872  into subchamber  970  through port  952 , from subchamber  970  to subchamber  972  through opening  990  in partition  974 , and will exit subchamber  972  through occludable port  982 . For a situation where treated blood or another liquid such as plasma or saline is being pumped with pump chamber  822  and/or  824  through line  959  to bypass valving chamber  860  to be reinfused into a patient, as discussed above, it is desirable to operate the bypass valving chamber so that the liquid flows along the second liquid flow path, which passes the liquid through filter element  862  prior to returning it to the patient. In such a situation, the second liquid flow path can be selected by occluding occludable port  982  in subchamber  972  and leaving non-occluded occludable port  980  in subchamber  970 . In which case fluid will flow along liquid flow path  959  and subsequently along liquid flow path  874  to the inlet port  904  of filter element  862 . Liquid will not be able to enter subchamber  972  due to the occlusion of occludable port  982 . The liquid, after entering filter element  862 , will pass through filter  882  and exit filter element  862  by entering subchamber  970  through occludable port  980 . The liquid will then exit subchamber  970  through port  952  and flow along liquid path  872  for return to the patient. 
     FIG. 11   f  shows an essentially equivalent bypass valving chamber  861  for an alternative embodiment of a pumping cartridge having an essentially rigid component  932  covered on only a single side by a flexible membrane. Analogous components of the alternative bypass valve embodiment of  FIG. 11   f  are given the same figure labels as in  FIG. 11   e  for comparison. 
   During other operations utilizing pumping cartridge  800 , it may be desirable to operate bypass valving chamber in order to block liquid flow along both the first liquid flow path (bypassing the filter element) and along the second liquid flow path (wherein the liquid is passed through the filter element). Flow can be blocked along both the above-mentioned liquid flow paths utilizing bypass valving chamber  860  simply by occluding both occludable port  980  and  982  simultaneously. 
   It should be understood that while the operation of bypass valving chamber has been described in the context of pumping blood and liquids to and from a patient and for the purpose of selectively passing such liquids through a filter or bypassing the filter, the bypass valving chamber provided by the invention can be used for a wide variety of other purposes, wherein it is desirable to selectively choose liquid flow along a first and second liquid flow path. It should also be understood that while in the above-mentioned embodiment liquids flowing along a first and second liquid flow path through bypass valving chamber  860  flow through the chamber in a particular direction, in other embodiments, the direction of liquid flows along the first and second liquid flow path could be reversed or could be co-directional in either direction. 
   Referring again to  FIG. 11   a , a variety of exemplary sources and destinations in fluid communication with pumping cartridge  800  are illustrated in the exemplary embodiment shown, in addition to anticoagulant source  980  and syringe/port  950 , pumping cartridge  800  is also connected to a source of saline  1000 , a plasma storage container  1002 , a centrifuge  1004  for separating blood cells from plasma and/or certain blood cells from each other, and a treatment chamber  1006  for performing a treatment on blood, plasma, or blood cells. By selectively operating the various pump chambers and valving chambers within the pumping cartridge, liquids can be pumped to and from various sources and destinations for a variety of purposes and treatments as would be apparent to those of ordinary skill in the art. 
   In one particular embodiment, pumping cartridge is utilized as part of a system designed for use in photopheresis treatment to the blood components of a patient as part of a therapy for the treatment of various blood disorders and treatments such as in the treatment of HIV infection, to prevent the rejection of transplants, or for treatment of various autoimmune disorders, for example scleroderma. In this embodiment, the patient is first given a dose of the drug psoralen about 30 min. prior to blood treatment. The psoralen molecules attach to specific undesirable blood components. In this embodiment, treatment chamber  1006  is configured to expose the fractionated blood components of a patient to ultraviolet A (UVA) light to activate the psoralen molecules which in turn modify the blood components to which they are bound so that upon reinfusion into the patient, the modified blood components are either recognized by the patient&#39;s immune system and eliminated, or they are immobilized and prevented from harming the patient (for guidance in performing the UVA treatment and configuring a UVA treatment chamber reference is made to U.S. Pat. No. 5,147,289 to Edelson, incorporated herein by reference in its entirety). Pumping cartridge  800 , for this embodiment, can be operated to initially remove blood from the patient, pump the blood to centrifuge  1004  to fractionate the various components according to the needs of the particular treatment protocol, direct one or more blood components to treatment chamber  1006  for UVA activation and, if desired one or more other components back to the patient or to a storage container, such as plasma return  1002 , and finally pump the UVA-treated blood components back to the patient, as well as, if desired or required, saline from saline container  1000  and/or any blood components contained in plasma return container  1002 . It will be apparent to those of ordinary skill in the art that the above outlined protocol may be modified in a variety of ways and customized for specific procedures without departing from the scope of the invention. 
   In general, pump chambers  822 ,  824  and  826  of pumping cartridge  800  can be operated utilizing a reusable component including a pump drive system constructed according to any of the embodiments previously described for such systems. Pump chambers  822 ,  824 , and  826 , when pumping a liquid to the body of a patient, preferably are operated utilizing pump stroke cycles including air detection and purging steps, as described previously.  FIG. 11   a  illustrates that pumping cartridge  800  includes several additional design safeguards for preventing air, or other gas, from being pumped to the body of a patient. For example, pump chamber  826 , which is configured in this example to pump an anticoagulant to the injection port of a patient for certain embodiments where the pumping cartridge is utilized for blood pumping, has an inlet port  1008  located at the top of the pump chamber and an outlet port  1010  located at the bottom of the pump chamber. This configuration results in any air in the pump chamber rising toward the top of the pump chamber so that it is less likely to be pumped through the outlet port before being detected by the system. Similarly, all liquid pumped to the patient by pump chambers  822  and  824  are pumped along liquid flow path  959 , which is in fluid communication with valving chambers  846  and  854  which, in turn, are in fluid communication with ports  1012  and  1014  located at the bottom of pump chamber  822  and  824 , respectively. Thus, as with pump chamber  826 , any liquid pumped to the body of a patient using pump chambers  822  or  824  must exit the pump chambers through the bottom port. Similarly, filter element  862  is constructed so that its inlet  904  is located near the top of the filter element, and its outlet  980  is located near the bottom. This arrangement provides an additional layer of protection in that any liquids being pumped to the patient from pump chambers  822  or  824  are first diverted through filter element  862  by bypass valving chamber  860 , and any gases contained in such liquids will tend to collect near the top of the filter element and will be inhibited from being pumped to the patient. In contrast,  FIG. 11   a  shows that the majority of liquid flow paths in fluid communication with destinations other than the body of a patient, for example plasma return  1002  and centrifuge  1004 , are, in turn, in fluid communication with ports  1016  and  1018  located at the top of pump chambers  822  and  824 , respectively. When pumping to such destinations, it is typically not critical if air is present in the pumped liquid. During operation, these destinations, for example port  808  and  812 , may be used by the system as locations to which to purge any air that is detected in pump chambers  822  and  824  during pump cycles in which a liquid is being pumped to the body of a patient. Any air detected in pump chamber  826  during operation may similarly by purged to port  820  in fluid communication with the anticoagulant supply. 
     FIG. 11   a  also shows that both pump chambers  822  and  824  contain similar fluidic connections to all of the sources and destinations provided by a pumping cartridge  800  (except ports  818  and  820  utilized solely by pump chamber  826 ). Accordingly, pump chambers  822  and  824  may be operated individually and independently of each other, in some embodiments, so that liquids pumped with each chamber have a different source and destination or, in other embodiments, pump chambers  822  and  824  may be operated so that their inlet and outlet ports are in fluid communication with common sources and destinations. In the latter embodiments, the pumping system utilizing pumping cartridge  800  can be operated so that the fill and pump strokes of pump chambers  822  and  824  are synchronized so that as one chamber is filling the other chamber is dispensing, and vice versa. Utilizing such an operating protocol, it is possible to operate pump chambers  822  and  824  to achieve a nearly continuous, uninterrupted flow between a desired source and destination. 
   For embodiments where pump chamber  826  is utilized as an anticoagulant pump, the desired average flow rate to be delivered by the pump chamber may be quite low. In such embodiments, it may be preferable to operate pump chamber  826  utilizing the pulsed delivery protocol described previously. As described previously, in such embodiments, pump chamber  826  is first filled with anticoagulant, inlet valve  832  is closed, a force is applied to flexible membrane  112  adjacent to the pump chamber, and outlet valve  830  is pulsed by selectively opening and closing the outlet valve for predetermined periods of time at predetermined intervals, which intervals and predetermined periods of time are controlled to yield a desired average liquid flow rate. Anticoagulant pump chamber  826  is typically operated to deliver anticoagulant only while either pump chamber  822  or  824  is being filled with blood withdrawn from the body of the patient. Additionally, anticoagulant pump chamber  826  may also be advantageously utilized to dispense anticoagulant when pump chambers  822  and  824  are not pumping liquids to or from the body of the patient but are being utilized for other purposes. In such cases, it may be desirable to continuously, or intermittently dispense a small quantity of anticoagulant with pump chamber  826  in order to assure that syringe/port  950  remains unoccluded. A pulsed delivery, as described above, may be utilized for operating the anticoagulant pump in such applications. For such applications, it is believed that the pulsed delivery of anticoagulant to the injection can have beneficial effects for keeping the site from clotting and dislodging small clots when compared to a continuous delivery of anti coagulant to the site. In addition, preferred embodiments of systems configured to provide pulsed delivery of anticoagulant are configured to continuously monitor the quantity/flow rate of anticoagulant to the patient and can adjust the flow rate by changing and controlling the positive pressure applied to the pump chamber during pulsed delivery as well as by changing the pulse duration and interval between pulses. Such capability allows for improved flow rate delivery volume control for applications where the anticoagulant is being delivered to a site at variable pressure, for example an artery of a patient. 
   When anticoagulant pump  826  is being utilized to dispense anticoagulant while pump chambers  822  and/or  824  are filling with blood from the patient, the pulse duration and interval between pulses of outlet valve  830  for delivering anticoagulant from pump chamber  826  can be selected, in preferred embodiments, so that the average liquid delivery rate of the anticoagulant is a desired predetermined fraction of the flow rate of blood to pump chambers  822  and/or  824  while they are being filled with blood from the patient. In other embodiments, it may be desirable to operate pump chamber  826  to provide an average liquid flow rate delivered from the pump chamber that is a predetermined fraction of the liquid flow rate of pump chamber  822  and/or  824  during a liquid delivery stroke. In yet other embodiments, pump chamber  826  may be operated so that the average liquid flow rate delivered from the chamber is a predetermined fraction of a liquid flow rate measured for a complete pump stroke (including fill and delivery) of pump chamber  822  and/or  824  or, in yet another embodiment, is a predetermined fraction of an average liquid flow rate (calculated over several pump stroke cycles) of pump chambers  822  and/or  824 . It is also to be understood that instead of pump chamber  826  being operated to provide a liquid flow rate that is a predetermined fraction of a liquid flow rate provided by pump chambers  822  and/or  824 , alternatively, pump chamber  822  could be operated to provide a liquid flow rate which is a predetermined fraction of a liquid flow rate of pump chamber  824 , or vice versa. 
   As discussed previously, preferred components of the pump housing component of the reusable system include an occluder bar and mechanism for actuating the bar to selectively occlude the tubing attached in fluid communication with a pumping cartridge. One embodiment of a pump housing component including an occluder bar and actuating mechanism is shown in  FIGS. 12   a  and  12   b . Pump housing component  1100  shown in  FIGS. 12   a  and  12   b  includes a spring occluder bar  1102 . In the illustrated embodiment, long arm  1104  is pivotally attached to the mating block  1105  of pump housing component  1100  at pivot  1106 . As discussed previously in the context of  FIG. 10 , mating block  1105  will also contain depressions (not shown) forming control and valving chambers, etc. and will be constructed and arranged to mate to the pumping cassette. Occluder bar  1102  has an occluder end that is preferably at about a right angle with respect to the rest of the occluder bar when the occluder is in an occluding configuration as shown in  FIG. 12   b . The occluder end  1108 , in the illustrated embodiment, attached to one end of a spring  1110  that is disposed in a spring housing  1112 . The spring housing, in turn, is preferably rigidly attached to mating block  1105 . Occluder end  1108  is able to move through the spring housing  1112  by compressing and expanding the spring  1110 . The occluder end  1108  terminates at an occluder tip  1114  which is positioned adjacent to, and preferably approximately perpendicular to, fluid lines  1116  attached to the inlet/outlet ports of pump cassette  800 . 
   As discussed previously, cassette  800  is held against the mating block  1105  on pump housing component  1100  cassette door  1118  disposed against the second side of the cassette and opposite the mating block. As shown in  FIG. 10  previously, cassette door  1118  preferably includes a piston bladder (not shown) that provides additional mating force to the cassette to create a fluid-tight seal with the mating component. The cassette door  1118  preferably extends beyond cassette  800 , thus forming an occluder backstop  1120  disposed adjacent to the fluid lines  1116  and opposite occluder tip  1114 . In the illustrated embodiment, an occluder bladder  1122  is disposed between long arm  1104  and mating component  1105 . Occluder bladder  1122  can be pressurized to unocclude tubes  1116  with any hydraulic fluid, but in a preferred embodiment the hydraulic fluid comprises air. The occluder bladder  1122  can be supplied with hydraulic fluid via a supply line (not shown), which line in turn can be connected to a pressure reservoir or a pump. The supply line also preferably includes a valve that can be selectively opened to deflate the bladder and occlude tubes  1116 . In a preferred embodiment, the valve will fail open, for example if power to the system is interrupted. When occluder bladder  1122  is inflated, the bladder expands against long arm  1104  and displaces occluder tip  1114  away from occluder backstop  1120 , thereby opening fluid lines  1116 . As the occluder tip  1114  is displaced away from occluder backstop  1120 , spring  1110  is compressed to a sufficient degree such that when released, the occluder tip preferably delivers at least a 10 lb closing force on each of the fluid lines  1116 . In one preferred embodiment, the maximum displacement of the occluder tip  1114  upon actuation is about 0.25 inch. 
   In the embodiment illustrated in  FIGS. 12   a  and  12   b , pivot  1106  is located at the end of long arm  1104 , opposite occluder end  1108  with occluder bladder  1122  disposed between long arm  1104  and mating block  1105 . In an alternative embodiment  1130  shown in  FIGS. 12   c  and  12   d , the pivot  1132  can be placed on the long arm  1134  at an intermediate location along its length, preferably close to occluder end  1136 , with the occluder bladder  1122  being disposed between long arm  1134  and an occluder frame  1138  that is located opposite and at a spaced distance from mating block  1140 . 
   Referring again to  FIGS. 12   a  and  12   b , the illustrated embodiment also includes a hinge  1124  that is incorporated into occluder bar  1102  thereby allowing the occluder end  1108  to rotate about the hinge as the occluder bar is pivotally displaced during opening and occlusion of tubing  1116 . Rotation of occluder end  1108  about hinge  1124  allows the occluder end to maintain a more parallel orientation with respect to spring  1110  in spring housing  1112 , and thereby reduces the possibility of any spring hold-up during operation. 
   A preferred arrangement of an occluder mechanism is shown in  FIGS. 12   e  and  12   f . Occluder mechanism  1150  eliminates the coil spring and spring housing of the previously illustrated embodiments by employing a novel spring plate  1152  mounted to an occluder frame  1154  attached to reusable component  1156 . In the embodiment illustrated, the spring plate is connected to occluder frame  1154  by a pair of pivot pins  1166 ,  1168  which are, in turn, mounted on the occluder frame. Spring mounts  1158 ,  1160  are preferably firmly attached to spring plate  1152 . In alternative embodiments, the spring plate can be attached directly to the occluder frame or attached to the occluder frame be any alternative means apparent to those of ordinary skill in the art. 
   The spring plate  1152  can be constructed from any material that is elastically resistant to bending forces and which has sufficient longitudinal stiffness (resistance to bending) to provide sufficient restoring force, in response to a bending displacement, to occlude a desired number of collapsible tubes. In the illustrated embodiment, the spring plate is essentially flat and in the shape of a sheet or plate. In alternative embodiments, any occluding member that is elastically resistant to bending forces and which has sufficient longitudinal stiffness (resistance to bending) to provide sufficient restoring force, in response to a bending displacement to occlude a desired number of collapsible tubes may be substituted for the spring plate. Such elongated members can have a wide variety of shapes as apparent to those of ordinary skill in the art, including, but not limited to cylindrical, prism-shaped, trapezoidal, square, or rectangular bars or beams, I-beams, elliptical beams, bowl-shaped surfaces, and others. 
   In one preferred embodiment, the spring plate  1152  is in the shape of an essentially rectangular sheet and is constructed of spring steel having a thickness that is preferably less than {fraction (1/10)} its length (the distance between pivot  1158  and  1160 ). While the particular dimensions of spring plate  1152  must be determined based on factors which will vary depending on the application, such as the modulus of elasticity of the material from which it is constructed, the shape and thickness of the occluding member the number of tubes to be occluded, the stiffness of the tubes, and other factors as apparent to those of ordinary skill in the art, in a particular preferred embodiment, the spring plate  1152  is constructed from spring steel with a thickness of about 0.035 in. The width (the dimension into the plane of the figures) of the spring plate  1152  is selected to enable the plate to occlude all the fluid lines going into or out of cassette  800 . The length of the spring plate  1152  can be determined by considering factors such as the required displacement of occluder blade  1164 , the mechanical properties of the fluid lines, the yield point and elastic modulus of the spring plate material, and the thickness of the spring plate as mentioned above. Those of ordinary skill in the art can readily select proper materials and dimensions for spring plate  1152  based on the requirements of a particular application. In one exemplary embodiment where the pumping cartridge includes five fluid lines to be occluded, the spring plate is constructed from spring steel and has a thickness of 0.035 inch, a width of 4 inches, and a length of 6.1 inches. 
   In the illustrated embodiment, rear spring mount  1158  is pivotally attached to the occluder frame  1154  by a rear pivot pin  1166  located at a fixed point on the occluder frame. The spring mount  1158  can, in some embodiments, be a separate piece from the spring plate  1152 , which piece is rigidly attached to the spring plate or, in other embodiments, the spring mount  1158  can be integrated into the spring plate, for example, by looping the edge of the spring plate to form a cylinder capable of accepting a pivot pin. The forward spring mount  1160  is attached to the occluder frame  1154  by a forward pivot pin  1168  that can slide in a direction parallel to the length of the spring plate  1152  in a pivot slot  1170  located on the occluder frame  1154 . An occluder blade  1164  which moves as the spring plate  1152  is bent, is pivotally attached to the forward pivot pin  1168 . 
   The force required to permit occluder blade  1164  to occlude tubing  1116  is provided by the longitudinal stiffness of spring plate  1152 . Upon applying a force to the surface of spring plate  1152  in a direction essentially perpendicular to the surface of the plate (as shown in  FIG. 12   e ), the column stability of the spring plate is disrupted resulting in a buckling of the spring plate causing it to bow and decreasing the longitudinal distance between pivot pins  1166  and  1168 . This decrease in distance upon bowing of spring plate  1152  in turn creates a displacement of forward pivot pin  1168  within pivot slot  1170 , which displacement causes withdraw of occluder blade  1164  from tubing  1116  thereby opening tubing  1116  to allow fluid in/out of pumping cartridge  800 . In alternative embodiments, the force for bending need not be applied directly to a surface of the occluding member with a component of the force in the direction of bending as illustrated. In some alternative embodiments forces utilized for bending the occluding member may be applied to a surface of the member indirectly via components attached to the surface, force creating fields (e.g. electrostatic or magnetic fields), etc., or, alternatively, force may be applied to one or more ends of the occluding member in a direction essentially perpendicular to the bending direction in order to bend the occluding member. 
   In other alternative embodiments, occluder blade  1164  may not include the pivot pin and pivot slot, but may instead be rigidly attached to the spring plate  1152 . In yet other embodiments, the occluder blade may be eliminated altogether with the edge of the spring plate or other occluding member positioned adjacent to the tubing so that the plate/member can open and occlude the tubing as it is during bending and relaxation respectively. 
   In the illustrated embodiment, occluder frame  1154  is mounted to mating block  1172 . The mating block  1172  mates to the first face of a pumping cartridge  800 . The pumping cartridge  800  is held in place by a door  1174  (mating block  1172  and door  1174  can include additional components (not shown), such as piston bladders, depressions for forming chambers, etc. as discussed previously). The mating block  1172  and door  1174  can extend beyond the pumping cartridge  800  as shown to allow the tubing  1116  to be occluded by occluder blade  1164 . The mating block  1172  incorporates a slot  1176  through which the occluder blade  1164  can be displaced. The slot can be sized and positioned to enable occlusion of all of the fluid lines  1116  entering and exiting the pumping cartridge  800  when the occluder blade  1164  is displaced through the slot  1176  so that it occludes the fluid lines  1116  by pinching them against an extended portion  1178  of the door. 
   In the illustrated embodiment, a force actuator for applying a bending force to the spring plate comprises an inflatable occluder bladder  1182 . The occluder frame  1154  includes a bladder support  1180  housing an inflatable occluder bladder  1182  disposed against the spring plate  1152 . The occluder bladder  1182  may be inflated with any hydraulic fluid but in a preferred embodiment air is used as the hydraulic fluid. The inflatable occluder bladder  1182  can be supplied with air via an air line  1184  for either inflating or deflating the bladder. In a preferred embodiment, the air line  1184  can be connected to a three-way valve  1186  controlled by a processor, wherein the occluder bladder  1182  can be placed in fluid communication with either a vent line  1188  for deflating the occluder bladder or a pressure supply line  1190  for inflating the occluder bladder. 
     FIG. 13  illustrates one embodiment for the overall architecture and configuration of a reusable component, including a pumping system, for coupling to and operating a pumping cartridge  800  shown in  FIG. 11   a . Reusable component  1050  includes three levels of control and includes a variety of individual systems or modules for controlling and operating various components of pumping cartridge  800 . Reusable system  1050  includes an overall system controller and user interface  1052  which sends commands to and receives inputs from a master pump system control module  1054 . The controller/interface may be implemented using a microprocessor and associated software or using some other mechanism. Master module  1054 , in turn, sends commands to and receives input from individual pump drive system modules  1056 ,  1058 ,  1060 , as well as a door control module  1062 . The master module  1054  may also include a microprocessor and appropriate software. Reusable system  1050  also includes a power supply  1064  for providing electrical power to the various modules, and an air pump  1066 , which is utilized for providing pressurized measurement gas to the fluid supply tanks of the system. Air pump  1066  is pneumatically connected to master module  1054  which, in turn, is pneumatically connected to the individual pump modules and the door module. 
   Door module  1062  contains all necessary hardware and pneumatic connections to provide fluid-tight coupling between pumping cartridge  800  and a pump housing component of the reusable system. Door module  1062  also preferably contains a piston bladder and piston, which bladder is in pneumatic communication with master module  1054  via pneumatic line  1068 . The configuration of door module  1062  can be similar to that shown previously in  FIG. 10 , with modifications made to accommodate the size, shape, and fluidic connections of pumping cartridge  800 , as would be apparent to one of ordinary skill in the art. In addition, in preferred embodiments, door module  1062  also includes an occluder, which can be similar to occluder  864  shown in  FIG. 11   a , which is operated by supplying pressurized measurement gas to an occluder bladder (not shown) which forces the occluder against tubing in fluid communication with the various inlet and outlet ports of pumping cartridge  800  to collapse and occlude the tubing, the structure and function of such tubing occluders being known and understood in the art. Pneumatic line  1068  from master module  1054  also, in such embodiments, provides pressurized measurement gas to the occluder bladder. 
   Each of pump modules  1056 ,  1058 , and  1060  are preferably similar in design, and each is dedicated to the operation of an individual pump chamber, and its associated valves, provided in pumping cartridge  800 . For example, pump module  1  ( 1056 ) can be configured to operate pump chamber  822 , and its associated valves, pump module  2  ( 1058 ) can be configured to operate pump chamber  824 , and its associated valves, and pump module  3  ( 1060 ) can be configured to operate pump chamber  826 , and its associated valves. Each pump module is in pneumatic communication with door module  1062 , in order to supply measurement gas to the various control and valve actuating chambers in the pump housing component, which are disposed adjacent to the pump chambers and valving chambers of pumping cartridge  800 , when the system is in operation. 
   In a preferred embodiment, each of the pump modules is configured in a similar fashion as pump drive system  502  shown previously in  FIG. 8 , except that pump  516 , positive pressure tank  508 , and negative pressure tank  512  are not contained in the pump module as suggested in  FIG. 8  but, instead, in reusable system  1050 , pump  516  is replaced by air pump  1066 , and the pressure tanks are resident in master module  1054  and are shared by the individual pump modules. Each pump module preferably includes valves, pressure transducers, and a reference chamber dedicated to its respective pump chamber. Each pump module also preferably contains additional pneumatic valves to selectively provide pressurized measurement gas to actuate the various valving chambers associated with its respective pump chamber. In addition, each pump module preferably contains a dedicated microprocessor for controlling the operation of the individual pump chamber and performing the various calculations associated with the operation of the pump chamber, as discussed previously. 
   Each of the microprocessors included in the various pump modules is preferably configured to communicate with a microprocessor in master module  1054 . Master module  1054  is preferably configured to control the pressure within the positive and negative pressure fluid supply tanks preferably included therein, as well as within the piston bladder and occluder bladder in door module  1062 . The microprocessor included in master module  1054  preferably acts as the primary communications interface between the user interface and system control module  1052  and the individual pump control modules  1056 ,  1058 , and  1060 . 
   Master module  1054  is preferably configured to handle all of the input/output communications with the user interface/system control module  1052 . The commands input to master module  1054  from module  1052  can be processed by the microprocessor of master module  1054  and in turn can be translated by the microprocessor into appropriate commands for input to the microprocessors that are resident in individual pump modules  1056 ,  1058 , and  1060 . In preferred embodiments, overall system control module  1052  includes the majority of application-specific programming and provides for communication between the reusable system and a user of the system. Upon receipt of a command from system control module  1052  by master module  1054 , the master module is preferably configured to: (1) determine which valves of the system are to be opened or closed; (2) determine which pump module/door module/master is module contains the valves; and (3) issue an appropriate command to open or close such valves. All valve mapping (i.e., physical location of the various valves in the system) that is unique to the operation of the particular pumping cartridge being utilized, is preferably resident in the microprocessor of master module  1054 . 
   Also, in preferred embodiments, embedded application programming for each of the microprocessors in the various pump modules may be similar. In some preferred embodiments, there is no application-specific programming resident in pump modules  1056 ,  1058 , and  1060 . In preferred embodiments, pump modules receive commands from master module  1054  and are configured to determine which commands from master module  1054  to act on and which to ignore based upon whether the specific valves or components which are the subject of the command are resident in the particular pump module. 
   It should be appreciated that the overall system architecture described in  FIG. 13  for reusable system  1050  is purely exemplary, and that those of ordinary skill in the art will readily envision a wide variety of other ways to select components and configure and control the system and various components thereof, each of which configurations is considered within the scope of the present invention. 
   Those skilled in the art would readily appreciate that all parameters and configurations described herein are meant to be exemplary and that actual parameters and configurations will depend upon the specific application for which the systems and methods of the present invention are used. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of the appended claims and equivalents thereto, the invention may be practiced otherwise than as specifically described. The present invention is directed to each individual feature, system, or method described herein. In addition, any combination of two or more such features, systems, or methods, provided that such features, systems, or methods are not mutually inconsistent, is included within the scope of the present invention.