US 20020004015 A1
A cassette for controlling fluid flow from a source to a sink, for example, a patient. The cassette comprises a housing, and a passive inlet valve for hydraulically controlling pressurized fluid flow from the inlet valve to a central chamber, and an actuatable outlet valve. The central chamber provides a fluid pathway between the inlet and outlet valves. The cassette further comprises a piston assembly for exerting pressure in the central chamber. The piston assembly comprises a movable member, a covering for the moveable member; and a flexible interface between the member and the housing for providing near frictionless movement between the member and the housing.
1. A cassette for controlling fluid flow, the cassette comprising:
a housing comprising a central chamber; an inlet valve for hydraulically controlling pressurized fluid flow to the central chamber; and an outlet valve for controlling fluid flow from the central chamber; and
a piston assembly for exerting pressure in the central chamber; the piston assembly comprising a movable member, a covering for the moveable member; and a flexible interface between the member and the housing for providing near frictionless movement of the member.
2. The cassette of
at least one inlet flexible tubing, the inlet tubing providing a fluid pathway from a source into the inlet valve; and
at least one outlet flexible tubing, the outlet tubing providing a fluid pathway from the outlet valve to a sink.
3. The cassette of
a valve element attached to the stem; and
an elastomeric dome for biasing the valve element to the closed position.
4. The cassette of
5. The cassette of
6. The cassette of
a valve element;
a stem attached to the valve element; and
a diaphragm for biasing the valve element to a closed position.
7. The cassette of
8. The cassette of
9. The cassette of
10. The outlet valve of
11. The outlet valve of
12. The outlet valve of
13. The outlet valve of
14. The cassette of
15. The cassette of
16. The cassette of
17. The cassette of
18. The cassette of
19. The cassette of
20. The cassette of
21. The cassette of
22. An inlet valve for use with a cassette of the type to be used with an infusion system, the inlet valve comprising:
an elastomeric dome; and
a geometrically preloaded valve element which strains the elastomeric dome;
wherein the inlet valve has an unbalanced surface area perpendicular to the axis of the valve.
23. The inlet valve of
24. The inlet valve of
25. The inlet valve of
26. An outlet valve for use with a cassette of the type to be used with an infusion system, the outlet valve comprising:
an outlet valve element;
a stem attached to the outlet valve element;
an elastomeric dome for biasing the outlet valve element to the closed position, wherein the cross-sectional area of the elastomeric dome is greater than the cross-sectional area of the outlet valve element; and
an actuator interface which opens the outlet valve.
27. The outlet valve of
28. The outlet valve of
29. The outlet valve of
30. The outlet valve of
31. The outlet valve of
32. A check valve for use with a cassette of the type to be used with an infusion system, the check valve comprising a valve element, and an elastomeric wall, wherein the valve element is connected to the elastomeric wall, and wherein the check valve prevents upstream fluid flow by moving between an open and closed position in response to a pressure differential between the atmospheric pressure and pressure on the check valve.
33. The check valve of
34. The check valve of
35. The check valve of
 This application claims the benefit of co-pending U.S. Provisional Patent Application Ser. No. 60/216,658, filed Jul. 7, 2000, the contents of which are incorporated herein by reference.
 The invention relates to control systems for a fluid pump, and in particular, to an infusion pump system, including a pump.
 Infusion pumps are generally well known in the medical field for administering medications to patients over an extended time period. Typical medications may include antibiotics, anesthetics, analgesics, cardiovascular drugs, chemotherapy agents, electrolytes, narcotics, whole blood and blood products, etc. Infusion pumps are typically designed for a particular clinical application: e.g., many pumps are designed principally for use on the hospital general floor; other pumps are designed for pediatric use; other pumps are designed for critical care use; still other pumps are designed for home healthcare use, etc. Also, infusion pumps are typically designed for either large volume fluid delivery (say from one liter bags or bottles of diluted medication) or for small volume fluid delivery (typically from syringes filled with up to 60 mL of undiluted medication), but not for both. Such a wide variety of specialized pumps requires hospitals and healthcare facilities to maintain a large diverse inventory of pumps, to ensure staff training is current on all pumps, and to provide a wide variety of service training. This diversity of specialized pumps leads to increased cost, increased capital investment, and increased medication administration errors.
 Therefore, there exists a need for a mechanism to control fluid delivery in a manner such that a single infusion pump can fully satisfy the drug infusion needs of multiple hospital and healthcare applications (including home healthcare), can deliver small volume as well as large volume doses over a wide range of required flow rates, and can provide small size and weight, power-efficient, cost-efficient implementation. The cassette described in this invention in conjunction with an infusion pump, such as the one disclosed in U.S. Patent Application No. 60/216,789, entitled “Controlled Force Fluid Delivery System,” filed concurrently herewith, to Carlisle and Patel, the contents of which are incorporated herein by reference, allows a drug infusion system to achieve these objectives.
 The present invention provides a fluid flow through a unique combination of valves, piston assembly, chambers and pathways. In one form, the invention comprises a cassette with a central chamber and inlet and outlet valves and a piston assembly capable of being pushed and pulled. The cassette central chamber provides a fluid pathway from the inlet valve to the outlet valve.
 Additionally, the invention includes an inlet valve that normally stays closed, but can open to low resistance with external activation and has high blowby pressures and low compliance on the chamber side. The invention further provides an outlet valve that normally stays closed and that opens with external activation and has low compliance.
 The invention also provides a low compliance check valve means of secondary, additional protection that prevents free flow of fluid to the patient when the chamber has negative pressure.
 The invention is a cost-efficient apparatus that may be made of disposable components, allowing for ease and convenience of replacement without affecting the multiple uses of an infusion pump system.
 The invention will be better understood by reference to the appended figures, in which
FIG. 1 shows an exploded perspective view of the cassette assembly of the invention;
FIG. 2 shows a cross-sectional view of the cassette central chamber;
FIG. 3 shows a perspective view of the cassette fluid path;
FIG. 4 shows a cross-sectional view of the piston assembly;
FIGS. 5a and 5 b illustrate the surfaces supporting the diaphragm during travel;
FIG. 6 illustrates a small, unsupported elastomer surface exposed to pressure;
FIG. 7 shows an exploded cross-sectional view of the unsupported elastomer surface exposed to pressure;
FIG. 8 shows a cross-sectional view of the inlet valve;
FIG. 9 shows the upstream and downstream inlet valve surfaces;
FIG. 10 shows the inlet valve forces;
FIG. 11 shows the pressure vs. displacement graph on the inlet valve;
FIGS. 12a and 12 b illustrate the two states of the inlet valve;
FIG. 13 shows a cross-sectional view of the outlet valve;
FIGS. 14a- 14 c show three opening states of an outlet valve;
FIG. 15 shows the forces acting on the outlet valve;
FIG. 16 shows a cross-sectional view of the check valve; and
FIGS. 17a and 17 b show the open and closed states of the check valve.
FIG. 1 is an exploded, perspective view of a cassette assembly constructed in accordance with the present invention. In this form, the assembly uses a piston 1 inserted into a piston receiving hole 2 in a top cover 3 of the cassette assembly. The piston is adapted to be connected to a shuttle of an infusion pump. Top cover 3 has two holes 4 a and 4 b, which may be placed equidistant and on opposite sides of piston receiving hole 2. Top cover holes 4 a and 4 b receive an actuator interface portion 6 for an outlet valve 7 and a button 8 for an inlet valve 9. Top cover 3 may be constructed of Zylar, an acrylic copolymer manufactured by Novacor, but may be made of any material which is inert to the fluids with which the cassette is used, such as polycarbonate material or ABS (Acrylonitrile-Butadienen-Styrene).
 Adjacent and attached to top cover 3 is a housing 10. Housing 10 defines a containment portion for outlet valve 7, inlet valve 9, and diaphragm 11 in a central housing chamber 21 (See FIG. 2). In one embodiment, housing 10 is ultrasonically welded to top cover 3. After welding, the interface between housing 10 and top cover 3 provides compression on annular seals on the fluid side of inlet valve 9, diaphragm 11, and outlet valve 7, thereby providing a fluid-tight path between the housing 10 and all of the elastomeric components.
 The housing further comprises at least one receptor 12, which connects with means for transporting the fluid from the source to the cassette and at least one receptor which connects with a means for transporting the fluid from the cassette to the sink, such as in the form of flexible plastic tubing (not shown).
 Inlet valve 9 fits into a shaped depression in housing 10 with button 8, which communicates with hole 4 b in top cover 3. The shaped depression has a receiving means for example, hole 15, for insertion of a stem 13 of inlet valve 9. Housing 10 also provides a receiving means 14 for the piston assembly, which includes piston cap 23. On the other side of the piston assembly is a shaped depression for receiving outlet valve 7. This depression has a hole 17 for inserting stem 16 of outlet valve 7. Actuator interface 6 of outlet valve 7 fits into hole 4 a in housing 10. Bottom cover 18 is attached to housing 10 and shaped to cover housing 10 with the sides flush with the edges of housing 10. In one embodiment, bottom cover 18 is ultrasonically welded to housing 10 around a dog-bone-shaped weld bead on bottom cover 18. This weld provides a hermetic seal between bottom cover 18 and housing 10. Bottom cover has receiving means 19 a and 19 b on opposite sides of the piston for receiving stems 13, 16, of both inlet valve 9 and outlet valve 7.
FIG. 2 shows a cross section of a cassette central chamber 21. In this embodiment, fluid enters the chamber via flexible tubing (not shown) and through inlet valve 9. Inlet valve 9 is normally closed and opens as a result of negative pressure in chamber 21, which is present while piston 1 is being retracted. Once central chamber 21 is filled, piston 1 pushes back into chamber 21, causing inlet valve 9 to close and applying pressure to check valve 22. Check valve 22 will open unless the atmospheric pressure exceeds the forces on the valve in central chamber 21. In this embodiment, outlet valve 7 is externally activated. Therefore, when fluid passes through check valve 22, it will be released through open outlet valve 7 when the outlet valve is activated and passes through flexible tubing (not shown) to the patient.
FIG. 3 shows a perspective view of the cassette to show the fluid flow from inlet valve 9 through central chamber 21 to outlet valve 7.
FIG. 4 shows a cross-sectional view of the piston assembly. The piston assembly comprises piston 1, diaphragm 11, and a piston cap 23. Piston 1 may be any vertically moveable member and may be cylindrical in shape. Diaphragm 11 is shaped to receive piston 1. Diaphragm 11 may be made of flexible material, such as a specially woven fabric, impregnated with a thin layer of elastomer. A thin-walled rolling diaphragm may provide low axial elastomeric forces. The fabric can be any fabric that gives high tensile strength to the diaphragm and allows for free rolling action while preventing axial distortion. In one embodiment, diaphragm 11 is a pre-convoluted diaphragm and is constructed of a silicon rubber with impregnated polyester or nylon mesh, a material with essentially no compliance and which withstands negative pressures with low volumetric degradation. One example of such a diaphragm is the Bellofram Rolling Diaphragm (BRDŽ). However, the diaphragm may also be constructed of polyisoprene with impregnated nylon or polyester mesh, or any other like material. Piston cap 23 may be constructed of Zylar, an acrylic copolymer manufactured by Novacor, but may also be made using a polycarbonate or ABS (Acrylonitrile-Butadienen-Styrene) material. Piston cap 23 is welded to piston 1, capturing diaphragm 11 between piston cap 23 and piston 1. This geometry prevents inversion of diaphragm 11 during the transition from empty to fill cycles and throughout the fill cycle.
 In operation, the piston assembly offers small rolling resistance to axial movement and significant resistance to radial movement within prescribed limits. Diaphragm 11 rolls against (instead of rubbing against) piston 1 and the interior upper housing.
FIGS. 5a and 5 b illustrate the surfaces supporting the diaphragm during travel which includes rolling surfaces 39, fabric side 40, and elastomer side 41. As shown in FIGS. 5a and 5 b, the movement of piston 1 results in volume changes [dV] that are linear with axial position changes [dL], yielding known and stable volume changes as a function of positive pressure changes, independent of starting position. For all practical purposes, dV/dL is a constant because the effective cross-sectional area [Ae] of the piston is constant throughout the linear stroke range. In this embodiment, the rolling diaphragm is a Bellofram “C” style pre-convoluted diaphragm. In other words, convolution has been molded into the installed shape. The elastomer in its natural shape appears as shown in the “empty state” in FIG. 5a. The effective pressure area [Ae] of the system is defined by a diameter midway between the cassette housing cylinder bore diameter 62, which is defined as D1, and the piston diameter, 63, which is defined as D2. The effective pressure area [Ae] can be calculated using the formula: Ae=0.7854 * (D1—(D1—D2)/2)2. The effective pressure area [Ae] remains constant regardless of stroke position. FIG. 5b shows the elastomer as it appears in the “filled state.”
FIG. 6 illustrates a small, unsupported elastomer surface 36 of diaphragm 11 exposed to pressure [P]. FIG. 7 shows an exploded cross-sectional view of surface 36. FIG. 7 shows the housing rolling surface 42, the piston rolling surface 46, the silicone side 45 and the mesh side 44. Low compliance results from both the diaphragm material choice (such as a nearly incompressible elastomer (e.g., silicon) impregnated with a polyester or nylon mesh) and the piston/chamber geometry (which by design provides very low unsupported surface area of diaphragm exposed to pressure). Also as a result of the choice of diaphragm geometry and materials, the piston assembly withstands negative pressure with low volumetric degradation, a property needed to obtain a rapid and complete fill of the chamber.
FIG. 8 shows a cross-sectional view of the inlet valve 9. Housing 10 also provides a containment means for inlet valve 9. Inlet valve 9 comprises button 8 that can be used for external activation. Button 8 is attached to a shaft 24. Positioned around shaft 24 is an elastomeric dome 25. Shaft 24 ends at a valve element 26. Attached to valve element 26 is stem 13. Elastomeric dome 25 communicates with top cover 3 forming a top cover seal 27 and abuts housing 10 forming a housing seal 28.
 The inlet valve 9 is an unbalanced, multifunction, passive flow control valve for a pumping scheme where central chamber 21 fills with negative pressure and empties with positive pressure. In operation, the fluid is forced from the fluid source through the flexible tubing (not shown) and to the inlet valve 9. FIG. 9 shows the upstream fluid 47 and downstream fluid 48 relative to inlet valve 9. FIG. 9 also shows the inlet valve diaphragm 49. Because the inlet valve 9 has a net unbalanced surface area perpendicular to the axis of the valve (higher net surface area on upstream side than on downstream side), the invention ensures that positive upstream pressure applies additional force to valve element 26, which tends to close the valve. In other words and as seen in FIG. 9, there is a higher net surface area on the upstream side 47 than on the downstream side 48. Inlet valve 9 closes in all cases where the upstream fluid pressure (Pu) exceeds the downstream fluid pressure (Pd). One practical result of this design is that an upstream syringe push forces fluid into the source container and not into the cassette chamber.
 Inlet valve 9 is constructed so that normal upstream negative pressure, for example pressure resulting from low source container height, will not cause inlet valve 9 to open. Inlet valve 9 achieves this by having built-in elastomeric forces created by geometrically preloading valve element 26 as shown in FIG. 10. The effect is to strain elastomeric dome 25. In the absence of fluid pressure on either side of the valve, a preload force 50, defined as Fp, maintains the valve in a closed and sealed state. Additionally, fluid pressure on upstream side applies additional axial forces on the valve element 26 approximately equal to the net cross sectional area perpendicular to the axis of the valve. This upstream fluid force can be approximated as Fu=Pu* π*[(D1/2)2−(D0/2)2], where Pu is the fluid pressure on the upstream side, D1 is the inside diameter 53 of the elastomeric dome, and D0 is the inside diameter 52 of the valve housing element 26. The downstream fluid force can be approximated as Fd=Pd* π* [(D2/2)2], where Pd is fluid pressure on downstream side 48 and D2 is the outside diameter 51 of the valve element 26. The total force, Ft, on valve element 26 can be modeled as Ft=Fp+Fu+Fd. Positive pressure on upstream side 47, Pu, adds to the force on the valve element 26 and keeps the valve closed. Positive pressure on downstream side 48, Pd, also increases the force on valve element 26 and keeps the valve closed. Conversely, negative pressure, Pu, on upstream side 47 reduces the compression on valve element 26; Fu is negative when Pu is negative. The design of inlet valve 9, however, has sufficient headroom to prevent the upstream fluid force, Fu, from being greater than elastomeric preload force 50, Fp, under peak upstream negative pressure conditions.
 An inlet valve constructed in accordance with the principles of the invention also provides very high blowby pressure. Blowby refers to retrograde flow going from the pump chamber to the source; in other words, fluid flow moving from downstream to upstream. Inlet valve 9 achieves this by tapering against a smaller interior diameter rounded housing as seen in FIG. 10. This design allows for positive pressure, Pd, on the downstream (pump chamber) side that increases the load, Fd, on the seat. The result is a very high blowby pressure.
 Inlet valve 9 normally stays closed and opens to low resistance with low force external activation. This normally closed state is a safety mechanism that prevents free flow and is achieved by a suitable preload design. Low force external activation of inlet valve 9 provides easy loading of the cassette into a pump and unloading of the cassette from the pump. In addition, inlet valve 9 tends to close more tightly with positive pressure distal to it. This property is achieved by the design of the cross-sectional area. Inlet valve 9, however, can also be opened without external activation. This is achieved when there is negative pressure in central chamber 21. The negative pressure opens inlet valve 9, allowing fluid to flow from the source into the chamber. The valve opens when the negative pressure, Pd, in the pump chamber is sufficient to overcome the sum of the elastomeric preload force of the valve, Fp, and any force, Fu, due to upstream fluid pressure.
 An inlet valve constructed in accordance with the principles of the invention is unstable, meaning that once it is opened, it will open further, thus providing a rapid, energy-efficient fill. This occurs because when Pd is negative, Pu may also be negative, which in turn applies a differential pressure across the diaphragm dome. Because Pu is now less than atmospheric pressure, this new pressure differential acts on elastomeric dome 25 to rapidly increase the opening force on inlet valve 9 with very little increase in the pressure of central chamber 21. The result is that the axial motion of inlet valve 9 increases rapidly. FIG. 11 shows the pressure vs. displacement graph on the inlet valve. For example and as shown in FIG. 11, at a negative pressure of about −0.55 psig, inlet valve 9 begins to overcome the elastomeric preload and the valve begins to open. The pressure at which the valve first starts to open (in this case ˜−0.55 psig) is called the cracking pressure. Almost immediately, inlet valve 9 opens wider with very little additional negative pressure, resulting in very efficient linear travel. This design reduces the power consumption required to fill central chamber 21. In addition, lower negative pressure required to initially crack and fully open the valve reduces fluid outgassing.
FIGS. 12a and 12 b illustrate the two states of the inlet valve. Significantly, FIGS. 12a and 12 b show how a passive inlet valve in accordance with the principles of the invention opens to forward flow with low chamber pressure. The opening of inlet valve 9 is due to the pressure differential forces on the valve. In the first state, and as seen in FIG. 12a, negative pressure, Pd, in central chamber 21 reaches a critical threshold when the force on the downstream side 48 of the valve is able to overcome the sum of the force, Fp, due to elastomeric preload and the force, Fu, due to flow 47 from upstream fluid pressure. When inlet valve 9 initially opens, and initial flow occurs, there is a pressure drop across the valve orifice, defined as Pu-Pd. For a valve with a sufficient orifice, this pressure drop can be very low, and the differential between Pu and Pd grows smaller as the valve opens.
 As shown in FIG. 12b, elastomeric dome 25 is protected from premature fatigue by a stop 29 in the bottom cover. Stem 13 of inlet valve 9 butts against stop 29 to prevent overtravel and excess strain on the elastomeric dome. The elastomeric dome design may be tuned to achieve a desired cracking pressure range by changing wall thickness, by changing durometer, or by choice of material.
 In addition, the cracking pressure of inlet valve 9 is relatively insensitive to manufacturing tolerances. The geometry of inlet valve 9 has approximately constant spring force over the long throw provided by the dome geometry. The inlet dome geometry provides a spring force versus distance profile that has as small a slope as possible while keeping the valve within reasonable manufacturing tolerances.
FIG. 13 shows a cross-sectional perspective of an outlet valve constructed in accordance with the principles of the invention. In this embodiment, outlet valve 7 is constructed of silicon rubber, but urethane or any other material which is stable under radiation sterilization, has very low compliance, has minimal drug interactions, and/or is easy to mold with required geometric tolerances may also be used. Outlet valve 7 comprises an actuator interface 6 attached to a stem 16. Similar to the inlet valve, the elastomeric web/flexible annulus 32 and the stem 16 provide the outlet valve springs. A portion of stem 16 is surrounded by a diaphragm 30. Diaphragm 30 extends into central chamber 21. Opposite actuator interface 6, stem 16 attaches to a valve element 31.
 Outlet valve 7 stays closed normally and opens with external activation on actuator interface 6. The opening of outlet valve 7 depends in part on the amount of activation force applied. For example, the externally activated outlet valve 7 can open incrementally, partially or fully, thereby providing a wide dynamic range of flow rates/flow resistance. FIGS. 14a- 14 c show three opening states of an outlet valve in one embodiment of the invention.
 Outlet valve 7 is internally damped through choice of material used in construction. Therefore, when external activation force is applied to outlet valve 7, it does not immediately open. Instead, the material first gives, and then as the activation force continues the valve barely opens as shown in the first state seen in FIG. 14a. The valve closes easily when the activation force is removed. For example, outlet valve 7 may be constructed and arranged to be opened for a period of time shorter than the period of time for the fluid flow to reach a stable velocity. This is the on/off ‘pulse’ mode where outlet valve 7 is opened incrementally.
 As seen in FIG. 14b, the valve is in the variable orifice (micro-metering) section where the taper of the valve/valve-housing seat opening determine the orifice. In this ‘nudge’ mode state, the valve orifice has a hydraulic annulus 37 which is defined as Dh, which allows precise metering of fluid or partial opening. The degree to which Dh increases is controlled by the relationship of the valve taper to the valve-housing seat 31. For example, the greater the taper (i.e., the steeper the taper angle), the less the increase in opening of the annulus 37 with linear actuation, and the better the metering characteristics. Accordingly, the fluid flow through the outlet valve in this state is controlled by the distance between the tapered surface and the valve seat. When the activation force is sufficient to open the outlet valve 7 past the taper, then the valve enters the constant orifice or full-open section, where the flow resistance is controlled by the diameters of the stem and the fluid channel. This other extreme of the ‘nudge’ mode state is illustrated in FIG. 14c. Dh is constant in this region, where maximum flow occurs. Here the fluid flow through the outlet valve is controlled by the distance between valve stem 16 and the valve -housing seat 31. Accordingly, in one embodiment of the invention, depending on the amount of activation force applied, outlet valve 7 can open incrementally, partially or fully.
 An electric motor and cam serve to operate the valve actuator in a portion of its cycle and to move the shuttle/piston in a portion of its cycle, so that the two are permanently mechanically synchronized. The opening of the outlet valve is ‘time-on-the-cam’ controlled; that is, by the amount of time to move the cam in the empty direction. To activate the ‘pulse mode’ of the outlet valve (FIG. 14a), the time-on-the-cam is selected so as to move part way up the cam in the empty direction without holding and then return, resulting in the outlet valve just opening. To activate the ‘nudge mode’ of the outlet valve, a longer time-on-the-cam is selected to move almost all the way up the cam in the empty direction without holding and then return, resulting in the outlet valve opening as depicted in FIG. 14b. To activate the full open, constant orifice flow state shown in FIG. 14c, the time-on-the-cam is selected to move all the way up the cam and then hold for a prescribed time. The third state, the ‘turbo’ mode, is achieved when the shuttle is fully filled and, in a continuous direction, the motor continues rotating to empty the entire amount in central chamber 21. The position of the shuttle which is, for example, determined by an optical position sensor (disclosed, for example, in U.S. patent application No. 60/217,885, entitled “Optical Position Sensor and Position Determination Method,” filed concurrently herewith, to Carlisle, Kaplan and Kirkman, the contents of which are incorporated herein by reference), in conjunction with the control algorithm and the user settings, is used to select the appropriate mode for the outlet valve.
 The normal state of outlet valve 7 is the closed state. This state is maintained by the unbalanced surface area and elastomeric preload force of the valve, even with peak positive pressures in central chamber 21. FIG. 15 shows the forces acting on the outlet valve. As can be seen in FIG. 15, this unbalanced surface area is achieved when the surface area on the upstream side is greater than the surface area on the downstream side. This is a safety feature of outlet valve 7 in that it prevents free flow. Positive downstream pressures also tend to seal/shut the outlet valve more tightly because the hydraulic force, FHd, increases the loading on valve-housing seat 31. The valve/valve-housing seat taper provides a differential cross-sectional area between the central chamber side and the patient side. Tapered seat 31 also helps keep valve stem 16 from being pushed through the seat opening.
 In addition, outlet valve 7 constructed in accordance with the principles of the present invention also possesses sufficiently high elastomeric preload to withstand negative pressure in central chamber 21 without opening. Outlet valve 7 has elastomeric preload on valve element 31 provided by a diaphragm preload force 55, which is defined as Fd, and post preload force 54, which is defined as Fp. As shown in FIG. 15, diaphragm 57 creates a diaphragm preload force 55, Fd, which is the result of tension placed on flexible annulus 32. The tension is achieved by geometrically constraining and compressing stem 16 between housing 10 and bottom cover 18. The resultant elastomeric force, Fe, is given by the equation: Fe=Fp+Fd. Without the influence of hydraulic forces, the elastomeric force, Fe, maintains the valve in a normally closed state.
 Hydraulic forces also play a role in the performance of outlet valve 7. As mentioned above, outlet valve 7 is designed to be hydraulically unbalanced. The design provides a diaphragm cross-sectional area that is significantly larger than valve element 31 cross sectional area. The diaphragm effective cross-sectional area, Ad, exposed to the fluid pressure in central chamber 21, Pc, is approximated by the following equation: Ad=π* ((Dd/2)2−(Ds/2)2), where Dd is diaphragm diameter 64 and Ds is valve element diameter 65. The cross-sectional area of valve element 31, As, is approximately: As=π* (D1/2)2. The hydraulic force, FHc, acting on valve element 31 due to the pressure in central chamber 21 can be approximated by the equation: FHc=(Pc−Pa)* Ad, where Pa is atmospheric pressure 56. The hydraulic force, FHs, acting on the downstream, or outlet, side of the valve can be approximated as FHs=(Pd−Pa) * As. The total hydraulic force, FH, acting on valve element 31 is given as FH=FHc+FHs. The total force, Ft, on valve element 31 is given as the sum of the elastomeric preloading forces, Fe, and the total hydraulic forces, FH, or Ft=Fe+FH.
 Cassette outlet valve 7 may also be designed such that the valve maintains a closed position (in the absence of external activation) due to the elastomeric preload, Fe. The elastomeric preload is sufficient to keep the valve closed even under negative pressure (Pd<Pa) on the downstream side. Such negative pressure may result, for example, from the suction of a syringe. The preload is determined by the valve element geometry relative to the housing, i.e. the distance between flexible annulus 32 and valve element 31. In addition, stem 16 presses on base 33 for additional preload. In the case where Pc is negative (Pc<Pa) during fill cycles, the hydraulic force in central chamber 21 tends to reduce the total force Ft, on valve element 31. By design, then, the total preload force, Fe, exceeds the greatest possible negative hydraulic force, FH.
 One embodiment of the outlet valve includes stem 16 being manufactured such that its nominal position, when inserted into the cassette housing, is slightly bent. This bent column exhibits nearly constant force over its travel, providing a force that is dependent only on the column thickness.
FIG. 16 shows a cross-sectional view of check valve 22. Check valve 22 may be included in the cassette as a secondary, backup safety feature. Check valve 22 has an elastomeric wall 35 and valve element 34. As in the inlet valve 9 and outlet valve 7, the elastomeric material of the elastomeric wall 35 provides the check valve spring. Check valve 22 may be molded into outlet valve 7 (See FIGS. 1 and 2). Check valve 22 is passively activated. Preferably, check valve 22 has a very thin wall thickness. The thickness of the check valve is determined by pressure-to-open specification (—1.5 psi). Thus it requires very low pressure Pc in central chamber 21 to open fully. Its preferred position in the cassette is where it is supported by housing 10 at its full open position. This position achieves low compliance. The small diameter of check valve 22 also offers low compliance. The check valve diameter is based on the housing orifice diameter. Flow resistance targets determine the housing orifice diameter. The housing orifice diameter may be selected so that it does not offer the highest flow resistance in the fluid path. As a result, the check valve diameter is set to be as small as possible within these constraints. Therefore, as pressure in central chamber 21 exceeds atmospheric pressure from vent 58 and any small elastomeric preload force of check valve 22, check valve 22 opens. In this open state, top cover housing 3 provides support, which ensures low compliance
 In addition, check valve 22 prevents retrograde flow. FIGS. 17a and 17 b show the open and closed states of the check valve. FIG. 17a shows the open state of check valve 22 and FIG. 17b shows the closed state of check valve 22. As illustrated in FIGS. 17a and 17 b, the pressure 59 in central chamber 21, which is defined as Pc, and which is negative during the fill state, will seat and close check valve 22. This occurs because the pressure, Pa, on the atmospheric side from vent 58 of check valve 22 is greater than the pressure in central chamber 21.
 Check valve 22 may also be used to prevent a free flow state (where fluid flows from the fluid source through inlet valve 9, central chamber 21, and outlet valve 7 to the patient). This situation can arise when, for example, outlet valve 7 fails to close with the cassette above the patient site. In this condition, the pressure 60, on the outlet side of check valve 22 which is defined as Pv is lower than atmospheric pressure, Pa. This pressure differential closes check valve 22, thus preventing free flow. In addition, check valve 22, prevents blood from being aspirated on the next fill cycle, because Pc is less than atmospheric pressure, Pa.