Blood urea nitrogen (BUN) sensor and method of sensing urea nitrogen in biological sample

Abstract

One embodiment of a blood urea nitrogen (BUN) sensor measures urea nitrogen in a biological sample by measuring a differential voltage signal based on first and second voltage signals, the first and second voltage signals each representing a detected amount of carbon dioxide. The first signal represents a detected amount of carbon dioxide resulting from an enzymatic reaction of a biological sample contacting a sensor surface having urease immobilized thereon. The second voltage signal represents a detected amount of background carbon dioxide in the biological sample. The differential voltage signal is indicative of the amount of urea nitrogen in the biological sample, which can be determined by an appropriate correlation. Other embodiments of a BUN sensor and a method of sensing a BUN are also provided, as are other aspects.

Description

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 514,397, filed July 19, 2023, under 35 USC §119(e). The entire contents of the patent application cited above are hereby expressly incorporated herein by reference. Technical Field

[0002] This disclosure relates to a blood urea nitrogen (BUN) sensor and a method for sensing urea nitrogen in biological samples. Background Technology

[0003] Blood urea nitrogen (BUN) is a waste product found in the human bloodstream. It originates from the liver, which produces BUN by breaking down proteins in the body. BUN is normally filtered from the bloodstream by the kidneys and removed from the body through urine. Some BUN in the bloodstream is normal.

[0004] Human kidney function can be assessed by measuring the amount of urea nitrogen in the blood. The test used to measure urea nitrogen is called the blood urea nitrogen (BUN) test. BUN values ​​ranging from 6 mg / dL to 24 mg / dL can be considered normal. BUN values ​​higher or lower than this range can indicate disease and / or unhealthy conditions (e.g., impaired kidney function, heart failure, liver failure, urinary tract obstruction, stress, malnutrition, dehydration, and / or excessive protein consumption).

[0005] However, the accuracy of conventional BUN testing can be adversely affected by factors such as the presence of potassium ions in the blood sample, the pH level of the blood sample, and / or the presence of background ammonia in the blood sample. Correction for these factors is required for measurement accuracy. Such correction can increase the cost and complexity of BUN sensors, and conventional BUN sensors may not be calibrated for background ammonia.

[0006] Therefore, improvements to the BUN sensor and the method for sensing urea nitrogen are desired. Summary of the Invention

[0007] In some embodiments, a sensor for measuring urea nitrogen in a biological sample is provided. The sensor includes first and second sensor components and a voltmeter. The first sensor component is operable to generate a first voltage signal indicating the amount of carbon dioxide detected in response to contact of the biological sample with the first sensor component. The first sensor component includes a first sensing membrane and a urease fixed above and in contact with the first sensing membrane. A second sensor component is operable to generate a second voltage signal indicating the amount of carbon dioxide detected in response to contact of the biological sample with the second sensor component. The second sensor component includes a second sensing membrane, which does not have any enzyme fixed thereon. The voltmeter is coupled to receive the first and second voltage signals and outputs a differential voltage signal value based on the first and second voltage signals. The differential voltage signal value corresponds to the amount of urea nitrogen in the biological sample.

[0008] In some embodiments, a method for measuring urea nitrogen in a biological sample is provided. The method includes generating a first voltage signal via the first sensor assembly in response to contact of the biological sample with the first sensor assembly. The first voltage signal indicates the amount of carbon dioxide, and the first sensor assembly has a first sensing membrane and a urease fixed above and in contact with the first sensing membrane. The method further includes generating a second voltage signal via the second sensor assembly in response to contact of the biological sample with the second sensor assembly. The second voltage signal indicates the amount of carbon dioxide, and the second sensor assembly has a second sensing membrane but does not have any enzyme fixed above and in contact with the second sensing membrane. The method further includes generating a differential voltage signal based on the first and second voltage signals via a voltmeter, and converting the value of the differential voltage signal into a corresponding amount of urea nitrogen in the biological sample via a computer processor.

[0009] In some embodiments, another sensor is provided for measuring urea nitrogen in a biological sample. The sensor includes a housing and a single electrode, wherein the single electrode is partially housed within the housing. The sensor also includes a buffer solution disposed within the housing and in which the electrode is partially immersed. The sensor further includes a pH-sensing membrane disposed above and in contact with the buffer solution, an electrolyte layer disposed above and in contact with the pH-sensing membrane, a permeable membrane disposed above and in contact with the electrolyte layer, and a single enzyme immobilized above and in contact with the permeable membrane. The electrode is operable to generate a voltage signal indicating the amount of urea nitrogen in response to the enzyme contacting the biological sample.

[0010] Other aspects, features, and advantages of this disclosure may readily become apparent from the following detailed description and illustrations of various exemplary embodiments and implementations, including the contemplated best mode for carrying out the invention. This disclosure may also have other and different embodiments, and several details therein may be modified in various respects without departing from the scope of the invention. For example, the BUN sensor described herein can be readily applied to online fluid flow pathways in dialysis systems and / or open-heart circulatory systems to monitor a patient's renal function. More particularly, the BUN sensor described herein can be installed in a dialysis system as an online testing unit to monitor a patient's renal function. This disclosure is intended to cover all modifications, equivalents, and substitutions falling within the scope of the appended claims below. Attached Figure Description

[0011] The accompanying drawings described below are for illustrative purposes and are not necessarily drawn to scale. Therefore, the drawings and description are intended to be illustrative in nature and not restrictive. The drawings are not intended to limit the scope of the invention in any way.

[0012] Figure 1 The illustration shows a side view of a blood urea nitrogen (BUN) sensor configured to measure urea nitrogen in a biological sample according to an embodiment provided herein.

[0013] Figure 2 A flowchart illustrating a method for measuring urea nitrogen in a biological sample according to an embodiment provided herein is shown.

[0014] Figure 3 The illustration shows a side view of another BUN sensor configured to measure urea nitrogen in a biological sample according to an embodiment provided herein. Detailed Implementation

[0015] Conventional blood urea nitrogen (BUN) sensors are typically based on ammonium ion (NH4+) selective electrodes using viable urease as an ammonium ion carrier, wherein urease is used on the electrode surface to convert blood urea in biological samples (e.g., blood or urine) into ammonium ions, as represented in equation (1) below: CO(NH2)2+H2O and [urease] -> 2NH3+ CO2 (1) In this context, CO(NH2)2 is urea, H2O is water, 2NH3 is ammonia, and CO2 is carbon dioxide.

[0016] The value (or amplitude) of the electrical signal (e.g., measured in millivolts) generated by an ammonium ion-selective electrode in response to the detection of ammonium ions can correspond to the amount or concentration of urea nitrogen in a biological sample. However, the measurement accuracy of such conventional BUN sensors can be adversely affected by several factors, including the presence of coexisting potassium ions (K+) in the biological sample. Coexisting potassium ions interfere with viable urea-based ammonium ion-selective electrodes. To correct for this interference, a selectivity coefficient (or selectivity factor) must be determined and applied to a correction algorithm.

[0017] The measurement accuracy of conventional BUN sensors can also be adversely affected by the pH level of biological samples, which may negatively influence the conversion of urea nitrogen to ammonium. To correct for this factor, the correlation between pH level and ammonia yield must be developed and applied to a calibration algorithm for conventional BUN sensors. Based on such an algorithm, the effect of pH on BUN recovery can be corrected using the onboard pH sensor assembly included in conventional BUN sensors.

[0018] The measurement accuracy of conventional BUN sensors is further adversely affected by background ammonia in biological samples. For example, background ammonia can be as high as 0.2 mmol / M in infants and may be even higher in adults with hepatitis, cirrhosis, Reye's syndrome, or heart and / or kidney disease. Such background ammonia can adversely increase the measured blood urea nitrogen. Currently, correction for background ammonia is unknown in conventional BUN sensors.

[0019] The BUN sensor according to embodiments described herein overcomes one or more of the aforementioned measurement inaccuracies by determining the amount (or concentration) of urea nitrogen in a biological sample (e.g., blood or urine) by measuring the CO2 byproduct from a single enzymatic reaction. In one embodiment described in more detail below, a specially designed sensor pair can be used to determine the amount (or concentration) of urea nitrogen in a biological sample. One sensor component of the sensor pair includes an enzyme, and the other sensor component does not include an enzyme. The amount of urea nitrogen in the biological sample can be measured by the specially designed sensor pair, i.e., by measuring the electrical (voltage) signal difference between a first voltage signal generated by a sensor component modified with urease attached to the surface of the sensor component and a second electrical signal generated by another sensor component not modified with any enzyme (which may be a standard carbon dioxide sensing component). The electrical signal difference (e.g., in millivolts) can be measured using a voltmeter or similar electronic measuring device. The differential voltage signal value output from the voltmeter corresponds to the amount of urea nitrogen.

[0020] In some embodiments, the amount of urea nitrogen can be determined by a computer processor executing programming instructions by accessing data stored in a non-transitory memory, which may include a Nernst equation for calculating the amount of urea nitrogen based on differential voltage signal values. Additionally or alternatively, the non-transitory memory may include multiple differential voltage signal values ​​corresponding to multiple amounts of urea nitrogen. In some embodiments, the correspondence may be based on Nernst behavior. Note that the BUN sensor according to the embodiments described herein does not directly measure or determine the carbon dioxide concentration in a biological sample, but instead measures the difference between voltage signals indicating the amount of detected carbon dioxide to determine the amount of urea nitrogen in the biological sample.

[0021] In another embodiment, described in more detail below, a modified Severinghaus-type pCO2 (partial pressure carbon dioxide) sensor can be used to determine the amount (or concentration) of urea nitrogen in a biological sample (e.g., blood or urine). This sensor is modified to include a single enzyme, urease, wherein direct electrical signal measurements (not differential electrical signal measurements) are performed and correlated to determine the amount of urea nitrogen in the biological sample.

[0022] Advantages of a BUN sensor employing a carbon dioxide sensing component according to embodiments described herein include the absence of measurement interference from coexisting potassium ions in the biological sample and the absence of adverse measurement results caused by background ammonia in the biological sample. Another advantage of a BUN sensor employing a carbon dioxide sensing component according to embodiments described herein includes the use of only a single enzyme to convert urea into ammonia and carbon dioxide. Some known BUN sensors use two enzymes (e.g., urease and carbonic anhydrase) to obtain pCO2 values, where the second enzyme is used to accelerate the response rate. However, using two enzymes increases the cost and complexity of such a BUN sensor.

[0023] According to one or more embodiments, the following will be combined with Figures 1-3 A more detailed explanation of the BUN sensor for measuring urea nitrogen in biological samples, which offers improved measurement accuracy.

[0024] Figure 1A BUN sensor 100 configured to measure urea nitrogen in a biological sample according to one or more embodiments is illustrated. The BUN sensor 100 includes a first sensor assembly 102 and a second sensor assembly 103, each partially housed in a housing 104 configured to house and contain a biological sample 106, such as blood or urine. The first sensor assembly 102 is operable to generate a first voltage signal V102 in response to the detection of carbon dioxide, wherein the value (or amplitude) of the first voltage signal corresponds to the amount of carbon dioxide detected. The first sensor assembly 102 may include an electrode 108A coupled to a voltmeter 110. The electrode 108A may be a silver / silver chloride electrode, which advantageously has a longer lifespan (e.g., four weeks) and a more stable response signal than other types of electrodes, making it suitable for reusable sensor arrays. Alternatively, platinum or gold electrodes may be used. The first sensor assembly 102 may also include an electrolyte layer 112A partially disposed on the electrode 108A. The electrolyte layer 112A may include 0.5% methylcellulose (e.g., Methocel). TM The first sensor assembly 102 uses a sodium bicarbonate electrolyte in solution, which forms a gel layer on electrode 108A. The gel layer is easily fabricated in a miniaturized form, thus facilitating the fabrication of the sensor on an electronic wafer / chip. Other electrolyte materials may include PVOH (polyvinyl alcohol). The first sensor assembly 102 may further include a sensing membrane 114A, which may be a plasticized PVC (polyvinyl chloride) or polyurethane membrane. The first sensor assembly 102 may also include urease 116 fixed above and in contact with the sensing membrane 114A. Urease 116 is preferably a thin layer, and in some embodiments, it may have a thickness ranging from 20 μm to 50 μm. Further, urease 116 may partially or completely cover the surface of the sensing membrane 114A on which urease 116 is fixed. In one exemplary embodiment, urease 116 covers at least 75% of the sensing membrane 114A to ensure that the majority of the first voltage signal V102 generated at electrode 108A is caused by the enzymatic reaction of the biological sample with urease 116.

[0025] The second sensor assembly 103 generates a second voltage signal V103 in response to the detection of background carbon dioxide (i.e., pre-existing carbon dioxide) in the biological sample 106, wherein the value (or amplitude) of the second voltage signal corresponds to the amount of background carbon dioxide detected. The second sensor assembly 103 may include an electrode 108B coupled to a voltmeter 110. The electrode 108B may also be a silver / silver chloride electrode, or alternatively, a platinum or gold electrode. The second sensor assembly 103 may also include a sodium bicarbonate electrolyte layer 112B partially disposed around the electrode 108B. The electrolyte layer 112B may include a 0.5% methylcellulose (e.g., methoxel) electrolyte layer. TMSodium bicarbonate electrolyte in solution forms a gel layer on electrode 108B. Other electrolyte materials may include PVOH. The second sensor assembly 103 may further include a sensing membrane 114B, which may be a plasticized PVC or polyurethane membrane, without any enzymes fixed above and in contact with the sensing membrane 114B, such as... Figure 1 As shown in the diagram.

[0026] Voltmeter 110 is coupled to receive first and second voltage signals V102 and V103 from first and second sensor assemblies 102 and 103, respectively, and is operable to determine and output a differential voltage signal value VDIFF based on the first and second voltage signals (VDIFF = V102-V103), the differential voltage signal value VDIFF corresponding to the detected amount of urea nitrogen in biological sample 106.

[0027] The output differential voltage signal value VDIFF of voltmeter 110 is coupled to computer 118. In some embodiments, computer 118 may communicate directly via wired and / or wireless connection or via network 120 with other computers, system controllers, or other devices (e.g., automated diagnostic analysis systems, laboratory information systems, medical facilities, etc.) to transmit urea nitrogen measurement results and / or to receive biological sample-related information, including, for example, one or more of patient information, the time and date the sample was acquired, medical facility information, tracking and routing information, and / or any other information related to the biological sample to be analyzed. Network 120 may be, for example, a local area network (LAN), a wide area network (WAN), or other suitable communication network, including wired and wireless networks. In some embodiments, computer 118 may be part of an automated diagnostic analysis system, laboratory information system, medical facility, etc.

[0028] Computer 118 may include user interface 122, which may include a display to enable a user to access a variety of control and status displays and to input commands and / or data into computer 118.

[0029] Computer 118 may also include a computer processor 118P, non-transitory memory 118M, and programming instructions 118PI (e.g., software, programs, algorithms, and the like). Programming instructions 118PI may be stored in non-transitory memory 118M and executed by computer processor 118P. Programming instructions 118PI may additionally or alternatively be stored in another non-transitory computer-readable medium. Non-transitory memory 118M may also include data 118D accessible by computer processor 118P. Data 118D may include, for example, a Nernst equation for calculating urea nitrogen amounts based on differential voltage signal values. Data 118D may additionally or alternatively include multiple differential voltage signal values ​​and corresponding multiple urea nitrogen amounts arranged in, for example, a lookup table, database, or other suitable structure. In some embodiments, the correspondence between differential voltage signal values ​​and urea nitrogen amounts may be based on Nernst behavior. Non-transitory memory 118M may include other data and / or information that can be used by computer processor 118P to convert or correlate differential voltage signal values ​​to corresponding urea nitrogen amounts. Although the non-transitory memory 118M is shown as being inside the computer 118, all or part of the non-transitory memory 118M may be outside the computer 118 and / or remote from the computer 118. The computer 118 may alternatively or additionally include other processing devices / circuits (including microprocessors, A / D converters, amplifiers, filters, etc.), storage devices, transceivers, interfaces, device drivers, and / or other electronic components.

[0030] The computer processor 118P, which executes programming instructions 118PI, becomes a dedicated machine, particularly suitable for performing various actions, operations, analyses, and the like according to the sensors and methods described herein and illustrated in the figures. In particular, the computer processor 118P, which executes programming instructions 118PI, is operable to receive, among other things, the differential voltage signal value (VDIFF) from the voltmeter 110 and determine the amount of urea nitrogen corresponding to the differential voltage signal value (VDIFF).

[0031] Figure 2 The illustration depicts a method 200 for measuring urea nitrogen in a biological sample according to one or more embodiments. At process block 202, method 200 may include generating a first voltage signal via the first sensor assembly in response to contact of the biological sample with the first sensor assembly, wherein the first voltage signal indicates the amount of carbon dioxide, and the first sensor assembly has a first sensing membrane and urease fixed above and in contact with the first sensing membrane. For example, refer to... Figure 1The first sensor assembly may be a first sensor assembly 102, which has a sensing membrane 114A and a urease 116 fixed above and in contact with the sensing membrane 114A, wherein the first sensor assembly 102 generates a first voltage signal V102. In response to contact with the first sensor assembly 102, the biological sample 106 reacts with the urease 116 to produce ammonia and carbon dioxide according to Equation 1, repeated below: CO(NH2)2+H2O and [urease] -> 2NH3+ CO2 (1) Depending on the amount of urea nitrogen present in the biological sample, the total carbon dioxide concentration in biological sample 106 can increase with the carbon dioxide produced by the enzyme.

[0032] At process block 204, method 200 may include generating a second voltage signal via the second sensor assembly in response to contact of a biological sample with the second sensor assembly, wherein the second voltage signal indicates the amount of carbon dioxide, and the second sensor assembly has a second sensing membrane without any enzyme fixed above and in contact with the second sensing membrane. For example, refer again Figure 1 The second sensor assembly can be a second sensor assembly 103 having a sensing membrane 114B but without any enzyme fixed above and in contact with the sensing membrane 114B, wherein the second sensor assembly 103 generates a second voltage signal V103. Background carbon dioxide in the biological sample 106 permeates through the sensing membrane 114B into the sodium bicarbonate electrolyte layer 112B, which increases the hydrogen ion concentration (H₂O) in the sodium bicarbonate electrolyte layer 112B. + The concentration of ) generates a second voltage signal (V103).

[0033] At process block 206, method 200 may include generating a differential voltage signal via a voltmeter based on the first and second voltage signals. For example, as Figure 1 As shown, voltmeter 110 can receive first and second voltage signals (V102 and V103) from first and second sensor assemblies 102 and 103 respectively, and can generate a differential voltage signal value (VDIFF = V102 – V103) for computer 118.

[0034] The amount of urea nitrogen in biological samples correlates with the differential signal value as follows: Higher urea nitrogen, higher CO2, greater VDIFF In some embodiments, for the signal (V102) generated by the enzyme reaction, the slope of the net signal change relative to the BUN concentration ranges from 30 mV to 50 mV / decimal.

[0035] At process block 208, method 200 may include converting the value of a differential voltage signal into the corresponding amount of urea nitrogen in a biological sample via a computer processor. For example, a computer processor 118P executing programming instructions 118PI of computer 118 may receive the differential voltage signal value from voltmeter 110 and convert the differential voltage signal value into the corresponding amount of urea nitrogen by accessing data 118D in non-transitory memory 118M of computer 118. Data 118D may include an equation for calculating the amount of urea nitrogen based on the differential voltage signal value, which in some embodiments may be a Nernst equation, as shown below: Standard Nernst equation: EMF = constant + =constant+ in: [M]: Ion concentration, in mol / L or mmol / L; EMF: Electrodynamic force (voltage). For ISE (ion-selective electrode), EMF is the response signal of the ion sensor; Constant: The standard signal (voltage) at a concentration [M] = 1 mol / L. For ISE, it is considered as an offset; RT / zF: A constant including temperature, ion charge number, etc. EMF is proportional to the logarithm of ion concentration; For monovalent ions, 2.303*RT / zF = 59.2 mV / decade conc. It changes at a temperature of 298K (25°C); and For divalent ions, 2.303*RT / zF = 29.8 mV / decade conc. It changes at a temperature of 298K (25C).

[0036] For BUN sensor 100: =Offset + Slope in: mV(BUN) is linearly correlated with log[BUN]. The offset and slope can be obtained from calibration prior to sample testing; and The recovered concentration of BUN in the sample can be calculated as follows: .

[0037] Data 118D may instead (or additionally) include multiple differential voltage signal values ​​corresponding to multiple urea nitrogen amounts, wherein in some embodiments, the correspondence may exhibit Nernst behavior (as described above).

[0038] Figure 3 Another embodiment of a BUN sensor configured to measure urea nitrogen in a biological sample (e.g., blood or urine) according to one or more embodiments is illustrated. The BUN sensor 300 is a modified Severinghaus-type pCO2 (partial pressure carbon dioxide) sensor that measures urea nitrogen via direct measurement of CO2 produced by a single enzyme reaction. Sensor assembly 302 may include a housing 304 having only a single electrode 308, which may be a silver / silver chloride electrode. Alternatively, electrode 308 may be a platinum or gold electrode. Electrode 308 is partially immersed in a buffer solution 324 having a known pH. Buffer solution 324 may be, for example, sodium citrate or MES buffer solution (MES is the generic name for the compound 2-ethanesulfonic acid). The BUN sensor 300 may also include a single enzyme 316 fixed above and in contact with a permeable membrane 326. The single enzyme includes urease and covers at least 75% of the permeable membrane 326 to ensure that most of the voltage signal V302 generated at electrode 308 is generated from the biological sample ( Figure 3 (Not shown) This is caused by the enzymatic reaction with urease 316. A permeable membrane 326 is disposed above the sodium bicarbonate electrolyte layer 312. In some embodiments, the permeable membrane 326 may be a cellulose acetate film or a polyurethane film, and may have a thickness ranging from 10 μm to 30 μm. In some embodiments, the sodium bicarbonate electrolyte layer 312 may be a thin layer having a thickness ranging from 100 μm to 500 μm after hydration. A pH sensing membrane 314 is disposed between the sodium bicarbonate electrolyte layer 312 and the buffer solution 324. In some embodiments, the pH sensing membrane 314 may have a thickness ranging from 80 μm to 120 μm.

[0039] The electrode 308 of the BUN sensor 300 can be coupled to a voltmeter 310, which is operable to receive a voltage signal V302 and output a voltage signal value VBUN, which corresponds to the amount of urea nitrogen detected in the biological sample applied to the BUN sensor 300 (i.e., applied to urease 316).

[0040] In some embodiments, the output of voltmeter 310 can be coupled to computer 318, and computer 318 can be configured to ( Figure 1This is a dedicated machine identical or substantially similar to computer 118. Specifically, computer 318 may include at least a processor, non-transitory memory, programming instructions (e.g., software, programs, algorithms, and the like) stored in the non-transitory memory and executable by the processor, and data stored in the non-transitory memory, which may include equations for calculating urea nitrogen levels and / or multiple voltage signal values ​​corresponding to multiple urea nitrogen levels. Computer 318 is operable to receive a voltage signal value VBUN from voltmeter 310 and executes the programming instructions stored in its non-transitory memory via its processor, converting the voltage signal value into a corresponding urea nitrogen level by accessing the data stored in its non-transitory memory.

[0041] In some embodiments, computer 318 may communicate directly with other computers, system controllers, or other devices (e.g., automated diagnostic analysis systems, laboratory information systems, medical facilities, etc.) via wired and / or wireless connections or via a network to transmit urea nitrogen measurement results and / or to receive information related to biological samples, including, for example, one or more of patient information, the time and date the sample was acquired, medical facility information, tracking and routing information, and / or any other information related to the biological sample to be analyzed. The network may be, for example, a local area network (LAN), a wide area network (WAN), or other suitable communication network, including wired and wireless networks. In some embodiments, computer 318 may be part of an automated diagnostic analysis system, laboratory information system, medical facility, etc.

[0042] While this disclosure allows for various modifications and alternatives, specific method and apparatus embodiments have been illustrated by way of example in the accompanying drawings and described in detail herein. However, it should be understood that the specific methods and apparatus disclosed herein are not intended to limit this disclosure or the following claims.

[0043] Regardless of the use of grammatical terms, individuals with male or female identities are included in this term.

[0044] Illustrative Examples The following is a non-limiting list of illustrative embodiments of this disclosure: Example 1: A sensor for measuring urea nitrogen in biological samples, comprising: A first sensor assembly operable to generate a first voltage signal indicating the amount of carbon dioxide detected in response to contact of a biological sample with the first sensor assembly, the first sensor assembly including a first sensing membrane and a urease fixed above and in contact with the first sensing membrane. A second sensor assembly operable to generate a second voltage signal indicating the amount of carbon dioxide detected in response to contact of a biological sample with the second sensor assembly, the second sensor assembly including a second sensing membrane without any enzymes fixed thereon; and A voltmeter operably coupled to receive first and second voltage signals, and operable to output a differential voltage signal value based on the first and second voltage signals, the differential voltage signal value corresponding to the amount of urea nitrogen in a biological sample.

[0045] Example Embodiment 2: The sensor according to Example Embodiment 1 further includes a computer processor operatively coupled to a voltmeter, the computer processor being operatively coupled to a non-transitory memory, the non-transitory memory including programming instructions executable on the computer processor and including data for associating differential voltage signal values ​​with corresponding urea nitrogen amounts; wherein the computer processor executing the programming instructions is operable to receive the value of the differential voltage signal from the voltmeter and determine the amount of urea nitrogen corresponding to the differential voltage signal value.

[0046] Example 3: A sensor according to any one of Example 1 or 2, wherein the data includes a Nernst equation for calculating urea nitrogen content based on differential voltage signal values, or includes multiple differential voltage signal values ​​corresponding to multiple urea nitrogen contents via Nernst behavior.

[0047] Example 4: The sensor according to any one of Example 1-3 further includes a housing, the housing including first and second sensor assemblies each partially housed therein, wherein the housing is operable to house and contain a biological sample therein.

[0048] Example 5: The sensor according to any one of Example 1-4, wherein: The first sensor assembly further includes a first silver / silver chloride electrode coupled to a voltmeter; and The second sensor assembly further includes a second silver / silver chloride electrode coupled to the voltmeter.

[0049] Example 6: The sensor according to any one of Example 1-5, wherein: The first sensor assembly further includes a first electrode and a first sodium bicarbonate electrolyte layer disposed around a portion of the first electrode; and The second sensor assembly further includes a second electrode and a second sodium bicarbonate electrolyte layer disposed around a portion of the second electrode.

[0050] Example 7: The sensor according to any one of Example 1-6, wherein the biological sample includes blood or urine.

[0051] Example 8: A method for measuring urea nitrogen in a biological sample, the method comprising: A first voltage signal is generated via the first sensor assembly in response to contact of a biological sample with the first sensor assembly, the first voltage signal indicating a first amount of carbon dioxide, the first sensor assembly having a first sensing membrane and a urease fixed above and in contact with the first sensing membrane; A second voltage signal is generated via the second sensor assembly in response to contact of a biological sample with the second sensor assembly. The second voltage signal indicates a second amount of carbon dioxide. The second sensor assembly has a second sensing membrane but does not have any enzyme fixed above and in contact with the second sensing membrane. A differential voltage signal is generated via a voltmeter based on the first and second voltage signals; and The value of the differential voltage signal is converted into the corresponding amount of urea nitrogen in the biological sample by a computer processor.

[0052] Example 9: The method according to any one of Example Examples 1-8, wherein the conversion further includes, via a computer processor, converting the value of a differential voltage signal into the corresponding amount of urea nitrogen in a biological sample based on data stored in a non-transitory memory accessible by a computer processor, wherein the data includes a Nernst equation for calculating the corresponding amount of urea nitrogen based on the value of the differential voltage signal, or includes multiple differential voltage signal values ​​corresponding to multiple amounts of urea nitrogen via Nernst behavior.

[0053] Example 10: The method according to any one of Example Examples 1-9, wherein: The first sensor assembly further includes a first silver / silver chloride electrode coupled to a voltmeter; and The second sensor assembly further includes a second silver / silver chloride electrode coupled to the voltmeter.

[0054] Example 11: The method according to any one of Example Examples 1-10, wherein: The first sensor assembly further includes a first electrode and a first sodium bicarbonate electrolyte layer disposed around a portion of the first electrode; and The second sensor assembly further includes a second electrode and a second sodium bicarbonate electrolyte layer disposed around a portion of the second electrode.

[0055] Example 12: The method according to any one of Example Examples 1-11, wherein the biological sample includes blood or urine.

[0056] Example 13: A sensor for measuring urea nitrogen in biological samples, comprising: shell; Only a single electrode, which is partially housed within the housing; A buffer solution is disposed within a housing and in which the electrodes are partially immersed; A pH sensing membrane positioned above and in contact with a buffer solution; An electrolyte layer disposed above and in contact with the pH sensing membrane; A permeable membrane disposed above and in contact with the electrolyte layer; and A single enzyme is immobilized above and in contact with the permeable membrane; wherein: In response to a contact enzyme in a biological sample, the electrode can be manipulated to generate a voltage signal indicating the amount of urea nitrogen.

[0057] Example 14: The sensor according to any one of Example Examples 1-13 further includes a voltmeter operably coupled to an electrode, the voltmeter being operable to output a voltage value based on a voltage signal.

[0058] Example 15: The sensor according to any one of Example Examples 1-14 further includes a computer operatively coupled to a voltmeter and operable to convert a voltage value into an amount of urea nitrogen.

[0059] Example 16: A sensor according to any one of Example Examples 1-15, wherein the electrode comprises a silver / silver chloride electrode.

[0060] Example 17: The sensor according to any one of Example Examples 1-16, wherein the buffer solution comprises sodium citrate or MES buffer solution.

[0061] Example 18: The sensor according to any one of Example Examples 1-17, wherein the electrolyte layer comprises a sodium bicarbonate electrolyte layer.

[0062] Example 19: A sensor according to any one of Example Examples 1-18, wherein the single enzyme comprises urease.

[0063] Example 20: A sensor according to any one of Example Examples 1-19, wherein urease covers at least 75% of the permeable membrane.

Claims

1. A sensor for measuring urea nitrogen in biological samples, comprising: A first sensor assembly operable to generate a first voltage signal indicating the amount of carbon dioxide detected in response to contact of a biological sample with the first sensor assembly, the first sensor assembly including a first sensing membrane and a urease fixed above and in contact with the first sensing membrane. A second sensor assembly operable to generate a second voltage signal indicating the amount of carbon dioxide detected in response to contact of a biological sample with the second sensor assembly, the second sensor assembly including a second sensing membrane without any enzymes fixed thereon. and A voltmeter operably coupled to receive first and second voltage signals, and operable to output a differential voltage signal value based on the first and second voltage signals, the differential voltage signal value corresponding to the amount of urea nitrogen in a biological sample.

2. The sensor of claim 1, further comprising a computer processor operatively coupled to a voltmeter, the computer processor being operatively coupled to a non-transitory memory, the non-transitory memory including programming instructions executable on the computer processor and including data for associating differential voltage signal values ​​with corresponding amounts of urea nitrogen; wherein the computer processor executing the programming instructions is operable to receive values ​​of the differential voltage signal from the voltmeter and determine the amount of urea nitrogen corresponding to the differential voltage signal values.

3. The sensor of claim 2, wherein the data includes a Nernst equation for calculating urea nitrogen levels based on differential voltage signal values, or includes multiple differential voltage signal values ​​corresponding to multiple urea nitrogen levels via Nernst behavior.

4. The sensor of claim 1, further comprising a housing including first and second sensor assemblies each partially housed therein, wherein the housing is operable to house and contain a biological sample therein.

5. The sensor according to claim 1, wherein: The first sensor assembly further includes a first silver / silver chloride electrode coupled to a voltmeter; and The second sensor assembly further includes a second silver / silver chloride electrode coupled to the voltmeter.

6. The sensor according to claim 1, wherein: The first sensor assembly further includes a first electrode and a first sodium bicarbonate electrolyte layer disposed around a portion of the first electrode; and The second sensor assembly further includes a second electrode and a second sodium bicarbonate electrolyte layer disposed around a portion of the second electrode.

7. The sensor of claim 1, wherein the biological sample comprises blood or urine.

8. A method for measuring urea nitrogen in a biological sample, the method comprising: A first voltage signal is generated via the first sensor assembly in response to contact of a biological sample with the first sensor assembly, the first voltage signal indicating a first amount of carbon dioxide, the first sensor assembly having a first sensing membrane and a urease fixed above and in contact with the first sensing membrane; A second voltage signal is generated via the second sensor assembly in response to contact of a biological sample with the second sensor assembly. The second voltage signal indicates a second amount of carbon dioxide. The second sensor assembly has a second sensing membrane but does not have any enzyme fixed above and in contact with the second sensing membrane. A differential voltage signal is generated via a voltmeter based on the first and second voltage signals; and The value of the differential voltage signal is converted into the corresponding amount of urea nitrogen in the biological sample by a computer processor.

9. The method of claim 8, wherein the conversion further comprises, via a computer processor, converting the value of the differential voltage signal into a corresponding amount of urea nitrogen in the biological sample based on data stored in a non-transitory memory accessible by a computer processor, said data comprising a Nernst equation for calculating the corresponding amount of urea nitrogen based on the value of the differential voltage signal, or comprising a plurality of differential voltage signal values ​​corresponding to a plurality of urea nitrogen amounts via Nernst behavior.

10. The method of claim 8, wherein: The first sensor assembly further includes a first silver / silver chloride electrode coupled to a voltmeter; and The second sensor assembly further includes a second silver / silver chloride electrode coupled to the voltmeter.

11. The method of claim 8, wherein: The first sensor assembly further includes a first electrode and a first sodium bicarbonate electrolyte layer disposed around a portion of the first electrode; and The second sensor assembly further includes a second electrode and a second sodium bicarbonate electrolyte layer disposed around a portion of the second electrode.

12. The method of claim 8, wherein the biological sample comprises blood or urine.

13. A sensor for measuring urea nitrogen in biological samples, comprising: shell; Only a single electrode, which is partially housed within the housing; A buffer solution is disposed within a housing and in which the electrodes are partially immersed; A pH sensing membrane positioned above and in contact with a buffer solution; An electrolyte layer disposed above and in contact with the pH sensing membrane; A permeable membrane positioned above and in contact with the electrolyte layer; and A single enzyme is immobilized above and in contact with the permeable membrane; wherein: In response to a contact enzyme in a biological sample, the electrode can be manipulated to generate a voltage signal indicating the amount of urea nitrogen.

14. The sensor of claim 13, further comprising a voltmeter operably coupled to the electrodes, the voltmeter being operable to output a voltage value based on a voltage signal.

15. The sensor of claim 14, further comprising a computer operatively coupled to a voltmeter and operable to convert a voltage value into an amount of urea nitrogen.

16. The sensor of claim 13, wherein the electrode comprises a silver / silver chloride electrode.

17. The sensor of claim 13, wherein the buffer solution comprises sodium citrate or MES buffer solution.

18. The sensor of claim 13, wherein the electrolyte layer comprises a sodium bicarbonate electrolyte layer.

19. The sensor of claim 13, wherein the single enzyme comprises urease.

20. The sensor of claim 19, wherein the urease covers at least 75% of the permeable membrane.

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