A system featuring optical and electrical sensors for characterizing the outflow from peritoneal dialysis patients.

Abstract

A system is provided for characterizing effluent samples from patients undergoing peritoneal dialysis. The system comprises a container (30) for enclosing the effluent sample, an optical system, an electrical system, and a processor (13). The optical system comprises a light source (18, 24) and a photodetector (14, 54), the light source emitting a beam of radiation that passes through the container and irradiates the effluent sample, and the photodetector detecting the radiation after it has irradiated the effluent sample to generate an optical signal. The electrical system comprises at least a pair of electrodes (38a, 38b) attached to the container and configured to measure the electrical properties of the effluent sample to generate a characteristic signal. The processor collectively processes the optical signal and the characteristic signal to operate an algorithm for characterizing the effluent sample.

Description

Technical Field

[0001] The present disclosure relates to a system for monitoring patients, particularly patients suffering from end-stage renal disease (hereinafter referred to as "ESRD") and undergoing peritoneal dialysis (hereinafter referred to as "PD"), in both hospital and home environments.

Background Art

[0002] PD is a type of dialysis that uses the peritoneum in a patient's abdomen as a membrane through which fluids and dissolved substances are exchanged with the blood. Typically, PD is used to remove excess body fluids, correct electrolyte problems, and remove toxins from patients suffering from ESRD. PD is typically less efficient at removing waste from the body than hemodialysis (hereinafter referred to as "HD"). However, PD typically has better results than HD during the first few years of introduction. Compared to HD, PD allows for greater patient mobility, has fewer symptom fluctuations due to its continuous nature, and is excellent at removing phosphate compounds. However, PD also typically requires constant monitoring of the patient's nutritional status because it removes a significant amount of albumin. The costs associated with PD are generally lower than those associated with HD in most regions of the world, which is most notable in developed countries. Other advantages of PD include greater flexibility and better tolerance for patients with serious heart disease.

[0003] PD can be performed throughout the day at regular intervals as continuous ambulatory peritoneal dialysis (hereinafter referred to as "CAPD") or at night with the assistance of a machine known as an automated peritoneal dialysis machine (hereinafter referred to as "APD") or "cycler". The solution is typically made from osmotic agents such as sodium chloride, bicarbonate, and glucose.

[0004] During PD, dialysate (also referred to herein as dialysate or dialysate fluid) is introduced through a permanent catheter placed in the patient's lower abdomen during the surgical procedure. One end of the catheter is inserted into the abdomen, and the other end protrudes from the skin. Naturally, the presence of the catheter carries a risk of peritonitis, as it can introduce bacteria into the abdomen. Typically, 2-3 liters of dialysate are introduced into the abdomen at the start of PD treatment. This volume, called the "filling volume," can be as much as 3 liters, and medications can be added to the solution immediately before infusion. This volume remains in the abdomen, and waste diffuses from the underlying blood vessels into the peritoneum. After a variable period, the "residence time" (usually 2-6 hours depending on the procedure), the fluid is removed, and the removed fluid is called "fluid." Removal of fluid can be done automatically while the patient is sleeping (e.g., during APD) or during the day by maintaining 2 liters of fluid in the abdomen at all times, with fluid changes 4-6 times daily (CAPD). APD involves 3 to 10 stool respirations per night, while CAPD involves 4 stool respirations per day, each containing 2 to 3 liters, and each remaining in the abdomen for 4 to 8 hours.

[0005] PD spillage can be monitored to determine whether a patient is experiencing early onset of peritonitis or suffering from any other adverse condition that may affect the color of the spillage. For example, pink spillage may suggest internal abdominal bleeding or menstruation, while the presence of brown or yellowish hues in the spillage may suggest feces, which may indicate bowel perforation. Cloudy spillage typically suggests infection. Often, the test to determine this condition involves holding the waste bag containing the spillage until it contains normally legible documents (e.g., magazines or newspapers) and determining whether the text can be read. Documents that are not clearly legible indicate cloudy spillage, which may indicate the presence of leukocytes (e.g., white blood cells) or other biological material, and thus peritonitis. Therefore, the evaluation of PD spillage is a manual process that is difficult to repeat with meaningful accuracy. The subjectivity of the process, particularly the need for individual visual evaluation, further affects the overall accuracy of this process.

[0006] Several automated systems have been developed to evaluate PD effluent. These include, for example, optical systems based on light absorption, scattering, or fluorescence to characterize PD effluent, while others describe the measurement of chemical properties of the effluent, such as pH. In yet another example, conventional systems measure physiological properties from patients (e.g., blood pressure, glucose) to estimate their condition, such as the presence of peritonitis. Patents issued in this field include, for example, U.S. Patent No. 11,013,843, U.S. Patent No. 10,983,124, U.S. Patent No. 10,925,549, U.S. Patent No. 10,758,659, U.S. Patent No. 10,744,253, U.S. Patent No. 10,537,673, U.S. Patent No. 10,155,081, U.S. Patent No. 10,010,289, U.S. Patent No. 9,518,914, U.S. Patent No. 9,215,985, U.S. Patent No. 9,125,989, U.S. Patent No. 8,945,936, and U.S. Patent No. 8,801,652.

[0007] Considering the above, it would be beneficial to improve the conventional approach to monitoring PD outflow from ESRD patients with the aim of determining conditions such as peritonitis as early as possible. [Overview of the project]

[0008] The technical solutions described herein provide an automated quantitative measurement system for detecting leukocytes and other biological substances in PD effluent. Thus, the technical solutions enable the detection of infections and other conditions in a patient's abdomen, such as peritonitis, hemorrhage, and the presence of feces, at their early stages, and thus enable clinicians to intervene and provide appropriate measures (e.g., prescribing antibiotics). Ultimately, this means that the system can help identify, address, and, in some cases, improve such infections, and thus allow for continued PD treatment and avoidance of hemodialysis (HD) treatment. This can be advantageous, as HD is typically relatively expensive, uncomfortable, and inconvenient for the patient. The system performing these measurements (referred to herein as a PD effluent analysis system, or "PDEAS") may feature optical sensors, impedance sensors, and other sensors that measure PD effluent either directly within the PD instrument or alternatively within a tube that discharges PD effluent from the patient (e.g., into a toilet). The PDEAS is a compact, low-cost system that requires little to no interaction from the user. After measuring time-dependent waveforms using various sensors, PDEAS analyzes this data and transmits the information directly to the APD (for example, for dynamic control by the APD). Additionally or alternatively, PDEAS can transmit the information to the cloud directly (e.g., via an internal cellular modem or Wi-Fi chipset) or via the user's device (e.g., a mobile phone or tablet computer). The algorithm then analyzes the information to facilitate the early detection of peritonitis and other health conditions, paving the way for early clinical intervention before these conditions worsen.

[0009] In consideration of the foregoing, in one embodiment, the present disclosure relates to a system for characterizing spillage samples from patients undergoing PD. The system typically comprises a container for containing the spillage sample, an optical system, an electrical system, and a processor. The optical system comprises a light source and a photodetector, the light source emitting a beam of radiation that passes through the container and irradiates the spillage sample, and the photodetector detecting the radiation (e.g., scattered radiation) after irradiating the spillage sample to generate an optical signal. The electrical system comprises at least a pair of electrodes attached to the container and configured to measure an electrical signal (e.g., capacitance) of the spillage sample to generate a measured electrical response (e.g., capacitance signal). For example, the processor processes the optical signal and the electrical signal collectively to operate an algorithm for characterizing the spillage sample. However, it should be understood that other electrical signals (other than capacitance) are also construed herein, as will be disclosed in more detail below. The at least pair of electrodes may be attached directly or indirectly to the container.

[0010] In one embodiment, the container is a sample cell comprising at least two surfaces. Each of these surfaces of the sample cell may include an optically transparent material such as glass, plastic, ceramic, diamond-based material, or a material comprising a derivative thereof. Typically, the electrode is a thin film, ideally an optically transparent and conductive thin film formed on at least one of the two surfaces. In one embodiment, for example, the thin film is composed mainly of gold. In another embodiment, the thin film comprises In2O5Sn or a derivative thereof (e.g., indium tin oxide, "ITO" herein). Alternatively, the thin film is composed of a thin metal having reasonable transparency to optical wavelengths in the spectral ranges of infrared, visible light, and ultraviolet light.

[0011] In an embodiment, both the first and second surfaces of the sample cell include optically transparent electrodes. Here, the light source is configured to emit a beam of radiation that passes through the first optically transparent electrode into the spill sample, and the photodetector is configured to receive the radiation after it has irradiated the spill sample and passed through the second optically transparent electrode. An electrical system integrated with such a system may feature a capacitor including two capacitor electrodes, where the first optically transparent electrode is the first capacitor electrode and the second optically transparent electrode is the second capacitor electrode.

[0012] In a related embodiment, the electrical system comprises a first pair of electrodes and a second pair of electrodes, both of which are not entirely optically transparent but have optically transparent openings (e.g., notched areas in other continuous conductive regions). Here, the light source is configured to emit a beam of radiation that passes through a first optically transparent opening in the first electrode into the spill sample, and the photodetector is configured to receive the radiation after it has irradiated the spill sample and passed through a second optically transparent opening in the second electrode.

[0013] In related embodiments, the optical system is further configured to measure the optical absorption of the spill sample, for example, a multi-frequency absorption spectrum. Here, the light source is configured to emit a beam of radiation entering the spill sample, the photodetector is configured to receive the radiation after it has irradiated the spill sample, and the processor is configured to analyze the radiation after it has irradiated the spill sample and to determine the amount of radiation absorbed by the spill sample. In this embodiment and other embodiments, the photodetector may be, for example, a standard photodiode, a CCD camera, a photodiode coupled to a computer-controlled optical filter, or several densely arranged photodiodes having different optical filters.

[0014] In other related embodiments, the optical system is further configured to measure light scattering caused by the spill sample, wherein the light source is configured to emit a beam of radiation entering the spill sample, the photodetector is configured to receive the radiation after it has irradiated the spill sample, and the processor is configured to analyze the radiation after it has irradiated the spill sample and to determine the amount of light scattering caused by the spill sample.

[0015] In yet another embodiment, the electrical system is further configured to measure one or more electrical parameters of the spill sample, such as capacitance, resistance, conductivity, complex impedance, impedance, reactance, inductance, dielectric constant, magnetism, and other related properties. To perform such measurements, for example, the first electrode is further configured to both induce a current in the spill sample by generating an electric field in the spill sample, either alone or in combination with another electrode such as the second electrode, either directly via DC or via AC, and to sense the electrical properties or related parameters of the spill sample. Here, for example, the electrical system can induce different currents in the sample, each characterized by a different frequency (typically in the range of 5 to 1000 kHz). By measuring the signals resulting from these induced currents, a spectrum of electrical properties (e.g., impedance or capacitance spectrum) can be obtained and analyzed to determine the compounds (components, compounds) in the spill sample.

[0016] In related embodiments, the electrical system further includes both third and fourth electrodes, where, for example, the system includes a first set (pair) of electrodes characterized by two electrodes configured to induce an electric current in the spill sample, and a second set (pair) of electrodes separate from the first set of electrodes, configured to sense the electrical properties of the spill sample.

[0017] In other embodiments, the processor used in the system is further configured to collectively process the optical and electrical signals to operate an algorithm that determines the amount of compounds (e.g., leukocytes, blood cells, proteins such as fibrin, lipid particles, triglycerides, chylomicrons, micelles, biological substances, and their derivatives) in the effluent sample. The processor may be included directly in the system and in the PD device. Alternatively, the processor may be included in the cloud or in a device connected to the PD device, such as a computer, tablet computer, or mobile device.

[0018] Most typically, the system described herein is directly integrated with an electromechanical cycla used for PD. For example, it can be directly incorporated into an electromechanical PD cycla, or it can be integrated with (or is actually part of) a portion of the tubing within the electromechanical cycla (e.g., an internal tubing component). Alternatively, the system is connected to (or is actually part of) an external tubing outside the cycla, which is connected to the patient and is typically used to drain the outflowing fluid from the patient's peritoneal cavity.

[0019] In another embodiment, the disclosure relates to a system similar to the one described above, the electrical system comprising a first and a second pair of electrodes, both electrode pairs mounted on the container and configured to measure electrical properties other than capacitance of the spill sample (e.g., resistance, conductivity, complex impedance, impedance, reactance, inductance, dielectric constant, magnetism, and related properties), wherein the processor operates an algorithm that collectively processes the optical and electrical signals to characterize the spill sample.

[0020] In one embodiment, the electrodes of the system are optically transparent. In another embodiment, a first pair of electrodes induces an electric current in the spill sample, and a second pair of electrodes measures an electrical signal of the spill sample that depends on the current induced in the sample. In a different embodiment, a single pair of electrodes is configured to do both (1) induce an electric current in the spill sample and (2) measure an electrical signal of the spill sample that depends on the current induced in the sample. In yet another embodiment, the system can be used to characterize not only PD spills but also any liquid sample.

[0021] The proposed technique features several advantages. Most importantly, combining multiple optical and additional electrical measurement techniques into a single measurement system can improve the sensitivity of the system, thereby enabling it to detect, for example, small amounts of leukocytes in PD effluent. Theoretically, this means that peritonitis can be detected at a very early stage, thereby allowing clinicians to intervene with therapeutic measures (e.g., administration of antibiotics) to prevent infection. Ultimately, this could enable ESRD patients to remain in PD, which has several advantages compared to HD as described above. Furthermore, by incorporating multiple measurement techniques into a single system, the proposed technique involves sensing different physiological components of PD effluent and thus reducing potentially erroneous readings (e.g., "false negatives" and "false positives") that could negatively impact clinical intervention. More specifically, optical measurements, particularly optical absorption spectroscopy, are highly sensitive to the specific molecular structures of particulate matter. Such measurements can be complemented by electrical techniques such as multi-frequency measurements of parameters including impedance, reactance, resistance, and capacitance, which are highly sensitive markers of the presence of particulate matter in PD effluent. Furthermore, such measurements can be complemented by optical measurements, particularly optical absorption spectroscopy, which are highly sensitive to the specific molecular structure of particulate matter. Combined, these techniques provide an effective method for evaluating PD efflux while avoiding false negatives and false positives that can impair the measurement.

[0022] Without limiting the scope in any way in light of the disclosure herein, a first aspect of the disclosure is a system for characterizing an effluent sample from a patient undergoing peritoneal dialysis (PD). The system includes a container, an optical system, an electrical system, and a processor. The container encloses the effluent sample. The optical system includes a light source and a photodetector, the light source being configured to emit a beam of radiation that passes through the container and irradiates the effluent sample, and the photodetector being configured to detect the radiation after it has irradiated the effluent sample in order to generate an optical signal. The electrical system includes at least a pair of electrodes, the at least a pair of electrodes being attached to the container and configured to measure the electrical properties of the effluent sample and generate a characteristic signal. The processor operates an algorithm configured to collectively process the optical signal and the characteristic signal to characterize the effluent sample.

[0023] Embodiments of the first aspect are presented below. Each such embodiment can be combined with any other embodiment listed herein unless otherwise specified.

[0024] In one embodiment, the container is a sample cell having at least two surfaces.

[0025] In one embodiment, each of the at least two surfaces of the sample cell includes an optically transparent material.

[0026] In one embodiment, the optically transparent material is selected from the group consisting of glass, plastic, ceramic, diamond-based material, or derivatives thereof.

[0027] In one embodiment, the at least pair of electrodes are thin films formed on at least one of the two surfaces.

[0028] In one embodiment, the thin film is a material that is optically transparent and conductive.

[0029] In one embodiment, the thin film is mainly composed of one of gold, In2O5Sn, or derivatives thereof.

[0030] In one embodiment, the at least one pair of electrodes includes a first pair of electrodes and a second pair of electrodes.

[0031] In one embodiment, the first surface of the container includes the first pair of electrodes that is the first optically transparent electrode pair. The second surface of the container includes the second pair of electrodes that is the second optically transparent electrode pair.

[0032] In one embodiment, the light source is configured to emit the beam of radiation that enters the effluent sample through the first optically transparent electrode pair. The photodetector is configured to receive the radiation after the radiation irradiates the effluent sample and passes through the second optically transparent electrode pair.

[0033] In one embodiment, the electrical system includes a capacitor having two capacitor electrodes. The first optically transparent electrode pair is the first capacitor electrode pair, and the second optically transparent electrode pair is the second capacitor electrode pair.

[0034] In one embodiment, both the first pair of electrodes and the second pair of electrodes include optically transparent openings.

[0035] In one embodiment, the light source is configured to emit the beam of radiation that enters the effluent sample through the first optically transparent opening in the first pair of electrodes. The photodetector is configured to receive the radiation after the radiation irradiates the effluent sample and passes through the second optically transparent opening in the second pair of electrodes.

[0036] In one embodiment, the optical system is further configured to measure the light absorption of the spill sample.

[0037] In one embodiment, the light source is configured to emit the beam of radiation entering the spill sample, the photodetector is configured to receive the radiation after it has irradiated the spill sample, and the processor is configured to analyze the radiation after it has irradiated the spill sample and to determine the amount of radiation absorbed by the spill sample.

[0038] In one embodiment, the optical system is further configured to measure light scattering caused by the spill sample.

[0039] In one embodiment, the light source is configured to emit the beam of radiation entering the spill sample, the photodetector is configured to receive the radiation after it has irradiated the spill sample, and the processor is configured to analyze the radiation after it has irradiated the spill sample and to determine the amount of light scattering caused by the spill sample.

[0040] In one embodiment, the electrical properties of the spill sample are selected from the group consisting of resistance, conductivity, complex impedance, impedance, reactance, inductance, dielectric constant, and magnetism.

[0041] In one embodiment, the at least pair of electrodes comprises a pair of electrodes configured to both induce an electric current in the spill sample and sense the electrical characteristics or related parameters of the spill sample.

[0042] In one embodiment, the at least pair of electrodes comprises a pair of electrodes configured to both generate an electric field within the spill sample and to sense the electrical properties or related parameters of the spill sample.

[0043] In one embodiment, the electrical system further comprises a third electrode and a fourth electrode.

[0044] In one embodiment, the at least pair of electrodes comprises a pair of electrodes configured to induce an electric current in the spill sample and another pair of electrodes configured to sense the electrical properties of the spill sample.

[0045] In one embodiment, the processor is further configured to operate an algorithm configured to collectively process the optical signal and the characteristic signal to determine the amount of compound in the spill sample.

[0046] In one embodiment, the compound is selected from the group consisting of leukocytes, blood cells, proteins, lipid particles, triglycerides, chylomicrons, micelles, biological substances, and derivatives thereof.

[0047] In one embodiment, the system is integrated with an electromechanical cyclorama used in the PD.

[0048] In one embodiment, the system is incorporated into the electromechanical cyclora.

[0049] In one embodiment, the container is part of the first tube within the electromechanical cyclora.

[0050] In one embodiment, the system is connected to a second tube that is connected to the patient and configured to discharge the outflowing fluid from the patient's peritoneal cavity and pass it through the container.

[0051] In one embodiment, the container is part of the second tube.

[0052] In one embodiment, the system transmits (communicates) the measurement results to the electromechanical cyclora.

[0053] A second aspect of this disclosure is a system for characterizing an effluent sample from a patient undergoing peritoneal dialysis (PD). The system in the second aspect comprises a container, an electrical system, an optical system, and a processor. The container encloses the effluent sample. The electrical system comprises a first pair of electrodes and a second pair of electrodes, both of which have optically transparent portions, are mounted on the container, and are configured to measure the electrical properties of the effluent sample. The optical system comprises a light source and a photodetector. The light source is configured to emit a beam of radiation that passes through the first pair of electrodes and irradiates the effluent sample. The photodetector is configured to detect the radiation after it has irradiated the effluent sample and passed through the second pair of electrodes in order to generate the optical properties of the effluent sample. The processor operates an algorithm configured to collectively process the optical and electrical properties to characterize the effluent sample.

[0054] A third aspect of this disclosure is a system for measuring leukocytes from an effluent sample from a patient undergoing peritoneal dialysis (PD). The system in the third aspect comprises a container, an electrical system, an optical system, and a processor. The container encloses the effluent sample. The electrical system comprises a first pair of electrodes and a second pair of electrodes, both of which are optically transparent and mounted on the container, the first pair of electrodes configured to induce an electric current in the effluent sample, and the second pair of electrodes configured to measure an electrical signal of the effluent sample that depends on the current induced in the sample. The optical system comprises a light source and a photodetector. The light source is configured to emit a beam of radiation that passes through one of the first pair of electrodes and the second pair of electrodes to irradiate the effluent sample. The photodetector is configured to detect the radiation after it has irradiated the spill sample and passed through one of the first pair of electrodes and the second pair of electrodes, in order to generate an optical signal. The processor operates an algorithm configured to collectively process the optical signal and the electrical signal to characterize the spill sample.

[0055] A fourth aspect of the present disclosure is a system for characterizing a liquid sample. The system in the fourth aspect includes a container, an optical system, an electrical system, and a processor. The container encloses the sample. The optical system comprises a light source and a photodetector. The light source is configured to emit a beam of radiation that passes through the container and irradiates the sample. The photodetector is configured to detect the radiation after it has irradiated the sample in order to generate an optical signal. The electrical system comprises at least a pair of electrodes, the at least a pair of electrodes attached to the container and configured to measure the electrical properties of the sample in order to generate a characteristic signal. The processor operates an algorithm configured to collectively process the optical signal and the characteristic signal to characterize the sample.

[0056] Further features and advantages of the disclosed devices, systems, and methods will be described and will become apparent from the following detailed description and drawings. The features and advantages described herein are not exhaustive, and many additional features and advantages will become apparent to those skilled in the art in consideration of the drawings and description. Furthermore, no particular embodiment is required to possess all of the advantages enumerated herein. In addition, it should be noted that the language used herein has been chosen primarily for readability and explanatory purposes and is not intended to limit the scope of the subject matter. [Brief explanation of the drawing]

[0057] It should be understood that the drawings illustrate only typical embodiments and should not be considered to limit the scope of this disclosure. This disclosure is described with additional specificities and details by using the accompanying drawings. The drawings are listed below. [Figure 1] Figure 1 is a schematic diagram showing a PDEAS (Patient-Defined Emergency Device) in an integrated embodiment with a PD (Patient-Distributed Medical Device) connected to the patient. [Figure 2] Figure 2 is a schematic diagram showing the PDEAS in Figure 1. [Figure 3A] Figure 3A is a mechanical drawing showing the sample cell used to contain the PD spillage within the PDEAS in Figure 2. [Figure 3B] Figure 3B is a schematic diagram showing the sensing electrode and driving electrode pair used for impedance measurement in the sample cell shown in Figure 3A. [Figure 3C] , [Figure 3D] Figures 3C to 3D are photographs of the sample cell shown in Figure 3A, which is itself integrated with a circuit board that controls both impedance and optical measurements. [Figure 4A] , [Figure 4B] , [Figure 4C]Figures 4A-C are mechanical drawings of an alternative sample cell according to one embodiment, shown from the front, bottom, and side views, of a cell having both driving and sensing capabilities for a single pair of electrodes, respectively. [Figure 5] Figure 5 is a photograph of a single tube used to transport PD effluent from a PDEAS, which is compressed during optical measurement, according to one embodiment. [Figure 6A] , [Figure 6B] Figures 6A and 6B are plots of light transmittance against the relative concentration of leukocytes, measured at wavelengths of λ=415nm and λ=910nm, respectively. [Figure 7] Figure 7 shows absorption measured over different wavelengths using a CCD-based optical spectrometer and an AS7262 spectral sensor. [Figure 8] Figure 8 shows a plot of light transmission versus time, measured using the optical system used in PDEAS from a sample of yeast cells dissolved in aqueous solution. [Figure 9A] Figure 9A is a collection of plots of light absorption versus frequency measured by the optical system used in PDEAS from blood samples dissolved in aqueous solution. [Figure 9B] Figure 9B is a plot of absorption peak intensity versus relative concentration of hemodilution measured at λ=600nm, and the data in the plot were extracted from the graph in Figure 9A. [Figure 10] Figure 10 shows a plot of transmitted laser current and scattered light current against the percentage of milk diluted in aqueous solution, measured using the optical system used in PDEAS. [Figure 11A] Figure 11A is a collection of light absorption versus wavelength plots measured by the optical system used in PDEAS from yeast samples dissolved in aqueous solution. [Figure 11B] Figure 11B is a plot of light absorption against the relative concentration of yeast, measured at a wavelength of λ = 688 nm. [Figure 12]Figure 12 is a plot of series resistance versus frequency measured using the impedance system used in PDEAS from a yeast sample dissolved in aqueous solution. [Figure 13] Figure 13 is a plot of series capacitance versus frequency measured using the impedance system used in PDEAS from a yeast sample dissolved in aqueous solution. [Figure 14A] Figure 14A is a plot of impedance versus relative concentration of yeast cells, and the data in the plot were extracted from a graph similar to that in Figure 12. [Figure 14B] Figure 14B is a plot of series capacitance versus relative concentration of yeast cells, and the data in the plot were extracted from a graph similar to that in Figure 13. [Modes for carrying out the invention]

[0058] The detailed description should be interpreted as illustrative only and does not describe all possible embodiments, as they are impractical, if not impossible. Those skilled in the art can implement numerous alternative embodiments, which are still included within the scope of the claims.

[0059] Figure 1 is a schematic diagram showing multiple PDEAS 12a, 12b integrated with a PD cycla 60 to measure PD efflux from patient 2, with the specific objective (goal) of characterizing the amount of leukocytes in the efflux, which may indicate peritonitis. PDEAS 12a, 12b may be incorporated into the PD cycla 60 (as shown by PDEAS 12a), attached to a tube 71 that transports the PD efflux to the patient's toilet 8 (as shown by PDEAS 12b), or incorporated into any or part of the PD cycla 60 that encloses the PD efflux. Although multiple PDEAS 12a, 12b are shown herein, it should be understood that only one PDEAS is needed to measure PD efflux.

[0060] In each case, PDEAS12a and 12b are compact measurement systems that perform one or more of the following measurements from PD effluent: i) optical spectroscopy, ii) light scattering, more typically laser scattering, iii) single or multi-frequency bioimpedance, and iv) light transmission.

[0061] Optical measurements may include, for example, the comparison of ratios of focused transmitted light, transmitted light at a single wavelength, small-angle scattered light, and large-angle scattered light for estimating particle concentration and / or turbidity; or spectroscopy for evaluating particle size, determining particle type by color (e.g., red blood cells / white blood cells, proteins, fats, etc.); and other similar optical measurements, such as the comparison of ratios of any combination of transmitted and / or scattered light with light of different wavelengths.

[0062] By combining several optical sensors, different optical properties can be distinguished from one another. For example, the estimation of particle concentration (e.g., leukocytes) can be achieved by using focused transmitted light. Cells pass through the beam and interact with this light (e.g., absorption, lensing effect, etc.), resulting in a measured change in transmitted intensity. The estimation of particle size can be achieved by measuring transmitted and / or scattered light at several different angles. Particles the size of cells scatter mainly at small angles (e.g., 0-10 degrees), while smaller particles with diameters less than the wavelength of light scatter at larger angles. Leukocytes and erythrocytes are typically larger than the wavelength of visible light and can be assumed to scatter light according to Mie scattering, while chylomicrons and cholesterol (e.g., VLDL, LDL, and HDL) are smaller than the wavelength of light and scatter according to Rayleigh scattering. Similar estimations of particle size can be established by using multiple wavelengths of light across multiple sensors; for example, cell-sized particles are more likely to scatter light at larger angles using longer wavelengths (e.g., infrared) than shorter wavelengths (e.g., ultraviolet).

[0063] For example, by measuring light at 0, 5, and 20 degrees, the number of blood cells can be estimated using 0 degrees (i.e., transmitted light) compared to an incident focused laser beam, and the particle size can be estimated using the ratio between 0, 5, and 20 degrees, thus allowing estimation of whether the turbidity of the effluent is primarily caused by blood cells or lipoproteins. In one embodiment, the presence of smaller particles can be estimated using larger detection angles, such as 45 or 90 degrees. The effluent can be characterized by determining the particle size diameter within it (detailed in Table 1 below).

[0064] [Table 1] Table 1. Particle sizes in human plasma and ascites fluid. For comparison, the wavelength of visible light is 0.5–0.7 μm.

[0065] Subsequently, a computing system located within PDEAS12a, 12b, gateway 11 (e.g., mobile phone), or cloud 10 analyzes information from these measurements to estimate both the concentration of leukocytes (e.g., white blood cells) in the PD effluent and the actual color of the PD effluent. The computing system further analyzes this information to determine the early onset of an infection, such as peritonitis. If this condition is detected, a clinician can, for example, provide the patient with antibiotics or other medications to address the condition.

[0066] For example, by incorporating both a white light source and a light spectrometer, the color of absorbed light can be measured. This can be used to determine the color of the effluent and, therefore, whether the estimated cell count, measured by focused transmitted light, is caused by red blood cells or white blood cells. The color of the effluent can further be used to detect other complications.

[0067] For PDEAS12a,12b to receive PD outflow, the PD cycla 60 is attached to patient 2 through a first tube 7. Tube 7 is connected to a catheter 5 which is sutured to the patient's peritoneum using a simple surgical procedure. The catheter 5 may protrude, for example, from an opening 9 in clothing worn by patient 2 lying on a bed 4. Attached to the PD cycla 60 through an assembly of tubes 69 are bags 65, 67 containing different mixtures of PD dialysate.

[0068] During treatment, typically 2-3 liters of dialysis fluid flow through the assembly of tube 69 and catheter 5, eventually flowing into the patient's peritoneum to form a filling volume. The filling volume remains in the abdomen, while waste diffuses across the peritoneum from the underlying blood vessels.

[0069] After a variable period (typically 2-6 hours depending on the procedure), the PD effluent flows through the catheter and through a collection of tubes to the PD cycla, where it is measured by the PDEAS 12a, 12b as described above to detect the leukocyte concentration or other fluid state. The PD cycla 60 may further include standard components such as a heating system 63 for warming the bags 65, 67 to the patient's body temperature, a display 61 that allows the patient 2 or a user associated with the patient to control the PD cycla 60, and an internal wireless module configured to transmit information from the PDEAS 12a, 12b to either the gateway 11 (indicated by arrow 75) or the cloud (indicated by arrow 73).

[0070] Figure 2 shows a schematic diagram illustrating the PDEAS 12 in more detail. Generally, it should be understood that this system includes optical and electrical sensors for measuring PD effluent as it passes through a cuvette 34 surrounded by an opening 40 of a sample holder 30 (also referred to herein as a measuring cell 30), as will be described in more detail below. Furthermore, while Figure 2 shows multiple optical and electrical sensors within the PDEAS 12, it should be understood that one or all of these can be used to measure the PD effluent and determine its characteristics, such as the color and concentration of leukocytes, or its electrical properties.

[0071] The PDEAS12 includes a computer processing unit 13 along with a customized circuit board. The circuit board may advantageously include a photodetector 14. The photodetector 14 is electrically coupled to a laser light source 24 via an electrical connection 16 and to the computer processing unit 13 via an electrical connection 19. For example, the laser light source 24 is a narrowband laser light source that emits laser radiation 42 of a given wavelength.

[0072] The PDEAS 12 may further include a light source 18 having a photodetector 54, such as a broadband photodetector and / or a segmented / multi-narrowband detector, configured to measure the light spectrum from the PD spill (similar to that shown in Figures 6A-6B). For example, the light source 18 is a white LED. In the illustrated example, the PDEAS 12 includes two separate light sources, a laser light source 24 and a light source 18. Each of these two separate light sources is configured to pass light (visible or other light) through the PD spill, as will be described in more detail herein. Each of these two separate light sources may be configured to be detected independently so that two separate light source readings can be easily determined. Finally, these two separate light sources may be configured to output a single coherent wavelength, or they may be configured to output different light sources (e.g., different wavelengths, different intensities, etc., such as red, green, or infrared) to provide a number of light source readings across the spectrum.

[0073] As shown in Figure 2, the laser light source 24 and the photodetector 14 are oriented orthogonal to the light source 18 and the detector 54. It should be understood that other orientations are also contemplated in this specification.

[0074] The light source 18 may be configured to output multiple different iterations of light (e.g., different wavelengths, different intensities, etc.). For example, the light source 18 may output a first set of radiation 20 (of a first wavelength) and a second set of radiation 22 (of a second wavelength).

[0075] Therefore, as shown in Figure 2, a total of three different radiations, namely laser radiation 42, a first set of radiation 20, and a second set of radiation 22, are output toward the measurement cell 30. Each of these three radiations is configured to pass through the measurement cell 30.

[0076] That is, the measuring cell 30 includes a metal holder 32 and an optically transparent cuvette 34 (e.g., a glass sample cell) surrounding the PD outflow flowing through the opening 40. Thus, the laser radiation 42, the first set of radiation 20, and the second set of radiation 22 are configured to pass through the transparent cuvette 34 and the PD outflow flowing through the opening 40. The PDEAS 12 further includes lens systems 36a-d. For example, the PDEAS 12 includes a first set of lenses 36a-b configured to receive one or more of the laser radiation 42, the first set of radiation 20, and the second set of radiation 22. Similarly, the PDEAS 12 includes a second set of lenses 36c-d, which are configured to receive one or more of the laser radiation 42, the first set of radiation 20, and the second set of radiation 22 after the radiation has passed through the optically transparent cuvette 34 and the PD outflow flowing through the opening 40.

[0077] The PDEAS12 further includes a first set of sensing / driving electrodes 38a and a second set of sensing / driving electrodes 38b. For example, the first set of sensing / driving electrodes 38a is configured to induce a current in the PD outflow flowing through the opening 40, and similarly, for example, the second set of sensing / driving electrodes 38b is configured to detect the current (induced from the first set 38a) from the PD outflow flowing through the opening 40. In general, via the first set of sensing / driving electrodes 38a and the second set of sensing / driving electrodes 38b, the PDEAS12 can perform impedance measurements of the PD outflow flowing through the opening 40.

[0078] Each of the first set of sensing / driving electrodes 38a and the second set of sensing / driving electrodes 38b may be electrically coupled to the impedance circuit 52 (for example, via the electrical connection 50).

[0079] As described above, the laser radiation 42, the first set of radiation 20, and the second set of radiation 22 each pass through the measurement cell 30. Specifically, each of the laser radiation 42, the first set of radiation 20, and the second set of radiation 22 passes through the PD outflow flowing through the aperture 40. The first set of radiation 20 passes through the PD outflow flowing through the aperture 40 and then exits the measurement cell 30 as indicated by arrow 48. The first set of radiation 20 can be detected by the photodetector 14. The second set of radiation 22 passes through the PD outflow flowing through the aperture 40 and then exits the measurement cell 30 as indicated by arrow 44. The second set of radiation 22 can be detected by the detector 54. The laser radiation 42 passes through the PD outflow flowing through the aperture 40 and then exits the measurement cell 30 as indicated by arrow 46. The laser radiation 42 can be detected by the photodetector 14.

[0080] Each of the detectors 54 and / or photodetectors 14 may be electrically coupled to the computer processing unit 13. For example, detector 54 may be coupled to the processing unit 13 via an electrical connection 56.

[0081] Specifically, the computer processing unit 13 controls the photodetector 54 and the light source 18, as indicated by connection 56. During measurement, the light source emits broadband radiation (also called “white light”), which typically includes light frequencies ranging from infrared (e.g., λ=700nm) to ultraviolet (e.g., λ=200nm). The light source is, for example, typically a light-emitting diode (“LED” as herein) or a tungsten light source. As indicated by the solid arrow 22, the white light passes through window 36b connected to the opening of the sample holder 30 and irradiates the PD outflow in the cuvette 34.

[0082] Therefore, depending on its composition, the PD effluent partially absorbs white light, resulting in transmitted radiation indicated by the solid arrow 44. The photodetector 54 detects and digitizes the transmitted radiation and transmits the associated signal to the computer processing unit 13 via connection 56. In some embodiments, this process is carried out by similar measurements of the dialysate solution used to form the stasis, in which case the photodetector 54 determines a “baseline measurement” or “reference measurement,” which is digitized as the transmitted radiation and transmitted as an associated signal via connection to the computing system. The computer processing unit 13 analyzes the difference between the signal associated with the baseline measurement and the transmitted radiation to determine the optical spectrum associated with the PD effluent.

[0083] In various embodiments, the computer processing unit 13 analyzes raw optical and / or raw electrical data to make a determination regarding PD efflux. The computer processing unit 13 may employ statistical processing, including variance, deviation, etc., with or without relevant spectral fingerprinting, to make a determination regarding PD efflux. The computer processing unit 13 may additionally or alternatively use time-dependent analysis of the raw data signals (e.g., criterion identification, beat picking, etc.) to make a determination regarding PD efflux. In one embodiment, the computer processing unit 13 executes one or more algorithms communicating with a database or lookup table to determine cell counts and make a relevant determination regarding PD efflux. The computer processing unit 13 may additionally or alternatively implement a neural network. Further disclosures relating to this analysis are included below.

[0084] As taught herein, the computer processing unit 13 may be configured to process optical signals from the optical system within the PDEAS to determine at least one of the particle concentration, particle size, particle type, or color of the PD spill ("spilled material sample"). Furthermore, the computer processing unit 13 may be configured to process electrical signals from the electrical system within the PDEAS to determine at least one of the particle concentration or particle type.

[0085] In one embodiment, the optical system is configured to emit broadband radiation by a light source 18 and to detect the broadband radiation after it has passed through the PD effluent by a photodetector 54 in order to determine the optical spectrum representing the PD effluent.

[0086] In one embodiment, the computer processing unit 13 is configured to process an optical signal when it represents an optical spectrum in order to determine at least one of the color, particle type, or particle concentration of the PD spill.

[0087] In one embodiment, the optical system is configured to emit broadband radiation by a light source 18, and to detect the broadband radiation by a photodetector 54 after it has passed through a reference sample of a fluid other than PD effluent, such as a dialysis fluid, in order to determine a reference spectrum representing the reference sample. A computer processing unit 13 is configured to determine at least one of the color, particle type, or particle concentration of the PD effluent based on the difference between the light spectrum and the reference spectrum.

[0088] In one embodiment, the optical system is configured to emit narrowband radiation by a light source 24, detect the narrowband radiation after it has passed through the PD outflow by a photodetector 14, determine the light transmission value of the PD outflow, and / or determine the scattering intensity at one or more transverse angles, by detecting the narrowband radiation at one or more transverse angles relative to the beam of radiation scattered by the PD outflow. As used herein, a transverse angle forms a non-zero angle with respect to the direction of the beam of radiation toward the PD outflow. Scattering intensity represents the intensity or magnitude of scattered radiation received by the photodetector at each transverse angle.

[0089] In one embodiment, the light source 24 is configured to sequentially emit narrowband radiation at two or more wavelengths in order to determine at least one of the light transmission value or scattering intensity at each of two or more wavelengths.

[0090] In one embodiment, the computer processing unit 13 is configured to process light transmission values ​​and / or scattering intensities in order to determine the size of at least one particle in the PD spill.

[0091] In one embodiment, the computer processing unit 13 is configured to determine at least one particle type in the PD spill based on at least one particle size.

[0092] In one embodiment, the computer processing unit 13 is further configured to determine the particle concentration of at least one particle type in the PD spill based on light transmission values ​​and / or scattering intensity.

[0093] In one embodiment, the particle type is selected from the group consisting of leukocytes, blood cells, proteins, lipid particles, triglycerides, chylomicrons, micelles, biological substances, and derivatives thereof.

[0094] In one embodiment, the measuring cell 30 can be cleaned / disinfected (e.g., the opening 40 can be cleaned / sterilized) between uses of the PDEAS 12. In a different embodiment, the measuring cell 30 is part of a disposable set and, as a result, can be removed (after use) and replaced with another sterilized measuring cell for subsequent use.

[0095] Figure 3A shows a mechanical drawing of a sample cell 80 used to contain PD spills within the PDEAS 12 of Figure 2. That is, the PD spills flow through the sample cell 80 from the fluid inlet 87a to the fluid outlet 87b. The sample cell 80 includes windows 84, 85 located on the relative side of the sample cell 80, which can allow light transmission "through" the sample cell 80. It should be understood that the sample cell 80 may include additional windows (e.g., a back surface) not shown. For example, a light source 90a could pass through a window, irradiate the PD spills within the sample cell 80, and then be detected through window 84 (90b).

[0096] In addition to optical measurements, the sample cell 80 further provides electrical measurements. For example, the sample cell 80 may include a first set of sensing / driving electrodes 89a, 89d and a second set of sensing / driving electrodes 89b, 89c. In one embodiment, the first set of sensing / driving electrodes 89a, 89b are configured to induce a current in the PD effluent flowing through the sample cell 80. Similarly, in one embodiment, the second set of sensing / driving electrodes 89c, 89d are configured to detect a current (induced from the first set 89a, 89b) from the PD effluent flowing through the sample cell 80. As shown in Figure 3A, the first set of sensing / driving electrodes 89a, 89b are positioned "outside" the window 85. In this embodiment, the first set of sensing / driving electrodes 89a, 89b induce a current in the PD effluent flowing through the sample cell 80 via capacitive coupling caused by an alternating current. In an alternative embodiment, the first set of sensing / driving electrodes 89a, 89b are positioned "inside" the window 85 to induce a current in the PD effluent flowing through the sample cell 80 via DC. As shown in Figure 3A, the second set of sensing / driving electrodes 89c, 89d are positioned "inside" the window 85.

[0097] In an alternative embodiment, one or more of the windows, such as window 85, include embedded surface electronics, and as a result, window 85 can induce and / or sense electrical signals without requiring additional electrodes, and thus can replace one or more of the electrodes 89a to d.

[0098] Next, Figure 3B shows a schematic diagram of the sensing and driving electrode pairs used for impedance measurement in the sample cell 80 of Figure 3A. For example, the driving electrode induces current at a first driving position 84b and a second driving position 84c in the sample cell 80. These induced currents are detected at the first sensing position 84a and the second sensing position 84d via the sensing electrode. As the signal moves from the driving position to the sensing position, the signal interacts with the PD outflow, and therefore the detected electrical signal at the sensing position differs from the initial induced current and driving position, since the induced current produces a voltage that depends on the impedance of the fluid. This measured difference is useful for characterizing the PD outflow. In one embodiment, four-point measurement ("four-terminal sensing") is used to reduce the undesirable influence of contact resistance.

[0099] Figures 3C–D are photographs of the sample cell 80 shown in Figure 3A, respectively, which is integrated with a circuit board that controls both impedance and optical measurements. Figure 3C shows the relative size of the sample cell 80. Figure 3D shows the sample cell 80 adjacent to a circuit board 100 configured to control the optical system (e.g., light source) and analyze data (e.g., from a photodetector). Figure 3D also shows a laser diode focusing assembly 102 directed to focus light through one of the windows of the sample cell 80.

[0100] Figures 4A–C show mechanical drawings of an alternative sample cell 108 according to embodiments shown from the front, bottom, and side of sample cell 108, respectively. This alternative sample cell 108 is configured to increase the surface area for improved electrical measurement. In sample cell 108, PD outflow flows through the sample cell 108 from the fluid inlet 114a to the fluid outlet 114b. Sample cell 108 includes windows 110, 112 positioned on the relative side of sample cell 108 to allow light transmission "through" sample cell 108. In one embodiment, each of windows 110, 112 includes built-in surface electronics, so that windows 110, 112 can induce and / or sense electrical signals as a single pair of electrodes without requiring additional electrodes. In the alternative embodiment, sample cell 108 includes access ports for electrodes to access PD outflow flowing between windows 110, 112.

[0101] Figure 5 is a photograph of a single tube 150 used to transport PD effluent from a PDEAS for use in optical measurements according to one embodiment. For example, the PD effluent flows through the interior 156 of the tube 150, which is a flexible / compressible tube. To obtain appropriate optical measurements across the tube 150, the tube 150 is compressed between transparent glass windows 158a, 158b. When compressed, the tube 150 forms a first flat side surface 154a parallel to window 158a, so that light 160a can easily pass through window 158a and the first flat side surface 154a to interact with the effluent inside the tube 156. Similarly, when compressed, the tube 150 forms a second flat side surface 154b parallel to window 158b, so that light 160b can easily pass through the second flat side surface 154b and window 158b for detection.

[0102] As previously stated herein, PDEAS12 includes optical and electrical sensors for measuring PD efflux. With respect to optical measurements, PDEAS12 can communicate with a database or lookup table to determine cell counts and make relevant determinations regarding PD efflux. Experimental data demonstrate specific trends and relationships regarding leukocyte concentrations.

[0103] For example, Figures 6A and 6B show plots of light transmittance versus relative concentration of leukocytes, measured at wavelengths of λ=415 nm and λ=910 nm, respectively. Figure 7 further shows the measured absorption of leukocytes across different wavelengths, with measurements acquired using both a CCD-based optical spectrometer and an AS7262 spectral sensor.

[0104] As shown in Figures 6A-6B and 7, the light spectrum typically contains frequency-dependent bands associated with both leukocytes and other compounds in PD effluent. To prove this concept, experiments were conducted in which suspended leukocytes were systematically diluted in a mixture of simulated PD effluent containing additional substances, in a leukocyte solution taken from a leukemia cell line called "HL60". The light absorption spectra, determined using the technique described above, were then analyzed at different dilutions ranging from 0 to approximately 180 cells / μl. A computational system measured the light intensity in numerous different bands. Figures 6A and 6B show the values ​​measured at λ=415 and λ=910 nm, respectively.

[0105] As is evident from these plots, a systematic increase in leukocytes from the HL60 line results in a very linear decrease in transmitted radiation detected by the photodetector. A linear regression model can be used to "fit" the data, as indicated by the dashed line in the figure. Mathematical models based on linear regression can be deployed within a computational system (e.g., in the form of computer code, such as embedded computer code running on an internal processor). Such models are typically determined by a series of experiments, such as those used to generate the plots in Figures 6A–6B. Ideally, these experiments are conducted using a diverse patient population characterized by a range of age, ethnicity, sex, weight, height, and elapsed time as an ESRD patient. Once a model is generated, it can be used to analyze subsequent samples of PD effluent to estimate leukocyte concentrations. That is, PDEAS12 can implement one or more of these linear regression models for subsequent PD effluent analysis and determination.

[0106] A similar approach based on optical spectroscopy can analyze the overall color of PD effusion, which is then analyzed by a computational system to estimate other conditions in the patient. For example, typical red PD effusion is characterized by a spectral band around λ=685nm. As mentioned above, this may indicate that the patient is experiencing internal bleeding (e.g., from a ruptured cyst or a problem with its catheter) or is ovulating or menstruating. Similarly, typical green PD effusion is characterized by a spectral band around λ=550nm. This may indicate that the patient is suffering from hypertriglyceridemia, lymphatic obstruction, pancreatitis, lymphoma, general trauma, or drug abuse. Typical brown or orange PD effusion is characterized by a spectral band around λ=600nm. This may indicate the presence of feces in the patient's peritoneum, possibly due to a ruptured bowel.

[0107] In this embodiment, the photodetector used to measure the light spectrum is a CCD camera featuring a pixel array. Typically, in this embodiment, transmitted radiation first illuminates an optical element such as a prism or diffraction grating that spatially diffuses the radiation on the CCD camera, allowing multiple pixels in the array to detect specific wavelengths. This approach has the advantage of measuring multiple light frequencies simultaneously, and the resolution of these frequencies depends on the type of prism or diffraction grating used, the distance between this element and the CCD camera (longer distances result in greater frequency spread), and the pixel density in the CCD camera. While this type of optical measurement is relatively fast and produces a high-density light spectrum, the components used to do so are typically large and expensive, and therefore may not meet the requirements of conventional PD cycling.

[0108] Another approach to measuring optical spectra is to use a small, integrated measurement system such as the AMS AS7262 or AMS AS7641 spectral sensor. This component combines a highly sensitive photodetector with a digital field-programmable gate array filter that can be controlled to allow specific bands of radiation to pass through. For example, by using computer code running on a microprocessor to set registers associated with the AMS component, different bands of radiation can be detected sequentially, allowing the optical spectrum to be "stitched together" at a limited number of data points (e.g., the AMS AS7262 and AS7641 can detect 6 and 10 distinct bands, respectively). Figure 7 shows the same sample (in this case, diluted red blood cells) measured at different times using, for example, a CCD-based optical spectrometer (solid line) and an AMS AS7262 (separate triangular marker). As is evident from these data, although the AMS component has limited resolution compared to the spectrometer, both detection systems yield similar data showing the optical spectrum corresponding to the red blood cells. Compared to spectrometers, AMS components have the advantages of being relatively small (area of ​​only a few square millimeters), inexpensive (typically under $5), and likely more compatible with conventional PD cyclizers.

[0109] Therefore, referring to the example in Figure 2, the photodetector 54 may include a programmable digital filter (not shown) that allows radiation in multiple wavelength ranges to pass through. The controller of the photodetector 54 (e.g., the computer processing unit 13) may be configured to operate the digital filter to sequentially pass radiation in a predetermined wavelength range while the light source 18 emits broadband radiation. The controller of the photodetector 54, or another processing unit, may be further configured to generate an optical spectrum based on optical data separately detected by the photodetector 54 for each of the predetermined wavelength ranges.

[0110] Figures 8–11B show additional optical experiments and related data that can be used with PDEAS12. For example, Figure 8 shows a plot of light transmittance versus time measured with the optics used in PDEAS12 from a sample of yeast cells dissolved in aqueous solution. As an example, data was collected using a red laser diode and a glass sample cell. A large laser spot size was used (e.g., the full width of the measurement cuvette). In general, milk protein diluents can be used as simulated samples of protein turbidity dialysate. Light transmittance shows an almost quadratic relationship, while scattering (at a 90-degree angle) shows a linear relationship with increasing protein concentration.

[0111] Figure 9A shows a collection of light absorption versus frequency plots measured with the optical system used in PDEAS from blood samples dissolved in aqueous solution, while Figure 9B shows a plot of absorption peak intensity versus relative concentration of blood dilution measured at λ=600nm, with the data extracted from the graph in Figure 9A. This experimental data is useful for PDEAS12 in the analysis and characterization of PD effluent.

[0112] Figures 10–11B include additional experimental results. Specifically, Figure 10 shows a plot of the percentage of milk diluted in aqueous solution versus transmitted laser current and scattered light current, measured with the optical system used in PDEAS12. Figure 11A shows a collection of plots of light absorption versus wavelength, measured with the optical system used in PDEAS12, from a sample of yeast dissolved in aqueous solution. Figure 11B shows a plot of relative concentration versus light absorption of yeast, measured at a wavelength of λ = 688 nm.

[0113] In general, the optical experiments and related data presented in Figures 8–11B demonstrate a strong correlation when tested with leukocytes, hemodilutions, and yeast cell dilutions.

[0114] In addition, and / or alternatively, with respect to electrical measurements, PDEAS12 can communicate with a database or lookup table to determine cell counts and make relevant determinations regarding PD efflux based on one or more of the measured resistance, capacitance, bioimpedance, bioreactance, and / or resonant frequencies. Experimental data demonstrate specific trends and relationships regarding yeast cell concentrations.

[0115] Specifically, Figure 12 shows a plot of series resistance versus frequency measured using the impedance system used in PDEAS12 from a yeast sample dissolved in aqueous solution. Figure 13 shows a plot of direct capacitance versus frequency measured using the impedance system used in PDEAS from a yeast sample dissolved in aqueous solution. Figure 14A shows a plot of impedance versus relative concentration of yeast cells, with the data extracted from a graph similar to that in Figure 12. Figure 14B shows a plot of series capacitance versus relative concentration of yeast cells, with the data extracted from a graph similar to that in Figure 13.

[0116] Therefore, similar to the optical analysis described above, electrical measurements can be used to generate regression models that fit the experimental data. Once a model is generated, it can be used to analyze subsequent samples of PD spills. That is, PDEAS12 can implement one or more of these linear regression models for the analysis and determination of subsequent PD spills using electrical measurements, as discussed herein.

[0117] It will be understood that all of the methods and procedures disclosed herein can be implemented using one or more computer programs or components. These components may be provided as a set of computer instructions on any conventional computer-readable medium, including RAM, ROM, flash memory, magnetic or optical disks, optical memory, or other storage media. The instructions may be configured to be executed by a processor that, when executing a set of computer instructions, performs or facilitates the execution of all or part of the disclosed methods and procedures.

[0118] It should be understood that it is also possible to configure a system for characterizing effluent samples from patients undergoing PD to include only the optical system according to any aspect or embodiment described herein, or only the electrical system according to any aspect or embodiment described herein.

[0119] As used herein, including in the claims, the term “and / or” is a combination that can be either inclusive or exclusive. Thus, the term “and / or” means either that there are two or more things in a group, or that one can be chosen from a group of choices.

[0120] Many of the features and advantages of this disclosure are evident from the description provided, and therefore the appended claims are intended to encompass all such features and advantages of this disclosure. Furthermore, since numerous modifications and changes are readily conceivable to those skilled in the art, this disclosure is not limited to the exact configurations and operations illustrated and described. Accordingly, the embodiments described should be considered illustrative and not limiting, and this disclosure should not be limited to the details given herein, but should be defined by the entire scope of the following claims and their equivalents, whether currently or in the future, whether foreseeable or unforeseen.

Claims

1. A system for characterizing outflow samples from patients undergoing peritoneal dialysis (PD), A container (30; 80; 108) for sealing the spilled material sample, An optical system comprising a light source (18, 24) and a photodetector (14, 54), wherein the light source (18, 24) is configured to emit a beam of radiation that passes through the container (30; 80; 108) and irradiates the spill sample, and the photodetector (14, 54) is configured to detect the radiation after it has irradiated the spill sample in order to generate an optical signal, An electrical system comprising at least one pair of electrodes (38a, 38b), wherein the at least one pair of electrodes (38a, 38b) are attached to the container (30; 80; 108) and configured to measure the electrical characteristics of the spill sample in order to generate a characteristic signal, A processor (13) that operates an algorithm configured to characterize the spill sample by collectively processing the optical signal and the characteristic signal, A system equipped with these features.

2. The system according to claim 1, wherein the container (30; 80; 108) is a sample cell having at least two surfaces.

3. The system according to claim 2, wherein each of the at least two surfaces of the sample cell comprises an optically transparent material.

4. The system according to claim 3, wherein the optically transparent material is selected from the group consisting of glass, plastic, ceramic, diamond-based material, or derivatives thereof.

5. The system according to any one of claims 2 to 4, wherein the at least pair of electrodes (38a, 38b) are thin films formed on at least one of the two surfaces.

6. The system according to claim 5, wherein the thin film is made of a material that is optically transparent and conductive.

7. The thin film is made of gold, in ２ O ５ The system according to claim 5 or 6, comprising mainly Sn or one of its derivatives.

8. The system according to any one of claims 1 to 7, wherein the at least pair of electrodes includes a first pair of electrodes (38a) and a second pair of electrodes (38b).

9. The system according to claim 8, wherein the first surface of the container (30; 80; 108) includes the first pair of electrodes (38a), which is a first optically transparent electrode pair, and the second surface of the container (30; 80; 108) includes the second pair of electrodes (38b), which is a second optically transparent electrode pair.

10. The system according to claim 9, wherein the light source (18, 24) is configured to emit the beam of radiation that passes through the first optically transparent electrode pair and enters the spill sample, and the photodetector (14, 54) is configured to receive the radiation after it has irradiated the spill sample and passed through the second optically transparent electrode pair.

11. The electrical system comprises a capacitor having two capacitor electrodes, wherein the first optically transparent electrode pair is a first capacitor electrode pair, and the second optically transparent electrode pair is a second capacitor electrode pair, according to claim 10.

12. The system according to any one of claims 1 to 8, wherein both the first pair of electrodes (38a) and the second pair of electrodes (38b) have optically transparent apertures.

13. The system according to claim 12, wherein the light source (18, 24) is configured to emit the beam of radiation that enters the spill sample through a first optically transparent opening in the first pair of electrodes (38a), and the photodetector (14, 54) is configured to receive the radiation after it has irradiated the spill sample and passed through a second optically transparent opening in the second pair of electrodes (38b).

14. The system according to any one of claims 1 to 8, wherein the optical system is further configured to measure the light absorption of the spill sample.

15. The system according to claim 14, wherein the light sources (18, 24) are configured to emit the beam of radiation entering the spill sample, the photodetectors (14, 54) are configured to receive the radiation after it has irradiated the spill sample, and the processor (13) is configured to analyze the radiation after it has irradiated the spill sample and to determine the amount of radiation absorbed by the spill sample.

16. The system according to any one of claims 1 to 8, 14, or 15, wherein the optical system is further configured to measure light scattering caused by the spill sample.

17. The system according to claim 16, wherein the light sources (18, 24) are configured to emit the beam of radiation entering the spill sample, the photodetectors (14, 54) are configured to receive the radiation after it has irradiated the spill sample, and the processor (13) is configured to analyze the radiation after it has irradiated the spill sample and to determine the amount of light scattering caused by the spill sample.

18. The system according to any one of claims 1 to 17, wherein the electrical characteristics of the spilled sample are selected from the group consisting of capacitance, resistance, conductivity, complex impedance, impedance, reactance, inductance, dielectric constant, and magnetism.

19. The system according to claim 18, wherein the at least pair of electrodes (38a, 38b) includes a pair of electrodes (38a; 38b) configured to both induce an electric current in the spill sample and sense the electrical properties or related parameters of the spill sample.

20. The system according to claim 18, wherein the at least pair of electrodes (38a, 38b) includes a pair of electrodes (38a; 38b) configured to both generate an electric field within the spill sample and to sense the electrical properties or related parameters of the spill sample.

21. The system according to claim 18, wherein the at least pair of electrodes (38a, 38b) includes a pair of electrodes (38a; 38b) configured to induce an electric current in the spill sample and another pair of electrodes (38b; 38a) configured to sense the electrical properties of the spill sample.

22. The system according to any one of claims 1 to 21, wherein the processor (13) is further configured to operate the algorithm configured to collectively process the optical signal and the characteristic signal to determine the amount of compound in the spill sample.

23. The system according to claim 22, wherein the compound is selected from the group consisting of white blood cells, blood cells, proteins, lipid particles, triglycerides, chylomicrons, micelles, biological materials, and derivatives thereof.

24. The system according to any one of claims 1 to 23, which is integrated with an electromechanical cyclorama (60) used in a PD.

25. The system according to claim 24, which is incorporated into the aforementioned electromechanical cyclorama (60).

26. The system according to claim 24 or 25, wherein the container (30; 80; 108) is part of the first tube within the electromechanical cyclorama (60).

27. The system according to claim 24, further connected to a second tube (71) which is connected to the patient and configured to drain the fluid outflowing from the patient's peritoneal cavity and pass it through the container (30; 80; 108).

28. The system according to claim 27, wherein the container (30; 80; 108) is part of the second tube (71).

29. The system according to any one of claims 1 to 28, configured to transmit the measurement results to the electromechanical cyclorama (60).

30. The system according to claim 1, wherein the processor (13) is configured to process the optical signal for determining at least one of the particle concentration, particle size, particle type, or color of the spill sample.

31. The system according to claim 30, wherein the processor (13) is configured to process the characteristic signal for determining at least one of particle concentration or particle type.

32. The system according to claim 30 or 31, wherein the optical system is configured to emit broadband radiation by the light source (18), and to detect the broadband radiation after it has passed through the spill sample by the photodetector (54) for the purpose of determining the light spectrum representing the spill sample.

33. The system according to claim 32, wherein the processor (13) is configured to process the optical signal representing the optical spectrum for determining at least one of the color, particle type, or particle concentration of the spill sample.

34. The system according to claim 32 or 33, wherein the optical system is configured to emit broadband radiation by the light source (18), and to detect the broadband radiation after it has passed the reference sample by the photodetector (54) for the purpose of determining a reference spectrum representing a reference sample of fluid other than the spill, and the processor (13) is configured to determine at least one of the color, particle type, or particle concentration of the spill sample based on the difference between the light spectrum and the reference spectrum.

35. The system according to any one of claims 30 to 34, wherein the optical system is configured to emit narrowband radiation by the light source (24), and to detect the narrowband radiation after it has passed through the spill sample for the purpose of determining the light transmission value of the spill sample, and / or to detect the narrowband radiation at one or more transverse angles with respect to the beam of radiation after it has been scattered by the spill sample for the purpose of determining the scattering intensity at one or more transverse angles.

36. The system according to claim 35, wherein the light source (24) is configured to sequentially emit narrowband radiation at each of the two or more wavelengths for the purpose of determining at least one of the light transmission value or the scattering intensity.

37. The system according to claim 35 or 36, wherein the processor (13) is configured to process the light transmission value and / or the scattering intensity for determining the size of at least one particle in the spill sample.

38. The system according to claim 37, wherein the processor (13) is configured to determine at least one particle type in the spill sample based on the at least one particle size.

39. The system according to claim 38, wherein the processor (13) is further configured to determine the concentration of at least one particle type in the spill sample based on the light transmission value and / or the scattering intensity.

40. The system according to any one of claims 30 to 39, wherein the particle type is selected from the group consisting of leukocytes, blood cells, proteins, lipid particles, triglycerides, chylomicrons, micelles, biological materials, and derivatives thereof.

41. A system for characterizing outflow samples from patients undergoing peritoneal dialysis (PD), A container (108) for sealing the spilled material sample, An electrical system comprising a first pair of electrodes (38a) and a second pair of electrodes (38b), wherein both the first pair of electrodes (38a) and the second pair of electrodes (38b) have optically transparent portions, are mounted on the container (108), and are configured to measure the electrical characteristics of the spill sample. An optical system comprising a light source (18, 24) and a photodetector (14, 54), wherein the light source (18, 24) is configured to emit a beam of radiation that passes through the first pair of electrodes (38a) and irradiates the spill sample, and the photodetector (14, 54) is configured to detect the radiation after it has irradiated the spill sample and passed through the second pair of electrodes (38b) to generate the optical properties of the spill sample, A processor (13) that operates an algorithm configured to characterize the spilled material sample by collectively processing the optical and electrical properties, A system equipped with these features.

42. A system for measuring white blood cells from effluent samples from patients undergoing peritoneal dialysis (PD), A container (108) for sealing the spilled material sample, An electrical system comprising a first pair of electrodes (38a) and a second pair of electrodes (38b), wherein both the first pair of electrodes (38a) and the second pair of electrodes (38b) are optically transparent and mounted on the container (108), the first pair of electrodes (38a) is configured to induce an electric current in the spill sample, and the second pair of electrodes (38b) is configured to measure an electrical signal of the spill sample that depends on the electric current induced in the sample, An optical system comprising a light source (18, 24) and a photodetector (14, 54), wherein the light source (18, 24) is configured to emit a beam of radiation that passes through one of the first pair of electrodes (38a) and the second pair of electrodes (38b) and irradiates the spill sample, and the photodetector (14, 54) is configured to detect the radiation after it has irradiated the spill sample and passed through one of the first pair of electrodes (38a) and the second pair of electrodes (38b) in order to generate an optical signal, A processor (13) that operates an algorithm configured to characterize the spill sample by collectively processing the optical signal and the electrical signal, A system equipped with these features.

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