A peritoneal dialysis system with a sensor configured to diagnose peritonitis

Abstract

To provide a peritoneal dialysis system configured to diagnose peritonitis using an appropriate sensor.SOLUTION: Peritoneal dialysis such as automated peritoneal dialysis ("APD") is characterized by the following sensing and feedback. One or more, or all of an impedance sensing for detecting peritonitis, temperature sensing for detecting peritonitis, bio MEMS sensing for detecting peritonitis, and glucose control for a diabetes patient are included. By each sensing and feedback characteristics, patient outflow fluid or fluid staying in the abdominal cavity of a patient is analyzed. The sensed impedance is transmitted to a control unit, and the control unit analyzes the sensed impedance.SELECTED DRAWING: Figure 13

Description

Technical Field

[0001] (Claim of Priority) This application claims the benefit and priority of U.S. Provisional Patent Application No. 62 / 703,749, filed on Jul. 26, 2018, titled “Dialysis Systems and Methods Including Sensor Feedback to Improve Patient Experience,” the entire contents of which are hereby incorporated by reference and relied upon herein.

Background Art

[0002] The present disclosure generally relates to the treatment of end-stage renal disease. More specifically, the present disclosure relates to methods and apparatus for monitoring and / or controlling the performance of peritoneal dialysis.

[0003] It is known to use dialysis to assist patients whose kidney function has declined to the point where the kidneys no longer function adequately. Two main dialysis methods are provided, namely hemodialysis and peritoneal dialysis.

[0004] In hemodialysis, a patient's blood is passed through an artificial kidney dialysis machine. A membrane within the machine functions as an artificial kidney for purifying the blood. Since it is an extracorporeal treatment that requires special machinery, there are certain inherent disadvantages associated with hemodialysis. To overcome the disadvantages associated with hemodialysis, peritoneal dialysis was developed. Peritoneal dialysis uses the patient's own peritoneum as a semipermeable membrane. The peritoneum is the membranous inner layer of the patient's abdominal body cavity. Due to good perfusion, the peritoneum functions as a natural semipermeable membrane.

[0005] In peritoneal dialysis, a sterile aqueous solution or dialysate is periodically infused into the abdominal cavity. Diffusion and osmotic exchange occur between the peritoneal dialysate and the blood across the natural body membrane. The exchange removes the waste products that the kidneys would normally excrete. The waste products consist of solutes such as urea and creatinine. Additionally, the kidneys maintain the levels of other substances such as sodium and water. Dialysis regulates the diffusion of water and solutes across the peritoneum during dialysis, which is called ultrafiltration.

[0006] In continuous ambulatory peritoneal dialysis ("CAPD"), the dialysis solution is introduced into the abdominal cavity via a catheter. The exchange of solutes between the dialysate and the blood is achieved by diffusion. Further solute removal is achieved via a dialysate that provides a favorable osmotic gradient from the blood to the dialysate. The osmotic gradient enables appropriate acid-base electrolyte and fluid balance to be achieved within the patient's body. The used dialysis solution or effluent fluid is manually drained by gravity from the body cavity through the catheter.

[0007] A variation of CAPD is automated peritoneal dialysis ("APD"). APD uses a machine called a cycler to automatically infuse, dwell, and drain peritoneal dialysis fluid into and from the patient's abdominal cavity. APD can be performed at night while the patient is sleeping, freeing the patient from the daily requirements of CAPD during their waking and working hours, making it attractive to peritoneal dialysis patients.

[0008] The APD sequence typically lasts for several hours. It often starts with an initial drain phase to remove the used dialysis fluid from the previous treatment and empty the abdominal cavity. The APD sequence then proceeds through a series of successive fill, dwell, and drain phases. Each fill / dwell / drain sequence is called a cycle.

[0009] The percentage of patients undergoing automated peritoneal dialysis (“APD”) is increasing worldwide, which is due in part to the ability of APD to meet the specific needs of patients regarding their private life and the patients’ therapy needs. The two main goals of dialysis, namely solute clearance and ultrafiltration (“UF”), depend on the modality or type of APD being performed (e.g., nocturnal intermittent peritoneal dialysis (“NIPD”), continuous cyclic peritoneal dialysis (“CCPD”), and high-dose CCPD), solution type, therapy time, and fill volume. Prescribing an APD therapy consists of selecting one of each of these. Thus, there are many combinations and possibilities to choose from.

[0010] APD devices typically do not have the ability to provide feedback to patients regarding the effectiveness of their most recent therapy. Further, APD devices typically initiate an open loop, whereby the APD device does not adjust therapy parameters (e.g., modality, solution type, therapy time, and fill volume) based on actual measured daily clearance and UF. As a result, some patients achieve less than their target expectations and develop adverse symptoms such as fluid overload and, in some cases, hypertension. Current methods for adjusting therapy typically involve the patient reporting in to the center for occasional evaluation. These methods place the burden of therapy adjustment only on the physician or clinician and do not occur frequently enough to adequately adapt to the patient’s weekly, monthly, seasonal, or other lifestyle changes.

[0011] APDs such as CAPD use a catheter implanted in the patient's peritoneum to deliver fresh dialysate and remove used dialysate from the patient's abdominal cavity. The placement of the peritoneal catheter provides an opportunity to sense desired parameters within the patient. In addition, both APD and CAPD remove used effluent PD fluid from the patient, which provides an opportunity to sense patient parameters or characteristics present within the effluent fluid. Thus, there is a need to provide systems and methods that utilize the placement of the patient catheter and / or the effluent PD fluid removed from the patient to assist in monitoring and / or controlling peritoneal dialysis treatments such as CAPD and APD. And more generally, there is a need for immediate or during-treatment feedback to assist with the various problems associated with peritoneal dialysis. SUMMARY OF THE INVENTION MEANS FOR SOLVING THE PROBLEM

[0012] The embodiments described herein disclose systems and methods for improved peritoneal dialysis ("PD") treatment. Three of the systems and methods described herein involve the detection of peritonitis, optimally with early detection. Peritonitis is an inflammation of the peritoneum, 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 usually caused by an infection from bacteria or fungi that can enter through the patient's membrane catheter.

[0013] If left untreated, peritonitis can rapidly spread into the bloodstream (sepsis) and other organs, leading to multiple organ failure and death. The first symptoms of peritonitis typically quickly change from anorexia and nausea, and a dull abdominal pain to persistent severe abdominal pain. Other signs and symptoms associated with peritonitis can include abdominal tenderness or distension, chills, fever, ascites, and vomiting.

[0014] The mortality rate from peritonitis depends on many factors and can be as high as 40% in patients with cirrhosis. 10% of patients can die from secondary peritonitis. Spontaneous primary peritonitis is an infectious disease that occurs within the peritoneal cavity and is associated with peritoneal dialysis treatment. Secondary peritonitis usually occurs when an injury or infection within the abdominal cavity allows infectious microorganisms to enter the peritoneum. Both types of peritonitis are life-threatening.

[0015] Current methods for determining peritonitis are subjective and burdensome to patients. For example, patients may be asked to observe the color and / or texture of their effluent fluid and look for peritonitis. Or patients may be asked to be aware of abdominal distension and / or fever. When a patient thinks peritonitis is occurring or present, the patient needs to take an effluent sample to a clinic for testing. The above methods are subjective and burdensome to patients. The systems and methods below are automatic and objective. (Temperature Sensing Regarding Peritonitis)

[0016] In one main embodiment, the temperature of the spent dialysis fluid exiting the patient is measured to detect peritonitis. In healthy patients, the temperature of the spent dialysis fluid is normal body temperature or about 37°C. In patients suffering from the onset of peritonitis, the spent dialysis fluid exiting the patient can be present at a high temperature. The systems and methods of the first main embodiment measure the effluent dialysis fluid and use the measurement to make a determination regarding whether a patient may be suffering from the onset of peritonitis.

[0017] Temperature measurement can be performed in several different ways. In one method, a temperature sensor such as a thermocouple or thermistor is installed within a connector such as a clam shell type connector that is removable and selectively clip-on onto the patient line. The clam shell connector can be installed at any desired location around the patient line, for example, in the vicinity of the patient, so that the temperature of the patient's effluent dialysis fluid can be measured immediately as it exits the patient. In one embodiment, the temperature of the effluent fluid is compared to the temperature of fresh dialysis fluid that can be heated up to body temperature or 37°C. In this way, any temperature offset caused by generally non-thermally conductive tubing is nullified. For example, if the temperature of 37°C fresh dialysis fluid is read from the tubing at an offset temperature of 32°C, the same offset will be assumed for the effluent fluid exiting the patient. The control unit that reads the temperature signal will thus look for a patient health signal of 32°C and trigger a potential peritonitis alert when the control unit senses a signal indicating a temperature above 32°C.

[0018] In an alternative embodiment, a more thermally conductive and medically safe material such as stainless steel is joined or inserted into the patient line. One or more thermally conductive electrodes are attached to the temperature sensor to enable more accurate temperature readings. Here, the control unit that reads the temperature signal, in one embodiment, looks for a patient health signal of 37°C and triggers a potential peritonitis alert when the control unit senses a signal indicating a temperature above 37°C. In this example, the control unit may or may not consider the inflow temperature of the fresh dialysis fluid.

[0019] In any embodiment where the temperature sensor is located remotely from the circulation device, the temperature sensor can transmit signals measured in a wired or wireless manner to the circulation device for investigation. The temperature sensor is, in one embodiment, a passive device (e.g., two wires that generate a voltage based on the fluid temperature). If the temperature sensor does not require power, power can be provided via a battery or via a power wire from the circulation device or a water purifier operating with the circulation device.

[0020] In a further alternative embodiment, a temperature sensor, such as a thermocouple or a thermistor, is located within the dialysis machine or the circulation device and operates with a disposable cassette or a patient line extending from the disposable cassette. The temperature sensor contacts, in one embodiment, the flexible sheet of the disposable cassette at one or more locations. One or more thermally conductive contacts may be formed or added to the disposable cassette to aid in temperature sensing accuracy. As described above, when sensing at or near the cassette, the control unit may or may not take into account the inflow temperature of the fresh dialysis fluid.

[0021] Temperature sensing is alternatively performed within the drain line extending from the disposable cassette. The drain line is advantageous as the drain line is inserted into a reusable thermally conductive contact provided with the circulation device or a water purification device operating with the circulation device, so that sterility is less of an issue.

[0022] In one embodiment, the control unit is programmed to warn the patient at the user interface of the circulation device if a high temperature indicating peritonitis is detected. Alternatively or in addition, the control unit operates via a network and one or more server computers to enable a clinician to determine whether there is a risk of peritonitis for the patient, for example, continuously, by enabling a physician or clinician to view the effluent temperature data. The data is, in one embodiment, displayed on a dashboard of a website for the patient, and the temperature data may be presented with a flag for the clinician when it rises and indicates peritonitis. (BioMEMS Sensing for Peritonitis)

[0023] As an alternative, or in a second main embodiment that can be used in addition to the first embodiment, a bio - microelectromechanical system (“bioMEMS”) sensor is used to detect peritonitis. The bioMEMS sensor is used to search for the presence of white blood cells from the patient in the effluent, which is an indicator of peritonitis. In one implementation, the effluent fluid from the circulation device is pumped to be discharged. The discharge line is connected to a lab - on - chip diagnostic detection device. The lab - on - chip or bioMEMS device includes a container in which a sampling line extends, and the sampling line can extend from or branch off the discharge line. The effluent sample entering the container of the bioMEMS device first encounters a microfluidic path that separates the patient's white blood cells from the effluent fluid. The white blood cells are then, in one embodiment, weighed using a piezoelectric biosensor. The piezoelectric biosensor resonates at a frequency proportional to the change in the deposition rate of the white blood cells.

[0024] Alternatively, the bioMEMS device is installed within the patient line via a sample line and is used to analyze the effluent returning from the patient. Thus, the bioMEMS device can also be used, if desired, to sense the fresh dialysate delivered to the patient.

[0025] In one embodiment, the bioMEMS device includes electronics and processing for processing the raw signal from the piezoelectric biosensor and making a determination regarding the presence or absence of white blood cells. The bioMEMS device may also include a user interface for indicating to the patient or caregiver present during treatment, regardless of whether an indication of peritonitis is present. In an alternative embodiment, either (i) the electronics and processing for processing the raw signal from the piezoelectric biosensor, or (ii) the user interface for patient or caregiver communication, or both, can be provided instead by the circulation device, or perhaps a water purification device operable with the circulation device.

[0026] Similar to the first main embodiment, the control unit and processes for the second main embodiment operate, alternatively or additionally, via a network and one or more server computers, enabling, for example, a clinician to continuously view the bioMEMS data so as to determine whether a patient is at risk of peritonitis. The data of the second main embodiment can be displayed in combination with the data of the first main embodiment to provide a combination of peritonitis indicators. (Impedance Monitoring Regarding Peritonitis)

[0027] Alternatively, or in a third main embodiment that can be used in addition to the first and / or second embodiments, an impedance monitor is used to detect peritonitis. The impedance monitor is again used to look for the presence of white blood cells from the patient in the effluent fluid, which is an indicator of peritonitis. In various implementations, the impedance monitor can be placed anywhere where the patient's effluent fluid can be sensed, for example, within the patient's indwelling catheter, along the patient line, or along the drain line. At any of these locations, the catheter or line is fitted with electrodes in any of the ways discussed above for temperature sensing, but here with the goal of establishing conductive contacts in communication with the effluent dialysate.

[0028] In one embodiment, a conductive and medically safe material such as stainless steel is joined or inserted into a catheter, patient line, or drain line, for example, via a connector that is joined into a clam shell connector or a connector within a drain line. A control unit that controls the impedance monitor generates, in one embodiment, an electrical frequency sweep within the effluent fluid. Such impedance spectroscopy (or obtaining complex impedance) can provide additional details about the contents of the effluent fluid. For example, the electrical properties of fibrin (which do not indicate peritonitis normally) can vary from the electrical properties of white blood cells (which indicate peritonitis). Once the electrical properties of different substances within the effluent fluid are learned, the properties are programmed into the control unit and can then be used to determine what happens if something contaminates the effluent dialysis fluid stream.

[0029] In any embodiment where the impedance monitor is located remotely from the circulation device, the impedance monitor can transmit signals measured in a wired or wireless fashion for investigation to the circulation device. An impedance monitor as described above has the ability to radiate a frequency sweep into the effluent fluid and can thus receive power either from a battery or from a water purifier that operates with or along with the circulation device via a power wire.

[0030] In an alternative embodiment, the impedance monitor is located within a dialysis machine or circulation device and operates with a disposable cassette or a patient or drain line extending from the disposable cassette. The impedance monitor extends, in one embodiment, through a rigid wall that holds the flexible sheet of the disposable cassette at one or more locations. In a further alternative embodiment, the impedance monitor is operable with a drain line located within a water purifier that supplies purified water to the dialysis machine or circulation device.

[0031] In one embodiment, the control unit is programmed to warn the patient or caregiver at the user interface of the circulation device when white blood cells indicating peritonitis are detected. Alternatively, or in addition, the control unit operates via a network and one or more server computers to enable a clinician to determine whether the patient is at risk of peritonitis, e.g., continuously, by enabling a physician or clinician to view effluent impedance data. The data is, in one embodiment, displayed on a dashboard of a website for the patient, and the effluent impedance data can be presented with a flag for the clinician when white blood cells are present and indicate peritonitis. The data of the third main embodiment can be displayed in combination with the data of the first and / or second main embodiments to provide a combination of peritonitis indicators.

[0032] When an impedance monitor is placed within an indwelling catheter or within a patient line via a sample line and used to analyze effluent within or returning from the patient, the impedance monitor can also be used, if desired, to sense fresh dialysate delivered to the patient. When the impedance monitor is placed within the drain line, it can also be used to detect whether the dialysate made at the point of use is properly mixed. (Glucose control for diabetic patients)

[0033] Glucose (or dextrose) is the main osmotic agent used with most PD solutions. Absorption of most of the peritoneal glucose load over the dwell period can have an adverse effect on patients suffering from diabetes. Diabetes is a common cause of kidney failure leading to the need for dialysis treatment. In addition, daily exposure to glucose can induce hyperglycemia in PD patients, which can have serious consequences. Some diabetic PD patients, therefore, receive insulin with their PD treatment to help maintain glucose balance. However, patients receiving insulin with their PD treatment risk trying to match the amount of insulin received to the amount of PD treatment received.

[0034] Alternatively, or in a fourth main embodiment that may be used in addition to the first, second, and / or third main 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 dialysate going out of the patient. That measurement is then used to appropriately administer insulin to the patient for the next patient PD fill. In one embodiment, the patient is filled with fluid from a previous treatment when starting the current treatment. The effluent fluid is removed and at least a portion of it is sent to a MEMS affinity glucose sensor that signals a control unit that determines the amount of insulin to be delivered to the PD supply volume to form insulin at a desired concentration for the initial fill. A corresponding amount of insulin is then delivered to the PD fluid supply bag to produce the desired concentration.

[0035] The MEMS affinity glucose sensor is used, in one embodiment, to measure glucose in the discharged effluent. In one implementation, the effluent fluid from the circulation device is pumped to discharge. The discharge line is fluidly connected to the MEMS affinity glucose sensor. The MEMS affinity glucose sensor includes a container in which a sampling line extends, and the sampling line may extend from or branch off the discharge line. The effluent sample entering the container of the MEMS affinity glucose sensor first encounters a microfluidic path that separates glucose molecules from the effluent fluid. The glucose molecules are then, in one embodiment, weighed using a piezoelectric biosensor. The piezoelectric biosensor resonates at a frequency proportional to the change in the deposition rate of the glucose molecules. The glucose absorbed at the end of the nth cycle is calculated using the equation for A n discussed below. To compensate for the glucose absorbed in the nth cycle, the insulin dosage during subsequent cycles will be calculated using equation I n+1 discussed below.

[0036] In one embodiment, the MEMS affinity glucose sensor includes electronics and processing for processing raw signals from a piezoelectric biosensor and making determinations regarding appropriate concentrations of insulin to be prepared with the PD solution. The MEMS affinity glucose sensor may also include a user interface for indicating to a patient or caregiver present during treatment that an appropriate insulin level has been determined. In an alternative embodiment, either or both of (i) the electronics and processing for processing raw signals from the piezoelectric biosensor, or (ii) the user interface for patient or caregiver communication, is instead provided by a cycler device, or perhaps a water purification device operable with the cycler device. The PD cycler device may operate with pre-prepared PD dialysate or PD dialysate prepared at the point of use. In the case of pre-prepared PD dialysate, insulin is added to a heater bag or an insulin port on top of a bag of the solution. In the case of PD dialysate prepared at the point of use, insulin may be added to the mixed dialysate or to any of its components (purified water, osmotic agent, or electrolyte).

[0037] In one embodiment, the control unit of the cycler device operates via a network and one or more server computers to enable a clinician to view insulin usage data, e.g., per treatment, so that the clinician can confirm that insulin is being delivered appropriately. The data is, in one embodiment, displayed on a dashboard of a website for the patient, and the insulin volume and concentration with the PD solution can be viewed. The data of the fourth main embodiment may be displayed in combination with the data of the first, second, and / or third main embodiments to provide a desired combination of data.

[0038] In a first aspect of the present disclosure, which can be combined with any other aspect listed herein without otherwise specified and without limiting the present disclosure in any way, a peritoneal dialysis ("PD") system includes a circulation device including a pump actuator and a control unit operably communicating with the pump actuator, a disposable set including a disposable cassette having a pump chamber, the disposable cassette being sized and arranged to be held by the circulation device such that the pump chamber operably communicates with the pump actuator, the disposable set including a patient line and a drain line extending from the disposable cassette, and a temperature sensor operably coupled to one of the patient line, the drain line, or the disposable cassette to sense the temperature of the effluent PD fluid removed from the patient, the sensed temperature being used to form a patient peritonitis determination, and the control unit being configured to communicate the peritonitis determination.

[0039] In a second aspect of the present disclosure, which can be combined with any other aspect listed herein without otherwise specified and without limiting the present disclosure in any way, the sensed temperature is transmitted to the control unit, and the control unit is configured to analyze the sensed temperature.

[0040] In a third aspect of the present disclosure, which can be combined with a second aspect in combination with any other aspect listed herein without otherwise specified and without limiting the present disclosure in any way, the sensed temperature is transmitted to the control unit either wired or wirelessly.

[0041] In a fourth aspect of the present disclosure, which can be combined with any other aspect listed herein without otherwise specified and without limiting the present disclosure in any way, the PD system includes a network and at least one physician or clinician computer communicating with the control unit via the network, and the control unit is configured to communicate the peritonitis determination to at least one of a patient or a caregiver via the network or via a user interface of the circulation device or the at least one physician or clinician computer.

[0042] In a fifth aspect of the disclosure that can be combined with any other aspect recited herein, unless otherwise specified, the PD system includes a water purifier configured to supply purified water to a disposable set, the water purifier includes a water purifier control unit, the sensed temperature is transmitted to the water purifier control unit, the water purifier control unit is configured to analyze the sensed temperature, and the circulation device control unit and the water purifier control unit communicate to enable the circulation device control unit to communicate a peritonitis determination.

[0043] In a sixth aspect of the disclosure that can be combined with the fifth aspect in combination with any other aspect recited herein, unless otherwise specified, either the circulation device control unit or the water purifier control unit is configured to analyze the sensed temperature.

[0044] In a seventh aspect of the disclosure that can be combined with any other aspect recited herein, unless otherwise specified, the temperature sensor is installed within a connector configured to couple to a patient line or a drain line.

[0045] In an eighth aspect of the disclosure that can be combined with the seventh aspect in combination with any other aspect recited herein, unless otherwise specified, the connector is (i) a clam shell connector that attaches around the patient line or the drain line, or (ii) configured to be joined between two segments of the patient line or the drain line.

[0046] In a ninth aspect of the disclosure that can be combined with the seventh aspect in combination with any other aspect recited herein, unless otherwise specified, the connector includes electrodes positioned and arranged to (a) contact effluent fluid flowing through the patient line or the drain line, or (b) directly contact the patient line or the drain line.

[0047] In a tenth aspect of the disclosure that can be combined with the ninth aspect in combination with any other aspect recited herein, unless otherwise specified, in (b), the thermally conductive segment is joined between sections of the patient line or the drain line, and the connector is directly connected to the thermally conductive segment.

[0048] In an eleventh aspect of the disclosure that can be combined with the ninth aspect in combination with any other aspect recited herein, unless otherwise specified, the connector includes a conductive wire extending from the electrode to (i) a control unit, (ii) a control unit of a water purifier configured to supply purified water to a disposable set, or (iii) a wireless module including the connector.

[0049] In a twelfth aspect of the disclosure that can be combined with any other aspect recited herein, unless otherwise specified, the PD system is configured to analyze the sensed temperature of the effluent PD fluid removed from the patient by comparing the sensed temperature delivered to the patient with the temperature of the fresh PD fluid sensed by the temperature sensor.

[0050] In a thirteenth aspect of the disclosure that can be combined with any other aspect recited herein, unless otherwise specified, the PD system is configured to analyze the sensed temperature of the effluent PD fluid removed from the patient by looking for an increase in temperature due to peritonitis or its onset.

[0051] In a fourteenth aspect of the disclosure that can be combined with the thirteenth aspect in combination with any other aspect recited herein, unless otherwise specified, the increase in temperature due to peritonitis or its onset is detectable regardless of whether the sensed temperature is offset due to sensing through the patient line, the drain line, or the disposable cassette.

[0052] In a 15th aspect of the disclosure, which can be combined with any other aspect recited herein unless otherwise specified, a peritonitis determination is a first peritonitis indicator and includes at least one different peritonitis indicator that can be used in combination with the first peritonitis indicator to form an overall peritonitis determination.

[0053] In a 16th aspect of the disclosure, which can be combined with the 15th aspect in combination with any other aspect recited herein unless otherwise specified, 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 white blood cell biosensor or a white blood cell impedance sensor.

[0054] In a 17th aspect of the disclosure, which can be combined with any other aspect recited herein unless otherwise specified, a peritonitis determination is provided in combination with an insulin injection that is performed using feedback from a patient effluent glucose biosensor.

[0055] In an 18th aspect of the disclosure, which can be combined with any other aspect recited herein unless otherwise specified, a peritoneal dialysis ("PD") system includes a circulation device including a pump actuator and a control unit operably communicating with the pump actuator, a disposable set including a disposable cassette having a pump chamber, the disposable cassette being sized and arranged to be held by the circulation device such that the pump chamber is operably communicating with the pump actuator, a disposable set, and a bioMEMS device in fluid communication with the disposable cassette, the bioMEMS device being configured to collect white blood cells from the effluent PD fluid removed from the patient, the collected white blood cells being used to form a patient peritonitis determination, and the control unit being configured to communicate the peritonitis determination.

[0056] In a 19th aspect of the disclosure that can be combined with an 18th aspect in combination with any other aspect recited herein, unless otherwise specified, an indication of collected white blood cells is transmitted to a control unit, and the control unit is configured to analyze the indication of collected white blood cells.

[0057] In a 20th aspect of the disclosure that can be combined with a 19th aspect in combination with any other aspect recited herein, unless otherwise specified, an indication of collected white blood cells is transmitted to the control unit, either wired or wirelessly.

[0058] In a 21st aspect of the disclosure that can be combined with an 18th aspect in combination with any other aspect recited herein, unless otherwise specified, the PD system includes a network and at least one physician or clinician computer that communicates with a control unit via the network, and the control unit is configured to communicate a peritonitis determination to at least one of a patient or a caregiver via the network or via a user interface of the at least one physician or clinician computer.

[0059] In a 22nd aspect of the disclosure that can be combined with an 18th aspect in combination with any other aspect recited herein, unless otherwise specified, the bioMEMS device is installed in fluid communication with a sample port of a disposable cassette.

[0060] In a 23rd aspect of the disclosure that can be combined with an 18th aspect in combination with any other aspect recited herein, unless otherwise specified, the bioMEMS device includes a control unit having at least one of electronics, processing, and memory, and either a circulation device control unit or a bioMEMS device control unit is configured to analyze the sensed temperature.

[0061] In a 24th aspect of the disclosure that can be combined with the 18th aspect in combination with any other aspect recited herein, unless otherwise specified, the bioMEMS device includes: (i) a microfluidic chip sized and configured to form a microfluidic pathway that separates white blood cells from the remaining effluent fluid; and (ii) a piezoelectric biosensor that resonates at a frequency proportional to the characteristics of the collected white blood cells.

[0062] In a 25th aspect of the disclosure that can be combined with the 24th aspect in combination with any other aspect recited herein, unless otherwise specified, the characteristics of the collected white blood cells include a change in the deposition rate of white blood cells.

[0063] In a 26th aspect of the disclosure that can be combined with the 24th aspect in combination with any other aspect recited herein, unless otherwise specified, the frequency proportional to the characteristics of the collected white blood cells is used to form a peritonitis determination.

[0064] In a 27th aspect of the disclosure that can be combined with the 24th aspect in combination with any other aspect recited herein, unless otherwise specified, the piezoelectric biosensor operates with a collection area for collecting white blood cells.

[0065] In a 28th aspect of the disclosure that can be combined with the 18th aspect in combination with any other aspect recited herein, unless otherwise specified, the bioMEMS device includes a wired communication with a control unit or a wireless module for wireless communication with the control unit.

[0066] In a 29th aspect of the disclosure that can be combined with the 18th aspect in combination with any other aspect recited herein, unless otherwise specified, the PD system is configured to analyze the amount of white blood cells removed from the effluent PD fluid and make a peritonitis determination.

[0067] In a 30th aspect of the disclosure that can be combined with the 18th aspect in combination with any other aspect recited herein, unless otherwise specified, the peritonitis determination is a first peritonitis indicator and includes at least one different peritonitis indicator that can be used in combination with the first peritonitis indicator to form an overall peritonitis determination.

[0068] In a 31st aspect of the disclosure that can be combined with the 30th aspect in combination with any other aspect recited herein, unless otherwise specified, 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.

[0069] In a 32nd aspect of the disclosure that can be combined with the 18th aspect in combination with any other aspect recited herein, unless otherwise specified, the peritonitis determination is provided in combination with an insulin injection that is performed using feedback from a patient effluent glucose biosensor.

[0070] In a 33rd aspect of the disclosure that can be combined with any other aspect recited herein unless otherwise specified, a peritoneal dialysis (“PD”) system includes a circulation device having a pump actuator and a control unit operably communicating with the pump actuator, a disposable set including a disposable cassette having a pump chamber, the disposable cassette being sized and arranged to be held by the circulation device such that the pump chamber is operably communicating with the pump actuator, the disposable set including a patient line and a drain line extending from the disposable cassette, a catheter for placement within the patient's peritoneal cavity and for fluid communication with the patient line, and an impedance sensor operably coupled to one of the catheter, the patient line, or the drain line to sense the impedance of PD fluid present within or removed from the patient, the sensed impedance being used to detect white blood cells and form a patient peritonitis determination, and the control unit being configured to communicate the peritonitis determination.

[0071] In a 34th aspect of the disclosure that can be combined with the 33rd aspect in combination with any other aspect recited herein unless otherwise specified, the sensed impedance is transmitted to the control unit, and the control unit is configured to analyze the sensed impedance.

[0072] In a 35th aspect of the disclosure that can be combined with the 34th aspect in combination with any other aspect recited herein unless otherwise specified, the sensed impedance is transmitted to the control unit either wired or wirelessly.

[0073] In a 36th aspect of the disclosure that can be combined with a 33rd aspect in combination with any other aspect recited herein, unless otherwise specified, the PD system includes a network and at least one physician or clinician computer that communicates with a control unit via the network, and the control unit is configured to communicate a peritonitis determination to at least one of a patient or a caregiver via the network or via a user interface of the at least one physician or clinician computer.

[0074] In a 37th aspect of the disclosure that can be combined with a 33rd aspect in combination with any other aspect recited herein, unless otherwise specified, the PD system includes a water purifier configured to supply purified water to a disposable set, the water purifier includes a water purifier control unit, a sensed impedance is transmitted to the water purifier control unit, the water purifier control unit is configured to analyze the sensed impedance, and the circulation device control unit and the water purifier control unit communicate to enable the circulation device control unit to communicate a peritonitis determination.

[0075] In a 38th aspect of the disclosure that can be combined with a 33rd aspect in combination with any other aspect recited herein, unless otherwise specified, the impedance sensor is located within a connector configured to couple to a catheter, a patient line, or a drain line.

[0076] In a 39th aspect of the disclosure that can be combined with a 38th aspect in combination with any other aspect recited herein, unless otherwise specified, the connector is (i) a clam shell connector that attaches around a catheter, a patient line, or a drain line, or (ii) configured to be joined between two segments of a catheter, a patient line, or a drain line.

[0077] In a 40th aspect of the disclosure that can be combined with a 33rd aspect in combination with any other aspect recited herein, unless otherwise specified, the impedance sensor is positioned within a catheter, patient line, or drain line and includes disposed electrodes, and the connector is positioned covering the electrodes.

[0078] In a 41st aspect of the disclosure that can be combined with a 40th aspect in combination with any other aspect recited herein, unless otherwise specified, the connector includes a conductor extending from the electrodes to (i) a control unit, (ii) a control unit of a water purifier configured to supply purified water to a disposable set, or (iii) a wireless module including the connector.

[0079] In a 42nd aspect of the disclosure that can be combined with a 33rd aspect in combination with any other aspect recited herein, unless otherwise specified, the PD system is configured to analyze the sensed impedance of PD fluid present within or removed from a patient via a frequency sweep that moves from a start frequency to a stop frequency.

[0080] In a 43rd aspect of the disclosure that can be combined with a 42nd aspect in combination with any other aspect recited herein, unless otherwise specified, the frequency sweep is provided by or generated by a frequency generator operable with or by a control unit.

[0081] In a 44th aspect of the disclosure that can be combined with a 42nd aspect in combination with any other aspect recited herein, unless otherwise specified, the PD system is configured to perform impedance measurements at two or more frequencies of the frequency sweep.

[0082] In a 45th aspect of the disclosure that can be combined with a 42nd aspect in combination with any other aspect recited herein, unless otherwise specified, the frequency sweep enables determination by measuring that a fluid having white blood cells, present within or removed from a patient, has a higher impedance over at least a portion of the frequency sweep than a fluid without white blood cells. And the measured impedance for a fluid without blood cells is determined (i) based on a standard impedance or (ii) based on an impedance established for the patient.

[0083] In a 46th aspect of the disclosure that can be combined with a 42nd aspect in combination with any other aspect recited herein, unless otherwise specified, the frequency sweep enables a fluid having white blood cells, present within or removed from a patient, to be distinguished from a fluid having fibrin, and the fluid having fibrin results in a higher impedance than the fluid having white blood cells over at least a portion of the sweep.

[0084] In a 47th aspect of the disclosure that can be combined with a 33rd aspect in combination with any other aspect recited herein, unless otherwise specified, the peritonitis determination is a first peritonitis indicator and includes at least one different peritonitis indicator that can be used in combination with the first peritonitis indicator to form an overall peritonitis determination.

[0085] In a 48th aspect of the disclosure that can be combined with a 47th aspect in combination with any other aspect recited herein, unless otherwise specified, 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.

[0086] In a 49th aspect of the disclosure that can be combined with a 33rd aspect in combination with any other aspect recited herein, unless otherwise specified, a peritonitis determination is provided in combination with an insulin injection that is performed using feedback from a patient effluent glucose biosensor.

[0087] In a 50th aspect of the disclosure that can be combined with a 33rd aspect in combination with any other aspect recited herein, unless otherwise specified, a peritoneal dialysis ("PD") system includes a circulation device including a pump actuator and a control unit operably communicating with the pump actuator, a disposable set including a disposable cassette having a pump chamber, the disposable cassette sized and positioned to be held by the circulation device such that the pump chamber is operably communicating with the pump actuator, a disposable set, an insulin source in fluid communication with the disposable set, 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 configured to provide a glucose assay regarding glucose absorbed by the patient, the glucose assay being used to determine an insulin dose, and the control unit configured to deliver an insulin dose from the insulin source to the patient by a pump actuator operating with the pump chamber of the disposable cassette.

[0088]

[0089] In a 51st aspect of the disclosure that can be combined with a 50th aspect in combination with any other aspect recited herein, unless otherwise specified, the PD system includes a dialysis fluid source in fluid communication with the disposable set, and the control unit is configured to deliver an insulin dose from the insulin source mixed with fresh dialysis fluid from the dialysis fluid source to the patient.In a 52nd aspect of the disclosure that can be combined with a 51st aspect in combination with any other aspect recited herein, unless otherwise specified, the dialysate source is a point-of-use dialysate source, and fresh dialysate is mixed in a mixing bag together with insulin from an insulin bag.

[0090] In a 53rd aspect of the disclosure that can be combined with a 50th aspect in combination with any other aspect recited herein, unless otherwise specified, the disposable set includes a patient line and a drain line in fluid communication with a disposable cassette, and the MEMS affinity glucose sensor is in fluid communication with the drain line.

[0091] In a 54th aspect of the disclosure that can be combined with a 53rd aspect in combination with any other aspect recited herein, unless otherwise specified, the MEMS affinity glucose sensor is positioned along the drain line upstream of the drain container.

[0092] In a 55th aspect of the disclosure that can be combined with a 50th aspect in combination with any other aspect recited herein, unless otherwise specified, the PD system includes a water purifier, the dialysate source is a point-of-use dialysate source that uses purified water from the water purifier, and the MEMS affinity glucose sensor is provided with the water purifier.

[0093] In a 56th aspect of the disclosure that can be combined with a 55th aspect in combination with any other aspect recited herein, unless otherwise specified, the water purifier communicates with the circulation device, either wired or wirelessly, and the water purifier is configured to determine an insulin dose from a glucose assay and deliver the insulin dose to the circulation device for delivery.

[0094] In a 57th aspect of the present disclosure that can be combined with the 50th aspect in combination with any other aspect recited herein, unless otherwise specified, the MEMS affinity glucose sensor communicates with the circulation device, either wired or wirelessly, and the control unit of the circulation device is configured to determine an insulin dose from a glucose assay transmitted from the MEMS affinity glucose sensor to the control unit.

[0095] In a 58th aspect of the present disclosure that can be combined with the 50th aspect in combination with any other aspect recited herein, unless otherwise specified, the MEMS affinity glucose sensor is configured to determine an insulin dose from a glucose assay.

[0096] In a 59th aspect of the present disclosure that can be combined with the 50th aspect in combination with any other aspect recited herein, unless otherwise specified, the glucose assay indicates the amount or concentration of glucose absorbed by the patient.

[0097] In a 60th aspect of the present disclosure that can be combined with the 50th aspect in combination with any other aspect recited herein, unless otherwise specified, the MEMS affinity glucose sensor includes (i) a microfluidic chip that is sized and configured to separate glucose molecules from the remaining effluent fluid and forms a microfluidic pathway, and (ii) a piezoelectric biosensor that resonates at a frequency proportional to the characteristics of the collected glucose molecules.

[0098] In a 61st aspect of the present disclosure that can be combined with the 60th aspect in combination with any other aspect recited herein, unless otherwise specified, the characteristics of the collected glucose molecules include a change in the deposition rate of the glucose molecules.

[0099] In a 62nd aspect of the present disclosure that can be combined with the 60th aspect in combination with any other aspect recited herein, unless otherwise specified, the frequency proportional to the characteristics of the collected glucose molecules is used to form an insulin determination.

[0100] In a sixty-third aspect of the present disclosure, which may be combined with the sixty-first aspect in combination with any other aspect enumerated herein unless otherwise specified, the piezoelectric biosensor operates with a collection area for collecting glucose molecules.

[0101] In a 64th aspect of the present disclosure, which may be combined with the 50th aspect in combination with any other aspect enumerated herein unless otherwise specified, the control unit is programmed assuming that the lower the concentration of glucose in the effluent, the greater the amount of glucose absorbed by the patient.

[0102] In a 65th aspect of the present disclosure, which may be combined with the 50th aspect in combination with any other aspect enumerated herein unless otherwise specified, the PD system includes a network and at least one physician or clinician computer in communication with a control unit via the network, the control unit configured to communicate an insulin dose to at least one of a patient or caregiver via the network and via a user interface of the circulation device or the at least one physician or clinician computer.

[0103] In a 66th aspect of the present disclosure, which may be combined with the 50th aspect in combination with any other aspect enumerated herein unless otherwise specified, the PD system includes at least one peritonitis indicating device selected from a patient effluent PD fluid temperature sensor, a leukocyte biosensor, or a leukocyte impedance monitor.

[0104] In a 67th aspect of the disclosure, which can be combined with any other aspect recited herein unless otherwise specified, a peritoneal dialysis ("PD") system includes a circulation device including a pump actuator and a control unit operably communicating with the pump actuator, and a disposable set sized and arranged to be held by the circulation device such that a pump portion thereof is operably communicating with the pump actuator, the disposable set including a patient line and a drain line extending from a disposable cassette, a catheter for placement within a patient's peritoneal cavity and fluid communication with the patient line, and an impedance sensor operably coupled to one of the catheter, the patient line, or the drain line to sense the impedance of PD fluid present within or removed from the patient, wherein the sensed impedance is used to detect white blood cells and form a patient peritonitis determination.

[0105] In a 68th aspect of the disclosure, which can be combined with any other aspect recited herein unless otherwise specified, a peritoneal dialysis ("PD") system includes a pump actuator and a control unit operably communicating with the pump actuator, a disposable set sized and arranged to be operably communicating with the pump actuator and including a pump portion, the disposable set including a patient line and a drain line extending from a disposable cassette, a catheter for placement within a patient's peritoneal cavity and fluid communication with the patient line, and an impedance sensor operably coupled to one of the catheter, the patient line, or the drain line to sense PD fluid present within or removed from the patient over a frequency sweep moving from a start frequency to a stop frequency, wherein the sensed impedance frequency sweep is used to detect white blood cells and form a patient peritonitis determination.

[0106] In a 69th aspect of the present disclosure, any of the structures and functionalities disclosed in connection with FIGS. 1-20B may be included or combined with any of the other structures and functionalities disclosed in connection with FIGS. 1-20B.

[0107] Based on the present disclosure and the above aspects, it is therefore an advantage of the present disclosure to provide an improved peritoneal dialysis ("PD") system and method.

[0108] It is another advantage of the present disclosure to provide a PD system and method that enables peritonitis to be determined based on objective criteria.

[0109] It is a further advantage of the present disclosure to provide a PD system and method that enables peritonitis to be automatically determined without overburdening the patient.

[0110] It is yet another advantage of the present disclosure to provide a PD system and method that enables peritonitis to be determined using a plurality of different techniques that provide verification tests.

[0111] It is a further advantage of the present disclosure to provide a PD system and method that still proportionally relates insulin infusion to dialysate infusion at a desired concentration.

[0112] It is yet another advantage of the present disclosure to provide a PD system and method that remotely communicates relevant peritonitis and insulin infusion data to a clinician.

[0113] The advantages discussed herein may be found in one or some, but perhaps not all, of the embodiments disclosed herein. Additional features and advantages will be apparent from the description herein and from the forms and drawings for carrying out the following invention. The present invention provides, for example, the following. (Item 1) A peritoneal dialysis ("PD") system, wherein the PD system is A circulation device including a pump actuator and a control unit operably communicating with the pump actuator, A disposable set including a disposable cassette having a pump chamber, the disposable cassette being sized and arranged to be held by the circulation device such that the pump chamber is operably communicating with the pump actuator, the disposable set including a patient line and a drain line extending from the disposable cassette, A catheter for placement within the patient's peritoneal cavity and for fluid communication with the patient line, An impedance sensor operably coupled to one of the catheter, patient line, or drain line Comprising, The impedance sensor senses the impedance of the PD fluid present within the patient or the PD fluid removed from the patient, the sensed impedance is used to detect white blood cells and form a patient peritonitis determination, and the control unit is configured to communicate the peritonitis determination. A PD system. (Item 2) The sensed impedance is transmitted to the control unit, and the control unit is configured to analyze the sensed impedance. The PD system according to Item 1. (Item 3) The sensed impedance is transmitted to the control unit either wired or wirelessly. The PD system according to Item 2. (Item 4) Including a network and at least one physician or clinician computer communicating with the control unit via the network, the control unit being configured to communicate the peritonitis determination to at least one of the patient or caregiver via the network or via a user interface of the at least one physician or clinician computer. The PD system according to Item 1. (Item 5) A PD system according to item 1, including a water purifier configured to supply purified water to the disposable set, the water purifier including a water purifier control unit, the sensed impedance being transmitted to the water purifier control unit, the water purifier control unit being configured to analyze the sensed impedance, and the circulation device control unit and the water purifier control unit communicating, enabling the circulation device control unit to communicate the peritonitis determination. (Item 6) The PD system according to item 1, wherein the impedance sensor is located within a connector configured to couple to the catheter, the patient line, or the drain line. (Item 7) The PD system according to item 6, wherein the connector is (i) a clam shell connector that attaches around the catheter, the patient line, or the drain line, or (ii) configured to be joined between two segments of the catheter, the patient line, or the drain line. (Item 8) The PD system according to item 6, wherein the impedance sensor includes electrodes positioned and disposed within the catheter, the patient line, or the drain line, and the connector is positioned to cover the electrodes. (Item 9) The PD system according to item 8, wherein the connector includes a conductive wire extending from the electrodes to (i) the control unit, (ii) the control unit of a water purifier configured to supply purified water to the disposable set, or (iii) a wireless module including the connector. (Item 10) The PD system according to item 1, configured to analyze the sensed impedance of the PD fluid present within the patient or the PD fluid removed from the patient via a frequency sweep that moves from a start frequency to a stop frequency. (Item 11) The frequency sweep is generated by a frequency generator provided by the control unit, or a frequency generator operable therewith, for the PD system according to item 10. (Item 12) The PD system according to item 10, configured to perform impedance measurements at two or more frequencies of the frequency sweep. (Item 13) The frequency sweep enables the PD system according to item 10 to be determined by measuring a higher impedance for a fluid having white blood cells, which is present in the patient or removed from the patient, than for a fluid without white blood cells over at least a portion of the frequency sweep. (Item 14) The frequency sweep enables a fluid having white blood cells, which is present in the patient or removed from the patient, to be distinguished from a fluid having fibrin, and the fluid having fibrin provides a higher impedance than the fluid having white blood cells over at least a portion of the sweep, for the PD system according to item 10. (Item 15) The peritonitis determination is a first peritonitis indicator, and the peritonitis determination includes at least one different peritonitis indicator that can be used in combination with the first peritonitis indicator to form an overall peritonitis determination, for the PD system according to item 1. (Item 16) The 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, for the PD system according to item 15. (Item 17) The peritonitis determination is provided in combination with an insulin injection performed using feedback from a patient effluent glucose biosensor, for the PD system according to item 1. (Item 18) A peritoneal dialysis (「PD」) system, wherein the PD system comprises: A circulation device including a pump actuator and a control unit operably communicating with the pump actuator; A disposable set including a disposable cassette having a pump chamber, the disposable cassette being sized and arranged to be held by the circulation device such that the pump chamber is operably communicated with the pump actuator, the disposable set including a patient line and a drain line extending from the disposable cassette; A temperature sensor operably coupled to one of the patient line, the drain line, or the disposable cassette for sensing the temperature of the outflow PD fluid removed from the patient; Comprising; The sensed temperature is used to form a patient peritonitis determination, and the control unit is configured to communicate the peritonitis determination, a PD system. (Item 19) The sensed temperature is transmitted to the control unit, and the control unit is configured to analyze the sensed temperature, the PD system according to item 18. (Item 20) The sensed temperature is transmitted to the control unit either wired or wirelessly, the PD system according to item 19. (Item 21) Including a network and at least one physician or clinician computer communicating with the control unit via the network, the control unit being configured to communicate the peritonitis determination to at least one of the patient or the caregiver via the network or via a user interface of the at least one physician or clinician computer, the PD system according to item 18. (Item 22) A PD system according to item 18, including a water purifier configured to supply purified water to the disposable set, the water purifier including a water purifier control unit, the sensed temperature being transmitted to the water purifier control unit, the water purifier control unit being configured to analyze the sensed temperature, the circulation device control unit and the water purifier control unit communicating, enabling the circulation device control unit to communicate the peritonitis determination. (Item 23) A PD system according to item 22, wherein either the circulation device control unit or the water purifier control unit is configured to analyze the sensed temperature. (Item 24) A PD system according to item 18, wherein the temperature sensor is installed in a connector configured to couple to the patient line or the drain line. (Item 25) A PD system according to item 24, wherein the connector is (i) a clam shell connector attached 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. (Item 26) A PD system according to item 24, wherein the connector includes (a) an outflow fluid flowing through the patient line or the drain line, or (b) electrodes positioned and arranged to be in direct contact with the patient line or the drain line. (Item 27) In (b), a thermally conductive segment is joined between sections of the patient line or the drain line, and the connector is directly connected to the thermally conductive segment. A PD system according to item 26. (Item 28) A PD system according to item 26, wherein the connector includes a wire extending from the electrode to (i) the control unit, (ii) the control unit of a water purifier configured to supply purified water to the disposable set, or (iii) a wireless module including the connector. (Item 29) The PD system according to item 18, configured to analyze the sensed temperature of the effluent PD fluid removed from the patient by comparing the sensed temperature to the temperature of fresh PD fluid sensed by the temperature sensor and delivered to the patient. (Item 30) The PD system according to item 18, configured to analyze the sensed temperature of the effluent PD fluid removed from the patient by looking for an increase in temperature due to peritonitis or its onset. (Item 31) The PD system according to item 30, wherein the increase in temperature due to peritonitis or its onset is detectable regardless of whether the sensed temperature is offset due to sensing through the patient line, the drain line, or the disposable cassette. (Item 32) The PD system according to item 18, wherein the peritonitis determination is a first peritonitis indicator, and the peritonitis determination includes at least one different peritonitis indicator that can be used in combination with the first peritonitis indicator to form an overall peritonitis determination. (Item 33) The PD system according to item 32, wherein the 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 white blood cell biosensor or a white blood cell impedance sensor. (Item 34) The PD system according to item 18, wherein the peritonitis determination is provided in combination with an insulin injection performed using feedback from a patient effluent glucose biosensor. (Item 35) A peritoneal dialysis (「PD」) system, the PD system comprising A circulation device including a pump actuator and a control unit operably communicating with the pump actuator, A disposable set including a disposable cassette having a pump chamber, the disposable cassette being sized and arranged to be held by the circulation device such that the pump chamber is operably in communication with the pump actuator, and a bio-MEMS device in fluid communication with the disposable cassette and comprising: The bio-MEMS device is configured to collect white blood cells from the outflow PD fluid removed from the patient, the collected white blood cells are used to form a patient peritonitis determination, and the control unit is configured to communicate the peritonitis determination. A PD system. (Item 36) The instruction of the collected white blood cells is transmitted to the control unit, and the control unit is configured to analyze the instruction of the collected white blood cells. The PD system according to item 35. (Item 37) The instruction of the collected white blood cells is transmitted to the control unit by wire or wirelessly. The PD system according to item 36. (Item 38) Including a network and at least one physician or clinician computer communicating with the control unit via the network, the control unit is configured to communicate the peritonitis determination to at least one of the patient or caregiver via the network or via a user interface of the at least one physician or clinician computer. The PD system according to item 35. (Item 39) The bio-MEMS device is installed in fluid communication with a sample port of the disposable cassette. The PD system according to item 35. (Item 40) The bio-MEMS device includes a control unit having at least one of an electronic device, processing, and memory, and either the circulation device control unit or the bio-MEMS device control unit is configured to analyze the sensed temperature. The PD system according to item 35. (Item 41) The bio-MEMS device includes: (i) a microfluidic chip sized and configured to form a microfluidic path that separates the white blood cells from the remaining effluent fluid; and (ii) a piezoelectric biosensor that resonates at a frequency proportional to the characteristics of the collected white blood cells. The PD system according to item 35 (Item 42) The characteristics of the collected white blood cells include a change in the deposition rate of the white blood cells. The PD system according to item 41 (Item 43) The frequency proportional to the characteristics of the collected white blood cells is used to form the peritonitis determination. The PD system according to item 41 (Item 44) The piezoelectric biosensor operates with a collection area for collecting the white blood cells. The PD system according to item 41 (Item 45) The bio-MEMS device includes a wired communication with the control unit or a wireless module for wireless communication with the control unit. The PD system according to item 35 (Item 46) The PD system according to item 35 is configured to analyze the amount of white blood cells removed from the effluent PD fluid and make the peritonitis determination (Item 47) The peritonitis determination is a first peritonitis indicator, and the peritonitis determination includes at least one different peritonitis indicator that can be used in combination with the first peritonitis indicator to form an overall peritonitis determination. The PD system according to item 35 (Item 48) The 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. The PD system according to item 47 (Item 49) The peritoneal inflammation determination is provided in combination with an insulin injection performed using feedback from a patient effluent glucose biosensor, the PD system of claim 35. (Claim 50) A peritoneal dialysis (「PD」) system, wherein the PD system comprises a circulation device including a pump actuator and a control unit operably communicating with the pump actuator, a disposable set including a disposable cassette having a pump chamber, the disposable cassette being sized and arranged to be held by the circulation device such that the pump chamber is operably communicating with the pump actuator, an insulin source in fluid communication with the disposable set, a microelectromechanical system (「MEMS」) affinity glucose sensor positioned and arranged to receive effluent PD fluid removed from a patient, and the MEMS affinity glucose sensor is configured to provide a glucose assay regarding glucose absorbed by a patient, the glucose assay being used to determine an insulin dosage, and the control unit is configured to deliver the insulin dosage from the insulin source to the patient by the pump actuator operating with the pump chamber of the disposable cassette, a PD system. (Claim 51) The PD system of claim 50, including a dialysis fluid source in fluid communication with the disposable set, the control unit being configured to deliver the insulin dosage from the insulin source mixed with fresh dialysis fluid from the dialysis fluid source to the patient. (Claim 52) The PD system of claim 51, wherein the dialysis fluid source is a point-of-use dialysis fluid source and the fresh dialysis fluid is mixed in a mixing bag with insulin from an insulin bag. (Claim 53) The disposable set includes a patient line and a drain line that are in fluid communication with the disposable cassette, and the MEMS affinity glucose sensor is in fluid communication with the drain line, the PD system according to item 50. (Item 54) The MEMS affinity glucose sensor is located along the drain line upstream of the drain container, the PD system according to item 53. (Item 55) Including a water purifier, the dialysate source is a point-of-use dialysate source that uses purified water from the water purifier, and the MEMS affinity glucose sensor comprises the water purifier, the PD system according to item 50. (Item 56) The water purifier communicates with the circulation device either wired or wirelessly, and the water purifier is configured to determine the insulin dose from the glucose assay and deliver the insulin dose to the circulation device for delivery, the PD system according to item 55. (Item 57) The MEMS affinity glucose sensor communicates with the circulation device either wired or wirelessly, and the control unit of the circulation device is configured to determine the insulin dose from the glucose assay transmitted from the MEMS affinity glucose sensor to the control unit, the PD system according to item 50. (Item 58) The MEMS affinity glucose sensor is configured to determine the insulin dose from the glucose assay, the PD system according to item 50. (Item 59) The glucose assay indicates the amount or concentration of glucose absorbed by the patient, the PD system according to item 50. (Item 60) The MEMS affinity glucose sensor includes (i) a microfluidic chip that forms a microfluidic path sized and configured to separate glucose molecules from the remaining effluent fluid, and (ii) a piezoelectric biosensor that resonates at a frequency proportional to the characteristics of the collected glucose molecules, the PD system according to item 50. (Item 61) The PD system according to item 60, wherein the characteristics of the collected glucose molecules include a change in the deposition rate of the glucose molecules. (Item 62) The PD system according to item 60, wherein the frequency proportional to the characteristics of the collected glucose molecules is used to form an insulin determination. (Item 63) The PD system according to item 60, wherein the piezoelectric biosensor operates with a collection area for collecting the glucose molecules. (Item 64) The PD system according to item 50, wherein the control unit is programmed on the assumption that the lower the concentration of glucose in the effluent, the greater the amount of glucose absorbed by the patient. (Item 65) The PD system according to item 50, comprising a network and at least one physician or clinician computer communicating with the control unit via the network, wherein the control unit is configured to communicate the insulin dose to at least one of a patient or a caregiver via the network or via a user interface of the at least one physician or clinician computer. (Item 66) The PD system according to item 50, comprising at least one peritonitis indicating device selected from a patient effluent PD fluid temperature sensor, a white blood cell biosensor, or a white blood cell impedance monitor.

Brief Description of the Drawings

[0114]

Figure 1

[0115]

Figure 2

[0116]

Figure 3

[0117]

Figure 4

[0118]

Figure 5

[0119]

Figure 6

[0120]

Figure 7

[0121]

Figure 8

[0122]

Figure 9

[0123]

Figure 10

[0124]

Figure 11

[0125]

Figure 12

[0126]

Figure 13

[0127]

Figure 14

[0128]

Figure 15

[0129]

Figure 16

[0130]

Figure 17

[0131]

Figure 18

[0132]

Figure 19

[0133]

Figure 20

DETAILED DESCRIPTION OF THE INVENTION

[0134] (System Overview) The feedback systems and methods described herein are applicable to peritoneal dialysis (“PD”). The feedback systems and methods are primarily applicable to automated peritoneal dialysis (“APD”) involving 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”). In the case of CAPD, the feedback systems and methods are implemented in a stand - alone device that reads data to the patient and / or communicates data remotely to a caregiver database for review by a physician or clinician. With respect to an APD machine, a suitable cycler is, for example, Baxter International Including the Amia® or HomeChoice® cycler commercially available by Inc. For example, the Amia® cycler is disclosed in U.S. Patent No. 9,981,079, while the HomeChoice® cycler is disclosed in U.S. Patent No. 5,350,357, and the contents of each of them are incorporated by reference and relied upon. Each of the patents incorporated above discloses the use of pre-packaged and pre-sterilized containers or bags of PD dialysate. The feedback system and method are applicable and implementable to cyclers that use pre-packaged and pre-sterilized PD solution. As discussed below, the feedback system and method are also applicable and implementable to cyclers that use PD solution made online or at the point of use.

[0135] Referring now to FIG. 1, one embodiment of a peritoneal dialysis system having point-of-use dialysate generation is illustrated by system 10. System 10 includes a circulation device 20 and a water purifier 210. Suitable circulation devices for circulation device 20 include, for example, Amia® or HomeChoise® circulation devices as described above, under the understanding that those circulation devices have updated programming for implementing and using point-of-use dialysate generated in accordance with system 10. For this purpose, circulation device 20 includes a control unit 22 having at least one processor and at least one memory. Control unit 22 further includes a wired or wireless transceiver for transmitting information to, and receiving information from, water purifier 210 and other wireless devices discussed herein. Water purifier 210 also includes a control unit 212 having at least one processor and at least one memory. Control unit 212 further includes a wired or wireless transceiver for transmitting information to, and receiving information from, control unit 22 of circulation device 20 and other wireless devices discussed herein. Wired communication may be via, for example, an Ethernet® connection. Wireless communication may be implemented via any one of Bluetooth®, WiFi®, Zigbee®, Z-Wave®, wireless universal serial bus (“USB”), or infrared protocol, or via any other suitable wireless communication technology.

[0136] The circulation device 20 includes a housing 24, which holds equipment programmed via a control unit 22 to prepare fresh dialysis solution at the point of use, pump the newly prepared dialysate to the patient P, allow the dialysate to remain in the patient P, and then pump the used dialysate to a drain line. In the illustrated embodiment, the water purifier 210 includes a drain line 214 connected to a drain pipe 216, which can be an indoor drain pipe or a drain container. The equipment programmed via the control unit 22 to prepare fresh dialysis solution at the point of use in one embodiment includes equipment for a pneumatic pump system, which includes, but is 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 under the control of the control unit 22 to provide the positive and negative pressures to be stored in the one or more positive and negative pressure reservoirs, or a single pump that generates both positive and negative pressures under the control of the control unit 22, (iv) a plurality of pneumatic valve chambers for delivering positive and negative pressures to a plurality of fluid valve chambers, (v) a plurality of pneumatic pump chambers for delivering positive and negative pressures to a plurality of fluid pump chambers, (vi) a plurality of electrically actuated on / off pneumatic solenoid valves under the control of the control unit 22 located between the plurality of pneumatic valve chambers and the plurality of fluid valve chambers, (vii) a plurality of electrically actuated variable orifice pneumatic valves under the control of the control unit 22 located between the plurality of pneumatic pump chambers and the plurality of fluid pump chambers, (viii) in one embodiment, a heater under the control of the control unit 22 for heating the dialysate as it is mixed, and (ix) a shutoff 26 under the control of the control unit 22 for closing off the patient and the drain line in the event of an alarm and other situations.

[0137] In one embodiment, the plurality of pneumatic valve chambers and the plurality of pneumatic pump chambers are located on the front or surface of the housing 24 of the circulation device 20. The heater is located inside the housing 24 and, in some embodiments, includes a heating coil that contacts a heating pan or tray, and the heating pan or tray is located at the upper part of the housing 24 under the heating lid (not visible in FIG. 1).

[0138] The circulation device 20 in the illustrated embodiment includes a user interface 30. The control unit 22 in some embodiments includes a video controller that may have its own processing and memory for interacting with the main control processing and memory of the control unit 22. The user interface 30 includes a video monitor 32, and the video monitor 32 may operate with a touch screen overlay installed on the video monitor 32 for inputting commands to 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 further include an audio controller for playing audio files such as voice activation commands in one or more speakers 34.

[0139] The water purifier 210 in the illustrated embodiment also includes a user interface 220. The control unit 212 of the water purifier 210 in some embodiments includes a video controller that may have its own processing and memory for interacting with the main control processing and memory of the control unit 212. The user interface 220 includes a video monitor 222, and the video monitor 222 may operate similarly with a touch screen overlay installed on the video monitor 222 for inputting commands to the control unit 212. The user interface 220 may also include one or more electromechanical input devices such as membrane switches or other buttons. The control unit 212 may further include an audio controller for playing audio files such as alarms or alert sounds in one or more speakers 224 of the water purifier 210.

[0140] In addition, referring to FIG. 2, an embodiment of the disposable set 40 is illustrated. The disposable set 40 is also illustrated in FIG. 1 and is adapted to be fitted to the circulation device 20 to move the fluid within the disposable set 40, for example, to mix the dialysate as discussed herein. The disposable set 40 in the illustrated embodiment includes a disposable cassette 42, and the disposable cassette 42 may include a planar rigid plastic component covered on one or both sides by a flexible membrane. The membrane pressed against the housing 24 of the circulation device 20 forms a pump and valve membrane. FIG. 2 illustrates that the disposable cassette 42 includes a fluid pump chamber 44 that operates with a pneumatic pump chamber located in the housing 24 of the circulation device 20, and a fluid valve chamber 46 that operates with a pneumatic valve chamber located in the housing 24 of the circulation device 20.

[0141] FIGS. 1 and 2 illustrate that the disposable set 40 includes a patient line 50 that extends from a patient line port of the cassette 42 and terminates at a patient line connector 52. FIG. 1 illustrates that the patient line connector 52 is then connected to a patient transfer set 54, and the patient transfer set 54 is connected to an indwelling catheter located within the abdominal cavity of the patient P (see FIG. 11). The disposable set 40 includes a drain line 56 that extends from a drain line port of the cassette 42 and terminates at a drain line connector 58. FIG. 1 illustrates that the drain line connector 58 is removably connected to a drain connector 218 of the water purifier 210.

[0142] Figures 1 and 2 further illustrate that the disposable set 40 includes a heater / mixing line 60 that extends from the heater / mixing line port of the cassette 42 and terminates at a heater / mixing bag 62, which is discussed in more detail below. The disposable set 40 includes an upstream water line segment 64a that extends to the water inlet 66a of the water accumulator 66. The downstream water line segment 64b extends from the water outlet 66b of the water accumulator 66 to the cassette 42. In the illustrated embodiment, the upstream water line segment 64a starts from a water line connector 68 and is located upstream from the water accumulator 66. FIG. 1 illustrates that the water line connector 68 is removably connected to the water outlet connector 228 of the water purifier 210.

[0143] The water purifier 210 outputs water, possibly water suitable for peritoneal dialysis (“WFPD”). However, to ensure WFPD, a sterilization grade filter 70a is installed upstream from a downstream sterilization grade filter 70b. Filters 70a and 70b can be installed within the upstream water line segment 64a of the water accumulator 66. The sterilization grade filters 70a and 70b can be pass-through filters without exclusion lines. Suitable sterilization grade filters 70a and 70b can be provided by the applicant of the present disclosure. In certain embodiments, only one of the upstream or downstream sterilization grade filters 70a and 70b is required to produce WFPD, and yet two sterilization grade filters 70a and 70b are provided in the illustrated embodiment for redundancy in case one fails.

[0144] FIG. 2 further illustrates that a last bag or sample line 72 can be provided that extends from the last bag or sample port of the cassette 42. The last bag or sample line 72 terminates at a connector 74 that can be connected to a connector of the pre-mixed last fill bag of the dialysate or to a sample bag or other sample collection container. The last bag or sample line 72, and the connector 74, can alternatively be used for a third type of concentrate, if desired.

[0145] Figures 1 and 2 illustrate that the disposable set 40 includes a first (e.g., glucose) concentrate line 76 that extends from a first concentrate port of the cassette 42 and terminates at a first (e.g., glucose) cassette concentrate connector 80a. A second (e.g., buffer) concentrate line 78 extends from a second concentrate port of the cassette 42 and terminates at a second (e.g., buffer) cassette concentrate connector 82a.

[0146] Figure 1 illustrates that a first concentrate container 84a holds a first (e.g., glucose) concentrate, and the first concentrate is pumped from the first concentrate container 84a through a container line 86 to a first container concentrate connector 80b that mates with the first cassette concentrate connector 80a. A second concentrate container 84b holds a second (e.g., buffer) concentrate that is pumped from the container 84b through a container line 88 to a second container concentrate connector 82b that mates with the second cassette concentrate connector 82a.

[0147] In certain embodiments, to initiate treatment, patient P loads the cassette 42 into the circulation device and, in a random or specified order, (i) installs a heater / mixing bag 62 on the circulation device 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 is still capped. When fresh dialysate is prepared and verified, the patient line 50 is primed with fresh dialysate, after which patient P may connect the patient line connector 52 to the transfer set 54 for treatment. Each of the above steps may be graphically illustrated on the video monitor 32 and / or provided via audio guidance from the speaker 34.

[0148] With respect to the disposable set 40, the rigid portion of the cassette 42 can be made of, for example, a medically acceptable rigid plastic. The flexible membrane of the cassette 42 can be made of, for example, a medically acceptable rigid plastic sheet. Any of the bags or containers such as the heater / mixing bag or container 62 discussed below can be made of a medically acceptable plastic sheet.

[0149] The control unit 22 can be programmed to cause the circulation device 20 to perform one or more mixing operations and to mix the dialysate appropriately and homogeneously for treatment. For example, any of the fluid pump chambers 44 can be caused to draw a certain amount of mixed fluid (e.g., made from one or both of the first and second concentrates 84a, 84b and WFPD) from the heater / mixing bag 62 into the pump chamber, return such a mixture to the heater / mixing bag 62, and be caused to repeat this procedure a plurality of times (described herein as a mixing sequence or "waffling"). In particular, to perform the mixing sequence, the control unit 22 in certain embodiments closes all of the fluid valve chambers 46 in the cassette 42, except for the fluid valve chamber 46 to the heater / mixing line 60 and the heater / mixing bag 62, to the circulation device 20. The fluid pump chamber 44 is caused to continuously and repeatedly stroke such that (i) it draws into the pump chamber a combination of WFPD and potentially unmixed fluid from the heater / mixing bag 62, followed by (ii) pushing the mixed WFPD and concentrate back from the pump chamber to the heater / mixing bag 62, and (iii) repeating (i) and (ii) at least once. The control unit 22 can be programmed to stroke the fluid pump chambers 44 together such that both push and pull simultaneously, or to stroke the fluid pump chambers 44 alternately such that one pump chamber 44 draws from the heater / mixing bag 62 and the other pump chamber 44 pushes to the heater / mixing bag 62 to create turbulent flow in the heater / mixing line 60.

[0150] The configuration of the container or bag 62 operable with the cassette 42 and the heater / mixing line 60 as illustrated in FIGS. 1 and 2 allows the WFPD from the accumulator 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. Further, even if the cassette 42 is not provided, the WFPD and at least one concentrate will be partially mixed within the heater / mixing line 60 prior to reaching the container or bag.

[0151] FIG. 1 also illustrates that in one embodiment, system 10 communicates operably with one or more caregiver servers 102 installed via communicating operably with one or more doctor or clinician computers 110 - 110c via network 100. In the illustrated embodiment, network 100 is a cloud network that uses one or more wide area networks (“WANs”) such as the Internet. Network 100 can alternatively be a more local area network (“LAN”). In the illustrated embodiment, the circulation device 20 of system 10 communicates wirelessly with network 100 via any of the protocols listed herein. In an alternative embodiment, the circulation device 20 of system 10 communicates with network 100 in a wired manner, for example, using an Ethernet (registered trademark) connection. In the illustrated embodiment, the circulation device 20 of system 10 communicates with network 100. In an alternative embodiment, the water purifier 210 communicates with network 100 wirelessly or in a wired manner alternatively or in addition. In the illustrated embodiment, one or more caregiver servers 102 communicate wirelessly with network 100 via any of the protocols listed herein. In an alternative embodiment, one or more caregiver servers 102 communicate with network 100 in a wired manner, for example, using an Ethernet (registered trademark) connection. In the illustrated embodiment, doctor or clinician computers 110 - 110c communicate with one or more caregiver servers 102 in a wired manner, for example, using an Ethernet (registered trademark) connection. In an alternative embodiment, doctor or clinician computers 110 - 110c communicate wirelessly with one or more caregiver servers 102 via any of the protocols listed herein. (Temperature Sensing Regarding Peritonitis)

[0152] Referring now to FIG. 3-8B, in one major embodiment, the temperature of the spent dialysate exiting the patient is measured to detect peritonitis. In a healthy patient, the temperature of the spent dialysate is normal body temperature or about 37° C. In a patient suffering from the onset of peritonitis, the spent dialysate exiting the patient can be present at an elevated temperature. The system and method of the first embodiment measure the effluent dialysate and use the measurement to make a determination regarding whether the patient is suffering from the onset of peritonitis.

[0153] Temperature measurements can be made in several different ways. The temperature sensing connector 120 of FIG. 3 illustrates one mechanism for reading the temperature of the effluent fluid removed from the patient P (FIG. 1). The connector 120 includes a main housing 122 that can be made of any suitable medical grade material such as medical grade plastic. In the illustrated embodiment, the housing 122 is joined into the patient line 50 (FIG. 1). The housing 122 includes a first port 124 that receives the first joined end 50a of the patient line 50 in a sealed state. The first port 124 can include, for example, a hose return port, or can be so, or can be sized to spread the first joined end 50a as shown. The first port 124 can alternatively be a luer connector that connects to the luer connector end 50a of the patient line 50. The housing 122 includes a second port 126 that receives the second joined end 50b of the patient line 50 in a sealed state. The second port 126 can be a male port just like the port 124, or can be a female port as shown that receives the second joined end 50b in a sealed state via a compression fitting (to do so, the second joined end 50b can have an internal rigid hose return attached to maintain its shape when under compression). The female port 126 allows the electrical conductors 128a and 128b to extend out of the housing 122 when an electrical signal is distributed via the wire to the control unit 22 of the circulation device 10 (or the control unit 212 of the water purifier 210).

[0154] Electrical conductors 128a and 128b each extend to probes or electrodes 130a and 130b, which contact the outflow fluid traveling through housing 122 and provide temperature readings regarding the fluid. Conductors 128a and 128b, and electrodes 130a and 130b, can be overmolded into or adhered to the inner cylindrical surface of housing 122. The temperature sensor of connector 120 can be, for example, a thermocouple or a thermistor. In the illustrated embodiment, electrodes 130a and 130b are the sensing portions of a type-K (chromel-alumel) thermocouple, generating a measurable voltage that is proportional to the temperature of the outflow fluid.

[0155] Connector 120 illustrates a plurality of ways in which the generated voltage can be analyzed (alternatively, thus, not all of the structures illustrated in FIG. 3 need to include connector 120, and only the structures are used). In one embodiment, conductors 128a and 128b carry the generated voltage back to the control unit 22 of the circulation device 20 (or the control unit 212 of the water purifier 210), and the electronics and processing of the control unit process the temperature-proportional voltage signal to determine whether the resulting temperature indicates peritonitis or its onset.

[0156] In another embodiment (shown by the dashed line), conductors 128a and 128b carry the generated voltage to a wireless module 132 located along the outside of housing 122. Wireless module 132 is powered in one embodiment by a battery 134, such as a long-lasting lithium battery, and includes electronics configured to convert the temperature-proportional voltage into a wireless signal, which is wirelessly transmitted to the control unit 22 of the circulation device 20. The control unit 22 of the circulation device 20 processes the wireless version of the temperature-proportional voltage signal to determine whether the resulting temperature indicates peritonitis or its onset.

[0157] Figure 3 illustrates an embodiment in which a connector is joined between two tubing segments. Figures 4A and 4B illustrate an alternative embodiment in which a clam shell temperature connector 140 instead fits over a tubing segment such as a portion of the patient line 50. In the illustrated embodiment, the clam shell temperature connector 140 first directly contacts and lies on top of 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 two polymer or plastic segments of the patient line 50. The more thermally conductive medical grade segment 150 can help achieve a more accurate temperature measurement.

[0158] Figures 4A and 4B illustrate that in the illustrated embodiment, the clam shell temperature connector 140 includes a housing 142 having clam shell halves 144 and 146 that are hingedly attached together along an integral hinge 148. The housing 142 is made of any suitable material such as a medical grade plastic. The housing 142 is sized to form a fit over the patient line 50 / 150 in the illustrated embodiment.

[0159] The connector 140 includes respective electrical leads 152a and 152b that extend to probes or electrodes 154a and 154b, which contact the patient line 50 / 150 and provide the temperature of the effluent fluid flowing through the line. The leads 152a and 152b, and the electrodes 154a and 154b, can be overmolded or adhered into the inner cylindrical surfaces of the respective clam shell halves 144 and 146. The temperature sensor of the connector 140 can again be a thermocouple or a thermistor. In the illustrated embodiment, the electrodes 154a and 154b are the sensing portions of a type K (chromel - alumel) thermocouple, which generates a voltage that can be sensed, and the voltage indicates the temperature of the effluent fluid.

[0160] Connector 140 illustrates a plurality of ways in which the generated voltage can be analyzed (as an alternative, thus, not all of the structures illustrated in FIGS. 4A and 4B need to include connector 140, only the structure is used). In one embodiment, conductors 152a and 152b carry the generated voltage back to the control unit 22 of the circulation device 20 (or the control unit 212 of the water purifier 210), and the electronics and processing of the control unit processes the temperature-proportional voltage signal to determine whether the resulting temperature indicates peritonitis or its onset.

[0161] In another embodiment (shown by the dashed line), conductors 152a and 152b carry the generated voltage to a wireless module 132 located along the outside of the housing 142. The wireless module 132 includes electronics configured to be powered by a battery 134, such as a long-lasting lithium battery, in one embodiment, and convert the temperature-proportional voltage into a wireless signal, which is wirelessly transmitted to the control unit 22 of the circulation device 20. The control unit 22 of the circulation device 20 processes the wireless version of the temperature-proportional voltage signal to determine whether the resulting temperature indicates peritonitis or its onset.

[0162] FIG. 5 illustrates a further alternative embodiment in which a snap-fit temperature connector 160 is attached to the wall of the housing 24 of the circulation device 20 (or the wall of the housing of the water purifier 210), either inside or outside the machine. The snap-fit temperature connector 160 includes a housing 162, and the connector 160 is bolted, adhered, or formed thereby to 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 sized to snap onto the patient line 50 / 150 in the illustrated embodiment, in combination with probes or electrodes 166a and 166b. The C-shaped collar 164 spreads slightly apart to receive the patient line 50 / 150 and then spreads slightly apart again to release the patient line 50 / 150 when the treatment is complete.

[0163] The electrodes 166a and 166b can be overmolded or adhered to the inner cylindrical surface of the C-shaped collar 164. The temperature sensor of the connector 160 can again be a thermocouple or a thermistor. In the illustrated embodiment, the electrodes 166a and 166b are the sensing portions of a type K (chromel-alumel) thermocouple, which generates a voltage that can be sensed, and the voltage indicates the temperature of the outflowing fluid. In the illustrated embodiment, the electrodes 166a and 166b each extend to the conducting wires 168a and 168b, and the conducting wires 168a and 168b carry the generated voltage through the wall of the housing 24 to the control unit 22 of the circulation device 20 (or the control unit 212 of the water purifier 210), and the electronics and processing of the control unit processes the temperature-proportional voltage signal and determines whether the resulting temperature indicates peritonitis or its onset.

[0164] FIG. 6 schematically illustrates a wireless version of the temperature sensing of the first main embodiment. The patient line 50 or the thermally conductive patient line segment 150 conveys the outflowing fluid. The electrode E (representing all the 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 outflowing fluid (FIG. 3). The temperature indicating the voltage is conveyed via the conducting wire L (representing all the conducting wires discussed above) to the wireless module 132. The wireless module 132 includes electronics configured to be powered by a battery 134 such as a long-lasting lithium battery and to convert the temperature-proportional voltage into a wireless signal that is wirelessly transmitted to a desired control unit.

[0165] FIG. 6 also illustrates another alternative embodiment where the electrode E is instead located along the sheet of the disposable cassette 42. Here, the electrode E is located inside the circulation device 20 and is automatically aligned with the cassette 42 when the cassette is installed. The patient or caregiver is not required to take any additional measures. In this scenario, the wireless module 132 is not needed and the conducting wire L extends directly to the control unit 22 instead.

[0166] As discussed above, examining the temperature of the effluent fluid of patient P is used to determine whether the patient has peritonitis. The effluent fluid flows from patient P through the patient transfer set 54, the patient line connector 52, the patient line 50, the disposable set 40, the drain line 56, the drain line connector 58, and the drain connector 218 of the water purifier 210. It is envisioned that the temperature sensing connectors 120, 140, or 160 are installed at any of those locations, including as part of the patient transfer set 54, the patient line connector 52, or the drain line connector 58. On one aspect, it is advantageous to install the temperature sensing connectors 120, 140, or 160 as close as possible to patient P (e.g., the patient transfer set 54 or the patient line connector 52) so as to sense the patient effluent temperature as accurately as possible. However, as shown below, temperature sensing can be useful for this purpose even if the true patient temperature is not sensed. Positioning the temperature sensing for peritonitis along the drain line within the water purifier 210 is advantageous, for example, if the temperature sensor is present for another purpose such as operating in combination with a conductivity sensor to examine the conductivity of the dialysate and determine the mixing accuracy.

[0167] Figures 7A and 7B illustrate exemplary data from either a direct fluid sensing embodiment (e.g., connector 120 of FIG. 3) or an embodiment of sensing through the thermally conductive patient tube segment 150, each of which should read the true fluid temperature. Each of FIGS. 7A and 7B shows temperature readings for two fill stages (Fi1 and Fi2) and two drain stages (Dr1 and Dr2). After each fill stage, a dwell period indicated by parallel lines follows. After each drain stage, the next fill stage, as indicated by a single vertical line, follows.

[0168] Prior to delivery to patient P via cassette 42 and patient line 50, the circulation device 20 heats the fresh dialysate in the heater / mixing bag 62 to body temperature or 37°C. In each filling stage case of FIGS. 7A and 7B, the temperature reading is 37°C or about 37°C when the heated fresh fluid passes the temperature sensor. The drain stage readings (Dr1 and Dr2) are readings of the outflow dialysate from patient P, and the outflow fluid has been present in the patient for an extended period, e.g., at least 1 hour, whereby the outflow fluid temperature provides a true indication of the patient's body temperature. FIG. 7A shows the outflow temperature readings from a healthy PD patient where the reading is at or slightly above body temperature or 37°C. FIG. 7B shows the outflow temperature readings from a PD patient who may be suffering from peritonitis or its onset where the reading is significantly above body temperature, about 38°C in the example shown.

[0169] In evaluating the temperature readings, it is contemplated to program temperature signal manipulation. For example, assume that the set point for generating a peritonitis alert is 38°C. The relevant processes and memory for evaluating the temperature readings can be programmed to average the temperature readings over the course of the drain flow of the outflow fluid passing the temperature sensor. In this way, a short temperature spike up to 38°C does not trigger an alert or flag. It is also contemplated to average the temperature readings prior to making a determination as to whether to generate a peritonitis alert by looking at the temperature readings over multiple outflow drains (e.g., Dr1 and Dr2). For example, in one embodiment, an alert is generated at the end of a treatment involving multiple outflow drains when the sum of the outflow temperature readings indicates peritonitis or its onset (e.g., 38°C or higher).

[0170] Figures 8A and 8B generally illustrate exemplary data from an embodiment of sensing through a non-thermally conductive patient tube segment 50, where the temperature readings can be below the true fluid temperature. Each of Figures 8A and 8B shows temperature readings for two fill phases (Fi1 and Fi2) and two drain phases (Dr1 and Dr2). After each fill phase, a dwell period indicated by parallel lines follows. After each drain phase, the next fill phase, as indicated by a single vertical line, follows.

[0171] Since it is known that the circulation device 20 heats the fresh dialysate 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, the temperatures during the fill phases of Figures 8A and 8B provide an accurate indication of the temperature reading offset due to the generally non-thermally conductive nature of the tubing (e.g., polyvinyl chloride (“PVC”)) of the patient line 50. In the illustrated example of Figures 8A and 8B, the temperature of the heated fresh PD fluid is read as 32 °C instead of being known to be 37 °C. The relevant control unit 22 or 212 thereby determines that the current offset for the current tubing under the current environmental conditions is 5 °C. The relevant control unit is then programmed to expect that the outflow fluid removed from the healthy patient P has approximately the same temperature offset (i.e., is about 32 °C). The relevant control unit is also programmed to determine that the patient P may have peritonitis if the temperature of the outflow fluid removed from the patient exceeds the offset temperature of about 32 °C by a predetermined amount.

[0172] In each filling stage instance of FIGS. 8A and 8B, the offset temperature readings through generally non - thermally conductive patient line tubing 50 are 32° C. or about 32° C. when the heated fresh fluid passes the temperature sensor. The drain stage readings (Dr1 and Dr2) are again the readings of the effluent dialysate from patient P, and the effluent fluid has been present within the patient for an extended period, e.g., for at least one hour, whereby the effluent fluid temperature provides a true indication of the patient's body temperature. FIG. 8A shows the effluent temperature readings from a healthy PD patient where the readings are at the expected offset temperature of 32° C. or can slightly exceed it. However, FIG. 8B shows the effluent temperature readings from a PD patient who may be suffering from peritonitis or its onset, where the readings significantly exceed the expected offset temperature, about 34° C. in the illustrated example. Regarding the expected offset examples of FIGS. 8A and 8B, again, it is assumed that in evaluating the temperature readings, temperature signal manipulation as described above, e.g., programming to average and accumulate over multiple fills and drains, is done.

[0173] In the examples of FIGS. 7A - 8B, when the relevant control unit 22 or 212 determines that patient P may be suffering from peritonitis or its onset, in one embodiment, the control unit causes the user interface 30 and / or 220 to provide an audio, visual, or audiovisual alert to the patient and / or caregiver in the circulation device 20 and / or the water purifier 210 of the system 10. In one embodiment, even when the control unit evaluating the temperature readings for peritonitis determination is the control unit 212 of the water purifier 210, nevertheless, the audio, visual, or audiovisual alert is provided at the user interface 30 of the circulation device 20 by wired or wireless communication from the control unit 212 of the water purifier 210 to the control unit 22 of the circulation device 20 to notify the alert condition. Thus, the user interface 30 is the primary communication means for a given treatment and patient P, and the user interface 220 is entrusted with displaying water purifier - related information.

[0174] In addition to, or perhaps as an alternative to, the alerts provided to the patient P or caregiver at the user interface 30 of the circulation device 20, the control unit 22 (or perhaps the control unit 212) operates via the networks 100 and one or more caregiver server computers 102 to enable a physician or clinician to determine, for example, continuously, whether the patient is at risk of having or developing peritonitis, such as by enabling a physician or clinician in one or more clinician computers 110a - 110c to receive and view effluent temperature data. The data is displayed on the clinician computers 110a - 110c via, in one embodiment, the dashboard of a website for the patient, and the temperature data can be presented with a flag for the clinician when it rises and indicates peritonitis.

[0175] Regardless of whether the data indicates peritonitis, it is contemplated that effluent temperature data regarding the patient P be transmitted after full treatment. In this way, a physician or clinician can create a pattern or profile of the effluent temperature regarding the patient. It is contemplated that the website create, for example, in addition to the dashboard, a graph or trend of the effluent temperature plotted against the treatment days displayed upon request. The trend and dashboard in one embodiment point out or flag temperature inputs that may indicate peritonitis or its onset. A physician or clinician viewing multiple flagged peritonitis days can thus determine with reasonable certainty that the patient requires treatment. (BioMEMS Sensing for Peritonitis)

[0176] Referring now to FIGS. 9 and 10, in a second major embodiment, a bio - microelectromechanical system (“bio - MEMS”) sensor is used to detect peritonitis. The bio - MEMS sensor is used to search for the presence of white blood cells from the patient in the effluent fluid, which is an indicator of peritonitis. FIG. 9 illustrates that in one implementation, the effluent fluid from patient P is pumped via patient line 50 into cassette 42 loaded in circulation device 20, and then from cassette 42 via discharge line 56 to the discharge pipe in water purifier 210. Discharge line 56 is connected in one embodiment to a lab - on - chip diagnostic detection or bio - MEMS device 170. However, in the illustrated embodiment of FIG. 9, an alternative is shown where the effluent fluid is selectively pumped to the lab - on - chip diagnostic detection device 170 via special sample port 48 and sample line 158. Using sample port 48 enables the control unit 22 of circulation device 20 to selectively deliver a desired amount of effluent fluid from patient P to the lab - on - chip diagnostic detection device 170 at a desired time and / or frequency.

[0177] As shown in FIG. 9, the lab - on - chip or bio - MEMS device 170 includes a container 172, and sampling line 158 extends to container 172 and connects to an inlet line 174 located within container 172 (e.g., via compression fittings, threaded fittings, luer connections, hose barb connections, and combinations thereof). Container 172 can be made from a medically acceptable metal or polymer such as plastic like stainless steel or PVC.

[0178] The effluent sample travels along the inlet line 174 of the bioMEMS device 170 to a microfluidic pathway 178 formed on or within the microfluidic chip 176. The microfluidic chip 176 in various embodiments is made of an inorganic material, a polymeric material, or paper. In various embodiments, the microfluidic chip 176 is made of silicon, glass, a polymeric substrate, a composite material, or paper. The microfluidic pathway 178 is sized and configured to separate the patient's white blood cells from the remaining effluent fluid.

[0179] The separated white blood cells are then delivered to a collection area 180 (made of the same material as the container 172 or the microfluidic chip 176 in various embodiments), where they are weighed by a piezoelectric biosensor 182 or otherwise quantified. The piezoelectric sensor 182 in various embodiments uses the piezoelectric effect to measure changes in pressure, strain, or force due to the collected white blood cells by converting the changes into an electric charge. In one embodiment, the piezoelectric biosensor 182 resonates at a frequency proportional to the change in the deposition rate of the white blood cells.

[0180] In the illustrated embodiment, the bioMEMS device 170 includes a control unit 184 having electronics, processing, and memory for converting the resonance frequency from the biosensor 182 into a quantified amount representative of the amount of white blood cells removed from the patient's effluent sample. The control unit 184 may also include a user interface 186, which displays an audio, visual, or audiovisual message indicating the presence or absence of white blood cells, and thus the presence or absence of peritonitis or its onset, to the patient or caregiver.

[0181] Alternatively, in one embodiment, the bioMEMS device 170 includes an electronic device configured to convert the white blood cell count proportional voltage into a wireless signal as shown in FIG. 9 that is wirelessly transmitted to the control unit 22 of the circulation device 20. Here, the user interface 186 is not required and the user interface 30 of the circulation device 20 is used instead. Processing and memory for the device 170 may also not be required.

[0182] The method 190 of FIG. 10 summarizes the methodology described above. In oval 192, the method 190 begins. In block 194, the effluent discharge of patient P is collected via, for example, a separate sample port 48 and sample line 158 of the cassette 42 discussed above. In block 196, white blood cells, if present, are separated from the patient's effluent fluid, for example, via the microfluidic chip 176. In block 198, the separated white blood cells are weighed or otherwise quantified, for example, via the piezoelectric biosensor 182. In block 200, the white blood cell weight is converted into an electrical signal, for example, via the piezoelectric biosensor 182. In block 202, the electrical signal is converted into a form that can be used by the control unit 22 (of the circulation device 20) or the control unit 184 (of the bioMEMS device 170) to determine whether the amount of collected white blood cells indicates peritonitis or its onset. An amount of white blood cells below which peritonitis is not presumed to be present may exist. In block 204, the results of the white blood cell analysis are displayed at the user interface 30 (of the circulation device 20) or the user interface 186 (of the bioMEMS device 170), and the patient or caregiver is alerted if necessary. In oval 206, the method 206 ends.

[0183] Networks 100, one or more caregiver server computers 102, and one or more clinician computers 110a - 110c are not shown in FIG. 9, but they can still exist. And in addition to, or perhaps as an alternative to, the alerts provided to the patient P or the caregiver at the user interface 30 or user interface 186, the control unit 22 operates via the network 100 and one or more caregiver server computers 102 to enable a physician or clinician to determine whether a patient has peritonitis or is at risk of developing it, for example, continuously, such that a physician or clinician at one or more clinician computers 110a - 110c can receive and view effluent white blood cell collection data. The data is displayed on clinician computers 110a - 110c via a dashboard of a website for the patient, and the effluent white blood cell collection data can be presented with a flag for the clinician when it rises and indicates peritonitis.

[0184] Regardless of whether the data indicates peritonitis, it is contemplated to transmit effluent white blood cell collection data regarding patient P after full treatment. Thus, a physician or clinician can create a pattern or profile of the effluent white blood cell collection data regarding the patient. Also, it is contemplated that the website can create, for example, in addition to the dashboard, a graph or trend of the effluent white blood cell collection amount plotted against the treatment days, which is displayed upon request. The trend and dashboard in one embodiment point out or flag white blood cell inputs that can indicate peritonitis or its onset. A physician or clinician viewing multiple flagged peritonitis days can thus determine with reasonable certainty that the patient requires treatment. The white blood cell collection data of the second main embodiment can be displayed as an alternative to, or in addition to, the effluent temperature data of the first main embodiment. Providing both white blood cell collection data and effluent temperature data enables a physician or clinician to view and analyze multiple peritonitis indicators to make medical decisions for the patient.

[0185] In an alternative embodiment, the bioMEMS device 170 is instead located within the patient line 50 via a sample line and is used to analyze the effluent returning from the patient P. In this way, the bioMEMS device can also be used to sense fresh dialysate delivered to the patient, if desired. Alternatively, the control unit 20 can be programmed to periodically send fresh dialysate into the bioMEMS device 170 via the sample port 48 and sample line 158 of the cassette 42 to sample the desired properties of the fresh dialysate. (Impedance Monitoring for Peritonitis)

[0186] Referring now to FIGS. 11 - 13, in a third main embodiment, an impedance monitor is used to detect peritonitis. The impedance monitor is again used to look for the presence of white blood cells from the patient in the effluent fluid, which is an indicator of peritonitis. In various implementations, the impedance monitor can be placed anywhere where the patient's effluent fluid can be sensed, for example, within the patient's indwelling catheter, within the patient line, or anywhere within the drain line. At any of these locations, the catheter or line is equipped with electrodes in any of the ways discussed above for temperature sensing, but here with the goal of establishing a conductive contact in communication with the effluent dialysate for impedance detection.

[0187] FIG. 11 illustrates impedance monitors 230 installed at multiple locations. At a first location, the impedance monitor 230 is installed along the indwelling catheter 55 of patient P, and the indwelling catheter 55 is connected to the patient transfer set 54 and is in fluid communication with the patient line 50. At a second location (not shown), the impedance monitor 230 is installed along the patient line 50. At a third location (not shown), the impedance monitor 230 is fixed within the circulation device 20 and is positioned to operate with the disposable cassette 42 or a line (patient line or discharge line) extending from the disposable cassette 42. At a fifth location, the impedance monitor 230 is positioned along the discharge line 56 between the circulation device 20 and the water purifier 210. At a sixth location, the impedance monitor 230 is fixed within the water purifier and is positioned along the discharge line extending within the water purifier. At any of the above locations, the impedance monitor 230 can sense the outflow fluid and detect peritonitis.

[0188] FIGS. 12 and 13 illustrate an embodiment of the impedance monitor 230. FIG. 12 illustrates, in one embodiment, that the cylindrical electrodes 240 and 244 are mounted within the patient line 50, the indwelling catheter 55 of the patient, or the discharge line 56. The cylindrical electrodes 240 and 244 in the illustrated embodiment are tubular segments or sections having an outer diameter slightly larger than the inner diameter of the lines 50, 56 or the catheter 55, whereby the electrodes 240 and 244 are press-fitted at desired locations within the lines 50, 56 or the catheter 55. The electrodes 240 and 244 are made of a conductive and medically safe material such as stainless steel, titanium, and combinations and alloys thereof. Each of the electrodes 240 and 244 in the illustrated embodiment includes a female port or socket 242 and 246, respectively, which are configured to receive and hold a conductive wire extending from the port.

[0189] FIG. 13 illustrates that in one embodiment, female ports or sockets 242 and 246 extend through lines 50, 56 or catheter 55 in such a way that the line or catheter wall seals around the female ports or sockets 242 and 246. FIG. 12, alternatively, illustrates ports or sockets that extend at least substantially coplanar with the outside of lines 50, 56 or catheter 55. In any embodiment, the outer diameters of ports or sockets 242 and 246 are larger than the holes created within lines 50, 56 or catheter 55, whereby the tube or catheter material is stretched around the port and sealed thereto. In a further alternative embodiment (not shown), ports or sockets 242 and 246 do not extend outwardly from cylindrical electrodes 240 and 244, and instead, conductive wires are passed through lines 50, 56 or catheter 55. Here, lines 50, 56 or catheter 55 serve to hold the conductive wires in place.

[0190] FIG. 13 illustrates that conductive leads 248a and 248b extend from ports or sockets 242 and 246, respectively. Similar to the temperature sensing connectors of FIGS. 3 - 4B, the conductive leads 248a and 248b of impedance monitor 230 in one embodiment extend to control unit 22 of circulation device 20 (or control unit 212 of water purifier 210) so that the electronics and processing of the control unit enable signal generation and processing to be carried out as discussed below. In an alternative embodiment (shown by the dashed line), leads 248a and 248b receive power from wireless module 132 positioned along the outside of housing 232 of impedance monitor 230 and / or carry the generated voltage thereto. Wireless module 132, again, includes electronics configured to be powered by a battery 134 such as a long - lasting lithium battery and to convert the voltage to a wireless signal and vice versa, and the wireless signal is communicated wirelessly to control unit 22 of circulation device 20 in one embodiment.

[0191] The housing 232 may have clam shell halves 234 and 236, which are hingedly attached together along an integral hinge discussed with respect to FIGS. 4A and 4B. The housing 232 is sized in the illustrated embodiment to form a fit over the patient line 50, catheter 55, or drain line 56. The housing 232 is alternatively joined between two segments of the patient line 50, catheter 55, or drain line 56 in a manner identical to or similar to the temperature sensing connector 120 of FIG. 3. The housing 232 in any of the above embodiments is made from any suitable material such as medical grade plastic.

[0192] The control unit 22 of the circulation device 20 or the control unit 212 of the water purifier 210 that controls the impedance monitor causes, in one embodiment, an electrical frequency sweep to be generated within the effluent fluid. The control unit may include or operate with a frequency sweep generator that moves from a start frequency to a stop frequency at a defined sweep rate. It is envisioned that the frequency will be swept up or down at linear or logarithmic intervals. It is also envisioned that the control unit will be programmed to sweep a sine, square, pulse, ramp, triangle, or arbitrary waveform. It is further envisioned to define a hold time (during which the sweep remains at the stop frequency) and a return time (during which the frequency linearly changes from the stop frequency to the start frequency).

[0193] As the impedance monitor 230 progresses through the sweep frequency, the impedance resulting from the effluent fluid within the indwelling catheter is measured at each different frequency. The impedance of the effluent fluid can be compared to that of the fresh dialysate to determine if a difference occurs. Impedance spectroscopy (or obtaining complex impedance) in one embodiment provides additional details about the contents of the effluent fluid. For example, the electrical properties of fibrin (which do not indicate peritonitis) can vary from those of white blood cells (which indicate peritonitis). When the control unit 22 (of the circulation device 20) or the control unit 212 (of the water purifier 210) learns the electrical properties of the different substances that may be present in the effluent fluid, those properties are programmed into the control unit and can then be used to determine what happens when something contaminates the effluent dialysate stream.

[0194] Figures 14A and 14B illustrate exemplary plots of impedance (Z) measured in ohms (Ω) with respect to normal patient effluent, patient effluent having white blood cells (indicating peritonitis), and patient effluent having other particulate matter such as fibrin. Figure 14A shows impedance measurements over time that can be continuous or discrete (on command). Exemplary time-based outputs show, for example, over the course of the dwell phase of a patient's peritoneal dialysis treatment, (A) normal effluent impedance (continuous line only), and (C) continuous data for effluent with increased fibrin content (dashed line). In the example shown, the plots of impedance over time for effluent with normal fibrin (A) and effluent with increased fibrin (C) start together, but then the impedance for effluent with increased fibrin rises well above that of effluent with normal fibrin. The curve regarding the onset of peritonitis will presumably be represented by a line extending within the area marked (B) between the line (A) for effluent with normal fibrin and the line (C) for effluent with increased fibrin as confirmed in Figure 14B. Figure 14B shows that as the patient's dwell phase progresses, a clear difference appears between effluent with normal fibrin and effluent with increased fibrin.

[0195] Figure 14B illustrates an impedance spectrogram corresponding to the curves illustrated in the time-based plot of Figure 14A. Exemplary frequency-based outputs show continuous data for (a) normal effluent impedance (continuous line only), (b) onset of peritonitis dissipated by antibiotics (continuous line with boxes), and (c) effluent with increased fibrin content (dashed line), the data at the points highlighted within the left frame. The spectrograms (a)-(c) cover a frequency range of 10 Hz to 10 6 Hz in one example.

[0196] The exemplary frequency-based output of FIG. 14B illustrates that there are likely to be one or more frequency ranges where the impedance difference between the effluent with leukocytes (b) and the normal effluent (a) is significantly different from other frequencies. In FIG. 14B, two such frequency ranges exist between f1 and f2, and between f3 and f4. Having multiple significantly different frequency ranges allows the control unit 22 or 212 to cross-check the result of one range against the other. If both or all of the frequency ranges indicate peritonitis, the control unit 22 or 212 (or the clinician computer 110a - 110c) outputs to the user interface 30, the user interface 220, and / or to the clinician computer 110a - 110c via the network 100 and the caregiver server computer 102 a determination that the patient has peritonitis or is starting to have it. In another embodiment, the control unit 22 or 212 integrates the area under the impedance curve (b) and compares it to the integration of the area under the impedance curve (a) to determine peritonitis or its onset.

[0197] In one embodiment, the curve (a) for normal effluent is determined empirically through testing on multiple patients and then averaged to develop a standardized impedance value over the frequency sweep range. The standardized values in certain embodiments are determined for each of the most commonly used glucose level peritoneal dialysis fluids in good standing, as impedance can vary based on the starting glucose level. The standardized impedance values can be provided as a range that takes into account different dwell times, different effluent temperatures, and other factors.

[0198] In another embodiment, the curve (a) for normal effluent is empirically determined again, here for a particular patient, using system 10 and circulation device 20. Impedance data is obtained over a plurality of treatments or for all treatments. A normal effluent impedance average is formed, which can be a rolling average that may move or shift over time. The curve (b) for peritoneal effluent is determined to be present in one embodiment when the impedance within a relevant frequency range or averaged via integration is a predetermined percentage higher than the patient-specific curve (a).

[0199] Regarding the increased fibrin content curve (c), FIG. 14B illustrates that there is at least one specific frequency range where the impedance (b) of the effluent with white blood cells indicating peritonitis is significantly higher than the impedance (c) of the effluent with increased fibrin, here between f1 and f2. Thus, in FIG. 14B, since the increased impedance between frequency ranges f3 and f4 can be attributed to either the effluent (b) with white blood cells indicating peritonitis or the effluent (c) with increased fibrin, it can be said that the most important range is between frequency ranges f3 and f4.

[0200] Alternatively, or in addition, it is envisioned that control unit 22 or 212 (or clinician computer 110a - 110c) looks at the shape of the impedance curve over a frequency range. If the shape is closest to curve (a), control unit 22 or 212 (or clinician computer 110a - 110c) determines that the patient effluent is normal. If the shape is closest to curve (b), control unit 22 or 212 (or clinician computer 110a - 110c) determines that the patient effluent indicates peritonitis or signs of its onset. If the shape is closest to curve (c), control unit 22 or 212 (or clinician computer 110a - 110c) determines that the patient effluent has an increased fibrin level.

[0201] In any embodiment where the impedance monitor 230 is located remotely from the circulation device 20 or the water purifier 210, the impedance monitor may transmit signals measured in a wired or wireless manner for investigation to the circulation device. The impedance monitor 230 as described above has the ability to radiate a frequency sweep into the effluent fluid and thus may receive power either via the battery 134 (in the wireless embodiment) or from either the circulation device or the water purifier via a power wire.

[0202] As discussed above, in an alternative embodiment, the impedance monitor 230 is located within the circulation device 20 or the water purifier 210. In such a case, the impedance monitor 230 radiates a frequency sweep into the effluent fluid by receiving power from the circulation device or the water purifier via a power wire. As described above, the impedance monitor 230 may operate with the disposable cassette 42 loaded within the circulation device 20. Here, the impedance monitor 230 may extend through a rigid wall that holds the disposable cassette sheet in one or more locations.

[0203] The control unit 22 or 212 is programmed in one embodiment to warn the patient or caregiver at the user interface 30 of the circulation device 20 if white blood cells indicating peritonitis are detected. In one embodiment, even if the control unit that evaluates the impedance sweep readings regarding white blood cells is the control unit 212 of the water purifier 210, nevertheless, an audio, visual, or audiovisual alert is provided at the user interface 30 of the circulation device 20 by wired or wireless communication from the control unit 212 of the water purifier 210 to the control unit 22 of the circulation device 20 to notify of the alert condition. Thus, the user interface 30 is the primary means of communication for a given treatment and patient P, and the user interface 220 is entrusted with displaying water purifier-related information.

[0204] In addition to, or perhaps as an alternative to, the alerts provided to the patient P or caregiver at the user interface 30, the control unit 22 operates via the networks 100 and one or more caregiver server computers 102 to enable a physician or clinician to determine whether a patient has peritonitis or is at risk of developing it. For example, continuously, the impedance acquisition effluent white blood cell data is received and viewed by a physician or clinician at one or more clinician computers 110a - 110c. The data is displayed on the clinician computers 110a - 110c via, for example, the dashboard of a website for the patient, and the effluent white blood cell collection data can be presented with a flag for the clinician when it rises and indicates peritonitis.

[0205] Regardless of whether the data indicates peritonitis, it is contemplated to transmit the impedance acquisition effluent white blood cell data regarding patient P after all treatments. In this way, a physician or clinician can create a pattern or profile of the effluent white blood cell data regarding the patient. It is also contemplated that the website creates, for example, in addition to the dashboard, a graph or trend of the effluent white blood cell volume plotted against the treatment days displayed upon request. The trend and dashboard in one embodiment point out or flag the white blood cell input that may indicate peritonitis or its onset. A physician or clinician viewing multiple flagged peritonitis days can thus determine with reasonable certainty that the patient requires treatment. The white blood cell data of the third main embodiment can be displayed as an alternative to, or in addition to, the white blood cell collection data of the second main embodiment and / or the effluent temperature data of the first main embodiment. Providing both the white blood cell data embodiment and the effluent temperature data enables a physician or clinician to view and analyze multiple peritonitis indicators to make medical decisions for the patient. (Glucose Control for Diabetic Patients)

[0206] Referring now to FIGS. 15 - 20B, in a fourth main embodiment, system 10 provides a MEMS affinity glucose sensor 250 that serves to match, or assist in matching, the amount of insulin provided to patient P with the amount of glucose delivered to the patient during treatment. FIG. 14 illustrates a version of system 10 that uses pre - prepared PD fluid in containers or bags 94a and 94b instead of making the PD fluid stored in accumulator 66 online or at the point of use using glucose concentrate 84a, buffer concentrate 84b, or purified water from water purifier 210 (shown in FIGS. 1, 9, 11, and 15). However, in any version, patient P receives glucose from the PD fluid. That is, the pre - prepared PD fluid in containers or bags 94a and 94b contains glucose at levels prescribed by a physician or clinician. It should be understood that any of the main embodiments discussed herein could alternatively be provided using the pre - prepared PD fluid version of system 10 illustrated in FIG. 14.

[0207] FIG. 15 illustrates that in one embodiment of pre - prepared PD fluid, an insulin container or bag 90 is connected to a port of cassette 42 that is connected to accumulator 66 in an example point of use. A MEMS affinity glucose sensor 250 is provided in drain line 56 upstream of drain bag 96. The MEMS affinity glucose sensor 250 measures the glucose level of the effluent dialysate exiting patient P via drain line 56.

[0208] FIG. 16 illustrates that in one embodiment, the MEMS affinity glucose sensor 250 includes a container 252, and a sampling line 254 extends into the container 252. The sampling line 254 may extend from or branch off the discharge line 56. The effluent sample entering the container 252 of the MEMS affinity glucose sensor 250 first encounters a microfluidic pathway 256 that splits glucose molecules from the effluent fluid. 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 proportional to the change in the deposition rate of the glucose molecules. The relationship between the resonance frequency and the glucose found in the effluent fluid is illustrated below in connection with FIG. 18. The glucose absorbed at the end of the nth PD cycle is calculated using the equation for A n discussed below. To compensate for the glucose absorbed in the nth PD cycle, the insulin dosage administered during the subsequent n + 1 PD cycles is calculated using the equation for I n+1 discussed below.

[0209] The MEMS affinity glucose sensor 250 includes, in one embodiment, electronics and processing for processing the raw signal from the piezoelectric biosensor 258 and making a determination regarding the appropriate concentration of insulin to be prepared with the PD solution. The MEMS affinity glucose sensor 250 may also include a user interface for indicating to the patient or caregiver present during treatment that an appropriate insulin level has been determined. In an alternative embodiment, either or both of (i) the electronics and processing for processing the raw signal from the piezoelectric biosensor 258, or (ii) the user interface for patient or caregiver communication, are instead provided by the control unit of the circulation device 20 or the water purifier 210 operable with the circulation device.

[0210] The MEMS - compatible glucose sensor 250 of FIG. 15 includes a wireless module 132 positioned along the outside of the housing of the device 250. The wireless module 132, as discussed herein, is powered by a battery 134 such as a long - lasting lithium battery and, in one embodiment, includes electronics configured to convert the measured patient effluent glucose level into a wireless signal that is transmitted wirelessly to the control unit 22 of the circulation device 20. The control unit 22 of the circulation device 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 patient P is sometimes filled with fluid from a previous treatment when starting the current treatment.

[0211] The amount of insulin to be delivered is based on a desired insulin concentration, which is related to the amount of glucose sensed via the sensor 250 and is transmitted to the control unit 22. Knowing the desired insulin concentration and the amount of fresh pre - prepared PD fluid from one of the containers or bags 92a or 92b to be delivered to the heater bag 62, the amount of insulin to be delivered from the container or bag 90 to the heater bag 62 is determined and then pumped to the heater bag 62 via the fluid pump chamber 44 of the disposable cassette 42. In an alternative embodiment, the amount of insulin is instead pumped from the insulin container or bag 90, via the fluid pump chamber 44 of the disposable cassette 42 or via a separate pump (not shown), to a pre - prepared PD fluid container or bag 92a or 92b. Insulin ports may be provided on the pre - prepared PD fluid containers or bags 92a and 92b to receive insulin.

[0212] FIG. 15 illustrates that in one embodiment, system 10 using MEMS affinity glucose sensor 250 also includes a glucose sensor 262 that is applied, for example, to the finger of patient P. Such glucose sensors are known in the art in either a lancet or non-lancet form. In the illustrated embodiment, glucose sensor 262 wirelessly outputs glucose readings to control unit 22, control unit 212, or MEMS affinity glucose sensor 250. Wired communication between glucose sensor 262 and control unit 22, control unit 212, or MEMS affinity glucose sensor 250 is also possible. The readings from glucose sensor 262 at the start of treatment are used to determine the amount of insulin to be injected in the next PD fill cycle in one embodiment discussed below. The readings from glucose sensor 262 can be used at the end of treatment to confirm that the blood glucose level of patient P remains within the safe zone using the glucose feedback and insulin injection of the present disclosure. All such information can also be transmitted to clinician computers 110a - 110c via network 100 and one or more caregiver server computers 102.

[0213] In the usage-site preparation version of FIG. 17, the MEMS affinity glucose sensor 250 is, in the illustrated embodiment, located within the water purifier 210 and electrically outputs to the control unit 212 of the water purifier, and thus does not require a wireless module 132 located along the outside 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 the circulation device 20 should deliver to the heater / mixing bag 62 for the next patient PD fill. It should be noted that patient P is typically filled with fluid from the previous treatment when starting the current treatment. The amount of insulin to be delivered is based on the desired insulin concentration, which in turn is related to the amount of glucose sensed via the device and is transmitted to the control unit 22. Knowing the desired insulin concentration and the amount of fresh pre-prepared PD fluid to be mixed online 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 is determined and then pumped to the heater / mixing bag 62 via the fluid 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 and transmits that amount to the control unit 22 of the circulation device 20, either wired or wirelessly, and the control unit 22 uses that amount and commands 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 to the control unit 22, either wired or wirelessly, and the control unit 22 determines the amount of insulin to be pumped and uses that amount and commands the pump chamber 44 of the disposable cassette 42 to pump the desired amount of insulin.

[0214] The control unit 22 operates via the networks 100 and one or more caregiver server computers 102 to enable a physician or clinician in one or more clinician computers 110a - 110c to view insulin usage data, for example, for each treatment, so that the clinician can confirm that insulin is being delivered appropriately. The data is, in one embodiment, displayed on the dashboard of a website for the patient, and the insulin volume and concentration can be viewed. The data of the fourth main embodiment can be displayed on a physician or clinician website for patient P in combination with the data of the first, second, and / or third main embodiments so as to provide a desired combination of data. FIG. 17 also illustrates that, in one embodiment, the system 10 using the MEMS affinity glucose sensor 250 also includes the glucose sensor 262 provided and used as described above.

[0215] Referring now to FIG. 18, method 290 summarizes one embodiment related to the closed-loop insulin delivery described above. At oval 292, method 290 begins. At block 294, the circulation device 20 operates the disposable cassette 42 to draw in fresh dialysate (pre-prepared or prepared at the point of use) from the heater bag 62 (pre-prepared) or the heater / mixing bag 62 (at the point of use) together with the calculated dose of insulin from the insulin bag or container 90, and (ii) push the heated fresh dialysis and insulin dose fluid into patient P. At block 296, the dialysate is allowed to remain intraperitoneally in patient P for the amount of time prescribed by the physician / clinician. At block 298, the circulation device 20 operates the disposable cassette 42 to draw in used dialysate or effluent from patient P's peritoneum, 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 (FIG. 14) or the drain pipe 216 (FIG. 15) in the water purifier 210. The MEMS affinity glucose sensor 250 is located at a location along the drain line as shown in FIGS. 14 and 15. At block 300, the MEMS affinity glucose sensor 250 monitors the effluent PD fluid with respect to the amount or concentration of glucose absorbed by the patient. At block 302, the MEMS affinity glucose sensor 250, or the control unit 22 of the circulation device 20, or the control unit 212 of the water purifier 210 calculates the insulin dosage based on the amount or concentration of glucose absorbed by patient P. In certain embodiments, if the control unit 22 of the circulation device 20 does not calculate the insulin dosage, the calculated dosage is transmitted to the control unit 22 of the circulation device 20.

[0216] In diamond 304, if there is another cycle in the current treatment, method 290 returns to block 294, and the control unit 22 of the circulation device 20 provides the next patient fill using the newly calculated dose of insulin based on the newly monitored amount or concentration of absorbed glucose. In diamond 304, if there is no other cycle in the current treatment, method 290 moves to block 306 and saves the newly calculated dose of insulin based on the newly monitored amount or concentration of absorbed glucose for the first fill of the next treatment. In oval 308, method 290 ends.

[0217] It should be understood that method 290 is applied to PD treatments that do not provide the patient with a "last fill" of fresh PD fluid to be retained through the day until the next treatment (possibly with mid-day exchanges). That is, patient P leaves the treatment empty. When a "last fill" is provided, method 290 after start oval 292 instead proceeds to a drain block 298 to drain the "last fill" effluent fluid from the patient, then to a monitoring block 300, then to a calculation block 302, and then to a fill with fresh fluid using insulin dose block 294. A decision diamond is provided instead after the fill with fresh fluid using insulin dose block 294, and the decision is whether there is another patient drain. If so, the modified method proceeds to a hold block 296 and returns through blocks 298, 300, 302, and 294. When there is no additional patient drain, the modified method ends in oval 308. Since the first step of the next treatment is to drain from patient P, there is no need for an insulin dose save block 306 in the "last fill" method.

[0218] FIG. 19 illustrates one exemplary relationship between the glucose absorbed in the effluent fluid and the frequency resonating from the cantilever 260 of the biosensor 258. In the exemplary plot, the effluent fluid without absorbed glucose (continuous line) resonates at a frequency ratio of about 0.66 and provides an output amplitude that is approximately (i) twice as large as the effluent fluid absorbed at a glucose concentration X1 mg / dL that resonates at a frequency ratio of about 0.8 (continuous line with boxes) and (ii) two-thirds larger than the effluent fluid absorbed at a glucose concentration X2 mg / dL (dashed line) that resonates at a frequency ratio of about 1.0. FIG. 18 illustrates that the biosensor 258 of the MEMS affinity glucose sensor 250 is effective in distinguishing different glucose concentrations present in the effluent fluid.

[0219] 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 initial glucose concentration of the fresh dialysate delivered to the patient P. The control unit is programmed to determine the amount of glucose absorbed by the patient at the end of the nth PD cycle (P n ) in a function as follows. P n = f(V n , μ, (D on - D in )) wherein n = cycle number, V n = the volume of the PD fluid delivered for the nth cycle, μ = glucose absorption coefficient (an empirically determined constant), D on = the glucose concentration of the effluent for the nth cycle as measured by the MEMS affinity glucose sensor 250 D in = the initial glucose concentration of the PD fluid for the nth cycle (the PD fluid is provided at standard concentrations such as 0.55%, 1.5%, 2.5%, and 4.25%) is.

[0220] At the end of the nth cycle (P n ), based on the amount of glucose absorbed by the patient, the amount of insulin to be provided to the patient in subsequent cycles is, in one embodiment, determined by a function as follows. I n+1 = f(G I , P n , α, β, t) Wherein, G I = In one embodiment, it is the initial blood glucose level before the start of therapy obtained from the glucose sensor 262, P n is calculated as discussed above, α and β are insulin absorption coefficients (empirically determined constants), t = time.

[0221] Figures 20A and 20B graphically illustrate how the glucose level (mg / dL) can exceed the upper threshold when not controlled but remain within the limits prescribed by a physician or clinician when controlled, using the glucose feedback and insulin injection of the system 10 of FIGS. 15 - 18 having the MEMS affinity glucose sensor 250. As illustrated in FIG. 20A, the glucose level (mg / dL) in the patient P steadily rises through each residence period and exceeds the upper threshold in the second residence. However, in FIG. 20B, the glucose level (mg / dL) in the patient P rises during the residence period according to the function discussed above programmed into the MEMS affinity glucose sensor 250, the control unit 22, or the control unit 212, but then drops during the subsequent filling stage while insulin is being injected.

[0222] It should be understood that various changes and modifications to the preferred embodiments of the present application described herein will be apparent to those skilled in the art. Such changes and modifications can be made without departing from the spirit and scope of the subject matter of the present application and without diminishing its intended advantages. Accordingly, such changes and modifications are intended to be covered by the appended claims. For example, although four main embodiments have been described in connection with an automated peritoneal dialysis system using a circulation device 20, it is also contemplated that the embodiments can be used with manual PD or continuous ambulatory peritoneal dialysis ("CAPD"). Although MEMS biosensing with respect to white blood cells and glucose molecules has been discussed in connection with various vibration frequencies, it is also contemplated that other properties used in a transducer can be detected to provide a sensed output property such as, but not limited to, a voltage including a change in capacitance within a microfluidic channel, or a change in light and its frequency. Further, although an impedance monitor 230 is illustrated and described as comprising an indwelling catheter 55 of a patient P, it is contemplated that any of the four main embodiments can be implemented with an indwelling catheter.

Claims

**Claim 1** An impedance measurement system comprising: an impedance monitor configured to sense the impedance of peritoneal dialysis ("PD") fluid present within a fluid line, the impedance monitor comprising: a first conductive wire disposed within a first port along the fluid line; and a second conductive wire disposed within a second port along the fluid line an impedance monitor; a control unit electrically coupled to the impedance monitor, the control unit being configured to: use the sensed impedance from the impedance monitor to detect white blood cells and form a patient peritonitis determination; and communicate the peritonitis determination a control unit configured to perform; An impedance measurement system comprising. **Claim 2** The impedance measurement system of claim 1, wherein the first conductive wire and the second conductive wire are located within a fluid connector configured to couple to the fluid line. **Claim 3** The impedance measurement system of claim 2, wherein the fluid connector is configured to be joined between two sections of the fluid line. **Claim 4** The impedance measurement system of claim 1, wherein the first conductive wire is coupled to a first cylindrical electrode disposed within the fluid line and the second conductive wire is coupled to a second cylindrical electrode disposed within the fluid line. **Claim 5** The impedance measurement system of claim 1, wherein the first conductive wire and the second conductive wire extend from the fluid line to (i) the control unit, (ii) a control unit of a water purifier configured to supply purified water to the disposable set, or (iii) a wireless module. **Claim 6** The impedance measurement system of claim 1, wherein the sensed impedance is transmitted to the control unit, either wired or wirelessly. **Claim 7** Further comprising at least one physician or clinician computer that communicates with the control unit via a network, The impedance measurement system of claim 1, wherein the control unit is configured to communicate the peritonitis determination to the at least one physician or clinician computer via the network. **Claim 8**: Further comprising a user interface, wherein the user interface is configured to receive the peritonitis determination from the control unit, and display information indicating the peritonitis determination The impedance measurement system according to claim 1. **Claim 9**: The impedance measurement system according to claim 8, wherein the control unit and the user interface are included within a PD cycler. **Claim 10**: The impedance measurement system according to claim 1, wherein the control unit is configured to analyze the sensed impedance of the PD fluid present in the fluid line via a frequency sweep that moves from a start frequency to a stop frequency using the first and second conductive leads. **Claim 11**: The impedance measurement system according to claim 10, wherein the frequency sweep is generated by a frequency generator provided by the control unit or a frequency generator operable with the control unit. **Claim 12**: The impedance measurement system according to claim 10, wherein the control unit is configured to perform impedance measurements at two or more frequencies of the frequency sweep. **Claim 13**: The impedance measurement system according to claim 10, wherein the frequency sweep enables determination by measuring that a PD fluid having white blood cells has a higher impedance over at least a portion of the frequency sweep than a PD fluid having no white blood cells. **Claim 14**: The impedance measurement system according to claim 13, wherein the impedance for a PD fluid having no white blood cells is determined based on (i) a set standard impedance or (ii) an impedance established for the patient. **Claim 15**: The impedance measurement system according to claim 10, wherein the frequency sweep enables a PD fluid having white blood cells to be distinguished from a PD fluid having fibrin, and the PD fluid having fibrin results in a higher impedance than the PD fluid having white blood cells over at least a portion of the frequency sweep. **Claim 16**: The peritonitis determination is a first peritonitis indicator, and the control unit is configured to obtain at least one different peritonitis indicator that can be used in combination with the first peritonitis indicator to form an overall peritonitis determination. The impedance measurement system according to claim 1. **Claim 17**: The 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. The impedance measurement system according to claim 16. **Claim 18**: The peritonitis determination is provided in combination with an insulin injection performed using feedback from a patient effluent glucose biosensor. The impedance measurement system according to claim 1. **Claim 19**: An impedance measurement system, An impedance monitor configured to sense the impedance of peritoneal dialysis ("PD") fluid present in a fluid line, the impedance monitor comprising: A first conductive wire disposed within a first port along the fluid line; A second conductive wire disposed within a second port along the fluid line And an impedance monitor; A water purifier configured to supply purified water to a disposable set, the water purifier including a water purifier control unit, the water purifier control unit being: Using the sensed impedance from the impedance monitor to detect white blood cells and form a patient peritonitis determination; Communicating the peritonitis determination And a water purifier configured to perform; An impedance measurement system comprising. **Claim 20**: Further comprising a PD circulation device, the PD circulation device being: Receiving the peritonitis determination from the water purifier control unit; Transmitting the peritonitis determination to a clinician computer via a network And an impedance measurement system according to claim 19, configured to perform.

Images