Patent Description:
The disclosed subject matter relates generally to devices, methods, systems, improvements, and components for preparing medicaments and making medicament available for use by a consumer, for example, a dialysis cycler.

Peritoneal dialysis is a mature technology that has been in use for many years. It is one of two common forms of dialysis, the other being hemodialysis, which uses an artificial membrane to directly cleanse the blood of a renal patient. Peritoneal dialysis employs the natural membrane of the peritoneum to permit the removal of excess water and toxins from the blood.

In peritoneal dialysis, sterile peritoneal dialysis fluid is infused into a patient's peritoneal cavity using a catheter that has been inserted through the abdominal wall. The fluid remains in the peritoneal cavity for a dwell period. Osmotic exchange with the patient's blood occurs across the peritoneal membrane, removing urea and other toxins and excess water from the blood. Ions that need to be regulated are also exchanged across the membrane. The removal of excess water results in a higher volume of fluid being removed from the patient than is infused. The net excess is called ultrafiltrate, and the process of removal is called ultrafiltration. After the dwell time, the dialysis fluid is removed from the body cavity through the catheter. It is referred to <CIT> and <CIT> as prior art.

A method of generating a custom mini batch of dialysate according to the present invention comprises the technical features as defined in independent claim <NUM>.

Methods, device, and systems for preparing medicaments such as, but not limited to, dialysis fluid are disclosed. In embodiments, medicament is prepared at a point of care (POC) automatically using a daily sterile disposable fluid circuit, one or more concentrates to make batches of medicament at the POC. The dialysis fluid may be used at the POC for any type of renal replacement therapy, including at least peritoneal dialysis, hemodialysis, hemofiltration, and hemodiafiltration.

In embodiments, peritoneal dialysis fluid is prepared at a point of use automatically using a daily sterile disposable fluid circuit and one or more long-term concentrate containers that are changed only after multiple days (e.g. weekly). The daily disposable may have concentrate containers that are initially empty and are filled from the long-term concentrate containers once per day at the beginning of a treatment.

Embodiments of medicament preparation, devices, systems, and methods are described herein. The features, in some cases, relate to automated dialysis such as peritoneal dialysis, hemodialysis and others, and in particular to systems, methods, and devices that prepare peritoneal dialysis fluid in a safe and automated way at a point of care. The disclosed features may be applied to any kind of medicament system and are not limited to dialysis fluid.

In embodiments, a system that prepares a medical fluid is configured in such a manner that it outputs the medical fluid to a consuming process (for example, a peritoneal dialysis cycler) wherein the consuming process does not distinguish between the system that prepares the medical fluid and pre-packaged bags of dialysate. This allows embodiments of the presently disclosed system for preparing the medical fluid to be used with any type of a cycler, without any special customization or modification of the cycler.

Objects and advantages of embodiments of the disclosed subject matter will become apparent from the following description when considered in conjunction with the accompanying drawings.

Embodiments will hereinafter be described in detail below with reference to the accompanying drawings, wherein like reference numerals represent like elements. The accompanying drawings have not necessarily been drawn to scale. Where applicable, some features may not be illustrated to assist in the description of underlying features.

<FIG> shows an embodiment of a system that uses water and up to two concentrated medicaments (also referred to as "medicament concentrates" or "concentrates") in containers <NUM> and <NUM> to make a therapeutic fluid that can be used for treatment according to embodiments of the disclosed subject matter. In embodiments, the concentrated medicament in container <NUM> is an osmotic agent. In embodiments, the osmotic agent includes concentrated dextrose solution. In other embodiments, the osmotic agent includes concentrated glucose solution. In embodiments, the concentrated medicament in container <NUM> is an electrolyte concentrate.

Each of the containers <NUM> and <NUM> may be connected to fluid lines <NUM> and <NUM> via a connector <NUM>, as shown. However, it is also possible that each or one of the containers are pre-connected to the fluid lines <NUM> and <NUM>, thus avoiding connectors <NUM>. Osmotic concentrate container <NUM> is fluidly connected to osmotic fluid line <NUM>. An optional one-way check valve (not illustrated) may be provided on fluid line <NUM>. Similarly, electrolyte concentrate container <NUM> is fluidly connected to electrolyte fluid line <NUM> and may include one-way check valve (not shown). These one-way check valves are optional and may be omitted. One-way check valves may be beneficial when multiple batches of medicament are made without changing concentrate containers, as they prevent contamination from reaching the concentrated medicament containers <NUM> and <NUM>. Osmotic fluid line <NUM> is controlled by osmotic valve <NUM>. Electrolyte fluid line <NUM> is controlled by electrolyte valve <NUM>. These valves can open and close under the control of a controller, such as controller <NUM>.

The concentrate lines <NUM> and <NUM> pass through the valves <NUM> and <NUM>, respectively. The lines and then continue and merge before they passed through a single sterilizing filter <NUM>. The sterilizing filter <NUM> may be a <NUM> filter, or similar. In an embodiment, the filter has a pore size of <NUM> micrometers. As can be appreciated from <FIG>, sterilizing filter <NUM> is fluidly connected to pressure sensor <NUM> and the peristaltic pump <NUM>. It will be appreciated that whenever of the peristaltic pump <NUM> operates (rotates to thereby convey fluid through a pumping tube segment) it generates pulsatile pressure in fluid line <NUM>. This pulsatile pressure acts on the membrane of sterilizing filter <NUM>. Because there are no valves disposed between peristaltic pump <NUM> and the sterilizing filter <NUM>, filter <NUM> always experiences this pulsatile pressure when the peristaltic pump <NUM> operates. Providing a single sterilizing filter <NUM> which sterilizes both the content of the osmotic concentrate container <NUM> as well as the contents of the electrolyte concentrate container <NUM> reduces the cost of the disposable unit <NUM> but exposes filter <NUM> to the pulsatile pressure of the pump <NUM>.

To mitigate the risk of damaging the membrane of sterilizing filter <NUM> in such a way that pathogens could pass through the membrane, a filter integrity test configuration is provided. An air pressure pump <NUM> is provided and connected through a connector <NUM> to a pressure test line <NUM> which further connects to filter <NUM>. In embodiments, connector <NUM> may include a pressure transducer and may provide an output to controller <NUM>.

Testing of sterilizing filter <NUM> using pressurized air testing can be done in various ways, for example, a bubble point test can be performed. Bubble point refers to the pressure at which the first flow of air through a liquid saturated membrane of filter <NUM> first occurs and it is a measure of the largest pore-throat in the membrane. The bubble point method is based on the principle that the critical pressure of an airflow applied across the thickness of a membrane evacuates the fluid trapped in the pore with the largest pore-throat. Therefore the applied pressure must exceed the capillary pressure of the fluid in the largest pore-throat. In testing, the membrane is saturated with a liquid. The gas pressure on the upstream face of the saturated membrane is then increased to a pressure when the first air bubble passes through the largest pore-throat in the saturated fabric. An expected bubble pressure of an intact filter membrane may be stored, and a new measurement of bubble pressure may be taken periodically (once the membrane of filter <NUM> is wetted with a fluid, whether a concentrated medicament, water, or a mixture of water and concentrated medicament). The new measurement may be compared with the stored expected bubble pressure, and if the new measurement is below the expected value by a threshold amount, a filter failure is signaled.

If a filter failure is signaled, the contents of the mixing container <NUM> may be deemed to be unusable and may be drained and discarded by placing the fluid circuit into the configuration illustrated in <FIG>. In an embodiment, the filter integrity test takes place after each of the osmotic concentrate and the electrolyte concentrate are provided into the mixing container <NUM>, and after water is mixed with the concentrate in the mixing container <NUM>. This way, the filter failure can be detected and signaled earlier in the process so that remedial steps can be taken. In embodiments, a filter integrity test takes place during the time that the contents for the mixing container <NUM> are being mixed which is illustrated in the configuration of <FIG>. In embodiments, the filter integrity test takes place after the final amount of water has been conveyed into the mixing container <NUM>, but before the mixing process is complete.

In embodiments, a pressure decay test can be done instead of a bubble test to test the integrity of the membrane of filter <NUM>, where fluid is pumped across the membrane and the pressure drop measured and compared with a pressure drop representative of an intact filter or pressure is increased on one side, pumping stopped, and the rate of decay of pressure compared to a predefined curve representative of an intact filter. In other embodiments, the filter <NUM> is housed in an air-tight container and the container is pressurized to a level that is below the expected bubble point, but high enough to guarantee that the membrane is sterilizing grade. The filter <NUM> may have air vents so this pressurizes the membrane. The rate of (air) pressure decay is then measured and if the decay rate is greater than a predefined threshold rate, the filter is indicated to have failed.

Other means of testing filter integrity may be used, for example, concentrates <NUM> and/or <NUM> can include a large-molecule excipient whose presence can be detected using automatic chip-based analyte detection (e.g., attachment of fluid samples to selective fluorophore after flowing through the filter and optical detection after concentration).

Still referring to <FIG>, a purified water source <NUM> with a water pump <NUM> supplies highly purified water through a connector <NUM> through a water line <NUM>. The water line <NUM> has a non-reopenable clamp <NUM>, another connector <NUM>, a manual tube clamp <NUM>, and a pair of redundant <NUM>-micron sterilizing filters <NUM>, as shown. In embodiments, different types of sterilizing filters may be used, and not limited to <NUM> micron, or to two redundant filters. For example, a single filter may be used, and a testing protocol provided to ensure that the filter does not fail before replacement.

A water inlet clamp <NUM>, batch release clamp <NUM>, and a conductivity sensor clamp <NUM> are controlled by a controller <NUM>, which may be operatively coupled to a user interface <NUM>, which may include a visual and/or audible output and various devices for receiving user input. The controller <NUM> controls the pinch clamps and a peristaltic pump <NUM> to make a batch of diluted concentrate in a mixing container <NUM> by diluting medicament concentrate (e.g., dialysis fluid concentrate) in the mixing container <NUM>. The mixing container <NUM> is supplied empty and permanently connected to a fluid circuit that includes fluid lines <NUM>, <NUM>, and <NUM>. In embodiments, the mixing container <NUM> may be detached initially, and attached to the rest of the fluid circuit which forms the disposable component <NUM> prior to the preparation of medicament.

A pressure sensor <NUM> is provided in the flow path as shown and outputs a signal representative of the pressure in the fluid lines that are fluidly connected to the pressure sensor. This pressure signal may be provided to controller <NUM>.

In embodiments, the pressure sensor <NUM> may be used, at least partially, to perform the filter integrity tests described above. The pressure sensor <NUM> is in fluid communication with the filter <NUM> and can be used to measure the pressure on one side of the membrane of the filter <NUM>, to perform e.g., a pressure decay test.

The mixing container <NUM> may be a part of a disposable unit or component <NUM> that is replaced regularly, such as with each batch, every day, every week, or every month. In an embodiment, the mixing container <NUM> is empty initially when the disposable component <NUM> is connected to the system.

The mixing container <NUM> may be made of a flexible material, such as a polymer so its shape is not rigid. To provide support for the mixing container <NUM>, it is held by a tub <NUM> which is sufficiently rigid to support the mixing container <NUM> when it is full of fluid. A leak sensor <NUM> is provided in the tub <NUM> and it detects leaks into the tub <NUM> while a temperature sensor <NUM> may also be provided in or on the tub <NUM> and it detects the temperature of the fluid in the mixing container <NUM>. A warmer <NUM> may be provided as shown to provide heat to tub <NUM>, but the warmer <NUM> may be omitted if another heater exists elsewhere in the system. Note that the concentrates <NUM> and <NUM> that will be supplied to the mixing container <NUM> may be used for making any type of medicament, not just dialysis fluid.

A cracking pressure check valve <NUM> is provided on inlet line <NUM>. The check valve <NUM> prevents flow in line <NUM> out of mixing container <NUM> and allows flow into mixing container <NUM> only when the cracking pressure is overcome. The cracking pressure may be selected at <NUM> PSI (<NUM> PSI = <NUM> Pa) in embodiments. As described in greater detail below, using the check valve <NUM> allows for different fluid line configurations. In addition to the check valve <NUM>, a controllable valve (supply line clamp <NUM>) is provided on the supply line <NUM>.

Likewise, a check valve may be added to the concentrate supply lines <NUM> and <NUM> (not shown), preventing back flow of concentrate into the containers <NUM> and <NUM>. In embodiments, this allows for the safe preparation of multiple batches of diluted medicament from the same containers of concentrate, as back flow (which is undesirable) into the concentrate container is prevented.

To supply water to mixing container <NUM>, pump <NUM> runs to move the water from water line <NUM> to supply line <NUM> and mixing container <NUM> while valve <NUM> is open, as shown in <FIG>. The water may be provided by the purified water source <NUM> and its pump <NUM> at a pressure that is below the cracking pressure of check valve <NUM>, so that no water will flow through inlet <NUM>, but only through inlet <NUM>, even if valve <NUM> were opened. But during normal water filling operation, valve <NUM> may remain closed, as shown in <FIG>.

The mixing container at <NUM> may be part of the disposable unit <NUM>. Included in a disposable unit <NUM> are the two concentrate supply lines <NUM> and <NUM>, transfer line <NUM>, water source line <NUM>, drain conductivity line <NUM>, medicament supply line <NUM> and the mixing container <NUM> with its respective fill lines <NUM> and <NUM>. The disposable unit <NUM> is permanently interconnected up to and including an end of each of the connectors <NUM>, through which various other components can be connected (including the medicament user <NUM>, the purified water source <NUM>, the osmotic agent concentrate <NUM>, the electrolyte concentrate <NUM>, and the drain connection <NUM>). Also included in the disposable unit <NUM> may be the check valve <NUM> that has a predefined cracking pressure (e.g., <NUM> PSI). The disposable unit <NUM> may also include the sterilizing filter <NUM> which further includes a test line <NUM> with a connector <NUM>. Connector <NUM> will be connected to an airline output of air pressure pump <NUM>. The disposable unit <NUM> can be connected to check valve <NUM> which prevents back flow in the drain line <NUM>.

A door lock <NUM> is provided adjacent a user interface door <NUM> to lock the user interface door. A physical door <NUM> that opens encloses and provides access to the interior of the fluid preparation system may have a user interface on it which may be a part of user interface <NUM>. A door sensor <NUM> detects whether the door lock is in an open or a locked position to ensure that all clamps and the peristaltic pump actuators are fully engaged with the disposable fluid circuit.

The door sensor <NUM> may include a plunger which is pressed in when the door is closed and outputs an electrical signal to indicate whether or not the door is closed. In other embodiments, the door sensor <NUM> may include a magnetic reed switch which detects the presence or the absence of a magnet which is located on the door <NUM> at a location which is detectable by the reed switch. Purified water flows into the disposable circuit where a pair of <NUM>-micron filters (also in the disposable unit <NUM>) are located to ensure that any touch contamination is prevented from flowing into the disposable circuit. An optional sterilizing filter <NUM> may be provided in a user medicament supply line <NUM>. The sterilizing filter <NUM> may be a <NUM> micron filter. The mixing container <NUM> of the disposable unit <NUM> may have sufficient volume for a single treatment or in embodiments, multiple treatments. To make a batch of dilute concentrate, water is pumped into the mixing container <NUM> which contains concentrate sealed in it as delivered.

A conductivity/temperature sensor 159c (control) is provided on or fluidly connected to transfer line <NUM>, as shown. The sensor 159c forms a part of the disposable component <NUM> and may be a type of a conductivity and temperature sensor that allows fluid to flow through it while it detects the temperature and/or the conductivity of the fluid flowing therethrough. In embodiments, the conductivity reading is calibrated by the measured temperature. The output of the sensor 159c is provided to a controller, such as controller <NUM>.

A second conductivity/temperature sensor <NUM> (system) is provided on or fluidly connected to inlet line <NUM>, as shown, and also forms a part of the disposable unit <NUM>. The physical structure of sensor <NUM> may be the same or similar to that of sensor 159c. The output signal from sensor <NUM> may be provided to controller <NUM>.

Both of sensors 159c and <NUM> are shown as being behind the door <NUM> of the system. In this configuration, the internal environment of the system provides temperature stability that isolates the sensors from the outside environment and may improve measurement accuracy. In embodiments, the sensors 159c and <NUM> physically mate to internal structures behind the door <NUM> and thereby allow the system to detect whether the sensors 159c and/or <NUM> are present. In embodiments, there are multiple different configurations of disposable element <NUM>, and some configurations do not include one or both of the sensors, and the position of the sensors on the disposable element <NUM>, as shown, allows the system to detect and in certain situations to self-configure to adapt based on the presence or absence of the two sensors. In embodiments, one or more separate optional conductivity sensors can be provided on line <NUM> (not shown in the figure) that can measure conductivity and/or temperature of fluid flowing through drain line <NUM> toward drain connection <NUM>. If sensors 159c and <NUM> are not detected on the disposable component <NUM>, the system may adapt and rely on the (unillustrated) conductivity/temperature sensor(s) on the drain line <NUM> to measure conductivity of fluid.

The medicament output line <NUM> may include an optional air removal filter <NUM>. The air removal filter <NUM> may be a <NUM> filter which removes air from the medicament supplied through medicament supply line <NUM> before it reaches the medicament user <NUM>.

A check valve <NUM> in drain conductivity line <NUM> ensures the flow does not reverse to safeguard against contamination in the medicament or water lines or other sterile fluid circuits.

Because conductivity/temperature sensor(s) 159c and <NUM> are provided on the fluid circuit as shown in <FIG>, it is possible to control various valves to establish a loop through which fluid from the mixing container flows while the conductivity of the fluid is tested, but little, if any, fluid is wasted. Various examples of a physical configuration of the fluid circuit are shown in <FIG>. Valves <NUM>, <NUM>, <NUM>, <NUM>, <NUM> are closed while valve <NUM> is opened and peristaltic pump <NUM> operates to draw fluid through inlet line <NUM> and to circulate the fluid along line <NUM> through or past sensor 159c and then through or past sensor <NUM>. The fluid is pumped at a pressure above the cracking pressure of valve <NUM> so the fluid continues to flow back into the mixing container <NUM> through inlet line <NUM>. This process continues as long as the valves remain closed and the peristaltic pump <NUM> operates. It will be understood that during this process the contents of the mixing container <NUM> is mixed, which helps provide stable reading of conductivity in the sensors 159c and <NUM>.

Referring now to <FIG>, at S201 the fluid circuit will be configured as shown in <FIG>. In this procedure multiple consecutive measurements are made of conductivity and temperature at consecutive times so that the conductivity is measured and a trend can be observed to determine whether the conductivity has reached a steady state value. At each measurement time, a separate value can be produced from sensor 159c and a separate value can be produced from sensor <NUM>. By comparing the two values, it is possible to confirm whether the sensors are within some expected range. If the two sensor readings are within an expected range of values, it may be determined that both sensors are working correctly. On the other hand, if the values differ by some predetermined threshold, the process may conclude that one or both of the sensors are malfunctioning at S205 and output a gross error warning at S227.

In embodiments, only a single sensor 159c or <NUM> may be provided. Multiple readings may be taken from such a single sensor, and compared to an expected value. If one or more of the multiple readings differ from the expected value by a predetermined threshold, another gross error in conductivity may be detected at output as a warning or an error message in S227.

The conductivity is sampled until it reaches a steady state at S203. If the steady state is reached before of time out, another comparison to an expected value can be performed at S205 to determine whether a gross error in conductivity has occurred. If the steady state is not reached before the time out, no measurement is output at S225.

If the steady state is reached and the value that is read does not indicate a gross error, a measurement is output and may be provided to controller <NUM>. The measurement may be an average between the values output from sensor 159c and sensor <NUM>. In embodiments, the measurement that is output may be a value that is output from only one of those sensors, or it may be a time average of multiple readings from that one sensor.

Note that temperature-compensated conductivity is intended to refer to a number that is proportional to concentration and may be determined in various ways including but not limited to a lookup table and a formula. For the remainder of this disclosure a reference conductivity the reference may be understood to mean temperature-compensated conductivity or an actual calculation of concentration. That is, the temperature-compensated conductivity may be a value that is generated by the controller by multiplying the measured conductivity with a value that represents the rate of change of concentration with temperature. In other embodiments, the controller <NUM> may calculate a concentration directly using a look-up table or formula.

<FIG> shows a flow chart for a procedure that may be executed by the controller <NUM> with respect to the embodiment of <FIG> to generate medicament. The procedure of <FIG> incorporates the procedure of <FIG> by the reference to "conductivity test" described with reference to the procedure of <FIG>. When the conductivity test is referenced it means the procedure of <FIG> is entered and upon exiting proceeds to the next procedure element in <FIG>.

At S440, water is added to the mixing container <NUM> in an amount that is a fraction of what is determined (or expected) to be required for a complete batch of medicament. The amount of fluid conveyed at S10 may be a fraction of the total estimate required for a sufficient level of dilution, such as <NUM>% of the expected total water volume.

Water is added by pumping it into the mixing container <NUM> from the purified water source <NUM>. This is done by placing the system in the configuration of <FIG>. The water pump <NUM> and the peristaltic pump <NUM> are activated for a predefined number of cycles or a predefined time interval, resulting in a quantify of water being conveyed along water line <NUM>, through opened valve <NUM>, through transfer line <NUM>, through peristaltic pump <NUM> and through connector line <NUM> into mixing container <NUM>.

At this time, a filter integrity test of filter <NUM> may be performed, as the water filling process will have wetted at least one side of the membrane of filter <NUM>. If the filter integrity test returns a filter error, the process may end at S454 with a failed batch. In embodiments the filter integrity test may be omitted in S440 and performed in a later step.

In an embodiment, the entire quantity of osmotic agent concentrate is transferred from container <NUM> to the mixing container <NUM> at S442. The fluid circuit takes on the configuration shown in <FIG> by controlling valve <NUM> to open and operating the peristaltic pump <NUM> in the forward direction as shown by the arrow under the pump <NUM> in <FIG>. Then the contents of the mixing container <NUM> are mixed by placing the fluid circuit into the configuration shown in <FIG>. In other embodiments, less than the entire quantity of osmotic agent concentrate from container <NUM> is conveyed to the mixing container <NUM>, leaving a quantity of the concentrate in the container <NUM> sufficient for making additional batches of dialysate in the future.

At this time, a filter integrity test of filter <NUM> may be performed, as the water filling process will have wetted at least one side of the membrane of filter <NUM> and the osmotic agent passing through filter <NUM> will have completely wetted the filter membrane. If the filter integrity test returns a filter error, the process may end at S454 with a failed batch. In embodiments the filter integrity test may be omitted in S442 and performed in a later step.

The conductivity test described above and illustrated in <FIG> is then performed at S444. If an output of gross error or no measurement is received at S446, then the batch is failed at S454. If a measurement is output control proceeds to S448 and additional water is added to the mixing container <NUM> short of the final amount required to achieve a batch that is usable for the medicament, and the contents of the mixing container <NUM> are mixed again as described above.

The conductivity test is performed again at S450 and if an output of gross error or no measurement is received S452 then the batch is failed at S454.

Otherwise, an amount of electrolyte is calculated, based on the conductivity measurement received, is at S453. Because the osmotic agent and the electrolyte concentrate are provided in separate containers <NUM> and <NUM>, it is possible to generate customized batches of medicament (e.g., dialysate) based on a prescription that is customized for a specific patient. It is also possible to generate smaller quantities of diluted medicament than in a situation where all of the concentrated medicament were to be used at once, which allows for a fast walkup time (e.g., less than <NUM> hour) so a patient can initiate preparation of medicament and then begin therapy in less than an hour.

After the calculation, the appropriate amount of electrolyte concentrate is added to the mixing container <NUM>. The fluid circuit is placed into the configuration illustrated in <FIG>. As shown in the figure, valve <NUM> is opened and the peristaltic pump <NUM> operates in the forward direction to convey the electrolyte concentrate into mixing container <NUM>. It will be appreciated that because the same pump <NUM> is used for metering both the osmotic agent concentrate from container <NUM> and the electrolyte concentrate from container <NUM>, the accuracy of the metering is increased, allowing for high precision in establishing the desired custom concentration of the medicament. Once all of the electrolyte concentrate is added, the contents of the mixing container <NUM> are mixed again as described above.

At this time, a filter integrity test of filter <NUM> may be performed. If the filter integrity test returns a filter error, the process may end at S454 with a failed batch. In embodiments the filter integrity test may be omitted in S456 and performed in a later step.

At S458 the conductivity test is performed again and if a valid measurement is not received at S460, then the batch is failed at S454. If the measurement is received then at S462 a final fraction of water is then calculated based on the valid measurement and added to the mixing container <NUM> by placing the fluid circuit into a configuration as shown in Figs. Then, the contents of the mixing container <NUM> are mixed again as described above.

The conductivity test is performed again at S464. If the measurement is valid at S466, then the batch is made available for use at S468. Otherwise, the batch is failed at S454. Before the batch is made available for use, a filter integrity test of filter <NUM> may be performed. If the filter integrity test returns a filter error, the process may end at S454 with a failed batch.

When the batch is made available, the fluid circuit is configured into the configuration shown in <FIG> or <FIG>, and described below.

Note there may be a single conductivity/temperature sensor, or a pair of conductivity/temperature sensors as shown. A pair of conductivity/temperature sensors may provide a check against poor accuracy or failure of one of the sensors.

<FIG> shows a water treatment plant <NUM> that may constitute an embodiment the purified water source <NUM>. The water treatment plant <NUM> has an initial pretreatment stage that includes a connector <NUM> to connect to an unfiltered water source <NUM>, for example a water tap. The water flows through a check valve <NUM>, through a pressure regulator <NUM>, and then through a sediment filter <NUM>. The check valve <NUM> prevents backflow of the water. The water then flows through an air vent <NUM> that removes air from the water. The water then flows through a connector <NUM> that connects to a water shutoff clamp <NUM>, a snubber <NUM>, and a water inlet pressure sensor <NUM>. Water is pumped by water pump <NUM> which has an encoder <NUM> for precise tracking of the water pump <NUM> speed. The snubber <NUM> reduces pressure fluctuations. The water then flows through a water output pressure sensor <NUM>, through an ultraviolet light lamp <NUM> and into a filter plant <NUM> that performs deionization, carbon filtration, and sterilizing filtration. A UV (ultraviolet) light sensor <NUM> may be provided to detect whether the ultraviolet light lamp <NUM> is operating, so that it can be replaced if it becomes inoperable. A first-use-fuse <NUM> together with a connector <NUM> is provided on the inlet of sterilizing filter plant <NUM>, such that the fuse indicates whether the filter plant <NUM> has been used. This helps reduce the likelihood that a previously-used filter plant is reused unintentionally. A combined control unit and leak sensor are indicated at <NUM>. In the sterilizing filter plant <NUM>, the water flows through a carbon filter <NUM> and three separated bed deionization filters <NUM> which may be resin separated bed filters. The water then flows through a mixed bed deionization filter <NUM>, which follows the separated bed filters <NUM>. The mixed bed deionization filter <NUM> may be a resin mixed bed filter. Thereafter, the water flows through first and second ultrafilters <NUM>, which follow the mixed bed deionization filter <NUM>, and into the consumer of pure water <NUM>. The embodiments of Figs. 1B and <FIG> are examples of a consumer of pure water <NUM>.

Between a last separated bed deionization filter <NUM> and the mixed bed deionization filter <NUM> is a resistivity sensor <NUM> which indicates when the separated bed deionization filters <NUM> are nearing exhaustion, or at exhaustion. The mixed bed deionization filter <NUM> is still able to hold a predefined minimum magnitude of resistivity but the separated bed deionization filters <NUM> and the mixed bed deionization filter <NUM> may be replaced at the same time. In embodiments, along with the separated bed deionization filters <NUM> and the mixed bed deionization filter <NUM>, the carbon filter <NUM> and ultrafilters <NUM> along with the interconnecting lines and other components may also be replaced as a single package. A current treatment can be completed in reliance on the mixed bed deionization filter <NUM> before the exhausted filters are replaced. A further resistivity sensor <NUM> detects unexpected problems with the separated bed deionization filter <NUM> upstream deionization filters which may require shutdown of the treatment and immediate replacement of the filters. Note that each of the ultrafilters <NUM> has an air vent <NUM>. A check valve <NUM> is located downstream of the ultrafilters <NUM>. The consumer of pure water <NUM> may be unit such as that of Figs. 1B or <FIG> which mixes a batch of medicament for use by a medicament user <NUM> such as a peritoneal dialysis cycler or any other type of medicament consuming device.

It should be evident from the above that the procedures of <FIG> in combination with those of <FIG> may be performed using the embodiments of Figs. 1B or <FIG>.

Note in any of the embodiments where the term clamp is used, it should be recognized that the functional element includes a tube or other flexible conduit and the clamp so that it functions as a valve. In any of the embodiments, another type of valve may be substituted for the clamp and conduit to provide the same function. Such a variation may be considered to alternative embodiments and clamp and conduit are not limiting of the subject matter conveyed herein.

Note that in any of the embodiments that identify the bag as the container, any bag may be replaced by any container including those of glass, polymer and other materials. In any embodiment where flow control is performed by a clamp, it should be understood that in any embodiment, including the claims, any clamp can be replaced by another type of valve such as a stopcock valve, a volcano valve, a ball valve, a gate valve or other type of flow controller. It should be understood that a clamp in the context of the disclosed subject matter is a clamp that closes around a tube to selectively control flow through the position of the clamp. Note that in any of the embodiments, the order of adding and mixing to the mixing container <NUM> can by reversed from what is described with respect to the embodiments. In any of the embodiments instead of dextrose concentrate being used, this can be substituted for glucose or another osmotic agent.

The process of providing purified water from the purified water source <NUM> is described next. As shown in <FIG>, water inlet clamp <NUM> is opened and the water pump <NUM> operates to convey purified water along water line <NUM>. All other controllable valves (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>) are closed. Water pump <NUM> together with the peristaltic pump <NUM> conveys water into the mixing container <NUM> through line <NUM> to line <NUM> as illustrated by the block arrows in <FIG>.

Line <NUM> can be provided with a check valve <NUM> (<FIG>) which prevents flow in one direction and has a cracking pressure which must be overcome for water to flow in the other direction. In the example of <FIG>, the check valve <NUM> permits water to flow through line <NUM> toward the mixing container <NUM> when the cracking pressure of the check valve <NUM> is overcome. Initially the purified water from the purified water source <NUM> is pumped by the water pump <NUM> with water inlet clamp <NUM> open and the batch release clamp <NUM> and the conductivity sensor clamp <NUM> closed such that water is pumped into the mixing container <NUM> through line <NUM> with the peristaltic pump <NUM> running so as to convey water into the mixing container <NUM>, as shown in <FIG>.

<FIG> illustrates the configuration of the system when the osmotic agent concentrate <NUM> (e.g., dextrose, glucose, etc.) flows through osmotic supply line <NUM> and eventually into the mixing container <NUM>. Even though <FIG> illustrates a fluid circuit configuration that corresponds to Fig. 1B, this description is equally applicable to the configuration shown in <FIG>. As shown in <FIG>, valve <NUM> is opened (all other valves remain closed) and peristaltic pump <NUM> can operate in in the direction shown (pictured to the right on the drawing sheet), such that the osmotic concentrate <NUM> flows through inlet line <NUM> into mixing container <NUM>. The peristaltic pump <NUM> can be controlled to precisely meter a desired quantity of the osmotic concentrate into mixing container <NUM>. In embodiments, only a fraction of the total quantity of the osmotic agent concentrate <NUM> present in its container is provided into mixing container <NUM>, such that multiple batches of the medicament can be prepared in the mixing container <NUM>; and each of the batches can be customized based on a desired concentration to create custom mini batches.

The osmotic agent concentrate <NUM> passes through the sterilizing filter <NUM> on its way to the mixing container <NUM>, thereby minimizing the risk of contamination.

In an alternate embodiment, the osmotic concentrate <NUM> can be positioned sufficiently high or above mixing container <NUM> that a gravity powered fill can be accomplished (if the cracking pressure of the check valve <NUM> can be overcome). In this scenario, valve <NUM> is opened and valve <NUM> is opened (not illustrated in <FIG>) which permits gravity to convey the osmotic agent concentrate through inlet line <NUM> into mixing container <NUM>, without the use of peristaltic pump <NUM>. In embodiments, the entirety of the osmotic agent concentrate <NUM> is allowed to flow into the mixing container <NUM> so that the quantity of the osmotic agent concentrate <NUM> that is present in the mixing container <NUM> is known based on the original amount of the osmotic agent concentrate that was present in its initial container.

<FIG> illustrates the configuration of the system when the electrolyte concentrate <NUM> flows through electrolyte supply line <NUM> and eventually into the mixing container <NUM>. As shown in <FIG>, valve <NUM> is opened (with all other valves closed) and peristaltic pump <NUM> can operate in in the direction shown (pictured to the right on the drawing sheet), such that the electrolyte concentrate <NUM> flows through inlet line <NUM> into mixing container <NUM>. The electrolyte concentrate <NUM> passes through the sterilizing filter <NUM> on its way to the mixing container <NUM>, thereby minimizing the risk of contamination.

The peristaltic pump <NUM> can be controlled to precisely meter a desired quantity of the electrolyte concentrate into mixing container <NUM>. In embodiments, only a fraction of the total quantity of the electrolyte concentrate <NUM> present in its container is provided into mixing container <NUM>, such that multiple batches of the medicament can be prepared in the mixing container <NUM>; and each of the batches can be customized based on a desired concentration to create custom mini batches.

In an alternate embodiment, the electrolyte concentrate <NUM> can be positioned sufficiently high or above mixing container <NUM> that a gravity powered fill can be accomplished. In this scenario, valve <NUM> is opened and valve <NUM> is opened which permits gravity to convey the electrolyte concentrate through inlet line <NUM> into mixing container <NUM>, without the use of peristaltic pump <NUM> (of the cracking pressure of the check valve <NUM> can be overcome). In embodiments, the entirety of the electrolyte concentrate <NUM> is allowed to flow into the mixing container <NUM> so that the quantity of the electrolyte concentrate <NUM> that is present in the mixing container <NUM> is known based on the original amount of the electrolyte concentrate that was present in its initial container.

Referring to <FIG>, to mix the contents of the mixing container <NUM> the peristaltic pump <NUM> pumps fluid in a circular path through lines <NUM>, <NUM>, and <NUM> in a direction designated with an arrow in the figure (to the left in the figure) with all the clamps closed except for clamp <NUM>. The peristaltic pump <NUM> generates sufficient pressure to overcome the cracking pressure of check valve <NUM>. Then the contents of the mixing container <NUM> are mixed by the flow circulating through the mixing container <NUM>. While the contents of the mixing container <NUM> circulate through the fluid path that is illustrated, they pass through or past conductivity/temperature sensors 159c and <NUM>, and the conductivity and/or the temperature of the fluid can be measured and the measurement provided to controller <NUM>, as described above. The mixing process may continue for a predetermined period of time, or it may continue until the conductivity a value that is measured by the conductivity sensors reaches a stable value that does not change any more.

Referring to <FIG>, a configuration of the fluid circuit that is used for draining the mixing container is shown. Drain valve <NUM> is opened with all other valves remaining closed, and the peristaltic pump <NUM> operates in the direction as shown which causes the contents of the mixing container to pass through inlet line <NUM> to transfer line <NUM>, to drain line <NUM> and ultimately to drain connection <NUM>. The mixing container <NUM> may be drained at the conclusion of a treatment cycle, or when it is determined that the contents of the mixing container is passed its expiration, and/or when the filter integrity test indicates a failure of filter <NUM>. In embodiments, the contents of the mixing container <NUM> may also be drained when it is determined that the conductivity measurement is grossly incorrect.

Referring now to <FIG> and <FIG>, once of the medicament is prepared and mixed in the mixing container at <NUM>, and the medicament is deemed to be ready for use based on conductivity checks described above and filter integrity test, the medicament is provided to the medicament user <NUM>. <FIG> and <FIG> illustrate various arrangements of the fluid circuit for providing the medicament. At this time, the water inlet clamp <NUM> and the drain line clamp <NUM> are closed. The medicament user <NUM> may be any type of treatment device or container that receives the mixed medicament from the mixing container <NUM>.

The batch release clamp <NUM> and valve <NUM> are open and the water inlet clamp <NUM> and the conductivity sensor clamp <NUM> are closed. A pump <NUM> in a medicament user <NUM> may then draw fluid from the circular path as the peristaltic pump <NUM> rotates to maintain fluid at the cracking pressure of the check valve <NUM> in <FIG>. In embodiments, the cracking pressure may be <NUM> PSI (pounds per square inch). It will be understood that this makes the medicament preparation system appear like a bag of dialysate with a head pressure of <NUM> PSI.

The medicament pump <NUM> in the medicament user <NUM> may see a positive pressure at the cracking pressure type check valve <NUM> cracking pressure which may facilitate the pump <NUM> of the medicament user <NUM> by mimicking the pressure of an elevated medicament container with a head pressure approximately at the cracking pressure of the check valve <NUM>. In embodiments, as shown in <FIG>, clamp <NUM> is closed while peristaltic pump <NUM> operates in the direction shown in the drawing. Clamp <NUM> is opened, and the medicament is conveyed through medicament output lines <NUM> and <NUM> to medicament user <NUM>. A pressure sensor <NUM> is provided to measure the pressure in this fluid channel and to provide a signal, which may be used in feedback control, to modulate the speed of the peristaltic pump <NUM> and thereby provide a predetermined pressure in the formed fluid channel.

<FIG> shows a block diagram of an example computer system according to embodiments of the disclosed subject matter. In various embodiments, all, or parts of system <NUM> may be included in a medical treatment device/system such as a renal replacement therapy system. In these embodiments, all, or parts of system <NUM> may provide the functionality of a controller of the medical treatment device/systems. In some embodiments, all, or parts of system <NUM> may be implemented as a distributed system, for example, as a cloud-based system.

System <NUM> includes a computer <NUM> such as a personal computer or workstation or other such computing system that includes a processor <NUM>. However, alternative embodiments may implement more than one processor and/or one or more microprocessors, microcontroller devices, or control logic including integrated circuits such as ASIC.

Computer <NUM> further includes a bus <NUM> that provides communication functionality among various modules of computer <NUM>. For example, bus <NUM> may allow for communicating information/data between processor <NUM> and a memory <NUM> of computer <NUM> so that processor <NUM> may retrieve stored data from memory <NUM> and/or execute instructions stored on memory <NUM>. In one embodiment, such instructions may be compiled from source code/objects provided in accordance with a programming language such as Java, C++, C#,. net, Visual Basic™ language, LabVIEW, or another structured or object-oriented programming language. In one embodiment, the instructions include software modules that, when executed by processor <NUM>, provide renal replacement therapy functionality according to any of the embodiments disclosed herein.

Memory <NUM> may include any volatile or non-volatile computer-readable memory that can be read by computer <NUM>. For example, memory <NUM> may include a non-transitory computer-readable medium such as ROM, PROM, EEPROM, RAM, flash memory, disk drive, etc. Memory <NUM> may be a removable or non-removable medium.

Bus <NUM> may further allow for communication between computer <NUM> and a display <NUM>, a keyboard <NUM>, a mouse <NUM>, and a speaker <NUM>, each providing respective functionality in accordance with various embodiments disclosed herein, for example, for configuring a treatment for a patient and monitoring a patient during a treatment.

Computer <NUM> may also implement a communication interface <NUM> to communicate with a network <NUM> to provide any functionality disclosed herein, for example, for alerting a healthcare professional and/or receiving instructions from a healthcare professional, reporting patient/device conditions in a distributed system for training a machine learning algorithm, logging data to a remote repository, etc. Communication interface <NUM> may be any such interface known in the art to provide wireless and/or wired communication, such as a network card or a modem.

Bus <NUM> may further allow for communication with one or more sensors <NUM> and one or more actuators <NUM>, each providing respective functionality in accordance with various embodiments disclosed herein, for example, for measuring signals.

It will be appreciated that the modules, processes, systems, and sections described above can be implemented in hardware, hardware programmed by software, software instruction stored on a non-transitory computer readable medium or a combination of the above. For example, a method for providing a medicament to a medicament user can be implemented, for example, using a processor configured to execute a sequence of programmed instructions stored on a non-transitory computer readable medium. For example, the processor can include, but not be limited to, a personal computer or workstation or other such computing system that includes a processor, microprocessor, microcontroller device, or is comprised of control logic including integrated circuits such as, for example, an Application Specific Integrated Circuit (ASIC). The instructions can be compiled from source code instructions provided in accordance with a programming language such as Java, C++, C#. net or the like. The instructions can also comprise code and data objects provided in accordance with, for example, the Visual Basic™ language, LabVIEW, or another structured or object-oriented programming language. The sequence of programmed instructions and data associated therewith can be stored in a non-transitory computer-readable medium such as a computer memory or storage device which may be any suitable memory apparatus, such as, but not limited to read-only memory (ROM), programmable read-only memory (PROM), electrically erasable programmable read-only memory (EEPROM), random-access memory (RAM), flash memory, disk drive and the like.

Furthermore, the modules, processes, systems, and sections can be implemented as a single processor or as a distributed processor. Further, it should be appreciated that the steps mentioned above may be performed on a single or distributed processor (single and/or multicore). Also, the processes, modules, and sub-modules described in the various figures of and for embodiments above may be distributed across multiple computers or systems or may be co-located in a single processor or system. Exemplary structural embodiment alternatives suitable for implementing the modules, sections, systems, means, or processes described herein are provided below.

The modules, processors or systems described above can be implemented as a programmed general purpose computer, an electronic device programmed with microcode, a hard-wired analog logic circuit, software stored on a computer-readable medium or signal, an optical computing device, a networked system of electronic and/or optical devices, a special purpose computing device, an integrated circuit device, a semiconductor chip, and a software module or object stored on a computer-readable medium or signal, for example.

Embodiments of the method and system (or their sub-components or modules), may be implemented on a general-purpose computer, a special-purpose computer, a programmed microprocessor or microcontroller and peripheral integrated circuit element, an ASIC or other integrated circuit, a digital signal processor, a hardwired electronic or logic circuit such as a discrete element circuit, a programmed logic circuit such as a programmable logic device (PLD), programmable logic array (PLA), field-programmable gate array (FPGA), programmable array logic (PAL) device, or the like. In general, any process capable of implementing the functions or steps described herein can be used to implement embodiments of the method, system, or a computer program product (software program stored on a non-transitory computer readable medium).

Furthermore, embodiments of the disclosed method, system, and computer program product may be readily implemented, fully or partially, in software using, for example, object or object-oriented software development environments that provide portable source code that can be used on a variety of computer platforms. Alternatively, embodiments of the disclosed method, system, and computer program product can be implemented partially or fully in hardware using, for example, standard logic circuits or a very-large-scale integration (VLSI) design. Other hardware or software can be used to implement embodiments depending on the speed and/or efficiency requirements of the systems, the particular function, and/or particular software or hardware system, microprocessor, or microcomputer being utilized. Embodiments of the method, system, and computer program product can be implemented in hardware and/or software using any known or later developed systems or structures, devices and/or software by those of ordinary skill in the applicable art from the function description provided herein and with a general basic knowledge of control systems of medical devices and/or computer programming arts.

Moreover, embodiments of the disclosed method, system, and computer program product can be implemented in software executed on a programmed general-purpose computer, a special purpose computer, a microprocessor, or the like.

Claim 1:
A method of generating a custom mini batch of dialysate with a proportioning system, the method comprising:
attaching a disposable component (<NUM>) to the proportioning system;
generating purified water with a water purification system (<NUM>, <NUM>);
adding a first quantity of the purified water to a mixing container (<NUM>) that is pre-attached to the disposable component (<NUM>);
conveying a second quantity of a first concentrated medicament through a sterilizing filter (<NUM>) and to the mixing container (<NUM>);
first mixing contents of the mixing container (<NUM>);
determining a concentration of the contents of the mixing container (<NUM>) by flowing the contents past at least one fluid quality sensor and back into the mixing container (<NUM>);
conveying a third quantity of a second concentrated medicament through the sterilizing filter (<NUM>) and to the mixing container (<NUM>);
second mixing the contents of the mixing container (<NUM>);
confirming a final concentration of the contents of the mixing container (<NUM>) by flowing the contents past at least one fluid quality sensor and back into the mixing container (<NUM>);
testing integrity of the sterilizing filter (<NUM>) ; and
if the testing indicates that the sterilizing filter (<NUM>) is acceptable, providing the contents of the mixing container (<NUM>) to a medicament user (<NUM>), and otherwise indicating an error condition.