Medical fluid system with flexible sheeting disposable unit.

MEDICAL FLUID SYSTEM WITH DISPOSABLE UNIT

FLEXIBLE SHEET

PRIORITY CLAIM

This application claims priority to and benefit as a continuation application in part of the US Patent Application entitled Hemodialysis / Domestic Hemofiltration of High Convection and Absorbent System, Series No. 10 / 982,170, filed on November 4. 2004

BACKGROUND

The examples discussed below generally refer to the supply of medical fluid. More particularly, the examples describe systems, methods and apparatus for fluid flow control in kidney failure treatment systems.

Due to several causes, a person's renal system may fail. Renal failure causes severe physiological disorders. The balance of water, minerals and the excretion of daily metabolic load is no longer possible and the toxic end products of nitrogen metabolism (urea, creatinine, uric acid, and others) can accumulate in the blood and tissue.

Kidney failure and reduced kidney function has been treated with dialysis. Dialysis removes waste, toxins and excess water from the body that would otherwise be removed by normally functioning kidneys. Dialysis treatment for kidney function replacement is critical for many people because the treatment can save their lives.

Hemodialysis and peritoneal dialysis are two types of dialysis therapies commonly used to treat kidney function loss. Hemodialysis (HD) treatment uses the patient's blood to remove waste, toxins and excess water from the patient. The patient is connected to a hemodialysis machine and the patient's blood pumps through the machine. The catheters are inserted into the veins and arteries of the patient so that blood can flow to and from the hemodialysis machine. Blood passes through a machine dialyzer, which removes waste, toxins and excess water from the blood. The cleaned blood is returned to the patient. A large amount of dialysate, for example approximately 120 liters, is consumed to dialyze the blood during an individual hemodialysis therapy. Hemodialysis treatment lasts several hours and is usually performed at a treatment center approximately three or four times a week.

Another form of kidney failure treatment that involves blood is hemofiltration (HF), which is an alternative kidney failure therapy that relies on convective transport of toxins from the patient's blood. The therapy is performed by adding replacement or replacement fluid to the extracorporeal circuit during treatment (typically ten or ninety liters of such fluid). That replacement fluid and the fluid accumulated by the patient between treatments are unfiltered over the course of the HF treatment, which provides a transport mechanism that conducts heat that is particularly beneficial in removing waste products from medium and large molecules.

Hemodiafiltration (HDF) is another modality of blood treatment that combines convective and diffusive cleanings. HDF uses dialysate to flow through a dialyzer, similar to standard hemodialysis, which provides diffusive cleaning. In addition, the replacement solution is provided directly to the extracorporeal circuit, which provides convective cleaning.

Peritoneal dialysis uses a dialysis solution, also called dialysate, that is infused into the patient's peritoneal cavity through a catheter. The dialysate contacts the peritoneal membrane of the peritoneal cavity. Waste, toxins and excess water pass from the patient's bloodstream, through the peritoneal membrane, in the dialysate due to diffusion and osmosis, that is, an osmotic gradient occurs through the membrane. The spent dialysate is drained from the patient, which removes waste, toxins and excess water from the patient. This cycle repeats.

There are several types of peritoneal dialysis therapies, including continuous transient peritoneal dialysis (CAPD), automated peritoneal dialysis (“APD), tidal flow APD and continuous flow peritoneal dialysis (CFPD).

CAPD is a good manual dialysis treatment. The patient manually connects an implanted catheter to a drain, which allows spent dialysate fluid to drain from the peritoneal cavity. The patient then connects the catheter to a fresh dialysate bag, which infuses made fresh through the catheter and into the patient. The patient disconnects the catheter from the fresh dialysate bag and allows the dialysate to remain inside the peritoneal cavity, where the transfer of waste, toxins and excess water is carried out. After a period of permanence, the patient repeats the manual dialysis procedure, for example, four times per day, each treatment lasting approximately one hour. Manual peritoneal dialysis requires a significant amount of time and effort from the patient, which leaves ample room for improvement.

Automated peritoneal dialysis (APD) is similar to CAPO in that the dialysis treatment includes drainage, filling, and permanence cycles. APD machines, however, perform the cycles automatically, typically while the patient sleeps. APD machines free patients from having to manually perform treatment cycles and having to transport supplies during the day. APD machines are fluidly connected to an implanted catheter, a fresh dialysate source or bag and a fluid drain. APD machines pump fresh dialysate from the dialysate source, through the catheter into the patient's peritoneal cavity, and allow the dialysate to remain inside the cavity, which causes the transfer of waste, toxins and excess water to perform . The source may be multiple bags of sterile dialysate solution.

APD machines pump dialysate spent from the peritoneal cavity, through the catheter, into the drain. As with the manual process, several cycles of drainage, filling and permanence occur during APD. A final filling occurs at the end of CAPD and APD, which remains in the peritoneal cavity of the patient until the next treatment.

Both CAPD and APD are group type systems that send spent dialysis fluid to a drain. Tidal flow systems are modified group systems. With tidal flow, instead of removing all of the patient's fluid over a longer period of time, a portion of the fluid is removed and replaced after smaller type increases.

Continuous flow systems, or CFPD clean or regenerate spent dialysate instead of discarding it. The systems pump fluid into and out of the patient, through a ring. The dialysate flows into the peritoneal cavity through a catheter lumen and out of another catheter lumen. The fluid that leaves the patient passes through a reconstitution device that removes waste from the dialysate, for example, through the urea removal column that uses urease to enzymatically convert urea to ammonia. The ammonia is then removed from the dialysate by absorption prior to the re-introduction of the dialysate into the cavity pe rito ne a I. Additional sensors are used to verify the removal of ammonia. CFPD systems are typically more complicated than group systems.

In each of the kidney failure treatment systems discussed above, it is important to control ultrafiltration, which is the process by which water (with electrolytes) moves through a membrane, such as a dialyzer or peritoneal membrane. For example, ultrafiltration in HD is a result of transmembrane and osmotic pressure differences between blood and dialysate through a dialyzer membrane. For a given osmotic pressure, the higher the transmembrane pressure, the faster ultrafiltration will be.

Many of the dialysis systems described above employ a pump cassette. The pump cassette typically includes a flexible membrane that moves mechanically to push and pull dialysis fluid out of and into, respectively, the cassette. Certain known systems include flexible foil on one side of the cassette, while others include foil on both sides of the cassette. The positive and / or negative pressure can be used to operate the pumping cassettes.

Pumping cassettes have many design problems. For example, a problem with the pump cassette is filtration. If the flexible membranes experience a small hole or breakage, the fluid and air can move from one side of the membrane to the other. Movement of the fluid from inside the cassette to the internal workings of the machine can damage the machine. The movement of air from the machine into the cassette can compromise the sterility of the fluid paths defined by the cassette.

Another problem with cassette-based pumping occurs when the cassette is improperly loaded into the machine. Proper alignment is important because the portions of the flexible membrane must match corresponding machine portions, for example, pump and valve actuators. Improper loading can lead to undue mechanical stress that is placed on the cassette, potentially damaging the cassette and / or the actuator. Improper cassette loading can also degrade or prohibit system performance.

An additional dilemma, especially in CFPD, is the coordination of multiple fluid supplies. Cassette-based peritoneal pumping systems that continuously deliver fluid to patients are required to remove fluid (ultrafiltrate) from and add fluid (concentrate) to a ring of continuously flowing dialysis fluid. Additional fluids typically have necessary additional dedicated pumps, which make the cassette and dialysis machine larger and louder. Programming the operation of multiple pumps also presents a challenge to system implementers.

Even another problem associated with cassette-based pumping is trapping air or other gas in the fluid paths. Air can enter the system through filtration connections, improper primer, defective tubing and defective cassettes. Patient therapy also produces several gases that enter the system. Cassette-based pumps are designed to pump fluid, not gas. In addition, the removal and supply of fluid to and from the patient needs to be monitored and controlled. For PD-type systems, air and gases alter the volume measurement systems that assume that there is no air or gas in the fluid paths. Air and gases can also be uncomfortable for the patient and prevent removal of appropriate waste. For HD-type systems, air in the bloodstream can be harmful to the patient.

Cost, ease of manufacture, duration and reliability are additional problems that are oriented towards cassette-based dialysis systems. There is a need therefore for improved cassettes for cassette based dialysis systems, which satisfy the problems described above.

BRIEF DESCRIPTION OF THE INVENTION

The examples described herein describe dialysis systems that employ a flexible pump cassette such as: hemodialysis (HD), hemofiltration (HF), hemodiafiltration (HDF), peritoneal dialysis (("PD), including transient peritoneal dialysis (CAPD), Automated peritoneal dialysis (APD), tidal flow APD and continuous flow peritoneal dialysis (CFPD)). The systems can also be used in any type of continuous renal replacement therapy (CRRT). Subsequent examples include a diffusion or filter membrane, such as a dialyzer, for example, for HD or HDF, a hemofilter, for example, for HF or the patient's peritoneum, for example, for PD. In addition, each of the systems described herein can be used in clinical or domestic configurations. For example, the systems can be used on an HD machine in the center, which runs virtually continuously throughout the day. Alternatively, the systems can be used in a domestic PD machine, which typically runs at night while the patient sleeps. A particularly suitable therapy for the modalities described herein is home hemodialysis (HHD'j in particular high convection domestic hemodialysis (HCHD).

Poster examples include a hoisted dial supply (replacement fluid), which may be multiple dialysate supply bags that are grouped and used one after the other. Alternatively, each of the systems shown below can be used with an in-line dialysate source, such as one or more concentrated pumps configured to combine one or more concentrates with water to form in-line dialysate. Online sources are commonly used with HD systems in the center for example. While the systems are described herein for use with dialysate, flexible foil cassettes and other apparatus with other medical fluids, such as saline, lactate, drugs and / or blood, are expressly contemplated for use.

Several flexible sheet cassettes are shown and described here.

Flexible sheet cassettes use a multitude of flexible sheets that are welded, heat sealed, adhered, chemically bonded, folded or otherwise formed together in desired locations to produce fluid flow paths, fluid heating paths, trajectories of peristaltic pump, volumetric pumping areas, balance chambers (equalized flow equalizers) and any combination thereof. The different sheets can be formed as separate sheets before joining them or be an individual sheet that bends one or more times to produce the different layers. The sheets provide an economical and easily produced alternative to known medical fluid pumping cassettes, which typically include a hard plastic component and one or more flexible sheets sealed to the hard plastic component.

However, it is expressly contemplated to provide a cassette where some components use a hard plastic member and others use flexible sheets only. For example, it may be advantageous to form the valves and certain paths using a hard plastic piece in combination with one or more flexible sheets and form the pumping portion (s), balance chamber (s) and / or heating fluid path It uses flexible sheets only. Certain modalities shown below combine flexible sheet cassettes with

one tubing, for example, tubing rings used in combination with a peristaltic pump roller. It is also expressly contemplated to provide a cassette where the flow paths, heating paths, pumping portion and volume control portion each is formed by using flexible foil, but which includes a rigid frame for ease of handling, loading, etc. .

In one embodiment a cassette is shown using two or three layers of laminate as needed to provide fluid paths, a peristaltic pump portion, a balance chamber portion, which are sealed together for and formed with connectors that connect to one or more supply bags, a drainage bag and a patient (as used here, patient ”generally refers to the peritoneum of a patient, a dialyzer, a hemofilter, an extracorporeal circuit and any combination thereof). In one implementation, a separate fluid heating path is provided and fluidly connected to the flexible sheet cassette through separate tubes.

In another embodiment, the fluid heating path is formed by using the same sheets that form other components of the dialysate fluid system, such as volumetric pump portions. The volumetric or membrane pumping portions pump a known volume of fluid with each pulse and therefore avoids the need for separate matching of flow equalizers or balance chambers.

Any of the flexible sheet cassettes described herein

two It can have one or more pumping portions. For example, flexible sheet cassettes can form multiple portions of peristaltic pumping in combination with multiple balance chambers, which operate to produce at least substantially stable flow of fresh and spent dialysate to the patient and drain, respectively. In another example, flexible sheet cassettes can form multiple volumetric or membrane pumping portions.

The flexible sheet membranes also incorporate a vent, which can be advantageously located just downstream of an integrated or separate heating path. This configuration allows air or gas generated through heating to be vented or released into the atmosphere. The ventilation for example can be located on the top of a vertically arranged cassette placed to allow automatic air purging. Or, the cassette will be mounted horizontally on the machine and operate with a valve, which opens when the air is detected. The system can ventilate / release gas / air to other parts of the disposable (such as a solution bag or drain lines), not just the atmosphere.

In one embodiment, flexible sheet cassettes include connectors that connect the tubes that guide fluid bags, the patient, a dialyzer, an extracorporeal circuit, etc. In one embodiment the connectors include a body, which can be rigid, and which is sealed between two of the flexible sheets. One or both of the

3 Flexible sheets may have a thermoformed flow path, which is sealed to the other flexible sheet to form a closed flow path that guides from the connector body to a desired destination within the flexible sheet cassette. An outer end of the connector body may include a compensated or reinforced end, which is configured to just seal a tube running from the cassette in flexible foil.

In one embodiment, one of the flexible sheets includes a substantially circular thermoformed path that leads to the inlet and outlet pump paths. A peristaltic pump roller or actuator operates with the substantially circular fluid path to form an integral peristaltic pumping portion of the flexible sheet cassette. As discussed above, one or more such pumping portions may be provided in any individual cassette. In this case, two modalities for using an individual roll to handle two different peristaltic pumping paths are described below. In one example, the flexible sheet cassette bends over a membrane, which causes two inwardly oriented peristaltic pump portions to operatively engage an individual peristaltic pump roller. In a second example, the peristaltic pump path is a semicircle as set to a substantially complete circle, where two of the semicircular flow paths operate with the same peristaltic pump roller, to handle two different fluids through two different paths. .

Multiple modalities for producing match flow equalizers or balance chambers using multiple flexible sheets are also described herein. In one implementation, three sheets are used to create upper and lower balance chamber compartments, primarily one between a top sheet and a middle sheet and the other compartment between the middle sheet and a bottom sheet. Each compartment may have individual or multiple fluid paths leading to and from such compartment. The pumping fluid in one compartment distributes a similar amount of fluid from the other compartment and vice versa. In one embodiment, each compartment includes two paths connected to this, where one path is an entry path to the compartment and the other path is an exit path from the compartment. In another implementation, only one individual trajectory communicates with each of the compartments, which causes the fluid entering and leaving each compartment to flow through the same individual trajectory.

In an alternative embodiment, two flexible sheets are formed with a rigid chamber, for example, of spherical plastic to form a balance chamber. Here, a compartment is formed between the rigid chamber and a flexible upper sheet. The second compartment is formed between the two flexible sheets. A rigid plate or backrest adjoins the lower flexible sheet, which causes the upper flexible sheet to only have one direction in which to move when the lower compartment is filled. When the lower compartment is filled the upper flexible sheet is moved upward towards an inner wall of the rigid chamber to distribute fluid from the upper compartment. Then the fluid is filled in the upper compartment, pushing the upper sheet down towards the lower sheet to distribute fluid from the lower compartment.

Even in another alternative balance chamber mode, a plurality of flexible sheets is formed with a plurality of balance chamber tubes to form the balance chamber. The tubes act as fluid inlets and fluid outlets, which are formed alternately through thermoforming of one or both flexible sheets. Again, each balance chamber compartment can include a single inlet / outlet tube or multiple dedicated inlet / outlet tubes to produce an individual fluid inlet / outlet or separate fluid inlet / outlet.

Balance chambers are described here generally operating with pumps, such as peristaltic pumps. In an alternative mode described below, the balance chamber is placed within a magnetic field. Here, the membrane (for example, inner membrane) of the balance chamber that was driven back and forth within the chamber is administered or otherwise coupled with a ferromagnetic material. For example, a thin carbon layer can be sandwiched between flexible outer layers of medical grade air-insert material. The magnetic field is modulated or polarized to move the impregnated membrane. A controller inside the dialysis unit energizes the electromagnetic located on either side of the balance chamber sequentially to remove the magnificent inner membrane on one side of the chamber and then the other, by dispersing and withdrawing the fluid with each press half. In this way, the balance chamber (or double balance chambers) is self-managed as opposed to being handled by a separate pump, which eliminates the need for the second pump. As described below, balance chamber systems sometimes use an ultrafiltration (UF) meter, which is also typically handled passively or non-automatically. The UF meter can also be operated superbly as described here. Alternatively, a of the magnetically managed balance chambers leads to the UF meter, as discussed further below, the volumetric pumps can also be modified to handle magnetically.

As shown below, a volumetric or integrated diaphragm pump can be formed by using two flexible blades and upper and lower chambers defined by the machine on which the cassette is loaded. The machine is configured to pull a vacuum in each of the separate sheets to pull the sheets towards the chamber wall and to provide positive pressure to push the sheet towards the opposite chamber wall as

7 need to remove or push the fluid. A fluid path inside and a fluid path outside communicate fluidly in the space between the flexible sheets.

The inlet and outlet paths are regulated to allow fluid to enter the volumetric pump chamber in one step to be removed from the volumetric pump chamber in a second step. As shown below, to enter fluid into the volumetric pump chamber, the positive pressure is removed and the negative pressure is applied to the outer surface of one of the flexible sheets to be removed from the other flexible sheet (which is under negative pressure from the other side of the chamber) towards its source of vacuum, which causes the pumping chamber between the sheets to open, which creates a vacuum and with which the fluid enters the chamber. Then, the positive pressure is applied to the sheets, which pushes the closed and fluid flexible membranes out of the pump outlet path.

Multiple modalities for forming an integrated fluid heating path are discussed here. The path can be a thermoformed path in a sheet that joins a second sheet. In another embodiment, three sheets are used, where the upper and lower paths are formed with a flat half sheet. In any of the embodiments described herein, the middle sheet includes one or more openings to allow fluid, for example, to travel from a higher fluid heating path to a fluid heating path.

8 lower. Or with respect to the balance chambers, an opening in the middle flexible membrane allows the fluid leaving a compartment (upper or lower) to be combined with fluid leaving the other compartment in an individual flow path.

Several embodiments are described herein to selectively form the seals between two of three limiting sheets and to seal three sheets together. For example, a curable adhesive pattern can be provided on one or more sides of the middle sheet to allow one or more outer sheets to selectively adhere and seal to it. Alternatively, the energy provided by a heating side may vary so that the heat generated by the die is set to seal only two of three sheets together or to seal the three sheets together.

As discussed above, any of the flexible sheet cassettes may include a rigid component, which for example may include flow paths, valve seats, portions of rigid balance chamber, etc. As shown below, that rigid portion can be made to communicate with the all flexible portion, which forms the remaining components of the cassette.

As discussed above, the peristaltic pumping portions may alternatively be tubes that fluidly connect to a flexible sheet cassette, which may include a heater flow path, balance chamber portion (s) and associated flow paths and seats. valve.

In one embodiment a flexible sheet cassette is provided for the dialysate portion of an HD, HF or HDF system, where a second blood cassette is provided. Both cassettes are loaded on the same machine in one mode. Alternatively, the blood and dialysate portions of an HD, HF or HDF system can be formed in the same cassette.

Therefore it is an advantage of the present description to provide improved dialysis systems.

It is another advantage of the present description to provide improved dialysis cassettes.

It is an additional advantage of the present description to provide improved home dialysis therapies.

It is even another advantage of the present description to incorporate peristaltic pumping portions in a cassette formed of multiple flexible sheets.

It is even a further advantage of the present description to incorporate membrane or volumetric pumping portions in a cassette formed of multiple flexible sheets.

It is a further advantage of the present description to provide multiple ways to form fluid paths in two or three flexible limiting membranes.

It is even another advantage of the present description to incorporate balancing chamber portions in a cassette formed of multiple flexible sheets.

It is even an additional advantage of the present disclosure to provide a relatively low cost flexible sheet cassette.

In addition, it is an advantage of the present disclosure to provide methods for selectively sealing two of three limiting sheets or three of three limiting sheets together, for example.

Even additionally, it is an advantage of the present description to provide a magnetically operated volumetric balancing or pumping device.

Additional features and advantages of the present description will be apparent from the following detailed description of the invention and the figures.

BRIEF DESCRIPTION OF THE FIGURES

Figure 1 is a schematic view of one embodiment of a cassette-based dialysis system employing a flexible sheet cassette having a peristaltic pumping portion, a volumetric control portion of an individual balance chamber and an external heater bag.

Figure 2 is a schematic view of one embodiment of a cassette-based dialysis system employing a flexible sheet cassette having a volumetric or membrane pumping portion and an in-line heating portion.

Figure 3 shows a schematic view of an embodiment of a cassette-based dialysis system that employs a flexible foil cassette that has double peristaltic pumping portions, double balance chamber portions and an external heater bag.

Figure 4 is a split perspective view of Detail IV shown in Figure 1, which highlights an embodiment of an input / output connector portion of the flexible sheet cassettes.

Figure 5 is a split perspective view of Detail V shown in Figure 1, which highlights an embodiment of a peristaltic portion for flexible sheet cassettes.

Figure 6 is a split perspective view of Detail VI shown in Figure 1, which highlights an embodiment of a balance chamber portion for flexible sheet cassettes.

Figure 7 is a split elevation view taken along line VII-VII of Figure 6, illustrating the balance chamber portion of the flexible sheet cassette in operation with a dialysis machine.

Figure 8 is a split view taken along the line VIll-VI 11 of Figure 6, showing upper and lower fluid paths leading to the balance chamber portion of the flexible sheet cassette shown in Figure 6 .

Figures 9A to 9C are split elevation views of Detail IX shown in Figure 2, illustrating different valve states of a pump cycle for a volumetric pump that operates when using flexible sheet cassettes.

Figure 10A is a split perspective view of Detail X shown in Figure 2, which highlights an embodiment of an in-line heater portion of the flexible sheet cassettes.

Figure 10B is a split elevation view of a double level in-line heater portion in operation with a dialysate fluid heater.

Figure 11 is a perspective view of Detail XI shown in Figure 2, illustrating an embodiment of an in-line air vent portion for flexible sheet cassettes.

Figure 12A is a split elevation view illustrating an embodiment for configuring an individual peristaltic pump actuator to handle fluid through two different flow paths of the flexible sheet cassettes.

Figure 12B is a flat view illustrating another embodiment for configuring an individual peristaltic pump actuator to handle fluid through two different flow paths of the flexible sheet cassettes.

Figure 13 is a split perspective view illustrating one embodiment of flexible sheet cassettes that employ a pressure sensing area (or other parameter) in combination with a pressure sensor (or other parameter).

Figure 14 is a perspective view of the flexible sheet cassettes showing a method and resulting in an apparatus for selectively sealing three flexible sheets together.

Figure 15 is a perspective view of an illustrative flexible sheet cassette showing a second method and resulting in apparatus for selectively sealing three flexible sheets together.

Figure 16 is an elevation view of a portion of a flexible sheet cassette illustrating a third method of selectively sealing three flexible sheets together.

Figure 17 is a perspective view of an embodiment for a total cassette that combines trajectory forming flexible sheets with a rigid cassette portion.

Figure 18 illustrates an embodiment for configuring a cassette having a flexible sheet portion and a rigid portion with corresponding valve drive, pump drive and heater.

Figure 19A and 19B are split elevation views showing another modality for a balance chamber portion that uses two flexible sheets in combination with a rigid plastic dome component.

Figures 20A to 20B are perspective views at various manufacturing stages of an additional alternative embodiment of a balance chamber portion produced through multiple flexible sheets.

Figures 21A to 21G are several views of a system employing a flexible foil dialyzer cassette in combination with a separate blood side cassette.

Figures 22A to 22D are perspective views of an additional alternative system employing a flexible sheet dialysate cassette in combination with a separate blood side cassette.

Figure 23 is a perspective view of even another alternative medical fluid cassette for use with a system employing a gravimetric volume control methodology.

Figures 24A and 24B are perspective views of an alternative flexible foil cassette system where the machine includes clamping members that comprehensively form pump, flow and fluid heating paths.

Figure 25A is a schematic view of a fluid heating path formed through comprehensive clamping and an operable fluid heater with the compressed fluid heating path.

Figure 25B is a perspective view of a separate heater bag with a fluid heating path formed through mechanical compression and a separate heater for the heater bag.

Figures 26A and 26B show a balance chamber portion of the disposable cassette formed through mechanical clamping and also illustrate a magnetic field that is used to handle the balance chamber.

Figure 27 illustrates a balance tube or balance piston driven by a magnetic field.

Figure 28 illustrates a volumetric pump driven by a magnetic field.

DETAILED DESCRIPTION

The examples described herein are applicable to any medical fluid therapy system (such as dialysate, replacement fluid and blood) that requires a disposable fluid pump cassette. The systems are particularly well suited for the control of kidney failure therapies, such as all forms of hemodialysis (HD) that include (HHD), hemofiltration (HF), hemodiafiltration (HDF), peritoneal dialysis (PD, which includes dialysis continuous transient peritoneal (CAPD), automated peritoneal dialysis (APD), tidal flow APD and continuous flow peritoneal dialysis (CFDP) modalities. The schemes can also be used in any type of continuous renal replacement therapy (CRRT).

Later examples include a diffusion or filter membrane, such as a dialyzer, for example, for HD or HDF, a hemofilter, for example, for HF or a peritoneum, for example, for PD. Certain examples show a cassette with an individual patient input and output, for example, for CAPD or group type APD. The dialysate in CAPD and APD is typically supplied to the patient, allowed for permanence for a period, and then pulled from the patient and discarded into the drain. Those cycles are then repeated a number of times. The lines to and from the patient are connected in T together and are properly regulated, for example, so that the dialysate can be supplied and removed at different times through the same individual line and connection to and from the patient.

Other systems include a dialysate input and a dialysate output, for example, for a dialyzer or hemofilter used with HD, HDF or HF. The systems can also each be modified for use with a single or double catheter as the case may be. CFPD typically uses a double lumen catheter and thus also requires separate inputs and outputs.

In addition, each of the cassette-based systems described herein can be used in clinical or domestic configurations. For example, the systems can be used in a center HD machine, which runs virtually continuously throughout the day. Alternatively, the systems can be used in a domestic PD machine, which typically runs at night while the patient sleeps. Domestic hemodialysis machines ("HHD) (which include domestic hemodialysis of convection can (" HCHD ")) are also of a preferred type of therapy machine for use with the modalities described herein.

Later examples include a supply of dialysate (or replacement fluid), which for convenience is shown as multiple bags of fluid. Alternatively, an individual dialysate supply bag is used. Alternatively, each of the systems shown below can be used with an in-line dialysate or replacement fluid source, such as one or more concentrate pumps configured to combine one or more concentrates with water to form in-line dialysate. For example, online sources with HD systems are commonly used.

Each of the systems here operates with a heater that heats the dialysate or replacement fluid to a desired temperature. The heaters can be in-line heaters located upstream or downstream of the fresh supply pump. The systems may alternatively operate with a group type heater and / or a heater located upstream of the pump.

The systems also include a cassette with an in-line air removal device (for example, hydrophobic ventilation). Alternatively, a group type air removal device, such as an air trap is used. The air removal device can be located at or near the heating path to capture air that left the solution due to heating.

The flow semantics shown here mainly involve the dialysate or replacement fluid portion of the kidney failure machine. The HD, HF and HDF machines also include blood pumping systems. Several examples of blood cassettes are also discussed later.

HD, HF and HDF also include dialysate ratio systems, mentioned above, which are also known and need not be described here. US Patent No. 5,247,434 (the '434 Patent), assigned to the agent of the present application, the complete contents of which are expressly incorporated herein by reference, describes an example of a suitable proportion system.

Referring now to the figures and in particular to Figure 1, one embodiment of a system using a flexible sheet cassette 10a is illustrated by system 10. System 100a is advantageous in one aspect because it employs a peristaltic pump 30 in combination with a volumetric balance device or balance chamber. Peristaltic pumps, such as a 3 0 pump, are typically used to pump clean or sterile fluids, such as dialysate or replacement fluid, because the pump hardware does not contact and thereby contaminates the fluid. The only part of the pump in contact with the dialysate / replacement fluid is the peristaltic pump path or tube segments, which are sterilized before therapy. Also, because peristaltic pumps include non-mobile pumps in contact with the dialysate / replacement fluid, the pumps are relatively cheap. Peristaltic pumps also lack the valves, seals and glands used in other types of pumps, which makes the pump 30 for example, comparatively cheap and easy to maintain.

The volumetric balance of the system 100a uses first and second chambers of substantially equal volume in one mode. Each chamber includes two compartments, one called a pre-dialyzer compartment and the other a post-dialyzer compartment. Each pre and post opposite compartment of a chamber is separated by a flexible diaphragm. Solenoid operated valves control the filling and emptying of each compartment. In general, each compartment is completely filled before its contents are downloaded. Also, the pre compartments are filled alternately and threads post compartments are filled and discharged alternately. Filling a pre-compartment causes a discharge of a corresponding and opposite post compartment, respectively. Filling a post compartment causes a discharge of a corresponding and opposite post compartment.

Since the opposite pre and post compartment volumes of the two chambers are equal, the system volumetrically balances the flow of dialysate to and from the dialyzer. A benefit of this volumetrically controlled system is that the dialysate flow to the dialyzer can be measured accurately in a wide variety of flow rates.

System 100a includes a plurality of supply bags 12a to 12c. The dialysate supply to system 100a is alternatively any of the systems described above, such as an online supply. System 100a also includes an initial drainage bag 14 in the illustrated mode. With PD for example, the patient's peritoneum is full of dialysate spent at the beginning of therapy. That spent dialysate is from a last filling of the previous night therapy. The first step in the PD treatment is therefore to drain the spent dialysate into the drainage bag 14. After that, the supply dialysate is pumped from the supply bags 12a to 12c through the cassette 10a towards the patient ( as used herein, patient refers to a dialyzer, an extracorporeal circuit, a patient peritoneum or a combination thereof depending on the therapy involved). 5 'Those supply bags can then be double as drainage bags in different treatment cycles, for example, after the dialysate was left inside the patient's peritoneum for a designated amount of time and after that it is pumped back through from the cassette to the drainage bag. For example, the dialysate 10 may initially be pumped from the supply bag 12a, through the cassette 10a, to the patient. After a prescribed period of permanence, the spent dialysate is then pumped from the patient, through the cassette 10a to the bag 12a, which is now a drainage bag. After that, the system 100a in a subsequent cycle pumps fresh dialysate from the supply bag 12b to the patient, and so on.

Supply bags 12a to 12c are fluidly connected to supply connectors 16a to 16c through supply tubes 18a to 18c, respectively. The supply connectors 16a to 16c 20 are connected in a sealed manner to the flexible sheet cassette 10a as illustrated in more detail later in connection with Figure 4. The drain bag 14 is fluidly connected to the drain connector 22 through the drain line 24. The drain connector 22 is connected in a sealed manner to the flexible sheet cassette 10a in the same way that the supply connectors 16a to 16c are connected in a sealed manner to the flexible sheet cassette 10a as shown in more detail later in connection with Figure 4.

Flexible sheet cassette 10a defines or includes flow paths 26a to 26d that allow fluid flowing through lines or tubes 18a to 18c and 24 to communicate fluidly with a peristaltic pump portion 30, whose flexible sheet cassette 1Oa also defines or includes. The peristaltic pump portion 30 is shown in more detail later in connection with Figure 4. The peristaltic pump portion 30 operates with a peristaltic pump actuator located in the dialysis machine. Each of the flow paths 26a to 26d defined by the flexible sheet cassette 10a includes or defines a valve contact portion 28a to 28d, respectively. The flow paths 26a to 26d and respective valve contact portions 28a to 28d were shown in more detail later in connection with Figure 4.

In the system 100a, the fluid from one of the supply bags 12a to 12d is pumped through the peristaltic pump portion 30, through a pump outlet path 32, through a path to the heater 34a, through a connector to the heater 36a, through a tube to the external heater 38a, and finally to an external in-line heater 40, which includes a fluid heating path 42a. The connectors to and from the heater 36a and 36b were sealed to the flexible sheet cassette 10a in the same way in an embodiment such as the connectors 16a to 16c and 22 shown in detail later in connection with Figure 4.

The external heater bag 40 defines a fluid heating path in serpentine 42a, through which the fluid or dialysate travels. While the fluid or dialysate travels through the fluid heating path 42a, a plate, converted, radiant, inductive or other type of heater is used alone or in combination to heat the fluid. The heater that heats the fluid flowing through the heating path 42a can be located external to the dialysis machine that houses flexible sheet cassette 10a or can be integrated into such a machine. As seen in Figure 2, a fluid heating path 42b is alternatively integrated into a flexible sheet cassette 10b. An example of a fluid heating path is shown in more detail later in connection with Figure 10A. Figure 10B shows a two-sided fluid heating path that operates with a fluid heater.

The dialysate fluid flows from the in-line heater 40, through a line or tube from the heater 38b, through a connector from the heater 36b of the cassette 10a, through a path from the heater 34b defined by the flexible sheet cassette 10a, and towards the volumetric control portion of the cassette and 10a, which was described in more detail below. The paths to and from the heating 34a and 34b each define or include a valve contact portion 28e and 28f, respectively. Examples of valve contact portions are shown in more detail below by valve contact portions 28a to 28d of Figure 4.

It should be appreciated that the valve contact portions 28e and 28f open when fluid is pumped to the patient, so that such fluid or dialysate can be heated. When fluid is removed from the patient and pumped to the drain, the associated valve actuators close lines 34a and 34b and the valve contact portions 28e and 28f. In the drain cycle, a valve actuator operates with a valve contact portion 28g defined by or included in the pump outlet path 32 to open the path 32. In this way, the heater and associated path and lines are avoided during sewer system.

The materials used for supply bag 12a to 12c and drainage bag 14 may be any suitable medical grade material, such as polyvinyl chloride ("PVC), etc., single layer PVC films, single layer PVC films non-DEHP, multi-layer non-PVC films (where different layers are chosen to provide strength, weldability, abrasion resistance, and minimal adhesion to other materials such as rigid cassette materials), polypropylene / polyethylene mixture, polypropylene mixture or Kraton, coextruded or laminated, with or without gas barrier, polyester, polyolefin, ULDPE. The materials used for external lines or tubes 18a to 18c, 24, 38a and 38b may be of any suitable medical grade tubing material, such as PVC, non-DEHP PVC, polybutadiene (PB), ethylene vinyl acetate (EVA), Polypropylene (PP) mixture, polyethylene (PE) mixture, Kraton mixture and polyolefin mixture. Materials used for external fluid heater bag 40 that include fluid path 42a include PVC, PP / Kraton mix.

The dialysis unit or machine (examples shown below in connection with Figures 21G and 22A) operating with flexible membrane cassette 10a includes an apparatus configured to detect air in the dialysate flow path. A highly suitable place to detect air or other gas bubbles in the system is at a point in the flow path just downstream of the fluid heater 40. The heat of the heater causes the air or other gas to escape from the solution. Accordingly, an air detection sensor is positioned to operate with trajectory from heater 34b in one mode. Suitable air directors were described in the patent application of the present description.

Cassette valve actuators 10a with valve contact portions 28h and 28i allow the dialysate to be desirably direct and alternatively to an in-line vent 44 or a volumetric balance device or balance chamber 50. If the air was detected in the system, the valve actuator that operates with the valve contact portion 28i closes, while the valve actuator that operates with a valve contact portion 28h opens, allowing the fluid reach ventilation 44, so that any air trained in the fluid can escape from the system 100a. An embodiment for ventilation 44 is shown in more detail later in connection with Figure 11. Once air is purged from the flexible sheet 10a, the valve actuator operating with the valve contact portion 28h closes, while the valve actuator operating in combination with the valve contact portion 28i opens, so which allows the purged dialysate to flow to the balance chamber 50.

In an alternative embodiment, the cassette 10a is mounted vertically on the ventilated machine 44 located in the upper part of the mounted cassette, so that any air in the path from the heater 34b automatically escapes from the ventilation 44. Here, the separate valve actuators and valve seats 28h and 2 8 i are not needed. Furthermore, if the vent 44 is pointed upwards, the separate valve actuators and valve seats 28h and 28i are not necessary even if the cassette 10a is mounted horizontally on the machine.

In an alternative embodiment, the air in the flexible sheet cassette 10a is pumped to the heater bag 40 or to the drain bag 14. For example, air can be allowed to be collected at the top of the heater bag 40, which It lies horizontally on a heater plate in one implementation. If the air was detected downstream of the heater bag 40, appropriate valve seats 28 are changed so that the fluid is pumped to the drain until no more air is detected.

The balance chamber 50 of the flexible sheet cassette 10a (and other components discussed herein) includes three flexible folds or sheets in one embodiment. One embodiment of the balance chamber 50 is subsequently shown in connection with Figures 6 to 8, which will be discussed. in more detail later. The three folds are sealed in a circular distribution 52 in an embodiment to form upper and lower fluid compartments 54a and 54b (best seen in Figure 7). The fluid pumping through the pump outlet paths 32 eventually flows through the balance chamber input paths 56a or 56b as determined selectively by valve actuators operating with valve contact portions 28j or 28k, respectively. . In the mode illustrated in connection with Figures 6 to 8, the balance chamber input path 56a is in fluid communication with the upper compartment 54a of the balance chamber 50, while the balance chamber input path 56b is in fluid communication with the lower balance chamber compartment 54b. As described in more detail below, the fluid flows from the compartments 54a and 54b, through the balancing chamber output paths 58a and 58b as determined selectively by actuators operating with valve contact portions 28I and 28m, respectively.

A fluid flowing through the balance chamber exit paths 58a or 58b flows in a path to the patient 60a as seen in Figure 1. Figures 6 and 8 show a modality for how the fluid flowing through of the separate balance chamber output paths 58a and 58b eventually connect in T together on a path to the individual patient 60a.

The illustrated system 100a of Figure 1 can be used with APD, tidal flow PD, or CAPD, for example, which typically uses an individual connection to the patient for group-type fill and drain cycles. In such a case, the path to the patient 60a also serves as a path from the patient that communicates with the connector 62a. To perform a drain cycle, the connector 62a becomes a connector from the patient, trajectory towards the patient 60a becomes a trajectory from the patient, exit paths 58a and 58b to balance chamber compartments become inputs, and the inputs previously described 56a and 56b in the balance chamber compartments become balance chamber outputs. The peristaltic pump opening with peristaltic pump portion 30 of cassette 10a runs in reverse, which pulls dialysate extracted from the patient's peritoneum, through the balance chamber 50 and associated paths and thereafter pushes the spent dialysate toward a drainage bag, household drainage or other appropriate drainage.

However, it is possible to use system 100a in a hemodialysis treatment, which typically includes a dialyzer having a dialysate inlet and a dialysate outlet (not illustrated). Or the system 100a can also be used with a PD system that employs a double lumen catheter. Here, a path from the separated patient 60b is connected at T in the path to the patient 60a. A connector from the separated patient 62b is provided and placed in fluid communication with the path from the patient 60b. The connectors 62a and 62b are fixed to the flexible sheet cassette 10a through the same apparatus and technique shown for example with connectors 16a to 16c and 22 in Figure 4. The valve actuators are configured to operate with valve contact portions 2 8n and 28o to selectively allow fluid to flow out of the connector to the patient 62a or through the connector from the patient 62b, respectively. To pump fluid out of! cassette 10a towards the patient or dialyzer, the valve actuator operating with the valve contact portion 28o closes, while the valve actuator operating with the valve contact portion 28n opens. To pump fluid into cassette 28a, the valve actuator that operates with the valve contact potion 28n closes, while the valve actuator that operates with the contact portion 28o opens.

If a single connector 62a is provided or double connectors 62a and 62b are provided, the system 100a is configured to pump fluid to and from a dialyzer using a desired sequence of pump pulsations to dialyzer and pump pulsations from dialyzer. For example, a peristaltic pump that operates with a peristaltic pump portion 30 can operate in a pump direction to hit the balance chamber 50 ten times, each time it supplies a known volume of fluid connector out 62a to the dialyzer. After that, the peristaltic pump is invested for a period of time, for example, causing 12 balance chamber pulses 50 that occur, each time a known amount of dialysate fluid is drawn through the connector 62b, through the cassette 10a towards one of the drainage bags. The additional number of pulsations that fluid is withdrawn from the dialyzer constitutes an amount of ultrafiltrate removed from the patient. Alternatively, the balance chamber 50 is conducted magnetically as described later in connection with Figures 26A and 26B.

It should be appreciated that the system 100a can also be used to perform hemofiltration. Here, the connector to the patient 62a is connected to the extracorporeal circuit directly, so that the replacement fluid of undetectable quality can be introduced upstream or downstream (or both) from the hemofilter. The hemofilter port is connected to the port from the patient 62b in a double port configuration or to an individual port 62a, where the described sequential pulse mode is used in any case. In a similar matter, hemodiafiltration can be performed, where the line connected to the connector towards the patient 62a is connected to both the extracorporeal circuit directly and an inlet of the dialyzer. Again, the dialyzer output in HDF can be connected to the port from the patient 62b or the individual port 62a depending on the configuration of the cassette 10a used.

Referring now to Figure 2, an alternative system 100b employs an alternative flexible sheet cassette 10b. System 100b includes many of the same components that system 100a includes. For example, system 100b includes supply containers 12a to 12c and drain container 14. As before, the supply containers 12a to 12c are fluidly connected to the cassette 10b through supply connectors 16a to 16c through supply lines 18a to 18c, respectively. Also, the drain bag 14 is fluidly connected to the drain connector 22 through the drain line 24. The connectors 16a to 16c and 22 are each connected to flow paths 26a to 26d, wherein each of the flow paths has a valve contact portion 28a to 28d, respectively. The flow paths 26a to 26d are all fed into a pump input manifold path 64a.

A primary difference between system 100b and system 100a is that system 100b uses volumetric or membrane pumps instead of peristaltic pumps. Here, an input manifold path 64a communicates fluidly with the pump input paths 66a and 66b, each fluidly leading to a respective volumetric or membrane pump portion 70a and 70b. Valve actuators that operate with valve contact portions 28p and 28q allow fluid to be selectively pumped through the volumetric pump portion 70a or 70b as desired. The volumetric pump portions 70a and 70b operate with a

one Pneumatic and / or mechanical pump actuator located inside the dialysis machine as described in more detail below in connection with Figures 9A to 9C. Alternatively, the volumetric pump portions are magnetically actuated as shown below in connection with Figure 28.

In Figure 2, the pump outlet paths 68a and 68b extend from the outer side of pump portions 70a and 70b, respectively, and are fed into a pump outlet manifold path 64b. The fluid leaves the pump outlet manifold path 64b which then enters an alternative integral line fluid heating path 42b. The integral fluid heating path, in line 42b is shown in more detail operating with a fluid heater in connection with Figure 10A. Any air that escapes dialysate or other medical fluid (including blood) during heating within the fluid heating path 42b can be selectively removed from the system through in-line ventilation 44. An embodiment for ventilation 44 is shown in detail later in connection with Figure 11. The air is alternately pumped to drain or leave fluid heating path 42b. The cassette 10b can be mounted on a machine vertically with the vent 44 pointing up to allow air to escape from the cassette 10b automatically and without valve actuator and valve seat 28h for such actuator. In addition, the vent 44 can be pointed upwards when the cassette 10b is loaded so that the valve actuator and the valve seat 28h can be removed even if the cassette 10b was located horizontally.

If no air is detected, the heated dialysate through the valve actuators operating with contact portions 28¡ and 28h is allowed to pump the patient (dialyzer or hemofilter, etc.) through the connector to the patient 62a. As described above with system 100a, system 100b may alternatively include a connector from patient 62b (not illustrated here). In any configuration, the system 100b can perform sequential HD (which includes HHD), HF or HDF as described above.

In the illustrated configuration of system 100, flexible sheet cassette 10b is configured to perform PDs, such as CAPD, tidal flow PDs and APD. Here, as described above, after the dialysate was allowed to remain within the peritoneum of the patient for a prescribed type period, the connector to the patient 62a becomes a connector from the patient, which receives spent dialysate from the patient. In the illustrated embodiment, the spent fluid is extracted through the fluid heating path 42b through pumps 70a and 70b, which push the spent dialysate into a suitable drainage bag or drain. In an alternative embodiment (not illustrated), the cassette 10b provides a suitable diverting path and corresponding valve contact portions that allow spent fluid to return to the diverting fluid heating path 42b.

As shown, a primary difference between system 10Ob and system 100a is the incorporation of the path of heating fluid 42b in the flexible sheet cassette 10b. Here, the corresponding heater is placed in the same machine housing as the pump actuator and the valve actuators. As described above, the separate in-line heater bag 40 of system 100a may alternatively operate with a heater housed in the same unit as the pump and valve actuators of system 100a or with a heater provided separately from the pump and the valve actuator unit. It should be appreciated that the integrated, in-line path 42b of system 100b can be used with the peristaltic pump portion 30 and / or balance chamber 50 of system 100a of Figure 1. In addition, the separate heater bag 40 of system 100a can used alternatively with volumetric pump portions 70a and 70b of Figure 2.

As discussed, a primary difference between system 100b and system 100a is the use of diaphragm volumetric pump portions 70a and 70b as opposed to peristaltic type pumps previously used for system 100a. Volumetric pump actuators that operate with portions 70a and 70b pump a known amount of dialysate volume with each pump pulse. The total volume pumped by membrane volumetric pump portions 70a and 70b is determined by counting the number of pump pulses. The advantage here is that a separate volumetric control apparatus, such as a balance chamber 50, is not needed. Two pump actuators operate out of phase with portions 70a and 70b to produce at least substantially continuous flow of dialysate to and from the patient.

All the materials described above for system 100a are also applicable to similar components of system 100b. In operation, one of the supply valves 28a to 28c is opened to allow fresh dialysate to flow from one of the supply bags 12a to 12c in one of the pump portions 70a and 70b, through a respective supply path 26a, 26b or 26c. The pumping fluid flows through manifold 64a, through the inlet path 65a or 66b in the pump portion 70a or 70b, respectively. The fluid then flows through the respective exit path 68a or 68b, through the outlet manifold 64b, through the heating path 42b where it is heated, through the fluid connector to the patient 62a in the patient .

The volumetric pump portions 70a and 70d can pump fluid to or from the patient by using different valve sequence. For example, to pump fluid to the patient, the pump through the portion 70a and to extract fluid in the pump portion 70a the valve actuator operable with the valve contact portion 28p opens, while in the valve actuator operable with the valve contact portion 28r closes.

Then, the valves change to pump the volume out of the portion 70a, through the heating path 42b to the patient. To run in reverse, for example, drain the patient, the valve states described above are reversed to extract spent fluid in the pump portion 70a and then to pump the spent fluid from the pump portion 70a to a suitable drain.

Referring now to Figure 3, a system 100c using a third flexible sheet cassette 10c is illustrated. System 100c is similar to system 100a of Figure 1 and includes many of the same components, such as supply bags 12a to 12c, drain bag 14, supply connectors 16a to 16c, drain connector 22, and lines 18a to 18c connecting the supply bags to input connectors 16a to 16c, respectively. The system 100c also includes a line 24 that leads from the drain connector 22 to the drain bag 14. The flexible sheet cassette 10c includes the same valve contact portions 28a to 28h as discussed above for the system 100a. System 100c operates with a separate heater bag 40 that has a fluid heating path 42a coupled to heater lines 38a and 38b and connectors 36a and 36b. Ventilation operation 44 is as described above. The air is pumped alternately to the drain bag 14 or left in the heater bag 40.

A primary difference between the system 100c and the system 100a is that it uses two operable separate peristaltic pump actuators with a separate peristaltic pumping portion 30a and 30b. The configuration illustrated for the pumping portions is upstream of the fresh and worn inlets of the 50a and 50b double balance chambers. This configuration allows simultaneous pumping, in two directions as discussed later.

The 100c system provides 50a and 50b double balance cameras. As noted, each balance chamber 50a and 50e operates with balance chamber input paths 56a and 56b and balance chamber output paths 58a and 58b. Each of these paths includes a respective valve contact portion 28j, 28k, 28I or 28m, respectively

Simultaneous two-way pumping requires a path to patient 60a fluidly connected to a connector to patient 62a and a path from patient 60b fluidly connected to a connector from patient 62b. The trajectory from the patient 60b is fluidly connected to the spent pump portion 30b and to balance balance chamber input paths 56a leading to balance chambers 50a and 50b. Thus the balance chamber inlet paths 56a are spent fluid inlets and the spent fluid is driven by a pump actuator that operates with peristaltic pump portion 30b.

The fluid inlet paths 56b on the other hand are fluidly connected to the pump outlet path 32 leading from the supply pump portion 30a. Thus, the balance chamber inlet paths 56b are fresh fluid inlets that receive fresh fluid driven by a pump actuator that operates with peristaltic pump portion 30a. As shown below however, the balance chambers 50a and 50b operate as secondary pumps, which accept a volume of fresh or spent fluid from the fresh supply pumping portion 30a or from the spent supply pumping portion 30b, respectively, and expel a similar amount of spent or fresh fluid, respectively.

On the exit side of the balance chambers 50a and 50b, the path to the patient 60a is fluidly connected to the exit paths 58b. This total path allows fresh fluid to be supplied from the balance chambers 60 (collectively referring to balance chambers 50a and 50b) to a dialyzer, extracorporeal circuit or other peritoneum of the patient depending on the therapy being used. The exit paths 58a are fluidly connected to the drain path 26d, which is fed to the drain bag 14 or one of the supply bags 12 that acts as a drain bag, as determined by valve contact portions of 28d, 28u, 28v and 28w drain. Alternatively, the drain 14 is adjusted to hold the volumes of each of the supply bags 12a to 12c, which eliminates contact portions 28u to 28w and simplifies drain path 26d.

In operation, the system 100c can simultaneously supply and remove fluid to and from the patient. To do that, in a medium cycle, for example, the valve actuators that operate with seats 28k and 28I of the balance chamber 50a and valve seats 28j and 28m of the balance chamber 50b are in an open valve state, while the valve actuators operating with valve seats 28 and 28m of the balance chamber 50a and valve seats 28k and 28I of the balance chamber 50b are in a closed valve state. This configuration allows the pump portion 30a to supply a volume of fresh solution through inlet path 56b in the balance chamber 50a, which in turn forces a similar volume previously supplied of spent solution to leave the balance chamber 50a, through the exit path 58a, drain path 26d, to drain 14 or one of the supply bags 12a or 12b that acts as a drain bag. Simultaneously, the pump portion 30b supplies a volume of solution spent through the input path 56a in the balance chamber 50b, which in turn forces a similar volume previously supplied with fresh solution to leave the balance chambers 50b, through the exit 58b and the line towards the patient 60a towards the patient.

Then, in a second half cycle, the valve seats 28k and 28I of the balance chamber 50a and valve seats 28j and 28m of the balance chamber 50b are closed, while the valve seats 28j and 28m of the balance chamber 50a and valve seats 28k and 28I of the balance chamber 50b open. This configuration allows the pump portion 30a to supply a volume of fresh solution through the inlet path 56b in the balance chamber 50b, which in turn forces a similar volume previously supplied of spent solution to leave the balance chamber 50b , through the exit path 58a and drain path 56b, for drainage or one of the supply bags 12a or 12b. Simultaneously, the pump portion 30b supplies a volume of solution spent through the line from the patient 60b and the inlet path 58a in the balance chamber 50a, which in turn forces a similar volume previously supplied with fresh dialysate from the balance chamber 50a through the exit path 58b, line towards patient 60a and towards him patient.

As shown and described, the balance chambers 50a and 50b ensure that a similar volume of fresh and spent dialysate is supplied to and removed from the patient in each half cycle. The 100c system can remove excess or ultrafiltered fluid in a number of ways. In one embodiment, both balance chambers 50a and 50b are filled with spent fluid. Then, the valve contact portions 28I, 28k and 28n open and the pump actuator operating with the pump portion 30a runs in reverse, which draws fluid from the patient through the line to the patient 62a in the reverse direction. This action causes the spent fluid to be expelled from the drain path 26d to a drain through the spent fluid extracted in the pump portion 30a. Now, both fresh compartments of balance chambers 50 are filled with spent fluid and the pump portion 30b causes the spent fluid again to fill both spent chamber compartments 50a and 5Ob with spent fluid. This causes a supply of spent fluid from both fresh chamber compartments 50 to the patient. A loss of net fluid occurs because this volume comes from the patient instead of the source. Alternatively, a regulated bypass line is provided (not illustrated) that leads from the lines to the patient 60a to the drain path 26d, so that the spent fluid is alternatively sent to a drain. The regulated diversion line increases the efficiency of a UF but adds extra values ​​and flow paths. However, the valve sequence described above is repeated as necessary to remove a necessary amount of ultrafiltrate.

The UF modalities described above are administered intermittently. That is, they occur in some sequence with non-UF or balanced pulsations. For example, the control unit that operates the pump and valve actuators can sequence the system 100c to deliver twelve balanced pulses and then three UF pulses. At the end of the therapy, the cumulative volume of the UF pulsations achieves the volume of target UF, which is the volume of fluid that needs to be removed for the patient to his dry weight, as the term is known in the art.

In an alternative embodiment, system 100c provides a third peristaltic pump that operates with a third peristaltic pumping portion of UF (not illustrated but configured and regulated at least substantially the same as pumping portions 30a and 30b) and a third balancing chamber of UF (not illustrated but configured and regulated at least substantially in the same balance chambers 50a and 50b). In one embodiment, the inlet of the pumping portion of UF is connected in T in the line from patient 60d or is connected separately to a tube from the patient extending from the patient to the connector from the patient 62b .

The output of the UF pump portion feeds into both compartments of the UF balance chamber. The valves are provided to allow the UF pump portion to fill a first compartment of the UF balance chamber with spent fluid, thereby emptying the second compartment of the spent fluid UF balance chamber. Then, the second compartment is filled, which empties the first spent fluid compartment to complete a complete cycle. In each cycle a known amount of spent fluid is removed as UF. The fluid emptied from the UF balance chamber is sent through the drain path 26d to the drain 14 or one of the supply bags 12 that acts as a drain bag as described above.

The UF cycle is repeated as necessary to achieve the target UF removal volume. Importantly, this can be done while pumping portions 30a and 30b and balance chambers 50a and 50b supply / remove a coincident volume of fresh / spent fluid to / from the patient. It may be beneficial to have the ability to run the pumping portion of UF and the UF balance chamber continuously, for example, a constant speed at a varying speed according to a patient profile in the course of therapy. To do this, the valves that control the UF balance chamber change at higher or lower frequencies. The UF balance chamber can be adjusted differently, for example, smaller than the 50a and 50b balance cameras for finer UF control.

The third pump that operates with the pumping portion of UF can run at any desired speed while operating pumps with balanced pumping portions 30a and 30b. Figures 12A and 12B show peristaltic pump modalities in which an individual roller handles two flexible sheet cassette pumping portions. Given the previous need to vary UF pump speed, the two pump portions handled by the same roller (and thus at the same speed) will be coincident flow portions 30a and 30b in one embodiment. The pumping portion of UF will then operate with its own roll.

In an additional alternative mode, the third UF balance chamber was provided but not a third pumping portion. Here, the spent fluid pumping portion 30b drives the UF balance chamber out of the return path 60b (downstream of the spent fluid pumping portion 30b) in addition to balance chambers 50a and 50c. That is, the first and second compartments of the UF balance chamber are fluidly connected with the return path 60b downstream of the spent fluid pumping portion 30b. The valves that control the UF balance chamber again change at higher or lower frequencies to control the UF speed.

It should be appreciated that separate UF pumping portions and volumetric control devices can also be provided for systems 100a and 100b of Figures 1 and 2. For example, a separate peristaltic pumping portion and balance chamber can be provided for the system 100a of Figure 1. A third volumetric UF pump can be provided for system 100b of Figure 2. Such configurations allow simultaneous balanced and UF pulses. In any of the configurations described above, any of the balance chambers and / or pumping portion of UF can alternatively be handled magnetically as shown later in connection with Figures 26A, 26B, and 27.

Referring now to Figure 4, Detail IV of Figure 1 is shown in detail and in perspective view. Figure 4 shows an embodiment for sealing connectors, such as supply connectors 16a to 16c and drain connector 22 between two folds or sheets 74a and 74b (which can be separate or folded sheets of the same piece of material) of cassette flexible sheet 10a. It should be appreciated, however, that the teachings of Figure 4 apply to any of the sheet cassettes 10 (referring collectively to flexible sheet cassettes 10a, 10b, 1Oc, etc.) and also to any type of connector, such as connectors to and from heater 36a and 36b and connectors to and from patient 62a and 62b.

In the illustrated embodiment, connectors 16 (referring to 16a to 16c collectively) and 22 each include a connector body 80, which can be semi-rigid or rigid. Suitable materials for the body 80 include semi-rigid or rigid polymers or plastics, such as, Acrylic and Cyclic Olefin Copolymers (COC). The body 80 includes or defines a sealing apparatus 82, such as a luer adjustment, reinforced adjustment, or other type of pressure adjustment or threaded seal. In one embodiment, the supply lines 18 and drain line 24 (not shown) are removable or permanently sealed around the adjustment 82. The seal can rely on the pressure adjustment alone or aided by a medically suitable adhesive, bond or chemical weld. , such as ultrasonic, heat or other welding.

In an alternative embodiment, lines 18 (referring to 18a and 18c of Figure 1 collectively) and 24 fit sealed and removable or permanently to body 80. A permanent seal may include any of the joining techniques discussed above, such as adhesive, heat energy, etc.

In another alternative mode (not illustrated) one or both of the first and second laminate 74a and 74b are thermoformed to form a male port extending out of the front edge 78a. The supply or drainage lines 18 and 24 may then be removable or permanently sealed around or within the term oformad port or through any of the techniques discussed above.

As illustrated by the rows of X's (used throughout the application to illustrate a sealed joint), the first laminate 74a is sealed longitudinally in seals 72a and 72b to the second laminate 74b on either side of the body 80. Them 72a and 72b may also include a laminate seal 74a and 74b to body 80. As noted, the seals 72a and 72b extend into the bodies 80 to the seal and form the supply of flow paths 26a to 26c and drain path 26d.

In the illustrated embodiment, the paths 26 were formed by longitudinal thermoforming, at least the substantially semicircular arc in one or both of the first and second folds or sheets 74a and 74b. Suitable processes for making such a longitudinal arc include thermoforming and injection molding. In an alternative embodiment, the arc is not preformed, instead, seals 72a and 72b define relatively flat flow paths 26 (collectively referring to flow paths 26a to 26d, etc.) and the pumps are adjusted and configured. to force the fluid through at least substantially flat folds 74a and 74b that form paths 26. In addition, alternatively, one or more temporary tube bars or other template instrument may lie on sheet 74a or 74b. Sheet 74a or 74b is stretched over the tube or template and welded to sheet 74b or 74a, respectively. The tube or template is removed by leaving the paths 26.

A seal 72c is made along the front edge 78a of the flexible sheet cassette 10a. The seal 72c includes a sheet 74a to the sheet 74b that seals in certain places and a circumferential sheet 74a / 74b to the body 80 seals in the connectors 16 and 22. A seal 72d is made along the side edge 78b of the sheet cassette flexible 10b. The seal 72 (collectively referring to seals 72a, 72b, 72c, 72d, etc., may be made through any of one or more of the adhesive, chemical or welding modalities discussed herein. In addition, the edges 78b may alternatively be formed by folding an individual piece of material at edge 78b to form first and second sheets 74a and 74b. In addition, edges 78a and 78b can be welded to a rigid frame that provides structural support for sheet cassettes 10a, 10b and 10c. The frame helps in handling and loading the cassette.

In the illustrated mode, the bodies 80 of the connectors 16 and 22 are at least substantially cylindrical. In an alternative embodiment, the bodies 80 widen or narrow to provide improved sealing surfaces to seal the upper and lower folds 74a and 74b. A configuration for narrow bodies 80 is shown and described in the Request for

US Patent Series No. 10/1 55,384, entitled Disposable Medical Fluid Unit that has Rigid Frame, filed on May 24, 2002, obtained by the representative of this application, the complete contents of which is incorporated herein by reference .

The valve contact portions or seals 28a to 28b in the embodiment illustrated are flat sections or indentations formed or made in appropriate positions along the flow paths 26. Flat sections or indentations can be formed in the process of forming paths 26 or be done on trajectories 26 after the trajectories are formed. The planes or indentations tend to increase the contact area with the flat head valve actuators. However, it is contemplated that the valve contact portions or seals 28 do not have a different configuration from the rest of the flow paths 26 and are simply areas in which the valve actuator contacts the flow paths 26. Here, the configuration head and valve actuator force is sufficient to close the semicircular or circular flow paths 26 when called to do that. The valve actuator can be operated pneumatically, mechanically, hydraulically and / or electrically. For example, a fail safe valve actuator is used mode, which is closed through a spring force and opened through a vacuum. The valve actuators open and close pneumatically alternately. In addition, valve actuators can be driven by cams on a cam shaft.

Referring now to Figure 5, Detail V of the Figure is shown in more detail and in perspective view. Figure 5 shows an embodiment for peristaltic pump portion 30 (which includes pump portions 30a, 30b, etc.). The pump portion 30 includes at least one substantially circular flow path 84, which is formed by using upper and lower folds 74a and 74b through any of the methods discussed and includes any of the configurations discussed above for fluid paths 26. The peristaltic pump inlet 86 and peristaltic pump outlet 88 communicate fluidly with the peristaltic flow path 84 and with supply path 26a to 26c and pump outlet path 32, respectively, shown above in connection with Figures 1 and 3 . Inlet 86 and outlet 88 were placed at least substantially parallel, adjacent relationship to each other in the illustrated mode to maximize the distance or launch of peristaltic pumping path 84.

As shown, the peristaltic pump portion 30 operates with a peristaltic pump actuator 90. The peristaltic pump actuator 90 generally includes components known to those skilled in the art, such as a drive shaft 92 and at least one driven roller 94 rotatably along the drive shaft 92. One difference between the peristaltic configuration of Figure 5 and that of known peristaltic pumps is that known pumps typically use round tubing that bends into a circular channel. That is, the outer circumference of the ring limits against the channel. The drive shaft rollers contact the inner surface of the ring and perforate the tube radially against the channel. In Figure 5, on the other hand, a channel or dam plate 126 is located behind the second sheet 74b. The channel or dam plate 126 is part of the dialysis machine in one embodiment and, for example, may be part of a door that closes against the flexible sheet cassette 10a or 10c after it was loaded into the machine. The rollers 94 are located inside the machine on the opposite side of the cassette 10a or 10c.

The rollers 94 rotate substantially in the same plane where the sheets 74a and 74b reside and the press path 84 in multiple places against the plate 126 to direct the fluid from the inlet 86 to the outlet 88. In particular, the shaft 92 rotates so that the rollers 94 create negative and positive pressure gradients to direct the fluid from the inlet 86 to the outlet 88. The thermoformed flow paths are configured to withstand, for example, not collapsing or closing, forces created by vacuum or negative peristaltic pressures. As noted through the arrows in Figure 5, axis 92 can be bidirectionally directed if needed as described above.

Referring now to Figure 6, an embodiment for balance chamber 50 (generally referring to balance cameras 50a, 50b, etc.) used in flexible sheet cassettes 10a and 10c is illustrated. Figure 6 shows Detail VI of Figure 1 shown in perspective view. Figures 7 and 8 are cross-sectional views of Figure 6 taken along lines VII-VII and VIII-VIII, respectively, shown in Figure 6. As observed in Figures S to 8, the balance chamber 50 uses three folds or sheets 74a to 74c of flexible material. Several modalities to seal three separate folds together were discussed here. Three sheets 74a 74c can be completely separated or folded twice from the same piece of material.

As seen in Figure 6 and as discussed above, the balance chamber 50 includes a sealed cycle 52 formed by a first seal 78e shown by the circular axis between the first sheet 74a and the second sheet 74b. The chamber formed within the circular seal 72e between the seals 74a and 74b, which form the upper balance chamber compartment 54a can also be seen in Figure 7. A second seal 74f is shown in phantom in Figure 6 where it resides under sheet 74a and is on the same sealed circle 52 between second sheet 74b and third sheet 74c, which form lower chamber chamber 54b. In one embodiment, seals 72e and 72f are made at the same time or as the same seal, so that an individual seal process, for example, a welding or chemical bonding process, forms both seals 72e and 72f simultaneously and comparatively associated . It is contemplated, however, to form one of the stamps 72e and 72f first and after that to form the second of the two stamps 72e and 72f. Seals 72e and 72f can be made through any of the methods described herein. Additional seals (not illustrated) are made along the edges of three sheets 74a to 74c and somewhere else in cassette 10a or 10c as discussed here.

In the illustrated mode the seals 72e extend to form the balance chamber input 56a and balance chamber output 58a. Enough of the balance chamber output 58a is seen so that the valve or seal contact portion 28I shown in Figure 1 is also seen in Figures 6 and 7. The seal 72f also extends to form the chamber entrance of balance 56b and output of balance chamber 58b. Enough of the balance chamber output 58b is illustrated so that the valve seat 28m is shown in hidden and phantom in Figure 6 and is also seen in Figure 8. As seen in Figure 1, the output paths Balance chamber 58a and 58b are combined into two patient paths 60a. Figures 6 and 8 illustrate a modality to allow fluid to travel between two pairs or levels of flexible sheet. As noted, the middle flexible sheet 74b defines an opening or crack 96, which is located directly on the distal end of the balance chamber output 58b and is in line with the balance chamber output 58a and the path to the patient. subsequent 60a. In this configuration, the fluid exiting the lower balance chamber compartment 54b travels through the balance chamber outlet 58b, upwardly through the second sheet 74b through the opening 96, at the chamber outlet. of balance 58b and towards the trajectory of the patient 60a, which are located and defined by flexible sheets 74a and 74b.

Figure 8 illustrates a cross-section of sealed folds 74a to 74c from a front view while cassette 10a is divided through paths 58a and 58b shown in Figure 6. As noted, in Figure 8 the valve seat 28m it is located laterally offset from the valve seat 28I, so that the valve cooperation actuators can open and close paths 58a and 58b independently. That is, a valve actuator can close the valve seat 28I or 28m without closing the flow path 58b or 58a, respectively. Figure 8 also shows the opening 96 in cross-section, which is formed in the sheet 74b and allows fluid communication between paths 58a and 58b, so that the flow of the upper and lower compartments 54a and 54b can be combined in the path of 60th patient. Figure 8 also shows that paths 58a and 58b can be lifted through thermoforming or other method to provide a space between the inner fold surfaces 74a and 74c and the outer fold surfaces 74d.

Referring now to Figure 7, an apparatus and method for operating balance chamber 50 is illustrated (generally referring to each of the balance cameras described herein). The balance chamber 50 is shown in operation with a portion of the dialysis machine 100a and 100c (which operates with cassettes 10a and 10c, respectively). The dialysis machine 100a or 100c includes or defines first and second chamber forming members 102a and 102b. For example, one of the members 102a or 102b is stationary and configured to accept a flexible sheet cassette, such as cassette 10a or 10c. The other of the chamber forming members 102a or 102b is part of a door that closes on the opposite side of the flexible sheet cassette 10a and 10c after it is loaded into the dialysis machine 100a or 100c.

The chamber forming members 102a and 102b each define or include a port 104 for which a tube (not illustrated) is secured liberally or permanently through any of the methods or modalities described above in connection with the connectors 16 and 22 of Figure 4. In one embodiment, after cassette 10a or 10c is loaded into machine 100a or 100c, negative or empty pressure is removed at ports 104, pushing the first and third folds or sheets 74a and 74c against the inside of shaped cavities at least substantially spherical defined by first and second members 102a and 102b. Although members 102a and 102b were shown when defining at least substantially spherical shapes, other suitable cross-sectional shapes can be used, such as substantially triangular or substantially trapezoidal shapes. In addition, although not illustrated, members 102a or 102b can define air channels that extend radially from ports 104 and various directions to help spread the void across a larger surface of folds 74a and 74c. Such channels were shown and described in the

US Patent No. 6,814,547, entitled "Medical Fluid Pump," assigned to the attorney in this application. Once the sheets 74a and 74c are pushed through the vacuum against the inner surface of the chamber forming members 102a and 102b, respectively, the balance chamber 50 is ready for operation. In an alternative embodiment, the negative pressure was not applied against sheets 74a and 74c and thus ports 104 are not necessary. Here, the positive pressure of the dialysate or fluid is sufficient to spread, respectively, sheets 74a and 74c against members 102a and 102b, respectively, and to handle the middle sheet 74b between sheets 74a and 74c.

Figure 7 illustrates an operating state in which fluid was not supplied to the balance chamber 50. Accordingly, the middle or operating sheet 74b was not pushed toward the top sheet 74a or bottom sheet 74c. Section VII-VII taken through the detail of Figure 6, for Figure 7 includes valve seat

231. As noted in Figure 8, the valve seat 28m did not align with the valve seat 28I with respect to the section plane along line VII-VII of Figure 6. Accordingly, the valve seat 28m it was not observed in the split view of Figure 7 because the sight valve seat 28m where it receives the list in front of the valve seat 28I. The valve seat 28I is shown when operating with a valve actuator 106, which is part of the machine 100a or 100c. For simplicity, the valve actuator 106 is shown as a fully pneumatically operated valve actuator. Here, the positive air pressure is applied to the port of the actuator 106 to force a plunger 108 that compresses the valve seat 28I against the second sheet 74b to close the balance chamber outlet 58a. The actuator 106 includes a ring seal or 110, which creates a sliding seal between the piston 108 inside, for example, cylindrical housing of the valve actuator 106. To open the balance chamber outlet 58a, a negative pressure is applied to the port 106, which pulls the plunger 108 up against the stopper 112, which allows the fluid to open the seat 28I and flows out of the balance chamber compartment upper 54a through the output of balance chamber 58a. Figures 6 to 8 do not show valve seats 28j, 28k or 28I that communicate with valve actuators, such as valve actuator 106. These actuators and seats control the balance chamber input 50a and the input and output of the balance chamber 50b of Figure 1.

In operation, to fill the upper balance chamber compartment 54a, the piston 108 is pressurized and closes the valve seat 28I and balance chamber outlet 58a. The valve actuator 106 operating with the balance chamber inlet 56a opens, allowing fluid to fill the upper balance chamber compartment 54a. If the fluid already filled the lower compartment 54b, the fluid entering the compartment 54a pushes the fluid from the lower balance chamber compartment 54b, through the balance chamber outlet 58b to its destination. To do that, a valve actuator 106 operating with the balance chamber output 58b opens, while a valve actuator 106 operating with inputs 56b closes. Because the volume defined by compartments 54a and 54b is fixed and because the second sheet 74b is pushed all the way against the sheets 74a or 74c each is half-press, the same volume of fluid is drawn through of the balance chamber output 58a and 58b at each half press. Accordingly, flexible sheets 74a and 74c are made of a suitably elastic material, condescending and free from filtration such as one of those materials listed above for sheets 74 (collectively referring to sheets 74a to 74c). As discussed later in connection with Figures 26A and 26B, the sheet 74b is alternately made to be magnetic and alternatively handled magnetically.

Referring now to Figures 9A to 9C, an apparatus and method for operating volumetric pumps 70 are illustrated. The cassette portion 10 shown in Figure 2 and marked as Detail IX is shown in front, cross-sectional view in Figures 9A to 9C, 20 showing the volumetric pump 70b. The teachings regarding 70b are applicable to the volumetric pump 70a.

The volumetric pump 70b is shown when operating with a dialysis machine 100b, which uses the cassette 10b. Machine 100b includes first and second chamber forming members of pump 114a and 114d, which define the shape of the volumetric pump

70b The cassette 10b is configured to be loaded into the machine 100b so that a circular flexible membrane portion of the cassette 10b as observed in Figure 2 is in alignment with the spherically formed chamber defined by the pump chamber forming the members 114a and 114b. Also, the valve seats 28q and 28s are aligned with valve actuators 106 shown in Figures 9A to 9C. The valve actuators 106 operate as described above in connection with Figure 7 and includes a piston 108, which slides back and forth within the actuator bulb.

Chamber 70b uses first and second flexible sheets 74a and 74b. The first and second pump chamber forming members 114a and 114b each include a port 104 described above in connection with Figure 7. As discussed below, the negative and positive pressure is used to drain sheets 74a and 74b. Alternatively, one of the sheets 74a or 74b can be handled mechanically. A suitable hybrid mechanical / pneumatic pump is shown and described in US Patent No. 6,819,547 listed above. Although the spherical shape shown in Figures 9A to 9C is a suitable shape, other shapes can be defined for volumetric pump 70 such as a trapezoid or triangular shape.

Figure 9A shows an initial state for volumetric pump 70b. Here, the negative pressure is applied to port 104 of chamber forming member 114b, which pulls the second flexible sheet

74b to fit the inner surface of the second chamber forming member 114b. At the same time, the positive pressure is applied to a port 104 of the first pump chamber forming member 114a. The positive pressure causes the first flexible sheet 74a to be pressed against the second flexible sheet 74b. In Figure 9A, a positive pressure is applied to both valve actuators 106, which close valve seats 28q and 28s. Again, the valve actuators 106 can be any combination of pneumatically, mechanically and / or electrically operated. As further observed in Figure 9A, the dialysate or medical fluid (which includes blood) 116 is pressurized against the valve seat 28q, but is prevented from entering the sealed chamber of the volumetric pump 70b.

In Figure 9B, the negative pressure at port 104 of the lower pump chamber forming member 114b is maintained as the positive pressure applied to the valve actuator 106 in the valve seat 28s. A negative pressure is applied to the valve actuator 106 in the valve seat 28q, which pulls and holds the module 108 towards and against the stop 112, which allows fluid 116 to flow through the pump inlet path 66b and in the volumetric pump chamber 70b. The fluid force 116, for example, through gravity may be sufficient to cause the first flexible member 74a to be pushed against the inner surface of the upper pump chamber that forms the member 114a. Alternatively, a negative pressure can be applied at the port

104 of member 114a to pull the first flexible sheet 74a against the inner surface of the member. This action causes a vacuum, which pulls the fluid 116 into the pump chamber. As with the peristaltic pump, thermoformed flow paths are configured to withstand, for example, not collapse, under the negative pressure of the membrane pump. In any case, the fluid 116 fills the at least substantially spherical cavity between sheets 74a and 74b and stops against the valve seat 28s, which is still in its closed position.

In Figure 9C, the valve seat 28q closes, while the valve seat 28s opens. The negative pressure is maintained in the lower port 104, so that the sheet 74b is pulled against the member 114b. Here, a positive pressure is applied to port 104, which closes the first flexible sheet 74a against the second flexible sheet 74b, which causes fluid 116 to be pushed out of the at least substantially spherical volumetric pump chamber 70b, through the pump exit path 68b, to its desired destination. The first and second membranes 74a and 74b are now in the position shown in Figure 9A, so that the pump 70b is able to repeat the cycle described above as soon as a valve seat 28s is closed. As shown below in connection with Figure 28, membranes 74a and 74b are alternately made to be magnetic and alternatively handled magnetically.

The pumping and pump filling pulsations 70a and 70b in Figure 2 can be divided into stages so that the flow of dialyzer or medical fluid (including blood) through cassette 10b is at least substantially continuous. Because the volume formed by the chamber of members 114a and 114b is known and because the first flexible sheet 74a repeatedly moved to the upper and lower surface of the chambers, the volume of fluid pumped with each pulse is known and is repeatable Therefore, the separate volumetric control apparatus, such as balance chamber 50, is not needed. The total volume of the pumping fluid is equal to the volume of each pulse multiplied by the number of pulsations. UF is controlled through one of the methods discussed above.

The volumetrically controlled balance chamber 50 and volumetric pumps 70 cameras are formed in one mode through the respective circular seals. In an alternative embodiment, the respective seals are made larger in diameter than necessary to achieve the desired volume. Here, a seal between the sheets 74 is created by the pressure of the door that presses against the machine, or a first part of the machine that presses against a second machine. As shown and discussed in connection with Figures 24A and 24B, the machine seal is adjusted to form the appropriate diameter wait to achieve the desired volume. The mechanical clamp seal reduces alignment limitations. The machine to the machine seal can be manually secured, for example, through a lever or latch, fasteners, cam action pressure settings, etc. or ensure additionally or alternatively formed with the help of pneumatic or electromechanical pressure. Figures 25A and 25B discussed below show modalities for fluid heating paths formed through mechanical clamping and an operable heater with such a fluid heating path. Figures 26A, 26B and 28 discussed below show balance chamber modalities and volumetric pump portions of the flexible sheet cassette, respectively, formed through mechanical clamping and a modality for handling the membranes within the balance and pumping chambers.

Referring now to Figures 10A and 10B, two different modalities of an integrated heater path for the flexible sheet cassette discussed here are illustrated. Figure 10A illustrates Detail X of flexible sheet cassette 10b shown in Figure 2. Figure 10B shows an alternative three-layer, portion of double-sided heater portion. Figure 10A shows the heater or heater plates 118, while Figure 10B shows double heaters or heater plates 118a and 118b. The heaters or heater plates 118 (collectively referring to heater 118 of Figure 10A and heater plates 118a and 118b of Figures 10B) can perform any suitable mode of heat transfer, such as electrical, inductive, radiant, convective resistance and any combination thereof. As shown in Figures 10A, heater 118 is continuous under the fluid heating path 42b. In Figures 10B, heater elements 118a and 118b are located around the fluid paths 42c and 42d of the flexible sheet cassette.

In Figure 10A, the fluid heating path 42b is made of first and second sheets 74a and 74b. A serpentine path with a semicircular shape or other suitable cross-sectional shape was formed in the sheet 74a through any of the apparatus and methods discussed above in connection with Figure 4. Alternatively, both sheets 74a and 74b can form semicircular halves, which together form a complete circle. If so, the heater 118 can be formed or adapted with an indented semicircular heating path to increase surface contact. A continuous outer seal 72g is made around the outside of the rings or serpentine that rotates from the fluid heating path 42b. The continuous inner seal 72h is made along the inner curve of the path 42b. Seals 72g and 72h are made through any of the methods discussed above. Edge seal 72¡ is also made along edge 78c as seen in Figure 10A. Alternatively, the edge 78c is made through a fold. In operation, the dialysate or fluid flows through the path 42b and is heated through heat energy from the heater 118.

In Figure 10A, the flexible sheet cassette 10b is loaded on top of or limited vertically against the heater

118. In Figure 10B, the flexible sheet cassette is loaded between two insulating housings 120a and 120b. The heater elements 118a are fixed inside the insulating heater housing 120a. The heater elements 118b similarly are fixed in the insulating heater housing 120d. The distances 120a and 120b may be part of the dialysis machine or part of a separate heater.

The fluid heating paths 42b and 42c of Figure 10B are formed of three sheets 74a, 74b and 74c. The second sheet 74b serves as a backup to the thermally formed paths 42c and 42d in the sheets 74a to 74c. The sheets 74a and 74c are sealed once or at different times to the middle sheet 74b through any of the sealing methods discussed above. As further noted in Figure 10B, openings 96 are made in the second sheet 74b to allow the dialysate to flow from the lower fluid heating path 42d of the third sheet 74c into the upper fluid heating path 42c of the sheet 74th or vice versa. Figures 10B therefore provides an efficient fluid heating apparatus, which essentially doubles the heating capacity for the same surface area against the flexible sheet cassette shown in Figures 10A. Double paths such as path 42d can also be made with a separate heater bag 40 of Figures 1 and 3.

Referring now to Figure 11, an embodiment for mounting ventilation 44 in one of the flexible sheet cassettes 10 (collectively referring to the flexible sheet cassettes 10a to 10c) is illustrated. In particular, Figure 11 shows detail XI of flexible sheet cassettes 10b of Figure 11. The flexible sheet cassette 10b includes first and second flexible sheets 74a and 74b. Those sheets are sealed around the vent 44, which includes a vent body 46 and a filter 48. The filter 48 in one embodiment is a hydrophobic membrane or other type of filter that allows air, but not fluid or dialysate, pass through said filter. Ventilation 44 is fixed to sheets 74a and 74b in the same manner as connectors on 16 and 22 of Figure 4. Towards that end, the seals 72a and 72b are made on either side of the body 46 of the filter 48 and / or the same body 46. The seals 72a and 72b extend to form a fluid path, which can be assisted by a thermoformed shape created or in one or both sheets 74a and 74b.

In operation, if air is detected in the heated dialysate, a valve seat 28h as shown in Figures 1 to 3 opens, allowing the fluid to reach ventilation 44 and push the air through ventilation 48. After that, the fluid is pumped to its desired destination. Alternatively, as described above, ventilation 44 is signaled vertically when its associated cassette is mounted, so that a separate valve actuator and the seat are not necessary.

Referring now to Figure 12A, an embodiment for handling fluid through two flow paths using an individual peristaltic pump actuator 90 is illustrated. The actuator 90 includes a drive shaft 92 and rollers 94 described above in connection with the Figure 5 The flexible sheet cassette .5, for example, two pump cassettes 10c, when loaded, slides horizontally or vertically on an axis 122, such as a groove 124 in sheets 74a and 74b that slides on an axis 98 of the actuator of peristaltic pump 90. The rollers 94 handle the fluid through both pumping portions 30a and 30b shown 10 for example in the cassette 10c of Figure 3. The cassette 10c is mounted so that the second sheet 74b boundary against channel plates 126a and 126b, which provide a rigid surface against which the flow paths of pumping portions 30a and 30b can be compressed by rollers 94, similar to the press plate 126 of Fig. 5. In the embodiment illustrated, rollers 94 direct the fluid in the same direction in and out of the pumping portions 30a and 30b. As discussed above, one use for the configuration of Figure 12 is to provide an individual peristaltic pump actuator 90 that handles two portions of firefighters 30a 20 and 30b, which in turn feed the balance chamber inputs 50a and 50b with fresh or spent fluid.

Referring now to Figure 12B, a second embodiment is illustrated for using an individual peristaltic pump actuator 90 to direct the fluid through two paths of pumping flow. Here, the 30th and peristaltic pump portions

30b are configured as semicircles or half circuits. The shaft 92 rotates the rollers 94 (actuator 90 can have any suitable number of rollers 94) through a full 260 degrees to direct the fluid through both fluid paths of pumping portions 30a and 30b. A suitable channel plate (not illustrated), such as a channel plate 126 of Figure 5, is mounted behind the flexible sheet cassette 10b to provide a rigid surface against which the rollers 94 can compress the raised paths 84a and 84b of pumping portions 30a and 30b. Unlike the modality of Figure 12A double pumping, the dual pumping mode of Figure 12B handles fluid in opposite directions as observed by oppositely arranged inputs 86a / 86b and outputs 88a / 88b. In both embodiments of Figures 12A and 12B, however, axis 92 may rotate in either of the two directions as shown by the arrows in Figure 12B.

The dialysis machine 100 (collectively referring to each of the machines 100a, 100b, etc.) uses many different sensors, such as pressure sensors, flow sensors, temperature sensors, air bubble detectors, identification detectors of solution to review the example of peritonitis, composition and pH, conductivity sensors and ultrasound sensors, for example, for air or blood detection. Those sensors are typically used to perceive some parameter of the dialysate or fluid that is pumped through one of the flexible sheet cassettes 10.

Referring now to Figure 13, an embodiment for operating a sensor 130 with any of one of the flexible sheet cassettes 10a to 10c is illustrated. The sensor 130 can be any of the above-described types of sensors and includes guides or cables 132 that guide a control unit or dialysis machine controller 100. The sensor 130 perceives a parameter of dialysate or medical fluid (which includes blood) that flows through a flow path 128. Cassette 10 (any cassette here) is mounted so that a perception area 134 aligns with the sensor 130. The perception area 134 is an expanded flow path area defined by seals 72a and 72b, which decreases the speed of the fluid flow, and can increase perception time and accuracy. Seals 72a and 72b are made through any of the methods and modalities discussed above. The perception area 134 has a shape and size to conform to the head of the sensor 130.

Referring now to Figure 14, an embodiment for making different seals between three sheets 74 of material is illustrated. In Figure 14, sheets 74b and 74c are illustrated. The sheet 74a (not polished) is sealed at the top of the sheet 74b. A flow path 128 is made between sheets 74b and 74c. As illustrated, a thermoformed indentation or raised portion is made in sheet 74c, which is then sealed to sheet 74b through any of the different methods discussed above for seals 72a and 72b. Then, a printable adhesive is deposited on the upper surface of the sheet 74b along the seal lines 72j and 72k. A suitable printable adhesive is cyclohexanone, for example, polyvinyl chloride (PVC) sheet, or a polyester elastomer for other types of sheet. Then, a sheet or laminate 74a is placed as desired on top of the sheet 74b. The radiofrequency (RF), ultraviolet (UV) energy or heat is then applied to the adhesive seal lines 72j and 72k to activate the printed adhesive along the applied pattern, sealing sheet 74a to 74b. In this way, the three sheets 72a to 72c can form any desired seal pattern (same or different) between sheets 74a and 74b and between sheets 74b and 74c.

Referring now to Figure 15, another method for selectively sealing three sheets 74a to 74c of flexible material to form a flexible sheet cassette is illustrated. A sealed joint 136 extends along a length of the cassette 10d, for example at or about half of the other length of the cassette. The joint 136 allows the cassette to be maneuvered and folded to make selectable joints in the three different sheets 74a to 74c. This method applies to any of the flexible sheet cassettes discussed above. For illustration purposes, the flexible sheet cassette 10d of Figure 15 includes the individual peristaltic pump 30 and balance chamber 50 of Figure 1 with a built-in fluid heating path 42b of Figure 2. As shown above, many Flexible sheet cassette features require only two sheets 74a and 74b. Other components such as balance chamber 50 require three sheets 74a to 74c. Therefore it is contemplated to provide a cassette 10d, which includes three sheets or folds 74 in areas that require three sheets and only two sheets 74a and 74b in other areas of cassette 10d that require only two sheets. In cassette 1 0d, three sheets 74a to 74c are used alternately in the complete cassette 10d. Again, sheets 74a to 74c can be separated or formed by folding an individual piece of material one or more times.

The left side of the cassette 10d is used to make the three double stratum heating flow paths 42c and 42d discussed above in connection with Figure 10B. As illustrated, one of the outwardly oriented flow paths, such as flow path 42d, is first formed by sealing sheets 74b and 74c together. Then, sheet 74a is sealed to the combination of sheets 74b and 74c. In one embodiment, sheet 74a is sealed to the combination of sheets 74b and 74c through the printable adhesive described above. In another embodiment, sufficient energy is applied to the outside of sheet 74a and 74c to chemically bonded or cast sheets 74a and 74b. In addition, alternatively, sheets 74a to 74c can be secured to form fluid heating paths 42c and 42d simultaneously. The middle sheet 74b defines openings 96 as discussed above that receive fluid heating paths 42c and 42d.

The right side of the cassette 10d is used to form a balance chamber 50, peristaltic pump 30, pressure sensing area 134, fluid flow paths 26a to 26d and other flow paths associated with the components listed above. Here, the flexible sheets 74a and 74b are sealed together first, after which the sheet 74c is sealed to the sheets 74b, for example, to complete the balance chamber 50. Although not illustrated, additional flow paths can be formed between sheets 74b and 74c, with one or more openings 96 that allow fluid to flow from flow paths or flow devices formed through sheets 74a and 74b and formed between sheets 74b and 74c. The sheet 74c can be sealed to the sheet 74b through the printable or alternative adhesive or additionally by applying energy through the three sheets 74a to 74c.

As illustrated, the pump outlet path 32 extends from the peristaltic pump portion 30 through the joint 136, through coupling openings defined in sheets 74a and 74b, in the lower fluid heating path 42d , through its serpentine trajectory, back through another group of coupling openings in sheets 74a and 74b, inside and through the upper fluid heating path 42c, before extending into balance chamber 50 and out towards patient connector 62a.

Referring now to Figure 16, another method for sealing three sheets 74a to 74C together is illustrated. In Figure 16, the layers

74a to 74c are sealed when using die sealing openings 136a and 136b using machinery constructed for example by Extrusion of KIEFEL GmbH Cornelius-Heyl-Str. 49, 67547 Worms / Germany. Apparatus 136a 136b apply heat to sheets 74a to 74c in a predefined die pattern. The die pattern includes areas in which the three sheets 74a to 74c are sealed together and other areas in which only two of the sheets 74a and 74b or 74b and 74c are sealed together.

In a sealing machine the conductor die, each die apparatus 136a and 136b is controlled to draw a desired amount of heat in direct contact with outer sheets 74a and 74c. For example, the dice apparatus 136a may be set to take out more heat than the dice apparatus 136b. When using this type of heating conductor, it is desirable to seal the middle layer 74b only to the sheet 74a or 74c, the apparatus 136a or 136b on the unsealed side of the sheets 74a or sheet 74b is set to supply a smaller amount of heat to prevent sealing between that sheet and the middle sheet 74b. The heat of the opposite die apparatus 136a or 136b that contacts the sheet 74a or 74c that will form a seal with the sheet 74b is set to remove a greater amount of heat, sufficient to melt the two sheets and seal the sheets in a pattern wanted. The temperatures of hot and cold die apparatus 136a and 136b are set to create a temperature profile that is higher than the melting temperature of the middle layer 136b on the side to be sealed and lower on the opposite side of the sheet 136b to prevent Let this side of the middle layer merge. Towards this end, it may be that one of the dice apparatus is completely eliminating energy. The die machine is therefore able to control the heat outputs of each apparatus 136a and 136b independently to heat the different sheets 74a to 74c to the desired temperatures.

In another embodiment, the die sealing machine is of a radio frequency (RF) type. Here, one of the apparatus 136a and 136b is positive and the other is negative and direct or indirect contact with sheets 74a and 74c. RF type sealing is especially suitable for sealing PVC, for example, PVC pipe and PVC sheet, although it can be used to seal other kinds of tubing and sheet materials listed here. The RF type seal can be used in the mode of Figure 15, for example, to seal the three sheets in multiple steps.

Referring now to Figures 17, 18, 19A and 19B, in an alternative embodiment, a cassette 10e includes a flexible portion 138 and a rigid portion 140. The flexible portion 138 includes first sheet 74a second sheets 74b. The peristaltic pump portion 30 and in-line fluid heating path 42b are formed through sheets 74a and 74b in the flexible portion 138 in any manner described above. With the cassette 10e, however, the balance chamber 50 is formed using two sheets 74a and 74b instead of the three sheet version described above. Here, the balance chamber 50 is partially formed through a rigid chamber 142 formed in the rigid portion 140. As noted in Figure 18, the flexible portion 138 bends below or otherwise joins the lower side of the rigid portion 140. When this occurs, the flexible membrane portion of the balance chamber 50 is aligned with and after that sealed to the rigid chamber 142 of the rigid portion 140.

Figure 18 also shows the heater 118 operating with the heating path 42b and peristaltic pump actuator 90 operating with peristaltic pump portion 30. Valve actuators, such as actuators 106 discussed above, are provided in the drive unit Valve 144. The valve drive unit 144 resides on the opposite side of the cassette 10e from the heater 118 and pump actuator 90. In the embodiment illustrated, the valve drive unit 144 may be part of a door that presses the valve actuators 106, heater 118 and pump actuator 90 in place against the appropriate positions of the cassette 10e.

The valve seats, such as seats 28a to 28d, are provided as part of the rigid portion 140 of the cassette 10e. Rigid group paths, such as flow paths 26a to 26d, 32, 58a and 58b, communicate with the pumping portion 30, balance chamber 50, their associated flow paths and fluid heating path 42b of the portion flexible 138 through openings, such as openings 96 provided in one or more sheets 74b and 74a with rigid fluid paths.

With respect to the balance chamber 50, the flow paths 56a and 58a flow from the flexible portion of the balance chamber 50 of the flexible portion 138 to the rigid paths defined by the rigid portion 140. The valve seats 28j to 28m they are located in the rigid portion 140. In addition, the paths 56b and 58b leading to the rigid chamber 142 are also provided in the rigid portion 140.

Referring now to Figures 19A and 19B, a balance chamber 50 constructed of rigid chamber 142 of rigid portion 140 and two flexible sheets 74a and 74b of flexible portion 138 of cassette 10e is illustrated. While the balance chamber 50 of Figures 19A and 19B is shown in connection with the cassette 10e having the rigid portion 140 and flexible portion 138, it is expressly contemplated to provide the balance chamber 50 of Figures 19A and 19B with a cassette of flexible sheet in which there is a single rigid portion 142. That is, the rigid chamber 142 can be provided independently or separately and is not required to be part of the larger rigid portion 140.

As illustrated, the sheet 74a abuts against a rigid backing member 146. The rigid backing member 146 can be provided with cassette 10d or is alternatively part of the dialysis machine 10Od operating with the cassette 10d. The backing plate 146 limits the lower balance chamber compartment 54b to expand in the cavity formed by the rigid chamber 142 when the lower balance chamber compartment 54d is filled.

Valve seats 28k and 28m were shown figuratively in cooperation with rigid chamber 142. Similarly, valve seats 28j and 28I were figuratively shown in cooperation with sheets 74a and 74b. For purposes of illustrations, the valve seats were shown with an X when it is in a closed fluid state and without an X when it is in an open or fluid flow state.

In Figures 19A, the valve actuators that operate with valve seats 28j and 28n cause the seats to close, while the valve actuators that operate with valve seats 28k and 28I cause the seats to open. In this valve state configuration, the upper balance chamber compartment 54a is filled with a volume of fluid 116, while the lower balance chamber compartment 54b expels a similar volume of fluid to a desired destination. In Figure 19B, valve actuators that operate with valve seats 28k and 28I cause those seats to close, while actuators that operate with valve seats 28j and 28m cause those seats to open. Here, the lower balance chamber compartment 54b is filled with fluid 116, while a similar volume of fluid is distributed from the upper balance chamber compartment 54a, valve seat passed 28m, to a desired destination.

The rigid chamber version of the balance chamber 50 can be provided individually in a cassette, for example as shown in Figures 1 and 17 with cassettes 28a and 28d. Alternatively, two or more versions of the 50-chamber rigid camera are provided in a cassette, as discussed in connection with the cassette 10c of Figures 3. Under normal coincident flow circumstances, the fresh fluid enters one of the compartments 54a or 54b that distributes spent fluid from the other compartment, and vice versa. The rigid chamber balance chamber 50 can alternatively be used for UF only, in which case the spent fluid is supplied to both compartments 54a and 54b.

Referring now to Figures 20A to 2OD, an alternative mode for balance chamber 50 using flexible sheet 74a to 74c is illustrated. The balance chamber in Figures 20A to 20D incorporates tube 156a and 156d as balance chamber input and tubes 158a and 158b as balance chamber outputs. Tubes 156a, 156b, 158a and 158b can be made of any suitable medical grade material, such as PVC, PVC without DEHP, polybutadiene, ("PD") ethylene vinyl acetate ("EVA"), polypropylene mixture ("PP"), polyethylene mixture ("PE"), craton mixture and polyolefin mixtures. The tubes are sealed in place along seals 721. The upper and lower seals 72e and 72f discussed above in connection with Figures 6 and 7 are made to form upper balance chamber compartment 54a and lower balance chamber compartment 54b. The inlet tube 156a and outlet tube 156a communicate fluidly with the upper balance chamber compartment 54a, while the inlet tube 156b and outlet tube 158b communicate fluidly with the lower balance chamber compartment 54b.

The lower ends 160 of the balance chamber inlet tubes 156a and 156b and balance chamber outlet tubes 158a and 158b are configured to align with the circular chambers formed by the seals 72e and 72f, to allow the first and third sheets 74a and 74c are pulled against respective inner walls of the former balance chamber members located within the dialysis machine, such as chamber walls 102a and 102b shown in Figure 7. The middle sheet 74b is sealed inside the tubes 156a and 158a so that the fluid entering from the tube 156a can only flow into the upper compartment 54a. The middle sheet 74b is sealed around the upper part of inner ends 160 of tubes 156b and 158b, so that the fluid entering the sheet and tube type balance chamber 50 through 156b can only enter the lower compartment 54b of the balance chamber 50. Otherwise, the middle sheet 74b is free to move back and forth within the outer sheets 74a and 74c when the balance chamber 50 is in operation.

Figures 20C and 20D illustrate that sheets 74a to 74c have semicircular mixtures 76. Mixtures 76 can be preformed or at least partially preformed, for example, through thermoforming. Alternatively, mixtures 76 are formed during the sealing process of sheets 74a to 74c on tubes 156 and 158. Mixtures 76 are made out on outer sheets 74a and 74c. The blends 76 in the middle sheet 74b are in the alternate direction as necessary. Depending on which side is welded, the seal 72I can weld two sheets 74a / 74b or 74b / 74c or one sheet 74a or 74b to tubes 156a or 156b.

In the illustrated mode, the sheet and tube type balance chamber 50 is provided as a separate apparatus that can be fluidly connected to another part of the disposable unit or dialysis system. Towards that end, tubes 156a to 158b can be as long as needed to connect to the other part of the dialysate circuit. In an alternative embodiment, two or more balance chambers 50 having the configuration of Figures 20A to 20D are formed through sheets 74a to 74c and two or more groups of tubes 156a to 158b. In addition, alternatively, one or more of the balance chambers 50 of Figures 20A to 20D is provided in a cassette such as cassettes 10a to 1 Od, which contain the majority but all the dialysate circuit components, regardless of the bags , patient connection and associated tubing.

Tubes 156a to 158b may have or include valve seats, such as valve seats 28j to 28I described above in connection with the balance chamber 50 of Figure 1. Alternatively, automated drilling or pipe fasteners are used to hold a pipe portion 156a to 158b without needing a modified valve seat area. The balance chamber 50 of Figures 20A to 20D can be used in any of the cassettes described herein that employ one or more balance chambers.

Referring now to Figures 21A to 21G, the alternative flexible sheet cassette 10e is shown in operation with a hemodialysis machine 100e, which in a preferred embodiment is a domestic hemodialysis machine (HHD). Alternatively, cassette 10e can be used with any of the dialysis therapies discussed herein. As discussed in the application for origin, hemodialysis is typically carried out in a clinic or center, in which online dialysate is performed when using a water source and concentrates. In a domestic configuration, a similar type of online dialysate generation unit is also typically used. These units are large and require the dialysis machine to be connected to a water source. In the mode illustrated in Figures 21A to 21G and in the application for origin, an alternative system is shown, which uses dialysate provided from one or more supply bags, and which can provide convective cleaning in addition to diffusive cleaning. Alternatively, the discarded blood is combined with the discarded dialysate. In Figures 21B and 21F, a separate blood cassette 150 is provided.

Figures 21A and 21C to 21E illustrate flexible sheet cassette

10e Cassette 21e differs from the cassettes described above in a number of ways. One difference is that the separate peristaltic pump tubes 148 and 154 are used instead of the flexible sheet cassette pumping portion 30 shown and described above for example in connection with Figures 1, 3 and 5. A second difference is that The manifold of different supply and drainage bags is made through external tubing to flexible sheets 74a to 74c of cassette 10e. In Figures 21A, the peristaltic pump actuators operating with the dialysate line 148 and UF line 154 direct fluid towards the balance chamber inlets 50a and 50b. In an HHD therapy the fluid leaves the regulated outlets of the balance chambers 50a and 50b to a dialyzer or drain as described above. As before, the balance chambers 50 operate as intermediate measuring devices that measure a similar volume of fluid to the drain and the dialyzer. Any of the methods for controlling ultrafiltration described above can be used with flexible sheet cassettes 10e. For example, a number of pulsations of the balance chamber 50 can be dedicated UF pulsations, in which spent fluid is pumped into both halves of the balance chambers 50a and 50b. Alternatively, a separate UF balance chamber can be provided.

As observed in Figures 21A and 21 E, the fresh dialysate is pumped from one of the supply bags through a respective supply line 18a to 18e, in a manifold 162 and a dialysate pumping tube 148 operating with a peristaltic dialysate pump actuator. The peristaltic dialysate pump pumps fresh dialysate through the inlet connector 16, through the integrated in-line fluid heating path 42b, and into one of the balance chambers 50a or 50b. Any air that leaves the heated solution is allowed to be vented through ventilation 44. In one embodiment, the cassette 10e is vertically mounted as shown in Figures 21A and 21E, so that the air automatically exits to the top of the cassette 10e and is released through the air vent 44 and vent line 164 ( Figures 21E). This reduces the number of valve actuators and seats as discussed above in connection with cassettes 10a to 10c. That is, any air is automatically purged without having to close the normal operation of the machine.

Fresh dialysate pumping into an inlet compartment of one of the balance chambers 50a and 50b causes a similar amount of spent fluid that already resides in the balance chamber to be pumped through the drain line 24 into the drain. At the same time, the UF pump actuator operating with the UF pump line 154 pumps spent fluid from the dialyzer, through the line from the patient 152b, into the inlet compartment of the other balance chambers 50a and 50b Such an action causes a similar volume of fresh fluid to be pumped through the patient connector 62a and line to the patient 152a towards the dialyzer.

As seen in Figure 21A, a pipe organizer

168 It is provided to support supply lines 18a to 18e, drain line 24, ventilation line 164, line to dialyzer 152a and line from dialyzer 152b in an organized manner to allow cassette 10e and associated tubes to be easily mounted. Figure 21A also shows darkened areas 188 that cooperate with manifold 162. Darkened areas 188 indicate portions of the associated tubes that are perforated in a closed manner to selectively allow fresh dialysate to be brought from a desired supply bag 12 and spent dialysate to be pumped to drain bag 14 or one of the supply bags 12 used as a drainage bag.

Referring now to Figures 21C and 21D, a number of additional features of flexible sheet cassette 10e are illustrated. The schematic side view of Figure 21D illustrates that sheets 74a, 74b and 74c are formed of a single sheet of material, which is folded twice to produce the three layers 74 (collectively referring to layers 24a to 24c). This allows the number of outer edge joints or seals to be reduced and also helps with the separate layer alignment 74a to 74c. It should be appreciated that any of the flexible sheet cassettes described herein can be formed by using a single folded sheet, two sheets with a fold or three separate sheets, etc.

Figures 21C and 21D also show first welding areas 190a in which only the first sheet 74a is welded or otherwise fixed to the sheet 74b. Also shown are welded areas 190b where three sheets 74a to 74c are welded or adhered together. Figure 21C also shows third areas 190c in which only the second layer 74b is welded or otherwise fixed to the third layer 74c. This selective welding allows the cassette 10e to be done efficiently. Three-sheet welding does not have to be done in areas where only two sheets need to be welded together. However, the three sheets can be welded otherwise joined in areas in which it is required to do so. In general, two layer welds or glue joints 190a and 190c are required when flow in one layer is desired but not in another layer. In an alternative embodiment, three layer welds 190b (except for three periphery layer welds and three layer welds for input and output ports) are removed and replaced with the compression seals described below in connection with Figures 24A, 24B , 25A, 25B, 26A, 26B and 28.

In Figure 21C, selective welding occurs in areas associated with 50a and 50b balance chambers. Figure 6 provides additional information on how three sheet balance chambers 50 can be welded. The serpentine paths 42b are formed from a three sheet weld. This allows the fluid heating path 42b to extend spatially efficiently between sheets 74a and 74b and sheets 74b and 74c.

Figures 20C and 20D illustrate that the fluid travels between different layers or sheet pairs using openings 96 made at desired locations in the middle sheet 74b. The fluid for example enters the individual supply connector 16 in a first path between sheets 74b and 74c. An aperture 96a allows the fluid to travel in a portion of fluid heating path 42b located between sheets 74a and 74b, in which it is first heated. Then, the fluid moves through an opening 96b in a second portion of fluid heating path 42b located between sheets 74b and 74c. Any air that comes out of the heater solution is vented through the top of the cassette 10e through! event 44. Next, the heated fluid enters the balance chamber area, which uses the three sheets 74a to 74c in one mode. The fresh fluid leaves the dialyzer through a balance chamber compartment located between the sheet 74b and 74c through two patient connectors 62a. The spent fluid returns from the dialyzer to the cassette 10e through the patient connector 62b in a balance chamber compartment located between sheets 74a and 74b. The spent fluid is sent to the drain through the drain connector 22 located between the sheets 74a and 74b.

Referring now to Figures 21B and 21F, an embodiment of a blood cassette 150 used with HD, HHD and HF is illustrated. Blood cassette 150 is also mounted vertically as illustrated in one embodiment. Cassette 150 includes a rigid portion 170 having a rigid housing 172 and a flexible membrane 174 made of any of the materials discussed above attached to housing 172. The right portion 170 is made of a suitable material, such as polyvinyl chloride (PVC), acrylic, ABS, polycarbonate, polyolefin mixture. Housing 172 includes or defines a port from patient 176, a port to patient 178, a saline port 180, a vent 44, a port to dialyzer 132 and a port from dialyzer 184. As observed in Figures 21B and 21F, ports, such as ports 178 and 180, port 184 and ventilation 44 can be formed in different relative locations along housing 172.

Figure 21B illustrates valve seats 28x to 28z that operate with the line from the patient, the line to the patient and the salt line, respectively. A peristaltic pump actuator operates with blood pump line 166 to pump blood from the patient, to the cassette 150 to the dialyzer, back to the cassette 150 and then back to the patient. The fluid received from the dialyzer enters an air separation chamber 192 before returning to the patient. Blood 186 is collected at the bottom of the air separation chamber, while any air in the blood exits to the top of the air separation chamber 192. The air separation chamber 192 may also include a vent 44, such as a hydrophobic membrane, which allows air to be purged from cassette 150.

The operation of the blood cassette 150 of Figure 21F is similar to the operation in connection with Figure 21B. Here, however, the valve seat 21y operates with the line towards the dialyzer connected to the port towards the dialyzer 182. The valve seat 28x controls the fluid inlet cassette 150 of the patient as shown in Figure 21B. The valve seat 21z controls the flow of saline in the cassette. The air separation chamber 192 operates as before, where the air in the upper part of the chamber 192 can exit the cassette 150 through the ventilation 44. Blood in the lower part of the air separation chamber 192 flows towards the patient through the port towards the patient 178. Figure 21F further illustrates that a flexible sheet 174 adheres to the rigid portion 172 of the housing 170. Flexible sheet 174 allows a valve actuator to press valve seats 28x to 28z to open / close a respective fluid flow path. As further illustrated in Figure 21F, blood cassette 150 includes or provides areas of perception 194a and 194b to perceive a blood parameter, such as blood pressure, venous pressure or blood temperature.

Cassette 150 illustrates components associated with a blood cassette used with HD, HHD, HF, HDF and any combination thereof as described in the present application. As noted, the blood cassette can be provided as a separate cassette 150 installed separately from a dialysate cassette 10a to 10b. Alternatively, the blood cassette components are integrated with any of the dialysate cassettes 10 described herein.

Referring now to Figure 21G, a top view of the hemodialysis machine 100e illustrates an embodiment for mounting the cassette 10e, the various supply bags 12 and drainage bag 14. The cassette 10e can be placed at an angle relative to the top of the machine 100e, to create at least one slightly vertical component for cassette assembly 10e for ventilation purposes discussed above. The supply bags 12 and drain bag 14 are supported by the top of the machine 100e and fluidly connected to the cassette 10e before or after the cassette is mounted to the machine 100e. The machine 100e includes the user profile 196, which allows the patient or caregiver to begin, control and verify the therapy. User ID 196 can use an operable touch screen cover with a touch screen controller and / or membrane switches as desired.

Referring now to Figures 22A to 22D, an additional alternative system 1 OOf is illustrated which employs an alternative flexible foil cassette 10f. The 100f system is suitable for performing hemodialysis, such as domestic hemodialysis. Here, the system 100f also uses a second blood cassette, which may be similar to or the same as the blood cassette 150 described above. Figure 22A illustrates an embodiment for loading cassettes 100f and 150 into machine 100f. Here, the dialysate components are located on one side of the user interface 196, while the blood components are located on the other side of the user interface 196. This configuration makes loading the cassettes relatively easy for the user and also It allows the valve and pump and heater actuators located within the machine 100e to be mounted efficiently, which reduces the overall size of the machine 1 OOf.

In the machine 100f, the cassettes 10f are placed vertically, which is advantageous for air purge purposes described above. The machine 10Of includes two peristaltic pump actuators 90, one of which handles the fluid out of a dialysate tube, while the other handles the fluid out of a UF tube, similar to the distribution described above for the cassette 10e. A separate heater bag 40 described above in connection with Figure 1 extends to the right of a rigid housing portion 200 of the cassette 100f. The rigid housing portion 200 as shown in more detail below defines flow path and associated valve seats. Accordingly, the valve actuators of the machine 10Of are located behind the rigid cassette portion 200 of the cassette 10f. A plate heater or other type of heater is located behind the heater bag 40. A flexible double chamber chamber membrane component 198 of the cassette 10f resides under the rigid portion 200. As discussed herein, peristaltic pump actuators 90 direct the fresh and spent fluid alternately through the inlet compartments of the balance chambers 50a and 50b. A hinged door 202 allows the cassette 10f, which includes its rigid portion 200, balance chamber component 198 and heater bag 40 to be easily inserted and removed from the machine 1 OOf.

Referring now to Figure 22B, a more detailed view of cassette 10f is illustrated. As discussed, cassette 1 Of includes a rigid portion 200 fluidly connected to a separate heater bag 40 and a balance chamber unit 198. The cassette 10f therefore differs from the cassette 10e in that the heating and balance chamber functions are performed through the flexible sheet membranes, while the valve actuation is performed by using a rigid member 200 in combination with a flexible sheet 202. Valve actuators, for example, spring loaded, pneumatically operated open actuators, operate with valve seats 28 to open and close selected flow path as desired. Cassette 10f also includes separate peristaltic pump tubes 148 and 154 described above in connection with cassette 10e. The heater bag 40 includes a serpentine heating path (not shown) and communicates with the rigid member 200 through lines to and from the heater 38a and 38b, respectively. The balance chamber unit 198 also communicates with the rigid valve member 200 through port connectors and tubes as illustrated.

Balance chamber unit 198 is illustrated in more detail in Figures 22C and 22D. The balance chamber unit 198 is similar to the flexible sheet balance chamber 50 described

100 previously in connection with Figures 20A to 2D. Here, unit 198 provides two balance chambers 50a and 50b, which are made of flexible sheets 74a to 74c, fresh fluid tubes 156 and spent fluid tubes 158. As best seen in Figure 22D, each chamber compartment of balance 50a and 50b communicates only with a fresh tube 156 or worn 158. The fresh tube 156 communicates with a first balance chamber compartment located between sheets 74a and 74b, while the spent tube 158 communicates fluidly with a second balance chamber compartment located between sheets 74b and 74c. The balance chambers 50a and 50b each include seals 72e, 72f and 72I as described above in connection with Figures 20A to 20D.

Figure 22D illustrates that sheets 74a to 74c have semicircular bends 76, similar to those of balance chamber 50 of Figures 20A to 20D. The bends 76 can be preformed or at least partially preformed, for example, through thermoforming. Alternatively, the bends 76 are formed during the sealing process of sheets 74a to 74c on tubes 156 and 158. The bends 76 are made outwardly on outer sheets 74a and 74c. The bends 76 in the middle sheet 74b alternate the direction for each of the balance chambers 50a and 50b. As noted, each tube 156 and 158 has an individual sheet 74a or 74c welded on one side of two sheet 74a or 74c in combination with the middle sheet 74b welded on its other side. In one embodiment, tubes 156 and 158 are welded to the middle sheet 74b first. Outer sheets

101

74a and 74c are then welded to the middle sheet 74b and the exposed portions of tubes 156 and 158.

In operation, fresh fluid enters and leaves through tube 156. The spent tube enters and leaves through tubes 158. That is, there is no separate inlet and outlet tube for each balance chamber compartment in the case with the balance chamber 50 of Figures 20A to 20D, which has two fresh tubes 156a and 156b and two worn tubes 158a and 158b. Instead, the same tube acts as the fluid inlet and outlet of fresh fluid spent for its compartment. The valves and flow paths are configured within the rigid member 200 to direct the flow into or out of the balance chambers 50a and 50b as desired.

Fresh fluid entering the fresh balance chamber compartment between sheets 74a and 74b through tube 156 causes the middle sheet 74b to visit a similar amount of fluid spent from the spent compartment between sheet 74b and 74c through the spent tube 158. While this occurs in one of the balance chambers 50a and 50b, the spent fluid enters the spent compartment between sheet 74b and 74c of the other balance chamber, which flexes the middle sheet 74b to dissipate a similar amount of fresh fluid from the compartment fresh between sheet 74a and 74b through the fresh tube 156. The sequence is then inverted. In this way, at least a semi-continuous flow of fluid is sent to the patient or dialyzer and into the drain.

Referring now to Figure 23, a cassette is illustrated

102 Additional alternative for the 10g cassette. The 10g cassette is a simplified version of the 10e cassette. Cassette 10g includes supply lines 18a to 18e, drain line 24, dialysate pump tube 148, return pump tube 154, line fluid heating path 42b, ventilation 44, ventilation line 164, patient connector 62a, line to dialyzer 152a, line from dialyzer 152b. The primary difference between cassette 10g and cassette 10e is that balance chambers 50a and 50b used with cassette 10e are not used with cassette 10g. That is, volumetric fluid control is not performed when using 50A and 5Od balance chamber equalized flow equalizers with 10g flexible foil cassette. Instead, another method is used, such as through gravimetric or fluid weight control that can be supplied and removed from the patient or through a flow management system (FMS) used with a HomeChoice dialysis machine. ® sold by the representative of this application. The sheet cassette body 10g may include valve seat and flow paths as necessary to direct flow in a desired manner. Alternatively, the flow can be controlled by holding and releasing the tubes connected to the cassette 1 Og, in which case the cassette 10g serves primarily as a fluid heating path. The flow paths, valve seats and fluid heating path 42b can be provided through two sheets 74a and 74b or three sheets 74a to 74c as described herein or may have a rigid component,

103 such as rigid frame.

Referring now to Figures 24A and 24B, an additional 100h alternative system using flexible 1 Oh membrane cassette is illustrated. The 100h system is suitable for hemodialysis, such as domestic hemodialysis. The 100h system uses a blood cassette, such as cassette 150. Figure 24A shows the 100h system without a 10h cassette loaded. Figure 24B shows the 100h system with 1 Oh cassette loaded.

The cassette 10h is simplified to a large extent because the coupling side plates 210a and 210b of the machine 100h are held together around the cassette 10h to form the balance chamber portion, fluid heating paths and other trajectories of Cassette fluid flow as installed. That is, the balance chamber portion, trajectories, etc., do not have to be preformed in the cassette 10h prior to loading. The closing of the door 202 against the wall 220 of the machine 100h in turn forms the fluid-tight passages mechanically. The cassette 10h is preformed as a bag 212 as seen in Figure 25B, which is made of three sheets 74a to 74c or two sheets 74a and 74b as necessary to form the desired components. The bag 212 is fluidly connected to the line towards the dialyzer 152a, line from the dialyzer 152b, ventilation line 164, input connector 16, supply line 18a to 18f and drain line 24 as further noted in the Figures 24b

The die plate 210a is formed of a hinged door 202.

04

The die coupling plate 210b is formed in the wall 220 of the machine or system 100h. In the illustrated embodiment, the side plate 210a includes heating path forming edges 214a that mate with the heating path forming edges 214b of the die plate 210b. The die plate 210a includes balance chamber formation edges 216a that mate with the balance chamber formation edges 216b of the die plate 210b. The die plates 210a and 210b also form or include tube / connector that accepts grooves 218a and 218b, respectively, with secure tubes 252a, 152b, and 164 is in place when the door 202 is closed without holding or closing the tubes. The die plates 210a and 210b alternatively or additionally form any other additional flexible sheet apparatus discussed herein, such as volumetric pumping portions 70, internal flow paths of UF meter portions 26, valve seats 28, etc.

At least one of the die plates 210a and 210b is integrated with component activation, such as a heater, pump actuator, balance chamber actuator and / or valve actuator. The heating is carried out through heating of electric resistance plate, inductor heating, radiant heating and / or ultrasonic heating. Figure 25A shows an embodiment of an in-line electrical resistance or plate heater configured to heat a fluid heating path formed by mechanical clamping. Figure 25B shows a heater

05 separated that has shell sides of warming path formation, the teachings of which are also applicable to the 100h system. Figures 26A and 26B show a balance chamber portion of a flexible sheet cassette formed through mechanical shell edges, which can be activated pneumatically, mechanically, hydraulically or in the case electromagnetically illustrated. Figure 28 shows a volumetric pump portion of a flexible sheet cassette formed through mechanical shell edges, which can also be activated pneumatically, mechanically, hydraulically or in the case electromagnetically polished. The 100h system can integrate any of these technologies into one or more die plates 210a and 210b.

In the illustrated mode, the bag 212 is shown without any of the inner joints, except those necessary to seal the connectors, for example, connector 16, and / or tubes 152a, 152b and 164. It is also contemplated to provide alternatively Internal security to mitigate damage due to filtration. For example, a joint can be provided to separate the fluid path portion of the bag 212 from the balance chamber portion of the bag. Another connection may be provided to separate or isolate the balance chamber portion 50a from the balance chamber portion 50b, and so on the security joints may have any desired shape or pattern but can advantageously be simpler than the necessary shape or pattern to form the flow component portions categorically. The unions

06 They can be between the plates 74a and 74b, 74b and 74c and between the three plates 74a to 74c.

It is alternatively contemplated expressly to form two sheet seals, for example, between sheets 74a and 74b or 74b and 74c, which use the bonding or welding methods described above to form the actual flow components having two-sheet seals. The mechanical shell seal here is used anywhere where a seal between the three sheets 74a to 74c is needed. Here again, the total number and pattern of welds or joints should be reduced and simplified, respectively.

Referring now to Figure 25A, the heating portion of the cassette 10h formed by mechanical holding heating path formation edges 214a and 214b is illustrated. Cassette 10h as shown in Figure 25B includes a bag 212, which receives fresh dialysate through connecting fresh fluid inlet 16. The edges 214a and 214b form a fluid heating path in line 42b, which receives the fluid cool of the input connect 16. The fluid heating path in line 42b streaks back and forth as shown above to collect heat. The heated dialysate exits through the internal path 222, which is also formed through the mechanical fastener. The fluid heated through the path 222 travels to the balance chambers 50a and 50b or to a volumetric pump 70 for example.

07

In the illustrated mode, the clamping edges 214a and 214g are also heating elements, for example, aluminum plate heating elements. Additional elements 224a and 224b are connected to the door 202 and machine wall 202, which can also be electrical resistance elements. In one implementation, the heat actuator is a power supply that supplies power, for example, 200 watts, to the resistance elements 214a, 214b, 224a and 224b. Alternative types of heat actuators include inductive, radiant, connective, ultrasonic or a combination of heating types. The clamping edges 214a and 214b may not have to provide heat.

As illustrated, the heater that uses any type (s) of heat transfer is capable in a mode of dialysate heating when starting from a temperature of about 5 to about 30 ° C at a temperature of about 37 ° C or body temperature and a flow rate from 0 to about 300 ml / minute. A controller (not illustrated) within the machine 100h controls a duty cycle or on / off cycle in a mode to accommodate different starting dialysate temperatures and different dialysate flow rates. The controller can be a delegate or a subordinate processor that operates with a monitoring processor and a security processor. An out-of-flow fluid temperature monitor 226 senses the temperature of the dialysate left by the

108 fluid heating path 42b and provides feedback to the controller to increase or decrease the duty cycle as needed to achieve the desired drain temperature.

Referring now to Figure 25B, a separable fluid heater 240 is illustrated that employs mechanical support to create a fluid heating path (for example, as path 42a of Figures 1 and 3) within the separate heater 240. Separate fluid heater 240 may be used for example in system 100a of Figure 1, system 100c of Figure 3, and cassette 10f of Figures 22A and 22B. Heater 240 employs any of the types of heating in any combination discussed herein.

A fluid heating bag 230 is connected to heater lines 38a and 38b through any method described herein. Bag materials 212, 230 include any of those for sheets 74a to 74c. The materials for tubes 38a and 38b include any of those for the tubing described herein. As noted, the heating bag 230 as formed is simpler than a fluid heating path 42a of the separate heater 40 of Figures 1 and 3.

The heater 240 in the polished mode includes a shell configuration, wherein the first and second heating closures 242 and 244 are connected by hinge together. When they close, the trajectory formation flanges of

109 heating 214a and 214b of closures 242 and 244, respectively, are coupled and secured with bag 230. Closures 242 and 244 also form or include slots 218a and 218b, respectively, which except lines 38a and 38b, respectively, allow the closures 242 and 244 fit fluidly together without holding those lines.

The flanges 214a and 214b may or may not themselves be heating elements as described above in connection with Figure 25A. The closures 242 and 244 in one embodiment may include a heating plate 246a and 246b, respectively. Heating plates 246a and 246b heat fluid within the fastened fluid heating path, for example, according to the temperatures and flow rates described above in connection with Figure 25A.

Referring now to Figures 26A and 26B, an alternative apparatus and method for operating a balance chamber 250 is illustrated. A primary difference illustrated by Figure 26A is that balance chamber 250 is handled magnetically and not through a separate pump as previously discussed. The middle sheet 74b includes outer folds 74d and 74e, which match a ferromagnetic material of layer 252, such as coal or iron. The ferromagnetic material 252 is sufficiently delegated to allow the middle sheet 74b to flex back and forth as necessary within a chamber formed by the chamber forming members 102a and 102b. Folds

one or exteriors 74b and 74e may be of any listed above for sheets 74a to 74c. Alternatively, the ferromagnetic material 252 is impregnated or intercalated, for example, as a powder or grain, in an individual laminate sheet 74b. In any case, the medium moving sheet 252 needs to be compatible with sterile or almost sterile medical fluids.

The balance chamber 250 is shown in operation with a portion of a dialysis machine 100 (for example, 100a, 100c, 100e, 10Of and 10Oh) operating with a cassette 10 (for example, cassette 10a, 10c, 10e, 10f and 10h, respectively). The dialysis machine 100 includes or defines first and second chamber forming members 102a and 102b. For example, one of the members of 102a or 102b is stationary and is configured to accept flexible sheet cassette 10 (for example, formed on the wall 220 of the machine 100h), while the other of the chamber forming members 102a or 102b is part of a door (eg, door 202) that closes on the opposite side of the flexible sheet cassette 10 after it is loaded into the dialysis machine 100.

The electromagnet 254a and 254b in the polished mode are inserted into members 102a and 102b, respectively, which creates a magnetic field around the chamber, which can be modulated and polarized to extract ferromagnetic sheet 74b to the top sheet 74a or sheet lower 74c of the cassette 10. The electromagnets 254a and 254b are wound alternately around the spherical chamber creation members 102a and 102b,

one 1 respectively, and in any case they are provided with sufficient mass to operate balance chamber 250 as discussed below.

The electromagnets 254a and 254b each connect through guides 256 and 258 to a controller 248. The controller 248 in one mode is a delegated or subordinate controller or printed circuit board (PCB) that operates with a supervisor processor and a security processor The controller 248 in one mode also controls the valves that operate with valve seats 28j at 28m (See Figures 1 and 3), which switch in synchronization with the change of electromagnet 254a and 254b.

To polarize electromagnet 254a, controller 248 causes guides 256 and 258 that guide electromagnet 254a to energize that electromagnet. To polarize electromagnet 254b, controller 248 causes guides 256 and 258 that guide electromagnet 254b to energize that electromagnet. When the electromagnet 254a is energized, the ferromagnetic sheet 74b is removed to the top of the balance chamber 250. When electromagnet 254b is energized, the ferromagnetic sheet 74b is removed to the bottom of the chamber. In this way, the balance chamber 250 self-energizes or self-operates and provides a pumping function in addition to a measurement function. A separate pump is not needed.

It is also contemplated that the magnetically administered middle layer 74b also allows for the measurement of the position of the

112 cap. By oscillating the energy to the electromagnetic 254a and 254b, it is possible to read the current generated by the motion of inertia of the layer in the electromagnetic spiral when the spiral is off. This information refers to or is dependent on the velocity of the magnetically administered middle layer 74b. By integrating the speed information it is possible to reliably determine the position. This information can be used to determine the flow rate outside or inside the chamber and determine when the camera pulse was finished.

In the illustrated mode, the chamber forming members 102a and 102b each define or include a port 104 to which a tube (not shown) is secured in a free or permanent manner through any of the methods and modalities discussed herein. . In one embodiment, after cassette 10 is loaded in machine 100, a static or empty negative pressure is removed at ports 104, which push the first and third folds or sheets 74a and 74c against the inside of at least substantially cavities with spherical shape by the first and second members 102a and 102b. Flexible sheets 74a to 74c are made of a material that is adequately expanded, condescending, non-magnetic and free from filtration.

Although members 102a and 102b were shown by defining at least substantially spherical shapes, other suitable cross-sectional shapes can be used, such as substantially triangular or substantially trapezoidal shapes.

1 3

In addition, although not illustrated, members 102a and 102b can define air channels that extend radially from ports 104 in several directions to help spread the vacuum across a larger surface of folds 74a and 74c. Once the sheets 74a and 74c are pushed through the vacuum against the inner surface of the chamber forming members 102a and 102b, respectively, the balance chamber 50 is ready for operation.

In an alternative embodiment, sheets 74a and 74c are rigid or semi-rigid and are preformed by having, for example, semicircular chamber shapes, which makes ports 104 and associated negative pressure unnecessary. In another alternative embodiment, the net electromagnet 254a and 254b and ferromagnetic sheets 74b are used with a balance chamber that is reused, that is, not disposable, so that the outer sheets 74a and 74c are not needed. That is, the magnetic drive can be used with any type of balance chamber and is not expressly limited to a cassette based or flexible sheet cassette based application as shown here.

Figure 26A illustrates an operating state in which fluid was not supplied to the balance chamber 250. In the illustrated mode, the valve seat 28I is shown when operating with a valve actuator 106, which is part of the machine. 100. Here, positive air pressure is applied to the port of the actuator 106 to force a plunger 108 to compress the valve seat 28I against

14 the second sheet 74b, which closes the output of balance chamber 58a. The actuator 106 includes a ring seal or 110, which creates a sliding seal between the piston 108 inside, for example, cylindrical housing of the valve actuator 106. To open the balance chamber outlet 58a, negative pressure is applied to the port at 106, which pulls the plunger 108 up against the stopper 112, which allows the fluid to open the seat 28I and flow out of the balance chamber compartment upper 54a through the output of balance chamber 58a.

In operation, to fill the upper balance chamber compartment 54a, the piston 108, which closes the valve seat 28I and the balance chamber outlet 58a, is pressurized. A similar valve and piston actuator closes the balance chamber inlet 56a. The electro magneto 254a is energized, by pulling the sheet 74b against the top sheet 74a. Then, the valve actuator and the piston operating with balance chamber input 56a opens, the electromagnet 254a is de-energized, the electromagnet 254b is energized, which pulls the sheet 74b completely through the chamber and against the lower sheet 74c , which creates a vacuum and fills the upper balance chamber compartment 54a.

To fill the upper balance chamber compartment 54a and fill the lower balance chamber compartment 54b, the valve and piston actuator operating with the balance chamber input 56a is closed, the piston 108 is pulled against the stop 112, operating valve seat 28I and balance chamber output

1 5

58a, the electromagnet 254b is de-energized, the electromagnet 254a is energized, which pulls the sheet 74b completely through the chamber and against the top sheet 74a, disseminates the fluid from the balance chamber compartment 54a, through the outlet of 5 balance chamber 58a and which simultaneously creates a vacuum within the balance chamber compartment 54b, which fills the chamber. The cycle is then reversed by using the second balance chamber input 56b and second balance chamber output 58b (See Figure 1) to disseminate fluid from the 10 balance chamber compartment 54b and simultaneously fill the balance chamber compartment 54a .

Because the volume defined by compartments 54a and 54b was set and because the second sheet 74b was pushed all the way against the upper and lower sheets 74a or 74c at every 15 average pulsation, the same volume of fluid is drawn out at through the balance chamber outputs 58a and 58b at each half press. In this way the fresh and spent balance fluid and the removal of UF can be controlled easily and precisely.

It is also contemplated to impregnate pistons 108 with a ferromagnetic material 20 and open and close valve seats 28 electromagnetically.

Referring now to Figure 26B, Figure 26A rotates 90 degrees over an access through ports 104 to show a mode for creating balance chamber seals through mechanical fastening. The chamber formation members 102a and

116

102b each defines or includes a balance chamber or ring clamping edge 216a and 216b (described above in connection with Figures 24A and 24B). The rings 216a and 216b in one embodiment extend around the circumference of the balance chamber 50 or 250, except to allow entry and exit paths 56 and 58. The rings 216a and 216b are held together to seal sheets 74a to 74c mechanically enough to withstand the positive and negative pressures and variations thereof within the chamber. Clamping rings 216a and 216b operate within any type of balance chamber operation, for example, through a separate pump or electromagnetic operation.

An outer safety ring seal 72m can optionally be provided. The 72m seal is formed through any of the techniques discussed here. It serves to mitigate damage from any dialysate that escapes the mechanical seal formed by mechanical rings 216a and 216b. It also allows tolerance by aligning cassette 10 inside machine 100.

Referring now to Figure 27, an embodiment of a magnetically operated balance tube 260 is illustrated. A balance tube was discussed in connection with Figure 45 of the current application. As discussed in the current application, balance tube 260 here includes a separator 262 that functions similar to flexible membrane 74b of balance chamber 250. In the illustrated embodiment, the separator 262 is a ball or spherical object that moves tightly within a cylindrical housing 264. A

17 Pair of covers 266 and 268 are provided at any end of the cylindrical housing 264. The covers 266 and 268 are sealed to the cylindrical tubing 264 through outer O rings 270. The spacer or ball 262 seals to the covers 266 and 268 through inner rings O 272. In an alternative embodiment, the covers 266 and 268 are permanently or hermetically sealed to the cylindrical tube 264. Ports 274 and 276 are integrally formed with or joined to covers 266 and 268, respectively. Ports 274 and 276 are sealed to coupling tubes through any mechanism known to those skilled in the art.

The separator 262 is impregnated with a ferromagnetic material, such as coal or iron. For example, a carbon core can be covered with a cover made of medically safe material. The electromagnet 254a and 254b are in an embodiment inserted inside the covers 266 and 268, respectively, which creates a magnetic field around the separator 262, which can be modulated and polarized to pull the ferromagnetic separator 262 to the upper cover 266 or lower cover 268 The electromagnet 254a and 254b each is connected via guides 256 and 258 to a controller 248 described above. The electromagnets 256a and 256b are alternately located outside the covers 266 and 268 and in turn are wound around the covers 266 and 268 and potentially end positions of the tube 264. Here, the magnets can be housed inside the machine as opposed to locate with the tube

260.

1 8

To polarize electromagnet 254a, controller 248 causes guides 256 and 258 that guide electromagnet 254a to energize that electromagnet. To polarize electromagnet 254b, controller 248 causes guides 256 and 258 that guide electromagnet 254b to energize that electromagnet. When electromagnet 256a is energized, ferromagnetic separator 252 is pulled to cover 266. When electromagnet 254b is energized, ferromagnetic separator 262 is pulled to cover 268. The movement of the ball 262 expels and pulls fresh / spent or spent / fresh fluid through port 274 or 276 at each press. In this way, the balance tube 260 is self-energizing or self-operating and provides a pumping function in addition to a measuring function. A separate pump is not needed. As discussed above, the magnetically impregnated separator 262 allows its placement to be determined within the housing 264.

In one embodiment, the cylindrical tube 264 is translucent or transparent, so that an optical sensor can detect its ferromagnetic ball or separator 262 that properly reached the end of the path. Ultrasonic sensors or other types can be used alternatively. The ferromagnetic separator ball 262 is adjusted to fit tightly but smoothly inside the cylinder 264. A small amount of mixture between fresh fluid and the fluent can occur without substantially affecting the performance of the system. In an alternative embodiment, a cylindrical piston type separator was provided. In any

19 In this case, the ferromagnetic separator 262 may have an additional sealing apparatus, such as rags or deformable edges that help to improve the sliding or rotating seal, as may be the case.

The balance tube 260 can be made of plastic or other suitable material. In one embodiment, the balance tube 260 is a disposable article, which can be integrally formed with cassette 10 or attached to the cassette through tubing. O-rings and adjustments may not be necessary if injection molded caps or assemblies are used. In addition, sensors such as ultrasonic or optical sensors, for placement of the separator can eliminate the need to seal at the end of the tube.

Referring now to Figure 28, an electromagnetically controlled volumetric pump 280 is illustrated. Volumetric pump 280 is shown when operating with a dialysis machine 100, such as machine 100b (Figure 2), which uses a cassette 10, such as cassette 10b (Figure 2). Pump 280 may operate out of phase with a second electromagnetically controlled volumetric pump 280 in a manner discussed herein.

The machine 100 includes first and second pump chamber forming members 114a and 114b, which defines the shape of the volumetric pump 280. The cassette 10 is configured to be loaded into the machine 100 so that a circular flexible membrane portion of the cassette 10 is in alignment with the spherically formed chamber defined by the forming members of

120 pump chamber 114a and 114b. Although the spherical shape shown in Figure 28 is a suitable shape, other shapes for volumetric pump 280 can be defined, such as a trapezoidal or triangular shape. Also, the valve seats 28q and 28s line up with the valve actuators 106 as shown. The valve actuators 106 operate as described above in connection with Figure 7 and include a piston 108, which slides back and forth within the actuator body.

Pump 280 uses first and second flexible blades 74a and 74b. The sheets 74a and 74b each are impregnated with a ferromagnetic material 252, such as a layer of carbon or inner iron. The electromagnet 254a and 254b are inserted into the pump chamber forming members 114a and 114b, respectively, which creates a magnetic field around the sheets 74a and 74b, which both can be energized to pull ferromagnetic sheets 74a and 74b away towards upper and lower limbs 114a and 114b, respectively. Alternatively, only one of the electromagnet 254a and 254b is energized, by pulling both sheets 74a and 74b towards that electromagnet. The electromagnets 254a and 254b each are connected through guides 256 and 258 to a controller 248 as described above. Alternatively they can be located outside a wrap around members 114a and 114b.

In an initial state (shown in Figure 28), electromagnet 254b is energized, which pulls the first and second flexible sheets 74a and 74b to adapt to the inner surface of the

121 lower chamber forming member 114b. Initially, a positive pressure is applied to both valve actuators 106, which close valve seats 28q and 28s. Again, the valve actuators 106 can be any combination of pneumatic, mechanical, electrical and / or electromagnetically operated. As noted in Figure 28, the dialysate or medical fluid (including blood) 116 is pressurized against the valve seat 28q, but is prevented from entering the sealed volumetric pump chamber 280.

In a second state, electromagnet 254b continues to energize while the positive pressure applied to the valve actuator 106 in the valve seat 28s. The negative pressure is applied to a valve actuator 106 in the valve seat 28q, which pulls and holds the piston 108 towards and against the stop 112, which allows fluid 116 to flow through the pump inlet path 66b and in the volumetric pump chamber 280. The fluid force 116, for example, through gravity may be sufficient to cause the first flexible member 74a to be pushed against the inner surface of the upper pump chamber forming member 114a. Alternatively or additionally, electromagnet 254a is energized to pull the first flexible sheet 74a against the inner surface of the upper member 114a. This action causes a vacuum, which pulls fluid 116 into the pump chamber.

In a third state, the valve seat 28q is closed, while the valve seat 28s is opened. The energy in the

122 electromagnet 254b is maintained, so that sheet 74b continues to be pulled against member 114b. The energy is removed from the electromagnet 254a which causes the electromagnet 254b to pull the upper flexible sheet 74a against the lower flexible sheet 74b in the members 114b, which in turn causes the fluid 116 to be pushed out of the chamber at least substantially spherical of the volumetric pump 280, through the pump outlet path 68b, to its desired destination. The first and second membranes 74a and 74b are now in the initial state shown in Figure 28, so that the pump 280 is able to repeat the cycle described above as soon as the valve seat 28s is closed.

Because the volume formed by the member chamber 114a and 114b is known and because the flexible sheets move repeatedly to the upper and lower surfaces of the chambers, the volume of fluid pumping with each pulse is known and repeatable. Therefore, a separate volumetric control apparatus, such as a 50 or 250 balance chamber, is not required. The total volume of fluid pumping is equal to the volume of each pulse multiplied by the number of pulsations. UF is controlled through one of the methods discussed above. As discussed above, the magnetically impregnated sheet 74a and 74b allows its position to be determined within chamber forming members 1 1245 and 114b.

Many modalities here were described for different flexible sheet cassettes that have varying degrees and types of

123 fluid flow components and functionality. The present application for this application referenced here includes many different modalities for hemodialysis, hemofiltration and hemosdiafiltration systems. In particular, many modalities were shown by using double dialyzers and a restriction of flow between the dialyzers, which causes both diffusive and convective cleanings associated with HHD. The flexible sheet cassettes described herein may be used for each of the systems described in the present application, which include but are not limited to: (i) the volumetric pump-based HCHDF systems of Figures 1, 4 and 5, which provide diffusive and convective cleaning; (¡I) the volumetric pump based HF systems of Figures 6 and 7; (iii) the alternative volumetric pump based HDF system of Figure 8; (iv) the volumetric pump-based regeneration systems of Figures 9 to 11; (v) the HDF and HF systems based on peristaltic pump of Figures 12 and 13; (vi) the jointly current flow system of Figure 14; the pneumatically controlled system of Figures 15 and 16; (vii) the individual balance chamber systems of Figures 17 to 22; (, vi¡¡) the tortuous trajectory system of Figures 24 and 29, wherein the tortuous paths are formed between the sheets or folds 74a to 74u in any of the forms described above; (ix) the double balance chamber systems of Figures 25 and 26; (x) the weight measurement system of Figures 30 and 31; the improved convection of the HDF filter of Figure 32; (x¡) linear pipe pump systems of

124 Figures 38 to 41; and (xii) the fluid heater of Figures 42 and 43.

It should be understood that several changes and modifications to the currently preferred embodiments described herein will be apparent to those skilled in the art. Such changes and modifications can be made without departing from the spirit and scope of this topic and without diminishing its intended advantages. Therefore, it is intended that such changes and modifications be covered by the appended claims.