Method and device for measuring urine osmotic pressure

Abstract

The urine osmotic pressure measuring method comprises the following steps: receiving a urine sample; mixing an adsorbent with the urine sample to obtain a urine-adsorbent mixture; determining the electrical impedance of the urine sample; measuring the refractive index of the urine-adsorbent mixture; and determining the osmotic pressure of the urine sample using the electrical impedance of the urine sample and the refractive index of the urine-adsorbent mixture simultaneously.

Description

Technical Field

[0001] The present disclosure generally relates to the measurement of urine osmolality. In particular, the present disclosure relates to methods and apparatus for measuring urine osmolality. Background Art

[0002] Urine osmolality is crucial for assessing health status. It reflects kidney function and hydration status and is typically expressed in mOsm / kg. High urine osmolality may indicate conditions such as dehydration or kidney problems, while low urine osmolality may be associated with conditions such as diabetes insipidus. Monitoring osmolality after a 12-14 hour period of dehydration can help diagnose diabetes insipidus.

[0003] Urine osmolality can also help diagnose nocturia, a condition characterized by the need to urinate at night. A variety of conditions, including nocturnal polyuria, can cause nocturia. Because the underlying cause is unknown, specific treatment options are difficult to identify, potentially rendering treatments ineffective.

[0004] Accurate diagnosis is crucial, and osmolality can serve as a supplementary data for clinical assessment and bladder recording, helping to guide treatment decisions. However, existing osmolality tests are often costly and inconvenient, requiring bulky testing equipment in specialized clinics. For example, the freezing point method used in specialized clinics measures osmolality by lowering the freezing point, requiring patients to visit the clinic for urine osmolality monitoring.

[0005] Recently, portable osmometers have been developed that can rapidly estimate urine osmolality based on urine specific gravity. However, studies have shown that the correlation between urine specific gravity and urine osmolality is poor, especially in pathological urine. Summary of the Invention

[0006] According to one aspect of the present disclosure, a method for measuring urine osmotic pressure is provided. The method comprises: receiving a urine sample; mixing an adsorbent with the urine sample to obtain a urine-adsorbent mixture; determining an electrical impedance of the urine sample; measuring a refractive index of the urine-adsorbent mixture; and determining the osmotic pressure of the urine sample using the electrical impedance of the urine sample and the refractive index of the urine-adsorbent mixture. The adsorbent may include activated carbon powder.

[0007] The adsorbent enables the refractive index of the urine-adsorbent mixture to accurately reflect the urea concentration of the urine sample. In this way, the method can accurately determine the osmotic pressure of the urine sample by combining electrical impedance and refractive index.

[0008] The electrical impedance of the urine sample may be determined in either of the following two ways: measuring the impedance of the urine sample before mixing the adsorbent with the urine sample; or measuring the electrical impedance of the urine-adsorbent mixture.

[0009] The process of determining the osmotic pressure of the urine sample may include: using an electrical impedance model to determine the molar concentration of the conductive solute in the urine sample based on the electrical impedance of the urine-adsorbent mixture, the electrical impedance model is a relationship model between the molar concentration of the conductive solute and the electrical impedance; using a refractive index model to determine the molar concentration of urea in the urine sample based on the refractive index of the urine-adsorbent mixture and the molar concentration of the conductive solute in the urine sample, the refractive index model is a relationship model between the refractive index and the molar concentrations of the conductive solute and urea; and determining the osmotic pressure of the urine sample using the molar concentration of the conductive solute and the molar concentration of urea.

[0010] Determining the osmotic pressure of the urine sample may further include: combining the conductive solute molar concentration with the urea molar concentration to obtain an initial result; and adjusting the initial result by an empirical factor to obtain the osmotic pressure of the urine sample.

[0011] The method may further comprise: selecting the electrical impedance model from a plurality of pre-calibrated electrical impedance models; and selecting the refractive index model from a plurality of pre-calibrated refractive index models.

[0012] The method may include: measuring the current ambient temperature, and selecting the electrical impedance model and the refractive index model based on the current ambient temperature, wherein each of the multiple pre-calibrated electrical impedance models is a relationship model between the molar concentration of the conductive solute and the electrical impedance at the corresponding ambient temperature, and each of the multiple pre-calibrated refractive index models is a relationship model between the refractive index and the molar concentrations of the conductive solute and urea at the corresponding ambient temperature.

[0013] According to another aspect of the present disclosure, a urine osmotic pressure measuring device is provided. The device includes: a container for holding a urine-adsorbent mixture comprising a urine sample and an adsorbent; a measuring unit for determining the electrical impedance of the urine sample and measuring the refractive index of the urine-adsorbent mixture; and a processing unit for determining the osmotic pressure of the urine sample using the electrical impedance of the urine sample and the refractive index of the urine-adsorbent mixture. The adsorbent may include activated carbon powder.

[0014] The device is simple to use and the only action required of the end user may be to collect urine in the container.

[0015] The processing unit may include: a memory storing: an electrical impedance model, the electrical impedance model being a relationship model between the molar concentration of the conductive solute and the electrical impedance; and a refractive index model being a relationship model between the refractive index and the molar concentrations of the conductive solute and urea; and a processor. The processor is configured to: determine the molar concentration of the conductive solute in the urine sample based on the electrical impedance of the urine-sorbent mixture using the electrical impedance model; determine the molar concentration of urea in the urine sample based on the refractive index of the urine-sorbent mixture and the molar concentration of the conductive solute using the refractive index model; and determine the osmotic pressure of the urine sample using the molar concentration of the conductive solute and the molar concentration of urea.

[0016] The processor may be configured to determine the osmotic pressure of the urine sample by combining the conductive solute molar concentration with the urea molar concentration to obtain an initial result; and adjusting the initial result by an empirical factor to obtain the osmotic pressure of the urine sample.

[0017] The memory may store a plurality of pre-calibrated electrical impedance models and a plurality of pre-calibrated refractive index models, and the processor may be configured to select the electrical impedance model from the plurality of pre-calibrated electrical impedance models and to select the refractive index model from the plurality of pre-calibrated refractive index models.

[0018] The measuring unit may further include a thermometer for measuring the current ambient temperature, and the processor is used to select the electrical impedance model and the refractive index model based on the current ambient temperature measured by the measuring unit, wherein each of the multiple pre-calibrated electrical impedance models is a relationship model between the molar concentration of the conductive solute and the electrical impedance at the corresponding ambient temperature, and each of the multiple pre-calibrated refractive index models is a relationship model between the refractive index and the molar concentrations of the conductive solute and urea at the corresponding ambient temperature.

[0019] The container and the measuring unit may be configured to be connectable in such a manner that, when the container is connected to the measuring unit, the measuring unit seals the container and mixes the adsorbent with the urine sample.

[0020] The measuring unit may be configured to determine the electrical impedance of the urine sample by measuring the electrical impedance of the urine sample.

[0021] The measuring unit may be configured to determine the electrical impedance of the urine sample by measuring the electrical impedance of the urine-sorbent mixture.

[0022] The adsorbent may be disposed in the container, wherein the container is further configured to receive the urine sample.

[0023] The container may contain a sealed space for containing the adsorbent, and the container and the measuring unit may be configured such that when the measuring unit is inserted, the sealed space is opened, thereby allowing the adsorbent to contact the urine sample and be mixed with the urine sample by the measuring unit.

[0024] The device may further include a display for displaying the value of the osmotic pressure of the urine sample.

[0025] In various embodiments, the device can be smaller than a laboratory test device and thus be less expensive to manufacture, thereby providing patients with an economical way to measure urine osmolality. In some embodiments, the device is portable, allowing patients to use it conveniently at home without having to go to a clinic.

[0026] The disclosure of the urine osmotic pressure measurement method and device of the present disclosure is as described herein. Various features, aspects and advantages of the present disclosure will become more apparent from the following detailed description of various embodiments of the present disclosure by way of non-limiting examples only in conjunction with the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Hereinafter, embodiments of the present invention will be described by way of non-limiting examples with reference to the accompanying drawings. In the drawings:

[0028] Figure 1 This is a flow chart of the urine osmotic pressure measurement method;

[0029] Figure 2 Shown is the process of the urine osmolality measurement method;

[0030] Figure 3 Shown is a prototype of a urine osmolality measurement device.

[0031] Figure 4 Shown is the electrical impedance model calibration process.

[0032] Figure 5 A diagram showing the electrical impedance model.

[0033] Figure 6 Shown is the refractive index model calibration process.

[0034] Figure 7 A diagram showing the refractive index model.

[0035] Figure 8 Shown is the relationship between urine osmolality estimated by this method and urine osmolality determined by clinical testing.

[0036] Figure 9A and Figure 9B Shown are the results of validation trials for the urine osmolality measurement method.

[0037] Figure 10 Shown is the first urine osmotic pressure measurement and the corresponding process.

[0038] Figure 11 Shown is a second urine osmotic pressure measurement device.

[0039] Figure 12 Shown is a third urine osmotic pressure measurement device.

[0040] Figure 13 The corresponding process of the third urine osmotic pressure measuring device is shown.

[0041] Figure 14A and Figure 14B Shown are the results of another validation test for the urine osmolality measurement method. DETAILED DESCRIPTION

[0042] For the sake of brevity and clarity, the description of the embodiment of the present disclosure is directed to the urine osmotic pressure measurement method and device in the accompanying drawings. Although the various aspects of the present disclosure are described below in conjunction with the various embodiments given herein, it should be understood that it is not intended to limit the present disclosure to such embodiments. On the contrary, within the scope of the present disclosure as defined by the appended claims, the present disclosure is intended to further cover alternatives, modifications and equivalents of the various embodiments described herein. In addition, specific details are given in the detailed description below to achieve a thorough understanding of the present disclosure. However, persons with conventional skills in the art (i.e., those skilled in the art) should know that the present disclosure can still be implemented even in the absence of such specific details and / or in the case of further adding multiple details resulting from the combination of various aspects of various specific embodiments. The objects described herein are various aspects of the various embodiments of the present disclosure. For well-known systems, methods, processes and components, in order to avoid distracting attention, in many cases, no detailed description beyond the necessary extent is given.

[0043] In the embodiments of the present disclosure, if a specific element is illustrated or described, or a marking symbol of a specific element is considered or used in a specific figure or a mentioned part of the corresponding description content, in addition to the element or element marking symbol itself, it may also cover equivalents or similar elements or element marking symbols in other figures or related description content.

[0044] When referring to "an embodiment / example," "another embodiment / example," "some embodiments / examples," "some other embodiments / examples," etc., it means that the embodiment / example described may include a particular feature, structure, characteristic, property, element, or limitation, but it does not mean that all embodiments / examples must include the particular feature, structure, characteristic, property, element, or limitation. In addition, when the phrase "in one embodiment / example" or "in another embodiment / example" is used in multiple places, it does not necessarily refer to the same embodiment / example.

[0045] When words such as "include," "comprising," or "having" are used, it does not mean that features / elements / steps other than those listed in the embodiment are not present. When certain features / elements / steps are mentioned in different embodiments, it does not mean that a certain embodiment cannot adopt a combination of such features / elements / steps.

[0046] In this document, when the specific number of an object is not specified, it can be either "one" or "more than one". Unless otherwise specified, the " / " used in the drawings or related descriptions should be understood as "and / or". According to known mathematical definitions, the term "set" is defined as a non-empty finite element organization form with at least one element in the mathematical sense (for example, the set defined in this document may correspond to a unit element, a single element, a single-element set, or a multi-element set). In this document, if a numerical value or a numerical range is given, it should be understood to include a numerical value or numerical range similar to it, or itself refers to the approximate numerical value or numerical range.

[0047] Figure 1 FIG1 is a flow chart of a method for measuring urine osmotic pressure according to an embodiment of the present invention. Figure 1 As shown, method 100 includes step 110 of receiving a urine sample and step 120 of mixing an adsorbent with the urine sample to form a urine-adsorbent mixture. Method 100 includes step 130 of determining the electrical impedance of the urine sample and step 140 of measuring the refractive index of the urine-adsorbent mixture. Step 130 can be performed by measuring the electrical impedance of the urine sample or the urine-adsorbent mixture. Method 100 includes a final step 150 of determining the osmotic pressure of the urine sample using both the electrical impedance of the urine sample and the refractive index of the urine-adsorbent mixture.

[0048] Adsorbents include materials capable of adsorbing large molecular weight components, such as activated carbon, activated charcoal, and / or charcoal.

[0049] In general urine samples, urine composition can be divided into conductive ions and non-conductive solutes. Conductive ions (about 44%) are composed of sodium ions (about 18%), potassium ions (about 7%), chloride ions (about 19%), and trace amounts of other dissolved ions. Non-conductive solutes (about 56%) are composed of urea (about 55%) as the main component and other solutes (about 1%) such as creatinine, inorganic sulfur, and other inorganic and organic compounds. Urine osmotic pressure can be determined by the summation method. By quantifying the conductive ions (about 44%) and non-conductive urea (about 55%) in urine samples, the urine osmotic pressure can achieve an accuracy of up to about 99%.

[0050] Electrical impedance measurements are effective in characterizing the molar concentration of conductive solutes in urine samples, but are unable to determine the concentration of urea, the largest non-conductive component in urine.

[0051] Liquid refractive index measurement is widely used to measure the concentration of solutes in solutions. However, the concentration of urea in a urine sample cannot be determined based on the total refractive index alone. The reason for this limitation is that urine samples further contain large molecular weight components and conductive solutes. Compared with the main components (conductive solutes and urea), large molecular weight components such as creatinine, uric acid, glucose and protein have a greater impact on the refractive index of urine samples. In addition, the presence of conductive solutes will also affect the reading of the total refractive index. For example, although the refractive index reading of a solution containing 1 mol / kg sodium chloride (the main conductive solute in urine) is almost exactly the same as that of a solution containing 1 mol / kg urea, the osmotic pressure of the former is twice that of the latter.

[0052] To address the above limitations, Figure 1 The illustrated method 100 combines refractive index and electrical impedance measurements to determine the osmotic pressure of a urine sample using activated carbon adsorption. Activated carbon adsorbs high-molecular-weight components in urine, such as creatinine, uric acid, glucose, and protein, thereby reducing their impact on the refractive index reading. The contribution of conductive solutes to osmotic pressure is first assessed using electrical impedance measurements, and then the contribution of urea is determined using refractive index measurements.

[0053] Figure 2 The urine osmotic pressure measurement process 200 is shown. In the process 200, a urine sample 210 is received and mixed with activated carbon 220 to obtain a urine-activated carbon mixture 230. Subsequently, the process includes steps 130 of measuring the electrical impedance of the urine-activated carbon mixture 230 and 140 of measuring the refractive index of the urine-activated carbon mixture 230.

[0054] The electrical impedance reading 242 measured in step 130 is input into the electrical impedance model 240 to determine the molar concentration of NaCl 244 in the urine sample 210. Simultaneously, the refractive index reading 252 measured in step 140 is input into the refractive index model 250 to determine the molar concentration of urea 254 in the urine sample 210. In step 150, the molar concentration of NaCl 244 is combined with the molar concentration of urea 254 using an empirical factor 270 to determine the osmotic pressure 260 of the urine sample 210.

[0055] The electrical impedance model 240 is a model for the relationship between the molar concentration of the conductive solute and the electrical impedance, while the refractive index model 250 is a model for the relationship between the refractive index and the molar concentrations of the conductive solute and urea.

[0056] Figure 3 Shown is a urine osmotic pressure measurement device 300. The device 300 includes a container 310 that holds a urine sample 210 and activated carbon 220 before step 120. After step 120, the contents of the container 310 are a urine-activated carbon mixture 230.

[0057] The first drop (300 μl) of urine-activated carbon mixture 230 is measured by an impedance analyzer 320. Alternatively, although not shown in the figure, the impedance analyzer 320 can also measure a drop of urine sample 210. The impedance analyzer 320 is composed of a printed circuit board (PCB) 322 with electrodes 324 and an impedance analysis module 326. The electrodes 324 are connected to the impedance analysis module 326. The first drop of urine-activated carbon mixture 230 is dropped on the PCB 322 to cover the electrode 324 area, thereby enabling the impedance analysis module 326 to determine the electrical impedance reading 242 of the urine-activated carbon mixture 230. The second drop (300 μl) of urine-activated carbon mixture 230 is measured by a refractometer 330. The refractometer 330 is composed of a light source 332, a measurement chamber 334 and a photodiode 336. A second drop of urine-activated carbon mixture 230 is dropped onto measurement chamber 334, allowing refractometer 330 to determine a refractive index reading 252 of urine-activated carbon mixture 230 using light source 332 and photodiode 336. Impedance analyzer 320 and refractometer 330 together constitute measurement unit 340.

[0058] The osmolality 260 of the urine sample 210 is determined by the processing unit 350 using both the electrical impedance reading 242 and the refractive index reading 252 .

[0059] Figure 4An exemplary calibration process 400 for the electrical impedance model 240 is shown. In an initial step 410 of the calibration process 400, six sodium chloride (NaCl) solutions having molar concentrations ranging from 0.05 mol / kg to 0.5 mol / kg are prepared. In step 420, each of the six NaCl solutions is applied to the electrode 324 area covering the printed circuit board (PCB) 322. In a subsequent step 430, the impedance analysis module 326 is activated to determine the electrical impedance of each NaCl solution. In a final step 440 of the calibration process 400, the electrical impedance model 240 is generated.

[0060] Figure 5 Graph 500 is shown representing the electrical impedance model 240 generated in step 440. Graph 500 shows the relationship between the molar concentration of the conductive solute and the electrical impedance, which is plotted as R NaCl The reciprocal of the NaCl solution impedance determined in step 430 changes with the NaCl molar concentration. The solid dots represent the R at 0.05M, 0.10M, 0.20M, 0.30M, 0.40M and 0.50M NaCl molar concentrations. NaCl The reciprocal experimental readings, the solid line is the best fit curve obtained under the constraint that the curve passes through the origin.

[0061] This constrained fitting method ensures that the fitting curve passes through the origin and has a goodness of fit as high as R 2 = 0.9936, which shows that 1 / R NaCl With NaCl molar concentration M NaCl (Unit: mol / kg) is linearly proportional. Alternatively, the electrical impedance model 240 can be expressed as the following formula:

[0062] 1 / R NaCl =C0M NaCl (1)

[0063] Wherein, coefficient C0 = 0.0266 kg / (mol·Ω).

[0064] Figure 6An exemplary calibration process 600 for the refractive index model 250 is shown. The calibration process 600 includes a step 610 for preparing a sample mixture, each sample containing NaCl at a concentration of 0.05 mol / kg, 0.10 mol / kg, 0.20 mol / kg, 0.30 mol / kg, 0.40 mol / kg, and 0.50 mol / kg and urea at a concentration of 0 mol / kg, 0.10 mol / kg, 0.20 mol / kg, 0.30 mol / kg, 0.40 mol / kg, and 0.50 mol / kg. In a subsequent step 620, 36 calibration samples are obtained. Referring to the apparatus 300, the calibration process 600 also includes a step 630 of applying 300 μl of each calibration sample to the refractometer 330 and a step 640 of obtaining the refractive index of the calibration samples at room temperature (25°C). In a final step 650 of the calibration process 600, the refractive index model 250 is generated.

[0065] Figure 7 Shown is a graph 700 representing the refractive index model 250 generated in step 650. Graph 700 includes: a graph 710 plotting the refractive index of the NaCl-urea mixture obtained in step 620 versus urea molar concentration; and a graph 720 plotting the refractive index of the NaCl-urea mixture obtained in step 620 versus NaCl molar concentration.

[0066] In the graph 710, the circular mark (○) represents the experimentally measured refractive index at 0.05 mol / kg NaCl, the square mark (□) represents the experimentally measured refractive index at 0.1 mol / kg NaCl, the cross mark (×) represents the experimentally measured refractive index at 0.2 mol / kg NaCl, the diamond mark (◇) represents the experimentally measured refractive index at 0.3 mol / kg NaCl, the star mark (*) represents the experimentally measured refractive index at 0.4 mol / kg NaCl, and the triangle mark ( ) represents the experimentally measured refractive index at 0.5 mol / kg NaCl. In the graph 720, the circular mark (○) represents the experimentally measured refractive index without urea, the square mark (□) represents the experimentally measured refractive index at 0.1 mol / kg urea, the cross mark (×) represents the experimentally measured refractive index at 0.2 mol / kg urea, the diamond mark (◇) represents the experimentally measured refractive index at 0.3 mol / kg urea, the star mark (*) represents the experimentally measured refractive index at 0.4 mol / kg urea, and the triangle mark ( ) represents the experimental measured refractive index under 0.5 mol / kg urea. In both graphs 710 and 720, the solid line represents the best fit curve. In graph 700, the goodness of fit R of all fitted lines is 2is at least 0.995, indicating a good linear relationship between the refractive index and the molar concentration of both urea and NaCl. s ) can be linearly modeled with the molar concentrations of urea and NaCl (denoted as M NaCl and M urea , in mol / kg) is related to:

[0067] n s =c NaCl M NaCl +c urea M urea +C0 (2)

[0068] Among them, C NaCl and C urea (Unit: kg / mol) is the contribution coefficient, which represents the contribution of each unit mole of NaCl and urea to the refractive index. Pure deionized (DI) water has C0 = 1.333, which is a constant. According to the data shown in Figure 700, C NaCl =0.01041 kg / mol and C urea =0.00966 kg / mol, the best fitting result is obtained. 2 =0.997.

[0069] Impedance readings may vary from device to device, and refractive index readings are affected by ambient temperature. Therefore, when the urine osmotic pressure measuring device is placed in a different ambient temperature, it may be necessary to recalibrate C0, C1, and C2 according to processes 400 and 600. NaCl 、C urea Three coefficients.

[0070] For simplicity, the end user of the urine osmotic pressure measuring device can achieve the above three coefficients (C0, C NaCl 、C urea For example, the end user can measure the electrical impedance and refractive index of 300 μl of 0.5 mol / kg NaCl solution and determine C0 and C according to equations (1) and (2). NaCl The final user can then measure the refractive index of 300 μl of a mixture of 0.5 mol / kg NaCl and 0.5 mol / kg urea and determine the final coefficient C according to formula (2): urea According to experimental estimation, the calibration process takes about 6 minutes.

[0071] After calibrating the effects of conductive solutes and urea on electrical impedance and refractive index, ie, generating the electrical impedance model 240 and the refractive index model 250, the osmotic pressure of the urine sample can be determined.

[0072] Referring to process 200, 600 μl of urine sample 210 is first mixed with 50 mg of activated carbon 220 to obtain a urine-activated carbon mixture 230. Referring to apparatus 300, the urine-activated carbon mixture 230 is then divided into two equal volumes. One portion is loaded into an impedance analyzer 320 to measure electrical impedance (R NaCl ). Another portion is dropped onto the refractometer 330 to obtain a refractive index reading (n).

[0073] Referring to step 150, the urine osmotic pressure is determined by combining the NaCl molar concentration and the urea molar concentration using equations (1) and (2) according to the following equation:

[0074]

[0075] Among them, (M osm ) estimate indicates that before combining with the empirical factor 270, Figure 1 The urine osmotic pressure estimated by method 100 is shown. Although activated carbon shows good adsorption rate for certain compounds in urine, such as creatinine and uric acid, such adsorption rate does not reach 100%, and activated carbon cannot adsorb many compounds other than conductive solutes and urea. Such chemicals tend to increase the refractive index reading of the urine sample, resulting in the estimated urine osmotic pressure being greater than the actual urine osmotic pressure. For this reason, the value of the urine osmotic pressure can be corrected using an empirical factor e. Referring to step 150, the exact urine osmotic pressure (M) can be determined by multiplying the estimated urine osmotic pressure by the empirical factor. osm ) exact :

[0076] (M osm ) exact =e·(M osm ) estimate (4)

[0077] The factor e can be determined empirically.

[0078] The empirical factor 270 was determined by ten calibration experiments. Urine osmolality was first measured by inputting the electrical impedance and refractive index readings into Equation (3), and then compared with the values ​​measured by a commercially available freezing point osmometer (6002 Touch MicroOSMETTE, Precision Systems, USA). Figure 8 Estimation of urine osmotic pressure ((M osm ) estimate ) and the urine osmotic pressure measured by the freezing point osmometer ((M osm ) exact) Relationship chart 800. In the relationship chart 800, the circle marks represent the experimental data, and the straight line is the best fitting curve forced through the origin. The constrained fitting method of forcing the straight line to pass through the origin shows good goodness of fit, and its R 2 =0.994, indicating that there is a good linear relationship between the two osmotic pressure readings. In this example, the empirical factor e can be calculated to be 0.9082.

[0079] In addition, a clinical validation trial was conducted to test the accuracy of Method 100 in measuring urine osmolality under blinded conditions. Urine samples were collected from 10 subjects at four time points: 1) before dinner; 2) before bed; 3) in the middle of the night; and 4) upon awakening in the morning. Table 1 summarizes the clinical trial results for the first 40 urine samples.

[0080]

[0081]

[0082] Table 1

[0083] As shown in Table 1 , compared with the results obtained in the validation test using a clinical freezing point osmometer, the urine osmolality prediction accuracy of method 100 was as high as 95.3±3.6%. Figure 9A The graph 900 shows the relationship between the urine osmotic pressure measured by the method 100 and the urine osmotic pressure measured by the freezing point osmometer (224 urine samples). In the graph 900, the constraint fitting method that forces the fitting line to pass through the origin has a higher goodness of fit, and its R 2 =0.9959. The linear correlation coefficient between the two osmolalities was 0.9975, and the average accuracy was 94.4±5.0%.

[0084] As an alternative to the linear empirical factor shown in formula (4), other curve fitting functions such as power function and polynomial function can also be used. For example, (M osm ) estimate and (M osm ) exact The power function relationship between can be expressed as:

[0085] (M osm ) exact =A·[(M osm ) estimate ] B (5)

[0086] Among them, the coefficients A and B are determined based on experimental data. Using the data from Table 1 and the other 103 urine samples, the two empirical values ​​are determined to be A=1.176 and B=0.9625. Among the other 103 urine samples, there are pathological urine samples from diabetic patients, whose glucose concentrations are as high as more than 1000 mg / dL. The presence of such glucose molecules will cause the urea concentration estimate of the refractometer to far exceed the actual urea concentration. Therefore, further additional solutions are needed. If the measured concentration of the conductive solute [Conductive] is less than 0.1M and the measured concentration of the non-conductive solute [non-conductive] is greater than 0.5M, the upper limit of the measured concentration of the non-conductive solute [non-conductive] is set to 0.5M to match Figure 7 The calibration range shown is consistent.

[0087] Figure 9B The relationship between the urine osmotic pressure obtained according to equation (5) and the urine osmotic pressure determined by a freezing point osmometer (143 urine samples) is shown in relational graph 910. As shown in relational graph 910, the linear correlation coefficient between the two osmotic pressures is 0.9962, with an average accuracy of 94.5 ± 4.7%.

[0088] Figure 10 FIG1000 is a schematic diagram of an exemplary point-of-care device 1010 derived from device 300. Device 1010 consists of a measuring unit 1020 and a disposable urine container 1030. Disposable urine container 1030 is designed for single use, pre-filled with a certain amount of activated carbon (e.g., 40 mg of activated carbon powder), and can be sealed with a plastic film 1032. It should be noted that other ratios of activated carbon amount to urine volume can also be used, and various empirical factors need to be determined. See Figure 1 The disposable urine container 1030 can receive a urine sample in step 110 so that the urine sample can be mixed with activated carbon in step 120 to obtain a urine-activated carbon mixture. The measurement unit 1020 includes a temperature probe 1022, a pair of impedance probes 1024, and a refractometer 1026. After the disposable urine container 1030 is assembled with the measurement unit 1020, the temperature probe 1022, the pair of impedance probes 1024, and a prism surface of the refractometer 1026 come into contact with the urine-activated carbon mixture.

[0089] Schematic diagram 1040 illustrates exemplary electronic components within the measurement unit. A power module 1042 with a DC power supply (e.g., two AA batteries) drives a mainboard 1044, which enables the mainboard to: obtain temperature, electrical impedance, and refractive index readings from the various probes (temperature probe 1022, impedance probe 1024, and refractometer 1026); process these readings; determine urine osmolality; and display the urine osmolality value on a display module 1046 (e.g., an LCD screen). Mainboard 1044 selects the electrical impedance model and refractive index model used to determine urine osmolality based on the temperature reading obtained by temperature probe 1022.

[0090] Referring to the device 300 , the disposable urine container 1030 serves as the container 310 , the measuring unit 1020 serves as the measuring unit 340 , and the main board 1044 serves as the processing unit 350 .

[0091] like Figure 10 As shown in step 1040 in the figure, the use of this device can include six steps. For example, the end user can first remove the plastic film 1032 on the disposable urine container 1030. Then, the end user can fill the urine sample to the position indicated by the thick marked line 1034. The end user can then hold the disposable urine container 1030 and rotate the measuring unit 1020 to seal the liquid. This allows the three probes to contact the urine sample and mix the urine sample with the pre-installed activated carbon. The neck of the disposable urine container 1030 is designed with threads 1036 to facilitate the following purpose: after the measuring unit 1020 seals the disposable urine container 1030, the temperature probe 1022 and a pair of impedance probes 1024 mix the activated carbon with the urine sample. After waiting for three minutes, the urine osmotic pressure reading can be displayed on the display module 1046. In the final step, the end user can open the point-of-care medical device 1010 and discard the disposable urine container 1030 in the trash.

[0092] Compared with existing commercially available devices, Figure 10 The design shown ensures that the volume of the instant medical device 1010 is much smaller than that of a freezing point osmometer using a laboratory method. Due to the excellent measurement accuracy of this method (as shown in Table 1), the device is simple to use and is expected to significantly reduce manufacturing costs. The device is not only suitable as an instant medical device for use by the elderly at home, but also can be used for large-scale diagnostic screening with rapid turnover. Among them, the consumables for each test are only a plastic container pre-filled with activated carbon. Its cost is expected to not impose a burden on the general public while ensuring continued revenue for the manufacturer.

[0093] Figure 11An exemplary tethered portable urine osmometer 1100 derived from device 300 is shown. Tethered portable urine osmometer 1100 comprises a reading unit 1110, a detachable measuring probe 1120, and a urine cup 1130 pre-filled with activated carbon powder. Reading unit 1110 may include a mainboard, a battery, and a display. Detachable measuring probe 1120 is used to measure electrical impedance, refractive index, and temperature. Reading unit 1110 can select an electrical impedance model and a refractive index model for determining urine osmotic pressure based on the temperature reading obtained by detachable measuring probe 1120.

[0094] Referring to the device 300 , the urine cup 1130 serves as the container 310 , the detachable measuring probe 1120 serves as the measuring unit 340 , and the reading unit 1110 serves as the processing unit 350 .

[0095] Figure 12 Shown is an exemplary integrated portable urine osmometer 1200 derived from device 300. The integrated portable urine osmometer 1200 consists of a reading unit 1210 and a urine cup 1220 pre-filled with a certain amount of activated carbon powder. The reading unit 1210 includes a refractive index module 1212, which may be composed of a light emitting diode (LED) lamp, a prism, and a linear charge coupled device (CCD) sensor. The reading unit 1210 also includes electrodes 1214 for measuring electrical impedance and a temperature sensor 1216. The refractive index module 1212 can be mounted on the vertical side walls of the reading unit 1210 to prevent air bubbles from being trapped. In addition, the reading unit 1210 also includes other necessary components such as a main board, a battery, a display, a probe, and a memory. The reading unit 1210 can select an electrical impedance model and a refractive index model for determining the urine osmotic pressure value based on the temperature reading obtained by the temperature sensor 1216.

[0096] The urine cup 1220 is used to receive urine samples and may contain a measuring chamber 1222 pre-filled with activated carbon powder. The urine cup 1220 is designed with a mechanism that enables the measuring chamber 1222 to open (for example, in a spring-loaded manner) when the probe contained in the reading unit 1210 is inserted, so that the activated carbon powder can be mixed with the urine sample. In addition, the urine cup 1220 may further include components such as a vibrator to achieve mixing of the activated carbon powder and the urine sample by vibration. As an alternative, the activated carbon powder and the urine sample may also be mixed by other feasible methods such as magnetic stirring or manual shaking. Before the probe is inserted, the measuring chamber 1222 may be a sealed space.

[0097] Although Figure 12 Although not shown, as a feasible solution, the device can be configured to measure the electrical impedance of the urine sample before mixing the urine sample with the activated carbon powder. This can be achieved by placing the electrode 1214 outside the measurement chamber 1222 so that the electrode 1214 can measure the electrical impedance of the urine sample before the mixing mechanism is activated.

[0098] The integrated portable urine osmometer 1200 can be further configured to automatically detect the presence of a urine sample; start a timer to measure a specific incubation time (e.g., 3 minutes); and transmit data to a digital device (e.g., a mobile phone) for viewing urine osmotic pressure trends. The probe within the reading unit 1210 can also have other features, such as being replaceable and waterproof to allow immersion in urine and facilitate cleaning.

[0099] Referring to apparatus 300 , urine cup 1220 serves as container 310 , and reading unit 1210 serves as both measurement unit 340 and processing unit 350 . Refractive index module 1212 , electrodes 1214 , and temperature sensor 1216 in reading unit 1210 serve as measurement unit 340 .

[0100] Figure 13 The flowchart in FIG. 1 shows an exemplary urine osmotic pressure measurement process 1300 for the integrated portable urine osmotic pressure meter 1200. Figure 12 , in the starting step 1310 of process 1300, urine sample is collected (such as by urination) in sampling bottle (urine cup 1220) by the end user.In next step 1320, sampling bottle (urine cup 1220) is loaded on urine osmotic pressure measuring device (integrated portable urine osmometer 1200) by the end user.In step 1330 of process 1300, measuring chamber 1222 opens (spring loading) when probe is inserted so that urine sample is mixed with activated carbon powder, for measurement.Subsequently, in step 1340, this device (integrated portable urine osmometer 1200) is such as by the change of electrical impedance, detects whether urine sample volume is sufficient.In subsequent step 1350, this device (integrated portable urine osmometer 1200) carries out the determination of temperature, electrical impedance and refractive index.

[0101] Step 1350 includes multiple sub-steps. In sub-step 1351, the temperature of the urine sample is measured. Referring to calibration process 400, in sub-step 1352, the electrical impedance of the urine sample is measured, and in another sub-step 1353 subsequently, according to the calibration curve generated in step 440, the NaCl concentration (denoted as [NaCl]) of the urine sample is determined. Referring to calibration process 600, sub-step 1354 includes: light intensity distribution is determined by a linear CCD sensor. In sub-step 1355 subsequently, according to the calibration curve generated in step 650, the refractive index of the urine sample is calculated. In addition, in another sub-step 1356, an equivalent urea concentration (denoted as [Urea]) is determined.

[0102] In step 1360, the NaCl concentration and urea concentration determined in step 1350 are combined to calculate the osmotic pressure of the urine sample according to the following formula:

[0103] Urine osmotic pressure = 2[NaCl] + [Urea]

[0104] The final step of process 1300 may be step 1370 , in which the urine osmotic pressure value is displayed on the device (integrated portable urine osmotic pressure meter 1200 ) via a display (such as a small-sized liquid crystal / organic light-emitting diode screen) contained in the reading unit 1210 .

[0105] To verify the accuracy of urine osmolality measurement using method 100, particularly under blinded conditions, a clinical validation trial was conducted. Urine samples were collected from 48 subjects: 41 with nocturnal polyuria (NP) and 7 healthy volunteers. Urine samples were collected at four different time points: 1) before dinner; 2) before bed; 3) in the middle of the night; and 4) upon awakening.

[0106] Figure 14A Graph 1400 shows the sensitivity and specificity of the freezing point osmometer and activated carbon method (i.e., method 100). Table 1402 shows the evaluation results of the freezing point osmometer. As shown in Table 1402, among the patients with nocturia, 28 tested positive and 13 tested negative. Among the healthy volunteers, 2 tested positive and 5 tested negative. Therefore, the sensitivity of this method (i.e., its ability to correctly identify true-positive nocturia patients) is 0.683, and the specificity (i.e., its ability to correctly identify true-negative healthy individuals) is 0.714.

[0107] Table 1404 in chart 1400 shows the results of the activated charcoal method evaluation: Among patients with nocturia, 29 tested positive and 12 tested negative; among healthy volunteers, 2 tested positive and 5 tested negative. Therefore, the sensitivity of this method is 0.707 and the specificity is 0.714.

[0108] Comparing the results shown in Table 1404 with those in Table 1402, the activated charcoal method appears to have slightly higher sensitivity, while the specificity is similar. Overall, the activated charcoal method performs better, or at least at a similar level, than the freezing point osmometer.

[0109] Figure 14B Shown is a graph 1410 comparing urine osmolality measurements from NP patients (unshaded) and healthy volunteers (shaded) using freezing point osmometer and activated charcoal method. As can be seen, urine osmolality obtained using the activated charcoal method exhibits a similar trend compared to freezing point osmometer.

Claims

1. A method for measuring urine osmotic pressure, characterized in that: The method comprises: receiving urine samples; mixing an adsorbent with the urine sample to obtain a urine-adsorbent mixture; determining the electrical impedance of the urine sample; measuring the refractive index of the urine-sorbent mixture; and The osmotic pressure of the urine sample is determined using the electrical impedance of the urine sample and the refractive index of the urine-sorbent mixture.

2. The method according to claim 1, characterized in that Determining the osmotic pressure of the urine sample comprises: Determining the molar concentration of a conductive solute in the urine sample based on the electrical impedance of the urine sample using an electrical impedance model, wherein the electrical impedance model is a model of the relationship between the molar concentration of the conductive solute and the electrical impedance; determining the urea molar concentration of the urine sample based on the refractive index of the urine-sorbent mixture and the molar concentration of the conductive solute in the urine sample using a refractive index model, wherein the refractive index model is a model of the relationship between the refractive index and the molar concentrations of the conductive solute and urea; and The osmotic pressure of the urine sample is determined using the molar concentration of the conductive solute and the molar concentration of urea.

3. The method according to claim 2, characterized in that Determining the osmotic pressure of the urine sample comprises: combining the conductive solute molar concentration with the urea molar concentration to obtain an initial result; and The initial result is adjusted by an empirical factor to obtain the osmotic pressure of the urine sample.

4. The method according to claim 2 or 3, characterized in that Also includes: selecting the electrical impedance model from a plurality of pre-calibrated electrical impedance models; and selecting the refractive index model from a plurality of pre-calibrated refractive index models.

5. The method according to claim 4, characterized in that Also includes: measuring the current ambient temperature, and selecting the electrical impedance model and the refractive index model according to the current ambient temperature, Among them, each of the multiple pre-calibrated electrical impedance models is a model of the relationship between the molar concentration of the conductive solute and the electrical impedance at the corresponding ambient temperature, and each of the multiple pre-calibrated refractive index models is a model of the relationship between the refractive index and the molar concentrations of the conductive solute and urea at the corresponding ambient temperature.

6. The method according to claim 1, characterized in that Determining the electrical impedance of the urine sample includes measuring the electrical impedance of the urine sample.

7. The method according to claim 1, characterized in that Determining the electrical impedance of the urine sample includes measuring the electrical impedance of the urine-sorbent mixture.

8. The method according to any one of claims 1 to 7, characterized in that The adsorbent includes activated carbon powder.

9. A device for measuring urine osmotic pressure, characterized in that: include: a container for holding a urine-adsorbent mixture comprising a urine sample and an adsorbent; A measuring unit, the measuring unit being configured to: determining the electrical impedance of the urine sample and measuring the refractive index of the urine-sorbent mixture; and a processing unit, the processing unit being configured to: The osmotic pressure of the urine sample is determined using the electrical impedance of the urine sample and the refractive index of the urine-sorbent mixture.

10. The device according to claim 9, characterized in that The processing unit includes: a memory storing: an electrical impedance model, the electrical impedance model being a model of the relationship between the molar concentration of the conductive solute and the electrical impedance; and a refractive index model, the refractive index model being a model of the relationship between the refractive index and the molar concentrations of the conductive solute and urea; and A processor, the processor being configured to: determining the molar concentration of a conductive solute in the urine sample based on the electrical impedance of the urine-sorbent mixture using the electrical impedance model; Determining the urea molar concentration of the urine sample based on the refractive index of the urine-adsorbent mixture and the molar concentration of the conductive solute using the refractive index model; and The osmotic pressure of the urine sample is determined using the molar concentration of the conductive solute and the molar concentration of urea.

11. The device according to claim 10, characterized in that The processor is configured to determine the osmotic pressure of the urine sample by: combining the conductive solute molar concentration with the urea molar concentration to obtain an initial result; and The initial result is adjusted by an empirical factor to obtain the osmotic pressure of the urine sample.

12. The device according to claim 10 or 11, characterized in that The memory stores a plurality of pre-calibrated electrical impedance models and a plurality of pre-calibrated refractive index models, and the processor is configured to select the electrical impedance model from the plurality of pre-calibrated electrical impedance models and select the refractive index model from the plurality of pre-calibrated refractive index models.

13. The device according to claim 12, characterized in that The measuring unit further includes a thermometer for measuring the current ambient temperature, and the processor is configured to select the electrical impedance model and the refractive index model according to the current ambient temperature measured by the measuring unit. Among them, each of the multiple pre-calibrated electrical impedance models is a model of the relationship between the molar concentration of the conductive solute and the electrical impedance at the corresponding ambient temperature, and each of the multiple pre-calibrated refractive index models is a model of the relationship between the refractive index and the molar concentrations of the conductive solute and urea at the corresponding ambient temperature.

14. The device according to any one of claims 9 to 13, characterized in that The container and the measuring unit are configured to be connectable in such a manner that, when the container is connected to the measuring unit, the measuring unit seals the container and mixes the adsorbent with the urine sample.

15. The device according to any one of claims 9 to 14, characterized in that The adsorbent is disposed in the container, wherein the container is also used to receive the urine sample.

16. The device according to claim 15, characterized in that The container contains a sealed space for containing the adsorbent. The container and the measuring unit are configured such that when the measuring unit is inserted, the sealed space is opened, thereby allowing the adsorbent to contact the urine sample and the adsorbent and the urine sample to be mixed by the measuring unit.

17. The device according to claim 9, characterized in that The measuring unit is configured to determine the electrical impedance of the urine sample by measuring the electrical impedance of the urine sample.

18. The device according to claim 9, characterized in that The measuring unit is configured to determine the electrical impedance of the urine sample by measuring the electrical impedance of the urine-sorbent mixture.

19. The device according to any one of claims 9 to 18, characterized in that The adsorbent includes activated carbon powder.

20. The device according to any one of claims 9 to 19, characterized in that Also includes: A display is provided for displaying the osmotic pressure value of the urine sample.

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