System for detecting vascular access severance

Abstract

To provide a system for detecting falling of a catheter or a needle in vascular access.SOLUTION: A system of the present invention includes: first and second lines for fluid-connecting first and second catheters or a needle to an inlet and an outlet of a pump respectively; a first connector for connecting the first line to the first catheter or the needle, and a second connector for connecting the second line to the second catheter or the needle, each connector having an electrode; an electronic circuit connected to the electrode of the first connector and the second connector electrically, which measures electric impedance of fluid between the first connector and the second connector through a conductive path; and a controller configured to receive an electric impedance value sampled from the electronic circuit and process it as a signal.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention generally relates to hemodialysis and similar dialysis systems, such as systems capable of treating blood or other body fluids extracorporeally.

Background Art

[0002] Due to many factors, hemodialysis is inefficient, difficult, and costly. These factors include the complexity of hemodialysis, concerns about the safety associated with hemodialysis, and the large amount of dialysis fluid required for hemodialysis. Furthermore, hemodialysis is usually performed in a dialysis center that requires skilled technicians.

Summary of the Invention

Problems to be Solved by the Invention

[0003] Therefore, simplifying and improving the efficiency of the dialysis method can potentially have a significant impact on the treatment cost or the patient's out-of-pocket expenses.

Means for Solving the Problems

[0004] Aspects of the present invention generally relate to hemodialysis and similar dialysis systems. The exemplary embodiments described herein may, in some cases, include related products, alternative solutions to specific problems, and / or multiple different uses of one or more systems and / or articles. Although the various systems and methods described herein are described with respect to hemodialysis, it should be understood that the various systems and methods described herein are also applicable in other dialysis systems such as hemofiltration, hemodiafiltration, and / or any extracorporeal system capable of treating blood or other body fluids.

[0005] In one aspect of the present invention, a method for detecting access disconnection comprises measuring electrical impedance from a venous line to an arterial line through a vascular access site; determining an electrical quantity from the measured electrical impedance; comparing the electrical quantity to a first predetermined threshold; starting a counter when the electrical quantity crosses the first threshold; and declaring access disconnection when the counter reaches a predetermined value before the electrical quantity crosses a second threshold. The counter can count units of time, the volume of blood pumped into the vascular access site, or the number of strokes of the blood pump. The electrical quantity may be the raw or filtered value of the impedance between probes, the time derivative of the impedance, or the difference between a first filtered value of the impedance having a first time constant and a second filtered value of the impedance having a second time constant longer than the first time constant. The method for detecting access disconnection can determine the electrical quantity from the measured impedance only while the blood pump is pumping fluid through the arterial or venous line. Furthermore, a controller communicating with the blood pump, closure unit, and user interface may, in response to an ADS algorithm declaring access disconnection, stop the operation of the blood pump, close the closure unit, and / or send a signal to the user. When access disconnection is declared, the controller may confirm the positions of the arterial and venous needles at the vascular access site and prompt the user to choose to resume or terminate treatment. In another aspect of the present invention, a method for detecting access disconnection comprises measuring the electrical impedance from the venous line to the arterial line through the vascular access site at regular intervals; determining an electrical quantity from the measured electrical impedance; completing the pump's stroke to deliver blood to the patient; reducing the driving force to the pump plunger to a lower value; and declaring access disconnection when the electrical quantity exceeds a first predetermined threshold.The electric quantity may be the unprocessed or filtered electrical impedance or the time derivative of the impedance, or the difference between a first filtered value of an impedance having a first time constant and a second filtered value of an impedance having a second time constant longer than the first time constant.

[0006] Another aspect of the present invention is a method for detecting access disconnection, the method comprising: measuring the electrical impedance from a venous line to an arterial line through a vascular access site; determining an electrical quantity from the measured electrical impedance; comparing the electrical quantity to a first predetermined threshold; setting a provisional flag when the electrical quantity crosses the first threshold; clearing the provisional flag when the electrical quantity crosses a second threshold; and declaring access disconnection when the provisional flag has remained set for a certain period of time or longer.

[0007] In another aspect of the present invention, a system for detecting access disconnection comprises a venous line and an arterial line, each having one end connected to a blood pump and the other end connected to a patient's vascular access site; a circuit capacitively coupled to the blood in the venous and arterial lines, capable of measuring the electrical impedance through a portion of the venous line, a portion of the arterial line, and the vascular access site; and a controller communicating with the blood pump and the circuit, the controller determining an electrical quantity from the measured electrical impedance, comparing the electrical quantity to a first predetermined threshold, starting a counter when the electrical quantity crosses the first threshold, and declaring access disconnection if the counter reaches a predetermined value before the electrical quantity crosses a second threshold.

[0008] The system controller can be configured to detect catheter or needle displacement in vascular access, including first and second catheters or needles in a blood vessel, fistula, or graft. The system comprises a first line that fluidly connects a first catheter or needle to the inlet of the pump, a second line that fluidly connects a second catheter or needle to the outlet of the pump, a first connector that connects the first line to the first catheter or needle, a second connector that connects the second line to the second catheter or needle, each connector having an electrode that fluidly communicates with the fluid-carrying lumen of the connector, an electronic circuit that is electrically connected to the electrodes of the first and second connectors and configured to measure the electrical impedance of the fluid between the first and second connectors via a conductive path through the blood vessel, fistula, or graft, and a controller configured to receive a series of sampled electrical impedance values ​​from the electronic circuit and process the electrical impedance values ​​as signals. The operation of the pump may include extracorporeal circulation of a portion of the user's blood.

[0009] In one embodiment, the controller is configured to sample, filter, or smooth a signal using a first time constant to generate a first filtered signal, sample, filter, or smooth a signal using a second longer time constant to generate a second filtered signal, provisionally set a transection flag and start a counter when the difference between the first filtered signal and the second filtered signal is greater than a first threshold, clear the transection flag if the difference between the first filtered signal and the second filtered signal falls below a second smaller threshold before the counter reaches a predetermined count, and declare a vascular transection if the transection flag is not cleared before the counter reaches a predetermined count.

[0010] Optionally, a declaration causes the controller to activate one or more mechanical line closures to stop fluid flow in the first and second lines, stop the pump, or notify the user that a potential vascular rupture has occurred. Notification to the user may include requiring the user to confirm the position of the first and second catheters or needles when accessing the vessel. The controller may be configured to receive commands from the user to restart the pump or to stop further pump operation. The controller may be configured to raise a first threshold if each of several declarations of vascular rupture is followed by a user command to restart the pump. The controller may continue to process electrical impedance values ​​when a declaration of vascular rupture is made and a mechanical line closure is activated, and the controller may be configured to confirm vascular rupture if the difference between the first filtered signal and the second filtered signal exceeds a third threshold greater than the first threshold.

[0011] The counter can count time units where a predetermined count is a predetermined time interval, count units of blood volume pumped into a vascular access where a predetermined count is a predetermined blood volume, or count the number of pump strokes where a predetermined count is a predetermined number of strokes.

[0012] The signal may also be the time derivative of the electrical impedance value. If the pump stops pumping fluid through the first and second lines, the controller can stop processing the electrical impedance values.

[0013] In one embodiment, the controller may perform any of the above processes without filtering the signal data, or using a filtered version of the signal data. The controller may perform any or all of the above processes by using the difference between a first filtered signal using a first time constant and a second filtered signal using a second, longer time constant. Alternatively, the processed signal may be a ratio between the first filtered signal and the second filtered signal, and the ratio may be compared to a first, second, and / or third value to set a provisional flag or start or stop a counter. The controller may perform any or all of the above processes without using a counter or without setting a provisional disconnection flag.

[0014] The controller can perform a signal test to determine whether the detachment event is obscured by a conductive path between electrodes outside the blood vessel, fistula, or graft. The controller can sample the signal using a first time constant and filter or smooth it to generate a first filtered signal, sample the signal using a second longer time constant and filter or smooth it to generate a second filtered signal, start a counter and set a provisional disconnection flag if the difference between the first filtered signal and the second filtered signal exceeds a first threshold, temporarily clear the provisional disconnection flag if the difference between the first filtered signal and the second filtered signal falls below a second lower threshold before the counter reaches a preset count, command the pump actuator to apply force to the pump chamber of the pump to complete the fluid supply stroke to the first or second catheter or needle, command the actuator to apply reduced force to the pump chamber, and declare access disconnection if the difference between the first filtered signal and the second filtered signal exceeds a third threshold greater than or equal to the first threshold.

[0015] In one embodiment, the controller can detect the transition from a blood-filled blood tubing set to a dialysate-filled blood tubing set during a rinseback procedure. A delayed or incomplete transition may indicate, for example, closure at or distal to the connector. The controller may measure a signal or a filtered signal as dialysate is pumped through the dialyzer to the blood tubing set, determine whether the signal or the filtered signal has a first value approximately equal to the expected value of the signal for blood in the first and second fluid lines, or a second value approximately equal to the expected value of the signal for dialysate in the first and second fluid lines, determine the point in time at which the signal or the filtered signal changes from the first value to the second value, and provide a first notification to the user when the controller detects the change from the first value to the second value, or provide a second notification to the user when the controller detects a change from the first value to approximately less than the second value within a predetermined period.

[0016] Other advantages and novel features of the present invention will become apparent from the following detailed description of various non-limiting embodiments of the invention, in conjunction with the accompanying drawings. Where this specification and any reference incorporated herein contain conflicting and / or contradictory disclosures, the present invention shall prevail. Where two or more referenced documents contain conflicting and / or contradictory disclosures, the document with the later effective date shall prevail. [Effects of the Invention]

[0017] As described above, the present invention provides a system for detecting catheter or needle dislodgement in vascular access, including first and second catheters or needles in a blood vessel, fistula, or graft. [Brief explanation of the drawing]

[0018] [Figure 1] A schematic diagram of the fluid processing components of a hemodialysis system according to an exemplary embodiment. [Figure 2] A diagram schematically showing the fluid flow of the dialysis system of FIG. 1. [Figure 3] A diagram schematically showing the fluid flow related to the blood flow circuit of the embodiment of FIG. 2. [Figure 4] A diagram schematically showing the fluid flow related to the equilibrium circuit of the embodiment of FIG. 2. [Figure 5] A diagram schematically showing the fluid flow related to the orientation circuit of the embodiment of FIG. 2. [Figure 5A] A schematic fluid flow diagram showing the flow path related to the drainage assembly in the exemplary embodiment. [Figure 6] A schematic diagram of the fluid flow related to the mixing circuit of the embodiment of FIG. 2. [Figure 7] Right front perspective view of the hemodialysis system of an exemplary embodiment. [Figure 7A] Perspective view of selected components of the power unit of the exemplary embodiment. [Figure 7B] Schematic diagram of the air dehumidifier device of the exemplary embodiment. [Figure 7C] Perspective view of the dehumidifier configuration of the embodiment of FIG. 7A. [Figure 8] Left rear perspective view of the hemodialysis system of FIG. 7. [Figure 9] Front view of the hemodialysis system of FIG. 7. [Figure 10] Right front perspective view of the hemodialysis system of FIG. 7 when the door is in the first open position. [Figure 11] Top view of the hemodialysis system of FIG. 10. [Figure 12] Front view of the hemodialysis system of FIG. 10. [Figure 13] Right side view of the hemodialysis system of FIG. 10. [Figure 14] Right front perspective view of the hemodialysis system of FIG. 7 when the door is in the second open position. [Figure 15] Top view of the hemodialysis system of FIG. 14. [Figure 16] Front view of the hemodialysis system of FIG. 14. [Figure 17]Front view of the hemodialysis system in Figure 7, when the door is in the open position, exposing the system's front panel. [Figure 17A] An exploded perspective view of a control port assembly configured to interface with a blood pump assembly in an exemplary embodiment. [Figure 17B] Side cross-sectional view of the embodiment shown in Figure 17A, in which the blood pump assembly is engaged. [Figure 17C] A perspective view of a control port assembly with a pair of blood pump cassette latches and take-off assemblies according to an exemplary embodiment. [Figure 17D] A standalone view of a latch assembly in which the ejector element of an exemplary embodiment is in the retracted position. [Figure 17E] A standalone view of the latch assembly in Figure 17D, where the ejector element of the exemplary embodiment is in the extended position. [Figure 17F] Front view of a blood pump cassette in a holding position on the panel of a dialysis unit in an exemplary embodiment. [Figure 17G] A cross-sectional view along line 17G-17G in Figure 17F. [Figure 17H] A cross-sectional view along line 17H-17H in Figure 17F. [Figure 17I] A front view of the blood pump cassette in the removed state in the illustrative embodiment. [Figure 17J] A cross-sectional view along line 17J-17J in Figure 17I. [Figure 17K] A cross-sectional view along the line 17K-17K in Figure 17I. [Figure 18] Front view of the blood circuit assembly used in the system shown in Figure 7. [Figure 18A] A perspective view of a blood pump having a drug holder in an exemplary embodiment. [Figure 19] Figure 18 shows a right-angle perspective view of the organizing tray for the blood circuit assembly. [Figure 20] Left posterior oblique view of the blood circuit assembly in Figure 18. [Figure 20A] Front view of another embodiment of the blood pump cassette. [Figure 20B]Figure 20A shows a rear view of the blood pump cassette. [Figure 20C] Front view of the lower or rear plate of the blood pump cassette in Figure 20A. [Figure 20D] Rear view of the lower or rear plate of the blood pump cassette shown in Figure 20A. [Figure 21] Figure 7 shows a left front perspective view of the system's front panel. [Figure 21A] Front view of another embodiment of the front panel assembly in the exemplary embodiment. [Figure 21B] Figure 21A shows the front panel assembly of the blood pump cassette with the upper and central plate components removed for clarity in an exemplary embodiment. [Figure 22] Front view of the front panel in the system shown in Figure 7. [Figure 23] Front view of the front panel of the system shown in Figure 7, which has a pair of mounted functions for a dialyzer. [Figure 24] Side view of a dialyzer equipped with quick-connect fittings attached to the dialysate inlet / outlet ports of the dialyzer. [Figure 25] Right-angle perspective view of the reagent supply source used with the system in Figure 7. [Figure 26] Figure 25 is a perspective view showing the E-shaped connector for the reagent supply source and the corresponding connection point on the front panel of the hemodialysis system. [Figure 27] A perspective view showing a pair of blood line connectors for a blood circuit assembly and the corresponding connection points on the front panel of a hemodialysis system. [Figure 28] A side view showing the blood line connector and connection point in Figure 27. [Figure 29] A perspective view of a blood circuit assembly in another embodiment. [Figure 30] A close-up view of a portion of the blood circuit assembly shown in Figure 29. [Figure 31] An exemplary modular drain cassette in an exemplary embodiment. [Figure 32]Figure 31 is an exploded view showing the drainage cassette, in which the decorative plate in the exemplary embodiment is positioned in front of the front wall of the drainage cassette. [Figure 33] A perspective view of the front wall of the drain cassette in Figure 31 in an exemplary embodiment. [Figure 34] Figure 31 shows the main housing of the drain cassette, with the front wall removed for clarity in an exemplary embodiment. [Figure 35] A rear perspective view of the drain cassette in Figure 31 in an exemplary embodiment. [Figure 36] A diagram showing the front panel with the drain cassette removed in an exemplary embodiment. [Figure 37] A schematic diagram of the conductivity circuit in the exemplary embodiment. [Figure 38] Figure 37 shows the electrical waveforms processed by the circuit. [Figure 39] A typical graph of the noise / error sensitivity of the circuit shown in Figure 37, plotted against the ratio of the unknown resistance to the reference resistance of the circuit. [Figure 40] A schematic diagram of an exemplary blood flow circuit in a hemodialysis system. [Figure 41A] A side view of a connector that can be used in the blood flow circuit shown in Figure 40. [Figure 41B] Cross-sectional view of the connector in Figure 41A. [Figure 42] Cross-sectional views of the connectors shown in Figures 41A and 41B, with wires and flexible tubing attached. [Figure 43A] A perspective view of a connector of another embodiment that can be used in the blood flow circuit shown in Figure 40. [Figure 43B] Top view of the connector in Figure 43A. [Figure 43C] Cross-sectional view of the connector in Figure 43B. [Figure 44A] Cross-sectional view of a flexible tube incorporating conductive wires. [Figure 44B] Cross-sectional view of a flexible tube incorporating conductive wires. [Figure 44C] Cross-sectional view of a flexible tube incorporating conductive wires. [Figure 44D] Cross-sectional view of a flexible tube incorporating conductive wires. [Figure 45] A perspective view of a flexible double-lubricated tube having a fluid-transporting lumen and a wire-transporting lumen. [Figure 46] Cross-sectional view of a connector similar to the connectors shown in Figures 43A-43C, to which wires and piping are attached. [Figure 47] A plan view of an extracorporeal blood flow circuit used in a typical hemodialysis system. [Figure 48] Figure 47 shows a perspective view of a hemodialysis machine configured to accept and operate an extracorporeal blood flow circuit. [Figure 49] Representative plots of resistance measured by the conductivity circuit shown in Figure 37 under various conditions. [Figure 50] An exploded perspective view of the closed assembly from a front angle according to an embodiment of the present disclosure. [Figure 51] Developed perspective view of the closed assembly of Figure 50 from a rear angle. [Figure 52] A front perspective view of the closing assembly in Figure 50, with the door open and the button pressed to indicate tube loading. [Figure 53] A close perspective view of the closing assembly in Figure 50, showing the door engaged with the switch when the door is closed. [Figure 54] Front view of the closing assembly in Figure 50, without the door and frame, to show the arm completely closing the flexible tube. [Figure 55] Figure 50 shows the front view of the closing assembly without the door and frame, indicating the arm in the unclosed position. [Figure 56] Rear / top perspective view of the closed assembly in Figure 50, with the actuator arm in the fully retracted position. [Figure 57] A rear perspective view of the closed assembly in Figure 50, with the actuator arm in the fully extended position. [Figure 58] A side perspective view of some of the operating parts of the closed assembly in Figure 50 in the unclosed state. [Figure 59]A side perspective view of some of the operating parts of the closed assembly in Figure 50 in the closed position. [Figure 60] A side cross-sectional view of the actuator of the closing assembly in Figure 50, showing the position of the main spring for the assembly. [Figure 61] Figure 50 shows the closing assembly mounted on the front panel assembly of a hemodialysis machine according to an embodiment of the present disclosure. [Figure 62] This shows the raw and processed signals from the access disconnection sensor system, as well as the pumping pressure for non-detachment events. [Figure 63] This shows the raw and processed signals from the access disconnection sensor system, as well as the pumping pressure for access disconnection events. [Figure 64] This shows raw and processed signals from the access disconnection sensor system, pumping pressure, and ADS signal tests for access disconnection events. [Figure 65] The raw and processed signals from the access disconnection sensor system, the pumping pressure, and the ADS signal test for access disconnection events are shown, with longer half-cycle durations than those shown in Figures 62-64. [Modes for carrying out the invention]

[0019] Aspects of the present invention will be described with reference to the drawings, with reference to exemplary embodiments. In the drawings, similar reference numerals indicate similar elements. Various aspects of the present invention generally relate to novel systems such as hemodialysis, including hemofiltration systems, hemodiafiltration systems, and plasma exchange systems. Therefore, although the various systems and methods described herein are described in relation to hemodialysis, it should be understood that they are also applicable to other dialysis systems and / or extracorporeal systems capable of processing other bodily fluids such as blood or plasma.

[0020] As described below, a hemodialysis system typically includes a blood channel and a dialysate channel. It should be noted that the fluid flow in these channels does not necessarily have to be linear, and there can be any number of "branchings" within the channel through which the fluid can flow from the inlet to the outlet. Examples of such branching are described in detail below. In the blood channel, blood is drawn from the patient, passes through the dialyzer, and then returns to the patient. The blood is processed by the dialyzer, and waste molecules (e.g., urea, creatinine, etc.) and water are removed from the blood through the semipermeable membrane of the dialyzer and into the dialysate solvent, which passes through the dialysate channel. In various embodiments, blood can be obtained from the patient through two lines (e.g., an arterial line and a venous line, i.e., a "double needle" flow), or in one embodiment, blood can be drawn from the patient and returned through the same, i.e., catheter needle (e.g., both lines or lumens are within the same needle, i.e., a "double lumen" flow). In further embodiments, a "Y-shaped" or "T-shaped" section is used, through a connection to a patient having two branches (one for the flow path of the extracted blood and the other for the flow path of the returning blood, i.e., in the shape of a "single needle" flow), blood is extracted from and returned to the patient. The patient can be any subject requiring hemodialysis or similar treatment, including non-human subjects such as dogs, cats, and monkeys, as well as humans.

[0021] In the dialysate channel, fresh dialysate is created and passed through the dialyzer to process blood from the blood channel. Furthermore, the dialysate can be precisely equalized, or in some embodiments, within at least about 1-2% of the blood pressure, for blood processing within the dialyzer (i.e., the pressure between the dialysate and the blood is equalized). In one embodiment, it may be desirable to maintain a large pressure difference (positive or negative) between the blood channel and the dialysate channel. After passing through the dialyzer, the used dialysate, including waste molecules (as described later), is discarded by a predetermined method. In one embodiment, the dialysate can be recirculated in a "multi-passage" configuration, which may be advantageous for capturing relatively large molecules with low mobility that cross the dialyzer. In one embodiment, the dialysate can be heated before processing the blood in the dialyzer using a suitable heater, such as an electric resistance heater. For example, the dialysate can also be filtered using an ultrafiltration filter to remove contaminants, infectious microorganisms, debris, etc. The ultrafiltration filter may have pore sizes selected to prevent such species from passing through. For example, the pore size can be less than approximately 0.3 micrometers, less than approximately 0.2 micrometers, less than approximately 0.1 micrometers, or less than approximately 0.05 micrometers. Dialysis fluid is used to remove waste molecules (e.g., urea, creatinine, potassium ions, phosphates, etc.) and water from the blood and deliver them into the dialysis fluid by solute transfer associated with osmosis or filtration, and dialysis fluid is well known to those skilled in the art.

[0022] Dialysis fluid typically contains various ions, such as sodium, chloride, bicarbonate, potassium, and calcium, at concentrations similar to those in normal blood. In one embodiment, the concentration of bicarbonate may be slightly higher than that in normal blood. Dialysis fluid is usually prepared by mixing water from a water dispenser with one or more components, where one or more components are "acid" (which may include various types such as acetic acid, dextrose, NaCl, CaCl, KCl, MgCl, etc.), sodium bicarbonate (NaHCO3), and / or sodium chloride (NaCl). The preparation of dialysis fluid, including the use of appropriate salt concentrations, osmolality, pH, etc., is well known to those skilled in the art. As will be described in detail below, dialysis fluid does not need to be prepared at the same time it is used to process blood. For example, dialysis fluid can be prepared at the same time as or before dialysis and stored in a dialysis fluid storage container or the like.

[0023] In a dialyzer, dialysate and blood are typically separated by a semipermeable membrane. The semipermeable membrane is usually made of a polymer such as cellulose, polyaryl ethersulfone, polyamide, polyvinylpyrrolidone, polycarbonate, or polyacrylonitrile, which allows the transport of ions and small molecules (e.g., urea, water) during blood processing but does not allow mass transport or solute transfer associated with filtration. In one embodiment (e.g., a high-flux dialyzer), larger molecules such as β2-microglobulin may pass through the membrane. Also, in one embodiment, for example, if a hydrostatic pressure difference exists within the semipermeable membrane, ions and molecules may pass through the dialyzer by convection.

[0024] It should be noted that as used herein, “fluid” means all substances that possess the properties of a fluid, and includes, but is not limited to, gases such as air, and liquids such as water, aqueous solutions, blood, and dialysate.

[0025] Figure 1 is a schematic block diagram of the fluid circuit of a hemodialysis system incorporating various embodiments of the invention. In this exemplary embodiment, the dialysis system 5 includes a blood flow circuit 141 that draws blood from the patient, passes the blood through a dialyzer 14, and returns the processed blood to the patient. The balancing circuit or internal dialysate circuit 143 receives dialysate from the ultrafiltration filter 73, passes the dialysate through the dialyzer 14, and receives used dialysate from the dialyzer 14. The directional circuit or external dialysate circuit 142 supplies fresh dialysate to the ultrafiltration filter 73 and receives used dialysate from the internal dialysate circuit 143 (directed towards the drain port 31). The directional circuit 142 may also receive water from a water source 30 and pass that water to the mixing circuit 25. The mixing circuit 25 prepares dialysate using the water from the directional circuit 142 and reagent components 49 such as citric acid, salts, and bicarbonates, which can be obtained from a renewable source. The mixing circuit 25 can, for example, prepare dialysate during and / or before dialysis as needed. The new dialysate prepared by the mixing circuit 25 is supplied to the directional circuit 142, which can then supply the dialysate to the ultrafiltration filter 73 as described above. The directional circuit 142 may include a heater to heat the dialysate to an appropriate temperature and / or to heat the fluid in the disinfection system. For example, for disinfection of a hemodialysis system, the blood flow circuit 141 and the directional circuit 142 can be connected by a conduit 67 (shown by a dotted line).

[0026] Figure 2 is a schematic diagram showing a more detailed circuit configuration for the dialysis system 5 shown in Figure 1. Naturally, Figure 2 represents only one possible embodiment of the general hemodialysis system shown in Figure 1, and it should be understood that other embodiments may include other fluid circuits, modules, flow paths, layouts, etc. Examples of such systems will be described in more detail later and are referenced in the following literature, each incorporated herein by reference. Specifically, these are U.S. Patent Application No. 12 / 072,908 filed on February 27, 2008; U.S. Provisional Patent Application No. 60 / 903,582 filed on February 27, 2007; U.S. Provisional Patent Application No. 60 / 904,024 filed on February 27, 2007; U.S. Patent Application No. 11 / 871,680 filed on October 12, 2007; U.S. Patent Application No. 11 / 871,712 filed on October 12, 2007; U.S. Patent Application No. 11 / 871,787 filed on October 12, 2007; U.S. Patent Application No. 11 / 871,793 filed on October 12, 2007; or U.S. Patent Application No. 11 / 871,803 filed on October 12, 2007.

[0027] The blood flow circuit 141 comprises an anticoagulant source 11 and a blood flow pump 13 that delivers blood from the patient through the dialyzer 14 and returns the blood to the patient. The anticoagulant source 11 is located in a blood path toward the dialyzer, and although not shown, it can be located in another suitable location, such as any location upstream or downstream of the blood flow pump 13. The balancing circuit 143 comprises two dialysate pumps 15 that pressurize dialysate into the dialyzer 14 and a bypass pump 35. In one embodiment, the blood flow through the blood flow circuit 141 is synchronized with the dialysate flow in the dialysate channel. In one embodiment, the dialysate flows entering and leaving the dialyzer 14 and the balancing circuit 143 are balanced using the balancing chamber of the balancing circuit 143. The directional circuit 142 comprises a dialysate pump 159 that pressurizes dialysate from the dialysate tank 169 through a heater 72 and / or an ultrafiltration filter 73 to the balancing circuit 143. Furthermore, the directional circuit 142 receives wastewater from the equilibrium circuit 143 and directs it toward the drain port 31. In one embodiment, the blood flow circuit 141 may be connected to the directional circuit 142 through a conduit 67 for disinfection, for example, as described above. The dialysate in the dialysate tank 169 is supplied by the mixing circuit 25. The mixing circuit 25 produces dialysate using water from the water source 30 supplied through the directional circuit 142 and dialysate components 49 (e.g., bicarbonate and acid). A series of mixing pumps 180, 183, and 184 are used to mix the various components to produce dialysate.

[0028] Figure 3 is a close-up view of the blood flow circuit 141 in this embodiment. Under normal operation, blood flows from the patient through the blood flow pump 13 through the arterial line 203 to the dialyzer 14 (the direction of flow during normal dialysis is indicated by arrow 205; however, in some operating modes, the flow may be in a different direction, as will be described later). Optionally, an anticoagulant can be introduced into the blood from an anticoagulant supply source through an anticoagulant pump 80. After passing through the dialyzer 14 and undergoing dialysis, the blood optionally passes through an air trap and / or blood sample port 19 and returns to the patient through the venous line 204. Pump 13 may include, for example, a pump 23 actuated by a control fluid.

[0029] For example, in one embodiment, the blood flow pump 13 may comprise two (or more) pod pumps 23. In this embodiment, each pod pump may comprise a rigid chamber having a flexible diaphragm or membrane that divides each chamber into a pump compartment and a control compartment. These compartments may be provided with four inlet / outlet valves, two for the pump compartment and two for the control compartment. The valves for the control compartment of the chamber may be bidirectional proportional valves, one end of which is connected to a first control fluid source (e.g., a high-pressure air source) and the other end of which is connected to a second control fluid source (e.g., a low-pressure air source) or a vacuum source. During the operation of the pod pump 23, the fluid valves can be opened and closed to direct the fluid flow. Non-limiting examples of pod pumps are described in U.S. Provisional Patent Application No. 60 / 792,073, filed April 14, 2006, or U.S. Patent Application No. 11 / 787,212, filed April 13, 2007, and are incorporated herein by reference, respectively. Where there are two or more pod pumps, they can be operated in any suitable form, for example, synchronously, asynchronously, in phase, or out of phase. For example, in some embodiments, two pumps can be operated out of phase to affect a pumping cycle, for example, one pump chamber being filled while the second pump chamber is empty. Any phase relationship between 0 degrees (both pod pumps are filled and empty simultaneously) and 180 degrees (one pod pump is filled while the other is empty) can be selected to impart a desired pumping cycle. A 180-degree phase relationship can create a continuous flow in and out of a set of pod pumps. For example, continuous flow is beneficial when used with a double needle or double lumen catheter flow. However, in the case of a single needle / single lumen flow, setting a 0-degree phase relationship is beneficial. In a 0-degree relationship, the pod pump first fills the needle, then carries the blood through the blood flow path, and returns the blood to the patient using the same needle.Furthermore, in order to achieve a push / pull relationship (hemodialysis or continuous backflush) across the entire dialyzer, in one embodiment, the execution of phases between 0 and 180 degrees can be utilized.

[0030] An anticoagulant (e.g., heparin or other suitable anticoagulant) can be contained in a vial 11 (or other anticoagulant supply source such as a tube or bag), and the blood flow circuit 141 may be equipped with a spike 201 (in one embodiment, a needle) that can penetrate the seal of the vial. The spike 201 may be made of plastic, stainless steel, or other suitable material, and in one embodiment may be made of a disinfectable material, for example, the material can withstand sufficiently high temperatures and / or radiation during disinfection.

[0031] In one embodiment, an anticoagulant pump 80, which acts as a metering chamber, can be used to control the flow of anticoagulant into the blood circuit. The anticoagulant pump 80 may be a pod pump or a diaphragm metering pump and / or can be operated by a control fluid such as air. For example, the anticoagulant pump 80 may comprise a rigid chamber having a flexible diaphragm that divides the chamber into a pump compartment and a control compartment. One valve for the control compartment of the chamber may be connected to a first control fluid source (e.g., a high-pressure air source), and the other valve may be connected to a second control fluid source (e.g., a low-pressure air source) or a vacuum source. The valve for the pump compartment of the chamber can be opened and closed in coordination with the control compartment to control the flow of anticoagulant into the blood. In one embodiment, air supplied through a filter 81 is introduced into the blood flow path by the anticoagulant pump 80, for example, to supply air into the vial 11 before or after the anticoagulant is drawn from the vial.

[0032] Fluid Management System ("FMS") measurements can be used to measure the volume of fluid pumped through a pump chamber during a single stroke of a membrane, or to detect air within the pump chamber. FMS methods are described in U.S. Patents 4,808,161, 4,826,482, 4,976,162, 5,088,515, and 5,350,357, which are incorporated herein by reference as a whole. In one exemplary embodiment, the volume of fluid delivered by an anticoagulant pump, dialysate pump, or other diaphragm fluid pump is determined using an FMS algorithm that utilizes changes in chamber pressure to calculate volume measurements at the end of a filling stroke and the end of a discharging stroke. The difference between the volumes calculated at the end of the filling stroke and the end of the discharging stroke can be used to determine the actual stroke volume. This actual stroke volume can be compared to an expected stroke volume for a chamber of a particular size. If the actual stroke volume differs significantly from the predicted stroke volume, the stroke may not have been completed properly, and an error message may be generated.

[0033] The blood flow circuit 141 may also include an air trap 19 for removing any air bubbles that may be present in the blood flow path. In one embodiment, the air trap 19 may include a port for separating any air present from the blood by gravity and / or for sampling the blood.

[0034] Figure 4 is a close-up view of the equilibrium circuit 143 in the embodiment of Figure 2. In the equilibrium circuit 143, dialysate flows from an optional ultrafiltration filter 73 into the dialysate pump 15. In this embodiment, the dialysate pump 15 comprises two pod pumps 161 and 162, two equilibrium chambers 341 and 342, and a pump 35 that bypasses the equilibrium chambers 341 and 342. The equilibrium chambers 341 and 342 consist of rigid chambers with a flexible diaphragm that divides the chamber into two separate fluid compartments, configured such that the entry of fluid into one compartment is used to expel fluid from the other compartment (and vice versa). Non-limiting examples of pumps that can be used as pod pumps and / or equilibrium chambers are described in U.S. Provisional Patent Application No. 60 / 792,073, filed April 14, 2006, or in U.S. Patent Application No. 11 / 787,212, filed April 13, 2007.

[0035] In one embodiment, the equalization of the flow in the internal dialysate circuit operates as follows: One set of pneumatic valves 211, 212, 213, 241, and 242 are controlled and operated synchronously, with valves 211, 212, and 213 grouped together and valves 241 and 242 grouped together. Similarly, a second set of pneumatic valves 221, 222, 223, 231, and 232 are controlled and operated synchronously, with valves 221, 222, and 223 grouped together and valves 231 and 232 grouped together. At a first point in time, the valves 211, 212, 213, 241, and 242 of the first set are opened, and the valves 221, 222, 223, 231, and 232 of the second set are closed. Fresh dialysate flows into the equilibrium chamber 341, and used dialysate flows from the dialyzer 14 into the pod pump 161. Because valve 221 is closed, fresh dialysate does not flow into the equilibrium chamber 342. As fresh dialysate flows into the equilibrium chamber 341, the used dialysate in the equilibrium chamber 341 is expelled and exits the equilibrium circuit 143 (because valve 223 is closed, used dialysate does not enter the pod pump 161). At the same time, the pod pump 162 pushes the used dialysate present in the pod pump into the equilibrium chamber 342 (through the open valve 213) (valves 242 and 222 are closed, ensuring that used dialysate flows into the equilibrium chamber 342). As a result, the fresh dialysate contained in the equilibrium chamber 342 exits the equilibrium circuit 143 and enters the dialyzer 14. Furthermore, the pod pump 161 draws used dialysate from the dialyzer 14 into the pod pump 161.

[0036] When the pod pump 161 and the equilibrium chamber 341 are filled with dialysate, the first set of valves 211, 212, 213, 241, and 242 are closed, and the second set of valves 221, 222, 223, 231, and 232 are opened. While valve 221 is open, valve 212 is also open, so fresh dialysate flows into equilibrium chamber 342 instead of equilibrium chamber 341. As fresh dialysate flows into equilibrium chamber 342, valve 213 is closed at this point, so the used dialysate in the chamber is expelled and leaves the equilibrium circuit. Furthermore, since valve 232 is now closed and valve 222 is also open, the used dialysate is prevented from flowing into the pod pump 161, while the pod pump 162 draws used dialysate from the dialyzer into the pod pump. As valves 232 and 211 are closed and valve 223 is opened, the pod pump 161 pushes the used dialysate contained in the pod pump (from the previous step) into the equilibrium chamber 341. This guides the fresh dialysate contained in the equilibrium chamber 341 into the dialyzer 14 (since valve 241 is now open and valve 212 is closed). At the end of this step, the pod pump 162 and the equilibrium chamber 342 are filled with dialysate. Thus, the system state returns to the initial configuration of this description, so that the cycle can be repeated to ensure a constant flow of dialysate to and from the dialyzer 14. In one embodiment, the fluid (e.g., air) pressure on the control side of the equilibrium chamber valve is monitored to ensure that the equilibrium chamber valve is functioning properly (e.g., opening and closing).

[0037] For example, a vacuum (e.g., 4 psi) can be applied to the ports of the first set of valves to open them, and a positive pressure (e.g., 20 psi) can be applied to the valves of the second set to close them (or vice versa). Each pod pump pumps dialysate to one of the equilibrium chambers 341, 342. By pushing the dialysate into a predetermined volume in the equilibrium chamber, an equal amount of dialysate is squeezed out of the remaining volume of the equilibrium chamber by the diaphragm. In each equilibrium chamber, a predetermined volume is occupied by fresh dialysate heading towards the dialyzer, and the remaining volume is occupied by used dialysate coming from the dialyzer. Thus, the volume of dialysate entering the dialyzer and the volume of dialysate leaving the dialyzer are kept approximately equal.

[0038] The bypass pump 35 can direct the dialysate flow from the dialyzer 14 through the equilibrium circuit 143 without passing through either of the pod pumps 161 or 162. In this embodiment, the bypass pump 35 is a pod pump similar to those described above, having a rigid chamber and a flexible diaphragm that divides each chamber into a fluid compartment and a control compartment. This pump may be identical or different to the other pod pumps and / or metering pumps described above. When a control fluid is used to operate the bypass pump 35, the pressure on the exit (used) dialysate side of the dialyzer is further reduced, causing the fluid to be further ultrafiltered from the blood in the dialyzer. This allows the net fluid to flow from the patient's blood through the dialyzer and finally to the drain. Such a bypass is effective in reducing the amount of fluid the patient has, for example, which may increase due to the patient's inability to excrete excess fluid (mainly water) through the kidneys. As shown in Figure 4, the bypass pump 35 can be controlled by a control fluid (e.g., air) regardless of the operation of the pod pumps 161 and 162. This structure eliminates the need to operate the dialysate pump in a disproportionate or phase-shifted manner with the blood pump to achieve the removal of the aforementioned fluid from the patient, making it easier to control the net fluid removal from the patient.

[0039] To balance the overall flow in the dialyzer, the blood flow pump, the balance circuit pump, and the direction circuit pump (described later) can be operated in conjunction to ensure that the flow entering the dialyzer is nearly equal to the flow leaving the dialyzer. If ultrafiltration is required, the ultrafiltration pump (if present) can be operated independently of some or all of the other blood pumps and / or dialysate pumps to achieve the desired ultrafiltration rate.

[0040] To prevent gas generation in the dialysate, the equilibrium circuit pump can be kept under pressure above atmospheric pressure. In contrast, the blood flow pump and direction circuit pump use pressure below atmospheric pressure to pull the diaphragm toward the chamber wall and complete the filling stroke. Because the fluid moves across the entire semipermeable membrane of the dialyzer, and the equilibrium circuit pump operates under positive pressure, the equilibrium circuit pump can utilize information from the blood flow pump to synchronize the delivery stroke of the equilibrium circuit chamber to the dialyzer with the delivery stroke of the blood pump.

[0041] In one embodiment, when operating in such a balancing mode, without delivery pressure from the blood flow pump, the diaphragm of the balancing circuit pump pushes the fluid from the entire dialyzer into the blood, and another pod in the balancing circuit is not fully filled. For this reason, the blood flow pump reports when it is actively delivering one stroke. When the blood flow pump is delivering one stroke, the internal dialysate pump operates. When the blood flow pump is not delivering blood, valves that control the flow from the dialyzer to the internal dialysate pump (and other balancing valves grouped with these valves as described above) are closed to prevent fluid transfer from the dialysate side to the blood side. While the blood flow pump is not delivering, the internal dialysate pump is effectively frozen, and when the blood flow pump resumes delivery, the delivery stroke of the internal dialysate pump resumes. The internal dialysate pump filling pressure can be set to the smallest positive value to ensure that the pump operates above atmospheric pressure with minimum impedance. Furthermore, the internal dialysate pump delivery pressure is set to the blood flow pump pressure so as to approximately match the pressure applied to either side of the dialyzer, thereby minimizing the flow across the dialyzer during the internal dialysate pump delivery stroke.

[0042] In another embodiment, the internal dialysate pump delivers dialysate to the dialyzer at a pressure slightly higher than the pressure at which blood is delivered. This ensures that clean dialysate from a perfectly balanced chamber is delivered to the dialyzer. On the return side, the internal dialysate pump fills the containment dialysate pump chamber with used dialysate from the dialyzer at a pressure slightly lower than the outlet pressure on the blood side of the dialyzer. As a result, enough dialysate is available to complete the entire process within the balanced chamber. The transverse flow across the semipermeable membrane caused by these pressure differences tends to cancel each other out, and in other ways the pumping algorithm attempts to match the average pressure on the dialysate and blood sides of the dialyzer.

[0043] Because stagnant blood flow can lead to thrombosis, it is generally beneficial to keep blood flow as continuous as possible during treatment. Also, if the blood flow pump's output is discontinuous, the balancing pump may pause its stroke more frequently, potentially resulting in discontinuous and / or low dialysate flow. However, the flow through the blood flow pump can be discontinuous for various reasons. For example, to provide a safe pumping pressure for the patient, the pressure within the blood flow pump may be limited to, for example, +600 mmHg and / or -350 mmHg. For example, in the case of a double needle flow, the two pod pumps of the blood flow pump can be programmed to operate 180 degrees out of phase with each other. If there were no pressure limitations, this phase alignment would always be feasible. However, these pressures are limited to provide a safe blood flow for the patient. High impedance in the filling stroke (due to small needles, very viscous blood, limited patient access, etc.) may reach the negative pressure limit, causing the filling flow rate to be slower than the desired rate. Therefore, the delivery stroke must wait for the preceding filling stroke to finish, resulting in a temporary pause in the delivery velocity of the blood flow pump. Similarly, in the case of a single needle flow, the blood flow pump operates at a 0-degree phase, and the pod pumps of the two blood flow pumps are emptied and filled simultaneously. Once both pod pumps are filled, the volume of both pod pumps is delivered. In one embodiment, in a continuous operation, the first pod pump is filled first, then the second pod pump, and then the first pod pump is emptied first, then the second pod pump. Therefore, the flow in a single needle or single lumen structure may be discontinuous.

[0044] One way to control the pressure saturation limit is to restrict the desired flow rate to the slowest filling and delivery strokes. As a result, the blood delivery flow rate is slower, but the flow rate is still known and more continuous, allowing for a more accurate and continuous dialysate flow rate. Another way to make the blood flow rate more continuous in a single-needle operation is to use the maximum pressure to fill the pod so that the filling time is minimized. The desired delivery time can then be set to the desired total stroke time minus the time taken for the filling stroke. However, the less continuous the blood flow becomes, the more the dialysate flow rate must be adjusted upward during blood delivery to the dialyzer to compensate for the time when the dialysate pump is stopped while the blood flow pump is filling. If this is done with precise timing, the average dialysate flow rate over multiple strokes can be matched to the desired dialysate flow rate.

[0045] Figure 5 is a close-up view of the directional circuit 142 in the embodiment of Figure 2. In this embodiment, the directional circuit 142 can supply dialysate from the dialysate tank 169 to the heater 72 and ultrafiltration filter 73 via the dialysate pump 159. The heater 72 can be used to heat the dialysate to a temperature such that body temperature and / or blood in the blood flow circuit are heated by the dialysate, and the blood returning to the patient is above body temperature. In one embodiment, the heater 72 is connected to a control system so that improperly heated dialysate (i.e., dialysate that is too hot or too cold) is recycled (e.g., returned to the dialysate tank 169) or sent to the drain port instead of being sent to the dialyzer. In some embodiments, the heater 72 can also be used for disinfection or sterilization. For example, water can be passed through the hemodialysis system and heated with the heater to a temperature that can disinfect or sterilize, such as about 70°C, about 80°C, about 90°C, about 100°C, or about 110°C.

[0046] The dialysate flow through the directional circuit 142 can be controlled (at least partially) by the operation of the dialysate pump 159. The dialysate pump 159 can also control the flow through the equilibrium circuit 143. For example, as described above, fresh dialysate from the directional circuit 142 flows into the equilibrium chambers 341, 342 of the equilibrium circuit 143. The dialysate pump 159 can be used as the driving force to bring fresh dialysate into these equilibrium chambers. In one embodiment, the dialysate pump 159 includes, for example, a pod pump similar to that described above. The dialysate can also be filtered using, for example, an ultrafiltration filter 73 to remove contaminants, infectious microorganisms, pathogens, pyrogens, debris, etc.

[0047] The ultrafiltration filter 73 can be positioned at an appropriate location within the dialysate flow path, such as between the directional circuit and the equilibrium circuit, as shown in the figure, and / or the ultrafiltration filter 73 can be incorporated into the directional circuit or the equilibrium circuit. When an ultrafiltration filter is used, the pore size can be selected to prevent seeds from passing through the filter.

[0048] In one embodiment, the ultrafiltration filter 73 may operate so that waste from the filter (e.g., retained fluid flow) is sent to a waste flow such as the waste line 39 in Figure 5. In one embodiment, the amount of dialysate flowing into the retained fluid flow can be controlled. For example, if the retained fluid is too cold (i.e., the heater 72 is not functioning or the heater 72 has not heated the dialysate to a sufficient temperature), the entire dialysate flow (or at least a portion of the dialysate) can be diverted to the waste line 39 and optionally recycled to the dialysate tank 169 using line 48. The flow from the filter 73 can also be monitored for several reasons, for example, using temperature sensors (sensors 251, 252, etc.) or conductivity sensors (for checking dialysate concentration, e.g., sensor 253, etc.). Examples of such sensors are described below, and further non-limiting examples are referenced in U.S. Patent Application No. 12 / 038,474, filed February 27, 2008.

[0049] Ultrafiltration filters and dialyzers can provide an extra sorting method for removing contaminants, infectious microorganisms, pathogens, pyrogens, and debris. Therefore, any contaminants must pass through both the ultrafiltration filter and the dialyzer before reaching the patient's blood. Even if the integrity of either the ultrafiltration filter or the dialyzer is compromised, the sterility of the dialysate can be maintained, and contaminants can be prevented from entering the patient's blood.

[0050] The directional circuit 142 can also direct used dialysate from the equilibrium circuit to the drain port, for example, through the waste line 39 to the drain port 31. The drain port may be, for example, a municipal drain port or a separate container that holds water (e.g., used dialysate) to be properly disposed of. In one embodiment, one or more check valves or "one-way" valves (e.g., check valves 215, 216) are used to control the waste flow from the directional circuit 142 and system 5. Furthermore, in one example, a blood leak sensor (e.g., sensor 258) can be used to determine whether blood is leaking through the dialysate flow path through the dialyzer 14. Alternatively, a liquid sensor can be placed in a collection tray at the bottom of the hemodialysis unit to indicate leaks of blood or dialysate, or both, from the fluid circuit.

[0051] The directional circuit 142 can receive water from a water source 30, such as a water container like a bag, and / or a device capable of generating water, such as a reverse osmosis device. In one embodiment, the water entering the system can be set to a specific purity, for example, having an ion concentration below a certain value. The water entering the directional circuit 142 can be sent to various locations, for example, a mixing circuit 25 that generates fresh dialysate and / or a waste line 39. In one embodiment, valves to the drain port 31 and various recycling lines are opened, and a conduit 67 is connected between the directional circuit 142 and the blood flow circuit 141, allowing water to flow continuously through the system. When the heater 72 is started, the water passing through the system is continuously heated to a temperature sufficient to disinfect the system, for example.

[0052] Figure 6 is a close-up view of the mixing circuit 25 in the exemplary embodiment of Figure 2. Water from the directional circuit 142 flows into the mixing circuit 25 by the action of the pump 180. In this embodiment, the pump 180 includes one or more pod pumps similar to those described above. In one embodiment, for example, when transporting components such as bicarbonate 28, a portion of the water is directed through the mixing circuit 25 to a reagent component 49. In one embodiment, sodium chloride and / or sodium bicarbonate 28 is supplied in powder or granular form and mixed with water supplied by the pump 180. Bicarbonate from the bicarbonate source 28 is delivered to the mixing line 186 through the bicarbonate pump 183, which also receives water from the directional circuit 142. Acid (which may be in liquid form) from the acid source 29 is also pumped to the mixing line 186 through the acid pump 184. Components 49 (water, bicarbonate, acid, NaCl, etc.) are mixed in the mixing chamber 189 to produce dialysate, which then flows out of the mixing circuit 25 to the directional circuit 142. Conductivity sensors 178 and 179 are positioned along the mixing line 186 to ensure that each component is added to the mixing line at the appropriate concentration. Since the volume delivered by the water pump 180 and / or other pumps is directly related to the conductivity measurement, the volume measurement can be used as a cross-check for the composition of the dialysate produced. This ensures that the composition of the dialysate remains safe even if the conductivity measurement becomes inaccurate during treatment.

[0053] Figure 7 is a perspective view of a hemodialysis system 5 incorporating various embodiments of the present invention. According to one embodiment of the present invention, the system 5 comprises a dialysis unit 51 and a power module 52, shown joined together. In this embodiment, the dialysis unit 51 has a housing that accommodates components suitable for performing hemodialysis, such as a dialyzer, one or more pumps for circulating blood through the dialyzer, a dialysate source, and one or more pumps for circulating dialysate through the dialyzer. For example, the dialysis unit 51 may include a mixing circuit 25, a blood flow circuit 141, a balancing circuit 143, and a direction circuit 142, as described above. The dialysis unit 51 may also include all blood circuit connections and dialysate fluid connections necessary for the operation of the system 5. Patient access and other connections can be exposed by opening a vertical parallel door 53 through a handle 54 on the front side of the housing of the dialysis unit 51. In this embodiment, the dialysis unit 51 includes a control interface 55 (mounted in this embodiment by a flexible cable on the housing) that can be used to control the operation of the dialysis unit 51. The control interface 55 includes a display screen with a touch-sensing overlay, enabling touch control and interaction with a graphical user interface presented on the screen. The control interface 55 may also include other functions such as push buttons, a speaker, a microphone for receiving voice commands, and a digital camera. On the back of the control interface 55, there may be a retractable "kickstand" (not shown) that allows the control interface 55 to be positioned on top of the housing of the dialysis unit 51. The deployment of the retractable "kickstand" positions the control interface 55 in a substantially vertical position so that the display screen can be viewed properly. In other embodiments, the control interface 55 may include a tablet computer or a handheld electronic communication device, both of which can communicate wirelessly with a controller housed in the dialysis unit 51. Examples of wireless communication means include Bluetooth® technology or wireless local area network technologies such as Wi-Fi®.

[0054] The housing of the power unit 52 may include components suitable for supplying air / vacuum to, for example, the pump, valves, and other components of the dialysis unit 51, which provide operating power to the dialysis unit 51. As used herein, “pneumatic pressure” means the use of air or other gases to move the flexible diaphragm or other members (it should be noted that air is used merely as an example, and in other embodiments, other control fluids such as nitrogen (N2), CO2, water, or oil may be used). As described above, the pumps and valves of the dialysis unit 51 are operated by pneumatic power, so the power unit 52 can provide one or more pneumatic sources for use by the dialysis unit 51. Thus, the dialysis unit 51 does not necessarily need to be configured to generate and / or store the required pneumatic power and can instead rely on the power unit module 52. The power unit 52 may include one or more pneumatic pumps that generate a desired air pressure and / or vacuum, one or more accumulators or other devices for storing air power, valves, pipelines and / or other devices for controlling the airflow in the power unit 52, and a controller having appropriate components such as a programmed general-purpose data processor, memory, sensors (for detecting pressure, temperature, etc.), relays, actuators, etc.

[0055] In one embodiment, pneumatic power (e.g., air under appropriate pressure / vacuum) can be supplied to the dialysis unit 51 by the power unit 52 through one or more supply tanks or other pressure sources. For example, if two tanks are used in the power unit 52, one supply tank can be a positive pressure reservoir and, in one embodiment, has a setpoint of 750 mmHg (gauge pressure) (1 mmHg is approximately 133.3 Pascals). The other supply tank can be a vacuum reservoir or a negative pressure reservoir and, in one embodiment, has a setpoint of -450 mmHg (gauge pressure). To enable precise control of the variable valve over the pod pump, this pressure difference can be utilized, for example, between the supply tank pressure and the required pod pump pressure. The limit of the supply pressure can be set based on the maximum pressure plus margin that can be set for the patient blood flow pump to provide a sufficient pressure difference for controlling the variable valve. Thus, in one embodiment, the two tanks are used to supply pressure and control the fluid for all the functions of the dialysis unit 51.

[0056] In one embodiment, the power unit 52 may include two independent compressors supplying the supply tank. The pressure in the tank can be controlled using appropriate techniques, such as a simple "bang-bang" controller (i.e., a controller with two states: on or open and off or closed), or a more advanced control mechanism, depending on the embodiment. As an example of a bang-bang controller, for the positive tank, if the actual pressure is less than the setpoint, the compressor supplying the positive tank is turned on. If the actual pressure is greater than the setpoint, the compressor supplying the positive tank is turned off. The same logic can be applied to the control of the vacuum tank and vacuum compressor, with the exception that the sign of the setpoint term is reversed. If the pressure tank is not regulated, the compressor is turned off and the valve is closed.

[0057] More precise control of pressure tanks can be achieved by reducing the size of the hysteresis band, but this may result in a higher compressor cycling frequency. When very precise control of these reservoirs is required, a Bang-Bang controller can be replaced with a Proportional-Integral-Derivative (PID) controller using a pulse-width modulation ("PWM") signal on the compressor. Other control methods are also possible.

[0058] Other pressure sources may be used in other embodiments, and in one embodiment, two or more positive pressure sources and / or two or more negative pressure sources may be used. For example, two or more positive pressure sources may be used to supply different positive pressures (e.g., 1000 mmHg and 700 mmHg) that are available to minimize leakage. For example, a higher positive pressure may be used to control a valve, while a lower positive pressure may be used to control a pump. This helps to limit the amount of pressure that may be delivered to the dialyzer or patient and to prevent the operation of the pump from overwhelming the pressure applied to adjacent valves. A non-limiting example of negative pressure is -400 mmHg. In one embodiment, the negative pressure source may be a vacuum pump and the positive pressure pump may be an air compressor.

[0059] In one embodiment, the power unit 52 includes a housing capable of accommodating components as shown in Figure 7a. In this example, the pump and pneumatic storage assembly are configured to fit within the power unit 52 and include a positive pressure pump 60, a negative pressure pump or vacuum pump 61, a high positive pressure storage unit 62, a low positive pressure storage unit 63, a negative pressure storage unit 64, and a dehumidifier or "cooler" unit 65. The high positive pressure storage unit 62 can store air at a pressure of, for example, about 1000 mHg to 1100 mHg or higher, and the low positive pressure storage unit 63 can store air at a pressure of, for example, about 700 mmHg to 850 mmHg. The storage unit 63 can be filled using pressurized air generated by the positive pressure pump 60 by interposing a pressure regulator (not shown) between the outlet of the pump 60 and the inlet of the storage unit 63.

[0060] A cooler 65 or other suitable dehumidifier can be interposed between the outlet of the positive pressure pump 60 and the inlet of one or more positive pressure reservoirs 62 and / or 63. Dehumidification of the pressurized air can prevent moisture condensation inside the pneumatic lines or manifold passages and valves driven by the positive pressure reservoirs 62 and / or 63. As schematically shown in Figure 7b, the cooler 65 may be equipped with a metal coil conduit 66 through which air from the compressor 60 passes, allowing water to condense from the compressed air in the compressor 60. A cooling element 67 can separate the compressed air coil from the heat exchanger 68, through which ambient air can be drawn in by a fan 69, heated, and discharged. The heat exchanger releases heat to the ambient environment, and a water trap 70 separates the condensed water from the compressed air. Next, dry compressed air can be stored in the reservoir 62 (or in the low-pressure reservoir 63 via the pressure regulator) or delivered to a downstream device 71 such as a pneumatic manifold with valves. The cooling element 67 may be a commercially available motorized Peltier element, such as the element model C1-34-1604 from Tellurex, Inc. Figure 7c shows an example in which the cooler 65 is positioned and configured to fit within the boundary of the power unit 52.

[0061] Furthermore, the power unit 52 can be selectively connected to the dialysis unit 51 so that it can be replaced with, for example, a different power unit 52. For example, the dialysis unit 51 can be configured to work with various types of power units 52, such as a power unit 52 that uses electricity to generate air power or a power unit 52 that uses stored air power (for example, pressurized air stored in one or more high-pressure tanks). Thus, the power unit 52 can be replaced with another unit 52 in case of failure or other requirements. For example, it may be desirable to use the system 5 in areas where noise generation is unacceptable, such as when someone nearby is sleeping. In this case, it is preferable to use a power unit 52 that uses stored air power rather than a unit 52 that generates air power by operating a pump or other noise-generating equipment. As shown in Figure 8, the power unit 52 can be disconnected from the dialysis unit 51 by operating a handle 521. For example, by turning the handle 521, the power unit 52 can be unlocked from the dialysis unit 51, disconnecting not only the mechanical connection between the housings but also the power and / or communication connections between them. An interface (not shown) between the dialysis unit 51 and the power unit 52 allows for the exchange of pneumatic power (from the power unit 52 to the dialysis unit 51), as well as electricity, control communication, and other information between the units. The dialysis unit 51 may have connection points for power (for example, standard 115V, 15Amp power from a household power outlet), external communication (Ethernet® or any other suitable connection for communication), water supply, etc. The dialysis unit 51 may, if desired, provide power or other connections to the power unit 52.

[0062] The dialysis unit 51 may include a controller that controls the flow of control fluid to various components of the system 5 and performs other desired functions. In one embodiment, the control fluid is held at various pressures in various tubes or conduits. For example, some control fluids may be held at positive pressure (i.e., greater than atmospheric pressure), while others may be held at negative pressure (less than atmospheric pressure). In another embodiment, the controller may have components that are held apart from the various fluid circuits. This structure has several advantages. For example, in one embodiment, the fluid circuits of the dialysis unit 51 may be heated to a disinfection temperature and / or exposed to relatively high temperatures or other harsh conditions (e.g., radiation) for disinfection, while electronic components of the controller may not be exposed to harsh conditions and may be held apart by an insulating wall (e.g., a "firewall"). That is, the dialysis unit housing may have two or more compartments, for example, a compartment having electronic components and other components that are sensitive to heat or other conditions, and a compartment having fluid circuit components that are heated or otherwise treated for disinfection.

[0063] Therefore, in some embodiments, System 5 includes a (unheated) "cold" section and a "hot" section that can be heated, for example, for disinfection. The cold section can be insulated from the hot section by an insulator. In one embodiment, the insulator is a molded foam insulation material, and in another embodiment, it includes, but is not limited to, any type of insulation such as spray insulation, voids, or insulation cut from a sheet. In one embodiment, the cold section includes a circulation system, such as a fan and / or a grid that can circulate air in and out of the cold box. In one embodiment, the insulator can be extended to cover access points to the "hot" section, such as doors, ports, and gaskets. For example, once the "hot" section is sealed, the insulator can, in one embodiment, completely cover the "hot" section.

[0064] Non-limiting examples of components that may be present in the "cold" section include power supplies, electronic components, power cables, and air controllers. In one embodiment, at least a portion of the fluid circulating between the "hot" sections passes through the "cold" section. However, in another case, the fluid can flow to the "hot" section without passing through the "cold" section.

[0065] Non-limiting examples of components that may be present in the “hot” section include cassettes (if present), fluid lines, temperature and conductivity sensors, blood leak sensors, heaters, other sensors, switches, and emergency lights. In one embodiment, some electronic components may also be included in the “hot” section. Examples include, but are not limited to, heaters. In one embodiment, in addition to the fluid, a heater may be used to heat the hot box itself. In some embodiments, a heater 72 heats the entire “hot” section until it reaches a desired temperature.

[0066] According to one aspect of the present invention, the housing of the dialysis unit 51 may be provided with vertical parallel doors that can be opened to expose all mechanical interface points for the blood flow circuit connections and dialysate circuit connections, i.e., all connection points for the patient blood connection and acid / bicarbonate connection that the user must make in order to use the dialysis unit 51. Figure 9 is a front view of the dialysis unit 51 having vertical parallel doors 53 in a closed state. In this configuration, the doors 53 can seal the inside of the unit housing to block access to the connection points for the patient blood connection and acid / bicarbonate connection and to allow the preservation of heat suitable for disinfection. The seal provided by the doors 53 can be airtight to prevent or substantially suppress air exchange between the internal and external environments of the housing, or it can be slightly reduced in quality to the extent that the disinfection effect can be maintained.

[0067] In this embodiment, the door 53 is connected to the housing of the dialysis unit 51 by a double-hinge structure so that the door 53 can be opened in two different open states. Figures 10-13 show the door 53 in the first open state. In this state, the door 53 exposes the blood circuit connections and all user connections for the dialyzer circuit, including the dialyzer 14 itself and reagent materials such as consumable acid / bicarbonate materials. This position also exposes other features such as a holder 531 for an acid / bicarbonate container (not shown) and a hook 532 that can be used to hold any suitable element such as a control interface 55, the control interface whose handle can be hooked onto the hook 532 (see Figure 7 showing the hook 532 at the front of the left door 53 which can be opened to accommodate the control interface 55 or other elements). The holder 531 in this embodiment can be folded in from the position shown in the figure (i.e., folded so as to extend horizontally from the door 53 and tucked into a recess in the door 53). The holder 531 has a "C"-shaped housing for accommodating and holding the acid / bicarbonate container, but of course it can be any suitable shape or configured in any other way.

[0068] Figures 14–16 show the doors 53 in a second open state, where the hinge plates 533 of each door 53 pivot away from the dialysis unit housing 51. In this embodiment, the hinge plates 533, which extend vertically along substantially the entire height of the dialysis unit housing 51, are pivotably mounted to the door 53 at a first outer end and pivotably mounted to the dialysis unit housing 51 at a second inner end. (Of course, the hinge plates 533 can be configured differently, for example, they can be positioned and / or located at the top and bottom of the door 53 as seen in many refrigerator door structures, and each plate 533 can have two or more parts separated longitudinally from each other.) The magnet 534 mounted on the hinge plate 533 interacts with a corresponding magnet (or other suitable component such as a steel element) mounted on the dialysis unit housing 51 to hold the hinge plate 533 in the position shown in Figures 10-13 by attracting the hinge plate 533 toward the dialysis unit housing 51 (of course, the magnet 534 is located on the unit housing, and the hinge plate 533 may have a suitable element (such as a steel piece) to which the magnet 534 is attached). Since the door 53 of this embodiment also has a magnet mounted on the hinge plate 533, when the door 53 is opened to the first state as shown in Figures 10-13, the magnet interacts with a corresponding magnet in the hinge plate 533 to help the door 53 be in the open position relative to the hinge plate 533. Furthermore, these magnets help maintain the relative position between the door 53 and the hinge plate 533 when the hinge plate 533 is opened to the second state as shown in Figures 13-16.

[0069] In this exemplary embodiment, magnets are used as part of the retaining member to assist in maintaining the door 53 and / or hinge plate 533 in a particular open or closed position, but other structures of the retaining member are also possible. For example, the hinge connection between the door 53 and the hinge plate 533 and / or the connection between the hinge plate 533 and the housing 51 may also be a stopper structure that serves to elastically hold the door 53 or hinge plate 533 in a particular position relative to other parts (hinge plate or housing). In another embodiment, one or more springs can be used to assist in holding the door 53 in the open position relative to the hinge plate 533. In yet another embodiment, the hinge plate 533 may frictionally or statically fit with a portion of the housing 51 that seeks to hold the hinge plate 533 in the closed position (close to the housing). Therefore, the retaining member that plays a role in holding the door 53 in a specific position relative to the hinge plate 533, and / or the role in holding the hinge plate 533 in a specific position relative to the housing 51, can take one of a number of possible structures.

[0070] According to another aspect of the present invention, when the door is opened toward the dialysis unit housing, all user connections for the blood circuit connections and dialysate fluid connections necessary for the operation of the system 5 are exposed. For example, as shown in Figure 17, when the door 53 is open (either the first or second open state), the front panel 511 of the dialysis unit 51 can be exposed. In this embodiment, the front panel 511 carries several elements or connection points that the user must access. For example, a dialyzer 14 that must be replaced periodically is mounted on the front panel 511. The dialyzer 14 must be connected not only to the blood flow circuit 141 but also to the equilibrium circuit 143. Furthermore, a connection point 512 for an acid / bicarbonate source 49 is located at the lower end of the front panel 511. At this connection point 512, the user can connect to a source of consumable reagent components 49 that the dialysis unit 51 uses when preparing dialysate. An occluder 513 is also mounted on the front panel 511. The closure unit 513 receives the tubing of the blood flow circuit and controls the open / closed state of the tubing based on system operation. The function of the closure unit 513 is described in detail in U.S. Patent Application No. 12 / 198,947 (Agent Reference Number D0570.70020US00(G28)), filed on 27 August 2008, and will be described in more detail below. In summary, unless there are system problems such as leaks, pump failures, or overpressure, the closure unit 513 allows flow to pass through the arterial and venous lines of the blood flow circuit. If any of the above problems occur, the closure unit 513 automatically closes the blood lines to block the flow to and from the patient. Blood line connection points 514 (as described with reference to Figures 2 and 3, the blood flow circuit 141 can be connected to the directional circuit 142) that connect the arterial and venous blood lines 203, 204 of the blood flow circuit 141 to the directional circuit 142 are exposed on the front panel 511. This connection is typically made at the end of treatment so that the system can clean and sterilize the blood flow circuit 141. The front panel 511 also has a set of control ports 515 that mate with the corresponding control ports on the blood pump section of the blood flow circuit 141.The control port 515 controls the open / closed state of the valve and supplies a controlled level of pneumatic and / or vacuum to power the pump in the blood flow circuit 141.

[0071] In another embodiment of the present invention, Figure 17A shows a perspective view of a control port assembly 615 on which a blood pump assembly 13 can be mounted and to which the fluid control ports of the blood pump assembly 13 can be connected. For example, a control port 616 for controlling the operation of the valves of the blood pump assembly 13 and a control port 617 for controlling the operation of the pumps of the blood pump assembly 13 are shown. A latch member or other engaging device may be provided on one or more surfaces of the control port assembly 615, within the control port assembly 615, or in a part adjacent to or within the position of the control port assembly 615 of the front panel assembly 511 to secure the blood pump assembly 13 to the control port assembly 615 (in the illustrated example, the control port assembly 615 can be reversibly mounted to the front panel assembly 511 via a retaining tab 619). Alternatively, or further, a separation or other removal function for the blood circuit assembly may be provided to facilitate the removal of the blood pump assembly or other parts of the blood circuit assembly from the front panel 511. For example, a pair of cassette latches and removal assemblies may be mounted on both sides of the control port assembly 615. In the embodiment shown in Figure 17A, the blood circuit assembly engagement device comprises latch or retainer members 618a and 618b pivotally mounted on the side of the control port assembly 615. Preferably, the pivot connections (e.g., pivot connection 620) of the latch members 618a and 618b are biased by appropriately positioned springs to rotate the latch members 618a and 618b toward each other and toward the surface of the control port assembly 615, thereby allowing them to maintain contact with the edge or other portion of the blood pump assembly 13 (shown in cross-section in Figure 17B) mounted on the control port assembly 615. This is clearly illustrated in Figure 17B, which is a top cross-sectional view of the control port assembly 615 on which the blood pump assembly 13 is mounted. In Figure 17B, the latch member 618b is shown in its normal biased position, securing the outer edge of the blood pump assembly 13 in relation to the control port assembly 615.On the other hand, the latch member 618a is shown in a partially retracted position, allowing the blood pump assembly 13 to be partially separated from the control port assembly 615. In the fully retracted position (not shown), the latch member 618a or 618b leaves the front edge of the blood pump assembly 13 open, allowing the blood pump assembly 13 to be removed from or installed on or mounted to the control port assembly 615.

[0072] As shown in Figures 17A and 17B, in addition to latches or retainer members 618a and 618b that can help hold the blood pump assembly 13 in the control port assembly 615, separation assist members (or ejector elements or ejector members) 622a or 622b may also be included to assist the user in separating the blood pump assembly 13 from the control port assembly 615 and lifting it away from the control port assembly 615. The separation assist members 622a or 622b may be pivotably mounted on the front panel assembly 511 in a position suitable for contacting the edge of the lower surface 113a of the blood pump assembly 13 when the separation assist members 622a or 622b rotate outward, thereby helping to lift it away from the control port assembly 615. The engagement device may include an actuator that acts on the retainer member 618 and / or ejector element 622, such as a thumb or finger contact element 626a or 626b, which the user can laterally press to pivot the separation assist member 622a or 622b outward, thereby engaging the contact portion 624a or 624b with the lower surface 113a of the blood pump assembly 13. Preferably, a spring 628 can be appropriately positioned to include a spring 628 near the pivot connection of the separation assist member 622a or 622b and bias the separation assist member 622a or 622b so as to move the contact portion 624a or 624b away from contact with the lower surface 113a of the blood pump assembly 13. In this way, the inherent force from the separation assist member 622a or 622b does not act to push the blood pump assembly 13 away from the control port assembly 615. In another preferred embodiment, as shown in Figure 17A, the separation assist member 622a or 622b can be pivotably mounted on the latch member 618a or 618b. In this embodiment, the user can separate the latch members 618a and 618b from contact with the front edge or surface of the blood pump assembly 13 by engaging the separation assist member 622a or 622b with the lower surface 113a of the blood pump assembly 13 and simultaneously pushing the thumb or finger contact element 626a or 626b outward once.Therefore, by pushing outward one or more actuators, such as a single element 626a or 626b, the blood pump assembly 13 can be alternately attached to or detached from the control port assembly 615, facilitating the installation and / or removal of the blood pump assembly 13.

[0073] Figure 17C shows another embodiment of the blood circuit assembly engagement device, which in this embodiment comprises a pair of blood pump cassette retainer and ejector elements. In this embodiment, the cassette retainer element 630 comprises a contact member 632 that contacts the ejector (or separation assist) element 634. In the retracted position, the ejector element 634 is positioned in a recessed area 636 of the blood pump pod recess 638 of the control port assembly 640. When the retainer element 630 pivots outward (in the direction of the arrow in Figure 17C), the contact member 632 presses the proximal end 642 of the ejector element 634, at which point the ejector element 634 rotates around the pivot axis 644, and the distal end 646 of the ejector element 634 rises out of the recess 636 and engages with the rigid rear wall of the operating chamber of the mounted pump cassette located in the blood pump pod recess 638. Figures 17D and 17E show standalone views of the engagement device with the ejector element 634 in the retracted position (Figure 17D) and the extended position (Figure 17E). In Figure 17D, the retainer element 630 is in the retaining position, the retainer element 648 is rotated inward toward the center of the control port assembly 640, and the ejector element 634 is in the retracted position with its proximal portion 642 raised and its distal portion 646 pushed down. In Figure 17E, the retainer element 630 is in the released position, the retainer element 648 is rotated outward toward the center of the control port assembly 640, and the ejector element 634 is in the raised position with its proximal portion 642 pushed down by the contact member 632, and its distal portion 646 rising out of the recess 636 to eject the cassette mounted on the control port assembly 640. The thumb rest (actuator) 650 is shaped to allow the user to conveniently apply outward force to release the cassette by placing one thumb on each of the opposing latch members 630 in the completed assembly as shown in Figure 17C. In one embodiment, the retainer element 630 rotates around an axis formed by a pinion 652, which has a spring 654 biased in the latching or retaining direction, to help keep the cassette fixed and mounted in the control port assembly 640.Figure 17F shows a front view of the blood pump cassette 1000 (part of the blood circuit assembly) mounted on the panel of the dialysis unit, such as the exposed front panel 511. Figures 17G and 17H show cross-sectional views of the blood pump cassette 1000 along lines 17G-17G and 17H-17H, respectively, showing the cassette 1000 properly mounted to the control port assembly 640. Figure 17G shows the relationship between the contact member 632, the ejector element 634, and the rigid rear wall 658 of the pump operating chamber of the cassette 1000. The ejector element 634 is shown fully retracted in their respective recessed areas 636 so that the pump cassette 1000 can be fully mounted. Figure 17H ​​shows the relationship between the retainer element 648 and the front plate 656 of the cassette 1000. In this case, the retainer element 648 is positioned alongside the front plate 656 to secure the cassette 1000 onto the control port assembly 640.

[0074] Figure 17I shows a front view of the blood pump cassette of Figure 17F in the process of being separated from the panel 511 of the dialysis unit. Figures 17J and 17K show cross-sectional views of the blood pump cassette 1000, in which the cassette 1000 is partially lifted from its engaged position with the control port assembly 640. Figure 17J shows the relationship between the contact member 632, the ejector element 634, and the rigid rear wall 658 of the pump operating chamber of the cassette 1000. In this case, the distal end 646 of the ejector element 634 contacts the cassette 1000, lifting the cassette 1000 from its fully mounted position within the control port assembly 640. Figure 17K shows the relationship between the retainer element 648 and the front plate 656 of the cassette 1000. In this case, the front plate 656 is raised above the retaining surface of the retainer element 648.

[0075] A user control panel 510 is also exposed on the front panel 511 in Figure 17. The user control panel 510 includes one or more buttons that can provide an alternative way for the user to control specific functions (e.g., critical functions) during hemodialysis, bypassing the graphical user interface on the control interface 55. This becomes critical, for example, if the control interface 55 fails during a dialysis treatment session. Non-limiting examples of critical functions include the "Stop Dialysis" or "Pause Dialysis" command and the "Inject Dialysis Solution" command.

[0076] According to this embodiment and another aspect of the present invention, the blood flow circuit 141 is formed as a blood circuit assembly removable from the front panel 511 of the dialysis unit 51, and since the blood circuit assembly is not mounted on the front panel 511 in Figure 17, Figure 17 does not show the arterial and venous lines 203, 204 for the blood flow circuit 141. Figure 18 shows a front view of the blood circuit assembly 17 of this embodiment together with the dialyzer 14. The blood circuit assembly 17 includes the various components described above, mounted on a blood circuit assembly tray 171, for example, referring to Figure 3. The arterial and venous lines 203, 204 (including, for example, the length of flexible silicone tubing) terminate in blood line connectors configured to provide a screw-type connection for use with a common patient access point (e.g., a Luer-type patient access connector), in addition to a push-in or press-fit connection to a blood line connection point 514, according to one aspect of the present invention. The arterial line 203 connects to an inlet located at the top of the blood pump 13, which includes two pod pumps 23, valves, and other components that control blood flow. The blood pump 13 is associated with an air filter 81, an anticoagulant pump 80 (not shown), and an anticoagulant supply source 11 (such as a heparin vial). (For further details regarding the blood pump 13 in this embodiment, see U.S. Patent Application No. 11 / 871,680, filed October 12, 2007, entitled "Pumping Cassette," U.S. Patent Application No. 11 / 871,712, filed October 12, 2007, entitled "Pumping Cassette," U.S. Patent Application No. 11 / 871,787, filed October 12, 2007, entitled "Pumping Cassette.") (Referenced in U.S. Patent Application No. 11 / 871,793, filed on October 12, 2007, entitled "Cassette System Integrated Apparatus") and U.S. Patent Application No. 11 / 871,803, filed on October 12, 2007, entitled "Cassette System Integrated Apparatus").Blood discharged from the blood pump 13 (with its outlet located at the bottom of the pump 13) enters the inlet of the dialyzer 14 (located at the top of the dialyzer 14), exits the dialyzer (with its dialyzer blood outlet located at the bottom of the dialyzer 14), and flows into the inlet of the air trap 19. The outlet of the air trap 19 is connected to the venous blood line 204. The inlet and outlet blood ports of the dialyzer 14 are connected by typical screw-type connections.

[0077] Figure 18a shows a perspective view of a blood pump 13, which includes another embodiment of a vial receiver or vial holder 1206 that holds or rests a vial of drug 11 (e.g., an anticoagulant) on a hollow spike 1208 that is in fluid communication with the pump 80 of the blood pump 13 (Schematically shown in Figure 3). In this embodiment, a flexible upper arm 1210 helps to hold the body of the vial 11 in place and can bend to accommodate vials of various sizes. A lower arm 1212 helps to align the inverted top of the vial 11 with the spike 1208 so that the vial 11 does not protrude at an angle to the inverted top of the vial 11. Having the top of the vial 11 protrude substantially vertically can help to avoid fluid leakage from inside the vial 11 around the outside of the spike 1208.

[0078] According to another aspect of the present invention, the air trap 19 is positioned in the blood flow path from the time the blood leaves the dialyzer until it returns to the patient. In one embodiment, the air trap 19 may have a spherical or ellipsoidal container (i.e., a container with a substantially spherical inner wall), an inlet port positioned near the top, offset from the longitudinal axis of the container, and an outlet at the bottom of the container (the longitudinal axis of the container is positioned longitudinally, passing through the “upper” and “lower” poles of the substantially spherical container). The inlet port is offset from the longitudinal axis (in this case, receding toward the tray 171), and blood is introduced into the container in a direction substantially perpendicular to the longitudinal axis of the container and nearly tangent to the spherical inner wall of the container. The curved shape of the inner wall of the trap guides the blood to circulate along the inner wall as the blood is drawn by gravity (for example, spirally) toward the lower end of the container, facilitating the removal of air bubbles from the blood. Air present in the blood leaving the dialyzer 14 outlet enters the upper end of the air trap 19 and remains at the upper end of the container while the blood flows out through the outlet at the lower end into the venous blood line 204. By positioning the inlet port near the top of trap 19, blood can be circulated in the trap with minimal or no air remaining in the container (as a "fully open" air trap). Avoiding contact between air and blood is effective for periodic circulation of blood in the trap. By positioning the inlet port at or near the top of the container, the fluid flow through the blood tube can be reversed (i.e., flow from the bottom to the top of trap 19 and exit through the inlet port of trap 19), removing most or all of the air present in the trap.

[0079] In one embodiment, a self-sealing port, such as a self-sealing stopper of a split diaphragm or membrane or other structure, is positioned at the upper end of the trap to allow air to be extracted from the container (e.g., by syringe). For example, the blood-side of the self-sealing membrane can be positioned substantially flush with the upper inner end of the trap to simplify cleaning the self-sealing port during disinfection by reversing the flow within the air trap using dialysate or other washing fluid. The inlet, outlet, and inner wall of the container and the self-sealing port can also be configured to virtually eliminate stagnant areas, i.e., there can be virtually or completely no areas where blood stagnates or coagulates. The self-sealing port can function as a blood sampling site and / or allow the introduction of liquids, drugs, or other compounds into the blood circuit. When needle access is intended, a sealing rubber stopper can be used. Self-sealing stoppers using split diaphragms allow sampling and fluid delivery using a needle-free system.

[0080] Figure 19 shows a blood circuit assembly tray 171 without any components of the various blood circuit assemblies 17 mounted on it. According to one aspect of the present invention, the assembly tray 171 is provided with a handle 172 (in this embodiment, pulled with the fingers) that the user can grasp when mounting the blood circuit assembly 17 onto the front panel 511 or removing the blood circuit assembly 17 from the front panel 511. Inside the handle 172 is an opening 173 that allows a spring tab on the front panel 511 to pass through the assembly tray 171 and / or the cassette of the blood pump 13 to engage with the blood circuit assembly 17 and hold the blood circuit assembly 17 in place on the front panel 511. According to another aspect of the present invention, the assembly tray 171 is provided with blood line engaging members 174, each having a C-shaped recess or other hole through which the corresponding blood lines 203, 204 pass (wherein “hole” includes recesses as shown in Figure 19, for example, through holes with continuous walls made by drilling, or other suitable openings). More specifically, the blood line engaging member 174 is used when the blood lines 203 and 204 are placed in the closure 513. In summary, when the blood lines 203 and 204 are placed in the closure 513, they must be pulled downward and stretched while being pushed horizontally into the slots of the closure 513 (to reduce the outer diameter of the lines). The blood line engaging member 174 has the function of resisting the downward pulling of the blood lines 203 and 204 (for example, each line 203 and 204 may be provided with a stop ring on the engaging member 174 so that it cannot be pulled through the recess of the engaging member 174), and also has the function of allowing the user to push the engaging member 174 inward to position the lines 203 and 204 in the closure slots. Since the engaging member 174 is formed integrally with the train tray 171, a "living hinge," or a relatively flexible part of the train tray, is positioned between the engaging member 174 and the main body of the train tray 171. This structure allows the connection between the engaging member 174 and the train tray body to flex, thereby pushing the engaging member 174 inward relative to the train tray 171.

[0081] Figure 20 is a rear view of the blood circuit assembly 17 with the organizing tray 171 removed. This figure shows the rear of the blood pump 13 with the control ports exposed. These control ports mate with corresponding ports 515 on the front panel 511 (see Figure 17) so that pneumatic control (e.g., appropriate air pressure or vacuum) is applied to the pump and valves to control their operation and the flow through the blood circuit assembly 17. Figure 20 also shows the displacement of the inlet port of the air trap 19. That is, the inlet port at the upper end of the air trap 19 is located behind the longitudinal axis of the nearly spherical container portion of the air trap 19.

[0082] Figures 20A and 20B show unfolded perspective views of another embodiment of the blood pump cassette 1000. Figure 20A shows an unfolded front perspective view of the cassette 1000 having a rear (operating side) plate 1001, the rear plate 1001 having a piping assembly section formed together with the rear plate in a single molded part of the material. Figure 20B shows an unfolded rear perspective view of the cassette 1000 of Figure 20A. The cassettes 1000 shown in Figures 20A-20D can be used as replacements for the cassette 13 of Figure 18A and the assembly tray 171 of Figure 19, combining many of the functions of these components and substantially reducing the cost and complexity of manufacturing and assembling them.

[0083] Cassette 1000 comprises a rear plate 1001 that forms the rigid outer wall of the working chambers of various valves and pumps, an intermediate plate 1002 that holds various valve and pump diaphragms and helps to form various flow paths in cassette 1000, and a front plate 1003 that forms the rigid outer wall of some of the fluid chambers of the various valves and pumps in cassette 1000. Cassette 1000 optionally further comprises a protective cover 1004 that can be attached to the front side of the rear plate 1001. The protective cover 1004 may be equipped with a retaining arm that can be used for later mounting in a vial holder 1037, the retaining arm which holds the vial. The protective cover 1004 can temporarily hold either an empty or filled vial before inserting the vial into the vial holder 1037 for use during treatment. In other words, the vial can be connected to the vial holder 1037, which has a hollow spike that positions the vial within the vial holder 1037 in fluid communication with the fluid port 1038 of the front plate 1003. For example, the vial can be filled with an anticoagulant used during dialysis, or the vial can be empty and used during cleaning and disinfection procedures either before or after dialysis treatment.

[0084] The cassette 1000 comprises fluid flow pumps 1013 and 1014 that move a liquid through the fluid flow side of the cassette 1000. That is, the cassette 1000 comprises a left-side pump 1013 and a right-side pump 1014 that pump a fluid, which may be blood in the case of a hemodialysis machine. Pumps 1013 and 1014 (also referred to herein as pod pumps) can be operated by a control fluid, such as air, liquid, gas, or other fluid that enters the cassette 1000 through a port on the rear plate 1001. The left-side pod pump 1013 comprises a rigid chamber wall 1005 formed on the front (or upper) plate 1003, a rigid chamber wall 1008 formed on the rear (or lower) plate 1001, a hole 1006 formed on the intermediate plate 1002, and a flexible membrane 1007 that can bend between the rigid chamber walls 1013 and 1008. The space between the rigid chamber wall 1013 and the flexible membrane 1007 forms the fluid or blood side (i.e., the fluid chamber) of the left pump 1013, and the space between the flexible membrane 1007 and the rigid chamber wall 1008 forms the pneumatic side (i.e., the control chamber) of the left pump 1013. Similarly, the right pod pump 1014 comprises a rigid chamber wall 1009 formed in the upper plate 1003, a rigid chamber wall 1012 formed in the lower plate 1001, a hole 1010 formed in the intermediate plate 1002, and a flexible membrane 1011 that can flex between the rigid chamber walls 1009 and 1012. The space between the rigid chamber wall 1009 and the flexible membrane 1011 forms the fluid or blood side (i.e., the fluid chamber) of the right pump 1009, and the space between the flexible membrane 1011 and the rigid chamber wall 1012 forms the pneumatic side (i.e., the control chamber) of the right pump 1014.

[0085] Each of the pod pumps 1013 and 1014 may be equipped with a pair of membrane-based inlet / outlet valves, each having a fluid flow compartment formed from an upper plate 1003 and a control compartment formed from a lower plate 1001. These valves can be actuated by applying positive or negative fluid (e.g., air) pressure to individual flexible membranes through control ports in the lower plate 1001. The fluid valves can be opened and closed to direct the fluid flow when the pod pump is pumping. Depending on the sequencing of valve operations in relation to the operation of the pumps associated with those valves, the fluid can be pumped in the forward or reverse direction. Non-limiting examples of pod pumps are described in U.S. Patent Application No. 11 / 787,212, filed April 13, 2007, entitled “Fluid Pumping Systems, Devices and Methods,” which is incorporated herein by reference. The pod pumps 1013 and 1014 can be operated by a fluid flow in either direction in any suitable manner, for example, synchronously, asynchronously, in phase, or with a phase shift.

[0086] For hemodialysis applications, in one embodiment, an anticoagulant (e.g., heparin, or any other anticoagulant known to those skilled in the art) can be mixed with blood in the blood flow cassette 1000. For example, the anticoagulant can be contained in a vial (or other anticoagulant source such as a tube or bag), and the blood flow cassette 1000 may receive an anticoagulant vial equipped with a vial holder 1037 that can pierce the seal of the vial (in one embodiment, equipped with a needle or hollow spike). The spike can be formed from plastic, stainless steel or other suitable material, and in one embodiment may be made of a sterilizable material, for example, the material may be able to withstand sufficiently high temperatures and / or chemical exposure to sterilize the material. As an example, the spike can be used to pierce the seal of the vial, thereby allowing the anticoagulant to flow into the blood flow cassette 1000 and mix with blood in the blood flow path. In other cases, the vial can be filled or partially filled with water or dialysate during washing, disinfection, or priming operations.

[0087] In one embodiment, a third pump 1015 within the cassette 1000, which can act as a metering pump, can be used to control the flow of a drug (such as an anticoagulant) from a mounted vial into the flow path within the cassette 1000. The metering pump 1015 may have the same or different design as pumps 1013 and 1014. For example, the metering pump 1015 can be a pod pump and can be operated by a control fluid such as air. For example, as shown in Figures 20A to 20D, the metering pump 1015 may comprise a rigid chamber wall 1015 formed in the rear plate 1001, a rigid chamber wall 1018 formed in the intermediate plate 1002 (see Figure 20B), and a flexible diaphragm 1015 that divides the pod into a fluid compartment or chamber and a control compartment or chamber. Valves 1028, 1029, and 1030 can be connected to fluid channels that connect a fluid port 1038, a vent port 1019, a fluid channel leading to or originating from a first or second pump (such as pump 1013), and a fluid channel leading to or originating from a metering pump 1015 in various combinations. Thus, the flow of a drug (e.g., an anticoagulant) or other fluid from the fitted vial into the main fluid channel in the cassette 1000 can be controlled by the metering pump 1015, and periodically, air can be introduced into the fitted vial from the vent port 1019 through port 1038 by the metering pump 1015 to equalize the pressure inside the fitted vial with the ambient pressure when the drug or other fluid is withdrawn from the vial.

[0088] Cassette 1000 may also be equipped with a vent connected to port 1019. Air can be introduced into the flow path of metering pump 1015 to equalize the pressure in the fitted vial with the ambient air. In this case, valve 1029 closes the flow between metering pump 1015 and the main flow path of the first pump 1013 (or second pump 1014). In one embodiment, metering pump 1015 may also introduce air into the main flow path of the first pump 1013 or second pump 1014 so that the system controller can control the emptying of the blood or liquid transport components of the system.

[0089] Pod pumps 1013 and 1014 are equipped with raised channels 1020 and 1021 in chambers 1005 and 1009, respectively. The raised channels 1020 and 1021 allow the fluid to continue flowing through pod pumps 1013 and 1014 after the diaphragms (i.e., flexible membranes) 1007 and 1011 have reached the end of the stroke.

[0090] The cassette 1000 comprises several valves 1022, 1023, 1024, and 1025 formed within the rear plate 1001. The operating (or pneumatic) sides of valves 1022-1025 and 1028-1030 are formed from the lower plate 1001 and have corresponding operating ports for the control (e.g., pneumatic) fluid to enter or exit. Several diaphragms 1026 and 1027, located on the intermediate plate 1002, complete the valves, and diaphragms 1007, 1011, and 1016 complete the pod pumps 1013, 1014, and the metering pump 1015. The metering pump 1015 is completed by diaphragm 1016. In a preferred embodiment, the valves are pneumatically actuated, and liquid is drawn out as the valve diaphragms are pulled away from adjacent holes in the intermediate plate 1002, and the liquid is pushed through as the diaphragms are pushed toward the holes. The fluid flow is directed by the proper sequence of opening and closing of valves 1022-1025 and 1028-1030.

[0091] The metering pump 1015 has three passages connected to a fluid chamber 1018 formed in the intermediate plate 1002. One passage allows air from a vent hole 1019 to be drawn into the metering pump 1015; a second passage allows air to be pushed into a spike / source container connected to a vial holder 1037, and alternately draw liquid from the source container or vial; and a third passage allows liquid from the source container to be pushed by the metering pump 1015 into a main fluid line connected to the first pump 1013 (or pump 1014 in another embodiment). Valves 1028, 1029, and 1030 determine whether the metering pump 1015 moves fluid or air, and in which direction.

[0092] Next, referring to Figure 20C, an internal view of the lower plate 1100 is shown. An internal view of the operating / air chambers of the pod pumps 1008 and 1012, metering pump 1015, and valves 1022, 1023, 1028, 1025, 1029, 1030, and 1024 is shown. The pod pumps 1008 and 1012, metering pump 1015, and valves 1022, 1023, 1028, 1025, 1029, 1030, and 1024 are operated by a pneumatic air source. Now referring to Figure 20D, the outside of the lower plate 1100 is shown. A control fluid source (e.g., air under positive or negative pressure) is connected to this outside of the cassette. In one embodiment, tubing is connected to various ports 1031. In other embodiments, port 1031 is configured to plug into a control port assembly (e.g., control port assembly 615 in Figure 17A) on the front panel of the dialysis unit 51 (e.g., front panel 511 in Figure 17).

[0093] Referring here to Figures 20A to 20D, the lower plate 1001 incorporates various organizing functions. The lower plate 1001 includes an air trap holding member 1032 having tube guides 1033 and 1034 formed in the lower plate 1001. The tube guides 1033 and 1034 guide tubes to and from the air trap located within the air trap holding member 1032. The lower plate 1001 also includes additional tube guides 1035 and 1039. The lower plate 1001 also forms a receiving section 1036 that can receive an electrical connector that can be used in the device to monitor whether an arterial or venous line has become disconnected from the patient during treatment. Figure 21 is a perspective view of the front panel 511 of a dialysis unit 51 having a blood circuit assembly 17 mounted on the front panel 511 without an organizing tray 171 (typically, the blood circuit assembly 17 includes an organizing tray 171, but the tray 171 is not shown in this example to more clearly illustrate the components of the front panel 511). Opposite the cassette of the blood pump 13, the front panel 511 has a spring tab 516 that extends flexibly forward with the blood pump cassette and / or organizing tray 171 to hold the blood circuit assembly 17 in place. The tab 516 may have a puncture or other function to assist in holding the blood circuit assembly 17 in place. The spring tab 516 can be bent outward to release its hold on the blood circuit assembly 17 and allow removal. However, if no outward force is applied to the spring tab 516, the tab 516 remains engaged with the blood circuit assembly 17. Figure 22 is a front view of the front panel 511 containing the organizing tray 171 of the blood circuit assembly 17. To remove the blood circuit assembly 17 from the front panel 511, the user places their thumb on the inside of the spring tab 516 (the side closest to the blood pump 23) and bends the spring tab 516 outward away from the pump 23 while simultaneously placing their index finger behind the handle 172. This causes the spring tab 516 to release the blood circuit assembly 17, for example, separating the tab 516 from the blood pump 13 and / or the organizing tray 171.Naturally, to remove the blood circuit assembly 17, other connections such as the connection to the dialyzer 14 and the blood line connection point 514 must be disconnected, and lines 203 and 204 must also be removed from the closure 513. When mounting the blood circuit assembly 17 onto the front panel 511, the assembly tray 171 can be properly positioned by gripping the handle 172, for example, so that the spring tab 516 passes through the opening 173 and the control port of the blood pump 13 cassette aligns with the corresponding port 515 on the front panel 511. The blood circuit assembly 17 is then pushed into place, and the spring tab 516 engages with the assembly tray 171 and / or the blood pump cassette. Other connections, such as the connection to the dialyzer 14 and the attachment of blood lines 203 and 204 to the closure 513, can then be made.

[0094] Figure 21 also shows slots 517 that hold the blood lines 203, 204 to guide them into the closure 513. Slots 517 form passages slightly smaller than the outer diameter of the blood lines 203, 204 so that the lines 203, 204 remain within slots 517 after being positioned within the slots. This helps to ensure proper association between the lines and the closure 513. Once the blood circuit assembly 17 is mounted on the spring tab 516, the user engages the blood lines 203, 204 with slots 517 by extending the lines 203, 204 downwards (with the engaging members 174 on the organizing tray 171 engaging with the stop rings or other features on each line 203, 204 and resisting downward pulling) and pushing the lines 203, 204 into the corresponding slots. As described above, lines 203 and 204 are flexible and can be pushed into place by pushing inward the engaging members 174, which are bent inward relative to the organizing tray 171. Lines 203 and 204 can then be advanced through the closing section 513.

[0095] According to another aspect of the present invention, the front panel 511 is provided with a blood line wrapping function on its outer periphery. In this exemplary embodiment, the front panel 511 is provided with flange portions 518 along the upper edge and lower corners of the front panel 511. Thus, the user can wrap the blood lines 203 and 204 around the outer periphery of the front panel 511 by positioning the lines 203 and 204 within the passages formed by the flange portions 518. The lines 203 and 204 can be wrapped clockwise from a point near the lower end of the dialyzer 14 to a point near the lower right corner of the front panel 511. The blood lines 203 and 204 can then be connected at a blood line connection point 514 to disinfect, for example, the fluid circulating through the blood lines 203 and 204. As a result, the blood lines 203 and 204 are properly held on the front panel 511, allowing easy access to other components on the front panel 511, and the user can close the door 53 with little concern about whether the blood lines 203 and 204 will get caught between the door 53 and the dialyzer unit housing 51. Alternatively, the blood lines 203 and 204 can first be connected at the blood line connection point 514, and then wound clockwise from near the lower end of the dialyzer 14 to near the lower right corner of the front panel 511. This ensures that the blood lines are properly distributed along the flange portion 518 and reach the connection point 514. Vertical fences 519 can also be provided on the left and right sides of the front panel 511 to assist in holding the blood lines 203 and 204 in a desired position away from the hinge plate 533 and other potential pinching points.

[0096] In another embodiment, as shown in Figure 21A, another embodiment of the front panel assembly 811 may include a modular drainage assembly (or drainage cassette) 815 having connection points 814 to which arterial and venous blood lines can be connected. As shown in Figure 5A, the drainage cassette 815 includes a common passage to the drainage line 31 for both arterial and venous blood lines during priming, washing, and disinfection operations. Water, dialysate, or other fluids can be introduced into the blood passages of the dialysis system 5 through the semipermeable membrane of the dialyzer 14 to expel air from the blood passages and prime the blood passages, or to wash and disinfect the blood passages. The drainage cassette 815 may optionally include valves for one or both of the arterial or venous blood passages. In one embodiment, an electronically controlled valve 831 in or near the modular drainage cassette 815 for the venous line may allow the blood pump of the blood pump cassette 13 to sequentially fill or empty the arterial line while the valve 831 for the venous line is closed, and then fill or empty the arterial line when the valve is opened. In this method, air or contaminants in the arterial line are forced to flow to the drain outlet of the drain cassette 815 rather than into the venous piping. Alternatively, valve 831 can be positioned to control the flow between the arterial line and the drain outlet, for example, so that the contents of the venous line can be forced to flow to the drain outlet rather than into the arterial line. The drain cassette 815 may also optionally be equipped with conductivity and / or temperature sensors 834, 835. The temperature sensor can be used to monitor the temperature of the fluid circulating in the blood line, for example, during thermal disinfection. The conductivity sensor can be used to monitor the conductivity of the water or dialysate circulating in the blood line, for example, during urea or sodium clearance testing in a dialyzer. An electronically controlled drain control valve 207 can be positioned at the drain outlet of the drain cassette 815 or (as shown in Figure 5A) outside the drain cassette 815. The drain control valve 207 may be useful, for example, when heated water or chemical disinfectants are circulating within the blood circuit components of the dialysis unit 51.The drain cassette 815 can be configured to facilitate connection to and disconnection from the front panel 511 or 811 of the dialysis unit 51. The drain cassette 815 may include a single-handle operating latch (e.g., a bayonet connection) that secures it to the front panel by turning a handle.

[0097] Figure 21A also shows another embodiment of the blood pump cassette and organizing tray assembly. In some embodiments, the organizing tray 822 can be incorporated into the pneumatically actuated plate (or rear plate) of the blood pump cassette 824. Figure 21B shows the front panel assembly 811 with the upper and middle plate components of the blood pump cassette 824 removed for clarity. In this example, the organizing tray 822 and the rear plate 816 of the blood pump cassette 824 are joined together to form a single molded part. In this example, the air trap 819 is supported by an extension of the organizing tray 822 and is positioned higher longitudinally than in the embodiments shown in Figures 19 and 29. By moving the air trap to a higher position relative to the closure 813 or in-line air detector 823, the blood pump's ability to draw air bubbles present in the venous tubing into the air trap 819 during backflow treatment can be increased. For example, the inlet of the air trap 819 can be supported by the organizing tray 822 at a position above the outlet of the air trap when the blood circuit assembly is mounted on the dialysis unit. Alternatively, the inlet and / or outlet of the air trap can be supported by the organizing tray at a position above the highest point of the flexible tube extending from the outlet of the air trap to the closure position. Such arrangements can help to drive air in the venous tubing into the air trap 819.

[0098] In another aspect of the present invention, a modular drain cassette may be included, having the function of monitoring and draining the fluid (such as water or dialysate) flowing through the blood circuit of the dialysis unit 51, the blood circuit comprising a blood pump, a dialyzer blood flow compartment, an air trap, and arterial and venous blood piping. As shown in Figure 5A, the arterial and venous blood piping may be connected to a drain chamber / air trap 4703 that ultimately leads to a drain line 31 when not connected to a patient. This connection allows heated water to be circulated, for example, for cleaning and disinfecting the blood circuit compartment, for determining dialyzer clearance characteristics, or for priming the blood circuit with dialysate. In one aspect of the present invention, the drain cassette 815 may comprise a drain chamber / air trap 4703, valves 831 for one or both of the arterial and venous blood lines, a check valve 836 for the drain line, and temperature and conductivity sensors 834, 835 in a single modular component that can be easily connected to or disconnected from the front panel of the dialysis unit 51. As shown in Figure 21A, in one embodiment, arterial and venous blood lines can be connected to a drain cassette 815 through connection point 814 of the front panel 811. The drain cassette 815 may include a channel or chamber that merges the fluid flows from the venous and arterial blood lines, which exit through a common outlet into the drain line 31.

[0099] As described above, the drain cassette 815 may optionally include a valve 831 in the venous pathway (or in the arterial pathway, or both pathways). In a preferred embodiment, the valve 831 is a pneumatically operated diaphragm valve, which is operated under the control of an electronic controller by an electromechanical valve piped to a pneumatic source. The drain cassette 815 may also optionally include conductivity and thermal probes 834, 835 in a fluid flow channel or chamber within the housing of the cassette 815. In a preferred embodiment, the electrical connections for the drain outlet port, the pneumatic control port, and the conductivity and thermal sensors are provided with paired connectors, one member of each pair being firmly mounted to the housing of the drain cassette 815, and the other member of each pair being firmly mounted to the front panel 811 of the dialysis unit 51 so that the user can quickly and easily load or unload the drain cassette 815 from the front panel 811. Similar to other blood circuit components of the front panel 511 or 811 (including the dialyzer 14, blood pump cassette 13 or 824, air trap 19 or 819, and arterial and venous blood lines), the drain cassette 815 can be configured to be easily attached to and detached from the dialysis unit 51.

[0100] Figure 31 shows an exemplary modular drainage cassette 815. In this figure, the decorative plate 825 of the drainage cassette 815 includes markings to identify arterial and venous line connection points 814. A front handle 821 on the decorative plate 825 allows for one-handed gripping and rotation to engage the drainage cassette 815 with or detach it from the front panel 811. Blood line connectors 802 for each of the arterial and venous blood lines are shown engaged within their respective connection ports or connection points 814 on the drainage cassette 815.

[0101] Figure 32 shows the drain cassette 815 in an exploded view, along with a decorative plate 825 in front of the front wall 826 of the drain cassette 815. In this example, the front wall 826 is formed by sealing the front wall of the housing 828 of the drain cassette 815 for a common channel or chamber 827. The common outlet 829 from the channel 827 to the drain line is equipped with a fluid connector 830 mounted on the rear wall of the housing 828, which may optionally include a one-way check valve (e.g., a duckbill valve) to prevent fluid in the drain line from re-entering the channel 827. The front panel 811 is equipped with a mating connector 830a, which connects to the fluid line that ultimately leads to the drain port. The outlet 829 is preferably positioned higher than either of the fluid connection points 814a and 814b to trap and ultimately expel any air that may be present in the arterial or venous blood line when connected to the drain cassette 815. In this regard, the fluid channel 827 may have a U-shape, and the venous and arterial blood line connectors 802 are fluidly connected to their respective connection ports 814a and 814b at the ends of the U-shape, with the drain outlet port 829 located in the bend of the U-shape. A valve 831 may be present in one or both portions of the fluid channel 827 leading from connection points 814a and 814b. The valve can then controllably open and close the fluid communication in the channel 827 between the connection port 814 and the drain outlet port 829. In embodiments where only one valve 831 is provided in the channel 827, the flow between one connection port 814 and the outlet drain port 829 can be controlled by the valve, while the fluid communication between the other connection port 814 and the drain outlet port 829 can be permanently opened. In the illustrated example, a pneumatically operated diaphragm valve 831 mounted at the rear of the housing 828 is positioned above the portion of channel 827a leading to the venous blood line connection point 814a. A mating pneumatic connector 831a mounted on the front panel 811 supplies positive or negative pneumatic pressure to the valve 831, thereby activating the valve, the pneumatic lines extending from the pneumatic distribution module to the front panel 811, or the manifold located in the rear part of the dialysis unit 51.Connectors 830 and 831 can both be configured to form a radial sealing engagement (for example, using an elastomer O-ring) with mating connectors 830a and 831a on the front panel 811, so that the drain cassette 815 can be inserted into or removed from the front panel 811 relatively easily. Similarly, an electrical connector 833 can be mounted on the rear wall of the housing 828 for electrical connection outside the channel 827 to a temperature and / or conductivity probe located within the channel 827. The electrical connector 833 can be configured to form a key-locking connection with the mating electrical connector 833a on the front panel 811 to facilitate engagement and disengagement of the connector when the drain cassette 815 is installed into or removed from the front panel 811. In some embodiments, the connection of the outlet drain port connector 830, the valve control port connector 831, and the electrical connector 833 to their respective connectors on panel 511 can be done essentially simultaneously and / or in a single operation, for example, by pushing the drain cassette 815 into place on panel 511.

[0102] Figure 33 shows a perspective view of the drain cassette front wall 826. The electrical connections between probes 834 and 835 and connector 833 are shown in the drain cassette front wall 826. In this example, probe 834 comprises a thermistor and one of a pair of conductivity sensors, extending into channel 827 to detect both fluid temperature and conductivity. Probe 835 similarly extends into channel 827 as the second probe of a pair of conductivity sensors extending into channel 827.

[0103] Figure 34 shows the main housing 828 of the drain cassette 815, with the front wall 826 removed for clarity. Thermal and / or conductivity probes 834 and 835 are shown to illustrate their positioning in portion 827b of the fluid flow channel 827 (each probe is installed sealed to the front wall 826 but has an elongated element that penetrates the front wall 826 to be present in any portion of the fluid channel 827). An electrical connector 833 is shown to be positioned in the area of ​​the housing 828 outside the channel 827. In one embodiment, a check valve such as a duckbill valve 836 may be mounted within the drain connector 830 (shown in Figure 32).

[0104] Figure 35 shows a rear perspective view of the drain cassette 815. A male fluid connector 830 is configured to connect to a mating connector 830a on the front panel 811, which is connected to the drain line. A male pneumatic connector 831 is configured to connect to a mating connector 831a on the front panel 811, which is connected to the pneumatic line. A male electrical connector 833 is configured to connect to a mating connector 833a on the front panel 811, which provides electrical connections from the thermal and / or conductivity sensor in the housing 828 to the system controller in the rear portion of the dialysis unit 51. A latching member 837 connected to the handle 821 is configured to be inserted into a keyhole on the front panel 811 in order to engage and lock the drain cassette 815 to the front panel 811.

[0105] Figure 36 shows the front panel 811 with the drain cassette 815 removed. The drain cassette recess 838 is configured to receive the drain cassette 815. The user simply needs to align the drain connector 830, pneumatic valve connector 831, and electrical connector 833 of the drain cassette 815 with their corresponding connectors 830a, 831a, and 833a on the front panel 811, push the cassette 815 into place, and make the necessary pneumatic and electrical connections. The latch member 837 of the handle 821 of the drain cassette 815 is inserted into the keyhole 837a, and the handle 821 can be rotated a quarter turn or half turn to lock the drain cassette 815 into the recess 838, thereby resulting in the front panel configuration shown in Figure 21B.

[0106] The modular functionality of the drain cassette 815 advantageously allows the user to easily install and remove substantially all of the blood-carrying components of the dialysis system (except in one embodiment the distal portion of the drain line 31). Thus, the dialysis unit 51 can be used by two or more individuals simply by replacing the blood-carrying components (e.g., blood circuit assembly and drain cassette), with each set assigned to each individual user. The dialyzer semipermeable membrane, the ultrafiltration filter for incoming water or dialysate in the dialysate-side circuit, and the microbiological barrier enabled by the dialysate-side disinfection procedure between each use of the dialysis unit 51 allow the dialysate-side components to be reused between different users. The modular drain cassette 815, along with other modular blood circuit components, allows the dialysis unit 51 to be conveniently used in multi-user clinical settings as well as in a single-user home environment.

[0107] According to another aspect of the present invention, the front panel 511 (or other suitable component) of the dialysis unit 51 may be configured to accommodate dialyzer units 14 of various sizes and / or shapes. Different dialyzers may be specified to provide different treatment conditions for different patients, and in one embodiment, even for the same patient over a long period of time. Thus, the dialysis unit 51 is preferably configured to work with multiple different types of dialyzers 14. Often, different dialyzers 14 will have different dimensions, such as the overall diameter and / or length of the dialyzer unit. In the exemplary embodiment shown in Figure 23, the front panel 511 includes a dialyzer mounting base having a pair of “keyhole” functions 520 configured to engage with each dialysate quick-connect fitting on the dialyzer 14. Each keyhole mechanism 520 includes an upper insertion area 520a sized to accommodate a portion of the quick-connect fitting and a lower flange portion 520b that is narrower than the overall diameter of the quick-connect fitting and engages with the groove area of ​​the quick-connect fitting. To aid in understanding these functions, Figure 24 shows a dialyzer 14 with quick-connect fittings 14a fitted to the dialysate inlet and outlet ports of the dialyzer 14 (the blood inlet and outlet ports are located at the upper and lower ends of the dialyzer 14 as shown in Figure 24). The illustrated quick-connect fittings 14a are of a standard type, and many, though not all, dialyzers 14 have dialysate inlet / outlet ports configured to engage with standard quick-connect fittings 14a. Each quick-connect fitting 14a includes a sliding element 14b that moves to the right relative to the base 14c (as shown in Figure 24) to engage the fitting 14a with the dialysate port on the dialyzer 14. As the sliding element 14b moves and the fitting 14a adheres to the dialysate port on the dialyzer 14, the groove 14d is closed. However, when the fitting 14a is properly positioned at the inlet / outlet port of the dialyzer 14, the sliding element 14b is released, and a spring (not shown) moves the sliding element to the left, as shown in Figure 24, resetting the groove 14d to the state shown in Figure 24. Therefore, if the quick-connect fitting 14a is properly engaged with the dialyzer 14, the groove 14d exists as shown in Figure 24.

[0108] To attach the dialyzer 14 to the keyhole mechanism 520, the quick-connect fittings 14a are partially inserted into the upper insertion areas 520a of the upper and lower keyhole mechanisms, respectively, such that the grooves 14d of each quick-connect fitting 14a are aligned with the flange of the lower flange portion 520b of the keyhole mechanism 520 (note that the upper insertion area 520 of the lower keyhole mechanism 520 can be longer than that shown in Figure 23 to accommodate a wider range of dialyzer lengths). Once the grooves 14d are aligned with the flange, the dialyzer 14 can be lowered so that the quick-connect fittings 14a are fully accommodated in the lower flange portion 520b of the keyhole mechanism 520.

[0109] According to another aspect of the present invention, one or both of the keyhole mechanisms 520 are adjustable so that the weight of the dialyzer 14 is shared by both lower flange portions 520b of the keyhole mechanism 520. For example, in this exemplary embodiment, the lower keyhole mechanism 520 has a portion of the lower flange portion 520b that is adjustable to a vertical position relative to the upper keyhole mechanism 520. Thus, since this portion of the lower flange portion 520b is adjustable to a vertical position, the lower quick-connect fitting 14a can also be supported by the flange portion 520b of the lower keyhole mechanism by moving the movable portion of the flange portion 520b of the lower keyhole mechanism, for example, upward, while the upper quick-connect fitting 14a is supported by the flange portion 520b of the upper keyhole mechanism 520. Therefore, the weight of the dialyzer 14 can be shared by both keyhole mechanisms 520. The flange portions 520b can be adjusted in any suitable way. In this embodiment, the flange portion 520b has a U-shaped member 520c that is slidable longitudinally along the longitudinal flange and can be fixed in place by tightening a set of wing nuts. The U-shaped member 520c can engage with the quick-connect fitting 14a so that it supports (at least partially) the weight of the dialyzer 14.

[0110] In the above embodiment, the dialyzer 14 is supported by a keyhole mechanism on the front panel 511, but the support structure for the dialyzer can be configured in other ways. For example, the upper insertion area 520a is not necessarily required. Alternatively, only a flange portion (for example, in the shape of a "U"-shaped flange with opposing flange portions) can be provided and engaged with the dialyzer quick-connect fitting. The flange portion can be offset from the front surface of the front panel 511 to provide a gap for the fitting and engage with the groove of the quick-connect fitting. Furthermore, the flange portion does not need to be provided in the longitudinal direction as shown, but can be angled from the longitudinal direction and oriented horizontally, for example. The flange portion can have other functions such as a stopper, a catch, or an aid in holding the dialyzer in place.

[0111] According to another aspect of the present invention, a bicarbonate, acid, and / or other reagent source can be selectively associated with a dialysis unit. As described above, the dialysis unit 51 requires a supply of specific chemicals to produce dialysate and / or other materials necessary for system operation. Figure 25 shows a reagent source 49 used to supply acid, bicarbonate, and / or other materials to the dialysis unit 52 (Figure 21 shows the reagent source 49 mounted on the acid / bicarbonate connection point 512 on the front panel 511). The reagent source 49 in this exemplary embodiment comprises an E-fork connector 491 configured to mate with the acid / bicarbonate connection point 512. As with other connections made by the user on the front panel 511, such as blood line connections at connection point 514, the mating connector may be color-coded or otherwise marked to ensure proper connection. For example, the E-shaped fork connector 491 and the acid / bicarbonate connection point 512 can be orange, the arterial line 203 and its mating connection at connection point 514 can be red, and the venous line 204 and its mating connection at connection point 514 can be blue. From the E-shaped fork connector 491, the bicarbonate supply line 492, the water supply line 493, and the acid supply line 494 extend (see Figure 6 and the relevant description of the function of these lines). The water supply line 493 supplies water to the bicarbonate supply source 28 (in this embodiment, a 750g Altracart Bicarbonate cartridge (#500750A) sold by Baxter International, Inc., containing powdered bicarbonate material, but any suitable supply source may be used). The bicarbonate supply source 28 supplies bicarbonate to the dialysis unit 51 through the bicarbonate supply line 492. In this embodiment, the acid supply line 494 is connected to an acid bag spike 495 which can be used to pierce a Type IV bag or other container and extract the appropriate acid therefrom. In this embodiment, the acid bag spike 495 includes a spike member 495a and a pair of spring clips 495b.The spring clips 495b are joined together at their center by a connecting bar, resulting in an "H" shape between the spring clips 495b and the connecting bar, and the spring clips 495b are rotatable relative to each other when their proximal ends are clamped together. The spring clips 495b are configured to engage with a connector element on an acid bag (or other acid source, not shown), so that the spike member 495a can remain engaged with the bag until the user removes the clip 495b. For example, the distal end of the clip 495b may include a barb that engages with the acid source, and the clip can be detached from the acid source by clamping the proximal ends of the clips 495b together and separating the barb at the distal end of the clip 495b from the acid source. The acid bag spike 495 may also include a valve 495c (in this case, a pinch clamp) for opening / closing the line of the acid bag spike 495. According to one aspect of the present invention, the acid bag spike 495 can be replaced with another component, such as an acid jug straw (not shown) or other structure (disconnected from the acid supply line 494 at the cap connector 496). When used with a jug straw, the cap connector 496 can engage with the opening of the acid jug so as to cover the opening of the acid jug like a cap. Alternatively, the jug straw may have a spiked end to allow it to penetrate a self-sealing (e.g., rubber) membrane covering the opening of the acid jug. Thus, various types of components can be attached to the acid supply line 494 depending on the acid supply structure (jug, bottle, bag, etc.).

[0112] Figure 26 is a close view of the E-fork connector 491 and the corresponding connection point 512 of the front panel 511. The E-fork connector 491 has three parallel forks (corresponding to the bicarbonate and acid supply lines 492, 494 and the water supply line 493) that engage with the corresponding housing hole of the connection point 512. The E-fork connector 491 and the housing hole of the connection point 512 are configured such that the central lumen (water supply line 493) is positioned above, or in other ways, outward from the common plane of the two outer lumen (bicarbonate and acid supply lines 492, 494). In this way, the E-fork connector 491 cannot engage with the connection point 512 unless properly oriented, thus ensuring that the bicarbonate and acid supply lines 492, 494 are properly connected. The E-fork connector 491 includes, for example, a pair of spring tabs 491a that can engage with the corresponding slot 512a of the connection point 512 when the forks are properly positioned in the housing hole of the connection point 512. With tab 491a engaged with slot 512a, the E-shaped connector 491 cannot easily detach from connection point 512, thus helping to reduce the possibility of accidental disconnection. The E-shaped connector 491 can be disconnected by pushing the tabs 491a toward each other so that the distal ends of the tabs 491a detach from slot 512a. Connection point 512 has a similar spring tab 512b that allows connection point 512 to be attached to and detached from the front panel 511.

[0113] According to another aspect of the present invention, a disinfection connector (not shown) engages with connection point 512 for use during the disinfection procedure. The disinfection connector has three parallel forks oriented similarly to the E-fork connector 491, so that the forks can engage with the housing holes of connection point 512. The passages within the forks of the disinfection connector terminate in a common chamber within the disinfection connector. Thus, during the disinfection procedure, the bicarbonate flow line, acid flow line, and water flow line are all interconnected, and each flow line can be disinfected during the disinfection procedure (this is shown as a dotted inverted "T" line in 49 of Figure 6).

[0114] According to another aspect of the present invention, the blood lines 203, 204 are provided with connectors capable of two types of connections. The first type of connection is a push-in or press-fit connection in which the connector is pushed into a housing lumen, and is a leak-free connection that does not require rotation of the connector or housing lumen. The second type of connection is a screw-type connection in which the leak-free connection is achieved by screw engagement between the connector and a complementary element. For example, Figures 27 and 28 are perspective and side views of a blood line connector 202 used with blood lines 203, 204 and capable of engaging with a blood line connection point 514 on a front panel 511. The connector 202 comprises a tube connection end 202a that connects to the corresponding blood lines 203, 204, and a patient access connection end 202b configured to connect to both patient access and the connection point 514 to establish a leak-free connection. At the patient access connection end 202b, the connector 202 comprises a frustoconical member 202c having a female threaded portion configured to engage with a male threaded patient access. For example, the frustoconical member 202c may be part of a male Luer connector having a central tube 202 extending from the center of the frustoconical member 202c. When making a Luer connection, the tube 202e extends into the female Luer connector at the patient access, and the internal threaded portion of the frustoconical member 202c can engage with the threads of the female Luer connector at the patient access (artery or vein). Such a Luer connection is standard when connecting a blood line to a patient access. However, the connector 202 can also engage with the connection point 514 by simply pushing the patient access connection end 202b into the housing hole of the connection point 514. When making this connection, the outside of the frustoconical member 202c can engage with a suitable sheet or other surface or element within the connection point 514 (e.g., a valve seat, O-ring, or other) to form a seal between the frustoconical member 202c and the connection point 514. Furthermore, or alternatively, the central tube 202e can be used to engage with the connection point 514 in order to establish a proper seal.A locking arm 202d extending rearward from the frustoconical member 202c can engage with the hole 514a of the connection point 514 (for example, the barbed portion of the arm 202d can engage with the hole 514a) to assist in holding the connector 202 in the housing hole of the connection point 514. The connector 202 can release the arms 202d by pressing them against each other (for example, by pressing the finger recess with the distal end of the arms 202d), separating the protrusions from the hole 514a and allowing the connector 202 to be withdrawn. It should be noted that the connection point 514 is provided with a spring tab 514b that can selectively engage / separate the connection point 514 from the front panel 511. The connector 202 can be manufactured by any suitable method, such as plastic molding, as a single, integrated part.

[0115] Figure 29 shows a perspective view of a blood circuit assembly 17 of another embodiment. This embodiment differs in several respects from those shown in Figures 18 and 19. For example, in this embodiment, blood lines 203 and 204 have a cross-section whose shape is similar to the letter “number 8”, with one part of the “number 8” containing a lumen through which blood or other fluids are transported, and the other part of the “number 8” transporting a conductor. That is, blood lines 203 and 204 have a lumen through which blood and other fluids can flow, and another lumen through which a conductor can pass. Further details regarding this and other arrangements will be discussed later with reference to Figures 37-49. Similarly, as will be discussed in more detail later, a conductor can be used to detect a break in blood lines 203, 204 from the patient or other connection point, or an interruption of vascular access in one or both of a pair of catheters inserted into a blood vessel or fistula. Furthermore, the organizing tray 171 in Figure 29 differs from that shown in Figure 19 in the following respects. That is, the engaging member 174 may have a slot or hole into which the blood lines 203, 204 engage, but in this embodiment, the engaging member 174 does not need to engage with the blood lines 203, 204 to resist downward tension on the lines 203, 204, for example, to mount the lines in the closure. Alternatively, in this embodiment, the blood lines 203, 204 can move freely with respect to the engaging member 174. Another modification of the embodiment is that the engaging member 174 includes a push plate spanning both lines 203, 204. This is in contrast to the configuration in Figure 19, in which each line 203, 204 is engaged by an independent engaging member 174. The configuration in Figure 29 can offer advantages in some embodiments where a user can engage the lines 203, 204 with respect to a slot 517 leading to the closure in a single operation (see Figure 22). In one embodiment, each slot 517 can be associated with an air detector that operates to detect whether or not there are bubbles in line 203 or 204 (for example, by an optical detection method or other detection method such that the air in line 203 or 204 can be detected by each air detector in one of the slots 517).Therefore, the engaging member 174 can function to associate the lines with an air detector or other function, in addition to or as an alternative to a closure or other mechanism for positioning the lines 203, 204 in a desired manner. In this embodiment, the engaging mechanism 174 includes a slot located on the underside of the push plate that engages with the narrower portion of the lines 203, 204 (e.g., the portion that carries the conductor) to position the conductor closer to the push plate. This can help position the lines 203, 204 within the slot 517 so as not to interfere with an air detector that operates to detect air in the lines 203, 204. As described above, the slot in the push plate that engages with the lines 203, 204 can engage with the lines so that the lines do not rotate relative to the push plate but can advance relative to the push plate along their length. Figure 30 shows a close-up view of a portion of the blood circuit assembly of Figure 29, showing the arrangement of a portion of the organizing tray 171 to at least partially match the shape of the blood lines 203, 204 held by the tray 171. Similar to the engaging member 174, the portion of the tray 171 that engages with lines 203 and 204 can be configured to orient lines 203 and 204 so that the conductor portion of the lines faces outward. This can help to properly position lines 203 and 204 relative to the engaging member 174 or other parts of the assembly 17.

[0116] It should be understood that any and all aspects of the invention described herein can be combined with or otherwise integrated with any other aspects of the invention and / or embodiments described herein. For example, a dialysis system incorporating one or more aspects of the invention described herein may have a line disconnection or line interruption function, such as those described in relation to Figures 37 to 49. Such a disconnection function may have features such as 1) an electrical circuit or other suitable circuit that detects a change in voltage, resistance or other characteristic indicating disconnection of blood lines 203, 204 with respect to the relevant connectors; 2) positioning of a detection electrode in appropriate proximity to the patient or other reference; 3) arrangement of one or more connectors; and 4) a blood line piping configuration or other suitable configuration in which the blood lines support both fluid flow lumen and conductive functions. For example, in one aspect of the present invention, a blood circuit assembly may comprise an electrical circuit component suitable for use in detecting disconnection / connection of one or more blood lines in a blood line, one or more blood pumps, an air trap, and a tidying tray. Such a configuration allows the user to make several different connections, whether fluid, pneumatic, and / or electrical, relatively easily and without complexity.

[0117] Accordingly, aspects of the present invention generally relate to systems and methods for detecting ruptures in indwelling vascular lines or their tubing used in dialysis treatment, such as catheters or needles. If ruptures are not detected quickly, they can lead to rapid bleeding, especially if the blood in the catheter or tubing is under positive pressure. Examples of environments with positive intravascular pressure include positive pressure associated with arterial or arteriovenous fistulas, or positive pressure associated with extracorporeal blood pump circuits. In hemodialysis, for example, the blood pump can generate blood flow rates of 400 ml / min to 500 ml / min, making rapid and reliable rupture detection particularly desirable. Indeed, any medical treatment involving relatively high flow or high pressure extracorporeal circulation (e.g., hemoperfusion or cardiopulmonary bypass) can be made safer by having an effective system for monitoring arterial (extraction) and venous (return) integrity.

[0118] In hemodialysis, for example, extracorporeal blood circulation can be achieved through vascular access using either a single indwelling catheter or two separate indwelling catheters. In a single-catheter system, blood is alternately drawn out of and returned to the body through the same cannula. Cuts in this system can be quickly detected by placing an air monitor at or near the pump inlet, as air will be drawn into the line from the cut site during the blood withdrawal phase of pumping. On the other hand, in a two-catheter system, blood is usually drawn out of the body through one catheter inserted into a blood vessel or fistula and returned to the body through a second catheter inserted at a distance from the first catheter in the same blood vessel, or in a completely separate blood vessel. In a two-catheter system, sensors can also be used to monitor whether the catheter or tubing has come loose during blood withdrawal, i.e., the “arterial” segment, by detecting the presence of trapped air in the arterial tubing when blood is drawn out of the blood vessel under negative pump pressure and / or positive fistula pressure. However, detecting air in the line cannot reliably detect a break in the venous (return) segment of the extracorporeal circuit. In this case, if the blood withdrawal pathway remains intact, air will not be introduced into the line. Therefore, it is particularly important to be able to detect a break in the continuity of the return line from the extracorporeal pump to the vascular access site.

[0119] In one embodiment, the present invention includes a system for detecting whether a vascular access device, such as a needle, cannula, or catheter, has been severed or detached from a blood vessel or vascular graft. In another embodiment, the system is configured to detect whether a vascular access device is closed by means of electrical conductivity or impedance. The system includes a fluid delivery device that provides a flow of fluid into the blood vessel through a tube or conduit via an indwelling needle or catheter at a first site in the blood vessel or graft. The fluid can be an electrolyte or another solution suitable for intravenous infusion, or it can be blood or a blood component. An electrode is positioned to be in contact with or in fluid communication with the lumen of the conduit, and a second electrode is positioned to be in fluid communication with the blood in the blood vessel or graft through a second in the blood vessel or graft. An electronic circuit is connected to the first and second electrodes and is configured to send control signals to the first and second electrodes to measure the electrical resistance of the fluid between the first and second electrodes, wherein at least one of the electrodes is positioned closer to the blood vessel or graft than the fluid delivery device. In some embodiments, electrodes are positioned approximately 50% to 70% of the distance from the fluid delivery device to the blood vessel or graft. In other embodiments, electrodes are positioned approximately 70% to 90% or more of the distance from the fluid delivery device to the blood vessel or graft. The fluid delivery device may comprise a pump for blood or other therapeutic or diagnostic fluids. The fluid delivery device may be part of a hemodialysis blood flow circuit, which may or may not include a blood pump, dialyzer cartridge or air trap and associated piping. A second electrode may be positioned in contact with the lumen of a second conduit or tube that fluidly communicates with the blood vessel or graft at a second site. The second conduit may form part of the fluid flow path from the blood vessel or graft to the fluid delivery device. The fluid in the second conduit may be blood being delivered to the extracorporeal blood flow circuit.

[0120] The system may include first and second connectors for connecting a pair of vascular access catheters that access vascular segments or vascular graft segments at two different sites. Each of the first and second connectors may be connected to a flexible tube leading to a fluid delivery device. Each connector may be equipped with electrodes exposed in the lumen of the connector. A wire may be attached to each connector, and the other end of the wire may be connected to an electronic circuit. The flexible tube may be a double-lumen tube having a first lumen for transporting fluid and a second lumen for transporting the wire. The wire of each tube may be connected to a connector at the other end of the tube for connection to an electronic circuit.

[0121] An electronic circuit or associated microprocessor can be configured to convert the voltage measured by the electronic circuit across terminals connected to electrodes into a resistance value. The system may include a controller configured to receive a signal from the electronic circuit or microprocessor, the signal representing the electrical resistance between the electrodes, and the controller is programmed to trigger an alarm signal when the electrical resistance exceeds a predetermined threshold. The alarm signal can be an audible or visual signal to the person whose blood vessel is being accessed, and optionally, the alarm signal can include an electrical command to a pipe closure device. The pipe closure device can be activated to mechanically close one or more tubes leading from the vascular access site. The pipe closure can operate in multiple ways, for example, electromechanically, hydraulically, or pneumatically.

[0122] In another embodiment, the present invention includes a device for monitoring continuity between a vascular access device and a blood vessel or vascular graft segment, comprising first and second vascular connectors, the first connector being fitted at its proximal end to the distal end of the fluid-carrying lumen of a first double-lumen tube, and the second connector being fitted at its proximal end to the distal end of the fluid-carrying lumen of a second double-lumen tube. The first connector comprises a first electrode in contact with the lumen of the first connector and electrically connected to a wire in the wire-carrying lumen of the first double-lumen tube, and the second connector comprises a second electrode in contact with the lumen of the second connector and electrically connected to a wire in the wire-carrying lumen of the second double-lumen tube. The wire in the first double-lumen tube and the wire in the second double-lumen tube are each connected to an electrical connector at the proximal end of the double-lumen tube. The distal end of each connector may be configured to have a locking function that provides a reversible airtight connection between the connector and the mating connector of a vascular catheter. The proximal end of the double-lumen tube can be connected to the arterial blood pump and the venous air trap, and in a hemodialysis system, the blood pump and air trap may each be reversibly connected to the dialyzer cartridge.

[0123] In another embodiment, the present invention comprises a vascular connector comprising a proximal fluid connection end, a distal fluid connection end, and an electrode configured to electrically connect the fluid-carrying lumen of the connector to a wire outside the vascular connector. The proximal end of the connector may be configured to connect to a flexible tube, and the distal end of the connector may be configured to connect to a mating connector of a vascular catheter. The electrode may be installed in the conduit of the connector, connecting the lumen of the connector to the outside of the connector. The electrode may be housed in the conduit to provide an airtight seal between the lumen and the outside of the connector. An elastomer, such as an O-ring, may be installed between the electrode and the conduit to contribute to the airtight seal.

[0124] In another embodiment, the present invention relates to an electrical circuit for measuring the resistance of a liquid between a first electrode and a second electrode, wherein the first electrode is connected to a first terminal of the electrical circuit, the second electrode is connected to a second terminal of the electrical circuit, a capacitor C1 connected to the first terminal at the first end and a capacitor C2 connected to the second terminal at the first end, a known reference resistor Rref connected to the second end of capacitor C1 at the first end, and (a) a first reference voltage V+ connected to the second end of Rref and the lower second reference voltage V- connected to the second end of C2 The electrical circuit comprises a switching means that connects to form a first switch configuration, or (b) connects a first reference voltage V+ to the second end of C2 and a lower second reference voltage V- to the second end of Rref to form a second switch configuration, and a measuring means that measures a voltage Vsense at the connection between C1 and Rref, thereby configuring the electrical circuit to determine a value of the resistance of a liquid based on a known reference voltage Rref and an observed voltage Vsense for each of the first and second switch configurations. The resistance Rref can be selected to enable conductivity measurement of an electrolyte or other solution suitable for intravenous infusion. The electrolyte may include dialysate. The resistance Rref can also be selected to enable measurement of the resistance of a certain volume of blood between the first and second electrodes.

[0125] Conductivity circuit An exemplary electrical circuit, as shown in Figure 37, can be used to measure the conductivity or resistance of a fluid of interest. In one embodiment, the fluid may be an electrolyte or a dialysis fluid, and the circuit can ultimately provide a measurement of the fluid's conductivity to ensure its suitability for intravascular administration. In addition to monitoring the concentration of dissolved solutes in the fluid, the electrical circuit can also monitor for any potential interruptions in the fluid's continuity between electrodes connected to the circuit. For example, it can be used to monitor an intravenous fluid line for the presence of air bubbles or contaminants. In another embodiment, the fluid may be blood, and the measured change in the electrical resistance of the blood flow path (e.g., in a conduit) can be used to indicate whether a discontinuity occurs between the blood flow path and the measuring electrode. For example, the blood flow path may include a column of blood between two electrodes, including an indwelling needle or catheter in a blood vessel, arteriovenous fistula, or graft segment. Disconnection of vascular access can introduce air into the blood flow path, potentially changing the resistance of the blood column between the electrodes. The electrical circuit can be easily modified (depending on its application) to adjust for the difference between the impedance of the blood flow path and the impedance of the dialysis fluid.

[0126] Using the circuit shown in Figure 37, the unknown resistance Rx of the target medium 1 can be measured using low-cost electronic components, especially when the unknown resistance includes a conductive path through the electrolytic fluid. A switching network 2 with a pair of multiplexers allows connection to reference voltages V+ and V- at node VA. The target medium 1, having the unknown resistance Rx, is connected to terminals VTA and VTB 3, forming a voltage divider with a reference resistor Rref 4. To perform conductivity measurements, an AC voltage can be supplied to the target medium 1 through the switching network 2 to the voltage divider generated by a known reference resistor Rref 4 (e.g., 680 ohms for dialysis fluid) and the unknown resistance Rx of the target medium 1. The midpoint of the voltage divider is measured. The signal Vsense at point 8 is buffered by amplifier 10 to generate the input signal Vin for the analog-to-digital converter (ADC) 111. Vsense switches between two values ​​as the voltage divider is driven first in one direction and then in the other. This signal is valid only for a short period after switching because the fluid in conductivity cell 1 is AC-coupled to the circuit through capacitors C1 and C2 6. Therefore, DC blocking capacitors C1 and C2 6 can be used to prevent DC current from passing through unknown resistances (which may include conductive paths through the electrolytic fluid or blood). In one embodiment, each series capacitor C may include two capacitors in parallel, one having a value of, for example, 0.1 μF and the other having a value of, for example, 10 μF. Series resistors 7 can be used to reduce exposure to noise and surge voltages by the switch network and other sensing circuits. The ADC 111 can acquire multiple samples of the signal when the circuit switches between two configurations.

[0127] The switching network 2 is driven by a pair of alternating binary control signals 131, 144 that connect VA to V+ and VB to V- during one half-cycle, and VB to V+ and VA to V- during the other half-cycle. The binary control signals 131, 144 may be characterized by the duration of the cycle (T) or the frequency of the signal (f=1 / T). The binary control signals 131, 144 may be further characterized by an active period in which the signals alternate between high and low values ​​and an inactive period in which both signals are off, as shown in Figure 38. In one embodiment, the active period consists of a first control signal that supplies three high half-cycles, while a second control signal supplies two high half-cycles. When the binary control signals 131, 141 are applied to a circuit similar to the circuit in Figure 37, a waveform similar to the waveform 20 shown in Figure 38 is generated at the Vsense node 58. In other embodiments, the number of high half-cycles for each control signal 131, 144 during the active period may be an integer of high half-cycles for signal 131, alternating with any integer of high half-cycles for signal 144. Alternatively, during the active period, control signal 131 may generate one high half-cycle alternating with one high half-cycle in control signal 144.

[0128] In this embodiment, Vref is 4 volts, and the Vsense amplitude is less than 4 volts, as shown in Figure 38. The voltage divider 8 provides voltages V+ and V-, respectively, that are close to the positive reference voltage Vref and close to ground. In one embodiment, R1 can have a value of 10 ohms and R2 can have a value of 2 kΩ. When both multiplexers of the switching network 2 are instructed to zero, the circuit is stopped and the lower voltage is applied to terminals VTA and VTB 3. If VA is high and VB is low, the higher voltage is applied to the reference resistor Rref 4 and the lower voltage is applied to the target medium 1 having an unknown resistance Rx. If VB is high and VA is low, the higher voltage is applied to the target medium 1 having an unknown resistance Rx and the lower voltage is applied to the reference resistor Rref 4.

[0129] The voltage change ΔVsense before and after each square wave edge can be shown to be determined only by the reference resistor Rref 4, the unknown resistance Rx of the medium 1, and any series resistor (including, for example, Rs 7), and generally independent of the series capacitance C1 or C2 6, because during this short period, the capacitor acts as an incremental short circuit. In particular, Δα=ΔVsense / (V+-V-)=(Ry-Rref-Rth) / (Ry+Rref+Rth)=(ρ-1) / (ρ+1) In the equation, Ry = Rx + 2Rs + Rth, where Rth = the source series resistance from multiplexer 2 and voltage divider 8, and ρ = Ry / (Rref + Rth) (the source series resistance Rth can be derived as the sum of the resistance of multiplexer 2 and the Thevenin equivalent resistance of voltage divider 8. For example, if R1 = 10 ohms and R2 = 2K ohms, then Rth = R1∥(R1 + R2) = 9.95 ohms). Thus, when Ry is a short circuit, ρ = 0 and Δα = -1. Then the change in voltage at the sense node ΔVsense is equal to the change in voltage at VB, which has the opposite amplitude to that at the drive node VA. When Ry is an open circuit, ρ = ∞ and Δα = 1. Then the change in voltage at the sense node ΔVsense is equal to the change in voltage at the drive node VA. Thus, if this change in voltage is measured, the above equation can be solved for an unknown resistance Rx.

[0130] Rx=ρ(Rref+Rth)-2Rs-Rth, where ρ=(1+Δα) / (1-Δa) As shown in Figure 37, a low-pass filter 9 can be formed by a resistor Rf and a capacitor Cf to remove high-frequency noise. In one exemplary configuration, Rf may have a value of 1 kΩ and Cf may have a value of 0.001 μF. The buffer amplifier 10 and analog-to-digital converter (ADC) 111 can then measure the sensed voltage to a computer or digital signal processor (not shown).

[0131] The reference voltages V+ and V- can be favorably derived from the voltage divider 8 such that V+ is close to the reference voltage Vref of the ADC111 and V- is close to the ground reference voltage of the ADC111. For example, if R1 = 10 ohms, R2 = 2 k ohms and Vref = 4.0 V, then V+ = 3.980 V and V- = 0.020 V. This brings both voltages within the active sensing region of the ADC111, but close to its edge, so they can be used for calibration (described later). Switch SW1 12 can be used to assist in the calibration of load resistance sensing.

[0132] Several improvements can reduce errors associated with variations in component values. Firstly, a calibration step can be introduced in which VA is switched to V+ for a relatively long period of time until it settles and becomes approximately equal to V+ (at which point the ADC111 can perform a measurement of Vsense). Secondly, a calibration step may include switching VA to V- for a relatively long period of time until Vsense settles and becomes approximately equal to V- (at which point the ADC111 can perform another measurement of Vsense). This allows the ADC111 to measure both V+ and V-.

[0133] Secondly, as shown in Figure 38, while the rectangular wave is switching, the dimensionless number Δα can be calculated using the ADC111 readings before and after both edges of the switching waveform, as follows. Δα=ΔVsense / (V+-V-)=[(V2-V1)+(V3-V4)] / 2(V+-V-) As a result, ΔVsense=[(V2-V1)+(V3-V4)] / 2 can be measured using both edges of the waveform, which may cancel out the asymmetric response to the circuit. Alternatively, the average voltage at approximately the midpoint of the waveform can be used, so for example, Δα=ΔVsense / (V+-V-)=[(V7-V6)+(V7-V8)] / 2(V+-V-) and ΔVsense=[(V7-V6)+(V7-V8)] / 2. Furthermore, only the difference measurement of the input signal Vin of ADC111 can be used. Thus, any offset errors of the buffer amplifier 10 and ADC111 can be canceled out. Also, Δα is a ratiometric quantity based on measurements using the same signal path. Thus, any gain errors of ADC111 can be canceled out.

[0134] The reference resistor Rref 4 can be arbitrarily selected to be equal to the geometric mean of the endpoints of the unknown resistance over a desired range, taking into account the series resistance Rs 7. For example, if Rs = 100 ohms and Rx varies from 100 ohms to 3000 ohms, then Ry = Rx + 2R varies from 300 ohms to 3200 ohms, and Rref should be approximately the square root of (300 ohms * 3200 ohms) = 980 ohms. To measure an unknown resistance in the range of 100k ohms to 300k ohms (for example, in a blood column extending from one electrode to another through an arteriovenous fistula), the reference resistor Rref 4 can be varied to approximately 200k ohms, which completely removes the filter capacitor Rf of the low-pass filter 9 at the input to the buffer amplifier 10.

[0135] Since the output of the voltage divider is a nonlinear function of its resistance ratio, errors or noise in the readings from the ADC111 contribute to their lowest partial error (sensitivity) in the calculation of Ry when Ry is equal to Rref, and as sensitivity increases, Ry diverges from the reference resistance Rref. Specifically, the sensitivity at the resistance ratio can be shown as follows:

[0136] Sρ=(1 / ρ)·∂Δρ / ∂Δα=2 / [(1+Δα)(1-Δα)]=2 / [1-(Δα) 2 ] When Ry = Rref, ρ = 1, Δα = 0, and Sρ = 2. Therefore, for a change in Δα of 0.001 (0.1% of the ADC full scale) around this point, the calculated resistance Ry changes by 0.002, or 0.2%. As shown in Table 1, sensitivity increases as ρ diverges from 1.

[0137] [Table 1]

[0138] Figure 39 shows that noise / error sensitivity doubles at an unknown / reference resistance ratio of approximately 6:1 and triples at a ratio of 10:1. Resistance measurements outside this range may be affected by increased sensitivity to noise and error.

[0139] For calibration purposes, resistance measurements can be performed using switch SW1 12 to eliminate the Rx=0 point during calibration. Preferably, this switch 12 should be placed at both ends of terminals VTA and VTB 3, or as close to them as possible, thereby providing true zero-point calibration. However, in practice, placing switch 12 close to terminals VTA and VTB 3 may make switch 12 more susceptible to external noise and surge voltages, potentially introducing DC leakage current into the target medium 1.

[0140] The use of series capacitors C1 and C2 6, along with the square wave voltage, is important for unknown resistances, including those in the electrolyte conduction path. There are at least two reasons for this. Firstly, in many applications, it may be important to prevent DC current from flowing through the electrolyte or a similar bodily fluid, otherwise electroplating and / or electrolysis of the electrodes at terminals VTA and VTB 3 could occur. In this circuit, capacitors C1 and C2 6 block the DC current. Furthermore, since capacitors can conduct very small currents (less than microamperes), using an alternating square wave voltage can help further limit the average current.

[0141] Secondly, if a small electrochemical DC voltage is induced in the target medium 1 (for example, the electrodes of the fluid path may oxidize at different rates over time), this DC voltage can be blocked by capacitors C1 and C2 6. Since the method for calculating resistance performs differential measurements, any residual DC voltage can be canceled out through the process of calculating the unknown resistance Rx of the target medium 1.

[0142] The high half-cycle applied voltage and duration during the active period are selected to saturate the capacitive element between voltages VA and VB, thereby making the determined impedance equal to the pure resistive component of the unknown impedance Rx. Furthermore, the duration during the active period may be selected to limit the leakage current to which the patient may be exposed.

[0143] Here, we refer to the circuit in Figure 37 and the waveform plot in Figure 38. The unknown resistance Rx in Figure 37 can have a complex impedance consisting of a pure resistance and a capacitive resistance. The pure resistance is the resistance to the flow of DC current, and the capacitive resistance is the resistance to AC current. In some embodiments, the lines between capacitors C1, C2 and terminals VTA, VTB may be capacitively coupled. Capacitive coupling provides a resistance that puts the measured voltage signal Vsense in parallel with the unknown impedance Rx, thus reducing the measured impedance. In applications such as measuring the conductivity of dialysate or detecting severed vascular access, the pure resistance portion of the complex impedance Rx is more important.

[0144] When a capacitive element is present in series with an unknown resistance Rx or in parallel with an unknown resistance, the measured voltage signal Vsense, and thus the measured impedance, depends on the voltage and frequency of the signal applied at VA and VB in Figure 37. In one embodiment, the binary voltage signals 131, 144 operate at a sufficiently low frequency during the active phase when the capacitive element in series or parallel with the unknown impedance Rx is fully charged or saturated. The resulting Vsense waveform 20 reaches a stable value during the half-cycle such that V7 is approximately equal to V3. The resistance calculated from the stabilized Vsense is minimized by the influence of the capacitive element, and the resulting measured resistance reflects primarily the pure resistive element of Rx. The frequencies of the binary voltage signals 131, 144 that produce measurements unaffected by the capacitive element at the unknown impedance Rx may be determined based on capacitance measurements or calculations, or they may be determined empirically.

[0145] In one embodiment, the controller determines a capacitance-rejecting frequency by varying the frequencies of binary voltage signals 131 and 144, below which the capacitive element does not affect the measurement of the unknown resistance Rx. The controller starts at a high frequency and decreases the frequencies of the voltage signals 131 and 144 to begin searching for a frequency that minimizes the capacitive element, while monitoring the resulting Vsense waveform 20 and extending the duration of the high half-cycle. The controller may continue to decrease the frequency of the voltage signals until it detects that the Vsense waveform 20 has reached a steady state by the end of the half-cycle. In one embodiment, the steady state can be defined as the Vsense voltage V7 at the middle of the half-cycle which is greater than a predetermined percentage of the final voltage V3 at the end of the half-cycle. In one embodiment, the Vsense waveform 20 has reached a steady state when V7 is greater than approximately 75% of V3. In another embodiment, the Vsense waveform 20 has reached a steady state when V7 is greater than approximately 90% of V3. Alternatively, the Vsense waveform 20 can be declared to have reached a steady state when the rate of change of V3 is less than a predetermined threshold.

[0146] Alternatively, the controller can initiate a frequency search at a low frequency value and increase the frequency until the Vsense waveform 20 is no longer in a steady state at the end of the half-cycle.

[0147] The controller can determine the volume exclusion frequency of the binary control signals 131 and 144 at the start of treatment and then use that frequency throughout the remainder of treatment. The determination of the volume exclusion frequency may be performed after a predetermined volume of blood has been pumped or after a predetermined number of blood pump strokes have occurred.

[0148] In another embodiment, the volume exclusion frequency may be determined periodically to ensure that the volume between the wires of the arterial blood circuit tubing 108 and the venous catheter tubing connector 128 (Figure 40) does not change. In one embodiment, the volume exclusion frequency is determined every 50 strokes of the blood pump.

[0149] In one embodiment, the inactive period of the binary voltage signal can be extended to limit current leakage from the circuit in Figure 37. The active period can have a short duration and include only a few cycles during which the circuit is turned off for a relatively long period. For example, the active period may consist of six pulses with a duration of 420 microseconds, and the active period may occur every 80 milliseconds.

[0150] Blood vessel cleavage detector By appropriately modifying conductivity measurement circuits as described above, it is possible to detect the conductivity of blood and changes in conductivity. More specifically, it is possible to detect changes in the conductivity of a certain volume of blood that occur when air enters that volume. This situation may occur, for example, when an intravascular access site becomes detached within an extracorporeal blood circuit.

[0151] The circuit shown in Figure 37 can be used to measure the resistance of a certain volume of fluid in a conductivity cell or conduit 1. When measuring the Rx of conductivity cell 1 representing the resistance or conductivity of a certain volume of dialysate, a convenient value for the reference resistor Rref 4 can be selected to be approximately 680 ohms. When measuring the Rx of conduit 1 representing the resistance or conductivity of a blood column extending from a first cannula or needle through an arteriovenous fistula to a second cannula or needle, a convenient value for the reference resistor Rref 4 can be selected to be approximately 200 kohms.

[0152] The advantages of using this circuit to monitor the continuity of a column of body fluids such as blood or plasma include the following: Capacitive coupling to the conductivity cell or conduit 1 prevents DC currents that could cause electrode plating and corrosion at terminals VTA and VTB, and for patient safety, the voltage and current levels are kept very low and intermittent, with current flowing only for short periods while measurements are being taken. No current flows between measurements.

[0153] Using the lower value of reference resistor Rref 4 (e.g., 680 ohms), this circuit is appropriately configured for measuring dialysate conductivity. Using the much higher value of reference resistor Rref 4 (e.g., 200 kohms), this circuit is appropriately configured to measure the resistance between the arterial and venous needles to detect when the vascular needle is dislodged from the arteriovenous fistula.

[0154] Electrode arrangement The continuity of the fluid column leading from the fluid delivery device to the patient's blood vessel or vascular graft can be monitored using the electronic circuit described above. The fluid being delivered may include blood or any electrolyte, including dialysis fluid. The following discussion includes a hemodialysis system, but the same principle of operation of the present invention can be applied to any device configured to deliver fluid to a patient through vascular access. In the embodiment shown in Figure 40, the conductivity of a volume of blood or other fluid in the fluid flow circuit 100 of the hemodialysis machine 200 can be electronically monitored using electrodes at each end of that volume that are in direct contact with the blood or other fluid. Using an electrical circuit such as that shown in Figure 37, one electrode can be connected to the VTA terminal and the other electrode can be connected to the VTB terminal of the circuit. The voltage applied to the electrodes by the circuit can be a DC voltage that is sufficiently small (e.g., about 4 volts or less), sufficiently short-lived, and sufficiently interrupted so as not to cause any harm to the patient. In this example, a fluid flow circuit 100 is shown, including an arterial access needle 102, arterial catheter tubing 104, arterial catheter tubing connector 106, arterial blood circuit tubing 108, a transition 110 between the vascular circuit tubing 108 and the hemodialysis machine 200, a blood pump inlet line 112, a blood pump 13, a blood pump outlet line 116, a dialyzer 14, a dialyzer outlet line 120, an air trap 122, a transition 124 between the hemodialysis machine 200 and the venous blood circuit tubing 126, a venous catheter tubing connector 128, a venous catheter tubing 130, a venous access needle 132, and the luminal volume of a portion of the patient's blood vessel or fistula 134 located between the arterial access needle 102 and the venous access needle 132. The invention described herein also encompasses situations in which the arterial access needle may be located in one of the patient's blood vessels, and the venous access needle may be located in a separate blood vessel somewhat distant from the arterial access site. Furthermore, the circuit described above can be used to monitor the integrity of vascular access in a fluid delivery system that does not have a venous return line, as shown in Figure 40. In this case, for example, the electrode at position B can be paired with an electrode that comes into contact with the fluid in a dead-end line communicating with a second needle or cannula accessing a blood vessel or vascular graft.In another example, a conductive wire may be fitted to an indwelling hollow cannula or solid trocar in a vascular segment, which can then serve as a second electrode in a monitoring system. The accessed vascular segment may be an arteriovenous fistula formed by surgery, or it may include an artificial conduit such as a Gore-Tex® vascular graft. The term “arterial” is used herein to refer to the portion of the blood flow circuit that leads blood away from the patient toward the hemodialysis machine 200. The term “venous” is used to refer to the portion of the blood flow circuit that leads blood away from the hemodialysis machine 200 toward the patient. The term “access needle” is used to refer to a needle or catheter device that penetrates the patient’s vascular segment or fistula. In various embodiments, it may be permanently fused to or reversibly connected to the corresponding catheter tubing 104, 130.

[0155] The continuity of any segment of the fluid flow circuit 100 can be monitored by positioning two electrodes in contact with the fluid on both sides of the fluid and blood-containing segment in question. To monitor for breaks in the arterial access needle 102 or arterial catheter tubing 104 or venous access needle 132 or venous catheter tubing 130, one electrode can be positioned in conjunction with the venous lumen of the blood flow circuit, and a second electrode can be positioned in conjunction with the arterial lumen of the blood flow circuit. In one embodiment, the two electrodes can be positioned in or near the dialyzer 200, with one electrode in contact with blood upstream of the blood pump 110 and the second electrode in contact with blood downstream of the dialyzer 14 and / or air trap 122. For example, the electrodes can be incorporated into transition positions 110 and 124.

[0156] In another embodiment, one of the electrodes can be positioned to contact the fluid in the fluid flow circuit 100 at a point closer to the vascular access site 134 than the equipment used to deliver the fluid flow to the accessed blood vessel or vascular graft (e.g., a dialysis machine). In a preferred embodiment, both electrodes can be positioned closer to the patient's blood vessel or vascular graft than the equipment associated with the dialysis machine 200. This can further reduce electrical interference associated with the dialysis machine 200. Electrode A can be conveniently positioned at or near the arterial catheter piping connector 106, and the second electrode B can be conveniently positioned at or near the venous catheter piping connector 128. In this configuration, the electrical conduction path from the first electrode through the patient's vascular access to the second electrode is much shorter, i.e., has lower electrical resistance, than the path extending back towards the dialysis machine 200. In one embodiment, the access catheters 104 and 130 can be shortened to about 1 foot, and the arterial piping 108 and venous piping 126 can be about 6 feet long. Due to the conductive properties of the fluids in the circuit, the electrical resistance associated with the pathways incorporating pipes 108 and 126 and the components of the dialysis machine 200 can be many times greater than the electrical resistance associated with the pathways passing through the patient's blood vessels or fistula 134.

[0157] Therefore, electrical interference associated with the dialysis machine 200 is reduced, and changes in electrical resistance due to access-related disconnections can be more easily detected. Preferably, electrodes A and B are positioned so as to be more than 50% of the distance from the dialysis machine to the patient. More preferably (and more conveniently), electrodes A and B are positioned near the last separable fluid connection before reaching the patient. In one embodiment of the hemodialysis system, blood tubing 108 and 126 are approximately 6 feet long, and arterial catheter tubing 104 and venous catheter tubing 130 are approximately 2 feet or less in length. A convenient position for electrodes A and B is then at the arterial line connector 106 and venous line connector 128 (which may be, for example, Luer connectors or a variation thereof) that connect the arterial blood circuit tubing 108 and venous blood circuit tubing 126 to the arterial catheter tubing 104 and venous catheter tubing 130.

[0158] Connector electrodes As shown in Figures 41A and 41B, in one embodiment, a blood line connector for a blood circuit in a hemodialysis system may incorporate an electrode that can come into contact with the fluid in the lumen of the connector. In one embodiment, the electrode may comprise an annular conductive cap 310 positioned on the tubular connection or proximal end 302 of any suitable connector, such as connector 300. The electrode is preferably made of a durable and corrosion-resistant material, such as stainless steel. The distal connecting end 304 of connector 300 may be configured to seal-engage with, for example, a corresponding Luer connector of an arterial or venous catheter. The inner annular surface 312 of the cap 310 can come into contact with the fluid present in the lumen 314 of the connector (partially or entirely). As shown in Figure 41B, an O-ring 316 or a suitable seal can be placed between the cap electrode 310 and the proximal end 302 of the connector to maintain a fluid-seal connection between the connector and any flexible tube fitted to the connector.

[0159] Elastomer O-rings may be particularly useful in hemodialysis systems or other extracorporeal systems where blood-carrying components are disinfected or sterilized using a heated fluid. The thermal expansion coefficient of the plastic components of the connector may differ significantly from that of the incorporated metal electrodes, which may prevent a permanent seal from being maintained after one or more sterilization or disinfection procedures. By adding an elastomer component, such as an O-ring, to the joint between the electrode and the connector seat where the electrode is placed, the seal can be maintained by accommodating the different expansion and contraction rates between the electrode and the connector.

[0160] As shown in Figure 42, in one embodiment, a conductive electrode 310 (made of, for example, stainless steel) can be incorporated into a portion of the connector 300 (either at its proximal end 302 or its distal connecting end 304), and the end of a flexible tube 318 can be positioned on that portion of the connector 300. In this embodiment, the electrode 310 is generally cylindrical and has a tapered portion 320 at its proximal end to allow for easier sliding mating of the end of the segment of the flexible tube 318 onto the outer surface of the electrode 310. As shown in Figure 42, the inner surface of the electrode 310 has an internal shelf projection 322, thereby allowing the electrode cap 310 to slide over and contact the proximal end 302 of the connector 300. The connector 300 can be made of any suitable rigid material, including metal or, more typically, plastic material. The shelf-like projection 322 helps ensure that the inner surface 312 of the electrode 310, which has a smaller diameter, is properly positioned to come into contact with the fluid (e.g., blood) passing through the lumen 314 of the connector 300. The connection between the connector 300 and the electrode 310, and the connection between the electrode 310 and the end of the overlaid flexible tube 318, can be made airtight or permanent using any suitable adhesive that is compatible with the composition of the components.

[0161] To ensure a more secure seal to prevent blood leakage between the connector and the electrode, and to limit the area below the electrode where blood components may migrate and remain, an O-ring 316 can be incorporated near the electrode internal shelf projection 320 on the inner surface of the electrode 310. This is shown in enlarged detail in Figure 42. In this example, the O-ring 316 seals between the stainless steel electrode 310 and the distal end 302 of the connector 300. To hold the extended end of the flexible tube 318 over the proximal end 302 of the connector 300, a puncture element 324 on the proximal end 302 of the connector 300 can be incorporated into the connector design. In one embodiment, the electrode 310 is held in place by the portion of the flexible tube extending over both the electrode 310 and the puncture 324 of the connector 300.

[0162] A wire 326 can be soldered, welded, or otherwise secured to the outer surface of the electrode 310, and the wire 326 can travel under the overlapping extension pipe 318 until it emerges more distally along the connector 300. Thus, the wire can transmit electrical signals to and from the electrode 310 as the inner surface 312 comes into contact with the intraluminal fluid (e.g., blood). In the illustrated example, the wire 326 is soldered to the distal portion of the electrode 310, travels under the pipe 318, and emerges at the point where the pipe 318 abuts against the corresponding stopper 326 of the connector 300.

[0163] In another embodiment, as shown in Figures 43A to 43C, the connector 400, as described in U.S. Patent Application Publication No. 2010 / 0056975 (the contents of which are incorporated herein by reference), is modified so that the central portion 406 of the connector 400 can accommodate electrodes. By positioning the electrodes along the central portion 406 of the connector 400, it is not necessary to modify the distal connecting end 404 of the connector, and there is no change in the interaction between the end of the flexible tube and the proximal end 402 of the connector. In this example, the blood line connector 400 is configured to have two different types of sealing connections at its distal connecting end 404, including a female threaded connector 405 for a Luer connector of a patient access line and an external press-fit connector 407 for a dialyzer port for recirculation of priming and disinfecting fluids through the blood carrying components of the dialysis system. The press-fit mechanism 407 is formed in a frustoconical shape on the outer surface of the distal end 404 of the connector 400, and the Luer-fit screw mechanism 405 is formed on the corresponding inner surface of the distal end 404 of the connector 400. The outer surface of the frustoconical member is configured to seal-engage with the seat of the mating connector of the dialyzer 200 or other device. A pair of locking arms 408 extending proximal from the distal connecting end 404 of the connector 400 may each have a barbed portion 409 that engages with the corresponding locking mechanism of the mating connector of the dialyzer, and a finger recess 410 that assists in removing the barbed portion 409 from the dialyzer. The barbed portion 409 helps to lock the frustoconical member that seal-engages with its mating connector of the dialyzer when making a press-fit connection. The distal ends of the locking arms may be configured to attach to the connector through a flange 411 located proximal to the frustoconical portion 407 of the connector 400. The connector 400 has a proximal pipe mounting end 402 that engages with the flexible tube. The pipe mounting end 402 may have one or more piercing mechanisms 412 that help prevent the end of the flexible tube from detaching from the connector 400.

[0164] Figure 43B shows a side view of the connector 400, revealing an access mechanism or port 420 that can allow for the placement of electrodes in direct communication with the lumen of the connector 400. In other embodiments, the access mechanism may house an elastomer stopper (with or without a diaphragm) to allow for the sampling of fluid from within the lumen 414 of the connector 400 using a syringe equipped with a sharp or blunt needle. Alternatively, the mechanism may serve as a port that allows for the connection of another fluid line to the lumen 414 of the connector 400.

[0165] In yet another embodiment, as shown in the cross-sectional view of Figure 43C, the intermediate portion 406 of the connector 400 may have two access ports. The fluid access port 420a may serve as a sampling port, and the electrode port 420b may serve as an electrode cradle. The elastomer stopper 422 within the sampling port 420a may be shaped to extend into the lumen 414 of the connector 400, allowing simultaneous sampling of the fluid in the lumen 414 by a needle while maintaining an airtight seal. Alternatively, a Luer connector with a diaphragm cap or seal may be incorporated into the port, and the port may be connected to a syringe or catheter having a mating Luer connector. The electrode port 420b may serve as a seat or cradle for an electrode 424. It may be press-fitted or cemented and sealed with adhesive or with an O-ring 416 as shown. The wire 426 can be soldered, welded, or otherwise secured to the outer surface of the electrode 424, and the wire 426 can advance proximal toward the dialysis machine 200 via an arterial tubing 108 or venous tubing 126 to which the connector 400 is attached.

[0166] In any of the above electrode embodiments, the electrodes can be replaced with appropriately sized thermistors or a combination of thermistors and conductors for the further purpose of measuring the temperature of the fluid passing through the connectors 300, 400 or their deformations.

[0167] Wire Assembly In one embodiment, a wire carrying electrical signals to or from a pair of electrodes on connectors 106, 128 (one on the arterial side of the blood flow circuit and the other on the venous side) can separately travel away from blood tubing 108, 126 and back toward the dialysis machine 200, where it finally terminates and connects to a conductivity detection circuit, such as the conductivity circuit shown in Figure 37. The conductivity circuit then provides a appropriately configured signal to the dialysis machine's processor to determine whether a change in fluid conductivity consistent with access disconnection has occurred. If a change in fluid conductivity occurs, the processor can trigger an alarm state or initiate a shutdown of the blood pump 13, for example, triggering a mechanical closure of blood tubing 108 and / or 126.

[0168] Wires extending together or separately between the dialysis machine and the patient are at risk of entanglement, breakage, or severance. Therefore, preferably, each wire 326 or 426 can be fitted, fused, or otherwise incorporated into its associated piping 108, 128. Integrating the wires into their associated piping provides a convenient method for protecting the wires and connections and simplifying the interface between the patient and the dialysis machine. Exemplary methods for achieving this are shown in Figures 44A-44D. In preferred embodiments, the piping is composed of a flexible material (e.g., silicone) that can be formed by extrusion. As shown in Figure 44A, a coarse wire mesh can be embedded in the flexible silicone piping as it is formed and extruded, similar to fiber reinforcement of flexible tubing. As shown in Figure 41A, a wire mesh 500 can be embedded within the wall of the flexible tubing 502 during extrusion, similar to the configuration of fiber-reinforced tubing. As shown in Figure 44B, insulating wires 504 can be bonded to the outer surface of adjacent pipes 506 during a secondary extrusion process or during a process in which two structures are joined, for example, with an adhesive. As shown in Figure 44C, a secondary extrusion can be performed to produce a secondary coaxial layer of pipe material 508, thereby capturing wires that extend along the outer surface of the pipe after primary extrusion. As shown in Figure 44D, pipe 502 being molded can also be co-extruded with wires 504 embedded in the pipe walls.

[0169] In some of the above methods, the resulting tube-wire combination may be prone to twisting due to the different coefficients of thermal expansion between the wire and the silicone material of the piping. As the material cools after extrusion, the silicone may tightly trap the embedded wire, causing the cooled tube-wire bundle to twist. In a preferred embodiment, the wire lumen of the extrusion die is configured to be large enough to accommodate a cross-sectional area significantly larger than the cross-sectional area of ​​the embedded wire. Then, as the silicone cools, the passage surrounding the wire does not shrink to the extent that it tightly encloses the wire. Co-extrusion processes incorporating insulated wires can produce tube-wire bundles as shown in Figure 45. In this example, the flexible tube 502 is a co-extruded product of a fluid-carrying lumen 601 and a wire-carrying lumen 602. Preferably, the wire 501 is multi-stranded for flexibility and durability and is coated or covered with a durable flexible synthetic insulating material 503 such as PTFE. The PTFE sheath 503 of the stranded wire 501 can withstand the high temperatures associated with the silicone piping extrusion process, thereby maintaining its integrity along the portion of the wire 504 that ultimately exits the piping for connection to either the dialysis machine 200 or the patient line connectors 106, 128. The coating or covering can also help prevent the wire from adhering to the sidewalls of the wire transport lumen after extrusion and during cooling. In another embodiment, the sheath 503 may be omitted, leaving the wire 301 exposed inside the wire transport lumen 602. Figure 46 shows a cross-sectional view of an exemplary connector-wire-piping assembly. The proximal piping connection end of the connector 400 is shown, with the end of the double-lumen piping 502 fitted. The fluid transport lumen 601 is press-fitted and / or cement-bonded to the proximal end of the connector 400, allowing fluid flow through the central lumen 414 of the connector 400. The stranded wire 501 is soldered to or otherwise attached to the electrode 424, which makes conductive contact with the fluid present in the lumen 414 of the connector 400. The unconnected portion of the wire 501 that passes outside the pipe 502 is preferably covered with an insulating synthetic coating such as PTFE.Optionally, this portion of both the exposed and coated wires may be sealed with a sealant such as RTV. The coated wire 503 enters the wire-carrying lumen 602 of the piping 502 near its termination to the connector 400. The wire / piping bundle then proceeds toward the dialyzer 200, where the wire emerges from the piping to connect to a conductivity circuit as shown in Figure 37.

[0170] Figure 47 shows an exemplary extracorporeal circuit 210 that can be used as a detachable and replaceable unit in a hemodialysis machine 220 as shown in Figure 48. In this embodiment, the extracorporeal circuit comprises a blood pump cassette 13, a dialyzer 14, a venous return air trap 122, an arterial blood tubing 108, a venous blood tubing 126, an arterial catheter connector 106, and a venous catheter connector 128. The arterial connector 106 and the venous connector 128 may be of the same type as the connector 300 shown in Figures 41A and 41B, or of the same type as the connector 400 shown in Figures 43A to 43C, or a variation thereof. The arterial blood tubing 108 and the venous blood tubing 126 may be of the type shown in Figures 44A to 44D or Figure 45. The wires forming terminal connections to the electrodes of connectors 106 and 128 emerge from arterial tubing 108 and venous tubing 126 as segments 504A and 504B and connect to the connectors, which ultimately pass their connections to terminals associated with conductivity circuits in a dialysis machine, as shown in Figure 37. In the illustrated embodiment, connector 526 is mounted on a support structure 214 for blood pump 13 and air trap 122. Segments 504A and 504B shown in Figure 47 may be insulated. In another example, segments 504A and 504B are exposed but may be covered by a shield 1004 (Figure 20A) connected to a bottom plate 1001 (Figure 20A). The arrangement of the wires 501 within the arterial and venous tubing 108 and 126, and the relative position of arterial tubing 108 with respect to venous tubing 126, can generate capacitive conductance between the wires 501 within each tube 108 and 126. This capacitive conductance acts as an additional conductive path between terminal VTA and VTB3 (Figure 37) and functions in parallel with the purely resistive impedance through the blood column of catheter tubes 104, 130 and fenestration 134 (Figure 40). The capacitive conductance between wire 501 in arterial tube 108 and venous tube 126 varies with the distance between the tubes.Vsense measurements performed with a circuit similar to that shown in Figure 37 can be made insensitive to the positions of arterial tube 108 and venous tube 126 by selecting frequencies of binary voltage signals 131, 144 low enough to saturate the capacitance between wires 501 in arterial tube 108 and venous tube 126. In an exemplary embodiment, the binary voltage signals are operated with a frequency of approximately 2174 Hz and a 50% duty cycle, respectively, during a periodic active phase. The active phase can be set to occur every 80 milliseconds.

[0171] Figure 48 shows an exemplary hemodialysis machine 220 configured to receive the extracorporeal circuit 210 shown in Figure 47. In this example, the dialyzer 14 is already mounted on the machine 220. The base 227 receives the control port of the mating blood pump cassette 13. A set of raceways or tracks 225 helps to organize pairs of arterial blood tubes 108 and venous blood tubes 126 when they are not extended and connected to the patient. Connector 224 receives the connection formed between wire segments 504A and 504B and connector 526 and passes it to the terminal connection of the conductivity circuit as shown in Figure 1. The piping closure 226 is positioned to receive the venous blood tube 126 after it leaves the air trap 122 and the arterial blood tube 108 after it reaches the blood pump cassette 13. The closure 226 can be activated pneumatically or electromechanically whenever an alarm condition occurs that requires the cessation of extracorporeal blood flow, for example. The set of arms of the closure unit 226 can be configured to rotate relative to the wall of the flexible tube, thereby restricting or stopping the fluid flow within it. Thus, a controller installed within the device 220 can receive signals from a conductivity circuit similar to that in Figure 37, which represent the electrical resistance of the fluid or blood column between electrodes installed in connectors 106 and 128. Because the connectors are positioned much closer fluidly to the patient's blood vessel or fistula 134 than the blood pump 13, dialyzer 14, and air trap 122, the signals related to the fluid path through the blood vessel or fistula 134 can distinguish between an intact column and an interrupted column of blood or fluid between connectors 106 / 128 and the patient's blood vessel or fistula 134. The controller can be programmed to respond to electrical resistance detected by the conductivity circuit when it is found to exceed a predetermined value. Depending on the environment, the controller can then trigger an alarm to warn the patient of a possible interruption of blood flow, and optionally, it can also command the closure unit 226 to stop extracorporeal flow to and from the patient.

[0172] Operation of the disconnection detection circuit Figure 49 shows the test results using the cut detection circuit described above and shown in Figure 37. In this case, a hemodialysis blood circuit and apparatus similar to those disclosed in U.S. Patent Application Publication No. 2009 / 0114582 and U.S. Patent Application Publication No. 2010 / 0056975 (the contents of which are incorporated herein by reference) were used. The extracorporeal circuit 210 shown in Figure 47 comprises a blood pump 13, a dialyzer 14, an air trap 122, venous blood circuit piping 126, and arterial blood circuit piping 108. The extracorporeal circuit 210 is fitted into a hemodialysis apparatus 220 similar to that shown in Figure 48. The blood flow circuit under test comprised a pair of membrane-based blood pumps arranged in a blood pump cassette 13 as shown in Figure 47, a dialyzer 14, a venous return air trap 122, an arterial blood piping set 108, a venous blood piping set 126, arterial connectors 106 and venous connectors 128, and catheter piping sets 104 and 130 connected to vascular access needles 102 and 132 as shown in Figure 40. The needles 102 and 132 were placed in containers holding anticoagulated bovine blood. The blood piping sets 108 and 126 were approximately 6 feet long, and the catheter piping sets 104 and 130 were approximately 2 feet or less long. The needles were alternately placed in or withdrawn from the containers in the blood flow to simulate needle severance from the wax or blood vessel. Periods A, C, and F in Figure 49 represent the time the needles were immersed in the blood in the containers. During these periods, the electrical resistance measured by the disconnection detection circuit shown in Figure 37 averaged between 120,000 ohms and 130,000 ohms. Periods B and E in Figure 49 represent the time when the venous return needle 132 (under positive pressure from the blood pump) is withdrawn from a few centimeters above the surface of the blood in the container, forming a blood flow mixed with air as the blood exits the venous return needle and enters the blood container below. The electrical resistance measured during these periods averaged between 140,000 ohms and 150,000 ohms. Period D represents the time when one of the needles is completely removed from the container, creating a completely open electrical circuit. The electrical resistance measured during this period averaged between approximately 160,000 ohms and 180,000 ohms.Therefore, the controller can be easily programmed to identify the difference in the monitored resistance of the electrical circuit between an uninterrupted flow of blood and an interrupted flow. These results show that an interruption in the continuity of blood between the arterial needle 102 and the venous needle 132 can reliably result in a detectable change in measured electrical resistance between the two electrodes when they are positioned relatively close to the arterial and venous access sites than the blood processing components 13, 14, and 122 of the external blood circuit. Furthermore, even a partial interruption in the continuity of blood flow (like blood flowing through air) can be reliably detected, even if the change in measured electrical resistance is slight.

[0173] ADS algorithm The operation of the access disconnection sensor (ADS) can be further understood by referring to Figures 40 and 48. A controller installed within the hemodialysis machine 220 (Figure 48) can control the position of the closure 226 and the operation of the blood pump through the base unit 227 to minimize blood loss when access disconnection is detected. Referring here to Figure 40, access disconnection or needle detachment is considered to occur when either the venous needle 132 or the arterial needle 102 is removed from the vascular access site, or either is partially dislodged from the vascular access site, or either is causing an obstruction to or from the fluid flow to or from the vascular access site. More generally, the use of the term “access disconnect” is understood to include any state in which the electrical impedance or conductivity between two electrodes in the fluid path from a first catheter (or cannula) through the vessel or fistula containing the vascular access to a second catheter (or cannula) is altered by the detection algorithm described below. The vascular access site refers to a vein, fistula, or shunt 134, at which point a needle 102, 132, or catheter from the dialysis machine 200 enters the body to access the patient's blood. Removal of either the venous or arterial needle 102, 132 from the vascular access site may result from a number of actions, including but not limited to loosening of the tape applied to cover the needle 102, 132, or the piping proximal to the needle, inadvertently pulling on the line 104, 108, 126, or 130 during movement of the patient's body or limbs, or actions by the patient to remove the needle 102, 132, or catheter from the vascular access site.

[0174] The controller can detect access disconnection based on one or more inputs, including but not limited to signals from a conductivity circuit similar to that shown in Figure 37, pressure information from one or more sensors monitoring the operation of the blood pump, or the commanded position of the blood pump valve and the pump operation commanded by the controller. A conductivity circuit similar to that shown in Figure 37, with data output signals from a conductivity circuit connected to the patient as described above, can be referred to as an Access Disconnect Sensor signal or ADS signal. In one embodiment, the ADS signal is the electrical impedance between probes in connectors 106, 128 shown in Figure 40. In another embodiment, the ADS signal is the filtered value of the data output signal in Figure 37, or the measured electrical impedance between probes in connectors 106, 128 in Figure 40. Other electrical quantities can be calculated from the measured electrical impedance or ADS signal, including, but not limited to, filtered values ​​of impedance at various time constants; time derivative of impedance; mean value, peak value, peak value on the data movement window, minimum value on the data movement window, or mean value on the data movement window.

[0175] Referring again to Figure 40, in one embodiment, upon detecting needle detachment or access disconnection, the controller commands a freeze state, stops the blood pump blood 13, and / or closes the closure 226 to notify the patient. In the case of access disconnection, the controller notifies the patient or user to check the status and / or position of needles 102 and 132. Once this is done, the patient may be given the option to resume or discontinue treatment. After confirming that the needles are properly positioned, the patient may resume treatment. If the patient chooses to resume treatment, the controller opens the closure 226 and restarts the blood pump 13 and other components of the hemodialysis machine 220 as necessary to resume treatment. If the patient chooses to terminate treatment without re-establishing vascular access, the controller instructs the patient to remove the device, and the controller will initiate the termination of the treatment procedure without returning the blood in the extracorporeal circuit 100 to the patient. In one embodiment, the controller may communicate with the patient via a control interface 55 (Figure 7).

[0176] In one example, the controller executes a software subroutine or function referred to herein as the ADS algorithm, which identifies access disconnection based on the ADS signal and other inputs generated by other sensors or other software components within the controller. Upon receiving an access disconnection signal from the ADS algorithm, the controller will control the blood pump, closure and / or control interface to minimize blood loss and allow the patient to select the next action for the hemodialysis machine 200. In another embodiment, a separate machine-level controller may track and / or filter the ADS signal, set signal thresholds, timing or pump stroke counters, flags or trigger events, and, if necessary, forward one or more trigger signals to higher-level controllers (e.g., a treatment controller and / or a user interface controller) to initiate stopping pump operation, closing blood lines, user notifications, or user commands.

[0177] As described above, an access disconnection will interrupt the conductive path between probes and generate a high ADS signal. The ADS algorithm preferably identifies an access disconnection based on the ADS signal and ignores other high ADS signals resulting from various non-dropout events. Referring here to Figure 40, non-dropout events include, but are not limited to, an air bubble in any of the needle lines 104, 130, a twisted, pinched, or closed needle line 104, 130, compression of a vein between two needles 102, 132, or electrical grounding of the patient. The ADS algorithm can distinguish between false ADS signals and those that are likely to represent an access disconnection via one or more software subroutines, functions, or classes that process the ADS signals and other information received from the controller. A higher-order function within the controller software can then control the blood pump, closure and / or control interface to minimize blood loss and allow the patient to select the next operation of the hemodialysis machine 200.

[0178] The ADS algorithm is preferably independent of various physical conditions that can alter the ADS signal, including but not limited to changes in hematocrit levels during treatment, daily and patient-to-patient changes in hematocrit levels, differences in venous, fistula, or access due to differences in patient characteristics or the type of needle used. The ADS algorithm is preferably able to reject false needle detachment signals resulting from such changes. The ADS algorithm can detect needle detachment and distinguish other events that cause a high ADS signal using one or more multi-stage methods. One embodiment of the ADS algorithm includes a first step in which a first value derived from measured electrical impedance between a probe on a venous line and a probe on an arterial line is recognized as potentially indicating needle detachment, triggering the start of a counter. In a second step, a second value derived from the measured impedance is monitored as the counter is incremented. If the second derived value falls below a second threshold, the counter is stopped. In the third step, if the counter reaches the third threshold and the second derived value remains above the second threshold, a needle drop or access disconnection is declared.

[0179] In an alternative embodiment, the multi-stage ADS algorithm may include the following steps: In the first step, the possibility of needle breakage is recognized based on a first value derived from the measured electrical impedance between a probe on a venous line and a probe on an arterial line. If the first value exceeds or crosses a first threshold, a counter is started. In the second step, a second value derived from the measured impedance is monitored as the counter is incremented. If the second derived value falls below or crosses a second threshold, the counter is stopped. In the third step, if the counter reaches a third threshold and the second derived value does not cross the second threshold, a closure is declared and the blood line is closed. In the fourth step, if the third value derived from the measured electrical impedance crosses a fourth predetermined threshold, the closure declaration is replaced with a needle detachment declaration.

[0180] In an alternative embodiment, the multi-stage ADS algorithm may include the following steps: In the first step, the possibility of needle detachment is recognized based on a first value derived from the measured electrical impedance between a probe on a venous line and a probe on an arterial line, which exceeds or crosses a first threshold. In the second step, a second value derived from the measured impedance is monitored as the counter is incremented. If the second derived value falls below or crosses a second threshold, the counter is stopped. In the third step, if the second value crosses a second threshold, the blood pump is paused and all valves are closed except the outlet valve from the pump chamber delivering blood. The pump chamber is fully delivered, and the delivery pressure is then reduced to approximately atmospheric pressure. In the fourth step, needle detachment or access detachment is declared if a third value derived from the measured electrical impedance between a probe on a venous line and a probe on an arterial line exceeds or crosses a third threshold related to the first threshold.

[0181] The ADS algorithm can be implemented in several ways. Embodiments are described with reference to the test data plotted in Figures 62 to 64. In these tests, intravenous and arterial needles were placed in a common bovine blood beaker, and a simulated dialysis treatment was initiated. Figure 62 plots the results of a test in which the intravenous line was closed for several seconds and then left open, temporarily increasing the ADS signal level. Figure 63 plots the results of a test in which the needle was cut, simulating the removal of the intravenous line from the beaker. Figure 62 shows plots of ADS-related signals, blood pump pressure, and software flags that may be part of the calculations in the ADS algorithm. The top of the plot in Figure 62 plots the ADS signal and several derived signals along with the thresholds used in the ADS algorithm. The signals are plotted in k-ohm resistance units. The state of one or more software flags is graphically represented at the bottom of the plot in Figure 62. Software flags are binary or Boolean values ​​stored in memory, and can be either off or on, represented as equal to 0 or 1, respectively. The blood pumping pressure (mmHg) is located between the software flag plot and the ADS derivation signal in Figure 62. In this example, two blood pumps alternately draw blood from arterial lines by applying negative pressure and deliver blood to venous lines by applying positive pressure. The pressure of the first blood pump is plotted as a thick line 1232 in mmHg units. The pressure of the second blood pump is plotted as a thin line 1234 in mmHg units. The nearly vertical lines represent the end of the stroke for each blood pump pod. The ADS signal, pumping pressure, and flags are plotted against the index of the measured values. In the plotted example, the index is updated at 20 Hz, so the horizontal axis values ​​can be converted to seconds in units of time by dividing the value by 20.

[0182] In Figure 62, the ADS signal 1210 rapidly increases from approximately 135 kΩ to approximately 180 kΩ in time element 1236. The ADS signal 1210 returns to approximately 130 in time element 1238.

[0183] In one embodiment, the ADS algorithm starts a counter when the ADS signal 1210 crosses a first predetermined threshold 1211 and continues to increment the counter until the ADS signal crosses a second predetermined threshold 1213. When the counter reaches a predetermined value, the ADS algorithm declares access disconnection. The counter may be reset to zero when the ADS signal crosses the second threshold 1213 or when access disconnection is declared. In one example, the counter is incremented by time, and the ADS algorithm declares access disconnection when the counter exceeds a predetermined amount of time. In another example, the counter is incremented by blood volume, and the ADS algorithm declares access disconnection when the counter exceeds a predetermined amount of blood volume. In yet another example, the counter is incremented by blood pump strokes, and the ADS algorithm declares access disconnection when the counter exceeds a predetermined number of blood pump strokes. For example, the ADS controller declares needle detachment if the ADS signal exceeds 180 kΩ and remains above 175 kΩ during multiple blood pumping strokes, or, for example, after three or more blood pumping strokes have been completed.

[0184] Figure 62 shows an example of a high ADS event that does not trigger an access disconnection signal. In Figure 62, the operation of the blood pump is indicated by pump pressures 1232 and 1234. In time element 1236, one blood pump stroke is completed and a second blood pump stroke is started after the ADS signal 1210 exceeds a first threshold 1211, but in time element 1238, it is not completed before the ADS signal 1210 falls below a second predetermined threshold 1213.

[0185] An example of a high ADS event that triggers an access disconnection signal is shown in Figure 63. In Figure 63, the ADS signal exceeds a first threshold 1211 at time element 1236. Three blood pump strokes are completed by time element 1239 by both pumps, combined as evidenced by pump pressures 1232, 1234, at which point the access disconnection signal 1220 is triggered by the ADS algorithm. When the access disconnection signal is triggered, the controller sets the “frozen” flag 1225 and enters a frozen state, during which the blood pump is stopped and the closure is closed (i.e., the fluid line is closed). (As described above, these functions may be performed by a single physical controller using multiple software-based subroutines, or by two or more physical controllers interacting to coordinate functions triggered by flags or counters.) The closure can be closed immediately, and the controller may record the percentage stroke completion time so that the blood pump can resume the current stroke when pump operation is resumed. At time element 1245, the user commands the resumption of treatment plotted as 1230, which commands the controller to open the closure and restart the blood pump.

[0186] In one embodiment, the ADS algorithm may include the step of programming the controller to ignore the ADS signal while the “freeze” flag is set and when the blood pump is not moving blood or other fluid through the venous or arterial line.

[0187] In another embodiment, the ADS algorithm sets a provisional disconnection flag based on the ADS signal, starts a counter, and declares access disconnection if the provisional flag is not cleared before the counter reaches a predetermined value. As described above, in one example the counter can increment time, and the predetermined value is the duration of time. In another example the counter measures blood flow, and the predetermined value is the volume of blood pumped. In yet another example the counter increments blood pump strokes, and the predetermined value is the number of blood pump strokes. In one example the ADS algorithm sets a provisional flag if the ADS signal exceeds a first predetermined threshold. In an exemplary embodiment, the first threshold is set to approximately 180 kΩ. The ADS algorithm will remove or clear the provisional flag if the ADS signal falls below a second threshold. For example, the second threshold may be set to approximately 175 kΩ. In an exemplary embodiment, the ADS algorithm declares a disconnection of access to a higher software level within the system or system controller if the provisional flag is set for a period of three or more blood pump strokes (although the number of pump stroke thresholds can be set to a different number if desired).

[0188] An example of an embodiment including a provisional flag that responds to high ADS signal events that are not access disconnections is plotted in Figure 62. The provisional flag 1218 is set in time element 1236 when the ADS signal 1210 exceeds a first threshold 1211 in time element 1236. In time element 1238, the provisional flag 1218 is cleared when the ADS signal 1218 falls below a second threshold 1213. Access disconnections are not notified by the ADS algorithm in Figure 2 because the provisional flag 1218 was cleared before three blood pump strokes were completed.

[0189] Applying this same embodiment, including the provisional flag, to an actual access disconnection yields the plot shown in Figure 63. In time element 1236, the provisional flag is set when the ADS signal 1210 exceeds the first threshold 1211. The ADS signal 1210 remains above the second threshold 1213, and the provisional flag 1218 remains set for the duration of the three completed strokes by the combined pumps, as plotted by the blood pump pressures 1232, 1234. At the completion of the third stroke in time element 1239, the ADS algorithm signals an access disconnection and sets the disconnection flag 1220. Upon receiving the access disconnection signal, the control unit enters a frozen state by setting the "freeze" flag 1225, during which time the blood pump is stopped and the closure is closed. The closure is closed, immediately stopping the pump or allowing the current stroke to be completed because the drawout from the arterial line is in a starting position for restarting the pump. At time element 1245, the user commands a restart plotted as 1230, which commands the controller to open the closure and restart the blood pump.

[0190] In another embodiment, the ADS algorithm sets a provisional flag if the ADS signal shows a sharp increase as expected in the event of an access disconnection, and clears the provisional flag if the ADS signal falls below a value calculated from the ADS signal while the provisional flag is set. In one example, the ADS algorithm sets a provisional flag if the time derivative of the ADS signal exceeds a first predetermined value. In this example, if the provisional flag is set as ADS-entry, the ADS algorithm records the ADS signal. The provisional flag is cleared only when the ADS signal falls below ADS-exit, which is a predetermined function of ADS-entry. In a further example, the provisional flag may be cleared when the ADS signal drops below ADS-exit and the ADS derivative falls below a second predetermined value.

[0191] Unfiltered ADS signal data may not provide sufficient distinction between signal changes resulting from vascular access transection events and other events (e.g., signal noise, arm movement, variations in blood composition and conductivity, signal drift during treatment, or small occlusions occurring at the catheter or fistula site). The baseline signal may also be modified patient-to-patient, dependent on the anatomical structure or quality of the fistula or graft, or based on its location on the body. Preferably, the access transection algorithm does not need to set individualization parameters based on a number of these variables. Simply filtering raw signal data may be insufficient to solve the problem of reliably and timely detection of transection events independently of patient-specific variables. One step to providing a more reliable detection algorithm may involve the use of provisional flags and timers to eliminate false declarations of transection events due to transient "noise" events. To address the impact of longer-term variables on the algorithm, it may be useful to compare signal data with its filtered counterpart. In one embodiment, the difference between the raw signal and its filtered counterpart is taken, and the filtering is sufficient to isolate existing bias or drift over time in the baseline signal. Alternatively, a loosely filtered signal can be compared to a more heavily filtered version of the same signal, which is the difference between a signal filtered with a first time constant and a signal filtered with a second, longer time constant. If there is a difference between the two values, a threshold impedance can be set for which a trigger event can be declared. The threshold impedance value may be programmed to change proportionally to the change in the value of the more heavily filtered version of the signal. A ratio between the two values ​​can be taken to set a threshold ratio for which a trigger event is declared.

[0192] Referring again to Figures 62 and 63, in another embodiment (shown as an embodiment of Delta ADS), the ADS algorithm compares two filtered values ​​of the ADS signal 1210 filtered with different time constants. In the Delta ADS embodiment, the controller looks for a sharp increase in the ADS signal compared to the long-term average value of the ADS signal by monitoring the difference between the ADS value filtered with a shorter time constant (lightly filtered) and the ADS value filtered with a longer time constant (more heavily filtered). In the Delta ADS embodiment, the controller evaluates a sharp increase in the ADS signal as an indication of a needle drop or access disconnection event. Embodiments of Delta ADS may not be very sensitive to differences in baseline impedance that vary from patient to patient, day to day, or during treatment. Baseline electrical impedance can vary from treatment method to treatment method for many reasons, including, but not limited to, different hematocrit levels, different vascular access locations, and different needles. Baseline electrical impedance can change during treatment due to changes in needle position, fluctuations in hematocrit levels, or various other causes. In embodiments of delta ADS, at least some of the thresholds are the difference between filtered values ​​(slowADS, medADS) such that changes in the absolute or baseline value of the ADS signal (e.g., due to signal drift or other factors) are less likely to trigger false positive detections. In another embodiment, the controller may take the ratio between two filtered values ​​and set a provisional flag based on a predetermined value in the ratio.

[0193] The delta-ADS embodiment of the ADS algorithm calculates a value -delta-ADS1216, which is the difference between a faster filtered (or lighter filtered) ADS (medADS)1212 and a slower filtered (or heavier filtered) ADS value (slowADS)1214. A provisional flag 1218 is set if the delta-ADS value 1216 is greater than a third predetermined threshold 1215 (the third predetermined threshold is adjustable upward or downward, for example, in proportion to the amount by which the slower filtered ADS value increases or decreases if there is signal drift). If the provisional flag is set as medADS-entry1212A and slowADS-entry1214A, the values ​​of medADS1212 and slowADS1214 may be recorded. The ADS-exit value 1217 can be calculated as a predetermined function of medADS-entry1212A and slowADS-entry1214A. The provisional flag is cleared when the medADS value 1212 falls below ADS-exit 1217. In one example, the provisional flag is cleared only if (1) the medADS value 1212 falls below ADS-exit 1217, and (2) the delta ADS 1216 is lower than a fourth predetermined value (not shown).

[0194] In some embodiments of the Delta ADS system, the slowADS and / or medADS values ​​may be reset by the controller after a specific pump event. The slowADS and medADS values ​​may be reset to improve detection and / or to reduce false positives of access disconnections in certain situations. In one example, to minimize false positives, the medADS value is set to equal the slowADS value whenever the blood pump resumes from a frozen state.

[0195] In another embodiment of the Delta ADS, when the blood pump resumes operation after a temporary disconnection, both the slowADS and MedADS values ​​are reset to the unfiltered ADS value. During the temporary disconnection, the user may temporarily disconnect the BTS lines 108, 126 (Figure 40) from the needle lines 104, 130 and connect the BTS lines 108, 126 to each other so that the blood pump 13 can flow blood through both BTS lines. The temporary disconnection ends after the user reconnects the needle lines 104, 130 to the BTS lines 108, 126.

[0196] In a further modification of the Delta ADS embodiment, the slowADS value can be reset to the medADS value while the blood pump 13 is operating in order to improve needle detachment detection. The first step of this embodiment is to detect the possibility of detachment if medADS is greater than slowADS by a predetermined amount as described above. In certain situations, the ADS signal drops rapidly, the ADAD value responds more slowly, and temporarily becomes greater than the medADS value. To maintain the ability to detect the possibility of needle detachment, the controller of the ADS algorithm resets the slowADS value to the medADS value if the slowADS value is greater than medADS by a predetermined amount. In certain conditions during treatment, the ADS signal may shift abruptly to a stable higher value. A rapid and sustained shift in the mean or baseline ADS signal can lead to repeated false detections of access disconnection. In one embodiment, the slowADS value can be reset to the medADS value when resuming treatment after a freeze state caused by repeated detection of access disconnection or closure. In one example, the slowADS value is reset to medADS when the user chooses to resume treatment after detecting an access disconnection or closure for the third time within the same treatment session.

[0197] In one example, if the user chooses to resume treatment after the third detection of closure within the same treatment session, the slowADS value is reset to the medADS value. In this example, the closure counter is incremented each time treatment is resumed after becoming frozen due to BTS or needle line closure. The closure counter is set to zero at the start of treatment and can be reset to zero if the controller under the ADS algorithm detects an access disconnection. Also, when the slowADS value is reset to the medADS value, the counter is also reset to zero.

[0198] Referring to Figures 62 and 63, in one implementation example, the medADS value 1212 is the first-order filtering value of the ADS signal 1210 with a time constant of 1 second. The slowADS value 1214 is the first-order filtering value of the ADS signal 1210 with a time constant of 20 seconds. The provisional flag is set when the delta ADS 1216 exceeds a third predetermined value of 16K ohms. For example, ADS-exit 1217 can be set to equal to 7 / 8*medADS-entry + 1 / 8*slowADS-entry. A fourth predetermined threshold for clearing the provisional flag can be set to 2K ohms.

[0199] An example of an embodiment including two filtered values ​​of the ADS signal in response to a high ADS signal event that is not an access disconnection is plotted in Figure 62. A provisional flag 1218 is set in the time element 1236 when the delta ADS 1216 exceeds a third threshold 1215, but before three full strokes occur as indicated by the pump pressures 1232, 1332, the medADS value 1212 falls below the ADS-exit value 1217.

[0200] Applying this same embodiment, which includes two filtered ADS values ​​and a provisional flag, to an actual access disconnection yields a plot as shown in Figure 63. The delta ADS 1216 exceeds the third threshold 1215 at time element 1236, and the provisional flag 1218 is set. The medADS value 1212 is maintained high by the completion of the next three blood pump strokes, as plotted by 1232, 1234. At the completion of the third stroke at time element 1239, the ADS algorithm signals an access disconnection and sets the disconnection flag 1220. Upon receiving the access disconnection signal, the controller sets the "freeze" flag 1225 and enters a frozen state, during which time the blood pump is stopped and the closure is closed. At time 1245, the user commands a restart, plotted as 1230, which commands the controller to open the closure and restart the blood pump.

[0201] In one embodiment, the ADS algorithm declares access disconnection if the ADS signal falls below a predetermined low threshold for a longer period than predetermined, or while more blood than predetermined is being pumped, or while more blood pump strokes than predetermined occur. In one example, a provisional flag is set when the ADS signal falls below a first low threshold and is cleared only when the ADS signal exceeds a second low threshold. If the provisional flag is set for a longer period than predetermined, or while more blood than predetermined is being pumped, or while more blood pump strokes than predetermined occur, the ADS algorithm declares access disconnection. In one example, the first low threshold may be set to 20 kΩ and the second low threshold to 25 kΩ.

[0202] In another embodiment, the ADS algorithm declares access disconnection if the ADS signal test fails. The ADS signal test includes monitoring the ADS signal while performing a pump delay operation. The pump delay operation includes completing the stroke of the delivery pump pod and then pausing both the blood pump pod and the internal dialysate circuit, closing all valves on the blood pump, preferably the valves between the internal dialysate circuit and the dialyzer, leaving the outlet valve of the delivery pump pod open, then completely delivering blood from the delivery pod by applying a first predetermined pressure for a first predetermined time, and finally reducing the pressure applied to the pump plunger or diaphragm to a second low pressure close to but greater than atmospheric pressure, and holding that second pressure for a second predetermined time. In one embodiment, the second pressure applied to the pump plunger or pump diaphragm of the pod pump is close to atmospheric pressure in order to apply nearly zero force to the fluid in the plunger and pump chamber. If the provisional flag is set, the ADS algorithm immediately notifies of access disconnection while applying a second pressure. The provisional flag can be set if the ADS signal meets any of the following conditions: an ADS signal exceeding the first threshold, the derivative of an ADS signal exceeding the second threshold, or a delta ADS signal exceeding the third threshold. The controller takes one or more actions on the ADS algorithm to notify of access disconnection, including but not limited to closing the closure, stopping the blood pump, or sending a signal to the user. The controller may also notify the user to check the needle placement, allowing the user to resume treatment if the needle is properly inserted.

[0203] In one embodiment, the ADS algorithm performs an ADS signal test only if a provisional flag is set and cleared without indicating access disconnection or closure. In this embodiment, the ADS algorithm uses an ADS signal test to identify needle detachment when a venous or arterial needle has been removed from a vascular access site but a conductive path has been re-established to another needle outside the vein or fistula of the vascular access site. In one experiment using arterial and venous needles in a simulated fistula, where a venous needle was withdrawn from the simulated fistula, the ADS signal initially rose, then returned to a lower value as blood flow from the detached venous needle came into contact with the arterial needle and a conductive path was re-established. The ADS signal test indicated that blood flow had stopped, resulting in a high ADS signal due to high resistance in the blood, which the ADS algorithm detected and indicated access disconnection. A similar algorithm can be used in an in vivo setting.

[0204] The ADS signal test can be used at any time to identify needle detachment based on other detected conditions (e.g., air inline detection) or via a pre-programmed periodic monitoring protocol during treatment. Events that create an electrical discontinuity between arterial and venous needles can be detected by the ADS signal test. For example, if a conductive path is re-established between a detached needle and its counterpart via an externally pooled collection of blood or other fluids, introducing a small air bubble to the distal end of either needle can create an electrical discontinuity sufficient for the controller to recognize that a vascular rupture has actually occurred. In a compliant blood circuit, the propulsive force of the blood column in the venous line may be sufficient to introduce a small air bubble to the tip of a detached needle. Such a bubble may enter the distal end of the needle, for example, during pump delay action.

[0205] Figure 64 shows an example of applying the ADS signal test after setting and clearing a provisional flag. In the test plotted in Figure 64, the intravenous and arterial needles are first placed in a first beaker of bovine blood to initiate a simulated dialysis treatment. The intravenous line is then removed from the first beaker and placed in a second beaker, ensuring that the intravenous needle does not come into contact with the blood pool at the bottom of the second beaker. Finally, a metal wire electrically connects the blood in the two beakers. When the intravenous needle is removed from the first beaker, the ADS signal temporarily rises. When the intravenous needle is placed in the second beaker, the blood flow from the intravenous needle, blood pool, and wire re-establishes an electrical connection back to the arterial needle, as long as the blood flows through the intravenous needle. Using the ADS signal test, the controller looks for a rise in the ADS signal to stop the blood flow through the intravenous needle and detect needle detachment.

[0206] The ADS signal rises sharply, setting a provisional flag 1218 at time element 1236. The provisional flag may be set by an ADS signal 1210 exceeding a first threshold 1211, or by a delta ADS 1216 exceeding a third predetermined threshold 1215. At time element 1238, the ADS signal 1210 falls, clearing the provisional flag 1218 based on the ADS signal 1210 falling below a second predetermined threshold 1213, or medADS 1212 falling below ADS-exit. The ADS signal test is initiated by applying high pressure 1232A to the blood pump pod that was delivering blood when the provisional flag 1218 was cleared at time element 1238. After a certain period of time, the pressure applied to the blood delivery pump pod was reduced to approximately atmospheric pressure 1232B at time 1243. Because the ADS signal 1210B exceeded the first threshold 1211 and the delta ADS 1216 exceeded the third threshold 1215, the provisional flag 1216 was reset and access disconnection 1220 was notified in time element 1243.

[0207] The ADS algorithm can combine some or all of the above thresholds to set a provisional flag and set corresponding tests to clear the flag. Similarly, access disconnection may be indicated for any of the above criteria. Referring here to Figure 63, in one embodiment, a provisional flag is set when any of the following conditions occur: namely, the ADS signal 1210 exceeds a first threshold 1212, the delta ADS 1216 exceeds a third threshold 1215, the ADS signal falls below a low threshold (not shown), or the derivative of the ADS signal exceeds a fifth predetermined threshold. The provisional flag may be cleared based on a condition corresponding to the condition that initially set the flag. For example, if the flag is set by an ADS signal exceeding a first threshold 1211, the flag is cleared only when the ADS signal falls below a second threshold 1213, or if the flag is set by a delta ADS 1216 exceeding a third threshold, the flag is cleared only when medADS 1212 falls below ADS-exit 1217 (see, for example, Figure 62). In another example, the flag may be cleared by requiring one or more of the above conditions. If the provisional flag is set continuously for a predetermined period, the ADS algorithm notifies a higher software level or the rest of the controller that the needle has detached while a certain amount of blood is being pumped or after several blood pump strokes have occurred.

[0208] The measured resistance values ​​reported in Figures 49, 62-64 were performed when the binary digital signals 131 and 144 in Figures 37 and 38 appeared alternately at a frequency of approximately 35 kHz. The frequencies of the digital signals 131 and 144 were high enough to allow capacitive coupling between the wires in the arterial and venous lines 108 and 126 (Figure 40). The parallel capacitance circuit reduced the resistance values ​​measured throughout the test, but the reduction was most significant under open-circuit conditions when the venous needle was removed from the first beaker.

[0209] In contrast, the measured resistances plotted in Figure 65 are from an experiment where the duration of the high half-cycle (Figure 38) is 16 times longer than the half-cycles in the experiments plotted in Figures 49, 62-64. In the experiment plotted in Figure 65, the duration of the half-cycle is approximately one-quarter of a millisecond. With respect to frequency, the binary control signals 131 and 144 alternate at a frequency of 2174 Hz during the active phase of the test plotted in Figure 65.

[0210] Referring here to Figure 38, in one example, signals 131 and 144 each contain pulses with a duration of 420 microseconds. The pulses are generated in sets of six pulses that repeat every 80,000 microseconds. Between sets of pulses, both signals 131 and 144 are low. The periods of low signal between pulses may limit the amount of current leakage reaching the patient.

[0211] The blood flow circuit tested included a pair of membrane-based blood pumps, a dialyzer, a venous return air trap, an arterial blood piping set, a venous blood piping set, a venous blood piping set, a venous blood piping set, an arterial and venous connector, arterial and venous connectors, a catheter piping set The period before 730 on the horizontal axis of Figure 65 represents the time the needle was submerged in the blood in the container.

[0212] Continuing to refer to Figure 65, the electrical resistance or ADS signal 1210 during these periods averaged 100 k ohms. At approximately 735 seconds, one of the needles was completely removed from the container, forming a fully open electrical circuit. The measured electrical resistance increased to approximately 670 k ohms. The controller set a provisional flag 1218 based on the large change in the ADS value 1210. The ADS value remained high during the next three pump strokes, and at approximately 748 seconds, needle detachment was declared, and the cut-off flag 1225 was set. The thick line 1232 plots one of the blood pump pod pressures in the range of (-)500 to 500 mmHg. Each transition between -500 and 500 mmHg represents one stroke of the blood pump. The blood pump operation is frozen when the cut-off flag 1225 is set and the closure 226 in Figure 40 is closed. Continuing to refer to Figure 40, closing the closure 226 interrupts the conductive path from one electrode A of connector 106 through the blood set tubing 108, 126, blood pump 13, blood pump lines 112, 116, dialyzer 14, dialyzer line 120, and air trap 122, via probe B in connector 128. As already described, the conductive path through the blood set tubing and cassette is a parallel path to conductance through the access site. If at least one wax needle is dislodged from the vascular access, the ADS value can become approximately equal to the resistance by the blood tubing set and pump, such as the ADS value 1210 between 735 and 748 seconds in Figure 65. When the closure is closed at time 748, the conductive path through the blood pump is interrupted, so the measured ADS value 1210 rises sharply to a value well above 1000 kΩ. In one embodiment, the controller distinguishes between occlusion or air bubbles in blood tubing 104, 130 (Figure 40) and the detachment of one of the needles 132, 102 from the vascular access site 134 in a two-step manner. When the controller detects needle detachment based on the ADS signal, the blood pump is frozen and the occlusion section 226 is closed. The controller first declares occlusion and displays an occlusion alert to the user. Needle detachment or access disconnection is not declared and the user is not warned about needle detachment until the ADS signal or the filtered value of the ADS signal exceeds a predetermined threshold.In one example, the controller does not declare needle detachment until the ADS signal exceeds 1000 kΩ. One possible theory is that a blockage or bubble in the blood lines 108, 126 increases the measured resistance between probes at fittings 106, 128 by blocking the conductive path through the blood pump and eliminating one of the conduit paths through the blood pump 13. In the case of a blockage in the blood lines 108, 126, the conductive path does not change by closing the blockage, as the blockage or bubble has already blocked the conductive path through the blood pump 13, while the conductive path through the vascular access 134 remains unchanged. In this case, closing the blockage does not change the ADS signal. Conversely, if one of the needles 102, 132 is withdrawn from the vascular access site 134, the only conductive path remaining between the probes is through the blood pump 13, and closing the blockage 226 closes that conductive path, causing a sharp increase in the ADS signal. In one embodiment, the ADS algorithm starts a counter when a quantity based on the ADS signal 1210 crosses a first threshold 1211, and the counter continues to increment until the ADS signal crosses a second threshold 1213 (see, for example, Figures 62-64). The ADS algorithm declares access disconnection when the counter reaches a predetermined value. The counter may be reset to zero when the ADS signal crosses the second threshold 1213 or when access disconnection is declared. In this embodiment, the first and second thresholds are calculated based on the measured ADS signal 1210. The first and second thresholds increase as the ADS signal increases. In one example, the first threshold has a minimum value of the ADS signal below a predetermined low value and a maximum value of the ADS signal above a predetermined high value. Between a predetermined high ADS value and a predetermined low ADS value, the first threshold changes proportionally to the change in the ADS value. The second threshold may depend on the ADS value in a similarly proportional manner.

[0213] In one example, the controller compares the difference between two filtered values ​​of the ADS signal 1210 to a threshold, so that the two values ​​are filtered with different time constants. The ADS algorithm can calculate a value delta ADS 1216, which is the difference between the faster filtered ADS (medADS) 1212 and the slower filtered ADS value (slowADS) 1214. A provisional flag 1218 is set if the delta ADS value 1216 is greater than the first threshold. In this example, the first and second thresholds are functions of the slowADS value 1214. In one example, the first threshold is 14K ohms for slowADS values ​​less than 60K ohms. The first threshold is 51K ohms for slowADS values ​​greater than 170K ohms. The first threshold increases proportionally to the slowADS value when the slowADS value is between 60 and 170K ohms. The second threshold may be a fixed function of the first threshold. Alternatively, the second threshold may be a fixed value less than the first threshold.

[0214] In some embodiments, the first and second thresholds are increased during a predetermined operating period to avoid false detection of needle deviation due to noise in the ADS signal. In one example, the first and second thresholds are increased by a certain amount until a predetermined amount of blood is pumped by the blood pump 13 (Figure 40). For example, the first and second thresholds may be increased by about 150% during the first 25 blood pump strokes.

[0215] In embodiments of the blood pump delay test, as described above, the third threshold may be greater than the first threshold by a predetermined factor. In one example of the blood pump delay test, a provisional flag is initially set when the electrical quantity based on the ADS signal exceeds the first threshold. The blood pump test is initiated when the provisional flag is cleared before needle detachment is declared. The blood pump test involves stopping the blood pump and applying maximum allowable pressure to the pump pod to force out all possible blood from the pod. The pumping pressure is then reduced to near zero, and after a delay, the electrical quantity is compared to the third threshold. In one example, the third threshold is a fixed factor greater than the first threshold. In another example, the third threshold may be approximately 150% of the first threshold. In yet another example, the delay before comparing the electrical quantity to the third threshold is approximately 10 seconds.

[0216] In embodiments to avoid false detections while the blood pump is not moving fluid toward the patient, the controller avoids calculating electrical quantities based on the ADS signal and does not evaluate or compare the ADS signal or quantities based on the ADS signal to a first threshold. In one example, the controller does not evaluate ADS values ​​for multiple strokes after the blood pump has resumed from a frozen state. The blood pump pressure can be started low enough so that no blood flows during the first few strokes of the pump. In one example, the controller does not evaluate the ADS signal for the first two strokes after resuming from a frozen state. In another example, during solution infusion, the external dialysate pump pumps dialysate toward the patient while the blood pump pauses. While the blood pump is paused, the controller does not evaluate the ADS signal.

[0217] Optionally, the controller evaluates the electrical resistance through needle lines 104, 130 (Figure 40) and the vascular access site 134 to reliably detect needle dislodgement. If the electrical resistance through needle lines 104, 130 and the vascular access site 134 approaches the resistance of a dislodged needle, the ADS algorithm may not detect the break. To ensure the controller's ability to detect a dislodged needle, the ADS algorithm measures the resistance of the needle lines and vascular access and compares it to a predetermined maximum allowable resistance. If the measured resistance exceeds the predetermined maximum allowable resistance, the controller may inform the user that the ADS system is not functioning properly. The user is given the option to continue without ADS system protection or to terminate the treatment.

[0218] In one example, the controller allows the ADS algorithm to operate for a sufficient amount of time to ensure the needle line is filled with the patient's blood, then stop the blood pump 13 and close the closure 226 before measuring the patient's resistance through the needle line and vascular access site. If the measured resistance is below a predetermined maximum allowable resistance value, the controller will resume treatment. If the measured resistance is greater than the maximum allowable resistance, the controller can warn the user that treatment may be terminated or that the ADS system is not active and treatment can continue without the ADS system. In one example, the blood pump performs 10 pump strokes before measuring the resistance through the needle line and vascular access. In one example, the measured allowable resistance is approximately 800 kΩ. In one embodiment, the ADS algorithm verifies the functionality of the ADS system by evaluating the ADS signal during one or more machine operations before initiating treatment or dialysis of the patient. In one example, the ADS algorithm verifies that the ADS signal is above a predetermined minimum value while the blood pump is primed with dialysate and the closure is open. In another example, the ADS algorithm ensures that the magnitude of the ADS signal changes substantially during the process of connecting the BTS lines 108, 126 (Figure 40) to the needle lines 104, 130. In this example, the highest ADS value during the connection process is compared to the lowest ADS value before the first stroke of the blood pump 13 is completed. If the difference between the highest and lowest ADS values ​​is less than or equal to a predetermined value, treatment is paused and the controller enters a frozen state. When the patient resumes treatment, the ADS algorithm completes one or more blood pump strokes and compares the lowest ADS value during those strokes to the highest ADS value. If the difference between the highest and lowest ADS values ​​is less than or equal to a predetermined value, treatment is paused and the controller enters a frozen state again.

[0219] Rinseback closure detected Referring here to Figures 5 and 5A, the ADS controller can also detect occlusion in the venous line 204 during the rinse-back process. The rinse-back process is performed at the end of treatment and returns blood to the patient from the blood pump 13 and dialyzer 14. The rinse-back process typically involves using an external dialysate pump 160 and blood pump 13 to push dialysate beyond the dialyzer 14, allowing any remaining blood in the blood pump 13 and dialyzer 14 to flow back to the patient through the venous line 204. Standard occlusion detection algorithms cannot detect occlusion during this process.

[0220] Referring here to Figure 40, at the end of treatment and before the start of the rinse-back operation, the BTS lines 108, 126 and needle lines 104, 130 are fully primed with the patient's blood. As the blood is washed away and returned to the patient, it is slowly replaced with dialysate, and the blood hematocrit decreases in the BTS and needle lines 104, 108, 126, 130. The decrease in hematocrit is the electrical impedance between the ADS probes attached to fittings 106, 128, which changes the electrical impedance measured by an ADS detection circuit similar to the circuit in Figure 37. When the venous side blood piping of the pump, including lines 120, 126, 130, is closed, the flow of dialysate is reduced or stopped, and the decrease in hematocrit values ​​in the piping is attenuated. The attenuated change in hematocrit corresponds to the attenuated reduction of the ADS signal (i.e., signal impedance or filtered value of signal impedance). In this way, closure in the venous lines 130, 126, 120 or in the dialyzer 14 can be detected by a decrease in the change in the ADS signal during the rinse-back process.

[0221] In one embodiment, the controller records an ADS signal at the start of the rinseback process and compares it with the ADS signal at the end of the rinseback process. If the ADS signal at the end of the rinseback process is greater than or equal to a predetermined percentage of the ADS signal at the start of the rinseback process, the controller declares closure. In one example, the predetermined percentage is less than 100%. In another example, the predetermined percentage is 99%. In yet another example, the predetermined percentage includes a range of values, for example, from 93% to 97%.

[0222] In one example, the controller records the high rinse-back ADS value as the highest medADS value during the first 12 seconds of the rinse-back process. After the rinse-back process is complete, the controller records the end rinse-back ADS value as the medADS value at the end of the rinse-back process. If the end rinse-back ADS value is 97% or higher of the high rinse-back ADS value, the controller declares closure.

[0223] closure part As described above, by using closures such as the closure 513 in Figure 17, the flow through the lines of the blood circuit assembly can be controlled, for example, between the patient connection points of blood lines 203 and 204 and other parts of the assembly. Hereinafter, various aspects of the present invention relating to closures, which can be employed alone or in any suitable combination with other features described herein, will be described along with one or more specific embodiments.

[0224] According to one aspect of the disclosed invention, a closure assembly is described for compressing at least one flexible tube, for example, a pair of flexible tubes. The closure assembly comprises a tube closure section having a mechanism configured to close off the fluid flow in one or more flexible tubes, and in some embodiments, one or more pairs of flexible tubes. In some embodiments, the tube closure section of the closure assembly comprises at least one closure member, and in specific embodiments, a closure member is provided for each section of piping arranged in the assembly. In some such embodiments, each closure member is pressed or otherwise pushed or biased to a closed position by an element sliding along the side of the closure member, so that the closure member pivots at its proximal end and translates toward the piping at its distal end. In one embodiment, the element is positioned between two closure members and acts to spread the distal ends of the closure members toward each other as the closure members press against their respective tubes. A preferred option is a main spring which pushes the spreading element toward the distal ends of the closure elements to the closed position. The expansion element can be moved against the biasing force of the main spring to an unclosed position near the proximal end of the closing element, either manually via a button and link assembly connected to the expansion element, or by control of a controller that operates an actuator similarly connected to the expansion element. A hinged door can be configured to cover the respective parts of the closing element and piping. The actuator can be prevented from operating if the door does not properly close over the closing element. Optionally, a retainer element can be made available to hold the expansion element in the unclosed position when the door is in the open position. Enabling the retainer element allows the expansion section to be held in the unclosed position without the user having to continuously apply force to the button or continuously operate the actuator. The retainer element can be disabled when the door is closed, thereby allowing the expansion element to move freely to and from the closed position, either manually or via the actuator.

[0225] Figures 50 and 51 show perspective views of the deployment of the closure assembly 700 according to an embodiment of the present disclosure. Figure 50 shows a perspective view of the deployment of the closure assembly 700 from a front angle, and Figure 51 shows a perspective view of the deployment of the closure assembly 700 from a rear angle.

[0226] The closure assembly 700 is configured to receive a pair of tubes 705 and close the tubes 705 using a pinching action at approximately the same level along the length of the assembly 700. The pinching action reduces the size of the internal fluid passage of each tube 705 to restrict the flow of the fluid flowing therethrough. The closure assembly 700 can be used with an infusion pump and in hemodialysis machines, hemodialysis, peritoneal dialysis, hemofiltration, hemodiafiltration, enterodialysis, etc.

[0227] The closure assembly 700 includes a frame 701. In some embodiments, the frame 701 includes tabs or snaps 709 that secure the frame to corresponding slots on the front panel of a blood filtration device such as a hemodialysis device.

[0228] The frame 701 comprises anvils or blocks 702 and 703 into which tubes 705 are compressed by the closing ends 713 of a pair of closing arms 710 and 711, and tube guides 704 that position each tube 705 relative to blocks 702 and 703. The tube guides 704 and blocks 702 and 703 are each configured to position the tubes 705 in predetermined positions adjacent to each of blocks 702 and 703. The closing assembly 700 also comprises a door 706 that is pivotably mounted on the frame 701. The door 706 can be closed relative to the frame 701 to secure the tubes 705 between each of blocks 702 and 703 and the tube guides 704. The door 706 has a latch 707 integrally molded to it via an elastic flexible base (e.g., via a living hinge) 708 that secures the door 706 to the frame 701 in the closed position. However, the latch 707 may be positioned in other suitable ways, such as including a latch element that is bonded, welded, bolted, or otherwise attached to the door 706. As shown in Figures 50, 52, and 53, the latch 707 can be pressed laterally to release the catch 740 from engagement with the corresponding slot 741 in the frame 701 and open the door 706.

[0229] The closing assembly 700 comprises two arms 710 and 711. The first arm 710 has a pivot end 712 and a closing end 713, and similarly, the second arm 711 has a pivot end 714 and a closing end 715. The two arms 710 and 711 work together to close the tube 705 when the button 716 is released and the door 706 is closed, or when the actuator 717 is stopped.

[0230] Figure 52 shows a front perspective view of a closing assembly 700 with the door 706 open and button 716 pressed, showing the release of closing arms 710 and 711 to allow loading and unloading of tube 705, according to one embodiment of the present disclosure. Figure 54 shows a front view of the closing assembly 700 of Figure 50 without the door 706 and frame 701, showing the arms 710 and 711 to completely close tube 705a,b, according to one embodiment of the present disclosure. As shown in Figure 54, a wedge element or spread portion 722 contacts the facing sides of the closing arms 710 and 711, and pressure can be applied to the closing arms 710 and 711 such that, under spring force, the closing ends 713 and 715 of the closing arms 710 and 711 press against portions of tube 705a, 705b. The user can release the closing arms 710 and 711 by pressing button 716, thereby causing the spreader 722 to retract away from the closing arms 710 and 711 and releasing the pressure on the spreader 722 applied to the distal ends of the closing arms 710 and 711. In some embodiments, the manual actuator (e.g., button 716) acts as an override mechanism for an automatic actuator (e.g., a pneumatically operated piston / cylinder device, etc.) connected to the pipe closure element (e.g., spreader 722). The manual actuator is operably coupled to the pipe closure to produce substantially linear motion of at least a portion of the pipe closure, moving the closing member from the closed position to the unclosed position when the override mechanism is manually operated by the user.

[0231] Similarly, the actuator can release the closing arms 710 and 711 by retracting the spread portion 722 away from the closing ends 713 and 715 of the closing arms 710 and 711. In one embodiment, as shown in Figure 50, the spread portion 722 can be formed from, integrally molded with, mounted to, or otherwise connected to a carriage assembly 723, the carriage assembly 723 is further connected to the actuating arm of the actuator (see, for example, Figures 56 and 57). The actuator may comprise, in particular, a motor and gear assembly (e.g., a rack and pinion assembly or a worm gear assembly), a solenoid, a hydraulic cylinder, or a pneumatic cylinder. In a preferred embodiment, the actuator comprises a pneumatic cylinder 717 that linearly extends an actuating arm comprising a piston arm 742 against a spring force (which may be a coil spring 745 in a cylinder 717 as shown in Figure 60). As shown in Figure 60, in a side perspective view of the pneumatically operated linear actuator 717, the piston arm 742 is connected to the carriage 723. When pneumatically actuated, the actuator 717 extends the piston arm 742, moving the carriage 723 and the mounted spreader 722 in a direction that retracts the spreader 722 from engagement with the distal ends 713, 715 of the closing arms 710 and 711 (for clarity, the closing arms 711, frame 701, door 706, block 703 and tube guide 704 have been removed from Figures 58-60). Preferably, a main spring external to or internal to the cylinder / actuator 717 applies a biasing force to the piston arm 742 or carriage 723, causing the closing arms 710 and 711 to move relative to the spreader 722 to the closed position. When power or air pressure is lost, the closing arms 710 and 711 default to the closed mode, blocking the flow of fluid in the tube 705. In one embodiment, as shown in the cross-sectional view of the closing assembly 700 in Figure 60, a coil spring 745 can be placed inside the cylinder 743 to provide a biasing force, which in turn allows the piston 744 to move the piston arm 742 under air pressure against it.Air pressure can be supplied to the linear actuator 717 from a pressure source (e.g., a tank pressurized by a pump) which is regulated by an electromechanical valve interposed under the control of an electronic controller.

[0232] As shown in Figures 54 and 59, when the linear actuator 717 is fully retracted, the carriage 723 supports the flared portion 722 along the sides facing the closing arms 710 and 711 and rotates them to the closed position. The first arm 710 pivots around its pivot end 712, causing the closing end 713 to press against the first tube 705a, which is constrained by the block 702 (see Figure 54). The second arm 711 pivots around its pivot end 714, thereby allowing the closing end 715 to press against the second tube 705, which is constrained by the block 703.

[0233] Figures 55 and 58 show the closed assembly 700 in an unclosed state (for clarity, the frame 701, door 706, blocks 702, 703 and other elements have been removed). When button 716 is pressed or linear actuator 717 is activated, the carriage 723 and mounted spreader 722 move distally away from actuator 717, allowing the closed arms 710 and 711 to rotate to an unclosed position around pivot points 712 and 714. Due to the elasticity of tubes 705a and 705b, the arms 710 and 711 can pivot toward each other. In some embodiments of the present disclosure, small magnets (not expressly shown) embedded in the arms 710 and 711 pull the arms 710 and 711 toward each other, facilitating the retraction of the closed ends 713 and 715 toward the tubes 705. In other embodiments, a small spring (not shown) can bias the closing arms 710 and 711 to pivot toward each other, and the spring constant is weak enough not to be overcome by a main spring (e.g., spring 745) that biases the carriage 723 or the spread section 722 to the retracted (closed) position.

[0234] Figure 53 shows a side perspective view of the closing assembly 700 of Figure 50 (frame 701 removed for clarity) showing the state in which the door 706 engages with the switch 720 when closed, according to one embodiment of the present disclosure. As shown in Figure 53, the hinge portion 708 of the latch 707 is connected to an engaging member or catch 740 which can fit into an interlocking slot 741 of the frame 701 (see, for example, Figures 50 and 53). When the door 706 is closed, a portion of the catch 740 of the latch 707 of the door 706 engages with a spring-loaded switch 720, which in one embodiment includes a spring arm 737 of the switch 720.

[0235] The engagement of switch 720 by the closing of door 706 informs an electronic controller (not shown) that door 706 is properly closed and that the linear actuator 717 can be activated to release the closures 710 and 711, allowing fluid to flow through tube 705. The door 706 closing signal may also enable the controller to perform other functions, such as commanding a pump connected to tube 705 to disclose the pumping of fluid within tube 705.

[0236] Figure 56 shows a rear view of the closing assembly 700 of Figure 50 with the linear actuator 717 in the fully retracted position (i.e., closed position) according to one embodiment of the present disclosure. Figure 56 shows the rear of the closing assembly 700 in the same configuration as shown for the front view of the closing assembly 700 in Figure 54. Figure 56 shows several working parts of the closing assembly 700 of Figure 50 to illustrate the operation of the actuator 717 and carriage 723 according to one embodiment of the present disclosure. The carriage 723 moves by extension or retraction of the piston arm 742 or by the actuation of button 716. The carriage 723 includes a guide 724 which is integrally molded with or otherwise mounted on the carriage 723. The guide 724 guides the carriage 723 as it moves via the actuation of the piston arm 742 or by the actuation of button 716. The guide 724 interfaces with a track 725 on the frame 701 (see, for example, Figure 51).

[0237] In any embodiment, when the door 706 is opened, the carriage 723 and spread portion 722 move to an unclosed position by the user's activation of a button 716 or the controller's activation of an actuator 717, and a retainer element or assembly can hold the unclosed position without further force being applied by the user or the actuator 717. In the exemplary embodiment shown in Figure 56, the carriage 723 may incorporate a latch pin 726 that interlocks with a slot or hole in a retaining member 718. The retaining member 718 has a surface 727 positioned to contact a pin 738 located inside the closed door 706 (see, for example, Figures 51 and 52). A through hole 739 allows the pin 738 to contact a portion of the retaining member 718 and displace it in the rearward direction. In the illustrated embodiment, the pin 738 contacts the front plate 727 of the retaining member 718. The retaining member 718 also has a surface having a slot or hole 729 positioned to receive the head of the latch pin 726, which includes a horizontal plate 728 forming a receiving portion 729 in the illustrated embodiment. The retaining member 718 is configured to slide within a groove or guide (not shown) of the frame 701 in response to contact by the pin 738 when the door 706 is closed or opened (see, for example, Figure 51). A spring 730 mounted on the frame 701 can bias the retaining member 718 to move forward to a stopper mechanism (not shown) of the frame 701, thereby allowing the retaining member 718 to slide forward by opening the door 706 and realigning the receiving portion 729 with respect to the latch pin 726. When the door 706 is closed (see Figures 50 and 51), the pin 738 of the door 706 presses against the front plate 727, and the front plate 727 compresses the spring 730, thereby positioning the receiving portion 729 of the horizontal plate 728 directly over the latch pin 726. Once the receiving portion 729 is aligned with the latch pin 726, the area of ​​the receiving portion 729 is large enough to release the latch pin 726 by the retaining member 718, thereby allowing the carriage 723 to receive the spring force of the main spring 745 in the actuator 717.Subsequently, if no air pressure is applied to the actuator 717, the carriage 723 can move freely to the closed position. The retaining member 718, which is in a non-operational state, allows the latch pin 726 to move freely through the receiving portion 729 as the carriage 723 moves between the fully extended position and the fully retracted position.

[0238] Figure 57 is a rear view of the closing assembly 700, with the actuator 717 in operation and the piston arm 742 in the extended position to open the closing arms 710, 711. In this figure, the head of the latch pin 726 is shown to be above the plane of the horizontal plate 728 of the retaining member 718, and the recessed area 731 of the latch pin 726 is shown to be aligned with the receiving portion 729 of the retaining member 718. In this figure, the door 706 is in the closed position, which means that the receiving portion 729 is positioned far enough back so that the latch pin 726 does not engage with the retaining member 718.

[0239] When the door 706 is fully open, the pin 738 of the door 706 does not press against the front plate 727, and the spring 730 applies force to the front plate 727, thereby positioning the receiving portion 729 of the retaining member 718 so that the latch pin 726 can engage with the edge of the receiving portion 729 and hook onto the retaining member 718. When the receiving portion 729 is positioned to hook onto the latch pin 726, the latch pin 726 moves into the receiving portion 729, pulling the front plate 727 backward against the force of the spring 730. When the head of the latch pin 726 has moved fully through the receiving portion 729, the recessed area 731 below the head of the latch pin 726 aligns with the horizontal plate 728, which moves as the edge of the receiving portion 729 moves into the recessed area 731 under the force of the spring 730 applied to the front plate 727. When the pin 738 of the door 706 is fully engaged with the front plate 727, the receiving portion 729 is positioned to release the latch pin 726 from the latch 718. Thus, when the door 706 is opened, the carriage 723 and the spread portion 722 can be held in the unclosed position without continuous application of force by the actuator 717 or by the user pressing the button 716. This allows the user to load and unload the piping into the closing assembly 700 without simultaneously applying force to the button 716. However, when the door 706 is closed, the retaining member 718 is no longer movable and there is no continuous application of force by the actuator 717 or through the button 716, so the carriage 723 and the spread portion 722 move into place and rotate the closing arms 710 and 711 to the closed position.

[0240] Figures 58 and 59 show side perspective views of some of the working parts of the closing assembly 700 of Figure 50, with the frame 701, blocks 702 and 703, tube guide 704, door 706, closing arm 711, and other parts removed for clarity. In Figure 58, the piston arm 742 is fully extended according to the embodiment of the present disclosure. Figure 58 shows the latch pin 726 hooked onto the retaining member 718. That is, with the door 706 in the open position, the horizontal plate 728 is positioned by the force of the spring 730 to engage with the recessed area 731 of the latch pin 726.

[0241] Figure 59 shows a side perspective view of the closing assembly 700 of Figure 50 with the piston arm 742 in the fully retracted position, with some elements removed as in Figure 58 for clarity. In this example, the latch pin 726 is shown to be completely detached from the retaining member 718, and since there is no acting force on the actuator 717 or pressing force on the button 716, the piston arm 742, carriage 723 and spread portion 722 can be freely retracted under the force of the main spring 745 (see Figure 60) biased against the extension of the piston arm 742. The spread portion 722 then moves toward the closing ends 713, 715 of the closing arms 710, 711. In one embodiment, as shown in Figures 58 and 59, when the button 716 is pressed, the button 716 pivots around the pivot axis 732 to raise the lever arm 733. The lever arm 733 is pivotably connected to the connecting member 734 via the proximal pivot axis 735. Next, the connecting member 734 is pivotably connected to the carriage 723 via the distal pivot shaft 736. When the button 716 is pressed or the piston arm 742 moves the carriage 723 toward the retaining member 718, the connecting member 734 moves with the carriage 723, as shown in Figure 58, causing the button 716 to rotate around the pivot shaft 732.

[0242] Figure 61 shows a closure assembly 700 of Figure 50 used in a front panel assembly 911 of a dialysis system according to one embodiment of the present disclosure. The closure assembly 700 closes the flexible tubes 901 and 902 through which blood flows to and from the patient. The right-side tube 902 carries blood from the patient to the blood pump assembly 1000 (arterial blood line), and the left-side tube 901 carries blood from the dialysis machine 14 through the air trap 19 and back to the patient (venous blood line). The closure assembly 700 can close the blood flow through both of these patient tubes 901 and 902 simultaneously.

[0243] As described in detail above, tubes 901 and 902 are connected to a blood pump cassette or assembly 1000, which is a modular unit that can be mounted on and removed from the front panel 911. Both patient tubes 901 and 902 can be supplied as an assembly including the blood pump cassette 1000 and the air trap 19, which can be loaded into the closure assembly 700 when the blood pump cassette 1000 is mounted on the front panel 911. In this embodiment, the closure assembly 700 forms a permanent part of the front panel 911.

[0244] When the closed assembly 700 is in an open state, the pump located in the blood pump cassette 1000 can be operated to pump blood from the patient through the right-side tube 902, through the blood pump, and through the dialyzer 14. The blood processed by the dialyzer 14 then returns to the patient through the tube 901, after first passing through the air trap 19 and the in-line air detector 823.

[0245] Although various embodiments of the present invention have been described and explained in this specification, those skilled in the art can easily conceive of various other means and / or structures for performing the functions described in this specification and / or obtaining the results and / or one or more advantages described in this specification. Such conceptions and / or modifications are considered to fall within the scope of the present invention. That is, those skilled in the art can easily recognize that all the parameters, dimensions, materials, and configurations described in this specification are exemplary, and the actual parameters, dimensions, materials, and / or configurations are determined by the specific applications in which the present invention is utilized. Those skilled in the art can recognize many equivalents of the specific embodiments of the present invention described in this specification by using experiments. Therefore, it should be understood that the above-described embodiments are merely illustrative, and the present invention can be implemented within the scope of the appended claims and their equivalents.

[0246] In this specification and the claims, the indefinite articles "a" and "an" should be understood to mean "at least one" unless there is an indication to the contrary.

[0247] Hereinafter, the technical ideas that can be grasped from the above embodiments will be described as appendices. [Appendix 1] A system for detecting the detachment of a catheter or needle in vascular access, including a first and a second catheter or needle in a blood vessel, a graft, or a shunt, the system comprising: A first line fluidly connecting the first catheter or needle to the inlet of a pump; A second line fluidly connecting the second catheter or needle to the outlet of the pump; A first connector connecting the first line to the first catheter or needle and a second connector connecting the second line to the second catheter or needle, each connector having an electrode in fluid communication with the fluid conveyance lumen of the connector; An electronic circuit that is electrically connected to the electrodes of the first connector and the second connector, and configured to measure the electrical impedance of the fluid between the first connector and the second connector via a conductive path through the blood vessel, wax, or graft, The system includes a controller configured to receive a series of sampled electrical impedance values ​​from the aforementioned electronic circuit and process the electrical impedance values ​​as signals, The aforementioned controller, The signal is sampled and filtered or smoothed using a first time constant to generate a first filtered signal. The signal is sampled and filtered or smoothed using a second time constant longer than the first time constant to generate a second filtered signal. If the difference between the first filtered signal and the second filtered signal is greater than the first threshold, the disconnection flag is provisionally set and the counter is started. Before the counter reaches a predetermined count, if the difference between the first filtered signal and the second filtered signal decreases to a second threshold lower than the first threshold, the disconnection flag is cleared, and The system is configured to declare a vascular transection if the transection flag is not cleared before the counter reaches the predetermined count. A system in which, upon the aforementioned declaration, the controller activates one or more mechanical line closures to stop the fluid flow in the first and second lines, to stop the pump, or to notify the user of the possibility of blood vessel rupture.

[0248] [Note 2] The system as described in Appendix 1, wherein the counter counts time units, and the predetermined count is a predetermined time interval.

[0249] [Note 3] The system as described in Appendix 1, wherein the counter counts units of blood volume pumped into the vascular access, and the predetermined count is a predetermined blood volume.

[0250] [Note 4] The system as described in Appendix 1, wherein the counter counts the strokes of the pump, and the predetermined count is a predetermined number of strokes.

[0251] [Note 5] The system described in Appendix 1, wherein the signal is the time derivative of the electrical impedance value. [Note 6] The system as described in Appendix 1, wherein the controller stops processing the electrical impedance value when the pump stops pumping fluid through the first and second lines.

[0252] [Note 7] The system as described in Appendix 1, wherein the user notification includes requesting the user to confirm the position of the first and second catheters or the needle when accessing a blood vessel.

[0253] [Note 8] The system as described in Appendix 7, wherein the controller is configured to receive a command from the user to restart the operation of the pump or to further stop the operation of the pump.

[0254] [Note 9] The operation of the pump is the system described in Appendix 8, which includes the extracorporeal circulation of a portion of the user's blood.

[0255] [Note 10] The system as described in Appendix 8, wherein the controller is configured to raise the first threshold if a user command to restart the pump operation follows each of several declarations of blood vessel transection.

[0256] [Note 11] The system as described in Appendix 1, wherein the controller continues to process the electrical impedance value when a declaration of vascular transection is made and the mechanical line closure unit is activated, and the controller is configured to confirm vascular transection when the difference between the first filtered signal and the second filtered signal exceeds a third threshold which is greater than the first threshold.

[0257] [Note 12] A system for detecting catheter or needle dislodgement in a vascular access, including first and second catheters or needles in a blood vessel, fistula, or graft, wherein the system is A first line that connects the fluid to the inlet of the pump, A second line connects a second catheter or needle to the outlet of the pump, The device comprises a first connector for connecting the first line to the first catheter or needle, and a second connector for connecting the second line to the second catheter or needle, each connector having an electrode that is in fluid communication with the fluid transport lumen of the connector. An electronic circuit that is electrically connected to the electrodes of the first connector and the second connector, and configured to measure the electrical impedance of the fluid between the first connector and the second connector via a conductive path through the blood vessel, wax, or graft, The system includes a controller configured to receive a series of sampled electrical impedance values ​​from the aforementioned electronic circuit and process the electrical impedance values ​​as signals, The signal is the difference between a first filtering value of the impedance value using a first time constant and a second filtering value of the impedance value using a second time constant longer than the first time constant, and the controller is If the aforementioned signal is greater than the first threshold, the disconnection flag is provisionally set and the counter is started. If the signal decreases to a second threshold lower than the first threshold before the counter reaches a predetermined count, the disconnection flag is cleared, and A system configured to declare a vascular transection if the transection flag is not cleared before a counter reaches a predetermined count.

[0258] [Note 13] The system described in Appendix 12, wherein the counter counts time units, and the predetermined count is at a predetermined time interval.

[0259] [Note 14] The system described in Appendix 12, wherein the counter counts units of blood volume pumped into the vascular access, and the predetermined count is a predetermined blood volume.

[0260] [Note 15] The system as described in Appendix 12, wherein the counter counts the strokes of the pump, and the predetermined count is a predetermined number of strokes.

[0261] [Note 16] The system described in Appendix 12, wherein the signal is the time derivative of the electrical impedance value.

[0262] [Note 17] The system as described in Appendix 12, wherein the controller stops processing the electrical impedance values ​​when the pump stops pumping fluid through the first and second lines.

[0263] [Note 18] The system according to Appendix 12, wherein, in accordance with the declaration, the controller activates one or more mechanical line closures to stop the fluid flow in the first and second lines, stop the pump, or notify the user of the occurrence of a blood vessel rupture.

[0264] [Note 19] The system according to Appendix 18, wherein the user notification includes requesting the user to confirm the position of the first and second catheters or the needle when accessing a blood vessel.

[0265] [Note 20] The system as described in Appendix 19, wherein the controller is configured to receive a command from the user to restart the operation of the pump or to further stop the operation of the pump.

[0266] [Note 21] The operation of the pump is the system described in Appendix 20, which includes the extracorporeal circulation of a portion of the user's blood.

[0267] [Note 22] The system as described in Appendix 20, wherein the controller is configured to raise the first threshold if a user command to restart the operation of the pump follows each of several declarations of blood vessel transection.

[0268] [Note 23] The system as described in Appendix 12, wherein the controller continues to process the electrical impedance value when a declaration of vascular transection is made and one or more mechanical line closures are activated, and the controller is configured to confirm vascular transection when the signal exceeds a third threshold which is greater than a first threshold.

[0269] [Note 24] The first threshold and the second threshold are based on the filtered values ​​of the electrical impedance values, as described in Appendix 12.

[0270] [Note 25] A system for detecting catheter or needle dislodgement in a vascular access, including first and second catheters or needles in a blood vessel, fistula, or graft, wherein the system is A first line that connects the fluid to the inlet of the pump, A second line connects a second catheter or needle to the outlet of the pump, A first connector for connecting the first line to the first catheter or needle, a second connector for connecting the second line to the second catheter or needle, and each connector having an electrode that is in fluid communication with the fluid transport lumen of the connector, An electronic circuit that is electrically connected to the electrodes of the first connector and the second connector, and configured to measure the electrical impedance of the fluid between the first connector and the second connector via a conductive path through the blood vessel, wax, or graft, The system includes a controller configured to receive a series of sampled electrical impedance values ​​from the aforementioned electronic circuit and process the electrical impedance values ​​as signals, The aforementioned controller, The signal is sampled and filtered or smoothed using a first time constant to generate a first filtered signal. The signal is sampled and filtered or smoothed using a second time constant longer than the first time constant to generate a second filtered signal. The disconnection flag is set when the difference between the first filtered signal and the second filtered signal is greater than the first threshold. A system configured to declare an angioruption, which involves stopping the fluid flow in the first and second lines, stopping the pump, or activating one or more mechanical line closures to notify the user of the possibility of an angioruption.

[0271] [Note 26] The system described in Appendix 25, wherein the signal is the time derivative of the electrical impedance value.

[0272] [Note 27] The...

Claims

1. A system for detecting catheter or needle dislodgement in a vascular access, wherein the vascular access includes first and second catheters or needles configured to be placed in a blood vessel, fistula, or graft, and the system is A first line for fluid connection between the first catheter or needle and the inlet of the pump, A second line for fluid connection of the second catheter or needle to the outlet of the pump, A first connector for connecting the first line to the first catheter or needle, a second connector for connecting the second line to the second catheter or needle, and each connector having an electrode that is in fluid communication with the fluid transport lumen of the connector, An electronic circuit is electrically connected to the electrodes of the first connector and the second connector, and is configured to measure the electrical impedance of the fluid between the first connector and the second connector via a conductive path. The system includes a controller configured to receive a series of sampled electrical impedance values ​​from the aforementioned electronic circuit and process the electrical impedance values ​​as signals, The aforementioned controller, If the signal is greater than a first threshold at a certain point in time, the disconnection flag is provisionally set and the counter is started. If the signal decreases below a second threshold lower than the first threshold before the counter reaches a predetermined count, the disconnection flag is cleared. A system configured to declare an alarm if the disconnection flag is not cleared before the counter reaches a predetermined count.

2. The system according to claim 1, wherein the counter counts time units, and the predetermined count is a predetermined time interval.

3. The system according to claim 1, wherein the counter counts units of blood volume pumped into the vascular access, and the predetermined count is a predetermined blood volume.

4. The system according to claim 1, wherein the counter counts the strokes of the pump, and the predetermined count is a predetermined number of strokes.

5. The system according to claim 1, wherein the signal is the time derivative of the electrical impedance value.

6. The system according to claim 1, wherein the controller stops processing the electrical impedance value when the pump stops.

7. The system according to claim 1, wherein the declaration of the alarm causes the controller to activate one or more mechanical line closure units to stop the fluid flow in the first line and the second line, to stop the pump, or to notify the user of the occurrence of a blood vessel rupture.

8. The system according to claim 7, wherein notifying the user includes requiring the user to confirm the position of the first and second catheters or needles when accessing the blood vessel.

9. The system according to claim 8, wherein the controller is configured to receive a command from the user to restart the operation of the pump or to stop further operation of the pump.

10. The system according to claim 1, wherein the operation of the pump includes extracorporeal circulation of a portion of the user's blood.

11. The system according to claim 1, wherein the controller continues to process electrical impedance values ​​when an alarm is declared and a mechanical line closure unit is activated, and the controller is configured to confirm blood vessel rupture when the signal exceeds a third threshold which is greater than the first threshold.

12. The system according to claim 7, wherein the notification to the user is a closing alarm.

13. The system according to claim 11, wherein the controller updates the notification to the user regarding the detachment of the needle.

14. The system according to claim 1, wherein the first threshold and the second threshold are compared with a filtering value of the electrical impedance value.

15. The system according to claim 1, wherein the signal is the difference between a first filtering value of the impedance value using a first time constant and a second filtering value of the impedance value using a second time constant longer than the first time constant.

16. The system according to claim 15, wherein the controller is configured to set a second filtering value relative to the first filtering value when a user command to restart the operation of the pump follows each of a plurality of declarations of blood vessel transection.

17. The system according to claim 1, wherein the second threshold is a fixed function of the first threshold.

18. The system according to claim 1, wherein the second threshold is a fixed value less than the first threshold.

19. The system according to claim 1, wherein the first threshold and the second threshold are determined based on the electrical impedance value.

20. The system according to claim 1, wherein the first threshold and the second threshold are adjusted in proportion to the change in the electrical impedance value.

21. The system according to claim 1, wherein the conductive path includes a liquid that fluidly connects the first connector and the second connector.

22. The system according to claim 21, wherein the conductive path includes blood in the needle, and blood vessels, wax, or grafts.

23. The system according to claim 21, wherein the conductive path includes the first line, the second line, and the blood in the pump.

24. A system for detecting catheter or needle dislodgement in a vascular access, wherein the vascular access includes first and second catheters or needles configured to be placed in a blood vessel, fistula, or graft, and the system is A first line for fluid connection between the first catheter or needle and the inlet of the pump, A second line for fluid connection of the second catheter or needle to the outlet of the pump, A first connector for connecting the first line to the first catheter or needle, a second connector for connecting the second line to the second catheter or needle, and each connector having an electrode that is in fluid communication with the fluid transport lumen of the connector, An electronic circuit is electrically connected to the electrodes of the first connector and the second connector, and is configured to measure the electrical impedance of the fluid between the first connector and the second connector via a conductive path. The system includes a controller configured to receive a series of sampled electrical impedance values ​​from the aforementioned electronic circuit and process the electrical impedance values ​​as signals, The aforementioned controller, If, at a certain point in time, the signal is greater than a first threshold, the disconnection flag is provisionally set and the counter is started. A system configured to declare an alarm if the disconnection flag is not cleared before the counter reaches a predetermined count.

25. The system according to claim 24, wherein if the signal decreases to a second threshold lower than the first threshold before the counter reaches a predetermined count, the controller clears the disconnection flag.

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