Blood component measuring device and blood component measuring method

Abstract

The present disclosure relates to a method and apparatus for determining hemoglobin levels in a mammal, the apparatus including a plurality of light emitting diodes, one or more sensors, and a processor.

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of both U.S. Provisional Patent Application No. 63 / 052,115, filed July 15, 2020, and U.S. Provisional Patent Application No. 63 / 072,504, filed August 31, 2020, which are incorporated herein by reference. [Background technology]

[0002] Measurement and monitoring of blood constituents, such as hemoglobin (Hb) and its related form, oxyhemoglobin (O-Hb), is often performed invasively. Blood sampling can be uncomfortable for patients and increase the risk of infection. The adverse effects of constant and often difficult blood sampling are even more pronounced in neonates and infants. Frequent and consistent hemoglobin measurements are clinically necessary in a wide range of conditions, including, but not limited to, patients infected with Coronavirus Disease 2019 (COVID-19), hemoglobinopathies such as sickle cell disease (Hb-S), hematologic malignancies, and anemia, including perioperative management after major surgery such as spinal surgery, emergency and critical care settings. Furthermore, these parameters are part of routine health maintenance in healthy subjects and are increasingly being used to monitor exercise capacity. Summary of the Invention [Problem to be solved by the invention]

[0003] Therefore, frequent measurement of Hb and O-Hb is widely applicable to healthy adults and children, athletes, patients recovering from various illnesses, and hospitalized patients. Although available invasive techniques are well established, they require the presence of medical personnel and laboratory equipment. Representative laboratory methods include the cyanomethemoglobin (CM) method, the copper sulfate chromatograph (CST), automated hematology analyzers (AHA), and color-based analyzers. These requirements not only increase costs but also increase the time it takes for laboratory results to become available for clinical use. Several "point-of-care" (POC) hemoglobin tests, such as the HemoCue™, are available in clinical settings and, in some cases, at the bedside. However, these tests still require obtaining a blood sample from the patient.

[0004] Non-invasive methods are also available, but they have problems such as fluctuations and limitations in hypoperfusion states such as shock, and the inability to measure a wide range of hemoglobin values. [Means for solving the problem]

[0005] Therefore, there is a need for non-invasive systems, devices, and methods for measuring various blood constituents. Embodiments of the present disclosure provide devices and methods that address the above needs.

[0006] The present disclosure relates to measuring hemoglobin concentration using reflectance spectroscopy. [Effects of the Invention]

[0007] An advantage of the present technology is that it provides a simple, portable, and easy-to-use handheld device (described below) and a continuous (or nearly continuous) noninvasive method for measuring hemoglobin (Hb) concentrations in real time, which also has the advantage of measuring the ratio of oxyhemoglobin (O-Hb) to deoxyhemoglobin (d-Hb) concentrations.

[0008] The present disclosure will be better understood by reference to the following drawings, which are not meant to limit the scope of the disclosure but are provided as illustrations of certain embodiments of the present application. [Brief explanation of the drawings]

[0009] [Figure 1] FIG. 1 illustrates the apparatus of the present disclosure. [Figure 2] FIG. 2 illustrates the probe of the device of the present disclosure. [Figure 3] FIG. 3 illustrates the probe and housing of the device of the present disclosure. [Figure 4] FIG. 4 is a diagram of a probe near the skin surface of a human mammal. [Figure 5] FIG. 5 is a diagram of a probe near the skin surface of a human mammal. [Figure 6] FIG. 6 is a graph of reflected light level versus hemoglobin level. [Figure 7] FIG. 7 is a graph of reflected light level versus hemoglobin level. [Figure 8] FIG. 8 is a graph of reflected light level versus hemoglobin level. [Figure 9] FIG. 9 is a graph of optical signal measurements for four different locations on the skin surface of a human mammal over four different time points in the same mammal. [Figure 10] FIG. 10 is a graph of the absorption percentage over various wavelengths for two types of hemoglobin: fetal hemoglobin (Hb-F) and adult hemoglobin (Hb-A). [Figure 11] FIG. 11 is a graph of reflected light level versus hemoglobin level. [Figure 12] FIG. 12 is a graph of R values ​​for various skin tones. [Figure 13] FIG. 13 is a graph of the E1 / E2 ratio over time. DETAILED DESCRIPTION OF THE INVENTION

[0010] In the description and claims of this specification, the term "about" indicates that the listed value may be slightly modified as long as the modification does not result in non-compliance of the method or apparatus. For example, for some elements, the term "about" may refer to a variation of ±0.1%, while for other elements, the term "about" may refer to a variation of ±1% or ±10%, or any point therein.

[0011] As used herein, the terms "substantially" or "substantial" are broad terms and are used in their ordinary sense, including but not limited to being largely, not necessarily fully specified, and when used in a negative sense, mean the complete or nearly complete absence of an action, characteristic, property, state, structure, item, or result; for example, a "substantially" flat surface means either completely flat or approximately flat such that the action is the same as if it were completely flat.

[0012] As used herein, terms such as "a," "an," and "the" are not intended to refer to only a single entity, but include generalities for which specific examples can be used for illustration.

[0013] As used herein, terms defined in the singular are intended to include terms defined in the plural and vice versa.

[0014] References herein to "one embodiment," "particular embodiment," "some embodiments," or "embodiments" indicate that the described embodiment may include a particular feature or characteristic, but that not all embodiments necessarily include the particular feature, structure, or characteristic. Moreover, such phrases do not necessarily refer to the same embodiment. Furthermore, when a particular feature, structure, or characteristic is described in connection with an embodiment, it is stated that it is within the knowledge of one of ordinary skill in the art to affect such feature, structure, or characteristic in connection with other embodiments, even if not explicitly described.

[0015] For purposes of the following description, the terms "upper," "lower," "right," "left," "vertical," "horizontal," "top," "bottom," and their derivatives, as they relate to the present invention, refer to orientation in the drawings. The terms "overlying," "atop," "positioned on," or "positioned atop" mean that a first element is above a second element, with an intervening element present as a contact point between the first and second elements. The terms "direct contact" or "attached to" mean that a first element and a second element are connected without an intermediate element at the interface of the two elements.

[0016] Any reference herein to a range of values ​​expressly includes each number (including decimals and integers) contained within that range. For purposes of illustration, reference herein to a range of "at least 50" or "at least about 50" includes integers such as 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, and the like, and decimals such as 50.1, 50.2, 50.3, 50.4, 50.5, 50.6, 50.7, 50.8, 50.9, and the like. For further explanation, reference herein to a range of "less than 50" or "less than about 50" includes integers such as 49, 48, 47, 46, 45, 44, 43, 42, 41, 40, and the like, and decimals such as 49.9, 49.8, 49.7, 49.6, 49.5, 49.4, 49.3, 49.2, 49.1, 49.0, and the like.

[0017] The present disclosure relates to devices and methods for measuring various blood constituents, such as different forms of hemoglobin, including oxyhemoglobin (O-Hb) and deoxyhemoglobin (d-Hb).

[0018] The hemoglobin molecule has two units: heme and globin. The heme portion contains Fe +2 Hemoglobin has one iron atom, either in the form of ferrous iron or ferrous iron, and a pyrrole ring. The globin portion is a tetramer, or four amino acid chains. These chains are alpha, beta, gamma, and delta globin chains. Thus, hemoglobin has one heme portion and four globin chains. For example, Hb-A has two alpha chains and two beta chains. Table 1 below summarizes the three types of hemoglobin in a healthy state.

[0019] [Table 1]

[0020] Oxyhemoglobin refers to the amount of hemoglobin with oxygen bound to the heme component, while deoxyhemoglobin refers to the amount of hemoglobin without oxygen bound. Oxyhemoglobin and total hemoglobin maintain a healthy ratio. As hemoglobin is broken down, globin chains are added to the amino acid pool. The heme splits, opening all the pyrrole rings, which are later metabolized into bilirubin. When concentrations are high, more light is absorbed. Therefore, by measuring reflected light, the concentrations of oxyhemoglobin and deoxyhemoglobin can be determined, as explained further below.

[0021] Based on the above, a probe device can be used to measure reflected light and determine the ratio of oxyhemoglobin to deoxyhemoglobin. For example, a probe device 100 is shown in FIG. 1. Oxyhemoglobin (O-Hb) and deoxyhemoglobin (d-Hb) have unique spectral characteristics compared to each other. O-Hb has an absorption peak between about 515 nm and about 535 nm, between about 520 nm and about 530 nm, or at about 525 nm. d-Hb has an absorption peak between about 540 nm and about 560 nm, between about 545 nm and about 555 nm, or at about 550 nm.

[0022] The device 100 may include a probe (device) 2 and a processor 4. As used herein, the term "processor" refers to a circuit, part of a circuit, or including a circuit capable of sequentially and automatically performing a series of arithmetic or logical operations, recording, storing, and / or transferring digital data. The term "processor" may refer to one or more application processors, one or more baseband processors, physical central processing units (CPUs), single-core or multi-core processors, and / or other devices capable of executing or manipulating computer-executable instructions, such as program code, software modules, and / or functional processes.

[0023] In this embodiment, the probe 2 is connected to the processor 4 via a suitable cable 3 configured to transmit electrical signals. However, in other embodiments, the probe 2 may communicate with the processor 4 via any suitable wireless protocol, including, but not limited to, Wi-Fi, Bluetooth, or near field communication (NFC). In still other embodiments, the processor 4 may be within the probe 2 itself.

[0024] The processor 4 may be contained in a housing 6. The housing 6 may also contain electronic storage 10. As used herein, the term "electronic storage" includes any type of integrated circuit, microcomputer, and / or other storage suitable for storing digital data, including but not limited to ROM, PROM, EEPROM, DRAM, SDRAM, DDR / 2 SDRAM, EDO / FPMS, RLDRAM, SRAM, "flash" memory (such as NAND / NOR), 3D memory, PSRAM, etc.

[0025] The housing 6 may also include a display 8. The display 8 may be any suitable display, such as a liquid crystal display (LCD), cathode ray tube display, or light emitting diode (LED) display, capable of displaying various information determined by the probe 2 and / or stored in the memory 10. Optionally, the display 8 may be configured for input by receiving touch input from a user on or near a portion of the display 8. Alternatively or in addition to the display 8 being an input portion, the housing 6 may include a control panel 12 that can accept various inputs from a user. These inputs are described in more detail below.

[0026] In this embodiment, the housing 6 may optionally include an internal power source 14, such as a battery. However, in other embodiments, the probe 2 and / or processor 4 may be powered by an external power source. In still other embodiments, the probe 2 itself may include the power source 14.

[0027] The probe 2, including its nozzle 23, is shown in more detail in Figure 2. The nozzle 23 may be any suitable hollow or tubular structure that can be formed to any suitable length to allow accurate measurement of reflected light by the probe 2.

[0028] As shown in FIG. 2, a plurality of light-emitting diodes 22 are provided within the probe housing 20. The wavelengths of the light-emitting diodes 22 may be the same or different, fixed or variable, and may be any suitable wavelength within any suitable range, such as about 450 nm to about 580 nm. Specific examples of such wavelengths include, but are not limited to, about 525 nm, about 545 nm, about 550 nm, and about 575 nm. However, in other embodiments, the wavelengths may vary from any of the above values ​​by about 0.001%, about 0.01%, about 0.1%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, about 7%, about 9%, about 10%, about 13%, about 15%, about 20%, or more.

[0029] The plurality of light emitting diodes 22 may be activated individually or in any suitable sequence to illuminate a surface, such as the skin surface (any suitable portion of the epidermis) of a mammal.

[0030] Upon irradiating light from the light-emitting diode 22, one or more sensors 24 (two sensors 24 are shown for illustrative purposes) configured to sense the amount of light, such as photodiodes, measure the light reflected from the surface. These one or more sensors 24 then convert the measured light into an appropriate electrical signal. In the present disclosure, the light-emitting diode 22 can emit light at any predetermined interval, from about 0.1 seconds or less to about 0.5 seconds or more, about 1 second or more, about 5 seconds or more, about 30 seconds or more, about 1 minute or more, about 2 minutes or more, about 5 minutes or more, or about 10 minutes or more. Thus, the one or more sensors 24 can be configured to sense the amount of reflected light at a time corresponding to any period selected for emission.

[0031] 3 shows one embodiment of probe 2 connected to housing 6, which contains display 8, various inputs, and controls. An opening in the vertical top of probe 2 is where light passes (from multiple light emitting diodes 22) and is collected (by one or more sensors 24). This opening may be a void or may include a substantially transparent barrier, such as a plastic and / or glass barrier.

[0032] A display 8, which can optionally be used as an input, can be used to display various data such as the name of the mammal to which the probe 2 is applied, the date, the time, the status of the probe 2, a power indicator, total hemoglobin, oxyhemoglobin level, deoxyhemoglobin level, and / or the ratio of oxyhemoglobin to deoxyhemoglobin.

[0033] As shown in Figure 4, probe 2 can be positioned to contact any portion of a mammal's skin (S), for example, a human wrist and / or hand as shown in Figure 1. As seen in Figure 4, nozzle 23 of probe 2 is positioned near or in contact with the wrist portion of the human and held there by another user (or the human themselves, or a wearable structure).

[0034] In another embodiment, the probe can be placed in contact with the person's forehead, as seen in FIG.

[0035] 4 and 5, the light emitting diode 22 and one or more sensors 24 may be included in a wearable structure, for example, similar to a watch. The wearable structure may further include a processor 4, or the wearable structure may be configured to transmit data to a processor 4 external to the wearable structure.

[0036] Regardless of the configuration of probe 2, during operation of the device of the present disclosure to determine oxyhemoglobin levels, deoxyhemoglobin levels, and / or the ratio of oxyhemoglobin to deoxyhemoglobin, light from the plurality of light-emitting diodes 22 is directed toward a portion of the mammal's skin.

[0037] If the mammal has a relatively low hemoglobin level, a large portion of the light emitted from the light-emitting diode 22 is reflected and received by the one or more sensors 24. For example, more light passes from the light-emitting diode 22 through the epidermis, is reflected by both the upper and lower vascular plexuses, and then exits through the epidermis again. Thus, in this example, less light is absorbed in the papillary dermis between the lower and upper vascular plexuses and between the upper vascular plexus and the epidermis.

[0038] In contrast, if the mammal has a relatively high hemoglobin level, some of the light emitted from the light-emitting diode 22 will be reflected and received by the one or more sensors 24. For example, less light will pass from the light-emitting diode 22 through the epidermis, be reflected by both the upper and lower vascular plexuses, and then exit through the epidermis again. Thus, in this example, more light will be absorbed in the papillary dermis between the lower and upper vascular plexuses and between the upper vascular plexus and the epidermis.

[0039] The relationship between light reflectance and hemoglobin levels is discussed below with reference to FIGS.

[0040] The relationship between the amount of reflected light (Y-axis) measured as an electrical signal (current) and the amount of hemoglobin in the blood (X-axis) is shown in Figures 6 and 7. These graphs are based on measurements from mammals, specifically humans, with different skin colors. Light-skinned mammals have less melanin in their skin compared to dark-skinned mammals. In Figure 6, the skin color is held constant, so the relationship between the electrical signal and hemoglobin concentration is linear.

[0041] 6, a graph shows the relationship between the amount of reflected light (Y-axis) measured as an electrical signal (current) by one or more sensors 24 and the amount of hemoglobin in the mammal's blood (X-axis). This relationship is approximately linear, as indicated by the straight line, and applies under the assumption that the melanin concentration in the mammal's skin (or the skins of multiple mammals) is approximately constant. The gray shaded area above the approximate straight line represents a symmetric vertical shift of this linear relationship as a function of the melanin concentration in the skin.

[0042] Unlike Figure 6, the graph in Figure 7 shows the relationship between the amount of reflected light (Y-axis) measured as an electrical signal (current) by one or more sensors 24 and the amount of hemoglobin in the mammal's blood (X-axis). The line in Figure 7 is approximately logarithmic as the measured human skin melanin level varies over the course of the data. The gray shaded area at the top represents the vertical shift of this relationship as the mammal's skin melanin concentration varies during the measurement.

[0043] The difference between Figures 6 and 7 illustrates the effect that the melanin content of mammalian skin has on the accuracy of hemoglobin measurements.

[0044] As further demonstration of the effect of melanin on hemoglobin measurements, data are presented and discussed with reference to Figures 7-10.

[0045] Figure 8 is a graphical representation of data from four different individuals with similar melanin content (measured with a Felix Von Luschan (VLS) skin color chart) using probe 2 at the same location (the back of the wrist) on each individual. The VLS scale provides a correlation between the estimated melanin content of human skin and a human skin color grade (1-36). Therefore, the VLS scale can be trusted to provide a fairly accurate estimate of a person's melanin content by assigning it to one of 36 skin colors.

[0046] Referring again to FIG. 8, the amount of reflected light, measured as an electrical signal (current), is measured by one or more sensors 24 and plotted on the Y-axis, while the individual's blood hemoglobin content (measured using a conventional blood draw) is plotted on the X-axis. As indicated by the nearly straight line, this relationship is nearly linear. For comparison, the blood hemoglobin of four different individuals was also measured using the standard cyanomethemoglobin laboratory method, as shown by the four data points in FIG. 8. Compared to the hemoglobin levels from blood tests, there is a nearly exact correlation between the measured light values ​​converted to hemoglobin content.

[0047] One way to compensate for the effect of changes in melanin levels on optical hemoglobin measurements is to fabricate probe 2 so that the size of the nozzle 23 opening is relatively small. In this embodiment, the melanin concentration in the subject's skin is finite and defined, so if the same amount of light passes through a smaller surface area of ​​a mammal's skin from multiple light-emitting diodes 22, the emitted light will strike a relatively small amount of melanin. Because melanin concentrations are typically in the microgram range and hemoglobin concentrations are typically in the gram range, the effect of changes in melanin concentration on optical hemoglobin measurements can be minimized.

[0048] Another way to correct for the effect of varying melanin levels on optical hemoglobin measurements is to take melanin level into account, as described below.

[0049] In another example, Figure 9 is a graphical representation of temporal and spatial data from one individual using Probe 2 at four different sites at four different time points, each approximately four weeks apart. The data points indicated by crosses are blood draws and laboratory measurements of hemoglobin (approximately constant at 14.4 g / dL).

[0050] The amount of reflected light measured as an electrical signal (current) by one or more sensors 24 is plotted on the Y-axis, with the corresponding time points plotted on the X-axis. As can be seen from the graph, the measurements are substantially repeatable over time across four different time points for the same location. However, there are significant differences between measurements taken from different locations. For example, the amount of reflected light from the wrist is high, gradually decreasing from the wrist to the thumb, palm, and forehead. Thus, each probe 2 can be designed for a specific measurement location, or the probe 2 and processor 4 can be adjusted to account for different measurement locations.

[0051] Figure 10 is a graphical representation of data from 25 mother-infant pairs demonstrating similar spectral characteristics of fetal hemoglobin (Hb-F) and adult hemoglobin (Hb-A) using the disclosed device. Hb-F is the predominant form of hemoglobin in newborns and is gradually replaced by Hb-A by 8-9 months of age. The percentage of absorbed light is plotted on the Y-axis, and the corresponding wavelength (in nanometers) is plotted on the X-axis. Hb-F and Hb-A have very similar spectral characteristics, with absorption peaks at 450-460 nm and 540-550 nm. Because blood hemoglobin-A and blood hemoglobin-F have similar spectral characteristics, the disclosed device can be used to measure hemoglobin concentrations in adults and infants under 9 months of age.

[0052] As further illustration, Figure 11 is a graphical representation of data from five infants with similar melanin content (measured on the VLS scale) using probe 2 on the same site on each infant (forehead). The amount of reflected light measured as an electrical signal (current) by one or more sensors 24 is plotted on the Y-axis, and the amount of hemoglobin in the blood is plotted on the X-axis. The five data points indicated by small circles are test results from a typical blood draw hemoglobin test. The relationship is approximately linear, as indicated by the approximately straight line, and the laboratory data approximates the linear measurement results of the device of the present disclosure.

[0053] Additionally, Table 2 below includes data from four subjects with light brown skin color (VLS scale 24-25). The corresponding R values ​​are calculated using the formula R=E*H, where E is obtained using the device of the present disclosure and the blood hemoglobin concentration (H) is obtained using conventional blood sampling. In Table 2 and the remainder of this disclosure, a "ratio" of E1 or E2 is the ratio of the emitted light from the plurality of light-emitting diodes 22 at a wavelength to the amount detected at that wavelength by at least one sensor 24.

[0054] [Table 2]

[0055] In Table 2 above and throughout this disclosure, the constant "R" relates not only to hemoglobin but also to skin color or the skin pigment melanin. The constant R is a function of the amount of skin melanin and / or hemoglobin in particular racial / ethnic subsets. Thus, this coefficient "R" varies by racial / ethnic group.

[0056] R can be further expressed as R=kM, where "M" represents the variable concentration of melanin in the skin (the concentration variable) and "k" is a constant coefficient related to hemoglobin.

[0057] With two variables E (1 or 2) and M, the nature of the mathematical relationship between E and H is approximately linear or approximately logarithmic, and the relationship can be expressed essentially using a logarithmic scale as R=log(E*H) (Figure 7 above).

[0058] The R value depends on the amount of melanin in the skin, M, since R = kM. If the M value is held approximately constant, the R value will be approximately constant. In other words, the R value will be approximately constant for subjects with the same skin melanin concentration (M). In such cases, the relationship tends to be approximately linear and can be expressed as R = E * H (Figure 6).

[0059] Since the device of the present disclosure measures E at various wavelengths, the amount of hemoglobin in the blood, H (grams / 100 ml), can be calculated by the processor 4 using the formula: H (grams / 100 ml) = R / E.

[0060] The R value can be obtained by measuring melanin concentration. As noted above, the R value varies depending on the melanin concentration in the skin and is constant for a particular melanin concentration. Light-skinned subjects (i.e., less melanin, e.g., Caucasian human subjects) have higher R values ​​compared to dark-skinned subjects (i.e., more melanin, e.g., African-American human subjects), and R is approximately constant for subjects with the same or similar melanin concentration.

[0061] The mean and standard deviation of the R values ​​obtained in Table 2 were calculated. In this case, the calculated mean R value and standard deviation (SD) are (mean = 18.35, SD = 0.23). Using the 95% confidence interval (CI) for the data in Table 2, we obtain the following: The mean + / - 2SD for the 95% CI is (17.89-18.81). Therefore, the R value for light-skinned subjects (VLS 24-25) is expected to be around 18.35, and at least 95% of the measured subjects would fall within the interval of 17.89 to 18.81.

[0062] Similarly to Table 2 above, Table 3 below presents data from three subjects with dark brown skin color (VLS scale 30-31). The corresponding R values ​​were calculated using the formula R = E*H. While Table 2 lists only one time point per subject, in other examples, multiple measurements can be taken per subject. These multiple measurements can be taken over the time ranges listed above, such as continuous or nearly continuous measurements, up to measurements every few minutes or more.

[0063] [Table 3]

[0064] Similar to the methodology described above for Table 2, the calculated mean and SD for the data in Table 3 were (mean = 11.73, SD = 0.42). Therefore, using the 95% confidence interval (CI) for Table 3, the 95% CI for the mean + / - 2SD is (10.89-12.57). Therefore, the R value for darker-skinned subjects (VLS scale 30-31) is expected to be approximately 11.73, falling within the 10.89-12.57 interval for at least 95% of the subjects measured.

[0065] Table 4 presents data from two subjects: Subject X, who has light brown skin (VLS grade 24), and Subject Y, who has dark brown skin (VLS grade 30).

[0066] [Table 4]

[0067] In Table 4, for each subject, an E value was obtained using the device of the present disclosure (column 4). Next, according to skin color, the mean R value (95% CI) corresponding to each skin color was selected (based on Tables 2 and 3 above), as shown in column 5. Hemoglobin values ​​were calculated using the formula H=R / E and are shown in column 6 along with the range of agreement. These values ​​were compared to values ​​obtained using conventional blood sampling methods (column 7).

[0068] As shown in column 8, the difference between the hemoglobin values ​​obtained using the disclosed device and those obtained using conventional blood sampling is remarkably small and well within the range of agreement. Specifically, for both subject X and subject Y, the disclosed device was able to accurately estimate blood hemoglobin levels. The calculated values ​​of 13.69 (grams / 100 ml) (for subject X) and 14.53 (grams / 100 ml) (for subject Y) are close to the values ​​measured using conventional blood sampling, 13.90 (grams / 100 ml) and 14.8 (grams / 100 ml), respectively. In both instances, the difference between the device-calculated hemoglobin values ​​and those measured using conventional blood sampling was approximately 0.2 to 0.3 (grams / 100 ml). This difference is small and significantly smaller than that of currently available noninvasive devices approved by the U.S. Food and Drug Administration (FDA).

[0069] As a further example, multiple measurements were taken from a number of subjects with different skin tones using a device of the present disclosure placed on the back of each wrist, and R values ​​and average values ​​were calculated for each individual based on the data in Tables 2 and 3.

[0070] The mean R values ​​were then plotted on the Y-axis, and the corresponding skin color (category VLS scale of 1-36) was plotted on the X-axis. These results are shown in Figure 12. For light-skinned subjects (VLS20), the mean R value was 19.5. For moderately dark-skinned subjects (VLS24), the mean R value was 18.35. For very dark-skinned subjects (VLS30), the R value decreased even further (mean value 11.73). The data demonstrate a relatively consistent, approximately linear, inverse relationship between VLS scale and R value. These findings confirm that R values ​​are significantly lower (approximately 5-10) for subjects with high VLS scales compared to subjects with low VLS scales (around 35-40). [Example]

[0071] In this example, the patient enters a clinical setting. The operator then places the probe 2 on a part of the patient, for example on the patient's wrist.

[0072] The one or more sensors 24 detect reflected light at, in this example, 525 nm and 545 nm, allowing the processor 4 to determine the ratio of both E1 and E2. The processor 4 does this by determining the ratio of the returned light detected by the one or more sensors compared to the emitted light from the plurality of light emitting diodes 22 at each wavelength.

[0073] Processor 4 then outputs the two ratios (E1) and (E2). Processor 4 can then add those values ​​((E1) + (E2)) (or the user may manually add these ratios) to determine a total E value. The VLS scale value is then determined in one of two ways:

[0074] The first method is for the user to estimate the value by visual inspection and assigning the patient a score of 1 to 36 on the VLS scale. In this first option, the operator can manually select the R value corresponding to the selected score (displayed in a provided chart containing all VLS scale scores and their corresponding R values). The operator may then manually divide the R value by the E value.

[0075] A second method is to configure probe 2 to include an optical sensor (one or more sensors 24, or additional sensors) capable of receiving a signal, and processor 4 can automatically assign the patient to a VLS scale (and corresponding R value) based on the signal. These VLS scale values ​​and R value are stored in electronic storage device 10. Processor 4 then determines the total hemoglobin value by dividing the R value by the resulting E value. [Example]

[0076] In addition to the total hemoglobin values ​​described in Example 1 above, the disclosed device can measure the ratio of oxyhemoglobin (O-Hb) to deoxyhemoglobin (d-Hb) and the change in ratio, as described in this example.

[0077] In this example, a patient enters a clinical setting. An operator then places probe 2 on a part of the patient, for example, the patient's wrist. A total hemoglobin value is then obtained, as described in Example 1.

[0078] Furthermore, E1 corresponds to data collected at a wavelength of approximately 525 nm and therefore represents oxyhemoglobin concentration, while E2 corresponds to data collected at approximately the 550 nm level (although in this example, a level of approximately 545 nm can also be used for data collection), and therefore represents deoxyhemoglobin concentration. The ratio of E1 to E2 may be determined once or may be determined sequentially to monitor the patient's condition.

[0079] In this example, the blood hemoglobin level of a patient experiencing an acute asthma attack was measured using the device of the present disclosure. Asthma causes inflammation and constriction of the airways, resulting in a decrease in blood oxygen levels. The patient's VLS skin color scale was 20, and the corresponding R value was 19.5, based on the values ​​shown in Figure 12.

[0080] Initially, the patient experienced shortness of breath and coughing. Measurements obtained using the disclosed device are shown immediately after symptom onset, i.e., at 2 minutes (Table 5). The patient continued to be observed and treated with medications to alleviate the cough and shortness of breath. However, the patient's condition worsened. Another series of measurements was obtained using the disclosed device at 21 minutes. The patient was then treated with a supplemental oxygen face mask. The patient's condition improved, and a series of observations was repeated using the disclosed device approximately 20 minutes after oxygen therapy (at 40 minutes).

[0081] [Table 5]

[0082] The ratio of E1 divided by E2 was obtained by Processor 4 at each time point. As can be seen in Table 5, as the patient's clinical condition worsened, the ratio increased from 1.038 to 1.109. After treatment with supplemental oxygen, the patient's condition improved and the E1 / E2 ratio decreased to 0.988. These results are shown in Figure 13.

[0083] Specifically, in Figure 13, the E1 / E2 ratio measured using the device of the present disclosure is plotted on the Y-axis, with the corresponding time point (in minutes) plotted on the X-axis. At onset, the patient was hypoxic (low oxygen content) with an E1 / E2 ratio of 1.038. Twenty minutes later, the patient's condition and hypoxia worsened, with a corresponding increase in the ratio to 1.109. The patient was then treated with supplemental oxygen. The patient's hypoxia improved, correlating with a ratio of 0.988.

[0084] As can be seen in Figure 13, as the E1 / E2 ratio increases, blood oxygen saturation (an index of oxyhemoglobin) decreases. Because E and H are inversely proportional, as previously discussed (Figure 6), the E1 / E2 ratio is expected to be inversely proportional to the relative concentration of oxyhemoglobin (O-Hb). Oxyhemoglobin is a form of hemoglobin attached to oxygen molecules and affects oxygen delivery to tissues.

[0085] The E1 / E2 ratio thus provides a tool for monitoring a patient's clinical status without the need for invasive arterial blood gas sampling. The ratio may be calculated by a user at the bedside, or processor 4 may determine the ratio. Currently available noninvasive methods for measuring blood oxygen saturation (pulse oximetry) have limitations in dark-skinned subjects and in hypoperfusion states such as shock. The device of the present disclosure does not have these limitations.

[0086] Because the relative ratio of oxyhemoglobin to deoxyhemoglobin varies from person to person, the absolute value of the E1 / E2 ratio varies from person to person. However, the E1 / E2 ratio is subject-specific and can be measured continuously as a noninvasive means of oxyhemoglobin monitoring, which can significantly reduce the need for invasive blood sampling.

[0087] The embodiments and examples described in this disclosure are intended to be illustrative rather than limiting, and are not intended to represent all embodiments or examples of the present disclosure. While essential novel features of the present disclosure as applied to various specific embodiments thereof have been shown, described, and pointed out, it will be understood that various omissions, substitutions, and changes in the form and details of the illustrated apparatus, and their operation, may be made by those skilled in the art without departing from the spirit of the present disclosure. For example, all combinations of these elements and / or method steps that perform substantially the same function in substantially the same way to achieve the same results are expressly intended to be within the scope of the present disclosure. Furthermore, it will be understood that structures and / or elements and / or method steps shown and / or described in connection with any disclosed form or embodiment of the present disclosure may be incorporated into any other disclosed or described or proposed form or embodiment as a matter of general design choice. Moreover, various modifications and variations may be made without departing from the spirit or scope of the disclosure, both literally and by the doctrine of equivalents recognized in law, as set forth in the following claims.

Claims

1. a plurality of light emitting diodes configured to emit light at two or more wavelengths toward the surface of the mammalian skin; one or more sensors configured to detect reflected light; a processor, the reflected light is the emitted light that passes through at least a portion of the skin of the mammal and is at least partially reflected towards the one or more sensors; The processor: receiving the detected reflected light; determining a first ratio of reflected light that is a percentage of emitted light in the range of 515 nm to 535 nm to reflected light in the range of 515 nm to 535 nm; determining a second ratio of reflected light that is a percentage of emitted light in the range of 540 nm to 560 nm to reflected light in the range of 540 nm to 560 nm; determining a total ratio by adding the first ratio of reflected light to the second ratio of reflected light; The apparatus is configured to determine a total hemoglobin value by dividing the melanin content R value by the total ratio.

2. the first ratio of reflected light is a percentage of emitted light in the range of 520 nm to 530 nm to reflected light in the range of 520 nm to 530 nm; 10. The apparatus of claim 1, wherein the second ratio of reflected light is a percentage of emitted light in the range of 540 nm to 550 nm to reflected light in the range of 540 nm to 550 nm.

3. the first ratio of reflected light is a percentage of emitted light in the 525 nm range to reflected light in the 525 nm range; 10. The apparatus of claim 1, wherein the second ratio of reflected light is a percentage of emitted light in the 545 nm range to reflected light in the 545 nm range.

4. The apparatus of claim 1 , wherein the processor is configured to output one or more levels to a display configured to display text and / or images of the one or more levels.

5. The device of claim 4 , wherein the display is configured to receive touch input.

6. 10. The device of claim 1, wherein the melanin content R value is based on a correlation between a Felix Von Luschan (VLS) skin color scale value and the melanin content R value.

7. 7. The apparatus of claim 6, wherein the VLS skin color scale values ​​are determined visually by an operator.

8. 7. The apparatus of claim 6, further comprising an optical sensor configured to detect a color signal of a skin surface of the mammal, and wherein the processor is configured to automatically assign the melanin content R value to the mammal based on the color signal.

9. 7. The device of claim 6, further comprising an electronic memory device configured to store the VLS skin color scale values ​​and associated melanin content R values.

10. 10. The apparatus of claim 1, wherein the processor is further configured to output a ratio of oxyhemoglobin to deoxyhemoglobin (E1 / E2 ratio).

11. 1. A method for determining hemoglobin levels in a mammal, comprising: The method comprises: contacting the skin of the mammal with a device; and outputting the total hemoglobin value; The device comprises: a plurality of light emitting diodes configured to emit light at two or more wavelengths toward a surface of the mammalian skin; one or more sensors configured to detect reflected light; a processor, the reflected light is the emitted light that passes through at least a portion of the skin of the mammal and is at least partially reflected towards the one or more sensors; The processor: receiving the detected reflected light; determining a first ratio of reflected light that is a percentage of emitted light in the range of 515 nm to 535 nm to reflected light in the range of 515 nm to 535 nm; determining a second ratio of reflected light that is a percentage of emitted light in the range of 540 nm to 560 nm to reflected light in the range of 540 nm to 560 nm; determining a total ratio by adding the first ratio of reflected light to the second ratio of reflected light; determining said total hemoglobin value by dividing said melanin content R value by said total ratio.

12. The method of claim 11 , wherein the output is received by a display configured to display one or more levels of text and / or images.

13. The method of claim 12 , wherein the display is configured to receive touch input.

14. 12. The method of claim 11, wherein the melanin content R-value is based on a correlation between Felix Von Luschan (VLS) skin color scale values ​​and the melanin content R-value.

15. the processor is further configured to determine a ratio of oxyhemoglobin to deoxyhemoglobin (E1 / E2 ratio); 12. The method of claim 11, wherein the method further comprises outputting a ratio of oxyhemoglobin to deoxyhemoglobin (E1 / E2 ratio).

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