Mixing system and method for in-line mixing of components of medical fluids

Abstract

A method and system for in-line mixing of components of a medical fluid in a mixing system (20) for mixing a medical fluid having a final predetermined composition of pure water, a small signal response (SSR) component, and optionally at least one electrolyte component. The method includes providing a fluid stream (S1) including pure water or a mixture of pure water and an electrolyte component into a main fluid line (21), monitoring the concentration of the fluid with a concentration sensor (26, 60), providing the SSR component into the fluid stream upstream of the concentration sensor (26, 60) with an SSR dosing mechanism (25a) (S3), and adjusting the dosing rate of the SSR component using the SSR dosing mechanism (25a) to determine a relationship between the dosing rate of the SSR component and the resulting concentration of the SSR component in the fluid, such that the concentration monitored with the concentration sensor (26, 60) corresponds to the intended final predetermined concentration (c) of the SSR component in the medical fluid. SSR_final ) is greater than the initial concentration of the SSR component in the fluid (c SSR_init and controlling (S4) the initial dosing rate to a value that indicates a final predetermined concentration (c) of the SSR component in the fluid using the SSR dosing mechanism (25a) based on the determined relationship. SSR_final ) is achieved. SSR_final ) (S5).

Description

[Technical Field]

[0001] The present disclosure relates generally to dialysis treatment, and more particularly to mixing medical fluids used in dialysis treatment from concentrate and purified water. [Background technology]

[0002] Dialysis therapy is used to treat people with acute or chronic kidney failure. Dialysis removes waste products, toxins, and excess water from the body that normally functioning kidneys would otherwise remove.

[0003] One type of dialysis treatment is extracorporeal (EC) blood therapy, in which blood from the patient is pumped through an EC blood circuit and then returned to the patient. A hemofiltration unit, commonly known as a dialyzer, is placed in the EC blood circuit and contacts the blood with dialysate via a semipermeable membrane. One EC blood therapy modality is hemodialysis (HD), which generally uses diffusion to remove waste products from the blood. A diffusion gradient occurs across the semipermeable membrane and the dialysate. Another modality is hemofiltration (HF), which relies on convective transport of toxins from the patient's blood. HF is achieved by adding a separate dialysate, called infusate, substitution fluid, or replacement fluid, to the extracorporeal blood circuit during dialysis treatment. Substitution fluid and excess fluid accumulated by the patient between treatment sessions are ultrafiltered over the course of HF treatment, providing a convective transport mechanism that is particularly beneficial in removing middle and large molecules. Yet another modality is hemodiafiltration (HDF), which combines convective and diffusive clearance. HDF uses dialysate flowing through a dialyzer, similar to standard hemodialysis, to provide diffusive clearance. In addition, substitution fluid is delivered directly to the extracorporeal blood circuit to provide convective clearance. Here, more fluid than the patient's excess fluid is removed from the blood, increasing convective transport of waste products from the blood. The additional fluid removed is replaced via substitution fluid. EC blood therapy can be used as intensive care (IC) therapy, for example, as continuous renal replacement therapy (CRRT), or as intermittent hemodialysis (IHD), with variations such as sustained low-efficiency dialysis / sustained low-efficiency daily dialysis (SLED / SLEDD) and extended daily dialysis (EDD).

[0004] Another type of dialysis treatment is peritoneal dialysis (PD), in which dialysate is infused into a patient's peritoneal cavity. The dialysate contacts a peritoneal membrane located within the patient's peritoneal cavity. Waste, toxins, and excess water pass from the patient's bloodstream through capillaries in the peritoneal membrane and enter the dialysate by diffusion and osmosis; an osmotic gradient is created across the membrane. An osmotic agent in the dialysate provides the osmotic gradient. The used or spent dialysate is drained from the patient, removing the waste, toxins, and excess water from the patient. This cycle may be repeated, for example, multiple times.

[0005] There are various types of PD treatments, including continuous ambulatory PD (CAPD), automated PD (APD), tidal PD (TPD), and continuous-flow PD (CFPD). CAPD is a manual dialysis treatment in which the flow of dialysate into and out of the patient is driven by gravity. APD is performed by a dialysis machine, commonly known as a cycler, which is fluidly connected to the peritoneal cavity and operates to automatically transfer dialysate to and from the peritoneal cavity according to a predetermined schedule, for example, overnight while the patient sleeps. TPD is a type of automated PD in which only a portion of the fill volume in the peritoneal cavity is replaced after the initial full fill. CFPD requires two catheters or a dual-lumen catheter to maintain a continuous flow of dialysate into the peritoneal cavity at a high flow rate after the initial fill.

[0006] Traditionally, dialysate for PD is delivered in pre-filled bags to the point of care, e.g., an intensive care (IC) unit or the patient's home. EC blood therapy may also use pre-filled bags of dialysate, e.g., in an IC unit, for the treatment of acute renal failure. Dialysis fluid for EC blood therapy of chronic renal failure is typically produced by the dialysis machine itself by mixing one or more concentrates with purified water. Recently, dialysis machines that produce dialysate for PD have also become commercially available. Hereinafter, dialysate, infusate, substitution fluid, and replacement fluid are referred to as medical fluids.

[0007] Point-of-use medical fluid generation is attractive because it reduces the cost and environmental impact of transporting large quantities of pre-made medical fluids and the burden of storing and handling pre-filled bags. Medical fluid generation requires access to purified water and concentrates. Typically, a water purifier is connected to a municipal water source, and a fluid generation unit operates to mix one or more concentrates with the purified water to produce the medical fluid. It is important that the final mixed medical fluid achieves a predetermined composition containing the intended concentrations of one or more concentrates. Concentrations are typically monitored using one or more concentration sensors, e.g., one or more conductivity sensors. The conductivity contribution of some concentrates, such as glucose and potassium, is difficult to measure because they are administered in low amounts and have low or no conductivity response. Such dosing may instead rely on volume dosing, where the concentration of the concentrate in the bag is assumed to be correct. However, evaporation from the bag and variations due to manufacturing specifications can cause concentration variations. Sometimes, multiple conductivity sensors are used to enable detection of different conductivity ranges. As a result, one conductivity sensor can sense, for example, in a low conductivity range, while another sensor can sense in a different, higher conductivity range. However, having many conductivity sensors adds cost to the system, and it is desirable to keep their number low. Also, it may be desirable to use conductivity sensors for protection purposes, whereby they may need to be configured to measure in a range that does not include the low conductivity range.

[0008] U.S. Patent No. 5,900,136 proposes measuring the concentration of a non-electrolyte, such as glucose, in an electrolyte solution based on a predetermined correlation between electrical conductivity and the concentration of the non-electrolyte in the same system. The data for determining the correlation must be determined in advance.

[0009] U.S. Patent Application Publication No. 2019 / 0262526 suggests adding an electrolyte concentrate marker to an osmotic agent concentrate or glucose concentrate so that the concentration of the osmotic agent can be inferred from a measurement of the diluent. However, prior knowledge of the ratio of the osmotic agent concentrate to the electrolyte concentrate marker must be known.

[0010] Therefore, there is room for improvement in providing a precisely mixed therapeutic solution. Summary of the Invention

[0011] It is an object of the present disclosure to alleviate at least some of the shortcomings of the prior art. A further object is to provide techniques for accurate dosing of components using concentration feedback that provide a small signal response when administered at the intended dosing rate. A further object is to provide techniques for accurate mixing of fluids used in dialysis.

[0012] These and other objects are achieved at least in part by methods and mixing systems according to the independent claims and by embodiments according to the dependent claims.

[0013] According to one aspect, the present disclosure relates to a method for in-line mixing of components of a medical fluid in a mixing system, the medical fluid having a final predetermined composition of pure water, an SSR component (small-signal-response component), and optionally at least one electrolyte component. The method includes supplying a fluid stream containing pure water or a mixture of pure water and the electrolyte component to a main fluid line (S1) and monitoring the concentration of the fluid using a concentration sensor (S2). The method further includes providing the SSR component into the fluid stream upstream of the concentration sensor (S3) using an SSR dosing mechanism. The method includes adjusting the dosing rate of the SSR component using the SSR dosing mechanism to determine a relationship between the dosing rate of the SSR component and the resulting concentration of the SSR component in the fluid, and determining whether the concentration monitored using the concentration sensor corresponds to the intended final predetermined concentration c of the SSR component in the medical fluid. SSR_final the initial concentration of the SSR component in the fluid, c, which is greater than SSR_init The method further includes controlling (S4) the initial dosing rate of the SSR component in the fluid based on the determined relationship using the SSR dosing mechanism to achieve a final predetermined concentration c of the SSR component in the fluid. SSR_final The final dose rate Q is achieved SSR_final S5.

[0014] Composition control using concentration feedback is beneficial because it allows for concentration errors, such as concentration fluctuations due to evaporation or manufacturing variations, to be taken into account. Composition control of small-signal-response (SSR) components has been found to be difficult due to the weak or small concentration response of the SSR component. The present invention solves this problem by temporarily overdosing the SSR component, thereby increasing the SSR component's contribution to concentration so that it is measurable within desired limits. By increasing the SSR component concentration before preparing the final solution, the impact on dosing accuracy from signal fluctuations due to measurement noise and flow rate fluctuation noise is minimized. This reduces the adverse effects of noise factors, and therefore the desired concentration of the SSR component can be more accurately determined. The method is easy to implement and results in more accurate mixing.

[0015] According to some embodiments, the initial concentration of the SSR component in the fluid, c SSR_init is the intended final predetermined concentration of the SSR component in the medical fluid, c SSR_final is greater than the initial administration rate Q SSR_init The ratio between the concentration response and the concentration signal noise resulting from administration of the SSR component at is above a predetermined limit.

[0016] According to some embodiments, the initial dosage rate Q of the SSR component SSR_init is the final administration rate Q SSR_final It is more than 1 to 20 times larger than

[0017] According to some embodiments, the SSR component is either a non-conductive or conductive solution, so that the final predetermined concentration of the SSR component in the fluid, c SSR_init The intended final dose rate Q is achieved SSR_final When added to the fluid flow in the main flow path at 1000 kJ / s, its contribution to the concentration monitored with the concentration sensor is too small to be measured with sufficient accuracy.

[0018] According to some embodiments, the concentration measured using the concentration sensor at the initial administration rate is greater than a predetermined target concentration κ of the fluid. SSR_init Corresponds to.

[0019] According to some embodiments, the initial administration rate is a predetermined initial administration rate Q SSR_init Corresponds to.

[0020] According to some embodiments, controlling S4 comprises controlling the final administration rate Q SSR_final is the intended final predetermined concentration of the SSR component, c SSR_final The final value F correlated with final and the initial concentration of the SSR component, c SSR_init The initial value F correlated with initial The initial dose rate Q is the ratio between SSR_init This includes determining the value of the sum of the two.

[0021] According to some embodiments, providing the fluid flow S1 includes controlling a main flow rate of the fluid flow to a predetermined flow rate of the medical fluid.

[0022] According to some embodiments, the predetermined fluid flow rate is the flow rate of a medical fluid configured for a downstream device or user.

[0023] According to some embodiments, providing a fluid flow S1 includes controlling a main flow rate using a main pump disposed in the main fluid line.

[0024] According to some embodiments, the reducing S5 is the final dosage rate Q of the SSR component. SSR_final and the main flow rate.

[0025] According to some embodiments, the concentration sensor is a conductivity sensor.

[0026] According to some embodiments, the concentration sensor has a measurement range of 0.1 to 50 mS / cm, more preferably 5 to 20 mS / cm.

[0027] According to some embodiments, the monitoring S2 is performed using the same concentration sensor.

[0028] According to some embodiments, providing the fluid flow S1 includes providing the electrolyte component at a dosage rate to the pure water flow in the main fluid line using an electrolyte component dosing mechanism to form a fluid flow including a mixture of pure water and an electrolyte component upstream of the concentration sensor.

[0029] According to some embodiments, providing the fluid stream S1 includes, prior to providing the SSR component into the fluid stream, controlling a dosing rate of the electrolyte component based on a concentration monitored by a concentration sensor of the mixture of pure water and the electrolyte component to achieve a final predetermined concentration c of the electrolyte component in the final medical fluid using an electrolyte component dosing mechanism. A_final Final dose rate Q A_final This includes controlling the

[0030] According to some embodiments, providing a fluid flow S1 may be performed at a final dosage rate Q of the electrolyte component. A_final and the main flow rate.

[0031] According to some embodiments, the SSR component reduces the conductivity of the fluid to which it is added.

[0032] According to some embodiments, the SSR component comprises glucose.

[0033] According to some embodiments, the SSR component is a liquid glucose concentrate containing between 40-75% glucose.

[0034] According to some embodiments, the initial concentration of the SSR component in the fluid, c SSR_init is between 4 and 20 percent, more preferably between 4 and 10 percent.

[0035] According to some embodiments, the SSR component increases the conductivity of the fluid to which it is added.

[0036] According to some embodiments, the SSR component includes potassium.

[0037] According to some embodiments, the SSR component includes potassium at a concentration of 400-3200 mmol / l.

[0038] According to some embodiments, the method includes providing S6 the additional electrolyte component into the fluid flow in the main fluid line using the additional electrolyte component dosing mechanism to form a mixture of pure water, the electrolyte component, the SSR component, and the additional electrolyte component.

[0039] According to some embodiments, providing S6 may include using an additional electrolyte component dosing mechanism to determine a final predetermined concentration c of the additional electrolyte component in the final predetermined composition of the medical fluid based on the concentrations monitored by the concentration sensors of the mixture of the pure water, the electrolyte component, and the additional electrolyte component. B_final Final dose rate Q B_final This includes controlling the

[0040] According to some embodiments, providing the fluid flow S1 includes providing the additional electrolyte component at a dosage rate to the pure water flow in the main fluid line using the additional electrolyte component dosing mechanism to form a fluid flow including a mixture of pure water, the electrolyte component, and the additional electrolyte component upstream of the concentration sensor.

[0041] According to some embodiments, providing the fluid stream S1 may include, prior to providing the SSR component to the fluid stream, controlling a dosing rate of the additional electrolyte component based on concentrations monitored by a concentration sensor of the mixture of the pure water, the electrolyte component, and the additional electrolyte component, using an additional electrolyte component dosing mechanism to achieve a final predetermined concentration c of the additional electrolyte component in the final medical fluid. B_final Final dose rate Q B_final This includes controlling the

[0042] According to some embodiments, the concentration sensor is a glucose sensor configured to measure glucose concentration.

[0043] According to a second aspect, the present disclosure relates to a mixing system for in-line mixing of components of a medical fluid having a final predetermined composition of purified water, an SSR (small-signal-response) component, and optionally at least one electrolyte component. The mixing system includes a fluid pathway including: a main fluid line arranged to be connected to a source of purified water; an SSR component line fluidly connected to the main fluid line and providing an SSR component line connector configured to be connected to an SSR component container; and optionally, an electrolyte component line fluidly connected to the main fluid line and providing an electrolyte component connector configured to be connected to an electrolyte component container. The mixing system further includes: a main pump arranged in the main fluid line to provide a main flow of fluid in the main fluid line; a concentration sensor arranged to measure the concentration of the fluid in the main fluid line; an SSR dosing mechanism arranged in the SSR component line to provide the SSR component at a dosing rate into the main fluid line upstream of the concentration sensor; and optionally, an electrolyte dosing mechanism arranged in the electrolyte component line to provide the electrolyte component at a dosing rate into the main fluid line upstream of the concentration sensor. The mixing system further includes a controller configured to provide, using the main pump, a flow of fluid including pure water from the pure water source or a mixture of pure water from the pure water source and electrolyte components from the electrolyte component containers into the main fluid line, and to monitor the concentration of the fluid using a concentration sensor. The controller adjusts the dosage rate of the SSR component using the SSR dosing mechanism to determine a relationship between the dosage rate of the SSR component and the resulting concentration of the SSR component in the fluid, and determines whether the concentration monitored using the concentration sensor corresponds to an intended final predetermined concentration c of the SSR component in the medical fluid. SSR_final the initial concentration of the SSR component in the fluid, c, which is greater than SSR_init The control device is further configured to control, using the SSR dosing mechanism, the dosing rate of the SSR component to a final predetermined concentration c of the SSR component in the fluid based on the determined relationship. SSR_final The final dose rate Q is achieved SSR_final is further configured to reduce the

[0044] According to some embodiments, the initial concentration of the SSR component in the fluid, c SSR_init is the intended final predetermined concentration of the SSR component in the medical fluid, c SSR_final is greater than the initial administration rate Q SSR_init The ratio between the concentration response and the concentration signal noise resulting from administration of the SSR component at is above a predetermined limit.

[0045] According to some embodiments, the initial dosage rate Q of the SSR component SSR_init is the final administration rate Q SSR_final It is more than 1 to 20 times larger than

[0046] According to some embodiments, the SSR component is either a non-conductive or conductive solution, so that the final predetermined concentration of the SSR component in the fluid, c SSR_final The intended final dose rate Q is achieved SSR_final When added to the fluid flow in the main flow path at 1000 kJ / s, its contribution to the concentration monitored with the concentration sensor is too small to be measured with sufficient accuracy.

[0047] According to some embodiments, the initial administration rate Q SSR_init The concentration measured using the concentration sensor at is equal to the predetermined target concentration κ of the fluid. SSR_init Corresponds to.

[0048] According to some embodiments, the initial administration rate is a predetermined initial administration rate Q SSR_init Corresponds to.

[0049] According to some embodiments, the controller determines the final dose rate Q SSR_final is the intended final predetermined concentration of the SSR component, c SSR_final The final value F correlated with final and the initial concentration of the SSR component, c SSR_init The initial value F correlated with initial The initial dose rate Q is the ratio between SSR_init The method is configured to determine the value of the sine wave as equal to the value multiplied by .

[0050] According to some embodiments, the controller is configured to control a main pump to provide a main flow rate to result in a predetermined flow rate of the medical fluid.

[0051] According to some embodiments, the predetermined fluid rate is a medical fluid flow rate configured for a downstream device or user.

[0052] According to some embodiments, the controller controls the final dosage rate Q of the SSR component. SSR_final and the main flow rate.

[0053] According to some embodiments, the concentration sensor is a conductivity sensor.

[0054] According to some embodiments, the concentration sensor has a measurement range of 0.1 to 50 mS / cm, more preferably 5 to 20 mS / cm.

[0055] According to some embodiments, the controller is configured to monitor using the same concentration sensor.

[0056] According to some embodiments, the controller is configured to provide the electrolyte component at a dosage rate to the stream of pure water in the main fluid line using the electrolyte component dosage mechanism to form a fluid stream including a mixture of pure water and the electrolyte component upstream of the concentration sensor.

[0057] According to some embodiments, the controller adjusts the dosing rate of the electrolyte component based on the concentration monitored by the concentration sensor of the pure water and electrolyte component mixture prior to providing the SSR component into the fluid stream, and controls the electrolyte component dosing mechanism to achieve a final predetermined concentration c of the electrolyte component in the final medical fluid. A_final Final dose rate Q A_final The control circuit is configured to control the

[0058] According to some embodiments, the controller controls the final dosing rate Q of the electrolyte component. A_final and the main flow rate.

[0059] According to some embodiments, the SSR component reduces the conductivity of the fluid to which it is added.

[0060] According to some embodiments, the SSR component comprises glucose.

[0061] According to some embodiments, the SSR component is a liquid glucose concentrate containing between 40-75% glucose.

[0062] According to some embodiments, the initial concentration of the SSR component in the fluid, c SSR_init is between 4 and 20 percent, more preferably between 4 and 10 percent.

[0063] According to some embodiments, the SSR component increases the conductivity of the fluid to which it is added.

[0064] According to some embodiments, the SSR component includes potassium.

[0065] According to some embodiments, the SSR component includes potassium at a concentration of 400-3200 mmol / l.

[0066] According to some embodiments, the fluid pathway includes an additional electrolyte component line fluidly connected to the main fluid line and providing an additional electrolyte component connector configured to connect to an additional electrolyte component container, the mixing system further including an additional electrolyte component dosing mechanism disposed in the additional electrolyte component line, and the controller configured to use the additional electrolyte component dosing mechanism to provide the additional electrolyte component at a dosing rate to the fluid flow in the main fluid line to form a mixture of pure water, the electrolyte component, the SSR component, and the additional electrolyte component.

[0067] According to some embodiments, the control device adjusts the dosing rate of the additional electrolyte component based on the concentrations monitored by the concentration sensors of the mixture of pure water, the electrolyte component, the SSR component, and the additional electrolyte component, using the additional electrolyte component dosing mechanism to achieve a final predetermined concentration c of the electrolyte component in the final predetermined composition of the medical fluid. B_final Final dose rate Q B_final The control circuit is configured to control the

[0068] According to some embodiments, the mixing system includes a concentration sensor and a waste line fluidly connected to the main line downstream of the main pump.

[0069] According to some embodiments, the mixing system comprises one or more valves configured to be controlled by the controller to direct fluid in the main line to waste or to an endpoint of the main line.

[0070] According to some embodiments, the concentration sensor is a glucose sensor configured to measure glucose concentration.

[0071] According to a third aspect, the present disclosure relates to a computer program comprising instructions for causing a system according to the second aspect to perform the steps of the method according to the first aspect.

[0072] According to a fourth aspect, the present disclosure relates to a computer-implemented medium having stored thereon the computer program of the third aspect. [Brief explanation of the drawings]

[0073] [Figure 1] FIG. 1 is a schematic diagram of an exemplary dialysis treatment system that includes a mixing system. [Figure 2] FIG. 2 is a schematic diagram of an exemplary mixing system according to some embodiments. [Figure 3] , [Figure 4]3A through 3C and 4A through 4D are diagrams of different steps for administering small signal response components in the system of FIG. 2 according to some embodiments of the present disclosure. [Figure 5] FIG. 5 is a flow chart of an exemplary method for mixing components of a medical fluid in the system of FIG. [Figure 6] FIG. 6 shows two diagrams illustrating an example of administration of a small signal response component. [Figure 7] FIG. 7 is a schematic diagram of an exemplary mixing system according to some embodiments. [Figure 8] 8A through 8E are diagrams of different steps for administering small signal response components in the system of FIG. 7 according to some embodiments of the present disclosure. [Figure 9] FIG. 9 is a flow chart of an exemplary method for mixing components of a medical fluid in the system of FIG. [Figure 10] FIG. 10 is a schematic diagram of an exemplary mixing system according to some embodiments. [Figure 11] 11A through 11E are diagrams of different steps for administering small signal response components in the system of FIG. 10 according to some embodiments of the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0074] In the following description, different exemplary mixing systems are illustrated along with techniques for achieving accurate dosing of components within these mixing systems, particularly small-signal-reaction (SSR) components, which, when added, form a medical fluid or form part of a medical fluid used in a medical device or medical treatment, such as dialysis treatment. The basic idea is to improve the concentration accuracy of the SSR component by using concentration feedback from the fluid to which the SSR component is administered. This is done by increasing the dosing rate of the SSR component during the initial setup phase compared to the intended dosing rate of the SSR component so that the SSR component's contribution to the concentration in the fluid increases, thereby ensuring that the signal-to-noise relationship of the concentration signal is sufficient for control. The dosing rate of the SSR component is then reduced to achieve the intended (nominal) concentration of the SSR component in the medical fluid.

[0075] A medical fluid, as used herein, is a mixture of pure water, at least one SSR component, and, in some embodiments, at least one electrolyte component. A medical fluid is, for example, a liquid used by the medical device itself. Alternatively, a medical fluid may be an IV fluid (intravenous fluid), a dialysis fluid, an infusion fluid, a substitution fluid, or a replacement fluid. Such medical fluids are sometimes referred to as therapy fluids.

[0076] In some embodiments, an SSR component is defined as a component that, when administered at its intended administration rate, provides a small contribution to the concentration profile of the fluid into which it is administered, such as pure water or a mixture of pure water and one or more electrolyte components of the medical fluid, in order to reach the nominal concentration of the component in the medical fluid. This means that the SSR component provides a small signal response when measured with a concentration sensor configured to measure the concentration profile in the fluid. The small signal response is so small that it is difficult to measure with the desired accuracy using the desired concentration sensor.

[0077] The nominal concentration of a component is the intended final predetermined concentration of the component in the final medical fluid according to the formulation. The intended administration rate of an SSR component is typically small (less than 5%) relative to the flow rate of the fluid into which the SSR component is administered. However, in some embodiments, the intended administration rate is greater, e.g., 5 to 30%, and the SSR component still provides a small signal response in the fluid into which it is administered. Thus, one aspect is the nature of the concentrate, i.e., the SSR component, and its ability to generate a sufficient signal when administered under normal conditions, and its concentration in the concentrate. Generally, when an SSR component is administered to reach the nominal concentration in the final solution, it provides a small contribution to the concentration profile measured in the final solution.

[0078] The concentration characteristic is, for example, glucose concentration or conductivity. Glucose concentration, or simply glucose, can be measured, for example, using a glucose sensor. The glucose sensor can measure the viscosity of the fluid, for example, via sound velocity (m / s) or refractive index measurement. Conductivity is typically measured with a conductivity sensor, also called a conductivity cell. Generally, conductivity and concentration are related, and by measuring conductivity and knowing the ionic composition of the fluid, concentration can be determined. The relationship between conductivity and concentration may be determined as a function. The conductivity sensor may also include a temperature sensor to compensate the sensed conductivity when conductivity varies with temperature. Conductivity is a measure of a solution's ability to conduct electric current, measured in S / m, mS / cm, or μS / cm.

[0079] A small signal response occurs, for example, for dialysate components, with concentrations between 1-5% (for glucose) or 1-4 mmol / L (for potassium). Typically, a small signal response corresponds to a change in concentration of up to 3% (compared to the base level at the start of the measurement), e.g., measured in conductivity or glucose concentration.

[0080] More generally, the SSR component may be either a non-electrolyte component or an electrolyte component, which generates a small signal response when administered to reach the component's nominal concentration in the medical fluid. Alternatively, the SSR component may itself be composed of a mixture of a non-electrolyte and an electrolyte. However, in some embodiments, the mixture of a non-electrolyte and an electrolyte should increase or decrease the conductivity of the fluid to which it is added, so that it can be measured by a concentration sensor that is a conductivity sensor. In one embodiment, the SSR component is either a non-conductive solution or a conductive solution, so that the final predetermined concentration c of the SSR component in the fluid is reached. SSR_final The intended final dose rate Q is achieved SSR_final When added to the fluid flow in the main flow path at 1000 kJ / s, its contribution to the concentration monitored with the concentration sensor is too small to be measured with sufficient accuracy.

[0081] A non-electrolyte component does not conduct electric current. The non-electrolyte component includes one or more non-electrolytes. For example, a non-electrolyte can be made from a solid substance that does not easily generate (dissociate) cations and anions when dissolved in a solvent. When a non-electrolyte component is mixed into a solution containing an electrolyte, the ability of ions to move decreases, i.e., the conductance of the solution decreases. A non-electrolyte component decreases the conductivity by increasing the viscosity of the solution (reducing the mobility of ions). For example, a non-electrolyte can be made from glucose (CH ) dissolved in water. 12 O6) (sometimes called dextrose), or icodextrin (C6H 10 Examples of non-electrolyte components of PD that are considered SSR components herein include monosaccharides such as glucose / dextrose (derived from maltodextrin), monosaccharides such as dextrose, glucose / dextrose (derived from maltodextrin), and monosaccharides such as dextrose, glucose / dextrose (derived from maltodextrin), ... monosaccharides such as dextrose, monosaccharides such as dextrose, monosaccharides such as dextrose, monosaccharides such as dextrose, monosaccharides such as dextrose, monosaccharides such as dextrose, monosaccharides such as dextrose, monosaccharides such as dextrose, monosaccharides such as dextrose, monosaccharides such as dextrose, monosaccharides such as dextrose, mono

[0082] An electrolyte component conducts electric current. An electrolyte component includes one or more electrolytes. An electrolyte is made from a solid substance that, when dissolved in a solvent, generates (dissociates) cations and anions. In other words, a solid substance, such as the salt NaCl, when dissolved in a solvent, turns the solution into an electrolyte. An electrolyte component is, for example, an aqueous solution in which freely moving ions exist. An electrolyte component administered in small doses can be considered an SSR component. For example, sodium (Na + ), potassium (K + ), calcium (Ca 2+ ), magnesium (Mg 2+ ), or chloride (Cl - ), bicarbonate (HCO3 - ), or citrate (C6H5O7 3- ), or combinations thereof, can be considered SSR components. Electrolyte components considered SSR components herein include, for example, potassium chloride (KCl), calcium chloride (CaCl), magnesium chloride (MgCl), and acid (Baxter's SelectBag). TM SelectBag is a liquid electrolyte concentrate containing TM One product is 200 mM / L KCl, 250 mM / L CaCl2, 100 mM / L MgCl2, and 600 mM / L acetic acid.

[0083] Additional electrolyte components may also be required to form the medical fluid. These electrolyte components are typically administered in larger amounts than the SSR components. Furthermore, their concentrations, when administered in amounts that reach the intended concentrations of the electrolyte components in the final fluid, can be easily measured using a desired concentration sensor, which is a conductivity sensor. Exemplary electrolyte components to be administered in larger amounts for PD include 1841.0 mmol / L NaCl, 25.0 mmol / L CaCl2, 5.0 mmol / L MgCl2, and 801.0 mmol / L NaLact. Exemplary electrolyte components to be administered in larger amounts for EC therapy include SelectCart 1000, which contains sodium chloride (NaCl). TMThese exemplary electrolyte components are not considered SSR components, but instead are considered regular electrolyte components.

[0084] The SSR and / or electrolyte components are typically embodied as liquid concentrates. The liquid concentrates may be prepared at the manufacturer or may be prepared on-site at the mixing system from purified water and a dry concentrate, such as a powder, granules, or tablet, or a more concentrated liquid concentrate. The liquid concentrates are typically contained in containers, such as bags. The containers may contain concentrates for one or several treatments. The containers are typically disposable.

[0085] The conductivity of the resulting liquid concentrate upon dilution with water reflects the conductivity contributions from all individual electrolytes in the liquid concentrate. In this disclosure, the electrolytes that form the liquid concentrate are collectively referred to as the electrolyte component. A liquid concentrate that includes electrolytes and / or non-electrolytes such that the contributions from all electrolytes and / or non-electrolytes in the liquid concentrate have a small conductivity response, such as an SSR component, is referred to as an SSR component.

[0086] As described, a medical fluid is, for example, a liquid used by the device itself. Such a medical fluid may include glucose from a glucose concentrate. The medical fluid may alternatively be an IV fluid, such as a nutritional solution. The nutritional solution may also include glucose from a glucose concentrate. In such cases, the glucose concentrate may be considered an SSR component that is mixed with purified water at the point of care to provide the medical fluid.

[0087] Medical fluids, such as therapeutic fluids for PD, include electrolytes, including buffers and osmotic agents. The electrolytes include sodium, calcium, magnesium, and, optionally, potassium. The buffer can be lactate and the osmotic agents glucose and / or icodextrin. In systems where PD medical fluids are mixed at the point of care, the components of the medical fluid can be provided as a single concentrate, including the osmotic agent and an additional concentrate containing electrolytes and a buffer. This minimizes the formation of glucose degradation products (GDPs). Having the osmotic agent in a separate container also allows for separate administration of the same medication. The osmotic agent concentrate can be considered an SSR component in such systems. The electrolyte and buffer concentrates can be considered electrolyte components. However, in other examples, the compartments are different to create separate therapeutic fluids for PD, such as Dianeal® or Physioneal®. For example, in the case of Physioneal®, glucose, CaCl, MgCl, and acid may be contained in one concentrate container (then considered the SSR component), and NaCl and NaHCO may be contained in another separate container (then considered the electrolyte component). The final mixed medical fluid for PD contains glucose (C6H 12 O6), sodium (Na + ), calcium (Ca 2+ ), magnesium (Mg 2+ ), chloride (Cl - In one exemplary embodiment for PD, the final predetermined composition or concentration in the dialysate for PD is 75.5 mmol / L (1.36%) glucose, 132 mmol / L Na + , 1.25 mmol / L Ca 2+ , 0.25 mmol / L Mg 2+ , 95.05 mmol / L Cl - , and 40 mmol / L lactate. However, the glucose concentration can vary from 1 to 5%, for example, 1.36%, 2.27%, 3.86, or 4.25%.

[0088] Medical fluids, such as treatment fluids for EC treatment, contain pure water, an acid component, and a base component. The acid component is typically sodium (Na + ), potassium (K + ), calcium (Ca 2+ ), magnesium (Mg 2+ ), glucose, and either acetic acid, lactic acid, or citric acid, or a combination thereof. A salt of each of the acids may be present in the components. The acid component may also include a phosphate salt. The base component typically includes only sodium bicarbonate (NaHCO3), but in some embodiments may also include sodium chloride (NaCl) (if not included in the acid component). The acid component concentrate and the bicarbonate component concentrate are kept in separate containers before mixing. One example of a base component is a BiCart containing dry sodium bicarbonate (NaHCO3) powder. TM It is dissolved "on-line" in pure water before being mixed with the remaining components of the produced dialysate. The acid component, e.g., potassium, may be contained in a separate container as a concentrate to allow for separate administration. Such a separate concentrate, which provides a small contribution to the final conductivity, is considered herein to be an SSR component. The acid component (here, e.g., excluding potassium) is one electrolyte component, and the base component is an additional electrolyte component. Medical fluids for EC treatment may contain, for example, glucose (CH 12 O6), sodium (Na + ), calcium (Ca 2+ ), magnesium (Mg 2+ ), chloride (Cl - ), bicarbonate (HCO3 - ), potassium (K + ) and citrate (C6H5O7 3- For EC treatment, in one exemplary embodiment, the final predetermined composition or concentration in the medical fluid for HD may include 1 g / L glucose, 140 mmol / L Na + , 1.50 mmol / L Ca 2+ , 0.5 mmol / L Mg 2+ , 109 mmol / L Cl - , 34 mmol / L HCO3 -, 2 mmol / L K + , and 1 mmol / L C6H5O7 3- Includes.

[0089] Here, "pure water" refers to water purified to a desired level of purity, such as water for dialysis, ultrapure water, or water for injection. Dialysis water is defined in accordance with ISO / ANSI / AAMI 23500-3:2019, which defines a range of maximum concentrations of substances and requires a total viable count of <100 CFU / ml and endotoxins of <0.25 EU / ml. Ultrapure water can be defined as Type 1 water in the ASTM and ISO laboratory water quality standards, with quality requirements documented by ASTM D5127 "Standard Guide for Ultrapure Water Used in the Electronics and Semiconductor Industries" and SEMI F63 "Guide for Ultrapure Water Used in Semiconductor Processing." Water for injection is defined, for example, according to USP 39 NF and USP 643 NF and requires a conductivity of <1.3 uS / cm, total organic carbon <500 ppb, bacteria <10 CFU / 100 ml and endotoxin <0.25 IU / ml at 25°C.

[0090] 1 is a schematic diagram of an example dialysis treatment system 1. Dialysis treatment system 1 is illustrated here with a water purification system 10, a mixing system 20, and a treatment delivery system 30. Any of these systems 10, 20, 30 may be integrated or separate units. For example, water purification system 10 and mixing system 20 may be integrated into a single unit that is not easily separable.

[0091] The water purification system 10 processes one or more of water from a water supply 5, used medical fluids and / or waste liquids, and / or water from the air and delivers pure water of a desired degree of purity to a mixing system 20. The water purification system 10 may include one or more of a sediment filter, a carbon bed, reverse osmosis technology, forward osmosis technology, membrane distillation technology, a nanofilter, an ultrafilter, an ion exchange technology, ultraviolet light, a heater, or a sterilizing filter. The water purification system 10 is connected to a water source, here a water supply 5.

[0092] The mixing system 20 receives the purified water from the water purification system 10. The mixing system 20 mixes the purified water with a concentrate to provide the medical fluid to the treatment delivery system 30. The concentrate is provided in a concentrate container connected to the mixing system 20.

[0093] The therapy delivery system 30 receives the medical fluid from the mixing system 20. The therapy delivery system 30 may be or include, for example, a cycler or a dialysis machine. In the case of a cycler, a catheter connects the therapy delivery system 30 to the abdomen of the patient 40. In the case of a dialysis machine, the medical fluid is directed to a dialyzer, where the fluid is passed through one side of a membrane of the dialyzer and blood from the patient 40 is passed through the other side of the membrane. The medical fluid may also be used as a substitution fluid / infusion fluid and infused into the blood upstream or downstream of the dialyzer. The medical fluid may also be collected in a medical fluid bag or container (not shown) within the therapy delivery system 30 before being transported further to the patient or dialysis system (the dialyzer or an upstream / downstream dialyzer). The therapy delivery system 30 is one of several tasks in safely delivering therapy to a patient, including handling the medical fluid and removing waste fluid from the patient.

[0094] Below, several different examples of mixing systems 20 that can be used in system 1 of FIG. 1 are described. The mixing systems 20 described herein are configured to generate fluids, including mixtures, at the point of care, for example, in a home or intensive care (IC) unit. Thus, the mixing systems 20 described herein can be configured to generate one or more medical fluids for PD or EC therapy, for use in any of PD therapy, HD, HF, HDF therapy, IC therapy, CRRT, IHD, SLED / SLEDD, or EDD, or in the mixing system 20 itself. In particular, the medical fluid may be any of the fluids used in the mixing system 20, IV fluids, dialysis fluids, infusion fluids, substitution fluids, or replacement fluids. Each of the mixing systems 20 illustrated herein is configured for so-called in-line mixing of components of a medical fluid having a final predetermined composition of pure water, an SSR component of a small-signal response, and, optionally, at least one electrolyte component. In this disclosure, in-line mixing refers to mixing components of a medical fluid within a line, such as the main fluid line 21 (see FIGS. 2, 7, and 10), which may include one or more fluid lines of the mixing system 20, while the components are added as concentrates from containers to the main fluid line 21. The main fluid line 21 may be equipped with a mixing means to ensure that the resulting fluid is homogeneous when it reaches the system's endpoint. Examples of such mixing means are one or more small mixing chambers, static mixers, or extensions of the main fluid line that support the mixing of the fluids. However, the fluids to be mixed flow continuously through the main fluid line 21 and then through the mixing chambers / static mixers / extensions. Such mixing may also be referred to as "on-line" mixing.

[0095] 2 is a schematic diagram of an exemplary mixing system 20. This exemplary mixing system 20 illustrates several general features of all mixing systems as illustrated herein, and like reference numbers in the figures refer to like features throughout this disclosure.

[0096] The mixing system 20 includes a fluid pathway 19. In one embodiment, the fluid pathway 19 is a durable pathway. The fluid pathway 19 is typically incorporated into a housing (not shown) having ports for the inlet / outlet of the fluid pathway 19. In another embodiment, the fluid pathway 19 is disposable. The fluid pathway 19 is then attached to the mixing system 20 by the user before mixing begins. The fluid pathway 19 includes one or more fluid lines and other components. In the present disclosure, a line can be a pipe, a tube, and / or a hose. The fluid pathway 19 includes a main fluid line 21. The main fluid line 21 includes one or several interconnected fluid lines. The main fluid line 21 is arranged to be connected to the pure water source 10. The mixing system 20 further includes a main pump 23. The main pump 23 is arranged in the main fluid line 21 and pumps a main flow rate Q into the main fluid line 21. mml / min. In one embodiment, the main pump 23 is a volumetric pump, such as a piston pump. In another embodiment, the main pump 23 is a non-volumetric pump and uses flow-sensing feedback for its control. The mixing system 20 further includes a concentration sensor 26, here located downstream of the main pump 23, configured to sense the concentration of the fluid in the main fluid line 21. The fluid pathway 19 further includes an SSR component line 25. The SSR component line 25 is fluidly connected at one end to the main pump 23 and the main fluid line 21 upstream of the concentration sensor 26. At the other end, the SSR component line 25 includes an SSR component line connector 25c configured to connect to a mating SSR component container connector 25d of the SSR component container 25b. Thus, the SSR component line 25 is fluidly connected to the main fluid line 21 and includes an SSR component line connector 25c configured to connect to the SSR component container 25b. In some embodiments, the fluid pathway 19 includes one or more electrolyte component lines 24, 61, as indicated by dashed lines. Each electrolyte component line 24, 61 includes an electrolyte component connector 24c, 61c configured to be connected at one end to the main fluid line 21 and to be connected at the other end to a mating electrolyte component container connector 24d, 61d of an electrolyte component container 24b, 61b. Thus, in some embodiments, one or more electrolyte component lines 24, 61 include a respective electrolyte component connector 24c, 61c fluidly connected to the main fluid line 21 and configured to be connected to an electrolyte component container 24b, 61b. In other words, in some embodiments, the electrolyte component line 24 includes an electrolyte component connector 24c fluidly connected to the main fluid line 21 and configured to be connected to an electrolyte component container 24b. In another embodiment, the additional electrolyte component line 61 also includes an additional electrolyte component connector 61c fluidly connected to the main fluid line 21 and configured to be connected to an additional electrolyte component container 61b.

[0097] The mixing system 20 further includes an SSR dosing mechanism 25a. The SSR dosing mechanism 25a is disposed in the SSR component line 25 and provides a dosing rate of the SSR component in the SSR component line 25. More specifically, the SSR dosing mechanism 25a is disposed to provide the SSR component at a dosing rate to the main fluid line 21 upstream of the concentration sensor 26. In one embodiment, the SSR mechanism 25a is a volumetric pump, such as a piston pump. In another embodiment, the SSR mechanism 25a is a non-volumetric pump and uses flow-sensing feedback for its control. In yet another embodiment, the SSR mechanism 25a includes one or more valves. In some embodiments, the mixing system 20 further includes one or more electrolyte dosing mechanisms 24a, 61a. Each such electrolyte dosing mechanism 24a, 61a is then disposed in a respective electrolyte component line 24, 61 and provides a dosing rate of the electrolyte component in the electrolyte component line 24, 61. More specifically, each such electrolyte dosing mechanism 24a, 61a is disposed to provide one of the at least one electrolyte component to the main fluid line 21 upstream of the concentration sensor 26 at a dosage rate. In other words, in some embodiments, the electrolyte dosing mechanism 24a is disposed in the electrolyte component line 24 and provides the electrolyte component to the main fluid line 21 upstream of the concentration sensor 26, 60 at a dosage rate. In some embodiments, the additional electrolyte dosing mechanism 61a is disposed in the additional electrolyte component line 61 and provides the additional electrolyte component to the main fluid line 21 upstream of the concentration sensor 26 at a dosage rate. In one embodiment, the electrolyte dosing mechanism 24a, 61a is a volumetric pump, such as a piston pump. In another embodiment, the electrolyte dosing mechanism 24a, 61a is a non-volumetric pump and uses flow-sensing feedback for its control. In another embodiment, the electrolyte dosing mechanism 24a, 61a includes one or more valves.

[0098] The concentration sensor 26 is disposed in the main fluid line 21 downstream of the main pump 23. Alternatively, the concentration sensor 26 is disposed upstream of the main pump 23, but downstream of any concentrate and pure water addition locations in the main fluid line 21. The concentration sensor 26 is positioned to sense the concentration of the fluid in the main fluid line 21 downstream of the main pump 23 (or upstream of the main pump 23 if disposed upstream of the same pump). The fluid in the main fluid line 21 can be pure water, a mixture of pure water and an SSR component, or a mixture of pure water, an SSR component, and one or more electrolyte components, depending on the stage of the mixing process and the type of medical fluid. In particular, the concentration sensor 26 is configured to sense the concentration of the final medical fluid. In some embodiments, the final medical fluid is the medical fluid delivered to the therapy delivery system 30. The mixing system 20 may include another concentration sensor 36 positioned to measure the concentration of the same fluid as the concentration sensor 26. The concentration sensor 26 is used to control the mixing system 20. Another concentration sensor 36 is used for protection measurements. If the measured values ​​differ, there is a malfunction in the concentration measurement. The concentration sensor readings can be temperature compensated using the temperature measurement of the temperature sensor. Therefore, a concentration sensor as disclosed herein can also include a temperature sensor (not shown) configured to sense the temperature of the same fluid that the concentration sensor is sensing. The concentration sensor can be, for example, a conductivity sensor or a glucose sensor. Such a conductivity sensor can also be referred to as a conductivity cell. Concentration sensors are typically configured to measure a specific measurement range with a predetermined accuracy. The measurement range is the range of concentration measurements that do not exceed a defined, agreed-upon, or guaranteed error limit.

[0099] The main fluid line 21 is configured to connect to the therapy delivery system 30 at an endpoint 29 to deliver the produced medical fluid to the therapy delivery system 30. In one embodiment, the main fluid line 21 includes a connector at the endpoint 29, which is configured to connect to a mating connector (not shown) on the therapy delivery system 30. The fluid pathway 19 further includes a waste line 22 fluidly connected to the main fluid line 22. The waste line 22 in FIG. 2 is fluidly connected to the main fluid line 22 downstream of the main pump 23 and the concentration sensors 26, 36 and upstream of the endpoint 29. The waste line 22 is configured to transport fluid to a drain 28 that is discarded for use. Such fluids are, for example, fluids that do not meet the requirements, e.g., concentration, for the final medical fluid. In some embodiments, a first valve 16 is arranged to control the flow of fluid in the main fluid line 21 downstream of the branch to the waste line 22. In some embodiments, a second valve 17 is arranged to control the flow of fluid in the waste line 22. The first valve 16 and the second valve 17 may be replaced with a three-way valve (not shown) fluidly disposed in the main fluid line 21 and the waste line 22. Until the medical fluids are properly and ultimately mixed for treatment, the controller 50 closes the first valve 16 and opens the second valve 17, allowing the medical fluid being prepared to flow through the second valve 17 and the waste line 22 to the drain 28. Once the medical fluids are properly mixed and ready for treatment, the controller 50 opens the first valve 16 and closes the second valve 17, allowing the prepared medical fluid to flow through the endpoint 29. In other words, in some embodiments, the mixing system 20 includes one or more valves 16, 17 configured to be controlled by the controller 50 to direct the fluids in the main fluid line 21 to the waste 28 or to the endpoint 29 of the main fluid line 21.

[0100] The fluid pathway 19 may also include at least one mixing chamber 18. One such mixing chamber 18 is disposed in the main fluid line 21 upstream of the main pump 23 and downstream of any concentrate connection points and pure water inlet points to the main fluid line 21. The mixing chamber 18 has an inlet through which fluid is received from the main fluid line 21 into the internal compartment and an outlet through which fluid is output from the internal compartment to the main fluid line 21. The purpose of the mixing chamber 18 is to facilitate mixing of the fluids and, in some embodiments, to remove gases from the fluids. During use, fluid flows continuously through the mixing chamber 18. It can typically accommodate a volume of fluid between 10 and 200 ml.

[0101] The pure water source is, for example, the water purification system 10 of FIG. 1 . In one embodiment, the water purification system 10 and the mixing system 20 share the same fluid path 19. A main fluid line 21 may then continue into and within the water purification system 10. In another embodiment, the main fluid line 21 includes a pure water inlet connector (not shown) for connecting to the pure water source. The water purification system 10 may include a mating pure water outlet connector (not shown) included in its fluid path. By connecting the pure water outlet connector to the pure water inlet connector, the two systems 10, 20 are fluidly connected. During operation, pure water having a desired degree of purification flows into the main fluid line 21 by, for example, a pumping mechanism included within the water purification system 10 or by a main pump 23. The speed of the main pump 23 determines the flow rate within the main fluid line 21. When only pure water flows through the main fluid line 21 , the flow rate of pure water discharged or withdrawn from the water purification system 10 is equal to the main flow rate pumped by the main pump 23 .

[0102] The mixing system 20 further includes a controller 50 configured to control the operation of the mixing system 20. In some embodiments, the controller 50 is also configured to control the operation of the water purification system 10. The controller 50 may be configured to be controlled, for example, by another controller (not shown) disposed in the treatment delivery system 30. The controller 50 includes a processing means 50a and a memory means 50b. The processing means 50a may include one or more processors. The memory means 50b may include one or more memories. The controller 50 further includes an interface means 50c. The interface means 50c may include one or more of a data interface for transmitting and receiving data and / or signals, a user interface for communicating information such as operational data and alarms, and a user interface for receiving user input to the mixing system 20. The controller 50 is configured to receive sensed data from one or more concentration sensors 26 (from concentration sensor 36 for protective applications), operational data from the pump 23 and mechanisms 24a, 25a, 61a, etc. The controller 50 is further configured to send control data and / or signals to other components, such as the pump 23, mechanisms 24a, 25a, 61a, and valves 16, 17. Communication may be wired or wireless. A user may start and / or stop the medical fluid mixing process by providing input to the mixing system 20 via the user interface. A user may also follow the progress of the production of the medical fluid via the user interface.

[0103] More specifically, the controller 50 is configured to use the main pump 23 to provide a flow of fluid including pure water from the pure water source in the main fluid line 21. To accomplish this, the controller 50 sends a control signal to the main pump 23 to provide a desired flow rate in the main fluid line 21. In response, the main pump 23 begins pumping at the desired flow rate, thereby drawing water from the water source at the desired flow rate. In some embodiments, the controller 50 is configured to provide a mixture of pure water from the pure water source and an electrolyte component from the electrolyte component container 24b in the main fluid line 21. To accomplish this, the controller 50 further sends a control signal to the electrolyte component mechanism 24a to provide a desired flow rate of the electrolyte component from the electrolyte component container 24b. In response, the electrolyte component mechanism 24a begins pumping the electrolyte component at the desired flow rate, thereby flowing through the electrolyte component line 24 and into the main fluid line 21, where it mixes with the pure water. In some embodiments, the controller 50 is configured to provide a mixture of purified water from the purified water source, an electrolyte component from the electrolyte component container 24b, and an additional electrolyte component from the additional electrolyte component container 61b in the main fluid line 21. To accomplish this, the controller 50 further sends a control signal to the additional electrolyte component mechanism 61a to provide a desired flow rate of the additional electrolyte component from the additional electrolyte component container 61b. In response, the additional electrolyte component mechanism 61a begins pumping the additional electrolyte component at the desired flow rate, thereby causing it to flow through the additional electrolyte component line 61 and into the main fluid line 21, where it mixes with the purified water and electrolyte component. The controller 50 is also configured to monitor the concentration of the fluid in the fluid line 21 using the concentration sensor 26. To accomplish this, the concentration sensor 26 sends sensed data from the concentration sensor 26 to the controller 50, or the controller 50 retrieves sensed data from the concentration sensor 26.The control device 50 uses the SSR dosing mechanism 25a to determine the relationship between the dosing rate of the SSR component and the resulting concentration of the SSR component in the fluid, and adjusts the dosing rate of the SSR component so that the concentration monitored using the concentration sensor 26 results in an intended final predetermined concentration c of the SSR component in the medical fluid. SSR_final the initial concentration of the SSR component in the fluid, c, which is greater than SSR_init To accomplish this, the controller 50 sends a control signal to the SSR component mechanism 25a to provide an initial dosing rate of the SSR component from the SSR component container 25b. The initial dosing rate is predetermined or is a dosing rate at which a certain concentration is achieved, as monitored using the concentration sensor 26. Thus, in some embodiments, the controller 50 uses feedback from the concentration sensor 26 to control the SSR component mechanism 25a to the initial dosing rate. In response, the SSR component mechanism 25a begins pumping the SSR component at the initial dosing rate, thereby causing it to flow through the SSR component line 25 into the main fluid line 21, where it mixes with the purified water. In some embodiments, it also mixes with the electrolyte component, and in further embodiments, it also mixes with additional electrolyte components, if provided in the main fluid line 21. The controller 50 uses the SSR dosing mechanism 25a to adjust the dosing rate of the SSR component to achieve a final predetermined concentration c of the SSR component in the fluid, based on the determined relationship. SSR_final The final dose rate Q is achieved SSR_final To accomplish this, the controller 50 determines a final dosing rate based on the relationship and sends a control signal to the SSR dosing mechanism 25a at the final dosing rate. In response, the SSR component mechanism 25a begins pumping at the final dosing rate.

[0104] One or more concentrates and purified water are used to mix medical fluids. Such concentrates, also referred to as components, are shown schematically in FIG. 2 with SSR component container 25b, electrolyte component container 24b, and additional electrolyte component container 61b. However, in some embodiments, the SSR component is mixed with purified water only, and thus, electrolyte component containers 24b, 61b are shown in dashed lines. The flow rate in main fluid line 21 is typically set to a predetermined main flow rate desired by the receiving consumer / device, e.g., therapy delivery system 30 or container (not shown). The predetermined main flow rate may be, for example, 10 to 1000 ml / min, e.g., 10 to 60 ml / min for CRRT, e.g., 20, 25, 30, 35, 40, or 45 ml / min, or 300 to 800 ml / min for intermittent hemodialysis (HD / HF / HDF), or 100 to 500 ml / min for PD, e.g., 200, 250, 300, 350, 400, 450, or 500 ml / min. An infusion unit / pump may be configured to pump infusion fluid from a container to the patient at the infusion rate. If only pure water is added to the main fluid line 21, the pure water flow into the main fluid line 21 will have the same flow rate as the predetermined main flow rate. When an SSR component is added, the flow rate of the pure water decreases by the same amount as the administration rate of the SSR component. This is also true when an electrolyte component is added; therefore, the flow rate of the pure water decreases along with the flow rate of the electrolyte component. In other words, the flow rate of the pure water decreases with the dosing rate of the SSR component and, if added, decreases with the flow rate of the electrolyte component. Accordingly, the water purification system 10 can be configured to provide various amounts of pure water to the mixing system 20. In some embodiments, the flow rate of the pure water is automatically adjusted when another component is introduced into the main flow line 21 so that the flow rate in the main flow line 21 remains constant. In other embodiments, the flow rate of the pure water is controlled to adjust to accommodate another component in the main flow line 21 so that the flow rate in the main flow line 21 remains constant.For example, the flow rate of the pure water is reduced along with the flow rate of the other components. Pure water not used by the mixing system 20 may be recirculated within the water purification system 10. Alternatively, the mixing system 20 may draw water from a pure water tank (not shown) into the water purification system 10, or into the mixing system 20 where it is continuously or repeatedly replenished from the water purification system 10.

[0105] In the following, several examples of mixing including the administration of SSR components are described, as illustrated by Figures 3 and 4 and the flowchart in Figure 5. The system that performs the mixing can be the mixing system 20 of Figure 2. More specifically, the flowchart in Figure 5 illustrates method steps that can be performed by the control device 50 of Figure 2. Thus, the control device 50 is configured to perform all steps, examples, and embodiments outlined below in connection with Figures 3A to 6.

[0106] In these mixing examples, and in all other mixing examples described herein, the mixing involves temporarily overdosing the SSR component so that the concentration of the SSR component can be accurately detected, and then scaling back the dosage rate of the SSR component to a final dosage rate according to a recipe that includes the final concentration of the SSR component in the final medical fluid. Thus, what is described with respect to such overdosing and scaling back in connection with the examples of Figures 3 through 5 may be equally applicable to the examples described with respect to Figures 6 through 11F, but will not always be repeated for ease of explanation.

[0107] 3A-3C show an example of dosing an SSR component, i.e., an SSR concentrate, using the system 20 of FIG. 2. A portion of the main fluid line 21 of the mixing system 20 is shown schematically in the figure, along with a concentration sensor 26. In this example, the concentration sensor 26 is a conductivity sensor. Furthermore, the SSR component is an electrolyte component that is dosed in small amounts into the pure water in the main fluid line 21. Therefore, adding the SSR component to the pure water in the main fluid line 21 increases the conductivity of the mixed solution compared to the conductivity of the pure water. The desired final composition of the medical fluid is predetermined and known, and therefore the intended final predetermined concentration c of the SSR component in the medical fluid is determined. SSR_final However, the final concentration of the SSR component in the medical fluid is so small that the flow rate continuously administered to provide the final concentration of the SSR component does not provide a reliable conductivity measurement using concentration sensor 26. Reference is also made to the flow chart of FIG. 5 to describe an exemplary method.

[0108] In the first step S1, a flow of a fluid containing pure water (W) is m The fluid flow is provided into the main fluid line 21 at a flow rate of 100 ml / min. The flow of pure water is provided as described above. In other words, providing a fluid flow S1 includes controlling the main flow rate of the fluid flow to a predetermined flow rate of the medical fluid. The main flow rate can be controlled using a main pump 23 disposed in the main fluid line 21. The predetermined fluid flow rate can be the flow rate of the medical fluid configured for a downstream device or user. More specifically, the fluid flow contains only pure water; therefore, no other fluids or concentrates are added to the main fluid line 21 at this stage. This is shown in FIG. 3A with the flow of pure water W in the main fluid line 21, with the arrow indicating the direction of flow. Because only pure water flows in the main fluid line 21, the flow rate pumped by the main pump 23 is equal to the pure water flow rate.

[0109] In a second step S2, the conductivity of the fluid is monitored using a concentration sensor 26. This is shown in FIG. 3A, where the concentration sensor 26 measures the conductivity of the fluid in the main fluid line 21. In the present disclosure, monitoring involves continuously, continuously, or repeatedly measuring the concentration of the fluid (or a property, substance, or component therein). The concentration measurement, in this example, conductivity, is provided to the controller 50. Because only pure water flows in the main fluid line 21, the expected conductivity is zero, or very close to zero. Monitoring S2 is typically performed using the same concentration sensor 26. Thus, in some embodiments, all monitoring of the concentration of the fluid in the main fluid line 21 used for control is performed using the same concentration sensor 26.

[0110] In a third step S3, the SSR component is supplied at a dosing rate using the SSR dosing mechanism 25a to the fluid flow upstream of the concentration sensor 26. This reduces the flow rate of the pure water at the dosing rate of the SSR component, so that the total flow rate in the main fluid line 21 remains the same, and therefore Q m ml / min.

[0111] The dosing rate of the SSR component is then increased in an overdosing step S4 using the SSR dosing mechanism 25a to the initial dosing rate Q SSR_init The initial administration rate Q is controlled at ml / min. SSR_init In this case, the conductivity monitored using the concentration sensor 26 is compared with the initial concentration c of the SSR component in the fluid. SSR_init The initial concentration c SSR_init is the intended final predetermined concentration of the SSR component in the medical fluid, c SSR_final Step S4, for example, determines the relationship between the administration rate of the SSR component and the resulting concentration of the SSR component in the fluid. The relationship is determined by determining the desired final concentration of the SSR component, c SSR_final , initial concentration of SSR component c SSR_init , and the initial administration rate of the SSR component Q SSR_init where the desired final concentration of the SSR component, c SSR_finalis predetermined, but the initial concentration of the SSR component, c SSR_init and the initial administration rate Q of the SSR component SSR_init Note that only one of the initial concentrations c of the SSR component is accurately determined in advance. The predetermined one is used as a control parameter by the control device 50, and the other one is accurately determined in the overdosing step S4. SSR_init can be either a predetermined exact value or a predetermined range. Furthermore, the initial administration rate Q of the SSR component SSR_init Q can be either a predetermined exact value or a predetermined range. Different control strategies are therefore possible here. The effect of step S4 on the flow rate is shown in FIG. 3B, where the total flow rate in the main fluid line 21 is still the same Q m ml / min, but the pure water flow rate W is Q m ml / min to Q SSR_init The initial administration rate Q is reduced by 1 ml / min. SSR_init The contribution of the SSR components to the pure water in ml / min can be measured by the concentration sensor 26.

[0112] In some embodiments, the initial concentration of the SSR component in the fluid, c SSR_init is the intended final predetermined concentration of the SSR component in the medical fluid, c SSR_final is greater than the initial administration rate Q SSR_init The ratio between the concentration response, here the conductivity response, resulting from the administration of the SSR component at , and the concentration, here the conductivity signal noise, is greater than or equal to a predetermined limit. The ratio may be expressed as a signal-to-noise ratio, SNR=S / N, where the level of the desired signal S is compared to the level of background noise N. The predetermined limit of the ratio is a predetermined minimum value of SNR. The desired signal S may be determined, for example, by the initial administration rate Q measured using the concentration sensor 26. SSR_initThe response signal resulting from the administration of the SSR component at σ is a measurement of the concentration, here conductivity. The measurement value may be, for example, a magnitude or average value. The noise N is the quantization of the concentration response signal noise, and therefore the variability of the signal from the concentration sensor 26 before the SSR component is administered. The noise N is, for example, predetermined by the control device 50 and calculated as one or more variations of the signal from the sensor, such as the standard deviation of the signal from the sensor, the range of the signal from the sensor, the interquartile range of the signal from the sensor, the mean absolute difference of the signal from the sensor, the median absolute deviation of the signal from the sensor, the mean deviation of the signal from the sensor, the time trend of the signal from the sensor, or the time derivative of the signal from the sensor. The larger the ratio, the better the accuracy of the measurement of the desired signal. The noise is due to the measurement itself, but also to concentration variations caused by differences in the homogeneity of the fluid mixture. In some embodiments, the noise N is calculated based on the initial concentration c of the SSR component. SSR_init and initial administration rate Q SSR_init One of the noise N is predetermined to give the desired SNR. In another embodiment, the noise N is calculated by the controller 50 based on the concentration response before the SSR component is administered. The required signal of the fluid when the SSR component is administered to achieve an SNR equal to or greater than the predetermined limit may be determined by multiplying the noise N by the predetermined limit. The magnitude of the overdose may then be adjusted to suit the noise and SSR component at hand. Thus, in some embodiments, the initial administration rate Q SSR_init Concentration at, for example, conductivity κ init depends on the magnitude of the noise N.

[0113] Initial administration rate Q SSR_init is the final administration rate of the SSR component, Q SSR_final The final dosage rate of the SSR component is the dosage rate that provides the intended final concentration of the SSR component in the medical fluid. In one embodiment, the initial dosage rate Q of the SSR component is SSR_init is the final administration rate Q SSR_finalIn one exemplary embodiment, the initial administration rate Q is greater than 1 to 20 times greater than . For example, it may be 1.5 times, 2 times, 5 times, or 10 times greater. SSR_init ml / min is predetermined. It represents a dosing rate at which it is known, established, for example, by measurement and / or experiment, that the contribution to conductivity of the SSR components in the pure water stream can be accurately measured using concentration sensor 26. The exact conductivity resulting from the predetermined initial dosing rate is unknown, but is within a known interval around a known nominal value. Controlling S4 is then performed by controlling the dosing rate to a predetermined initial dosing rate value, where it is known that the conductivity can be measured with the desired accuracy using concentration sensor 26. In other words, the initial dosing rate here is the predetermined initial dosing rate Q SSR_init The exact conductivity at a given initial dose rate is unknown in this exemplary embodiment, but is expected to be within a known interval. Therefore, controlling S4 corresponds to the conductivity at a given initial dose rate Q SSR_init This may include controlling the dosing rate of the SSR component until 100 ml / min is achieved. The conductivity at a predetermined initial dosing rate is then determined. In another exemplary embodiment, the conductivity is determined by a method typically established by empirical calculation, e.g., here conductivity κ. init Instead, a target concentration, denoted by Q, is predetermined. At this predetermined target concentration, the concentration sensor 26 can measure the contribution to conductivity of the SSR components in the fluid, for example, in pure water. In other words, the initial dosing rate Q SSR_init The conductivity measured using the concentration sensor 26 at init where the exact initial dose rate Q SSR_init Instead, is initially unknown but is expected to be within a known interval. init , the initial administration rate is determined. Typically, the determined initial administration rate is sent to the control device 50 as administration rate data. Therefore, the controlling step S4 is performed by controlling the concentration of the liquid to a predetermined target concentration, for example, the conductivity κ initThis may include controlling the rate of administration of the SSR component until this predetermined target conductivity κ is achieved. init In this case, the administration rate of the SSR component is the initial administration rate Q SSR_init Both of these control methods eliminate dosing errors that may occur due to inaccuracies in the nominal concentration values ​​given by the SSR ingredient manufacturer, for example, when water evaporation from the SSR ingredient concentrate container changes its initial concentration.

[0114] In some embodiments, controlling S4 comprises controlling whether the final administration rate QSSR_final is equal to the desired final concentration c of the SSR component. SSR_final The final value F correlated with final and the initial concentration of the SSR component, c SSR_init The initial value F correlated with initial The initial dose rate Q is the ratio between SSR_init This includes determining the relationship between ∑ ∑ a ∑ b ...

[0115]

number

[0116] In a further step S5, the method comprises using the SSR dosing mechanism 25a to adjust the dosing rate of the SSR component to a final predetermined concentration c of the SSR component in the fluid based on the determined relationship. SSR_final The final dose rate Q is achieved SSR_final Therefore, the final dose rate Q SSR_final Q is determined, for example, using the value established in equation (1), and used to control the SSR dosing mechanism 25a. This is shown in Figure 3C, where the total flow rate in the main fluid line 21 is still the same Q m ml / min, but the pure water flow rate W is Q m ml / min to Q SSR_final ml / min minus the increase. Therefore, once the relationship is determined, the final administration rate Q SSR_final is also determined, which is the desired dosing rate of the SSR component to provide the intended final medical fluid. The SSR component can thereby be dosed at the desired final dosing rate without having to measure the SSR component's contribution to conductivity at this final dosing rate. In some embodiments, the reducing S5 is the final dosing rate Q of the SSR component. SSR_finalThis involves fixing the ratio between the SSR component and the main flow rate, so that if the main flow rate changes, the SSR component dosing rate also changes accordingly to maintain the ratio, thereby maintaining the final composition of the medical fluid. This ratio may be called the dilution ratio of the SSR component.

[0117] For ease of explanation, the embodiments and examples herein generally describe the concentration sensor as being a conductivity sensor. However, such a conductivity sensor may be replaced with a glucose sensor if the SSR component is a glucose component, i.e., a glucose concentrate, and is initially mixed only with pure water. Thus, in some embodiments, the concentration sensor 26 is a glucose sensor. The additional concentration sensor 36 may be an additional glucose sensor used as a protection sensor. The glucose sensor is then used to determine the concentration of the SSR component, which is a glucose concentrate, using the overdose principle as described herein. In some embodiments, the system 20 may additionally include a conductivity sensor and a protection conductivity sensor (not shown), both arranged to measure the conductivity in the main fluid line 21 upstream of the main pump 23. These conductivity sensors may be used to determine any other concentrations of the fluid in the main fluid line 21, such as the concentrations of electrolyte components and / or the concentrations of intermediate and / or final fluids.

[0118] Thus, in one exemplary embodiment, the concentration sensor 26 is a glucose sensor and the SSR component is a glucose component. In such an exemplary embodiment, in a first step S1, a fluid flow comprising pure water is provided in the main fluid line 21. The concentration of glucose in the fluid is monitored in step S2 using the glucose sensor.

[0119] A glucose component is provided in the fluid stream upstream of concentration sensor 26. The glucose sensor monitors the concentration of glucose in the fluid, which is a mixture of glucose concentrate and pure water. Then, in step S4, the glucose component dosing rate is adjusted using SSR dosing mechanism 25a to determine a relationship between the glucose component dosing rate and the resulting concentration of the glucose component in the fluid, such that the concentration monitored using the glucose sensor corresponds to an intended final predetermined concentration c of the glucose component in the medical fluid. SSR_final the initial concentration of glucose in the fluid, c, SSR_init Then, in step S5, the SSR dosing mechanism 25a is used to adjust the dosing rate of the glucose component to a final predetermined concentration c of the glucose component in the fluid based on the determined relationship. SSR_final The final dose rate Q is achieved SSR_final The other steps of the method outlined in relation to Figures 1-3 may be equally applicable in relation to this example using a glucose sensor as the concentration sensor.

[0120] 4A-4D show another example of administering an SSR component, i.e., an SSR concentrate, using the system 20 of FIG. 2. Also in this example, a portion of the main fluid line 21 of the mixing system 20 is shown schematically in the figure, along with a concentration sensor 26. In this example, the concentration sensor 26 is a conductivity sensor. Furthermore, in this example, the SSR component reduces the conductivity of the fluid being added to the main fluid line 21. The SSR component is, for example, a non-electrolyte, such as glucose concentrate or icodextrin. The desired final composition of the medical fluid is predetermined and known, and therefore, the SSR component c in the medical fluid can be determined. SSR_final The intended final predetermined concentration of the SSR component c in the medical fluid has also been determined. SSR_finalThe final concentration of the SSR component is so small that the flow rate continuously administered to provide the final concentration of the SSR component does not provide a reliable conductivity measurement using the concentration sensor 26. Also, because the SSR component reduces conductivity, an electrolyte component must first be added to the pure water to make the fluid more conductive so that it can be measured by the concentration sensor, which is a conductivity sensor. When the SSR component is then added, it reduces the conductivity from the higher conductivity established by the added electrolyte component to a low enough value that it can be accurately measured with the concentration sensor 26, which is a conductivity sensor. The desired final composition of the medical fluid is predetermined and known. Therefore, the SSR component c in the final predetermined composition of the medical fluid is SSR_final and the intended final predetermined concentration of electrolyte component c in the final predetermined composition of the medical fluid. A_final The final predetermined concentration of is also known. To illustrate an exemplary method, reference is also made to the flow chart of FIG.

[0121] In a first step S1, a fluid flow comprising a mixture of pure water (W) and one of at least one electrolyte component is provided in the main fluid line 21. The total flow is Q m ml / min.

[0122] In the second step S2, the conductivity of the fluid is monitored by the concentration sensor 26. The first step S1 and the second step S2 are typically performed simultaneously, so that the conductivity of the fluid is monitored while the fluid is flowing through the main fluid line 21. The pure water is provided in the same manner as in the example described with reference to FIGS. 3A to 3C, and typically has the same purity. Thus, as shown in FIG. 4A, first, only the flow of pure water W is provided in the main fluid line 21 (the arrows indicate the direction of flow). When only pure water flows through the main fluid line 21, the flow rate provided by the main pump 23 is equal to the pure water flow rate.

[0123] 3A-3C, this example also includes adding an electrolyte component to the main fluid line 21 before the SSR component is added. Thus, providing includes providing S1a an electrolyte component at a dosage rate to the pure water stream in the main fluid line 21 using an electrolyte component dosing mechanism 24A to form a fluid stream including a mixture of pure water and the electrolyte component upstream of the concentration sensor 26. This is shown in FIG. 4B, where a dosage rate of electrolyte component "A" is added to the stream or pure water. This reduces the flow rate of the pure water with the dosage rate of the electrolyte component, so that the total flow rate in the main fluid line 21 remains the same, and therefore, Q m ml / min. The addition of the electrolyte component increases the conductivity of the fluid compared to the conductivity of the pure water stream alone. In some embodiments, providing S1a includes, prior to providing the SSR component into the fluid stream, using an electrolyte component dosing mechanism 24A to determine a final predetermined concentration c of the electrolyte component in the final medical fluid based on the conductivity of the pure water and electrolyte component mixture as monitored by concentration sensor 26. A_final Final dose rate Q A_final In other words, the electrolyte dosing mechanism 24A is controlled using conductivity feedback from the concentration sensor 26 to provide the electrolyte component at a flow rate that will provide a desired concentration of the electrolyte component in the medical fluid. The target conductivity is predetermined to provide a predetermined concentration of the electrolyte component for the desired final medical fluid. Thus, by controlling the dosing rate of the electrolyte component dosing mechanism 24A to a dosing rate where the conductivity of the concentration sensor 26 is the target conductivity, the desired concentration of the electrolyte component in the medical fluid is achieved. This dosing rate is referred to as the final dosing rate Q. A_final In some embodiments, the supply S1 is referred to as the final administration rate Q of the electrolyte component. A_final and main flow rate Q mThis involves fixing the ratio between the main flow rate and the electrolyte component so that if the main flow rate changes, the administration rate of the electrolyte component changes accordingly to maintain the ratio and thereby the final composition of the medical fluid. The total flow rate in the main fluid line 21 still remains the same Q m ml / min, but the pure water flow rate W is Q m ml / min to Q A_final It has decreased to minus ml / min.

[0124] Steps S3 to S5 are then performed in the same way as described with reference to Figures 3A to 3C and Figure 5, and reference is made to these sections to explain the method, but will be briefly described below.

[0125] Therefore, in a third step S3, the SSR component is supplied at a dosing rate using the SSR dosing mechanism 25a to the fluid flow upstream of the concentration sensor 26. This reduces the fluid flow at the dosing rate of the SSR component, so that the total flow rate in the main fluid line 21 remains the same, and therefore Q m ml / min.

[0126] The dosing rate of the SSR component is then determined using the SSR dosing mechanism 25a by measuring the initial concentration c of the SSR component in the fluid as monitored by the conductivity sensor 26. SSR_init The initial dose rate Q SSR_init The initial concentration of the SSR component is controlled to ml / min (S4). SSR_init is the intended final predetermined concentration c of the SSR component in the medical fluid to determine the relationship between the administration rate of the SSR component and the resulting concentration of the SSR component in the fluid. SSR_final This is shown in FIG. 4C. Also, because of the addition of electrolyte components, the pure water flow rate W becomes larger than Q after step S4, as shown in FIG. 4C. m ml / min to Q SSR_init , Q A_final The signal to noise ratio, SNR = S / N, is the signal S minus the initial dose rate Q, for example.LCR_init is the response of the measured conductivity in a given time period, and the noise quantification N is the final dose rate Q measured during a given time period, for example A_final is the standard deviation of the measured conductivity response at 1000 kJ / s. The noise quantification may be predetermined for a given system or may be determined by the controller 50 while performing the method, based on conductivity measurements over a period of time.

[0127] In a further step S5, the method comprises using the SSR dosing mechanism 25a to adjust the dosing rate of the SSR component to a final predetermined concentration c of the SSR component in the fluid based on the determined relationship. SSR_final The final dose rate Q is achieved SSR_final Next, the pure water flow rate W is reduced to Q after step S5, as shown in FIG. m ml / min to Q SSR_final , Q A_final The initial administration rate Q SSR_init The conductivity at is determined based on both the electrolyte component and the added conductivity from the SSR component, and is determined based on the predetermined target conductivity κ of the fluid. init In some embodiments, the intended final predetermined concentration of the SSR component in the medical fluid, c SSR_final is up to 5%, e.g., 1.36%, 2.27%, or 3.86%. An exemplary SSR component having such an intended final predetermined concentration is glucose in a medical fluid for PD. The predetermined initial concentration c of the SSR component in the fluid is SSR_init may in this case be 4 to 20 percent, more preferably 4 to 10 percent. For example, when using formula (1) here, in one embodiment, the final value F final is 1.36%, and the initial value F initial is 5%. In another exemplary embodiment, the final value F final and the initial value F initial are the intended final predetermined concentrations of the SSR components in the medical fluid, c SSR_final and a given initial concentration of the SSR component, c SSR_initand is established as the conductivity difference in the fluid measured from a common baseline. The common baseline can be established experimentally or by calculation.

[0128] In some embodiments, the method includes providing S6 the additional electrolyte component at a dosage rate into the fluid flow in the main fluid line 21 using the additional electrolyte component dosing mechanism 61A to form a mixture of pure water, the electrolyte component, the SSR component, and the additional electrolyte component, thereby allowing the medical fluid to be made using three separate concentrates and pure water. In some embodiments, providing S6 includes determining the dosage rate of the additional electrolyte component using the additional electrolyte component dosing mechanism 61A based on the conductivity monitored by the concentration sensor 26 of the mixture of the pure water, the electrolyte component, and the additional electrolyte component to achieve a final predetermined concentration c of the electrolyte component in the final medical fluid. B_final Final dose rate Q B_final In other words, the additional electrolyte dosing mechanism 61A is controlled using conductivity feedback from the concentration sensor 26 to provide the additional electrolyte component at a flow rate that provides a desired concentration of that additional electrolyte component in the medical fluid. The target conductivity is predetermined to provide a predetermined concentration of the additional electrolyte component for the desired medical fluid. Thus, when the conductivity of the concentration sensor 26 is the target conductivity and an additional electrolyte component is included, the desired concentration of the additional electrolyte component in the medical fluid is achieved by controlling the dosing rate of the additional electrolyte component dosing mechanism 61A to the dosing rate. The additional electrolyte component may be referred to as electrolyte component B.

[0129] In some embodiments, the additional electrolyte component has already been added in step S1. The SSR component is then added to the mixture of pure water, the electrolyte component, and the additional electrolyte component. Thus, in such cases, providing a fluid flow S1 includes providing the additional electrolyte component to the pure water flow in the main fluid line 21 at a dosage rate using the additional electrolyte component dosing mechanism 61A to form a fluid flow including a mixture of pure water, the electrolyte component, and the additional electrolyte component upstream of the concentration sensor 26. In some embodiments, providing a fluid flow S1 includes determining the dosage rate of the additional electrolyte component using the additional electrolyte component dosing mechanism 61A based on the concentration of the mixture of pure water, the electrolyte component, and the additional electrolyte component monitored by the concentration sensor 26 prior to providing the SSR component to the fluid flow, to provide a final predetermined concentration c of the additional electrolyte component in the final medical fluid. B_final Final dose rate Q B_final An overdose of the SSR component is then administered to the fluid containing the mixture of pure water, electrolyte component, and additional electrolyte component. As will be appreciated, more electrolyte component may be added before or after the SSR component is administered for overdose or if required by the final fluid composition.

[0130] The target conductivity is typically predetermined. However, the actually achieved conductivity, i.e., the conductivity response, may differ to some extent from the target conductivity. Therefore, a subsequent target conductivity that depends on a previous conductivity control step may be corrected based on the previous conductivity response. Such a procedure may increase the accuracy of the control.

[0131] The use of the master conductivity cell / sensor, ie, concentration sensor 26, described herein means that all mixing steps are set up using the same cell / sensor.

[0132] FIG. 6 shows, in two diagrams, an exemplary dosage of an SSR component that decreases the conductivity of the fluid to which it is added. In this example, the SSR component includes glucose, and the electrolyte component includes NaCl, CaCl2, MgCl2, and the buffer NaLact. The final medical fluid to be mixed is, for example, the fluid product Dianeal®. In some embodiments, the SSR component is a liquid glucose concentrate containing between 40 and 75% glucose. For example, 40, 45, 50, 55, 60, 65, 70, or 75% glucose. As will be appreciated, electrolytes (Na, Ca, Mg, Lact, Cl) increase the conductivity of the solution to which they are added, in this case, pure water.

[0133] Instead, the SSR component includes one or more conductive substances and one or more non-conductive substances, and the resulting SSR component reduces the conductivity of the fluid. One example of such an SSR component includes glucose, which reduces conductivity, and hydrochloric acid (HCl), which increases conductivity. Overall, such an SSR component reduces the conductivity of the fluid with which it is mixed.

[0134] The conductivity contributions of the individual solutes are additive. The conductivity response from electrolytes (electrolyte components) is large at their intended dose (nominal dose rate) for the final medical fluid, making it suitable for direct control. However, the conductivity response from glucose (SSR component) at its intended dose (nominal dose rate) for the final medical fluid is small, giving an unfavorable conductivity signal-to-noise relationship.

[0135] The diagram in Figure 6 outlines the electrolyte and SSR component control steps S1-S5 that are performed to find the flow rate of the dosing mechanism that results in the correct fluid composition. In a non-limiting embodiment, the concentration sensor 26 has a measurement range of 0.1 to 50 mS / cm, more preferably 5 to 20 mS / cm.

[0136] The upper diagram of Figure 6 shows the conductivity in mS / cm during dosing of the electrolyte and SSR components. The solid line shows the first target conductivity κ of the mixture of electrolyte components and pure water. A The first target conductivity κ A is calculated based on the desired final electrolyte component composition and conductivity equation for each solute / electrolyte present in the mixture. As will be appreciated, the electrolyte component may contain different types of dissolved substances, and the first target conductivity κ corresponds to the sum of the conductivities from all these dissolved substances. The first target conductivity κ A corresponds to a final predetermined concentration of the electrolyte component in the final predetermined composition of the medical fluid. A The dashed line in the figure above indicates the target conductivity κ of the medical fluid for the mixture of SSR components, electrolyte components, and pure water. SSR_final The target conductivity of medical fluids is κ. SSR_final is calculated based on the final predetermined composition of the medical fluid, including purified water, electrolyte components, and SSR components, where the target conductivity κ of the medical fluid is SSR_final is the first target conductivity κ according to the desired target SSR component concentration. A The first target conductivity κ is typically 0.35 to 1.05 mS / cm lower than the first target conductivity κ. Therefore, the SSR component reduces the conductivity of the fluid to which it is added by 0.35 to 1.05 mS / cm. A and the medical fluid target conductivity κ SSR_final This difference between SSR_final The first target conductivity κA cannot be reached exactly. Therefore, the medical fluid target conductivity κ SSR_final is the calculated first target conductivity κ A and the first target conductivity reached. The dotted line represents the response of the conductivity measured by the concentration sensor 26.

[0137] The bottom diagram in Figure 6 shows the flow rates of the dosing mechanisms in ml / min. For volumetric pumps, the flow rate is proportional to the pump speed. The solid line shows the flow rate of the electrolyte component dosing mechanism 24a. The dashed line shows the flow rate of the SSR component dosing mechanism 25a.

[0138] The diagram in Figure 6 includes a first phase and a second phase. The first phase includes the dosing control of the electrolyte composition, including steps S1 and S2, and here spans from about 250 s to 650 s. During the first phase, the electrolyte dosing rate is adjusted to a first target conductivity κ of the electrolyte component + pure water mixture, as shown in the diagram below. A The electrolyte component dosing mechanism 24a is controlled using conductivity feedback from the concentration sensor 26 until the flow rate Q of the electrolyte component dosing mechanism 24a is sufficiently close to the conductivity feedback. In one embodiment, a PID controller is used to control the electrolyte component dosing mechanism 24a using conductivity feedback until certain conductivity magnitude and stability criteria are met. This adjustment proceeds during a first phase from time 250 s to approximately 500 s. The flow rate Q of the electrolyte component dosing mechanism 24a is then adjusted. A_final The speed of the electrolyte component dosing mechanism 24a relative to the main pump 23 is also locked and stored in memory 50b. As can be seen in the diagram below, the electrolyte dosing mechanism 24a is controlled to a flow rate of about 10 ml / min, where the resulting conductivity is equal to the first target conductivity κ A , and then the resulting conductivity exceeds the first target conductivity κ A When the conductivity stabilizes at 1000 kJ / min, the flow rate drops to just below 10 ml / min. This is followed by an optional stabilization period with the pump speed / dosing mechanism ratio locked, during which the conductivity can be stabilized without actively controlling the electrolyte component dosing mechanism 24a using conductivity feedback in the first phase. This stabilization phase lasts approximately 100-200 s. The resulting filtered average value of the conductivity is then saved for later use as a baseline for the second phase. In some embodiments, this stabilization period is not performed.

[0139] The second phase involves controlling the glucose composition, and therefore a type of SSR component dosing. This involves providing and overdosing glucose using the SSR dosing mechanism 25a, as in steps S3-S4, and then scaling back the flow rate of the SSR dosing mechanism 25a based on equation (1), as in step S5. The second phase lasts from about 650 s to about 1100 s. As can be seen in the diagram below, the control involves increasing the flow rate of the SSR dosing mechanism 25a in steps from 0 to 20 ml / min. Therefore, the flow rate of the SSR dosing mechanism is controlled by a certain target flow rate, i.e., the initial dosing rate Q. SSR_init This target flow rate may be, for example, a percentage of the main flow rate, e.g., 10 percent. In response to the overdose, the resulting conductivity of the fluid increases to a first target conductivity κ A From the medical fluid target conductivity κ SSR_final The resulting conductivity of the overdose flow rate of the SSR dosing mechanism 25a is measured and the initial conductivity κ SSR_init Here, it is measured to be 11.5 mS / cm, typically ranging from 10.3 to 11.70 mS / cm. The magnitude of the glucose component overdose is selected to produce a glucose concentration in the mixed fluid of between 4 and 10% (nominal / target concentrations in PD medical fluids are typically 1.36%, 2.27%, or 3.86%). The first target conductivity κ A and initial conductivity κ SSR_init The difference between SSR_final Using equation (1), the final value F final is Δκ SSR_final is equal to the initial value F init is Δκ SSR_init The first target conductivity κ is equal to A is 12.686 mS / cm, and the medical fluid target conductivity κ final is 12.35 mS / cm, and the overdose rate Q SSR_initis 20.0 ml / min, the final dosing rate of SSR dosing mechanism 25a is:

[0140]

number

[0141] The SSR component dosing mechanism 25a then performs a final dosing rate Q SSR_final = 5.67 ml / min. The speed ratio of the SSR component dosing mechanism 25a to the main pump 23 is locked and stored in memory 50b. For example, if the flow rate of the main pump is 200 ml / min, the speed ratio is 200 / 5.67 = 35.3. If the flow rate of the main pump is changed, this ratio is used to determine the new flow rate of the SSR component dosing mechanism 25a. This ratio may be referred to as the SSR component dilution ratio, as previously described. This is followed by an optional stabilization period using the locked ratio, during which the conductivity can be stabilized in a second phase. This stabilization phase lasts approximately 100 to 200 seconds.

[0142] Compared to direct control of SSR component dosing mechanism 25a based on conductivity feedback, this overdosing control, coordinated with steps S1-S5, provides an improved conductivity signal-to-noise ratio. After electrolyte component dosing mechanism 24a and SSR component dosing mechanism 25a lock their speeds relative to the speed of main pump 23, mixing system 20 produces dialysis medical fluid with the desired composition. Fluid is sent to drain 28 until the correct, desired composition of dialysis medical fluid is reached. Once the correct composition is produced, first valve 16 is opened, second valve 17 is closed, and the dialysis medical fluid can be sent to outlet point 29.

[0143] FIG. 7 is a schematic diagram of an exemplary mixing system 20 according to some embodiments. The mixing system 20 of FIG. 7 is similar to the mixing system of FIG. 2 and the same references refer to the description of the mixing system of FIG. 2. More specifically, the fluid pathway 19 within the mixing system 20 of FIG. 7 includes an electrolyte component line 24, an additional electrolyte component line 61, an electrolyte dosing mechanism 24a, and an additional electrolyte dosing mechanism 61a, with associated connectors as described above in connection with FIG. 2. The electrolyte component line 24 is fluidly connected to the main fluid line 21 upstream of the connection point of the SSR component line 25 to the main fluid line 21. The additional electrolyte component line 61 is fluidly connected to the main fluid line 21 downstream of the connection point of the SSR component line 25 to the main fluid line 21 but upstream of the main pump 23. 2, the mixing system 20 of FIG. 7 includes a first conductivity sensor 62 configured to sense the conductivity of the fluid in the main fluid line 21 downstream of the connection point of the first electrolyte component line 24 to the main fluid line 21 but upstream of the connection point of the SSR component line 25 to the main fluid line 21. The mixing system 20 of FIG. 7 further includes a second conductivity sensor 60 configured to sense the conductivity of the fluid in the main fluid line 21 downstream of the connection point of the SSR component line 25 to the main fluid line 21 but upstream of the connection point of the second electrolyte component line 61 to the main fluid line 21.

[0144] Below, examples of mixing including the administration of SSR components are described, as illustrated by the flowcharts of Figures 8A to 8E and 9, in which the mixing system of Figure 7 may be used. More specifically, the flowchart of Figure 9 illustrates method steps for mixing components of a medical fluid that may be performed by the control device 50 of Figure 7. Thus, the control device 50 is configured to perform all steps, examples, and embodiments outlined below in connection with Figures 8A to 9.

[0145] Again, in these steps, examples, and embodiments, mixing involves temporarily overdosing the SSR component so that the concentration of the SSR component can be accurately detected, and then scaling back the dosing rate of the SSR component to a final dosing rate according to a recipe that includes the final concentration of the SSR component in the final medical fluid. Thus, what is described with respect to such overdosing and scaling back in connection with the examples of Figures 1 through 6 is equally applicable to the examples described in connection with Figures 7 through 9.

[0146] 8A through 8E are diagrams of different steps for accurately dosing the SSR component in the mixing system 20 of FIG. 7 , according to some embodiments. The different steps are described here in a particular order, but may have a different order in other embodiments. A portion of the main fluid line 21 of the mixing system 20 is shown schematically in the figure, along with a concentration sensor 26. In this example, the SSR component is an electrolyte component that is dosed in small amounts into a mixture of pure water and an additional electrolyte component (A) in the main fluid line 21. Thus, adding the SSR component to the mixture of pure water and electrolyte component A in the main fluid line 21 increases the conductivity of the mixed fluid compared to the conductivity of the mixture of pure water and electrolyte component A. Compared to the example shown in FIGS. 3A through 3C , adding electrolyte component A before the SSR component is added shifts the range in which the conductivity must be measured to a range in which the conductivity can be more accurately measured by the concentration sensor 26. The desired final composition of the medical fluid is predetermined and known, and therefore the intended final concentration of the SSR component in the medical fluid is also known. The final concentration of the SSR component in the medical fluid is so small that the flow rate continuously dosed to provide the final concentration of the SSR component does not provide a reliable conductivity measurement using concentration sensor 26 .

[0147] Referring to the flowchart of FIG. 9, in a first step S1, a flow of a fluid containing a mixture of pure water (W) and an electrolyte component A is, for example, Q m It is provided in the main fluid line 21 at a flow rate of 100 ml / min.

[0148] In the second step S2, the conductivity of the fluid is monitored by the concentration sensor 26. The first step S1 and the second step S2 are typically performed simultaneously, so that the conductivity of the fluid is monitored while the fluid is flowing through the main fluid line 21. The pure water is provided in the same manner and has the same purity as in the example described with reference to FIGS. 3A to 3C. Thus, as shown in FIG. 8A, only pure water W is provided in the main fluid line 21 (the arrows indicate the direction of flow). Because only pure water flows through the main fluid line 21, the flow rate provided by the main pump 23 is equal to the pure water flow rate. Similar to the example of FIGS. 4A to 4D, this example also includes adding electrolyte component A to the main fluid line 21 before the SSR component is added. Providing step S1a includes providing electrolyte component A to the pure water flow in the main fluid line 21 at a dosage rate using an electrolyte component dosing mechanism 24A to form a fluid flow including a mixture of pure water and electrolyte component A upstream of the concentration sensor 26. This is shown in Figure 8B, where the dosing rate of electrolyte component A is added to the flow of pure water. This reduces the flow rate of pure water with the dosing rate of electrolyte component A, so the total flow rate in main fluid line 21 remains the same, and therefore Q m ml / min. The addition of electrolyte component A increases the conductivity of the fluid compared to the conductivity of a pure water-only stream. Also, in the example of FIGS. 4A to 4D, providing may include step S1a controlling the dosing rate of electrolyte component A using conductivity feedback from concentration sensor 26. This dosing rate is the final dosing rate Q of electrolyte component A. A_final In some embodiments, providing S1 is referred to as a final administration rate Q of the electrolyte component. A_final and the main flow rate, so that if the main flow rate changes, the administration rate of electrolyte component A also changes accordingly to maintain the ratio, and thereby the final composition of the medical fluid. The total flow rate in the main fluid line 21 still remains the same Q M ml / min, but the pure water flow rate W is Qm ml / min to Q A_final It has decreased to minus ml / min.

[0149] Steps S3 to S5 are then performed in a similar manner to those described with reference to Figures 3A to 3C, but will now be briefly described. Thus, in a third step S3, the SSR component is supplied at a dosing rate to the fluid flow upstream of the concentration sensor 26 using the SSR dosing mechanism 25a. This reduces the fluid flow at the dosing rate of the SSR component, so that the total flow rate in the main fluid line 21 remains the same, and therefore Q m ml / min.

[0150] The dosing rate of the SSR component is then determined using the SSR dosing mechanism 25a so that the conductivity, monitored using the concentration sensor 26, reaches a predetermined initial concentration c of the SSR component in the fluid. SSR_init The initial dose rate Q SSR_init The initial concentration of the SSR component is controlled to ml / min (S4). SSR_init is the intended final predetermined concentration c of the SSR component in the medical fluid to determine the relationship between the administration rate of the SSR component and the resulting concentration of the SSR component in the fluid. SSR_final This is shown in FIG. 8C. Also, because of the addition of the SSR component, the pure water flow rate W is greater than Q after step S4, as shown in FIG. 8C. m ml / min to Q SSR_init , Q A_final The signal to noise ratio, SNR = S / N, is the signal S minus the initial dose rate Q, for example. SSR_init is the response of the measured conductivity to the final dosage rate Q during a period, for example, A_final is the standard deviation of the measured conductivity response.

[0151] In a further step S5, the method comprises using the SSR dosing mechanism 25a to adjust the dosing rate of the SSR component to a final predetermined concentration c of the SSR component in the fluid based on the determined relationship. SSR_finalThe final dose rate Q is achieved SSR_final Next, the pure water flow rate W is reduced to Q after step S5, as shown in FIG. m ml / min to Q SSR_final , Q A_final The initial administration rate Q SSR_init The conductivity at is determined based on the added conductivity from the electrolyte components to achieve a predetermined target conductivity κ of the fluid. init After the SSR component has been administered at the correct dosage rate, additional electrolyte component B may be administered as shown in step S6 of the flowchart in FIG. 9 and further described with reference to the examples in FIGS. 4A-4D.

[0152] In one embodiment, the mixing system 20 of FIG. 7 may be a system configured to mix medical fluids, for example, for EC blood therapy. The SSR component, in such a case, may be a potassium concentrate. Electrolyte component A may be a concentrate containing an acid and electrolytes, such as sodium, calcium, and magnesium chloride, and may also contain glucose. Electrolyte component B in such a system is a bicarbonate concentrate. Separate dosing of potassium allows for any concentration of potassium in the medical fluid, within reasonable limits. In some embodiments, the SSR component includes potassium at a concentration of 400 to 3200 mM / L.

[0153] In this example, the main pump 23 starts pumping pure water from the water purification system 10 at a predetermined rate, corresponding to step S1. Then, the first electrolyte administration mechanism 24a starts administering electrolyte component A from the electrolyte component container 24b, corresponding to step S1a. The flow rate of the first electrolyte administration mechanism 24a is set to a value equal to the first target conductivity κ AThe concentration sensor 26 is controlled by conductivity feedback to reach the first target conductivity κ. The use of the master concentration cell / sensor, i.e., concentration sensor 26, described herein means that all mixing steps are set up using the same cell / sensor. This corresponds to step S2. This also means that the following potassium and bicarbonate mixing steps, which do not add comparable conductivity, will reach the first target conductivity κ. A This significantly improves the accuracy of the mixing by the mixing system 20. When a predetermined conductivity value is reached, the speed of the first electrolyte dosing mechanism 24a at the predetermined conductivity value is locked relative to the speed of the main pump 23. Therefore, the final dosing rate Q of the electrolyte component is A_finalThe ratio between the flow rate and the main flow rate is fixed. The first electrolyte dosing mechanism 24a and the main pump 23 are, for example, piston pumps. The first conductivity sensor 62 is "tuned" (an offset may be added) at this point so that it reads the same as the concentration sensor 26. The first conductivity sensor 62 is used as a protective measure to ensure that the dosing of electrolyte component A functions as intended during the subsequent mixing of another component. Once the speed of the first electrolyte dosing mechanism 24a is fixed, the SSR component mechanism 25a begins dosing potassium into the main fluid line 21, corresponding to step S3. The conductivity contribution of potassium is small. Therefore, the mixing system 20 needs to overdose potassium in the overdose step, and the SSR component mechanism 25a operates at a flow rate much higher than the flow rate that would provide the desired potassium content in the final medical fluid. This corresponds to step S4. By overdosing potassium in this way, a sufficiently high increase in conductivity at the concentration sensor 26 is achieved, which can be accurately measured using the same sensor, i.e., enabling component conductivity control. In one exemplary embodiment, the potassium in SSR component container 25b has a concentration of 800 mmol / L. This results in a flow rate of 0.625 ml / min when the main flow rate is 250 ml / min to result in a potassium concentration of 2 mmol / L in the dialysate. The set conductivity increases from 11.61 to 11.85 mS / cm in the example calculations when going from adding electrolyte component A only to adding electrolyte component A and potassium. This increase cannot be accurately measured by concentration sensor 26. On the other hand, if the potassium flow rate is increased ten-fold, i.e., to 6.25 ml / min, the step instead increases from 11.61 to 14.02 mS / cm, and this change can be accurately measured by concentration sensor 26. The predetermined target conductivity κ corresponding to the increased potassium flow rate is SSR_initcan be calculated, and the SSR dosing mechanism is controlled to a dosing rate corresponding to the predetermined target conductivity using conductivity feedback, as described above. Once the predetermined target conductivity value of the fluid is reached, the controller 50 then uses equation (1) to relate the actual composition in the potassium container 25b to the dosing rate of the SSR mechanism 25a to obtain the desired concentration of potassium in the final medical fluid. The dosing rate of the SSR dosing mechanism 25a is then scaled down to meet that final desired potassium concentration, corresponding to step S5. Alternatively, as described above, the controller 50 may instead control the SSR dosing mechanism 25a to a fixed flow rate Q such that the resulting conductivity step is sufficiently high. SSR_init The resulting stable conductivity is measured and κ SSR_init This conductivity and the predetermined target conductivity κ SSR_final The relationship between a fixed flow rate Q SSR_init Multiplying by , the final flow rate of the SSR dosing mechanism 25a is obtained to reach the desired final concentration of the SSR component. The rotation speed of the SSR mechanism 25a is locked to the speed of the main pump 23, similar to the first electrolyte dosing mechanism 24a described above, thus establishing the dilution ratio of the SSR component. After the dosing of electrolyte component A and potassium is established, the second dosing mechanism 61a begins adding bicarbonate to the fluid in the main fluid line 21. This routine is the same as the first dosing step. The target conductivity κ for control by the concentration sensor 26 is final represents the composition of the final medical fluid. In one embodiment, the conductivity is 12-16 mS / cm. Because the composition exiting second electrolyte component container 61b changes due to temperature, it is important that the flow of bicarbonate concentrate is constantly controlled for conductivity during processing.

[0154] FIG. 10 shows a schematic diagram of an exemplary mixing system according to some embodiments. The mixing system 20 of FIG. 10 is very similar to the mixing system of FIG. 7, and reference is made to the description of FIG. 7 to explain the same references. The mixing system 20 of FIG. 10 differs from the mixing system of FIG. 7 in that the components for administering electrolyte component A are replaced with components for administering electrolyte component B. Thus, electrolyte component A is mixed into the main fluid line 21 downstream of the point where the SSR components are mixed into the main fluid line 21, but upstream of the main pump 23. The controller 50 is configured to perform all steps, examples, and embodiments outlined below in connection with FIGS. 11A through 11F.

[0155] Again, in these steps, examples, and embodiments, mixing involves temporarily overdosing the SSR component so that the concentration of the SSR component can be accurately detected, and then scaling back the dosage rate of the SSR component to a final dosage rate according to a recipe containing the final concentration of the SSR component in the final medical fluid. Thus, what is described with respect to such overdosing and scaling back in connection with the examples of Figures 1 through 9 is equally applicable to the examples described in connection with Figures 10 and 11.

[0156] 11A to 11F are diagrams of different steps for accurately dosing an SSR component in the mixing system 20 of FIG. 10, according to some embodiments of the present disclosure. A portion of the main fluid line 21 of the mixing system 20 is shown schematically in the figure, along with a first conductivity sensor 62, a second conductivity sensor 62, and a concentration sensor 26. In this example, the SSR component includes both conductive and non-conductive components. The effect is such that the SSR component increases the conductivity of the fluid into which it is dispensed. The SSR component is dispensed in small amounts into the main fluid line 21. For example, the SSR component may be potassium (K + ), calcium (Ca2 + ) and glucose (G). Such SSR components are available, for example, in Baxter's SelectBag TM, e.g., concentrates in SelectBag One or SelectBag Citrate. Such SSR components are typically administered at a dilution ratio of 1:200. This means that if the main flow rate is 500 ml / min, the SSR component should be administered at a low flow rate of approximately 2.5 ml / min compared to the main flow rate. Electrolyte component A can be, for example, Baxter's SelectCart, which contains sodium chloride (NaCl) as a powder. TM The electrolyte component B is, for example, Baxter's BiCart with sodium bicarbonate (NaHCO3) powder. TM Cartridge. BiCart TM The vessel provides a bicarbonate concentrate of approximately 1200 mmol / L. In one embodiment, the final medical fluid contains 140 mmol / L sodium, 34 mmol / L bicarbonate, 2 mM / L potassium, 1 mM Ca. 2+ 1.5mM / l, Mg 2+ 0.5mM / l, Ac - 3mM / l, glucose 5.55mM / l and Cl - It has a concentration of 109 mM / l.

[0157] In the example shown in FIG. 11A, the main pump 23 pumps water from the water purification system 10 at a predetermined rate Q m 11B, the first electrolyte dispensing mechanism 24a then starts dispensing electrolyte component A from the electrolyte component container 24b. The flow rate of the first electrolyte dispensing mechanism 24a is set to 1 / 2 ml / min, and the target conductivity κ A When the predetermined conductivity value is reached, the dosing rate Q of the first electrolyte dosing mechanism 24a at the target conductivity value is controlled by the conductivity feedback from the concentration sensor 26. A_final is locked to the speed of the main pump 23. Therefore, the final dosing rate Q of the electrolyte component A_finalThe ratio between the SSR component and the main flow rate is fixed. This ratio is stored in memory, and the dosing of electrolyte component A is stopped to conserve concentrate. The SSR component mechanism 25a then begins dosing the SSR component into the main flow line 21, and thus into the pure water flow. The conductivity of the SSR component and pure water mixture is measured with the second conductivity sensor 60. + ), calcium (Ca 2+ The contribution of the SSR component conductivity due to the electrolyte component B and glucose (G) is small. However, the second conductivity sensor 60 is used as a protective conductivity sensor during continuous mixing and is therefore configured for a separate conductivity range configured for a fluid containing electrolyte component B, SSR component, and pure water. Therefore, the mixing system 20 must overdose the SSR component during an "overdose phase," in which the SSR component mechanism 25a operates at a flow rate much higher than the flow rate that will provide the desired SSR component content in the final medical fluid. By "overdosing" the SSR component in this manner, a sufficiently high increase in conductivity at the second conductivity sensor 60 is achieved, enabling conductivity control. When the SSR component is overdosed, the predetermined target conductivity κ of the mixture of SSR component, electrolyte component A, and pure water increases, as shown in FIG. 11C. A is achieved, the mixing system 20 then uses equation (1) to relate the actual composition in the SSR component container 25b to the rotational speed of the SSR mechanism 25a to obtain the desired concentration of the SSR component in the final medical fluid. As shown in FIG. 11D, the rotational speed of the SSR mechanism 25a is then reduced to meet the final desired SSR component concentration. The rotational speed of the SSR mechanism 25a is rate locked to the speed of the main pump 23, similar to the first electrolyte dosing mechanism 24a described above, resulting in a dosing ratio for the SSR mechanism.

[0158] Alternatively, administration of electrolyte component A is continued instead of stopped.

[0159] After the dosing of electrolyte component A and the SSR component has been established, the dosing of the SSR component is stopped and the second dosing mechanism 61a begins adding bicarbonate concentrate, and thus electrolyte component B, to the fluid in the main fluid line 21, as shown in FIG. 11E. If the dosing of electrolyte component A was continued, it can also be stopped. Alternatively, the dosing of electrolyte component A and the dosing of the SSR component continue, but more concentrate is discarded. The first conductivity sensor 62 is configured to measure the conductivity of the fluid including pure water and bicarbonate. When a predetermined target conductivity value of the pure water and bicarbonate mixture is reached, the speed Q of the second electrolyte dosing mechanism 61a at the predetermined target conductivity value is increased. B_final is locked to the speed of the main pump 23. Therefore, the final dosing rate Q of the electrolyte component B_final The ratio between the predetermined target conductivity value κ and the main flow rate is fixed. LCR_final corresponds to the desired final concentration of bicarbonate in the final medical fluid. At this stage, the first conductivity sensor 62 and / or the second conductivity sensor 60 are adjusted, if necessary, to ensure that they measure the same level.

[0160] After the dosing rates for electrolyte component A, SSR component, and electrolyte component B are established, dosing of all components begins (if not already underway) at the determined ratio of flow rates, and the main concentrate sensor 26 monitors the conductivity of the final medical fluid, as shown in FIG. 11F. The first conductivity sensor 62 monitors the fluid containing only pure water and electrolyte component B. The second conductivity sensor 60 monitors the fluid containing only pure water, electrolyte component B, and SSR component. All conductivity measurements should correspond to a predetermined conductivity value. In particular, the difference between the measurements from the first conductivity sensor 62 and the second conductivity sensor 60 should be consistent. If this is not the case, an alarm is generated and the different conductivity measurements can be used to identify the source of the error.

[0161] Alternatively, the concentration of electrolyte component B may be adjusted immediately after the concentration of electrolyte component A is adjusted, with first conductivity sensor 62 and / or second conductivity sensor 60 adjusted, as necessary, to ensure they measure the same level. The dosing of electrolyte component B is then stopped while the dosing of electrolyte component A continues. Then, the SSR component is first dosed into the pure water and electrolyte component A flow according to the overdose phase as described above, and the exact dosing flow rate of the SSR component is determined and set. The dosing of electrolyte component B is then resumed at the determined rate. The conductivity measured using the conductivity sensor is then measured as described in the previous example.

[0162] While the present invention has been described in connection with what are presently considered to be the most practical and preferred embodiments, it is to be understood that the invention is not limited to the disclosed embodiments, but on the contrary, is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims.

Claims

1. 1. A method for in-line mixing of components of a medical fluid in a mixing system (20), said medical fluid having a final predetermined composition of purified water, small signal reactive components (SSR components), and optionally at least one electrolyte component, said method comprising: providing (S1) a fluid flow comprising pure water or a mixture of pure water and an electrolyte component in a main fluid line (21); monitoring (S2) the concentration of said fluid using a concentration sensor (26, 60); providing (S3) the SSR component into the fluid stream upstream of the concentration sensor (26, 60) using an SSR dosing mechanism (25a); The SSR dosing mechanism (25a) is used to determine a relationship between the dosing rate of the SSR component and the resulting concentration of the SSR component in the fluid, and the concentration monitored using the concentration sensor (26, 60) is monitored to determine a relationship between the dosing rate of the SSR component and the resulting concentration of the SSR component in the fluid. ＳＳＲ＿ｆｉｎａｌ ) the initial concentration of the SSR component in the fluid (c ＳＳＲ＿ｉｎｉｔ (S4) controlling the initial administration rate to an initial administration rate that indicates Using the SSR dosing mechanism (25a), the dosing rate of the SSR component is adjusted to the final predetermined concentration (c) of the SSR component in the fluid based on the determined relationship. ＳＳＲ＿ｆｉｎａｌ ) is achieved. ＳＳＲ＿ｆｉｎａｌ ) (S5), A method comprising:

2. 2. The method of claim 1, wherein the initial concentration (c ＳＳＲ＿ｉｎｉｔ ) is the intended final predetermined concentration (c ＳＳＲ＿ｆｉｎａｌ ) and the initial administration rate (Q ＳＳＲ＿ｉｎｉｔ ) the ratio between the concentration response and the concentration signal noise resulting from administration of the SSR component at 1000 rpm is greater than or equal to a predetermined limit.

3. 3. The method of claim 1 or 2, wherein the initial administration rate (Q ＳＳＲ＿ｉｎｉｔ ) is the final administration rate (Q ＳＳＲ＿ｆｉｎａｌ ) is more than 1 to 20 times larger than the method.

4. 4. The method of claim 1, wherein the SSR component is either a non-conductive solution or a conductive solution, and the final predetermined concentration (c ＳＳＲ＿ｉｎｉｔ ) is achieved. ＳＳＲ＿ｆｉｎａｌ ) to the flow of fluid in the main flow path, its contribution to the concentration monitored using the concentration sensor (26, 60) is too small to be measured with sufficient accuracy.

5. 5. The method of claim 1, wherein the concentration measured with the concentration sensor (26, 60) at the initial administration rate is greater than a predetermined target concentration (κ ＳＳＲ＿ｉｎｉｔ ) A method corresponding to

6. 6. The method according to claim 1, wherein the initial administration rate is a predetermined initial administration rate (Q ＳＳＲ＿ｉｎｉｔ ) A method corresponding to

7. 7. The method according to any one of claims 1 to 6, wherein the controlling (S4) comprises controlling the final administration rate (Q ＳＳＲ＿ｆｉｎａｌ ) to the intended final predetermined concentration (c ＳＳＲ＿ｆｉｎａｌ ) and the final value (F ｆｉｎａｌ ) and the initial concentration of the SSR component (c ＳＳＲ＿ｉｎｉｔ ) and the initial value (F ｉｎｉｔｉａｌ ) to the ratio between the initial administration rate (Q ＳＳＲ＿ｉｎｉｔ ) multiplied by .

8. 8. The method of claim 1, wherein the providing (S1) of a fluid flow comprises controlling a main flow rate of the fluid flow to a predetermined flow rate of medical fluid.

9. 9. The method of claim 8, wherein the predetermined fluid flow rate is a medical fluid flow rate configured for a downstream device or user.

10. 10. The method of claim 8 or 9, wherein the providing (S1) of a fluid flow comprises controlling the main flow rate using a main pump (23) arranged in the main fluid line (21).

11. 11. The method of any one of claims 1 to 10, wherein said reducing (S5) comprises reducing the final administration rate (Q ＳＳＲ＿ｆｉｎａｌ ) and said main flow rate.

12. 12. The method of any one of claims 1 to 11, wherein the concentration sensor (26, 60) is a conductivity sensor.

13. 13. The method of claim 12, wherein the concentration sensor (26) has a measurement range of 0.1 to 50 mS / cm, more preferably 5 to 20 mS / cm.

14. 14. The method of claim 12 or 13, wherein said monitoring (S2) is performed using the same concentration sensor (26).

15. 15. The method of claim 12, wherein providing (S1) a fluid flow comprises providing the electrolyte component at a dosage rate to the flow of pure water in the main fluid line (21) using an electrolyte component dosing mechanism (24A) to form a fluid flow including a mixture of pure water and the electrolyte component upstream of the concentration sensor (26).

16. 16. The method of claim 15, wherein the providing (S1) of a fluid flow includes controlling the dosing rate of the electrolyte component using the electrolyte component dosing mechanism (24A) to achieve a final predetermined concentration (c) of the electrolyte component in the final medical fluid based on the concentration of the mixture of pure water and the electrolyte component monitored by the concentration sensor (26) prior to the providing of the SSR component into the fluid flow. Ａ＿ｆｉｎａｌ ) to provide a final dose rate (Q Ａ＿ｆｉｎａｌ ) controlling the

17. 17. The method of any one of claims 8 and 12 to 16, wherein the providing (S1) of a fluid flow comprises providing a final dosage rate (Q Ａ＿ｆｉｎａｌ ) and said main flow rate.

18. 18. The method of any one of claims 12 to 17, wherein the SSR component reduces the conductivity of the fluid to which it is added.

19. 19. The method of any one of claims 1 to 18, wherein the SSR component comprises glucose.

20. 20. The method of claim 19, wherein the SSR component is a liquid glucose concentrate containing between 40-75% glucose.

21. 21. The method of claim 19 or 20, wherein the initial concentration (c ＳＳＲ＿ｉｎｉｔ ) is between 4 and 20 percent, more preferably between 4 and 10 percent.

22. 18. The method of any one of claims 12 to 17, wherein the SSR component increases the conductivity of the fluid to which it is added.

23. 23. The method of claim 22, wherein the SSR component comprises potassium.

24. 24. The method of claim 23, wherein the SSR component comprises potassium at the concentration of 400 to 3200 mmol / l.

25. 25. The method of any one of claims 12 to 18, and optionally any one of claims 19 to 21 or 22 to 24, comprising providing (S6) the additional electrolyte component into the flow of fluid in the main fluid line (21) using an additional electrolyte component dosing mechanism (61A) to form a mixture of pure water, the electrolyte component, the SSR component and the additional electrolyte component.

26. 26. The method of claim 25, wherein the providing (S6) comprises controlling the dosing rate of the additional electrolyte component based on the concentrations monitored by the concentration sensor (26) of the mixture of pure water, the electrolyte component, and the additional electrolyte component, using the additional electrolyte component dosing mechanism (61A) to achieve a final predetermined concentration (c) of the additional electrolyte component in the final predetermined composition of the medical fluid. Ｂ＿ｆｉｎａｌ ) to provide a final dose rate (Q Ｂ＿ｆｉｎａｌ ) controlling the

27. 17. The method of claim 15 or 16, wherein providing (S1) a fluid flow comprises providing the additional electrolyte component at a dosage rate to the flow of pure water in the main fluid line (21) using an additional electrolyte component dosing mechanism (61A) to form a fluid flow including a mixture of pure water, the electrolyte component, and an additional electrolyte component upstream of the concentration sensor (26).

28. 28. The method of claim 27, wherein the providing (S1) of a fluid flow includes, prior to the providing of the SSR component to the fluid flow, controlling the dosing rate of the additional electrolyte component using the additional electrolyte component dosing mechanism (61A) to achieve a final predetermined concentration (c) of the additional electrolyte component in the final medical fluid based on the concentrations of the mixture of pure water, the electrolyte component, and the additional electrolyte component monitored by the concentration sensor (26). Ｂ＿ｆｉｎａｌ ) to provide a final dose rate (Q Ｂ＿ｆｉｎａｌ ) controlling the

29. 12. The method of any one of claims 1 to 11, wherein the concentration sensor (16) is a glucose sensor configured to measure a glucose concentration.

30. 1. A mixing system (20) for in-line mixing of components of a medical fluid having a final predetermined composition of purified water, small signal reactive components (SSR components), and optionally at least one electrolyte component, said mixing system (20) comprising: - a fluid path (19) a main fluid line (21) arranged to be connected to a pure water source (10); an SSR component line (25) fluidly connected to the main fluid line (21) and comprising an SSR component line connector (25c) configured to connect to an SSR component container (25b); Optionally, an electrolyte component line (24) fluidly connected to the main fluid line (21) and comprising an electrolyte component connector (24c) configured to connect to an electrolyte component container (24b); a fluid path (19) comprising: a main pump (23) arranged in said main fluid line (21) and providing a main flow of fluid to said main fluid line (21); a concentration sensor (26, 60) arranged to measure the concentration of said fluid in said main fluid line (21); an SSR dosing mechanism (25a) arranged in the SSR component line (25) for providing the SSR component at a dosing rate to the main fluid line (21) upstream of the concentration sensor (26, 60); - optionally an electrolyte dosing mechanism (24a) arranged in said electrolyte component line (24) for providing an electrolyte component at a dosing rate to said main fluid line (21) upstream of said concentration sensor (26, 60); a control device (50), providing a fluid flow containing pure water from the pure water source or a mixture of pure water from the pure water source and the electrolyte component from the electrolyte component container (24b) into the main fluid line (21) using the main pump (23); monitoring the concentration of the fluid using the concentration sensor (26, 60); The SSR dosing mechanism (25a) is used to determine a relationship between the dosing rate of the SSR component and the resulting concentration of the SSR component in the fluid, and the dosing rate of the SSR component is adjusted to a value that satisfies the relationship between the concentration monitored using the concentration sensor (26, 60) and the intended final predetermined concentration (c) of the SSR component in the medical fluid. ＳＳＲ＿ｆｉｎａｌ ) the initial concentration of the SSR component in the fluid (c ＳＳＲ＿ｉｎｉｔ ) is controlled to the initial administration rate shown, Using the SSR dosing mechanism (25a), the dosing rate of the SSR component is adjusted to the final predetermined concentration (c ＳＳＲ＿ｆｉｎａｌ ) is achieved. ＳＳＲ＿ｆｉｎａｌ ) A control device (50) configured as described above; A mixing system (20) comprising:

31. 31. The mixing system of claim 30, wherein the initial concentration (c ＳＳＲ＿ｉｎｉｔ ) is the intended final predetermined concentration (c ＳＳＲ＿ｆｉｎａｌ ) and the initial administration rate (Q ＳＳＲ＿ｉｎｉｔ ) the ratio between the concentration response and the concentration signal noise resulting from administration of said SSR component in a mixed system is equal to or greater than a predetermined limit.

32. 32. The mixing system (20) of claim 30 or 31, wherein the initial dosage rate (Q ＳＳＲ＿ｉｎｉｔ ) is the final administration rate (Q ＳＳＲ＿ｆｉｎａｌ ) more than 1 to 20 times larger than the mixed system (20).

33. 33. The mixing system (20) of any one of claims 30 to 32, wherein the SSR component is either a non-conductive solution or a conductive solution, and the final predetermined concentration (c) of the SSR component in the fluid is ＳＳＲ＿ｆｉｎａｌ ) is achieved. ＳＳＲ＿ｆｉｎａｌ ) to the flow of fluid in the main flow path, its contribution to the concentration monitored using the concentration sensors (26, 60) is too small to be measured with sufficient accuracy.

34. 34. The mixing system (20) of any one of claims 30 to 33, wherein the initial dosage rate (Q ＳＳＲ＿ｉｎｉｔ ) using the concentration sensor (26, 60) is adjusted to a predetermined target concentration (κ ＳＳＲ＿ｉｎｉｔ ) corresponding to the mixing system (20).

35. 35. The mixing system (20) of any one of claims 30 to 34, wherein the initial dosage rate is a predetermined initial dosage rate (Q ＳＳＲ＿ｉｎｉｔ ) corresponding to the mixing system (20).

36. 36. The mixing system (20) of any one of claims 30 to 35, wherein the control device (50) controls the final dosage rate (Q ＳＳＲ＿ｆｉｎａｌ ) to the intended final predetermined concentration (c ＳＳＲ＿ｆｉｎａｌ ) and the final value (F ｆｉｎａｌ ) and the initial concentration of the SSR component (c ＳＳＲ＿ｉｎｉｔ ) and the initial value (F ｉｎｉｔｉａｌ ) to the ratio between the initial administration rate (Q ＳＳＲ＿ｉｎｉｔ ) multiplied by the mixing system (20).

37. 37. The mixing system (20) of any one of claims 30 to 36, wherein the control device (50) is configured to control the main pump (23) to provide the main flow rate to achieve a predetermined flow rate of medical fluid.

38. 38. The mixing system (20) of claim 37, wherein the predetermined fluid flow rate is a medical fluid flow rate configured for a downstream device or user.

39. 39. The mixing system (20) of any one of claims 30 to 38, wherein the control device (50) controls the final dosing rate (Q ＳＳＲ＿ｆｉｎａｌ a mixing system (20) configured to fix the ratio between the main flow rate and the flow rate of the mixed gas.

40. 40. The mixing system (20) of any one of claims 30 to 39, wherein the concentration sensor (26, 60) is a conductivity sensor.

41. 41. The mixing system (20) of claim 40, wherein the concentration sensor (26) has a measurement range of 0.1 to 50 mS / cm, more preferably 5 to 20 mS / cm.

42. 42. The mixing system (20) of claim 40 or 41, wherein the control device (50) is configured to monitor using the same concentration sensor (26).

43. 43. The mixing system (20) of any one of claims 40 to 42, wherein the control device (50) is configured to provide the electrolyte component at a dosage rate to the flow of pure water in the main fluid line (21) using an electrolyte component dosage mechanism (24A) to form a fluid flow including a mixture of pure water and the electrolyte component upstream of the concentration sensor (26).

44. 44. The mixing system (20) of claim 43, wherein the control device (50) controls the dosing rate of the electrolyte component using the electrolyte component dosing mechanism (24a) to achieve a final predetermined concentration (c) of the electrolyte component in the final medical fluid based on the concentration monitored by the concentration sensor (26) of the mixture of pure water and the electrolyte component prior to the provision of the SSR component into the flow of fluid. Ａ＿ｆｉｎａｌ ) to provide a final dose rate (Q Ａ＿ｆｉｎａｌ ).

45. 45. The mixing system (20) of claim 37 and any one of claims 40-44, wherein the controller (50) controls the final dosing rate (Q Ａ＿ｆｉｎａｌ a mixing system (20) configured to fix the ratio between the main flow rate and the flow rate of the mixed gas.

46. 45. The mixing system (20) of any one of claims 40 to 44, wherein the SSR component reduces the conductivity of the fluid to which it is added.

47. 47. The mixing system (20) of any one of claims 30 to 46, wherein the SSR component comprises glucose.

48. 48. The mixing system (20) of claim 47, wherein the SSR component is a liquid glucose concentrate containing between 40-75% glucose.

49. 49. The mixing system (20) of claim 47 or 48, wherein the initial concentration (c ＳＳＲ＿ｉｎｉｔ ) is between 4 and 20 percent, more preferably between 4 and 10 percent.

50. 46. ​​The mixing system (20) of any one of claims 40 to 45, wherein the SSR component increases the conductivity of the fluid to which it is added.

51. 51. The mixing system (20) of claim 50, wherein the SSR component comprises potassium.

52. 52. The mixing system (20) of claim 51, wherein the SSR component comprises potassium at a concentration of 400 to 3200 mmol / l.

53. 52. The mixing system of claim 40, wherein the fluid path comprises an additional electrolyte component line fluidly connected to the main fluid line and providing an additional electrolyte component connector configured to connect to an additional electrolyte component container, the mixing system further comprising an additional electrolyte component dosing mechanism disposed in the additional electrolyte component line, and the control device configured to use the additional electrolyte component dosing mechanism to provide the additional electrolyte component at a dosing rate to the flow of fluid in the main fluid line to form a mixture of pure water, the electrolyte component, the SSR component, and the additional electrolyte component.

54. 54. The mixing system (20) of claim 53, wherein the control device (50) controls the dosing rate of the additional electrolyte component based on the concentrations monitored by the concentration sensor (26) of the mixture of pure water, the electrolyte component, the SSR component, and the additional electrolyte component, to achieve a final predetermined concentration (c) of the electrolyte component in the final predetermined composition of the medical fluid using the additional electrolyte component dosing mechanism (61A). Ｂ＿ｆｉｎａｌ ) to provide a final dose rate (Q Ｂ＿ｆｉｎａｌ ).

55. 55. The mixing system (20) of any one of claims 30 to 54, comprising a waste line (22) fluidly connected to the concentration sensor (26) and the main line (21) downstream of the main pump (23).

56. 56. The mixing system (20) of claim 55, comprising one or more valves (16, 17) configured to be controlled by the control device (50) to direct fluid in the main line (21) to waste (28) or to an end point (29) of the main line (21).

57. 40. The mixing system (20) of any one of claims 30 to 39, wherein the concentration sensor (16) is a glucose sensor configured to measure a glucose concentration.

58. A computer program comprising instructions for causing a system according to any one of claims 30 to 57 to carry out the steps of the method according to any one of claims 1 to 29.

59. 59. A computer-implemented medium having stored thereon the computer program of claim 58.

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