More than 2 million end-stage renal disease (ESRD) patients worldwide receive dialysis to sustain life, with this number likely to represent less than 10% of the actual need. In the United States alone, over 460,000 people are on kidney dialysis, over 89,000 of whom die annually with a 5-year survival rate being only 35%. The intermittent character of hemodialysis causes large fluctuations in blood metabolite concentrations. Observations show that long-term survival in dialysis is improved for the patients treated by extended hemodialysis (i.e., more frequent or with longer hours of treatment) when compared to conventional hemodialysis.
Dialysate 12 is a fluid that helps remove the unwanted waste products (e.g., urea) from patient's blood. During the dialysis, dialysate 12 and patient's blood flow through the dialysis system 10, but the two flows do not physically mix. Instead, fresh dialysate 12 from the machine is separated by a membrane from the blood flow. Impurities from patient's blood stream are filtered out through the membrane into dialysate 12. For example, typically 12-24 g of urea needs to be removed daily in a normal adult, but with a reduced protein diet 15 g day is a sufficient goal. Other impurities are also filtered out of the blood stream into the dialysate. Dialysate containing unwanted waste products and excess electrolytes leave the dialyzer for disposal.
Since hemodialysis works on the principle of diffusion into a dialysate having low target concentration, inherently large volumes of fluid are required. The conventional hemodialysis achieves the removal of excessive metabolic waste from the body by running about 120 liters of dialysate per session, which typically requires 3-4 hours of treatment. The dialysis may be required three times a week. Patients are subjected to significant life disruptions, including having to be immobilized for hours and having to arrange transportation to dialysis centers, which impact their quality of life. Accordingly, systems and method for improved dialysis, including improved urea removal, are required.
This summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description. This summary is not intended to identify key features of the claimed subject matter.
Briefly, the inventive technology is directed to urea removal from a dialysate. The inventive technology may be used for dialysis, including kidney dialysis, hemodialysis, hemofiltration, hemodiafiltration, removal of impurities, etc.
In some embodiments, a photo-chemical oxidation (also referred to as “dialysis-fluid regeneration” or “urea treatment”) removes urea from dialysate. A dialysis system fluid regeneration system may include: a nanostructured anode; a source of light configured to illuminate the anode; and a cathode that is oxygen permeable. The nanostructures may be TiO2 nanowires that are hydrothermally grown. The source of light may be provided by an array of LEDs. The oxygen permeable or air permeable cathode may be a platinum-coated (Pt-coated) cloth or paper.
In some embodiments, the system may be sized down enough to become wearable and/or portable. Wearable dialysis devices not only achieve continuous dialysis, but also help reduce clinic related treatment costs and improve quality of life through enhanced mobility.
In one embodiment, a dialysis fluid regeneration system includes: a nanostructured anode; a source of light configured to illuminate the anode; and a cathode that is oxygen permeable.
In one aspect, the dialysis fluid is a dialysate. In another aspect, the system is a kidney dialysis system. In one aspect, the system is a hemofiltration system. In one aspect, the system is a hemodialysis system. In one aspect, the system is a hemodiafiltration system.
In one aspect, the system also includes a source of electrical voltage operationally coupled to the anode and the cathode. In another aspect, the source of electrical voltage is portable.
In one aspect, the dialysis fluid regeneration system is portable. In another aspect, the dialysis fluid regeneration system is wearable. In another aspect, the dialysis fluid regeneration system is stationary.
In one aspect, the anode, the source of light, and the cathode that is oxygen permeable are parts of a first dialysis-fluid regeneration cell, and the system includes a plurality of dialysis-fluid regeneration cells.
In one aspect, the cathode is an air-breathable cathode. In another aspect, the cathode is a conductive cloth-based cathode. In one aspect, the cloth is a platinum-coated (Pt-coated) cloth. In one aspect, the cathode is a conductive paper-based cathode.
In one aspect, the cathode is configured to electrochemically split water. In another aspect, the nanomaterial of the anode is configured to generate photo-electrons or holes when exposed to light.
In one aspect, the source of light comprises an array of light emitting diodes (LEDs). In one aspect, the LEDs are arranged in a two-dimensional (2D) array. In another aspect, the LEDs generate an irradiance of less than 4 mW/cm2 at a surface of the anode. In one aspect, the LEDs emit light at 365 nm wavelength.
In one aspect, the source of light comprises a source of UV. In another aspect, the source of light comprises a source of visible light. In one aspect, an incident photon to photoelectron efficiency is about 51%.
In one aspect, the nanostructured anode comprises TiO2 nanowires. In another aspect, the individual nanowires have a thickness of about 500 nm. In one aspect, the TiO2 nanowires are prepared hydrothermally. In one aspect, the nanowires are disposed on a substrate, and the individual nanowires are individually electrically coupled to a substrate that carries the nanowires.
In one aspect, a dialysate solution has a concentration of urea of 10 mM or less. In another aspect, the system also includes a radical scavenger configured to remove oxidative byproducts, radical byproducts, and chlorine.
In one aspect, the system also includes a membrane configured for passing small molecules through and for blocking large molecules from passing through. In another aspect, the membrane is a reverse osmosis (RO) membrane.
In one embodiment, a dialysis fluid regeneration system includes: a nanostructured substrate configured to generate photo-electrons or holes when exposed to light; a source of light configured to illuminate the substrate; and an oxygen permeable barrier.
In one aspect, the source of light is naturally occurring.
In one embodiment, a method for regenerating a dialysis fluid includes: flowing the dialysis fluid through a system of any of the preceding claims; and illuminating the anode with the source of light as the dialysis fluid passes over the anode, thereby photo-electrochemically eliminating urea in the dialysis fluid.
In one embodiment, a method for regenerating a dialysis fluid includes: flowing the dialysis fluid between an anode and a cathode of a dialysis system, wherein the anode comprises a plurality of nanostructures; illuminating the anode with a source of light; flowing oxygen through the cathode toward the dialysis fluid; and converting urea in the dialysis fluid into CO2, N2 and H2O thereby regenerating the dialysis fluid.
In one aspect, the method also includes recirculating the dialysis fluid within a dialysis system.
In one aspect, the method also includes: coupling a positive voltage to the anode; and coupling a negative voltage to the cathode.
In one aspect, the voltage differential between the positive voltage and the negative voltage is within a range from about 0.6 V to about 0.8 V.
In one aspect, the source of light includes a source of UV light and visible light.
In one aspect, flowing oxygen through the cathode toward the dialysis fluid includes flowing ambient air through the cathode.
In one aspect, the method also includes: flowing the dialysis fluid through a radical scavenger; and removing chlorine from the dialysis fluid in the radical scavenger.
In one embodiment, a method for preparing a dialysis fluid includes: flowing water to be treated between an anode and a cathode of a dialysis fluid regeneration system, wherein the anode comprises a plurality of nanostructures; illuminating the anode with a source of light; flowing oxygen through the cathode toward water to be treated; and oxidizing impurities in the water to be treated, thereby generating the dialysis fluid.
In one aspect, the method also includes recirculating the dialysis fluid within a dialysis system. In one aspect, the method also includes: coupling a positive voltage to the anode; and coupling a negative voltage to the cathode.
The foregoing aspects and many of the attendant advantages of the inventive technology will become more readily appreciated as the same are understood with reference to the following detailed description, when taken in conjunction with the accompanying drawings, wherein:
While several embodiments have been illustrated and described, it will be appreciated that various changes can be made therein without departing from the spirit and scope of the claimed subject matter.
In some embodiments, after urea and/or other small molecule toxins are removed from the blood flow 410, thus partially cleaned blood flow 414 continues to flow toward a protein-bound toxin selective removal unit 600. The blood flow 414 is separated from cellular components by a membrane 612 that is configured for passing large molecular weight proteins and small molecules, commonly referred to as blood plasma. On the permeate side of membrane 612 are selective sorbents for clearance of larger molecular weight and/or protein-bound toxins. This solution 614 flows through a membrane 613 into unit 650 with a mixture of sorbents and selective membranes for the removal of small molecule toxins through flow 610. Nutrients are returned to blood stream 416 as flow 651 as well as desorbed proteins in flow 616 on permeate/plasma side of membrane 612. Some non-exclusive examples of toxins 610 removed by the unit 600 are indoxyl sulfate that was bound to human albumin. Generally, the urea oxidation unit 700 removes small toxic molecules, while the toxin selective removal unit 600 removes large toxic molecules or those bound to proteins such as albumin. However, in different embodiments different arrangements of the toxin removal units are also possible. The blood and/or blood plasma flow 616 that exits from the toxin selective removal unit 600 continues to flow toward further elements/steps of the dialysis process or returns to the patient.
The dialysate 715 may have a concentration of urea of 10 mM or less. In some embodiments, a controller 794 may control operation of pumps 810 and 716 to regulate the flow of blood input 410 and the dialysate 715.
The required source of light may be provided by an ultraviolet (UV) lamp 22. The reaction also requires oxygen for the electrochemical reaction. Providing required oxygen is described with reference to
Anode: CO(NH2)2+6OH−→CO2+N2+5H2O+6e−
Cathode: O2+2H2O+4e−→4OH−
Net: CO(NH2)2+3/2O2→CO2+N2+2H2O (Eq. 1)
In some embodiments, dialysate 715 flows through a spacer 732 from an inlet 734 to an outlet 736. Dialysate 715 carries urea that is to be electrochemically decomposed into CO2 and N2. The spacer 732 may be sandwiched between an anode 722 and a cathode 742, each individually connected to a source of voltage 792 (e.g., a source of DC voltage). In some embodiments the source of voltage 792 provides voltage differential within a range from about 0.6 V to about 0.8 V. In some embodiment of spacer 732, the entire dialysate flow is directed to flow over TiO2 layer.
In some embodiments, the anode 722 is fitted with nanostructures (e.g., TiO2 nanowires). In operation, the anode 722 is illuminated by a source of light that emits light (e.g., UV light) for the electrochemical reaction shown in equation 1. At the anode, photo-excited TiO2 nanostructures provide holes for the oxidation of solution species on the surface, while electrons are collected on underlying conducting oxide (e.g., fluorine doped thin oxide or FTO), and then transported to the cathode electrode to split water into OFF. The photo-excitation may be provided by a source of light 750 or by natural light.
In some embodiments, the cathode 742 may be gas permeable (e.g., air permeable or oxygen permeable). In operation, flow of gas 760 that includes oxygen can pass through the cathode 742 toward the dialysate that includes urea.
In some embodiments, the urea treatment unit 720 may be used for preparing a dialysis fluid. For example, water to be treated may be passed between the anode 722 and the cathode 742 to oxidize impurities in the water to be treated, thereby generating the dialysis fluid. Some embodiments of the urea treatment unit 720 are further described with reference to
As explained with reference to
With at least some embodiments of the inventive technology, significant performance improvements were observed when compared to the performance of the conventional technology. For example, matching a daily urea production to the 6e-oxidation process for 15 gram (0.25 moles) a day target requires electrical current of 1.7 A over a 24 hour period. With a target 1 mA/cm2 photocurrent density on the TiO2 nanostructured anode, the required total device area becomes about 1700 cm2, or 1.82 ft2. With such total device area it becomes feasible to deploy a backpack sized device that oxidizes about 15 g of urea per day. The backpack sized device would require about twelve 8000 mAh batteries for 8 hour operation without recharging and proportionally less batteries for shorter operations.
Furthermore, the high conversion efficiency of urea decomposition at low concentrations shows a high selectivity of TiO2 to oxidize urea vs. generating oxochloro-species that are generally undesirable. Additionally, photocurrent density is more than one order of magnitude higher than that achieved by the prior art without nanostructures or LEDs.
Sample Calculation of Device Performance
For the illustrated embodiment, the operating current of the UV LED was kept at 50 mA. With 6.7% of photons being geometrically incident on the TiO2 sample, we can obtain the incident LED current to photoelectron current efficiency by
where ILED and Iphotocurrent are the current used to drive the LED and the resultant photocurrent, respectively. Since the LED quantum efficiency is 40%, the incident photon to photoelectron efficiency
The total amount of photocurrent passing through the circuit is calculated with Qtotal=∫Iphotocurrentdt. Cumulative photocurrent that was used for urea decomposition can be calculated from urea concentration change, that is Qurea=6×96485×(Cstart−Cend)×V, where 6 is the number of electrons involved in oxidizing a single urea molecule times Faraday's constant, Cstart and Cend are urea concentrations measured before and after the photo-oxidation experiment, and V is 0.3 ml. Selectivity of the photocurrent towards urea decomposition is
Urea removal rate is assumed to be constant during the operation. To calculate the required electrode area and operating current, we may assume 15 g of urea needs to be removed daily.
In contrast with the inventive technology, the prior art technology requires much higher operating current. To calculate the incident photon to photoelectron efficiency for the prior art technology as shown in Table 1 below, the solar AM 0.15 spectrum from NREL is used, which the light source in the literature was emulating. For the 100 mW/cm2 intensity used in the literature, the total photon flux becomes 3.89×1017 s−1cm−2, out of which the photons between 280 nm and 380 nm have the flux of 1.16×1016 s−1cm−2. Thus the incident photo to photonelectron efficiency is 0.28%. Even considering only the wavelengths below 380 nm, the efficiency remains only 9.3%. Assuming 40% quantum efficiency of the light source, same as the UV LED used in this study, this would require an operating current of 2000 A that is not practical in clinical, home or portable use.
Some comparisons of the performance of the present technology and the conventional technology is shown in Table 1 below.
Many embodiments of the technology described above may take the form of computer- or controller-executable instructions, including routines executed by a programmable computer or controller. Those skilled in the relevant art will appreciate that the technology can be practiced on computer/controller systems other than those shown and described above. The technology can be embodied in a special-purpose computer, controller or data processor that is specifically programmed, configured or constructed to perform one or more of the computer-executable instructions described above. Accordingly, the terms “computer” and “controller” as generally used herein refer to any data processor and can include Internet appliances and hand-held devices (including palm-top computers, wearable computers, cellular or mobile phones, multi-processor systems, processor-based or programmable consumer electronics, network computers, mini computers and the like). The term “about” means+/−5% of the stated value.
From the foregoing, it will be appreciated that specific embodiments of the technology have been described herein for purposes of illustration, but that various modifications may be made without deviating from the disclosure. Moreover, while various advantages and features associated with certain embodiments have been described above in the context of those embodiments, other embodiments may also exhibit such advantages and/or features, and not all embodiments need necessarily exhibit such advantages and/or features to fall within the scope of the technology. Accordingly, the disclosure can encompass other embodiments not expressly shown or described herein.
This application is a continuation of U.S. Nonprovisional application Ser. No. 16/536,275 (published on Feb. 20, 2020, now U.S. Pat. No. 10,973,971), filed Aug. 8, 2019, which is a continuation of International Application No. PCT/US2019/44285, filed Jul. 31, 2019, which claims the benefit of U.S. Provisional Application No. 62/719,549, filed Aug. 17, 2018; which applications are incorporated herein by reference in their entireties.
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Parent | PCT/US2019/044285 | Jul 2019 | US |
Child | 16536275 | US |