Sterilization of Analyte Sensor Components

Abstract

A sensor component is sterilized for use in a system for measuring the concentration of one or more analytes in a fluid in a fluid line. The sensor component comprises one or more sensing elements having optical properties that vary with the concentration of one or more analytes in the fluid and is configured to engage the fluid line, thereby exposing the sensing elements to the fluid. The method comprises the steps of introducing a gaseous sterilant into the sealed cavity through one or more ports providing a fluid connection to the cavity, exposing the one or more sensing elements to the cavity, replacing the gaseous sterilant with a sterilant liquid through the ports, and sealing the ports. A sensor component configured to facilitate application of the method is also disclosed.

Description

[Technical field]

[0001] The present invention relates to a method for sterilizing sensor components used in systems for measuring the concentration of an analyte in a fluid, particularly sensor components that determine the concentration of an analyte by a change in the optical properties of one or more sensing elements. [Background technology]

[0002] In many fields, it is desirable to be able to determine the concentration of an analyte in a fluid that may contain a mixture of multiple different substances. For example, in clinical settings, it is important to be able to accurately determine the oxygen concentration in a patient's blood in real time to detect and prevent hypoxia. Examples of clinical settings where monitoring of blood analytes is important include cardiopulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), and continuous renal replacement therapy (CRRT). Continuous monitoring provides clinicians with ongoing patient status information to aid in treatment, eliminates blind intervals, and reduces risk to the patient.

[0003] For the types of sensor components considered here, changes in analyte concentration are detected through changes in the optical properties of one or more sensing elements. These are ideal for continuous monitoring because they can be designed to have low levels of drift in their optical properties over time due to factors other than analyte concentration. This means they can provide accurate measurements regularly over long periods of time, reducing the need to periodically take blood samples or perform frequent and time-consuming calibration procedures.

[0004] In order to measure the concentration of an analyte in a fluid, a portion of the sensor component must come into contact with the fluid. However, at least a portion of the sensing element and other materials used in this type of sensor component become hydrated when exposed to a fluid during use. If the sensor component is provided with a non-hydrated sensing element, it may take several hours for the optical properties of the sensing element to stabilize after exposure to a fluid. This is impractical in a real-world context, so the sensor component must be provided with a sensing element that is already hydrated.

[0005] Furthermore, especially in a clinical context, it is important that the sensor components are supplied to the end user in a sterile state: since the sensor components must come into contact with fluids during use, sterilization reduces the risk of contamination, e.g., of the patient's blood by biological foreign bodies that may be introduced into the sensor components during manufacture.

[0006] Thus, the challenge is to supply the sensor components to the user in sealed sterile packaging while at the same time maintaining the sensing element hydrated throughout the shelf life of the sensor components, potentially for extended periods of time.

[0007] Currently, this is accomplished by packaging and sealing the sensor components with a hydrating fluid, and then sterilizing the entire sealed package using gamma irradiation while the sensor components are wet. However, ionizing radiation generates highly reactive free radicals and active oxygen species that can be harmful to the sensing element and connector materials, which can result in drift in the optical properties of the sensor components and loss of signal when the sensor components are in use.

[0008] Sterilization with a gaseous sterilant such as ethylene oxide is an even more benign sterilization method, however, it must be performed in a dry state to prevent the gaseous sterilant from interacting with the fluid, which can create or deposit chemicals within the sensor components that themselves can damage the sensing elements and materials of the sensor components, or create a risk of contamination of the sensor components that could harm the patient.

[0009] It is therefore desirable to provide a sterilization method that reduces damage to the sensor components and allows the sensor components to be supplied in a sterile, hydrated state. Summary of the Invention

[0010] According to a first aspect of the present invention, there is provided a method of sterilizing 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 in response to the concentration of one or more analytes in the fluid, the sensor component being configured to engage the fluid line such that the sensing elements are exposed to fluid in the fluid line, and 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, the method comprising the steps of introducing a gaseous sterilant into a sealed cavity via one or more ports providing a fluid connection to the cavity, such that the one or more sensing elements are exposed to the cavity, replacing the gaseous sterilant with a sterilant liquid via the ports, and sealing the ports.

[0011] By exposing the sensing element to the cavity, the environment of the sensing element can be controlled and maintained in a sterile state as the gas sterilant is replaced with a sterile liquid. Furthermore, the sterile liquid filled cavity is sealed with a port to ensure that the sensing element is exposed to the sterile liquid and maintained in a hydrated state until the sensor component is to be used. This method allows for the use of a more harmless gas sterilant and improves the accuracy of subsequent measurements using the sensor component.

[0012] In some embodiments, introducing the gaseous sterilant into the cavity comprises placing the sensor component in a sealed environment and introducing the gaseous sterilant into the sealed environment, and replacing the gaseous sterilant is performed without removing the sensor component from the sealed environment. The use of a sealed environment, e.g. a sterile bag, means that the exterior surface of the sensor component can also be maintained sterile during the procedure, further reducing the chance of contamination of surfaces of the sensor component that will come into contact with fluids during use.

[0013] In some embodiments, the gas sterilant remains in the cavity for at least one hour before performing the step of replacing the gas sterilant, allowing sufficient time to ensure that the relevant portions of the sensor components are thoroughly sterilized.

[0014] In some embodiments, the method further comprises preconditioning the sensor component by exposing it to a predetermined temperature and / or humidity for a predetermined length of time prior to introducing the gas sterilant, thereby ensuring that optimal conditions for sterilization using the gas sterilant are most effective.

[0015] In some embodiments, displacing the gaseous sterilant with the sterilant liquid through the port comprises displacing the gaseous sterilant with a sterilizing gas through the port followed by introducing the sterilant liquid through the port, thereby reducing any chance of the gaseous sterilant remaining in the cavity or coming into contact with the sterilant liquid.

[0016] In one embodiment, replacing the gaseous sterilant with a sterilizing gas through the port comprises removing the gaseous sterilant by exhausting through the port, followed by introducing the sterilizing gas through the port, the exhausting further enhancing the removal of the gaseous sterilant to prevent it from remaining in the cavity after sterilization.

[0017] In some embodiments, the method is carried out at a temperature ranging from 35° C. to 65° C. This provides optimal conditions under which the gas sterilant is most effective.

[0018] In some embodiments, the gas sterilant is one of ethylene oxide, ozone, hydrogen peroxide, nitrogen dioxide, and formaldehyde, which are readily available and suitable for sterilizing equipment used in a clinical setting.

[0019] In some embodiments, the sterile liquid is a calibration solution that includes predetermined concentrations of one or more analytes, which facilitates calibration of the sensor components at the point of use.

[0020] In some embodiments, the one or more ports include two ports, and the steps of introducing the gas sterilant and replacing the gas sterilant are performed by flowing the gas sterilant and the sterilant liquid between the two ports. Using gas and liquid flow between the two ports can more effectively ensure that the fluid passes through all portions of the cavity.

[0021] In some embodiments, sealing the port comprises permanently sealing the port, which reduces the chance of subsequent contamination of the cavity in embodiments where the port is only used during a calibration procedure.

[0022] In some embodiments, sealing the port comprises sealing the port with a removable element, which can reduce the chance of contamination of the cavity if the port needs to be reused at a point after sterilization.

[0023] In some embodiments, the method further comprises connecting tubing to the one or more ports prior to introducing the gas sterilant into the cavity, where introducing the gas sterilant comprises flowing the gas sterilant through the tubing, where replacing the gas sterilant comprises flowing a sterilant liquid through the tubing, and where sealing the one or more ports comprises sealing the tubing and disconnecting the tubing outside of where the tubing is sealed such that the sealed portion of the tubing remains connected to the port. The use of tubing can provide additional flexibility in positioning and connecting parts required during sterilization and can also provide a convenient manner of sealing the ports.

[0024] In some embodiments, the tubing includes a tubing valve configured to open and close the tubing, the step of introducing the gaseous sterilant is performed with the tubing valve in an open state, the step of replacing the gaseous sterilant is performed with the tubing valve in an open state, the tubing is disconnected between the location where the tubing is sealed and the tubing valve, and the method further includes the step of closing the tubing valve prior to the step of sealing the port. Including the tubing valve facilitates a user's control of the flow of fluid through the tubing during a sterilization procedure.

[0025] In some embodiments, the tubing is sealed using ultrasonic welding or solvent sealing, which are convenient methods for sealing tubing, which may typically be made of plastic.

[0026] In some embodiments, the sensor component further comprises a component valve for the or each port configured to open and close the port, wherein the step of introducing the gas sterilant is performed with the component valve in an open state, the step of replacing the gas sterilant is performed with the component valve in an open state, and the step of sealing the one or more ports comprises closing the component valve. Including a component valve allows the sensor component to be provided with a valve that allows access to the cavity through the port. This can be particularly advantageous when the sensor component is designed to be engaged with a fluid line in a shunt or bypass configuration.

[0027] In some embodiments, the sensor component defines a sealed cavity and includes one or more ports, which may be advantageous depending on the application of the sensor component.

[0028] In some embodiments, the sensor component is configured to engage a wall of the fluid line. In some embodiments, the sensing element is covered by a removable seal, and the cavity is defined between the sensing element and the removable seal. This is advantageous when the sensor component engages a wall of the fluid line, because the removable seal is removed immediately prior to engagement of the sensor component with the fluid line, thereby allowing exposure of the cavity and the sensing element to the fluid in the fluid line.

[0029] In some embodiments, the cavity is a conduit configured to be inserted into a fluid line for engagement of the sensor component with the fluid line. Inserting the cavity into the fluid line ensures that the sensing element is exposed to the fluid.

[0030] In some embodiments, the conduit is configured to be inserted into the fluid line in an in-line configuration, which may be appropriate depending on the particular application of the sensor component and provide direct exposure to liquid in the main fluid line.

[0031] In some embodiments, the conduit is configured to be inserted into the fluid line in a shunt configuration, which may allow the sensor components to be changed without stopping the flow of fluid in the fluid line.

[0032] In some embodiments, the container defines a cavity, and the sensor component is removably inserted into the cavity prior to introducing the gas sterilant, which may be advantageous depending on the type and configuration of the sensor component, and the sensor component is removable from the cavity immediately prior to use.

[0033] 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 in response to the concentration of one or more analytes in the fluid; a connector configured to connect to one or more optical waveguides, where the sensor component is configured to transmit light between the one or more optical waveguides and the one or more sensing elements; a removable seal covering the sensing elements; a sealing cavity between the sensing elements and the removable seal, where the one or more sensing elements are exposed to the cavity; and one or more sealing ports in the cavity, where the sensor component is configured to engage a wall of the fluid line following removal of the removable seal such that the sensing elements are exposed to fluid in the fluid line.

[0034] A sensor component comprising a cavity with a sealing port and a removable seal in the cavity is particularly suitable for use in the sterilization method embodiment of the first aspect of the invention. The cavity allows the sensing element to be maintained exposed to the sterilizing fluid, thereby allowing the sensing element to remain hydrated until immediately prior to use. The removable seal provides a quick and simple way to open the cavity to allow exposure of the sensing element to fluid in the fluid line.

[0035] In some embodiments, the sensor component includes at least two sealed ports that allow gas or liquid to flow into the cavity during sterilization.

[0036] In some embodiments, the removable seal is configured to prevent the sensor component from engaging a wall of the fluid line prior to removal of the removable seal, thereby ensuring adequate exposure of the sensing element to fluid within the fluid line following engagement of the sensor component with the fluid line.

[0037] Embodiments of the invention will now be described, by way of non-limiting example, with reference to the accompanying drawings, in which: [Brief description of the drawings]

[0038] [Figure 1] FIG. 1 is a cross-sectional view of the sensor components. [Diagram 2] FIG. 2 is an isometric view of the sensor component engaged to the wall of a fluid line. [Diagram 3] FIG. 3 is an enlarged view of the cross section of FIG. 1 showing the ports and cavities. [Figure 4] FIG. 4 shows an embodiment of a sensor component in which the port includes a filter. [Diagram 5] FIG. 5 is a flow chart of an embodiment of a sterilization method. [Figure 6] FIG. 6 shows the sensor components upon introduction of gas sterilant. [Figure 7] FIG. 7 shows the sensor components during replacement of the gas sterilant with a sterilant liquid. [Figure 8] FIG. 8 shows the sensor components when the port is sealed. [Figure 9] FIG. 9 is an exploded view of the sensor component with the conduit and shows how the conduit can be joined to the remainder of the sensor component. [Figure 10] FIG. 10 illustrates a sensor component with a conduit engaged to a fluid line in a bypass configuration. [Figure 11] FIG. 11 shows the sensor component with the conduit and component valve upon introduction of gas sterilant. [Figure 12] FIG. 12 shows the sensor component with conduit and component valve during replacement of gas sterilant with sterilant liquid. [Figure 13] FIG. 13 shows the sensor component with the conduit and component valve when the port is sealed. [Figure 14] FIG. 14 shows the sensor component with the conduit and component valve after the sterilization process has been completed. [Figure 15] FIG. 15 illustrates an intravascular sensor component where the sensor component does not include a cavity through which the sensing element is exposed during sterilization. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0039] 1 and 2 show an example of a sensor component 1 in which the sterilization method described herein may be used. The sensor component 1 is 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 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 essential and the sensor component 1 may also be used in other contexts, for example monitoring analyte concentrations in fluids other than blood. 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.

[0040] The sensor component 1 comprises one or more sensing elements 5. Although the sensor component 1 comprises four sensing elements, this is not required and other embodiments may comprise one, two, three or more sensing elements 5. Each of the sensing elements 5 comprises a luminescent compound, preferably a fluorescent compound, more preferably a fluorescent organic dye. The luminescent compound may be different for the different sensing elements 5 and will depend on the analyte to be measured. Examples of suitable luminescent compounds include seminaphtharhodafluor (SNARF), mag-fluo-4 and derivatives thereof. The sensing element 5 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.

[0041] The sensing elements 5 have optical properties that change depending on the concentration of one or more analytes in the fluid. The optical property can be emission or absorption of light. If the sensing elements 5 include a luminescent compound, the optical property can be luminescence lifetime. The optical property can be the same for all of the sensing elements 5 or can be different between the sensing elements 5. Various measurement formats can be used to minimize drift in the sensor. Fluorescence lifetime and ratiometric formats are commonly used when available because they are less susceptible to common sources of error that can cause drift. Ratiometric formats measure the light from the luminescent compound twice, for example at different wavelengths, and calculate the ratio. However, because linear intensity measurement methods are often the only available formats, it is important that aspects of the design of the sensor component 1 are selected to minimize drift and inaccuracies.

[0042] 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 with the sensing element 5 exposed to the interior of the fluid line 3 such that fluid passing through the sensor component 1 and flowing through the fluid line 3 contacts portions of the sensor component 1 that face the interior of the fluid line 3.

[0043] The sensor component 1 comprises a connector 7 configured to connect with one or more optical waveguides. In the embodiment shown in Figures 1-3, the connector 7 comprises a recess in the sensor component 1. However, in general 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 one or more optical waveguides relative to the connector 7.

[0044] The optical waveguide may transmit light to and from one or more light sources elsewhere in the system in which the sensor component 1 is used. Suitable light sources include LEDs or laser diodes. The optical waveguide may comprise an optical fiber or optical fiber bundle for transmitting excitation light to the sensing element 5. Light emitted from (or transmitted through) the sensing element 5 is also returned via the optical waveguide to a detector in the system that detects the intensity of light from the sensing element 5. In some embodiments, the sensor component 1 may comprise one or more optical waveguides and / or one or more light sources and detectors. 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 element 5 may be measured.

[0045] Medical devices are typically terminally sterilized by gamma irradiation, electron beam, or gaseous agents such as ethylene oxide. Both gamma irradiation and electron beam are ionizing radiations that generate highly reactive free radicals through the decomposition of polymers. This can cause progressive plastic embrittlement of parts of medical devices, leading to a shortened lifespan. The generation of free radicals upon irradiation also generates color centers in plastic and glass materials that are often used for optical components such as optical waveguides, thus causing a decrease in light transmission. This decrease in light transmission can usually be accommodated during calibration of the sensor component 1, as long as the light transmission is not reduced to a point where the optical excitation used to measure the optical properties of the sensing element 5 is prevented. However, the material transmission can be restored by passing visible light through the optical component. This is exactly what happens during continuous monitoring, leading to a drift in the properties of the optical component during use (effectively causing a gradual and continuous change in the intensity of light incident on the sensing element 5).

[0046] Furthermore, in the presence of small amounts of oxygen and water, peroxy and hydroxyl free radicals are generated during irradiation. These are highly reactive and tend to react with the sensing element 5 and change their optical properties (e.g. by causing an effective change in the concentration of the luminescent compound in the sensing element, or even in the luminescent ability of the luminescent compound by changing its quantum efficiency). In an attempt to minimize this, the sensor component 1 can be gamma-irradiated under anhydrous and nitrogen. On the one hand, this has the effect of stabilizing the organic free radicals, and when the sensor component is eventually introduced to oxygen and water (typically during use), peroxy and hydroxyl free radicals will be generated again, leading to a drift in the properties of the sensing element 5 during use.

[0047] To avoid the above drawbacks of using radiation to sterilize the sensor component 1, it is preferable to use a more harmless gas sterilant such as ethylene oxide. Gas sterilization must usually be performed when the sensor component 1 is dry to avoid reaction of the gas sterilant with water. For example, if the sensor component 1 is wet with water, ethylene oxide will react with the water to form ethylene glycol.

[0048] On the other hand, the properties of the sensing element 5 may change with the hydration level. For example, the luminescent compound of the sensing element 5 may be suspended in a hydrogel that is up to 90% water. Changes in hydration may cause changes in the intensity of light reaching the luminescent compound and an effective change in the concentration of the luminescent compound. Even hydrophobic components may gradually take up water. Therefore, the sensor component 1 needs to be given to the user with the sensing element 5 fully hydrated. This ensures stability of the measurement and low hydration drift immediately upon request by the user. Otherwise, if the hydration of the sensing element 5 changes at the point of use, either during calibration or during continuous monitoring, the optical properties of the sensing element 5 will change gradually as the sensing element 5 becomes hydrated. This results in significant drift, typically over a time range of several hours. To stabilize the hydration at the point of use, the user would be required to subject the sensor component 1 to a stabilization phase that may last for several hours before the sensor component 1 can be used. This may be impractical for real-world field use.

[0049] The sterilization method described herein addresses this tradeoff in the requirement to perform dry sterilization yet have the sensor component 1 sterile and hydrated to minimize drift.

[0050] To facilitate this method, the sensor component 1 is provided with a removable seal 47 covering the sensing element 5, with a sealed cavity 45 defined between the sensing element 5 and the removable seal 47. The one or more sensing elements 5 are exposed in the cavity 45. The removable seal 47 in Figure 1 is a tabbed aluminum foil layer that is adhesively affixed to the underside of the sensor component 1. However, this is not required and the removable seal 47 may generally be formed in any suitable manner, for example a removable plastic film or a rigid cover.

[0051] The sensor component 1 of Figure 1 is configured to engage a wall of the fluid line 3. As shown in Figure 3, the sensor component 1 is further configured to engage a wall of the fluid line 3 following removal of the removable seal 47, thereby exposing the sensing element 5 to fluid within the fluid line 3. Once the removable seal 47 is removed and the sensor component 1 engages the wall of the fluid line 3, the cavity 45 becomes part of the interior of the fluid line 3 and is filled with fluid from the fluid line 3 during use.

[0052] As shown in Figure 3, the removable seal 47 is configured such that the sensor component 1 cannot engage the walls of the fluid line 3 prior to removal of the removable seal 47. This prevents a user from engaging the sensor component 1 with the fluid line 3 without removing the removable seal 47, and as a result, the sensing element 5 is not exposed to fluid in the fluid line 3. In the example of Figure 3, this is achieved by means of a recess 46 in the sensor component 1 that provides engagement with the walls of the fluid line 3 but is covered by the removable seal 47. However, this is not required and any other suitable method may be used.

[0053] The sensor component 1 includes two sealed ports 41 that provide fluid connection to the cavity 45. The ports 41 are sealed when the sensor component 1 is provided to an end user, but may be unsealed to allow fluid connection to the cavity 45 from outside the sensor component 1 during a sterilization method. Two ports 41 are preferred because they allow for continuous flow of a fluid, such as a gas sterilant, from one port 41 to the other. However, it is not required that the sensor component 1 include two ports 41, and in some embodiments the sensor component 1 may include one port 41 or more than two ports 41.

[0054] As shown in FIG. 4, in some embodiments, the port 41 may include a filter 42, which may, for example, help maintain the connector in a sterile state after sterilization. The filter 42 may be configured to block bacteria from passing through the filter 42. This may help prevent bacteria from entering the component when a sterilizing liquid is used to replace a gas sterilant. For example, the filter 42 may be a 0.22 micron filter. The filter 42 may be removable so that it may be removed from the component at the appropriate stage of connection to a fluid line at the point of use.

[0055] As described further below, it is generally not required for the present method that the sensor component sterilized using the present method define a sealed cavity 45 and include one or more ports 41. However, the sensor component 1 shown in Figures 1-3 is particularly suited for the present method.

[0056] A method for sterilizing 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 is shown in Figure 5. The method allows for sterilization with a gas sterilant while also allowing the sensor component 1 to be delivered to an end user in a sterile, hydrated state.

[0057] The method comprises a step S1 of preconditioning the sensor component 1 by exposing the sensor component 1 to a predetermined temperature and / or humidity for a predetermined length of time prior to introducing the gas sterilant. The predetermined length of time may be 4 hours or more, optionally 8 hours or more, optionally 1 day or more, optionally 2 days or more. The step S1 of preconditioning the sensor component 1 by prehumidification and / or preheating is to bring the sensor component 1 to a condition where the gas sterilant will have optimal effect and be most effective in sterilizing the sensor component 1. The preconditioning step S1 is preferred but not required and may be omitted in some embodiments depending, for example, on the choice of the gas sterilant. Preferably, the method is carried out at a temperature in the range of 35°C to 65°C. If the preconditioning step S1 comprises exposing the sensor component 1 to a predetermined temperature, the predetermined temperature may be in the range of 35°C to 65°C.

[0058] The method further comprises the step S3 of introducing a gaseous sterilant into the sealed cavity 45 via one or more ports 41 providing a fluid connection to the cavity 45, exposing the one or more sensing elements 5 to the cavity 45. The gaseous sterilant is preferably one of ethylene oxide, ozone, hydrogen peroxide, nitrogen dioxide and formaldehyde. Most preferably, the gaseous sterilant is ethylene oxide.

[0059] 1-3, a cavity is defined by the sensor component 1, which may include one or more ports 41. In particular, the sensing element 5 may be covered by a removable seal 47, with a cavity 45 defined between the sensing element 5 and the removable seal 47. In this case, the method is performed with the removable seal 47 in place. However, as described further below, it is not necessary that a cavity be defined by the sensor component or that the sensor component include ports 41.

[0060] 6 illustrates step S3 of introducing a gaseous sterilant. In this embodiment, prior to step S3 of introducing the gaseous sterilant into cavity 45, piping 51 is connected to port 41. Pipe 51 includes a pipe valve 53 configured to open and close pipe 51. Pipe 51 and pipe valve 53 allow for better control of the flow of gaseous sterilant into and out of cavity 45 during the sterilization method, but this is not required and may be omitted in some embodiments of the method.

[0061] The sensor component 1 includes two ports 41, and the step S3 of introducing the gaseous sterilant includes flowing the gaseous sterilant between the two ports 41. This is generally not necessary, and in embodiments having only a single port 41, the gaseous sterilant may be introduced through that single port 41. In some embodiments, the flow of the gaseous sterilant may be actively facilitated, for example, using a pressure gradient between the ports 41. In other embodiments, the gaseous sterilant may flow passively between the ports 41, for example, by diffusion.

[0062] The step S3 of introducing the gaseous sterilant then comprises opening the piping valve 53 and flowing the gaseous sterilant through the piping 51, thereby allowing the gaseous sterilant to flow into the cavity 45 through the piping 51 and the piping valve 53. This sterilizes the interior of the cavity 45, including the sensing element 5 and other parts of the sensor component 1 that will come into contact with the fluid in the fluid line 3 when the sensor component 1 is in use. The gaseous sterilant is preferably left in the cavity 45 for at least 1 hour, optionally 2 hours, optionally 4 hours, optionally 6 hours, before performing the step of replacing the gaseous sterilant. This ensures that the interior of the cavity 45 is completely sterilized.

[0063] Step S3 of introducing a gaseous sterilant into the cavity 45 as shown in FIG. 6 comprises placing the sensor component 1 in a sealed environment and introducing the gaseous sterilant into the sealed environment. The sealed environment can be, for example, a sterile bag or other container. This is an advantageous manner of ensuring that the sensor component 1 is fully exposed to the gaseous sterilant, allowing the entire sensor component 1 to be sterilized, not just the inside of the cavity 45. The gaseous sterilant can diffuse into the cavity 45 and the internal space of the sensor component 1 through the port 41, with or without the piping 51 and piping valve 53.

[0064] As shown in FIG. 7, following step S3 of introducing the gas sterilant into cavity 45, the method comprises replacing the gas sterilant with a sterilant liquid via port 41. Similar to step S3 of introducing the gas sterilant, the step of replacing the gas sterilant comprises flowing the sterilant liquid between two ports, but can also be applied correspondingly when there is only one port 41. The sterilant liquid is flowed through piping 51 with piping valve 53 in an open state. The sterilant liquid is preferably a water-based buffer solution, such as, for example, a phosphate buffer solution. Preferably, the sterilant liquid is a calibration solution containing one or more analytes at a predetermined concentration. This can be useful for subsequent calibration of sensor component 1 at the point of use. In FIG. 7, the sterilant liquid is contained in a syringe 54, which is connected to piping 51 and is used to flow the sterilant liquid through piping 51 between ports 41 and into cavity 45. Following the step of replacing the gas sterilant with sterilant liquid, cavity 45 is maintained filled with sterilant liquid, thereby ensuring that sensing element 5 remains hydrated when sensor component 1 is delivered to an end user.

[0065] The step of replacing the gaseous sterilant with a sterilizing liquid via port 41 comprises step S9 of replacing the gaseous sterilant with a sterilizing gas via port 41 followed by introducing a sterilizing liquid via port 41. During step S9 of introducing the sterilizing liquid, the sterilizing liquid will displace the sterilizing gas. This reduces the chance of any liquid coming into contact with the gaseous sterilizing agent, which may be undesirable depending on the choice of gaseous sterilizing agent. Introducing the sterilizing liquid with syringe 54 in FIG. 7 is performed only after the gaseous sterilizing agent has been replaced with a sterilizing gas. The sterilizing gas is preferably a relatively inert gas such as nitrogen or a noble gas to ensure that it does not chemically react with the sensor component 1. Alternatively, the sterilizing gas may be sterile air, which may be easier and cheaper to provide. The gaseous sterilizing agent is removed and replaced by a sterilizing gas such as air before the sterilizing liquid is introduced, otherwise water in the sterilizing liquid would react with the gaseous sterilizing agent. For example, ethylene oxide reacts with water to form ethylene glycol, which is toxic and difficult to remove from the sensor component 1 once formed. If contact between the gas sterilant and water is not an issue, the step of replacing the gas sterilant with a sterilizing gas may be omitted and replacing the gas sterilant with a sterilizing liquid may comprise directly replacing the gas sterilant with a sterilizing liquid.

[0066] Replacing the gaseous sterilant with sterilizing gas via port 41 comprises step S5 of removing the gaseous sterilant by exhaust through port 41, followed by step S7 of introducing sterilizing gas through port 41. This ventilation / aeration ensures that the gaseous sterilant is completely removed from sensor component 1 and cavity 45. This may be necessary, for example, because ethylene oxide and other gaseous sterilants are toxic, and it is a regulatory requirement that all gaseous sterilant be removed as part of the sterilization process to ensure that no residues are left behind that could be harmful to the patient.

[0067] If the step S3 of introducing the gaseous sterilant into the cavity 45 comprises subjecting the sensor component 1 to a sealed environment, the step of replacing the gaseous sterilant with a sterilant liquid is performed without removing the sensor component 1 from the sealed environment. The syringe 54 may be sterilized in the same sealed environment as the sensor component 1, the tubing 51, and the tubing valve 53 to ensure that no contaminants are introduced when the syringe 54 is connected to the tubing 51.

[0068] Following replacement of the gas sterilant with sterilant liquid via port 41, the method comprises sealing port 41, as shown in Figure 8. The sensor component 1 shown in Figures 1-3 and 6-8 includes a dedicated port 41 that is used for the sterilization method and is not required for subsequent use of the sensor component 1. In this case, the method may comprise permanently sealing port 41. Alternatively, sealing port 41 may comprise sealing port 41 with a removable element 43.

[0069] As shown in FIG. 8, the method includes a step S11 of closing the tubing valve 53 before the step of sealing the port 41. This ensures that the sterilizing liquid remains in the cavity 45. The step of sealing the port 41 then includes a step S13 of sealing the tubing 51 and a step S15 of cutting the tubing 51 outside the position where the tubing 51 is sealed so that the sealed portion of the tubing 51 remains connected to the port 41. Specifically, the tubing 51 is cut between the position where the tubing 51 is sealed and the tubing valve 53. Referring to FIG. 8, the tubing 51 can be sealed between the tubing valve 53 and the port 41. The sealed portion of the tubing can function as a removable element 43 that seals the port 41 or can be permanently joined to the port 41, in which case they will permanently seal the port 41. The tubing 51 can be sealed using any suitable method, for example, ultrasonic welding or solvent sealing.

[0070] All of the steps of the method may not be performed at the same location. For example, the introduction of the gaseous sterilant S3 and the replacement of the gaseous sterilant with a sterile gas may be performed at one location. The sterile sensor component 1 may then be transferred to another location in the sterile container (e.g., a sterile bag constituting the sealed environment described above). The replacement of the sterile gas with a sterile liquid and the sealing of the port may then be performed at another location. This may be facilitated by sterilizing a syringe 54 containing the sterile liquid together with the sensor component 1 in the sealed environment as described above. The replacement of the sterile gas with a sterile liquid and the step S11 of closing the piping valve 53 may then be performed without removing the sensor component 1 from the sealed environment.

[0071] The method has been described thus far in the context of the sensor component 1 of Figures 1-3 configured to engage a wall of a fluid line 3. In other cases, the method may be applied to a sensor component configured to engage a fluid line 3 in an in-line or bypass (shunt) configuration. An example of such a sensor component 100 is shown in Figure 9. In this example, the sensor component 100 defines a cavity 145, but the cavity 145 is not defined between the sensing element 5 and the removable seal 47. Instead, the cavity 145 is defined by a conduit 29 configured to be inserted into the fluid line 3 for engagement of the sensor component 100 with the fluid line 3. In this case, just as the port 41 providing a fluid connection to the cavity 145 is used during sterilization, the port 41 is also used to allow fluid from the fluid line 3 to contact the sensing element 5 during use.

[0072] In some embodiments, the conduit 29 is configured to be inserted into the fluid line 3 in an in-line configuration, in which case the conduit 29 becomes part of the main fluid line 3. In such circumstances, it may be preferable for the port 41 to be sealed with a removable element 43, as described above, allowing the port 41 to be unsealed immediately prior to inserting the conduit 29 into the fluid line 3.

[0073] 10 illustrates another embodiment in which the conduit 29 is configured to be inserted into the fluid line 3 in a shunt configuration, which may be preferred in some circumstances as it allows the sensor component to be connected and disconnected from the fluid line 3 without having to interrupt the flow of fluid in the fluid line 3.

[0074] 11-13 show an embodiment of the method applied to a sensor component 100 having a cavity 145 defined by a conduit 29. The sensor component 100 further comprises a component valve 55 for each port 41 configured to open and close the port 41. The component valves 55 may be preferred, particularly when the sensor component 100 is configured to be inserted in a shunt configuration in a fluid line, but are generally not required. The steps of the method are not significantly modified from those described with respect to the sensor component 1 of FIGS. 1-3, except as described below.

[0075] The step S1 of preconditioning the sensor component 100 is as described above for the sensor component 100.

[0076] Figure 11 shows step S3 of introducing a gaseous sterilant. In Figure 11, piping 51 and piping valve 53 are present, but this is generally not required. The sensor component 100 includes component valve 55 connected to port 41, and connecting piping 51 to port 41 includes connecting the piping to component valve 55. Step S3 of introducing a gaseous sterilant is as described above, but with the addition that component valve 55 is open. As described above, this step is performed with piping valve 53 open.

[0077] 12 illustrates the step of replacing the gaseous sterilant with a sterilant liquid. As with step S3 of introducing the gaseous sterilant, this step is as described for sensor component 1 above, but with component valve 55 open.

[0078] 13 shows the step of sealing one or more ports 41. This is as described above for the sensor component 1, but the valve blocking step S11 also comprises blocking the component valve 55. The tubing sealing step S13 is performed by blocking the component valve 55, which at least to some extent seals the tubing 51. For the sensor component 100, step S15 comprises cutting the tubing 51 outside the location where the tubing 51 is sealed by the component valve 55, such that the component valve 55 remains connected to the port 41. The tubing 51 can be further sealed in step S13 by one of the methods described above, outside the component valve 55, for example between the component valve 55 and the tubing valve 53, and cut in step S15, as shown in FIG. 14, such that the sealed portion 43 of the tubing 51 remains connected to the component valve 55. This sealed portion of the tubing 51 thereby provides a removable element 43.

[0079] The methods may also be applied to other types of sensor components, such as sensor components that do not themselves define a cavity and do not include a port 41. In all of the embodiments described thus far, the cavity is defined by the sensor component, for example by a removable seal 47 or by a conduit 29, although this is not generally necessary to make the sterilization methods described herein applicable.

[0080] FIG. 15 illustrates an intravascular sensor component 200 comprising an optical waveguide with a sensing element 5 disposed at the end of the waveguide. The intravascular sensor component 200 may be configured to engage a fluid line, such as a blood vessel, within a patient's body. The intravascular sensor component 200 does not define a cavity. Instead, the container 60 defines a cavity 245, and the container further comprises a port 41. In FIG. 15, the container 60 also comprises a component valve 55, although this is generally not required. The methods described above are also applicable to this type of intravascular sensor component 200.

[0081] The step S1 of preconditioning the sensor component 200 is also carried out as described above.

[0082] Prior to step S3 of introducing the gaseous sterilant, the intravascular sensor component 200 is removably inserted into the cavity 245. The container 60 is configured such that when inserted into the cavity 245, the sensor component 200 forms a seal with the container. This prevents fluid (e.g., gaseous sterilant, sterilizing gas or sterilizing liquid) from entering or leaving the cavity 245 other than through the port 41 during the sterilization method. This also ensures that the sterilizing liquid is maintained in contact with the sensing element 5 after completion of the sterilization method, thereby ensuring that the intravascular sensor component 200 is delivered to the end user in a hydrated state.

[0083] Plumbing 51 and plumbing valve 53 may be connected to component valve 55 as described above for sensor component 100 in Figure 11. Step S3 of introducing gas sterilant will be performed with component valve 55 of container 60 in an open state.

[0084] The steps of replacing the gas sterilant with a sterilant liquid and sealing the one or more ports 41 would also be performed as described above for the sensor component 100. In the case of the sensor component 200 of Figure 15, no portion of the tubing 51 remains attached to the component valve 55. This same embodiment is applicable to the intravascular sensor component 200 as well as other types of sensor components that do not define a cavity.

Claims

1. 1. A method of sterilizing a sensor component for use in a system for measuring the concentration of one or more analytes in a fluid in a fluid line, comprising: The sensor component comprises: 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 being configured to engage the fluid line such that the sensing elements are exposed to the fluid in the fluid line; and 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; Equipped with The method comprises: introducing a gaseous sterilant into the cavity through one or more ports providing a fluid connection to the cavity, wherein the one or more sensing elements are exposed to the cavity; replacing the gas sterilant with a sterilant liquid through the port; sealing the port; A method comprising:

2. 2. The method of claim 1, wherein the step of introducing the gaseous sterilant into the cavity comprises the steps of placing the sensor component in a sealed environment and introducing the gaseous sterilant into the sealed environment, and wherein the step of replacing the gaseous sterilant is performed without removing the sensor component from the sealed environment.

3. 10. The method of claim 1, wherein the gas sterilant remains in the cavity for at least one hour before performing the step of replacing the gas sterilant.

4. 10. The method of claim 1, further comprising preconditioning the sensor component by exposing the sensor component to a predetermined temperature and / or humidity for a predetermined length of time prior to introducing the gaseous sterilant.

5. 10. The method of claim 1, wherein displacing the gaseous sterilant with a sterilant liquid through the port comprises displacing the gaseous sterilant with a sterilant gas through the port, followed by introducing the sterilant liquid through the port.

6. 6. The method of claim 5, wherein replacing the gaseous sterilant with a sterilant gas through the port comprises removing the gaseous sterilant by evacuation through the port, followed by introducing the sterilant gas through the port.

7. 10. The method of claim 1 carried out at a temperature ranging from 35°C to 65°C.

8. 10. The method of claim 1, wherein the gas sterilant is one of ethylene oxide, ozone, hydrogen peroxide, nitrogen dioxide, and formaldehyde.

9. 10. The method of claim 1, wherein the sterile liquid is a calibration solution containing predetermined concentrations of the one or more analytes.

10. 2. The method of claim 1, wherein the one or more ports comprise two ports, and the steps of introducing the gas sterilant and replacing the gas sterilant comprise flowing the gas sterilant and a sterilant liquid between the two ports.

11. The method of claim 1 , wherein sealing the port comprises permanently sealing the port.

12. The method of claim 1 , wherein sealing the port comprises sealing the port with a removable element.

13. further comprising the step of connecting tubing to the one or more ports prior to the step of introducing the gas sterilant into the cavity; the step of introducing the gaseous sterilant comprises the step of circulating the gaseous sterilant through the piping; the step of replacing the gas sterilant comprises the step of circulating the sterilant liquid through the piping; 2. The method of claim 1, wherein sealing the one or more ports comprises sealing the tubing and severing the tubing outside of the location where the tubing is sealed such that the sealed portion of the tubing remains connected to the port.

14. the piping includes a piping valve configured to open and close the piping; the step of introducing the gaseous sterilant is performed with the piping valve in an open state; the step of replacing the gas sterilant is performed with the piping valve in an open state; the piping is cut between the location where the piping is sealed and the piping valve; The method of claim 13 , further comprising the step of closing the plumbing valve before the step of sealing the port.

15. The method of claim 13 , wherein the tubing is sealed using ultrasonic welding or solvent sealing.

16. the sensor component comprises a component valve for the or each port configured to open and close the port; the step of introducing the gaseous sterilant is performed with the component valve in an open state; the step of displacing the gas sterilant is performed with the component valve open; The method of claim 1 , wherein sealing the one or more ports comprises closing the component valve.

17. The method of claim 1 , wherein the sensor component defines the sealed cavity and includes the one or more ports.

18. The method of claim 17 , wherein the sensor component is configured to engage a wall of the fluid line.

19. 20. The method of claim 18, wherein the sensing element is covered by a removable seal, and the cavity is defined between the sensing element and the removable seal.

20. The method of claim 17 , wherein the cavity is a conduit configured to be inserted into the fluid line for engagement of the sensor component with the fluid line.

21. The method of claim 20 , wherein the conduit is configured to be inserted into the fluid line in an in-line configuration.

22. 21. The method of claim 20, wherein the conduit is configured to be inserted into the fluid line in a shunt configuration.

23. The method of any one of claims 1 to 16, wherein a container defines the cavity, and the sensor component is removably inserted into the cavity prior to introducing the gaseous sterilant.

24. 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, comprising: one or more sensing elements having optical properties that vary in response to the concentration of the one or more analytes in the fluid; 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 removable seal covering the sensing element; a sealed cavity defined between the sensing element and the removable seal, the one or more sensing elements being exposed to the cavity; one or more sealing ports providing fluid connection to the cavity, the one or more sealing ports configured to engage the sensor component with a wall of the fluid line following removal of the removable seal such that the sensing element is exposed to the fluid in the fluid line; A sensor component comprising:

25. 25. The sensor component of claim 24, comprising at least two sealing ports.

26. 25. The sensor component of claim 24, wherein the removable seal is configured to prevent the sensor component from engaging a wall of the fluid line prior to removal of the removable seal.

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