A wearable device using spatially scanned induced Raman spectroscopy for reliable detection of blood sample concentration

Abstract

The present disclosure provides methods, systems, and devices for non-invasively measuring a level of an analyte in a user using stimulated Raman scattering. The device may include a Raman pump light source that emits pump light at a pump wavelength toward the tissue, and a Stokes light source that emits Stokes light at one or more Stokes wavelengths toward the tissue. The device may further include one or more mirrors and lenses. The device may further include a beam controller that controls the one or more mirrors and the one or more lenses to target the pump light emitted by the Raman pump light source and the Stokes light emitted by the Stokes light source to an optimal target position. The device may further include a photodetector that measures light emanating from the tissue. The device may further include a processor that estimates a level of the analyte in the user.

Description

Technical Field

[0001] Field The present disclosure generally relates to non-invasive monitoring of molecules in a user's body.

Background Art

[0002] Background There are many human medical conditions that can give rise to the need to measure the amount of certain molecules present in an individual. For example, currently, it is estimated that approximately 463 million adults have diabetes. For many of these individuals, regular monitoring of the amount of glucose present in the bloodstream is part of everyday life in order to avoid serious medical complications. Conventionally, invasive measurement methods (e.g., sample tissue extraction or blood sampling, etc.) have been used to measure the chemical composition inside a user's body. Exemplary techniques include fingerstick blood glucose measurement and continuous glucose monitoring (CGM). These systems are often painful and / or expensive to use. For users who must undergo such measurements repeatedly, the pain and expense associated with glucose monitoring can significantly impact the quality of life.

Summary of the Invention

Means for Solving the Problems

[0003] Summary Aspects and advantages of embodiments of the present disclosure may be shown in part in the following description, may be learned from the description, or may be learned through the practice of the embodiments.

[0004] One exemplary embodiment includes an apparatus for non-invasively measuring the level of an analyte within a user using stimulated Raman scattering. The apparatus can include a Raman pump light source that emits pump light towards the user's tissue at a pump wavelength. The apparatus further includes a Stokes light source that emits Stokes light towards the tissue at one or more Stokes wavelengths. The apparatus further includes one or more mirrors. The apparatus further includes one or more lenses. The apparatus further includes a beam controller that controls the one or more mirrors and the one or more lenses to direct the target of the pump light emitted by the Raman pump light source and the Stokes light emitted by the Stokes light source to an optimal target position. The apparatus further includes a photodetector that measures the light emitted from the tissue. The apparatus further includes a processor that processes the measured light and provides an estimated analyte level of the analyte within the user.

[0005] Another exemplary aspect of the present disclosure is a computer-implemented method for non-invasively measuring the level of an analyte within a user using stimulated Raman scattering. The method includes emitting, by a Raman pump light source, pump light towards the user's tissue at a pump wavelength. The method further includes emitting, by a Stokes light source, Stokes light towards the tissue at one or more Stokes wavelengths. The method further includes controlling, by a beam controller, one or more mirrors and one or more lenses to direct the target of the pump light emitted by the Raman pump light source and the Stokes light emitted by the Stokes light source to an optimal target position. The method further includes measuring, by a photodetector, the light emitted from the tissue. The method further includes processing, by a processor, the measured light and providing an estimated analyte level of the analyte within the user.

[0006] Another exemplary aspect of the present disclosure is a sample estimation system. The system includes a Raman pump light source that emits pump light toward a user's tissue at a pump wavelength. The system further includes a Stokes light source that emits Stokes light toward the tissue at one or more Stokes wavelengths. The system further includes one or more mirrors and one or more lenses. The system further includes a beam controller that controls the one or more mirrors and the one or more lenses to direct the target of the pump light emitted by the Raman pump light source and the Stokes light emitted by the Stokes light source to an optimal target position. The system further includes a photodetector that measures light emitted from the tissue. The system further includes a processor that processes the measured light and provides an estimated sample level of a sample within the user.

[0007] Other exemplary aspects of the present disclosure relate to systems, apparatuses, computer program products (such as tangible non-transitory computer-readable media, but also software that can be downloaded through a communication network without necessarily being stored in a non-transitory format), user interfaces, memory devices, and electronic devices for measuring stimulated Raman scattering using an embedded computing system.

[0008] These and other features, aspects, and advantages of the various embodiments will be better understood with reference to the following description and the appended claims. The accompanying drawings, which are incorporated herein and constitute a part of this specification, illustrate embodiments of the present disclosure and, together with the description, serve to explain the relevant principles.

[0009] A detailed description of embodiments directed to those skilled in the art is shown herein with reference to the accompanying drawings.

Brief Description of the Drawings

[0010]

Figure 1

Figure 2A

Figure 2B

Figure 2C

Figure 2D

Figure 2E

Figure 3

Figure 4A

Figure 4B

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9A

Figure 9B

Figure 10A

Figure 10B

Figure 10C

Figure 10D

Figure 11

Figure 12A

Figure 12B

Figure 13

Figure 14

Figure 15

Figure 16

Figure 17

Figure 18

Figure 19

Figure 20

Figure 20

Figure 21

Figure 22

Figure 23

Figure 24

Figure 25

Figure 26

Figure 27

Figure 28

[0011] DETAILED DESCRIPTION Here, embodiments are referred to in detail, one or more examples of which are shown in the figures. Each example is provided by way of explanation of the embodiments, and not a limitation of the present disclosure. In fact, it will be apparent to those skilled in the art that various modifications and changes can be made to the embodiments without departing from the scope or spirit of the present disclosure. For example, features illustrated or described as part of one embodiment can be used with another embodiment and can result in yet another embodiment. Accordingly, aspects of the present disclosure are intended to cover such modifications and changes.

[0012] Generally, the present disclosure relates to a system for improving the performance of a specimen measurement system that non-invasively monitors one or more specimens within a user's body. For example, a specimen measurement system for monitoring a specimen according to an exemplary embodiment can use Raman spectroscopy to estimate the amount of a specimen within a target substance (e.g., a user's tissue) by projecting light onto the target substance and measuring the wavelength and intensity of the light emitted from the substance. To ensure that the power density of the light is high enough to produce measurable Raman scattering, the targeted area of the light projected can be made extremely small (e.g., about 1 micrometer in diameter). As a result, small variations in a particular area of the tissue targeted by the light source can significantly affect the ability of the specimen measurement system to accurately measure the amount of the specimen present. This is because the tissue type (also referred to herein as the tissue composition) can vary significantly. As a result, the specimen measurement system can identify the optimal target location within the user's tissue and then control the targeting of the light source to focus on the optimal target location (e.g., by one or more mirrors and one or more lenses). Accurately targeting the portion of the tissue within the user's skin can result in improved accuracy and efficiency in measuring the specimen within the target substance.

[0013] Accordingly, the sample measurement system can be improved by using one or more mirrors and one or more lenses to control one or more beams projected by a pump light source and one or more Stokes light sources so as to specifically target an optimal target position within the user's tissue. To do so, the sample measurement system can include a beam controller that controls the area targeted by the light source (e.g., by controlling one or more mirrors and one or more lenses).

[0014] To identify an optimal target position within the user's tissue, the sample detection system can perform a sparse sampling of the area of the tissue that the sample measurement system can access. For example, the target position may have a diameter of 1 micrometer to achieve a desired optical density. To identify the optimal target position, the system may sample 1-micrometer areas over an area spanning 200 micrometers × 200 micrometers to identify the optimal target position for measurement. The optimal target position may be the position of the tissue that exhibits a measurement response that enables the identification of a particular sample. The various areas sampled within the sampling area can be compared to identify the area that exhibits the best response characteristics. In some examples, the optimal target position may depend on the particular sample that the system is trying to detect. Accordingly, the system can store data related to the optimal type of tissue for each potential sample. For example, if the target sample is glucose, the optimal type of tissue may be inside a blood vessel. The system may compare the measurement responses of different areas in the sampling area to identify the internal blood vessel area. In other examples, the optimal type of tissue can vary.

[0015] The optimal target location may be a location that provides an accurate measurement of the presence of a particular analyte. The system can store an identification of the tissue type that results in the most accurate measurement of the presence of a particular analyte in the user's tissue. This data can be stored in a database accessible to the analyte measurement system. The analyte measurement system can compare the data in the database to the type of tissue determined when the system performs sparse sampling. In some examples, factors other than tissue type can be used to determine the optimal target location. For example, the depth within the tissue at a particular location can be used when determining the optimal target location. For example, if two locations have the same tissue type, the analyte measurement system can select the location with a smaller depth within the user's tissue.

[0016] Sparse sampling can be achieved by defining an area that can be targeted by the analyte measurement system and determining a plurality of points arranged in a three-dimensional grid to cover this area. The three-dimensional grid (or target sampling grid) can include points at different positions relative to the surface of the skin (along the x-axis and y-axis) and at different depths within the skin (along the z-axis). For each point in the target sampling grid, the analyte detection system can use a beam controller to project light onto each point. The analyte detection system can measure the absorption of light at each point.

[0017] In some examples, the size of the central grid can be determined by the characteristics of the laser, mirrors, and lenses that can be controlled to define the target of the laser. For example, the target sampling grid can be 200 micrometers by 200 micrometers. The specimen measurement system can place sampling points at intervals of 5 micrometers along the surface of the target sampling grid in two dimensions. In addition, the specimen measurement system can sample at different depths within the tissue. For example, the target sampling grid can include three depth layers, each layer being 5 micrometers deeper than the other layers, with the first layer on the surface, the second layer at a depth of 5 micrometers within the tissue, and the third layer at a depth of 10 micrometers within the tissue. Other dimensions of the target sampling grid and the depth of target sampling can be used.

[0018] To determine the type of substance in the sampled tissue, absorption of light at different wavelengths can be used. For example, different substances can absorb light at different wavelengths and can emit light at different wavelengths. The amount and intensity of the light emitted from the tissue can be measured and compared with the amount and intensity of the light wavelengths transmitted into the light, thereby determining the amount of different laboratory lengths absorbed.

[0019] By comparing the absorption at different wavelengths and comparing it with the tissue type wavelength absorption data, the specimen measurement system can estimate the type of tissue at that location. For example, the location can be one or more of interstitial fluid, cells associated with the epidermis, cells associated with the dermis, adipocytes, glands, nerve cells, blood vessels, follicles, etc. The specimen estimation system can use the same light source and photodetector used during specimen detection to perform sparse sampling. However, the amount and intensity of the light used can be reduced during the sparse sampling process. Thus, the specimen estimation system can use less power and can quickly identify the type of tissue at multiple points within a specific region.

[0020] In some examples, the type of tissue at a particular location can affect the accuracy of the sample measurement system. Thus, the sample measurement system can select a particular location having a tissue type that most contributes to accurately measuring the subject sample, based on sparse scanning. The selected location can be stored as an optimal target location for measuring the sample. The sample measurement system can use a beam controller to focus beams from one or more light sources (e.g., a Raman pump light source and one or more Stokes light sources) to the optimal target location. A photodetector can measure the light emitted from the target location. Based on the emitted light, the sample measurement system can determine the amount of a particular sample in the user's body.

[0021] More generally, Raman spectroscopy uses Raman scattering to determine whether a sample is present in a particular target substance (e.g., the user's tissue). Raman scattering is an optical process in which an excitation light can be projected onto a target sample by a light source (e.g., a pump laser). The incident excitation light can excite molecules in the target sample to a higher energy state. The excited molecules emit photons, thereby reducing the energy of the molecules to a lower energy level. In some examples, the higher energy state can be a virtual excitation state such that the molecule is not actually excited to that state. Instead, both excitation and relaxation (when the photon is emitted) occur simultaneously through the virtual state.

[0022] The particular wavelength present in the photons generated by Raman scattering can be determined by the vibrational modes of the chemical bonds of the molecules excited by the excitation light and the wavelength of the incident light. A system that uses Raman scattering to determine the presence of a sample can perform either spontaneous Raman scattering or stimulated Raman scattering. Note that other types of Raman scattering can be used to implement the systems and methods described herein.

[0023] The analyte detection system can be included in a computing device and can be used to identify the amount and / or density of a specific analyte within a user's tissue. In some examples, the analyte detection system can be integrated into a wearable computing device. Such wearable computing devices can include smartwatches, fitness bands, or any other type of wearable computing device. In some examples, the wearable computing device can be worn such that the analyte detection system can be placed directly against the user's skin. In this way, the analyte detection system can measure the analyte unobtrusively without any special action being taken by the user.

[0024] The analyte detection system can include a Raman pump light source that projects light at a specific wavelength (e.g., 850 nanometers). A detector can measure the light reflected at the wavelength of the Raman pump light source. This can be light that has the same wavelength as the light generated by the pump laser and has not been Raman scattered. The peak detected at the wavelength (e.g., 850 nanometers) emitted by the Raman pump light source can be called the Rayleigh peak. Rayleigh scattering can refer to light emitted by the target sample and having the same wavelength as the pump light. Rayleigh scattering is much more common than Raman scattering, and thus the intensity of the light at the Rayleigh peak can be higher than the intensity measured for the light that is the result of Raman scattering.

[0025] The Raman scattered light can be detected at one or more specific wavelengths (depending on the specific analyte being measured) or within a predetermined wavelength range. This light is the result of spontaneous Raman scattering where the light emitted by the target substance has a different wavelength from the light generated by the pump laser. The range of wavelengths generated by Raman scattering by a specific molecule can be called the Stokes range for that molecule for emitted photons having a higher wavelength than the originally projected photons, or the anti-Stokes range for photons having a lower wavelength than the originally projected photons.

[0026] To increase the amount of Raman-scattered light, one or more Stokes lasers can be included in the analyte detection system and can project light onto the target substance. In some examples, the Stokes light source can provide light over a wavelength range associated with the analyte. The Stokes light source can be a broadband light source that provides light at all wavelengths within the wavelength range. As a result of the presence of one or more Stokes light sources, the Raman response can be significantly higher. As a result, the presence of the analyte can be more easily identified.

[0027] An important factor in determining the amount of Raman scattered light that is generated (and thus more easily detected) is the power density of the light projected onto the area of the target tissue. Thus, the light from the light source can be focused onto a relatively small area of the user's tissue (to increase the power density in that small area). For example, the target area can have a diameter of about 1 micrometer. When the light is focused onto a small area within the tissue, the type of tissue at that location can significantly affect the effectiveness of the system in identifying the presence, amount, and / or density of the analyte.

[0028] Accordingly, the specimen detection system can identify tissue types at various different positions within a possible target zone. Thus, the specimen detection system can identify a specific position having an optimal tissue type for detecting a specific specimen. To do so, the specimen detection system can perform a sparse sampling process. To perform the sparse sampling process, the specimen detection system can determine a three-dimensional region that can be targeted by one or more light sources (e.g., a Raman pump light source and one or more Stokes light sources). The three-dimensional region that can be targeted can be based on a control mechanism available to the beam controller. For example, one or more mirrors can be included in or accessible to the specimen detection system. The one or more mirrors can be tilted so that the target of the light generated by the one or more light sources can be defined at different points along the surface of the user's tissue. The total possible target range can be the boundary of the region that can be targeted.

[0029] In addition, it can include one or more lenses that can be adjusted to control the depth of focus of the light source. The one or more lenses can be moved closer to or farther from each other, thereby adjusting the depth at which the light is focused. In some examples, one or more of the lenses are fixed and one or more can be moved up and down by rotation of a screw. In some examples, the adjustable lens is circular and rotating the lens does not affect the light as it passes through. The extent to which the lens can adjust the depth of focus of the light source can determine the depth of the region that can be targeted (e.g., the z-axis of the region).

[0030] A target sampling grid of points can be generated to cover the entire area where the target can be defined at a specific density. In some examples, a higher density of points can be used to obtain a higher resolution of the type of tissue in the area. However, increasing the number of points can result in an increase in time and power used.

[0031] Once the target sampling grid of points is established, the specimen detection system can emit light (e.g., Raman pump light and / or Stokes light) from one or more light sources at each grid position. In some examples, when used to determine the type of tissue at a specific location, the light source operates at a lower power and for a shorter amount of time than when used to perform specimen detection. Thus, the time and power used to identify the type of tissue at each point within the sparse sampling grid can be reduced. In some examples, the specimen detection system can sequentially project light at each point in the grid of points. To do so, the beam controller can adjust one or more light sources to target each point. One or more of the Raman pump light source and one or more Stokes light sources can be activated to emit light at each point. The photodetector can then determine the frequencies absorbed by each point based on the frequency of the detected light. Any frequency of the projected light that is not detected by the photodetector can be determined to be absorbed. Similarly, if the intensity of the light at one or more specific frequencies is reduced relative to other frequencies, the system can determine that the light at these frequencies is at least partially absorbed. This process can then be repeated for each point in the target sampling grid of points.

[0032] The specimen detection system can detect the light absorbed by each point. As described above, the photodetector can detect the light emitted from the tissue and determine which wavelength has been absorbed. In some examples, the wavelengths determined to be absorbed at each point in the target sampling grid can be analyzed. Different types of tissue can absorb light at different frequencies. As a result, the wavelength at which the light is absorbed can be used to estimate the type of tissue at each respective point of the target sampling grid. The specimen detection system can store the type of tissue estimated for each point in the target sampling grid. In some examples, each time the specimen detection system detects a specimen in the user's tissue, a new sparse sampling of the target area can be performed.

[0033] In other examples, the specimen detection system can store tissue type data for future use. In this way, a map of the type of the user's tissue can be generated. In some examples, when a map of the type of the user's body is generated, the specimen detection system can scan fewer points within the target sampling grid and use that data to accurately determine which parts of the user's tissue are currently within the target area. Thus, if the specimen detection system is included in a user computing device such as a fitness band or smartwatch, a small change in the position of the user computing device does not result in the need for a new scan of all points. Instead, a reduced number of point scans can enable the specimen detection system to determine the current position of the user computing device from a relatively small number of possible positions that have already been sufficiently mapped.

[0034] In some examples, the user computing device can include an accelerometer for measuring the movement of the user computing device in an absolute sense and with respect to the user's body. In this way, the user computing device can determine whether to perform a new scan (if a significant movement of the user's body has occurred).

[0035] In some examples, the specimen detection system can select one point from a plurality of points within the target sampling grid as the optimal target position. In some examples, the optimal target position can be selected based on the type of tissue at that position and / or the specific specimen being detected. Thus, some specimens are more easily detected in blood vessels or interstitial fluid.

[0036] Once the optimal target position is determined, the beam controller can direct the targets of the light sources (e.g., a Raman pump light source and one or more Stokes light sources) to the optimal target position. The specimen detection system can measure the light emitted by the tissue and detect the presence of one or more specimens as described above.

[0037] Embodiments of the disclosed technology provide many technical effects and benefits, particularly in the field of detecting specimens in target substances. In particular, embodiments of the disclosed technology provide an improved technique for detecting specimens in a user's tissue. For example, one particular technical problem that occurs in the field of specimen detection is that in some types of tissue, detection is more easily achieved than in other types. When the light source focuses on a very small area of the tissue, focusing on a tissue type that is not optimal for detecting the specimen can potentially fail to accurately detect the specimen. To solve this problem, the disclosed technology describes using an initial scan to determine the type of tissue at a plurality of different points and select the appropriate type of point. Doing so increases the accuracy and effectiveness of the specimen estimation system while reducing the total power consumption. Reducing the power consumption while increasing the accuracy and effectiveness of the system results in significant benefits for the user.

[0038] Referring to the drawings, exemplary embodiments of the present disclosure will be described in more detail. FIG. 1 shows an exemplary analyte estimation system for non-invasively scanning an area of a user's arm, according to an exemplary embodiment of the present disclosure. In this example, the analyte measurement system can measure analytes in the tissue of the user's arm 130. One or more light sources 134 of the analyte measurement system can project light onto any portion of the scanning area 132 of the user's arm.

[0039] The analyte measurement system can first determine an optimal target position for the projected light within the scanning area 132 onto which the light can be projected. To determine which specific area of the total area 132 one or more light sources 134 should target, the analyte measurement system can first sample the total area 132. To do so, one or more light sources 134 can target at a series of positions, for example, the positions can include 140-1, 140-2, and 140-3. Although many additional positions are shown, they are not labeled for ease of explanation. One or more light sources 134 can first target target 142-1 at the first position 140-1. One or more light sources 134 can then target target 142-2 at the second position 140-2. One or more light sources 134 can then target target 142-3 at the second position 140-3. One or more light sources 134 can continue to target at each position within the grid. For each position, one or more light sources 134 can project light at that position. A photodetector can then measure the amount, wavelength, and intensity of the light radiated from the target position. By comparing the wavelength and intensity of the radiated light, the analyte detection system can determine the light absorption characteristics of the target position.

[0040] FIG. 2A shows a graph of the wavelength 162 and intensity 160 of light resulting from spontaneous Raman scattering when light is projected onto a target substance. In this example, the pump laser 112 can project light at a specific wavelength (e.g., 850 nanometers). As seen in the exemplary graph, light having a high intensity is measured at the wavelength of the pump laser 112. This represents light that is not Raman scattered and instead has the same wavelength as the light generated by the pump laser 112. The peak detected at the specific wavelength (e.g., 850 nanometers) emitted by the Raman pump light source can be referred to as the Rayleigh peak. Rayleigh scattering can refer to light emitted by the target sample and having the same wavelength as the pump light. Rayleigh scattering is much more common than Raman scattering, and thus the intensity of the light at the Rayleigh peak can be higher than the intensity measured for the light that is the result of Raman scattering.

[0041] In this particular example, the Raman scattered light is detected at wavelengths between approximately 900 nanometers and 1000 nanometers. However, depending on the particular specimen being measured, other ranges of wavelengths can be measured. This light is the result of spontaneous Raman scattering where the light emitted by the target substance has a different wavelength than the light generated by the pump laser 112. The range of wavelengths generated by Raman scattering by a particular molecule can be referred to as the Stokes range for that molecule for emitted photons having a higher wavelength than the initially projected photons, or the anti-Stokes range for photons having a lower wavelength than the initially projected photons. Certain features of the detected Stokes range, including but not limited to the wavelengths at which peak intensities are measured, can be analyzed to generate a Raman signature for the molecule. The Raman signature can represent certain features (e.g., peaks) of the detected Stokes range associated with a particular molecule. In this way, the Raman signature can enable the identification of this particular molecule by analyzing the Stokes range that occurs when the particular molecule is present in the target substance. The anti-Stokes range, which can occur on the other side of the Rayleigh peak and represents Raman scattering where the emitted light has a lower wavelength than the light generated by the pump laser 112, is not shown. Much of the present disclosure is explained from the perspective of the Stokes range, but it will be understood that the disclosed concepts can be utilized with wavelengths within the anti-Stokes range as well.

[0042] In FIG. 2A, three peaks (166, 168, and 170) are present in the Stokes range. Using this information, and other information about the Stokes range, it is possible to determine whether a particular specimen is present in the target substance and at what concentration. However, the amount of Raman scattering that occurs with spontaneous Raman scattering is extremely low. As a result, the information needed to identify the molecule by the corresponding Stokes range or Raman signature can be difficult to detect.

[0043] Figure 2B shows a graph of the wavelength 162 and intensity 160 of light resulting from stimulated Raman scattering when light is projected onto a target substance. In addition to the pump laser 112, one or more Stokes lasers 116 can project light onto the target substance. In some examples, the Stokes light source 116 can provide light over a wavelength range associated with the analyte. Conventionally, the Stokes light source can be an LED that provides broadband light at all wavelengths within the wavelength range when the LED is turned on.

[0044] As a result of the Stokes laser 116, the Raman response becomes significantly higher. As a result, the Stokes range of the molecules, and thus the Raman signature, can be more easily detected, and the analyte can be more easily identified.

[0045] Figure 2C shows an exemplary analyte estimation system for non-invasively measuring an analyte on a user's arm according to an exemplary embodiment of the present disclosure. A pump laser 188 (e.g., a first light source) can project light onto a target substance 180. In this example, the target substance 180 is the skin and other tissues of the user's arm. The projected light can be generated by the pump laser 188 at a first wavelength. The analyte estimation system can also include one or more Stokes lasers 189. To facilitate stimulated Raman scattering, one or more Stokes lasers 189 can be configured to generate light at a wavelength associated with the Raman signature of the target analyte. The pump laser 188 and one or more Stokes lasers 189 can be vertical-cavity surface-emitting lasers (VCSELs) and can be integrated onto a printed circuit board (PCB) 184.

[0046] One or more Stokes lasers 189 can be narrowband light sources. The pump laser 188 can also be a narrowband light source in some examples. As used herein, a narrowband light source can project light such that photons have wavelengths that fall within a narrow wavelength range relative to a relevant wavelength range (e.g., the Stokes range) associated with Raman scattered radiation for a subject sample. In some examples, a narrowband light source can be defined based on the proportion of its wavelength range that occurs at a particular time. For example, a narrowband laser can generate light that is within a bandwidth of 10% of the total wavelength range that the laser can project. For example, if a particular Stokes laser 189 is adjustable to generate light in the range of 500 nanometers to 1500 nanometers, the narrowband laser can project light such that the wavelength of each photon falls within a 100-nanometer range (e.g., 10% of the total range of the laser). In another example, a narrowband laser can be defined as a laser that projects light having a wavelength bandwidth of 1% of the total wavelength range of the laser. According to this definition, a narrowband laser can generate light that falls within a 10-nanometer range (e.g., such that all projected light has a wavelength within 5 nanometers of the target wavelength).

[0047] In some examples, the Stokes laser 189 can be a single wavelength tunable laser that can sweep a narrowband laser over a range of wavelengths that a wavelength tunable laser can generate. In some examples, the wavelength tunable laser can sweep over wavelengths within the Stokes range of the target sample. In another example, the Stokes laser 189 can include a plurality of laser diodes, each of which generates narrowband light centered around a wavelength within the Stokes range of the target sample.

[0048] In some examples, a narrowband VCSEL light source can be adjustable over a relatively small range (e.g., about a 5 nm range) using temperature and current. Thus, the narrowband VSCEL light source can obtain a larger range without the extra components typically included in wavelength-variable lasers, such as additional mechanical components (e.g., MEMS mirrors) integrated into the chip to allow for greater wavelength variability.

[0049] In some examples, other configurations can be used. For example, the analyte estimation system can include two or more pump lasers combined with a wavelength-variable Stokes laser. Thus, the analyte estimation system can include two pump lasers 188 separated by 20 nm and a single wavelength-variable Stokes laser 189 adjustable over a 20 nm range, resulting in a total possible Raman shift range of 40 nm. Additionally, or alternatively, with three pump lasers separated by 20 nm, the range can be tripled. Additionally, or alternatively, one or more fixed-wavelength Stokes lasers 189 and wavelength-variable pump lasers 188.

[0050] The light projected by the pump laser 188 can excite one or more molecules within the target substance 180 (e.g., electrons within the molecule can be raised to a higher energy level). The molecule can return to a lower energy level and emit one or more photons. The photodetector 182 can detect the light emitted from the target substance 180. The detected light can be represented as a graph of the intensity of light at various wavelengths.

[0051] The detected light can form a Stokes range for molecules excited by the incident light. The spectral intensity at wavelengths across the Stokes range for a particular analyte can form a particular Raman signature. In some examples, the Raman signature can be associated with a particular pattern based on the wavelength at which a peak is detected, the spacing between peaks, and / or the intensity of the light detected at one or more wavelengths. The features detected in the Stokes range can be compared to a predetermined Raman signature to determine one or more analytes present in the target substance.

[0052] Data representing the Stokes range can include information representing the amount or intensity of light at each wavelength within the range of wavelengths included in the Stokes range. The data representing the Stokes range can be analyzed to determine one or more features, including the peak wavelength (e.g., the wavelength at which the measured intensity is higher than other nearby wavelengths), the trough, the distance between peaks, the distance between each peak wavelength, and the wavelength of the pump laser.

[0053] FIG. 2D shows an exemplary analyte estimation system comprising a plurality of laser diodes that generate light at one or more specific wavelengths within the Stokes range, according to an exemplary embodiment of the present disclosure. As in FIG. 1C, a pump laser 188 projects light onto the target substance. The plurality of Stokes lasers (189-1, 189-2, and 189-3) can project narrowband light having a center wavelength different from the center wavelength of the pump laser 188 onto the target substance 180. A photodetector 182 can be arranged to measure the light emitted by the analyte within the target substance 180.

[0054] Stokes lasers 189 can each generate narrow-band light for different wavelengths within the Stokes range (e.g., the light generated by a Stokes laser can fall within a specific wavelength band that can be expressed as a percentage of the total wavelength range of the Stokes laser or as a specific number of wavelengths within 1 nanometer of a target wavelength). In one exemplary embodiment, the pump laser (e.g., the first light source) and the Stokes lasers (e.g., one or more second light sources) are VCSELs each using 40 milliwatts of power. In other examples, different lasers using different amounts of power can be used.

[0055] It should be noted that light can be measured based on its wavenumber rather than its wavelength. The wavenumber can represent the spatial frequency of an electromagnetic wave and can be measured relative to a reference value (e.g., in this case, the light generated by the pump laser can be considered to have a wavenumber of 0, and the light generated by one or more second light sources can be given a wavenumber relative to the wavenumber of the light generated by the pump laser).

[0056] FIG. 2E shows an exemplary analyte estimation system comprising a single wavelength-variable Stokes laser 189 that generates light at different wavelengths within the Stokes range, according to an exemplary embodiment of the present disclosure. As in FIG. 1C, the pump laser 188 can project light onto the target substance. The wavelength-variable Stokes laser 189 can generate light that can project narrow-band light onto the target substance 180, which can be adjusted to any wavelength within the target Stokes range. In some examples, the wavelength-variable laser can start with narrow-band light at the lower end of the Stokes range and adjust the wavelength to sweep along the entire Stokes range at any point without expanding the wavelength of the narrow-band light wave. The photodetector 182 can be arranged to measure the light emitted by the analyte within the target substance 180.

[0057] FIG. 3 shows an exemplary computing environment including a computing device 100 according to an exemplary embodiment of the present disclosure. The computing device 100 can include a sample estimation system for non-invasively determining the presence and amount of one or more samples inside a user. In some examples, the computing device 100 can be a user computing device such as a smartphone or a wearable computing device. In other examples, the computing device 100 can be a computing device not intended for portable use but for home use. In this example, the user computing device 100 can include one or more processors 102, a memory 104, and a sample estimation system 110.

[0058] More specifically, the one or more processors 102 can be any suitable processing device for the computing device 100. For example, such a processor can include one or more of a processor core, a microprocessor, an ASIC, an FPGA, a controller, a microcontroller, etc. The one or more processors can be one processor or multiple processors operably connected. The memory 104 can include one or more non-transitory computer-readable storage media such as RAM, ROM, EEPROM, EPROM, flash memory devices, and combinations thereof.

[0059] In particular, in some devices, the memory 104 can store instructions 108 for implementing the analyte estimation system 110. It will be understood that the term "system" can refer to dedicated hardware, computer logic executed on a more general processor, or a combination thereof. Thus, the system can be implemented in hardware, application-specific circuitry, firmware, and / or software that controls a general-purpose processor. In one embodiment, the system can be implemented as a program code file stored in a storage device, loaded into memory, and executed by a processor, or provided from a computer program product, e.g., computer-executable instructions, stored on a tangible computer-readable storage medium such as RAM, a hard disk, or an optical or magnetic medium.

[0060] The memory 104 can also include data 106 that can be retrieved, manipulated, created, or stored by one or more processors 102. In some exemplary embodiments, such data can be accessed and used as input to the analyte estimation system 110. In some examples, the memory 104 can include data used to execute instructions that describe one or more processes and how these processes can be executed.

[0061] In some examples, the analyte estimation system 110 can include a pump laser 112, one or more Stokes lasers 116, a photodetector 122, and a Raman scattering estimation system 120. Although not shown, the analyte estimation system 110 can also include an optical filter and one or more optical lenses (e.g., microlenses) for focusing the lasers on the same region (e.g., the same part of the user's skin). The pump laser 112 (e.g., a first light source) can be a laser diode that emits light (e.g., a stream of photons) within a narrow wavelength band such that the emitted light has a specific wavelength within a certain range of target wavelengths. In some examples, the pump laser can generate narrowband light having an average wavelength of 780 nanometers. Other wavelengths of the pump laser 112 may be used, and the wavelengths of the one or more Stokes lasers 116 are determined at least in part based on the wavelength of the pump laser 112. In some examples, the pump laser 112 can be a vertical-cavity surface-emitting laser (VCSEL) included in a semiconductor chip. In some examples, the wavelength of the light emitted by the pump laser 112 is 850 nanometers. Other wavelengths can be used.

[0062] The pump laser 112 can include (or be associated with) a modulation system 114. The modulation system 114 can include a waveform generator that can generate a waveform that can be used to modulate the light generated by the pump laser 112. The pump laser can be referred to as a first light source. By modulating the light generated by the pump laser 112, the analyte estimation system 110 can distinguish (e.g., using a filter or a lock-in amplifier) between the light emitted by the target substance after being excited by the light originating from the pump laser 112 and the light emitted by the target substance after being excited by the light originating from the one or more Stokes lasers 116.

[0063] One or more Stokes lasers 116 can include a wavelength tunable laser that can generate light having a wavelength within a predetermined range as needed. Thus, the wavelength tunable laser can be adjusted so that the wavelength of the light generated by the light source can vary within a certain range. For example, in some examples, the wavelength tunable laser can be adjusted to emit light having a wavelength that can vary from 910 nanometers to 980 nanometers. In some examples, the wavelength of the light generated by the wavelength tunable laser can be determined based on the Raman signature of a particular analyte that the analyte estimation system 110 is attempting to identify. In some examples, both the pump laser and one or more Stokes lasers can use approximately 40 milliwatts of power to operate.

[0064] In some examples, one or more Stokes lasers 116 can include a modulation system 114. Thus, in some configurations, the pump laser 112 is modulated from the light generated by one or more Stokes lasers 116 to distinguish the light generated by the pump laser 112. In other examples, one or more Stokes lasers 116 are modulated to distinguish two light sources.

[0065] In some examples, one or more Stokes lasers 116 can provide light having a wavelength tuned to the Raman signature of a particular analyte (e.g., glucose) that the analyte estimation system 110 is attempting to identify. By providing additional light (e.g., a stream of photons) having a wavelength determined based on the Raman signature of the analyte, the analyte estimation system 110 can cause stimulated Raman scattering. As a result of the stimulated Raman scattering, the light provided by one or more Stokes lasers 116 can induce more Raman scattering than would be predicted in the absence of the additional light provided by one or more Stokes lasers 116. Thus, introducing the light provided by one or more Stokes lasers 116 increases the likelihood of Raman scattering and can enhance the detectability of a particular analyte within the sample material.

[0066] In some examples, the analyte estimation system 110 can include a photodetector 122. The photodetector 122 can be a sensor such as a photodiode (e.g., a semiconductor device that converts light (e.g., photons) into an electric current). The photodiode can be configured to detect light over a range of wavelengths. In some exemplary embodiments, the light can be optically filtered such that only light within a particular wavelength range is detected by the photodetector. The amount of light can also be understood as the number of photons detected and / or the intensity of the light measured at a particular wavelength.

[0067] In some examples, the filter can be used to remove target emission light associated with one or more Stokes lasers 116 so that only the light generated from the pump laser 112 is detected. Similarly, the optical filter can remove light having a wavelength associated with the pump laser 112 so that only the target emission light generated from the Stokes laser 116 or Raman scattering is detected by the photodetector. In some examples, the filter (or lock-in amplifier) can remove modulated light if one or more Stokes lasers 116 are modulated, and can remove unmodulated light if the pump laser 112 is modulated.

[0068] The Raman scattering estimation system 120 can be used to detect the amount of light (e.g., light intensity or number of photons) generated by Raman scattering associated with an analyte in a sample substance. In some examples, the Raman scattering estimation system 120 can determine the amount of light (e.g., either the number of photons or light intensity) Raman scattered to identify an analyte in a target substance. In a first example, the user computing device can determine the amount of light (induced Raman loss) at a lost pump wavelength (e.g., a first wavelength). Alternatively, the user computing device can determine the amount of light (e.g., induced Raman gain) at an obtained Stokes-related wavelength. Any of the measurements or combinations thereof can be used to estimate the amount of a particular analyte in a target substance (e.g., the user's skin). The detected Stokes range can be compared to a reference spectrum to non-invasively measure the presence or absence of a target analyte.

[0069] For example, the sample substance can be a part of the user's body. The analyte can be, for example, glucose. The Raman scattering estimation system 120 can estimate the amount of analyte in a target sample based on the amount of light having a predetermined second wavelength. In some examples, the estimated amount of analyte can be provided for display to the user.

[0070] Figure 4A shows an example of different types of photon scattering by a substance. As seen in this example, an incident photon 200 (e.g., incident light) can interact with a particular sample molecule. One or more photons of the incident laser can interact with the sample molecule (e.g., an electron of the sample molecule) and temporarily raise the energy level of the electron. When the energy level of the electron returns to a lower level, a photon is emitted. In some examples, this process can be called scattering. Scattering can include Rayleigh scattering and Raman scattering. In Rayleigh scattering (a type of elastic scattering), the emitted photon has the same energy (and thus the same wavelength) as the incident photon, but the trajectory of the photon is potentially altered. In Raman scattering, the energy level of the electron is changed, such that when a photon is emitted, the energy level (and thus the wavelength) of the photon is different from that of the incident photon. As a result, the presence of a particular sample molecule can be determined based on the presence or absence of Raman scattered light having a particular changed wavelength.

[0071] In some examples, the energy level of the target molecule can increase, resulting in a decrease in the energy of the Raman scattered light (referred to as Stokes Raman scattered light), or the energy levels of the target and molecule can decrease, resulting in an increase in the energy of the Raman scattered light (referred to as anti-Stokes Raman scattered light).

[0072] Note that when the incident light has a consistent wavelength, the Raman scattered light produces a particular Stokes range. The Stokes range can have a consistent Raman signature, which can enable a sample estimation system to distinguish Raman scattering arising from one sample from Raman scattering arising from a second sample. Thus, identifying the presence of a particular Raman signature can be used to estimate the presence of a target sample and may also be used to estimate the amount of the sample within the target substance.

[0073] FIG. 4B shows an example of the energy level change of a sample as a result of light scattering. As can be seen here, the electron 304 can have a first energy level 306 (e.g., the ground energy level). In response to the interaction with the incident light, the energy level of the electron increases. After a certain period, the electron 304 can emit a photon and return to the lower first energy level 306.

[0074] In the first example 302, the electron 304 is initially at the first energy level 306 (low energy level). In response to the incident light, the electron 304 gains energy to the second energy level 310, which is higher than the first energy level 306. The electron 304 can emit light as Rayleigh scattered light 312. In this example 302, the energy of the Rayleigh scattered light 312 is the same as that of the incident light (thus having the same wavelength). The electron 304 can return to the first energy level 306, thereby maintaining the total energy level of the system.

[0075] In the second example 320, the electron 304 is initially at the first energy level 306 (low energy level). In response to the incident light, the electron gains energy to the second energy level 310, which is higher than the first energy level 306. However, in this example, some of the energy is obtained by the molecule as vibrational energy. As a result, when the Raman scattered light is emitted by the electron 304, the energy (and thus the wavelength) of the emitted photon 322 is reduced, but it does not drop back to the first energy level 306. Instead, the electron remains at a third energy level 324, which is higher than the first energy level 306 but lower than the second energy level 310. Thus, the electron 304 reaches a third energy level 324 that is higher than the first energy level 306, but the scattered photon 322 is at a lower energy level than the incident light, so the total energy of the system is maintained.

[0076] In the third example 330, the electron 304 is initially at a fourth energy level 332 that is higher than the first energy level 306. In response to the incident light, the electron 304 gains energy to a fifth energy level 334 that is higher than the second energy level 310. When Raman scattered light is emitted, the electron 304 loses energy from its initial starting position at the fourth energy level 332 and returns to the first energy level 306. The scattered light 334 (referred to as anti-Stokes Raman scattered light) can have an energy level higher than the incident light.

[0077] Figure 5 shows the relative amount of scattered light. In this example, it is clear that the amount of Raman scattered light is a small portion of the total amount of scattered light. Thus, if Rayleigh scattered light represents more than 99.99 percent of all scattered light, Raman scattered light can represent only 0.000001 percent of the scattered light. As a result, the amount of Raman scattered light is significantly less than the total amount of scattered light. Therefore, any technique for increasing the amount of Raman scattered light can result in a significant improvement in the ability of a detection system to determine whether a sample is present.

[0078] Figure 6 shows a graph representing the wavelengths of scattered light in the Stokes range. In this exemplary graph, the detected scattered light can be represented as a Stokes range showing the wavelength and intensity of the detected light. As can be seen, most of the scattered light can be Rayleigh scattered light having the same wavelength as the incident light generated by the pump laser. Thus, the peak at a wavelength of 532 nanometers (wave number 0) is very high. Other peaks (such as those at 800 nanometers, etc.) can represent Stokes Raman scattered light (where the light has lost energy) or anti-Stokes Raman scattered light (where the light has gained energy) within the Stokes range associated with the sample.

[0079] Figure 7 shows spontaneous Raman scattering. Due to spontaneous Raman scattering, the light generated by the first light source (or pump laser) can interact with specific molecules. A small portion of the photons emitted by the molecules has less energy and thus has a different wavelength from the incident photons. As described above, particles (e.g., electrons) within the molecule can acquire increasing energy from the ground state to a virtual state. In some cases, instead of returning to the ground state, one or more particles in the molecule can retain some of the energy as vibrational energy. Thus, the emitted photons have less energy than the incident photons.

[0080] As a result, most of the emitted light retains the same wavelength as the incident light. However, a small portion of the incident light is scattered, whereby the energy level and thus the wavelength of the scattered light are different from the incident light that excited the molecule. As described above, the Raman signature of the scattered light can be used to determine what kind of analyte is present in the target substance.

[0081] Figure 8 shows stimulated Raman scattering. In the case of stimulated Raman scattering, two or more light sources can be used to amplify or increase the amount of light scattered by Raman scattering, thereby enhancing the average intensity in the Stokes range. In some examples, the pump laser can generate light having a first wavelength (as in spontaneous Raman scattering). Additionally, one or more Stokes lasers can generate light having a second wavelength. The second wavelength can be a wavelength associated with the Raman signature of a particular analyte.

[0082] The light having the first wavelength and the light having the second wavelength can be combined and projected towards the target sample. A dichroic mirror (or one or more optical lenses) can be used, but is not essential. The light having the second wavelength can produce coherently driven molecular vibrations that have the effect of increasing the amount of Raman-scattered light. As a result, less light is required from the pump laser to produce a detectable amount of Raman-scattered light.

[0083] In some examples, when the generated light can be equally divided between a first wavelength and a second wavelength, the light emitted by the molecules in the target sample can have more light having the second wavelength. The difference between the amount of light having the second wavelength generated by one or more Stokes lasers and the amount of light having the second wavelength measured after emission can be the amount of light emitted at different wavelengths by stimulated Raman scattering.

[0084] The light generated by the pump laser (or first light source) can excite specific molecules to a higher energy level. A small fraction of the photons emitted by the molecules are emitted with less energy (e.g., the particles of the molecule can retain some energy as vibrational energy) and at different wavelengths. As described above, the particles of the molecule (e.g., electrons) can gain energy that raises them from the energy of the reference level to a higher virtual energy level. In some cases, rather than returning to the reference level, one or more particles of the molecule can retain some vibrational energy, and thus the photons emitted when the electron energy level returns to a lower level have less energy than the incident photons.

[0085] As a result, most of the emitted light retains the same wavelength as the incident light. However, a small portion of the incident light is Raman scattered, whereby the emitted light has different energy levels and thus different wavelengths. As described above, the wavelengths detected for the emitted light can be used to determine what analyte is present in the target substance.

[0086] FIG. 9A shows an exemplary graph representing the amount of light Raman scattered by spontaneous Raman scattering. As described above, during spontaneous Raman scattering, a single light source can provide light having a first wavelength 802. A small portion of the light provided at the first wavelength 802 can excite molecules to a higher energy level. Since a portion of the energy is retained as vibrational energy by particles within one or more target molecules, light having a second wavelength 804 can be emitted.

[0087] FIG. 9B shows an exemplary graph representing the amount of light Raman scattered by stimulated Raman scattering. In this example, a pump laser can generate light of a first wavelength 802, and a Stokes laser can generate light whose wavelength is a second wavelength 804. As a result of resonance, the amount of Raman scattered light can be increased by only a first amount 806, enabling the detection of scattered light to be more efficient and with less required power.

[0088] FIG. 10A shows an exemplary configuration of a system 900 for detecting a specimen within a user's skin, according to an exemplary embodiment of the present disclosure. In this example, the relevant portion of the specimen estimation system 110 includes two printed circuit boards (PCBs). The first PCB 902 can include two light sources (VCSELs). The first light source 904 can be a pump laser that generates light at one or more first wavelengths, and the second light source 906 can be a Stokes laser that generates light at one or more second wavelengths. The second wavelength can be associated with a Raman signature related to the target specimen.

[0089] The second printed circuit board 908 can include one or more photodiodes 910 configured to detect light. The one or more photodiodes 910 can generate a signal based on the detected light. In some examples, the signal generated by the photodiode can be processed to remove a modulated portion of a signal resulting from the light generated by the Stokes laser 906. Thus, the processed signal can represent light generated by Raman scattering of the pump laser 904. The analyte estimation system 110 can be pressed against the user's skin 912, whereby light is projected into the user's skin and molecules contained in the user's skin and / or tissue can emit light to the photodiode 910. Two PCBs are used in this example, but it should be noted that in some exemplary embodiments, only a single PCB is used. If so, the photodiode can be lifted slightly from the surface.

[0090] The analyte estimation system 110 includes a single window 914 through which light from both light sources passes and interacts with the user's skin 912. The light interacts with molecules within the user and, in response, light is emitted from the user's skin 912. The emitted light can pass through the optical filter 909 and reach the photodiode 910.

[0091] FIG. 10B shows an exemplary configuration of a system 920 for detecting an analyte in a user's skin according to an exemplary embodiment of the present disclosure. In this example, the relevant part of the computing system includes two printed circuit boards (PCBs). The first PCB 902 can include two light sources (VCSELs). The first light source 904 can include a pump laser capable of generating light at one or more first wavelengths, and the second light source 906 can include a Stokes laser capable of generating light at one or more second wavelengths. The second wavelength can be associated with the Raman signature of the target analyte. Light from both light sources passes through an optical element 922 (e.g., a lens) before passing through two or more windows 924.

[0092] The second printed circuit board 908 can include one or more photodiodes 910 configured to detect light. One or more optical filters can be used to filter the received light for one or more target frequencies. For example, a long-pass optical filter can be used to pass the Stokes frequency and reject the pump frequency. One or more photodiodes 910 can generate a signal based on the detected light. In some examples, the signal generated by the photodiode can be processed to remove the modulated portion of the signal generated in response to the light generated by the Stokes laser 906. Thus, the processed signal can represent the light generated by the Raman scattering of the pump laser 904. The analyte estimation system 110 can be pressed against the user's skin 912, whereby light is projected onto the user's skin and molecules contained in the user's skin and / or tissue can emit the light to the photodiode 910.

[0093] In this example, the analyte estimation system 110 can include two or more windows 924. Light from both light sources 904 and 906 can be projected through the two or more windows 924 at a beam divergence angle of 45 degrees. Other angles may be used.

[0094] FIG. 10C shows an exemplary configuration of a system for detecting a sample within a user's skin, according to an exemplary embodiment of the present disclosure. In this example, the relevant portion of the computing system includes two printed circuit boards (PCBs). The first PCB 902 can include two light sources (VCSELs). The first light source 904 can include a pump laser capable of generating light at one or more first wavelengths, and the second light source 906 can include a Stokes laser capable of generating light at one or more second wavelengths. The second wavelength can be associated with the Raman signature of the target sample. The sample estimation system 110 includes two or more windows, and each light source passes its associated light through its respective window 932 or 934.

[0095] The second printed circuit board 908 can include one or more photodiodes 910 configured to detect light. The one or more photodiodes 910 can generate a signal based on the detected light. In some examples, the signal generated by the photodiode can be processed to remove a modulated portion of the signal generated in response to the light generated by the Stokes laser 906. Thus, the processed signal can represent light generated by Raman scattering of the pump laser 904. The sample estimation system 110 can be pressed against the user's skin 912, whereby light is projected onto the user's skin and molecules contained in the user's skin and / or tissue can emit the light toward the photodiode 910.

[0096] FIG. 10D shows an exemplary configuration of a system 940 for detecting a specimen within a user's skin, according to an exemplary embodiment of the present disclosure. In this example, the relevant portion of the computing system includes two printed circuit boards (PCBs). The first PCB 902 can include two light sources (VCSELs). The first light source 904 can include a pump laser capable of generating light at one or more first wavelengths, and the second light source 906 can include a Stokes laser capable of generating light at one or more second wavelengths. The second wavelength can be associated with the Raman signature of the target specimen.

[0097] The second printed circuit board 908 can include one or more photodiodes 910 configured to detect light. The one or more photodiodes 910 can generate a signal based on the detected light. In some examples, the signal generated by the photodiode can be processed to remove a modulated portion of the signal generated in response to the light generated by the Stokes laser 906. Thus, the processed signal can represent the light generated by the Raman scattering of the pump laser 904. The specimen estimation system 110 can be pressed against the user's skin 912, whereby light is projected onto the user's skin and molecules contained in the user's skin and / or tissue can emit light towards the photodiode 910.

[0098] The specimen estimation system 110 includes a single window 914 through which light from both light sources passes, interacts with the user's skin 912, and the light emitted from the user's skin 912 can pass through to the photodiode 910. Thus, light is projected towards the user's skin 912 through the window. The light can be emitted from the user's skin 912 to reach the photodiode 910 after passing through one or more filters. The width of the region where the specimen estimation system 110 contacts the skin 912 is 5 millimeters.

[0099] FIG. 11 shows an exemplary system for detecting the presence of a specimen in a user's skin, according to an exemplary embodiment of the present disclosure. The system can include a pump laser (e.g., a VCSEL) that generates light having a wavelength of 850 nanometers.

[0100] The second light source can be one or more Stokes lasers that can generate light in the range of 910 - 980 nanometers. Light from both the pump laser and the one or more Stokes lasers can be projected towards the user's skin, where the light collides with cells and blood vessels containing a plurality of molecules. At least a portion of the light generated by the pump laser can excite molecules within the user's skin and can be Raman scattered, whereby the photons emitted by the molecules have a wavelength different from the incident light.

[0101] The system can include a band - pass filter that filters the light emitted from the user's epidermis to remove light having wavelengths outside the Stokes range. By removing wavelengths outside the Stokes range, the system can ensure that the measured light can be used to identify the Raman signature of any specimen in the user's skin and / or blood. The unfiltered light can then be detected by a photodiode. The photodiode can generate an electrical signal. The electrical signal can be demodulated (e.g., using a lock - in amplifier) and amplified. Additionally, if the Stokes laser generates light at multiple wavelengths, the photodiode can collect a spectrum from the various wavelengths. The amplified, demodulated, and collected information can be analyzed to determine what molecules are present in the user's skin and at what concentrations.

[0102] FIG. 12A shows an exemplary analyte estimation system 110 according to an exemplary embodiment of the present disclosure. In this example, the analyte estimation system 110 can include a pump laser 1102. The pump laser 1102 can be referred to as a first light source. In some examples, the pump laser 1102 can generate light having a wavelength of 850 nanometers, although other wavelengths may be used. In some examples, the pump laser 1102 can receive the output of a waveform generator 1104 as an input. The waveform generator 1104 can generate a signal for modulating the amplitude of the light generated by the pump laser 1102. In this way, the light generated by the pump laser 1102 can be distinguished from the light generated by other light sources. Thus, the analyte estimation system 110 can determine whether a particular light wavelength is the result of Raman scattering based on the modulation.

[0103] The light generated by the pump laser 1102 can pass through a bandpass filter 1106. The bandpass filter 1106 can ensure that only light within a particular frequency (e.g., the frequency associated with 850 nanometers) passes through the filter and reaches the sample tissue. For example, the bandpass filter can ensure that only light having a wavelength of 850 nanometers passes through the filter and reaches the sample tissue. The analyte estimation system 110 can also include a Stokes laser 1108 (e.g., referred to as a second light source) that generates light in a narrow band near one or more second wavelengths.

[0104] In some examples, the Stokes laser 1108 can be a wavelength-variable light source. The wavelength-variable light source can be controlled to generate light at a narrow-band wavelength near any wavelength within a given predetermined range (e.g., within 0.1 nanometer of the target wavelength). In some examples, the wavelength-variable light source can be controlled to generate narrow-band light that sweeps across a wavelength range of 910 nanometers to 980 nanometers. In another example, the Stokes laser 1108 can include a plurality of different light sources (e.g., laser diodes or other light-emitting diodes), and each light source is configured to output light having a specific wavelength related to the Raman signature of a particular analyte. For example, the Stokes laser 1108 can include a set of VCSELs, and each VCSEL is tuned to provide light at a different wavelength within the Stokes range of the analyte.

[0105] In some examples, the plurality of Stokes lasers 1108 can be activated one at a time, such that only one Stokes laser 1108 is activated at any given point. In other examples, the plurality of Stokes lasers 1108 can be activated simultaneously.

[0106] In this example, each Stokes laser 1108 at a different respective optical wavelength can be amplitude-modulated at a different respective time frequency, and then the response for each different respective optical wavelength can be extracted from the measured signal at the combined wavelength using a time-based Fourier transform or other demodulation technique. Exemplary time modulation frequencies for amplitude-modulating the different Stokes lasers 1108 can be in the range of 10 kHz to 1 MHz, but the scope of the present teachings is not limited thereto.

[0107] The sample estimation system 110 can include a dichroic mirror 1110 configured to ensure that the light emitted from the pump laser 1102 and the Stokes laser 1108 is projected in the same direction. The dichroic mirror 1110 can, for example, pass light from either the pump laser 1102 or the Stokes laser 1108 and reflect light from the other. By correctly orienting the dichroic mirror 1110, the light from both light sources can be projected in the same direction.

[0108] The sample estimation system 110 can include a focusing lens 1112 that focuses the light from both the pump laser 1102 and the Stokes laser 1108 and ensures that this light is directed towards the target sample. When the light from the pump laser 1102 and the Stokes laser 1108 interacts with the sample 1114, the sample 1114 can emit light, which can be filtered by one or more filters 1116. For example, the emitted light can pass through a long-pass filter, which can remove light having a first wavelength generated by the pump laser 1102 and allow light having a second wavelength to pass through. In this way, the light from the Stokes laser 1108 and any Raman-scattered light from the pump laser 1102 can pass through the filter 1116.

[0109] The sample estimation system 110 can include a photodiode 1120 that detects the light passing through the long-pass filter. In some examples, the photodiode 1120 can be configured to measure light of any wavelength within a predetermined wavelength range. The light detected by the photodiode 1120 can be used to generate an electrical signal. The electrical signal can retain the characteristics of the light based on which the light was generated. For example, if a portion of the detected light is amplitude-modulated, the resulting electrical signal can include both a direct current (DC) portion (e.g., related to non-modulated light) and an alternating current (AC) portion related to the modulated light.

[0110] In some examples, the amount of Raman scattering can be determined by using a lock-in amplifier to distinguish the modulated portion of the electrical signal from the unmodulated portion of the electrical signal. The modulated portion of the light can be determined to be associated with stimulated Raman gain (SRG), where SRG represents the amount of light from the pump laser 1102 that is scattered through Raman scattering such that the emitted light has a different wavelength from the incident light (e.g., emitted from the target substance at a different wavelength from the light generated by the pump laser).

[0111] The remaining electrical signal can be passed from the lock-in amplifier 1124 to the rest of the computing device for analysis. By removing the light generated by the pump laser 1102, the analyte estimation system 110 can accurately calculate the stimulated Raman gain. In some examples, the stimulated Raman gain can be calculated using the signal analysis system 1152. This method can enable non-invasive measurements of a variety of different analytes including, but not limited to, glucose, ethanol, lipids, hemoglobin, lactate, cortisol, etc. In other examples, a spectrometer is not used.

[0112] FIG. 12B shows an exemplary analyte estimation system 110 according to an exemplary embodiment of the present disclosure. In this example, instead of the pump laser 1102, the Stokes light source 1108 is modulated. Similar to the configuration in FIG. 11A, the light from the pump laser 1102 and the modulated light from the Stokes light source 1108 can pass through the dichroic mirror 1110 and the focusing lens 1112 and enter the sample substance 1114.

[0113] In this configuration, the system includes a short-pass filter 1150 that can filter out light having a second wavelength (e.g., light from the Stokes light source 1108) and pass light having a first wavelength from the pump laser 1102.

[0114] The light detected by the photodiode 1120 can be used to generate an electrical signal. The electrical signal can be passed to the signal analysis system 1152 for analysis. The electrical signal is generated based on the Rayleigh scattered light emitted from the target substance. As described above, the Rayleigh scattered light has the same wavelength as the light generated by the pump laser 1102. Since the Stokes light source 1108 is modulated, the intensity of the Rayleigh scattered light can change. In one particular example, when the amplitude of the Stokes light source 108 is at a low point (e.g., when the modulated amplitude reaches zero), the amount of Rayleigh scattered light emitted by the target substance can reach a high intensity level (because less light is Raman scattered without the Stokes light source 1108). Similarly, when the amplitude of the Stokes light source 1108 reaches a high value during modulation, the intensity of the Rayleigh scattered light emitted by the target substance at the wavelength associated with the pump light source 1102 can reach a low point (because more light is Raman scattered by the Stokes light source 1108 at peak intensity). The electrical signal representing the intensity of the light at the pump wavelength (since other wavelengths are filtered by the short - pass filter 1108) can be measured at a high point (e.g., when the intensity of the Rayleigh scattered light is maximum) and at a low point (e.g., when the intensity of the Rayleigh scattered light is minimum).

[0115] The difference in the electrical signal between the low point and the high point can be measured by the signal analysis system 1152 to determine the amount of Raman scattered light. This amount can be referred to as stimulated Raman loss (SRL). Stimulated Raman loss can represent the amount of light emitted at different wavelengths after exciting the molecules to a higher energy level in the target tissue.

[0116] FIG. 13 shows an exemplary system for non-invasively measuring a sample in a user's body according to some exemplary embodiments of the present disclosure. According to an exemplary embodiment of the present disclosure. In this example, the sample estimation system 110 can include two light sources. The first light source can be a pump laser 112 that can generate light having a first wavelength. The second light source can be one or more Stokes lasers 116. In FIG. 12, the Stokes laser 116 can be a single wavelength tunable laser that can generate narrowband light near any wavelength within a range of wavelengths. In another example, the Stokes laser 116 can include a plurality of different laser diodes that each generate light at a specific wavelength and can be selectively turned on and off as needed during the detection process.

[0117] The pump laser controller 1202 can be associated with the pump laser 112. The pump laser controller 1202 can determine when the pump laser 112 is turned on and how long it remains on. The Stokes laser controller 1204 can be associated with the Stokes laser 116 and can control when the Stokes laser 1204 is turned on, and when the Stokes laser 116 is a wavelength tunable laser, can control which wavelength of light the Stokes laser 116 is outputting at any given time.

[0118] The waveform generator 1206 can generate a waveform that is provided to the Stokes laser controller 1204. This waveform can be used to modulate the light generated by the Stokes laser 116. Modulating the output of the Stokes laser 116 can ensure that at a later point in the process, the light emitted by the Stokes laser 116 can be separated from the light emitted by the pump laser 112.

[0119] The temperature controller 1210 can control the thermoelectric cooler 1212. The thermoelectric cooler 1212 can adjust the output of the pump laser 112 as directed by the temperature controller 1210. The XY adjuster 1214 can control the direction of the light emitted by the pump laser 112, and the fiber coupler 1216 can enable the light generated by the pump laser 112 to be provided to the bifurcated fiber bundle associated with the Stokes laser 116.

[0120] The combined light in the bifurcated fiber bundle 1218 can be projected towards the target sample 1220, which in this case is the participant's hand. The light can be emitted from the participant's hand towards the spectral measurement system 1222. The spectral measurement system 1222 can include one or more photodiodes 1224. In some examples, the photodiodes 1224 have associated optical filters 1226. The optical filters 1226 can remove the wavelengths of light not required by the spectral measurement system 1222. The output of the spectral measurement system 1222 is provided to the bias module 1228. The biased module has a DC power supply 1230. The lock-in amplifier 1232 can remove the modulated light, thereby separating and analyzing the unmodulated light.

[0121] The output of the lock-in amplifier can be provided to the computer 1240. The computer 1240 can analyze the data to determine the presence or absence of the target molecule in the target tissue, which in this case is the participant's hand.

[0122] FIG. 14 shows an exemplary system comprising a light source and a photodiode according to an exemplary embodiment of the disclosure. As can be seen, the two light sources can include a pump laser 112 and a Stokes laser 116 positioned to project light through fiber 1302 in the detection unit. The light travels forward through the aperture and enters the user's skin. The user's skin can emit light towards the sensor unit. The detection unit includes an optical filter 1304 that can remove light of a certain wavelength. A plurality of photodiodes can then detect the unfiltered emitted light. The information collected by the photodiodes can be transmitted back to a computing system and analyzed to determine the content of the tissue where the light was projected.

[0123] FIG. 15 shows the layout of a plurality of light emitting sources according to some exemplary embodiments of the present disclosure. The plurality of pump lasers can be centralized to provide light of a certain wavelength. The pump lasers and one or more Stokes lasers can be arranged in a pattern such that the Stokes lasers provide a plurality of different wavelengths of light. In some examples, the wavelengths of light provided by the Stokes lasers are related to the target molecule.

[0124] FIG. 16 shows an exemplary analyte detection system 110 according to some exemplary embodiments of the present disclosure. The analyte estimation system 110 can include a pump laser 112 (e.g., a VCSEL) and two Stokes lasers 116 (e.g., an off-peak Stokes laser 116-1 and an on-peak Stokes laser 116-2). However, in other configurations, the Stokes laser 116 can include multiple Stokes lasers, each configured to generate light having a specific wavelength. One or more outputs of the pump laser 112 and / or the Stokes laser 116 may be modulated using a square wave at 10 kilohertz or higher. Generally, higher frequencies are more preferred when using modulation to distinguish light from different light sources. A multiplexer (MUX) 1502 can be used to sequentially activate two or more Stokes lasers 116.

[0125] Accordingly, the pump laser 112 can consistently generate light at 850 millimeters, and two or more Stokes lasers 116 can be sequentially activated to generate light having a narrow band centered around a specific wavelength. The light from the pump laser 112 and two or more Stokes lasers 116 is projected forward through a focusing lens 1504 onto the tissue of the user 1506. The user's tissue can emit light, which passes through one or more filters 1508. For example, the light can pass through a bandpass filter 1508 that restricts the light passing through to a predetermined band of wavelengths, or a long-pass filter that removes light of one or more wavelengths.

[0126] When light passes through the filter, one or more photodiodes 1510 can detect the light (e.g., detect the intensity of light having a specific wavelength or the number of photons having a specific wavelength). The photodiode can generate an electrical signal based on the interaction of photons with the photodiode 1510. The electrical signal can be demodulated, amplified, and transmitted to a computing device, and the computing device can collect the entire spectrum of light by wavelength. Based on the amount of light (e.g., Raman signature) at various points in the spectrum, the spectrum can be analyzed to determine whether one or more analytes are present in the user's tissue. As described above, when multiple laser diodes are activated simultaneously to provide light at each of the multiple Stokes frequencies, each laser diode can be modulated at a different respective frequency. The resulting signal can be analyzed using a Fourier transform (e.g., a fast Fourier transform) to determine the intensity of light at each different wavelength.

[0127] FIG. 17 is a flowchart showing an exemplary process for detecting molecules within a target according to an exemplary embodiment of the present disclosure. One or more portions of the method can be implemented by one or more computing devices, such as, for example, the computing devices described herein. Further, one or more portions of the method can be implemented as an algorithm on the hardware components of the devices described herein. FIG. 17 shows elements performed in a specific order for purposes of illustration and description. Those skilled in the art will understand, using the disclosure provided herein, that the elements of any method described herein can be adapted, rearranged, extended, omitted, combined, and / or modified in various ways without departing from the scope of the present disclosure. The method can be implemented by one or more computing devices, such as one or more of the computing devices shown in FIGS. 1, 11-14.

[0128] The computing device can project light from the first light source and the second light source towards a part of the user's body. The first light source can project light having a first wavelength at 1714, and one or more second light sources can generate light having a second wavelength. The light source (e.g., a laser) can project the generated light onto the user's skin. The light can interact with the molecules in the skin. The molecules in the skin can radiate the light into the system. In some examples, the light is Raman scattered by interacting with the molecules in the user's skin.

[0129] At 1716, the computing device can use a photodiode to detect the intensity of the emitted light having a specific wavelength. For example, the photodiode can measure the intensity of the light of the second wavelength. At 1718, the computing device can determine the concentration of each of a plurality of molecules in the user's body based on the emitted light.

[0130] At 1724, the computing device can generate a user profile based on the concentration of each of a plurality of molecules in the user's body. For example, the computing device can determine the relative concentrations of hemoglobin, glucose, lipids, etc. in a specific user's body based on the information from the photodiode. This information can be compiled into a standard user profile format.

[0131] In some examples, with the user's permission, the computing device can access a locally stored user profile or a user profile available via a computer network. At 1726, the computing system can compare the user profile with a plurality of stored user profiles to identify the user. For example, the specific concentrations of various molecules and chemicals in the user's body can function as a fingerprint for uniquely identifying each user. However, considering user privacy, no profile is generated and no comparison is made unless the user consents.

[0132] In some examples, when the system determines a user's identity based on a matching user profile, the computer system can access data associated with the user account and provide that information and services to the user.

[0133] FIG. 18 shows a block diagram of an exemplary data analysis model 1810 according to an exemplary embodiment of the present disclosure. The machine-learned data analysis model can obtain information about the intensity of light at various wavelengths as input 1842. For example, data analysis model 1810 can identify values at wavelengths predicted for glucose. When trained, the machine-learned data analysis model can achieve a sufficient accuracy of R2 = 0.84, which corresponds to a mean absolute error of about 30 mg / dl. Thus, data analysis model 1810 can output 1844 information that describes whether a particular analyte is present and at what concentration.

[0134] In some examples, glucose concentrations found in human blood (<300 mg / dl, typically <140 mg / dl) produce glucose peaks that are not easily separable from the background. This is because the Raman signal is extremely weak. The model picks up important features that match some of the predicted Raman peaks of glucose at wavenumbers 514, 1060, 1025, 1366 cm -1 and these peaks are clearly visible in spectra measured for very high glucose concentrations (>5000 mg / dl). This model can then be used to predict glucose levels for 200 new measurements with an R2 of 0.84. This corresponds to a mean absolute error of about 30 mg / dl.

[0135] In some examples, the machine-learned data analysis model 1810 can include, among other things, various machine-learned models such as neural networks (e.g., deep neural networks), non-linear models, and / or linear models, or other types of machine-learned models including binary classifiers. Neural networks can include feedforward neural networks, recurrent neural networks (e.g., long short-term memory recurrent neural networks), convolutional neural networks, or other forms of neural networks.

[0136] To train the machine-learned data analysis model 1810, various training techniques can be used. In particular, the machine-learned data analysis model 1810 can be trained using one of a plurality of semi-supervised training techniques. The machine-learned data analysis model 1810 can also be trained using a supervised training technique such as, for example, backpropagation. For example, the loss function can be backpropagated through the model to update one or more parameters of the model (e.g., based on the gradient of the loss function). Various loss functions can be used such as mean squared error, likelihood loss, cross-entropy error, hinge loss, and / or various other loss functions. Gradient descent techniques can be used to iteratively update the parameters over multiple training iterations. In some implementations, performing backpropagation of the error includes performing truncated backpropagation through time. To enhance the generalization ability of the trained model, generalization techniques (e.g., weight decay, dropout, etc.) can be performed.

[0137] FIG. 19 is a flowchart showing an exemplary process for detecting a specimen within a target tissue according to an exemplary embodiment of the present disclosure. One or more parts of the method can be implemented by one or more computing devices, such as, for example, the computing devices described herein. Further, one or more parts of the method can be implemented as an algorithm on the hardware components of the devices described herein. FIG. 19 shows elements executed in a particular order for purposes of illustration and description. Those skilled in the art will be able to adapt, rearrange, extend, omit, combine and / or modify any of the elements of the methods described herein in various ways without departing from the scope of the present disclosure using the disclosure provided herein. The method can be implemented by one or more computing devices, such as one or more of the computing devices shown in FIGS. 1, 11-14.

[0138] A computing device for non-invasively measuring glucose levels in a user using stimulated Raman scattering can include a lamp pump laser, a Stokes laser, and a photodetector. At 1812, the computing device can use the pump laser to emit pump light onto the user's skin surface, the pump light being at a fixed wavelength. It should be noted that while the light can be directed towards the surface of the skin, the light can be focused into the user's subcutaneous region so that the light interacts more readily with molecules in the user's blood. Thus, as the present disclosure shows when the light is directed onto or received from the surface of the user's skin, the target of the light can be beneath the surface of the user's skin. At 1814, the computing device can use the Stokes laser to emit Stokes light onto the skin surface at a plurality of Stokes wavelengths within the window of Raman measurement wavelengths.

[0139] The Stokes light source can include a variable wavelength narrowband laser that is continuously swept from one end to the other end of the window of the Raman measurement wavelength during the non-invasive glucose measurement. In some examples, the Stokes light source can include a plurality of fixed wavelength narrowband laser light sources, and each laser light source has a different center wavelength within the window of the Raman measurement wavelength.

[0140] In some examples, the Raman pump light source and the fixed wavelength narrowband laser light source of the Stokes light source are VCSELs, and no optical fiber or mirror is used anywhere in the device. The computing device can measure, at 1816, the light emitted from and returning from the skin surface using a photodetector.

[0141] In some examples, the photodetector can detect light over a wavelength range that includes both the Raman pump light source wavelength and the window of the Raman measurement wavelength, and time modulation of the Raman pump light source, time modulation of the Stokes light source, and / or different time modulations of both the Raman pump light source and the Stokes light source are used to enable discrimination of the Raman pump wavelength light from the light having wavelengths within the window of the Raman measurement wavelength.

[0142] In some examples, the photodetector is a photodiode that detects light over the entire window of the Raman measurement wavelength, and during the non-invasive glucose measurement, the plurality of fixed wavelength narrowband laser light sources are activated one at a time.

[0143] The computing device can process, at 1818, the measured light to provide an estimated glucose level of the user. In some examples, the Stokes light source emits narrowband light with respect to the window of the Raman measurement wavelength, and the Stokes light includes a plurality of emissions of the narrowband light at respective multiple center wavelengths across the window of the Raman measurement wavelength.

[0144] FIG. 20 shows an exemplary computing environment including a user computing device 1900 according to an exemplary embodiment of the present disclosure. The computing device 1900 can include a specimen estimation system 1910 for non-invasively determining the presence and amount of one or more specimens inside a user. In some examples, the computing device 1900 can be a user computing device such as a smartphone or a wearable computing device. In other examples, the computing device 1900 can be a computing device that is not portable and is intended for home use. In this example, the user computing device 1900 can include one or more processors 1902, a memory 1904, a specimen estimation system 1910, one or more collimators 1930, and a control circuit 1940.

[0145] More specifically, the one or more processors 1902 can be any suitable processing device for the computing device 1900. For example, such a processor can include one or more of a processor core, a microprocessor, an ASIC, an FPGA, a controller, a microcontroller, etc. The one or more processors can be one processor or multiple processors operably connected. The memory 1904 can include one or more non-transitory computer-readable storage media such as RAM, ROM, EEPROM, EPROM, flash memory devices, and combinations thereof.

[0146] In particular, in some devices, the memory 1904 can store instructions 1908 for implementing the analyte estimation system 1910. It will be understood that the term "system" can refer to dedicated hardware, computer logic executed on a more general-purpose processor, or a combination thereof. Thus, the system can be implemented in hardware, application-specific circuitry, firmware, and / or software that controls a general-purpose processor. In one embodiment, the system can be implemented as a program code file stored in a storage device, loaded into memory, and executed by a processor, or provided from a computer program product, e.g., computer-executable instructions, stored on a tangible computer-readable storage medium such as RAM, a hard disk, or an optical or magnetic medium.

[0147] The memory 1904 can also include data 1906 that can be retrieved, manipulated, created, or stored by one or more processors 1902. In some exemplary embodiments, such data can be accessed and used as an input to the analyte estimation system 1920. In some examples, the memory 1904 can include data used to execute one or more processes and instructions describing how these processes can be executed.

[0148] In some examples, the analyte estimation system 1920 can include a pump laser 1912, one or more Stokes lasers 1916, a photodetector 1922, and a Raman scattering estimation system 1910. Although not shown, the analyte estimation system 1920 can also include an optical filter and one or more optical lenses (e.g., microlenses) for focusing the lasers onto the same area (e.g., the same portion of a user's skin). The pump laser 1912 (e.g., a first light source) can be a laser diode that emits light (e.g., a stream of photons) at a target wavelength. In some examples, the pump laser can generate light having an average wavelength of 780 nanometers. Other wavelengths of the pump laser 1912 can be used, and the wavelengths of the one or more Stokes lasers 1916 are determined, at least in part, based on the wavelength of the pump laser 1912. In some examples, the pump laser 1912 can be a vertical cavity surface emitting laser (VCSEL) included in a semiconductor chip. In some examples, the wavelength of the light emitted by the pump laser 1912 is 850 nanometers. Other wavelengths can be used.

[0149] The pump laser 1912 can be controlled by a control circuit that can send a signal to operate or turn off the pump laser according to at least one duty cycle. In some examples, the pump laser 1912 can be pulse modulated. Pulse modulating the pump laser 1912 can include controlling the pump laser 1912 to generate square wave pulses.

[0150] The pump laser 1912 can include (or can be associated with) a modulation system. The modulation system can be used to modulate the light generated by the pump laser 1912 in cooperation with a control circuit. The pump laser can be referred to as a first light source. By modulating the light generated by the pump laser 1912, the analyte estimation system 1920 can distinguish (e.g., using a filter or a lock-in amplifier) the light emitted by the target substance after being excited by the light emitted from the pump laser 1912 from the light emitted by the target substance after being excited by the light emitted from one or more Stokes lasers 1916.

[0151] One or more Stokes lasers 1916 can include a wavelength-variable laser that can generate light having a wavelength within a predetermined range as needed. Thus, the wavelength-variable laser can be adjusted so that the wavelength of the light generated by the light source can vary within a predetermined range. For example, in some examples, the wavelength-variable laser can be adjusted to emit light having a wavelength that can vary from 910 nanometers to 980 nanometers. In some examples, the wavelength of the light generated by the wavelength-variable laser can be determined based on the Raman signature of a particular analyte that the analyte estimation system 1920 is attempting to identify. In some examples, both the pump laser and one or more Stokes lasers can use about 40 milliwatts of power to operate.

[0152] One or more Stokes lasers 1916 can be controlled by a control circuit that can send a signal to operate or turn off the pump laser according to at least one duty cycle. In some examples, one or more Stokes lasers 1916 can be pulse-modulated. Pulse-modulating the pump laser 1912 can include controlling one or more Stokes lasers 1916 to generate square-wave pulses.

[0153] In some examples, one or more Stokes lasers can include a modulation system. Thus, in some configurations, the pump laser 1912 can modulate the light generated by the pump laser 1912 to distinguish it from the light generated by one or more Stokes lasers 1916. In other examples, one or more Stokes lasers 1916 are modulated to distinguish two light sources.

[0154] In some examples, one or more Stokes lasers 1916 can provide light having a wavelength tuned to the Raman signature of a particular analyte (e.g., glucose) that the analyte estimation system 1920 is attempting to identify. By providing additional light (e.g., a stream of photons) having a wavelength determined based on the Raman signature of the analyte, the analyte estimation system 1920 can cause stimulated Raman scattering. As a result of the stimulated Raman scattering, the light provided by one or more Stokes lasers 1916 can induce more Raman scattering than would be predicted without the additional light provided by one or more Stokes lasers 1916. Thus, introducing the light provided by one or more Stokes lasers 1916 can increase the likelihood of Raman scattering and thus enhance the detectability of a particular analyte within a sample material.

[0155] In some examples, the analyte estimation system 1920 can include a photodetector 1922. The photodetector 1922 can be a sensor such as a photodiode (e.g., a semiconductor device that converts light (e.g., photons) into an electric current). The photodiode can be configured to detect light over a predetermined range of wavelengths. In some exemplary embodiments, the light can be optically filtered so that only light within a particular wavelength range is detected by the photodetector. The amount of light can also be understood as the number of detected photons and / or the intensity of the light measured at a particular wavelength.

[0156] In some examples, a filter can be used to remove target emission light associated with one or more Stokes lasers 1916 so that only the light generated from the pump laser 1912 is detected. Similarly, an optical filter can remove light having a wavelength associated with the pump laser 1912 so that only the target emission light resulting from the Stokes laser 1916 or Raman scattering is detected by the photodetector. In some examples, the filter (or lock-in amplifier) can remove modulated light if one or more Stokes lasers 1916 are modulated, or can remove unmodulated light if the pump laser 1912 is modulated.

[0157] The Raman analyte estimation system 1910 can be used to detect the amount of light (e.g., light intensity or number of photons) generated by Raman scattering associated with an analyte within a sample substance. In some examples, the Raman scattering estimation system 1910 can determine the amount of light (e.g., either the number of photons or light intensity) Raman scattered to identify an analyte within a target substance. In a first example, the user computing device can determine the amount of light (induced Raman loss) at a lost pump wavelength (e.g., a first wavelength). Alternatively, the user computing device can determine the amount of light (e.g., induced Raman gain) at an obtained Stokes-related wavelength. Either the measurements or combinations thereof can be used to estimate the amount of a particular analyte within a target substance (e.g., the user's skin). The detected Stokes range can be compared to a reference spectrum to non-invasively measure the presence or absence of a target analyte.

[0158] For example, the sample substance can be a part of the user's body. The analyte can be, for example, glucose. Based on the amount of light having a predetermined second wavelength, the analyte estimation system 1910 can estimate the amount of analyte within the target sample. In some examples, the estimated amount of analyte can be provided for display to the user.

[0159] In some examples, the user computing device 1900 can include one or more collimators 1930. The collimator, along with a mirror (e.g., dichroic mirror 1932), can be used to make the light from the pump laser 1912 and one or more Stokes lasers 1916 collinear so that the beam does not diverge (or diverges less). By using one or more collimators 1930, the user computing device 1900 can focus the laser beam on a portion of a smaller target tissue than would otherwise be possible. Focusing the light on a small area (e.g., with a diameter of less than 10 μm) results in an increase in the power density of the light. The power density in this context can be measured based on the amount of light projected per unit area onto which the light is projected. Thus, focusing the light on a smaller area can result in a higher power density without the need to increase the total amount of light projected.

[0160] The user computing device 1900 can include one or more dichroic mirrors 1932. The dichroic mirror 1932 can be configured so that light of one or more frequencies is reflected from the dichroic mirror 1932. In addition, light of one or more other frequencies can pass through the dichroic mirror 1932 without being affected. Thus, the dichroic mirror 1932 can be used to combine light from two or more light sources (e.g., the pump laser 1912 and one or more Stokes lasers 1916) into a single light beam. Combining light from multiple light sources can result in more tightly focused light, which in turn allows the light to be targeted to a relatively small area and increases the power density of the light.

[0161] The user computing device 1900 can include a control circuit 1940. The control circuit 1940 can be used to increase the amount of light (e.g., light power density) projected onto the region of the target tissue. In particular, the control circuit can be used to turn the light source on and off according to a duty cycle. By turning the light source on and off, the light source can operate at a higher power level than would be possible if the light source were operated continuously. In particular, as a result of operating the light source at a higher power for a short time, a higher power density can be produced during the period when the light source is on without exceeding the maximum allowable dose for the light source. The maximum allowable dose limit can describe the maximum amount of light (or other electromagnetic radiation) to which tissue (or other substance) can be exposed without harmful effects or biological changes. The maximum allowable dose can be determined by the wavelength of the light, the energy of the light, and the exposure time.

[0162] Thus, by pulse modulating the light source, the control circuit 1940 can reduce the exposure time and enable higher power (light energy) to be used during the time the light source is on. The control circuit 1940 can be configured to turn on one or more of the light sources during a particular period and turn them off during other periods. By activating the light source only for a portion of the total time, the control circuit 1940 can ensure that the power consumption of the system remains low and that the amount of light to which the tissue is exposed does not exceed a predetermined exposure limit for any of the plurality of light sources.

[0163] The control circuit 1940 can operate light sources (e.g., Raman light source and Stokes light source) according to at least one duty schedule. For example, the control circuit can control the light source to be activated according to a 1% duty cycle. Thus, after the light source is activated for 10 nanoseconds, the light source cannot be activated for 990 nanoseconds. By activating the light source for only a very short time, the light source can obtain (when activated) a higher power than would be possible if the light source were continuously activated. Thus, during the time the light source is activated, the analyte detection system can have high accuracy while remaining within the exposure limit.

[0164] In some examples, different light sources can have different duty cycles. For example, the control circuit 1940 can pulse-modulate one or more Stokes light sources at 10 MHz and pulse-modulate the pump light source at 5 MHz. Thereby, the Stokes signal spectrum can have a center frequency of 10 MHz, and the pump signal spectrum can have a center frequency of 5 MHz. By having a first center frequency for one or more Stokes light sources and a second center frequency for the pump signal spectrum, the analyte estimation system can more easily distinguish between the two using signal processing.

[0165] FIG. 21 is a diagram of a sample detection system that collineates light from different light sources according to an exemplary embodiment of the present disclosure. In some examples, the sample detection system 1910 can include a pump light source 2002, a first Stokes light source 2004, and a second Stokes light source 2006. To ensure that light from all three light sources is combined into one light stream so that light from all three light sources is effectively focused on the same region of the target tissue, the sample detection system 1910 includes a plurality of dichroic mirrors and collimators. These components can be used to combine the light from each light source into the combined light stream. Thus, the light from the pump light source 2002 can be directed towards the first dichroic mirror 2010. This dichroic mirror 2010 can be configured such that light at the frequency of the pump light source 2002 is reflected at the mirror 2010. The dichroic mirror 2010 can be configured to direct the reflected light towards the second dichroic mirror 2012. The second dichroic mirror 2012 can be configured to allow the light from the pump light source 2002 to pass through without changing its trajectory.

[0166] The first Stokes light source 2004 can project light towards the second dichroic mirror 2012. The second dichroic mirror 2012 can be configured such that light having a frequency associated with the first Stokes light source 2004 is reflected at the dichroic mirror 2004 towards the third Stokes light source 2016, while light having a frequency associated with the pump light source passes through the dichroic mirror and merges into the beam of light projected from the first Stokes light source 2004. The light from the first Stokes light source 2004 can be reflected along the same path as the light from the pump light source 2002. The light from the pump light source 2002 and the first Stokes light source can be effectively combined into one light stream.

[0167] The combined light flow can be directed towards a third dichroic mirror 2014. The third dichroic mirror 2014 can be configured such that light having frequencies associated with the pump light source 2002 and the first Stokes light source 2004 passes through unchanged. The light from the second Stokes light source 2006 is directed towards the third dichroic mirror 2014. The third dichroic mirror 2014 is configured to reflect the light from the second Stokes light source 2006 and direct this light along the same path as the combined light from the pump light source 2002 and the first Stokes light source. Thereby, the light from the pump light source 2002, the first Stokes light source 2004, and the second Stokes light source 2006 can be effectively combined here into one collinear flow. The specimen estimation system 1910 also includes lenses (2022, 2024, and 2026) associated with each light source.

[0168] The combined light can be directed towards an x / y mirror 2016 that reflects light of all frequencies. The x / y mirror 2016 can direct the combined collinear light towards a target area on the measurement position 2040. The measurement position 2040 can include a photodetector 2042. The x / y mirror 2016 can be tilted to direct the beam along the surface of the tissue and change the targeted area. One or more lenses 2030 can be adjusted so that the light beam is focused at the desired depth at the target depth. In some examples, the lens can be circular and can be adjusted by rotating a screw to move one or more lenses up and down to adjust the focal depth of the mirror.

[0169] FIG. 22 is a diagram showing the influence of the polarity in the generated light according to an exemplary embodiment of the present disclosure. In this example, the light 2102 generated by the pump light source and the light 2104 (both examples of electromagnetic radiation) generated by one or more Stokes light sources are shown together with the electric and magnetic fields of their respective components.

[0170] FIG. 23 is a graph 2200 showing the effects of parallel polarization and orthogonal polarization in the generated light according to an exemplary embodiment of the present disclosure. As can be seen in this graph, when the Stokes light and the pump light have parallel polarization, the resulting power is significantly higher than the power that occurs when the light has orthogonal polarization. Thus, the analyte estimation system can ensure that the light generated by the pump light source and the one or more Stokes light sources has parallel polarization.

[0171] FIG. 24 includes two graphs 2300 showing a light source that generates pulses according to a specific duty cycle according to an exemplary embodiment of the present disclosure. In this example, the pump light source can be controlled according to a first duty cycle, and the one or more Stokes light sources can be controlled according to a second duty cycle. For example, the one or more Stokes light sources can be operated in a duty cycle so as to be turned on at twice the frequency of the pump light source. Importantly, whenever the pump light source generates a pulse, the one or more Stokes light sources are also pulsed on.

[0172] FIG. 25 is a flowchart showing an exemplary process for detecting an analyte in a target tissue according to an exemplary embodiment of the present disclosure. One or more portions of the method can be implemented by one or more computing devices, such as, for example, the computing devices described herein. Further, one or more portions of the method can be implemented as an algorithm on the hardware components of the devices described herein. FIG. 25 shows elements performed in a specific order for purposes of illustration and explanation. Those skilled in the art will understand that any of the elements of the methods described herein can be adapted, rearranged, extended, omitted, combined, and / or modified in various ways without departing from the scope of the present disclosure using the disclosure provided herein. The method can be implemented by one or more computing devices, such as one or more of the computing devices shown in FIG. 20.

[0173] An apparatus for non-invasively measuring the level of an analyte within a user using stimulated Raman scattering can include a Raman pump light source that, when activated, emits pump light at a pump wavelength towards the skin surface of the user at 2402. The apparatus can further include a Stokes light source that, when activated, emits Stokes light at one or more Stokes wavelengths towards the skin surface at 2404. The apparatus can further include a photodetector at 2406 for measuring light emitted from the skin surface.

[0174] In some examples, the Raman pump light source and the Stokes light source can be laser diodes. For example, the laser diode can be a vertical-cavity surface-emitting laser (VCSEL). The Raman pump light source and the Stokes light source can be single-mode VCSELs. In another example, the laser diode can be an edge-emitting diode laser. Thus, the Raman pump light source and the Stokes light source can be an edge-emitting diode laser, a VCSEL, or another type of laser diode. In some examples, both the Raman pump light source and the Stokes light source can be the same type of laser diode. In other examples, the Raman pump light source and the Stokes light source can be different.

[0175] The apparatus can further include a control circuit that controls the Raman pump light source and the Stokes light source within a predetermined exposure limit according to at least one duty cycle related to maximizing the associated power of the light generated by the Raman pump light source and the Stokes light source. The at least one duty cycle can operate the Raman pump light source and the Stokes light source over a first period, after which the Raman pump light source and the Stokes light source are not operated during a longer second period. The apparatus can further include a processor that, at 2408, processes the measured light and provides an estimated analyte level of the analyte within the user.

[0176] In some examples, at least one duty cycle can instruct a control circuit to operate the Raman pump light source and the Stokes light source over less than one percent of the time in a particular period. More specifically, at least one duty cycle can be a 0.1 percent duty cycle. In some examples, the light source can be operated for a period of 10 nanoseconds or less, and then, for a period of 990 nanoseconds or more, the light source is not operated. In a particular example, at least one particular duty cycle can operate the Raman pump light source and the Stokes light source over a 1 ns pulse duration, and then, at 999 ns, the Raman pump light source and the Stokes light source are not operated.

[0177] In some examples, at least one duty cycle includes a first duty cycle and a second duty cycle. For example, the Raman pump light source is pulse - modulated according to the first duty cycle, and the Stokes light source is pulse - modulated according to the second duty cycle. In an example where the Raman pump light source is pulse - modulated according to a different duty cycle than one or more Stokes light sources, at least one Stokes light source is operated whenever the pump light source is operated.

[0178] In some examples, the control circuit can use pulse modulation to control the Raman pump light source and the Stokes light source. In some examples, a first pulse frequency can be associated with the Raman pump light source, and a second pulse frequency can be associated with one or more Stokes light sources. In some examples, the first pulse frequency can be less than the second pulse frequency. For example, the first pulse frequency can be 5 MHz, and the second pulse frequency can be 10 MHz. In some examples, the second pulse frequency can be less than the first pulse frequency. In some examples, the control circuit can control the Raman pump light source and the Stokes light source to generate pulse signals in phase.

[0179] In some examples, the apparatus can include a collimator to ensure that the light emitted by the Raman pump light source and the light emitted by the Stokes light source are projected parallel to the user's skin surface. In some examples, one or more dichroic mirrors can combine the light from the Raman pump light source and the Stokes light source into a single light beam. The apparatus can include focusing optics that focus the single light beam onto a specific region of the target sample (e.g., a region of the user's skin having a diameter of less than 10 microns). The focusing optics can include one or more lenses. In some examples, the apparatus can include a waveguide instead of a dichroic mirror. In some examples, the apparatus can include both a waveguide and one or more dichroic mirrors.

[0180] The Raman pump light generated by the Raman pump light source and the Stokes light generated by the Stokes light source can be polarized. The light generated by the Raman pump light source and the light generated by the Stokes light source can be polarized such that the light beams are parallel.

[0181] In some examples, the Raman pump light source and the Stokes light source can be configured to project light onto a region having a diameter of less than 10 microns. The Raman pump light source and the Stokes light source can be operated at a higher power level while operating in pulsed mode than is possible during continuous operation mode. In some examples, a predetermined exposure limit can be based on the maximum allowable dose for the Raman pump light source and the Stokes light source. In some examples, the Stokes light includes multiple narrowband emissions at respective center wavelengths within the window of the Raman measurement wavelength.

[0182] FIG. 26 shows an exemplary computing environment including a user computing device 2600 according to an exemplary embodiment of the present disclosure. The computing device 2600 can include a sample estimation system 2610 for non-invasively determining the presence and amount of one or more samples inside a user. In some examples, the computing device 2600 can be a user computing device such as a smartphone or a wearable computing device. In other examples, the user computing device 2600 can be a computing device not intended for portability but for home use. In this example, the user computing device 2600 can include one or more processors 2602, a memory 2604, a sample estimation system 2610, one or more lenses 2630, one or more mirrors 2632, and a control circuit 2640.

[0183] More specifically, the one or more processors 2602 can be any suitable processing device for the computing device 2600. For example, such a processor can include one or more of a processor core, a microprocessor, an ASIC, an FPGA, a controller, a microcontroller, etc. The one or more processors can be one processor or multiple processors operably connected. The memory 2604 can include one or more non-transitory computer-readable storage media such as RAM, ROM, EEPROM, EPROM, flash memory devices, etc., and combinations thereof.

[0184] In particular, in some devices, the memory 2604 can store instructions 2608 for implementing a specimen estimation system 2610. It will be understood that the term "system" can refer to dedicated hardware, computer logic executed on a more general-purpose processor, or a combination thereof. Thus, the system can be implemented in hardware, application-specific circuitry, firmware, and / or software that controls a general-purpose processor. In one embodiment, the system can be implemented as a program code file stored in a storage device, loaded into memory, and executed by a processor, or provided from a computer program product, e.g., computer-executable instructions, stored on a tangible computer-readable storage medium such as a RAM, hard disk, or optical or magnetic medium.

[0185] The memory 2604 can also include data 2606 that can be retrieved, manipulated, created, or stored by one or more processors 2602. In some exemplary embodiments, such data can be accessed and used as an input to the specimen estimation system 2610. In some examples, the memory 2604 can include data used to execute instructions that describe one or more processes and how these processes can be executed.

[0186] In some examples, the analyte estimation system 2610 can include a pump laser 2612 (also referred to as a Raman pump laser), one or more Stokes lasers 2616, a photodetector 2622, a Raman scattering estimation system 2620, a beam controller 2622, and a composition determination system 2624. The pump laser 2612 (e.g., a first light source) can be a laser diode that emits light (e.g., a stream of photons) at a target wavelength. In some examples, the pump laser can generate light having an average wavelength of 780 nanometers. Other wavelengths may be generated by the pump laser. The wavelength of one or more Stokes lasers 2616 can be determined, at least in part, based on the wavelength of the pump laser 2612. In some examples, the pump laser 2612 can be a vertical cavity surface emitting laser (VCSEL) included in a semiconductor chip. In some examples, the wavelength of the light emitted by the pump laser 2612 is 850 nanometers. Other wavelengths may be used.

[0187] The light generated by the pump laser 2612 can be directed by the beam controller 2622. The beam controller 2622 can control one or more mirrors and one or more lenses to ensure that the light emitted by the pump laser 2612 is directed toward an optimal target area and focused at an appropriate depth. The optimal target area can be determined by the composition determination system 2624.

[0188] The pump laser 2612 can include (can be associated with) a modulation system. The modulation system can be used to modulate the light generated by the pump laser 2612 in cooperation with a control circuit. The pump laser can be referred to as a first light source. By modulating the light generated by the pump laser 2612, the analyte estimation system 2610 can distinguish (e.g., using a filter or a lock-in amplifier) the light emitted by the target substance after being excited by the light generated from the pump laser 2612 from the light emitted by the target substance after being excited by the light generated from one or more Stokes lasers 2616.

[0189] One or more Stokes lasers 2616 can include a wavelength tunable laser that can generate light having a wavelength within a predetermined range as needed. Thus, the wavelength tunable laser can be adjusted so that the wavelength of the light generated by the light source can vary within a predetermined range. For example, the wavelength tunable laser can be adjusted to emit light having a wavelength that can vary from 910 nanometers to 980 nanometers. In some examples, the wavelength of the light generated by the wavelength tunable laser can be determined based on the Raman signature of a particular analyte that the analyte estimation system 2620 is attempting to identify. In some examples, both the pump laser and one or more Stokes lasers can use about 40 milliwatts of power to operate.

[0190] In some examples, the pump laser 2612 and one or more Stokes lasers 2616 can be operated at two or more power levels. For example, the lasers (e.g., the pump laser 2612 and one or more Stokes lasers 2616) can have a lower power level that is used when determining the type of tissue found at one or more points within the user's tissue. The lasers (e.g., the pump laser 2612 and one or more Stokes lasers 2616) can have a higher power level that is used when analyzing the tissue to determine whether the tissue contains a particular analyte and, if so, at what concentration.

[0191] The light generated by one or more Stokes lasers 2616 can be directed by a beam controller 2622. The beam controller 2622 can control one or more mirrors 2632 and one or more lenses 2630 to ensure that the light emitted by one or more Stokes lasers 2616 is directed towards an optimal target area and focused at an appropriate depth. The optimal target area can be determined by a composition determination system 2624.

[0192] In some examples, one or more Stokes lasers 2616 can include a modulation system. Thus, in some configurations, the pump laser 2612 can be modulated to distinguish the light generated by the pump laser 2612 from the light generated by one or more Stokes lasers 2616. In other examples, one or more Stokes lasers 2616 are modulated to distinguish between two light sources.

[0193] In some examples, one or more Stokes lasers 2616 can provide light having a wavelength tuned to the Raman signature of a particular analyte (e.g., glucose) that the analyte estimation system 2620 is attempting to identify. By providing additional light (e.g., a stream of photons) having a wavelength determined based on the Raman signature of the analyte, the analyte estimation system 2620 can cause induced Raman scattering. Induced Raman scattering can result in the light provided by one or more Stokes lasers 2616 inducing more Raman scattering than would be predicted in the absence of the additional light provided by one or more Stokes lasers 2616. Thus, introducing the light provided by one or more Stokes lasers 2616 can increase the likelihood of Raman scattering, and thus increase the detectability of a particular analyte within a sample material.

[0194] In some examples, the analyte estimation system 2610 can include a photodetector 2618. The photodetector 2618 can be a sensor such as a photodiode (e.g., a semiconductor device that converts light (e.g., photons) into an electric current). The photodiode can be configured to detect light over a predetermined wavelength range. In some exemplary embodiments, the light can be optically filtered so that only light within a particular wavelength range is detected by the photodetector. The amount of light can also be understood as the number of detected photons and / or the intensity of the light measured at a particular wavelength.

[0195] In some examples, a filter can be used to remove the target emission light associated with one or more Stokes lasers 2616 so that only the light generated from the pump laser 2612 is detected. Similarly, an optical filter can remove light having a wavelength associated with the pump laser 2612 so that only the target emission light generated from the Stokes laser 2616 or Raman scattering is detected by the photodetector. In some examples, the filter (or lock-in amplifier) can remove the modulated light if one or more Stokes lasers 2616 are modulated, or the unmodulated light if the pump laser 2612 is modulated.

[0196] The Raman scattering estimation system 2620 can be used to detect the amount of light (e.g., light intensity or number of photons) generated by Raman scattering associated with an analyte within a sample substance. In some examples, the Raman scattering estimation system 2620 can determine the amount of Raman scattered light (e.g., either the number of photons or the light intensity) to identify an analyte within a target substance. In a first example, the user computing device can determine the amount of light at the lost pump wavelength (e.g., the first wavelength) (induced Raman loss). Alternatively, the user computing device can determine the amount of light at the obtained Stokes-related wavelength (e.g., induced Raman gain). Any of the measurements or combinations thereof can be used to estimate the amount of a particular analyte in a target substance (e.g., the user's skin). The detected Stokes range can be compared to a reference spectrum to non-invasively measure the presence or absence of the target analyte.

[0197] For example, the sample substance can be a part of the user's body. The analyte can be, for example, glucose. Based on the amount of light having a predetermined second wavelength, the Raman scattering estimation system 2620 can estimate the amount of analyte within the target sample. In some examples, the estimated amount of analyte can be provided for display to the user.

[0198] In some examples, the user computing device 2600 can include a beam controller 2622. The beam controller can include a system that can control the direction of the beams generated by the pump laser 2612 and one or more Stokes lasers 2616. The beam controller 2622 can control the direction of the beams via one or more lenses 2630 and one or more mirrors 2632. In particular, one or more of the mirrors can be tilted to direct the beam along the surface of the target area. Thus, the direction of the beam can be modified along the x-axis and y-axis (length and height along the user's skin).

[0199] One or more of the lenses 2630 can be adjusted to update the depth of focus at which the beam is focused. Thus, the z-axis of the target position can be adjusted. In this way, the beam controller can adjust the target position of the beam to target any position within the three-dimensional space accessible to the specimen detection system 2610. For example, if the user computing device 2600 is a wearable device held against the user's skin by a band or other means, the three-dimensional position accessible to the specimen detection system 2610 can be approximately equal to the area of skin under the device having a width approximately equal to the width of the specimen detection system 2610 and a depth related to the maximum depth of focus of the specimen detection system 2610. This maximum depth of focus can be based on the degree to which the lens can be adjusted and the characteristics of the tissue itself. In this way, the beam controller 2622 can enable the specimen detection system 2610 to target the optimal target position within the user's tissue wherever it may occur.

[0200] The user computing device 2600 can include a composition determination system 2624. The composition determination system 2624 can determine the type of tissue at a plurality of positions within a target area. The target area can be determined based on the scope of the user's tissue that can be targeted by the beam controller. To determine the type of tissue throughout the target area, the composition determination system 2624 can generate a target sampling grid. Sampling can include a plurality of points sampled by the composition determination system 2624.

[0201] Once the target sampling grid is established, the composition determination system 2624 can project light at each point in the target sampling grid. The projected light can be from the pump laser 2612 and / or one or more Stokes lasers 2616. The amount and duration of the emitted light can be lower than that projected when attempting to detect the specimen through Raman scattering. This is because the detection of the tissue type is possible based on skin absorption without the need for the high power density used to induce Raman scattering at detectable levels. When lower levels of light are projected at each point within the target sampling grid, the composition determination system 2624 can analyze the absorption of light by each point. By determining which wavelength of light is absorbed by the substance at that target point, the composition determination system 2624 can estimate the type of substance at that point. For example, different types of tissue absorb different wavelengths of light. The type of tissue can be one or more of interstitial fluid, cells associated with the epidermis, cells associated with the dermis, adipocytes, glands, nerve cells, blood vessels, follicles, etc.

[0202] Once the composition determination system 2624 analyzes each point within the target sampling grid, the composition determination system 2624 can determine the optimal target position. In some examples, the optimal target position can be based on a particular type of tissue at that position. In other examples, the optimal target position can be based on the specimen being detected.

[0203] In some examples, the user computing device 2600 includes one or more lenses 2630. The one or more lenses can focus the light beam at different depths. The depth at which the beam is focused can be adjusted by moving the lens up and down. In some examples, the depth of focus of the lens 2630 is moved by being attached to a rotatable screw. Since the rotatable screw is circular, the lens can be adjusted up and down without affecting any other aspect of the light beam.

[0204] The user computing device 2600 can include one or more mirrors 2632. The one or more mirrors 2632 can be configured to direct light towards a particular portion of the target tissue. In some examples, the one or more mirrors 2632 can be tilted to be at the targeted position.

[0205] The user computing device 2600 can include a control circuit 2640. The control circuit 2640 can be used to increase the amount of light (e.g., light power density) projected onto the area of the target tissue. In some examples, the control circuit 2640 can reduce the light intensity when determining the type of tissue at a particular position.

[0206] FIG. 27 is a diagram showing sampling using a target sampling grid 2700. The area associated with the target sampling grid 2700 is determined based on the characteristics of the specimen detection system. In particular, the dimensions of the target sampling grid 2700 represent the area that can be targeted by the specimen detection system. Thus, the x-axis 2710 and the y-axis 2712 are determined based on the extent to which one or more mirrors can adjust the light beam along the surface of the user's skin. The depth of the z-axis 2714 represents the depth that can be targeted by adjusting one or more lenses. In some examples, the depth to which a laser can penetrate tissue can be determined at least in part based on the composition of that tissue.

[0207] The target sampling grid 2700 can include a plurality of points to be targeted for analysis (e.g., 2702, 2704, and 2706). The targets can be arranged in three-dimensional space. Thus, some of the target points are deeper in the target tissue than others. In this example, the target points can be arranged at the depths of three layers. Layer 1 (the deepest layer) is indicated by black dots and includes point 2702. Layer 2 (the middle layer) is indicated by right diagonal lines and includes point 2704. Layer 3 (the topmost layer) is indicated by vertical lines and includes point 2706. By orienting potential target points at different layer depths, the specimen estimation system can determine the types of tissue that make up the entire section of the user's tissue.

[0208] FIG. 28 is a flowchart showing an exemplary process for detecting a specimen within a target tissue according to an exemplary embodiment of the present disclosure. One or more parts of the method can be implemented by one or more computing devices, such as, for example, the computing devices described herein. Further, one or more parts of the method can be implemented as algorithms on the hardware components of the devices described herein. FIG. 28 shows elements executed in a particular order for purposes of illustration and explanation. Those skilled in the art will understand that any of the elements of the methods described herein can be adapted, rearranged, extended, omitted, combined and / or modified in various ways without departing from the scope of the present disclosure using the disclosure provided herein. The method can be implemented by one or more computing devices, such as one or more of the computing devices shown in FIG. 26.

[0209] An apparatus for non-invasively measuring the level of a specimen within a user using stimulated Raman scattering can include, at 2802, a Raman pump light source that emits pump light towards the skin surface of the user at a pump wavelength. The apparatus can further include, at 2804, a Stokes light source that emits Stokes light towards the skin surface at one or more Stokes wavelengths. The apparatus can further include one or more mirrors that are controlled to determine the region of the skin surface where the pump light and the Stokes light are targeted. The mirrors can be controlled to tilt one or more of the mirrors. Each mirror can be tilted independently. In other examples, the mirrors can be connected such that the tilt of one mirror depends on the tilt of one or more other mirrors. By tilting the mirrors, the position where the light projected by the Stokes light source and the Raman pump laser is targeted can be changed.

[0210] In some examples, the Raman pump light source and the Stokes light source can be laser diodes. For example, the laser diode can be a vertical cavity surface emitting laser (VCSEL). The Raman pump light source and the Stokes light source can be single-mode VCSELs. In another example, the laser diode can be an edge-emitting diode laser. Thus, the Raman pump light source and the Stokes light source can be an edge-emitting diode laser, a VCSEL, or another type of laser diode. In some examples, both the Raman pump light source and the Stokes light source can be the same type of laser diode. In other examples, the Raman pump light source and the Stokes light source can be different types of laser diodes.

[0211] In some examples, the apparatus includes one or more lenses that are controlled to determine the depth of focus of the Raman pump light source and the Stokes light source within the user's skin. The one or more lenses can be moved up and down (with respect to the apparatus and / or with respect to each other). For example, the one or more lenses can be attached to or otherwise connected to a screw that can be rotated to adjust the position of the lens. As long as the lens is circular, the rotation of the screw cannot change any characteristic of the projected light other than the depth of focus.

[0212] In 2806, the apparatus includes a beam controller that controls one or more mirrors and one or more lenses to target the pump light emitted by the Raman pump light source and the Stokes light emitted by the Stokes light source to an optimal target position. To do so, the beam controller can control the tilt of the one or more mirrors and the depth of focus of the one or more lenses.

[0213] The device can further include, at 2808, a photodetector that measures light emitted from the skin surface. In some examples, the device can include a collimator to ensure that the light emitted by the Raman pump light source and the light emitted by the Stokes light source are projected parallel to the user's skin surface. In some examples, one or more dichroic mirrors can combine the light from the Raman pump light source and the Stokes light source into a single light beam. The device can include focusing optics that focus the single light beam onto a specific region of the target sample (e.g., a region of the user's skin having a diameter of less than 10 microns). The focusing optics can include one or more lenses. In some examples, the device can include a waveguide instead of a dichroic mirror. In some examples, the device can include both a waveguide and one or more dichroic mirrors.

[0214] In some examples, the Raman pump light source and the Stokes light source can be configured to project light onto a region having a diameter of less than 10 microns. In some examples, the diameter of the region onto which the light is projected is 1 micron.

[0215] The device can include a target analysis system that identifies an optimal target position within the user's tissue for measuring a specimen. Identifying an optimal target position within the user's tissue can include generating a target sampling grid that includes a plurality of potential target points within a region of the tissue that can be targeted by a beam controller. In some examples, the points within the target sampling grid are arranged in a three-dimensional array. Thus, the target sampling grid includes points at different depths within the three-dimensional space within the tissue.

[0216] In some examples, for each of a plurality of potential target points, the apparatus uses a beam controller to direct the target of one or more light sources to each point. One or more of the light sources are initiated at a lower power. The lower power can be defined as lower than the power at which the light source is set when detecting the analyte. The apparatus can determine one or more frequencies absorbed by each point. The absorbed frequency can be determined based on a comparison between the frequency of the light projected by one or more light sources and the frequency of the light detected by a photodetector. One or more of the light sources include one or more of a Raman pump light source and a Stokes light source.

[0217] In some examples, the frequency of the light selected to be projected can be determined based on one or more specific tissue types. For example, the apparatus can select one or more frequencies that are most useful for differentiating between two or more tissue types that are most likely to be found at the current target location. If the apparatus determines that the two most likely tissue types (based on past measurements of tissue types from nearby measurements) are artery and interstitial fluid, the apparatus can select one or more frequencies that are most useful for differentiating between these two tissue types. In this way, the apparatus can minimize the number of frequencies used to detect the tissue type.

[0218] When the apparatus determines one or more frequencies absorbed by each target point, the apparatus can determine the tissue type at the target point. In some examples, the apparatus can determine that the tissue type at the target point can be one of blood vessels, interstitial cavities, nerve tissue, hair, or hair follicles, etc.

[0219] Once the type of tissue has been determined for each of the target points, the device can rank one or more potential target points based at least in part on the type of tissue associated with each of the one or more potential target points. The device can select an optimal target point from the one or more potential target points based on the ranking. In some examples, the one or more potential target points are ranked based at least in part on the specimen being detected. For example, a specimen is more easily detected in different types of tissue. Thus, the device can select an optimal target point at a location having a type of tissue useful for detecting the current target specimen.

[0220] The techniques described herein refer to servers, databases, software applications and other computer-based systems, as well as actions being performed, and information being transmitted to or from such systems. Those skilled in the art will recognize that the inherent flexibility of computer-based systems allows for various possible configurations, combinations and divisions of tasks and functions among components. For example, the server processes described herein may be implemented using a single server or multiple servers operating in combination. The database and application may be implemented in a single system or distributed among multiple systems. The distributed components may operate sequentially or in parallel.

[0221] Although the subject matter has been described in detail with respect to its particular exemplary embodiments, it will be understood by those skilled in the art that, having obtained the foregoing understanding, they can readily generate alterations to such embodiments, variations of such embodiments, and equivalents of such embodiments. Accordingly, the scope of the present disclosure is not limiting but exemplary, and the disclosure of the subject matter does not exclude the inclusion of such modifications, changes and / or additions to the subject matter that would be readily apparent to those skilled in the art.

Claims

1. An apparatus for non-invasively measuring the level of an analyte within a user using stimulated Raman scattering, a Raman pump light source that emits pump light towards the user's tissue at a pump wavelength, a Stokes light source that emits Stokes light towards the tissue at one or more Stokes wavelengths, one or more mirrors, one or more lenses, a beam controller that controls the one or more mirrors and the one or more lenses to direct the target of the pump light emitted by the Raman pump light source and the Stokes light emitted by the Stokes light source to an optimal target position, a photodetector that measures the light emitted from the tissue, a processor that processes the measured light and provides an estimated analyte level of the analyte within the user, and a target analysis system that identifies an optimal target position in the user's tissue for measuring the analyte. Identifying the optimal target position in the user's tissue includes generating a target sampling grid that includes a plurality of potential target points within the region of the tissue that can be targeted by the beam controller, Identifying the optimal target position in the user's tissue for each point of the plurality of potential target points, directing the target of one or more light sources to the respective point by the beam controller, starting the one or more light sources at a lower power, determining one or more frequencies absorbed by the respective point, An apparatus further comprising determining a type of tissue at each of the plurality of potential target points based on the one or more frequencies absorbed by the respective points. Claims 2. Determining the type of tissue at each of the plurality of potential target points includes selecting one or more frequencies that are most useful for distinguishing between two or more types of tissue that are most likely to be found at the current target point based on past measurement results of the type of tissue. The apparatus according to claim 1.

3. The one or more light sources include one or more of the Raman pump light source and the Stokes light source. The apparatus according to claim 1.

4. Identifying the optimal target position in the tissue of the user Ranking the plurality of potential target points based at least in part on the type of tissue associated with each of the plurality of potential target points; And selecting an optimal target point from the plurality of potential target points based on the ranking. The apparatus according to claim 1.

5. The plurality of potential target points are ranked based on the detectability of the specimen for each type of tissue. The apparatus according to claim 4.

6. The plurality of potential target points in the target sampling grid are arranged in a three-dimensional array. The apparatus according to claim 1.

7. The one or more lenses are adjusted by moving the one or more lenses up and down to adjust the depth of focus. The apparatus according to any one of claims 1 to 6.

8. The apparatus according to any one of claims 1 to 6, wherein the one or more mirrors are adjusted by tilting the mirrors to direct the pump light and the Stokes light to a specific target on the surface of the user's tissue.

9. The apparatus according to any one of claims 1 to 6, wherein the Raman pump light source and the Stokes light source are VCSELs.

10. The apparatus according to any one of claims 1 to 6, wherein the Raman pump light source and the Stokes light source are single-mode VCSELs.

11. The apparatus according to any one of claims 1 to 6, wherein the Raman pump light source and the Stokes light source are end-emitting diode lasers.

12. The apparatus according to any one of claims 1 to 6, wherein the Stokes light includes a plurality of narrowband emissions at respective center wavelengths within a window of Raman measurement wavelengths.

13. The apparatus according to any one of claims 1 to 6, wherein the beam controller controls the one or more lenses to adjust the depth of focus of the pump light emitted by the Raman pump light source and the Stokes light emitted by the Stokes light source.

14. The apparatus according to any one of claims 1 to 6, wherein the beam controller controls the one or more mirrors to direct the pump light emitted by the Raman pump light source and the Stokes light emitted by the Stokes light source onto the surface of the tissue where the target is defined.

15. A method implemented by a computer for non-invasively measuring the level of an analyte in a user using stimulated Raman scattering, comprising: emitting pump light from a Raman pump light source towards the user's tissue at a pump wavelength; emitting Stokes light from a Stokes light source towards the tissue at one or more Stokes wavelengths; The beam controller controls one or more mirrors and one or more lenses to determine the targets of the pump light emitted by the Raman pump light source and the Stokes light emitted by the Stokes light source at an optimal target position; The photodetector measures the light emitted from the tissue; The processor processes the measured light to provide an estimated analyte level of the analyte within the user; The target analysis system includes identifying an optimal target position in the tissue of the user for measuring an analyte; Identifying the optimal target position in the tissue of the user includes: Generating a target sampling grid, the target sampling grid including a plurality of potential target points within the region of the tissue that can be targeted by the beam controller; Identifying the optimal target position in the tissue of the user includes: For each point among the plurality of potential target points, Determining the targets of one or more light sources at each respective point by the beam controller; Starting the one or more light sources at a lower power; Determining one or more frequencies absorbed by each respective point; Further including determining the type of tissue at each of the plurality of potential target points based on the one or more frequencies absorbed by each respective point, a method implemented by a computer. The method according to claim 15, wherein the step of determining the type of tissue at each of the plurality of potential target points includes selecting one or more frequencies that are most useful for distinguishing between two or more types of tissue that are most likely to be found at the current target point based on past measurement results of the type of tissue. Claim 17 A specimen estimation system for non-invasively measuring the level of a specimen within a user using stimulated Raman scattering, the specimen estimation system comprising: A Raman pump light source that emits pump light toward the tissue of the user at a pump wavelength; A Stokes light source that emits Stokes light toward the tissue at one or more Stokes wavelengths; One or more mirrors; One or more lenses; A beam controller that controls the one or more mirrors and the one or more lenses to direct the target of the pump light emitted by the Raman pump light source and the Stokes light emitted by the Stokes light source to an optimal target position; A photodetector that measures the light emitted from the tissue; A processor that processes the measured light and provides an estimated specimen level of the specimen within the user; And a target analysis system that identifies an optimal target position in the tissue of the user for measuring the specimen. Identifying the optimal target position in the tissue of the user includes: Generating a target sampling grid that includes a plurality of potential target points within the region of the tissue that can be targeted by the beam controller; Identifying the optimal target position in the tissue of the user includes: For each point of the plurality of potential target points; The beam controller determines a target of one or more light sources at each of the respective points, starts the one or more light sources at a lower power, determines one or more frequencies absorbed at each of the respective points, and further includes determining the type of tissue at each of the plurality of potential target points based on the one or more frequencies absorbed at each of the respective points. A specimen estimation system. **Claim 18**: Determining the type of tissue at each of the plurality of potential target points includes selecting one or more frequencies that are most useful for distinguishing between two or more tissue types that are most likely to be found at the current target point based on past measurement results of the type of tissue. The specimen estimation system according to claim 17.

Images