Patent ID: 12201759

DETAILED DESCRIPTION

Previous sodium-control systems for dialysis have used a dual-phase sodium regulation. This regulation is in accordance with a prescription guide, generally input by a user, and indicates what desired level of sodium concentration of the dialysate is desired when averaged over the treatment. During the first treatment phase, a sodium chloride solution is added to the dialysate to regulate its conductivity. The amount of sodium chloride added during a treatment can be significant. Then follows a second phase where the system compensates for excess sodium present above the desired prescription amount by adding dilution water. The amount of dilution water added during a treatment can be significant. Methods are described herein for regulating sodium content in dialysate while avoiding addition of excess sodium and of dilution water. In these methods, the sorbent cartridge used for filtering used dialysis solution in connection with a sodium control system in fluid communication regulates the sodium levels within the dialysis solution by controlling conductivity.

FIGS.1-4illustrate a fluid conditioning system100that can be operated to prepare conditioned dialysate for use in a dialysis system. For example, the fluid conditioning system100can be fluidly communicated with the dialysis system to deliver “fresh” (e.g., cleaned, conditioned) dialysate to the dialysis system, collect “spent” (e.g., contaminated, unconditioned) dialysate from the dialysis system, and regenerate (e.g., cleanse) and condition the spent dialysate in a continuous fluid flow loop to recycle the spent dialysate. Example dialysis systems with which the fluid conditioning system100can be fluidly communicated include hemodialysis (HD) systems, peritoneal dialysis (PD) systems, hemofiltration (HF), hemodiafiltration (HDF) and other related systems.

The fluid conditioning system100includes a housing101that contains or supports components of the fluid conditioning system100, a fluid cassette102that includes multiple fluid lines defining various fluid pathways, two relatively high capacity pumps103that can circulate fluid within the fluid lines of the fluid cassette102, and two relatively low capacity pumps104that can deliver (e.g., infuse) conditioning agents into the fluid circulating within the fluid lines of the fluid cassette102. The fluid conditioning system100has a compact footprint that facilitates lifting and transport of the fluid conditioning system100. For example, the fluid conditioning system100typically has a length of about 30 cm to about 50 cm, a width of about 30 cm to about 50 cm, a height of about 30 cm to about 50 cm, and a weight of about 15 kg to about 20 kg.

The housing101includes left and right side panels105,106, handles107positioned along the side panels105,106for carrying the fluid conditioning system100, a door assembly108that can be opened and closed to insert a heater bag, a front panel109to which the door assembly108is secured, rear and bottom panels110,111that further enclose the interior components, an upper panel112that supports the fluid cassette102and the pumps103,104, and a cover113that protects the fluid cassette102and the pumps103,104. Example materials from which the exterior panels of the housing101may be made include plastics, such as acrylonitrile butadiene styrene (ABS) and polycarbonate blends, among others.

The cover113is typically made of ABS or polycarbonate and is transparent or translucent to allow visualization of the fluid cassette102and the pumps103,104. The cover113can be pivoted at a rear hinge114disposed along the upper panel112to open or close the cover113. The upper panel112carries two latches115that can be closed upon a front edge116of the cover113to secure the cover113in a closed position. The latches115can also be pulled up and apart from the cover113to release the cover113from the closed position for accessing the fluid cassette102and the pumps103,104.

Referring toFIG.5, the fluid conditioning system100also includes left and right side interior support frames117,118to which the left side, right side, front, rear, bottom, and upper panels105,106,109,110,111,112are attached. The interior support frames117,118are typically formed from sheet metal.

Each pump103,104is a peristaltic pump that includes multiple rollers positioned about the circumference of a rotatable frame (e.g., a motor) that carries a fluid line extending from the fluid cassette102. As the rotatable frame is rotated, the rolling members apply pressure to the fluid line, thereby forcing fluid to flow through the fluid line.

FIGS.6-8illustrate certain interior components of the fluid conditioning system100. For example, the fluid conditioning system100further includes multiple pressure transducers119, two temperature sensors120, and an ammonia sensor121that are respectively positioned within holes122,123,124in the upper panel112for engagement with the fluid cassette102. The pressure transducers119are embodied as thin, flexible membranes that contact corresponding thin, flexible membranes164within the fluid cassette102(refer toFIG.15) for detecting fluid pressures within certain fluid pathways of the fluid cassette102. The temperature sensors120are infrared (IR) sensors that detect temperatures of the dialysate flowing through certain points of the fluid pathways of the fluid cassette102. The ammonia sensor121is a red-green-blue (RGB) color sensor that can detect color changes on a paper strip within the fluid cassette102to measure a concentration of ammonium within the dialysate flowing through a certain fluid pathway of the fluid cassette102. The fluid conditioning system100also includes circuitry that acquires and conditions signals generated by conductivity sensors that are provided on the fluid cassette102, which will be discussed in more detail below.

The fluid conditioning system100also includes multiple actuators125that are aligned with holes126in the upper panel112for respectively and selectively moving multiple valves of the fluid cassette102. Each actuator125is mounted to a platform127of an internal frame128of the fluid conditioning system100and includes a motor129and a drive unit130that can be moved (e.g., rotated or otherwise manipulated) by the motor129. The drive unit130is equipped with a coupling member131that is formed to engage a respective valve of the fluid cassette102such that movement of the drive unit130produces movement of the valve. The internal frame128also includes columnar support members132that support and locate the upper panel112of the housing101. The upper panel112further defines holes133that are positioned and sized to receive locating pins134for appropriately positioning the fluid cassette102with respect to the upper panel112. With the fluid cassette102in place, the locating pins134can be snapped down toward the upper panel112to lock the position of the fluid cassette102. The fluid conditioning system100also includes a circuit board135equipped with electronics for operating the various electromechanical components of the fluid conditioning system100. For example, the electronics execute codes for carrying out the various stages of a fluid conditioning cycle (as discussed below with reference toFIGS.18-20), operating the pumps103,104, turning valves for the fluid cassette102, processing sensor signals, operating the actuators125, operating a heater assembly151, and running control loops (e.g., control loops for regulating dialysate temperature, regulating pump speeds to achieve desired flow rates, regulating pump speeds to achieve desired dialysate chemical compositions, and ensuring device safety).

Referring again toFIG.5, the fluid conditioning system100further includes a support bracket136and a fan137carried therein for cooling the circuit board135and other internal components of the fluid conditioning system100. The fluid conditioning system100also includes a power supply138, as well as a support bracket that carries an A/C-in port140.

FIGS.9-13illustrate various views of a front assembly141of the fluid conditioning system100. The front assembly141includes the door assembly108and the front panel109of the housing101. The door assembly108is pivotable at hinges142with respect to the front panel109to allow loading of the heater bag153into the fluid conditioning system100. The hinges142are friction hinges located along opposite sides of the door assembly108, as shown inFIG.12.

The front panel109carries a latch assembly143that cooperates with a button144carried by the upper panel112(shown inFIGS.1-4) to releasably secure the door assembly108to the front panel109in a closed position. For example, depression of the button144adjusts the latch assembly143so that the door assembly108can be unlocked from a closed position and pivoted to an open position. The door assembly108can alternatively be pivoted inward from an open configuration until oppositely positioned screws145(e.g., shoulder screws, shown inFIG.12) engage the latch assembly131to lock the door assembly108in the closed position. The latch assembly131has a contact switch for determining whether the door assembly108is open or closed. Referring particularly toFIGS.11and13, the door assembly108includes an optical switch147that indicates whether or not the heater bag is inserted. In some embodiments, the fluid conditioning system100may be inoperable when the door assembly108is open.

Referring particularly toFIG.9, the door assembly108supports a display screen148(e.g., a touchscreen display) on which graphical user interfaces (GUIs) can be displayed and two control panels149that can each be equipped with selectors150(e.g., buttons) for providing inputs at the GUIs to operate the fluid conditioning system100. Example parameters and processes that may be controlled by a user via the display screen148using the selectors150include starting and stopping a treatment, initiating a drain cycle, changing a flowrate, a priming stage of a fluid conditioning cycle, initiating system preparation to start a fluid conditioning cycle, adjusting a temperature according to patient comfort, and confirming correct placement of the fluid cassette102, or fluid lines that interface with the pumps103,104.

Referring toFIGS.10-13, the front assembly141includes components of a heater assembly151that is designed to regulate fluid temperatures of dialysate transported along the fluid pathways of the fluid cassette102. Referring particularly toFIG.12, the heater assembly151includes a heater bag153that is equipped with an input connection154and an output connection155that can interface with the fluid cassette102for allowing dialysate to circulate through the heater bag153to be warmed. The heater bag153is formed as a plastic channel that has a generally flat, collapsed shape when empty, that inflates upon filling with fluid, and that transfers heat from an exterior surface to dialysate flowing through the heater bag153.

Referring as well toFIGS.13and14, the heater assembly151further includes two plates156that position and support the heater bag153and that are heated for transferring heat to fluid within the heater bag153. For example, with the door assembly108in the open configuration, the heater bag153can be slid between heater plates156. Referring particularly toFIGS.10-12, the heater assembly151further includes a heating element by which fluid in the heater bag153can be warmed and two insulation pads158disposed on opposite sides of the heater bag153, or an arrangement with {insulation pad} {heating pad} {metal plate} {heater bag} {metal plate} {heating pad} {insulation pad}. The heating element is attached to a metal (e.g., aluminum) plate156. The heater assembly151also includes a circuit board159that provides electronics for operating the heater assembly151, a feed line160for each heating pad156that provides power, and thermocouple connections162for determining a temperature of the respective heating plates156.

Referring toFIG.15, the fluid cassette102is a single-use, disposable cartridge that includes a housing200, multiple fluid lines201arranged within the housing200, multiple valves202positioned along the fluid lines201, two conductivity sensors203positioned along the fluid lines201, two fluid line connectors (e.g., pump segment clips)204, and two fluid line connectors (e.g., pump segment clips)205. The fluid lines201cooperate with the heater bag153and a dialysis system to form a fluid circuit350for carrying out a fluid conditioning cycle. For example, the fluid lines201include ports to which the input and output connections154,155of the heater bag153can be connected for providing fluid communication between the fluid lines201and the heater bag153. The fluid line connectors204locate fluid line segments206about the high-capacity pumps103, and the fluid line connectors205locate fluid line segments207about the low-capacity pumps104. The fluid cassette102also includes additional fluid lines that extend from the fluid cassette102to various fluid containers, as illustrated inFIG.17.

The valves202are three-way valves by which two alternative fluid pathways can be selected by a control system of the fluid conditioning system100. Lower portions of the valves202are formed to engage with the coupling members131of the actuators125for movement of the valves202. Example types of valves202that may be included in the fluid cassette102include rotary valves, push-pull valves, sliding valves, and shuttle valves.

FIG.16illustrates an operational diagram300by which the fluid conditioning system100can cooperate with a dialyzer337of a dialysis system301to form the fluid circuit350(indicated by solids lines) for carrying out a fluid conditioning cycle, whileFIG.17illustrates an example setup of the fluid conditioning system100with the dialysis system301. Example types of dialysis systems301that may be coupled to the fluid conditioning system100include HD systems, PD systems, HF systems, and HDF systems. The fluid circuit350incorporates components of the fluid cassette102, as well as various other components of the fluid conditioning system100.

For example, in addition to the components discussed above with respect toFIGS.1-15, the fluid conditioning system100also includes a control system161(e.g., including the circuit boards135,159, as well as additional circuit boards for sensor circuitry) for controlling various operations of the fluid conditioning system100and several other, peripheral components positioned along the fluid circuit350. These components include a prime tank302for collecting water to produce dialysate (e.g., sometimes referred to as dialysis fluid), a sorbent cartridge303for filtering tap water to provide purified water suitable for creating dialysate and for cleansing dialysate exiting the dialysis system301, a primary reservoir304for collecting fluid (e.g., unconditioned water or dialysate) exiting the sorbent cartridge303, a secondary reservoir305for collecting fluid that exceeds a capacity of the primary reservoir304, a bag306for containing an electrolyte solution, a bag307for containing a salt-dextrose (SD) solution, a bag308for containing dilution water (DW), and a bag309for containing a bicarbonate (BC) solution that are positioned along the fluid flow path arrangement300.

The bags306,307,309are pre-loaded with appropriate amounts of dry chemicals that can be dissolved in water to produce the electrolyte solution, the salt-dextrose solution, and the bicarbonate solution. Each bag306,307,309includes a nozzle that is designed to increase a velocity of a fluid flow entering the bag306,307,309and to create turbulence needed for adequate mixing and dissolution of the dry chemicals in water.

Table 1 lists approximate capacities of the various fluid-containing components of the fluid conditioning system100.

TABLE 1Capacities of fluid-containing componentsof the fluid conditioning system 100.ComponentCapacity (mL)Prime Tank (302)8000Primary Reservoir (304)7500Secondary Reservoir (305)4500Electrolyte Bag (306)500Salt/Dextrose Bag (307)160Dilution Water Bag (308)4000Bicarbonate Bag (309)1000

The three-way valves202of the fluid cassette102are indicated as V1-V7in the fluid circuit350. Each valve includes three fluid ports (a), (b), (c) by which a flow path in the valve can be adjusted. A valve may be referred to as closed when two or three of its ports are closed and may be referred to as open when two or three of its ports are open. The valves include a prime valve V1, a dissolution valve V2, a bypass out valve V3, a bypass in valve V4, a BC/DW valve V5, an S/D/Electrolyte valve V6, and a condo salt selector valve V7. The fluid lines201of the fluid cassette102will be referenced individually further below with respect to an operation of the fluid conditioning system100. The high-capacity pumps103and the low-capacity pump104of the fluid conditioning system100are indicated respectively as P1, P2and P3, P4in the fluid circuit350. The pumps include a cassette-in pump P1, a dialysate pump P2, a conductivity control pump P3, and an electrolyte/salt-dextrose pump P4. Table 2 lists approximate operational (e.g., fluid flow rate) ranges of the pumps P1-P4.

TABLE 2Operational ranges of pumps of the fluid conditioning system 100.PumpOperational Range (mL/min)P120-600P220-600P30.1-100P40.1-100

The heater assembly151and the ammonia sensor121of the fluid conditioning system100are respectively indicated as a heat exchanger HX and an ammonia sensor NH in the fluid circuit350. The conductivity sensors203of the fluid cassette102are indicated as a conductivity sensor CT1associated with a fluid temperature upstream of the heat exchanger HX and a conductivity sensor CT2associated with a fluid temperature downstream of the heat exchanger HX. In addition to having a capability measure fluid conductivity, conductivity sensors CT1and CT2also have a capability to measure fluid temperature. Given that conductivity changes with temperature, the temperatures measured by the conductivity sensors CT1and CT2may, in some implementations, be used to correct conductivity values measured by the conductivity sensors CT1and CT2to provide temperature-compensated conductivity measurements. In some implementations, a fluid temperature measured by the conductivity sensor CT2may also provide a safety check on a final temperature of dialysate that exits the fluid conditioning system100to flow into the dialysis system303. The temperature sensors120of the fluid conditioning system100are indicated as a cassette-in temperature sensor T1and a heat exchanger temperature sensor T2in the fluid circuit350. The pressure transducers119of the fluid conditioning system100are indicated as pressure transducers PT1, PT2, PT3, and PT4in the fluid circuit350.

The fluid conditioning system100can be operated in multiple stages to cooperate with the dialysis system301(e.g., with the dialyzer337) for carrying out a fluid conditioning cycle in which a dialysis treatment is administered to a patient via the dialysis system301. For example, the fluid conditioning cycle includes a priming stage, an infusion stage, and a treatment stage. The fluid conditioning cycle typically has a total duration of about 135 min to about 300 min.

FIG.18illustrates operation of the fluid conditioning system100during the priming stage, in which an initial volume of water is drawn into the fluid circuit350for subsequent creation of dialysate. At the beginning of the priming stage, the prime tank302is filled to about 7.6 L with water (e.g., tap water, bottled water, reverse osmosis water, distilled water, or drinking water) from a water source (e.g., a container134of water, shown inFIG.17), pump P1is turned on, and heat exchanger HX is turned on. The water is pumped by pump P1from the prime tank302into a fluid line310, through ports (a) and (c) of valve V1, into a fluid line311, past temperature sensor T1, and into pump P1. At this stage of operation, pump P1pumps water at a flow rate in a range of about 200 mL/min to about 600 mL/min, and heat exchanger HX is powered to maintain a fluid temperature at a set point in a range of about 15° C. to about 42° C.

If temperature sensor T1detects a water temperature of greater than about 42° C., then a message is displayed on the display screen148to advise a user that the water temperature is too warm, valve V1is closed, and pump P1is turned off and to prevent additional water from entering the fluid circuit350. If temperature sensor T1detects a water temperature of less than or equal to about 42° C., then ports (a) and (c) of valve V1remain open, and pump P1pumps the water through a fluid line312into the sorbent cartridge303, into a fluid line313, past ammonia sensor NH, and into the primary reservoir304. At this stage of operation, the sorbent cartridge303purifies the water circulating in the fluid circuit350, such that the water meets or exceeds water quality standards for drinking water as set by the Environmental Protection Agency (EPA) and water quality standards for hemodialysis water as set by the Association for the Advancement of Medical Instrumentation (AAMI) standard.

Once the primary reservoir304collects about 100 mL to about 500 mL of water, then pump P2is turned on and pumps water into a fluid line314, through pump P2, into a fluid line315, past conductivity sensor CT1, and past the heat exchanger HX1, which heats the water in the fluid line315to the set point temperature. Pump P2is controlled to pump water at a flow rate that is about equal to the flow rate at which water is pumped by pump P1. Water moves from the fluid line315through ports (c) and (a) of valve V2, into a fluid line316, through ports (b) and (a) of valve V7, into a fluid line317, through ports (c) and (a) of valve V5, into a fluid line318, and further into the bag308until the bag308is filled to about 3.5 L to about 4.0 L with water (e.g., dilution water).

Next, ports (a) and (c) of valve V5are closed, port (a) of valve V7is closed, and port (c) of valve V7is opened such that the pump P2pumps water into a fluid line319, through ports (c) and (a) of valve V6, into a fluid line320, and further into the bag306until the bag306is filled to capacity with water to produce the electrolyte solution. Ports (a) and (c) of valve V6are closed, port (c) of valve V7is closed, port (a) of valve V7is reopened, and ports (b) and (c) of valve V5are opened. Pump P2then pumps water into the fluid line317, through ports (c) and (b) of valve V5, into a fluid line321, and further into the bag309until the bag309is filled to capacity with water to produce the bicarbonate solution.

At this point in the priming stage, the set point temperature of the heat exchanger HX is increased to a range of about 31° C. to about 39° C. (e.g., where 39° C. is the maximum temperature achievable by heat exchanger HX), and the flow rate of pump P2is reduced to a value within a range of about 100 mL/min to about 300 mL/min to increase an exposure time of the water within the heat exchanger HX for achieving the higher set point temperature. Ports (b) and (c) of valve V5are closed, port (a) of valve V7is closed, port (c) of valve V7is opened, and ports (b) and (c) of valve V6are opened. Accordingly, pump P2pumps water into the fluid line319, though ports (c) and (b) of valve V6, into a fluid line322, and further into the bag307until the bag307is filled to capacity to produce the salt-dextrose solution. The higher set point temperature of heat exchanger HX facilitates dissolution of the salt-dextrose substance with the water flowing into the bag309. At this point during the fluid conditioning cycle, the priming stage concludes, the prime tank302has substantially emptied, the pumps P1, P2are turned off and the infusion stage can begin. The priming stage typically lasts a duration of about 10 min to about 30 (e.g., about 20 min).

FIG.19illustrates operation of the fluid conditioning system100during the infusion stage, in which bicarbonate, salt, and dextrose are added to the water in the fluid circuit350to produce dialysate. In particular, bicarbonate, salt, and dextrose are added to the water in a controlled manner (e.g., under flow rate control) until the salt and dextrose reach physiologically acceptable concentrations and until the bicarbonate yields a physiologically acceptable fluid conductivity and fluid pH. During the infusion stage, heat exchanger HX is powered to maintain a fluid temperature at a set point in a range of about 35° C. to about 39° C.

At the beginning of the infusion stage, valve V7is closed, port (a) of valve V2closes, port (b) of valve V2opens, ports (a) and (b) of both valves V3and V4open, port (b) of valve V1opens, port (a) of valve V1closes, ports (b) and (c) of valve V6remain open, and ports (b) and (c) of valve V5open. Pumps P1, P2are immediately turned on to pump water at a flow rate in a range of about 300 mL/min to about 600 mL/min within the fluid circuit350. At the same time, pumps P3and P4are turned on. Pump P3pumps bicarbonate solution out of the bag309at a flow rate of about 10 mL/min to about 100 mL/min, into the fluid line317, through the pump P3, and into the fluid line314. Pump P4pumps salt-dextrose solution out of the bag307at a variable flow rate into the fluid line319, through pump P4, and into the fluid line314. The flow rate at which P4initially pumps fluid is in a range of about 1 mL/min to about 100 mL/min. The flow rate is gradually stepped down by a factor of 2 at periodic time increments of about 1 min. The flow rates of pumps P3and P4are set to completely add the infusion volume respectively of the BC solution and the SD solution over a single revolution around the fluid circuit350. Accordingly, the flow rates of pumps P3and P4depend on the flow rates of pumps P1and P2during the infusion stage. For example, if the flow rates of pumps P1and P2are set to 200 mL/min, then the flow rates of pumps P3and P4will be relatively slow. Conversely, if the flow rates of pumps P1and P2are set to 600 mL/min, then the flow rates of pumps P3and P4will be relatively fast.

Once the bag307empties of the salt-dextrose solution, port (b) of valve V6closes, and port (a) of valve V6opens to allow pump P4to pump the electrolyte solution out of the bag306at a flow rate of about 0.1 mL/min to about 5 mL/min into the fluid line314. Once the electrolyte solution reaches valve V3, the infusion stage concludes, and the treatment stage can begin. The dialysate may continue to circulate around the fluid circuit350through fluid lines311,312,313,314,315,323,336,326until the treatment stage begins. The infusing stage typically lasts a duration of about 5 min to about 6 min.

FIG.20illustrates operation of the fluid conditioning system100during the treatment stage, in which bicarbonate, salt, and dextrose are added to the water in the fluid circuit350to produce dialysate. The treatment stage includes a first phase in which bicarbonate solution is used to regulate a conductivity of the dialysate and a second phase in which dilution water is used to regulate a conductivity of the dialysate. Pumps P1, P2pump dialysate at a flow rate in a range of about 200 mL/min to about 600 mL/min. The set point temperature of heat exchanger HX is maintained at a physiologically acceptable temperature in an acceptable range of about 35° C. to about 39° C. (e.g., about 37° C.), as specifically selected by a user of the fluid conditioning system100to suit patient comfort. At any point during the treatment stage, if the dialysate fluid temperature measured at CT2is outside of a range of about 35° C. to about 42° C., then the fluid conditioning system100will enter a bypass mode in which dialysate will flow through fluid line336to bypass flow through the dialysis system301via fluid lines324,325. While the fluid conditioning system100is operating in the bypass mode, a message will displayed on the display screen148indicating that the fluid temperature is too low or too high. The fluid conditioning system100will remain in bypass mode until the fluid temperature stabilizes within the acceptable range.

During the first phase of the treatment stage, port (b) of valve V3is closed, port (c) of valve V3is opened to allow pump P2to pump “fresh” dialysate (e.g., cleaned, conditioned dialysate) through a fluid line324and into the dialysis system301, port (a) of valve V4is closed, and port (c) of valve V4is opened to allow pump P1to pump “spent” dialysate (e.g., contaminated dialysate) through a fluid line325out of the dialysis system301and further into a fluid line326. Accordingly, a bypass fluid line336that extends between valves V3, V4is closed. The spent dialysate has been infused with ultra-filtrate from the patient's blood within the dialysis system301. The ultra-filtrate carries toxic substances, such as urea, all of the small water-soluble uremic toxins, and other toxic substances (e.g., guanidosuccinic acid, methylguanidine, 1-methyladenosine, 1-methylinosine, N2,N2-dimethylguanosine, pseudouridine, arab(in)itol, mannitol, α-N-acetylarginine, orotidine, oxalate, guanidine, erythritol, creatine, orotic acid, phenylacetylglutamine, creatinine, myoinositol, γ-guanidinobutyric acid, β-guanidinopropionic acid, (symmetric dimethyl-arginine) SDMA, asymmetric dimethyl-arginine (ADMA), sorbitol, uridine, and xanthosine).

From the fluid line326, the spent dialysate is pumped through ports (b) and (c) of valve V1, the fluid line311, pump P1, the fluid line312, and into the sorbent cartridge303. Within the sorbent cartridge303, the toxic substances are removed from (e.g., filtered out of) the spent dialysate to produce “regenerated” dialysate (e.g., cleaned, unconditioned dialysate) that flows out of the sorbent cartridge303and into the fluid line313, past the ammonia sensor NH, and into the primary reservoir304. In some cases, a volume of the regenerated dialysate within the primary reservoir304exceeds a capacity of the primary reservoir304and therefore flows through a fluid line327into the secondary reservoir305, which remains in fluid communication with the primary reservoir304throughout the treatment stage. Pump P2pumps regenerated dialysate out of the primary reservoir304, into the fluid line314, and into pump P2. While the regenerated dialysate exiting the sorbent cartridge303has been stripped of toxic substances that were absorbed from the patient's blood in the dialysis system301, the regenerated dialysate must be further conditioned to meet acceptable physiological properties before being circulated back into the dialyzer337of the dialysis system301as fresh dialysate.

Accordingly, pump P4continues to pump the electrolyte solution out of the bag306and into the fluid line320, through ports (a) and (c) of valve V6, into an upper segment of the fluid line319, through pump P4, and into the fluid line314at a flow rate that depends on (e.g., is a fraction of) the flow rate at which pump P2pumps dialysate. Thus, pumps P2, P4together form a closed pump control loop332that governs the flow rate at which pump P4pumps the electrolyte solution, which is in a range of about 0.5 mL/min to about 5 mL/min. Furthermore, pump P3continues to pump either the bicarbonate solution out of the bag309or the dilution water out of the bag308, through port (c) of valve V5, into an upper segment of the fluid line317, through pump P3, and into the fluid line314to further condition the dialysate.

As the dialysate passes through pump P2and conductivity sensor CT1, the conductivity sensor CT1detects a conductivity of the dialysate. Based on continuous measurements of the conductivity of the dialysate, either the bicarbonate solution or the dilution water will be continuously selected for addition to the dialysate through port (c) of valve V5, and the flow rate at which pump P3pumps dialysate will be continuously adjusted to maintain a conductivity of the dialysate within a physiologically acceptable range of 13.5 mS/cm to 14.2 mS/cm. Generally, as a difference between the measured conductivity and an acceptable conductivity increases, the flow rate at which the pump P3pumps fluid increases. Accordingly, as the difference between the measured conductivity and the acceptable conductivity decreases, the flow rate at which the pump P3pumps fluid decreases. In this manner, the conductivity meter CT1and the pump P3together form a closed pump control loop331that regulates a flow rate at which the pump P3pumps fluid. If the conductivity of the dialysate is too low during the first phase of the treatment stage, then bicarbonate solution is infused into the dialysate to raise the conductivity.

After passing the conductivity sensor CT1, the dialysate flows past the heat exchanger HX and temperature sensor T2. Based on a fluid temperature detected by temperature sensor T2, a power level of the heat exchanger HX will be adjusted to maintain the temperature of the dialysate at the set point temperature of the heat exchanger HX. In this way, temperature sensor T2and heat exchanger HX form a closed heater control loop333. The dialysate flows from the fluid line315through ports (c) and (b) of valve V2into the fluid line323and past conductivity sensor CT2. As the dialysate passes conductivity sensor CT2, conductivity sensor CT2performs a second check (e.g., downstream of heat exchanger HX) to detect a conductivity of the dialysate.

If the conductivity of the dialysate is outside of the acceptable range (e.g., either too low or too high), but within a predetermined range (e.g., that is broader than the acceptable range), then a safety system in electrical communication with the conductivity sensor will adjust a flow rate of infusion of the bicarbonate solution or the dilution water to achieve a conductivity within the acceptable range. If the conductivity level of the dialysate is outside of the predetermined physiologically safe range, then, in some implementations, the fluid conditioning system100will attempt to restore the safe fluid parameters and continue the treatment. For example, valves V3and V4will adjust to direct fluid through the bypass fluid line336and close fluid lines324,325until a time at which the conductivity has again stably reached a physiologically safe range, at which time valves V3, V4will adjust to close the bypass fluid line336and direct fluid to and from the dialysis system301via fluid lines324,325. In some implementations, a user may also be instructed to check that fluid levels of the bicarbonate solution and the dilution water are non-zero upon return of the conductivity to a physiologically safe range.

Over time, the sorbent cartridge303changes a composition of the regenerated dialysate exiting the sorbent cartridge303during the first phase of the treatment stage (e.g., an early, initial phase in which the patient's blood is initially circulated through the dialysis machine301). For example, during the first phase of the treatment stage, levels of toxic substances within the spent dialysate are relatively high. The sorbent cartridge303converts urea into ammonium and captures the ammonium within one or more filtration layers within the sorbent cartridge303to remove the ammonium from the dialysate. While the filtration layers capture the ammonium, the filtration layers release sodium cations and other cations into the dialysate via cation exchange, which increases the conductivity and/or decreases the pH of the regenerated dialysate exiting the cartridge303.

Over the course of the first phase of the treatment stage, spent dialysate entering the sorbent cartridge303contains fewer toxic substances (e.g., as uremic toxins are removed from the patient's blood), and the sorbent cartridge303releases more sodium cations. Therefore, the conductivity of the dialysate exiting the sorbent cartridge303gradually increases over time. Once the conductivity of the dialysate reaches a predetermined value in a range of about 13.8 mS/cm to about 14.0 mS/cm, the first phase of the treatment stage in which bicarbonate is used to regulate the conductivity of the dialysate concludes, and the second phase of the treatment stage begins.

During the second (e.g., later, final) phase of the treatment stage, bicarbonate is no longer used to regulate (e.g., increase) the conductivity of the dialysate, and dilution water is the sole substance at valve V5that is used to regulate (e.g., decrease) the conductivity of the dialysate until the end of the treatment stage (e.g., the end of the second phase). Accordingly, port (b) of valve V5is closed, while port (a) of valve V5is opened. If the conductivity of the dialysate is too high during the second phase of the treatment stage, then dilution water is infused into the dialysate to lower the conductivity of the dialysate.

Over the course of the second phase of the treatment stage, an amount of ammonium captured in the sorbent cartridge303increases, such that a capacity of the sorbent cartridge303to absorb additional ammonium gradually decreases, and a level of ammonia within the regenerated dialysate eventually increases, once the capacity of the sorbent to adsorb ammonium is exhausted. The ammonia sensor NH detects the level of ammonia within the regenerated dialysate at a location downstream of the sorbent cartridge303.

The treatment stage (e.g., including both the first and second phases) typically lasts a duration of about 120 min to about 300 min. For example, 240 minutes (e.g., 4 hours) is a standard duration that typically achieves adequate treatment for the vast majority of patients. Furthermore, most treatment stages will end after four hours without reaching the threshold ammonium concentration of 2 mg/dL (e.g., without ever approaching exhaustion of the filtering capabilities of the sorbent cartridge303). The fluid conditioning system100will sound an audio alert signifying that the treatment completed successfully and that the patient can disconnect himself or herself from the dialyzer337. However, if the ammonium level in the dialysate (e.g., as detected by the ammonia sensor NH) indicates that the sorbent cartridge303is no longer absorbing enough ammonium from the spent dialysate to maintain the ammonium level at or below an acceptable value of about 2 mg/dL prior to the standard treatment duration, then the treatment stage will conclude prematurely. Such conditions may occur occasionally for larger patients that have very high blood urea nitrogen (BUN) levels.

Throughout the fluid conditioning cycle, pressure transducers PT1, PT2, PT3, PT4detect fluid pressures to regulate pump flow rates. For example, during all stages (e.g., the priming, infusion, and treatment stages) of the fluid conditioning cycle, pressure transducer PT1forms a closed pump control loop328with pump P1by detecting a fluid pressure of the dialysate within the fluid line312(e.g., located downstream of pump P1) and providing a feedback signal to pump P1indicative of the fluid pressure. Based on the fluid pressure of the dialysate, an angular speed (e.g., an RPM level) of pump P1is adjusted to maintain the flow rate within a desired range. During the treatment stage of the fluid conditioning cycle, pressure transducer PT4forms an additional closed pump control loop329with pump P1by detecting a fluid pressure of the dialysate exiting the dialysis system301(e.g., upstream of pump P1) and providing a forward signal to pump P1indicative of the fluid pressure. Based on the fluid pressure of the dialysate, the angular speed of pump P1is adjusted to closely match the flow rate at pump P1with that of the dialysate exiting the dialysis system301. Accordingly, the fluid pressure of the dialysate within the fluid line312(e.g., downstream of pump P1) is at least in part affected by the fluid pressure of the dialysate exiting the dialysis system301(e.g., upstream of pump P1).

Similarly, during all stages (e.g., the priming, infusion, and treatment stages) of the fluid conditioning cycle, pressure transducer PT2forms a closed pump control loop330with pump P2by detecting a fluid pressure of the dialysate within the fluid line315(e.g., located downstream of pump P2) and providing a feedback signal to pump P2indicative of the fluid pressure. Based on the fluid pressure of the dialysate, an angular speed of pump P2is adjusted to maintain the flow rate within a desired range. During the treatment stage of the fluid conditioning cycle, the flow rate at which pump P3pumps fluid is regulated by a feedback signal from conductivity meter CT1to form the pump control loop331, and the flow rate at which pump P4pumps the electrolyte solution is regulated by a feedback signal from pump P2to form the pump control loop332, as discussed above.

During all stages of the fluid conditioning cycle, pressure transducers PT3and PT4detect operation of the dialyzer337. If measurements at pressure transducers PT3and PT4indicate that there is no fluid flow through the dialyzer337, then the fluid conditioning system100will enter the bypass mode to flow dialysate through fluid line336and to avoid delivering dialysate to the dialysis system301via fluid lines324,325.

FIG.21provides a block diagram of the control system161. The control system161includes a processor410, a memory420, a storage device430, and an input/output interface440. In some embodiments, the control system161includes more than one processor410, memory420, storage device430, and/or input/output interface440. Each of the components410,420,430, and440can be interconnected, for example, using a system bus450. The processor410is capable of processing instructions for execution within the control system161. The processor410can be a single-threaded processor, a multi-threaded processor, or a quantum computer. The processor410is capable of processing instructions stored in the memory420or on the storage device430.

The memory420stores information within the control system161. In some implementations, the memory420is a computer-readable medium. The memory420can, for example, be a volatile memory unit or a non-volatile memory unit. The storage device430is capable of providing mass storage for the control system161. In some implementations, the storage device430is a non-transitory computer-readable medium. The storage device430can include, for example, a hard disk device, an optical disk device, a solid-state drive, a flash drive, magnetic tape, or some other large capacity storage device. The storage device430may alternatively be a cloud storage device, e.g., a logical storage device including multiple physical storage devices distributed on a network and accessed using a network.

The input/output interface440provides input/output operations for the control system161. In some implementations, the input/output interface440includes one or more of network interface devices (e.g., an Ethernet card), a serial communication device (e.g., an RS-232 10 port), and/or a wireless interface device (e.g., an 802.11 card, a 3G wireless modem, or a 4G wireless modem). In some implementations, the input/output device includes driver devices configured to receive input data and send output data to other input/output devices, e.g., keyboard, printer and display devices (e.g., the display screen148). In some implementations, mobile computing devices, mobile communication devices, and other devices are used.

In some implementations, the input/output interface440includes at least one analog-to-digital converter441. An analog-to-digital converter converts analog signals to digital signals, e.g., digital signals suitable for processing by the processor410. In some implementations, one or more sensing elements are in communication with the analog-to-digital converter441, as will be discussed in more detail below.

In some implementations, the control system161is a microcontroller. A microcontroller is a device that contains multiple elements of a computer system in a single electronics package. For example, the single electronics package could contain the processor410, the memory420, the storage device430, and input/output interfaces440.

FIGS.22and23provide block diagrams of a hardware system500and a software system600of the fluid conditioning system100that are provided by the control system161. As shown inFIG.22, the hardware system500is provided by a circuit board for generating GUIs for display on the display screen148and one or more circuit boards135for controlling the electromechanical peripheral components of the fluid conditioning system100, and the various electromechanical peripheral components. The software system600can be broken down into an external view610, an application layer620, and a driver layer630. The external view610includes user interfaces provided by the GUIs, lights, sounds, and debug ports. The application layer620includes business logic, and the driver layer630is configured to implement peripheral-specific code (e.g., communication protocols and stepper motor drivers).

Once the treatment stage concludes, the fluid conditioning system100will drain the fluid circuit350of spent dialysate and dispose of the spent dialysate as waste. There are several ways that the drainage can occur. In one embodiment, the fluid line from that provides spent dialysate to the dialysis system is disconnected. The end of that line is then connected to a drain line, and the other end of that line is clamped shut. The user opens the door on the dialyzer, and the cartridge begins to gravity drain. The system opens fluid paths to initiate its own drain through. Other options involve partially draining the system and allowing the user to remove bags still containing liquid.

Referring toFIGS.24-27, various drain procedures are illustrated, including a gravity drain, an active drain followed by gravity drain, and a fast drain procedure.

FIG.24shows a gravity drain. The dialysis system301is connected to drain as is typical for that system. The fluid line325bringing spent dialysate from the dialysis system301is no longer connected. However, the fluid line324taking fresh dialysate to the dialysis system301is still connected. All pumps are disengaged, and all valves are fully open in all three directions. The dialysis system301is also configured to gravity drain. As a variation of this procedure, either or both fluid lines324,325may be directly connected to a drain line.

FIG.25shows the first step of the combined active drain/gravity drain procedure. The dialysis system301is connected to drain as is typical for that system. The fluid line325bringing spent dialysate from the dialysis system301is no longer connected. However, the fluid line324taking fresh dialysate to the dialysis system301is still connected. This step lasts for a maximum of 33 min, or until PT2and PT3sense a drop in pressure to near atmosphere, whichever comes first. As a variation of this procedure, the fluid line324may be connected directly to a drain line.

FIG.26shows the second step of the combined active drain/gravity drain procedure that allows the system to gravity drain any residual fluid, including fluid in the sorbent and prime tank. Three-way valves are positioned to open all ports. All pumps are disengaged to allow fluid to freely flow through the pump loops. As a variation of this step, one or both fluid lines324,325may be connected to a drain line.

FIG.27shows the fast drain procedure. Both lines that would typically be connected to the dialysis system301are now each connected to drain lines. P1flows in reverse at its maximum flow rate until the primary reservoir304is empty. Meanwhile, P2, P3, and P4are also set to their maximum flow rates in the forward direction. First, valve V5is set to drain BiCarb from bag309, and valve V6is set to drain electrolyte from bag306. The salt/dextrose bag307is already empty, as it is designed to be completely used during the infusion step. Once the system decides that bag309is empty, valve V5changes to empty dilution water from bag308. The system is able to determine when the bags309,308,306are emptied through accounting of pump revolutions, by monitoring pressure, by monitoring conductivity, through the use of flow totalizers (not shown), and/or through user interaction. Once the system detects that all bags are drained, and the sorbent cartridge303is drained, the drain function is over. Some residual fluid may remain in lines.

Methods are described herein for regulating sodium content in the dialysate while using the system100. In these methods, the sorbent cartridge303is used for filtering used dialysis solution in connection with a sodium control system in fluid communication with the sorbent cartridge303and conductivity sensors203, which together regulate the sodium levels within the dialysis solution by controlling conductivity.

Previous sodium-control systems have used a dual-phase sodium regulation. This regulation is in accordance with a prescription guide, generally input by a user, which indicates what desired level of sodium concentration of the dialysate is desired, when averaged over the treatment. During the first treatment phase, a sodium chloride solution is added to the dialysate to regulate its conductivity. Typically, the amount of sodium chloride solution added to drive the relatively low level of sodium in the dialysate up to the prescription average concentration. The amount of sodium chloride added during a treatment can be significant. Then follows a second phase where the sodium concentration increases past the prescription average concentration. During this phase, the system compensates for the excess sodium present above the desired prescription amount by adding dilution water. The amount of dilution water added during a treatment can be significant. The sodium concentration in the dialysate over time thus fluctuates around the prescription average, as the system attempts to maintain the concentration at the prescription average at all times.

Similar toFIG.20described above, the flow path arrangement300ofFIG.28is operated as part of a fluid conditioning system400used with a sodium bicarbonate-based method of regulating sodium in the dialysate. The method used by the fluid conditioning system400ensures that the average sodium concentration of the dialysate for an overall treatment will be about equal to the desired prescription average concentration. The system400includes a sodium controller163that regulates the conductivity. The sodium control system163can be part of, or separate from the control system161.

Referring toFIG.29, the sodium bicarbonate-based method of regulating sodium content used by system400sodium regulation has three phases. Similar to the first phase described above with respect toFIG.20, during the first phase of the treatment (e.g., the early phase in which the patient's blood is initially circulated through the dialysis machine301) the sorbent cartridge303changes the composition of the regenerated dialysate entering the sorbent cartridge303. As the conductivity of the dialysate is too low during the phase I of the treatment stage (e.g., far below the prescription value) bicarbonate solution in the form of sodium bicarbonate contained in the bag309for containing a BC solution is infused into the dialysate.

During use, the sorbent cartridge303converts patient urea into ammonium and captures the ammonium within the filtration layers within the sorbent cartridge303to remove the ammonium from the dialysate. As the ammonium is captured, the filtration layers release sodium (and other cations) into the dialysate via cation exchange. This exchange depends on the concentration of cations in the dialysate entering the sorbent cartridge303, as well as the properties of the sorbent cartridge303. This exchange and the addition of BC solution increases the conductivity of the regenerated dialysate exiting the sorbent cartridge303, as measured by the conductivity sensors203and shown in phase I.

As treatment progresses, the amount of ammonium that has been absorbed by the sorbent cartridge303and amount of sodium ions consequently released eventually results in a dialysate sodium concentration that is the prescribed average concentration. If left unchecked, the conductivity will continue to rise due to exchange caused by the patient's urea, even when BC solution is not added. Dilution water must be added at this stage.

The controller163of system400does not permit the dialysate conductivity to reach the prescribed value. Instead, the controller163directs the system400to stop adding sodium to the dialysate when the measured conductivity range is at a threshold dialysate conductivity value DC1. DC1is lower than target desired prescription conductivity. For example, DC1can be about 12.5 mS/cm. When DC1is reached at time t1, the controller system163stops the influx of sodium bicarbonate. Phase I of the treatment stage concludes, and phase II begins.

During phase II, the conductivity of the dialysate continues to increase. However, this increase is due to the urea (or blood urea nitrogen or BUN) level of the patient, and not from the contents of the bag309. Each patient has a native patient sodium concentration that varies across individuals. The sodium concentrations resulting in ion exchange across the dialyzer337and thus in the effluent exiting the sorbent cartridge303therefore has differing values for each patient. The sodium concentration in the dialysate exiting the sodium cartridge303during phase II is in effect customized to each patient, and his or her native urea level continues to drive the conductivity to the desired level. As a result, the conductivity continues to rise. The rising sodium concentration in dialysate is also a result of urea conversion in the sorbent. Patient urea crosses the dialyzer and enters the sorbent, which contains urease. Urease converts the urea to ammonia and CO2. The ammonia is then converted to ammonium, NH4+, and is captured by the zirconium phosphate (a cation exchanger) in the cartridge that exchanges the NH4+ for hydronium ions and sodium cations.

Phase II stops and phase III begins when the measured conductivity reaches the prescription value DC2. This conductivity prescription value DC2is typically around 13.8 mS/cm. The prescription level can be altered slightly, from about 13.6 mS/cm to about 14.2 mS/cm. For example, the threshold concentration can be 13.6 mS/cm or 13.7 mS/cm, or can be 14.1 mS/cm or 14.2 mS/cm or more for a patient with a larger mass. As in phase II described above with respect to operation of the fluid conditioning system100, during phase III for system400dilution water is infused into the circuit. From this time t2dilution water is then used to regulate (e.g., decrease) the conductivity of the dialysate until the end of the treatment. As illustrated inFIG.29, the dialysate conductivity can fluctuate somewhat around DC2.

In some examples, the system400can detect when the rate of change of the conductivity nears zero. A near-zero value (within a given tolerance) indicates that very little ion exchange is taking place, that is the value of the concentration slows as the final value is reached. The system400then starts phase III.

Advantageously, the bicarbonate-based sodium control method used by system400reduces the amount of total sodium added. The system400stops short of the desired final conductivity level and then lets the patient's own physiology drive the remaining increase in conductivity. In other modes of operation, sodium BiCarb can continue to be dosed to keep the dialysate conductivity higher. The exact choice of how the move from Phase I to II, or from II to III is triggered can depend on patient size, system features, and user preferences (e.g., the physician, technical, or patient). Tens of grams of sodium can be saved compared to adding sodium until the concentration reaches the desired level and then maintaining it at that level. There is less acidic sorbent, less sodium in the dialysate, and the system does not add more sodium than needed for a treatment. Consequently, less dilution water is needed during a treatment. For example, a maximum of 4.5 liters of dilution water is used. Advantageously, patient comfort is increased and the possibility of error reduced.

The system400uses a single prescription, and controls the volume of solution delivered based on conductivity. Individualized prescriptions are not necessary, e.g., prescriptions requiring solutions with differing amounts of powder in the supply bags306,307,309based on each patient's native BUN and prescription sodium concentration. Calculating and mixing of these solutions is not necessary, nor is a prescription guide for each patient. Instead, prior studies of the patient population allow the calculation of the maximum amount of powder that would be required for a treatment (e.g., driving to the threshold value, and a universal bag309can be used. A wide segment of the population can be treated with no system changes. Other benefits of the system400include reduced interaction needed from the patient and prescriber to carry out a treatment.

The sorbent cartridge303is designed such that the system400results in the desired final conductivity prescription. The resulting concentration of the dialysate is based on the amount of cation exchanger in the sorbent cartridge303when it is initially added to the flow path arrangement300. For example, the sorbent cartridge303can include the following layers and materials: hydrous zirconium oxide-chloride (HZO-Cl), acetate, sodium zirconium carbonate or other alkali metal-Group IV metal-carbonate; zirconium phosphate or other ammonia adsorbents; alumina or other like material; alumina supported urease or other immobilized enzyme layer or other material to convert urea to ammonia, such as diatomaceous earth (or silica, ZSM-5, MM-22, etc.) or zirconium oxide; and granular activated carbon, such as charcoal, or other adsorbent. The sodium zirconium carbonate component acts as a phosphate adsorbent. The zirconium oxide can be capable of acting as a counter ion or ion exchanger to remove phosphate, and can be in the form of hydrous zirconium oxide (e.g., hydrous zirconium oxide containing acetate, or chloride).

FIG.30is an example experiment showing dialysate conductivity during the treatment phase of with a simulated 20 L, 30 BUN patient. The different phases of treatment are highlighted. The initial oscillations (before Phase I) result from the infusion pattern used for this experiment. During this time, bicarbonate solution is being infused at 20 mL/min. During Phase I, conductivity is controlled at 13.5 mS/cm with addition of 0.6 M sodium bicarbonate. Once the fluid leaving the reservoir reaches a conductivity of 13.0 mS/cm, or equivalently, once dialysate conductivity reaches 13.5 mS/cm with little to no bicarb addition, then Phase I ends and Phase II begins. In Phase II, no adjustment is made to conductivity with either bicarb or dilution water. Once dialysate conductivity naturally rises to 14.0 mS/cm, Phase III begins. In Phase III, dilution water is infused into the dialysate stream to control dialysate conductivity. In this experiment, conductivity was controlled to 14.0 mS/cm for the first 30 minutes of Phase III; and then at 13.9 mS/cm for the next 30 min; and finally at 13.8 mS/cm for the remainder of treatment.

FIG.31is an example experiment showing dialysate conductivity during the treatment phase of with a simulated 40 L, 60 BUN patient (e.g., a larger patient than for the results shown inFIG.30). The different phases of treatment are highlighted. The initial oscillations (before Phase I) result from the infusion pattern used for this experiment. During this time, bicarbonate solution is being infused at 20 mL/min. During Phase I, conductivity is controlled at 13.8 mS/cm with addition of 0.6 M sodium bicarbonate. Once the fluid leaving the reservoir reaches a conductivity of 13.0 mS/cm, or equivalently, once dialysate conductivity reaches 13.5 mS/cm with little to no bicarb addition, then Phase I ends and Phase II begins. In Phase II, no adjustment is made to conductivity with either bicarb or dilution water. Once dialysate conductivity naturally rises to 13.875 mS/cm, Phase III begins. In Phase III, dilution water is infused into the dialysate stream to control dialysate conductivity. In this experiment, conductivity was controlled to 13.8 mS/cm for the remainder of treatment.

FIG.32is an example experiment showing dialysate conductivity during the treatment phase of with a simulated 60 L, 70 BUN patient (the largest patient of the examples shown). The different phases of treatment are highlighted. The initial oscillations (before Phase I) result from the infusion pattern used for this experiment. During this time, bicarbonate solution is being infused at 20 mL/min. During Phase I, conductivity is controlled to between 13.5 and 13.8 mS/cm with addition of 0.6 M sodium bicarbonate. Once the fluid leaving the reservoir reaches a conductivity of 13.3 mS/cm, or equivalently, once dialysate conductivity reaches 13.8 mS/cm with little to no bicarb addition, then Phase I ends and Phase II begins. In Phase II, no adjustment is made to conductivity with either bicarb or dilution water. Once dialysate conductivity naturally rises to 13.875 mS/cm, Phase III begins. In Phase III, dilution water is infused into the dialysate stream to control dialysate conductivity.

In this experiment, conductivity was controlled to 14.0 mS/cm for the first 30 minutes of Phase III; and then at 13.9 mS/cm for the next 30 min; and finally at 13.8 mS/cm for the remainder of treatment. This experiment shows a brief rise above 14.0 mS/cm within the first 30 minutes of Phase III, which resulted from a momentary suspension of dilution water infusion.

In some embodiments, the rate of change of the conductivity in the dialysate can determine when the system400moves to Phase II and to Phase III. In some embodiments, the transition point from phase I to II depends on the conductivity of the incoming fluid stream. Historically, a conductivity sensor that is post-reservoir but before the infusion point determined the transition point. Here, that conductivity measurement is not used for measurement, since that device no longer exists. Historically there have been phases: first with bicarb conductivity control; second with no infusion since already near the level desired; third being beyond desired level so add dilution water. Urea coming from patient to cartridge is converted to ammonia and adds sodium to the stream.

The conductivity sensor between reservoir304,305and the infusion point (would be located on the fluid line314) determines phase changes. If the conductivity sensor is not located there, the system cannot use sensor CT1between the dialysate pump P2and the heat exchanger HX1since CT1is a conductivity control sensor that is already being used. In normal conditions, sensor CT1is measuring the set point or thereabouts.

Sensor CT1is not used for determining out transition points. Instead, the response of the control system is used to determine transitions by indirectly using a conductivity meter as a readout device (as well as for control) and using response of the meter to the measurement. When the system is close to end of Phase I, due to the nature of the control loop the bicarb pump P3slows down. When beginning Phase I, the bicarb dose is at 40 ml/min. When nearing the end of Phase I, dosing is at lower rate to maintain the same conductivity, approximately 1 ml/min or close to 0 or 5 ml/min. At DC1slope is quite close to zero. After the reservoirs304,305and before infusion (along fluid line314), that curve has increasing dialysate conductivity with time throughout treatment. Bicarb solution is dosed in response to the difference between 13.8 mS/cm (or other desired dose) at t1, and the value before the infusion point and after the reservoir.

In some embodiments, the treatment begins with a low incoming concentration (e.g., below 13.3 mS/cm or 12.5 mS/cm) and gains conductivity at a set amount throughout treatment by dosing from pump4, and dosing in response to the difference to 13.8 mS/cm, which determines concentration added by pump3, in phase I. In Phase II, bicarb is no longer added. Incoming solution from the reservoirs304,305is close to 13.3 mS/cm and additional of electrical solution is ˜0.5 mS/cm. Without dilution or bicarb added it is around 13.8 mS/cm. As treatment continues, patient urea turns into sodium and increases conductivity beyond 13.3 mS/cm coming from reservoirs, and Phase III starts that is the opposite of Phase I. That is, it begins with a low rate of dilution water, and by end of the treatment the flow rate of dilution water has likely increased.

As there is no conductivity meter between the reservoirs and infusion port, the system can use the response of the control system to determine at a given moment the treatment is at which part of a phase. The control system will feedback loop to keep conductivity at CT1to be 13.8 mS/cm. Transition from Phase I to II depends on activity of the P3pump. If the increased flow rate being asked for is very small (near zero) then transition to Phase II. Once in Phase II, the conductivity control loop is reading conductivity, but that measurement is not controlling the pump. CT1is solely a conductivity readout as it is not used as part of the loop. The conductivity of the system will still gradually rise; after reach the set threshold it will return to conductivity control process once again with CT1, switching valves for dilution water rather than bicarb, dependent on the difference to 13.8 mS/cm the system would otherwise be or how much above 13.3 mS/cm the fluid is before the electrolyte is infused but after the reservoir.

In this embodiment, during Phase III there is a plateau and the conductivity value post reservoir and pre-infusion continues to rise and thus progressively the increase amount of dilution water added. Thus the curve shown inFIG.29does not include the oscillation during Phase III. Additionally, the Y axis conductivity measurement refers to the value of the fluid pre-dialysate and post-reservoir before chemical dosing.

Non-limiting examples of urea-degrading enzymes that can be employed in either embodiment of the sorbent cartridge include enzymes that are naturally occurring (e.g. urease from jack beans, other seeds or bacteria), produced by recombinant technology (e.g., in bacterial, fungal, insect or mammalian cells that express and/or secrete urea-degrading enzymes) or produced synthetically (e.g., synthesized). In some embodiments, the enzyme is urease.

In certain embodiments, the sorbent cartridge303includes hollow fibers. The hollow fibers can reject positively charged ions, as well as increase the capacity of the cartridge. The hollow fibers can be coated with an ion-rejecting material, which through a water-purification like mechanism allows the urea through but rejects positively charged ions such as calcium and magnesium. The material coating the hollow fibers can be any such material known to one of skill in the art (e.g., fatty acids or polymer chains like polysulfone) that can effectively reject calcium and magnesium and therefore retain the ions in the dialysis solution. Alternatively, the hollow fibers can include an ion-selective nanofiltration membrane with pores sizes that prevent ionic substances from diffusing through the membrane.

A number of embodiments have been described in detail above. However, various modifications to these embodiments may be made without departing from the spirit and scope of the above disclosures. For example, while the fluid conditioning system100has been described and illustrated as including the pressure transducers119(PT1, PT2, PT3, PT4) for regulating pump flow rates, in some embodiments, a fluid conditioning system that is otherwise similar in construction and function to the fluid conditioning system100may alternatively include flow meters instead of pressure transducers for regulating pump flow rates. In some embodiments, a fluid conditioning system that is otherwise similar in construction and function to the fluid conditioning system100may not include pressure transducers or flow meters and may instead be RPM-controlled based on a detailed knowledge of the system operation to regulate pump flow rates.

While the fluid conditioning system100has been described and illustrated as including peristaltic pumps103,104(P1, P2, P3, P4), in some embodiments, a fluid conditioning system that is otherwise similar in construction and function to the fluid conditioning system100may alternatively include a different type of pump, such as an impeller pump, a linear displacement pump, positive displacement pump, or a centrifugal pump.

While the fluid conditioning system100has been described and illustrated as including one overflow reservoir (e.g., the secondary reservoir305), in some embodiments, a fluid conditioning system that is otherwise similar in construction and function to the fluid conditioning system100may include one or more additional overflow reservoirs. For example, in some embodiments, an additional reservoir may be connected to the fluid circuit350upstream of pump P1or downstream of pump P2. In some embodiments, an additional reservoir may have a capacity different than that of either reservoir304or reservoir305or may have a zero volume capacity. In some embodiments, a reservoir may be permanently connected to a drain.

While the heater bag153has been described and illustrated as being arranged downstream of pump P2of the fluid conditioning system100, in some embodiments, a fluid conditioning system that is otherwise similar in construction and function to the fluid conditioning system100may include a heater bag or other heating element that is arranged at a different location along the fluid circuit350in order to achieve optimal temperature control of fluid flowing through the fluid circuit350. For example, in some embodiments, a heater bag may be positioned immediately downstream of the sorbent cartridge303and may be powered based on signals from temperature sensor T1to ensure that the temperature of the dialysis fluid is not high enough to damage internal components of the sorbent cartridge303. In some embodiments, a heater bag may be located along the fluid circuit350anywhere between valve V1and valve V2, as advantageous (e.g., to promote dissolution of the dry chemicals in the supply bags306,307,309).

While the fluid conditioning system100has been described as including three-way valves V1-V7, in some embodiments, a fluid conditioning system that is otherwise similar in construction and function to the fluid conditioning system100may alternatively include one or more two-way valves to achieve the fluid flow path scenarios discussed above.

While an operation of the fluid conditioning system100has been described and illustrated with respect to certain flow rates, fluid volumes, temperatures, pressures, and time periods, in some embodiments, the fluid conditioning system100may be operated to carry out a fluid conditioning cycle with one or more different flow rates, fluid volumes, temperatures, pressures, and time periods, while still functioning to adequately condition dialysate for use in a cooperating dialysis system.

Although the example control system161, the example hardware system500, and the example software system600have been described respectively inFIGS.21-23, implementations of the subject matter and the functional operations described above can be implemented in other types of digital electronic circuitry, or in computer software, firmware, or hardware, including the structures disclosed in this specification and their structural equivalents, or in combinations of one or more of them. Implementations of the subject matter described in this specification can be implemented as one or more computer program products, i.e., one or more modules of computer program instructions encoded on a tangible program carrier, for example a computer-readable medium, for execution by, or to control the operation of, a processing system. The computer readable medium can be a machine readable storage device, a machine readable storage substrate, a memory device, a composition of matter effecting a machine readable propagated signal, or a combination of one or more of them.

The term “computer system” may encompass all apparatus, devices, and machines for processing data, including by way of example a programmable processor, a computer, or multiple processors or computers. A processing system can include, in addition to hardware, code that creates an execution environment for the computer program in question, e.g., code that constitutes processor firmware, a protocol stack, a database management system, an operating system, or a combination of one or more of them.

A computer program (also known as a program, software, software application, script, executable logic, or code) can be written in any form of programming language, including compiled or interpreted languages, or declarative or procedural languages, and it can be deployed in any form, including as a standalone program or as a module, component, subroutine, or other unit suitable for use in a computing environment. A computer program does not necessarily correspond to a file in a file system. A program can be stored in a portion of a file that holds other programs or data (e.g., one or more scripts stored in a markup language document), in a single file dedicated to the program in question, or in multiple coordinated files (e.g., files that store one or more modules, sub programs, or portions of code). A computer program can be deployed to be executed on one computer or on multiple computers that are located at one site or distributed across multiple sites and interconnected by a communication network.

Computer readable media suitable for storing computer program instructions and data include all forms of non-volatile or volatile memory, media and memory devices, including by way of example semiconductor memory devices, e.g., EPROM, EEPROM, and flash memory devices; magnetic disks, e.g., internal hard disks or removable disks or magnetic tapes; magneto optical disks; and CD-ROM and DVD-ROM disks. The processor and the memory can be supplemented by, or incorporated in, special purpose logic circuitry. The components of the system can be interconnected by any form or medium of digital data communication, e.g., a communication network. Examples of communication networks include a local area network (“LAN”) and a wide area network (“WAN”), e.g., the Internet.

Other embodiments are within the scope of the following claims.