Hemofiltration devices with sensors

Abstract

Hemofiltration systems have been designed that include a variety of sensors. In some cases, the sensors monitor blood pressure and dialysate pressure within the device. By monitoring these liquid pressures, the device can detect events such as the rupture of a filtration membrane, allowing that membrane to be isolated from other filtration membranes in the device. Dialysate pressure can also be repeatedly cycled up and down in a procedure that achieves more efficient hemofiltration compared to constant pressure filtration. Other sensors can detect various biological, chemical, electrical, and temperature parameters of the blood and the dialysate liquid. These sensors can monitor the speed of hemofiltration while also detecting any chemical imbalances in the patient's blood, thereby allowing the system to adjust parameters and respond accordingly. The systems also have certain mechanical aspects that increase safety and convenience.

Description

HEMOFILTRATION DEVICES WITH SENSORSCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The current application claims priority to U.S. Provisional Patent Application No.63 / 778,256, filed March 26, 2025, entitled “Hemofiltration Devices with Sensors’' the disclosure of which is hereby incorporated by reference in its entirety.INTRODUCTION

[0002] End Stage Renal Disease (ESRD) remains a major public health problem in the United States, afflicting over 615,000 people with nearly 116,000 new patients initiating treatment each year. Due to the shortfall in organ availability, the majority of ESRD patients in the United States undergo in-center. 3-4 hour, thrice weekly dialysis, such as hemodialysis or peritoneal dialysis.

[0003] Hemodialysis involves passing a patient's blood against a synthetic or semisynthetic membrane and inducing diffusive transport of toxins from the blood into a bath of dialysate on the other side of the membrane. In peritoneal dialysis, the patient's parietal peritoneal epithelium performs the function of the dialysis membrane.

[0004] However, traditional hemofiltration devices can simply operate according to a predetermined plan. For example, this predetermined plan can include flowing dialysate liquid through the device at a constant rate. However, new circumstances can develop during the course of hemofiltration, and a completely predetermined plan will not adapt to these new circumstances.SUMMARY

[0005] Hemofiltration systems have been designed that include a variety of sensors. In some cases, the sensors monitor blood pressure and dialysate pressure within the device. By monitoring these liquid pressures, the device can detect events such as the rupture of a filtration membrane, allowing that membrane to be isolated from other filtration membranes in the device. Dialysate pressure can also be repeatedly cycled up and down in a procedure that achieves more efficient hemofiltration compared to constant pressure filtration. Other sensors can detect various biological, chemical, electrical, and temperature parameters of the blood and the dialysate liquid. These sensors can monitor the speed of hemofiltration while also detecting any chemical imbalances in the patient’s blood, thereby allowing the system to adjust parameters and respond accordingly. The systems also have certain mechanical aspects that increase safety and convenience.BRIEF DESCRIPTION OF THE DRAWINGS

[0006] FIG. 1 A shows a general system with an ex vivo companion device, two dialysate tubes, an implantable in vivo hemofiltration device, and blood vessels. The elements are system 100, disposable tubing set 101, dialysate inlet 102, implanted hemofilter 103, blood inlet 104, vascular grafts 105, vein and artery pair 106, blood outlet 107, semipermeable membranes 108. blood chamber 109, dialysate chamber 110, dialysate outlet 111, and permanent transcutaneous catheters 112.

[0007] FIG. IB shows an enlarged view of the companion device in FIG. 1A.

[0008] FIG. 2 shows phases one. two, and three of a pressure-cycling procedure. Procedure 200 includes first phase 201, second phase 202, and third phase 203. First phase 201 is pulling fluid (forward filtration, convective clearance). Second phase 202 is purge (diffusive clearance). Third phase 203 is pushing fluid (backfiltration, replacing fluid).

[0009] FIG. 3A shows an exemplary implantable device. In some cases, there are mirrored isolation chambers for R1 / FC1 and R2 / FC2. FC3 can be exposed but presents an ingress point (along with USB cable). System 300 includes USB Type-C 301, connector 302, and InletPr TiSense 303. The short element connecting element 303 to the large rectangle is FC1. The large rectangular region on the top of the device is R1 Region. The band leaving R1 region and traveling to the right and down the device and arriving on the bottom side is FC3. The rectangle on the bottom part of the device is R2 Region. The small band connecting R2 region to the separate cylinder 304 is FC2. On R2 Region is cylinders 305 and 306. The device also includes pathway 307 along with port 308 and port 309.

[0010] FIG. 3B shows features associated with the FIG. 3A device. This figure includes USB Type-C 301. FC1 302. InletPr TiSense 303, OutletPr TiSense 304, FC2305, R2 Region 306. FC3 307, and R1 region 308. R1 Region 308 includes MCU, INletPr Halfbridge, InletPr Amp / ADC, InletHct LED, INletHct Photodiode, InletHct Amp / ADC, USB out, and Power components. R2 Region 306 includes OuletPr Halfbridge, OutletPr Amp / ADC, OutletHct LED, OutletHct Photodiode, and OutletHct Amp / ADC. Additionally, the optical array operates by reflectance on single side, against flat region of widening flow channel just upstream of the inlet pressure sensor (mirrored on outlet).

[0011] FIG. 4 shows electrical power and digital communication transmission between an implantable in vivo device of FIG. 3 and an ex vivo companion device. Flowchart 400 includes AC N 401, logging 402. prescription 403, companion primary processor 404, USB-C 405 which provides power in moving towards the right and data out when moving to the left, implant satellite processor 406, implant-side sensors 407, companion-side sensors 408, user interface 409, and companion-side actuators (pumps, valves) 410.

[0012] FIG. 5 shows different types of proximal ends of an umbilical that transmits dialysate liquid and electrical power to the in vivo hemofiltration device. The figure shows electrical component 501, sensor reagent reservoir 502, blood chamber 503, housing 504, dialysate chamber 505, and umbilical 506. The device also includes a blood access line, which is the bottom line exiting the umbilical and that travels below dialysate chamber 505 before connecting to the other element below blood chamber 503.

[0013] FIG. 6 A shows an example of a circular guard element that has adhesive for attaching to the skin. The arrangement includes skin adhesive patch 601, disinfectant light source 602, dialysate lines from umbilical 503, power / data cable 604, and the direction 605 towards the exit site. The power / data cable 604 is shown connected and plugged into the socket. Cable 604 is capable of transferring data that was logged.

[0014] FIG. 6B shows dialysate lines along with a digital communication and electrical power cable. The arrangement includes adhesive patch 601 and umbilical exit site 602.

[0015] FIG. 7 shows an implantable device 700 with optical sensors 701, pressure sensors 702, and electrical architecture 703. The figure also shows electrical lumen 704, fluid out lumen 705, fluid in lumen 706, and LED 707. Optical sensors 702 can transmit LED / VSCEL and photodiode with 540 nm + 576 nm light. They can be arranged on opposing across inlet and outlet blood flow channel. They can utilize the optical clarity of PC / PMMA. The electrical architecture 703 has four sensors total (inlet pressure, outlet pressure, inlet hematocrit, PCA with signal condition and processing (MCU). Power to the implant is provided by umbilical connection.

[0016] FIG. 8 shows sensors and interactions between an external companion device and an implantable device. The implantable device can be the implantable device of FIG. 3A. The companion device can be a companion device of FIG. IB. Flowchart 800 includes CAN IN 801, logging 802, prescription 803, companion primary processor 804, USB-C 805 with power in going to the right and one-way data flow going to the left, implant satellite processor 806, inlet pressure 807, outlet pressure 808, inlet hematocrit 809, outlet hematocrit 810, dialysate pressure 811, predialyzer flow 812, post-dialyzer flow 813, blook leak 814, GUI 815. calibration / flow valve or valves 816, bag heater 817, post-dialyzer pump 818, and pre-dialyzer pump 819.

[0017] FIG. 9 shows a section of an external companion device. The non-contact pressure monitor can measure positive and negative pressure without touching the fluid path (e.g. interface with a component on the disposable tubing set). Device 900 includes inlet and outlet pumps 901, heated tray 902, blood leak sensor 903, inlet and outlet flow sensors 904, and non-contact pressure monitor 905.

[0018] FIG. 10A shows an exemplary device 1000 including drain 1001, outlet How sensor 1002, outlet calibration valve 1003, outlet pump 1004, blood leak detector 1005, implant dialy sisdevice 1006. bypass / calibration line 1007, inlet calibration valve 1008, dialysate pressure sensor 1009, inlet pump 1010, inlet flow sensor 1011, inlet heater with feedback 1012, and fluid source 1013.

[0019] FIG. 10B shows a flow diagram corresponding to the FIG. 10A device.

[0020] FIG. 11 shows a three phase hemofiltration scheme. In phase one, the companion pulls fluid from the blood side through the membrane, increasing the clearance of solutes. In phase two, dialysate is flowed through the chamber to clear and purge the solutes. In phase three, the companion pushes dialysate into the blood through the membrane, maintaining overall fluid balance. Scheme 1100 includes first step 1001, second step 1002, and third step 1103. Scheme 1100 includes filtration membrane 1104. iliac vein and artery 1105, vascular grafts 1106, implanted dialysis device 1107, transcutaneous catheter 1108, companion device (bedside) 1109, and tubing 1110.DETAILED DESCRIPTION

[0021] Hemofiltration systems have been designed that include a variety of sensors. In some cases, the sensors monitor blood pressure and dialysate pressure within the device. By monitoring these liquid pressures, the device can detect events such as the rupture of a filtration membrane, allowing that membrane to be isolated from other filtration membranes in the device. Dialysate pressure can also be repeatedly cycled up and down in a procedure that achieves more efficient hemofiltration compared to constant pressure filtration. Other sensors can detect various biological, chemical, electrical, and temperature parameters of the blood and the dialysate liquid. These sensors can monitor the speed of hemofiltration while also detecting any chemical imbalances in the patient’s blood, thereby allowing the system to adjust parameters and respond accordingly. The systems also have certain mechanical aspects that increase safety and convenience.

[0022] Before the present invention is described in greater detail, it is to be understood that this invention is not limited to particular embodiments described, as such may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims.

[0023] Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limits of that range is also specifically disclosed. Each smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in that statedrange is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range, and each range where either, neither or both limits are included in the smaller ranges is also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention.

[0024] The term “equal” as used herein refers to two numerical quantities that have exactly identical values, or that have values that only differ based on experimental errors or measurement errors. For example, pressure values of 100.0 kPa and 100.0 kPa are exactly identical. Also, pressure values of 100.0 kPa and 100.2 kPa are considered identical if the pressure gauge performing the measurement is listed as having a random error of 0.5 kPa.

[0025] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary' skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, some potential and exemplary methods and materials may now be described. Any and all publications mentioned herein are incorporated herein by reference to disclose and describe the methods and / or materials in connection with which the publications are cited. It is understood that the present disclosure supersedes any disclosure of an incorporated publication to the extent there is a contradiction.

[0026] It must be noted that as used herein and in the appended claims, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise. It is further noted that the claims may be drafted to exclude any element, e.g., any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely”, “only” and the like in connection with the recitation of claim elements, or the use of a “negative” limitation.

[0027] The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Further, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed. To the extent the definition or usage of any term herein conflicts with a definition or usage of a term in an application or reference incorporated by reference herein, the instant application shall control.

[0028] As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present invention. Any recitedmethod can be carried out in the order of events recited or in any other order which is logically possible.DEFINITIONS

[0029] The terms “patient” and “subject” are used interchangeably herein.

[0030] The term “fluid” includes substances in a liquid state of matter and substances in a gaseous state of matter.DEVICES USABLE WITH THE METHODS

[0031] The methods of dialyzing blood can utilize any suitable dialy sis devices. For example, the device can include: a blood inlet port, a blood chamber, a blood outlet port, a dialysate inlet port, a dialysate chamber, a dialysate outlet port, and a filtration membrane. The filtration membrane has a blood side adjacent to the blood chamber along with a dialysate side adjacent to the dialysate chamber. The blood side is opposite the dialysate side. The blood side can also be referred to as a blood side surface. The dialysate side can also be referred to as a dialysate side surface. FIG. 1A shows an example of such a device.

[0032] There is fluid communication between the blood inlet port, the blood chamber, and the blood outlet port. Therefore, blood can flow from the blood inlet port, into the blood chamber, and to the blood outlet port. There is fluid communication between the dialysate inlet port, the dialysate chamber, and the dialysate outlet port. Therefore, the dialysate can flow from the dialysate inlet port, into the blood chamber, and to the dialysate outlet port.METHODS INVOLVING TIME PERIODS

[0033] The present disclosure provides methods of dialyzing blood of a patient. In some cases, these methods include utilizing two different time periods, e.g. a push step and a pull step. The push step is performed during the push time period and the pull step is performed during the pull time period.General method

[0034] In some cases, the method includes (a) providing a dialysis device and (b) performing one or more cycles, which are also referred to as dialysis cycles. Each cycle includes exactly one pull step and exactly one push step.

[0035] Each pull step includes simultaneously flowing blood through the blood conduit at a blood pull flow rate and flowing dialysate through the dialysate conduit at a dialysate pull flow rate. Additionally, there is a lower pressure at the dialysate side than at the blood side, thereby causing a net flow of liquid through the filtration membrane from the blood side to the dialysate side.

[0036] Each push step includes simultaneously flowing blood through the blood conduit at a blood push flow rate and flowing dialysate through the dialysate conduit at a dialysate push flow rate. Additionally, there is a higher pressure at the dialysate side than at the blood side, thereby causing a net flow of liquid through the filtration membrane from the dialysate side to the blood side.

[0037] For example, the one or more cycles can include a first cycle and a second cycle. The first cycle can begin with a first pull step. Once the first pull step ends, then the method can continue by immediately beginning a first push step. The term “immediately” in the previous sentence means that the end of the first push step occurs at the same time as the beginning of the first push step. After the first push step ends, then the method can continue with a second pull step and then a second push step. In this situation, the first cycle includes the first pull step and the first push step. However, since each cycle includes only one pull step, then the second pull step cannot be part of the first cycle. Instead, the second pull step is part of the second cycle. Therefore, the second cycle includes the second pull step and the second push step. If the method continues with a third pull step, then the third pull step represents the beginning of the third cycle.

[0038] A pull time period is a period of time when a pull step is being performed. A push time period is a period of time when a push step is being performed.

[0039] The pull step includes simultaneously : flowing blood from the patient through the blood conduit at a blood pull flow rate: and flowing dialysate through the dialysate conduit at a dialysate pull flow rate, wherein there is a lower pressure at the dialysate side than at the blood side, thereby causing a net flow of liquid through the filtration membrane from the blood side to the dialysate side.

[0040] In some cases, flowing blood from the patient through the blood conduit includes directly flowing blood from a blood vessel of the patient through the blood conduit. In other words, the blood moves from the blood vessel through the blood conduit continuously without stopping. In other words, the speed of the blood is always a positive number, i.e. speed is never zero. In other cases, flowing blood from the patient through the blood conduit includes collecting blood in a temporary storage container for a storage time period, and afterwards flowing the blood from the temporary storage container through the blood conduit. In this embodiment, the blood has zero speed during the storage time period.

[0041] The phrase “a lower pressure at the dialysate side than at the blood side” is used interchangeably herein with the phrase “a pressure at the dialysate side that is lower than a pressure at the blood side”.

[0042] Any suitable mechanism can be used to create the desired pressure differential. For example, the relative blood pull flow rate and the dialysate pull flow rate can be utilized. Forexample, Bernoulli’s principle is a concept in fluid dynamics stating that increasing the speed of a fluid causes a reduction in its pressure. Therefore, the pressure at the dialysate side can be reduced by increasing the dialysate flow rate. At the same time, the blood flow rate can remain constant, and therefore the pressure at the blood side will remain constant. Overall, this can cause the dialysate side to have a lower pressure than the blood side. As another example, the blood flow rate can be decreased, thereby increasing the blood side pressure.

[0043] In some cases, the blood is flowed from the patient, through the blood conduit, and back into the patient. In other cases, the blood is flowed from the patient, through the conduit, and to an alternative destination, e.g. a blood container. For instance, the blood can be temporarily collected in the blood container and then put back into the patient at a future time. e.g. 5 minutes or more after the blood is collected in the blood container.

[0044] Similarly, the push step includes simultaneously : flowing blood from the patient through the blood conduit at a blood push flow rate; and flowing dialysate through the dialysate conduit at a blood push flow rate, wherein there is a higher pressure at the dialysate side than at the blood side, thereby causing a net flow of liquid through the filtration membrane from the dialysate side to the blood side.

[0045] In some cases, the method includes a flushing step. Each flushing step includes simultaneously: flowing blood from the patient through the blood conduit at a blood flushing flow rate; and flowing dialysate through the dialysate conduit at a dialysate flushing flow rate, wherein the blood flushing flow rate and the dialysate flushing flow rate create a pressure at the dialysate side that is equal to the blood side, thereby causing no net flow of liquid through the filtration membrane from the blood side to the dialysate side.

[0046] As stated above, the method includes one or more cycles. In some cases, the 1 or more cycles is 2 or more cycles, 3 or more cycles, 4 or more cycles, 5 or more cycles, 10 or more cycles, 25 or more cycles, 50 or more cycles, 100 or more cycles, or 500 or more cycles.

[0047] In some cases, the one or more cycles occur over a total time period of 1 minute or more, such as 10 minutes or more, 50 minutes or more. 100 minutes or more, 250 minutes or more, or 500 minutes or more. In some cases, the one or more cycles occur over a total time period ranging from 1 minute to 6,000 minutes, e.g. from 10 minutes to 600 minutes, or from 30 minutes to 300 minutes.

[0048] In some cases, there are 3 or more cycles that include a first cycle, a final cycle, and 1 or more intermediate cycles that each occur after the first cycle but before the final cycle. In some cases, the beginning of each intermediate cycle occurs simultaneously with the end of a different cycle. In some cases, the end of each intermediate cycle occurs simultaneously with the end of adifferent cycle. For instance, the 3 or more cycles can occur during a single, cohesive block of time that has no gaps.Pull step

[0049] The pull step involves to a net flow (i.e. a net pull) of liquid from the blood side of the filtration membrane to the dialysate side of the filtrate membrane. In some cases, net flow is achieved because liquid flows from the blood side to the dialysate side, whereas there is zero flow from the dialysate side to the blood side. In other cases, net flow is achieved because the volume of liquid flowing from the blood side to the dialysate side is greater than the non-zero flow from the dialysate side to the blood side.

[0050] Due to this net flow, the dialysate experiences a net increase in volume and the blood experiences a net decrease in volume. This net flow is caused by a pressure differential wherein there is a lower pressure at the dialysate side than at the blood side.

[0051] For example, the pressure on the dialysate side can be lowered by pumping liquid out of the dialysate chamber faster than liquid enters the dialysate chamber. As another example, the pressure on the dialysate side can be lowered by inhibiting liquid from entering the dialysate chamber, e.g. by closing a valve upstream of the dialysate chamber, stopping a pump upstream of the dialysate chamber, or a combination thereof.

[0052] The terms “upstream’" and "downstream" can be explained by considering the flow of liquid. The term upstream refers to a location that is opposite the direction of flow. Also, the term downstream refers to a location that is in the direction of flow. For example, if liquid flows from location A to location B, then location A is upstream of location B. Additionally, location B is downstream of location A. In relation to the discussion above, pressure in the dialysate chamber can be reduced by closing a valve upstream of the dialysate chamber. In this example, the valve is at location A and the dialysate chamber is location B. By reducing or stopping flow at location A (i.e. the valve), then flow from location A to location B (i.e. the dialysate chamber) is reduced. Therefore, pressure is also reduced.

[0053] The term “closing a valve"’ includes both partially closing a valve and completely- closing a valve. Completely closing a valve reduces liquid flow to zero. Partially closing the valve causes a reduction in flow', but the new flow rate is above zero.

[0054] In relation to the discussion above, pressure can be reduced by stopping a pump upstream of the dialysate chamber. Hence, the pump w ill no longer exert a force that pushes the liquid towards the downstream chamber. Therefore, pressure will be reduced.

[0055] In some cases, the pull time period is about 180 seconds, e.g. 10 seconds to 1000 seconds, or 40 seconds to 500 seconds, 80 seconds to 300 seconds, or 100 seconds to 250 seconds.In some cases, there is a net flow across the filtration membrane of about 300 ml during the pull time period, e.g. from 30 ml to 3000 ml, from 100 ml to 1000 ml, or from 200 ml to 500 ml. Push step

[0056] The push step involves to a net flow (i.e. a net push) of liquid from the dialysate side of a filtration membrane into the blood side of a filtration membrane. As such, the dialysate experiences a net decrease in volume and the blood experiences a net increase in volume. This net flow is caused by a pressure differential wherein there is a higher pressure at the dialysate side than at the blood side.

[0057] Due to this net flow, the dialysate experiences a net decrease in volume and the blood experiences a net increase in volume. This net flow is caused by a pressure differential wherein there is a higher pressure at the dialysate side than at the blood side.

[0058] For example, the pressure on the dialysate side can be increased by inhibiting liquid from exiting the dialysate chamber. In some cases, this inhibiting is completely inhibiting any liquid from exiting the dialysate chamber. In other cases, this inhibiting is partially inhibiting liquid from exiting the dialysate chamber, i.e. reducing the volume of liquid exiting the dialysate chamber to a non-zero volume. For example, this inhibition can include closing a valve downstream of the dialysate chamber. As another example, this inhibiting can include stopping a pump downstream of a dialysate chamber, i.e. wherein the pump had been actively pulling dialysate out of the dialysate chamber.

[0059] In some cases, the push time period is about 180 seconds, e.g. 10 seconds to 1000 seconds, or 40 seconds to 500 seconds, 80 seconds to 300 seconds, or 100 seconds to 250 seconds. In some cases, there is a net flow7across the filtration membrane of about 300 ml during the push time period, e.g. from 30 ml to 3000 ml, from 100 ml to 1000 ml, or from 200 ml to 500 ml. Flushing step

[0060] The method can also include a flushing step performed during a flushing time period. For example, the optional flushing time period can be performed between the pull time period and the push time period. In some cases, the method includes a flushing time period. In some cases, the method does not include a flushing time period and the method simply changes directly between only the pull time period and the push time period.

[0061] During the flushing time period, the pressures on the blood and dialysate side of the filtration membrane are the same. Stated in another manner, the pressure at the blood side is equal to the pressure at the dialysate side.

[0062] In some cases, creating an equal pressure on the dialysate side and the blood side comprises flowing liquid into and out of the dialysate chamber.

[0063] In some cases, the flushing time period is about 15 seconds, e.g. 1 second to 100 seconds, or 5 seconds to 50 seconds.Blood flow and dialysate flow

[0064] The blood is flowed from the patient and through the blood conduit. For example, the blood can be flowed from a blood vessel of the patient (e.g. an artery), through a first needle inserted into the patient, through blood inlet tubing, and into the blood inlet port of the dialysis device. Also, the blood can be flowed from the blood outlet port, through blood outlet tubing, through a second needle inserted into the patient, and into a blood vessel of the patient (e.g. a vein). However, these are only some examples of how the blood can be flowed. The methods can use any suitable technique for moving the blood from the patient to the dialysis device.

[0065] The dialysate is flowed through the device as described above. However, there is also a dialysate source. For example, the dialysate can be flowed from a dialysate source, through dialysate source tubing, and into the dialysate inlet port. For example, the dialysate source can be a container holding a fixed volume of dialysate, e.g. 1 liter to 100 liters. In other cases, the dialysate is a continuous source, e.g. a domestic water supply such as a water tap in patient room in a hospital or a water tap in a bedroom of a residential house.

[0066] Also, dialysate exiting the dialysate outlet port can be directed towards any suitable destination. For example, the dialysate can be flowed from the dialysate outlet port, through dialysate outlet tubing, and into a dialysate waste container. As a different example, the dialysate can be flowed from the dialysate outlet port, through dialysate outlet tubing, and then recirculated directly or indirectly to the dialysate inlet port.

[0067] The method involves flowing blood during a pull time period and flowing dialysate during a pull time period. Therefore, these flows of blood and dialysate occur simultaneously.

[0068] The method involves flowing blood during a push time period and flowing dialysate during a push time period. Therefore, these flows of blood and dialysate occur simultaneously.

[0069] The method can include flowing about 25 liters of liquid through the dialysate chamber, such as 1 L to 500 L, 5 L to 250 L, 10 L to 150 L, or 20 L to 75 L.

[0070] The method can include an overall net flow of liquid from the blood side to the dialysate side of about 1140 ml, such as 100 ml to 10,000 ml, 250 ml to 4,000 ml, or 500 ml to 2,000 ml.Alternative description of a general method

[0071] The discussion above describes the method as including one or more cycles, wherein each cycle includes exactly one pull step and exactly one push step. However, the method can also be framed as flowing blood and flowing dialysate.

[0072] In some embodiments, the method includes flowing blood through the blood inlet port, into the blood chamber, and out of the blood outlet port during a pull time period, during an optional flushing time period if present, and during a push time period. The method also includes flowing dialysate through the dialysate inlet port, into the dialysate chamber, and out of the dialysate port during the pull time period, the optional flushing time period if present, and the push time period.

[0073] These methods can also be referred to as a method of dialyzing blood of a patient with a pull time period and a push time period. These methods can also be referred to as a method of dialyzing blood of a patient with two or more phases. These methods can also be referred to as a method of dialyzing blood in a patient with a pull phase and a push phase.

[0074] The device can be described as having a blood conduit and a dialysate conduit. The blood conduit includes the blood inlet port, the blood chamber, and the blood outlet port. Flowing blood though the blood conduit is flowing blood from the blood inlet port, through the blood chamber, and to the blood outlet port. The dialysate conduit includes the dialysate inlet port, the dialysate chamber, and the dialysate outlet port. Flowing dialysate through the dialysate conduit is flowing dialysate from the dialysate inlet port, through the dialysate chamber, and to the dialysate outlet port.

[0075] The pull time period includes flowing blood and dialysate and the push time period also includes flowing blood and dialysate. However, in some cases, the blood flow rate in the pull time period is different than the blood flow rate in the push time period. Also, in some cases, the dialysate flow rate in the pull time period is different than the dialysate flow rate in the push time period. These differences in flow rate can cause changes in pressure at a membrane that separates the blood chamber from the dialysate chamber. Correspondingly, these changes in pressure can cause changes in the net flow of liquid across the membrane.

[0076] In some cases, the dialysis device is located inside a body cavity of the patient. For example, the body cavity can be an abdominal cavity, e.g. near a kidney. In other cases, the dialysis device is located outside the patient.

[0077] In some cases, method occurs over a total time period ranging from 1 minute to 6,000 minutes, e.g. from 10 minutes to 600 minutes, or from 30 minutes to 300 minutes.

[0078] The methods including at least one pull time period and at least one push time period. However, these time periods can also be repeated. In some cases, the method includes one flushing time period. In some cases, flushing time period can be repeated.

[0079] For example, the pull time period, the optional flushing time period if present, and the push time period can be repeated one or more times. This one or more times can be about 76 times. This one or more times can be 2 or more times, such as 3 or more times, 5 or more times,25 or more times, 50 or more times, 100 or more times, or 250 or more times. This one or more times can be about 76 times, such as 10 times to 500 times, 20 times to 250 times, or 50 times to 125 times.METHODS INVOLVING SENSORS

[0080] Provided are methods of dialyzing blood of a patient. Such methods can involve the use of sensors, e.g. physical, chemical, or electrical (PCE) sensors.General method

[0081] The methods of dialyzing blood while utilizing one or more physical, chemical, or electrical (PCE) sensors can include:

[0082] providing a dialysis system comprising: (i) a blood conduit comprising a blood inlet port, a blood chamber, and a blood outlet port, (ii) a dialysate conduit comprising a dialysate inlet port, a dialysate chamber, and a dialysate outlet port, (iii) a filtration membrane comprising a blood side adjacent to the blood chamber and a dialysate side adjacent to the dialysate chamber, and (iv) one or more PCE sensors;

[0083] flowing blood through the blood conduit;

[0084] flowing dialysate through the dialysate conduit;

[0085] recording PCE sensor data from the one or more PCE sensors;

[0086] determining that the recorded PCE sensor data fulfills a criteria; and

[0087] taking an action based on the determination that the recorded PCE sensor data fulfills the criteria.

[0088] In some cases, the one or more PCE sensors includes a sensor selected from the group consisting of: a pressure sensor, a temperature sensor, a biomolecule sensor, an ion concentration sensor, a flow rate sensor, a pump speed sensor, an accelerometer, a hematocrit sensor, and combinations thereof.

[0089] In some cases, the one or more PCE sensors record a property of the blood, e.g. concentration of a biomolecule, concentration of an ion, a hematocrit level, a pH level, an electrical property, and a temperature. In some cases, the biomolecule is glucose, urea, or creatine. In some cases, the one or more PCE sensors record two or more properties of the blood, e.g. the concentration of two or more biomolecules, e.g. both urea and creatine. In some cases, the property of blood is an ion concentration, e.g. a group 1 or group 2 ion or group 17, e.g. potassium, calcium, sodium, magnesium, or chloride.

[0090] In some cases, taking the action includes modifying operation of the dialysis system, providing a visual alert, providing an auditory alert, or a combination thereof. For example, modifying operation of the dialysis system can include increasing or decreasing blood flow rate,increasing or decreasing dialysate flow rate, increasing or decreasing blood pressure in the blood conduit, increasing or decreasing dialysate pressure in the dialysate conduit, increasing or decreasing a dialysate pump, deploying a treatment to remove biofouling of the filtration membrane, or a combination thereof.

[0091] For example, the alerting can alert the patient or a medical professional (e.g. nurse, doctor). For example, the visual alert can be a visual indication of the alert on a visual display (e g. a computer monitor, a tablet, a cell phone, a smart watch, or a laptop screen). For example, the auditory alert can be created by a laptop speaker or a cell phone speaker.Another description of a general method

[0092] The methods can also be described in an alternative way. In some cases, the methods of dialyzing blood while utilizing PCE sensors can include:

[0093] wherein a dialysis system comprises: (i) a blood conduit comprising a blood inlet port, a blood chamber, and a blood outlet port, (ii) a dialysate conduit comprising a dialysate inlet port, a dialysate chamber, and a dialysate outlet port, (iii) a filtration membrane comprising a blood side adjacent to the blood chamber and a dialysate side adjacent to the dialysate chamber, and (iv) one or more PCE sensors;

[0094] flowing blood through the through the blood inlet port, into the blood chamber, and out through the blood outlet port;

[0095] flowing dialysate through the dialysate inlet port, into the dialysate chamber, and out through the dialysate outlet port;

[0096] monitoring one or more PCE sensors;

[0097] determining if a criteria is fulfilled, wherein the criteria involves the one or more PCE sensors; and

[0098] taking an action when the criteria is fulfilled.General Aspects

[0099] Methods are provided of dialyzing blood that include the use of sensors. Examples of sensors include physical, chemical, or electrical (PCE) sensors. Examples of PCE sensors include sensors that monitor pressure, biologically relevant molecules (i.e. biomolecules, such as glucose, urea, or creatine), pH, common ions (e.g. potassium, calcium, sodium, magnesium, and chloride), hematocrit, electric properties of blood, temperature, and acceleration. In some cases, the sensors monitor pressure in one or more location of the blood conduit, one or more locations of the dialysate conduit, or a combination thereof.

[0100] The PCE sensors can monitor its physical property’ at any suitable frequency. For example, in some cases, the PCE sensor monitors its physical property at a frequency rangingfrom 0.001 Hz to 100 Hz. For example, if pressure is monitored at 100 Hz then the pressure sensor measures pressure 100 times each second. As another example, if glucose is monitored at 0.01 Hz, then the glucose sensor measures the glucose concentration once every 100 seconds.

[0101] As used herein, the term “monitoring” means measuring at 2 or more different times. The monitoring can be performed for any suitable length of time, e.g. 1 minute or more, 5 minutes or more, 15 minutes or more, 1 hour or more, or 5 hours or more.Pressure Sensors

[0102] In some cases, the method of dialyzing blood of the patient utilizes one or more pressure sensors.

[0103] In some cases, the method includes:

[0104] providing a dialysis system comprising: a blood conduit compnsing a blood inlet port, a blood chamber, and a blood outlet port, a dialysate conduit comprising a dialysate inlet port, a dialysate chamber, and a dialysate outlet port, a filtration membrane comprising a blood side adjacent to the blood chamber and a dialysate side adjacent to the dialysate chamber,

[0105] flowing blood through the blood inlet port, into the blood chamber, and out through the blood outlet port,

[0106] flowing dialysate through the dialysate inlet port, into the dialysate chamber, and out through the dialysate outlet port,

[0107] monitoring blood conduit pressure at one or more locations within the blood conduit with one or more blood conduit pressure sensors; and

[0108] optionally monitoring dialysate pressure at one or more locations within the blood conduit with one or more dialysate pressure sensors;

[0109] optionally monitoring dialysate pump flow rate associated with a dialysate pump in fluid communication with the dialysate conduit;

[0110] determining if a criteria is fulfilled, wherein the criteria comprises one or more blood pressures, one or more dialysate pressures, the dialysate pump flow7rate, or a combination thereof; and

[0111] taking an action when the criteria is fulfilled.

[0112] As described above, the method includes monitoring blood conduit pressure at one or more locations within the blood conduit with one or more blood pressure sensors. “Blood conduit pressure” is used interchangeably with “blood pressure”. Any suitable sensor that can measure pressure of a liquid or gas can be utilized. The pressure sensor can also be referred to as a pressure gauge. Pressor sensors are manufactured and sold by numerous companies, including McMaster-Carr Corporation of Elmhurst, Illinois, United States. In some cases, there are 2 or more bloodconduit pressure sensors that each monitor pressure at a different location, such as 3 or more, 4 or more, 5 or more, or 10 or more.

[0113] In some cases, the method also includes monitoring dialysate pressure, i.e. dialysate conduit pressure. Identical or similar ty pes of pressure sensors can be used to monitor the blood conduit pressure and the dialysate conduit pressure. In some cases, there are 2 or more dialysate conduit pressure sensors that each monitor pressure at a different location, such as 3 or more, 4 or more, 5 or more, or 10 or more.

[0114] In some cases, the method includes monitoring dialysate pump flow rate associated with a dialysate pump in fluid communication with the dialysate conduit. For example, the flow rate can be recorded in ml / min.

[0115] As described above, the method includes determining if a criteria is fulfilled and then taking an action when the criteria is fulfilled. These two steps can also be simply described as “taking an action when a criteria is fulfilled”. The criteria comprises one or more blood conduit pressures, one or more dialysate pressure, the dialysate pump flow rate, or a combination thereof. In some cases, the criteria comprises two or more of the options recited above, e.g. one or more blood conduit pressure and one or more dialysate pressure.

[0116] In some cases, a first pressure sensor (i.e. a first blood conduit pressure sensor) is located adjacent to the blood inlet port. In some cases, a pressure sensor is located in an indentation in a wall of the blood flow path. In some cases, the indentation is a cylindrical indentation. In some cases, a diaphragm of the pressure sensor is flush with an edge of the indentation, i.e. the diaphragm and the edge are coplanar.

[0117] In some embodiments, each pressure sensor is independently selected from the group consisting of strain-gauge resistive pressure sensors, capacitive pressure sensors, optical pressure sensors, resonance-based pressure sensors, interferometry-based sensors, microelectromechanical system (MEMS)-based sensors.

[0118] In some cases, the criteria includes: (i) a difference between a blood conduit pressure and a dialysate pressure and (ii) a dialysate pump flow rate. For example, over time the filtration membrane can experience fouling, which can increase the flow resistance that liquid experiences when traveling through the filtration membrane. In order to detect this, the dialysate pump flow rate can be compared to the dialysate pressure and the blood pressure. Comparing these three data points can indicate fouling. Correspondingly, the action can include clearing fouling of the filtration membrane, e.g. clearing biofouling. In some cases, clearing the biofouling includes contacting the filtration membrane with urokinase, citrate, heparin, a thrombolytic, an antithrombogenic, or a combination thereof.

[0119] In some cases, the criteria is a difference in blood pressure and dialysate pressure that exceeds a numerical value, wherein the criteria suggests and increased chance of the filtration membrane breaking due to a pressure imbalance between the blood side and the dialysate side. In some cases, taking the action comprises changing a flow rate of the dialysate pump in a manner that reduces the absolute pressure differential between the dialysate side and the blood side.

[0120] In some cases, the criteria involves changes in blood pressure over time,

[0121] wherein the criteria is indicative of the blood pressure waveform generated by the heart muscle of the patient,

[0122] optionally wherein the criteria includes systolic pressure and diastolic pressure,

[0123] optionally wherein the criteria indicates a heart problem, optionally wherein the heart problem is a heart attack (myocardial infarction), cardiac arrhythmias, or pulseless ventricular tachycardia, optionally wherein taking the action comprises alerting the patient to the heart problem.

[0124] In some cases, the blood pressures and dialysate pressure are used as absolute pressures with regards to the criteria.

[0125] In some cases, the blood pressures and dialysate pressures are used as atmospheric (gauge) pressures with regards to the criteria, wherein an atmospheric pressure sensor measures atmospheric pressure outside the patients body and the measured atmospheric pressure is used to calibrate the measured absolute pressures to atmospheric pressure by comparison between pressures along the dialysate conduit.Chemical and electrical sensors

[0126] In some cases, the one or more PCE sensors include a PCE sensor measuring the blood.

[0127] In some cases, the sensor can measure dialysate that has exited the dialysate chamber, i.e. downstream of the dialysate chamber. For instance, the PCE sensor can detect a biomolecule. The term “biomolecule’’ as used herein refers to a molecule that has an effect on a biochemical process, e.g. an enzyme that catalyzes a biological chemical reaction, a source of energy for a biological mechanism (e.g. glucose), a hormone, a cofactor, a biologically interacting salt (e.g. sodium cation and calcium cation), a protein, a carbohydrate, a lipid, a nucleic acid, and a vitamin.

[0128] In some cases, the PCE sensor measure a physical property of the blood, such as hematocrit, which is the volume percentage of red blood cells in the blood. In some cases, the criteria is a high level of hematocrit that indicates that the blood is undesirably concentrated and has an undesirably high propensity to coagulate, wherein taking the action comprises adjusting dialysate pressure to favor flow of liquid from the dialysate side to the blood side, thereby diluting the blood returning to the patient.

[0129] In some cases, the PCE sensor detects a biomolecule, such as glucose. For example, the biomolecule can be glucose and criteria indicates that the blood returning to the patient is undesirably high or low in glucose, wherein taking the action comprises alerting the patient or adjusting dialysate pressure, flow rate, or a combination thereof. For example, if blood glucose is low, then dialysate pressure or flow rate or both can be adjusted in order to reduce the amount of glucose the travels from the blood into the dialysate, thereby partially protecting the patient from hypoglycemia. In the opposite direction, if blood glucose is high, then dialysate pressure or flow rate or both can be adjusted in order to increase the amount of glucose that travels through the filtration membrane into the dialysate, thereby reducing glucose levels and partially protecting the patient from hyperglycemia.

[0130] Alerting the patient can be performed with any suitable manner. For instance,

[0131] In some cases, the one or more PCE sensors detect urea, creatine or both. In such cases, the level of urea or creatine or both can indicate the extent that the blood was filtered by solutes passing through the filtration membrane. Hence, taking the action can include alerting the patient or adjusting dialysate pressure or flow or both.SYSTEMS

[0132] Provided are systems for performing the methods of dialyzing blood.

[0133] In some cases, the systems include a hemofiltration device including a filtration membrane that is located between a blood chamber and a dialysate chamber. The hemofiltration device can also multiple sets of filtration membranes and chambers. The systems can include various additional components that perform various functions. For example, an umbilical can be used to perform several different functions such as moving dialysate to and from the hemofiltration device, supplying electrical power, transferring digital communications, processing sensor data, transferring sensor data, and disinfecting dialysate (e.g. with UV-C light).

[0134] In some cases, the systems for dialyzing blood of a patient include:

[0135] a blood conduit comprising a blood inlet port, a blood chamber, and a blood outlet port;

[0136] a dialysate conduit comprising a dialysate inlet port, a dialysate chamber, and a dialysate outlet port;

[0137] a filtration membrane comprising a blood side adjacent to the blood chamber and a dialysate side adjacent to the dialysate chamber; and

[0138] a controller configured to perform a method according to any of the methods described herein.

[0139] In some cases, the system also includes a dialysate pump configured to pump dialysate liquid through the dialysate conduit. The system can also include an electrical power sourceselected from the group consisting of a wired electrical power receiver, a wireless electrical charging receiver, a device generating electrical power through motion, and a device generating electrical power through heat transfer. In some cases, the system includes a digital communication device selected from the group consisting of a wireless digital communication device and a wired digital communication device. In some cases, the system includes an umbilical configured to transfer dialysate to and from the dialysate chamber and optionally configured to: transfer electrical power, transfer processed sensor data from the sensor processor, transfer digital instruction to one or more valves, transfer digital instructions to the dialysate pump, or a combination thereof.

[0140] In some cases, the controller of the system is configured to perform a method with two or more time periods, e.g. the pull step and the push step described above.

[0141] In some cases, the controller of the system is configured to perform a method utilizing one or more PCE sensors, e.g. wherein the system further includes the one or more PCE sensors.

[0142] In some cases, the system includes the umbilical. For instance, the umbilical can have two uses, e.g. a dialysate lumen in fluid communication with both the dialysate inlet and outlet port. The umbilical can also include a digital communication wire, such as a metal wire or a fiber optic wire, e.g. for computerized communications. The umbilical can also provide electrical power through an electrical wire. The umbilical can include an electric battery.

[0143] In some cases, there is also a direct access tubing that is in fluid communication with a lumen of the umbilical and the blood conduit, e.g. the blood chamber. For example, this can allow the sampling of patient blood for biochemical analysis, such as large components that do not pass through the filtration membrane.

[0144] There can also be a valve in fluid communication with the direct access tubing, e.g. an umbrella valve, a ball valve, or a spring valve.

[0145] In some cases, the direct access tubing is configured for fluid flow in both directions, e.g. with controllable one-directional check valves facing in opposite directions to control fluid flow.

[0146] The system can include a sensing reagent reservoir configured to deliver reagents to the blood conduit or dialysate conduit to facilitate the sensing of biomolecules through sensors.

[0147] The system can include a sensing reagent inlet port configured to allow the delivery' of sensing reagents through the sensing reagent inlet port and into the sensing reagent reservoir, e.g. to refill the sensing reagent reservoir.

[0148] The system can include a medication inlet port located along the umbilical that allows medications to be delivered into the umbilical, optionally to a medication reservoir, and then to the blood conduit. For example, the medication can be an antibiotic or insulin. In some cases, themedication inlet port is in fluid communication with the direct access tubing, optionally wherein a medication pump pumps the medication solution to the blood conduit.

[0149] In some cases, the umbilical has two or more internal lumens, e.g. for containing each of the tubes or lumens or wires traveling therethrough.

[0150] In some embodiments, the umbilical has a single distal end, preferably with a flat end surface approximately parallel to the body surface of the patient.

[0151] In some cases, the system further includes a guard element, e g. a patch, configured to attach to the patient’s body and partially surround or cover the one or more distal ends of the umbilical.

[0152] In some cases, the system includes a photonic disinfection device, preferably a UV-C light source.

[0153] In some cases, one or more components of the system are enclosed by a housing that is transparent to disinfection light, such as UV-C light.

[0154] In some cases, the system includes one or more valves located along the one or more dialysate lumens, optionally wherein the valves are configured to default to closed, optionally wherein the valves are selected from spring-loaded valves and elastomeric sealing valves.

[0155] In some cases, the system includes an overpressure protection element in fluid communication with the one or more dialysate lumens, optionally wherein the overpressure protection member is a valve, optionally wherein the overpressure protection member defaults to closed and only opens given an appropriate pressure range.

[0156] In some cases, the system includes ahousing enclosing one or more components selected from the group consisting of: the blood chamber, the dialysate chamber, the filtration membrane, the electrical power source, the digital communication device, and the processor.

[0157] In some cases, the housing is transparent to disinfection light, such as UV-C light, thereby allowing disinfection light to transmit through and inhibit biofilm or colonization around the housing.

[0158] In some cases, the housing is connected to an osseous structure of the patient’s body, such as the iliac crest, optionally using orthopedic suture anchors.

[0159] In some cases, the system also includes a blood filter located downstream of the blood chamber, such as an inferior vena cava (IVC) filter, which is optionally configured to filter on the iliac vein and prevent debris from traveling to the lungs.

[0160] In some cases, the system further includes a companion device. For example, the companion device can comprise one or more of:

[0161] (a) a controller configured to: receive PCE sensor data; determine if a criteria is fulfilled based on the received PCE sensor data; and take an action based on the determination that the recorded PCE sensor data fulfills the criteria;

[0162] (b) an electricity transferring element that transfers electrical power to the wired electrical power receiver or a wireless electrical charging receiver; and

[0163] (c) a photonic disinfection device, preferably a UV -C light source, and a fiber optic wire configured to transmit the disinfecting light to a target disinfection location, such as a section of lumen carrying dialysate towards the dialysate chamber, a section of the blood conduit, or an exterior surface of the umbilical.

[0164] In some cases, the photonic disinfection device is a UV-C light source. In some cases, the companion device includes the photonic disinfection device. In some case, the companion device includes the processor, the electricity transferring element, and the photonic disinfection device.

[0165] In some cases, the companion device comprises an attachment element configured to attach the companion device to an external body region of the patient.

[0166] In some cases, the attachment element is a shoulder strap configured to be placed over a shoulder of the patient.CONTROLLERS, PROCESSORS, AND NON-TRANSITORY COMPUTER READABLE STORAGE MEDIUM

[0167] Provided are non-transitory computer readable storage medium with computer executable instructions stored thereon executed by a processor to perform the methods of dialyzing blood of the patient.

[0168] Also provided are controllers configured to perform methods of dialyzing blood of the patient.

[0169] For example, the non-transitory computer readable storage medium can be a solid-state storage device (SSSD) that uses integrated circuits to store data for long periods of time, e.g. even when electrical power is disconnected. For example, the SSSD can be a solid-state drive (SSD) or a hard drive disk (HDD). When connected to other components of a computer, the executable instructions from the storage medium can be transferred or copied to a processor, e.g. a central processing unit (CPU). Thereafter, the processor can execute the instructions and thereby perform the method.

[0170] For example, the processor can electronically send electronic instructions to a blood pump to flow blood through the blood circuit while also sending instructions to a dialysate pump to flow dialysate through the dialysate circuit. The processor can also electronically communicate with one or more PCE sensors. For example, the processor can instruct a PCE sensor to beginrecording PCE sensor data. Afterwards, the processor can receive the PCE sensor data and then determine if it fulfills a criteria, e.g. wherein the criteria is provided by the instructions of the non-transitory computer readable storage medium.

[0171] Afterwards, if the criteria was fulfilled, then the processor can send electronic instructions to a device in order to take the action. For example, the processor can send electronic instructions to a pump to change its flow rate or send instructions to a valve to open or close. The processor can instruct a device to deploy an antifouling agent to remedy fouling on the filtration membrane. The processor can also electronically instruct a visual display device to visually display an alert. The processor can electronically instruct an audio speaker to emit an auditory- alert. For example, the auditory alert can be the sound of a gong, or the sound of wind chimes. In some cases, the visual alert is a blinking icon on a screen, such as a red blinking icon.

[0172] The different components of the system can be part of the same device or different devices. For example, in some cases, both the controller and the visual display providing the alert are both part of the same laptop computer. In other cases, the controller is part of a first computer (e.g. a server located far from the patient) whereas the visual display is part of a second computer (e.g. a tablet computer in the same room as the patient).

[0173] The present disclosure provides controllers for performing the methods of dialyzing the blood of a patient, wherein the controller includes both the non-transitory computer readable storage medium and the processor.EXAMPLES

[0174] The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how- to make and use the present invention, and are not intended to limit the scope of what the inventors regard as their invention nor are they intended to represent that the experi2ments below are all or the only experiments performed. Efforts have been made to ensure accuracy with respect to numbers used (e.g. amounts, temperature, etc.) but some experimental errors and deviations should be accounted for.Example 1: High level system description

[0175] There is an implanted hemofilter disposed within a housing that has at least one connection to the patient’s vasculature, and in the preferred embodiment two connections. In the preferred embodiment, one of the connections is to the patient’s arterial vasculature, and the other connection is to the patient’s venous vasculature. A blood flow chamber is disposed between the arterial inlet, and the vascular outlet, such that the patient's intrinsic blood pressure and cardiac output drives the flow through the implanted hemofilter. The blood flow chamber may be configured as a single serpentine pathway, multiple parallel pathways or any other configurationpreferably defining flow from an arterial inlet to a venous outlet. The implanted hemofilter further comprises a dialysate chamber, that is in contact with the blood flow chamber through at least one, and preferably a plurality of semi-permeable membranes, such that exchange of mass and / or energy between the blood chamber and the dialysate chamber may occur through said membranes. The dialysate chamber has at least one fluidic connection that sen es as both an inlet and an outlet, and in the preferred embodiment both a defined outlet and a defined inlet, such that a directional flow path is established from inlet to outlet. In the preferred embodiment, the dialysate flow path is interleaved with the blood flow path, such that the blood flow path and the dialysate flow path alternate layers in a stack, separated by the semi-permeable membranes. The inlet and outlet of the dialysate chamber are connected to catheters that are tunneled through the patient's abdominal fascia and skin and emerge on the exterior of the patient’s abdomen. While the patient is not undergoing therapy, these catheters are covered with caps and / or other mechanisms which prevent all flow into and out of the catheters. While the patient is undergoing therapy, these catheters are connected to a preferably disposable tubing set. which is then connected to a bedside companion pump, which supplies preferentially sterile, non-pyrogenic dialysate flow to the implanted hemofilter through the dialysate inlet and has the capacity to pump fluid from the implantable hemofilter via the dialysate outlet. (FIGS. 1A and IB)Example 2: Sequential hemodiafiltration

[0176] In the preferred embodiment, therapy is delivered in a primarily convective mode through sequential hemodiafiltration, which can be described in three general phase which form a single cycle, which is repeated many times over the course of therapy. In the first phase, the companion pumps fluid out of the dialysate outlet at a rate greater than it pumps fluid into the dialysate inlet, and preferentially while it is not supplying fluid at all into the dialysate inlet. This produces a transmembrane pressure drop across the semi-permeable membranes which drives fluid from the blood chamber into the dialysate chamber, which drags solutes such as urea, creatinine and middle molecules along with it, clearing it from the blood. In an exemplary embodiment, 300mL of fluid is pulled out over 180 seconds to avoid depleting the patient’s blood volume. In the second phase, the companion pumps fluid into and out of the dialysate chamber at an equal rate, establishing a substantially zero transmembrane pressure drop, which purges the dialysate chamber of fluid that was pulled from the blood side, loaded with solutes that are intended to be cleared. As the fresh dialysate enters the dialysate chamber, a concentration gradient is established across the semi-permeable membranes, and some solutes will cross the membrane and be cleared by diffusion. In the exemplary embodiment, 50mL of fluid is cycled through the dialysate chamber over 30 seconds during this phase. In the third phase, the companion pumps fluid into the dialysate chamber through the dialysate inlet at a rate greater than it pumpsfluid out of the dialysate chamber through the dialysate outlet, preferentially while it is not pumping fluid out of the dialysate outlet at all. This produces a transmembrane pressure drop oriented in the opposite direction as in the first phase, which drives fluid from the dialysate chamber into the blood chamber. This fluid replaces the fluid that was lost in the first phase, ensuring that in subsequent cycles the patient’s blood volume is not depleted. It is generally an aim of renal replacement therapy to remove some volume fluid from the patients’ blood to replace lost urinary excretory function (ultrafiltration), so the amount that is pushed into the patient over the course of therapy is less than the amount that is pulled out. This results in a net loss of fluid that achieves the desired ultrafiltration. In the exemplary embodiment, 285mL of fluid is pushed in over 180 seconds during this phase. In the exemplary embodiment, the three described phases form a single cycle taking 375 seconds, which repeats 76 times over the course of an 8-hour treatment, consuming 25L of dialysate and producing a net ultrafiltration of 1140mL. The repeated bidirection flow through the membrane may be useful in reducing the occurrence of fouling or clotting within the membrane. It should be understood that the exemplary embodiment may be modified with different flow rates, phase timings during cycles, or cycles with parameters that are not constant throughout the therapy. (FIG. 2)

[0177] The hemofiltration device can operate with certain parameters. Such parameters can be selected to cause certain types of diffusion across a filtration membrane of the hemofiltration device. In some cases, the one or more filtration membranes of the hemofiltration device have a total membrane surface area of 0.01 m2or more, such as from 0.01 m2to 1 m2, or from 0.05 m2to 0.2 m2In some cases, one or more of the filtration membranes has a membrane permeability ranging from 100 ml / (hrm2-Torr) to 2000 ml / (hrm2-Torr), such as 500 ml / (hrm2-Torr) to 2000 ml / (hr-m2-Torr). As used herein, the units “ml / (hr-m2-Torr)” are also written as ml / hr / m2 / Torr. The term “transmembrane pressure” refers to the difference in pressure between the dialysate side and blood side of a filtration membrane. In some cases, the transmembrane pressure of one or more filtration membranes ranges from 50 Torr to 500 Torr, such as from 50 Torr to 200 Torr.Example 3: Pressure sensors

[0178] There are sensors to monitor the therapy and safety systems to be built in. One embodiment comprises pressure sensors disposed within the hemofilter blood flow path, preferably at the blood inlet and at the blood outlet. These may be strain-gauge resistive pressure sensors, capacitive pressure sensors, optical pressure sensors, resonance-based pressure sensors, interferometry-based sensors or any other sensor known in the art to measure pressure. In some embodiments these sensors may be MEMS-based sensors that are manufactured into the substrate of the semi-permeable membranes themselves. In a preferred embodiment, the pressure sensor is disposed within a cylindrical opening in the housing that faces the blood flow path, such that thediaphragm of the sensor is flush with the cylindrical opening and presents no disruption to the blood flow path. Because the flow geometry within the blood chamber is well established and characterized between the sensors, the measured pressure drop across the inlet and outlet sensor will be proportional to the blood low rate at steady state. This would alert the user if intervention was needed if the blood flow rate drops, i.e. a thrombus within the vascular grafts connecting the implanted hemofilter to the vasculature. The companion pump can also monitor the pressure within the dialysate flow path inlet and outlet during therapy, which allows for a '‘four-comers” transmembrane pressure monitoring. An increase in this transmembrane pressure at a known infusion or withdrawal rate would indicate some type of membrane fouling, and be a signal for intervention. Said intervention may comprise a specialized lock solution placed within the catheters and dialysate chamber between therapy, for example one that contains urokinase, citrate or heparin, or other thrombolytic or antithrombogenic substances to clear any biofouling of the semipermeable membranes. Another safety feature allowed by the pressure sensors is to prevent over-pressurization of the semipermeable membranes, which could result in membrane failure and loss of function of the implant. The pumping algorithm could be structured such that a ramp or step-up to a desired flow' rate is established which allows for response time of the transmembrane pressure to rise or fall and establish equilibrium, prior to moving to the next step-up of the pump rate . Another aspect of the blood-facing pressure sensors is to be able to measure the blood pressure waveform from the patient’s cardiac output to determine at least parameters such as systolic pressure, diastolic pressure and heart rate. Other signals related to the shape of the w aveform, such as the slope of the rising pulse may be used as a tool for detecting and managing heart failure, especially when monitored by machine learning or artificial intelligence algorithms. Because the implanted hemofilter is fully internal, a pressure sensor disposed within it can not easily establish a reference port for atmospheric pressure, and thus can only generally measure absolute pressure of the blood. However, systolic and diastolic pressures are reported as gauge pressures (relative to the ambient atmospheric pressure). In some embodiments, the companion pump comprises an absolute pressure sensor disposed to measure the ambient atmospheric pressure, which can then be used to with the measured absolute blood pressure to establish the systolic and diastolic pressure. In other embodiments, there is an absolute pressure sensor disposed within the external portion of the catheter that provides the ambient atmospheric pressure measurement. The blood pressure is also indicative of adequate blood volume to support circulation; if too much fluid is removed over the course of therapy, the blood pressure would drop and compromise circulatory function.. As fluid is removed from the blood through the repeated cycles of therapy, ideally this fluid in the blood is replaced by fluid entering the blood from extracellular spaces (where the excess fluid primarily resides). Excessive fluid removed fromthe blood too quickly in the absence of extracellular refilling causes circulatory stress and has been linked to long term negative outcomes for dialysis patients. During traditional dialysis, patients wear a non-invasive blood pressure cuff to monitor blood pressure during treatment, which is uncomfortable and can only take periodic measurements. The blood-facing pressure sensors would be able to monitor the blood pressure seamlessly without the patient needing to wear such a cuff. If a large blood pressure drop were detected, the net ultrafiltration rate could be slowed or even reversed (wherein a net fluid gain is enacted each cycle) at least temporarily to restore blood volume required to maintain a proper blood pressure.Example 4: Hematocrit sensors

[0179] One embodiment comprises sensors to measure the hematocrit or water content of the blood. These may be through optical scattering, absorption, reflection refractive index differences, electrical impedance (Coulter principle), ultrasound wave attenuation, ultrasound backscatter or any other sensor t pe known in the art to measure cell or water content in blood. In a preferred embodiment, an optical sensor is disposed within the housing, separated from the blood flow by the transparent material of the housing but able to interact optically with the blood. In some embodiments, the sensor may comprise a single printed-circuit assembly comprising the light source, such as an LED (light emitting diode) or VCSEL (vertical cavity surface-emitting laser) or other photoemitter known in the art that emits a wavelength or w avelengths of light relevant to optical properties of hemoglobin, such as 540nm and 576 nm which are strongly absorbed by hemoglobin. On the same printed-circuit assembly would be disposed a photodetector, such as a Si-based photodiode sensitive to the wavelength or plurality of wavelengths emitted by the photoemitter. Light emitted by the photoemitter w ould reflect off of the opposite side of the blood channel and / or be scattered and be detected by the photodetector through the optically transparent wall of the blood channel. If multiple photoemitters are utilized, they may sequentially be activated at known intervals with time-sliced multiplexing such that a single photodetector may be used to measure the intensity' of the received light from multiple photoemitters. In other embodiments, the underlying physics of determining the hematocrit or water content may comprise other methods associated with the sensor types described above. This allows several important safety features. First, since the preferential therapy mode is primarily convective, fluid is being pulled from the blood, which causes hemoconcentration, which may promote clotting or other deposition-based mechanisms which could foul the semipermeable membranes. Assuming a high enough blood flow through the membrane, it would be beneficial to keep the flow fraction ratio (the ratio of fluid being pulled from the blood to the total blood flow) under a certain level. This would be possible with the hematocrit sensors on the inlet and outlet, which would give the relative increase in hematocrit caused by the known volume of fluid removed, and the flow' ratecould be modulated to ensure it stays under a certain value, or a backfiltration phase initiated early to restore the proper concentration. Because a known volume of fluid is being pushed into or pulled out of the blood precisely in the region betw een the inlet and outlet hematocrit sensors during the therapy cycles, the total blood flow rate through may be calculated by mass dilution principles knowing the incoming and outgoing hematocrit. Monitoring the incoming blood hematocrit may also be used as a marker for adequate blood volume and vascular refdling, as described in the previous section. This may be done by directly monitoring the change in hematocrit at the blood inlet over time, and ensuring it stays within a given range, or other derived signals. For example, a known dilution volume is infused into the blood during the therapy cycle, and a dilution curve can be generated at the outlet hematocrit sensor as it leaves the implant and enters the venous circulation. The diluted blood will then disperse throughout the rest of the patient’s circulation, with some portion of it returning to the blood inlet over time. The shape and timing of the returning dilution curve at the blood inlet may be used to derive parameters such as cardiac output and circulating blood volume. These can be used as biomarkers for various aspects of health, particularly when combined with other signals and processed through machine learning and artificial intelligence algorithms. The hematocrit sensor and the pressure sensor, as well as processing circuitry may be disposed within the implant housing using arigid / flex printed circuit assembly. This printed circuit assembly could be secured into cavities in the hemofilter housing and then potted into place, or otherwise covered and protected from fluid ingress in any manner known in the art. (FIGS. 3 A and 3B)Example 5: Other sensors and uses

[0180] There are other sensors disposed within the implant to detect blood parameters, or disposed within the companion to detect parameters of the fluid pulled from the blood. Biochemical parameters are of particular interest, and could be measured at either location.

[0181] In some embodiments, the device comprises at least one glucose sensor which can help ensure that the level is stable through therapy. Dialysate typically contains glucose which is imparted into the blood during the infusion phase. Monitoring blood glucose concentration could be helpful in determining the proper amount of glucose within the dialysate and is of especial importance to patients suffering from metabolic comorbidities such as diabetes. Glucose could be measured using an amperometric, potentiometric or conductometric glucose-oxidase enzymatic sensor, glucosensitive fluorescence-based, or other method known in the art. A glucose-sensing component may be disposed either within the implant, facing the blood, or on the companion, measuring the concentration within the spent dialysate.

[0182] In some embodiments, the device comprises at least one lactate sensor which may be useful in detecting signs of tissue hypoxia. Of note, dialysate comprises an organic acid whichacts as a buffer and is typically either lactate, citrate, bicarbonate or less commonly acetate. These are typically metabolized through the citric acid cycle or reduced to carbon dioxide within the lungs. Tracking lactate levels in the blood or dialysate could be helpful in determining if there is any metabolic dysregulation introduced by the extra loading from the dialysate. Lactate could be measured using amperometric, potentiometric or conductometric enzyme (lactose oxidase or lactose dehydrogenase) sensors, optical means (fluorescence, colorimetric, surfaced plasmon resonance), or enzyme-l'ree electrodes which directly catalyze lactate oxidation, or any other method known in the art. A lactate-sensing component may be disposed either within the implant, facing the blood, or on the companion, measuring the concentration within the spent dialysate.

[0183] In some embodiments, the device comprises at least one urea sensor which can be used to assess the efficiency of the removal of waste products. Urea is the most commonly used marker for determining clearance and is a surrogate for many other small molecules. Urea could be measured using electrochemical (amperometric, potentiometric) approaches related to urease hydrolyzation, optical means (fluorescence or colorimetric) or any other means known in the art. A urea-sensing component may be disposed either within the implant, facing the blood, or on the companion, measuring the concentration within the spent dialysate.

[0184] In some embodiments, the device comprises at least one creatinine sensor which can be used to assess the efficiency of the removal of waste products. Creatinine is another commonly used marker for clearance. Creatinine may be measured using electrochemical approaches related to enzy matic action of creatinine amidohydrolase, creatinase or sarcosine oxidase, optical means (fluorescence or colorimetric), molecularly imprinted polymer sensors or any other means known in the art. A creatinine-sensing component may be disposed either within the implant, facing the blood, or on the companion, measuring the concentration within the spent dialysate.

[0185] In some embodiments, the device comprises at least one pH sensor which can be used to assess acid-base balance and homeostasis. The buffer content of dialysate should ideally be matched to the patient’s metabolic needs, and improper acid-base balance may lead to alkalosis, acidosis and cardiac or other complications. pH may be measured using electrochemical approaches such as traditional glass electrodes, ion-selective field-effect transistors and solid-state metal sensors, optical means (fluorescence of colorimetric) or any other means known in the art. A pH sensing-component is preferably disposed w ithin the implant facing the blood, but may also be disposed on the companion, measuring the pH within the spent dialysate.

[0186] In some embodiments, the device comprises at least one ion-specific electrode sensor to measure at least one of potassium, calcium, sodium, magnesium, chloride or any other ion. It is important to maintain proper electrolyte balance within the blood, and the electrolyte composition of the dialysate, particularly potassium and calcium is matched to the patient's metabolic needs.Improper electrolyte loading may lead to imbalances and cardiac or other complications. Electrolytes may be measured using electrochemical approaches such as traditional glass electrodes, ion-selective field-effect transistors or solid-state metal sensors, or any other means known in the art. An electrolyte sensing component may be disposed either within the implant, facing the blood, or on the companion, measuring the concentration within the spent dialysate.

[0187] In some embodiments, the device comprises at least one electrical impedance sensor which can be used to assess one or more of the conductivity, resistivity, capacitance or inductance of blood. These electrical characteristics are tied closely with the biochemical and cellular composition of the blood, and may be used to assess homeostasis or other parameters. An electrical impedance sensing-component is preferably disposed within the implant facing the blood, but may also be disposed on the companion, measuring the impedance within the spent dialysate.

[0188] In some embodiments, the device comprises at least one temperature sensor used to monitor the temperature of the patient’s blood or other anatomical site or structure. A rise or fall in blood temperature may correspond to important signals such as onset of infection or metabolic dysregulation. By adjusting the temperature of the dialysis fluid supplied, the device may be adapted to regulate the patient’s body temperature for either therapeutic outcomes or patient comfort. Measuring the patient’s blood temperature would be an important feedback point. Temperature may be measured with contact or non-contact means, including a thermocouple sensor, thermsistor sensor, resistance-based techniques, infrared or other optical means, or any other means known in the art. A temperature-sensing component is preferentially disposed within the implant to measure the temperature in the blood.

[0189] In some embodiments, the device comprises at least one accelerometer or other motion sensor which can be used to track biomarkers associated with physical movement within or around the patient’s body. For example, the device could track the physical forces of the heart’s movement (ballistocardiography), respiratory function, gastrointestinal motility or other signals where a sensor placed deep within the retroperitoneal cavity, or other space within the body would be able to detect a signal.Example 6: Electrical architecture

[0190] The aforementioned sensing components require electrical power to function, and any disposed within the implant will either need a local powder source, i.e. a battery, or some means to receive power externally. In one embodiment, the implant is supplied power via a wired connection to the companion that exits the patient’s anatomy at the same site as the fluidic catheters. In these embodiments, the combined fluidic and electrical connections may be disposed within a single tubular umbilical structure with multiple lumens for fluid and electrical wiring. In some embodiments, the companion connects to the electrical connector of the umbilical using auniversal serial bus type-C (USB-C) or other electrical connector know n in the art that is capable of transmitting power and transmi tting / receiving data simultaneously. The implant may comprise a satellite processor to manage and package signals to and from the implant-side sensors. In such embodiments, the implant electronics depend on the umbilical connection for power, and typically would not be active during while the patient is not on therapy. A portable, preferably wearable battery-powered datalogging device could also be provided which connects into the electrical connector of the umbilical when the patient is disconnected from the companion. This portable device could then power the implant electronics and record physiologic data while the patient is not on therapy. The portable device may further be expanded to connect into the umbilical fluidic connectors for controlled ultrafiltration during non-therapy time, or to circulate lock solution into the dialysate chamber. (FIG. 4).

[0191] In other embodiments, the implant has a built-in battery and onboard data storage to effectuate its own datalogging while the Companion is not connected. In some embodiments, the implant further comprises a separate, sealed subcutaneous compartment that houses the battery and / or components that allows wireless charging through inductive, magnetic, radiofrequency, ultrasonic or any other means of wireless power transduction known in the art. In other embodiments, the implant further comprises means for energy harvesting from the body such as from heat or movement, without the need for external power sources. In these embodiments without a wired attachment through the umbilical, data may be transmitted to the outside world via low-energy Bluetooth (BLE) or Radiofrequency Medical Implant Communication System (RF MICS) protocols. In some embodiments, the Companion may directly receive wireless communication from the implant. In other embodiments, a separate transceiver may be placed approximate to the implant, exterior to the patient's body to receive wireless communication from the implant. This transceiver could further comprise wireless power transmission means to recharge the implant’s battery.Example 7 : Umbilical attachments

[0192] There are some additional aspects of the umbilical attachment that connects the implanted hemofilter to the exterior of the patient, and can be used for the transfer of mass and / or energy to and from the implant. In some embodiments, the umbilical comprises a single lumen to deliver fluid to and from the dialysate chamber of the implant. In other embodiments, the umbilical comprises a plurality of fluid lumens, wherein at least one is for delivery of fluid to the dialysate chamber, and at least one is for the withdrawal of fluid from the dialysate chamber. Other than the dialysate chamber, some embodiments of the implant comprise further regions where it would be desirous to deliver fluid to, or withdraw fluid from. For example, the implantable hemofilter could comprise a line in direct fluid communication with the blood chamber, not mediated by the semi-permeable membranes. Access to this line via the umbilical would allow for direct sampling of the patient’s blood, including cellular and protein components too large to pass through the semi-permeable membranes. A direct access line to the patient’s blood would preferentially be disposed near the venous outlet of the hemofdter, where the blood pressure is lower. The access line would further preferentially comprise a mechanism for self-sealing, for example an umbrella valve, a ball valve, a spring valve, or any other mechanism known in the art that must be intentionally activated. This access line may further be used to introduce substances directly into the patient’s blood, although in most cases it would be possible to do so through the dialysate chamber and semipermeable membranes. In some instances, large molecule agents which would be excluded by the membranes could be delivered by this route. In these embodiments that allow bi-directional flow through the access line, the sealing mechanism would have to be such that allows flow, such as two different or similar valves facing in opposite directions in parallel channels

[0193] In some embodiments, the implant comprises sensing components which require a consumable reagent to function. While it could be envisioned to supply a large enough onboard reservoir that would allow function through the desired device lifetime, in some embodiments the umbilical attachment further comprises lumens connected to sensing-component reagent reservoirs that allow the replenishment of these reagents. These reservoirs may further comprise compliant structures which allow volumes to be withdrawn and introduced into them without needing to displacement.

[0194] In some embodiments, channels within the umbilical are in fluid communication with the exterior of the umbilical or the exterior of the implanted hemofdter, for example through a porous diffusive matrix. These channels would allow the user to inject antibiotics or other anti-infectives if an infection were suspected along the umbilical tunnel or the implant pocket.

[0195] The structure of the umbilical itself is preferentially a single tubular structure, either cylindrical or rounded rectangular in cross section. The umbilical would comprise multiple interior lumens for the purposes described above. Upon exiting the patient’s body, in some embodiments the umbilical would terminate in a substantially flat structure parallel to the plane of the patient’s body, with discrete ports to access the various lumens which tubing may be attached to, or electrical cables for data and power transfer. In other embodiments, the body of the umbilical proceeds and extends out from the patient as a single tubular structure with discrete ports on the termination to access the various internal lumens. In other embodiments, the umbilical exits the body and the lumens each split into discrete tubes and / or wires for their connections. (FIG. 5)

[0196] There are wearable tubing management systems for the externalized portions of the umbilical, particularly for embodiments where the umbilical splits into multiple tubes / wires, orwhere it proceeds as a singular tubular structure. An adhesive patch would be placed on the skin in proximity to the umbilical exit site. The patch would comprise a three dimensional structure, such as a dome with gently sloping slides. The dome would further comprise elongate tubular cutouts in which the tubes exiting the umbilical would rest. This would allow the patient to substantially avoid pressure points or discomfort associated with having tubes left dangling or simply taped onto their body. Additionally, the patch may have additional active components which could convey benefits, particularly for an implanted hemofilter. For example, an electrical connection could be provided within the patch, in order to provide power to the implant electronics and log physiological data while the patient is not connected to the bedside companion, as described above. The patch could further comprise a UV-C LED light source, or other means of disinfection, which the dialysate or other access tubing connected to the umbilical could rest in and undergo either continuous or intermittent disinfection while not in use. (FIG. 6)

[0197] The ports at the termination of the umbilical, whether built into separate lines or not, would preferentially comprise self-sealing elements such as spring-loaded valve, elastomeric sealing valve, or other valve known in the art. This valve would automatically close and prevent flow whenever the mating connector is not connected. The umbilical, or tubing set which connects to the umbilical, may further comprise overpressure protection mechanisms which prevent the semipermeable membranes from exposure to inordinate events which cause excessively high pressures to be transduced to the semipermeable membranes. These pressure relief mechanisms are well known in the art and generally comprise a spring or other compliant member which keeps a sealing member over an orifice, until the internal pressure builds up to a point that overcomes the resistance provided by the compliant member, unsealing the orifice and relieving the pressure.Example 8: Active implant components

[0198] There are further active components of the implantable hemofilter which may relay on the power sources described above. In some embodiments, the blood chamber of the hemofilter comprises active flow control valves that modulate flow through the entire implant blood flow path or portions thereof. For example, a flow control valve at the inlet or outlet may be allowed to reduce flow through the implant while therapy is not being conducted to an extent to prevent stagnation and thrombus, while reducing the cardiovascular load of the implant shunt. In some embodiments, the blood flow chamber has a plurality of substantially similar but parallel flow paths, each of which comprises an active flow control valve to regulate flow through that flow path. If a particular membrane section were to be compromised, the flow to the affected flow path could be stopped, while flow to the other intact flow paths could be maintained and therapy could continue. These valves may be activated by electrical signals, such as conventional miniaturesolenoid valves, or actuated by applied electromagnetic fields, or any other method known in the art.

[0199] In some embodiments, the implanted hemofilter comprises mechanisms for deliver}' of therapeutic agents apart from delivery through dialysate convection. For example, the device may comprise a reservoir for the delivery of insulin, stored in a reservoir that is controlled by signals from an onboard glucose-sensing component. The reservoir may be refilled by an additional channel within the umbilical. The insulin or other agent could be delivered via a piston-driven pump, an osmotic pressure pump, or any other means know n in the art.

[0200] In some embodiments, the implant comprises photonic disinfectant means, such as UV-C or blue-spectrum light. In some embodiments, the light is produced by onboard light sources such as LEDs within the implant housing. In some embodiments, the light is produced from an external source, such as the companion, and is optically coupled via fiber optic line within the umbilical to the implant. The implant’s housing is preferentially optically transparent and has optical diffusive properties, allowing the light to spread substantially to all exterior surfaces of the implant. This functionality7would mitigate biofilm or colonization of the implant pocket. The light may also be directed through, or inward towards the lumens of the umbilical, or outwards against the exterior surface of the umbilical, to provide disinfection of those areas. In some embodiments, the light may be directed toward the blood flow for therapeutic means.

[0201] In some embodiments, the implant comprises active conducting means disposed on the exterior surface or within the interior such as on the semipermeable membranes. In some embodiments, the conducting means is a metallic covering. In some embodiments, the conductive means are discrete wires. In some embodiments, the conductive means are traces embedded into the semipermeable membranes themselves during their manufacture. Cunent. either direct, alternating or complex frequency-based waveform can be passed through these conducting means which could break down a biofilm’s polymeric matrix, or cause fouling substances to be expelled from the semipermeable membranes.

[0202] In some embodiments, the implanted hemofilter is affixed to an osseous structure within the patient’s anatomy such as the iliac crest. Features on the exterior of the implant would be disposed to interface with and capture fixturing components, such as orthopedic suture anchors.

[0203] In some embodiments, the device further comprises an IVC filter, or another ty pe of filter on the iliac vein downstream to prevent debris from traveling to the lungs.

[0204] Notwithstanding the appended claims, the disclosure set forth herein is also defined by the following clauses:Clause 1. A method of dialyzing blood of a patient,wherein a dialysis device comprises:a blood inlet port, a blood chamber, and a blood outlet port,a dialysate inlet port, a dialysate chamber, and a dialysate outlet port, a filtration membrane comprising a blood side adjacent to the blood chamber and a dialysate side adjacent to the dialysate chamber,the method comprising:flowing blood through the blood inlet port, into the blood chamber, and out of the blood outlet port during a pull time period, during an optional flushing time period if present, and during a push time period.flowing dialysate through the dialysate inlet port, into the dialysate chamber, and out of the dialysate port during at least one of the pull time period, the optional flushing time period if present, and the push time period,wherein:during the pull time period there is a lower pressure at the dialysate side than at the blood side, thereby causing a net flow of liquid through the filtration membrane from the blood side to the dialysate side,during the flushing time period, if present, there is an equal pressure at the dialysate side and at the blood side,during the push time period there is a higher pressure at the dialysate side than at the blood side, thereby causing a net flow of liquid through the filtration membrane from the dialysate side to the blood side.Clause 2. The method of any of the preceding clauses, wherein the dialysis device is located inside a body cavity of the patient.Clause 3. The method of any of the preceding clauses, further comprising creating the lower pressure on the dialysate side by pumping fluid out of the dialysate chamber faster than liquid enters the dialysate chamber.Clause 4. The method of any of the preceding clauses, further comprising creating the lower pressure on the dialysate side by inhibiting liquid from entering the dialysate chamber, preferably by closing a valve upstream of the dialysate chamber or stopping a pump upstream of the dialysate chamber.Clause 5. The method of any of the preceding clauses, wherein the pull time period is about 180 seconds.Clause 6. The method of any of the preceding clauses, wherein a net flow of about 300 ml occurs during the pull time period.Clause 7. The method of any of the preceding clauses, wherein the method comprises creating an equal pressure the dialysate side and the blood side of the membrane for the flushing time period.Clause 8. The method of any of the preceding clauses, wherein the creating an equal pressure the dialysate side and the blood side comprises flowing liquid into and out of the dialysate chamber.Clause 9. The method of any of the preceding clauses, wherein the flushing time period is about 15 seconds.Clause 10. The method of any of the preceding clauses, further comprising creating a higher pressure on the dialysate side by inhibiting liquid from exiting the dialysate chamber, preferably by closing a valve downstream of the dialysate chamber of stopping a pump downstream of the dialysate chamber.Clause 11. The method of any of the preceding clauses, wherein the push time period is about 180 seconds.Clause 12. The method of any of the preceding clauses, wherein a net flow of about 275 ml occurs during the push time period.Clause 13. The method of any of the preceding clauses, further comprising repeating the pull time period, repeating the optional flushing time period if present, and repeating the push time period one or more times.Clause 14. The method of any of the preceding clauses, wherein the one or more times is about 76 times.Clause 15. The method of any of the preceding clauses, wherein the method includes flowing about 25 liters of liquid through the dialysate chamber.Clause 16. The method of any of the preceding clauses, wherein the method includes an overall net flow of about 1140 ml of liquid from the blood side to the dialysate side.Clause 17. A method of dialyzing blood of a patient while utilizing pressure sensors, wherein a dialysis system comprises:a blood conduit comprising a blood inlet port, a blood chamber, and a blood outlet port,a dialysate conduit comprising a dialysate inlet port, a dialysate chamber, and a dialysate outlet port,a filtration membrane comprising a blood side adjacent to the blood chamber and a dialysate side adjacent to the dialysate chamber,the method comprising:flowing blood through the blood inlet port, into the blood chamber, and out through the blood outlet port,flowing dialysate through the dialysate inlet port, into the dialysate chamber, and out through the dialysate outlet port,monitoring blood pressure at one or more locations within the blood conduit with one or more blood pressure sensors,optionally monitoring dialysate pressure at one or more locations within the blood conduit with one or more dialysate pressure sensors,optionally monitoring dialysate pump flow rate associated with a dialysate pump in fluid communication with the dialy sate conduit,determining if a criteria is fulfilled, wherein the criteria involves one or more blood pressures, one or more dialysate pressures, the dialysate pump flow rate, or a combination thereof,taking an action when the criteria is fulfilled.Clause 18. The method of clause 17, wherein a first pressure sensor is located adjacent to the blood inlet port.Clause 19. The method of any one of clauses 17-18, wherein the first pressure sensor is located in an indentation in a wall of the blood flow path.Clause 20. The method of any one of clauses 17-19, w herein the indentation is a cylindrical indentation.Clause 21. The method of any one of clauses 17-20, wherein a diaphragm of the first pressure sensor is flush with an edge of the indentation.Clause 22. The method of any one of clauses 17-21, wherein each pressure sensor is independently selected from the group consisting of strain-gauge resistive pressure sensors,capacitive pressure sensors, optical pressure sensors, resonance-based pressure sensors, interferometry-based sensors, MEMS-based sensors.Clause 23. The method of any one of clauses 17-22, wherein the criteria is a difference between blood pressure and dialysate pressure that does not correspond to a dialysate pump flow rate, wherein the criteria suggests fouling or an increase in flow resistance of the filtration membrane.Clause 24. The method of any one of clauses 17-23, wherein taking the action comprises clearing biofouling of the filtration membrane.Clause 25. The method of any one of clauses 17-24, wherein clearing biofouling of the filtration membrane comprises contacting the filtration membrane with urokinase, citrate or heparin, or other thrombolytic or antithrombogenic.Clause 26. The method of any one of clauses 17-25, wherein the criteria is a difference in blood pressure and dialysate pressure that exceeds a numerical value, wherein the criteria suggests and increased chance of the filtration membrane breaking due to a pressure imbalance between the blood side and the dialysate side.Clause 27. The method of any one of clauses 17-26, wherein taking the action comprises changing a flow rate of the dialysate pump in a manner that reduces the absolute pressure differential between the dialysate side and the blood side.Clause 28. The method of any one of clauses 17-27, wherein the criteria involves changes in blood pressure over time,wherein the criteria is indicative of the blood pressure waveform generated by the heart muscle of the patient,optionally wherein the criteria includes systolic pressure and diastolic pressure, optionally wherein the criteria indicates a heart problem, optionally wherein the heart problem is a heart attack (myocardial infarction), cardiac arrhythmias, or pulseless ventricular tachycardia, optionally wherein taking the action comprises alerting the patient to the heart problem.Clause 29. The method of any one of clauses 17-28, wherein the blood pressures and dialysate pressure are used as absolute pressures with regards to the criteria.Clause 30. The method of any one of clauses 17-29, wherein the blood pressures and dialysate pressures are used as atmospheric (gauge) pressures with regards to the criteria, wherein an atmospheric pressure sensor measures atmospheric pressure outside the patients body and the measured atmospheric pressure is used to calibrate the measured absolute pressures to atmospheric pressure by comparison between pressures along the dialysate conduit.Clause 31. The method of any one of clauses 17-30, wherein the criteria involves blood pressure,wherein the criteria indicates too much liquid diffused through the filtration membrane and the blood pressure of blood returning to the patients body is undesirably low,wherein taking the action comprises increasing the dialysate pressure, thereby reducing the net flow of liquid from the blood side to the dialysate side or causing a net flow of liquid from the dialysate side to the blood side.Clause 32. A method of dialyzing blood of a patient while utilizing physical, chemical, or electrical (PCE) sensors,wherein a dialysis system comprises:a blood conduit comprising a blood inlet port, a blood chamber, and a blood outlet port,a dialysate conduit comprising a dialysate inlet port, a dialysate chamber, and a dialysate outlet port,a filtration membrane comprising a blood side adjacent to the blood chamber and a dialysate side adjacent to the dialysate chamber,the method comprising:flowing blood through the blood inlet port, into the blood chamber, and out through the blood outlet port,flowing dialysate through the dialysate inlet port, into the dialysate chamber, and out through the dialysate outlet port,monitoring PCE sensors,determining if a criteria is fulfilled, wherein the criteria involves PCE sensors, taking an action when the criteria is fulfilled.Clause 33. The method of clause 32, wherein the one or more PCE sensors comprise a PCE sensor measuring the blood.Clause 34. The method of any one of clauses 32-33, wherein the one or more PCE sensors comprise a PCE sensor measuring dialysate that has exited the dialysate chamber.Clause 35. The method of any one of clauses 32-34, wherein the PCE sensor detects a biomolecule.Clause 36. The method of any one of clauses 32-35, wherein PCE sensor measures hematocrit, wherein the criteria is a high level of hematocrit that indicates that the blood is undesirably concentrated and has an undesirably high propensity to coagulate, wherein taking the action comprises adjusting dialysate pressure to favor flow of liquid from the dialysate side to the blood side, thereby diluting the blood returning to the patient.Clause 37. The method of any one of clauses 32-36, wherein the biomolecule is glucose, wherein the criteria indicates that the blood returning to the patient is undesirably high or low in glucose, wherein taking the action comprises alerting the patient or adjusting dialysate pressure or flow rate.Clause 38. The method of any one of clauses 32-37, wherein the biomolecule is urea or creatine, wherein the level of urea or creatine indicates the extent that the blood was filtered by solutes passing through the filtration membrane, wherein taking the action comprises alerting the patient or adjusting dialysate pressure or flow rate.Clause 39. The method of any one of clauses 32-38, wherein PCE sensor detects pH or the concentration of an ion selected from the group consisting of potassium, calcium, sodium, magnesium, and chloride, wherein taking the action comprises alerting the patient or adjusting dialysate pressure or flow rate.Clause 40. The method of any one of clauses 32-40, wherein the PCE sensor detects an electrical property of the blood, preferably wherein the electrical property is selected from the group consisting of conductivity, resistivity, impedance, capacitance, and inductance, wherein taking the action comprises alerting the patient or adjusting dialysate pressure or flow rate. Clause 41. The method of any one of clauses 32-40, wherein the PCE sensor is a temperature sensor, wherein taking the action comprises alerting the patient or adjusting dialysate pressure or flow rate.Clause 42. The method of any one of clauses 32-41, wherein the PCE sensor is an accelerometer, wherein acceleration indicates motion of the patient’s body, wherein taking the action comprises alerting the patient or adjusting dialysate pressure or flow rate.Clause 43. A dialysis system comprising:a blood conduit comprising a blood inlet port, a blood chamber, and a blood outlet port, a dialysate conduit comprising a dialysate inlet port, a dialysate chamber, and a dialysate outlet port,a filtration membrane comprising a blood side adjacent to the blood chamber and a dialysate side adjacent to the dialysate chamber,an electrical power source selected from the group consisting of a wired electrical power receiver, a wireless electrical charging receiver, a device generating electrical pow er through motion, and a device generating electrical pow er through heat transfer,a digital communication device selected from the group consisting of a wireless digital communication device and a wired digital communication device,optionally a processor configured to receive sensor data from one or more sensors, optionally process the sensor data, transmit the optionally processed sensor data to the digital communication device, optionally transmit digital instructions to one or more valves, and optionally transmit digital instructions to a dialysate pump,optionally a dialysate pump configured to pump dialysate liquid to or from the dialysate chamber,an umbilical configured to transfer dialysate to and from the dialysate chamber and optionally configured to: transfer electrical power, transfer processed sensor data from the sensor processor, transfer digital instruction to one or more valves, transfer digital instructions to the dialysate pump, or a combination thereof.Clause 44. The system of any one of the preceding clauses, wherein the umbilical comprises a dual-use dialysate lumen in fluid communication with both the dialysate inlet port and the dialysate outlet port.Clause 45. The system of any one of the preceding clauses, wherein the umbilical comprises a dialysate inlet lumen in fluid communication with the dialysate inlet port and a dialysate outlet lumen in fluid communication with the dialysate outlet port.Clause 46. The system of any one of the preceding clauses, wherein the umbilical comprises a digital communication wire, such as a metal wire or a fiber optic wire.Clause 47. The system of any one of the preceding clauses, wherein the umbilical comprises an umbilical electrical wire connected to the wired electrical power receiver.Clause 48. The system of any one of the preceding clauses, further comprising an electrical battery.Clause 49. The system of any one of the preceding clauses, further comprising a direct access tubing that is in fluid communication with a lumen of the umbilical and the blood conduit (e.g. the blood chamber) (e.g. for sampling patient blood for biochemical analysis, such as large components that do not pass through the fdtration membrane)Clause 50. The system of any one of the preceding clauses, wherein the direct access tubing connects near the venous outlet of the hemofilter.Clause 51. The system of any one of the preceding clauses, further comprising valve located in fluid communication with the direct access tubing, preferably wherein the valve is an umbrella valve, a ball valve, or a spring valve.Clause 52. The system of any one of the preceding clauses, wherein the direct access tubing is configured for fluid flow in both directions, e.g. with controllable one-directional check valves facing in opposite directions to control fluid flow.Clause 53. The system of any one of the preceding clauses, further comprising a sensing reagent reservoir configured to deliver reagents to the blood conduit or dialysate conduit to facilitate the sensing of biomolecules through sensors.Clause 54. The system of any one of the preceding clauses, further comprising a sensing reagent inlet port configured to allow the delivery of sensing reagents through the sensing reagent inlet port and into the sensing reagent reservoir (e.g. to refill the sensing reagent reservoir)Clause 55. The system of any one of the preceding clauses, further comprising a medication inlet port located along the umbilical that allows medications (e.g. antibiotics, or insulin) to be delivered into the umbilical, optionally to a medication reservoir, and then to the blood conduit, preferably wherein the medication inlet port is in fluid communication with the direct access tubing, optionally wherein a medication pump pumps the medication solution to the blood conduit.Clause 56. The system of any one of the preceding clauses, wherein the umbilical has an external housing that has a cross section selected from the group consisting of circular, rectangular, or rectangular with rounded edges.Clause 57. The system of any one of the preceding clauses, wherein the umbilical comprises two or more internal lumens (e.g. for containing each of the tubes or lumens or wires traveling therethrough).Clause 58. The system of any one of the preceding clauses, wherein the umbilical has a single distal end, preferably with a flat end surface approximately parallel to the body surface of the patient.Clause 59. The system of any one of the preceding clauses, wherein the umbilical has two or more ends that each correspond to one of the two or more internal lumens traversing the length of the umbilical.Clause 60. The system of any one of the preceding clauses, further comprising a guard element (e.g. a patch) configured to attach to the patient’s body and partially surround or cover the one or more distal ends of the umbilical.Clause 61. The system of any one of the preceding clauses, wherein the guard element is attached to the surface of the patient’s body with an adhesive.Clause 62. The system of any one of the preceding clauses, wherein the guard element has a hemispherical shape or a dome shape.Clause 63. The system of any one of the preceding clauses, wherein the guard element has one or more holes corresponding to the one or more distal ends of the umbilical.Clause 64. The system of any one of the preceding clauses, wherein the guard element has one or more holes corresponding to the one or more distal ends of the umbilical, wherein the guard element has one or more tubular members that terminate at each of the one or more holes, wherein the one or more tubular members contain and protect each of the ends.Clause 65. The system of any one of the preceding clauses, wherein the guard element comprises an electrical socket for receiving electrical energy.Clause 66. The system of any one of the preceding clauses, further comprising a photonic disinfection device, preferably aUV-C light source.Clause 67. The system of any one of the preceding clauses, wherein the guard element comprises a light source capable of emitting UV-C light, thereby optionally helping to disinfect dialysate passing toward the dialysate chamber, thereby optionally helping to disinfect theregion where components enter the patient’s body, wherein the system is configured to continuously or intermittently turn on the light source emitting UV-C light.Clause 68. The system of any one of the preceding clauses, wherein one or more components of the system are enclosed by a housing that is transparent to disinfection light, such as UV-C light.Clause 69. The system of any one of the preceding clauses, further comprising one or more valves located along the one or more dialysate lumens, optionally wherein the valves are configured to default to closed, optionally wherein the valves are selected from spring-loaded valves and elastomeric sealing valves.Clause 70. The system of any one of the preceding clauses, further comprising an overpressure protection element in fluid communication with the one or more dialysate lumens, optionally wherein the overpressure protection member is a valve, optionally wherein the overpressure protection member defaults to closed and only opens given an appropriate pressure range.Clause 71. The system of any one of the preceding clauses, further comprising one or more blood chamber valves configured to modify the flow rate of blood into and out of the blood chamber.Clause 72. The system of any one of the preceding clauses, further comprising one or more additional filtration membranes that are each adjacent to additional blood chambers and additional blood dialysate chambers,optionally wherein the device is configured to detect if a filtration membrane has ruptured and close one or more blood valves accordingly to isolate the section containing the ruptured filtration membrane and route blood, dialysate, or a combination thereof to other sections that contain filtration membranes that have not ruptured,optionally wherein detecting if a filtration membrane has ruptured comprises detecting that the pressure differential between the blood side and the dialysate side has decreased, optionally to zero pressure differential.Clause 73. The system of any one of the preceding clauses, wherein the blood chamber and the additional blood chambers are located in parallel, wherein the dialysate chamber and additional dialysate chambers are located in parallel.Clause 74. The system of any one of the preceding clauses, wherein the blood chamber and the additional blood chambers are located in series, wherein the dialysate chamber and additional dialysate chambers are located in series.Clause 75. The system of any one of the preceding clauses, further comprising a housing enclosing one or more components selected from the group consisting of the blood chamber, the dialysate chamber, the filtration membrane, the electrical power source, the digital communication device, and the processor.Clause 76. The system of any one of the preceding clauses, wherein the housing is transparent to disinfection light, such as UV-C light, thereby allowing disinfection light to transmit through and inhibit biofilm or colonization around the housing.Clause 77. The system of any one of the preceding clauses, wherein the housing is connected to an osseous structure of the patient’s body, such as the iliac crest, optionally using orthopedic suture anchors.Clause 78. The system of any one of the preceding clauses, further compnsing an anti-fouling electrically conductive element located adjacent to, within, or passing through the filtration membrane.Clause 79. The system of any one of the preceding clauses, further comprising a blood filter located downstream of the blood chamber, such as an IVC filter, which is optionally configured to filter on the iliac vein and prevent debris from traveling to the lungs.Clause 80. The system of any one of the preceding clauses, one or more flow sensors selected from the group consisting of: upstream dialysate flow sensor located upstream of the dialysate chamber, downstream dialysate flow sensor located downstream of the dialysate chamber, upstream blood flow7sensor located upstream of the blood chamber, and dow nstream blood flow sensor located downstream of the blood chamber.Clause 81. The system of any one of the preceding clauses, further comprising a companion device configured to be located outside the body of the patient and comprising one or more of:a processor configured to:receive optionally processed sensor data;optionally process sensor data;determining if a criteria is fulfilled based on the processed sensor data;take an action if the criteria is fulfilled;an electricity transferring element that transfers electrical power to the wired electrical power receiver or a wireless electrical charging receiver;a photonic disinfection device, preferably a UV-C light source, and a fiber optic wire configured to transmit the disinfecting light to a target disinfection location, such as a section of lumen carrying dialysate towards the dialysate chamber, a section of the blood conduit, or an exterior surface of the umbilical.Clause 82. The system of any one of the preceding clauses, wherein the companion device comprises an attachment element configured to attach the companion device to an external body region of the patient.Clause 83. The system of any one of the preceding clauses, wherein the attachment element is a shoulder strap configured to be placed over a shoulder of the patient.

[0205] Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it is readily apparent to those of ordinary skill in the art in light of the teachings of this invention that certain changes and modifications may be made thereto without departing from the spirit or scope of the appended claims.

[0206] Accordingly , the preceding merely illustrates the principles of the invention. It will be appreciated that those skilled in the art will be able to devise various arrangements which, although not explicitly descnbed or shown herein, embody the principles of the invention and are included within its spirit and scope. Furthermore, all examples and conditional language recited herein are principally intended to aid the reader in understanding the principles of the invention and the concepts contributed by the inventors to furthering the art, and are to be construed as being without limitation to such specifically recited examples and conditions. Moreover, all statements herein reciting principles, aspects, and embodiments of the invention as well as specific examples thereof, are intended to encompass both structural and functional equivalents thereof. Additionally, it is intended that such equivalents include both currently known equivalents and equivalents developed in the future, i.e., any elements developed that perform the same function, regardless of structure. Moreover, nothing disclosed herein is intended to be dedicated to the public regardless of whether such disclosure is explicitly recited in the claims.

[0207] The scope of the present invention, therefore, is not intended to be limited to the exemplary embodiments shown and described herein. Rather, the scope and spirit of present invention is embodied by the appended claims. In the claims, 35 U.S.C. §112(f) is expresslydefined as being invoked for a limitation in the claim only when the exact phrase "means for" or the exact phrase "step for" is recited at the beginning of such limitation in the claim; if such exact phrase is not used in a limitation in the claim, then 35 U.S. C. § 112(f) is not invoked.

Claims

CLAIMSWhat Is Claimed Is:

1. A method of dialyzing blood of a patient, the method comprising:(a) providing a dialysis device comprising:a blood conduit comprising a blood inlet port, a blood chamber, and a blood outlet port,a dialysate conduit comprising a dialysate inlet port, a dialysate chamber, and a dialysate outlet port,a filtration membrane comprising a blood side adjacent to the blood chamber and a dialysate side adjacent to the dialysate chamber; and(b) performing one or more cycles, wherein each of the one or more cycles comprises performing exactly one pull step and performing exactly one push step,wherein each pull step comprises simultaneously:flowing blood from the patient through the blood conduit at a blood pull flow rate; andflowing dialysate through the dialysate conduit at a dialysate pull flow rate, wherein there is a lower pressure at the dialysate side than at the blood side, thereby causing a net flow of liquid through the filtration membrane from the blood side to the dialysate side, andwherein each push step comprises simultaneously:flowing blood from the patient through the blood conduit at a blood push flow rate; andflowing dialysate through the dialysate conduit at a blood push flow rate, wherein there is a higher pressure at the dialysate side than at the blood side, thereby causing a net flow of liquid through the filtration membrane from the dialysate side to the blood side.

2. The method of claim 1, wherein the pull step comprises pumping dialysate out of the dialysate chamber with a downstream dialysate pump located downstream of the dialysate chamber, thereby lowering pressure on the dialysate side and helping to create the lower pressure on the dialysate side than on the blood side.

3. The method of any one of claims 1-2, wherein the pull step comprises inhibiting dialysate from entering the dialysate chamber, thereby lowering pressure on the dialysate side and helping to create the lower pressure on the dialysate side than on the blood side.

4. The method of claim 3, wherein inhibiting the dialysate from entering the dialysate chamber comprises partially closing or completely closing a valve located upstream of the dialysate chamber.

5. The method of any one of claims 3-4, wherein inhibiting the dialysate from entering the dialysate chamber comprises reducing speed of or stopping an upstream dialysate pump located upstream of the dialysate chamber.

6. The method of claims 1-5, wherein the pull step comprises reducing the blood pull flow rate, thereby increasing pressure on the blood side, thereby helping pressure on the dialysate side to be lower than pressure on the blood side.

7. The method of any one of claims 1-6, wherein the pull step is performed for 10 seconds to 1000 seconds.

8. The method of any one of claims 1-7, wherein the pull step has a net flow across the fdtration membrane of 100 ml to 1000 ml.

9. The method of any one of claims 1-8, wherein the push step comprises reducing speed of or stopping a downstream dialysate pump located downstream of the dialysate chamber, thereby increasing pressure on the dialysate side, thereby helping to create the higher pressure on the dialysate side than on the blood side.

10. The method of any one of claims 1-9, wherein the push step comprises allowing dialysate to enter the dialysate chamber more freely, thereby increasing pressure on the dialysate side and helping to create the higher pressure on the dialysate side than on the blood side.

11. The method of claim 10, wherein allowing dialysate to enter the dialysate chamber more freely comprises partially opening or completely opening a valve located upstream of the dialysate chamber.

12. The method of any one of claims 10-11, wherein allowing dialysate to enter the dialysate chamber more freely comprises increasing speed of or starting an upstream dialysate pump located upstream of the dialysate chamber.

13. The method of any one of claims 1-12, wherein the push step comprises increasing the blood push flow rate, thereby decreasing pressure on the blood side, thereby helping the pressure on the dialysate side to be higher than pressure on the blood side.

14. The method of any one of claims 1-13, wherein the push step is performed for 10 seconds to 1000 seconds.

15. The method of any one of claims 1-14, wherein the push step has a net flow across the filtration membrane of 100 ml to 1000 ml.

16. The method of any one of claims 1-15, wherein at least one of the one or more cycles further comprises performing a flushing step, wherein each flushing step comprises simultaneously: flowing blood from the patient through the blood conduit at a blood flushing flow rate: andflowing dialysate through the dialysate conduit at a dialysate flushing flow rate, wherein there is a pressure at the dialysate side that is equal to the blood side, thereby causing no net flow of liquid through the fdtration membrane from the blood side to the dialysate side.

17. The method of claim 16, wherein the flushing step is performed for 1 second to 100 seconds.

18. The method of any one of claims 1-17, wherein the one or more cycles is two or more cycles.

19. The method of claim 18. wherein the two or more cycles comprise a first cycle and second cycle, wherein the second cycle begins immediately after completion of the first cycle.

20. The method of any one of claims 18-19, wherein the two or more cycles is 10 cycles to 500 cycles.

21. The method of any one of claims 1-20, wherein the one or more cycles includes an overall net flow of 100 ml to 10,000 ml from the blood side to the dialysate side.

22. The method of any one of claims 1-21, wherein the one or more cycles includes flowing 1 L to 500 L of dialysate through the dialysate chamber.

23. The method of any one of claims 1-22, wherein the dialysis device is located inside a body cavity of the patient24. The method of claims 1-22, wherein the dialysis device is located outside the patient.

25. The method of any one of claims 1-24, wherein flowing blood from the patient through the blood conduit at a blood pull flow rate comprises flowing blood from a first blood vessel of the patient, through the blood conduit, and back into the first blood vessel or into a second blood vessel of the patient.

26. A method of dialyzing blood of a patient while utilizing one or more physical, chemical, or electrical (PCE) sensors, the method comprising:providing a dialysis system comprising:a blood conduit comprising a blood inlet port, a blood chamber, and a blood outlet port;a dialysate conduit comprising a dialysate inlet port, a dialysate chamber, and a dialysate outlet port;a filtration membrane comprising a blood side adjacent to the blood chamber and a dialysate side adjacent to the dialysate chamber; andthe one or more PCE sensors;flowing blood through the blood conduit;flowing dialysate through the dialysate conduit;recording PCE sensor data from the one or more PCE sensors;determining that the recorded PCE sensor data fulfills a criteria; andtaking an action based on the determination that the recorded PCE sensor data fulfills the criteria.

27. The method of claim 26, wherein taking the action comprises modifying operation of the dialysis system.

28. The method of any one of claims 26-27. wherein taking the action comprises providing a visual alert, an auditory alert, or a combination thereof.

29. The method of any one of claims 26-28, wherein the one or more PCE sensors comprise a physical sensor, wherein the physical sensor is a pressure sensor, and wherein the criteria comprises a pressure criteria.

30. The method of claim 29, wherein the pressure sensor is located adjacent to the blood inlet port.

31. The method of claim 30, wherein the pressure sensor is located in an indentation in a wall of the blood flow path.

32. The method of claim 30. wherein the indentation is a cylindrical indentation.

33. The method of any one of claims 31-32, wherein a diaphragm of the pressure sensor is flush with an edge of the indentation.

34. The method of any one of claims 29-33, wherein the pressure sensor is selected from the group consisting of strain-gauge resistive pressure sensors, capacitive pressure sensors, optical pressure sensors, resonance-based pressure sensors, interferometry -based sensors, microelectromechanical system (MEMS)-based sensors.

35. The method of any one of claims 29-34, wherein the criteria comprises: (i) a difference between a blood conduit pressure and a dialysate conduit pressure, and (ii) a flow rate of a dialysate pump located along the dialysate conduit.

36. The method of claim 35, wherein taking the action comprises modifying operation of the dialysis system, wherein the modifying comprises clearing biofouling of the filtration membrane.

37. The method of claim 36, wherein the clearing of the biofouling comprises contacting the filtration membrane with urokinase, citrate, heparin, a thrombolytic drug, an antithrombogenic drug, or a combination thereof.

38. The method of any one of claims 29-34, wherein the criteria is a difference in blood pressure and dialysate pressure that exceeds a numerical value, wherein the criteria suggests an increased chance of the filtration membrane breaking due to a pressure imbalance between the blood side and the dialysate side.

39. The method of claim 38, w herein taking the action comprises modifying operation of the dialysis system, wherein the modifying comprises changing a flow rate of the dialysate pump in a manner that reduces an absolute pressure differential between the dialysate side and the blood side.

40. The method of any one of claims 29-34. wherein the criteria comprises changes in blood pressure over time, wherein the criteria is indicative of the blood pressure waveform generated by the heart muscle of the patient.

41. The method of claim 40. wherein the criteria further comprises systolic pressure, diastolic pressure, a known heart problem, and a combination thereof.

42. The method of claim 41. wherein the blood pressures and dialysate pressure are used as absolute pressures with regards to the criteria.

43. The method of claim 41 or 42, wherein the known heart problem is a myocardial infarction, cardiac arrhythmias, or a pulseless ventricular tachycardia.

44. The method of any one of claims 40-43, wherein taking the action comprises providing a visual alert, providing an auditory alert, or a combination thereof.

45. The method of any one of claims 29-34, wherein the criteria involves blood pressure, wherein the criteria indicates too much liquid diffused through the filtration membrane and the blood pressure of blood returning to the patients body is undesirably low,wherein taking the action comprises increasing the dialysate pressure, thereby reducing the net flow of liquid from the blood side to the dialysate side or causing a net flow of liquid from the dialysate side to the blood side.

46. The method of any one of claims 26-28. wherein the one or more PCE sensor comprises a hematocrit sensor that measures hematocrit, wherein the criteria is a high level of hematocrit that indicates that the blood is undesirably concentrated and has an undesirably high propensity to coagulate,47. The method of claim 46. wherein taking the action comprises modifying operation of the dialysate system, wherein the modifying comprises adjusting dialysate pressure to favor flow of liquid from the dialysate side to the blood side, thereby diluting the blood returning to the patient.

48. The method of any one of claims 26-28, wherein one or more PCE sensors comprises a biomolecule sensor that detects a biomolecule.

49. The method of claim 48. wherein the biomolecule is glucose, wherein the criteria indicates that the blood returning to the patient is undesirably high or low in glucose,50. The method of claim 49. wherein taking the action comprises providing a visual alert, providing an auditory alert, adjusting dialysate pressure, adjusting dialysate flow rate, or a combination thereof.

51. The method of claim 48. wherein the biomolecule is urea, creatine, or both, wherein the criteria comprises an extent to which the blood was filtered by solutes passing through thefiltration membrane, wherein the recorded concentration of urea, creatine, or both indicates the extent of the blood filtration.

52. The method of claim 48. wherein the one or more PCE sensors comprises an ion concentration sensor that detects pH or the concentration of an ion selected from the group consisting of potassium, calcium, sodium, magnesium, and chloride or both,53. The method of any one of claims 26-28, wherein the one or more PCE sensors comprises an electrical sensor that detects an electrical property’ of the blood.

54. The method of any one of claims 26-28, wherein the one or more PCE sensors comprises a temperature sensor.

55. The method of any one of claims 26-28, wherein the one or more PCE sensors comprises an accelerometer, wherein acceleration indicates motion of the patient,56. The method of claim 55. wherein taking the action comprises providing a visual alert, providing an auditory alert, adjusting a dialysate pressure, adjusting a flow rate, or a combination thereof.

57. A dialysis system comprising:a blood conduit comprising a blood inlet port, a blood chamber, and a blood outlet port; a dialysate conduit comprising a dialysate inlet port, a dialysate chamber, and a dialysate outlet port;a filtration membrane comprising a blood side adjacent to the blood chamber and a dialysate side adjacent to the dialysate chamber; anda controller configured to perform a method according to any one of claims 1-25 and 26-56, wherein if the controller is configured to perform a method according to any one or claims 26-56 then the system further comprises one or more physical, chemical, or electrical (PCE) sensors.

58. The dialysate system of claim 57, further comprising a dialysate pump configured to pump dialysate liquid through the dialysate conduit.

59. The dialysate system of any one of claims 57-58, further comprising an electrical power source selected from the group consisting of a wired electrical power receiver, a wireless electrical charging receiver, a device generating electrical power through motion, and a device generating electrical power through heat transfer.

60. The dialysate system of any one of claims 57-59, further comprising a digital communication device selected from the group consisting of a wireless digital communication device and a wired digital communication device.

61. The dialysate system of any one of claims 57-60, further comprising an umbilical configured to transfer dialysate to and from the dialysate chamber and optionally configured to: transfer electrical power, transfer processed sensor data from the sensor processor, transfer digital instruction to one or more valves, transfer digital instructions to the dialysate pump, or a combination thereof.

62. The dialysate system of any one of claims 57-61, wherein the controller is configured to perform a method according to any one of claims 1-25.

63. The dialysate system of any one of claims 57-61, wherein the is controller configured to perform a method according to any one of claims 26-56 and the system further comprises one or more physical, chemical, or electrical (PCE) sensors.

64. The dialysate system of any one of claims 57-63, wherein the umbilical comprises a dual -use dialysate lumen in fluid communication with both the dialysate inlet port and the dialysate outlet port.

65. The dialysate system of any one of claims 57-64, wherein the umbilical comprises a dialysate inlet lumen in fluid communication with the dialysate inlet port and a dialysate outlet lumen in fluid communication with the dialysate outlet port.

66. The dialysate system of any one of claims 57-65, wherein the umbilical comprises a digital communication wire.

67. The dialysate system of any one of claims 57-66, wherein the umbilical comprises an umbilical electrical wire connected to the wired electrical power receiver.

68. The dialysate system of any one of claims 57-67, further comprising an electrical battery'.

69. The dialysate system of any one of claims 57-68, further comprising a direct access tubing that is in fluid communication with a lumen of the umbilical and the blood conduit.

70. The dialysate system of claim 69, wherein the direct access tubing connects near the venous outlet of the hemofilter.

71. The dialysate system of claim 69 or 70, further comprising valve located in fluid communication with the direct access tubing.

72. The dialysate system of any one of claims 69-71, wherein the direct access tubing is configured for fluid flow in both directions.

73. The dialysate system of any one of claims 57-72, further comprising a sensing reagent reservoir configured to deliver reagents to the blood conduit or dialysate conduit to facilitate the sensing of biomolecules through sensors.

74. The dialysate system of claim 73, further comprising a sensing reagent inlet port configured to allow the delivery of sensing reagents through the sensing reagent inlet port and into the sensing reagent reservoir.

75. The dialysate system of any one of claims 57-74, further comprising a medication inlet port located along the umbilical that allows medications to be delivered into the umbilical, optionally to a medication reservoir, and then to the blood conduit.

76. The dialysate system of any one of claims 57-75, wherein the umbilical has an external housing that has a cross section selected from the group consisting of circular, rectangular, or rectangular with rounded edges.

77. The dialysate system of any one of claims 57-76, wherein the umbilical comprises two or more internal lumens.

78. The dialysate system of any one of claims 57-77, wherein the umbilical has a single distal end.

79. The dialysate system of any one of claims 57-78, wherein the umbilical has two or more ends that each correspond to one of the two or more internal lumens traversing the length of the umbilical.

80. The dialysate system of any one of claims 57-79, further comprising a guard element configured to attach to the patient’s body and partially surround or cover the one or more distal ends of the umbilical.

81. The dialysate system of claim 80, wherein the guard element is attached to the surface of the patient’s body with an adhesive.

82. The dialysate system of any one of claims 80-81, wherein the guard element has a hemispherical shape or a dome shape.

83. The dialysate system of any one of claims 80-82, wherein the guard element has one or more holes corresponding to the one or more distal ends of the umbilical.

84. The dialysate system of any one of claims 80-83, wherein the guard element has one or more holes corresponding to the one or more distal ends of the umbilical, wherein the guard element has one or more tubular members that terminate at each of the one or more holes, wherein the one or more tubular members contain and protect each of the ends.

85. The dialysate system of any one of claims 80-84, wherein the guard element comprises an electrical socket for receiving electrical energy.

86. The dialysate system of any one of claims 57-85, further comprising a photonic disinfection device.

87. The dialysate system of any one of claims 80-86, wherein the guard element comprises a light source capable of emitting UV-C light, thereby optionally helping to disinfect dialysate passing toward the dialysate chamber, thereby optionally helping to disinfect the region where components enter the patient’s body, wherein the system is configured to continuously or intermittently turn on the light source emitting UV-C light.

88. The dialysate system of any one of claims 57-87, wherein one or more components of the system are enclosed by a housing that is transparent to disinfection light.

89. The dialysate system of any one of claims 57-88, further comprising one or more valves located along the one or more dialysate lumens.

90. The dialysate system of any one of claims 57-89, further comprising an overpressure protection element in fluid communication with the one or more dialysate lumens.

91. The dialysate system of any one of claims 57-90, further comprising one or more blood chamber valves configured to modify the flow rate of blood into and out of the blood chamber.

92. The dialysate system of any one of claims 57-91, further comprising one or more additional filtration membranes that are each adjacent to additional blood chambers and additional blood dialysate chambers,wherein the device is configured to detect if a filtration membrane has ruptured and close one or more blood valves accordingly to isolate the section containing the ruptured filtration membrane and route blood, dialysate, or a combination thereof to other sections that contain filtration membranes that have not ruptured,wherein detecting if a filtration membrane has ruptured comprises detecting that a pressure differential between the blood side and the dialysate side has decreased.

93. The dialysate system of any one of claims 57-92, wherein the blood chamber and the additional blood chambers are located in parallel, wherein the dialysate chamber and additional dialysate chambers are located in parallel.

94. The dialysate system of any one of claims 57-92, wherein the blood chamber and the additional blood chambers are located in series, wherein the dialysate chamber and additional dialysate chambers are located in series.

95. The dialysate system of any one of claims 57-94, further comprising a housing enclosing one or more components selected from the group consisting of: the blood chamber, the dialysate chamber, the filtration membrane, the electrical power source, the digital communication device, and the controller.

96. The dialysate system of claim 95, wherein the housing is transparent to disinfection light, thereby allowing disinfection light to transmit through and inhibit biofilm or colonization around the housing.

97. The dialysate system of any one of claims 95-96, wherein the housing is connected to an osseous structure of the patient’s body.

98. The dialysate system of any one of claims 57-97, further comprising an anti-fouling electrically conductive element located adjacent to, within, or passing through the filtration membrane.

99. The dialysate system of any one of claims 57-98, further comprising a blood filter located downstream of the blood chamber.

100. The dialysate system of any one of claims 57-99, further comprising one or more flow rate sensors selected from the group consisting of: upstream dialysate flow7sensor located upstream of the dialysate chamber, downstream dialysate flow sensor located downstream of thedialysate chamber, upstream blood flow sensor located upstream of the blood chamber, and downstream blood flow sensor located downstream of the blood chamber.

101. The dialysate system of any one of claims 57-100, further comprising a companion device configured to be located outside the body of the patient and comprising one or more of:a controller configured to:receive PCE sensor data;determine that a criteria is fulfilled based on the received PCE sensor data; and take an action based on the determination that the recorded PCE sensor data fulfills the criteria;an electricity transferring element that transfers electrical power to the wired electrical power receiver or a wireless electrical charging receiver; anda photonic disinfection device and a fiber optic wire configured to transmit the disinfecting light to a target disinfection location.

102. The dialysate system of claim 101, wherein the companion device comprises an attachment element configured to attach the companion device to an external body region of the patient.

103. The dialysate system of claim 102, wherein the attachment element is a shoulder strap configured to be placed over a shoulder of the patient.

104. A non-transitory computer readable storage medium with computer executable instructions stored thereon executed by a processor to perform a method of dialyzing blood of a patient according to a method of any one of claims 1-25 and 26-56.

105. A controller comprising:a non-transitory computer readable storage medium with computer executable instructions stored thereon executed by a processor to perform a method of dialyzing blood of a patient according to a method of any one of claims 1-25 and 26-56; andthe processor configured to received computer executable instructions and perform the method of dialyzing blood of a patient according to the method of any one of claims 1-25 and

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