Peritoneal dialysis system configured so as to diagnose peritonitis using sensor

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] (Priority Claim) This application claims priority to and the benefit of U.S. Provisional Patent Application No. 62 / 703,749, filed July 26, 2018, entitled "Dialysis Systems and Methods Including Sensor Feedback to Improve Patient Experience," the entire contents of which are incorporated herein by reference. [Background technology]

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

[0003] It is known to use dialysis to support patients whose kidney function has declined to the point where the kidneys no longer function adequately. Two major dialysis methods are offered: hemodialysis and peritoneal dialysis.

[0004] In hemodialysis, a patient's blood is passed through an artificial kidney dialysis machine. A membrane within the machine acts as an artificial kidney to purify the blood. Because it is an extracorporeal treatment that requires a specialized machine, certain inherent disadvantages exist with hemodialysis. To overcome the disadvantages associated with hemodialysis, peritoneal dialysis was developed. Peritoneal dialysis uses the patient's own peritoneal membrane as a semipermeable membrane. The peritoneal membrane is the membranous lining of the patient's abdominal cavity. Due to good perfusion, the peritoneal membrane functions as a natural semipermeable membrane.

[0005] Peritoneal dialysis involves the periodic infusion of a sterile aqueous solution, or dialysate, into the peritoneal cavity. Diffusion and osmotic exchange occur between the peritoneal dialysate and the blood across natural body membranes. The exchange removes waste products that the kidneys normally excrete. The waste products consist of solutes such as urea and creatinine. In addition, the kidneys maintain levels of other substances, such as sodium and water. Dialysis regulates the diffusion of water and solutes across the peritoneal membrane during dialysis, a process called ultrafiltration.

[0006] In continuous ambulatory peritoneal dialysis ("CAPD"), dialysis solution is introduced into the peritoneal cavity through a catheter. Solute exchange between the dialysate and blood is achieved by diffusion. Further solute removal is achieved through the dialysate providing a suitable osmotic gradient from the blood to the dialysate. The osmotic gradient allows for the proper acid-base electrolyte and fluid balance to be achieved within the patient's body. Spent dialysate, or effluent, is manually drained via gravity from the body cavity through the catheter.

[0007] A variation of CAPD is automated peritoneal dialysis ("APD"). APD uses a machine called a circulator to automatically infuse, dwell, and drain peritoneal dialysis fluid into and out of the patient's peritoneal cavity. APD is attractive to peritoneal dialysis patients because it can be performed overnight while the patient is asleep, freeing them from the daily demands of CAPD during their waking and working hours.

[0008] An APD sequence typically lasts for several hours. It often begins with an initial drain phase, which empties the peritoneal cavity of spent dialysate from the previous treatment. The APD sequence then progresses 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, due in part to the ability of APD to be tailored to a patient's specific needs regarding their personal life and their therapy needs. The two primary 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 cycling peritoneal dialysis ("CCPD"), and high-dose CCPD), solution type, therapy time, and fill volume. Prescribing an APD therapy constitutes selecting one of each of these. Thus, there are many combinations and possibilities from which to choose.

[0010] APD devices typically lack the ability to provide patients with feedback regarding the effectiveness of their current therapy. Furthermore, APD devices typically operate open-loop, whereby they do not adjust therapy parameters (e.g., modality, solution type, therapy time, and fill volume) based on actual measured daily clearance and UF. Thus, some patients underachieve their targets and develop adverse symptoms, such as fluid overload and, in some cases, hypertension. Current methods for adjusting therapy typically involve patients reporting to a center for evaluation on an occasional basis. These methods place the burden of therapy adjustment solely 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] APD, such as CAPD, uses a catheter implanted in the patient's peritoneum to deliver fresh dialysate and remove spent dialysate from the patient's peritoneal cavity. The placement of the peritoneal catheter provides an opportunity to sense desired parameters within the patient. Additionally, both APD and CAPD remove spent effluent PD fluid from the patient, which provides an opportunity to sense patient parameters or characteristics present in the effluent fluid. Thus, a need exists for systems and methods that utilize the placement of the patient catheter and / or the effluent PD fluid removed from the patient to help monitor and / or control peritoneal dialysis therapy, such as CAPD and APD. And, more generally, a need exists for immediate or intratherapy feedback to address various issues 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") therapy. Three of the systems and methods described herein involve the detection, optimally, early detection, of peritonitis. 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 infection from bacteria or fungi that can enter through the patient's membrane catheter.

[0013] If left untreated, peritonitis can rapidly spread into the blood (sepsis) and other organs, resulting in multiple organ failure and death. The first symptoms of peritonitis are typically loss of appetite and nausea, and dull abdominal pain that quickly turns into persistent, severe abdominal pain. Other signs and symptoms associated with peritonitis may include abdominal tenderness or distension, chills, fever, ascites, and vomiting.

[0014] Mortality from peritonitis depends on many factors but can be as high as 40% in patients who also have cirrhosis. As many as 10% of patients may die from secondary peritonitis. Primary spontaneous peritonitis is an infection that develops within the peritoneum and is the type associated with peritoneal dialysis treatment. Secondary peritonitis usually develops when an injury or infection within the peritoneal cavity introduces infectious organisms into the peritoneum. Both types of peritonitis are life-threatening.

[0015] Current methods for determining peritonitis are subjective and burdensome to the patient. For example, the patient may be asked to observe the color and / or texture of their effluent fluid to look for peritonitis. Or, the patient may be asked to be aware of stomach bloating and / or fever. When the patient believes peritonitis is developing or present, the patient must take an effluent sample to a clinic for testing. The above methods are subjective and burdensome to the patient. The following system and method are automatic and objective. (Temperature sensing for peritonitis)

[0016] In one main embodiment, the temperature of spent dialysate exiting a patient is measured to detect peritonitis. In a healthy patient, the temperature of the spent dialysate is normal body temperature, or approximately 37°C. In a patient suffering from a peritonitis episode, the spent dialysate exiting the patient may be at an elevated temperature. The system and method of the first main embodiment measures the effluent dialysate and uses the measurement to make a determination as to whether the patient is likely suffering from a peritonitis episode.

[0017] Temperature measurements can be performed in several different ways. In one method, a temperature sensor, such as a thermocouple or thermistor, is placed in a connector, such as a clamshell-type connector, that removably and selectively clips onto the patient line. The clamshell connector can be placed anywhere desired around the patient line, for example, near the patient, so that the temperature of the patient's effluent dialysate can be measured immediately as it leaves the patient. In one embodiment, the temperature of the effluent fluid is compared to body temperature or the temperature of fresh dialysate, which can be heated to 37°C. In this way, any temperature offset caused by the generally non-thermally conductive tubing is nullified. For example, if a fresh dialysate temperature of 37°C is read from tubing at an offset temperature of 32°C, the same offset will be assumed for the effluent fluid leaving the patient. A control unit reading the temperature signal will therefore 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, medically safe material, such as stainless steel, is bonded or inlaid into the patient line. One or more thermally conductive electrodes are attached to the temperature sensor, allowing for more accurate temperature readings. Here, the control unit reading the temperature signal looks for a patient health signal of 37°C in one embodiment 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 take into account the inlet temperature of the fresh dialysate.

[0019] In any embodiment in which the temperature sensor is located remotely from the circulator, the temperature sensor may transmit the measured signal to the circulator in a wired or wireless manner for interrogation. The temperature sensor, in one embodiment, is 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 may be provided via a battery or via a power wire from the circulator or a water purifier operating with the circulator.

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

[0021] Temperature sensing is alternatively performed in the drain line extending from the disposable cassette, which is advantageous because sterility is less of an issue, as the drain line is plugged into a reusable thermally conductive junction provided, in one embodiment, with the circulator or a water purification device that operates with the circulator.

[0022] The control unit, in one embodiment, is programmed to alert the patient at the circulator's user interface if a high temperature indicative of peritonitis is detected. Alternatively, or in addition, the control unit operates via a network and one or more server computers to allow a doctor or clinician to view effluent temperature data, for example, on a continuous basis, so that the clinician can determine whether the patient is at risk for peritonitis. The data, in one embodiment, is displayed on a website dashboard for the patient, and temperature data may be presented with a flag for the clinician when it is elevated and indicates peritonitis. (BioMEMS sensing of peritonitis)

[0023] In a second main embodiment, which can be used alternatively or in addition to the first embodiment, a bio-microelectromechanical system ("bio-MEMS") sensor is used to detect peritonitis. The bio-MEMS sensor is used to look for the presence of white blood cells from the patient in the effluent, which is an indicator of peritonitis. In one implementation, the effluent fluid from the circulatory system is pumped to discharge. The discharge line is connected to a lab-on-a-chip diagnostic detection device. The lab-on-a-chip or bio-MEMS device includes a container into which a sampling line extends, which may extend from or branch off from the discharge line. The effluent sample entering the container of the bio-MEMS device first encounters a microfluidic pathway that separates the patient's white blood cells from the effluent fluid. The white blood cells are then weighed, in one embodiment, using a piezoelectric biosensor. The piezoelectric biosensor resonates at a frequency proportional to the change in white blood cell sedimentation rate.

[0024] The BioMEMS device can alternatively be placed in the patient line via a sample line and used to analyze the effluent returning from the patient. Thus, the BioMEMS device can additionally be used to sense the fresh dialysate being delivered to the patient, if desired.

[0025] In one embodiment, the BioMEMS device includes electronics and processing for processing the raw signals 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 whether or not an indication of peritonitis is present. In an alternative embodiment, either or both of (i) the electronics and processing for processing the raw signals from the piezoelectric biosensor or (ii) the user interface for patient or caregiver communication may instead be provided by the circulator or, possibly, a water purification device operable with the circulator.

[0026] As with the first main embodiment, the control unit and processing for the second main embodiment may alternatively or additionally operate via a network and one or more server computers to allow a doctor or clinician to view the bioMEMS data, for example, on a continuous basis, so that the clinician may determine whether the patient is at risk for peritonitis. The data of the second main embodiment may be displayed in combination with the data of the first main embodiment to provide a combined peritonitis indicator. (Impedance monitoring for peritonitis)

[0027] In a third main embodiment, which may be used alternatively or 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 may be placed anywhere the patient's effluent fluid can be sensed, for example, in 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 now with the goal of placing a conductive contact in communication with the effluent dialysate.

[0028] A conductive, medically safe material, such as stainless steel, is bonded or fitted into the catheter, patient line, or drain line in one embodiment, for example, via a clamshell connector or a connector that is bonded into the drain line. A control unit controlling the impedance monitor, in one embodiment, generates an electrical frequency sweep in the effluent fluid. Such impedance spectroscopy (or complex impedance acquisition) can provide additional details about the contents of the effluent fluid. For example, the electrical properties of fibrin (normal, not indicative of peritonitis) can vary from the electrical properties of white blood cells (indicative of peritonitis). Once the electrical properties of different substances in the effluent fluid are learned, the properties can be programmed into the control unit and then used to determine what will happen if something gets into the effluent dialysate stream.

[0029] In any embodiment in which the impedance monitor is located remotely from the circulator, the impedance monitor may transmit the measured signal in a wired or wireless manner to the circulator for interrogation. Impedance monitors such as those described above have the ability to emit a frequency sweep into the outflow fluid and therefore may receive power either via a battery or via a power wire from the circulator or a water purifier operating with the circulator.

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

[0031] In one embodiment, the control unit is programmed to alert the patient or caregiver at the circulator's user interface if white blood cells indicative of peritonitis are detected. Alternatively, or in addition, the control unit operates via a network and one or more server computers to allow a doctor or clinician to view the effluent impedance data, for example, continuously, so that the clinician can determine whether the patient is at risk for peritonitis. In one embodiment, the data is displayed on a website dashboard for the patient, and the effluent impedance data may be presented with a flag for the clinician when white blood cells are present, indicating peritonitis. Data from the third main embodiment may be displayed in combination with data from the first and / or second main embodiments to provide a combined peritonitis indicator.

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

[0033] Glucose (or dextrose) is the primary osmotic agent used with most PD solutions. Absorption of a large portion of the peritoneal glucose load over the dwell period can adversely affect patients with diabetes. Diabetes is a common cause of renal 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 PD treatment run the risk of trying to match the amount of insulin to the amount of PD treatment they receive.

[0034] In a fourth main embodiment, which may be used alternatively or in addition to the first, second, and / or third main embodiments, a BioMEMS insulin system and method is provided to match the amount of insulin to the amount of PD fluid being used. The BioMEMS insulin system and method measures the glucose level of the effluent dialysate leaving the patient. The measurement is then used to appropriately administer insulin to the patient for the patient's next PD fill. In one embodiment, the patient is filled with fluid from a previous treatment when starting a current treatment. The effluent fluid is removed, and at least a portion of it is delivered to a MEMS affinity glucose sensor, which sends a signal to a control unit that determines the amount of insulin to deliver to the PD supply volume to form the desired concentration of insulin for the initial fill. A corresponding amount of insulin is then delivered to the PD fluid supply bag to produce the desired concentration.

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

[0036] In one embodiment, the MEMS affinity glucose sensor includes electronics and processing for processing the raw signal from the piezoelectric biosensor and making a determination regarding the appropriate concentration of insulin to prepare with the PD solution. The MEMS affinity glucose sensor may also include a user interface for indicating to the patient or caregiver present during treatment that the 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 or (ii) the user interface for patient or caregiver communication are instead provided by the circulator or, perhaps, a water purification device operable with the circulator. The PD circulator can operate with pre-prepared PD dialysate or with PD dialysate prepared at the point of use. For pre-prepared PD dialysate, insulin is added to the heater bag or to an insulin port on the solution bag. For PD dialysate prepared at the point of use, insulin can be added to the mixed dialysate or any of its components (purified water, osmotic agent, or electrolytes).

[0037] The control unit of the circulatory device, in one embodiment, operates via a network and one or more server computers, allowing a doctor or clinician to view insulin usage data, for example, on a treatment-by-treatment basis, so that the clinician can verify that insulin is being delivered appropriately. The data, in one embodiment, is displayed on a website dashboard for the patient, where insulin volume and concentration with PD fluid can be viewed. The data of the fourth main embodiment can be displayed in combination with data from the first, second, and / or third main embodiments to provide a desired combination of data.

[0038] In light of the disclosure herein, in a first aspect of the present disclosure, which may be combined with any other aspect recited herein unless otherwise specified without limiting the disclosure in any way, a peritoneal dialysis ("PD") system includes: a circulator including a pump actuator and a control unit in operative communication 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 circulator such that the pump chamber is in operative communication 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 effluent PD fluid removed from the patient, the sensed temperature being used to form a patient peritonitis determination, and the control unit configured to communicate the peritonitis determination.

[0039] In a second aspect of the present disclosure, which may be combined with any other aspect enumerated herein unless otherwise specified, the sensed temperature is transmitted to a control unit, and the control unit is configured to analyze the sensed temperature.

[0040] In a third aspect of the present disclosure, which may be combined with the second aspect in combination with any other aspect enumerated herein unless otherwise specified, the sensed temperature is transmitted to a control unit via wire or wirelessly.

[0041] In a fourth aspect of the present disclosure, which may be combined with any other aspect enumerated herein unless otherwise specified, a 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 a peritonitis determination to at least one of a patient or a caregiver via the network and via a user interface of the circulatory device or the at least one physician or clinician computer.

[0042] In a fifth aspect of the present disclosure, which may be combined with any other aspect recited herein unless otherwise specified, a PD system includes a water purifier configured to supply purified water to a disposable set, the water purifier including a water purifier control unit, a sensed temperature transmitted to the water purifier control unit, the water purifier control unit configured to analyze the sensed temperature, the circulator control unit and the water purifier control unit in communication, enabling the circulator control unit to communicate a peritonitis determination.

[0043] In a sixth aspect of the present disclosure, which may be combined with the fifth aspect in combination with any other aspect enumerated herein unless otherwise specified, either the circulator control unit or the water purifier control unit is configured to analyze the sensed temperature.

[0044] In a seventh aspect of the present disclosure, which may be combined with any other aspect enumerated herein unless otherwise specified, the temperature sensor is located within a connector configured to couple to a patient line or an exhaust line.

[0045] In an eighth aspect of the present disclosure, which may be combined with the seventh aspect in combination with any other aspect enumerated herein unless otherwise specified, the connector is (i) a clamshell connector that fits around the patient line or the exhaust line, or (ii) configured to be joined between two sections of the patient line or the exhaust line.

[0046] In a ninth aspect of the present disclosure, which may be combined with the seventh aspect in combination with any other aspect enumerated herein unless otherwise specified, the connector includes an electrode positioned and arranged to contact (a) the outflow fluid flowing through the patient line or the drain line, or (b) directly with the patient line or the drain line.

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

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

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

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

[0051] In a fourteenth aspect of the present disclosure, which may be combined with the thirteenth aspect in combination with any other aspect enumerated herein unless otherwise specified, an 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 a disposable cassette.

[0052] In a fifteenth aspect of the present disclosure, which may be combined 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 usable in combination with the first peritonitis indicator to form an overall peritonitis determination.

[0053] In a sixteenth aspect of the present disclosure, which may be combined with the fifteenth aspect in combination with any other aspect enumerated herein unless otherwise specified, at least one different peritonitis indicator usable in combination with the first peritonitis indicator is obtained from at least one of a leukocyte biosensor or a leukocyte impedance sensor.

[0054] In a seventeenth aspect of the present disclosure, which may be combined with any other aspect recited herein unless otherwise specified, peritonitis determination is provided in combination with insulin injections performed using feedback from a patient effluent glucose biosensor.

[0055] In an eighteenth aspect of the present disclosure, which may be combined with any other aspect recited herein unless otherwise specified, a peritoneal dialysis ("PD") system includes a circulator including a pump actuator and a control unit in operative communication 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 circulator such that the pump chamber is in operative communication with the pump actuator; and a bioMEMS device in fluid communication with the disposable cassette, the bioMEMS device configured to collect white blood cells from effluent PD fluid removed from a patient, the collected white blood cells being used to form a patient peritonitis determination, and the control unit configured to communicate the peritonitis determination.

[0056] In a nineteenth aspect of the present disclosure, which may be combined with the eighteenth aspect in combination with any other aspect enumerated herein unless otherwise specified, an indication of the collected white blood cells is transmitted to a control unit, and the control unit is configured to analyze the indication of the collected white blood cells.

[0057] In a twentieth aspect of the present disclosure, which may be combined with the nineteenth aspect in combination with any other aspect enumerated herein unless otherwise specified, an indication of the collected white blood cells is transmitted to a control unit via wire or wirelessly.

[0058] In a 21st aspect of the present disclosure, which may be combined with the 18th aspect in combination with any other aspect enumerated herein unless otherwise specified, a PD system includes a network and at least one physician or clinician computer in communication 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 and via a user interface of the circulatory device or the at least one physician or clinician computer.

[0059] In a 22nd aspect of the present disclosure, which may be combined with the 18th aspect in combination with any other aspect enumerated herein unless otherwise specified, the bioMEMS device is placed in fluid communication with a sample port of a disposable cassette.

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

[0061] In a 24th aspect of the present disclosure, which may be combined with the 18th aspect in combination with any other aspect enumerated herein unless otherwise specified, a bioMEMS device includes (i) a microfluidic chip forming a microfluidic channel sized and configured to separate white blood cells from the remaining outflow fluid, and (ii) a piezoelectric biosensor resonating at a frequency proportional to a characteristic of the collected white blood cells.

[0062] In a twenty-fifth aspect of the present disclosure, which may be combined with the twenty-fourth aspect in combination with any other aspect enumerated herein unless otherwise specified, the characteristics of the collected white blood cells include a change in the sedimentation rate of the white blood cells.

[0063] In a twenty-sixth aspect of the present disclosure, which may be combined with the twenty-fourth aspect in combination with any other aspect enumerated herein unless otherwise specified, a frequency proportional to a characteristic of the collected white blood cells is used to form a peritonitis determination.

[0064] In a twenty-seventh aspect of the present disclosure, which may be combined with the twenty-fourth aspect in combination with any other aspect enumerated herein unless otherwise specified, the piezoelectric biosensor operates in conjunction with a collection area for collecting white blood cells.

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

[0066] In a 29th aspect of the present disclosure, which may be combined with the 18th aspect in combination with any other aspect enumerated herein unless otherwise specified, the PD system is configured to analyze the amount of leukocytes removed from the effluent PD fluid and perform a peritonitis determination.

[0067] In a thirtieth aspect of the present disclosure, which may be combined with the eighteenth aspect in combination with any other aspect enumerated herein unless otherwise specified, the peritonitis determination is a first peritonitis indicator and includes at least one different peritonitis indicator usable in combination with the first peritonitis indicator to form an overall peritonitis determination.

[0068] In a thirty-first aspect of the present disclosure, which may be combined with the thirty-first aspect in combination with any other aspect enumerated herein unless otherwise specified, at least one different peritonitis indicator usable 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 thirty-second aspect of the present disclosure, which may be combined with the eighteenth aspect in combination with any other aspect enumerated herein unless otherwise specified, peritonitis determination is provided in combination with insulin injections performed using feedback from a patient effluent glucose biosensor.

[0070] In a thirty-third aspect of the present disclosure that may 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 in operative communication 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 so that the pump chamber is in operative communication 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 in 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 impedance of PD fluid present in 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 thirty-fourth aspect of the present disclosure, which may be combined with the thirty-third aspect in combination with any other aspect enumerated herein unless otherwise specified, the sensed impedance is transmitted to a control unit, and the control unit is configured to analyze the sensed impedance.

[0072] In a thirty-fifth aspect of the present disclosure, which may be combined with the thirty-fourth aspect in combination with any other aspect enumerated herein unless otherwise specified, the sensed impedance is transmitted to a control unit via wire or wirelessly.

[0073] In a thirty-sixth aspect of the present disclosure, which may be combined with the thirty-third aspect in combination with any other aspect enumerated herein unless otherwise specified, a PD system includes a network and at least one physician or clinician computer in communication 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 and via a user interface of the circulatory device or the at least one physician or clinician computer.

[0074] In a thirty-seventh aspect of the present disclosure, which may be combined with the thirty-third aspect in combination with any other aspect enumerated herein unless otherwise specified, a PD system includes a water purifier configured to supply purified water to a disposable set, the water purifier including a water purifier control unit, sensed impedance is transmitted to the water purifier control unit, the water purifier control unit is configured to analyze the sensed impedance, and the circulator control unit and the water purifier control unit are in communication, enabling the circulator control unit to communicate a peritonitis determination.

[0075] In a thirty-eighth aspect of the present disclosure, which may be combined with the thirty-third aspect in combination with any other aspect enumerated 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 thirty-ninth aspect of the present disclosure, which may be combined with the thirty-eighth aspect in combination with any other aspect enumerated herein unless otherwise specified, the connector is (i) a clamshell connector that fits around a catheter, patient line, or exhaust line, or (ii) configured to be joined between two sections of a catheter, patient line, or exhaust line.

[0077] In a fortieth aspect of the present disclosure, which may be combined with the thirty-third aspect in combination with any other aspect enumerated herein unless otherwise specified, the impedance sensor includes an electrode positioned and disposed within the catheter, patient line, or drain line, and a connector is positioned over the electrode.

[0078] In a forty-first aspect of the present disclosure, which may be combined with the fortieth aspect in combination with any other aspect enumerated herein unless otherwise specified, the connector includes a conductor extending from the electrode to (i) a control unit, (ii) a control unit of a water purifier configured to supply purified water to the disposable set, or (iii) a wireless module having the connector.

[0079] In a forty-second aspect of the present disclosure, which may be combined with the thirty-third aspect in combination with any other aspect enumerated herein unless otherwise specified, a PD system is configured to analyze the sensed impedance of PD fluid present in or removed from a patient via a frequency sweep moving from a start frequency to a stop frequency.

[0080] In a forty-third aspect of the present disclosure, which may be combined with the forty-second aspect in combination with any other aspect enumerated herein unless otherwise specified, the frequency sweep is generated by a frequency generator provided by or operable in conjunction with the control unit.

[0081] In a forty-fourth aspect of the present disclosure, which may be combined with the forty-second aspect in combination with any other aspect enumerated herein unless otherwise specified, the PD system is configured to perform impedance measurements at two or more frequencies of a frequency sweep.

[0082] In a forty-fifth aspect of the present disclosure, which may be combined with the forty-second aspect in combination with any other aspect enumerated herein unless otherwise specified, a frequency sweep enables fluid having leukocytes and present in or removed from a patient to be determined by measuring a higher impedance for the fluid having leukocytes than an impedance for fluid not having leukocytes over at least a portion of the frequency sweep, and the measured impedance for the fluid not having leukocytes is determined based on (i) a standard impedance or (ii) an impedance established for the patient.

[0083] In a forty-sixth aspect of the present disclosure, which may be combined with the forty-second aspect in combination with any other aspect enumerated herein unless otherwise specified, the frequency sweep enables fluid having leukocytes and present in or removed from a patient to be distinguished from fluid having fibrin, the fluid having fibrin providing a higher impedance than the fluid having leukocytes over at least a portion of the sweep.

[0084] In a forty-seventh aspect of the present disclosure, which may be combined with the thirty-third aspect in combination with any other aspect enumerated herein unless otherwise specified, the peritonitis determination is a first peritonitis indicator and includes at least one different peritonitis indicator usable in combination with the first peritonitis indicator to form an overall peritonitis determination.

[0085] In a forty-eighth aspect of the present disclosure, which may be combined with the forty-seventh aspect in combination with any other aspect enumerated herein unless otherwise specified, at least one different peritonitis indicator usable 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 forty-ninth aspect of the present disclosure, which may be combined with the thirty-third aspect in combination with any other aspect enumerated herein unless otherwise specified, peritonitis determination is provided in combination with insulin injections performed using feedback from a patient effluent glucose biosensor.

[0087] In a fiftieth aspect of the present disclosure, which may be combined with the thirty-third aspect in combination with any other aspect enumerated herein unless otherwise specified, a peritoneal dialysis ("PD") system includes a circulation device including a pump actuator and a control unit in operative communication 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 so that the pump chamber is in operative communication with the pump actuator; an insulin source in fluid communication with the disposable set; and a microelectromechanical systems ("MEMS") affinity glucose sensor positioned and arranged to receive effluent PD fluid removed from the patient, the MEMS affinity glucose sensor configured to provide a glucose assessment related to glucose absorbed by the patient, the glucose assessment being used to determine an insulin dose, and the control unit configured to deliver the insulin dose from the insulin source to the patient by the pump actuator operating with the pump chamber of the disposable cassette.

[0088] In a 51st aspect of the present disclosure, which may be combined with the 50th aspect in combination with any other aspect enumerated herein unless otherwise specified, a PD system includes a dialysate source in fluid communication with the disposable set, and a control unit configured to deliver to the patient an insulin dose from an insulin source mixed with fresh dialysate from the dialysate source.

[0089] In a fifty-second aspect of the present disclosure, which may be combined with the fifty-first aspect in combination with any other aspect enumerated herein unless otherwise specified, the dialysate source is a point-of-use dialysate source, and fresh dialysate is mixed in a mixing bag with insulin from an insulin bag.

[0090] In a fifty-third aspect of the present disclosure, which may be combined with the fiftieth aspect in combination with any other aspect enumerated herein unless otherwise specified, the disposable set includes a patient line and a drain line in fluid communication with the disposable cassette, and the MEMS affinity glucose sensor is in fluid communication with the drain line.

[0091] In a fifty-fourth aspect of the present disclosure, which may be combined with the fifty-third aspect in combination with any other aspect enumerated herein unless otherwise specified, the MEMS affinity glucose sensor is located along the discharge line upstream of the discharge container.

[0092] In a 55th 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 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 together with the water purifier.

[0093] In a 56th aspect of the present disclosure, which may be combined with the 55th aspect in combination with any other aspect enumerated herein unless otherwise specified, the water purifier is in wired or wireless communication with the circulation device, and the water purifier is configured to determine an insulin dose from the glucose assessment and deliver the insulin dose to the circulation device for delivery.

[0094] In a 57th aspect of the present disclosure, which may be combined with the 50th aspect in combination with any other aspect enumerated in this specification unless otherwise specified, the MEMS affinity glucose sensor is in wired or wireless communication with the circulation device, and the control unit of the circulation device is configured to determine an insulin dose from a glucose assessment transmitted from the MEMS affinity glucose sensor to the control unit.

[0095] In a fifty-eighth aspect of the present disclosure, which may be combined with the fifty-first aspect in combination with any other aspect enumerated herein unless otherwise specified, the MEMS affinity glucose sensor is configured to determine an insulin dose from a glucose assessment.

[0096] In a fifty-ninth aspect of the present disclosure, which may be combined with the fifty-ninth aspect in combination with any other aspect enumerated herein unless otherwise specified, the glucose assessment indicates the amount or concentration of glucose absorbed by the patient.

[0097] In a sixtieth aspect of the present disclosure, which may be combined with the fiftieth aspect in combination with any other aspect enumerated herein unless otherwise specified, a MEMS affinity glucose sensor includes (i) a microfluidic chip forming a microfluidic channel sized and configured to separate glucose molecules from the remaining outflow fluid, and (ii) a piezoelectric biosensor resonating at a frequency proportional to a characteristic of the collected glucose molecules.

[0098] In a sixty-first aspect of the present disclosure, which may be combined with the sixtieth aspect in combination with any other aspect enumerated 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 sixty-second aspect of the present disclosure, which may be combined with the sixtieth aspect in combination with any other aspect enumerated herein unless otherwise specified, a frequency proportional to a characteristic 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 sixtieth 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 sixty-fourth aspect of the present disclosure, which may be combined with the fiftieth aspect in combination with any other aspect enumerated herein unless otherwise specified, the control unit is programmed to assume 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, a PD system includes a network and at least one physician or clinician computer in communication with a control unit via the network, and the control unit is configured to communicate insulin doses to at least one of a patient or a caregiver via the network and via a user interface of the circulatory 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 outflow PD fluid temperature sensor, a leukocyte biosensor, or a leukocyte impedance monitor.

[0104] In a sixty-seventh aspect of the present disclosure that may 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 in operative communication with the pump actuator; a disposable set including a pump portion sized and arranged to be held by the circulation device so that the pump portion is in operative communication 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 in 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 in 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 sixty-eighth aspect of the present disclosure that may be combined with any other aspect recited herein unless otherwise specified, a peritoneal dialysis ("PD") system includes a pump actuator and a control unit in operative communication with the pump actuator; a disposable set including a pump portion sized and arranged for placement in operative communication 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 in 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 in or removed from the patient over a frequency sweep moving from a start frequency to a stop frequency, the sensed impedance frequency sweep being used to detect leukocytes and form a patient peritonitis determination.

[0106] In a sixty-ninth aspect of the present disclosure, any of the structures and functionality disclosed in connection with Figures 1-20B may be included or combined with any of the other structures and functionality disclosed in connection with Figures 1-20B.

[0107] In light of the present disclosure and the above aspects, it is therefore an advantage of the present disclosure to provide improved peritoneal dialysis ("PD") systems and methods.

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

[0109] It is a further advantage of the present disclosure to provide a PD system and method that allows for peritonitis to be determined automatically without undue burden on the patient.

[0110] It is yet another advantage of the present disclosure to provide a PD system and method that allows peritonitis to be determined using a number of different techniques that provide cross-checking tests.

[0111] Yet it is a further advantage of the present disclosure to provide a PD system and method that proportionates insulin infusion with 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 are described herein and will be apparent from the following detailed description and drawings. The present invention provides, for example, the following. (Item 1) 1. A peritoneal dialysis ("PD") system, the PD system comprising: a circulation device including a pump actuator and a control unit in operative communication with the pump actuator; a disposable set including a disposable cassette having a pump chamber, the disposable cassette sized and arranged to be held by the circulator such that the pump chamber is in operative communication 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 abdominal cavity and in fluid communication with said patient line; an impedance sensor operably coupled to one of the catheter, the patient line, or the drain line; Equipped with The PD system, wherein the impedance sensor senses the impedance of PD fluid present in the patient or removed from the patient, the sensed impedance is used to detect leukocytes and form a patient peritonitis determination, and the control unit is configured to communicate the peritonitis determination. (Item 2) Item 10. The PD system of item 1, wherein the sensed impedance is transmitted to the control unit, and the control unit is configured to analyze the sensed impedance. (Item 3) 3. The PD system of claim 2, wherein the sensed impedance is transmitted to the control unit via a wire or wirelessly. (Item 4) 2. The PD system of claim 1, comprising a network and at least one physician or clinician computer in communication with the control unit via the network, the control unit configured to communicate the peritonitis determination to at least one patient or caregiver via the network and via a user interface of the circulatory device or the at least one physician or clinician computer. (Item 5) Item 10. The PD system of item 1, further comprising: 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 circulator control unit and the water purifier control unit being in communication, enabling the circulator control unit to communicate the peritonitis determination. (Item 6) Item 10. The PD system of 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) 7. The PD system of item 6, wherein the connector is (i) a clamshell connector that fits around the catheter, the patient line, or the drain line, or (ii) configured to be joined between two sections of the catheter, the patient line, or the drain line. (Item 8) 7. The PD system of claim 6, wherein the impedance sensor includes an electrode positioned and disposed within the catheter, the patient line, or the drain line, and the connector is positioned over the electrode. (Item 9) 9. The PD system of claim 8, wherein the connector includes electrical leads extending from the electrodes 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 comprising the connector. (Item 10) 2. The PD system of claim 1, configured to analyze the sensed impedance of the PD fluid present in the patient or the PD fluid removed from the patient via a frequency sweep moving from a start frequency to a stop frequency. (Item 11) Item 11. The PD system of item 10, wherein the frequency sweep is generated by a frequency generator provided by or operable with the control unit. (Item 12) Item 11. The PD system of item 10, configured to perform impedance measurements at two or more frequencies of the frequency sweep. (Item 13) 11. The PD system of claim 10, wherein the frequency sweep enables fluid present in the patient having leukocytes or fluid removed from the patient having leukocytes to be determined by measuring a higher impedance for fluid having leukocytes than an impedance for fluid not having leukocytes over at least a portion of the frequency sweep. (Item 14) 11. The PD system of claim 10, wherein the frequency sweep allows fluid present in the patient or fluid removed from the patient having leukocytes to be distinguished from fluid having fibrin, the fluid having fibrin providing a higher impedance than fluid having leukocytes over at least a portion of the sweep. (Item 15) Item 10. The PD system of item 1, wherein the peritonitis determination is a first peritonitis indicator, and the peritonitis determination includes at least one different peritonitis indicator usable in combination with the first peritonitis indicator to form an overall peritonitis determination. (Item 16) Item 16. The PD system of item 15, wherein the at least one different peritonitis indicator usable 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. (Item 17) 2. The PD system of item 1, wherein the peritonitis determination is provided in combination with insulin injections performed using feedback from a patient effluent glucose biosensor. (Item 18) 1. A peritoneal dialysis ("PD") system, the PD system comprising: a circulation device including a pump actuator and a control unit in operative communication with the pump actuator; a disposable set including a disposable cassette having a pump chamber, the disposable cassette sized and arranged to be held by the circulator such that the pump chamber is in operative communication 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 effluent PD fluid removed from the patient; Equipped with The PD system, wherein the sensed temperature is used to form a patient peritonitis determination, and the control unit is configured to communicate the peritonitis determination. (Item 19) Item 19. The PD system of item 18, wherein the sensed temperature is transmitted to the control unit, and the control unit is configured to analyze the sensed temperature. (Item 20) 20. The PD system of claim 19, wherein the sensed temperature is transmitted to the control unit via a wire or wirelessly. (Item 21) 20. The PD system of claim 18, including a network and at least one physician or clinician computer in communication with the control unit via the network, the control unit configured to communicate the peritonitis determination to at least one patient or caregiver via the network and via a user interface of the circulator or the at least one physician or clinician computer. (Item 22) Item 19. The PD system of item 18, further comprising 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 circulator control unit and the water purifier control unit being in communication, enabling the circulator control unit to communicate the peritonitis determination. (Item 23) Item 23. The PD system of item 22, wherein either the circulator control unit or the water purifier control unit is configured to analyze the sensed temperature. (Item 24) Item 19. The PD system of item 18, wherein the temperature sensor is located within a connector configured to couple to the patient line or the drain line. (Item 25) Item 25. The PD system of item 24, wherein the connector is (i) a clamshell connector that fits around the patient line or the exhaust line, or (ii) configured to be joined between two sections of the patient line or the exhaust line. (Item 26) 25. The PD system of claim 24, wherein the connector includes an electrode positioned and arranged to directly contact (a) an outflow fluid flowing through the patient line or the drain line, or (b) the patient line or the drain line. (Item 27) 27. The PD system of claim 26, wherein 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. (Item 28) 27. The PD system of claim 26, wherein the connector includes electrical leads extending from the electrodes 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 comprising the connector. (Item 29) 20. The PD system of claim 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 delivered to the patient and sensed by the temperature sensor. (Item 30) 20. The PD system of claim 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 development. (Item 31) 31. The PD system of claim 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) Item 19. The PD system of item 18, wherein the peritonitis determination is a first peritonitis indicator, and the peritonitis determination includes at least one different peritonitis indicator usable in combination with the first peritonitis indicator to form an overall peritonitis determination. (Item 33) Item 33. The PD system of item 32, wherein the at least one different peritonitis indicator usable in combination with the first peritonitis indicator is obtained from at least one of a leukocyte biosensor or a leukocyte impedance sensor. (Item 34) 20. The PD system of item 18, wherein the peritonitis determination is provided in combination with insulin injections made using feedback from a patient effluent glucose biosensor. (Item 35) 1. A peritoneal dialysis ("PD") system, the PD system comprising: a circulation device including a pump actuator and a control unit in operative communication with the pump actuator; a disposable set including a disposable cassette having a pump chamber, the disposable cassette sized and arranged to be held by the circulation device such that the pump chamber is in operative communication with the pump actuator; a bioMEMS device in fluid communication with the disposable cassette; Equipped with The bioMEMS device is configured to collect leukocytes from effluent PD fluid removed from a patient, the collected leukocytes are used to form a patient peritonitis determination, and the control unit is configured to communicate the peritonitis determination, a PD system. (Item 36) 36. The PD system of claim 35, wherein an indication of the collected white blood cells is transmitted to the control unit, and the control unit is configured to analyze the indication of the collected white blood cells. (Item 37) Item 37. The PD system of item 36, wherein the indication of the collected white blood cells is transmitted to the control unit via wire or wirelessly. (Item 38) 36. The PD system of claim 35, including a network and at least one physician or clinician computer in communication with the control unit via the network, the control unit configured to communicate the peritonitis determination to at least one patient or caregiver via the network and via a user interface of the circulator or the at least one physician or clinician computer. (Item 39) Item 36. The PD system of item 35, wherein the bioMEMS device is placed in fluid communication with a sample port of the disposable cassette. (Item 40) Item 36. The PD system of item 35, wherein the bioMEMS device includes a control unit having at least one of electronics, processing, and memory, and either the circulatory apparatus control unit or the bioMEMS device control unit is configured to analyze the sensed temperature. (Item 41) Item 36. The PD system of item 35, wherein the bioMEMS device includes: (i) a microfluidic chip forming a microfluidic channel sized and configured to separate the white blood cells from the remaining outflow fluid; and (ii) a piezoelectric biosensor resonating at a frequency proportional to a characteristic of the collected white blood cells. (Item 42) Item 42. The PD system of item 41, wherein the characteristics of the collected white blood cells include a change in sedimentation rate of the white blood cells. (Item 43) Item 42. The PD system of item 41, wherein the frequency proportional to the characteristic of the collected white blood cells is used to form the peritonitis determination. (Item 44) Item 42. The PD system of item 41, wherein the piezoelectric biosensor operates in conjunction with a collection area for collecting the white blood cells. (Item 45) Item 36. The PD system of item 35, wherein the bioMEMS device is in wired communication with the control unit or includes a wireless module for wireless communication with the control unit. (Item 46) 36. The PD system of item 35, configured to analyze the amount of leukocytes removed from the effluent PD fluid to make the peritonitis determination. (Item 47) Item 36. The PD system of item 35, wherein the peritonitis determination is a first peritonitis indicator, and the peritonitis determination includes at least one different peritonitis indicator usable in combination with the first peritonitis indicator to form an overall peritonitis determination. (Item 48) Item 48. The PD system of item 47, wherein the at least one different peritonitis indicator usable 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. (Item 49) 36. The PD system of claim 35, wherein the peritonitis determination is provided in combination with insulin injections made using feedback from a patient effluent glucose biosensor. (Item 50) 1. A peritoneal dialysis ("PD") system, the PD system comprising: a circulation device including a pump actuator and a control unit in operative communication with the pump actuator; a disposable set including a disposable cassette having a pump chamber, the disposable cassette sized and arranged to be held by the circulation device such that the pump chamber is in operative communication with the pump actuator; an insulin source in fluid communication with the disposable set; a microelectromechanical systems ("MEMS") affinity glucose sensor positioned and arranged to receive effluent PD fluid removed from the patient; Equipped with The PD system, wherein the MEMS affinity glucose sensor is configured to provide a glucose assessment of glucose absorbed by the patient, the glucose assessment being used to determine an insulin dose, and the control unit is configured to deliver the insulin dose from the insulin source to the patient by the pump actuator operating in conjunction with the pump chamber of the disposable cassette. (Item 51) 51. The PD system of claim 50, including a dialysate source in fluid communication with the disposable set, wherein the control unit is configured to deliver the insulin dose from the insulin source mixed with fresh dialysate from the dialysate source to the patient. (Item 52) 52. The PD system of claim 51, wherein the dialysate source is a point-of-use dialysate source, and the fresh dialysate is mixed in a mixing bag with insulin from an insulin bag. (Item 53) Item 51. The PD system of item 50, wherein the disposable set includes a patient line and a drain line in fluid communication with the disposable cassette, and the MEMS affinity glucose sensor is in fluid communication with the drain line. (Item 54) Item 54. The PD system of item 53, wherein the MEMS affinity glucose sensor is located along the exhaust line upstream of an exhaust container. (Item 55) 51. The PD system of claim 50, including a water purifier, wherein 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. (Item 56) Item 56. The PD system of item 55, wherein the water purifier is in wired or wireless communication with the circulation device, and the water purifier is configured to determine the insulin dose from the glucose assessment and deliver the insulin dose to the circulation device for delivery. (Item 57) Item 51. The PD system of item 50, wherein the MEMS affinity glucose sensor is in wired or wireless communication with the circulatory device, and the control unit of the circulatory device is configured to determine the insulin dose from the glucose assessment transmitted from the MEMS affinity glucose sensor to the control unit. (Item 58) Item 51. The PD system of item 50, wherein the MEMS affinity glucose sensor is configured to determine the insulin dose from the glucose assessment. (Item 59) 51. The PD system of claim 50, wherein the glucose assessment indicates the amount or concentration of glucose absorbed by the patient. (Item 60) Item 51. The PD system of item 50, wherein the MEMS affinity glucose sensor includes: (i) a microfluidic chip forming a microfluidic channel sized and configured to split glucose molecules from the remaining outflow fluid; and (ii) a piezoelectric biosensor resonating at a frequency proportional to a characteristic of the collected glucose molecules. (Item 61) Item 61. The PD system of item 60, wherein the characteristics of the collected glucose molecules include a change in deposition rate of the glucose molecules. (Item 62) Item 61. The PD system of item 60, wherein the frequency proportional to the characteristic of the collected glucose molecules is used to form an insulin determination. (Item 63) Item 61. The PD system of item 60, wherein the piezoelectric biosensor operates in conjunction with a collection area to collect the glucose molecules. (Item 64) Item 51. The PD system of item 50, wherein the control unit is programmed to assume that the lower the concentration of glucose in the effluent, the greater the amount of glucose absorbed by the patient. (Item 65) 51. The PD system of claim 50, comprising a network and at least one physician or clinician computer in communication with the control unit via the network, the control unit configured to communicate the insulin dose to at least one patient or caregiver via the network and via a user interface of the circulatory device or the at least one physician or clinician computer. (Item 66) Item 51. The PD system of item 50, including at least one peritonitis indicating device selected from a patient effluent PD fluid temperature sensor, a leukocyte biosensor, or a leukocyte impedance monitor. [Brief explanation of the drawings]

[0114] [Figure 1]FIG. 1 is a front elevation view of one embodiment of a peritoneal dialysis delivery system with point-of-use dialysate generation in communication with a remote physician or clinician data collection system.

[0115] [Figure 2] FIG. 2 is a top plan view of one embodiment of a disposable set for use with the system illustrated in FIG.

[0116] [Figure 3] FIG. 3 is a front elevational view of one embodiment of a temperature sensing connector of the present disclosure.

[0117] [Figure 4] 4A and 4B are front elevation and perspective views, respectively, of another embodiment of the temperature sensing connector of the present disclosure.

[0118] [Figure 5] FIG. 5 is a side elevational view of a further embodiment of a temperature sensing connector of the present disclosure.

[0119] [Figure 6] FIG. 6 is a schematic diagram of one embodiment of a wirelessly operated temperature sensing connector of the present disclosure.

[0120] [Figure 7] 7A and 7B are schematic plots showing the outputs of various temperature sensing connectors of the present disclosure.

[0121] [Figure 8] 8A and 8B are schematic plots showing the output of another temperature sensing connector of the present disclosure.

[0122] [Figure 9] FIG. 9 is a front elevation view of a medical fluid delivery system with point-of-use dialysate generation operating with one embodiment of the white blood cell sensing device of the present disclosure.

[0123] [Figure 10]FIG. 10 is a schematic flow diagram of one embodiment of a white blood cell sensing method that can be used with the system of FIG.

[0124] [Figure 11] FIG. 11 is a front elevation view of a medical fluid delivery system with point-of-use dialysate generation operating in conjunction with one embodiment of the output fluid impedance assessment device of the present disclosure.

[0125] [Figure 12] FIG. 12 is a front isometric view of one embodiment for electrode placement within a catheter or vessel that operates in conjunction with the outflow fluid impedance assessment device of the present disclosure.

[0126] [Figure 13] FIG. 13 is a front elevation view of one embodiment of a catheter impedance effluent assessment device of the present disclosure.

[0127] [Figure 14] 14A and 14B are schematic plots showing the impedance output over a frequency sweep over time for normal patient effluent, patient effluent with white blood cells (indicating peritonitis), and patient effluent with fibrin, respectively.

[0128] [Figure 15] FIG. 15 is a front elevational view of a medical fluid delivery system operating with a pre-sterilized container of peritoneal dialysis fluid that also operates with one embodiment of the effluent glucose sensing and insulin control device of the present disclosure.

[0129] [Figure 16] FIG. 16 is a front elevation view of one embodiment of a MEMS affinity glucose sensor that can be used with the systems of FIGS.

[0130] [Figure 17]FIG. 17 is a front elevation view of a medical fluid delivery system with point-of-use dialysate generation operating in conjunction with one embodiment of the effluent glucose sensing and insulin control device of the present disclosure.

[0131] [Figure 18] FIG. 18 is a schematic flow diagram of one embodiment of an effluent glucose sensing and insulin control method that can be used with the systems of FIGS.

[0132] [Figure 19] FIG. 19 is a schematic plot showing the relationship between frequency output and effluent glucose level of a MEMS affinity glucose sensor.

[0133] [Figure 20] 20A and 20B are schematic plots showing patient glucose levels when uncontrolled during peritoneal dialysis treatment and when controlled via glucose feedback and insulin injections of FIGS. 15-18. 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"), which involves the use of a PD machine or circulator. 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 remotely communicates the data to a caregiver database for review by a physician or clinician. With respect to APD machines, suitable circulators include, for example, the Amia® or HomeChoice® circulators marketed by Baxter International Inc. For example, the Amia® circulator is disclosed in U.S. Pat. No. 9,981,079, while the HomeChoice® circulator is disclosed in U.S. Pat. No. 5,350,357, the contents of each of which are incorporated by reference. Each of the above-incorporated patents discloses the use of prepackaged, presterilized containers or bags of PD dialysis fluid. The feedback systems and methods are applicable to and implementable in circulators that use prepackaged, presterilized PD fluid. As discussed below, the feedback systems and methods are also applicable to and implementable in circulators that use PD fluid made online or at the point of use.

[0135] Referring now to FIG. 1 , one embodiment of a peritoneal dialysis system with point-of-use dialysate generation is illustrated by system 10. System 10 includes a circulator 20 and a water purifier 210. Suitable circulators for circulator 20 include, for example, the Amia® or HomeChoise® circulators described above, with the understanding that those circulators include updated programming for implementing and using the point-of-use dialysate generated in accordance with system 10. To this end, circulator 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 and receiving information to and from control unit 22 of circulatory apparatus 20 and other wireless devices discussed herein. Wired communication may be via an Ethernet connection, for example. Wireless communication may be implemented via any of Bluetooth, WiFi, Zigbee, Z-Wave, wireless universal serial bus ("USB"), or infrared protocols, or via any other suitable wireless communication technology.

[0136] Circulator 20 includes a housing 24 that holds equipment programmed via control unit 22 to prepare fresh dialysis solution at the point of use, pump the freshly prepared dialysate to patient P, allow the dialysate to dwell within patient P, and then pump the spent dialysate to drain. In the illustrated embodiment, water purifier 210 includes a drain line 214 that leads to drain 216, which can be an indoor drain or a drain container. In certain embodiments, equipment programmed via the control unit 22 to prepare fresh dialysis solution at the point of use includes equipment for a pneumatic pump system, which may include, but is not limited to, (i) one or more positive pressure reservoirs, (ii) one or more negative pressure reservoirs, (iii) a compressor and vacuum pump, each under the control of the control unit 22, for providing positive and negative pressure to be stored in the one or more positive and negative pressure reservoirs, or a single pump that generates both positive and negative pressure under the control of the control unit 22, (iv) a plurality of pneumatic valve chambers for delivering the positive and negative pressure to a plurality of fluid valve chambers, and (v) a valve for controlling the positive and negative pressure. (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 dialysis fluid as it is mixed; and (ix) a shutoff device 26 under the control of the control unit 22 for closing the patient and drain lines in 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 housing 24 of circulator 20. The heater is located inside housing 24 and, in certain embodiments, includes a heating coil that contacts a heating pan or tray that is located on top of housing 24 under a heating lid (not visible in FIG. 1 ).

[0138] The circulation device 20 in the illustrated embodiment includes a user interface 30. In some embodiments, the control unit 22 includes a video controller, which 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, which may operate in conjunction with a touchscreen overlay located 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-activated commands, on 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, which 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, which may also operate with a touchscreen overlay located on the video monitor 222 for inputting commands into the control unit 212. The user interface 220 may also include one or more electromechanical input devices, such as membrane switches or other buttons. The control unit 212 may further include an audio controller for playing audio files, such as alarm or alert sounds, on one or more speakers 224 of the water purifier 210.

[0140] Additionally, referring to FIG. 2, one embodiment of a disposable set 40 is illustrated. The disposable set 40, also illustrated in FIG. 1, mates with the circulator 20 to move fluids within the disposable set 40, for example, to mix dialysis fluid as discussed herein. In the illustrated embodiment, the disposable set 40 includes a disposable cassette 42, which may include a planar, rigid plastic part covered on one or both sides by a flexible membrane. The membrane, pressed against the housing 24 of the circulator 20, forms a pump and valve membrane. FIG. 2 illustrates that the disposable cassette 42 includes a fluid pump chamber 44 that operates in conjunction with a pneumatic pump chamber located in the housing 24 of the circulator 20, and a fluid valve chamber 46 that operates in conjunction with a pneumatic valve chamber located in the housing 24 of the circulator 20.

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

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

[0143] Water purifier 210 outputs water, potentially water suitable for peritoneal dialysis ("WFPD"). However, to ensure WFPD, sterilizing-grade filter 70a is installed upstream from downstream sterilizing-grade filter 70b. Filters 70a and 70b may be installed in water line segment 64a upstream of water accumulator 66. Sterilizing-grade filters 70a and 70b may be pass-through filters without exclusion lines. Suitable sterilizing-grade filters 70a and 70b may be provided by the applicant of the present disclosure. In certain embodiments, only one of the upstream or downstream sterilizing-grade filters 70a and 70b is required to generate WFPD; nevertheless, two sterilizing-grade filters 70a and 70b are provided in the illustrated embodiment for redundancy in case one fails.

[0144] 2 further illustrates that a last bag or sample line 72 may be provided extending from the last bag or sample port of cassette 42. Last bag or sample line 72 terminates in a connector 74 that may be connected to a connector on a premixed last fill bag of dialysate or to a sample bag or other sample collection container. Last bag or sample line 72 and connector 74 may alternatively be used for a third type of concentrate, if desired.

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

[0146] 1 illustrates a first concentrate container 84a holding a first concentrate (e.g., glucose) that is pumped from the 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 concentrate (e.g., buffer) 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 one embodiment, to begin treatment, patient P loads cassette 42 into the circulator and, in a random or designated order, (i) installs heater / mixing bag 62 on circulator 20, (ii) connects upstream water line segment 64a to water outlet connector 228 of water purifier 210, (iii) connects drain line 56 to drain connector 218 of water purifier 210, (iv) connects first cassette concentrate connector 80a to first container concentrate connector 80b, and (v) connects second cassette concentrate connector 82a to second container concentrate connector 82b. At this point, patient connector 52 is still capped. Once fresh dialysate is prepared and verified, patient line 50 is primed with the fresh dialysate, after which patient P may connect patient line connector 52 to transfer set 54 for treatment. Each of the above steps may be graphically illustrated on video monitor 32 and / or provided via audio guidance from speaker 34.

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

[0149] The control unit 22 can be programmed to cause the circulator 20 to perform one or more mixing operations to help mix the dialysate appropriately and homogeneously for therapy. For example, any of the fluid pump chambers 44 can be caused to draw a quantity of mixed fluid (e.g., made from one or both of the first and second concentrates 84a, 84b and the WFPD) from the heater / mixing bag 62 into the pump chamber, pump such mixture back to the heater / mixing bag 62, and repeat this procedure multiple times (described herein as a mixing sequence or “waffling”). In particular, to perform a mixing sequence, the control unit 22 in some embodiments causes the circulator 20 to close all fluid valve chambers 46 in the cassette 42 except for the fluid valve chambers 46 to the heater / mixing line 60 and the heater / mixing bag 62. The fluid pump chamber 44 is continuously and repeatedly stroked to (i) draw a potentially unmixed fluid combination of WFPD and concentrate from the heater / mixing bag 62 into the pump chamber, followed by (ii) pushing the mixed WFPD and concentrate from the pump chamber back into 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 so that both push and pull at the same time, or can be programmed to stroke the fluid pump chambers 44 alternately so 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, thereby creating turbulence within the heater / mixing line 60.

[0150] 1 and 2, the configuration of the container or bag 62 operable with the cassette 42 and heater / mixing line 60 allows the WFPD from the accumulator 66 and the concentrate from the first and second concentrate containers 84a and 84b to at least partially mix before entering the container or bag. Furthermore, even if the cassette 42 is not provided, the WFPD and at least one concentrate will partially mix within the heater / mixing line 60 prior to reaching the container or bag.

[0151] FIG. 1 also illustrates that system 10, in one embodiment, communicates with one or more caregiver servers 102 via network 100, which in turn are in operative communication with one or more physician or clinician computers 110-110c. In the illustrated embodiment, network 100 is a cloud network using, for example, one or more wide area networks (“WANs”) such as the Internet. Network 100 may alternatively be a more local area network (“LAN”). In the illustrated embodiment, circulator 20 of system 10 communicates with network 100 wirelessly via any of the protocols enumerated herein. In alternative embodiments, circulator 20 of system 10 communicates with network 100 in a wired manner, for example, using an Ethernet connection. In the illustrated embodiment, circulator 20 of system 10 communicates with network 100. In alternative embodiments, water purifier 210 alternatively or additionally communicates with network 100 in a wireless or wired manner. In the illustrated embodiment, one or more caregiver servers 102 communicate with the network 100 wirelessly via any of the protocols enumerated herein. In alternative embodiments, one or more caregiver servers 102 communicate with the network 100 in a wired manner, for example, using an Ethernet connection. In the illustrated embodiment, the physician or clinician computers 110-110c communicate with one or more caregiver servers 102 in a wired manner, for example, using an Ethernet connection. In alternative embodiments, the physician or clinician computers 110-110c communicate with one or more caregiver servers 102 wirelessly via any of the protocols enumerated herein. (Temperature sensing for peritonitis)

[0152] 3-8B, in one primary 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 approximately 37°C. In a patient suffering from a peritonitis episode, the spent dialysate exiting the patient may be at an elevated temperature. The system and method of the first embodiment measures the effluent dialysate and uses the measurement to make a determination as to whether the patient is suffering from a peritonitis episode.

[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 effluent fluid being removed from the patient P (FIG. 1). The connector 120 includes a main housing 122, which may be made from any suitable medical-grade material, such as medical-grade plastic. In the illustrated embodiment, the housing 122 is mated within the patient line 50 (FIG. 1). The housing 122 includes a first port 124 that sealingly receives the first mating end 50a of the patient line 50. The first port 124 may include or be a hose return port, for example, or may be sized to widen the first mating end 50a as shown. The first port 124 may alternatively be a luer connector that connects to the mating luer connector end 50a of the patient line 50. The housing 122 includes a second port 126 that sealingly receives the second mating end 50b of the patient line 50. Second port 126 may be a male port just like port 124, or it may be a female port as shown that sealingly receives second mating end 50b via a compression fitting (to do so, second mating end 50b may be fitted with an internal rigid hose barb to maintain its shape when placed under compression). Female port 126 allows electrical leads 128a and 128b to extend out of housing 122 when electrical signals are delivered via wires to control unit 22 of circulation device 10 (or control unit 212 of water purifier 210).

[0154] Electrical leads 128a and 128b extend to probes or electrodes 130a and 130b, respectively, which contact the effluent fluid traveling through housing 122 and provide a temperature reading for the fluid. Leads 128a and 128b and electrodes 130a and 130b may be overmolded into or bonded to the inner cylindrical surface of housing 122. The temperature sensor in connector 120 may be, for example, a thermocouple or a thermistor. In the illustrated embodiment, electrodes 130a and 130b are the sensing portion of a K-type (chromel-alumel) thermocouple, which generates a senseable voltage that is proportional to the temperature of the effluent fluid.

[0155] Connector 120 illustrates multiple ways in which the generated voltage can be analyzed (alternatively, therefore, not all of the structures illustrated in FIG. 3 need include connector 120, but only the structure may be used). In one embodiment, leads 128a and 128b carry the generated voltage back to control unit 22 of circulator 20 (or control unit 212 of water purifier 210), where the control unit electronics and processing process the temperature-proportional voltage signal and determine whether the resulting temperature is indicative of peritonitis or its onset.

[0156] In another embodiment (indicated by dashed lines), conductors 128a and 128b carry the generated voltage to a wireless module 132 located along the outside of housing 122. Wireless module 132, in one embodiment, is powered 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 that is transmitted wirelessly to control unit 22 of circulator 20. Control unit 22 of circulator 20 processes the wireless version of the temperature-proportional voltage signal and determines whether the resulting temperature is indicative of peritonitis or the onset of peritonitis.

[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 clamshell temperature connector 140 instead fits over a tubing segment, such as a portion of patient line 50. In the illustrated embodiment, the clamshell temperature connector 140 first directly overlies and contacts the medical-grade polymer or plastic of the patient line 50. In an alternative embodiment, a more thermally conductive medical-grade segment 150, such as a stainless steel segment, is joined between the two polymer or plastic segments of the patient line 50. The more thermally conductive medical-grade segment 150 can help achieve more accurate temperature measurements.

[0158] 4A and 4B illustrate that clamshell temperature connector 140, in the illustrated embodiment, includes a housing 142 having clamshell halves 144 and 146 hinged together along living hinge 148. Housing 142 is made from any suitable material, such as medical-grade plastic. Housing 142, in the illustrated embodiment, is sized to form a fit over patient line 50 / 150.

[0159] Connector 140 includes respective electrical leads 152a and 152b extending to probes or electrodes 154a and 154b, which contact patient line 50 / 150 and provide the temperature of the effluent fluid flowing therethrough. Leads 152a and 152b and electrodes 154a and 154b may be overmolded into or bonded to the inner cylindrical surface of each clamshell half 144 and 146. The temperature sensor in connector 140 may again be a thermocouple or thermistor. In the illustrated embodiment, electrodes 154a and 154b are the sensing portion of a K-type (chromel-alumel) thermocouple, which generates a senseable voltage that indicates the temperature of the effluent fluid.

[0160] Connector 140 illustrates multiple ways in which the generated voltage can be analyzed (alternatively, therefore, not all of the structures illustrated in FIGS. 4A and 4B need include connector 140, but only the structure may be used). In one embodiment, leads 152a and 152b carry the generated voltage back to control unit 22 of circulator 20 (or control unit 212 of water purifier 210), where the control unit electronics and processing process the temperature-proportional voltage signal and determine whether the resulting temperature is indicative of peritonitis or its onset.

[0161] In another embodiment (indicated by dashed lines), conductors 152a and 152b carry the generated voltage to a wireless module 132 located along the outside of housing 142. Wireless module 132, in one embodiment, is powered 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 that is transmitted wirelessly to control unit 22 of circulator 20. Control unit 22 of circulator 20 processes the wireless version of the temperature-proportional voltage signal and determines whether the resulting temperature is indicative of peritonitis or the onset of peritonitis.

[0162] 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 circulator 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, which is bolted to, glued to, or formed by the housing 24. The housing 162 is made from any suitable material, such as medical-grade plastic. The housing 162, in combination with probes or electrodes 166a and 166b, includes a snap-fit ​​collar 164 that, in the illustrated embodiment, is sized to snap over the patient line 50 / 150. The C-shaped collar 164 spreads apart slightly to receive the patient line 50 / 150, and then spreads apart again slightly to release the patient line 50 / 150 once treatment is complete.

[0163] Electrodes 166a and 166b may be overmolded into or bonded to the inner cylindrical surface of C-shaped collar 164. The temperature sensor in connector 160 may again be a thermocouple or thermistor. In the illustrated embodiment, electrodes 166a and 166b are the sensing portions of a K-type (chromel-alumel) thermocouple, which generates a senseable voltage that indicates the temperature of the outflow fluid. In the illustrated embodiment, electrodes 166a and 166b extend to leads 168a and 168b, respectively, which carry the generated voltage through the wall of housing 24 to control unit 22 of circulator 20 (or control unit 212 of water purifier 210), whose electronics and processing process the temperature-proportional voltage signal and determine 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. A patient line 50 or thermally conductive patient line segment 150 carries an outflow fluid. An electrode E (representing all electrodes discussed above) contacts the outer wall of the patient line 50 or thermally conductive patient line segment 150 as shown, or directly contacts the outflow fluid (FIG. 3). The temperature, indicative of a voltage, is carried via a conductor L (representing all conductors discussed above) to a wireless module 132. The wireless module 132 is powered by a battery 134, such as a long-lasting lithium battery, and includes electronics configured to convert the temperature-proportional voltage into a radio signal that is transmitted wirelessly to a desired control unit.

[0165] 6 also illustrates another alternative embodiment in which electrodes E are instead located along the seat of disposable cassette 42. Here, electrodes E are located inside circulator 20 and are automatically aligned with cassette 42 when the cassette is installed. The patient or caregiver is not required to take any additional steps. In this scenario, wireless module 132 is not needed, and leads L instead extend directly to control unit 22.

[0166] As discussed above, testing the temperature of patient P's outflow fluid is used to determine whether the patient has peritonitis. Outflow fluid flows from patient P through patient transfer set 54, patient line connector 52, patient line 50, disposable set 40, drain line 56, drain line connector 58, and drain connector 218 of water purifier 210. It is envisioned that temperature sensing connector 120, 140, or 160 may be located in any of these locations, including as part of patient transfer set 54, patient line connector 52, or drain line connector 58. In one aspect, it is advantageous to locate temperature sensing connector 120, 140, or 160 as close to patient P as possible (e.g., patient transfer set 54 or patient line connector 52) to sense the patient effluent temperature as accurately as possible. However, as shown below, temperature sensing can be useful for this purpose even when true patient temperature is not sensed. Locating temperature sensing for peritonitis along the drain line in the water purifier 210 is advantageous, for example, if the temperature sensor is present for another purpose, such as working in combination with a conductivity sensor to test the conductivity of the dialysis fluid and determine mixing accuracy.

[0167] 7A and 7B illustrate example data from either a direct fluid sensing embodiment (e.g., connector 120 of FIG. 3) or an embodiment of sensing through a thermally conductive patient tube segment 150, each of which would read 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). Each fill stage is followed by a dwell period indicated by the parallel lines. Each drain stage is followed by the next fill stage as indicated by a single vertical line.

[0168] The circulator 20 heats the fresh dialysate in the heater / mixing bag 62 to body temperature or 37°C prior to delivery to patient P via cassette 42 and patient line 50. In each fill phase example in FIGS. 7A and 7B, the temperature reading is at or about 37°C as the heated fresh fluid passes the temperature sensor. The drain phase readings (Dr1 and Dr2) are readings of effluent dialysate from patient P, where the effluent fluid has been in the patient for an extended period of time, e.g., at least one hour, such that the effluent fluid temperature provides a true indication of the patient's internal temperature. FIG. 7A shows effluent temperature readings from a healthy PD patient, where the reading may be at or slightly above body temperature or 37°C. FIG. 7B shows effluent temperature readings from a PD patient who may be suffering from peritonitis or its onset, where the reading, in the illustrated example, is significantly above body temperature, approximately 38°C.

[0169] It is contemplated that temperature signal operations may be programmed to evaluate temperature readings. For example, assume the set point for generating a peritonitis alert is 38°C. The associated processing and memory that evaluates the temperature readings may be programmed to average the temperature readings over the course of the effluent fluid discharge flow past the temperature sensor. In this way, a brief temperature spike to 38°C will not trigger an alert or flag. It is also contemplated that temperature readings may be noted over multiple effluent discharges (e.g., Dr1 and Dr2) and averaged prior to making a decision on whether to generate a peritonitis alert. For example, in one embodiment, an alert is generated at the end of a treatment involving multiple effluent discharges when the sum of the effluent temperature readings indicates peritonitis or its onset (e.g., 38°C or higher).

[0170] 8A and 8B generally illustrate example data from an embodiment of sensing through a non-thermally conductive patient tube segment 50, where temperature readings may be below true fluid temperature. Each of FIGS. 8A and 8B shows temperature readings for two fill stages (Fi1 and Fi2) and two drain stages (Dr1 and Dr2). Each fill stage is followed by a dwell period, indicated by the parallel lines. Each drain stage is followed by the next fill stage, indicated by the single vertical line.

[0171] Because it is known that the circulator 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 fill stage temperatures in FIGS. 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”)) in the patient line 50. In the illustrated example of FIGS. 8A and 8B, the temperature of the heated fresh PD fluid reads 32°C instead of what is known to be 37°C. The associated control unit 22 or 212 thereby determines that the current offset for the current tubing under the current environmental conditions is 5°C. The associated control unit is then programmed to expect the effluent fluid removed from a healthy patient P to have approximately the same temperature offset (i.e., approximately 32°C). The associated control unit is also programmed to determine that patient P may have peritonitis if the temperature of the effluent fluid removed from the patient is a predetermined amount above an offset temperature of approximately 32°C.

[0172] In each fill phase example of FIGS. 8A and 8B , the offset temperature reading through the generally non-thermally conductive patient line tubing 50 is at or about 32° C. as the heated fresh fluid passes the temperature sensor. The drain phase readings (Dr1 and Dr2) are again readings of effluent dialysate from patient P, where the effluent fluid has been present within the patient for an extended period of time, e.g., at least one hour, such that the effluent fluid temperature provides a true indication of the patient's internal temperature. FIG. 8A shows an effluent temperature reading from a healthy PD patient whose reading may be at or slightly above the expected offset temperature of 32° C. However, FIG. 8B shows an effluent temperature reading from a PD patient who may be suffering from peritonitis or its onset, where the reading, in the illustrated example, is significantly above the expected offset temperature, approximately 34° C. With respect to the expected offset example of FIGS. 8A and 8B , again, it is contemplated that the temperature signal operations described above, e.g., averaging and accumulating over multiple fills and drains, may be programmed in evaluating the temperature readings.

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

[0174] In addition to, or perhaps alternatively to, alerts provided to patient P or a caregiver at user interface 30 of circulator 20, control unit 22 (or perhaps control unit 212) operates via network 100 and one or more caregiver server computers 102 to enable a physician or clinician at one or more clinician computers 110a-110c to receive and view, e.g., continuously, effluent temperature data so that the physician or clinician can determine whether the patient is at risk of having or developing peritonitis. The data, in one embodiment, is displayed on clinician computers 110a-110c via a website dashboard for the patient, and temperature data may be presented with a flag for the clinician when elevated and indicative of peritonitis.

[0175] It is envisioned that effluent temperature data for patient P will be transmitted after all treatments, regardless of whether the data indicates peritonitis. In this manner, a physician or clinician can create a pattern or profile of effluent temperatures for the patient. It is envisioned that the website will create, for example, a dashboard as well as a graph or trend of effluent temperatures plotted against treatment days that is displayed upon request. The trends and dashboard in one embodiment will point out or flag temperature entries that may indicate peritonitis or its onset. A physician or clinician viewing multiple flagged peritonitis days can therefore determine with reasonable certainty that the patient requires treatment. (BioMEMS sensing of peritonitis)

[0176] 9 and 10, in a second primary embodiment, a bio-microelectromechanical systems (“bioMEMS”) sensor is used to detect peritonitis. The bioMEMS sensor is used to look for the presence of white blood cells from the patient in the outflow fluid, which is an indicator of peritonitis. FIG. 9 illustrates that, in one implementation, outflow fluid from the patient P is pumped via a patient line 50 to a cassette 42 loaded into the circulator 20, and then from the cassette 42 via a drain line 56 to a drain in the water purifier 210. The drain line 56, in one embodiment, is connected to a lab-on-a-chip diagnostic detection or bioMEMS device 170. However, in the illustrated embodiment of FIG. 9, an alternative is shown in which the outflow fluid is selectively pumped to the lab-on-a-chip diagnostic detection device 170 via a special sample port 48 and sample line 158. The use of the sample port 48 allows the control unit 22 of the circulator 20 to selectively deliver a desired amount of outflow fluid from the patient P to the lab-on-a-chip diagnostic detection device 170 at a desired time and / or frequency.

[0177] 9, the lab-on-a-chip or bioMEMS device 170 includes a container 172, and the sampling line 158 extends to the container 172 and connects (e.g., via a compression fitting, a threaded fitting, a luer connection, a hose barb connection, and combinations thereof) to an inlet line 174 located within the container 172. The container 172 may be made from a medically acceptable metal or polymer, such as stainless steel or a plastic such as PVC.

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

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

[0180] In the illustrated embodiment, bioMEMS device 170 includes a control unit 184 having electronics, processing, and memory for converting the frequency of resonance from biosensor 182 into a quantified quantity representing the amount of leukocytes removed from the patient's effluent sample. Control unit 184 may also include a user interface 186 that displays audio, visual, or audiovisual messages to the patient or caregiver indicating the presence or absence of leukocytes and, therefore, the presence or absence of peritonitis or its development.

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

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

[0183] Although network 100, one or more caregiver server computers 102, and one or more clinician computers 110a-110c are not shown in FIG. 9 , they may still be present. And, in addition to, or perhaps instead of, alerts provided to patient P or a caregiver at user interface 30 or user interface 186, control unit 22 operates via network 100 and one or more caregiver server computers 102 to enable a physician or clinician at one or more clinician computers 110a-110c to receive and view, for example, on a continuous basis, shed leukocyte collection data so that the physician or clinician can determine whether the patient has or is at risk for developing peritonitis. The data, in one embodiment, is displayed on clinician computers 110a-110c via a website dashboard for the patient, and the shed leukocyte collection data may be presented with a flag for the clinician when elevated and indicative of peritonitis.

[0184] It is contemplated that effluent leukocyte collection data for patient P will be transmitted after the entire treatment, regardless of whether the data indicates peritonitis. In this manner, a physician or clinician can create a pattern or profile of effluent leukocyte collection data for the patient. It is also contemplated that the website may create graphs or trends of effluent leukocyte collection volume plotted against treatment days, which may be displayed upon request, for example, in addition to a dashboard. The trends and dashboard in one embodiment may point out or flag leukocyte entries that may indicate peritonitis or its onset. A physician or clinician viewing multiple flagged peritonitis dates can therefore determine with reasonable certainty that the patient requires treatment. The leukocyte collection data of the second main embodiment may be displayed as an alternative to, or in addition to, the effluent temperature data of the first main embodiment. Providing both leukocyte collection data and effluent temperature data allows a physician or clinician to view and analyze multiple peritonitis indicators to make medical decisions for the patient.

[0185] In an alternative embodiment, bioMEMS device 170 is instead located in patient line 50 via a sample line and used to analyze the effluent returning from patient P. In this manner, the bioMEMS device may additionally be used to sense the fresh dialysate delivered to the patient, if desired. Alternatively, control unit 20 may be programmed to periodically route fresh dialysate through bioMEMS device 170 via sample port 48 of cassette 42 and sample line 158 to sample desired properties of the fresh dialysate. (Impedance monitoring for peritonitis)

[0186] 11-13, in a third primary 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 the patient's effluent fluid can be sensed, for example, in the patient's indwelling catheter, in the patient line, or in the drain line. In any of these locations, the catheter or line is equipped with electrodes in any of the ways discussed above for, for example, temperature sensing, but now with the goal of placing conductive contacts in communication with the effluent dialysate for impedance detection.

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

[0188] 12 and 13 illustrate one embodiment of the impedance monitor 230. FIG. 12 illustrates that, in one embodiment, cylindrical electrodes 240 and 244 are mounted within the patient line 50, the patient's indwelling catheter 55, or the drain 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 line 50, 56, or catheter 55, thereby allowing the electrodes 240 and 244 to be press-fit at the desired location within the line 50, 56, or catheter 55. The electrodes 240 and 244 are made from a conductive and medically safe material, such as stainless steel, titanium, and combinations and alloys thereof. The electrodes 240 and 244 in the illustrated embodiment each include a female port or socket 242 and 246, respectively, configured to receive and hold a lead extending from the port.

[0189] FIG. 13 illustrates that in one embodiment, the female ports or sockets 242 and 246 extend through the line 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 the ports or sockets extending to be at least substantially flush with the outside of the line 50, 56 or catheter 55. In either embodiment, the outer diameter of the ports or sockets 242 and 246 is larger than the hole created in the line 50, 56 or catheter 55, thereby allowing the tubing or catheter material to stretch around the port and seal thereto. In a further alternative embodiment (not shown), the ports or sockets 242 and 246 do not extend outward from the cylindrical electrodes 240 and 244, and instead, the electrical leads are threaded through the line 50, 56 or catheter 55. Here, the line 50, 56 or catheter 55 helps hold the electrical leads 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 , conductive leads 248a and 248b of impedance monitor 230 in one embodiment extend to control unit 22 of circulator 20 (or control unit 212 of water purifier 210), where the control unit's electronics and processing enable the signal generation and processing discussed below. In an alternative embodiment (shown by dashed lines), leads 248a and 248b receive power from and / or carry a generated voltage to wireless module 132 located along the outside of housing 232 of impedance monitor 230. Wireless module 132 is again powered by battery 134, such as a long-lasting lithium battery, and includes electronics configured to convert the voltage into a wireless signal, and vice versa, which is wirelessly communicated to control unit 22 of circulator 20 in one embodiment.

[0191] Housing 232 may have clamshell halves 234 and 236, which are hinged together along the living hinge discussed with respect to Figures 4A and 4B. Housing 232, in the illustrated embodiment, is sized to form a fit over patient line 50, catheter 55, or drain line 56. Housing 232 may alternatively be joined between two segments of patient line 50, catheter 55, or drain line 56 in a manner identical to or similar to temperature sensing connector 120 of Figure 3. Housing 232 in any of the above embodiments is made from any suitable material, such as medical-grade plastic.

[0192] In one embodiment, the control unit 22 (of the circulator 20) or the control unit 212 (of the water purifier 210), which controls the impedance monitor, causes an electrical frequency sweep to be generated in the outflow 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 specified sweep rate. Sweeping the frequency up or down in linear or logarithmic intervals is contemplated. It is also contemplated to program the control unit to sweep sine, square, pulse, ramp, triangle, or arbitrary waveforms. It is further contemplated to define a hold time (during which the sweep remains at the stop frequency) and a return time (during which the frequency changes linearly from the stop frequency to the start frequency).

[0193] As the impedance monitor 230 progresses through the frequency sweep, the resulting impedance of the effluent fluid in the indwelling catheter is measured at each different frequency. The impedance of the effluent fluid can be compared to that of fresh dialysate to determine if differences occur. In one embodiment, impedance spectroscopy (or complex impedance acquisition) provides additional details about the contents of the effluent fluid. For example, the electrical properties of fibrin (normal, not indicative of peritonitis) may vary from the electrical properties of white blood cells (indicative of peritonitis). Once the control unit 22 (of the circulator 20) or the control unit 212 (of the water purifier 210) learns the electrical properties of different substances that may be present in the effluent fluid, the properties can be programmed into the control unit and then used to determine what will happen if something gets into the effluent dialysate stream.

[0194] 14A and 14B illustrate exemplary plots of impedance (Z), measured in ohms (Ω), for normal patient effluent, patient effluent with white blood cells (indicating peritonitis), and patient effluent with other particulate matter such as fibrin. FIG. 14A shows impedance measurements over time, which can be continuous or discrete (on command). An exemplary time-based output shows continuous data for (A) normal effluent impedance (continuous line only) and (C) effluent with increased fibrin content (dashed line), for example, over the course of a dwell phase of a patient's peritoneal dialysis treatment. In the illustrated example, the plots of impedance over time for the effluent with normal fibrin (A) and the effluent with increased fibrin (C) start together, but then the impedance for the effluent with increased fibrin rises significantly above that of the effluent with normal fibrin. It is expected that the curve for the development of peritonitis would be represented by the line extending within the area marked (B) between the line for effluent with normal fibrin (A) and the line for effluent with increased fibrin (C) seen in Figure 14B. Figure 14B shows that a clear distinction between effluent with normal fibrin and effluent with increased fibrin appears as the patient progresses through the retention phase.

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

[0196] The exemplary frequency-based output in FIG. 14B illustrates that there are likely one or more frequency ranges where the impedance difference between the effluent with white blood cells (b) and the normal effluent (a) is more significantly different than 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 results of one of the ranges against the other. If both or all frequency ranges indicate peritonitis, the control unit 22 or 212 (or clinician computers 110a-110c) outputs a determination that the patient has or is beginning to suffer from peritonitis to the user interface 30, the user interface 220, and / or to the clinician computers 110a-110c via the network 100 and the caregiver server computer 102. In another embodiment, the control unit 22 or 212 integrates the area under the impedance curve (b) and compares it to the integral of the area under the impedance curve (a) to determine peritonitis or its onset.

[0197] In one embodiment, the curve (a) for normal effluent is empirically determined through testing on multiple patients and then averaged to develop standardized impedance values ​​across a frequency sweep range. In some embodiments, standardized values ​​are determined for each of the popular and most frequently used glucose level peritoneal dialysis fluids, since impedance can vary based on starting glucose levels. Standardized impedance values ​​can be provided as a range to account for different dwell times, different effluent temperatures, and other factors.

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

[0199] With respect to the increased fibrin content curve (c), Figure 14B illustrates that there is one or more particular frequency ranges, here between f1 and f2, where the impedance of the effluent with white blood cells indicative of peritonitis (b) is significantly higher than the impedance of the effluent with increased fibrin (c). Thus, in Figure 14B, it can be said that the most significant range is between frequency ranges f3 and f4, since the increased impedance between frequency ranges f3 and f4 can be attributed to either the effluent with white blood cells indicative of peritonitis (b) or the effluent with increased fibrin (c).

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

[0201] In any embodiment in which the impedance monitor 230 is located remotely from the circulator 20 or the water purifier 210, the impedance monitor may transmit the measured signal in a wired or wireless manner to the circulator for interrogation. The impedance monitor 230, as described above, has the capability to emit a frequency sweep into the outflow fluid and therefore may receive power either via the battery 134 (in wireless embodiments) or from the circulator or water purifier via a power wire.

[0202] As discussed above, in alternative embodiments, the impedance monitor 230 is located within the circulator 20 or the water purifier 210. In such cases, the impedance monitor 230 emits a frequency sweep into the outflow fluid by receiving power from the circulator or water purifier via a power wire. As mentioned above, the impedance monitor 230 may operate in conjunction with a disposable cassette 42 loaded into the circulator 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, in one embodiment, is programmed to alert the patient or caregiver at the user interface 30 of the circulator 20 if white blood cells indicative of peritonitis are detected. In one embodiment, even if the control unit evaluating the impedance sweep readings for white blood cells is the control unit 212 of the water purifier 210, an audio, visual, or audiovisual alert is nevertheless provided at the user interface 30 of the circulator 20 by wired or wireless communication from the control unit 212 of the water purifier 210 to the control unit 22 of the circulator 20 to notify of the alert condition. In this manner, 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, alerts provided to patient P or a caregiver at user interface 30, control unit 22 operates via network 100 and one or more caregiver server computers 102 to enable a physician or clinician at one or more clinician computers 110a-110c to receive and view, for example, on a continuous basis, impedance-acquired shed leukocyte data so that the physician or clinician can determine whether the patient has or is at risk for developing peritonitis. The data, in one embodiment, is displayed on clinician computers 110a-110c via a website dashboard for the patient, and the shed leukocyte collection data may be presented with a flag for the clinician when elevated and indicative of peritonitis.

[0205] It is envisioned that impedance acquisition effluent leukocyte data for patient P will be transmitted after the entire treatment, regardless of whether the data indicates peritonitis. In this manner, a physician or clinician can create a pattern or profile of effluent leukocyte data for the patient. It is also envisioned that the website may create graphs or trends of effluent leukocyte volume plotted against treatment days, which may be displayed upon request, for example, in addition to a dashboard. The trends and dashboard in one embodiment point out or flag leukocyte entries that may indicate peritonitis or its onset. A physician or clinician viewing multiple flagged peritonitis dates can therefore determine with reasonable certainty that the patient requires treatment. The leukocyte data of the third main embodiment may be displayed as an alternative to, or in addition to, the leukocyte collection data of the second main embodiment and / or the effluent temperature data of the first main embodiment. Providing both the leukocyte data embodiment and the effluent temperature data allows a physician or clinician to view and analyze multiple peritonitis indicators to make medical decisions for the patient. (Glucose control for diabetics)

[0206] 15-20B, in a fourth main embodiment, system 10 provides a MEMS affinity glucose sensor 250 that matches or helps match the amount of insulin provided to patient P with the amount of glucose delivered to the patient during treatment. FIG. 14 illustrates a version of system 10 that uses pre-prepared PD fluid in containers or bags 94a and 94b instead of using glucose concentrate 84a, buffer concentrate 84b, or purified water from water purifier 210 to prepare the PD fluid stored in accumulator 66 online or at the point of use (as shown in FIGS. 1, 9, 11, and 15). However, in either 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] 15 illustrates that in one pre-prepared PD fluid embodiment, an insulin container or bag 90 is connected to a port on cassette 42 that, in an example point-of-use scenario, is connected to accumulator 66. A MEMS affinity glucose sensor 250 is provided in drain line 56 upstream of drain bag 96. MEMS affinity glucose sensor 250 measures the glucose level in the effluent dialysate exiting patient P via drain line 56.

[0208] FIG. 16 illustrates that, in one embodiment, a MEMS affinity glucose sensor 250 includes a container 252 into which extends a sampling line 254, which may extend or branch from the exhaust line 56. An effluent sample entering the container 252 of the MEMS affinity glucose sensor 250 first encounters a microfluidic pathway 256 that separates glucose molecules from the effluent fluid. The glucose molecules are then, in the illustrated embodiment, weighed using a piezoelectric biosensor 258. The piezoelectric biosensor 258 includes a cantilever 260 that resonates at a frequency proportional to the change in deposition rate of the glucose molecules. The relationship between the resonant 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 determined by the A frequency, as discussed below. n To compensate for the glucose absorbed in the nth PD cycle, the following n+1 The administration of insulin doses during PD cycles is discussed below. n+1 It is calculated using the formula for

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

[0210] 15 includes a wireless module 132 located 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 outflow glucose level into a wireless signal that is transmitted wirelessly to the control unit 22 of the circulator 20. The control unit 22 of the circulator 20 processes the glucose level wireless signal and determines the amount of insulin from the insulin container or bag 90 to deliver to the heater bag 62 for the next patient PD fill. Note that the patient P will sometimes be filled with fluid from a previous therapy when starting a current therapy.

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

[0212] FIG. 15 also illustrates that, in one embodiment, system 10 using MEMS-affinity glucose sensor 250 also includes a glucose sensor 262 applied to patient P's finger, for example. Such glucose sensors, in either cutaneous or non-cutaneous forms, are known in the art. 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. Readings from glucose sensor 262 at the beginning of therapy are used to determine the amount of insulin to inject in the next PD fill cycle, in one embodiment discussed below. Readings from glucose sensor 262 can be used at the end of therapy to ensure patient P's blood glucose level remains within a safety zone using the glucose feedback and insulin injections of the present disclosure. All such information may also be transmitted via network 100 and one or more caregiver server computers 102 to clinician computers 110a-110c.

[0213] The MEMS affinity glucose sensor 250 in the point-of-use preparation version of FIG. 17 is located within the water purifier 210 in the illustrated embodiment and outputs electrically to the water purifier's control unit 212, thus eliminating the need for a wireless module 132 located along the outside of the sensor's 250 housing. 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 circulator 20 should deliver to the heater / mixing bag 62 for the next patient PD fill. Note that the patient P is typically filled with fluid from the previous treatment when the current treatment begins. The amount of insulin to be delivered is based on the desired insulin concentration, which, again, correlates 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 water purifier control unit 212 determines the amount of insulin to pump and transmits that amount wired or wirelessly to the control unit 22 of the circulator 20, which uses that amount to command the pump chamber 44 of the disposable cassette 42 to pump the desired amount of insulin. In another embodiment, the control unit 212 relays a glucose signal wired or wirelessly from the bioMEMS glucose measuring device 250 to the control unit 22, which determines the amount of insulin to pump and uses that amount to command the pump chamber 44 of the disposable cassette 42 to pump the desired amount of insulin.

[0214] The control unit 22 operates via the network 100 and one or more caregiver server computers 102 to allow a doctor or clinician at one or more clinician computers 110a-110c to view insulin usage data, for example, on a treatment-by-treatment basis, so that the clinician may verify that insulin is being delivered appropriately. The data, in one embodiment, is displayed on a website dashboard for the patient, and insulin volumes and concentrations may be viewed. Data from the fourth main embodiment may be combined with data from the first, second, and / or third main embodiments and displayed on the doctor or clinician website for patient P 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 a glucose sensor 262, provided and used as described above.

[0215] 18 , method 290 summarizes one embodiment for closed-loop insulin delivery described above. At oval 292, method 290 begins. At block 294, circulator 20 activates disposable cassette 42, (i) drawing fresh dialysate (pre-prepared or made at the point of use) from heater bag 62 (pre-prepared) or heater / mixing bag 62 (point of use) along with a calculated dose of insulin from insulin bag or container 90, and (ii) pushing the heated fresh dialysate and insulin dose fluid into patient P. At block 296, the dialysate is allowed to dwell within patient P's peritoneum for a physician / clinician-prescribed amount of time. In block 298, the circulator 20 activates the disposable cassette 42, drawing spent dialysate or effluent from the 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 tube 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 . In block 300, the MEMS affinity glucose sensor 250 monitors the effluent PD fluid for the patient's absorbed glucose amount or glucose concentration. In block 302, the MEMS affinity glucose sensor 250, or the control unit 22 of the circulator 20, or the control unit 212 of the water purifier 210, calculates an insulin dose based on the glucose amount or concentration absorbed by the patient P. In one embodiment, if the control unit 22 of the circulatory device 20 does not calculate the insulin dose, the calculated dose is sent to the control unit 22 of the circulatory device 20 .

[0216] At diamond 304, if there is another cycle in the current therapy, method 290 returns to block 294, where control unit 22 of circulatory device 20 provides the next patient fill using a newly calculated dose of insulin based on the newly monitored amount or concentration of absorbed glucose. If there is not another cycle in the current therapy at diamond 304, method 290 moves to block 306, where the newly calculated dose of insulin based on the newly monitored amount or concentration of absorbed glucose is saved for the first fill of the next therapy. At oval 308, method 290 ends.

[0217] It should be understood that method 290 applies to PD therapies that do not provide a "final fill" of fresh PD fluid that the patient holds throughout the day until the next treatment (perhaps with a midday change). That is, the patient P leaves the treatment empty. When a "final fill" is provided, method 290 after start oval 292 instead proceeds to drain block 298 to drain the "final fill" effluent fluid from the patient, then to monitor block 300, then to calculate block 302, and then to fill fresh fluid using insulin dose block 294. A decision diamond is instead provided after fill of fresh fluid using insulin dose block 294, and the determination is whether another patient drain exists. If so, the modified method proceeds to dwell block 296 and back through blocks 298, 300, 302, and 294. When there is no additional patient drain, the modified method ends at oval 308. In the "last fill" method, there is no need for the insulin dose storage block 306 because the first step of the next treatment is to drain the patient P.

[0218] 19 illustrates one example relationship between absorbed glucose in the effluent fluid and the frequency at which the cantilever 260 of the biosensor 258 resonates. In the example plot, the effluent fluid with no absorbed glucose (continuous line) resonates at a frequency ratio of about 0.66, resulting in an output amplitude that is approximately (i) twice as large as the effluent fluid absorbed with a glucose concentration of X1 mg / dL (continuous line with boxes), which resonates at a frequency ratio of about 0.8, and (ii) two-thirds larger than the effluent fluid absorbed with a glucose concentration of X2 mg / dL (dashed line), which 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 at distinguishing between 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 outflow fluid from the initial glucose concentration of the fresh dialysate delivered to the patient P. The control unit calculates the glucose concentration present in the outflow fluid for the nth PD cycle (P n ) is programmed to determine the amount of glucose absorbed by the patient at the end of the P n =f(V n ,μ,(D on -D in )) During the ceremony, n = cycle number, V n = volume of PD fluid delivered for the nth cycle, μ = glucose absorption coefficient (empirically determined constant), D on = glucose concentration of the effluent for the nth cycle as measured by the MEMS affinity glucose sensor 250 D in = initial glucose concentration of the PD fluid for the nth cycle (PD fluids are provided in standard concentrations such as 0.55%, 1.5%, 2.5%, and 4.25%) is.

[0220] nth cycle (P n Based on the amount of glucose absorbed by the patient at the end of the next cycle, the amount of insulin to provide to the patient in the following cycle is determined, in one embodiment, by a function such as: I n+1 =f(G I ,P n ,α,β,t) During the ceremony, G I = initial blood glucose level before the start of therapy, obtained in one embodiment from glucose sensor 262, P n is calculated as discussed above, α and β are insulin absorption coefficients (empirically determined constants), t = time.

[0221] 20A and 20B graphically illustrate how, using glucose feedback and insulin injection of the system 10 of FIGS. 15-18 with a MEMS affinity glucose sensor 250, a glucose level (mg / dL) can exceed an upper threshold when uncontrolled, but remain within the limits prescribed by a physician or clinician when controlled. As illustrated in FIG. 20A, the glucose level (mg / dL) in patient P steadily rises through each dwell period, exceeding the upper threshold during the second dwell. However, in FIG. 20B, the glucose level (mg / dL) in patient P rises during the dwell period, but then drops during the subsequent fill phase while insulin is being injected, according to the above-discussed function programmed into the MEMS affinity glucose sensor 250, control unit 22, or control unit 212.

[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 present subject matter and without diminishing its intended advantages. Accordingly, such changes and modifications are intended to be covered by the appended claims. For example, while the four main embodiments have been described in connection with an automated peritoneal dialysis system using circulator 20, it is also contemplated that the embodiments may be used with manual PD or continuous ambulatory peritoneal dialysis ("CAPD"). While MEMS biosensing of white blood cells and glucose molecules has been discussed in connection with various vibration frequencies, it is also contemplated that other properties may be used in a transducer to provide a sensed output property, such as, but not limited to, voltage, including changes in capacitance within a microfluidic channel, or changes in light and its frequency. Furthermore, while impedance monitor 230 is shown and described as comprising an indwelling catheter 55 of patient P, it is contemplated that any of the four main embodiments may be implemented with an indwelling catheter.

Claims

1. A peritoneal dialysis ("PD") system, the PD system comprising: a circulation device including a pump actuator and a control unit in operative communication with the pump actuator; a disposable set including a disposable cassette having a pump chamber, the disposable cassette sized and arranged to be held by the circulator such that the pump chamber is in operative communication 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 effluent PD fluid removed from the patient; Equipped with The PD system, wherein the control unit is configured to form a patient peritonitis determination using the sensed temperature and to communicate the peritonitis determination.

2. The PD system of claim 1, wherein the sensed temperature is transmitted from the temperature sensor to the control unit, and the control unit is configured to analyze the sensed temperature.

3. A PD system as described in claim 2, wherein the sensed temperature is transmitted to the control unit via a wired or wireless connection.

4. The PD system of claim 1, further 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 peritonitis determination to at least one patient or caregiver via the network and via a user interface of the circulatory device or the at least one physician or clinician computer.

5. The method further comprises a water purifier configured to supply purified water to the disposable set, the water purifier including a water purifier control unit; 2. The PD system of claim 1, wherein 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 circulator control unit and the water purifier control unit are in communication, enabling the control unit of the circulator to communicate the peritonitis determination.

6. A PD system as described in claim 5, wherein either the control unit of the circulation device or the water purifier control unit is configured to analyze the sensed temperature.

7. The PD system of claim 1, wherein the temperature sensor is configured to be installed within a connector configured to couple to the patient line or the exhaust line.

8. The PD system of claim 7, wherein the connector is (i) a clamshell connector that fits around the patient line or the exhaust line, or (ii) configured to be joined between two sections of the patient line or the exhaust line.

9. The PD system of claim 7, wherein the connector includes an electrode, the electrode positioned and arranged to (a) contact the outflow fluid flowing through the patient line or the exhaust line, or (b) directly contact the patient line or the exhaust line.

10. A PD system as described in claim 9, wherein in (b), a thermally conductive segment is joined between sections of the patient line or the exhaust line, and the connector is directly connected to the thermally conductive segment.

11. The PD system of claim 9, wherein the connector includes a conductor extending from the electrode 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 comprising the connector.

12. The PD system of claim 1, wherein the control unit is configured to analyze the sensed temperature of the effluent PD fluid removed from the patient by comparing the sensed temperature with the temperature of fresh PD fluid delivered to the patient and sensed by the temperature sensor.

13. The PD system of claim 1, wherein the control unit is configured to analyze the sensed temperature of the effluent PD fluid removed from the patient by determining an increase in temperature due to peritonitis or its onset.

14. The PD system of claim 13, 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.

15. The PD system of claim 1, 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.

16. The PD system of claim 15, wherein the at least one different peritonitis indicator usable in combination with the first peritonitis indicator is obtained from at least one of a leukocyte biosensor or a leukocyte impedance sensor.

17. The PD system of claim 1, wherein the peritonitis determination is provided in combination with insulin injections performed using feedback from a patient effluent glucose biosensor.

18. Further comprising a user interface, The user interface includes: receiving the peritonitis determination from the control unit; displaying information indicative of said peritonitis determination. The PD system of claim 1 configured to:

19. The PD system of claim 18, wherein the control unit and the user interface are contained within the circulation device.

20. The PD system of claim 1, wherein the temperature sensor includes at least one of a thermocouple or a thermistor.

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