Peritoneal dialysis system having sensor and configured for diagnosing peritonitis

Abstract

The present invention relates to a peritoneal dialysis system having a sensor and configured for diagnosing peritonitis. Peritoneal dialysis, such as automated peritoneal dialysis ("APD"), is equipped with one or more or all of the following sensing or feedback features: impedance sensing for detection of peritonitis, temperature sensing for detection of peritonitis, biological MEMS sensing for detection of peritonitis, and glycemic control for diabetic patients, each sensing or feedback feature analyzes the patient's effluent liquid or liquid residing within the patient's abdominal cavity.

Description

[0001] This application is a divisional application, and the original application it is directed to is a Chinese invention patent application with the applicants being "Baxter International Corporation" and "Baxter Healthcare Co., Ltd.", the application date being July 25, 2019, the invention name being "Peritoneal dialysis system with sensor configured for diagnosing peritonitis", and the application number being 201980049640.2.

[0002] Priority claim

[0003] This application claims priority to and the benefit of U.S. Provisional Patent Application No. 62 / 703,749, filed on July 26, 2018, entitled “Dialysis Systems and Methods Including Sensor Feedback to Improve Patient Experience,” the entire contents of which are incorporated herein by reference and relied upon. Technical Field

[0004] The present disclosure relates generally to the treatment of end stage renal disease. More specifically, the present disclosure relates to methods and devices for monitoring and / or controlling the performance of peritoneal dialysis. Background Art

[0005] It is known to use dialysis to support patients whose renal function has decreased to the point where their kidneys are no longer adequate to function. Two main methods of dialysis are provided, hemodialysis, and peritoneal dialysis.

[0006] In hemodialysis, the patient's blood is passed through an artificial kidney dialysis machine. The membrane in this machine acts as an artificial kidney for cleaning the blood. Because it is an extracorporeal treatment that requires special machinery, hemodialysis presents certain inherent disadvantages. To overcome the disadvantages associated with hemodialysis, peritoneal dialysis has been developed. Peritoneal dialysis uses the patient's own peritoneum as a semipermeable membrane. The peritoneum is the membranous lining of the patient's abdominal body cavity. Due to good perfusion, the peritoneum acts as a natural semipermeable membrane.

[0007] Peritoneal dialysis periodically infuses a sterile aqueous solution, or dialysis fluid, into the peritoneal cavity. Diffusion and osmotic exchange occurs between the peritoneal dialysis fluid and the bloodstream across the natural body membrane. This exchange removes waste products that the kidneys normally excrete. The waste products include solutes such as urea and creatinine. The kidneys also maintain levels of other substances such as sodium and water. Dialysis regulates the diffusion of water and solutes across the peritoneal membrane during the dialysis process, which is called ultrafiltration.

[0008] In continuous ambulatory peritoneal dialysis ("CAPD"), a dialysis solution is introduced into the peritoneal cavity via a catheter. Solute exchange between the dialysis fluid and the blood is achieved by diffusion. Further removal of solutes can be achieved via the dialysis fluid providing an appropriate osmotic gradient from the blood to the dialysis fluid. The osmotic gradient can achieve proper acid-base, electrolyte, and fluid balance in the patient's body. Spent dialysis fluid or effluent fluid is manually drained from the body cavity through the catheter via gravity.

[0009] A variation of CAPD is automated peritoneal dialysis (“APD”). APD uses a machine called a cycler to automatically infuse, retain, and drain peritoneal dialysis fluid into the patient’s peritoneal cavity. APD is attractive to peritoneal dialysis patients because it can be performed at night while the patient is asleep, freeing the patient from the daily demands of CAPD during waking and work hours.

[0010] An APD sequence usually lasts several hours. It usually begins with an initial drain phase to empty the peritoneal cavity from the dialysate used in the previous treatment. The APD sequence will then proceed through a series of fill, dwell, and drain phases. Each fill / dwell / drain sequence is called a cycle.

[0011] The proportion of patients undergoing automated peritoneal dialysis ("APD") is increasing worldwide, in part because APD can be adapted to the patient's specific needs with respect to the patient's personal life and the patient's treatment needs. The two main goals of dialysis, solute removal and ultrafiltration ("UF"), depend on the mode or type of APD performed (e.g., nocturnal intermittent peritoneal dialysis ("NIPD"), continuous cycle peritoneal dialysis ("CCPD"), and high-dose CCPD), solution type, treatment duration, and fill volume. Prescribing an APD therapy constitutes choosing one among them. Therefore, there are many combinations and possibilities from which to choose.

[0012] APD devices typically do not have the ability to provide the patient with feedback on the effectiveness of his / her recent therapy. Moreover, APD devices typically operate in an open-loop manner so that they do not adjust treatment parameters (e.g., mode, solution type, treatment time, and fill volume) based on actual measured daily clearance and UF. As a result, some patients fail to achieve their goals and develop adverse conditions, such as fluid overload, and hypertension in some cases. Current methods for adjusting treatment typically involve patients reporting to a center at intervals for evaluation. These methods place the burden of treatment adjustment entirely on the physician or clinician, and cannot occur frequently enough to appropriately adjust for changes in the patient's weekly, monthly, quarterly, or other lifestyles.

[0013] Similar to CAPD, APD uses a catheter implanted in the patient's peritoneum to deliver fresh dialysis fluid to and remove spent dialysis fluid from the patient's peritoneal cavity. The placement of a peritoneal catheter provides an opportunity to sense desired parameters within the patient. In addition, both APD and CAPD remove spent or outflow PD fluid from the patient, which provides an opportunity to sense patient parameters or characteristics retained in the outflow fluid. Therefore, there is a need to provide a system and method that utilizes the placement of a patient catheter and / or outflow PD fluid removed from the patient to help monitor and / or control peritoneal dialysis treatments, such as CAPD and APD. And more generally, there is a need for immediate or in-treatment feedback to help solve various problems associated with peritoneal dialysis. Summary of the invention

[0014] Examples described herein disclose systems and methods for improved peritoneal dialysis ("PD") treatment. Three of the systems and methods described herein relate to the detection and optimized early detection of peritonitis. Peritonitis is an inflammation of the peritoneum, which is the tissue that lines the inner wall of the abdomen and covers and supports most of the abdominal organs. The peritoneal wall is also the membrane used for peritoneal dialysis as described above. Peritonitis is often caused by a bacterial or fungal infection that can enter through a patient's peritoneal catheter.

[0015] If left untreated, peritonitis can quickly spread to the blood (sepsis) and other organs, leading to multiple organ failure and death. The first symptoms of peritonitis are usually loss of appetite and nausea, as well as dull abdominal pain that quickly turns into persistent, severe abdominal pain. Other signs and symptoms associated with peritonitis may include: abdominal tenderness or distension, chills, fever, fluid in the abdomen, and vomiting.

[0016] The mortality rate from peritonitis depends on many factors but can be as high as 40% in patients who also have cirrhosis. Up to 10% may die from secondary peritonitis. Primary spontaneous peritonitis is an infection that develops in the peritoneum and is the type associated with peritoneal dialysis treatment. Secondary peritonitis usually develops when an injury or infection in the abdominal cavity allows infectious organisms to enter the peritoneum. Both types of peritonitis can be fatal.

[0017] Current methods for determining peritonitis are subjective and burdensome to the patient. For example, the patient may be told to observe the color and / or texture of their effluent fluid to look for peritonitis. Alternatively, the patient may be told to pay attention to a feeling of fullness and / or fever. When the patient believes that peritonitis is imminent or present, the patient must bring an effluent sample to a clinic for testing. The above methods are subjective and burdensome to the patient. The following system and method are automatic and objective.

[0018] Temperature sensing for peritonitis

[0019] In one main embodiment, the temperature of spent dialysis fluid leaving a patient is measured to detect peritonitis. In healthy patients, the temperature of spent dialysis fluid is normal body temperature or about 37°C. In patients experiencing an episode of peritonitis, spent dialysis fluid leaving the patient may be at an elevated temperature. The system and method of the first main embodiment measures the effluent dialysis fluid and uses this measurement to make a determination whether the patient may be experiencing an episode of peritonitis.

[0020] This temperature measurement can be performed in a variety of different ways. In one approach, a temperature sensor such as a thermocouple or thermistor is placed in a connector such as a clamshell connector that is removably and selectively clamped on a patient line. The clamshell connector can be placed at any desired location around the patient line, such as close to the patient, so that the temperature of the patient's effluent dialysis fluid can be obtained immediately when leaving the patient. In one embodiment, the temperature of the effluent fluid is compared to the temperature of the fresh dialysis fluid, which can be heated to body temperature or 37°C. In this way, any temperature offset caused by the conductive tubing, which is usually not thermally conductive, is eliminated. For example, if the temperature of fresh dialysis fluid at 37°C is read through the tubing as being at an offset temperature of 32°C, the same offset will be assumed for the effluent fluid leaving the patient. Therefore, the control unit for reading the temperature signal will look for a patient health signal of 32°C, and when the control unit sees a signal indicating a temperature above 32°C, an alarm for potential peritonitis will be triggered.

[0021] In an alternative embodiment, a more thermally conductive and medically safe material such as stainless steel is bonded or fitted into the patient line. One or more thermally conductive electrodes are attached to the temperature sensor and allow for more accurate temperature readings. Here, the control unit for reading the temperature signal looks for a patient health signal of 37°C in one embodiment and triggers an alarm for potential peritonitis when the control unit sees a signal indicating a temperature above 37°C. In an example, the control unit may or may not take into account the incoming temperature of the fresh dialysis fluid.

[0022] In any embodiment where the temperature sensor is located remote from the cycler, the temperature sensor can send a measurement signal to the cycler in a wired or wireless manner for interrogation. In one embodiment, the temperature sensor is a passive device (e.g., two wires that produce a voltage based on the temperature of the liquid). If the temperature sensor does require power, power can be provided from the cycler or from a water purifier operating with the cycler via a battery or via a power cord.

[0023] In another alternative embodiment, a temperature sensor, such as a thermocouple or thermistor, is positioned within the dialysis machine or cycler and operates with the disposable cassette or a patient line extending from the disposable cassette. In one embodiment, the temperature sensor contacts the flexible sheet of the disposable cassette at one or more locations. One or more thermally conductive contacts may be formed in or added to the disposable cassette to aid in the accuracy of temperature sensing. As above, the control unit may or may not take into account the incoming temperature of the fresh dialysis fluid when sensing at or near the cassette.

[0024] Temperature sensing is optionally performed in a drain line extending from the disposable cartridge. Since sterility is not an issue, the drain line is advantageous so that in one embodiment the drain line is inserted into a reusable thermally conductive contact that is provided with the cycler or a water purification device that operates with the cycler.

[0025] In one embodiment, the control unit is programmed to alert the patient in a user interface of the cycler if an elevated temperature indicative of peritonitis is detected. Alternatively or additionally, the control unit operates via a network and one or more server computers to enable a physician or clinician to view the effluent temperature data, for example on an ongoing basis, so that the clinician can determine if the patient is at risk for peritonitis. In one embodiment, the data is displayed on a dashboard of a web page for the patient, where the temperature data may be marked with a clinician-indicative label for peritonitis when the temperature data is elevated.

[0026] BioMEMS Sensing for Peritonitis

[0027] In a second major embodiment, which may be used instead of or in addition to the first embodiment, a bio-microelectromechanical system ("bio-MEMS") sensor is used to detect peritonitis. The bio-MEMS sensor is used to look for the presence of white blood cells from the patient in the effluent, which is an indicator of peritonitis. In one embodiment, the effluent liquid from the cycler is pumped to a drain. The drain line is connected to a diagnostic detection device of a lab-on-a-chip. The lab-on-a-chip or bio-MEMS device includes a container into which a sampling line extends, wherein the sampling line may extend or branch from the drain line. The effluent sample entering the container of the bio-MEMS device first encounters a microfluidic path that separates the patient's white blood cells from the effluent liquid. In one embodiment, the white blood cells are then weighed using a piezoelectric biosensor. The piezoelectric biosensor resonates at a frequency that is proportional to the change in the white blood cell sedimentation rate.

[0028] Alternatively, the bioMEMS device is placed in the patient line via a sampling line and used to analyze the effluent returning from the patient. In this way, the bioMEMS device can be used to additionally detect fresh dialysis fluid delivered to the patient if desired.

[0029] In one embodiment, the bio-MEMS device includes electronics and a processor to process the raw signals from the piezoelectric biosensor and make a determination whether white blood cells are present. The bio-MEMS device may also include a user interface to indicate to the patient or a caregiver present during treatment whether peritonitis is indicated. In alternative embodiments, one or both of the following may be provided alternatively by the cycler or, possibly, by a water purification device operable with the cycler: (i) electronics and a processor for processing the raw signals from the piezoelectric biosensor, or (ii) a user interface for communicating with the patient or caregiver.

[0030] As with the first main embodiment, the control unit and processor of the second main embodiment may alternatively or additionally operate via a network and one or more server computers to enable a physician or clinician to view the bio-MEMS data, for example on an ongoing basis, so that the clinician can determine if the patient is at risk for peritonitis. The data of the second main embodiment may be displayed in conjunction with the data of the first main embodiment to provide a combination of peritonitis indicators.

[0031] Impedance Monitoring for Peritonitis

[0032] In a third major embodiment, which may be used instead of or in addition to the first and / or second embodiments, an impedance monitor is used to detect peritonitis. The impedance monitor is used to look for the presence of white blood cells from the patient in the effluent fluid, which is also an indicator of peritonitis. In various embodiments, the impedance monitor may be placed anywhere that the patient's effluent fluid can be sensed, for example, in an indwelling catheter of the patient, along a patient line, or anywhere along a drain line. In any of these locations, the catheter or line is equipped with electrodes, for example, in any of the ways described above for temperature sensing, but the purpose now is to place a conductive contact in communication with the effluent dialysis fluid.

[0033] In one embodiment, a conductive and medically safe material such as stainless steel is joined or assembled into a catheter, patient line, or discharge line, for example via a clamshell connector or a connector joined into the discharge line. In one embodiment, a control unit controlling an impedance monitor causes an electrical frequency sweep to be generated in the effluent liquid. Such an impedance spectrum (or obtaining a complex impedance) can provide additional details about the content of the effluent liquid. For example, the electrical properties of fibrin (normal, not indicative of peritonitis) may be different from the electrical properties of white blood cells (indicative of peritonitis). Once the electrical properties of different substances in the effluent liquid are known, the properties can be programmed into the control unit and thereafter used to determine whether any substance is entrained in the effluent dialysate flow.

[0034] In any embodiment where the impedance monitor is located remotely from the cycler, the impedance monitor can send a measurement signal to the cycler in a wired or wireless manner for interrogation. The impedance monitor as above has the ability to transmit a frequency sweep into the effluent liquid and can therefore receive power from the cycler or a water purifier operating with the cycler via a battery or via a power cord.

[0035] In an alternative embodiment, the impedance monitor is positioned within the dialysis machine or cycler and operates with a disposable cassette or a patient or drain line extending from the disposable cassette. In one embodiment, the impedance monitor extends through a rigid wall that holds the disposable cassette sheet in one or more positions. In another alternative embodiment, the impedance monitor may operate with a drain line positioned within a water purifier that supplies purified water to the dialysis machine or cycler.

[0036] In one embodiment, the control unit is programmed to alert the patient or caregiver at a user interface of the cycler if white blood cells indicative of peritonitis are detected. Alternatively or additionally, the control unit operates via a network and one or more server computers to enable a physician or clinician to view the effluent impedance data, for example on an ongoing basis, so that the clinician can determine if the patient is at risk for peritonitis. In one embodiment, the data is displayed on a dashboard of a web page for the patient, where the effluent impedance data can be presented along with a flag for the clinician indicating peritonitis when white blood cells are present. The data of the third main embodiment can be displayed in conjunction with the data of the first and / or second main embodiments to provide a combination of peritonitis indicators.

[0037] When an impedance monitor is placed in an indwelling catheter or in a patient line via a sampling line and used to analyze effluent in or returning from a patient, the impedance monitor can additionally be used to sense fresh dialysis fluid being delivered to the patient if desired. When an impedance monitor is placed in a drain line, it can additionally be used to detect whether the dialysis fluid made at the point of use has been properly mixed.

[0038] For blood sugar control in patients with diabetes

[0039] Glucose (or dextrose) is the primary osmotic agent used with most PD solutions. Absorption of a large portion of the peritoneal glucose load over the dwell period may have adverse effects on patients with diabetes. Diabetes is a common cause of kidney failure, leading to the need for dialysis therapy. In addition, daily exposure to glucose may induce hyperglycemia in PD patients, which may have serious consequences. Therefore, some diabetic PD patients receive insulin along with their PD therapy to help maintain blood sugar balance. However, patients who receive insulin along with PD therapy are at risk of trying to match the amount of insulin to the amount of PD therapy they are receiving.

[0040] In a fourth major embodiment, which may be used in place of or in addition to the first, second, and / or third embodiments, a bioMEMS-insulin system and method are provided to match the amount of insulin to the amount of PD fluid used. The bioMEMS-insulin system and method measure the glucose level of the effluent dialysis fluid leaving the patient. The measurement is then used to correctly dose insulin to the patient for the next patient PD fill. In one embodiment, when the current treatment begins, the patient is filled with fluid from a previous treatment. The effluent fluid is removed and at least a portion of it is delivered to a MEMS affinity glucose sensor, which sends a signal to a control unit that determines how much insulin to deliver to the PD supply to form the desired insulin concentration for the initial fill. A corresponding amount of insulin is then delivered to the PD fluid supply bag to produce the desired concentration.

[0041] In one embodiment, a MEMS affinity glucose sensor is used to measure glucose in the discharged effluent. In one embodiment, the effluent liquid from the cycler is pumped for discharge. The discharge line is fluidly connected to the MEMS affinity glucose sensor. The MEMS affinity glucose sensor includes a container into which a sampling line extends, wherein the sampling line may extend or branch from the discharge line. The effluent sample entering the container of the MEMS affinity glucose sensor first encounters a microfluidic path that separates the glucose molecules from the effluent liquid. In one embodiment, the glucose molecules are then weighed using a piezoelectric biosensor. The piezoelectric biosensor resonates at a frequency that is proportional to the change in the deposition rate of the glucose molecules. Using the method discussed below for A n The equation for calculating the glucose absorbed at the end of the nth cycle is used. To compensate for the glucose absorbed in the nth cycle, the insulin dose during the subsequent cycles will be administered using the equation for insulin discussed below. n +1 equation to calculate.

[0042] In one embodiment, the MEMS affinity glucose sensor includes electronics and a processor to process the raw signal from the piezoelectric biosensor and make a determination of the appropriate concentration of insulin to be prepared with the PD solution. The MEMS affinity glucose sensor may also include a user interface to indicate to the patient or a caregiver present during treatment that an appropriate insulin level has been determined. In an alternative embodiment, alternatively, one or both of the following are provided by the cycler or, possibly, a water purification device operable with the cycler: (i) electronics and a processor for processing the raw signal from the piezoelectric biosensor, or (ii) a user interface for communicating with the patient or caregiver. The PD cycler can be operated with pre-prepared PD dialysis fluid or with PD dialysis fluid prepared at the point of use. For pre-prepared PD dialysis fluid, insulin is added to the heater bag or to the insulin port on the solution bag. For PD dialysis fluid prepared at the point of use, insulin can be added to the mixed dialysis fluid or any of its components (purified water, osmotic agent, or electrolytes).

[0043] In one embodiment, the control unit of the cycler operates via a network and one or more server computers to enable a physician or clinician to view insulin usage data, for example on a per-treatment basis, so that the clinician can confirm that insulin is being delivered appropriately. In one embodiment, the data is displayed on a dashboard of a patient web page where the insulin volume and concentration of the PD fluid can be viewed. The data of the fourth main embodiment can be displayed in conjunction with the data of the first main embodiment, the second main embodiment, and / or the third main embodiment to provide a desired combination of data.

[0044] In accordance with the disclosure herein and without limiting the disclosure in any way, in a first aspect of the disclosure which may be combined with any other aspect listed herein, unless otherwise specified, a peritoneal dialysis ("PD") system comprises: a cycler including a pump actuator and a control unit in operative communication with the pump actuator; a disposable kit including a disposable cassette having a pump chamber, the disposable cassette being sized and arranged to be held by the cycler so that the pump chamber is in operative communication with the pump actuator, the disposable kit including a drain line and a patient line extending from the disposable cassette; and a temperature sensor operatively connected to one of the patient line, the drain line or the disposable cassette to sense a temperature of effluent PD fluid removed from a patient, the detected temperature being used to form a determination of peritonitis in the patient, the control unit being configured to communicate the determination of peritonitis.

[0045] In a second aspect of the present disclosure, which may be combined with any other aspect listed herein unless stated otherwise, the sensed temperature is sent to a control unit, and wherein the control unit is configured to analyze the sensed temperature.

[0046] In a third aspect of the present disclosure, which may be combined with the second aspect and with any other aspect listed herein unless otherwise stated, the sensed temperature is transmitted to the control unit by wire or wirelessly.

[0047] In a fourth aspect of the present invention, which may be combined with any other aspect listed herein unless otherwise specified, the PD system comprises a network and at least one physician or clinician computer communicating with a control unit via the network, the control unit being configured to transmit a determination of peritonitis to at least one of the patient or the caregiver via a user interface of the cycler, or to at least one physician or clinician computer via the network.

[0048] In a fifth aspect of the present disclosure, which may be combined with any other aspect listed herein unless otherwise stated, the PD system includes a water purifier configured to supply purified water to the disposable kit, the water purifier including a water purifier control unit, wherein the sensed temperature is sent to the water purifier control unit, wherein the water purifier control unit is configured to analyze the sensed temperature, and wherein the cycler control unit and the water purifier control unit communicate to allow the cycler control unit to transmit a determination of peritonitis.

[0049] In a sixth aspect of the present disclosure, which may be combined with the fifth aspect and with any other aspect listed herein unless otherwise stated, the cycler control unit or the water purifier control unit is configured to analyze the sensed temperature.

[0050] In a seventh aspect of the present disclosure, which may be combined with any other aspect listed herein unless otherwise stated, the temperature sensor is placed in a connector configured to be coupled to a patient line or a drain line.

[0051] In an eighth aspect of the present disclosure, which, unless otherwise stated, can be combined with the seventh aspect and with any other aspect listed herein, the connector (i) is a clamshell connector that fits around a patient line or a discharge line, or (ii) is configured to be engaged between two sections of a patient line or a discharge line.

[0052] In a ninth aspect of the present disclosure, unless otherwise stated, the ninth aspect may be combined with the seventh aspect and with any other aspect listed herein, unless otherwise stated, the connector includes being positioned and arranged to (a) contact effluent liquid flowing through a patient line or a drain line, or (b) directly contact a patient line or a drain line.

[0053] In the tenth aspect of the present disclosure, unless otherwise stated, the tenth aspect can be combined with the ninth aspect and with any other aspect listed herein, unless otherwise stated, in (b), the thermally conductive segment is joined between segments of the patient line or the discharge line, and the connector is directly connected to the thermally conductive segment.

[0054] In the eleventh aspect of the present disclosure, unless otherwise stated, the eleventh aspect can be combined with the ninth aspect and with any other aspect listed herein, and the connector includes a lead extending from the electrode to (i) a control unit, (ii) a control unit of a water purifier configured to supply purified water to the disposable kit, or (iii) a wireless module provided together with the connector.

[0055] In a twelfth aspect of the present disclosure, which aspect may be combined with any other aspect listed herein unless otherwise stated, the PD system is configured to analyze the sensed temperature of the effluent PD fluid removed from the patient by comparing the sensed temperature with the temperature of fresh PD fluid delivered to the patient and sensed by the temperature sensor.

[0056] In a thirteenth aspect of the present disclosure, which aspect may be combined with any other aspect listed herein unless otherwise stated, the PD system is configured to analyze the sensed temperature of effluent PD fluid removed from the patient by looking for temperature increases due to peritonitis or an episode thereof.

[0057] In a fourteenth aspect of the present disclosure, which may be combined with the thirteenth aspect and with any other aspect listed herein unless otherwise stated, an increase in temperature due to peritonitis or an onset thereof may be detected, regardless of whether the sensed temperature is offset due to detection through a patient line, a drain line, or a disposable cassette.

[0058] In the fifteenth aspect of the present disclosure, unless otherwise stated, the fifteenth aspect can be combined with any other aspect listed herein, the determination of peritonitis is a first peritonitis indicator, and it includes at least one different peritonitis indicator used in combination with the first peritonitis to form an overall peritonitis determination.

[0059] In a sixteenth aspect of the present disclosure, which may be combined with the fifteenth aspect and with any other aspect listed herein unless otherwise stated, at least one different peritonitis indicator that may be used in combination with the first peritonitis indicator is obtained from at least one of a white blood cell biosensor or a white blood cell impedance sensor.

[0060] In a seventeenth aspect of the present disclosure, which may be combined with any other aspect listed herein unless otherwise stated, determination of peritonitis is provided in conjunction with insulin infusion using feedback from a patient effluent glucose biosensor.

[0061] In an eighteenth aspect of the present disclosure, which can be combined with any other aspect listed herein unless otherwise stated, a peritoneal dialysis (PD) system comprises: a cycler including a pump actuator and a control unit in operative communication with the pump actuator; a disposable kit including a disposable cassette having a pump chamber, the disposable cassette being sized and arranged to be held by the cycler so that the pump chamber is in operative communication with the pump actuator; and a bio-MEMS device in fluid communication with the disposable cassette, the bio-MEMS device being configured to collect white blood cells from effluent PD fluid removed from a patient, the collected white blood cells being used for determination of peritonitis in the patient, the control unit being configured to transmit the determination of peritonitis.

[0062] In a nineteenth aspect of the present disclosure, unless otherwise stated, the nineteenth aspect can be combined with the eighteenth aspect and with any other aspect listed herein, an indication of the collected white blood cells is sent to a control unit, and wherein the control unit is configured to analyze the indication of the collected white blood cells.

[0063] In a twentieth aspect of the present disclosure, which may be combined with the nineteenth aspect and with any other aspect listed herein unless otherwise stated, an indication of the collected white blood cells is sent to a control unit by wire or wirelessly.

[0064] In the twenty-first aspect of the present disclosure, unless otherwise stated, the twenty-first aspect can be combined with the eighteenth aspect and with any other aspect listed herein, the PD system includes a network and at least one doctor or clinician computer communicating with the control unit via the network, and the control unit is configured to transmit the determination of peritonitis to at least one of the patient or the caregiver via the user interface of the cycler or to at least one doctor or clinician computer via the network.

[0065] In a twenty-second aspect of the present disclosure, which may be combined with the eighteenth aspect and with any other aspect listed herein unless otherwise stated, the bio-MEMS device is placed in fluid communication with the sampling port of the disposable cartridge.

[0066] In a twenty-third aspect of the present disclosure, which can be combined with the eighteenth aspect and with any other aspect listed herein unless otherwise stated, the bio-MEMS device comprises a control unit having at least one of an electronic device, a processor and a memory, wherein the cycler control unit or the bio-MEMS device control unit is configured to analyze the sensed temperature.

[0067] In a twenty-fourth aspect of the present disclosure, which can be combined with the eighteenth aspect and with any other aspect listed herein unless otherwise stated, the bio-MEMS device comprises (i) a microfluidic chip for forming a microfluidic path, the microfluidic path being sized and configured to separate white blood cells from the rest of the effluent liquid; and (ii) a piezoelectric biosensor that resonates at a frequency proportional to a property of the collected white blood cells.

[0068] In a twenty-fifth aspect of the present disclosure, which may be combined with the twenty-fourth aspect and with any other aspect listed herein unless otherwise stated, the property of the collected white blood cells comprises a change in the sedimentation rate of the white blood cells.

[0069] In a twenty-sixth aspect of the present disclosure, which can be combined with the twenty-fourth aspect and with any other aspect listed herein unless otherwise stated, a frequency proportional to a property of the collected white blood cells is used to form a determination of peritonitis.

[0070] In a twenty-seventh aspect of the present disclosure, which may be combined with the twenty-fourth aspect and with any other aspect listed herein unless otherwise stated, the piezoelectric biosensor operates with a collection area for collecting white blood cells.

[0071] In the twenty-eighth aspect of the present disclosure, unless otherwise stated, the twenty-eighth aspect can be combined with the eighteenth aspect and any other aspect listed herein, and the bio-MEMS device communicates with the control unit by wire, or includes a wireless module for wirelessly communicating with the control unit.

[0072] In a twenty-ninth aspect of the present disclosure, which may be combined with the eighteenth aspect and with any other aspect listed herein unless otherwise stated, the PD system is configured to analyze the amount of white blood cells removed from the effluent PD fluid to form a determination of peritonitis.

[0073] In the thirtieth aspect of the present disclosure, unless otherwise stated, the thirtieth aspect can be combined with the eighteenth aspect and with any other aspect listed herein, the determination of peritonitis is a first peritonitis indicator, and the system includes at least one different peritonitis indicator, and the at least one different peritonitis indicator can be used in combination with the first peritonitis indicator to form an overall peritonitis determination.

[0074] In the thirty-first aspect of the present disclosure, unless otherwise stated, the thirty-first aspect can be combined with the thirtieth aspect and with any other aspect listed herein, and at least one different peritonitis indicator that can be used in combination with the first peritonitis indicator is obtained from at least one of a patient effluent PD fluid temperature sensor or a white blood cell impedance sensor.

[0075] In a thirty-second aspect of the present disclosure, which may be combined with the eighteenth aspect and with any other aspect listed herein unless otherwise stated, determination of peritonitis is provided in conjunction with insulin infusion formed using feedback from a patient effluent glucose biosensor.

[0076] In a thirty-third aspect of the present disclosure, which can be combined with any other aspect listed herein unless otherwise stated, a peritoneal dialysis (PD) system comprises: a cycler having a pump actuator and a control unit in operative communication with the pump actuator; a disposable kit comprising a disposable box having a pump chamber, the disposable box being sized and arranged to be held by the cycler so that the pump chamber is in operative communication with the pump actuator, the disposable kit comprising a drain line and a patient line extending from the disposable box; a catheter for placement within the peritoneal cavity of a patient and in fluid communication with the patient line; and an impedance sensor operatively coupled to one of the catheter, the patient line, or the drain line to sense impedance of PD fluid residing in or removed from the patient, the sensed impedance being used to detect white blood cells to form a determination of peritonitis in the patient, the control unit being configured to transmit the determination of peritonitis.

[0077] In a thirty-fourth aspect of the present disclosure, unless otherwise stated, the thirty-fourth aspect can be combined with the thirty-third aspect and with any other aspect listed herein, the sensed impedance is sent to a control unit, and wherein the control unit is configured to analyze the sensed impedance.

[0078] In a thirty-fifth aspect of the present disclosure, which may be combined with the thirty-fourth aspect and with any other aspect listed herein unless otherwise stated, the sensed impedance is transmitted to a control unit by wire or wirelessly.

[0079] In a thirty-sixth aspect of the present disclosure, unless otherwise stated, the thirty-sixth aspect can be combined with the thirty-third aspect and with any other aspect listed herein, the PD system includes a network and at least one doctor or clinician computer communicating with the control unit via the network, and the control unit is configured to transmit the determination of peritonitis to at least one of the patient or the caregiver via the user interface of the cycler or to at least one doctor or clinician computer via the network.

[0080] In a thirty-seventh aspect of the present disclosure, unless otherwise stated, the thirty-seventh aspect can be combined with the thirty-third aspect and with any other aspect listed herein, the PD system includes a water purifier, the water purifier is configured to supply purified water to the disposable kit, the water purifier includes a water purifier control unit, wherein the sensed impedance is sent to the water purifier control unit, wherein the water purifier control unit is configured to analyze the sensed impedance, and wherein the cycler control unit and the water purifier control unit communicate to allow the cycler control unit to transmit a determination of peritonitis.

[0081] In a thirty-eighth aspect of the present disclosure, unless otherwise stated, the thirty-eighth aspect can be combined with the thirty-third aspect and with any other aspect listed herein, the impedance sensor is located within a connector, and the connector is configured to be coupled to a catheter, a patient line, or a discharge line.

[0082] In the thirty-ninth aspect of the present disclosure, unless otherwise stated, the thirty-ninth aspect can be combined with the thirty-eighth aspect and with any other aspect listed herein, the connector (i) is a clamshell connector assembled around a catheter, a patient line or a discharge line, or (ii) is configured to be engaged between two sections of a catheter, a patient line or a discharge line.

[0083] In the fortieth aspect of the present disclosure, unless otherwise stated, the fortieth aspect can be combined with the thirty-third aspect and with any other aspect listed herein, the impedance sensor includes an electrode positioned and arranged in a catheter, a patient line or a discharge line, and the connector is located above the electrode.

[0084] In the forty-first aspect of the present disclosure, unless otherwise stated, the forty-first aspect can be used in combination with the fortieth aspect and with any other aspect listed herein, the connector includes a lead extending from the electrode to (i) a control unit, (ii) a control unit of a water purifier, or (iii) a wireless module provided with the connector, and the water purifier is configured to supply purified water to the disposable kit.

[0085] In a forty-second aspect of the present disclosure, which may be combined with the thirty-third aspect and with any other aspect listed herein unless otherwise stated, the PD system is configured to analyze the sensed impedance of the PD fluid residing in or removed from the patient via a frequency scan moving from a starting frequency to a stop frequency.

[0086] In the 43rd aspect of the present disclosure, unless otherwise stated, the 43rd aspect can be combined with the 42nd aspect in combination with any other aspect listed herein, and the frequency scan is generated by a frequency generator provided by the control unit or a frequency generator operable with the control unit.

[0087] In a 44th aspect of the present disclosure, which may be combined with the 42nd aspect and with any other aspect listed herein unless otherwise stated, the PD system is configured to perform impedance measurements at two or more frequencies of a frequency sweep.

[0088] In a 45th aspect of the present disclosure, which can be combined with the 42nd aspect and with any other aspect listed herein unless otherwise stated, the frequency sweep enables determination, by measuring over at least a portion of the frequency sweep, that a fluid having white blood cells and residing in a patient, or removed from a patient, has a higher impedance than an impedance for a fluid without white blood cells, and the measured impedance for the fluid without white blood cells is (i) determined based on a standard impedance, or (ii) determined based on an impedance established for the patient.

[0089] In a forty-sixth aspect of the present disclosure, which can be combined with the forty-second aspect and with any other aspect listed herein unless otherwise stated, the frequency scan enables fluid with white blood cells and residing in a patient, or being removed from a patient, to be distinguished from fluid with fibrin, wherein the fluid with fibrin produces a higher impedance over at least a portion of the scan than the fluid with white blood cells.

[0090] In the forty-seventh aspect of the present disclosure, unless otherwise stated, the forty-seventh aspect can be combined with the thirty-third aspect and with any other aspect listed herein, the determination of peritonitis is a first peritonitis indicator, and the system includes at least one different peritonitis indicator, and the at least one different peritonitis indicator can be used in combination with the first peritonitis indicator to form an overall peritonitis determination.

[0091] In a forty-eighth aspect of the present disclosure, which can be combined with the forty-seventh aspect and with any other aspect listed herein, unless otherwise stated, at least one different peritonitis indicator that can be used in combination with the first peritonitis indicator is obtained from at least one of a patient effluent PD fluid temperature sensor or a white blood cell biosensor.

[0092] In a forty-ninth aspect of the present disclosure, which may be combined with the thirty-third aspect and with any other aspect listed herein unless otherwise stated, determination of peritonitis is provided in combination with insulin infusion using feedback from a patient effluent glucose biosensor.

[0093] In a fiftieth aspect of the present disclosure, which may be combined with the thirty-third aspect and with any other aspect listed herein unless otherwise stated, a peritoneal dialysis ("PD") system comprises: a cycler including a pump actuator and a control unit in operative communication with the pump actuator; a disposable kit including a disposable cassette having a pump chamber, the disposable cassette being sized and arranged to be held by the cycler so that the pump chamber is in operative communication with the pump actuator; an insulin source in fluid communication with the disposable kit; and a microelectromechanical system ("MEMS") affinity glucose sensor positioned and arranged to receive effluent PD fluid removed from a patient, the MEMS affinity glucose sensor being configured to provide an assessment of glucose absorbed by the patient, the glucose assessment being used to determine an insulin dose, and wherein the control unit is configured to deliver the insulin dose from the insulin source to the patient via the pump actuator operating in conjunction with the pump chamber of the disposable cassette.

[0094] In the fifty-first aspect of the present disclosure, unless otherwise stated, the fifty-first aspect can be combined with the fiftieth aspect and with any other aspect listed herein, the PD system includes a dialysis fluid source fluidly connected to the disposable kit, and wherein the control unit is configured to deliver a dose of insulin from the insulin source mixed with fresh dialysis fluid from the dialysis fluid source to the patient.

[0095] In a fifty-second aspect of the present disclosure, which may be combined with the fifty-first aspect and with any other aspect listed herein unless otherwise stated, the dialysis fluid source is a point-of-use dialysis fluid source in which fresh dialysis fluid is mixed with insulin from an insulin bag in a mixing bag.

[0096] In the fifty-third aspect of the present disclosure, unless otherwise stated, the fifty-third aspect can be combined with the fiftieth aspect and with any other aspect listed herein, the disposable kit includes a discharge line and a patient line connected to the disposable box, and the MEMS affinity glucose sensor is liquid-connected to the discharge line.

[0097] In a fifty-fourth aspect of the present disclosure, which may be combined with the fifty-third aspect and with any other aspect listed herein unless otherwise stated, the MEMS affinity glucose sensor is located upstream of the discharge container along the discharge line.

[0098] In the fifty-fifth aspect of the present disclosure, unless otherwise stated, the fifty-fifth aspect can be combined with the fiftieth aspect and with any other aspect listed herein, the PD system includes a water purifier, wherein the dialysis fluid source is a point-of-use dialysis fluid source that uses purified water from the water purifier, and wherein the MEMS affinity glucose sensor is provided together with the water purifier.

[0099] In the fifty-sixth aspect of the present disclosure, unless otherwise stated, the fifty-sixth aspect can be combined with the fifty-fifth aspect and with any other aspect listed herein, the water purifier communicates with the cycler by wire or wirelessly, wherein the water purifier is configured to determine an insulin dose based on a glucose assessment and deliver the insulin dose to the cycler for delivery.

[0100] In a fifty-seventh aspect of the present disclosure, unless otherwise stated, the fifty-seventh aspect can be combined with the fiftieth aspect and with any other aspect listed herein, the MEMS affinity glucose sensor communicates with the cycler by wire or wirelessly, wherein the control unit of the cycler is configured to determine the insulin dose based on the glucose assessment sent from the MEMS affinity glucose sensor to the control unit.

[0101] In a fifty-eighth aspect of the present disclosure, which may be combined with the fiftieth aspect and with any other aspect listed herein unless otherwise stated, the MEMS affinity glucose sensor is configured to determine insulin dosage based on glucose assessment.

[0102] In a fifty-ninth aspect of the present disclosure, which may be combined with the fiftieth aspect and with any other aspect listed herein unless otherwise stated, the glucose assessment indicates an amount or concentration of glucose absorbed by the patient.

[0103] In the sixtieth aspect of the present disclosure, unless otherwise stated, the sixtieth aspect can be combined with the fiftieth aspect and with any other aspect listed herein, the MEMS affinity glucose sensor includes (i) a microfluidic chip for forming a microfluidic path, the microfluidic path being sized and configured to separate glucose molecules from the rest of the effluent liquid, and (ii) a piezoelectric biosensor, the piezoelectric biosensor resonating at a frequency proportional to the properties of the collected glucose molecules.

[0104] In the sixty-first aspect of the present disclosure, unless otherwise stated, the sixty-first aspect can be combined with the sixtieth aspect and with any other aspect listed herein, and the properties of the collected glucose molecules include a change in the sedimentation rate of the glucose molecules.

[0105] In a sixty-second aspect of the present disclosure, which sixty-second aspect may be used in combination with the sixtieth aspect and any other aspect listed herein unless otherwise stated, a frequency proportional to a property of the collected glucose molecules is used for insulin determination.

[0106] In a sixty-third aspect of the present disclosure, which may be combined with the sixtieth aspect and with any other aspect listed herein unless otherwise stated, the piezoelectric biosensor operates with a collection region for collecting glucose molecules.

[0107] In a sixty-fourth aspect of the present disclosure, which can be combined with the fiftieth aspect and with any other aspect listed herein unless otherwise stated, the control unit is programmed to assume that the lower the glucose concentration in the effluent, the higher the amount of glucose absorbed by the patient.

[0108] In the sixty-fifth aspect of the present disclosure, unless otherwise stated, the sixty-fifth aspect can be combined with the fiftieth aspect and with any other aspect listed herein, the PD system includes a network and at least one doctor or clinician computer that communicates with the control unit via the network, and the control unit is configured to transmit the insulin dose to at least one of the patient or the caregiver via the user interface of the cycler, or to at least one doctor or clinician computer via the network.

[0109] In the sixty-sixth aspect of the present disclosure, unless otherwise stated, the sixty-sixth aspect can be combined with the fiftieth aspect and with any other aspect listed herein, the PD system includes at least one peritonitis indication device selected from a patient effluent PD fluid temperature sensor, a white blood cell biosensor or a white blood cell impedance monitor.

[0110] In a sixty-seventh aspect of the present disclosure, which may be combined with any other aspect listed herein unless otherwise stated, a peritoneal dialysis (PD) system comprises: a cycler including a pump actuator and a control unit in operative communication with the pump actuator; a disposable kit including a pump portion, the pump portion being sized and arranged to be held by the cycler so that the pump portion is in operative communication with the pump actuator, the disposable kit comprising a drain line and a patient line extending from a disposable cassette; a catheter for placement within a patient's peritoneal cavity and in fluid communication with the patient line; an impedance sensor operatively coupled to one of the catheter, the patient line, or the drain line to sense impedance of PD fluid residing in or removed from the patient, the sensed impedance being used to detect white blood cells to form a determination of peritonitis in the patient.

[0111] In a sixty-eighth aspect of the present disclosure, which can be combined with any other aspect listed herein unless otherwise stated, a peritoneal dialysis (PD) system comprises: a pump actuator and a control unit operably communicating with the pump actuator; a disposable kit including a pump portion, the pump portion being sized and arranged to operably communicate with the pump actuator, the disposable kit comprising a discharge line and a patient line extending from a disposable box; a catheter for placement within the peritoneal cavity of a patient and in fluid communication with the patient line; an impedance sensor operably coupled to one of the catheter, the patient line, or the discharge line to sense PD fluid residing in or removed from the patient at a frequency sweep moving from a starting frequency to a stopping frequency, the sensed impedance frequency sweep being used to detect white blood cells to form a determination of peritonitis in the patient.

[0112] In the sixty-ninth aspect of the present disclosure, in combination Figures 1 to 20B Any of the disclosed structures and functions may be included in the combination Figures 1 to 20B In or in combination with any of the other structures and functions disclosed.

[0113] In view of the present disclosure and the above aspects, therefore, it is an advantage of the present disclosure to provide an improved peritoneal dialysis ("PD") system and method.

[0114] Another advantage of the present disclosure is to provide a PD system and method that enables determination of peritonitis on an objective basis.

[0115] Yet another advantage of the present disclosure is to provide a PD system and method that enables automatic determination of peritonitis without placing an undue burden on the patient.

[0116] Yet another advantage of the present disclosure is to provide a PD system and method that enables determination of peritonitis by using a variety of different procedures that provide a cross-check.

[0117] Yet another advantage of the present disclosure is to provide a PD system and method for proportional insulin infusion at a desired concentration along with dialysate infusion.

[0118] Yet another advantage of the present disclosure is to provide a PD system and method that remotely transmits relevant peritonitis and insulin perfusion data to a clinician.

[0119] The advantages discussed herein may be found in one or more, but not all, of the embodiments disclosed herein.Additional features and advantages are described herein and will be apparent from the following detailed description and accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0120] Figure 1 is an elevation view of one embodiment of a peritoneal dialysis delivery system with point-of-use dialysis fluid production in communication with a remote physician or clinician data collection solution.

[0121] Figure 2 is with Figure 1 A top view of one embodiment of a disposable kit for use with the system is shown.

[0122] Figure 3 is a front view of one embodiment of a temperature sensing connector of the present disclosure.

[0123] Figure 4A and Figure 4B 1 and 2 are respectively a front view and a perspective view of another embodiment of the temperature sensing connector of the present disclosure.

[0124] Figure 5is a side view of another embodiment of a temperature sensing connector of the present disclosure.

[0125] Figure 6 is a schematic diagram of one embodiment of a wirelessly operated temperature sensing connector of the present disclosure.

[0126] Fig. 7A and 7B is a schematic diagram showing the output of various temperature sensing connectors of the present disclosure.

[0127] Fig. 8A and 8B is a schematic diagram showing the output of other temperature sensing connectors of the present disclosure.

[0128] Fig. 9 is an elevation view of a medical fluid delivery system with point-of-use dialysis fluid production, operating with one embodiment of the white blood cell sensing device of the present disclosure.

[0129] Fig.10 It is available with Fig. 9 Schematic flow chart of one embodiment of a white blood cell sensing method for use with a system.

[0130] Fig.11 is an elevation view of a medical fluid delivery system with point-of-use dialysis fluid production, operating with one embodiment of the effluent fluid impedance assessment device of the present disclosure.

[0131] Fig.12 is an isometric view of an embodiment for placing electrodes within a catheter or tube for operation with the effluent fluid impedance assessment device of the present disclosure.

[0132] Fig.13 is a front view of one embodiment of a catheter impedance effluent assessment device of the present disclosure.

[0133] Fig.14A and 14B are graphical diagrams showing impedance output over time and over a frequency sweep for normal patient effluent, patient effluent with white blood cells (indicative of peritonitis), and patient effluent with fibrin, respectively.

[0134] Fig.15 is a front view of a medical fluid delivery system operative with a pre-sterilized container of peritoneal dialysis fluid, and also operative with one embodiment of the effluent glucose sensing and insulin control apparatus of the present disclosure.

[0135] Fig.16 It is available with Fig.15 and 17 A front view of one embodiment of a MEMS affinity glucose sensor for use with the system.

[0136] Fig.17 is an elevation view of a medical fluid delivery system with point-of-use dialysis fluid production operating with one embodiment of the effluent glucose sensing and insulin control apparatus of the present disclosure.

[0137] Fig.18 It is available with Fig.15 and 16 Schematic flow chart of one embodiment of an effluent glucose sensing and insulin control method for use with a system.

[0138] Fig.19 is a schematic diagram showing the relationship between the frequency output of a MEMS affinity glucose sensor and the effluent glucose level.

[0139] Fig. 20A and 20B Figure 2 shows the patient's glucose levels during peritoneal dialysis treatment when uncontrolled and during Figures 15 to 18 Schematic diagram of glucose feedback and insulin injection to control patient glucose levels. DETAILED DESCRIPTION

[0140] System Overview

[0141] The feedback systems and methods described herein may be applied to peritoneal dialysis ("PD"). The feedback systems and methods are primarily applicable to automated peritoneal dialysis ("APD"), which involves the use of a PD machine or cycler. However, it should be understood that the feedback systems and methods are also applicable to continuous ambulatory peritoneal dialysis ("CAPD"). With CAPD, the feedback systems and methods are implemented in a stand-alone device that reads data to the patient and / or transmits the data remotely to a caregiver database for review by a physician or clinician. With respect to APD machines, suitable cyclers include, for example, the Amia 3000, sold by Baxter International Inc., and the Amia 3000, sold by Baxter International Inc. ® or HomeChoice ® Cycler. For example, Amia ® The cycler is disclosed in U.S. Pat. No. 9,981,079, and the HomeChoice ® Cycler is disclosed in U.S. Pat. No. 5,350,357, the contents of each of which are incorporated herein by reference and relied upon. Each of the incorporated patents discloses the use of containers or bags of prepackaged, presterilized PD dialysis fluid. Feedback systems and methods can be applied and implemented in cyclers that use prepackaged, presterilized PD fluid. Feedback systems and methods are also applicable and implemented in cyclers that use PD fluid performed online or at the point of use, as follows.

[0142] Reference now Figure 1 One embodiment of a peritoneal dialysis system with point-of-use dialysis fluid production is illustrated by system 10. System 10 includes a cycler 20 and a water purifier 210. With the understanding that these cyclers are provided with updated programs to execute and use point-of-use dialysis fluid produced in accordance with system 10, suitable cyclers for cycler 20 include, for example, Amia, as described above. ® or HomeChoice ® Circulator. To this end, the circulator 20 includes a control unit 22 having at least one processor and at least one memory. The control unit 22 also includes a wired or wireless transceiver for sending information to and receiving information from the water purifier 210 and other wireless devices discussed herein. The water purifier 210 also includes a control unit 212 having at least one processor and at least one memory. The control unit 212 also includes a wired or wireless transceiver for sending information to and receiving information from the control unit 22 of the circulator 20 and other wireless devices discussed herein. Wired communication can be via, for example, an Ethernet connection. Wireless communication can be via Bluetooth™, WiFi™, Zigbee ® 、Z-Wave ® , wireless Universal Serial Bus ("USB"), or infrared protocols, or via any other suitable wireless communication technology.

[0143] The cycler 20 includes a housing 24 that houses facilities programmed via the control unit 22 to prepare fresh dialysis solution at the point of use, pump the freshly prepared dialysis fluid to the patient P, allow the dialysis fluid to reside in the patient P, and then pump the spent dialysis fluid to a drain. In the illustrated embodiment, the water purifier 210 includes a drain line 214 leading to a drain 216, which can be a house drain or a drain container. In an embodiment, the facilities programmed via the control unit 22 to prepare fresh dialysis solution at the point of use include facilities for a pneumatic pumping system, including but not limited to: (i) one or more positive pressure reservoirs, (ii) one or more negative pressure reservoirs, (iii) a compressor and a vacuum pump, each of which is under the control of the control unit 22, or a single pump that generates both positive and negative pressures under the control of the control unit 22 to provide positive and negative pressures to be stored in the one or more positive and negative pressure reservoirs, (iv) a plurality of pneumatic valve chambers for delivering positive and negative pressures to a plurality of liquid valve chambers, (v) a plurality of pneumatic pump chambers , for delivering positive and negative pressures to multiple liquid pump chambers, (vi) multiple electrically actuated on / off pneumatic solenoid valves located between multiple pneumatic valve chambers and multiple liquid valve chambers under the control of control unit 22, (vii) multiple electrically actuated variable orifice pneumatic valves located between multiple pneumatic pump chambers and multiple liquid pump chambers under the control of control unit 22, (viii) a heater under the control of control unit 22 for heating the dialysis fluid when the dialysis fluid is mixed in one embodiment, and (ix) an occluder 26 under the control of control unit 22 for closing the patient line and the drain line in warning and other situations.

[0144] In one embodiment, a plurality of pneumatic valve chambers and a plurality of pneumatic pump chambers are located on the front or surface of a housing 24 of the cycler 20. A heater is located inside the housing 24 and, in one embodiment, comprises a heating coil that contacts a heater located at the top of the housing 24, under a heating cover ( Figure 1 A heating plate or tray is provided below the heating plate or tray (not shown).

[0145] The cycler 20 in the illustrated embodiment includes a user interface 30. The control unit 22 in the embodiment includes a video controller, which may have its own processor and memory, for interacting with the main control processor and memory of the control unit 22. The user interface 30 includes a video monitor 32, which may operate with a touch screen overlay placed on the video monitor 32 for inputting commands into the control unit 22 via the user interface 30. The user interface 30 may also include one or more electromechanical input devices, such as membrane switches or other buttons. The control unit 22 may also include an audio controller for playing sound files, such as voice activated commands, at one or more speakers 34.

[0146] The water purifier 210 in the illustrated embodiment also includes a user interface 220. In an embodiment, the control unit 212 of the water purifier 210 includes a video controller, which may have its own processor and memory for interacting with the main control processor and memory of the control unit 212. The user interface 220 includes a video monitor 222, which may similarly operate with a touch screen overlay placed on the video monitor 222 for inputting commands into the control unit 212. The user interface 220 may also include one or more electromechanical input devices, such as a membrane switch or other buttons. The control unit 212 may also include an audio controller for playing sound files, such as warning or alarm sounds, on one or more speakers 224 of the water purifier 210.

[0147] Additional references Figure 2 , shows an embodiment of a disposable kit 40. The disposable kit 40 is also Figure 1 4, and cooperates with the cycler 20 to move fluid within the disposable set 40, for example, to mix with the dialysis fluid as discussed herein. The disposable set 40 in the illustrated embodiment includes a disposable cassette 42, which may include a planar rigid plastic sheet covered on one or both sides by a flexible membrane. The membrane pressed against the housing 24 of the cycler 20 forms a pumping and valving membrane. Figure 2 The disposable cassette 42 is shown to include a liquid pump chamber 44 that operates with a pneumatic pump chamber located at the housing 24 of the cycler 20 and a liquid valve chamber 46 that operates with a pneumatic valve chamber located at the housing 24 of the cycler 20 .

[0148] Figure 1 and 2 The disposable set 40 is shown to include a patient line 50 extending from a patient line port of the cassette 42 and terminating in a patient line connector 52 . Figure 1 The patient line connector 52 is shown connected to a patient transfer set 54, which in turn is connected to an indwelling catheter located in the peritoneal cavity of the patient P (see Fig.11 ). The disposable kit 40 includes a drain line 56 extending from a drain line port of the cassette 42 and terminating in a drain line connector 58 . Figure 1 The drain line connector 58 is shown removably connected to the drain connector 218 of the water purifier 210 .

[0149] Figure 1 and 2The disposable kit 40 is also shown to include a heater / mixing line 60 that extends from a heater / mixing line port of the cartridge 42 and terminates at a heater / mixing bag 62, which will be discussed in more detail below. The disposable kit 40 includes an upstream water line segment 64a that extends to a water inlet 66a of a water reservoir 66. A downstream water line segment 64b extends from a water outlet 66b of the water reservoir 66 to the cartridge 42. In the illustrated embodiment, the upstream water line segment 64a begins at a water line connector 68 and is located upstream of the water reservoir 66. Figure 1 The water line connector 68 is shown removably connected to the water outlet connector 228 of the water purifier 210 .

[0150] The water purifier 210 outputs water and possibly water suitable for peritoneal dialysis ("WFPD"). However, to ensure WFPD, a sterilizing grade filter 70a is placed upstream of a downstream sterilizing grade filter 70b, respectively. The filters 70a and 70b can be placed in the water line segment 64a upstream of the water reservoir 66. The sterilizing grade filters 70a and 70b can be through filters without a drain line. Suitable sterilizing grade filters 70a and 70b can be provided by the assignee of the present disclosure. In an embodiment, only one of the upstream or downstream sterilizing grade filters 70a and 70b is required to produce a WFPD, however, two sterilizing grade filters 70a and 70b are provided in the illustrated embodiment to provide redundancy in the event that one of them fails.

[0151] Figure 2 It is also shown that a last bag or sampling line 72 may be provided extending from the sampling port of the last bag or cassette 42. The last bag or sampling line 72 terminates in a connector 74, which may be connected to a mating connector of a last fill bag of premixed dialysis fluid, or to a sample bag or other sample collection container. If desired, the last bag or sampling line 72 and connector 74 may alternatively be used for a third type of concentrate.

[0152] Figure 1 and 2 The disposable kit 40 is shown to include a first concentrate line 76 extending from a first concentrate port of the cartridge 42 and terminating in a first cartridge concentrate connector 80a, such as glucose. A second concentrate line 78, such as buffer, extends from a second concentrate port of the cartridge 42 and terminates in a second cartridge concentrate connector 82a, such as buffer.

[0153] Figure 1A first concentrate container 84a is shown containing a first concentrate, such as glucose, which is pumped from container 84a through container line 86 to a first container concentrate connector 80b mating with a first cartridge concentrate connector 80a. A second concentrate container 84b contains a second concentrate, such as a buffer, which is pumped from container 84b through container line 88 to a second container concentrate connector 82b mating with a second cartridge concentrate connector 82a.

[0154] In an embodiment, to begin treatment, the patient P loads the cassette 42 into the cycler and, in a random or specified order, (i) places the heater / mixing bag 62 onto the cycler 20, (ii) connects the upstream water line segment 64a to the water outlet connector 228 of the water purifier 210, (iii) connects the drain line 56 to the drain connector 218 of the water purifier 210, (iv) connects the first cassette concentrate connector 80a to the first container concentrate connector 80b, and (v) connects the second cassette concentrate connector 82a to the second container concentrate connector 82b. At this point, the patient connector 52 remains capped. Once fresh dialysis fluid is prepared and verified, the patient line 50 is primed with fresh dialysis fluid, after which the patient P can connect the patient line connector 52 to the transfer kit 54 for treatment. Each of the above steps can be graphically shown on the video monitor 32 and / or provided via voice guidance from the speaker 34.

[0155] For disposable kit 40, the rigid portion of the cartridge 42 can be made of, for example, a medically acceptable rigid plastic. The flexible membrane of the cartridge 42 can be made of, for example, a medically acceptable rigid plastic sheet. Any bag or container, such as the heater / mixing bag or container 62 discussed below, can be made of a medically acceptable plastic sheet.

[0156] The control unit 22 can be programmed to cause the cycler 20 to perform one or more mixing actions to help properly and evenly mix the dialysis fluid for treatment. For example, any liquid pump chamber 44 can be caused to draw a certain amount of mixed liquid (e.g., made from one or both of the first and second concentrates 84a, 84b and the WFPD) from the heater / mixing bag 62 into the pump chamber, and return this mixture to the heater / mixing bag 62, and repeat this process multiple times (described herein as a mixing sequence or "waffling"). In particular, to perform a mixing sequence, in an embodiment, the control unit 22 causes the cycler 20 to close all liquid valve chambers 46 at the cassette 42, except for the liquid valve chambers 46 leading to the heater / mixing line 60 and the heater / mixing bag 62. The liquid pump chambers 44 sequentially and repeatedly stroke: (i) pull the possibly unmixed liquid combination of WFPD and concentrate from the heater / mixing bag 62 into the pump chamber, then (ii) push the mixed WFPD and concentrate from the pump chamber back to the heater / mixing bag 62, and (iii) repeat (i) and (ii) at least once. The control unit 22 can be programmed to stroke the liquid pump chambers 44 together so that they are both pulled and pushed simultaneously, or alternatively so that one pump chamber 44 is pulled from the heater / mixing bag 62 while the other pump chamber 44 is pushed back to the heater / mixing bag 62 to create turbulence in the heater / mixing line 60.

[0157] like Figure 1 and 2 The configuration of the container or bag 62 shown to be operable with the cartridge 42 and the heater / mixing line 60 allows the WFPD from the water reservoir 66 and the concentrates from the first and second concentrate containers 84a and 84b to be at least partially mixed before entering the container or bag. Moreover, even if the cartridge 42 is not provided, the WFPD and at least one concentrate will be partially mixed in the heater / mixing line 60 before reaching the container or bag.

[0158] Figure 1It is also shown that in one embodiment the system 10 communicates with one or more caregiver servers 102 via a network 100, which in turn is placed in operable communication with one or more doctor or clinician computers 110 to 110c. In the illustrated embodiment, the network 100 is a cloud network, for example using one or more wide area networks ("WAN"), such as the Internet. The network 100 may alternatively be a more local network ("LAN"). In the illustrated embodiment, the cycler 20 of the system 10 communicates with the network 100 wirelessly via any protocol listed herein. In an alternative embodiment, the cycler 20 of the system 10 communicates with the network 100 in a wired manner, for example by using an Ethernet connection. In the illustrated embodiment, the cycler 20 of the system 10 communicates with the network 100. In an alternative embodiment, the water purifier 210 communicates with the network 100 alternatively or additionally in a wireless or wired manner. In the illustrated embodiment, one or more caregiver servers 102 communicate wirelessly with the network 100 via any protocol listed herein. In an alternative embodiment, the one or more caregiver servers 102 communicate with the network 100 in a wired manner, such as by using an Ethernet connection. In the illustrated embodiment, the doctor or clinician computers 110 to 110c communicate with the one or more caregiver servers 102 in a wired manner, such as by using an Ethernet connection. In an alternative embodiment, the doctor or clinician computers 110 to 110c communicate with the one or more caregiver servers 102 wirelessly via any of the protocols listed herein.

[0159] Temperature sensing for peritonitis

[0160] Reference now Figures 3 to 8B In one main embodiment, the temperature of spent dialysis fluid leaving a patient is measured to detect peritonitis. In healthy patients, the temperature of spent dialysis fluid is normal body temperature or about 37°C. In patients experiencing an episode of peritonitis, spent dialysis fluid leaving the patient may be at an elevated temperature. The system and method of the first embodiment measures the effluent dialysis fluid and uses that measurement to make a determination whether the patient may be experiencing an episode of peritonitis.

[0161] Temperature measurement can be performed in a number of different ways. Figure 3 The temperature sensing connector 120 is shown for reading the temperature from the patient P ( Figure 1 ) A mechanism for determining the temperature of the effluent liquid removed. The connector 120 includes a main housing 122, which may be made of any suitable medical grade material, such as a medical grade plastic. In the illustrated embodiment, the housing 122 is coupled to the patient line 50 ( Figure 1). The housing 122 includes a first port 124 that sealably receives the first engagement end 50a of the patient line 50. The first port 124 may, for example, include or be a hose barb port, or be sized to stretch the first engagement end 50a as shown. The first port 124 may alternatively be a Luer connector that connects to the mating Luer connector end 50a of the patient line 50. The housing 122 includes a second port 126 that sealably receives the second engagement end 50b of the patient line 50. The second port 126 may be a male port similar to port 124, or a female port as shown that sealably receives the second engagement end 50b via a compression fit (so that the second engagement end 50b may be fitted with an internal rigid hose barb to maintain the shape of its engagement end 50b when placed in compression). The female port 126 enables electrical leads 128a and 128b to extend outside the housing 122 in the event that an electrical signal is delivered to the control unit 22 of the cycler 10 (or the control unit 212 of the water purifier 210) via electrical wires.

[0162] Electrical leads 128a and 128b extend to probes or electrodes 130a and 130b, respectively, which contact the effluent liquid flowing through the housing 122 and provide a temperature reading of the liquid. The leads 128a and 128b and the electrodes 130a and 130b can be overmolded or adhered to the cylindrical inner surface of the housing 122. The temperature sensor of the connector 120 can be, for example, a thermocouple or a thermistor. In the illustrated embodiment, the electrodes 130a and 130b are the sensing portion of a K-type (Nichrome-Alomere) thermocouple, which generates a voltage that can be sensed and is proportional to the temperature of the effluent liquid.

[0163] Connector 120 shows a number of ways in which the generated voltage can be analyzed (as an alternative, therefore in Figure 3 Not all of the configurations shown need to be provided with connector 120, but are merely configurations that are used). In one embodiment, leads 128a and 128b carry the generated voltage back to control unit 22 of cycler 20 (or control unit 212 of water purifier 210), where the electronics and processor of the control unit processes the voltage signal that is proportional to the temperature and determines whether the generated temperature indicates peritonitis or the onset thereof.

[0164] In another embodiment (indicated by dashed lines), leads 128a and 128b carry the generated voltage to a wireless module 132 located along the exterior of the housing 122. The wireless module 132 is powered by a battery 134, such as a long-lasting lithium battery, and includes electronics configured to convert the voltage proportional to temperature into a wireless signal, which in one embodiment is wirelessly transmitted to the control unit 22 of the cycler 20. The control unit 22 of the cycler 20 processes the wireless version of the voltage proportional to temperature signal and determines whether the resulting temperature is indicative of peritonitis or the onset thereof.

[0165] Figure 3 An embodiment is shown in which a connector is engaged between two pipe segments. Figure 4A and 4B An alternative embodiment is shown in which a clamshell temperature connector 140 is instead mounted on a tubing segment, such as a portion of a patient line 50. In the illustrated embodiment, the clamshell temperature connector 140 is first directly on and in contact with the medical grade polymer or plastic of the patient line 50. In an alternative embodiment, a more thermally conductive medical grade segment 150, such as a stainless steel segment, is joined between the two polymer or plastic segments of the patient line 50. The more thermally conductive medical grade segment 150 can help achieve more accurate temperature measurements.

[0166] Figure 4A and 4B The clamshell temperature connector 140 is shown to include a housing 142 having clamshell halves 144 and 146 that, in the illustrated embodiment, are hinged together along a living hinge 148. The housing 142 is made of any suitable material, such as a medical grade plastic. In the illustrated embodiment, the housing 142 is sized to form a fit on the patient line 50 / 150.

[0167] The connector 140 includes electrical leads 152a and 152b extending to probes or electrodes 154a and 154b, respectively, which contact the patient line 50 / 150 to provide the temperature of the effluent liquid flowing through the line. The leads 152a and 152b and the electrodes 154a and 154b can be overmolded or adhered to the cylindrical inner surface of the corresponding clamshell halves 144 and 146. The temperature sensor of the connector 140 can also be a thermocouple or a thermistor. In the illustrated embodiment, the electrodes 154a and 154b are the sensing portions of a K-type (chromel) thermocouple that generates a voltage that can be sensed and indicates the temperature of the effluent liquid.

[0168] Connector 140 shows a number of ways in which the generated voltage can be analyzed (as an alternative, therefore in Figure 4A and Figure 4BNot all of the configurations shown need to have connector 140, only the configurations used). In one embodiment, leads 152a and 152b carry the generated voltage back to control unit 22 of cycler 20 (or control unit 212 of water purifier 210), where the electronics and processor of the control unit processes the voltage signal proportional to the temperature and determines whether the generated temperature indicates peritonitis or the onset thereof.

[0169] In another embodiment (indicated by the dashed lines), leads 152a and 152b carry the generated voltage to a wireless module 132 located along the exterior of the housing 142. The wireless module 132 is powered by a battery 134, such as a long-lasting lithium battery, and includes electronics configured to convert the voltage proportional to temperature into a wireless signal, which in one embodiment is wirelessly transmitted to the control unit 22 of the cycler 20. The control unit 22 of the cycler 20 processes the wireless version of the voltage proportional to temperature signal and determines whether the resulting temperature indicates peritonitis or the onset thereof.

[0170] Figure 5 Another alternative embodiment is shown, in which a snap-fit ​​temperature connector 160 is mounted on the wall of the housing 24 of the cycler 20 (or the wall of the water purifier 210), either outside or inside the machine. The snap-fit ​​temperature connector 160 includes a housing 162 that is bolted or bonded to or formed by the housing 24. The housing 162 is made of any suitable material, such as medical grade plastic. The housing 162 includes a snap-fit ​​collar 164, which, in the illustrated embodiment, is sized in combination with probes or electrodes 166a and 166b to snap fit onto the patient line 50 / 150. The C-shaped collar 164 is slightly spread apart to accept the patient line 50 / 150, and then spread apart again to release the patient line 50 / 150 once the treatment is completed.

[0171] Electrodes 166a and 166b can be overmolded or adhered into the cylindrical inner surface of the C-shaped collar 164. The temperature sensor of connector 160 can also be a thermocouple or a thermistor. In the illustrated embodiment, electrodes 166a and 166b are the sensing portion of a K-type (chrome-aluminum alloy) thermocouple, which generates a voltage that can be sensed, and the voltage indicates the temperature of the effluent liquid. In the illustrated embodiment, electrodes 166a and 166b extend to leads 168a and 168b, respectively, which carry the generated voltage through the wall of the housing 24 and reach the control unit 22 of the cycler 20 (or the control unit 212 of the water purifier 210), where the electronic device and processor of the control unit process the voltage signal proportional to the temperature and determine whether the resulting temperature indicates peritonitis or its onset.

[0172] Figure 6A wireless version of the temperature sensing of the first main embodiment is schematically shown. The patient line 50 or the thermally conductive patient line segment 150 carries the effluent liquid. The electrode E (representative of all electrodes discussed above) contacts the outer wall of the patient line 50 or the thermally conductive patient line segment 150 as shown or directly contacts the effluent liquid ( Figure 3 ). The voltage indicative of the temperature is carried to the wireless module 132 via lead L (representative of all the leads described above). The wireless module 132 is powered by a battery 134, such as a long-lasting lithium battery, and includes electronics configured to convert the voltage proportional to the temperature into a wireless signal that is wirelessly transmitted to the desired control unit.

[0173] Figure 6 Another alternative embodiment is also shown, where the electrodes E are instead located along the sheet of disposable cassette 42. Here, the electrodes E are located inside the cycler 20 and automatically align with the cassette 42 when the cassette is installed. No additional steps are required by the patient or caregiver. In this case, the wireless module 132 is not required, and instead the leads L are routed directly to the control unit 22.

[0174] As above, the test of the temperature of the effluent liquid of the patient P is used to determine whether the patient has peritonitis. The effluent liquid flows out from the patient P, passes through the patient transfer kit 54, the patient pipeline connector 52, the patient pipeline 50, the disposable kit 40, the discharge line 56, the discharge line connector 58 and the discharge connector 218 of the water purifier 210. It is expected that the temperature sensing connector 120, 140 or 160 will be placed in any of those positions, including as a component of the patient transfer kit 54, the patient pipeline connector 52 or the discharge line connector 58. In one aspect, it is advantageous to place the temperature sensing connector 120, 140 or 160 as close to the patient P as possible, such as at the patient transfer kit 54 or the patient pipeline connector 52, so as to sense the patient effluent temperature as accurately as possible. However, as shown below, temperature sensing is useful for this purpose even if the true patient body temperature is not sensed. Positioning the temperature sensing of the peritonitis along the discharge line within the water purifier 210 is advantageous if, for example, a temperature sensor is already there for other purposes, such as working with a conductivity sensor to test the conductivity of the dialysate to determine mixing accuracy.

[0175] Fig. 7A and 7B Examples from direct liquid sensing are shown (e.g., Figure 3 connector 120 ) or by a thermally conductive patient tubing segment 150 , each embodiment should read the true fluid temperature. Fig. 7A and 7BThe temperature readings for two filling phases (Fi1 and Fi2) and two discharge phases (Dr1 and Dr2) are shown respectively. Each filling phase is followed by a dwell period indicated by parallel lines. Each discharge phase is followed by the next filling phase indicated by a single vertical line.

[0176] The cycler 20 heats the fresh dialysis fluid in the heater / mixing bag 62 to body temperature or 37° C. before delivery to the patient P via the cassette 42 and the patient circuit 50. Fig. 7A and 7B In each fill phase instance, as heated fresh fluid flows through the temperature sensor, the temperature reading is at or about 37°C. The drain phase readings (Dr1 and Dr2) are readings of the effluent dialysis fluid from patient P, where the effluent fluid has been in the patient's body for a long period of time, such as at least one hour, so that the effluent fluid provides a true indication of the patient's body temperature. Fig. 7A Effluent temperature readings from a healthy PD patient are shown, where the readings may be at or slightly above body temperature, or 37°C. Figure 7B Effluent temperature readings from a PD patient who may be experiencing peritonitis or an attack thereof are shown, with the readings being significantly above body temperature, approximately 38°C in the example shown.

[0177] It may be considered to program temperature signal manipulation when evaluating temperature readings. For example, assume that the set point for generating a peritonitis alarm is 38°C. The associated processor and memory used to evaluate temperature readings may be programmed to average the temperature readings during the discharge flow of the effluent liquid past the temperature sensor. In this way, a short-term spike in temperature to 38°C does not trigger an alarm or flag. It may also be considered to look for temperature readings on multiple discharge lines (e.g., Dr1 and Dr2) and average them before making a determination whether to generate a peritonitis alarm. For example, in one embodiment, an alarm is generated at the end of a process that includes multiple effluent discharges when the total effluent temperature reading indicates peritonitis or an onset thereof, such as 38°C or higher.

[0178] Fig. 8A and 8B Example data from sensing through an embodiment of a substantially thermally non-conductive patient tubing segment 50 is shown, where the temperature reading may be lower than the true fluid temperature. Fig. 8A and 8B The temperature readings for two filling phases (Fi1 and Fi2) and two discharge phases (Dr1 and Dr2) are shown respectively. Each filling phase is followed by a dwell time indicated by parallel lines. Each discharge phase is followed by the next filling phase indicated by a single vertical line.

[0179] Since it is known that the cycler 20 heats the fresh dialysis fluid in the heater / mixing bag 62 to body temperature or 37° C. prior to delivery to the patient P via the cassette 42 and the patient line 50, Fig. 8A and 8B The temperature during the fill phase provides an accurate indication of the temperature reading offset caused by the substantially non-thermally conductive nature of the tubing (eg, polyvinyl chloride (“PVC”)) of the patient line 50. Fig. 8A and 8B In the example shown, the temperature of the heated fresh PD fluid reads 32°C, rather than the known 37°C. The associated control unit 22 or 212 thereby determines that the current offset for the current tubing under the current ambient conditions is 5°C. The associated control unit is then programmed to expect that the effluent fluid removed from a healthy patient P will have approximately the same temperature offset, i.e., approximately 32°C. The associated control unit is also programmed to determine that the patient P may have peritonitis if the temperature of the effluent fluid removed from the patient is above the compensated temperature of approximately 32°C by a predetermined amount.

[0180] exist Fig. 8A and 8B In each fill phase instance, as heated fresh fluid flows past the temperature sensor, the offset temperature reading through the substantially non-thermally conductive patient line 50 is at or about 32° C. The drain phase readings (Dr1 and Dr2) are also readings of the effluent dialysis fluid from patient P, where the effluent fluid has been in the patient's body for a long period of time, such as at least one hour, so that the temperature of the effluent fluid provides a true indication of the patient's body temperature. Fig. 8A The effluent temperature readings from a healthy PD patient are shown, where the readings may be at or slightly above the expected excursion temperature of 32°C. However, Figure 8B Shown is an effluent temperature reading from a PD patient who may be experiencing peritonitis or an attack thereof, where the reading is significantly higher than the expected excursion temperature, approximately 34°C in the example shown. Fig. 8A and 8B As an example of the expected offset of, consider again programming the temperature signal manipulation described above, for example, averaging and accumulating multiple fills and drains when evaluating the temperature reading.

[0181] exist 7A to 8BIn the example of FIG. 1 , when the associated control unit 22 or 212 determines that the patient P may be experiencing peritonitis or an onset thereof, the control unit, in one embodiment, causes the user interface 30 and / or 220 to provide an audible, visual, or audio-visual alarm to the patient P and / or caregiver listener at the cycler 20 and / or water purifier 210 of the system 10. In one embodiment, even if the control unit evaluating the temperature reading for determining peritonitis is the control unit 212 of the water purifier 210, an audible, visual, or audio-visual alarm is provided at the user interface 30 of the cycler 20 via wired or wireless communication from the control unit 212 of the water purifier 210 to the control unit 22 of the cycler 20 to notify the alarm condition. In this manner, the user interface 30 is the primary communication tool for a given treatment and patient P, and wherein the user interface 220 is relegated to displaying information related to the water purifier.

[0182] In addition or possibly alternatively to providing an alert to the patient P or a caregiver at the user interface 30 of the cycler 20, the control unit 22 (or possibly the control unit 212) operates via the network 100 and one or more caregiver server computers 102 to enable a physician or clinician to receive and view effluent temperature data at one or more clinician computers 110a to 110c, for example on an ongoing basis, so that the physician or clinician can determine whether the patient has peritonitis or is at risk of developing peritonitis. In one embodiment, the data is displayed on the clinician computers 110a to 110c via a web dashboard for the patient, wherein when the temperature data is elevated, the temperature data may be marked with a marker for the clinician indicating peritonitis.

[0183] It is contemplated that the effluent temperature data for patient P is sent after each treatment, regardless of whether the data indicates peritonitis. In this manner, a physician or clinician is able to develop a pattern or curve of effluent temperature for a patient. It is contemplated that the website develops a graph or trend of effluent temperature plotted against treatment date, which may be displayed, for example, as required by the case, in addition to the dashboard. In one embodiment, the trend, as well as the dashboard pinpointing, may indicate or flag temperature entries for peritonitis or an episode thereof. Thus, a physician or clinician, by viewing multiple flagged peritonitis days, may determine with reasonable certainty that a patient requires treatment.

[0184] BioMEMS Sensing for Peritonitis

[0185] Now refer to Fig. 9 and Fig.10 In a second main embodiment, a bio-microelectromechanical system ("bio-MEMS") sensor is used to detect peritonitis. The bio-MEMS sensor is used to look for the presence of white blood cells from the patient in the effluent fluid, which is an indicator of peritonitis. Fig. 9In one embodiment, effluent fluid from patient P is pumped via patient line 50 to cartridge 42 loaded into cycler 20, and thereafter pumped from cartridge 42 to the drain of water purifier 210 via drain line 56. In one embodiment, drain line 56 is connected to a lab-on-a-chip diagnostic test or bio-MEMS device 170. However, in Fig. 9 In the illustrated embodiment, an alternative is shown in which the effluent liquid is selectively pumped to the lab-on-a-chip diagnostic test device 170 via an additional sampling port 48 and sampling line 158. The use of the sampling port 48 enables the control unit 22 of the cycler 20 to selectively deliver a desired amount of effluent liquid from the patient P to the lab-on-a-chip diagnostic test device 170 at a desired time and / or frequency.

[0186] like Fig. 9 As shown, the lab-on-a-chip or bio-MEMS device 170 includes a container 172 to which the sampling line 158 extends and is connected (e.g., via a compression fitting, a threaded fitting, a Luer fitting, a hose barb connection, or a combination thereof) to an inlet line 174 located within the container 172. The container 172 can be made of a medically acceptable metal or polymer, such as stainless steel or a plastic such as PVC.

[0187] The effluent sample travels along the inlet line 174 of the bioMEMS device 170 to a microfluidic path 178 formed on or in a container 172 of a microfluidic chip 176. In various embodiments, the microfluidic chip 176 is made of an inorganic material, a polymer material, or paper. In various embodiments, the microfluidic chip 176 is made of silicon, glass, a polymer substrate, a composite material, or paper. The microfluidic path 178 is sized and configured to separate the patient's white blood cells from the rest of the effluent liquid.

[0188] The separated white blood cells are then delivered to a collection area 180 (in various embodiments, made of the same material as the container 172 or microfluidic chip 176), where they are weighed or otherwise quantified by a piezoelectric biosensor 182. In various embodiments, the piezoelectric sensor 182 uses the piezoelectric effect to measure changes in pressure, strain, or force due to the collected white blood cells by converting these changes into electrical charge. In an embodiment, the piezoelectric biosensor 182 resonates at a frequency that is proportional to the change in the sedimentation rate of the white blood cells.

[0189] In the illustrated embodiment, the bio-MEMS device 170 includes a control unit 184 having electronics, a processor, and a memory to convert the resonant frequency from the biosensor 182 into a quantified number representing the number of white blood cells removed from the patient's effluent sample. The control unit 184 may also include a user interface 186 that displays an audio, visual, or audio-visual message to the patient or caregiver to indicate the presence or absence of white blood cells, and therefore the presence or absence of peritonitis or its onset.

[0190] Alternatively, if Fig. 9 As shown, the bio-MEMS device 170 includes an electronic device configured to convert a voltage proportional to the number of white blood cells into a wireless signal, which in one embodiment is wirelessly transmitted to the control unit 22 of the cycler 20. Here, the user interface 186 is not required, and the user interface 30 of the cycler 20 is used instead. The processor and memory of the device 170 may also not be required.

[0191] Fig.10 Method 190 summarizes the method just described. At oval 192, method 190 begins. At box 194, effluent discharge from patient P is collected, for example, via the separate sampling port 48 of the cartridge 42 and the sampling line 158 discussed above. At box 196, white blood cells, if present, are separated from the patient's effluent fluid, for example, via the microfluidic chip 176. At box 198, the separated white blood cells are weighed or quantified, for example, via the piezoelectric biosensor 182. At box 200, the weight of the white blood cells is converted into an electrical signal, for example, via the piezoelectric biosensor 182. At box 202, the electrical signal is processed into a form that can be used by the control unit 22 (of the cycler 20) or the control unit 184 (of the bioMEMS device 170) to determine whether the number of white blood cells collected is indicative of peritonitis or the onset thereof. There may be a certain number of white blood cells below which it will be assumed that peritonitis is not present. At box 204, the results of the white blood cell analysis are displayed at the user interface 30 (of the cycler 20) or the user interface 186 (of the bio-MEMS device 170), and the patient or caregiver is alerted if necessary. At oval box 206, the method 206 ends.

[0192] Although in Fig. 9The network 100, one or more caregiver server computers 102, and one or more clinician computers 110a to 110c are not shown in the figure, but they may still exist. And, in addition to or in lieu of providing an alert to the patient P or the caregiver at the user interface 30 or the user interface 186, the control unit 22 operates via the network 100 and the one or more caregiver server computers 102 to enable a doctor or clinician at one or more clinician computers 110a to 110c to receive and view the effluent white blood cell collection data, for example, on an ongoing basis, so that the doctor or clinician can determine whether the patient has peritonitis or is at risk of peritonitis. In one embodiment, the data is displayed on the clinician computers 110a to 110c via a dashboard of a web page for the patient, wherein when the effluent white blood cell collection data is elevated, a marker for the clinician indicating peritonitis can be provided.

[0193] It is contemplated that the effluent leukocyte collection data of patient P is sent after each treatment, regardless of whether the data indicates peritonitis. In this way, a doctor or clinician is able to develop a pattern or curve of effluent leukocyte collection data for a patient. It is also contemplated that a website develops a chart or trend of effluent leukocyte collection volume plotted relative to treatment date, which can be displayed, for example, on request, in addition to the dashboard. In one embodiment, the trend and dashboard indicate or mark leukocyte collection entries that may indicate peritonitis or its onset. Therefore, by viewing multiple marked peritonitis dates, a doctor or clinician can determine with reasonable certainty that a patient needs treatment. Alternatively or in addition to the effluent temperature data of the first main embodiment, the leukocyte collection data of the second main embodiment can be displayed. Providing both leukocyte collection data and effluent temperature data enables a doctor or clinician to view and analyze a variety of peritonitis indicators in order to make a medical judgment for the patient.

[0194] In an alternative embodiment, the bio-MEMS device 170 is instead located in the patient line 50 via a sampling line and used to analyze the effluent returning from the patient P. In this way, the bio-MEMS device can additionally be used to sense fresh dialysis fluid delivered to the patient if desired. Alternatively, the control unit 20 can be programmed to periodically send fresh dialysis fluid to the bio-MEMS device 170 via the sampling port 48 of the cassette 42 and the sample line 158 to sample the desired properties of the fresh dialysis fluid.

[0195] Impedance Monitoring for Peritonitis

[0196] Reference now Figures 11 to 13In a third main embodiment, an impedance monitor is used to detect peritonitis. The impedance monitor is used to look for the presence of white blood cells in the patient's effluent fluid, which is also an indicator of peritonitis. In various embodiments, the impedance monitor can be placed anywhere that the patient's effluent fluid can be sensed, for example, in the patient's indwelling catheter, in the patient's line, or anywhere in the drain line. In any of these locations, the catheter or line is equipped with electrodes in any of the ways discussed above for temperature sensing, for example, but the purpose now is to connect conductive contacts to the effluent dialysis fluid for impedance detection.

[0197] Fig.11 The impedance monitor 230 is shown placed in multiple positions. In the first position, the impedance monitor 230 is placed along the indwelling catheter 55 of the patient P, which is connected to the patient transfer kit 54 and is in fluid communication with the patient line 50. In the second position (not shown), the impedance monitor 230 is placed along the patient line 50. In the third position (not shown), the impedance monitor 230 is fixed within the cycler 20 and is positioned so as to operate with the disposable cassette 42 or the line extending from the disposable cassette 42 (patient line or drain line). In the fifth position, the impedance monitor 230 is positioned along the drain line 56 between the cycler 20 and the water purifier 210. In the sixth position, the impedance monitor 230 is fixed within the water purifier and is positioned along the drain line extending within the water purifier. In any of the above positions, the impedance monitor 230 is capable of sensing effluent fluid to detect peritonitis.

[0198] Fig.12 and 13 One embodiment of an impedance monitor 230 is shown. Fig.12 In one embodiment, cylindrical electrodes 240 and 244 are shown to be mounted within the patient line 50, the patient's indwelling catheter 55, or the drainage line 56. In the illustrated embodiment, the cylindrical electrodes 240 and 244 are tubular segments or sections having an outer diameter slightly larger than the inner diameter of the line 50, 56, or catheter 55, so that the electrodes 240 and 244 are press-fitted at the desired location within the line 50, 56, or catheter 55. The electrodes 240 and 244 are made of conductive and medically safe materials, such as stainless steel, titanium, and combinations and alloys thereof. The electrodes 240 and 244 in the illustrated embodiment each include a female port or socket 242 and 246, respectively, which is configured to receive and hold a lead extending from the port.

[0199] Fig.13 The female ports or sockets 242 and 246 in one embodiment are shown extending through the tubing 50, 56 or conduit 55 so that the tubing or conduit wall seals around the female ports or sockets 242 and 246. Alternatively, Fig.12The ports or sockets are shown extending so as to be at least substantially flush with the exterior of the tubing 50, 56 or catheter 55. In either embodiment, the outer diameter of the ports or sockets 242 and 246 is larger than the hole created in the tubing 50, 56 or catheter 55 so that the tubing or catheter material is forced to stretch and seal the ports. In another alternative embodiment (not shown), the ports or sockets 242 and 246 do not extend outwardly from the cylindrical electrodes 240 and 244, but instead pierce the lead through the tubing 50, 56 or catheter 55. Here, the tubing 50, 56 or catheter 55 helps to keep the lead in place.

[0200] Fig.13 Conductive leads 248a and 248b are shown extending from ports or sockets 242 and 246, respectively. Figures 3 to 4B In one embodiment, the leads 248a and 248b of the impedance monitor 230 extend to the control unit 22 of the cycler 20 (or the control unit 212 of the water purifier 210), wherein the electronics and processor of the control unit enable the signal generation and processing discussed below to be performed. In an alternative embodiment (indicated by the dashed lines), the leads 248a and 248b receive power from the wireless module 132 located along the exterior of the housing 232 of the impedance monitor 230 and / or carry the generated voltage to the wireless module 132. The wireless module 132 is also powered by a battery 134, such as a long-lasting lithium battery, and includes electronics configured to convert the voltage into a wireless signal or vice versa, which, in one embodiment, is wirelessly communicated to the control unit 22 of the cycler 20.

[0201] The housing 232 may have clamshell halves 234 and 236 that are connected along the Figure 4A and 4B In the illustrated embodiment, the housing 232 is sized to form an assembly on the patient line 50, catheter 55, or discharge line 56. The housing 232 is sized to fit over the patient line 50, catheter 55, or discharge line 56. Figure 3 The temperature sensing connector 120 in the same or similar manner is alternatively engaged between two sections of the patient line 50, catheter 55, or discharge line 56. In any of the above embodiments, the housing 232 is made of any suitable material, such as medical grade plastic.

[0202] In one embodiment, the control unit 22 (of the cycler 20) or the control unit 212 (of the water purifier 210) controls the impedance monitor 230 so that an electrical frequency sweep is generated in the effluent liquid. The control unit may include or operate with a frequency sweep generator that moves from a starting frequency to a stopping frequency at a specified sweep rate. It is contemplated that the frequency may be swept up or down at linear or logarithmic intervals. It is also contemplated that the control unit may be programmed to sweep a sine wave, a square wave, a pulse wave, a ramp wave, a triangle wave, or an arbitrary waveform. It is also contemplated that a hold time and a return time may be specified, during which the sweep is held at the stopping frequency, and during which the frequency changes linearly from the stopping frequency to the starting frequency.

[0203] As the impedance monitor 230 steps through the swept frequencies, the resulting impedance of the effluent fluid in the indwelling catheter is measured at each different frequency. The impedance of the effluent fluid can be compared to the impedance of the fresh dialysate fluid to determine if a difference occurs. In one embodiment, impedance spectroscopy (or obtaining complex impedance) provides additional details about the contents of the effluent fluid. For example, the electrical properties of fibrin (normal, not indicative of peritonitis) may be different from the electrical properties of white blood cells (indicative of peritonitis). Once the control unit 22 (of the cycler 20) or the control unit 212 (of the water purifier 210) learns the electrical properties of different substances that may be present in the effluent fluid, these properties can be programmed into the control unit and then used to determine if anything is entrained in the effluent dialysate stream.

[0204] Fig.14A and 14B Exemplary plots of impedance (Z) measured in Ohms (Ω) are shown for normal patient effluent, patient effluent with white blood cells (indicative of peritonitis), and patient effluent with other particulates such as fibrin. Fig.14A Impedance measurements over time are shown, which can be continuous or discrete (depending on the command). Example output based on time shows continuous data for (A) normal effluent impedance (continuous line only) and (C) effluent with increased fibrin content (dashed line), for example, during the dwell phase of a patient's peritoneal dialysis treatment. In the example shown, impedance over time for effluent with normal fibrin (A) and effluent with increased fibrin (C) Figure 1 The impedance of the effluent with increased fibrin then rises significantly above the impedance of the effluent with normal fibrin. It is expected that the curve for the onset of peritonitis will be represented by a line extending in the area marked (B), between the effluent with normal fibrin (A) and the effluent with increased fibrin (C), which is already in the Fig. 14B was confirmed. Fig. 14B It was shown that as the patient's residence phase progressed, a clear difference emerged between the effluent with normal fibrin and the effluent with increased fibrin.

[0205] Fig. 14B Shows the corresponding Fig.14A The impedance spectrogram of the curve shown in the time-based graph of . The example frequency-based output shows the following continuous data: (a) normal effluent impedance (continuous line only), (b) peritonitis episode resolved by antibiotics (solid line with squares), and (c) effluent with increased fibrin content (dashed line), with the data at the points highlighted in the left frame. The spectrograms (a) to (c) cover the 10 Hz to 10 6 Frequency range of Hz.

[0206] Fig. 14B The frequency-based example output of shows that there are likely one or more frequency ranges where the impedance difference between the effluent with white blood cells (b) and the normal effluent (a) is more pronounced than at other frequencies. Fig. 14B , there are two such frequency ranges, between f1 and f2 and between f3 and f4. Having multiple distinct frequency ranges enables the control unit 22 or 212 to cross-check the results of one range with the results of another range. If both or all frequency ranges indicate peritonitis, the control unit 22 or 212 (or the clinician computers 110a to 110c) outputs a determination that the patient has or is beginning to experience peritonitis to the user interface 30, the user interface 220, and / or to the clinician computers 110a to 110c via the network 100 and the care server computer 102. In another embodiment, the control unit 22 or 212 integrates the area under the impedance curve (b) and compares it to the integral of the area under the impedance curve (a) to determine peritonitis or its onset.

[0207] In one embodiment, the curve (a) for normal effluent is empirically determined via testing of multiple patients and then averaged to develop a standardized impedance value over the frequency sweep range. In an embodiment, a standardized value is determined for each popular and most commonly used glucose level peritoneal dialysis fluid, since the impedance may vary based on the starting glucose level. The standardized impedance values ​​may be provided as a range to account for different residence times, different effluent temperatures, and other factors.

[0208] In another embodiment, a curve (a) for normal effluent is determined for a particular patient, again empirically but here by using the system 10 and cycler 20. Impedance data is acquired over multiple treatments or over all treatments. A normal effluent impedance average is formed, which may be a rolling average that is shifted or offset over time. In one embodiment, when the impedance over the frequency range of interest, or the impedance averaged by integration, is some predetermined percentage higher than the patient-specific curve (a), it is determined that a curve (b) for peritonitis effluent is present.

[0209] Curves for increasing fibrin content (c), Fig. 14B It is shown that there are one or more specific frequency ranges between f1 and f2 in which the impedance of the effluent with white blood cells indicating peritonitis (b) is significantly higher than the impedance of the effluent with increased fibrin (c). Fig. 14B The most important range is arguably between the frequency ranges f1 and f2, since the impedance increase between the frequency ranges f3 and f4 may be due to effluent having white blood cells indicating peritonitis (b) or effluent having increased fibrin (c).

[0210] Alternatively or additionally, it may be considered that the control unit 22 or 212 (or clinician computer 110a to 110c) observes the shape of the impedance curve over the entire frequency range. If the shape is closest to curve (a), the control unit 22 or 212 (or clinician computer 110a to 110c) determines that the patient effluent is normal. If the shape is closest to curve (b), the control unit 22 or 212 (or clinician computer 110a to 110c) determines that the patient effluent shows signs of peritonitis or an onset thereof. If the shape is closest to curve (c), the control unit 22 or 212 (or clinician computer 110a to 110c) determines that the patient effluent has an increased level of fibrin.

[0211] In any embodiment where the impedance monitor 230 is located remotely from the cycler 20 or water purifier 210, the impedance monitor can transmit the measured signal to the cycler in a wired or wireless manner for interrogation. The impedance monitor 230 as described above has the ability to transmit a frequency sweep into the effluent liquid, and thus can receive power from the cycler or water purifier via the battery 134 (in a wireless embodiment) or via a power cord.

[0212] As described above, in an alternative embodiment, the impedance monitor 230 is located within the cycler 20 or water purifier 210. In this case, the impedance monitor 230 transmits a frequency sweep into the effluent liquid by receiving power from the cycler or water purifier via a power cord. As described above, the impedance monitor 230 can operate with the disposable cartridge 42 loaded in the cycler 20. Here, the impedance monitor 230 can extend through a rigid wall that holds the disposable cartridge sheet in one or more positions.

[0213] In one embodiment, the control unit 22 or 212 is programmed to alert the patient or caregiver on the user interface 30 of the cycler 20 if white blood cells indicative of peritonitis are detected. In one embodiment, even if the control unit evaluating the impedance scan readings for white blood cells is the control unit 212 of the water purifier 210, an audio, visual, or audio-visual alarm is still provided at the user interface 30 of the cycler 20 to notify the alarm state through wired or wireless communication from the control unit 212 of the water purifier 210 to the control unit 22 of the cycler 20. In this way, the user interface 30 is the primary communication tool for a given treatment and patient P, and wherein the user interface 220 is relegated to displaying water purifier related information.

[0214] In addition to or in lieu of providing an alert to the patient P or caregiver on the user interface 30, the control unit 22 operates via the network 100 and one or more caregiver server computers 102 to enable a physician or clinician at one or more clinician computers 110a to 110c to receive and view impedance-derived effluent white blood cell data, for example, on an ongoing basis, so that the physician or clinician can determine whether the patient has peritonitis or is at risk for peritonitis. In one embodiment, the data is displayed on the clinician computers 110a to 110c via a dashboard of a web page for the patient, wherein when the effluent white blood cell collection data is elevated, a marker for the clinician can be provided to the data indicating peritonitis.

[0215] It is contemplated that the effluent white blood cell data obtained for the impedance of the patient P is sent after each treatment, regardless of whether the data indicates peritonitis. In this way, the doctor or clinician is able to develop a pattern or curve of the effluent white blood cell data for the patient. It is also contemplated that the web page develops a chart or trend of the number of effluent white blood cells plotted relative to the treatment date, for example, in addition to the dashboard, the chart or trend can be displayed on demand. In one embodiment, the trend and the beginning or mark of the dashboard may indicate peritonitis or the onset of white blood cell entries. Therefore, a doctor or clinician who views multiple marked peritonitis days can determine with reasonable certainty that the patient needs treatment. The white blood cell data of the third main embodiment can replace the white blood cell collection data of the second main embodiment and / or the effluent temperature data of the first main embodiment or be displayed in addition. Providing both the white blood cell data embodiment and the effluent temperature data enables the doctor or clinician to view and analyze a variety of peritonitis indicators in order to make a medical judgment for the patient.

[0216] For blood sugar control in patients with diabetes

[0217] Now refer to Figures 15 to 20B In a fourth main embodiment, system 10 provides a MEMS affinity glucose sensor 250 that matches or helps match the amount of insulin provided to patient P with the amount of glucose delivered to the patient during treatment. FIG. 14 shows a version of system 10 that uses pre-prepared PD liquids in containers or bags 94a and 94b, rather than alternatively making the PD liquids on-line or at the point of use by using glucose, concentrate 84a, buffer concentrate 84b, or purified water from water purifier 210 and stored in water reservoir 66, as in Figure 1 , 9 , 11 and 15. However, in either version, the patient P receives glucose from the PD liquid. That is, the pre-prepared PD liquid in the containers or bags 94a and 94b includes glucose at a level prescribed by a physician or clinician. It should be understood that any of the main embodiments discussed herein can be alternatively provided by using the pre-prepared PD liquid version of the system 10 shown in FIG.

[0218] Fig.15 In one embodiment of pre-prepared PD fluid, in a point of use example, an insulin container or bag 90 is connected to a port of the cassette 42, which is connected to the water reservoir 66. A MEMS affinity glucose sensor 250 is provided in the drain line 56 upstream of the drain bag 96. The MEMS affinity glucose sensor 250 measures the glucose level of the effluent dialysis fluid leaving the patient P via the drain line 56.

[0219] Fig.16In one embodiment, a MEMS affinity glucose sensor 250 is shown to include a container 252 into which a sampling line 254 extends, wherein the sampling line 254 may extend or branch from the discharge line 56. An effluent sample entering the container 252 of the MEMS affinity glucose sensor 250 first encounters a microfluidic path 256 that separates glucose molecules from the effluent liquid. The glucose molecules are then weighed using a piezoelectric biosensor 258 in the illustrated embodiment. The piezoelectric biosensor 258 includes a cantilever 260 that resonates at a frequency that is proportional to the change in the deposition rate of the glucose molecules. Fig.18 The relationship between the resonant frequency and the glucose found in the effluent liquid is shown. The glucose absorbed at the end of the nth PD cycle is calculated using A discussed below. n To compensate for the glucose absorbed in the nth PD cycle, the I n+1 The equation was used to calculate insulin dosing during the subsequent n+1 PD cycles.

[0220] In one embodiment, the MEMS affinity glucose sensor 250 includes electronics and a processor to process the raw signal from the piezoelectric biosensor 258 and determine the appropriate concentration of insulin to be prepared with the PD solution. The MEMS affinity glucose sensor 250 may also include a user interface to indicate to the patient or a caregiver present during treatment that the appropriate insulin level is being determined. In alternative embodiments, one or both of the following may be provided alternatively by a control unit of the cycler 20 or a water purifier 210 operable with the cycler: (i) electronics and processing for processing the raw signal from the piezoelectric biosensor 258, or (ii) a user interface for communicating with the patient or caregiver.

[0221] Fig.15 The MEMS affinity glucose sensor 250 in the device 250 includes a wireless module 132 positioned along the exterior of the housing of the device 250. As described herein, the wireless module 132 is powered by a battery 134, such as a long-lasting lithium battery, and includes electronics configured to convert the measured patient effluent glucose level into a wireless signal, which, in one embodiment, is wirelessly transmitted to the control unit 22 of the cycler 20. The control unit 22 of the cycler 20 processes the glucose level wireless signal and determines the amount of insulin from the insulin container or bag 90 to be delivered to the heater bag 62 for the next patient PD fill. It should be noted that the patient P is sometimes filled with fluids from a previous treatment when starting a current treatment.

[0222] The amount of insulin to be delivered is based on a desired insulin concentration that is correlated to the amount of glucose sensed via sensor 250 and sent to control unit 22. Knowing the desired insulin concentration and the amount of fresh pre-prepared PD liquid from one of the containers or bags 92a or 92b to be delivered to heater bag 62, the amount of insulin delivered from container or bag 90 to heater bag 62 can be determined and then pumped to heater bag 62 via liquid pump chamber 44 of disposable cassette 42. In an alternative embodiment, the amount of insulin is alternatively pumped from insulin container or bag 90 to container or bag 92a or 92b of pre-prepared PD liquid via liquid pump chamber 44 of disposable cassette 42 or via a separate pump (not shown). Insulin ports may be provided on pre-prepared PD liquid containers or bags 92a and 92b to receive insulin.

[0223] Fig.15 It is also shown that in one embodiment, the system 10 in which the MEMS affinity glucose sensor 250 is used also includes a glucose sensor 262, which is applied to the finger of the patient P, for example. Such glucose sensors are known in the art as acupuncture or non-acupuncture forms. In the illustrated embodiment, the glucose sensor 262 outputs the glucose reading wirelessly to the control unit 22, the control unit 212, or the MEMS affinity glucose sensor 250. Wired communication between the glucose sensor 262 and the control unit 22, the control unit 212, or the MEMS affinity glucose sensor 250 is also possible. In one embodiment discussed below, the reading from the glucose sensor 262 is used at the beginning of treatment to determine the amount of insulin to be injected in the next PD filling cycle. The reading from the glucose sensor 262 can also be used to confirm at the end of treatment: the blood sugar level of the patient P has been kept within the safety belt by using the glucose feedback and insulin injection of the present disclosure. All of this information can also be sent to the clinician computer 110a to 110c via the network 100 and one or more caregiver server computers 102.

[0224] exist Fig.17The MEMS affinity glucose sensor 250 in the point-of-use preparation version is located within the water purifier 210 in the illustrated embodiment, with electrical output to the control unit 212 of the water purifier 210, and therefore does not require a wireless module 132 positioned along the exterior of the housing of the sensor 250. The control unit 212 of the water purifier 210 processes the glucose level signal from the MEMS affinity glucose sensor 250 and determines the amount of insulin from the insulin container or bag 90 that should be delivered by the cycler 20 to the heater / mixing bag 62 for the next patient PD fill. It should be noted that at the start of the current treatment, the patient P is typically filled with fluids from the previous treatment. The amount of insulin delivered is again based on the desired insulin concentration, which is associated with the amount of glucose sensed via the device and sent to the control unit 212. Knowing the desired insulin concentration and the amount of fresh pre-prepared PD liquid to be mixed in-line and delivered to the heater / mixing bag 62, the amount of insulin to be delivered from the container or bag 90 to the heater / mixing bag 62 can be determined and then pumped to the heater / mixing bag 62 through the liquid pump chamber 44 of the disposable cassette 42. In one embodiment, the control unit 212 of the water purifier determines the amount of insulin to be pumped, sends the amount by wire or wirelessly to the control unit 22 of the cycler 20, where the control unit 22 uses the amount to command the pump chamber 44 of the disposable cassette 42 to pump the desired amount of insulin. In another embodiment, the control unit 212 relays the glucose signal from the bio-MEMS glucose measurement device 250 by wire or wirelessly to the control unit 22, which determines the amount of insulin to be pumped and uses the amount to command the pump chamber 44 of the disposable cassette 42 to pump the desired amount of insulin.

[0225] The control unit 22 operates via the network 100 and one or more care servers 102 to enable a doctor or clinician at one or more clinician computers 110a to 110c to view insulin usage data, for example, on a per-treatment basis, so that the clinician can confirm whether insulin is properly delivered. In one embodiment, the data is displayed on a dashboard of a web page for the patient, where insulin volume and concentration can be viewed. The data of the first main embodiment can be combined with the data of the first, second and / or third main embodiments and displayed on a doctor or clinician web page for the patient P to provide the required data combination. Fig.17 Also shown is system 10 that uses MEMS affinity glucose sensor 250 in one embodiment also includes glucose sensor 262, which is provided and used as above.

[0226] Reference now Fig.18, method 290 summarizes one embodiment of the closed-loop insulin delivery just described. At oval 292, method 290 begins. At box 294, the cycler 20 actuates the disposable cassette 42 to (i) draw fresh dialysis fluid (pre-prepared or made at the point of use) from the (pre-prepared) heater bag 62 or (point of use) heater / mixing bag 62, and the calculated dose of insulin from the insulin bag or container 90, and (ii) push the heated fresh dialysis fluid and insulin dose fluid into the patient P. At box 296, the dialysis fluid is allowed to reside in the peritoneum of the patient P for the time prescribed by the physician / clinician. At box 298, the cycler 20 actuates the disposable cassette 42 to pull the spent dialysis fluid or effluent out of the peritoneum of the patient P, through the patient line 50, into the disposable cassette 42, and from the disposable cassette 42 into the drain line 56, to the drain bag 96 (Figure 14) or the drain port 216 (at the water purifier 210) Fig.15 ). The MEMS affinity glucose sensor 250 is located somewhere along the discharge line, as shown in Figures 14 and 15. At box 300, the MEMS affinity glucose sensor 250 monitors the effluent PD liquid for the amount of glucose or glucose concentration absorbed by the patient. At box 302, the MEMS affinity glucose sensor 250 or the control unit 22 of the cycler 20 or the control unit 212 of the water purifier 210 calculates an insulin dose based on the amount of glucose or concentration absorbed by the patient P. In an embodiment, if the control unit 22 of the cycler 20 does not calculate the insulin dose, the calculated dose is sent to the control unit 22 of the cycler 20.

[0227] At diamond 304, if there is another cycle in the current therapy, the method 290 returns to box 294 and the control unit 22 of the cycler 20 provides the next patient fill by using the new calculated insulin dose based on the new monitored amount or concentration of absorbed glucose. At diamond 304, if there is not another cycle in the current therapy, the method 290 moves to box 306 and saves the new calculated insulin dose for the first fill of the next therapy based on the newly monitored amount or concentration of absorbed glucose. At oval 308, the method 290 ends.

[0228] It should be understood that method 290 is applied to PD treatments that do not provide a "last fill" of fresh PD fluid, which is carried by the patient across the date to the next PD treatment (possibly swapped between dates). That is, patient P leaves the treatment empty. When a "last fill" is provided, then method 290 instead advances to discharge box 298 after starting at oval box 292 to discharge the effluent fluid of the "last fill" from the patient, then advances to monitoring box 300, then advances to calculation box 302, and then fills fresh fluid at insulin dose box 294. After the insulin dose box 294 is filled with fresh fluid, a determination diamond box is instead provided, wherein the determination is whether there is another patient discharge. If so, the modified method advances to the resident box 296, and then returns through boxes 298, 300, 302 and 294. When there are no additional patient discharges, the modified method ends at oval box 308. Because the first step of the next therapy is to drain the patient P, the insulin dose storage block 306 is not required in the "last fill" method.

[0229] Fig.19 An exemplary relationship between glucose absorbed in the effluent liquid and the resonant frequency of the cantilever 260 from the biosensor 258 is shown. In the exemplary graph, the effluent liquid without glucose absorption (continuous line) resonates at a frequency ratio of about 0.66 and produces an output amplitude that is approximately (i) twice that of the effluent liquid absorbed at a glucose concentration of X1 mg / dL that resonates at a frequency ratio of about 0.8 (solid line with squares), and (ii) two-thirds greater than the effluent liquid absorbed at a glucose concentration of X2 mg / dL that resonates at a frequency ratio of about 1.0 (dashed line). Fig.18 The biosensor 258 of the MEMS affinity glucose sensor 250 is shown to be effective for distinguishing between different glucose concentrations present in the effluent liquid.

[0230] In one embodiment, the MEMS affinity glucose sensor 250, the control unit 22, or the control unit 212 subtracts the glucose concentration present in the effluent fluid from the original glucose concentration of the fresh dialysis fluid delivered to the patient P. The control unit is programmed to determine the glucose concentration present in the nth PD cycle (P) as a function of n ) The amount of glucose absorbed by the patient at the end of

[0231] P n = f(V n , µ, (D on -D in )),in

[0232] n = number of cycles,

[0233] V n = volume of PD fluid delivered in the nth cycle,

[0234] µ = glucose absorption coefficient (an empirically determined constant),

[0235] D on = the glucose concentration of the effluent for the nth cycle as measured by the MEMS affinity glucose sensor 250, and

[0236] D in = the original glucose concentration of the PD fluid used for the nth cycle (PD fluid is provided in standard concentrations, such as 0.55%, 1.5%, 2.5% and 4.25%).

[0237] Based on the nth PD cycle (P n ) at the end of the cycle, the amount of glucose absorbed by the patient is determined, in one embodiment, by the following function:

[0238] I n+1 = f(G1,P n ,α,β,t), where

[0239] G1 = initial blood glucose level before treatment begins, which in one embodiment is obtained from glucose sensor 262,

[0240] P n is calculated as above,

[0241] α and β are the insulin absorption coefficients (empirically determined constants), and

[0242] t = time.

[0243] Fig. 20A and 20B The graph shows how glucose levels (mg / dL) can exceed an upper limit when uncontrolled, but can be controlled by using a MEMS affinity glucose sensor 250. Figures 15 to 18 The glucose feedback and insulin injection of the system 10 are controlled within the limits prescribed by the physician or clinician. Fig. 20A As shown in Figure 2, the glucose level (mg / dL) in patient P steadily increased during each dwell period, exceeding the upper limit in the second dwell period. Fig. 20B In the embodiment of the present invention, while insulin is injected according to the above-discussed function programmed into the MEMS affinity glucose sensor 250, control unit 22 or control unit 212, the glucose level (mg / dL) in the patient P rises during the dwell period and then falls during the subsequent fill phase.

[0244] It should be understood that various changes and modifications to the currently preferred embodiments described herein will be apparent to those skilled in the art. Such changes and modifications may be made without departing from the spirit and scope of the subject matter and without reducing its intended advantages. Therefore, it is intended that such changes and modifications be covered by the appended claims. For example, although the four main embodiments have been described in conjunction with an automated peritoneal dialysis system using a cycler 20, it is contemplated that these embodiments may also be used with manual PD or continuous ambulatory peritoneal dialysis (“CAPD”). Moreover, although MEMS biosensing for white blood cells and glucose molecules has been discussed in conjunction with varying vibration frequencies, it is contemplated that other properties may be detected that may be used in a transducer to provide a sensed output property, such as a voltage, including but not limited to changes in capacitance within a microfluidic channel, or changes in light and its frequency. In addition, although the impedance monitor 230 is illustrated and described as being provided with a resident catheter 55 of a patient P, it is contemplated that any of the four main embodiments may be implemented with a resident catheter.

Claims

1. A peritoneal dialysis ("PD") system comprising: a cycler comprising a pump actuator and a control unit capable of operatively communicating with the pump actuator; a disposable kit including a disposable cassette having a pump chamber, the disposable cassette being sized and arranged to be held by the cycler such that the pump chamber is in operable communication with the pump actuator, the disposable kit including a drain line and a patient line extending from the disposable cassette; as well as a temperature sensor operably coupled to one of the patient line, drain line or disposable cassette to sense a temperature of effluent PD fluid removed from the patient, the sensed temperature being used to form a determination of peritonitis in the patient, the control unit being configured to transmit the determination of peritonitis.

2. The PD system according to claim 1, wherein: The sensed temperature is sent to the control unit, and Therein, the control unit is configured to analyze the sensed temperature.

3. The PD system according to claim 2, wherein: The sensed temperature is sent to the control unit by wire or wirelessly.

4. The PD system of claim 1, comprising a network and at least one doctor or clinician computer, the at least one doctor or clinician computer communicating with the control unit via the network, The control unit is configured to transmit the determination of peritonitis to at least one of a patient or a caregiver via a user interface of the cycler, or to the at least one physician or clinician computer via the network.

5. The PD system according to claim 1, comprising a water purifier configured to supply purified water to the disposable kit, The water purifier comprises a water purifier control unit, in, The sensed temperature is sent to the water purifier control unit, wherein the water purifier control unit is configured to analyze the sensed temperature, and wherein the cycler control unit communicates with the water purifier control unit to allow the cycler control unit to transmit the determination of peritonitis.

6. The PD system according to claim 5, wherein: The cycler control unit or the water purifier control unit is configured to analyze the sensed temperature.

7. The PD system according to claim 1, wherein: The temperature sensor is placed in a connector configured to couple to the patient line or the drain line.

8. The PD system according to claim 7, wherein: The connectors are: (i) a clamshell type connector fitted around the patient line or the drain line, or (ii) configured to be joined between two sections of the patient line or the drain line.

9. The PD system according to claim 7, wherein: The connector comprises electrodes positioned and arranged as follows: (a) contact with effluent fluid flowing through said patient line or said drain line, or (b) directly contacting the patient line or the drain line.

10. The PD system according to claim 9, wherein: In (b), a thermally conductive segment is joined between segments of the patient line or the drain line, the connector being directly connected to the thermally conductive segment.

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