Analyte sensor components

Abstract

A sensor component for use in a system for measuring a concentration of an analyte in a fluid in a fluid line includes one or more sensing elements having optical properties that vary with the concentration of the analyte and engages the fluid line such that the sensing elements are exposed to the fluid. The sensor component includes a connector that connects to one or more optical waveguides and transmits light between the waveguides and the sensing elements. The sensor component includes one or more sampling ports configured to provide fluid access to the fluid line, a data storage medium that stores data representative of information about the sensor component, and a reflective element. When including a reflective element, the sensor component transmits light between the waveguide and the reflective element on an optical path separate from the optical path between the waveguide and the sensing element.

Description

Technical Field

[0001] The present invention relates to sensor components used to measure the concentration of an analyte in a fluid, particularly using the optical properties of a sensing element.

Background Art

[0002] In many areas, it is desirable to be able to determine the concentration of an analyte in a fluid containing a mixture of several different substances. For example, in a clinical setting, it is important to accurately determine in real time the concentration of oxygen in a patient's blood in order to detect and prevent hypoxia. Clinical settings where monitoring of blood analytes is important include, by way of example, cardiopulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), and continuous renal replacement therapies (CRRT).

[0003] Cardiopulmonary bypass (CPB) technology allows cardiac surgery to be performed in a stationary, bloodless surgical field. The new CPB machine features systems for monitoring pressure, temperature, oxygen saturation, and hemoglobin, as well as bubble detectors and low-level alarms for the reservoir. Cardiopulmonary bypass patients are susceptible to physiological fluctuations in blood gas levels due to oxygenation, electrolyte changes, and fluid movement during CPB. Potentially adverse patient outcomes from these fluctuations may include hypoxia and hyperxia, hypocapnia and hypercapnia, and acid-base denaturation. The American Society of Extracorporeal Technology, "Standards and Guidelines for Perfusion Practice," Appendix D, May 2017, suggests that PO2, PCO2, pH, SO2, potassium, ionized calcium, sodium, lactate, glucose, and hemoglobin / hematocrit should be measured frequently or continuously. From these measured blood gas data, other useful parameters such as base excess, bicarbonate, oxygen transport, oxygen consumption, and oxygen uptake can be calculated.

[0004] ECMO is a recent evolution from CPB and is applicable to patients with hypoxemia despite maximum conventional ventilatory support, patients with significant ventilator-induced lung injury, or patients in cardiogenic shock. The setup of the device is similar to that of CPB, but it is generally used for very long periods (e.g., 30 days is not uncommon) and is usually located in the intensive care unit. CRRT is a hemodialysis treatment delivered as a 24-hour continuous therapy and is suitable for patients with hemodynamically unstable acute renal failure (ARF). Intermittent hemodialysis is suitable for patients with chronic renal impairment.

[0005] One known type of sensor employed in these settings uses a luminescent compound, such as a fluorescent organic dye, which has a luminescence lifetime dependent on the concentration of the analyte. By exciting the luminescent compound and measuring its luminescence lifetime, the concentration of the analyte can be determined. This type of system has the advantage of being able to operate continuously, thus eliminating the need to periodically collect blood samples for analysis or other similarly inconvenient procedures. The clinical utility of continuous real-time monitoring is particularly important when monitoring clinically significant and rapidly changing analytes in critically ill patients. The information provided allows clinicians to respond by titrating administered therapies. Thus, continuous real-time data can be considered to provide feedback to treatment.

[0006] In intermittent testing, the clinician's view of the patient's condition at the time a new blood sample is taken is governed by the analyte values ​​given by previous samples. Gaps in knowledge of the patient's condition between blood samples (known as blind intervals) can pose a risk to the patient. These gaps can be eliminated by using continuous sensors. Continuous monitoring should allow for accurate measurement of a given analyte over long periods, providing indications of changes in analyte concentration (showing trends), and thereby providing clinicians with continuous, minute-by-minute patient condition information. This helps deliver effective treatment, eliminates blind intervals, and thereby reduces risk to the patient.

[0007] To provide these benefits, a crucial requirement for continuous sensors is maintaining accuracy over long periods. Inaccuracies can be caused by continuous drift of sensor readings or more abrupt changes, such as damage to the sensor. These inaccuracies are particularly important because they may not be immediately distinguishable from true physiological changes in analyte concentration. Consequently, clinicians may be provided with misinformation that incorrectly impacts administered treatment, thereby endangering patients. This is less of a concern for intermittent monitoring where blood samples are taken and introduced into sensors such as blood gas analyzers. This is because, although the sensor may drift relatively quickly, there is little drift time between calibration and measurement, so it is not significant in terms of accuracy, as the sensor is calibrated immediately before each measurement. [Prior art documents] [Non-patent literature]

[0008] [Non-Patent Document 1] The American Society of Extracorporeal Technology, "Standards and Guidelines for Perfusion Practice," Appendix D, May 2017. [Overview of the project] [Means for solving the problem]

[0009] A first aspect of the present invention relates to providing a sensor component for continuous monitoring that is more accurate and less prone to drift.

[0010] According to a first aspect of the present invention, a sensor component for use in a system for measuring the concentration of one or more analytes in a fluid in a fluid line, the sensor component comprising: one or more sensing elements having optical properties that vary with the concentration of one or more analytes in the fluid, wherein the sensor component is configured to engage with a fluid line such that the sensing elements are exposed to the fluid in the fluid line; a connector configured to connect to one or more optical waveguides, wherein the sensor component is configured to transmit light between one or more optical waveguides and one or more sensing elements; and a sampling port configured to provide fluid access to the fluid line when the sensor component is engaged with the fluid line.

[0011] A sampling port provided as part of the sensor component means that, either during the initial installation of the sensor component or if readings from one or more of the sensing elements are found to drift, the readings will be inaccurate for a certain period of time, after which a fluid sample can be taken from the local port. The sample can be analyzed with an approved analyzer and values ​​used to calibrate the readings from the sensing elements to compensate for the inaccuracy. Including a sampling port as part of the sensor component also has the advantage that the fluid sample is taken in physical proximity to the sensing elements, and the concentration of the analyte in the fluid sample reflects the concentration at the sensing elements as accurately as possible.

[0012] In some embodiments, the sampling port includes a one-way valve configured to allow unidirectional fluid flow from the fluid line. Using a one-way valve prevents the sampling port from being used to introduce substance into the fluid line, which may be inappropriate at the location of the sensor component or may cause erroneous readings from the sensor component by locally affecting the concentration of the analyte.

[0013] In some embodiments, the sampling port includes a component fitting configured to engage with an external fitting. The component fitting ensures that the sampling port is securely and reliably engaged by the external fitting of the device used to collect the sample. This prevents possible contamination or other errors during sampling. In some embodiments, the component fitting includes a Luer fitting, a type of fitting commonly available in clinical settings.

[0014] In some embodiments, the sampling port is configured to open when the external fitting engages with the component fitting. This reduces the number of operations required to acquire a sample, thereby improving ease of use.

[0015] In some embodiments, the sampling port is self-closing. This also improves ease of use by reducing the operation required by the user and reduces the chance of contamination if the sampling port is not quickly and properly closed after sample collection.

[0016] In some embodiments, the sampling port is up to 20 cm from one or more sensing elements. Physical proximity to the sensing elements ensures that the sample taken using the sampling port has the analyte concentration that reflects the concentration at the sensing element at the time of sampling. This helps improve the accuracy of calibrations performed using the sample.

[0017] In some embodiments, the sampling port is provided with a removable cap configured to seal the sampling port. This allows the port to be more securely sealed and protected from potential damage, especially when not in use for extended periods.

[0018] A second aspect of the present invention also relates to providing a sensor component for continuous monitoring that is more accurate and less prone to drift.

[0019] A second aspect of the present invention provides a sensor component for use in a system for measuring the concentration of one or more analytes in a fluid in a fluid line, the sensor component comprising: one or more sensing elements having optical properties that vary with the concentration of one or more analytes in the fluid, wherein the sensor component is configured to engage with a fluid line such that the sensing elements are exposed to the fluid in the fluid line when the sensor component is engaged with the fluid line; a connector configured to connect to one or more optical waveguides, wherein the sensor component is configured to transmit light between one or more optical waveguides and one or more sensing elements; and a reflecting element, wherein the sensor component is also configured to transmit light between one or more optical waveguides and the reflecting element on an optical path separate from the optical path between one or more optical waveguides and one or more sensing elements.

[0020] By incorporating a reflective element, light can be transmitted along an optical path that does not include the sensing element. This provides additional measurements that can be compared with measurements obtained from the optical path that includes the sensing element. Such comparisons then ensure that any inaccuracies caused by factors such as small mechanical misalignments in the optical interface, or by optical loss due to minor damage to one or more optical waveguides, can be distinguished from changes in transmission caused by changes in the concentration of the analyte in the fluid. This allows for an assessment of whether the accuracy of the analyte concentration measurements has deteriorated sufficiently to require corrective action, such as recalibration or replacement of the sensor components.

[0021] In some embodiments, the reflective element is concave. The concave reflector can concentrate light, allowing the reflected light to be more effectively transmitted back into the optical waveguide.

[0022] In some embodiments, the reflector is planar. Planar reflectors may be easier to manufacture and assemble than concave reflectors.

[0023] In some embodiments, the reflective element is configured to reflect at least 10% of the light incident thereon and return it to one or more waveguides. This achieves a minimum level of reflectivity so that the signal from the reflective element can be reliably detected.

[0024] Another important requirement for sensor components is that, especially in the case of replaceable or disposable ones, the individual sensor components and related information are not confused with each other. The sensor components may have properties that vary between batches, may be associated with a particular device or patient, and may have various other relevant metadata. Tracking such information is important for providing accurate information and ensuring patient safety, but can be difficult when multiple individual sensor components are stored or used in the same environment.

[0025] A third aspect of the present invention relates to providing a replaceable sensor component for continuous monitoring that is accurate and the information can be easily and robustly associated with the sensor component.

[0026] According to a third aspect of the present invention, there is provided a replaceable sensor component for use in a system for measuring the concentration of one or more analytes in a fluid within a fluid line, the sensor component comprising one or more sensing elements having an optical property that varies depending on the concentration of one or more analytes in the fluid, the sensor component being configured to engage with the fluid line such that the sensing elements are exposed to the fluid within the fluid line when the sensor component is engaged with the fluid line, a connector configured to connect to one or more optical waveguides, the sensor component being configured to transmit light between the one or more optical waveguides and the one or more sensing elements, and a data storage medium configured to store data representing information about the sensor component.

[0027] Storing information regarding a sensor component in a data storage medium is advantageous when the sensor component is replaceable, for example, disposable and / or single-use. This ensures that information regarding parameters specific to each sensor component is essentially tied to that particular sensor component, thereby reducing the likelihood of errors caused by confusion between different sensor components.

[0028] In some embodiments, the replaceable sensor component further comprises an interface circuit configured to transmit signals between the data storage medium and the system. This simplifies the retrieval or storage of information in the data storage medium. In some embodiments, the interface circuit is configured to transmit signals wirelessly. This can improve usability by eliminating the need for a physical connection to the data storage medium.

[0029] In some embodiments, the information includes one or more characteristics of one or more sensing elements. Since the characteristics of the sensing elements may vary between manufacturing batches, storing those characteristics in the data storage medium ensures that the exact characteristics of each sensor component are readily available.

[0030] In some embodiments, the information includes calibration information regarding variations in the optical properties of the sensing element due to the concentration of one or more analytes and / or the temperature of the sensing element. In this case, storing the information in the data storage medium of the sensor component ensures that calibration information specific to each sensor component is available, thereby improving the accuracy of determining the concentration of the analyte.

[0031] In some embodiments, the information includes one or more characteristics of the calibration fluid used to calibrate interchangeable sensor components. This simplifies the calibration process when a particular calibration fluid is used such that its characteristics do not need to be provided by the user. In some embodiments, the information includes the pH variation of the calibration fluid with respect to temperature. This allows the accuracy of the calibration to be further improved depending on the conditions at the time of calibration.

[0032] In some embodiments, the information includes an identifier for the patient to whom the interchangeable sensor component is associated. This prevents the sensor component from being reused with multiple patients, which could lead to cross-contamination or other problems. In some embodiments, the data storage medium is configured to receive the identifier during system initialization and to store the identifier so that the interchangeable sensor component is permanently associated with a patient. Permanently storing the patient identifier further helps prevent the reuse of the sensor component with multiple patients.

[0033] In some embodiments, the information includes an identifier for the system to which the interchangeable sensor component is associated. Since the behavior or performance of a sensor component may vary depending on the connected system, reusing a sensor component in a different system may result in inaccurate calibration. Storing a system identifier can help prevent or identify when this occurs.

[0034] In some embodiments, the information may include one or more of the following: an indication of the previous use of the replaceable sensor component, an indication of whether damage has occurred to the replaceable sensor component, a usage period after which the replaceable sensor component should not be used, the service life of the replaceable sensor component, the length of time the replaceable sensor component has been used, a unique identifier for the replaceable sensor component, the manufacturing date of the replaceable sensor component, the time the replaceable sensor component was last calibrated, and an indication of the number and / or type of errors that occurred during the use of the replaceable sensor component. All of these parameters can be used to assess the effectiveness of the calibration of the sensor component and whether its continued use is recommended, thereby improving the accuracy of the readings obtained and patient safety. Knowing some of these parameters may also be required for compliance with regulations, so storing them on the sensor component itself reduces the burden on the user of recording the information elsewhere.

[0035] The following additional features may be combined with any of the three embodiments of the present invention discussed above.

[0036] In some embodiments, the sensor component further comprises a fluid-permeable support element for supporting the sensing element, which is positioned between the sensing element and the fluid in the fluid line when the sensor component is engaged with the fluid line. This can protect the sensing element from mechanical influences that have an effect on the position of the sensing element and on the measurement of its optical properties due to its position, for example, due to the pulsating flow of the fluid through the fluid line. In some embodiments, the permeable support element includes a mesh. This is a particularly simple method for providing a fluid-permeable support element that is easy to manufacture and assemble.

[0037] In some embodiments, the sensing element comprises a permeable membrane to at least one of the analytes configured to be exposed to the fluid in the fluid line when the sensor component is engaged with the fluid line. This can provide permeability specific to the analyte so that each sensing element is not exposed to other components of the fluid that would affect its interaction with the analyte.

[0038] In some embodiments, the sensor component comprises two or more sensing elements. This allows a single sensor component to simultaneously detect multiple analytes, thereby reducing the number of components required to monitor the concentration of analytes in a fluid.

[0039] In some embodiments, the sensor component further includes a light-absorbing element located between the sensing elements. This prevents cross-stimulation of the sensing elements by light directed at other sensing elements, thereby reducing a potential source of error.

[0040] In some embodiments, the connector includes a transparent optical element configured to transport light between the sensing element and one or more optical waveguides, or to each of the sensing elements. This protects the sensing element from mechanical or chemical damage when the sensor component is not connected to one or more optical waveguides. In some embodiments, the transparent optical element includes a waveguide. This reduces light loss due to the transparent optical component.

[0041] In some embodiments, the sensor component further comprises a temperature sensor arranged to sense the temperature of one or more sensing elements. This allows the measurement to be adjusted to account for changes in optical properties or the dependence of the analyte concentration as a function of temperature. In some embodiments, the temperature sensing element is a thermistor or thermocouple. These are readily available and well-understood components for measuring temperature.

[0042] In some embodiments, the sensor component is configured to engage with the wall of the fluid line. This provides a convenient engagement mechanism and minimizes the size of the sensor component.

[0043] In some embodiments, the sensor component further comprises a conduit, the sensing element is exposed to the fluid within the conduit, and the conduit is configured to be inserted into the fluid line for engagement of the sensor component with the fluid line. This can be more convenient in some situations depending on the configuration of the fluid line with which the sensor component engages.

[0044] In some embodiments, the conduit is configured to be inserted into the fluid line in an in-line configuration. This minimizes interruptions to the fluid flow within the fluid line.

[0045] In some embodiments, the conduit is configured to be inserted into the fluid line in a shunt configuration. This allows the sensor components to be attached and detached without interrupting the fluid flow in the fluid line.

[0046] Embodiments of the present invention will now be described as non-limiting examples with reference to the accompanying drawings. [Brief explanation of the drawing]

[0047] [Figure 1] This is an isometric projection of the sensor components before they are connected to one or more waveguides and engaged with the fluid line. [Figure 2] This is a cross-sectional view of the sensor component shown in Figure 1, which engages with a fluid line and is connected to one or more waveguides. [Figure 3] Figures 1 and 2 are exploded isometric projection views of the sensor components. [Figure 4] This is an exploded view showing further elements of the sensor components. [Figure 5] These are isometric projection views of the sensor components shown in Figures 1 to 3, engaged with the fluid line. [Figure 6] This figure shows an embodiment of a sensor component equipped with a conduit. [Figure 7] Figure 6 is an exploded view of some of the sensor components. [Figure 8]This figure shows the sensor component of Figure 6 engaged with the fluid line in a shunt configuration. [Modes for carrying out the invention]

[0048] As described above, the present invention has three embodiments, all relating to improving measurement accuracy using sensor components and assisting in the detection and reduction of drift in measurements when sensor components are used continuously for long periods. The features that differ among the three embodiments are the sampling port, the reflector element, and the data storage medium, respectively. Each of these features will be discussed in more detail below. In the embodiments discussed herein, all three of these features are provided simultaneously in the same sensor component. This achieves the greatest benefit from all combinations of the features. However, it should be understood that it is not necessary to provide all three features in combination, and it is equally possible to provide any one of the three features individually in the sensor component, as represented by the three embodiments described above. It is also possible to provide a sensor component having any combination of two of the three features, and so as to, the corresponding benefits and advantages are still provided.

[0049] Figure 1 shows a sensor component 1 used in a system for measuring the concentration of one or more analytes in a fluid in a fluid line 3. The system is preferably used in a clinical setting, for example, as part of an ECMO, CPB, or CRRT machine as described above. In such cases, the fluid in the fluid line 3 is the patient's blood. However, this is not mandatory, and the sensor component 1 may also be used in other settings, for example, to monitor the concentration of analytes in gases. Analytes measured by a system using sensor component 1 may include oxygen, carbon dioxide, hydrogen ions (i.e., pH), potassium, sodium, calcium, magnesium, ammonia, nitric oxide, or anesthetic gases.

[0050] Sensor component 1 comprises a black plastic construction. The plastic can be readily manufactured to the desired specifications and can be sterilized for use in clinical settings. However, the use of plastic is not mandatory, and other suitable materials, such as resin or metal, may be used. The black color of sensor component 1 helps to eliminate optical crosstalk between the sensing elements 5. However, generally, sensor component 1 may have any color. Preferably, when used in blood-contact medical devices, the material of sensor component 1 is biocompatible and non-leaching, thus preventing contamination of the patient's blood. When used in continuous monitoring applications, especially if the final calibration before use depends on constants determined during manufacturing, potential unforeseen changes to the properties of sensor component 1 (particularly the sensing elements 5 and optical components) during its post-manufacturing shelf life should also be considered. Therefore, materials with chemical and optical properties that are stable over time are preferred. Care should also be taken to ensure that foreign matter generated during manufacturing or sterilization does not adversely affect the drift of sensor measurements during use, resulting in inaccuracies.

[0051] The sensor component 1 is preferably packaged and provided to the user in such a way that it is sterile and hydrated with a buffer / calibration solution having a known or predetermined concentration of the analyte to be detected. For some analytes (such as any of the exemplary analytes described above, excluding hydrogen ions / pH), the predetermined concentration may, in some embodiments, preferably be zero. When oxygen and / or carbon dioxide are detected, their concentrations can be reduced to zero by an impurity removal material sealed in the packaging with the sensor component 1. The buffer / calibration solution provides the first of two calibration points. In some embodiments, the hydration and sterility of the blood contact surface of the sensor component 1 are maintained by a removable aluminum tab.

[0052] The sensor component 1 comprises one or more sensing elements 5. The sensor component shown herein comprises four sensing elements, but this is not essential, and other embodiments may include one, two, three, or more than four sensing elements 5. Each sensing element 5 comprises a luminescent compound, preferably a fluorescent compound, more preferably a fluorescent organic dye. The luminescent compound may differ for different sensing elements 5 and depends on the analyte being measured. Suitable luminescent compounds include, for example, seminaphsalnodafluor (SNARF), Mag-Fluor-4, and derivatives thereof. The sensing elements may contain luminescent compounds suspended, dissolved, or molecularly bonded in a matrix. The matrix may contain a polymer, such as PMMA or polystyrene. Alternatively, the matrix may contain a sol gel or a hydrogel.

[0053] Fluorescent optical continuous monitoring sensors are susceptible to photobleaching of the fluorescent dye in fluorescent compounds, resulting in an effective loss of the concentration of the fluorescent compound in the sensing element 5. This can introduce drift into the measurement over time. Photobleaching is typically the result of some of the fluorescent dye molecules being excited into a highly reactive triplet state, which can then react with materials in the local environment to produce non-fluorescent molecules. Fluorescent compounds are preferably selected for their robustness in minimizing photobleaching of the fluorescent dye. Another way to minimize photobleaching is to optimize the intensity of the light used to stimulate the luminescent compound and optimize the working cycle of the incident excitation light. For example, if a data point is required every 15 seconds to generate a continuous trend of analyte concentration, the light source may then only be "turned on" for a mere 10 milliseconds every 15 seconds, being on for only 0.07% of that time. In a 4-hour CPB example, the fluorescent dye is excited for a total of only 10 seconds.

[0054] The sensing element 5 has optical properties that vary with the concentration of one or more analytes in the fluid. The optical properties may be light emission or absorption. If the sensing element 5 contains a light-emitting compound, the optical properties may be the luminescence lifetime. The optical properties may be the same for all of the sensing elements 5, or they may differ among the sensing elements 5. Various measurement modes may be used to minimize drift in the sensor. Modes proportional to fluorescence lifetime and supply voltage are commonly used when available because they are less vulnerable to common error sources that can cause drift. The supply voltage proportional mode, for example, involves taking two measurements of light from the light-emitting compound at different wavelengths and calculating the ratio. However, since linear intensity measurement methods are often the only modes available, it is important that the design of the sensor component 1 is chosen to minimize drift and inaccuracy.

[0055] The sensor component 1 is configured to engage with the fluid line 3 so that the sensing element 5 is exposed to the fluid in the fluid line 3. As shown in Figure 2, the sensor component 1 engages with the fluid line 3 so that the sensing element 5 is exposed to the interior of the fluid line 3 so that the fluid flowing through the fluid line 3 past the sensor component 1 comes into contact with the part of the sensor component 1 facing the interior of the fluid line 3.

[0056] As shown in Figure 3, two of the sensing elements 5 are provided with a membrane 21 that is permeable to at least one of the analytes configured to be exposed to the fluid in the fluid line 3 when the sensor component 1 is engaged with the fluid line 3. The membrane 21 may be provided for any or all of the sensing elements 5 as a whole. The membrane 21 is permeable to at least the analyte sensed by the sensing element 5 to which the membrane 21 is provided. Providing the membrane 21 ensures higher specificity by preventing the sensing element 5 from interacting with other components of the fluid that could affect the optical properties of the sensing element 5, thereby ensuring that the sensing element 5 is not affected by interactions with analytes other than those it is intended to sense. For example, the membrane 21 can prevent large biomolecules such as proteins or blood cells from interacting with the sensing element 5. If the analyte is O2, CO2, NO, NH3, or an anesthetic gas, the membrane 21 may be a hydrophobic gas permeable membrane. If the analyte is soluble in water or plasma, the membrane 21 may be a hydrophilic membrane, such as a hydrogel. Preferred membranes may include microporous membranes or dialysis membranes.

[0057] As shown in Figure 4, the sensor component 1 includes a fluid-permeable support element 19 for supporting the sensing element 5, which is positioned between the sensing element 5 and the fluid in the fluid line 3 when the sensor component 1 is engaged with the fluid line 3. The fluid-permeable support element 19 provides mechanical support and protection to the sensing element 5. This can be advantageous when the fluid flow in the fluid line 3 is highly pulsating and has significant pressure fluctuations, such as in a CPB or ECMO machine. Without the fluid-permeable support element 19, such fluctuations could cause small movements or deformations of the sensing element 5, changing the optical path length through the sensing element, affecting the measurement of its optical properties, and potentially introducing errors. The permeable support element 19 preferably includes a mesh, such as stainless steel or plastic mesh. Although a permeable support element 19 is provided for each sensing element 5 in the figure, it may not be necessary depending on the mechanical properties of the individual sensing element 5.

[0058] Figure 4 also shows that the sensor component 1 further comprises a light-absorbing element 23 located between the sensing elements 5. This element may be provided in any embodiment in which the sensor component 1 comprises two or more sensing elements 5. The light-absorbing element 23 prevents optical crosstalk between the sensing elements 5, which could introduce errors into the measurement of the optical properties of the sensing elements.

[0059] The sensor component 1 includes a connector 7 configured to connect to one or more optical waveguides. In the illustrated embodiment, the optical waveguides are comprised of an optoelectric interface 9, and the connector 7 has a recess in the sensor component 1 that engages with the interface 9. However, the connector 7 as a whole may take any preferred form and may include retaining elements such as clips or screws to prevent movement of one or more optical waveguides relative to the connector 7.

[0060] The optical waveguide allows light to be transmitted to one or more light sources at other locations in the system in which the sensor component 1 is used. In the illustrated embodiment, light is transmitted along the interface 9 through the optical waveguide from one or more light sources. Suitable light sources include LEDs or laser diodes. The photoelectric interface 9 is entirely waste-free and connects the sensor component 1 to a system for measuring analyte concentrations, such as a patient data module (PDM). The optical waveguide may comprise an optical fiber or optical fiber bundle that transmits excitation light to the sensing element 5. The light emitted from (or transmitted through) the sensing element 5 is also returned via the optical waveguide in the interface 9 to a detector in the PDM that detects the intensity of the light from the sensing element 5. The optical waveguide is abutted against a transparent optical element 25. The interface 9 also provides means for electrically connecting to a temperature sensor 27 and a data storage medium 15.

[0061] In other embodiments, the sensor component 1 may comprise one or more optical waveguides and / or one or more light sources and detectors, and the interface 9 may only provide electrical connections to other components of the system, or may not be present at all. Since the sensor component 1 is configured to transmit light between one or more optical waveguides and one or more sensing elements 5, the optical properties of the sensing elements 5 can be measured.

[0062] As shown in Figure 2, the connector 7 includes a transparent optical element 25 to each of the sensing elements 5, configured to transport light between the sensing element 5 and one or more optical waveguides. This protects the sensing element 5 from physical or chemical damage, especially when the interface cable 9 is not connected. The transparent optical element 25 may itself include a waveguide to ensure optimal transmission of light to and from the sensing element 5. The transparent optical element 25 acts as a window of light connecting the optical waveguide to the sensing element 5.

[0063] As shown in Figures 1 to 3, the sensor component 1 comprises a temperature sensor 27 arranged to sense the temperature of one or more sensing elements 5. The optical properties of the sensing element 5, and / or its dependence on the concentration of the analyte, may vary depending on the temperature of the sensing element 5. Therefore, knowing the temperature of the sensing element 5 can improve the accuracy of determining the concentration of the analyte in the fluid. Preferably, the temperature sensing element 27 is a thermistor or a thermocouple. The sensor component 1 may comprise one or more electrical contacts or contact wells to allow electrical connection to the temperature sensing element 27 for the purpose of measuring temperature. The temperature sensor 27 may be used to measure blood temperature.

[0064] There are two main options for placing the sensor component 1 in the fluid line 3, which may be an extracorporeal blood line. The sensor component 1 may be placed within the main fluid line 3 itself, or it may be placed as a shunt in a peripheral line of the main fluid line 3. The sensor components in Figures 1 to 5 are configured to engage with the wall of the fluid line 3. This embodiment is therefore engaged with the main fluid line 3.

[0065] In some embodiments, the sensor component 1 further comprises a conduit 29, and the sensing element 5 is exposed to the fluid in the conduit 29. The conduit 29 may comprise a section of piping of the same type as the fluid 3, for example, the section of piping in which the sensor component 1 engages in Figure 5. The conduit 29 may be configured to be inserted into the fluid line 3 in order to engage the sensor component with the fluid line 3. As described above, the conduit 29 may be configured to be inserted into the fluid line 3 in an in-line configuration or in a shunt configuration (also called a bypass configuration).

[0066] Accurate pre-use calibration is crucial for achieving accurate monitoring thereafter. Calibration at the point of use should also be as easy as possible for the user, if not completely invisible. Sensor component 1 described herein uses a calibration method that requires two calibration measurements at the point of use.

[0067] In the embodiment shown in Figure 5, the sensor component 1 engages with the main line of the fluid line 3, but the installation process for using the sensor component 1 may be as follows.

[0068] Before engaging the sensor component 1 with the fluid line 3, the sensor component 1 is provided sterile by being hydrated in a separate pack (the sensing elements 5 are exposed to the buffer). The in-line connector 33 with which the sensor component 1 engages is already incorporated into the fluid line 3, with a protective cap / plug in place covering the opening 31. If the sensor component 1 includes a conduit 29, the in-line connector 33 may function as the conduit 29. The sensor component 1 is then connected to the interface 9 and receives light transmitted at an appropriate wavelength to measure the optical properties of each sensing element 5 via one or more optical waveguides. One or more optical waveguides can also return the light to a detector in the system. The buffer in the packaging of the sensor component 1 preferably contains a known or predetermined concentration of the analyte to be measured.

[0069] The system automatically measures the first calibration point of one or more analytes when sensor component 1 is connected to the interface, but this process is invisible to the user, thus improving ease of use. Hydration / buffer solution may be trapped behind the aluminum foil layer, but acts as the first calibration solution.

[0070] The inline connector 33 is filled with a priming fluid, which may have known concentrations of one or more analytes different from those in the buffer solution. The protective cap / plug is removed from the opening 31 as the protective cover is removed from the sensing element 5, and the sensor component 1 is immediately attached to the inline connector 33. The priming fluid is replaced with a fluid (e.g., blood).

[0071] When the sensor component 1 is placed inline and the sensing element 5 comes into contact with the fluid, a fluid sample is taken adjacent to the sensor component 1 either upstream or downstream of the fluid line 3. The concentration of one or more analytes in the sample is measured by an approved external analyzer, such as a blood gas analyzer. The data is fed back into the system to provide a second calibration point.

[0072] As just explained, an alternative to the sensor component 1, which engages with the main line of fluid line 3, is a shunt system that bypasses the main line. In such an embodiment, the sensor component 1 comprises a conduit 29 incorporated into a sterilization device, as shown in Figure 6. The conduit 29 is then configured to be inserted into the fluid line 3 in a shunt configuration, also known as a shunt configuration. The conduit 29 may be joined to the rest of the sensor component 1 by any preferred means, for example, ultrasonic welding.

[0073] In the embodiment shown in Figure 6, the sensor component 1 engages with the fluid line 3 in a shunt configuration, but the installation process for using the sensor component 1 may be as follows.

[0074] In the in-line configuration described above, the sensor component 1 is hydrated and sterilized and placed in a separate pack. However, in this embodiment, the sensor component 1 also includes a conduit 29. The sensor component is packaged together with a shunt pipe 35 and a shunt tap 37, which are attached and sterile. The main fluid line 3 is provided with a tap 39 that receives the shunt pipe 35. The main fluid line 3 is sterilized in an extracorporeal piping set. In the in-line configuration, the sensor component 1 is connected to interface 9 to measure the first calibration point.

[0075] Next, the protective cap is removed from the shunt tap 37, and the shunt tap 37 is connected to the tap 39 in the main fluid line. Then, the shunt tap 37 is opened, and the fluid flows through the shunt piping and through the conduit 29. The sensing element 5 is exposed to the fluid in the conduit 29. Finally, for the in-line configuration, a fluid sample is taken and used to establish a second calibration point.

[0076] Numerous factors can affect the accuracy and drift in the measurement of the optical properties of the sensing element 5. If the sensing element 5 contains a fluorescent compound, the fluorescence emission F1 is given by the following equation. F1 = I0(2.303εcl)φ In the above equation, I0 is the intensity of the light entering the sensing element 5. This light is generated from one or more light sources and transmitted to the sensing element 5 via one or more optical waveguides. ε is the absorption coefficient or molar decay coefficient, which is constant for a given fluorescent compound. It is defined as the light absorbed by a 1 molar concentration of the detected fluorescent compound with a path length of 1 cm. c represents the concentration of the absorbing species, which in this example is a fluorescent compound. l is the optical path length between the light source and the detector containing the fluorescent compound. φ is quantum efficiency, a measure of the energy change when a molecule is excited to a high energy level and then reduced to a lower energy level through fluorescence emission.

[0077] All of these parameters are taken into consideration and kept constant during the calibration process. Changes in values ​​after calibration can be continuous or sudden due to damage to sensor component 1, resulting in inaccurate measurement of analyte concentration due to either gradual drift or more sudden changes in the signal. In the design of a continuous sensor component, these parameters should be kept as constant as possible. After all means of reducing drift have been applied to the design of sensor component 1, only low levels of drift may be encountered. Thus, inaccuracy becomes significant only over long periods. This is unlikely to be a problem in CPD, but it is possible in long-term dialysis and ECMO treatment.

[0078] As discussed above, a fluid sample is required to establish a second calibration point. A first aspect of the present invention relates to a sampling port 11 as shown in Figures 2 and 3. The sampling port 11 is configured to provide fluid access to the fluid line 3 when the sensor component 1 is engaged with the fluid line 3, as shown in Figure 2.

[0079] By providing a sampling port 11 incorporated within the sensor component 1, the accuracy of calibration is ensured by making sure that the fluid sample is taken from the fluid flowing over the sensing element 5, in close proximity to or as close as possible to the sensing element 5. In some embodiments, the sampling port 11 is up to 20 cm, preferably up to 10 cm, and more preferably up to 5 cm, from one or more sensing elements 5.

[0080] The proximity of the sampling port 11 to the sensing element 5 is advantageous because a fluid sample taken away from the sensing element 5 will have a different analyte concentration than that measured by the sensing element 5 at the time the fluid sample was taken. For example, this can occur due to the metabolism of the analyte. This means that the concentration in the fluid sample does not represent the concentration measured by the sensing element 5, leading to calibration errors and subsequent measurement errors. The sample may be taken through the sampling port 11 by any preferred method, for example, using a syringe.

[0081] The sampling port 11 is equipped with a one-way valve configured to allow a one-way flow of fluid from the fluid line 3. This allows the fluid sample to be taken without compromising the sterility of the fluid line 3 or posing any risk of contamination of the fluid within the fluid line 3. The sampling port 11 is equipped with a component fitting configured to engage with an external fitting. This allows for a secure connection when taking a sample. Specifically, the component fitting is a Luer fitting, thereby making the sampling port 11 a Luer-activated sampling port. While a Luer fitting is preferred, it is not mandatory, and other suitable types of component fittings may be used.

[0082] The sampling port 11 is configured to open when an external fitting engages with a component fitting. The sampling port 11 may also be self-closing. This improves ease of use for the user, ensures sterility, and helps eliminate fluid leakage from the fluid line 3 through the sampling port 11. The sampling port 11 may further include, but is not required, a removable cap 13 configured to seal the sampling port 11. The removable cap 13 can protect the sampling port 11 from damage or contamination if the sampling port 11 is not used for an extended period.

[0083] A second aspect of the present invention relates to a data storage medium 15 configured to store data representing information about a sensor component 1. This is particularly useful when the sensor component 1 is replaceable. For example, when the sensor component 1 is designed to be disposable and intended to be used only in a single treatment for a single patient. The data storage medium 15 may include a microchip.

[0084] To enable the calibration method described above, which requires only two calibration points at the point of use, some of the properties of the sensing element 5 and the sensor component 1 may be determined during or after manufacturing, before the replaceable sensor component 1 is supplied to the end user. These properties are transferred along with the replaceable sensor component 1 stored in memory in the data storage medium 15. This is particularly useful, for example, when the detection characteristics of the sensor component 1 vary between manufacturing batches. The data storage medium 15 may also store data to ensure that the replaceable sensor component 1 operates correctly during calibration and use, and / or to ensure compliance with various legal and / or clinical requirements regarding the replaceable sensor component 1 and its use.

[0085] In some embodiments, the sensor component 1 may include an interface circuit configured to transmit signals between the data storage medium 15 and the system. This allows data to be accessed from and written to the data storage medium 15. The interface circuit may perform optical and / or electrical transmission of signals to and from the data storage medium 15. Alternatively, it may be configured to transmit signals wirelessly, in which case the interface circuit may include an antenna. In some embodiments, the data storage medium 15 may include an interface circuit. In other embodiments, the data storage medium may not require an interface circuit for accessing or modifying the stored data, and may simply include, for example, electrical contacts for external connections via interface 9.

[0086] The data storage medium 15 may be read-only with respect to some or all of the information stored in it. For example, information determined at the time of manufacture may not be modifiable by the end user. Other types of information may be modifiable or settable by the end user. The data storage medium 15 may be configured so that some or all of the information can be set only once by the end user and not subsequently modifiable.

[0087] The information includes the characteristics of one or more of the sensing elements 5. In particular, the information may include calibration information regarding the variation in the optical properties of the sensing elements 5 due to the concentration of one or more analytes and / or the temperature of the sensing elements 5.

[0088] The information may further include one or more characteristics of the calibration fluid used to calibrate the interchangeable sensor component 1. The calibration fluid may include the buffer described above. For example, the information may include the variation in the pH of the calibration fluid with respect to temperature. This improves the accuracy of the calibration, which can be determined from two calibration points.

[0089] The information may include information regarding the use of the interchangeable sensor component 1. For example, the information may include an identifier for the patient to whom the interchangeable sensor component 1 is associated. This information may be used to prevent the reuse of the sensor component 1. The data storage medium 15 may be configured to receive the identifier during system initialization and to store the identifier so that the interchangeable sensor component 1 is permanently associated with the patient. As described above, this may be achieved by allowing the information regarding the patient identifier to be set in the data storage medium 15 only once. Similarly, the information may include an identifier for the system to which the interchangeable sensor component 1 is associated. This can be used to prevent the reuse of the sensor component 1. Storing the system identifier can also reduce inaccuracies in the determined concentration of the analyte because the properties of the light source and detector used to measure the optical properties of the sensing element 5 vary between systems. For patient identifiers, the system identifier may be permanently set during system initialization.

[0090] Other information stored by the data storage medium 15 is: Instructions for the previous use of the replaceable sensor component 1, An indication of whether the replaceable sensor component 1 is damaged. From this point forward, the replaceable sensor component 1 should not be used until its expiration date. The service life of the replaceable sensor component 1, i.e., the maximum length of time for which the sensor component 1 should be used, for example, 128 hours. Length of time the replaceable sensor components were used, A unique identifier for interchangeable sensor components, Manufacturing date of replaceable sensor components, The time when the replaceable sensor components were last calibrated, The report may include an indication of the number and / or type of errors that occurred while using interchangeable sensor components.

[0091] A third aspect of the present invention relates to a reflector element 17 as shown in Figures 3 and 7. As described above, one of the parameters that affects the measurement of the optical properties of the sensing element 5 is the optical path length between the light source in the system and the detector that detects the light after it has passed through the sensing element 5. This optical path length may be affected, for example, by small mechanical misalignments in the optical interface between the optical waveguide and the sensing element. It may also be affected by damage to one or more of the optical waveguides.

[0092] To mitigate the adverse effects of such errors, the sensor component 1 includes a reflector 17. The sensor component 1 is also configured to transmit light between one or more optical waveguides and the reflector 17 on an optical path separate from the optical path between one or more optical waveguides and one or more sensing elements 5. This provides a reference beam to generate a reference signal at the detector, against which the light transmitted between the optical waveguides and one or more sensing elements 5 can be compared. The reflector may be, for example, a mirror.

[0093] The optical path between one or more optical waveguides and the reflecting element 17 is preferably a reproduction of the optical path between one or more optical waveguides and the sensing element 5, except that the optical path between one or more optical waveguides and the reflecting element 17 does not pass through the sensing element 5. Therefore, the light reflected by the reflecting element 17 does not change with the concentration of the analyte. This means that the ratio between the signal obtained from the sensing element 5 and the reference signal during calibration and continuous measurement can be calculated. This results in a measurement result in which the optical path length in the above equation is canceled out, and by using the ratio, it is ensured that any inaccuracies caused by small mechanical deviations in the optical interface do not affect the measurement. Furthermore, if the same light source as the reference beam is used to measure the optical properties of the sensing element 5, the initial intensity I0 is also canceled out in the above equation, so the occurrence of optical loss due to minor damage to the optical fiber (which causes changes in I0) does not affect the measurement.

[0094] The reference beam must be distinguishable from the light that has passed through one or more sensing elements 5 so that the ratio can be calculated. The reference beam may be optically distinguishable, for example, by having a different wavelength from the light that has passed through the sensing elements, and / or physically distinguishable by moving from the optical path between the light source, the sensing elements 5, and the detector along another optical path between the light source, the reflecting elements 17, and the detector. Therefore, if the same light source used for the reference beam is used to measure the optical properties of the sensing elements 5, the reference beam must be physically distinguishable from the light that has passed through the sensing elements 5.

[0095] The use of ratios typically allows for adjustment of only minor damage or deviations to the calibrated optical interface while still allowing sensor component 1 to function normally. Catastrophic damage results in a sudden change in the signal (in either the reference signal or the signal from sensing element 5, or both) that the system recognizes as not being due to physiological changes. In this case, the system generates an alarm to warn the user that the data is suspicious and should be handled with caution.

[0096] To obtain the advantages, it is not essential that the optical path between one or more optical waveguides and the reflecting element 17 is the same as the optical path between one or more optical waveguides and the sensing element 5. For example, if the same light source used for the reference beam is used to measure the optical properties of the sensing element 5, the ratio of the reference signal to the signal from the sensing element 5 can still reduce the effect of changes in the initial intensity I0. Furthermore, for a sensor component 1 having multiple sensing elements 5, the presence of a reference beam makes it possible to identify whether a sudden large change in the signal from the sensing element 5 is due to a failure of the sensing element 5 or to other causes.

[0097] In the illustrated embodiment, the reflective element 17 is concave, i.e., a concave reflector. This is preferable because it improves the light-gathering ability of the light reflected by the reflective element 17. However, this is not essential, and in other embodiments, the reflective element 17 may be planar.

[0098] The amount of light reflected by the reflecting element 17 (i.e., as a percentage of the amount of light incident on the reflecting element 17) is not important to the function of the reflecting element 17, as long as the reflected percentage is consistent over time. However, a larger percentage of the incident light reflected improves the signal-to-noise ratio at the detector and reduces the impact of noise on the ratio measurement. Therefore, it is preferable that the reflecting element 17 is configured to reflect at least 10%, preferably at least 25%, and more preferably at least 50% of the light incident on it back to one or more waveguides.

Claims

1. A sensor component for use in a system for measuring the concentration of one or more analytes in a fluid in a fluid line, wherein the sensor component is One or more sensing elements having optical properties that vary with the concentration of one or more analytes in the fluid, wherein the sensing element is configured to engage with the fluid line such that the sensing element is exposed to the fluid in the fluid line when the sensing element is engaged with the fluid line, A connector configured to connect to one or more optical waveguides, wherein the sensor component is configured to transmit light between the one or more optical waveguides and the one or more sensing elements, Reflecting element and Equipped with, The sensor component is configured to transmit light between the one or more optical waveguides and the reflecting element. The reflective element is configured to reflect at least 10% of the light incident thereon back to the one or more waveguides. A sensor component wherein the light transmitted by the sensor component between the one or more optical waveguides and the reflecting element has a different wavelength from the light transmitted between the one or more optical waveguides and the one or more sensing elements.

2. The sensor component according to claim 1, wherein the reflective element is concave.

3. The sensor component according to claim 1, wherein the reflective element is planar.

4. The sensor component according to any one of claims 1 to 3, wherein the sensor component is configured to transmit light between the one or more optical waveguides and the reflecting element on an optical path separate from the optical path between the one or more optical waveguides and the one or more sensing elements.

5. The sensor component according to any one of claims 1 to 4, further comprising a fluid-permeable support element for supporting the sensing element, which is positioned between the sensing element and the fluid in the fluid line when the sensor component is engaged with the fluid line.

6. The sensor component according to claim 5, wherein the transparent support element includes a mesh.

7. The sensor component according to any one of claims 1 to 6, wherein the sensing element comprises a membrane that is permeable to at least one of the analytes, configured to be exposed to the fluid in the fluid line when the sensor component is engaged with the fluid line.

8. The sensor component according to any one of claims 1 to 7, wherein the sensor component comprises two or more sensing elements.

9. The sensor component according to claim 8, further comprising a light-absorbing element located between the sensing elements.

10. The sensor component according to any one of claims 1 to 9, wherein the connector comprises a transparent optical element configured to transfer light between the sensing element and the one or more optical waveguides, or to each sensing element.

11. The sensor component according to claim 10, wherein the transparent optical element comprises a waveguide.

12. The sensor component according to any one of claims 1 to 11, further comprising a temperature sensor arranged to sense the temperature of one or more of the aforementioned sensing elements.

13. The sensor component according to claim 12, wherein the temperature sensor is a thermistor or a thermocouple.

14. The sensor component according to any one of claims 1 to 13, wherein the sensor component is configured to engage with the wall of the fluid line.

15. The sensor component according to any one of claims 1 to 13, further comprising a conduit, wherein the sensing element is exposed to the fluid in the conduit, and the conduit is configured to be inserted into the fluid line for engagement of the sensor component with the fluid line.

16. The sensor component according to claim 15, wherein the conduit is configured to be inserted into the fluid line in an in-line configuration.

17. The sensor component according to claim 15, wherein the conduit is configured to be inserted into the fluid line in a shunt configuration.

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