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 in particular to sensor components used to measure the concentration of an analyte in a fluid using the optical properties of a sensing element. [Background technology]

[0002] In many areas, it is desirable to be able to determine the concentration of an analyte in a fluid that contains a mixture of several different substances. For example, in clinical settings, it is important to accurately determine the concentration of oxygen in a patient's blood in real time to be able to detect and prevent hypoxia. Clinical settings in which 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] CPB technology allows cardiac surgery to be performed in a stationary, bloodless surgical field. Newer CPB machines have systems for monitoring pressure, temperature, oxygen saturation, and hemoglobin, as well as air bubble and reservoir low level detection alarms. Cardiopulmonary bypass patients are subject to physiological fluctuations in blood gas levels due to oxygenation, electrolyte changes, and fluid shifts that occur during CPB. Potentially adverse patient outcomes from these fluctuations can include hypoxia and hyperoxia, hypo- and hypercarbia, and acid-base alterations. 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 be measured frequently or continuously. From these measured blood gas data, other useful parameters such as base excess, bicarbonate, oxygen delivery, oxygen consumption, and oxygen uptake rate can be calculated.

[0004] ECMO is a recent evolution from CPB and is applicable to patients who are hypoxemic despite maximal conventional ventilatory support, have significant ventilator-induced lung injury, or are in cardiogenic shock. Installation is similar to that of CPB, but is typically used for much longer periods (e.g., 30 days is not uncommon), usually in an intensive care unit. CRRT is a hemodialysis treatment delivered as continuous therapy 24 hours a day and is appropriate for patients with acute renal failure (ARF) who are hemodynamically unstable. Intermittent hemodialysis is appropriate for patients with chronic renal dysfunction.

[0005] One known type of sensor employed in these settings uses a luminescent compound, e.g., a fluorescent organic dye, with a luminescence lifetime that depends 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, so that it does not require periodic taking of samples of, e.g., blood, 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 the clinician to respond by titrating the administered therapy. Continuous real-time data can therefore be thought of as providing feedback to therapy.

[0006] With 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 the previous sample. Gaps in knowledge of the patient's condition between blood samples (known as blind intervals) can pose risks to the patient. These gaps can be eliminated by using continuous sensors. Continuous monitoring should provide accurate measurements of a given analyte over time and provide an indication of the movement of the analyte concentration (trending), thereby providing continuous, minute-by-minute patient condition information to the clinician. This aids in the delivery of effective treatment and eliminates the blind intervals, thereby reducing risks to the patient.

[0007] To provide these benefits, a key requirement for a continuous sensor is to maintain accuracy over an extended period of time. Inaccuracies can be due to continuous drift in the sensor readings or more abrupt changes, for example due to damage to the sensor. These inaccuracies are of great importance as they may not be immediately distinguishable from true physiological changes in the concentration of the analyte. Thus, clinicians may be provided with erroneous information that erroneously affects the administered treatment, thereby putting the patient at risk. This is less of a concern for intermittent monitoring, where a blood sample is taken and introduced into a sensor such as a blood gas analyzer. This is because the sensor is calibrated immediately prior to each measurement, so although the sensor may drift relatively quickly, this is not critical in terms of accuracy as there is little time for it to drift between calibration and 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 Summary of the Invention [Means for solving the problem]

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

[0010] According to a first aspect of the present invention, there is provided 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, the sensor component configured to engage a fluid line such that the sensing elements are exposed to fluid in the fluid line; a connector configured to connect to one or more optical waveguides, the sensor component configured to transmit light between the one or more optical waveguides and the 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] The sampling port provided as part of the sensor component means that either upon initial installation of the sensor component, or if the readings from one or more of the sensing elements are found to drift and become inaccurate over a period of time, then a sample of fluid can be taken from the local port. The sample can be analyzed by an approved analyzer, and the value used to adjust the readings from the sensing elements to compensate for the inaccuracy. The inclusion of a sampling port as part of the sensor component also has the advantage that the fluid sample is taken in close physical proximity to the sensing element, such that the concentration of analyte in the fluid sample reflects the concentration at the sensing element as accurately as possible.

[0012] In some embodiments, the sampling port comprises a one-way valve configured to allow one-way fluid flow from the fluid line. The use of a one-way valve prevents the sampling port from being used to introduce substances into the fluid line that may not be appropriate at the location of the sensor component or that may cause erroneous readings from the sensor component by locally affecting the concentration of the analyte.

[0013] In some embodiments, the sampling port comprises a component fitting configured to engage with an external fitting. Using a component fitting, the sampling port can be securely and safely engaged by an external fitting of a device used to collect a sample. This can prevent possible contamination or other errors during sampling. In some embodiments, the component fitting comprises a Luer fitting, which is 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 the component fitting, reducing the number of manipulations required to obtain a sample, thereby improving ease of use.

[0015] In some embodiments, the sampling port is self-closing, which also improves ease of use by reducing the manipulation required by the user and reduces the opportunity for contamination if the sampling port is not closed promptly and correctly after the sample is taken.

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

[0017] In some embodiments, the sampling port includes a removable cap configured to seal the sampling port, thereby more securely sealing and protecting the port from potential damage, especially during extended periods of non-use.

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

[0019] According to a second aspect of the present invention, there is provided 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 the one or more analytes in the fluid, the sensor component configured to engage a fluid line such that the sensing elements are exposed to 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, the sensor component configured to transmit light between the one or more optical waveguides and the one or more sensing elements; and a reflective element, the sensor component also configured to transmit light between the one or more optical waveguides and the reflective element on an optical path separate from an optical path between the one or more optical waveguides and the one or more sensing elements.

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

[0021] In some embodiments, the reflective element is concave. A concave reflector can concentrate the light so that it can be more efficiently transmitted back into the light guide after reflection.

[0022] In some embodiments, the reflective element is planar. A planar reflective element may be easier to manufacture and assemble than a concave reflector.

[0023] In some embodiments, the reflective element is configured to reflect at least 10% of the light incident on it back into the one or more waveguides, which achieves a minimum level of reflectivity such that a signal from the reflective element can be reliably detected.

[0024] Another important requirement of sensor components, especially if replaceable or disposable, is that the individual sensor components and associated information are not mixed up with one another. Sensor components may have properties that vary from batch to batch, may be associated with a particular device or patient, and may have a variety of other associated metadata. Tracking such information is important to provide accurate information and ensure patient safety, but can be difficult when multiple individual sensor components are housed or used in the same environment.

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

[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 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, the sensor component configured to engage a fluid line such that the sensing elements are exposed to 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, the sensor component 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 representative of information relating to the sensor component.

[0027] Storing information about the sensor components on a data storage medium is advantageous when the sensor components are replaceable, e.g., disposable and / or single-use, to ensure that information about parameters specific to each sensor component is inherently tied to the particular sensor component, thereby reducing the possibility 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 can simplify retrieval or storage of information on the data storage medium. In some embodiments, the interface circuit is configured to transmit signals wirelessly. This can improve ease of use 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 the one or more sensing elements, which may vary between manufacturing batches and are stored in a data storage medium to ensure that the exact characteristics of each sensor component are readily available.

[0030] In some embodiments, the information includes calibration information regarding variations in optical properties of the sensing element due to one or both of the concentration of one or more analytes and the temperature of the sensing element, where storing the information in a data storage medium of the sensor component improves the accuracy of the determination of the concentration of the analytes by ensuring that calibration information specific to each sensor component is available.

[0031] In some embodiments, the information includes one or more properties of a calibration fluid used to calibrate the replaceable sensor component, thereby simplifying the calibration process when a particular calibration fluid is used such that the properties do not have to be provided by the user. In some embodiments, the information includes the variation of pH of the calibration fluid with temperature, thereby allowing 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 a patient with which the replaceable sensor component is associated. This can prevent the sensor component from being reused across multiple patients, potentially leading to cross-contamination or other issues. In some embodiments, the data storage medium is configured to receive the identifier during initialization of the system and store the identifier such that the replaceable sensor component is permanently associated with the patient. Permanently storing the patient identifier further helps prevent reuse of the sensor component across multiple patients.

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

[0034] In some examples, the information includes one or more of an indication of previous use of the replaceable sensor component, an indication of whether damage has occurred to the replaceable sensor component, a use-by date after which the replaceable sensor component should not be used, a useful 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, a date of manufacture 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 use of the replaceable sensor component. All of these parameters can be used to assess the validity of the calibration of the sensor component and whether its continued use is advisable, thereby improving the accuracy of the readings obtained and patient safety. Knowing some of these parameters may also be required for regulatory compliance, so storing them on the sensor component itself reduces the burden on the user to record the information elsewhere.

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

[0036] In some embodiments, the sensor component further comprises a fluid-permeable support element for supporting the sensing element, arranged 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 effects, e.g., due to pulsatile flow of fluid through the fluid line, on the position of the sensing element and therefore the optical property measurements. In some embodiments, the permeable support element comprises a mesh. This is a particularly simple way to provide a fluid-permeable support element that is easy to manufacture and assemble.

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

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

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

[0040] In some embodiments, the connector comprises a transparent optical element for the or each sensing element configured to transfer light between the sensing element and the one or more optical waveguides. This can protect the sensing element from mechanical or chemical damage when the sensor component is not connected to the one or more optical waveguides. In some embodiments, the transparent optical element comprises a waveguide. This reduces light loss through the transparent optical component.

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

[0042] In some embodiments, the sensor component is configured to engage with a wall of the fluid line, which 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 being exposed to fluid within the conduit, and the conduit being configured to be inserted into the fluid line for engagement of the sensor component with the fluid line, which may be more convenient in some circumstances depending on the configuration of the fluid line that the sensor component engages.

[0044] In some embodiments, the conduit is configured to be inserted into the fluid line in an in-line configuration, which minimizes disruption of 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, such that the sensor component can be installed and removed without interrupting fluid flow in the fluid line.

[0046] Embodiments of the invention will now be described, by way of non-limiting examples, with reference to the accompanying drawings, in which: [Brief description of the drawings]

[0047] [Figure 1] FIG. 1 is an isometric view of the sensor components prior to connection to one or more waveguides and engagement with fluid lines. [Diagram 2] 2 is a cross-sectional view of the sensor component of FIG. 1 engaged with a fluid line and connected to one or more waveguides. [Diagram 3] FIG. 3 is an exploded isometric view of the sensor components of FIGS. 1 and 2. [Figure 4] FIG. 13 is an exploded view showing further elements of the sensor component. [Diagram 5] FIG. 4 is an isometric view of the sensor component of FIGS. 1-3 engaged with a fluid line. [Figure 6] FIG. 1 illustrates an example of a sensor component comprising a conduit. [Figure 7] FIG. 7 is an exploded view of a portion of the sensor components of FIG. [Figure 8]FIG. 7 shows the sensor component of FIG. 6 engaged with a fluid line in a shunt configuration. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0048] As mentioned above, the present invention has three aspects, all of which relate to using a sensor component to improve the accuracy of measurements and to aid in the detection and reduction of drift in measurements when the sensor component is used continuously over long periods of time. The features that differ between the three aspects are the sampling port, the reflective element, and the data storage medium, respectively. Each of these features will be discussed in further detail below. In the examples discussed herein, all three of these features are provided simultaneously in the same sensor component, thereby achieving maximum benefit from all combinations of the features. However, it should be understood that the three features do not have to be provided in combination, and that any one of the three features can equally well be provided in the sensor component alone, as represented by the three aspects described above. It is also possible to provide a sensor component having any combination of two of the three features, and thus still provide the corresponding benefits and advantages.

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

[0050] The sensor component 1 comprises a black plastic construction. The plastic can be readily manufactured to the desired specifications and can also be sterilized for use in a clinical context. However, the use of plastic is not mandatory and other suitable materials may be used, e.g., resin or metal. The black color of the sensor component 1 helps to eliminate optical crosstalk between the sensing elements 5. In general, however, the sensor component 1 may have any color. Preferably, when used in blood-contacting medical devices, the material of the sensor component 1 is biocompatible and non-leaching, thus preventing contamination of the patient's blood. When used in continuous monitoring applications, potential unforeseen changes to the properties of the sensor component 1 (particularly the sensing element 5 and the optical components) during the shelf life after manufacture should also be considered, especially if the final calibration before use relies on constants determined during manufacture. 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 manufacture or sterilization does not adversely affect the drift of the sensor measurement during use, resulting in inaccuracies.

[0051] The sensor component 1 is preferably provided to the user packaged to be 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 listed above except hydrogen ion / pH), the predetermined concentration may preferably be zero in some embodiments. When oxygen and / or carbon dioxide are detected, their concentrations can be zeroed by an impurity remover enclosed 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 contacting surface of the sensor component 1 is maintained by an aluminum removable 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 required and other embodiments may include one, two, three or more than four sensing elements 5. The sensing elements 5 each comprise a luminescent compound, preferably a fluorescent compound, more preferably a fluorescent organic dye. The luminescent compound may be different for different sensing elements 5 and depends on the analyte to be measured. Suitable luminescent compounds include, by way of example, seminaphtharnodafluor (SNARF), mag-fluo-4, and derivatives thereof. The sensing element may comprise a luminescent compound suspended, dissolved, or molecularly bound in a matrix. The matrix may comprise a polymer, for example PMMA or polystyrene. Alternatively, the matrix may comprise a sol-gel or a hydrogel.

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

[0054] The sensing elements 5 have optical properties that vary with the concentration of one or more analytes in the fluid. The optical property may be light emission or absorption. If the sensing elements 5 contain a luminescent compound, the optical property may be luminescence lifetime. The optical property may be the same for all of the sensing elements 5 or may differ between the sensing elements 5. Various measurement formats may be used to minimize drift in the sensor. Fluorescence lifetime and proportional to supply voltage formats are commonly used when available, as they are less vulnerable to common sources of error that can cause drift. Relative to supply voltage formats take two measurements of the light from the luminescent compound, for example at different wavelengths, and calculate a ratio. However, since linear intensity measurement methods are often the only formats available, it is important that aspects of the design of the sensor component 1 are chosen to minimize drift and inaccuracies.

[0055] The sensor component 1 is configured to engage the fluid line 3 such that the sensing element 5 is exposed to fluid in the fluid line 3. As shown in Figure 2, the sensor component 1 engages the fluid line 3 such that the sensing element 5 is exposed to the interior of the fluid line 3 such that fluid flowing through the fluid line 3 past the sensor component 1 contacts parts of the sensor component 1 that face the interior of the fluid line 3.

[0056] As shown in FIG. 3, two of the sensing elements 5 are provided with a membrane 21 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 at least to the analyte sensed by the sensing element 5 with which the membrane 21 is provided. Providing the membrane 21 can ensure higher specificity by ensuring that the sensing element 5 is not affected by interactions with analytes other than those it is intended to sense, and by preventing the sensing element 5 from interacting with other components of the fluid that may affect the optical properties of the sensing element 5. For example, the membrane 21 can prevent large biomolecules such as proteins, or blood cells from interacting with the sensing element 5. The membrane 21 may be a hydrophobic gas-permeable membrane if the analyte is O2, CO2, NO, NH3, or anesthesia gas. If the analyte is soluble in water or plasma, the membrane 21 may be a hydrophilic membrane, e.g., a hydrogel. Suitable membranes may include microporous membranes or dialysis membranes.

[0057] As shown in FIG. 4, the sensor component 1 comprises a fluid-permeable support element 19 for supporting the sensing element 5 arranged to be 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 pulsatile and has significant pressure fluctuations, for example, as in a CPB or ECMO machine. Without the fluid-permeable support element 19, such fluctuations can cause small movements or deformations of the sensing element 5, changing the optical path length through the sensing element and affecting the measurement of its optical properties and introducing errors. The permeable support element 19 preferably comprises a mesh, for example a stainless steel or plastic mesh. Although a permeable support element 19 is provided for each sensing element 5 in the figure, this may not be necessary depending on the mechanical properties of the individual sensing elements 5.

[0058] 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 that may introduce errors into the measurement of the optical properties of the sensing elements.

[0059] The sensor component 1 comprises a connector 7 configured to connect to one or more optical waveguides. In the illustrated embodiment, the optical waveguides are constituted by an optical-electrical interface 9, and the connector 7 comprises a recess in the sensor component 1 that engages with the interface 9. Overall, however, the connector 7 may take any suitable form and may comprise a retaining element, such as a clip or screw, that prevents movement of the optical waveguide or waveguides relative to the connector 7.

[0060] The optical waveguide allows light to be transmitted to or from one or more light sources elsewhere in the system in which the sensor component 1 is used. In the illustrated embodiment, light is transmitted through the optical waveguide from one or more light sources along the interface 9. Suitable light sources include LEDs or laser diodes. The opto-electrical interface 9 is entirely disposable and connects the sensor component 1 to a system that measures 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. 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 light from the sensing element 5. The optical waveguide is butted against a transparent optical element 25. The interface 9 also provides means for electrical connection 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 parts of the system, or may not be present at all. The sensor component 1 is configured to transmit light between one or more optical waveguides and one or more sensing elements 5 such that optical properties of the sensing elements 5 can be measured.

[0062] As shown in Fig. 2, the connector 7 comprises a transparent optical element 25 for the or each sensing element 5 configured to transfer light between the sensing element 5 and one or more optical waveguides. This protects the sensing element 5 against physical or chemical damage, especially when the interface cable 9 is not connected. The transparent optical element 25 may itself comprise a waveguide to ensure optimal transmission of light to and from the sensing element 5. The transparent optical element 25 acts as an optical window connecting the optical waveguides with 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 their dependence on the concentration of the analyte may vary depending on the temperature of the sensing element 5. Knowing the temperature of the sensing element 5 can therefore improve the accuracy of the determination of the concentration of the analyte in the fluid. Preferably, the temperature sensitive 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 sensitive element 27 for the purpose of measuring the 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 into 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 component in Figures 1-5 is 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, sensor component 1 further comprises a conduit 29, where sensing element 5 is exposed to fluid in conduit 29. Conduit 29 may comprise a section of the same type of tubing as fluid 3, e.g., the section of tubing that sensor component 1 engages in FIG. 5. Conduit 29 may be configured to be inserted into fluid line 3 to engage the sensor component with fluid line 3. As discussed above, conduit 29 may be configured to be inserted into fluid line 3 in an in-line configuration or in a shunt configuration (also referred to as a bypass configuration).

[0066] Accurate calibration up front is important to achieve accurate monitoring thereafter. Point-of-use calibration should also be as easy as possible for the user, if not completely invisible. The sensor component 1 described herein uses a calibration method that requires two calibration measurements at the point-of-use.

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

[0068] Prior to engaging the sensor component 1 with the fluid line 3, the sensor component 1 is provided sterile and hydrated (with the sensing element 5 exposed to a buffer solution) in a separate pack. The in-line connector 33 that the sensor component 1 engages is already assembled into the fluid line 3, with a protective cap / plug in place covering the opening 31. If the sensor component 1 comprises a conduit 29, the in-line connector 33 may also function as the conduit 29. The sensor component 1 is then connected to the interface 9, which obtains light transmitted via one or more optical waveguides at a wavelength appropriate for measuring the optical properties of each sensing element 5. The optical waveguide(s) may also return light to a detector in the system. The buffer solution 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 a first calibration point of one or more analytes when the sensor component 1 is connected to the interface, a process that is invisible to the user, thus improving ease of use. A hydration / buffer solution, which may be trapped behind the aluminum foil layer, serves as the first calibration liquid.

[0070] The in-line connector 33 is filled with a priming fluid, which may have a known concentration of one or more analytes different from the concentration in the buffer. The protective cap / plug is removed from the opening 31 at the same time that the protective cover is removed from the sensing element 5, and the sensor component 1 is immediately attached to the in-line connector 33. The priming fluid replaces the fluid (e.g., blood).

[0071] Once the sensor component 1 is placed in-line and the sensing element 5 is in contact with the fluid, a fluid sample is taken adjacent to the sensor component 1 either upstream or downstream in the fluid line 3. The concentration of one or more analytes in the sample is measured with 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] An alternative to the sensor component 1 engaging the main line of the fluid line 3 as just described is a shunt system that bypasses the main line. In such an embodiment, the sensor component 1 comprises a conduit 29 that is assembled into one 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 referred to as a shunt configuration. The conduit 29 may be joined to the remainder of the sensor component 1 by any suitable means, for example ultrasonic welding.

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

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

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

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

[0077] All of these parameters are considered and kept constant during the process of calibration. Changes in the values ​​after calibration can be either continuous or sudden due to damage to the sensor component 1, resulting in inaccurate measurements of the analyte concentration, either due to gradual drifts in the signal or more sudden changes. In a continuous sensor component design, these parameters should be kept as constant as possible. After all of the drift-reducing measures have been applied in the design of the sensor component 1, only low levels of drift can be faced. Thus, inaccuracies only become significant over long periods of time. This is unlikely to be an issue in CPD, but is possible in long-term dialysis and ECMO treatments.

[0078] As discussed above, a sample of fluid is required to provide 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] The provision of a sampling port 11 integrated into the sensor component 1 ensures that the fluid sample is taken from the fluid flowing over the sensing element 5 in close proximity or as close as possible to the sensing element 5, ensuring accuracy of the calibration. In some embodiments the sampling port 11 is up to 20cm, preferably up to 10cm, more preferably up to 5cm from the sensing element or elements 5.

[0080] The proximity of the sampling port 11 to the sensing element 5 is advantageous as 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 metabolism of the analyte. This means that the concentration in the fluid sample is not representative of the concentration measured by the sensing element 5, causing calibration errors and subsequent measurement errors. The sample may be taken through the sampling port 11 in any suitable manner, for example using a syringe.

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

[0082] The sampling port 11 is configured to open when the external fitting engages with the component fitting. The sampling port 11 may further 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 further comprises a removable cap 13 configured to seal the sampling port 11, although this is not required. The removable cap 13 can protect the sampling port 11 from damage or contamination when the sampling port 11 is not used for an extended period of time.

[0083] A second aspect of the invention relates to a data storage medium 15 configured to store data representative of information regarding the 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 is intended to be used only in a single treatment for a single patient. The data storage medium 15 may comprise a microchip.

[0084] To enable the above-mentioned calibration method requiring 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 manufacture, before the replaceable sensor component 1 is supplied to the end user. These properties travel with the replaceable sensor component 1 stored by 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 properly 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 comprise an interface circuit configured to transmit signals between the data storage medium 15 and the system, whereby data can be accessed from and written to the data storage medium 15. The interface circuit may provide 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 comprise an antenna. In some embodiments, the data storage medium 15 may comprise the interface circuit. In other embodiments, the data storage medium may not require an interface circuit for the stored data to be accessed or modified, and may simply comprise, for example, electrical contacts for external connection via the interface 9.

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

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

[0088] The information may further include one or more properties of a calibration fluid used to calibrate the replaceable sensor component 1. The calibration fluid may include a buffer solution as described above. For example, the information may include the variation of pH of the calibration fluid with temperature. This increases the accuracy with which the calibration can be determined from the two calibration points.

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

[0090] Other information stored by the data storage medium 15 is: An indication of the previous use of the replaceable sensor component 1; an indication of whether damage has occurred to the replaceable sensor component 1; a use-by date, after which the replaceable sensor component 1 should not be used; The service life of the replaceable sensor component 1, i.e. the maximum length of time the sensor component 1 should be used, e.g. 128 hours; the length of time that the replaceable sensor components have been used; A unique identifier for the replaceable sensor component; Date of manufacture of the replaceable sensor components; the time when the replaceable sensor components were last calibrated; It may also include an indication of the number and / or type of errors that occurred during use of the replaceable sensor component.

[0091] A third aspect of the invention relates to a reflective element 17 as shown in figures 3 and 7. As mentioned above, one of the parameters that influences the measurement of the optical properties of the sensing element 5 is the optical path length in the system between the light source and the detector that detects the light after passing through the sensing element 5. This optical path length can be affected by, for example, small mechanical misalignments of the optical interface between the optical waveguides and the sensing element. It can also be affected by damage to one or more of the optical waveguides.

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

[0093] The optical path between the optical waveguide(s) and the reflecting element 17 is preferably a replica of the optical path between the optical waveguide(s) and the sensing element 5, except that the optical path between the optical waveguide(s) and the reflecting element 17 does not pass through the sensing element 5. The light reflected by the reflecting element 17 therefore does not vary with the analyte concentration. This means that a ratio can be calculated between the signal obtained from the sensing element 5 and the reference signal during calibration and continuous measurement. This results in a measurement where the optical path length in the above formula is cancelled out, and the use of the ratio ensures that any inaccuracies caused by small mechanical misalignments 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 cancelled out in the above formula, so that the occurrence of light losses due to minor damage to the optical fiber (causing a change in I0) does not affect the measurement.

[0094] The reference beam must be distinguishable from the light passing through one or more sensing elements 5 so that a ratio can be calculated. The reference beam may be optically distinguishable, for example by having a different wavelength from the light passing through the sensing elements, and / or may be physically distinguished from the optical path between the light source, the sensing elements 5 and the detector, by moving along a different optical path between the light source, the reflecting element 17 and the detector. Thus, if the same light source as 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 passing through the sensing elements 5.

[0095] The use of the ratio typically allows only minor damage or deviations to be accommodated after calibration while still allowing the sensor component 1 to operate normally. Catastrophic damage would result in a sudden change in signal (in either the reference signal or the signal from the sensing element 5, or both) that is recognized by the system as not being due to a physiological change. In this case, the system will generate an alarm to warn the user that the data is suspect and should be taken with caution.

[0096] To obtain the advantages, it is not necessary that the optical path between the optical waveguide(s) and the reflective element 17 is the same as the optical path between the optical waveguide(s) and the sensing element 5. For example, if the same light source as 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 the reference beam can distinguish whether a sudden large change in the signal from the sensing element 5 is due to a failure of the sensing element 5 or due to other causes.

[0097] In the illustrated embodiment, the reflective element 17 is concave, i.e., a concave reflector. This is preferred as it improves the concentration of light reflected by the reflective element 17. However, this is not required and in other embodiments the reflective element 17 may be planar.

[0098] The amount of light reflected by reflective element 17 (i.e. as a proportion of the amount of light incident on reflective element 17) is not critical to the function of reflective element 17, so long as the proportion reflected is consistent over time. However, reflecting a greater proportion of the incident light improves the signal-to-noise ratio at the detector, making the effect of noise on the ratiometric measurement less significant. Thus, reflective element 17 is preferably configured to reflect at least 10%, preferably at least 25%, and more preferably at least 50% of the light incident thereon back into the waveguide or waveguides.

Claims

1. 1. A sensor component for use in a system for measuring a 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 the one or more analytes in the fluid, the sensor component configured to engage the fluid line such that the sensing element is 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, the sensor component configured to transmit light between the one or more optical waveguides and the one or more sensing elements; a reflective element, wherein the sensor component is also configured to transmit the light between the one or more optical waveguides and the reflective element on an optical path separate from an optical path between the one or more optical waveguides and the one or more sensing elements.

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

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

4. A sensor component according to claim 1 , wherein the reflective element is configured to reflect at least 10% of light incident thereon back into the one or more waveguides.

5. 5. A sensor component as described in any one of claims 1 to 4, further comprising a fluid-permeable support element for supporting the sensing element 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 of claim 5 , wherein the permeable support element comprises a mesh.

7. 7. The sensor component of claim 1 , wherein the sensing element comprises a membrane permeable to at least one of the analytes and 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 of claim 1 , wherein the sensor component comprises two or more sensing elements.

9. The sensor component of claim 8 further comprising a light absorbing element located between the sensing elements.

10. 10. A sensor component according to claim 1, wherein the connector comprises a transparent optical element for the or each sensing element configured to transfer light between the sensing element and the one or more optical waveguides.

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

12. A sensor component according to claim 1 , further comprising a temperature sensor arranged to sense a temperature of the one or more sensing elements.

13. The sensor component of claim 12 , wherein the temperature sensitive element is a thermistor or a thermocouple.

14. The sensor component of claim 1 , wherein the sensor component is configured to engage a wall of the fluid line.

15. 14. The sensor component of claim 1, further comprising a conduit, the sensing element being exposed to fluid in the conduit, the conduit being configured to be inserted into the fluid line for engagement of the sensor component with the fluid line.

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

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

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