Optical fibre

Abstract

The present disclosure relates to an optical fibre for simultaneously measuring an analyte and an additional parameter in blood. The fibre comprises a hydrogel provided at a tip of the optical fibre for interferometrically measuring the analyte and a Fibre Bragg Grating, FBG, configured to measure the additional parameter. The fibre is configured to transmit a broadband optical signal, measure the analyte using a first part of the broadband optical signal and measure the additional parameter using a second part of the broadband optical signal. The disclosure further relates to a corresponding system and method.

Description

[0001] OPTICAL FIBRE

[0002] The present disclosure relates to an optical fibre for simultaneously measuring an analyte and an additional parameter in blood as well as a corresponding system and method.

[0003] Hemodynamic monitoring is performed on hospitalised patients to detect, find the root of, and evaluate treatment of circulatory instability. Moreover, a blood glucose measurement is also often performed in hospitalised patients to detect, find the root of, and treat glycaemic instability.

[0004] In patients under extreme stress or critical illness, hormonal systems that affect the hemodynamic system can also affect the glycaemic system. For instance, the severe physiological stress of trauma or major surgery can lead to increased sympathetic activity, resulting in changes in cardiac output and vascular tone, while also inducing insulin resistance and hyperglycemia. In acute respiratory distress syndrome (ARDS) hemodynamic instability can be seen due to the pulmonary vascular dysfunction, while inflammatory processes release cytokines that affect glycemia. Similarly, acute heart failure can lead to hemodynamic compromise and impaired tissue perfusion, exacerbating insulin resistance and glucose dysregulation. Moreover, glycemic control may reduce risk of infection which has a detrimental effect on patients vulnerable enough to warrant hemodynamic monitoring.

[0005] Simultaneous monitoring of the hemodynamic and glycemic system allows for more timely therapies in patients that need this monitoring than by only monitoring one. However, the measurements require a plurality of catheters or aditus to a patient's blood circuit and are often complex and cost intensive.

[0006] It is thus an object of the present disclosure to provide a simple and compact system for simultaneously measuring an analyte and an additional parameter utilising an optical fibre. It is a further object to provide a minimally invasive device and thus reduce the effort or number of aditus required for performing these measurements. The object is achieved with the features of the present disclosure.

[0007] The invention is specified by the independent claims. Preferred embodiments are defined in the dependent claims. In the following description, although numerous features may be designated as optional, it is nevertheless acknowledged that all features comprised in the independent claims are not to be read as optional.

[0008] The present disclosure relates to an optical fibre for simultaneously measuring an analyte and an additional parameter in blood. The fibre comprises a hydrogel provided at a tip of the optical fibre for interferometrically measuring the analyte and a Fibre Bragg Grating, FBG, configured to measure the additional parameter. The fibre is configured to transmit a broadband optical signal, measure the analyte using a first part of the broadband optical signal and measure the additional parameter using a second part of the broadband optical signal.

[0009] Various embodiments may preferably implement the following features.

[0010] Preferably, the second part of the broadband optical signal is different from the first part of the broadband optical signal.

[0011] Preferably, the second part of the broadband optical signal is a narrowband signal located within the first part of the broadband optical signal.

[0012] Preferably, the optical fibre is a single mode fibre or a double-clad fibre, which consists of a single mode core and a surrounding second cladding which acts as a multi-mode core.

[0013] Preferably, the second part of the broadband optical signal is located within the blue wavelength range of the first part of the broadband optical signal to avoid the appearance of short wavelength radiation modes from the FBG in the broadband optical signal, due to a sharp change in refractive index between core and cladding in the grating zone, transmitted in the optical fibre cladding.

[0014] Preferably, the optical fibre further comprises an interferometer configured to measure the analyte, wherein the interferometer comprises the hydrogel. Preferably, the hydrogel is configured to change a volume in response to the analyte. Preferably, the interferometer is a Fabry-Perot interferometer. Preferably, the FBG is provided towards a tip of the optical fibre.

[0015] Preferably, the additional parameter is a temperature of blood. Preferably, the analyte is a glucose level.

[0016] The present disclosure further relates to a system for simultaneously measuring an analyte and an additional parameter. The system comprises an optical fibre as described above, a broadband light source configured to emit the broadband optical signal to the optical fibre for transmitting the broadband optical signal through the optical fibre and at least one detector configured to receive light from the optical fibre for measuring the analyte and the additional parameter.

[0017] Various embodiments may preferably implement the following features.

[0018] The system may further comprise a hydrogel cavity, wherein the hydrogel is located in the hydrogel cavity; and a photonic integrated circuit, PIC, which is connected to the hydrogel cavity via input-output, IO, links. The PIC preferably comprises the at least one light source, which is a broadband emitting light source generating the optical signal as a broadband optical signal; a spectrometer, wherein the spectrometer splits the broadband optical signal, which was previously reflected by the hydrogel cavity and then received by the spectrometer, into multiple channels; and the at least one detector, which is a photodiode array having multiple photodiodes, wherein the multiple channels are each connected to a respective photodiode and the multiple photodiodes each receive a narrow range signal simultaneously.

[0019] Preferably, the broadband emitting light source is a superluminescent light emitting diode, SLED.

[0020] Preferably, the spectrometer is based on an arrayed waveguide grating, AWG.

[0021] In another embodiment, the system may further comprise a hydrogel cavity, wherein the hydrogel is located in the hydrogel cavity; and a photonic integrated circuit, PIC, which is connected to the hydrogel cavity via input-output, IO, links. The PIC preferably comprises the at least one light source, which is a wavelength tuneable narrow light source generating the optical signal as a broadband optical signal; and the at least one detector, which is a broadband photodetector receiving the broadband optical signal. Preferably, the at least one wavelength tuneable narrow light source is a wavelength tuneable laser configured to perform quasi-continuous tuning to obtain a broad wavelength tuning range.

[0022] Preferably, the broadband photodetector is a single photodiode.

[0023] In another embodiment, the system may further comprise a hydrogel cavity, wherein the hydrogel is located in the hydrogel cavity; and a photonic integrated circuit, PIC, which is connected to the hydrogel cavity via input-output, IO, links. The PIC preferably comprises the at least one light source, which is an array of narrow light sources together generating the optical signal as a broadband optical signal; an arrayed waveguide grating, AWG, wherein the AWG splits the broadband optical signal, which was previously reflected by the hydrogel cavity, into multiple channels; and the at least one detector, which is a broadband photodetector receiving the broadband optical signal.

[0024] Preferably, the array of narrow light sources is a combination of distributed feedback, DFB, lasers and vertical cavity surface emitting lasers, VCSELs, with their wavelengths tuned to align with the passband of the AWG.

[0025] Preferably, the at least one light source is an arrayed waveguide grating laser, AWGL, using the AWG as laser cavity for wavelength filtering to achieve single mode lasing.

[0026] The system of this present embodiment may further comprise facets and on-chip mirrors configured to provide laser feedback. The facets and on-chip mirrors may provide multimode interference reflectors to obtain a reflective semiconductor optical amplifier, SOA, array.

[0027] Preferably, the broadband photodetector is a single photodiode.

[0028] Preferably, the system further comprises a thermistor for measuring temperature within the system to obtain an approximation and to account for any potentially falsely measured phase change.

[0029] Preferably, the system further comprises at least one processor, wherein the at least one processor is configured to determine the analyte using a first part of the broadband optical signal and to determine the additional parameter using a second part of the broadband optical signal based on the light received at the at least one detector. Preferably, the processor is configured to control the broadband light source. Preferably, the light received at the detector is reflected light.

[0030] The present disclosure further relates to a method for simultaneously measuring an analyte and an additional parameter in blood. The method comprises providing an optical fibre. The optical fibre may be provided in the blood. The fibre comprises a hydrogel provided at a tip of the optical fibre for interferometrically measuring the analyte and a Fibre Bragg Grating, FBG, configured to measure the additional parameter. The method further comprises transmitting a broadband optical signal through the optical fibre, measuring the analyte using a first part of the broadband optical signal and measuring the additional parameter using a second part of the broadband optical signal.

[0031] Various embodiments may preferably implement the following features.

[0032] Preferably, the second part of the broadband optical signal is different from the first part of the broadband optical signal. Preferably, the second part of the broadband optical signal is a narrowband signal located within the first part of the broadband optical signal.

[0033] Preferably, the optical fibre is a single mode fibre or a double-clad fibre which consists of a single mode core and a surrounding second cladding which acts as a multi-mode core.

[0034] Preferably, the second part of the broadband optical signal is located within the blue wavelength range of the first part of the broadband optical signal to avoid the appearance of short wavelength radiation modes from the FBG in the broadband optical signal, due to a sharp change in refractive index between core and cladding in the grating zone, transmitted in the optical fibre cladding.

[0035] Preferably, the analyte is measured using an interferometer, wherein the interferometer comprises the hydrogel. Preferably, the hydrogel is configured to change a volume in response to the analyte. Preferably, the interferometer is a Fabry-Perot interferometer.

[0036] Preferably, the FBG is immersed in the blood. Preferably, the additional parameter is a temperature of the blood. Preferably, the analyte is a glucose level.

[0037] Preferably, the method is performed in vivo. Preferably, the temperature measurement is a thermodilution measurement, more preferably a transpulmonary thermodilution measurement.

[0038] Other aspects, features, and advantages will be apparent from the summary above, as well as from the description that follows, including the figures and the claims.

[0039] Embodiments of the present disclosure will now be described by way of example only and with reference to the following accompanying drawings. In the figures, the same reference numerals denote the same or similar elements.

[0040] Fig. 1 shows an optical fibre according to an embodiment of the present disclosure.

[0041] Fig. 2 schematically shows a distal end of an optical fibre according to an embodiment of the present disclosure.

[0042] Fig. 3 shows an exemplary graph according to an embodiment of the present disclosure.

[0043] Fig. 4 shows a flow chart of a method according to an embodiment of the present disclosure.

[0044] Fig. 5 schematically shows a first type electronic circuit 1 (Cl) according to an embodiment of the present disclosure.

[0045] Fig. 6 schematically shows a different second type electronic circuit 2 (C2) according to an embodiment of the present disclosure.

[0046] Fig. 7A-B schematically show different third types of electronic circuits 3a (C3a) and 3b (C3b) according to an embodiment of the present disclosure.

[0047] In Fig. 1, an optical fibre 1 according to an embodiment is shown. The fibre 1 comprises a hydrogel 2 provided at a tip of the optical fibre 1 for interferometrically measuring the analyte and a Fibre Bragg Grating, FBG 3, configured to measure an additional parameter. The fibre 1 is configured to transmit a broadband optical signal, measure the analyte using a first part of the broadband optical signal and measure the additional parameter using a second part of the broadband optical signal. In the following, it will first be briefly referred to the working principle of a Fabry-Perot Sensor and a Fibre Bragg Grating (FBG).

[0048] The abrupt variation of the refractive index between the fibre 1 (in particular a silica fibre), hydrogel 2 and fluid can be modelled as two weakly reflecting mirrors depicted by the boundary between the fibre 1 and the hydrogel 2, and the hydrogel 2 and surrounding fluid. The system represents a Fabry- Perot (FP) cavity. The model is shown in Fig. 2 (without FBG).

[0049] In Fig. 2, the hydrogel 2 makes up the Fabry- Perot cavity. The refractive indexes neff, ng, nf are the effective index of the fibre 1, index of the hydrogel 2 and index of the fluid, respectively. The spacing of the two boundaries is indicated as Lg.

[0050] The reflection coefficients are ri and r2. The second and weakest reflection at r2 interferes with the reflected light at ri, which creates a sinusoidal intensity interference pattern in the spectrum. The FP interferogram is described by where k = (2TTH5) / is the wavenumber inside the cavity. Solving this equation determines the length and length changes of the hydrogel 2 cavity.

[0051] The basic principle of a Fibre Bragg Grating as used in the present disclosure is to detect a shift in a returned "Bragg" wavelength in response to a stimulus. In the present case, the stimulus may, e.g., be a change in temperature.

[0052] The refractive index profile is periodic with a given Bragg-period A over a grating length L. The incoming wavelengths undergo some amount of reflection at each boundary of a changing index. The incident mode, with propagation constant |3, on the FBG which accumulates a phase difference equal to an integer multiple of 2n after travelling one round trip within the space of A, will add up in phase and constructively interfere in the backward direction and deconstructively interfere in the forward direction. If the reflectance is strong, the FBG 3 can act as a perfect mirror on a range of wavelengths around the central Bragg wavelength.

[0053] When the FBG 3 is subject to an increase in temperature, the period of the grating A will increase due to thermal expansion and a change in the effective refractive index neff will occur due to the thermo-optic effects. In the case of silica fibres, the thermal response is dominated by the change in the effective refractive index, which accounts for 95% of the shift in the Bragg reflection. In addition, an FBG 3 can be used for measuring deformation due to its sensitivity to strain but this is not of particular relevance to the present case. In a broad sense, the thermal response can be found by considering the Bragg peak AB at an initial temperature To subject to a change AT.

[0054] T = To+ AT,

[0055] AB(T) = 2neff(T) (T .

[0056] Using the temperature coefficients and thermal expansion coefficients of the materials, a temperature change can be determined based on the detected wavelength shift (see also [1]).

[0057] Turning back to Fig. 1, the optical fibre 1 may comprise a core 11 and a cladding 12. The optical fibre 1 may be a single mode fibre or a double-clad fibre which consists of a single mode core and a surrounding second cladding which acts as a multi-mode core. At the tip of the fibre 1, a dome-shaped measuring material 2 is formed. However, the measuring material may also have other shapes which are equally suitable for measuring the analyte. In the present embodiment, the measuring material 2 is a hydrogel 2, in particular a cross-linked polymer hydrogel. The hydrogel 2 may be immobilised on the tip of the fibre 1 using a silanisation technique. To ensure uniform gelation with an optical quality surface, the gelation may be performed in an oxygen-free atmosphere in an oxygen-free organic solution. The gelation may be triggered by light that induces a photo-initiator to decompose into a free radical species that triggers the polymerisation. The light may be guided either from the optical fibre or may be irradiated from the outside.

[0058] The above described properties of the hydrogel 2 and the FBG 3 enable the use of two parts of the broadband signal. While the wavelengths around the Bragg wavelength are used to measure the additional parameter, e.g., a temperature (change), the remaining parts of the signal (i.e., higher and lower wavelengths) can be used for interferometrically measuring the analyte. An exemplary graph showing the simultaneous use or detection of an FBG peak and a Fabry-Perot interferogram is depicted in Fig. 3. Depending on the FBG 3 and the hydrogel 2, the spectrum might look differently. E.g., the FBG 3 reflection spectrum may be broader than depicted in the exemplary Fig. 3 and may also be located at a different wavelength.

[0059] FBG may be inscribed by either femtosecond laser inscriptions with and without a phase mask, or UV inscription with phase mask. The FBG grating zone may be confined to the core only in the single mode fibre to minimise forward propagating radiation modes in the cladding, which would show up as peaks (noise) in the blue wavelength part of the Fabry-Perot signal. The FBG grating refractive index modulation amplitude may be small (weak grating, low reflection) to minimise forward propagating radiation modes in the cladding, which would show up as peaks (noise) in the blue wavelength part of the Fabry-Perot signal.

[0060] The FBG grating zone may be confined to the core only in the double-clad fibre to minimise forward propagating radiation modes in the second cladding (multi-mode core), which would show up as peaks (noise) in the blue wavelength part of the Fabry-Perot signal. The FBG grating index modulation amplitude may be small (weak grating) to minimise forward propagating radiation modes in the cladding, which would show up as peaks (noise) in the blue wavelength part of the Fabry-Perot signal.

[0061] In use, a beam of light, in particular the broadband optical signal, is passed along the optical fibre core 11. A portion of the light is reflected back from the boundary between the fibre core 11 and the hydrogel 2. This may form a reference beam for a Fabry-Perot interferometer. The rest of the light is transmitted into the hydrogel 2 which forms a cavity between the fibre core / hydrogel boundary and the hydrogel / external boundary. The light beam reflected back from this cavity causes an interference pattern which may be seen as curve A on a detector.

[0062] The free end of the sensor, i.e., the end where the hydrogel is located (also referred to the distal end), may be placed into a solution containing the target analyte(s). This could, for example, be in-vivo, in which case the probe will be suitably sterilised. When the hydrogel 2 comes into contact with the analyte, the hydrogel 2 will change in volume and / or refractive index. Said change can be interferometrically measured and analysed. The material of the hydrogel 2 is adapted to the target analyte and configured to react to contact with said target analyte by change in volume and / or refractive index. As the hydrogel 2 changes volume, e.g., swells, the physical path length of the light through it is increased. Correspondingly, the wavelengths at which constructive and destructive interference with the reference beam occur are shifted slightly. This can be detected by a detector connected to the other end of the optical fibre 1 at which the hydrogel 2 is not provided. By measuring this shift in wavelength, the swelling of the hydrogel 2 may be determined and hence the concentration of analyte may be deduced.

[0063] The FBG 3 may be written into the optical fibre 1 close to or towards the distal end of the optical fibre 1. In use, the part of the optical fibre 1 where the FBG 3 is provided may by immersed in the fluid in which the target analyte is to be measured.

[0064] In some embodiments, the maximum distance may be limited by a temperature difference between gel and the FBG 3. In particular, in case the distance between the FBG 3 and the hydrogel 2 (or end of the optical fibre 1, respectively) is too large, the FBG 3 may not sense local temperature changes in the hydrogel 2.

[0065] In general, longer separation lengths between the FBG 3 and the hydrogel 2 (Fabry-Perot sensor / fibre end) may result in a mismatch of the temperature at the hydrogel and the temperature at the FBG. The minimum length / distance may determine the shape of the FBG signal. Significantly short separation lengths between FBG 3 and the hydrogel 2 may cause a noisy ripple effect in the FBG peak signal due to the reflective cavity formed between FBG 3 and Hydrogel 2. In some embodiments, the distance may be between 1 mm and 8 mm, preferably not shorter than 2 mm.

[0066] The distance may be measured from a distal end of the FBG 3 to the distal end (tip) of the optical fibre 1.

[0067] In general, despite a fixed distance between the distal end of the FBG 3 and the distal top of the optical fibre, a significantly long FBG 3 grating zone may result in a mismatch of the temperature between the FBG 3 and the local temperature of the hydrogel 2. In some embodiments, the FBG 3 grating zone length may be between 2 mm and 10 mm, preferably not longer than 10 mm.

[0068] Due to thermal impact on the material, the FBG 3 may physically change (as outlined above mainly due to the change in refractive index) and thus the wavelength of reflected light. This change in wavelength can be detected using an optical detector to derive the change in temperature.

[0069] The additional parameter may be a temperature of a fluid, in particular blood. The analyte may be a glucose level. This may be of particular importance for patient monitoring, e.g., in an intensive care unit (ICU). The optical fibre 1 may be introduced into the blood circuit, e.g., through a catheter. Hence, glucose level and temperature of a patient may be simultaneously measured.

[0070] The present disclosure further relates to a system for simultaneously measuring an analyte and an additional parameter. The system comprises an optical fibre 1 as described above, a broadband light source configured to emit the broadband optical signal to the optical fibre 1 for transmitting the broadband optical signal through the optical fibre 1 and at least one detector configured to receive light from the optical fibre 1 for measuring the analyte and the additional parameter.

[0071] The system may further comprise at least one processor. The at least one processor may be configured to determine the analyte using a first part of the broadband optical signal and to determine the additional parameter using a second part of the broadband optical signal based on the light received at the at least one detector.

[0072] The processor may be configured to control the broadband light source. The light received at the detector may be reflected light. In particular, the received light may be light reflected from the FBG 3 and / or the hydrogel 2 as described above.

[0073] The present disclosure further relates to a method for simultaneously measuring an analyte and an additional parameter in blood. The method corresponds to the above description of the disclosed fibre 1 and system.

[0074] The method may comprise providing an optical fibre 1 in the blood. The fibre 1 comprises a hydrogel 2 provided at a tip of the optical fibre for interferometrically measuring the analyte and a Fibre Bragg Grating, FBG 3, configured to measure the additional parameter. The method further comprises transmitting SI a broadband optical signal through the optical fibre 1, measuring S2 the analyte using a first part of the broadband optical signal and measuring S3 the additional parameter using a second part of the broadband optical signal. The method steps SI to S3 are depicted in the flowchart in Fig. 4.

[0075] The second part of the broadband optical signal may be different from the first part of the broadband optical signal. The second part of the broadband optical signal may be a narrowband signal located within the first part of the broadband optical signal.

[0076] The optical fibre 1 may be a single mode fibre or a double-clad fibre. The double-clad fibre may consist of a single mode core and a surrounding second cladding which acts as a multimode core.

[0077] The analyte may be measured using an interferometer. The interferometer may comprise the hydrogel 2. The hydrogel 2 may be configured to change a volume in response to the analyte. The interferometer may be a Fabry-Perot interferometer.

[0078] In use, the FBG 3 may be immersed in the blood. The method may be performed in vivo.

[0079] Since the behaviour of the hydrogel 2 may change with temperature, the temperature data gathered by the FBG 3 sensor may be used for correcting a temperature shift.

[0080] However, the continuous temperature measurement may also be used for a thermodilution measurement, in particular a transpulmonary thermodilution measurement. That is, the optical fibre 1 can be configured to simultaneously measure a glucose level and perform a thermodilution measurement for cardiac output (CO) estimation.

[0081] Cardiac Output (CO) is an important haemodynamic parameter to measure since the heart is one of our most vital organs, supplying all parts of the body with oxygen carried by the blood. CO represents the blood flow through the heart, and is therefore one of the primary determinants of the global oxygen transport from the heart to other body parts and organs.

[0082] Thermodilution is an indicator dilution technique using the temperature of the indicator to measure CO. The indicator of a known volume and temperature is injected rapidly into the right side on the heart. This volume will travel as a bolus with the circulation through the heart, and mix with the blood. As this happens, the bolus diffuses and the temperature of the bolus will be warmed by the blood, at body temperature (typically 37 °C). A detector, i.e., the optical fibre 1 having the FBG 3 written into it, is positioned downstream in an artery, measuring the blood temperature over time. Once the bolus reaches the detection site (FBG 3), a dilution curve will appear as a negative change in temperature over time.

[0083] The injection site and detection site depend on the thermodilution method. Two common methods are Pulmonary Artery Thermodilution (PATD) and Transpulmonary Thermodilution (TPTD). Research articles including PATD list the right atrium as the injection site, and the pulmonary artery as detection site. Other articles, describing TPTD, used a central vein, typically the femoral vein, as the injection site, while the detection site was the femoral artery. The major difference is that PATD measures the bolus on its way from the right side of the heart to the lungs while TPTD, on the other hand, measures the bolus after having travelled through the right side of the heart, the lungs, the left side of the heart and the aorta.

[0084] The temperature sensor may be inserted through a catheter and placed on the detection site.

[0085] In another embodiment, the present disclosure further describes three types of measurement options based on three different circuit designs, Cl to C3, which are suitable for continuous glucose monitoring, CGM, applications in photonic integrated circuits, PIC, like in the optical fibre 1 applying an interferometric measurement method as discussed in some embodiments of the present disclosure. Each circuit presented herein and illustrated in Figs. 5 to 7b, possesses electrical and optical interfaces and is interrelated to a hydrogel cavity 6 of the hydrogel 2. The following passages intend to clarify within the context of the present disclosure how the broadband reflection spectrum of the hydrogel 2 previously described may be measured using different setups comprising various components, specifically different types of light sources, e.g. lasers, which emit a broadband optical signal to the optical fibre 1. The alternative circuit designs contribute to enabling the optical fibre 1 to use different wavelength ranges of the measured broadband spectrum for diverse measurements, such as monitoring the analyte, which may be a glucose level and recording an additional parameter, which may be the temperature of a fluid, for example, blood of a patient.

[0086] Fig. 5 schematically shows a first type electronic circuit Cl, which applies a broadband emitter and spectrometer approach. A reflection spectrum of the hydrogel 2 is measured using at least one broadband superluminescent light emitting diode, SLED 5, emitter and an arrayed waveguide grating, AWG 7, based spectrometer 4. The advantages of using an AWG over other known spectrometers are that an AWG is suitable for applications using multiple channels, a wide free spectral range, i.e., spectrum periods, of more than 40 nm may be achieved and AWGs involve maturely developed technology widely applied in various applications such as telecoms, for example.

[0087] In particular, a broadband optical signal is generated from the SLED 5 and is coupled via an A- OIO-1 input-output, 10, link into the single mode fibre leading to a hydrogel cavity 6. The cavity 6 reflects the signal back via a B-OIO-1 10 and inputs the reflected signal to the PIC 8 again via the A-OIO-1 10. The signal is coupled into the spectrometer 4, which measures the spectrum. The spectrometer 4 consists of a 1x16 AWG 7, the input of which receives the reflected signal and splits the signal into 16 channels connected to photodiodes (photodiode array 9). Two individual SLEDs 5 are illustrated in Fig. 5 to represent the possibility of hybrid integration of two individual dies at different wavelengths thereby extending their operating range. In other words, multiple photodetectors may each probe a narrow part of the spectrum. Hence, Cl may rely on a parallel readout of photodiode signals since all photodiodes receive their signal concurrently. The present disclosure is not limited to the use of two SLEDs 5 as shown in Fig. 5, but also covers the possibility of using one or more SLEDs 5.

[0088] In contrast to Cl, a second type electronic circuit C2, schematically illustrated in Fig. 6, shows one or more tuneable narrow sources, which together cover the entire spectrum as desired, and a broad photodetector. The at least one tuneable narrow source may include a broad source and at least one tuneable narrow filter. Exemplarily, C2 may use a wavelength tuneable laser, which operates in a time domain multiplexing mode. Furthermore, C2 as illustrated in Fig. 6, may involve a single photodiode 13 and a wavelength tuneable laser 14 as a light source to measures the hydrogel 2 spectrum. The wave wavelength tuneable laser 14 may be a sampled grating distributed Bragg reflector, SG-DBR, though may also be substituted by other widely tuneable designs, such as a digital supermode distributed Bragg reflector, DS-DBR. Such tuneable lasers are capable of quasi-continuous tuning over relatively large wavelength ranges, with ranges of ~ 60 nm. In quasi-continuous tuning, the laser may completely cover, without gaps, a certain wavelength range even though mode hops may be required to achieve this in real-life applications. More complex tuneable laser designs may also achieve up to 100 nm tuning ranges, though this value may be considered as the approximate general limit to the tuning range due to a limited gain bandwidth. In C2, the spectrum is successively built up as the laser will tune to the individual wavelength channels sequentially in time. Despite the simplicity in the theoretical design of C2, the control of C2 is more complex compared to, for example, Cl. In the present embodiment, four current controllers, C-EIO-1 to C-EIO-4 as shown in Fig. 6, may be necessary to control the wavelength of the laser 14 and a lookup table for the laser may be stored in the device for selecting the correct wavelength.

[0089] An important area of development is understanding the characteristics of lasers under the influence of thermal cycling. As the laser is un-cooled, one may expect its wavelength to shift at ~ 0.1 nm °C-1, or in terms of glucose concentration ~ 0.005 mM °C-1. Provided that the laser 14 behaviour does not deteriorate too significantly under the influence of changing temperature, a likely measure may be to apply a simple correction factor by measuring the local temperature within the setup surroundings via a thermistor 10 comprised within the assembly of each of the circuits, Cl to C3, as shown in Figs. 5 to 7b, to obtain an approximation and to account for any potentially falsely measured phase change by the thermistor 10 reading.

[0090] The final circuit variant that is discussed within the scope of this disclosure, is the electronic circuit design C3, which uses the concept of an array of narrow sources, that together are equivalent to a broadband source, and is divided into two different circuit designs. The first of the third circuit designs C3a exemplarily uses an array 17 of distributed feedback, DFB, lasers 15 or a series 17 of vertical cavity surface emitting lasers, VCSELs 16, and the second of the third circuit design types C3b uses an arrayed waveguide grating laser, AWGL 18, as a light source, with a single photodiode 13 measuring the reflected signal array 20. Figs. 7A and 7B schematically show the electronic circuit assembly of the design types C3a and C3b, respectively.

[0091] In the present embodiment, circuit C3a requires N lasers to be multiplexed into an AWG 7, with high wavelength accuracy on the part of the DFBs 15 and / or VCSELs 16. Difficult wavelength tolerance requirements may render the integration of DFBs 15 monolithically on a single chip as shown in Fig. 7A, challenging from a yield perspective. This is due to the fact that DFB lasers 15 have inherent variability to their wavelength, and as the tuning capacity is limited in pulsed mode, the lasers are not guaranteed to line up with the AWG's 7 passband. Typically, it is possible to align DFB 15 emission wavelengths with the AWG 7 passbands via thermal tuning. However, in an application such as the optical fibre 1 suggested by the present disclosure, this is not desirable as thermally tuning an array of DFBs 15 is not practical from an energy budget point of view. In addition, thermal tuning is typically slow requiring on the order of milliseconds for thermal transients to pass. As such, the present embodiment requires that the DFB 15 wavelength is accurate enough to align with the AWG 7 passbands without wavelength tuning. Hybrid-integration of DFBs 15 and VCSELs 16 may alleviate this issue, as DFBs 15 and VCSELs 16 may be pre-selected to match the AWG 7. Exemplary, multiple VCSELs 16 may be integrated on a single silicon on insulator, SOI, platform chip and may be tuned to align with the AWG 7 passband, wherein VCSEL 16 misalignment is anticipated to be a major challenge in this circuit setup C3a when trying to obtain the most accurate measurement results possible.

[0092] In contrast, circuit C3b as illustrated in Fig. 7b, preferably contains at least one AWGL 18. This circuit structure uses the AWG 7 as part of the laser cavity and, hence, the AWG 7 transfer function acts as a wavelength filter to achieve single mode lasing. Laser feedback may be provided by facets and on-chip mirrors such as multimode interference reflectors 19 resulting in a reflective semiconductor optical amplifier, SOA, array 20 as shown in Fig. 7b. Thus, the previously mentioned issue of difficult wavelength alignment is not a concern with the design of C3b, as by using the AWG 7 for wavelength selection, the laser inherently lasers on the necessary wavelength passbands of the AWG 7.

[0093] It is important to note that the above-mentioned circuits C1-C3 are particularly advantageous for the present CGM application. While there are in principle also other possible circuits that may be used with the present CGM application, the circuits C1-C3 have several advantages over such alternative circuits. For example, circuits involving two individual PICs may be disadvantageous due to packaging constraints not allowing the use of discrete circulators or combiners. Circuits using MEMs tuneable VCSELs may be disadvantageous because the MEMs elements require a > 10 V voltage supply to tune the wavelength, which may be impractical for a wearable device. Circuits using LED light sources may be disadvantageous, because the high beam divergence of LEDs mean optical coupling may not be practical in a small form factor.

[0094] Thus, in the present disclosure, an optical fibre, a system having the same and measurement methods using various approaches have been presented. The FBG integrated into the optical fibre can be used in a multiparameter frequency based optical sensor, where part of the spectrum is used by the FBG (e.g., for intravenous transpulmonary thermodilution) and other parts of the spectrum are used by the optical sensor, e.g., for Fabry-Perot or fluorescence or plasmonics, in a single fibre optical sensor.

[0095] With measuring a gaseous phase of a Fabry-Perot cavity as performed in some systems, only physical properties such as gas pressure difference may be measured. The use of a hydrogel as the Fabry-Perot cavity, as done in the present disclosure, allows to measure chemical reactions between analyte and hydrogel or changes of the hydrogel geometry caused by absorption of the analyte leading to a change of the Fabry-Perot cavity. This allows the measurement of analytes. Moreover, the FBG additionally allows the measurement of a further parameter.

[0096] The single fibre sensing principle not only reduces the manufacturing effort but also minimises the profile, thus reducing the clotting risk on the sensor and allowing access through a thin catheter without disrupting their other uses, such as continuous blood pressure measurements.

[0097] In that manner, an efficient simultaneous measurement of an analyte and an additional parameter using only a single optical fibre can be ensured.

[0098] In contrast to existing flow-directed system s / sensors such as pulmonary artery catheters (PACs) or Swan-Ganz catheters, the sensor according to the present disclosure can be inserted through an existing catheter. Moreover, such systems may be used for pulmonary artery thermodilution (PATD) only rather than transpulmonary artery thermodilution (TPTD) as the sensor presented herein. With TPTD, it is, for example, additionally possible to measure extravascular lung water.

[0099] As outlined above, the present disclosure presents a sensor, which is significantly smallerthan previous systems (e.g., smaller than 24 gauge) and may enter the bloodstream through arterial catheters. Catheters (including PAC or prior art TPTD solutions) all have lumens so that they can monitor pressure, and allow blood samples through said lumen. Catheters are generally not used in blood with a size smaller than 24 gauge because the blood may clot inside the lumen rendering them unusable. Because the presented solution is so small, it does not need a lumen but can access the intravascular space through an indwelling catheter (without disrupting the pre-existing applications of the catheter). This has two benefits: less invasiveness for the patient (fewer punctures) and it is superior for the healthcare personnel who can decide to use the sensor after the decision was made to introduce a catheter. Also, the "two sensors in one fibre"-approach is advantageous for this ability because known systems using two fibres with a sensor each have a larger diameter, making it harder to enter through the smallest intravascular catheters.

[0100] While various embodiments of the present disclosure have been described above, it should be understood that they have been presented by way of example only, and not by way of limitation. Likewise, the various diagrams may depict an example architectural or configuration, which are provided to enable persons of ordinary skill in the art to understand exemplary features and functions of the present disclosure. Such persons would understand, however, that the present disclosure is not restricted to the illustrated example architectures or configurations, but can be implemented using a variety of alternative architectures and configurations. Additionally, as would be understood by persons of ordinary skill in the art, one or more features of one embodiment can be combined with one or more features of another embodiment described herein. Thus, the breadth and scope of the present disclosure should not be limited by any one of the above-described exemplary embodiments.

[0101] It is also understood that any reference to an element herein using a designation such as "first," "second," and so forth does not generally limit the quantity or order of those elements. Rather, these designations can be used herein as a convenient means of distinguishing between two or more elements or instances of an element. Thus, a reference to first and second elements does not mean that only two elements can be employed, or that the first element must precede the second element in some manner.

[0102] Additionally, a person having ordinary skill in the art would understand that information and signals can be represented using any one of a variety of different technologies and techniques. For example, data, instructions, commands, information, signals, bits and symbols, for example, which may be referenced in the above description can be represented by voltages, currents, electromagnetic waves, magnetic fields or particles, optical fields or particles, or any combination thereof. A skilled person would further appreciate that any one of the various illustrative logical blocks, units, processors, means, circuits, methods and functions described in connection with the aspects disclosed herein can be implemented by electronic hardware (e.g., a digital implementation, an analogue implementation, or a combination of the two), firmware, various forms of program or design code incorporating instructions (which can be referred to herein, for convenience, as "software" or a "software unit"), or any combination of these techniques.

[0103] To clearly illustrate this interchangeability of hardware, firmware and software, various illustrative components, blocks, units, circuits, and steps have been described above generally in terms of their functionality. Whether such functionality is implemented as hardware, firmware or software, or a combination of these techniques, depends upon the particular application and design constraints imposed on the overall system. Skilled artisans can implement the described functionality in various ways for each particular application, but such implementation decisions do not cause a departure from the scope of the present disclosure. In accordance with various embodiments, a processor, device, component, circuit, structure, machine, unit, etc. can be configured to perform one or more of the functions described herein. The term "configured to" or "configured for" as used herein with respect to a specified operation or function refers to a processor, device, component, circuit, structure, machine, unit, etc. that is physically constructed, programmed and / or arranged to perform the specified operation or function.

[0104] Furthermore, a skilled person would understand that various illustrative logical blocks, units, devices, components and circuits described herein can be implemented within or performed by an integrated circuit (IC) that can include a general purpose processor, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA) or other programmable logic device, or any combination thereof. The logical blocks, units, and circuits can further include antennas and / or transceivers to communicate with various components within the network or within the device. A general purpose processor can be a microprocessor, but in the alternative, the processor can be any conventional processor, controller, or state machine. A processor can also be implemented as a combination of computing devices, e.g., a combination of a DSP and a microprocessor, a plurality of microprocessors, one or more microprocessors in conjunction with a DSP core, or any other suitable configuration to perform the functions described herein. If implemented in software, the functions can be stored as one or more instructions or code on a computer- readable medium. Thus, the steps of a method or algorithm disclosed herein can be implemented as software stored on a computer-readable medium.

[0105] Computer-readable media includes both computer storage media and communication media including any medium that can be enabled to transfer a computer program or code from one place to another. A storage media can be any available media that can be accessed by a computer. By way of example, and not limitation, such computer-readable media can include RAM, ROM, EEPROM, CD-ROM or other optical disk storage, magnetic disk storage or other magnetic storage devices, or any other medium that can be used to store desired program code in the form of instructions or data structures and that can be accessed by a computer.

[0106] In this document, the term "unit" as used herein, refers to software, firmware, hardware, and any combination of these elements for performing the associated functions described herein. Additionally, for purpose of discussion, the various units are described as discrete units; however, as would be apparent to one of ordinary skill in the art, two or more units may be combined to form a single unit that performs the associated functions according to embodiments of the present disclosure.

[0107] Additionally, memory or other storage, as well as communication components, may be employed in embodiments of the present disclosure. It will be appreciated that, for clarity purposes, the above description has described embodiments of the present disclosure with reference to different functional units and processors. However, it will be apparent that any suitable distribution of functionality between different functional units, processing logic elements or domains may be used without detracting from the present disclosure. For example, functionality illustrated to be performed by separate processing logic elements, or controllers, may be performed by the same processing logic element, or controller. Hence, references to specific functional units are only references to a suitable means for providing the described functionality, rather than indicative of a strict logical or physical structure or organization.

[0108] Various modifications to the implementations described in this disclosure will be readily apparent to those skilled in the art, and the general principles defined herein can be applied to other implementations without departing from the scope of this disclosure. Thus, the disclosure is not intended to be limited to the implementations shown herein but is to be accorded the widest scope consistent with the novel features and principles disclosed herein, as recited in the claims below.

Claims

New PCT-Patent Application Vossius & PartnerGlucoSet AS Patentanwalte Rechtsanwalte mbBVossius Ref.: AG3344 PCT BS SiebertstraRe 3 81675 Munchen March 21, 2025Claims1. Optical fibre (1) for simultaneously measuring an analyte and an additional parameter in blood, wherein the optical fibre (1) comprises: a hydrogel (2) provided at a tip of the optical fibre (1) for interferometrically measuring the analyte; and a Fibre Bragg Grating, FBG (3), configured to measure the additional parameter; the optical fibre (1) being configured to: transmit an optical signal; measure the analyte using a first part of the optical signal; and measure the additional parameter using a second part of the optical signal, wherein the second part of the optical signal is different from the first part of the optical signal, and wherein the second part of the optical signal is a narrowband signal located within the first part of the optical signal.

2. Optical fibre (1) according to claim 1, wherein the optical signal is a broadband optical signal.

3. Optical fibre (1) according to claim 1 or 2, wherein the optical fibre (1) is a single mode fibre or a double-clad fibre.

4. Optical fibre (1) according to any one of claims 1 to 3, further comprising an interferometer configured to measure the analyte, wherein the interferometer comprises the hydrogel (2), wherein the hydrogel (2) is preferably configured to change a volume in response to the analyte, and wherein the interferometer preferably is a Fabry-Perot interferometer.

5. Optical fibre (1) according to any one of claims 1 to 4, wherein the FBG (3) is provided towards a tip of the optical fibre (1), wherein preferably, the FBG (3) is provided at a distance of 1 mm to 8 mm from the tip of the optical fibre (1), more preferably not less than 2 mm, and the FBG (3) grating zone is preferably provided with a length between 2 mm and 10 mm.

6. Optical fibre (1) according to any one of claims 1 to 5, wherein the additional parameter is a temperature of blood, and / or wherein the analyte is a glucose level.

7. System for simultaneously measuring an analyte and an additional parameter, the system comprising: an optical fibre (1) according to any one of claims 1 to 6; at least one light source configured to emit the optical signal to the optical fibre (1) for transmitting the optical signal through the optical fibre (1); and at least one detector configured to receive light from the optical fibre (1) for measuring the analyte and the additional parameter.

8. System according to claim 7 further comprising: a hydrogel cavity (6), wherein the hydrogel (2) is located in the hydrogel cavity (6); and a photonic integrated circuit, PIC (8), which is connected to the hydrogel cavity (6) via input-output, IO, links, and which comprises: the at least one light source, which is a broadband emitting light source generating the optical signal as a broadband optical signal, a spectrometer (4), wherein the spectrometer (4) splits the broadband optical signal, which was previously reflected by the hydrogel cavity (6) and then received by the spectrometer (4), into multiple channels, and the at least one detector, which is a photodiode array (9) having multiple photodiodes, wherein the multiple channels are each connected to a respective photodiode and the multiple photodiodes each receive a narrow range signal simultaneously.

9. System according to claim 8, wherein the broadband emitting light source is a superluminescent light emitting diode, SLED (5).

10. System according to claim 8 or 9, wherein the spectrometer (4) is based on an arrayed waveguide grating, AWG (7).

11. System according to claim 7 further comprising: a hydrogel cavity (6), wherein the hydrogel (2) is located in the hydrogel cavity (6); and a photonic integrated circuit, PIC (8), which is connected to the hydrogel cavity (6) via input-output, IO, links, and which comprises: the at least one light source, which is a wavelength tuneable narrow light source generating the optical signal as a broadband optical signal, and the at least one detector, which is a broadband photodetector receiving the broadband optical signal.

12. System according to claim 11, wherein the at least one wavelength tuneable narrow light source is a wavelength tuneable laser (14) configured to perform quasi-continuous tuning to obtain a broad wavelength tuning range.

13. System according to claim 11 or 12, wherein the broadband photodetector is a single photodiode (13).

14. System according to claim 7 further comprising: a hydrogel cavity (6), wherein the hydrogel (2) is located in the hydrogel cavity (6); and a photonic integrated circuit, PIC (8), which is connected to the hydrogel cavity (6) via input-output, IO, links, and which comprises: the at least one light source, which is an array of narrow light sources (17) together generating the optical signal as a broadband optical signal; an arrayed waveguide grating, AWG (7), wherein the AWG (7) splits the broadband optical signal, which was previously reflected by the hydrogel cavity (6), into multiple channels, andthe at least one detector, which is a broadband photodetector receiving the broadband optical signal.

15. System according to claim 14, wherein the array of narrow light sources (17) is a combination of distributed feedback, DFB, lasers (15) and vertical cavity surface emitting lasers, VCSELs (16), with their wavelengths tuned to align with the passband of the AWG (7).

16. System according to claim 14 or 15, wherein the at least one light source is an arrayed waveguide grating laser, AWGL (18), using the AWG (7) as laser cavity for wavelength filtering to achieve single mode lasing.

17. System according to claim 16, further comprising facets and on-chip mirrors configured to provide laser feedback.

18. System according to claim 17, wherein the facets and on-chip mirrors provide multimode interference reflectors (19) to obtain a reflective semiconductor optical amplifier, SOA, array (20).

19. System according to any one of claims 14 to 18, wherein the broadband photodetector is a single photodiode (13).

20. System according to any one of claims 7 to 19, further comprising a thermistor (10) for measuring temperature within the system to obtain an approximation and to account for any potentially falsely measured phase change.

21. System according to any one of claims 7 to 20, further comprising at least one processor, wherein the at least one processor is configured to determine the analyte using a first part of the broadband optical signal, and determine the additional parameter using a second part of the broadband optical signal based on the light received at the at least one detector, wherein preferably, the at least one processor is configured to control the at least one light source.

22. System according to any one of claims 7 to 21, wherein the light received at the at least one detector is reflected light.

23. Method for simultaneously measuring an analyte and an additional parameter in blood, the method comprising: providing an optical fibre (1) in the blood, wherein the fibre comprises: a hydrogel (2) provided at a tip of the optical fibre (1) for interferometrically measuring the analyte; and a Fibre Bragg Grating, FBG (3), configured to measure the additional parameter; the method further comprising: transmitting (SI) a broadband optical signal through the optical fibre (1); measuring (S2) the analyte using a first part of the broadband optical signal; and measuring (S3) the additional parameter using a second part of the broadband optical signal, wherein the second part of the broadband optical signal is different from the first part of the broadband optical signal, and wherein the second part of the broadband optical signal is a narrowband signal located within the first part of the broadband optical signal.

24. Method according to claim 23, wherein the optical fibre (1) is a single mode fibre or a double-clad fibre.

25. Method according to claim 23 or 24, wherein the analyte is measured using an interferometer, wherein the interferometer comprises the hydrogel (2), wherein the hydrogel (2) is preferably configured to change a volume in response to the analyte, and wherein the interferometer is preferably a Fabry-Perot interferometer.

26. Method according to any one of claims 23 to 25, wherein the FBG (3) is immersed in the blood, and / or wherein the additional parameter is a temperature of the blood, and / orwherein the analyte is a glucose level.

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