Spectrophotometric device for measuring blood oxygen saturation

Abstract

According to a first aspect, the present invention relates to a spectrophotometric device for measuring blood oxygen saturation in tissue of a subject, comprising one or more light sources for emitting optical signals into the tissue of the subject, one or more detectors for detecting optical signals reflected by the tissue of the subject, an electronic data processing unit configured to calculate blood oxygen saturation based on the optical signals measured by the one or more detectors, and a motion sensor for detecting a motion signal indicative of the motion of the light sources and / or the detectors.Further, the present invention relates to a spectrophotometric device for measuring blood oxygen saturation in tissue of a subject, comprising at least one light source for emitting optical signals into the tissue of the subject, at least one detector for detecting optical signals reflected by the tissue of the subject, an electronic data processing unit configured to calculate blood oxygen saturation taking into account the optical signals measured by the at least one detector, and a contact sensor for detecting a contact signal indicative of contact between the skin of the subject and the light sources and / or the detectors.

Description

[Technical field]

[0001] The present invention relates to a spectrophotometric device for measuring blood oxygen saturation in tissue of a subject and a method for measuring blood oxygen saturation in tissue of a subject. [Background technology]

[0002] Monitoring blood oxygen saturation in the tissues of a subject is clinically important because low blood oxygen saturation is a sign of potentially fatal damage. This is the case, for example, in premature infants, who often suffer from gastrointestinal damage such as necrotizing enterocolitis or ileus and are at constant risk of developing shock. Therefore, abdominal oxygen saturation must be monitored accurately at all times in premature infants.

[0003] The blood oxygen saturation in the tissue of a subject is defined as follows: StO 2 = c(HbO 2 ) / (c(HbO 2 )+c(Hb)) In the formula, c(HbO 2 ) and c(Hb) are the concentrations of oxygenated and deoxygenated hemoglobin, respectively.

[0004] Near-infrared spectroscopy (NIRS) is a technique for non-invasively measuring blood oxygen saturation in the tissues of a subject. NIRS measures the amount of oxygenated hemoglobin (HbO 2 ) and deoxygenated hemoglobin (Hb) have different absorption characteristics in the near infrared region, 2 NIRS can be performed noninvasively by placing a spectroscopic sensor on the subject's skin and measuring the attenuation of an optical signal after passing through the subject's tissue.

[0005] The measured light attenuation is related to the concentration of specific light-absorbing substances (chromophores) by the Lambert–Beer law. A λ =-log(I λ / Iλ0 )=ε λ CD In the formula, A λ is the attenuation of light at a particular wavelength λ, c is the concentration of a particular chromophore, ε λ is the extinction coefficient of a particular chromophore at a particular wavelength, and d is the separation distance from the "source" to the detector. With a known extinction coefficient, the concentration of the chromophore can be calculated from the measured attenuation of light. For a mixture of different chromophores, the relative concentrations of the chromophores can be determined by measuring the attenuation of light at several distinct wavelengths where the chromophores have different extinction coefficients. For a mixture containing N different chromophores, to do this it is necessary to measure the attenuation at at least N different wavelengths.

[0006] In a typical NIRS device, a light signal of known wavelength and intensity is sent into the tissue of the subject, the light transmitted or diffusely reflected from the tissue is detected, and the light attenuation is calculated. In order to accurately determine the concentration of the chromophore from the measured light attenuation from the tissue, the optical properties of the tissue must be taken into account, in particular the absorption by other chromophores present in the tissue and the scattering properties of the tissue. In practice, the scattering properties of the tissue must be taken into account by a calibration measurement. HbO 2 To account for chromophores other than Hb and Hb, it is necessary to measure the absorption spectra of these chromophores to estimate their wavelength-dependent extinction coefficients, and to measure the attenuation of light at 2+M wavelengths, where M is the number of additional chromophores to be considered. In the prior art, several methods have been developed to address these issues. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] European Patent Registration No. 1259791 [Patent Document 2] US Patent Application Publication No. 2012 / 0136225

[0008] US Patent No. 5,399,633 discloses a NIRS method for measuring total blood oxygen saturation in the tissue of a subject by measuring the attenuation of light at three or more wavelengths and calculating the difference in attenuation between the wavelengths. This approach is also known as the "difference wavelength method." In this method, measurements must be made at N+1 different wavelengths to determine the concentrations of N different chromophores. By determining the differential attenuation, the contributions of tissue light scattering, fixed light absorbing components, and measurement device characteristics can be calculated to determine the total blood oxygen saturation in the tissue of a subject by calculating the difference in attenuation between the HbO 2 and the attenuation due to Hb is minimized, improving the accuracy of the measured blood oxygen saturation.

[0009] US Patent No. 5,399,663 discloses a method for determining blood oxygen saturation in the lower gastrointestinal tissue of a subject, which includes taking into account the presence of wavelength-dependent absorbing substances not present in blood. Specifically, US Patent No. 5,399,663 proposes taking into account the attenuation of light by stool, particularly meconium, present in the lower gastrointestinal tract of a subject, particularly in the gastrointestinal tract of a newborn. US Patent No. 5,399,663 also teaches the use of a differential wavelength method for the analysis of NIRS data.

[0010] Although the differential wavelength method minimizes the contribution of the scattering properties of tissues, it still requires calibration to account for scattering and non-specific background absorption. This calibration is performed by determining the blood oxygen saturation of a given reference tissue, assuming that the oxygen saturation of the given reference tissue is a weighted sum of the oxygen saturation of the venous and arterial blood of the subject. However, this requires knowledge of the relative contributions of venous and arterial blood in that tissue. Although empirical data exists on the relative contributions of venous and arterial blood oxygen saturation, the reliability of this data is questionable. Thus, the available calibration methods are potential sources of error for the differential wavelength method.

[0011] Another method for measuring NIRS is to measure the attenuation of light at several wavelengths and at several different distances between the light source and the photodetector. Absorption μ at a specific wavelength λ a,λ can be calculated based on the following formula: μ a,λ = 1 / (3 μs,λ ) (ln(10) ∂A λ / ∂d - 1 / d) 2 Here, μ s,λ is an empirically determined value to account for attenuation of the optical signal due to optical scattering in the subject's tissue at a particular wavelength λ, and A λ is the attenuation at a particular wavelength λ, d is the average distance between the source and the detector, ∂A λ / ∂d is the slope of the attenuation versus distance from the "source" to the detector. Using the Lambert-Beer law, the absorption μ a,λ From the chromatic aberration, the concentration of the chromophores can be calculated. This approach is also known as the "multi-distance method". It has been applied to measure blood oxygen saturation in muscle tissue (Tachtsidis, Ilias et al. "A Hybrid Multi-Distance Phase and Broadband Spatially Resolved Spectrometer and Algorithm for Resolving Absolute Concentrations of Chromophores in the Near-Infrared Light Spectrum." Advances in Experimental Medicine and Biology 662 (2010): 169-175).

[0012] Conventional spectrophotometric devices for measuring blood oxygen saturation can be attached to the subject's finger or placed flat on the subject's skin. To measure the blood oxygen saturation of a newborn or premature baby, it is important to wear the device as loosely as possible so as not to cause discomfort or injury to the baby. Therefore, clamp-on devices that are worn on the finger are not well suited for monitoring newborns or premature babies. Instead, spectrophotometric devices that are more or less loosely placed on the subject's abdomen are suitable for monitoring newborns or premature babies. However, the device needs to be worn tightly enough so that it does not fall off or is subject to interference from ambient light. Because it cannot be worn too tightly, conventional spectrophotometric devices for measuring blood oxygen saturation can suffer from measurement artifacts caused, for example, by the subject's movements or loss of skin contact with the subject. Summary of the Invention [Problem to be solved by the invention]

[0013] It is an object of the present invention to provide an improved spectrophotometric device for measuring blood oxygen saturation in tissues of a subject, in particular in newborns or premature infants, which should have improved measurement accuracy and / or provide information on other vital parameters in addition to blood oxygen saturation. [Means for solving the problem]

[0014] According to a first aspect, the invention relates to a spectrophotometric device for measuring blood oxygen saturation in tissue of a subject, comprising one or more light sources for emitting optical signals into the tissue of the subject, one or more detectors for detecting optical signals reflected by the tissue of the subject, an electronic data processing unit configured to calculate blood oxygen saturation based on the optical signals measured by the one or more detectors, and a motion sensor for detecting a motion signal indicative of a movement of the light sources and / or the optical detectors, the device being characterized in that the electronic data processing unit is configured to discard the optical signals measured by the one or more detectors if the motion signal detected by the motion sensor exceeds a predefined threshold.

[0015] According to a first aspect, the present invention further relates to a method for non-invasively measuring blood oxygen saturation in tissue of a subject, comprising the steps of using at least one light source for emitting an optical signal into the tissue of the subject, using at least one detector for detecting the optical signal reflected from the tissue of the subject, using an electronic data processing unit for calculating blood oxygen saturation based on the optical signals measured by the one or more detectors, and using a motion sensor for detecting a motion signal indicative of a movement of the light source and / or the optical detector, characterized in that the electronic data processing unit discards the optical signals measured by the one or more detectors if the motion signal detected by the motion sensor exceeds a predefined threshold.

[0016] By detecting and accounting for motion signals indicative of light source and / or photodetector movement, spectrophotometric devices can eliminate one source of measurement artifacts, thereby improving the accuracy of measured blood oxygen saturation. This is particularly important when monitoring newborns or premature infants, who often exhibit sudden movements that cause measurement artifacts in conventional spectrophotometric devices.

[0017] In the context of the present invention, discarding the optical signal means that the normal processing of the optical signal is interrupted. This can mean, for example, that blood oxygen saturation is not calculated, i.e., that the calculation of blood oxygen saturation is interrupted, that blood oxygen saturation is calculated but not reported to the user, or that blood oxygen saturation is calculated and reported but labeled as an uncertain value. If blood oxygen saturation is calculated under such conditions, it may be stored in an electronic record for later use, but is preferably labeled as an uncertain value. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0018] The spectrophotometric device is configured to transmit an optical signal into the tissue of the subject and detect the optical signal after passing through the tissue of the subject. The spectrophotometric device can thereby measure the attenuation of the optical signal after passing through the tissue of the subject. The optical signal transmitted into the tissue of the subject is partially absorbed, partially transmitted and partially reflected by the tissue of the subject. The spectrophotometric device according to the invention measures the optical signal reflected from inside the tissue of the subject. Therefore, the at least one light source and the at least one detector are preferably arranged on the same side with respect to the tissue of the subject.

[0019] Thereby, the spectrophotometric device differs from conventional clamp-on devices in which a light source and a detector are placed on opposite sides of a subject's tissue to measure the light signal transmitted through the tissue. Such conventional clamp-on devices can only be attached to a subject's extremities, such as a subject's finger, and therefore cannot be used to measure blood oxygen saturation in other body parts, such as the abdomen. In contrast, the spectrophotometric device according to the present disclosure can be placed on any body part, such as the abdomen, of a subject to specifically measure blood oxygen saturation in that body part.

[0020] Preferably, the spectrophotometric device is configured to measure the blood oxygen saturation of the subject's head, torso, abdomen, arms or legs, more preferably the subject's head, torso or abdomen. Most preferably, the spectrophotometric device is configured to measure the blood oxygen saturation of the subject's abdomen. This requires that the spectrophotometric device is configured so that the light source and the light detector can be placed flat on the subject's skin. Preferably, the spectrophotometric device also comprises a fixing means by which the light source and the light detector can be fixed on the subject's skin. This can be, for example, a belt or an adhesive patch. In a preferred embodiment, the spectrophotometric device comprises an adhesive patch, preferably a Velcro patch or a hook-and-loop fastener, by which the spectrophotometric device can be attached to the subject's clothing, for example under the subject's diaper.

[0021] The light source may be a broadband light source that emits light over a range of wavelengths. Alternatively, the light source may be a collection of light sources, each of which emits light in a narrow spectral bandwidth, such as a collection of light emitting diodes. In a preferred embodiment, the light source comprises a collection of light emitting diodes, each of which emits light at a different wavelength.

[0022] A spectrophotometric device may comprise one or more such light sources, either a broadband light source or a collection of light sources emitting light in a narrow spectral bandwidth.

[0023] The light detector can be, for example, a CCD sensor, a photodiode, or any other device capable of converting light into a current or voltage. The detector may comprise a collection of individual detectors, each configured to detect light of a different wavelength. For example, the detector may comprise an array of photodiodes, each with a filter, which transmits light of a particular wavelength onto each photodiode. Alternatively, the detector may comprise an array of photodiodes or a CCD sensor and a diffraction grating that splits the optical signal into different light components having different wavelengths and images each light component onto a separate photodiode of the array of photodiodes or onto a separate area of ​​the CCD sensor. As yet another option, the spectrophotometric device may employ time or frequency multiplexing for wavelength separation. This allows the detector to measure the intensity of the optical signal as a function of wavelength. This allows the spectrophotometric device to measure the attenuation of the optical signal as a function of wavelength.

[0024] The spectrophotometric device may comprise one or more such photodetectors, such as an array of photodiodes, a single CCD chip, or a single photodiode. Preferably, the spectrophotometric device comprises two to six, most preferably four, such photodetectors located at different distances from the light source.

[0025] Preferably, the spectrophotometric device is configured to measure the attenuation of the reflected light signal at two or more distinct wavelengths. By measuring the attenuation at two or more distinct wavelengths, the relative concentrations of oxygenated and deoxygenated hemoglobin in the tissue of the subject can be calculated, thereby calculating blood oxygen saturation.

[0026] To measure attenuation at a given number of distinct wavelengths, it is sufficient that the light source and photodetector are configured to measure attenuation at distinct wavelength ranges that include at least the specified wavelengths. The spectral bandwidth of each wavelength range may vary, so long as the wavelength ranges are clearly distinguishable. Preferably, attenuation is measured at distinct wavelength ranges with a bandwidth of ±25 nm or less, more preferably ±15 nm or less, even more preferably ±10 nm or less, and most preferably ±5 nm or less.

[0027] To increase the accuracy of the measurement, the attenuation is preferably measured at three or more distinct wavelengths, more preferably four or more distinct wavelengths, most preferably five or more distinct wavelengths, and most preferably seven or more distinct wavelengths. Measuring at three or more distinct wavelengths allows the use of differential wavelength methods to calculate the relative concentrations of oxygenated and deoxygenated hemoglobin.

[0028] In order to distinguish between deoxygenated and oxygenated hemoglobin, it is preferable to measure at least two different wavelengths where the extinction coefficients of the two species are significantly different, i.e., at least one wavelength where deoxygenated hemoglobin has a higher extinction coefficient than oxygenated hemoglobin and at least a second wavelength where oxygenated hemoglobin has a higher extinction coefficient than deoxygenated hemoglobin.

[0029] Preferably, the spectrophotometric device is configured to measure the attenuation of the reflected light signal at distinct wavelengths in the range of 650 nm to 3 μm, more preferably in the range of 650 nm to 1 μm, and most preferably in the range of 690 nm to 910 nm.

[0030] When measuring in the abdomen of a patient, there are several wavelength combinations that provide improved measurement accuracy. These wavelengths are Hb, HbO 2 These optimized wavelength combinations can be selected to better distinguish between the luminal cavity, luminal cavity septum, and other absorbing bodies present in the subject's abdomen, such as feces.

[0031] In one embodiment, the spectrophotometric device is configured to measure the attenuation of the optical signal at distinct wavelengths selected from 695 nm, 712 nm, 733 nm, 743 nm, 762 nm, 783 nm, 790 nm, 805 nm, 880 nm, 894 nm, and 909 nm. Preferably, the wavelengths are selected from 695 nm, 733 nm, 762 nm, 790 nm, 805 nm, 894 nm, and 909 nm. Preferably, these wavelengths are measured with a spectral bandwidth of ±10 nm, more preferably ±5 nm. Preferably, the spectrophotometric device is configured to measure the attenuation of the optical signal at at least three distinct wavelengths selected from these wavelengths.

[0032] In one embodiment, the spectrophotometric device is configured to measure the attenuation of the optical signal at least at 712 nm, 733 nm, 762 nm, 783 nm, and 909 nm. Preferably, these wavelengths are measured in a spectral bandwidth of ±10 nm, more preferably ±5 nm.

[0033] In another embodiment, the spectrophotometric device is configured to measure the attenuation of the optical signal at at least 712 nm, 733 nm, 762 nm, 783 nm, 894 nm, and 909 nm. Preferably, these wavelengths are measured with a spectral bandwidth of ±10 nm, more preferably ±5 nm.

[0034] Most preferably, the spectrophotometric device is configured to measure the attenuation of the optical signal at 695 nm, 733 nm, 762 nm, 790 nm, 805 nm, 894 nm, and 909 nm. Preferably, these wavelengths are measured in a spectral bandwidth of ±10 nm, more preferably ±5 nm.

[0035] In a preferred embodiment, the spectrophotometric device is configured to measure the attenuation of the optical signal over distances from two or more "light sources" to the detector, allowing the use of a multi-distance method to calculate the relative concentrations of oxygenated and deoxygenated hemoglobin.

[0036] To implement this feature, the spectrophotometric device preferably comprises at least two photodetectors located at different fixed distances from the light source. In a preferred embodiment, the spectrophotometric device comprises a light source at a first location and two or more photodetectors located at different distances from the light source. However, it is equally possible for the spectrophotometric device to comprise at least two light sources located at different fixed distances from the photodetectors. It is further possible for the spectrophotometric device to comprise a single light source and a single photodetector, where the light source and / or the photodetector are movable to vary the distance from the "light source" to the detector during the measurement. This embodiment has the advantage that the attenuation of the optical signal as a function of the distance from the "light source" to the detector can be sampled over a wide range and over a large number of data points.

[0037] In a preferred embodiment, the spectrophotometric device is configured to measure attenuation over distances from more than two "light sources" to the detector to improve the accuracy of the multi-distance method. In a preferred embodiment, the spectrophotometric device is configured to measure attenuation over distances from three "light sources" to the detector.

[0038] The distance between the light source and the photodetector may be optimized, for example, based on the sensitivity of the detector and the optical properties of the tissue of the subject. In the case of a spectrophotometric device for measuring abdominal blood oxygen saturation in a neonate, the distance from the shortest "light source" to the detector is preferably at least 0.8 cm, more preferably at least 0.9 cm, and most preferably at least 1.0 cm. Preferably, the shortest distance between the light source and the detector is in the range of 0.8 to 2 cm, more preferably at least 0.9 to 1.5 cm, and most preferably in the range of 0.95 to 1.2 cm. The distance from the longest "light source" to the detector is preferably in the range of 2 to 10 cm, preferably in the range of 2.2 to 6 cm, and most preferably in the range of 2.5 to 5 cm.

[0039] Preferably, the at least one light source and the at least one light detector are configured to be in direct contact with the subject's skin to avoid interference from ambient light.

[0040] The one or more light sources and the one or more light detectors are preferably disposed within a single housing. The housing is preferably configured to be attached to or placed on the skin of the subject. More specifically, the housing is preferably configured to be attached to or placed on the abdomen of the subject.

[0041] The housing may be made of any suitable material, preferably a plastic material. The housing has at least one surface facing the subject's skin, and the one or more light sources and the one or more light detectors are disposed on this surface. Preferably, the housing has a single surface facing the subject's skin, and both the light source and the light detector are disposed on this surface.

[0042] The surface facing the subject's skin may be planar or shaped to correspond to the surface of the body part on which the spectrophotometric device is to be placed, for example, the surface of the housing may be concavely curved to correspond to the convex curvature of the subject's abdomen.

[0043] In a preferred embodiment, the housing is provided with an adhesive patch for attaching the housing to the subject's clothing. The adhesive patch is preferably provided on the side of the housing opposite the subject's skin, preferably opposite the side on which the light source and the photodetector are provided. For example, the adhesive patch may be used to attach the housing to a diaper worn by the subject. Thereby, the spectrophotometric device can be fixed under the subject's clothing, such as a diaper. The adhesive patch is preferably a Velcro patch or a hook-and-loop fastener.

[0044] Preferably, the housing is made of a rigid material so that the distance between the light source and the detector remains constant. This is particularly preferred when the spectrophotometric device uses a multi-distance method to calculate blood oxygen saturation. Alternatively, the housing may be made of a flexible material. This has the advantage that the shape of the housing can be adapted to the shape of the individual subject and the individual body part. This improves the fit between the spectrophotometric device and the subject's skin and can help to eliminate measurement artifacts resulting from ambient light hitting the photodetector.

[0045] According to a first aspect, the spectrophotometric device further comprises a motion sensor. The motion sensor generates a motion signal indicative of the motion of the light source and / or the photodetector. The motion sensor is therefore preferably arranged in the vicinity of the light source and / or the photodetector. More preferably, the motion sensor is arranged together with the one or more light sources and the one or more photodetectors in the above-mentioned housing. In this case, the motion signal is preferably indicative of the motion of the entire housing. However, it is also possible that the motion signal specifically indicates the motion of one light source and / or one photodetector.

[0046] The motion sensor may comprise, for example, a linear accelerometer configured to measure linear displacement, or a gyroscope configured to measure rotational displacement. A combination of a linear accelerometer and a gyroscope may be used to measure both linear and rotational displacement. Preferably, the motion sensor is a piezoelectric element or a micro-electromechanical system (MEMS).

[0047] Preferably, a linear accelerometer is used. Suitable linear accelerometers may measure displacement along three axes, two axes, or a single axis. Most preferably, a linear three-axis accelerometer is used.

[0048] The motion sensor preferably has a sampling rate of 1 kHz to 5.3 kHz. The motion sensor preferably measures acceleration in the range of ±16 g, more preferably in the range of ±8 g, most preferably in the range of ±4 g, more preferably in the range of ±2 g.

[0049] The electronic data processing unit configured to calculate the blood oxygen saturation is configured to receive data from both the motion sensor and the one or more light sources and the one or more light detectors. The electronic data processing unit may be physically connected to the motion sensor, the light source and the light detector, for example by wire connection. However, the electronic data processing unit may be located at a remote location and wirelessly connected to the motion sensor, the light source and the light detector. The electronic data processing unit may be a central processing unit that is part of a multiple spectrophotometric device. In this case, the electronic data processing unit receives the signals of the multiple motion sensors, the light source and the light detector to calculate the blood oxygen saturation of the multiple subjects.

[0050] The electronic data processing unit may for example be implemented on a personal computer comprising a central processing unit, a random access memory, a data storage device and a data connection for receiving the measurement data from the motion sensor and the light detector.

[0051] The electronic data processing unit executes an algorithm for calculating the blood oxygen saturation. In this context, the blood oxygen saturation StO 2 is the oxygenated hemoglobin HbO according to the following formula: 2 Oxygenated hemoglobin (HbO) 2 It is defined as the ratio of total hemoglobin (Hb) to deoxygenated hemoglobin (Hb). StO 2 = c(HbO 2 ) / (c(HbO 2 ) + c(Hb)) where c(HbO 2 ) is the concentration of oxygenated hemoglobin and c(Hb) is the concentration of deoxygenated hemoglobin.

[0052] The algorithm calculates the optical attenuation A as a function of wavelength λ of an optical signal emitted by one or more light sources and detected by one or more photodetectors. λ This involves determining the light attenuation A λFrom this, the algorithm calculates the oxygenated hemoglobin c (HbO 2 The algorithm calculates the concentration of oxygenated hemoglobin c(Hb) and the concentration of deoxygenated hemoglobin c(Hb). Specifically, the algorithm uses empirically determined extinction coefficients of oxygenated hemoglobin and deoxygenated hemoglobin, as well as empirically determined calibration data that accounts for light scattering in the subject's tissue. The extinction coefficients of oxygenated hemoglobin and deoxygenated hemoglobin can be determined from the absorption spectra of isolated oxygenated hemoglobin and deoxygenated hemoglobin. Preferably, the algorithm determines only the relative concentrations of oxygenated hemoglobin and deoxygenated hemoglobin. Since blood oxygen saturation is defined as the ratio of the concentrations of oxygenated hemoglobin and deoxygenated hemoglobin, it is not necessary to determine absolute concentrations.

[0053] In one embodiment, the algorithm uses a differential wavelength method to calculate oxygenated hemoglobin c (HbO 2 The method includes calculating the concentration of deoxygenated hemoglobin c (Hb) and the concentration of deoxygenated hemoglobin c (Hb). This involves measuring the attenuation of light at at least three separate wavelengths and calculating the difference in attenuation between the wavelengths. The differential wavelength method is described, for example, in US Pat. No. 5,399,363.

[0054] In another embodiment, the algorithm uses a multi-distance method to calculate oxygenated hemoglobin (HbO 2The method includes calculating the concentration of hemoglobin c (Hb) and the concentration of deoxygenated hemoglobin c (Hb). This involves measuring the attenuation of light at two or more different "light source" to detector distances, calculating the slope of the attenuation of the light signal with respect to the distance from the "light source" to the detector as a function of wavelength, and calculating the blood oxygen saturation in the tissue of the subject based on the slope of the attenuation of the light signal. The multi-distance method is described, for example, in "A Hybrid Multi-Distance Phase and Broadband Spatially Resolved Spectrometer and Algorithm for Resolving Absolute Concentrations of Chromophores in the Near-Infrared Light Spectrum" by Tachtsidis, Ilias et al. Advances in Experimental Medicine and Biology 662 (2010): 169-175.

[0055] Relative absorption μ can be determined using a multi-distance approach by measuring the attenuation as a function of distance from the “source” to the detector. a,λ This makes it possible to calculate the blood oxygen saturation of a given reference tissue by assuming that the blood oxygen saturation of the reference tissue is a weighted sum of the oxygen saturation of the subject's venous and arterial blood. In this method, only the light scattering of the tissue needs to be considered. This eliminates a source of systematic error, since no assumptions about the relative contributions of venous and arterial blood are required.

[0056] The electronic data processing unit may further be configured to use the pulsatile component of the measured light attenuation to determine the subject's pulse rate and / or breathing frequency, which requires the electronic data processing unit to continuously sample the optical signal of the photodetector over a predetermined period of time.

[0057] In preferred embodiments, the algorithm takes into account absorption from other chromophores in addition to oxygenated and deoxygenated hemoglobin. The algorithm preferably takes into account empirically determined data that takes into account light absorption by wavelength-dependent light absorbers other than hemoglobin. Preferably, the algorithm takes into account light absorption by other light absorbing materials within the subject's abdomen. Most preferably, this includes absorption by stool, infant faeces, meconium, and / or biliverdin.

[0058] In one particular embodiment, the algorithm takes into account the wavelength-dependent extinction coefficients of these other light absorbers. The extinction coefficients can be determined, for example, by measuring the absorption spectrum of isolated samples of stool, transitory stool, meconium, and / or biliverdin. In a preferred example, the extinction coefficient is determined by measuring the absorption spectrum of an isolated sample of meconium.

[0059] Meconium is the first feces of a mammalian infant. Meconium is composed of materials ingested during the infant's time in utero, namely intestinal epithelial cells, fetal hair, mucus, amniotic fluid, bile, and water. It has been found that the average absorption spectrum of meconium samples taken from a number of different subjects can be used as a source of absorbance data for the above calculations. In one embodiment, the data that accounts for attenuation of the optical signal by optical absorbers includes the wavelength-dependent extinction coefficient of meconium samples taken from newborns.

[0060] Transitional stool is the stool produced by a newborn during the first few days after birth. Transitional stool differs in composition from meconium and contains a high amount of biliverdin. Therefore, the data considering the attenuation of the light signal by the light absorber preferably includes the wavelength-dependent extinction coefficient of transitional stool samples taken from a newborn, preferably during the first two weeks after birth, more preferably during the first week after birth, and most preferably during the first five days after birth.

[0061] In another preferred embodiment, the data accounting for attenuation of the optical signal by the optical absorber includes the wavelength-dependent extinction coefficient of biliverdin.

[0062] The electronic data processing unit is preferably configured to continuously sample the measurement data of the one or more photodetectors and calculate the blood oxygen saturation. The sampling rate is preferably in the range of 0.1 kHz to 10 kHz, more preferably in the range of 0.5 kHz to 3 kHz, and most preferably in the range of 0.6 kHz to 2 kHz. The electronic data processing unit may perform some form of downsampling by calculating an average light signal from a group of consecutive discrete measurements provided by the one or more photodetectors. Preferably, the electronic data processing unit calculates a moving average of the measurement data of the one or more photodetectors and calculates the light attenuation and blood oxygen saturation based on this moving average.

[0063] Preferably, the spectrophotometric device comprises an electronic storage device connected to the electronic data processing unit, which stores data identifying the spectrophotometric device and calibration data specific to the spectrophotometric device. In operation, the electronic data processing unit can use this information to calculate blood oxygen saturation. Preferably, the electronic storage device is an integral part of the electronic data processing unit. However, this is not essential. The electronic storage device does not necessarily have to be located at the same location or in the vicinity of the electronic data processing unit. The electronic storage device may be provided in a housing containing the light source and detector described above, or may be located in a connector connecting the housing to the electronic data processing unit. The electronic storage device may also be located in a remote location and connected to the electronic data processing unit, for example via a wireless location.

[0064] According to a first aspect of the invention, the electronic data processing unit is configured to discard the optical signal measured by the at least one detector if the motion signal detected by the motion sensor exceeds a predefined threshold, thereby allowing to identify and discard measurement artefacts caused by motion of the spectrophotometric device and / or motion of the subject, thereby improving the accuracy of the measurement and reducing false alarms.

[0065] The electronic data processing unit is preferably configured to continuously sample the motion signal provided by the motion sensor, preferably at the same sampling rate as the sampling of the measurements of the photodetector. The electronic data processing unit may perform a down-sampling of the measurement data received from the motion sensor, for example by calculating a moving average of the motion signal, as described for the optical signal received by the photodetector above.

[0066] Preferably, the electronic data processing unit is configured to continuously sample the measurement data of the one or more photodetectors and continuously sample the motion signal provided by the motion sensor to calculate the blood oxygen saturation. In this embodiment, if the motion signal exceeds a predetermined threshold, the calculation of the blood oxygen saturation is interrupted.

[0067] In one embodiment, the electronic data processing unit discards the optical signal as soon as the movement signal exceeds a predefined first threshold and resumes processing of the optical signal as soon as the movement signal falls below a predefined second threshold. The first and second thresholds do not necessarily have to be the same. Instead, the first threshold may be greater or less than the second threshold. In one embodiment, the first threshold is greater than the second threshold. In this case, the optical signal is discarded only if the movement signal is relatively high. Thereby, minor fluctuations in the movement signal do not unnecessarily interrupt the processing of the optical signal. At the same time, the processing of the optical signal is resumed only if the movement signal falls below a relatively low second threshold. Thereby, the processing is resumed only if it can be safely excluded that the movement does not interfere with the optical measurement.

[0068] In one embodiment, the electronic data processing unit is configured to issue a warning to the user if the movement signal exceeds a predefined threshold, which can be an optical warning, such as a light indicator or a message displayed on an electronic display, and / or an acoustic warning.

[0069] In a preferred embodiment, the electronic data processing unit executes an iterative algorithm, each iteration of which comprises the following steps: (1) receiving an optical signal measured by at least one detector and a motion signal detected by a motion sensor; (2) Check the quality of optical and motion signals. (3) If the quality of the optical signal and the motion signal is sufficient, accept the calculation of blood oxygen saturation based on the optical signal, optionally report the calculated blood oxygen saturation to the user, and reset the signal quality timer value to zero. (4) If the quality of the optical signal and / or the motion signal is insufficient, discard the optical signal or blood oxygen saturation calculation and increment the value of a signal quality timer. (5) If the signal quality timer value exceeds a predetermined threshold, a warning is issued to the user.

[0070] In this embodiment, the electronic data processing unit stores and modifies the value of the signal quality timer during each iteration of the above algorithm. This allows the electronic data processing unit to issue a warning to the user if the signal quality timer exceeds a predefined threshold. In other words, if the signal quality is insufficient for multiple consecutive iterations of the algorithm, a warning is issued to the user. A typical threshold for the signal quality timer is in the range of 1 to 10 minutes.

[0071] To check the quality of the light and motion signals, an algorithm reports insufficient quality if the motion signal exceeds a predefined threshold, otherwise it reports sufficient quality.

[0072] Preferably, the algorithm further checks the quality of the optical signal.

[0073] Preferably, the algorithm performs the following steps to check the quality of the light and motion signals. (1) Report insufficient quality if the motion signal exceeds a given threshold. (2) Otherwise, report insufficient quality if the signal-to-noise ratio of the optical signal is below a predetermined threshold. (3) if not, report sufficient quality.

[0074] Here, the noise level for calculating the signal-to-noise ratio is determined based on measurements of the ambient light when all light sources of the spectrophotometric device are turned off.

[0075] More preferably, the algorithm performs the following steps to check the quality of the light and motion signals. (1) Report insufficient quality if the motion signal exceeds a given threshold. (2) Otherwise, report insufficient quality if the signal-to-noise ratio of the optical signal is below a predetermined threshold. (3) Otherwise, report insufficient signal quality if the reduction in optical signal as a function of distance from the “source” to the detector does not follow an exponential law. (4) if not, report sufficient quality.

[0076] Here, the reduction in the optical signal as a function of the distance from the "light source" to the detector is preferably evaluated by curve fitting. Preferably, the logarithm of the signal amplitude as a function of the distance from the "light source" to the detector is determined, and a curve fit is performed using a linear regression model to determine the coefficient of determination. The coefficient of determination (R-squared) is determined according to known statistical methods. If the coefficient of determination exceeds a predefined threshold, preferably a threshold of 0.97, the reduction in the optical signal as a function of the distance from the "light source" to the detector is considered to follow an exponential law.

[0077] In a further embodiment of the invention, the electronic data processing unit is configured to determine the quality of the optical signal and to discard the optical signal only if the quality of the optical signal is insufficient and the movement signal exceeds a predefined threshold. However, if the quality of the optical signal is determined to be sufficient, the optical signal is not discarded. Preferably, in this embodiment, even if the movement signal exceeds a predefined threshold, the optical signal is not discarded as long as the quality of the optical signal is determined to be sufficient. Preferably, the quality of the optical signal is evaluated by determining the coefficient of determination of a linear regression model fitted to the logarithm of the signal amplitude as a function of the distance from the "source" to the detector, as described above.

[0078] In the embodiment described above, the electronic data processing unit executes an iterative algorithm, each iteration of which includes the following steps: (1) receiving an optical signal measured by at least one detector and a motion signal detected by a motion sensor; (2) Check the quality of the optical signal. (3) If the quality of the optical signal is sufficient, accept the calculation of blood oxygen saturation based on the optical signal, optionally report the calculated blood oxygen saturation to the user, and proceed to step 1. (4) If the quality of the optical signal is insufficient, determining whether the motion sensor signal exceeds a predetermined threshold. (5) Discarding the optical signal or blood oxygen saturation calculation if the motion sensor signal exceeds a predetermined threshold.

[0079] If the electronic data processing unit receives a motion signal from the linear accelerometer and / or gyroscope, the electronic data processing unit may calculate a processed motion signal indicative of a motion in a particular direction. The processed motion signal is then compared to a predefined threshold to determine whether to interrupt the blood oxygen saturation calculation. For example, the electronic data processing unit may calculate a processed motion signal indicative of a motion tangential or perpendicular to the subject's skin. This can be achieved, for example, by using the gyroscope to determine the three-dimensional orientation of the motion sensor relative to the subject's skin and the linear accelerometer to determine the linear motion in a particular direction relative to the subject's skin. The electronic data processing unit may also calculate the processed motion signal based on a weighted average of the motion in different directions. For example, motion perpendicular to the subject's skin may be given a greater weight than motion tangential to the subject's skin. Thereby, the algorithm for calculating blood oxygen saturation is more sensitive to motion perpendicular to the subject's skin than motion tangential to the subject's skin. Movement perpendicular to the skin may indicate that the motion sensor is moving away from the skin, compromising the measurement of the optical signal.

[0080] In a further embodiment, the electronic data processing unit is configured to determine the breathing frequency of the subject based on a movement signal provided by the movement sensor. Preferably, the electronic data processing unit is configured to determine the breathing frequency based on a periodic change in the movement signal. More preferably, the measurement is based on a movement signal provided by a linear movement sensor. More preferably, the measurement is based on a measurement of a linear movement perpendicular to the subject's skin. The periodic change in the movement signal is indicative of a periodic movement of the movement sensor, which is caused by a movement of the subject's body, e.g. the subject's abdomen, and is therefore indicative of the breathing frequency.

[0081] The spectrophotometric device may further include an electronic display for displaying the currently calculated blood oxygen saturation to the user.

[0082] The spectrophotometric device may further comprise a temperature sensor for measuring the skin temperature and / or the core body temperature of the subject, which may be, for example, a resistance temperature detector, a thermocouple, or a pyrometer. A heat flux sensor may be used to determine the core body temperature.

[0083] According to a second aspect, the present invention relates to a spectrophotometric device for measuring blood oxygen saturation in tissue of a subject, comprising at least one light source for emitting an optical signal into the tissue of the subject, at least one detector for detecting an optical signal reflected by the tissue of the subject, an electronic data processing unit configured to calculate blood oxygen saturation taking into account the optical signal measured by the at least one detector, and a contact sensor for detecting a contact signal indicative of contact between the skin of the subject and the light source and / or the detector.

[0084] According to a second aspect, the present invention further relates to a method for non-invasively measuring blood oxygen saturation in tissue of a subject, comprising the steps of using at least one light source for emitting an optical signal into tissue of the subject, using at least one detector for detecting the optical signal reflected from the tissue of the subject, using an electronic data processing unit for calculating blood oxygen saturation based on the optical signals measured by the one or more detectors, and using a contact sensor for detecting a contact signal indicative of contact between the skin of the subject and the at least one light source and / or the at least one detector, characterized in that the electronic data processing unit discards the optical signal measured by the at least one detector and / or issues a warning to a user if the contact signal indicates that the at least one light source and / or the at least one detector has lost contact with the skin of the subject.

[0085] The spectrophotometry device according to the second aspect corresponds to the spectrophotometry device according to the first aspect described above, except for the above-mentioned modifications, i.e. the spectrophotometry device according to the second aspect does not necessarily comprise the above-mentioned motion sensor. The spectrophotometry device according to the second aspect may therefore have all the optional features described for the spectrophotometry device according to the first aspect above. The spectrophotometry device according to the second aspect may also comprise the above-mentioned motion sensor. Similarly, the spectrophotometry device according to the first aspect may optionally comprise a contact sensor as disclosed for the second aspect.

[0086] According to a second aspect, the spectrophotometric device comprises a contact sensor for detecting a contact signal indicative of contact between the subject's skin and the light source and / or detector. This allows for continuous monitoring of the correct positioning of the light source and / or detector. Loss of contact between the subject's skin and the light source or detector may lead to an erroneous determination of the light attenuation, for example due to the influence of ambient light. This source of error can be eliminated by continuous monitoring of the contact signal measured by the contact sensor. The spectrophotometric device according to the second aspect therefore improves the accuracy of the measured blood oxygen saturation. This is particularly important when monitoring newborns or premature babies, who often exhibit sudden movements that lead to loss of skin contact in conventional spectrophotometric devices.

[0087] In this context, the term "skin contact" in relation to the light source and detector means that the light source and detector are at an optimal distance from the skin, which may mean that the surface of the light source and / or detector is in direct physical contact with the skin, or may mean that the surface is located at a particular close distance that allows optimal transmission and reception of optical signals to and from the subject's skin.

[0088] The contact sensor may be, for example, a capacitive sensor, a conductive sensor or a pressure sensor. Preferably, the contact sensor provides a distance signal indicative of a distance between the contact sensor and the skin of the subject. A distance signal below a predefined threshold indicates that the contact sensor has lost contact with the skin of the user. Preferably, the contact sensor is positioned such that loss of skin contact of the contact sensor indicates that the at least one light source and / or the at least one detector have also lost contact with the skin of the subject.

[0089] In a preferred embodiment, the contact sensor is provided within a housing along with the light source and detector, which may be constructed as described with respect to the first embodiment above.

[0090] Preferably, the contact sensor is provided on a surface of the housing facing the subject's skin. Preferably, the electronic data processing unit is configured to discard the light signal measured by the at least one detector and / or to issue a warning to a user if the contact signal indicates that the at least one light source and / or the at least one detector has lost contact with the subject's skin.

[0091] In one embodiment, the electronic data processing unit is configured to continuously sample the measurement data of the one or more photodetectors to calculate blood oxygen saturation and to continuously sample the contact signal provided by the contact sensor. If the contact signal indicates that at least one light source and / or at least one detector has lost contact with the subject's skin, the light signal is discarded. More preferably, the contact sensor is configured to determine which light source and / or photodetector has lost contact with the subject's skin and to discard only the light signal emitted or measured by that particular light source and / or photodetector.

[0092] Furthermore, the electronic data processing unit may also be configured to issue a warning to the user if the contact signal indicates that the at least one light source and / or the at least one detector has lost contact with the subject's skin, which may be an optical warning, such as a light indicator or a message displayed on an electronic display, and / or an acoustic warning.

Claims

1. 1. A spectrophotometric device for measuring blood oxygen saturation in tissue of a subject, comprising: one or more light sources for emitting optical signals into tissue of the subject; one or more detectors for detecting optical signals reflected by the tissue of the subject; an electronic data processing unit configured to calculate blood oxygen saturation based on the optical signals measured by the one or more detectors; and a motion sensor for detecting a motion signal indicative of a motion of the light sources and / or the detectors, 11. A spectrophotometric apparatus, characterized in that the electronic data processing unit is configured to discard optical signals measured by one or more of the detectors if a motion signal detected by the motion sensor exceeds a predetermined threshold.

2. 2. The spectrophotometric device according to claim 1, 1. A spectrophotometric apparatus configured to measure blood oxygen saturation in an abdominal region of a subject.

3. 3. The spectrophotometric device according to claim 1, 1. A spectrophotometric device configured to measure the attenuation of an optical signal at two or more wavelengths and / or at two or more distances from said light source to said detector.

4. A spectrophotometric device according to any one of claims 1 to 3, 11. A spectrophotometry apparatus, wherein the motion sensor comprises a linear accelerometer configured to measure linear displacement and / or a gyroscope configured to measure rotational displacement.

5. 5. A spectrophotometric device according to claim 1, the electronic data processing unit is configured to continuously sample the measurement data of the one or more detectors in order to calculate blood oxygen saturation and to continuously sample the motion signal provided by the motion sensor; 20. A spectrophotometric apparatus, comprising: a motion sensor for detecting a motion of a subject; a first motion sensor for detecting a motion of the subject; a second motion sensor for detecting a motion of the subject;

6. 6. A spectrophotometric device according to claim 1, The spectrophotometric apparatus, characterized in that the electronic data processing unit is configured to discard the optical signal as soon as the movement signal exceeds a first predetermined threshold and to resume processing the optical signal as soon as the movement signal falls below a second predetermined threshold.

7. 7. The spectrophotometric device according to claim 6, A spectrophotometric apparatus, wherein the first threshold value is greater than the second threshold value.

8. A spectrophotometric device according to any one of claims 1 to 7, A spectrophotometric apparatus, further comprising an electronic memory connected to said electronic data processing unit for storing data identifying said spectrophotometric apparatus and calibration data specific to said spectrophotometric apparatus.

9. A spectrophotometric device according to any one of claims 1 to 8, The electronic data processing unit is configured to determine a breathing frequency of the subject based on a movement signal provided by the movement sensor.

10. A spectrophotometric device according to any one of claims 1 to 9, The electronic data processing unit is adapted to generate a warning to a user if the motion signal exceeds a predetermined threshold.

11. A spectrophotometric device according to any one of claims 1 to 10, A spectrophotometric device, characterized in that one or more of the light sources and one or more of the detectors are disposed within a single housing, the housing having an adhesive patch for attaching the housing to a subject's clothing.

12. A spectrophotometric device according to any one of claims 1 to 11, The spectrophotometric device, characterized in that the electronic data processing unit is configured to determine the quality of the optical signal and to discard the optical signal only if the quality of the optical signal is insufficient and the movement signal exceeds a predetermined threshold.

13. using at least one light source for emitting an optical signal into tissue of a subject; using at least one detector to detect optical signals reflected from tissue of the subject; using an electronic data processing unit for calculating blood oxygen saturation based on the optical signals measured by one or more of said detectors; and using a motion sensor to detect a motion signal indicative of movement of the light source and / or the detector.

1. A method for non-invasively measuring blood oxygen saturation in tissue of a subject, comprising:

4. A method according to claim 3, wherein said electronic data processing unit discards the optical signals measured by one or more of said detectors if the motion signal detected by said motion sensor exceeds a predetermined threshold.

14. at least one light source for emitting a light signal into tissue of the subject; at least one detector for detecting an optical signal reflected by tissue of the subject; an electronic data processing unit configured to calculate blood oxygen saturation taking into account the optical signal measured by at least one said detector; a contact sensor for detecting a contact signal indicative of contact between the skin of a subject and the light source and / or the detector. A spectrophotometric device for measuring blood oxygen saturation in the tissue of a subject.

15. 15. The spectrophotometric device of claim 14, A spectrophotometric device, characterized in that the electronic data processing unit is configured to discard the light signal measured by at least one of the detectors and / or to issue a warning to a user when a contact signal indicates that at least one of the light sources and / or at least one of the detectors has lost contact with the subject's skin.

16. using at least one light source for emitting an optical signal into tissue of a subject; using at least one detector to detect optical signals reflected from tissue of the subject; using an electronic data processing unit for calculating blood oxygen saturation based on the optical signals measured by one or more of said detectors; and using a contact sensor to detect a contact signal indicative of contact between the skin of a subject and at least one of the light sources and / or at least one of the detectors.

1. A method for non-invasively measuring blood oxygen saturation in tissue of a subject, comprising: The method, characterized in that when the contact signal indicates that at least one of the light sources and / or at least one of the detectors has lost contact with the subject's skin, the electronic data processing unit discards the light signal measured by at least one of the detectors and / or issues a warning to a user.

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