System and method for non-invasive measurement of analytes in automobile drivers

Abstract

To provide a system and a method for non-invasively measuring a material to be analyzed in an automobile driver.SOLUTION: There is provided a system for non-invasively measuring a material to be analyzed in an automobile driver and controlling an automobile based on a measurement value of the material to be analyzed. At least one solid light source is configured to emit light of different wavelengths. A sample device is configured to introduce the light emitted by the at least one solid light source to a tissue of the automobile driver. One or more light detectors are configured to detect part of the light that is not absorbed by the tissue of the automobile driver. A controller is configured to calculate a measurement value of the material to be analyzed in the tissue of the automobile driver based on the light detected by the one or more light detectors, determine whether or not the measurement value of the material to be analyzed in the tissue of the automobile driver exceeds a predetermined value, and provide a signal to a device configured so as to control the automobile.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] (Citation of related patent applications) This application claims priority from U.S. Provisional Application No. 61 / 528,658, filed on 29 August 2011, which is incorporated herein by reference in its entirety.

[0002] This application relates, in general, to a system and method for non-invasively measuring analytes in motor vehicle drivers. More specifically, this application relates to a quantitative spectroscopic system for measuring the presence or concentration of analytes, such as alcohol, alcohol by-products, alcohol adducts, or abuse substances, using non-invasive techniques in combination with multivariate analysis. [Background technology]

[0003] Current practices for alcohol measurement are based on either blood testing or breath testing. Blood testing provides a benchmark for determining the level of alcohol dependence. However, blood testing requires either venous or capillary samples and involves significant handling care to minimize health risks. Once extracted, blood samples must be properly labeled and transported to a clinical laboratory or other suitable location, where clinical gas chromatography is typically used to measure blood alcohol levels. Due to the invasiveness of the procedure and the volume of sample handling involved, blood alcohol testing is usually limited to critical situations such as traffic accidents, violations in which a suspect requests this type of test, and accidents resulting in injury.

[0004] Due to its minimally invasive nature, breath testing is more commonly encountered in the field. In breath testing, the subject must exhale air into the device for sufficient time and volume to achieve a stable respiratory flow originating from the alveoli deep within the lungs. The device then measures the alcohol content in the air, related to blood alcohol, through the breath-blood partition coefficient. The breath-blood partition coefficient used in the United States is 2100 (implicit units of mg EtOH / dL blood per mg EtOH / dL air), while it varies between 1900 and 2400 in other countries. The variability of the partition coefficient is due to its highly subject-dependent nature. In other words, each subject will have a partition coefficient ranging from 1900 to 2400, depending on their own physiology. Because knowledge of each subject's partition coefficient is not available for field use, countries assume a single partition coefficient value that applies holistically to all measurements. In the United States, defendants in drunk driving cases often use the holistically applied partition coefficient as an argument to prevent prosecution.

[0005] Breath alcohol measurement has additional limitations. Firstly, the presence of "oral alcohol" can falsely inflate breath alcohol levels. This necessitates a 15-minute waiting period before measurement to ensure the absence of oral alcohol. For similar reasons, a 15-minute delay is required for individuals who are observed to belch or vomit. Often, a delay of 10 minutes or more is required between breath measurements to allow the device to return to equilibrium with ambient air and zero alcohol levels. In addition, the accuracy of breath alcohol measurement is sensitive to numerous physiological and environmental factors.

[0006] Multiple government agencies and the general public are seeking non-invasive alternatives to blood and breath alcohol measurement. Quantitative spectroscopy offers the possibility of completely non-invasive alcohol measurement, unaffected by the limitations of current measurement methodologies. Non-invasive determination of biological attributes by quantitative spectroscopy has proven highly desirable but is extremely difficult to achieve. Attributes of interest include, as examples, the presence of the analyte, the concentration of the analyte (e.g., alcohol concentration), the direction of change in the analyte concentration, the rate of change in the analyte concentration, the presence of a disease (e.g., alcoholism), the disease state, and combinations and subsets thereof. Non-invasive measurement via quantitative spectroscopy is desirable because it is painless, does not require fluid sampling from the body, carries little risk of contamination or infection, generates no hazardous waste, and can have a short measurement time.

[0007] Several systems have been proposed for non-invasive determination of biological tissue attributes. These systems have included techniques incorporating polarization analysis, mid-infrared spectroscopy, Raman spectroscopy, dye analysis, fluorescence spectroscopy, nuclear magnetic resonance spectroscopy, radio spectroscopy, ultrasound, transcutaneous measurements, photoacoustic spectroscopy, and near-infrared spectroscopy. However, these systems have not replaced direct and invasive measurements.

[0008] As an example, Robinson et al., in Patent Document 1, disclose a method and apparatus for measuring unknown properties in biological samples using infrared spectroscopy, in conjunction with a multivariate model experimentally derived from a wide variety of biological samples with a set of known characteristic values. The aforementioned properties are generally the concentration of the analyte, such as alcohol, but can also be any chemical or physical properties of the sample. Robinson et al.'s method involves a two-step process, including both calibration and prediction steps.

[0009] In the calibration step, infrared light is coupled to a calibration sample with known characteristic values, such that there is attenuation of infrared radiation at at least several wavelengths as a function of various components and analytes, including a sample with known characteristic values. The infrared light is coupled to the sample by passing the light through it or by reflecting the light from the sample. The absorption of infrared light by the sample causes variations in the intensity of the light, which is a function of the wavelength of the light. The resulting intensity variations at a minimum of several wavelengths are measured for a set of calibration samples with known characteristic values. The original, or transformed, intensity variations are then experimentally related to the known characteristics of the calibration sample using a multivariate algorithm to obtain a multivariate calibration model. The model preferably takes into account subject variability, instrument variability, and environmental variability.

[0010] In the prediction step, infrared light is coupled to a sample of unknown characteristic values, and a multivariate calibration model is applied to the original or converted intensity variations of the appropriate wavelength of light measured from this unknown sample. The results of the prediction step are estimates of the characteristics of the unknown sample. The disclosure by Robinson et al. is incorporated herein by reference.

[0011] Further methods for constructing calibration models and using these models to predict the attributes of the analyte and / or tissue are disclosed in Patent Document 2 by the same applicant to Thomas et al., entitled "Method and Apparatus for Tailoring Spectrographic Calibration Models," which is incorporated herein by reference.

[0012] In Patent Document 3, Robinson describes a general method for robust sampling of tissue for non-invasive analyte measurement. The sampling method utilizes a tissue sampling attachment whose path length is optimized by the spectral range for measuring the analyte, such as alcohol. This patent discloses several spectrometers for measuring the spectrum of tissue from 400 to 2500 nm, including acousto-optically variable filters, discrete wavelength spectrometers, filters, diffraction grating spectrometers, and FTIR spectrometers. Robinson's disclosure is incorporated herein by reference. [Prior art documents] [Patent Documents]

[0013] [Patent Document 1] U.S. Patent No. 4,975,581 [Patent Document 2] U.S. Patent No. 6,157,041 [Patent Document 3] U.S. Patent No. 5,830,112 [Overview of the Initiative] [Problems that the invention aims to solve]

[0014] Despite extensive research into producing commercially viable, non-invasive near-infrared spectroscopy-based systems for determining biological attributes, such devices are not currently available. The conventional systems discussed above are believed to have failed to fully address the challenges posed by the spectral characteristics of tissues, which make the design of non-invasive measurement systems an insurmountable task for one or more reasons. Therefore, there is a great need for a commercially viable device that incorporates subsystems and methods with sufficient accuracy and precision to perform clinical relevance determination of biological attributes in human tissues. [Means for solving the problem]

[0015] One embodiment of the present invention relates to a system for non-invasively measuring an analyte in a motor vehicle driver and controlling a motor vehicle based on the measured value of the analyte. The system includes at least one solid-state light source, a sample device, one or more photodetectors, and a controller. The at least one solid-state light source is configured to emit different wavelengths of light. The sample device is configured to introduce light emitted by the at least one solid-state light source into the motor vehicle driver's tissue. One or more photodetectors are configured to detect a portion of the light that is not absorbed by the motor vehicle driver's tissue. The controller is configured to calculate a measured value of the analyte in the motor vehicle driver's tissue based on the light detected by one or more photodetectors, determine whether the measured value of the analyte in the motor vehicle driver's tissue exceeds a predetermined value, and provide a signal to a device configured to control the motor vehicle.

[0016] Another embodiment of the present invention relates to a method for non-invasively measuring an analyte in a motor vehicle driver and controlling a motor vehicle based on the measured value of the analyte. A sample device introduces different wavelengths of light emitted by at least one solid-state light source into the motor vehicle driver's tissue. One or more photodetectors detect a portion of the light that is not absorbed by the motor vehicle driver's tissue. A controller calculates a measured value of the analyte in the motor vehicle driver's tissue based on the light detected by one or more photodetectors. The controller determines whether the measured value of the analyte in the motor vehicle driver's tissue exceeds a predetermined value and controls the motor vehicle based on the measured value of the analyte in the motor vehicle driver's tissue.

[0017] Additional features, advantages, and embodiments of this disclosure may be described by consideration of the embodiments, drawings, and claims for carrying out the invention described below. It should also be understood that both the above summary of this disclosure and the embodiments for carrying out the invention described below are illustrative and intended to provide further explanation without further limiting the claimed scope of this disclosure. For example, the present invention provides the following items: (Item 1) A system for non-invasively measuring an analyte in an automobile driver and controlling an automobile based on a measured value of the analyte, comprising: At least one solid light source configured to emit different wavelengths of light; A sample device configured to introduce the light emitted by the at least one solid light source into the tissue of the automobile driver; One or more photodetectors configured to detect a portion of the light not absorbed by the tissue of the automobile driver; Based on the light detected by the one or more photodetectors, calculate a measured value of the analyte in the tissue of the automobile driver, determine whether the measured value of the analyte in the tissue of the automobile driver exceeds a predetermined value, and provide a signal to a device configured to control the automobile; A system comprising: (Item 2) The system according to item 1, further comprising a biometric device configured to identify or verify the identity of the automobile driver. (Item 3) The biometric device collects a set of biometric data from the automobile driver, compares the set of biometric data with a set of registered data corresponding to an authorized automobile driver stored in the biometric device, and if applicable, identifies who among the authorized automobile drivers provided the set of biometric data. The system according to item 2. (Item 4) A predicted automobile driver provides an intended identity to the automobile, the biometric device collects a set of biometric data from the predicted automobile driver, and the biometric device compares the set of biometric data of the predicted automobile driver with the set of registered data corresponding to the intended identity of the predicted automobile driver to verify whether the actual identity of the predicted automobile driver is the intended identity of the predicted automobile driver. The system according to item 2. (Item 5) The system according to item 1, wherein the intensity of each solid-state light source is configured to be modulated independently. (Item 6) The system according to item 5, wherein the light emitted from each solid-state light source is configured to be incorporated into a single beam such that the light is always introduced into and collected from the tissue of the motor vehicle driver. (Item 7) The system according to item 6, wherein the light emitted from the at least one solid-state light source and the light detected by the one or more photodetectors have wavelengths between 1,000 nm and 2,500 nm. (Item 8) The system according to item 1, further comprising a microcontroller configured to turn on and off the at least one solid-state light source according to a set of states defined by a predetermined modulation scheme. (Item 9) The system according to item 1, wherein each solid-state light source is configured to be tuned to locations of a plurality of peak wavelengths such that the system is capable of measuring locations of more wavelengths than the number of solid-state light sources provided in the system. (Item 10) The system according to item 1, further comprising an optical homogenizer configured to provide uniform radiant luminance of the light introduced into the tissue of the motor vehicle driver by the sample device. (Item 11) The system according to item 1, wherein the measured value of the analyte includes the presence, concentration, rate of change of the concentration, direction of change of the concentration, or a combination thereof. (Item 12) The system according to item 1, wherein the measured value of the analyte is obtained using multivariate analysis. (Item 13) The system according to item 1, wherein a plurality of solid-state light sources are arranged in a planar array. (Item 14) The system according to item 1, wherein multiple solid light sources are divided into one or more groups, and each solid light source within one or more groups is placed on a common carrier for each group with a predetermined spacing between it and other solid light sources placed on the same common carrier. (Item 15) The system described in item 1, wherein multiple solid-state light sources are arranged so that they are located within a single semiconductor to form a laser bar. (Item 16) The laser bar comprises one or more groups of solid light sources, each group of solid light sources having the same wavelength but different from the wavelengths of adjacent groups of solid light sources, as described in item 1. (Item 17) The system described in item 1 is configured to measure more than one analyte. (Item 18) A method for non-invasively measuring an analyte in a motor vehicle driver and controlling the vehicle based on the measured value of the analyte, The sample device includes the step of introducing different wavelengths of light emitted by at least one solid-state light source into the tissue of the automobile driver, The steps include detecting a portion of the light that is not absorbed by the tissue of the automobile driver using one or more photodetectors, The controller performs the steps of calculating the measured value of the substance to be analyzed in the tissue of the automobile driver based on the light detected by the one or more photodetectors, The controller determines whether the measured value of the substance to be analyzed in the tissue of the automobile driver exceeds a predetermined value. A step of controlling the automobile based on the measured values ​​of the substance to be analyzed in the tissue of the automobile driver, Methods that include... (Item 19) The steps include: collecting a set of biometric data using a biometric device to identify the vehicle driver; The steps include comparing the set of biometric data with a set of registration data corresponding to an authorized motor vehicle driver previously stored in the biometric device using the biometric device, If applicable, the step of identifying which of the aforementioned certified motor vehicle drivers provided the set of biometric data, The method described in item 18, further including the method described in item 18. (Item 20) The steps include providing the vehicle with the intended identity by the predictive vehicle driver, The steps include: collecting a set of biometric data from the predicted vehicle driver using the biometric device; The steps include comparing the set of biometric data with the set of registration data corresponding to the intended identity of the predicted vehicle driver using the biometric device, The steps include: verifying, based on the comparison, whether the actual identity of the predicted driver is the intended identity of the predicted driver using the biometric device; The method described in item 18, further including the method described in item 18. (Item 21) The intensity of each solid-state light source is modulated independently, as described in item 18. (Item 22) The method according to item 18, further comprising the step of turning on and off the at least one solid light source by a microcontroller in accordance with a set of states defined by a predetermined modulation scheme. (Item 23) The measurement of the analyte according to the method of item 18, wherein the measurement of the analyte includes the presence, concentration, rate of change of the concentration, direction of change of the concentration, or a combination thereof. (Item 24) The measured values ​​of the analyte are obtained using multivariate analysis, as described in item 18. (Item 25) The method of item 18, further comprising the step of measuring more than one analyte. [Brief explanation of the drawing]

[0018] The accompanying drawings, incorporated herein and constituting part thereof, serve to illustrate preferred embodiments of the present invention and, together with the description, illustrate the principles of the present invention. No attempt has been made to illustrate structural details of the present disclosure in more detail than may be necessary for a basic understanding of the present disclosure and the various methods in which it may be put into practice. [Figure 1] Figure 1 is a schematic diagram of a non-invasive spectrometer system incorporating the disclosed subsystems. [Figure 2] Figure 2 is a schematic representation of the concept of net attribute signals within a three-component system. [Figure 3] Figure 3 shows an embodiment of an electronic circuit designed to control the drive current of a solid-state light source, including means for turning the light source on and off. [Figure 4] Figure 4 shows an embodiment of an electronic circuit designed to control the drive current of a solid-state light source, including means for turning the light source on and off and for changing a desired drive current. [Figure 5] Figure 5 shows an embodiment of an illumination / modulation subsystem comprising multiple individual solid-state light sources arranged in an array, the outputs of which are introduced into an internally reflective optical homogenizer with a hexagonal cross-section. [Figure 6] Figure 6 shows an embodiment of a single laser emitter within a semiconductor chip. [Figure 7] Figure 7 shows an embodiment of an illumination / modulation subsystem in which multiple laser emitters are mounted on a common carrier. [Figure 8] Figure 8 shows an embodiment of the illumination / modulation subsystem, depicting a laser bar consisting of a single semiconductor chip containing 24 emitters (12 different wavelengths, 2 emitters per wavelength). [Figure 9] Figure 9 is a schematic diagram of an optical fiber coupler embodiment that collects light emitted from each pair of emitters in the laser bar embodiment shown in Figure 8 and incorporates individual optical fibers into an output bundle or cable. [Figure 10]Figure 10 shows an embodiment in which the outputs of four different fiber couplers, each connected to a different laser bar, are combined into a single output aperture / bundle. [Figure 11] Figure 11 shows an example of an optical homogenizer suitable for homogenizing light from the output aperture / beam of an illumination / modulation subsystem. [Figure 12] Figure 12 is a perspective view of the elements of the tissue sampling subsystem. [Figure 13] Figure 13 is a plan view of the sampling surface of the tissue sampling subsystem, showing the arrangement of illumination and collection optical fibers. [Figure 14] Figure 14 shows an alternative embodiment of the sampling surface of the tissue sampling subsystem. [Figure 15] Figure 15 shows an alternative embodiment of the sampling surface of the tissue sampling subsystem. [Figure 16] Figure 16 shows an alternative embodiment of the sampling surface of a tissue sampling subsystem, optimized for small light-emitting regions of several solid-state light source-based illumination / modulation subsystems. [Figure 17] Figure 17 is a schematic diagram of the interface between the sampling surface and the tissue when a local interfering substance is present on the tissue. [Figure 18] Figure 18 is a schematic diagram of the data acquisition subsystem. [Figure 19] Figure 19 is a schematic diagram of the hybrid calibration formation process. [Figure 20] Figure 20 demonstrates the effectiveness of multivariate calibration outlier metric for detecting the presence of local interfering substances. [Figure 21] Figure 21 shows the normalized NIR spectrum of a 1300-3000K blackbody radiator in the range of 100-33000 cm⁻¹ (100-0.3 μm). [Figure 22] Figure 22 is a schematic diagram of the components of an exemplary embodiment of the present invention. [Figure 23] Figure 23 depicts non-invasive tissue spectra collected using 22 wavelengths. [Figure 24]Figure 24 compares the non-invasive tissue alcohol concentration obtained from the spectrum in Figure 23 with the simultaneous capillary blood alcohol concentration. [Figure 25] Figure 25 depicts non-invasive tissue spectra acquired using 39 wavelengths. [Figure 26] Figure 26 compares the non-invasive tissue alcohol concentration obtained from the spectrum in Figure 25 with the simultaneous capillary blood alcohol concentration. [Figure 27] Figure 27 depicts one of many possible embodiments of the measurement time series, including system calibration, measurement, and countermeasure time periods. [Figure 28] Figure 28 depicts a non-invasive monitoring system integrated into the vehicle's instrument panel as a vehicle start button. [Figure 29a] Figure 29a depicts a side view of a non-invasive measurement portal interface, where the emitter is a wavelength homogenizer directly connected to a wavelength light source. [Figure 29b] Figure 29b depicts a top view of the non-invasive measurement portal interface of Figure 29a, where the emitter is a wavelength homogenizer directly connected to a wavelength light source. [Figure 30] Figure 30 depicts the components of a non-invasive monitoring system that utilizes a wide-range tunable laser emitter to provide means for spectrally separated absorption measurements. [Figure 31] Figure 31 depicts one of many possible embodiments of a measurement time series that improves the average required measurement time, in which the first measurement detects the presence of the analyte and subsequent measurements determine the actual concentration of the analyte. [Figure 32] Figure 32 illustrates a non-invasive monitoring system in which primary analyte measurements are performed via a touch system and secondary measurements are performed via an alternative analyte detection system. [Figure 33] Figure 33 illustrates the components of a non-invasive monitoring system that utilizes a blackbody light source with filter elements to provide a selection of discrete wavelengths for the radiation source. [Figure 34]Figure 34 illustrates that, prior to intensity determination, the intensity of the light source is measured during the transition from the off state to the on state. [Modes for carrying out the invention]

[0019] Before referring to the drawings illustrating exemplary embodiments in detail, it should be understood that this disclosure is not limited to the details or methodologies described or illustrated in the description or in the drawings. It should also be understood that the terminology is for illustrative purposes only and should not be considered limiting. Efforts have been made to use the same or similar reference numerals throughout the drawings to refer to identical or similar parts.

[0020] For the purposes of this application, the term “analyte concentration” generally refers to the concentration of the analyte, such as alcohol. The term “analyte properties” includes the analyte concentration and other properties that can be measured in conjunction with or instead of the analyte concentration, such as the presence or absence of the analyte, the direction or rate of change of the analyte concentration, or biometrics. While this disclosure generally refers to alcohol as the “analyte” of interest, other analytes, including but not limited to abuse substances, alcohol biomarkers, and alcohol by-products, are also intended to be subject to the systems and methods disclosed herein. The term “alcohol” is used as an example of the “analyte” of interest, and is intended to include ethanol, methanol, ethyl glycol, or any other chemical substance commonly referred to as alcohol. For the purposes of this application, the term “alcohol by-products” includes, but not limited to, acetone, acetaldehyde, and acetic acid, adducts and by-products of the body’s metabolism of alcohol. The term “alcohol biomarkers” includes, but is not limited to, gamma glutamine transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), mean corpuscular volume (MCV), carbohydrate-deficient transferrin (CDT), ethyl glucuronide (EtG), ethyl sulfate (EtS), and phosphatidylethanol (PEth). The term “abuse substance” refers to, but is not limited to, THC (tetrahydrocannabinol or marijuana), cocaine, M-AMP (methamphetamine), OPI (morphine and heroin), oxycontin, oxycodone, and PCP (phencyclidine). The term “biometric” refers to an analyte or biological characteristic that can be used to identify or verify the identity of a particular individual or subject. This application discloses systems and methods that address the need for measuring the analyte of a sample using spectroscopy, where the term “sample” generally refers to a biomeasurement. The term "subject" generally refers to the individual from whom the sample measurement was collected.

[0021] The terms “solid-state light source” or “semiconductor light source” refer to all semiconductor-based light sources, whether spectrally narrow (e.g., lasers) or broad (e.g., LEDs), including but not limited to light-emitting diodes (LEDs), vertical-cavity surface-emitting lasers (VCSELs), horizontal-cavity surface-emitting lasers (HCSELs), quantum cascade lasers, quantum dot lasers, diode lasers, or other semiconductor diodes or lasers. The term “diode laser” refers to any laser based on a semiconductor, including but not limited to double heterostructure lasers, quantum well lasers, quantum cascade lasers, separate confinement heterostructure lasers, distributed-recovery-based (DFB) lasers, VCSELs, VECSELs, HCSELs, external cavity diode lasers, and Fabry-Perot lasers, where the active medium is a semiconductor. Furthermore, plasma light sources and organic LEDs, although not strictly semiconductor-based, are also considered in embodiments of the present invention and are therefore included under the definitions of solid-state light sources and semiconductor light sources for the purposes of this application.

[0022] For the purposes of this application, the term “dispersive spectrometer” refers to a spectrometer based on any device, component, or group of components that spatially separates one or more wavelengths of light from other wavelengths. Examples include, but are not limited to, spectrometers using one or more diffraction gratings, prisms, or holographic gratings. For the purposes of this application, the term “interference / modulation spectrometer” refers to a type of spectrometer based on the optical modulation of different wavelengths of light to different frequencies in time, or on the properties of optical interference that selectively transmit or reflect certain wavelengths of light. Examples include, but are not limited to, Fourier transform interferometers, Sagnac interferometers, Mock interferometers, Michelson interferometers, one or more etalons, or acousto-optically tuned filters (AOTFs). Those skilled in the art will recognize that spectrometers based on a combination of dispersion and interference / modulation properties, such as spectrometers based on lamellar gratings, are also considered to be used in conjunction with the systems and methods disclosed herein.

[0023] The present application discloses the use of “signals” as absorbance or other spectroscopic measurements in some of its embodiments. The signals may include any measurements obtained in relation to a spectroscopic measurement of a sample or a change in the sample, e.g., absorbance, reflectance, intensity of light to be restored, fluorescence, transmittance, Raman spectrum, or various combinations of measurements at one or more wavelengths. Some embodiments utilize one or more models, which may be any model that relates the signal to a desired property. Some embodiments of models include those derived from multivariate analysis methods such as partial least squares regression (PLS), linear regression, multiple linear regression (MLR), classical least squares regression (CLS), neural networks, discriminant analysis, principal component analysis (PCA), principal component regression (PCR), discriminant analysis, neural networks, cluster analysis, and K-nearest neighbors. Single or multi-wavelength models based on the Lambert-Beer law are special cases of classical least squares and are therefore included in the term multivariate analysis for the purposes of the present application.

[0024] For the purposes of this application, the term “approximately” applies to all numerical values, whether expressly indicated or not. Generally, the term “approximately” refers to a set of numbers that a person skilled in the art would consider equivalent to (i.e., having the same function or result as) the stated value. In some cases, the term “approximately” may include numbers rounded to the nearest significant figure.

[0025] Spectroscopic measurement systems typically require several means to resolve and measure different wavelengths of light in order to acquire a spectrum. Some common approaches to achieving a desired spectrum include dispersion (e.g., lattice and prism-based) spectrometers and interference (e.g., Michelson, Sagnac, or other interferometers) spectrometers. Non-invasive measurement systems incorporating such approaches are often limited by the expensive nature of dispersion and interference devices, as well as their inherent size, fragility, and susceptibility to environmental impacts. This application discloses a system and method that can provide an alternative approach to resolving and recording the intensity of different wavelengths using solid-state light sources such as light-emitting diodes (LEDs), vertical-cavity surface-emitting lasers (VCSELs), horizontal-cavity surface-emitting lasers (VCSELs), diode lasers, quantum cascade lasers, or other solid-state light sources.

[0026] In general, referring to the figures, the disclosed system overcomes the challenges posed by the spectral characteristics of tissue by incorporating a design that includes optimized subsystems in some embodiments. This design addresses the complexities of tissue spectra, high signal-to-noise ratio and photometric accuracy requirements, tissue sampling errors, calibration maintenance issues, calibration shift issues, and numerous other problems. The subsystems may include an illumination / modulation subsystem, a tissue sampling subsystem, a data acquisition subsystem, a computer subsystem, and a calibration subsystem.

[0027] Apparatus and methods for non-invasive determination of human tissue attributes by quantitative near-infrared spectroscopy are disclosed herein. The system includes subsystems optimized to address complexities such as noise ratio and photometric accuracy requirements, tissue sampling errors, calibration maintenance issues, and calibration shift issues. These subsystems include an illumination / modulation subsystem, a tissue sampling subsystem, a data acquisition subsystem, and a computer subsystem.

[0028] The present invention further discloses apparatus and methods that enable the implementation and integration of each of these subsystems in order to maximize the net attribute signal-to-noise ratio. The net attribute signal is a portion of the near-infrared spectrum that is specific to the attribute of interest because it is perpendicular to all other spectral dispersion sources. The orthogonality of the net attribute signal makes it perpendicular to the space defined by any interference species, and as a result, the net attribute signal is uncorrelated with these dispersion sources. The net attribute signal-to-noise ratio is directly related to the accuracy and precision of non-invasive determination of attributes by quantitative near-infrared spectroscopy.

[0029] This application discloses the use of near-infrared radiation for analysis in the wavelength range of 1.0 to 2.5 microns (or 10,000 to 4,000 cm²). -1 Emissions within the wavelength range (wavenumber range) may be suitable for some non-invasive measurements because they exhibit acceptable specificity to several analytes, including alcohols, along with a tissue light transmission depth of up to several millimeters, accompanied by acceptable absorbance characteristics. In the spectral region of 1.0–2.5 microns, numerous optically active substances constituting tissue complicate the measurement of any given substance due to the overlapping nature of their absorbance spectra. Multivariate analytical techniques can be used to resolve these overlapping spectra so that accurate measurement of the substance of interest can be achieved. However, multivariate analytical techniques may require that the multivariate calibration remain robust over time (calibration maintenance) and be applicable to multiple instruments (calibration shift). Other wavelength regions, such as visible light and infrared light, may also be suitable for the disclosed systems and methods.

[0030] This application discloses a multi-specialized approach to the design of spectroscopic instruments that incorporates an understanding of instrument subsystems, tissue physiology, multivariate analysis, near-infrared spectroscopy, and overall system operation. Furthermore, the interactions between subsystems have been analyzed to ensure that the behavior and requirements of the entire non-invasive measurement device are well understood, leading to the design of a commercial instrument that will perform non-invasive measurements with sufficient accuracy and precision at a commercially viable price and size.

[0031] The present invention also discloses systems and methods for use with the unique sensing requirements of transport systems, including but not limited to motorcycles, automobiles, trucks, ships, trains, and aircraft, the systems of which must operate across a wide range of environments including temperature, atmospheric pressure, altitude, humidity, mechanical orientation, ambient lighting, and environmental components (e.g., salt, sand, dust, smoke). The disclosed systems may operate across a full range of potential users, identifiable through differences in weight, height, age, race, sex, health, health level, and other factors that distinguish humans. The disclosed systems may remain functional throughout the entire lifespan of the vehicle and may maintain diagnostics and indicators indicating required maintenance or available unit replacement. The disclosed systems may provide a human-machine interface that provides visual, tactile, and audible feedback to inform the system user of correct or incorrect measurements. The systems may provide diagnostics and user feedback indicating correct or incorrect measurements, including detection of intentional or unintentional system tampering or measurement spoofing. The systems may maintain an operating model that can be enabled / disabled based on administrative controls (e.g., passwords). This system can provide one or more communication and / or power interfaces to external transport enablement or human-machine interface systems using one or more existing or developed communication protocols to receive data and / or power required for system operation, or to enable, disable, or modify the operation of external systems. This system can support the ability to enable measurement accuracy and precision verification or calibration during manufacturing, installation, and / or inspection through prosthetic reference devices.

[0032] The non-invasive monitor subsystem is highly optimized to provide tissue reproducibility, preferably uniform radiance, low tissue sampling error, depth targeting of tissue layers containing the desired properties, efficient collection of diffuse reflectance spectra from tissue, high optical throughput, high photometric accuracy, wide dynamic range, excellent thermal stability, effective calibration maintenance, effective calibration transfer, built-in quality control, and ease of use.

[0033] Referring here to Figure 1, a non-invasive monitor capable of achieving an acceptable level of accuracy and precision in measuring the properties of the analyte is schematically depicted. For discussion purposes, the overall system can be considered to comprise five subsystems. Those skilled in the art will understand the other subdivisions of the disclosed functionality. This subsystem includes an illumination / modulation subsystem 100, a tissue sampling subsystem 200, a data acquisition subsystem 300, a processing subsystem 400, and a calibration subsystem (not shown).

[0034] This subsystem can be designed and integrated to achieve a desired net attribute signal-to-noise ratio. The net attribute signal is the portion of the near-infrared spectrum that is specific to the desired attribute because it is perpendicular to other spectral dispersion sources. Figure 2 shows a schematic representation of the net attribute signal in a three-dimensional system. The net attribute signal-to-noise ratio is directly related to the accuracy and precision of non-invasive attribute determination by quantitative near-infrared spectroscopy.

[0035] This subsystem provides tissue reproducibility and, preferably, spatially uniform radiance, low tissue sampling error, appropriate depth targeting of tissue layers, efficient collection of diffuse reflectance spectra from tissue, high optical throughput, high photometric accuracy, wide dynamic range, excellent thermal stability, effective calibration maintenance, effective calibration transfer, built-in quality control, and ease of use. Each of the subsystems will be discussed in further detail below.

[0036] (Lighting / Modulation subsystem) The illumination / modulation subsystem 100 generates light used to examine a sample (e.g., human skin tissue). In classical spectroscopy using a dispersion or interference spectrometer, the spectrum of a multicolor light source (or light emitted from a sample of interest) is measured by spatially dispersing different wavelengths of light (e.g., using a prism or diffraction grating) or by modulating different wavelengths of light to different frequencies (e.g., using a Michelson interferometer). In these cases, the spectrometer (a subsystem distinct from the light source) is required to perform the function of "encoding" different wavelengths, either spatially or temporally, so that each wavelength can be measured substantially independently of the others. While dispersion and interference spectrometers are well known in the art and can adequately perform their functions in some environments and applications, they may be limited in other applications and environments by their cost, size, fragility, signal-to-noise ratio (SNR), and complexity.

[0037] An advantage of the solid-state light sources incorporated into the disclosed system is that the intensity of the light sources can be independently modulated. Therefore, multiple solid-state light sources emitting different wavelengths of light can be used, each modulated at a different frequency or collectively modulated according to a predefined scheme such as that defined by Hadamard or a similar approach. The independently modulated solid-state light sources can be optically incorporated into a single beam and introduced into the sample. A portion of the light can be collected from the sample and measured by a single photodetector. The result is an effective integration of solid-state light sources and a spectrometer into a single illumination / modulation subsystem, which can provide significant benefits in size, cost, energy consumption, and overall system stability, as the spectrometer as a separate subsystem is eliminated from the measurement system. Furthermore, since all wavelengths can be independently modulated and incorporated into a single beam, a single-element photodetector (rather than an array of photodetectors) is preferred for detecting all analytical light. This can represent a significant reduction in system complexity and cost compared to systems and embodiments involving multiple photodetector elements.

[0038] While not a limitation, several parameters of the system for measuring the properties of the analyte, incorporating solid-state light sources, must be considered, including the number of solid-state light sources required to perform the desired measurement, the emission profiles of the solid-state light sources (e.g., spectral width, intensity), the stability and control of the solid-state light sources, and their optical combination. Since each solid-state light source is a discrete element, it may be advantageous to combine the outputs of multiple solid-state light sources into a single beam so that they are always introduced and collected from the sample.

[0039] Furthermore, since some types of light sources may be susceptible to sinusoidal modulation of intensity, and others may be affected by switching on and off or by square wave modulation, the modulation scheme for solid-state light sources must also be considered. In the case of sinusoidal modulation, multiple solid-state light sources can be modulated at different frequencies based on the electronic design of the system. The light emitted by multiple light sources can be optically combined, for example, using an optical pipe or other homogenizer, introduced and collected from the sample of interest, and then measured by a single detector. The resulting signal can be converted to intensity relative to the wavelength spectrum via Fourier or analogous transforms.

[0040] Alternatively, some solid-state light sources, which are susceptible to the Hadamard transform approach, are switched between on and off states or square-wave modulated. However, in some embodiments, the Hadamard method can be implemented in electronic devices because the solid-state light source can be circulated at higher frequencies, rather than the conventional Hadamard mask which blocks or passes different wavelengths at different times during measurement. The Hadamard or analogous transform can be used to determine the intensity compared to the wavelength spectrum. Those skilled in the art will recognize that there are alternatives to the Hadamard coding approach that are equally suitable for the present invention.

[0041] In one embodiment, a 47-wavelength Hadamard coding approach is used and is depicted as a binary matrix. Each row corresponds to one state in the Hadamard scheme, and each column corresponds to a wavelength in the measurement system. For each state, a value of "1" indicates that the wavelength (e.g., a laser diode) is on for that state, while a value of "0" indicates that the wavelength is off for that state. Each measurement for each state corresponds to one scan. Light emitted by the illumination / modulation subsystem 100 is delivered to the sample by the sampling subsystem 200. A portion of this light is collected, detected, digitized, and recorded by a photodetector in the data acquisition subsystem 300. The next state in the Hadamard scheme (e.g., a different set of wavelengths is on for that state) is then measured and recorded. This continues until all Hadamard states have been measured (referred to herein as a "Hadamard cycle"). Once the Hadamard cycle is complete, the intensity relative to the wavelength spectrum is determined by calculating the dot product of the recorded intensity-vs-state data and the inverse matrix of the Hadamard scheme. The embodiment of Hadamard coding described above consists of 47 wavelengths, but those skilled in the art will recognize that Hadamard schemes with other numbers of wavelengths are equally suitable for the present invention.

[0042] Another advantage of solid-state light sources is that many types (e.g., laser diodes and VCSELs) emit within a narrow range of wavelengths (partially determining the effective resolution of the measurement). As a result, because the range is already narrow enough, it is not necessary to shape or reduce the emission profile of the solid-state light source using optical filters or other approaches. This can be advantageous in terms of reduced system complexity and cost. Furthermore, the emission wavelengths of some solid-state light sources, such as diode lasers and VCSELs, can be tuned across a range of wavelengths, either via supplied drive current, drive voltage, or by varying the temperature of the solid-state light source. The advantage of this approach is that, if a given measurement requires a specific number of wavelengths, the system can achieve the requirements using fewer discrete solid-state light sources by tuning across a viable range of those wavelengths. For example, if a non-invasive measurement requires 20 wavelengths, 10 discrete diode lasers or VCSELs could be used, each of which tunes to two different wavelengths during the course of the measurement. In this type of scheme, the Fourier or Hadamard approach remains appropriate by varying the modulation frequency for each tuning point of the solid-state light source, or by combining the modulation scheme with the scanning scheme. Furthermore, if the emission wavelength for a given laser shifts or changes over time, the tuning properties of the diode laser allow it to be returned to its target emission wavelength by changing its drive current / voltage, temperature, or a combination thereof.

[0043] The properties of the analyte can be measured at various wavelengths in the electromagnetic spectrum, extending to the ultraviolet and infrared regions. For in vivo measurements of alcohol or abused substances in the skin, the near-infrared (NIR) region from 1,000 nm to 2,500 nm may be important depending on the sensitivity and specificity of the spectral signal to the target analyte and other chemical species present in human skin (e.g., water). Furthermore, the absorbency of the analyte is low enough that near-infrared light can penetrate several millimeters into the skin where the target analyte is present. The wavelength range of 2,000 nm to 2,500 nm may be particularly useful because it contains a complex band rather than the weaker, less specific harmonics encountered in the 1,000 to 2,000 nm portion of the NIR spectrum.

[0044] In addition to commercially available LEDs, VCSELs, and diode lasers in the visible region of the spectrum, solid-state light sources are available with emission wavelengths throughout the entire NIR region (1,000–2,500 nm). These solid-state light sources are suitable for the disclosed analytes and biometric property measurement systems. Some examples of available NIR solid-state light sources are VCSELs produced by Vertilas MmbH, VCSELs available from Laser Components MmbH, quantum cascade lasers, laser diodes, or lasers and diodes available from Roithner Laser, Sacher Lasertechnik, NanoPlus, Mitsubishi, Epitex, Dora Texas Corporation, Microsensor Tech, SciTech Instruments, Laser 2000, Redwave Labs, and Deep Red Tech. These examples are included for demonstration purposes and are not intended to limit the types of solid-state light sources suitable for use with the present invention.

[0045] A microcontroller can be used to control each solid light source in an embodiment of the illumination / modulation subsystem 100. The microcontroller can be programmed to include states defined by Hadamard or other coding schemes (for example, individual solid light sources are turned on and off according to a set of states defined by the scheme). The microcontroller can then repeat each state with a predetermined measurement time for each state. There is no restriction that the measurement times for each state must be equal. In addition to "off" and "on" control of each solid light source, the microcontroller can also provide global (across all solid light sources) and individual setpoints for the temperature and drive current / voltage of the solid light sources. Such embodiments enable improved control and / or stability of the wavelength tuning of the illumination / modulation subsystem 100. Those skilled in the art will recognize that alternative microcontrollers are available that perform substantially the same functions as the microcontroller embodiments described.

[0046] (Measurement resolution and resolution enhancement) In dispersive spectrometers, the effective resolution of a spectroscopic measurement is often determined by the width of the aperture in the system. The resolution limit aperture is often the width of the entrance slit. At the focal plane where light is detected within the spectrometer, multiple images of the slit are formed at different wavelengths located at different spatial positions on the focal plane. Therefore, the ability to detect a single wavelength independent of its vicinity depends on the width of the slit. A narrower width allows for better resolution between wavelengths at the expense of the amount of light that can pass through the spectrometer. As a result, resolution and signal-to-noise ratio generally cancel each other out. Interferometric spectrometers have a similar cancellation between resolution and signal-to-noise ratio. In the case of a Michelson interferometer, the spectral resolution is partly determined by the distance the movable mirror is translated, with longer distances yielding better resolution. The result is that the greater the distance, the more time is required to complete the scan.

[0047] In measurement systems, spectral resolution is determined by the spectral width of each discrete solid-state light source (whether different solid-state light sources, solid-state light sources tuned to multiple wavelengths, or a combination thereof). For measuring the properties of the analyte requiring high resolution, diode lasers or other suitable solid-state lasers can be used. The emission width of the laser can be very narrow, resulting in high resolution. For measurement applications requiring modulation to low resolution, LEDs may be preferable because they typically have a broader emission profile (output intensity distributed over a wide range of wavelengths) than solid-state laser alternatives.

[0048] The effective resolution of a solid-state light source can be enhanced through the use or combination of different types of optical filters. The spectral width of a solid-state light source can be reduced or attenuated using one or more optical filters to achieve higher resolution (e.g., a tighter range of emission wavelengths). Examples of optical filters considered in embodiments of the present invention include, but are not limited to, linearly variable filters (LVFs), dielectric stacks, distributed Bragg gratings, photocrystal grating filters, polymer films, absorption filters, reflection filters, dispersion elements such as etalons, prisms and gratings, and quantum dot filters.

[0049] Another means for improving the resolution of measurements obtained from embodiments of the present invention is deconvolution. Deconvolution and other similar approaches can be used to isolate signal differences present between two or more overlapping broad solid light sources. For example, two solid light sources with partially overlapping emission profiles can be incorporated into a measurement system. Measurements can be collected from a sample, and spectra can be generated (via Hadamard, Fourier transform, or other suitable transforms). Having obtained the emission profiles of the solid light sources, the profiles can be deconvolved from the spectra to enhance the resolution of the spectra.

[0050] (Stabilization and control of wavelength and intensity of solid-state light sources) The peak emission wavelength of solid-state light sources, particularly lasers, can be affected by changing the thermal state or electrical properties (e.g., drive current or voltage) of the solid-state light source. In the case of semiconductor lasers, changing the thermal state or electrical properties alters the optical properties or physical dimensions of the semiconductor lattice structure. The result is a change in the spacing of cavities within the device, which alters the emitted peak wavelength. Because solid-state light sources exhibit these effects, the stability of the peak emission wavelength and its associated intensity can be important parameters when they are used in spectroscopic measurement systems. Consequently, measurement control of both the thermal state and electrical properties of each solid-state light source can be advantageous in terms of overall system robustness and performance. Furthermore, changes in optical properties caused by the thermal state or electrical properties can be leveraged to enable a single solid-state light source to be tuned to multiple peak wavelength locations. This can result in an analyte property measurement system that can measure more wavelength locations than the number of discrete solid-state light sources, which can reduce system cost and complexity.

[0051] Temperature stabilization can be achieved using multiple approaches. In some embodiments, one or more solid-state light sources can be stabilized by raising (or cooling) their temperature above (or below) ambient conditions without additional temperature control. In other embodiments, one or more solid-state light sources can be actively controlled (either cooled or heated) to a set temperature using a control loop. For example, a suitable temperature loop circuit for embodiments of the present invention may include a TE-Cooled VCSEL package comprising a thermoelectric cooler and a precision thermistor. The precision thermistor may be connected to a Wheatstone bridge, which can be connected to a current-driven circuit configured to drive the thermoelectric cooler.

[0052] The electrical properties of a solid-state light source also affect its emission profile (e.g., the location of the emission wavelength). Stabilizing the current and / or voltage supplied to one or more solid-state light sources can be advantageous. For example, the peak emission of VCSELs and many diode lasers depends on the drive current. For embodiments where peak wavelength stability is important, drive current stability becomes a key performance indicator. In such cases, electronic circuits can be designed to supply a stable drive current to the VCSEL or diode laser. The complexity and cost of the circuit may depend on the required stability of the drive current. Figure 3 shows a current drive circuit suitable for use with embodiments of the present invention. Those skilled in the art will recognize that alternative embodiments of the current control circuit are known in the art and may also be suitable for the present invention. Furthermore, some solid-state light sources require control of the drive voltage rather than the drive current, and those skilled in the art will recognize that electronic circuits designed to control voltage rather than current are readily available.

[0053] In some embodiments, a single solid-state light source, such as a VCSEL or diode laser, is tuned to multiple wavelengths during the course of the measurement. To achieve tuning of the solid-state light source, the circuit shown in Figure 3 can be modified to include temperature setpoint and current control, respectively. In some embodiments, tuning of either temperature or drive current / voltage may be sufficient to achieve the desired tuning of the peak emission wavelength. In other embodiments, control of both temperature and drive current / voltage may be required to achieve the desired tuning range.

[0054] Furthermore, optical means for measuring and stabilizing the peak emission wavelength can also be incorporated into the system described in relation to embodiments of the present invention. A Fabry-Perot etalon can be used to provide a relative wavelength standard. The free spectral range and finesse of the etalon can be specified to provide an optical passband that enables active measurement and control of the peak wavelength of the VCSEL or diode laser. An example embodiment of this etalon uses a thermally stabilized, flat fused silica plate with a partial mirror surface. For a system in which each VCSEL or diode laser is required to provide multiple wavelengths, the free spectral range of the etalon can be selected such that its transmitted peaks match a desired wavelength interval for tuning. Those skilled in the art will recognize that there are many optical configurations and electronic control circuits that are viable for this application. Alternative wavelength coding schemes use dispersed gratings and secondary array detectors to code the VCSEL or diode laser wavelengths to spatial positions on an array. For either the dispersed or etalon-based scheme, secondary photodetectors can be used that have less stringent performance requirements than the primary photodetector. Active control can reduce the stability requirements of VCSEL temperature and current control circuits by enabling real-time compensation for arbitrary drifts.

[0055] (Embodiments and approaches for multi-wavelength illumination / modulation subsystems) Figure 5 shows an example embodiment of an illumination / modulation subsystem 100 in which 10 individual solid-state light sources 101 are arranged in a planar array. In some embodiments of Figure 5, the solid-state light sources 101 are individually housed in their own packages, such as TO-9, TO-56, or other standard packages. These packages may or may not be sealed with a translucent window. In other embodiments, the solid-state light sources 101 may be placed on a common carrier, and the resulting assembly may be placed in a housing. The housing may or may not be sealed. The temperature of each solid-state light source 101 may be controlled independently, and each solid-state light source 101 may have its own means for controlling the temperature, or may collectively use a single means for controlling the temperature.

[0056] Light emitted by the solid-state light source 101 is collected and homogenized by the homogenizer 102 (Figure 5) and delivered to the input of the sampling subsystem 200. In some embodiments of the present invention, packaging density (how close the individual solid-state light sources 101 can be placed relative to each other) is disadvantageous and limits the number of solid-state light sources 101 that can be used. In such embodiments, means for aggregating the light emitted by the solid-state light sources 101 into a smaller area may be advantageous. Means for efficient aggregation of light and coupling to the sampling subsystem 200 are discussed in subsequent paragraphs.

[0057] In some embodiments, alternatives to a planar array of discrete solid-state light sources are employed. An example of a discrete solid-state light source 101, a laser diode, is shown in Figure 6 and consists of a semiconductor chip 103 and a laser emission aperture 104.

[0058] In another embodiment, a cumulative number of individual solid-state light sources 101 are divided into one or more groups. Each solid-state light source 101 within one or more groups is placed on a common carrier 105 with a predetermined spacing between it and the other solid-state light sources 101 (one carrier per group). This approach is referred to as the light source "carrier" 104 and is illustrated in Figure 7. The carrier 105 may be formed from, for example, ceramic. In this embodiment, different wavelengths can originate from different light sources, e.g., different wafers diced into laser chips. Multiple laser chips may form the solid-state light source 101. This allows multiple wavelengths to be adapted by combining lasers from several light sources (wafers, different vendors, etc.). The advantages of this approach are a smaller number of solid-state light source assemblies and known relationships between the locations of the solid-state light sources. This, in turn, allows for the possibility of a reduced number of temperature-controlled packages for controlling individual solid-state light sources. Furthermore, because the solid-state light sources within the package are in fixed, known locations relative to each other, a more efficient photo-coupling approach is enabled.

[0059] In other embodiments, multiple solid-state light sources are located within the same physical semiconductor to further reduce the number of components in the illumination / modulation subsystem 100. In such embodiments, the solid-state light sources 101 within the semiconductor may be of the same wavelength, different wavelengths, or a combination thereof. When the solid-state light sources 101 are laser diodes or other solid-state lasers, these embodiments are referred to as a “laser bar” 106. Similar to the carrier embodiments, the advantage of the laser bar 106 is the very well-characterized and identified location of each solid-state light source 101. Overall, the laser bar 106 results in a significant reduction in the number of discrete semiconductors, the total number of system components, and therefore the subsystem complexity and cost.

[0060] To increase the light intensity at the same wavelength, multiple solid-state light sources 101 of that wavelength can be used. In some embodiments, solid-state light sources 101 of the same wavelength are adjacent to and very close to each other to enable efficient optical coupling. Figure 8 shows a laser bar 106 consisting of 12 groups of two laser diodes (24 laser emitters in total). Two lasers forming a pair 107 have a common wavelength, and each pair 107 has a different wavelength from the other pair (in this embodiment, 12 distinctly different wavelengths across the bar 106). Each pair 107 is spaced 480 microns apart from adjacent pairs 107, and the distance between the two emitters 101 of a pair 107 is 5 microns. In embodiments employing DFB diode lasers, different wavelengths are achieved using a single semiconductor chip by applying gratings with different pitches to each pair 107. The emission of a DFB laser is generally single-mode, which is advantageous in some embodiments. Those skilled in the art will recognize the all-solid-state light sources 101 and numerous permutations of their emission wavelengths, which are encompassed by the carrier 105 and bar embodiment 106. The embodiments disclosed herein are not intended to limit the scope of the present invention.

[0061] In some embodiments, dedicated thermoelectric coolers for each emitter can be orders of magnitude more expensive and larger, and a single global cooler or temperature control may not provide sufficient local temperature control. In such cases, local temperature control within the semiconductor can be achieved using local heating equipment near a solid light source. Embodiments of the heating equipment are local resistors near a solid light source that allow the applied current to be converted into local heat. This approach allows a single temperature control equipment to apply the majority of the heating / cooling load, while the local equipment allows for fine-tuning of each solid light source. This enables both a greater degree of stability and the ability to tune the emission wavelength of each laser by varying the local temperature.

[0062] (Strategies for efficient coupling of solid-state light sources to sampling subsystems) Regardless of whether the solid light sources of the embodiment reside in individual packages or are grouped on a smaller number of carriers or bars, there is always a finite distance between adjacent solid light sources, and therefore the density of emission apertures of solid light sources is not ideal. This spacing can be driven, for example, by the size of the individual solid light source packages, as well as the need for the finite spacing to allow heat to dissipate. In some embodiments of the present invention, the density of emission apertures is not a concern, and the outputs of the individual solid light sources can be collected, combined, and homogenized using an optical homogenizer whose cross-section is large enough to encompass the emission apertures of all solid light sources in the illumination / modulation subsystem 100. However, in this case, the photon flux at the output of the optical homogenizer is lower than ideal because the light from the solid light sources is distributed substantially uniformly across the entire cross-sectional area. This corresponds to a reduction in the etendue of the system, which can be disadvantageous in some embodiments.

[0063] In embodiments where etendue reduction should be minimized, there are several strategies for more efficiently combining the outputs of the emission apertures of individual solid-state light sources. Some embodiments of the present invention incorporate optical fibers 108 as means for collecting light from a solid-state light source 101 or a pair of solid-state light sources 107 and combining it with light collected from other solid-state light sources 101 or pairs of solid-state light sources 107 in the system (see Figure 9). Multiple individual optical fibers 108 may be bundled together in a cable 109. In one embodiment, as shown in Figure 13, the fiber 108 collects light from each of 12 solid-state light sources 101 or pairs of solid-state light sources 107. The 12 fibers 108 can be bundled together in a cable 109. The emission apertures of many solid-state light sources may have a diameter of about a few microns. Some embodiments of the present invention may use large-core multimode optical fibers (in contrast to small-core single-mode fibers often used in telecommunications). The large fiber diameter relative to the small diameter of the emission aperture allows the optical fiber to collect light from the emission aperture with matching tolerances of tens of microns across all diameters. Depending on the spacing of the emission apertures and the size of the optical fiber 108, a given optical fiber can collect light from more than one aperture (see Figure 9).

[0064] The advantage of such an approach is that it allows the outputs of any number of solid-state light sources to be combined by using an equal or fewer number of optical fibers. The opposing ends of the optical fibers can then be incorporated into a bundle. In some embodiments, the bundle is a circular hexagonal pack. For a given number of fibers of a given diameter, this configuration represents the minimum cross-sectional area and therefore maintains the maximum photon flux and etendue. Furthermore, the optical fibers allow linear or other geometrical arrangements of solid-state light sources (e.g., laser bars) to be fabricated while retaining the ability to incorporate their outputs into a narrow-area aperture, enabling efficient coupling of the collected light to the sampling subsystem 200. The laser bar assembly may comprise a laser bar 106, a ceramic carrier 105 with electrical contacts, an optical fiber coupler (not shown), a copper microbench (not shown), and a thermoelectric cooler (not shown). The assembly can be housed in a sealed package, such as an industry-standard butterfly package. In some embodiments, an optical homogenizer may be placed at the output of the optical fiber bundle to spatially and / or angularly homogenize the outputs of the individual optical fibers. In such embodiments, the cross-sectional area can be matched to the region of the optical fiber bundle in order to minimize any reduction in photon flux and etendue. In some embodiments, the arrangement of optical fibers in the output bundle can be matched to the cross-section of the optical homogenizer (e.g., square, hexagon, etc.).

[0065] The optical fiber coupling approach also allows multiple assemblies with solid-state light source apertures to be incorporated into a single output aperture. For example, Figure 10 shows four laser bars 106, each with a pair of 12 laser emitters 107 (see Figure 8). A multimode optical fiber 110 may be used to collect light from each emitter pair 107 (a total of 48 fibers 108). The opposing ends of the 48 fibers 108 are then incorporated into a circular hexagonal packed output ferrule 111.

[0066] (Method and apparatus for homogenizing the output of an illumination / modulation subsystem) At the input to the tissue sampling subsystem 200, an optical homogenizer 112, such as an optical diffuser, optical pipe, and other scrambler, can be incorporated into some embodiments of the illumination / modulation subsystem 100 to provide reproducible and preferably uniform radiance. Figure 11 shows an example of an optical homogenizer 112, comprising a ground diffuser with two opposing bends and an optical pipe with a hexagonal cross-section. Uniform radiance can ensure good photometric accuracy and uniform illumination of the tissue. Uniform radiance can also reduce errors associated with manufacturing differences between solid light sources. Uniform radiance can be utilized in various embodiments of the present invention to achieve accurate and precise measurements. See, for example, U.S. Patent No. 6,684,099, incorporated herein by reference.

[0067] A frosted glass plate is an example of an optical diffuser. The polished surface of the plate effectively scrambles the radiation angles diverging from a solid light source and its transmission optics. An optical pipe can be used to homogenize the radiation intensity so that it is spatially uniform at the output of the optical pipe. In addition, an optical pipe with a double bend will scramble the radiation angles. For the creation of uniform spatial intensity and angular distribution, the cross-section of the optical pipe should not be circular. Square, hexagonal, and octagonal cross-sections are effective scrambling geometric shapes. The output of the optical pipe can be directly coupled to the input of a tissue sampler or used in conjunction with additional transmission optics before the light is transmitted to the tissue sampler. See, for example, U.S. Patent Application No. 09 / 832,586, “Illumination Device and Method for Spectroscopic Analysis,” incorporated herein by reference.

[0068] (Sampling subsystem) Figure 1 shows that the orientation of the tissue sampling subsystem 200 is between the illumination / modulation (100) and data acquisition (300) subsystems. Referring to Figure 1, the tissue sampling subsystem 200 introduces radiation generated by the illumination / modulation subsystem 100 into a sample (e.g., the tissue of interest), collects a portion of the radiation not absorbed by the sample, and transmits that radiation to a photodetector in the data acquisition subsystem 300 for measurement. Figures 12 to 17 depict elements of an example tissue sampling subsystem 200. Referring to Figure 12, the tissue sampling subsystem 200 has an optical input 202, a sampling surface 204 that forms a tissue interface 206 for examining the tissue, and an optical output 207. The subsystem further includes an ergonomic device 210, depicted in Figure 13, which holds the sampling surface 204 and positions the tissue at the interface 206. The output 211 transmits a signal to a processing circuit, which may be, for example, a microprocessor. In some embodiments of the exemplary subsystem, a device for temperature auto-regulating the tissue interface is included. In other embodiments, refractive index-matching fluids can be used to improve the optical interface between the tissue and the sampling surface. The improved interface can reduce errors, increase efficiency, and thereby improve the net attribute signal. See, for example, U.S. Patents 6,622,032, 6,152,876, 5,823,951, and 5,655,530, which are incorporated herein by reference.

[0069] The optical input 202 of the tissue sampling subsystem 200 receives radiation (e.g., light exiting the optical pipe) from the illumination / modulation subsystem 100 and transmits that radiation to the tissue interface 206. In one embodiment, the optical input may comprise a bundle of optical fibers arranged in a geometric pattern to collect an appropriate amount of light from the illumination / modulation subsystem. Figure 14 depicts one example arrangement. The plan view geometrically depicts the ends of the input and output fibers on the sampling surface, including six clusters 208 arranged in a circular pattern. Each cluster contains four central output fibers 212 that collect light diffusely reflected from the tissue. Around each grouping of the four central output fibers 212 is a cylinder 215 of material, ensuring a gap of approximately 100 μm between the edges of the central output fibers 212 and the inner ring of the input fiber 214. The 100 μm gap may be important for measuring ethanol in the dermis. As shown in Figure 14, the two concentric rings of the input fiber 214 are arranged around the cylindrical material 215. As shown in one embodiment, 32 input fibers surround 4 output fibers.

[0070] Figure 15 demonstrates an alternative cluster geometry for the sampling subsystem. In this embodiment, the illumination and collection optical fibers are arranged in a linear geometric shape. Each row may be for either illumination or optical collection and may be of any length suitable for achieving a sufficient signal-to-noise ratio. In addition, the number of rows may be two or more to modify the physical area covered by the sampling subsystem. The total number of potential illumination fibers depends on the physical size of the radiating area of ​​the solid light source subsystem (e.g., the area of ​​the cross-section of the fiber bundle or optical homogenizer, depending on the embodiment) and the area of ​​each fiber. In some embodiments, multiple solid light source subsystems can be used to increase the number of illumination fibers. If the number of collection fibers results in an area larger than the photodetector of the data collection subsystem (300), an optical pipe or other homogenizer followed by an aperture can be used to reduce the size of the output area of ​​the sampling subsystem. The purpose of the optical pipe or other homogenizer is to ensure that each collection fiber contributes substantially equally to the light passing through the aperture. In some embodiments, the optical homogenizer can be omitted, and the aperture can be used alone. In other embodiments, the active region of the detector functions as an aperture (for example, there is no distinctly different aperture). In this case, light that does not enter the active region is effectively vignetted.

[0071] In some embodiments of the sampling subsystem (200) of the present invention, a portion of the optical probe interacting with the sample may consist of a stack of two or more linear ribbons of optical fiber. These arrays allow the size and shape of the optical probe interface to be appropriately designed for the sample of interest and the measurement location (e.g., hand, finger). Figure 16 shows an example embodiment of the sampling subsystem based on a linear stack of ribbons. Further details relating to preferred embodiments for use in the present invention can be found in concurrently pending U.S. Patent Applications 12 / 185,217 and 12 / 185,224, which are incorporated herein by reference, respectively.

[0072] In many embodiments of tissue analyte measurement devices, the photodetector is the system's limiting aperture. In such systems, the system's throughput (and correspondingly the signal-to-noise ratio, SNR) can be optimized by incorporating an optical probe design that illuminates a wider area of ​​the sample (tissue) while collecting light from a smaller aperture that matches the stereoreceptor angle of the photodetector. Referring to the optical probe design in Figure 16, each collection fiber (black circle) is surrounded by eight illumination fibers (white circles). For each collection fiber, the geometric difference in this area allows each of the eight illumination fibers to contribute to the collected light. The net effect of this approach is that more light is collected from the blackbody light source and delivered to the sample without being eclipsed by the limiting aperture. This can be advantageous for light sources that inherently have a wide emission area (e.g., many blackbody emitters).

[0073] However, the photon flux of semiconductor light sources, such as diode lasers, can be much higher than that of blackbody light sources. As a result, a limited number of semiconductor light sources can deliver equivalent or superior photon fluxes with smaller solid angles to their blackbody references. This can result in a solid angle of photon emission (the combined solid angle of all semiconductor light sources) smaller than the stereoreceptor angle of the detector. In other words, the light sources, rather than the photodetector, are the effective limiting aperture of the system. In such cases, optical probe designs such as those shown in Figure 16 do not optimize the system's throughput and SNR. While such optical probes are suitable in some embodiments of the present invention, alternative embodiments may be preferred. In other embodiments, the number of illumination optical fibers may be less than or equal to the number of collection optical fibers. These optical probe designs have a sampling surface that allows for a smaller illumination area, matching a smaller area of ​​emission from the solid light source, along with a wider collection area, matching a wider area of ​​emission from the photodetector. As a result, the overall efficiency of the system is improved.

[0074] The sampling subsystem may also use one or more channels, each referring to a specific orientation of the illumination and collection fibers. The orientation consists of the angle of one or more illumination fibers, the angle of one or more collection fibers, the numerical aperture of one or more illumination fibers, the numerical aperture of one or more collection fibers, and the separation distance between one or more illumination and collection fibers. Multiple channels can be used together, either simultaneously or sequentially, to improve the accuracy of non-invasive measurements. In one embodiment, a two-channel sampling subsystem is utilized. In this embodiment, two channels measure the same tissue structure. Thus, each channel provides measurements of the same tissue from a different viewpoint. The second viewpoint helps provide additional spectral information, which aids in signal decoupling through scattering and absorption. Referring to Figure 17, a group of fibers (in this embodiment, one light source, one receptor #1, and one receptor #2) can be duplicated 1 to N times to increase the sampler area and improve optical efficiency. Each fiber may have a different numerical aperture and angle (0). The distance between fibers X and Y determines the light source-receptor separation. Furthermore, additional light source channels can be added to create a 4-channel sampling subsystem. Those skilled in the art will recognize numerous possible variations in the number and relationships between channels.

[0075] In experiments where a multi-channel sampler was used for non-invasive glucose measurement, the results showed that a combination of two channels provided superior measurement accuracy compared to either channel individually. This example uses two channels, but an additional channel can provide additional information that can further improve the measurement.

[0076] Another aspect of the multi-channel sampling subsystem is its ability to improve the detection and reduction of local interfering substances, such as sweat or lotion, present on the sample. Figure 17 is a schematic diagram of the multi-channel sampling subsystem in the presence of a local interfering substance. Figure 17 shows the sampling subsystem, the layer of local interfering substance, and the tissue at the tissue interface. In this embodiment, the contribution of the local interfering substance to the measurement of each channel is identical. This allows for the possibility of decoupling of the common local interfering substance signal present in both channels from tissue signals that would otherwise differ for the two channels.

[0077] Referring to Figure 12, the clustered input and output fibers are placed within cluster ferrules, which are mounted within the sampling head 216. The sampling head 216 includes a sampling surface 204 that is polished flat to allow for the formation of a good tissue interface. Similarly, the input fibers are clustered within a ferrule 218 connected at the input end to work in conjunction with the illumination / modulation subsystem 100. The output end of the output fibers is clustered within a ferrule 220 to work in conjunction with the data acquisition subsystem 300.

[0078] Alternatively, the optical input can use a combination of optical pipes, refractive and / or reflective optics to transmit the input light to the tissue interface. It is important that the input optics of the tissue sampling subsystem collect sufficient light from the illumination / modulation subsystem 100 to achieve an acceptable net attribute signal.

[0079] A tissue interface can illuminate tissue in a manner that targets tissue sections relating to desired attributes and can discriminate light that does not travel a significant distance through these sections. For example, a 100 μm gap between the illumination and collection optical fibers can discriminate light containing little attribute information. In addition, the tissue interface can be averaged across a region of tissue to reduce errors due to the non-uniform nature of the tissue. A tissue sampling interface can reject specularly reflective, short-path-length rays and collect a portion of the light traveling a desired path length through the tissue with high efficiency to maximize the net attribute signal of the system. As discussed above, the tissue sampling interface can employ optical fibers to guide light from the input to the tissue in a predetermined geometric shape. The optical fibers can be arranged in a pattern that targets a particular layer of tissue containing good attribute information.

[0080] The spacing, angle, numerical aperture, and arrangement of input and output fibers can be configured in a manner that achieves effective depth targeting. In addition to the use of optical fibers, the tissue sampling interface can utilize a non-fiber-based arrangement that places patterns of input and output regions on the surface of the tissue. Proper masking of the non-fiber-based tissue sampling interface ensures that the input light travels the minimum distance within the tissue and contains valid attribute information. Finally, the tissue sampling interface can be temperature-controlled to control the tissue temperature in a predetermined manner. The temperature of the tissue sampling interface can be set to reduce prediction errors due to temperature fluctuations. Furthermore, reference errors are reduced when constructing calibration models. These methods are disclosed in U.S. Patent Application No. 09 / 343,800, entitled "Method and Apparatus for Non-Invasive Blood Analyte Measurement with Fluid Compartment Equilibration," which is incorporated herein by reference.

[0081] The tissue sampling subsystem 200 may employ an ergonomic device or guide 213 that covers the sampling interface 204 and positions the tissue in a reproducible manner. An example of an ergonomic device 213 that reproducibly guides a finger to the sampling surface is depicted in Figure 13. The ergonomic device 213 includes a base 217, which includes an opening 219 through which it passes. The opening 219 is sized to receive a sample head 216 therein, so as to position the sampling surface 204 substantially coplanar with the upper surface of the base. Careful attention must be paid to the ergonomics of the tissue sampling interface; otherwise, significant sampling errors may occur. Alternative sites, such as the upper or palmar side of the fingertip or the forearm, can also be adapted using the variations of the system described herein.

[0082] The output of the tissue sampling subsystem 200 transmits a portion of the light that has traveled through the tissue to a photodetector in the data acquisition subsystem 300 via an acceptable path, without being absorbed by the tissue. The output of the tissue sampling subsystem 200 may utilize any combination of refractive and / or reflective optics to focus the output light onto the photodetector. In some embodiments, the collected light is homogenized to mitigate sample-dependent spatial and angular effects (see U.S. Patent No. 6,684,099, Apparatus and Methods for Reducing Spectral Complexity in Optical Sampling, incorporated herein by reference).

[0083] (Data acquisition subsystem) The data acquisition subsystem 300 converts the optical signal from the sampling subsystem into a digital representation. Figure 18 is a schematic diagram of the data acquisition subsystem 300. An advantage of at least one embodiment of the present invention is that, as with interferometers, only a single-element detector is required to measure all desired wavelengths. Array detectors and their supporting electronics are a significant disadvantage due to their expensive nature.

[0084] A photodetector converts incident light into an electrical signal as a function of time. Examples of detectors sensitive in the spectral range of 1.0–2.5 μm include InGaAs, InAs, InSb, Ge, PbS, and PbSe. Embodiments of the present invention can utilize a 1 mm thermoelectrically cooled extended-range InGaAs detector sensitive to light in the 1.0–2.5 μm range. The 2.5 μm extended-range InGaAs detector has low Johnson noise, resulting in shot noise limiting performance for the photon flux diverging from the tissue sampling subsystem. The extended InGaAs detector has peak sensitivity in the 2.0–2.5 μm spectral region, where three very important alcohol absorption features are located. Compared with a liquid nitrogen cooled InSb detector, the thermoelectrically cooled extended-range InGaAs may be more practical for commercial use. This detector also exhibits linearity of 120 dBc or more in the 1.0–2.5 μm spectral region. If the alcohol measurement system utilizes an alternative wavelength range, an alternative detector may be preferable. For example, if the target wavelength range is within the range of 300 to 1100 nm, a silicon detector may be suitable. Any photodetector can be used as long as the desired photodetector meets the basic sensitivity, noise, and speed requirements.

[0085] The remainder of the data acquisition subsystem 300 amplifies and filters the electrical signal from the detector, and then converts the resulting analog electrical signal into its digital representation using an analog-to-digital converter, digital filtering, and resampling of the digital signal from equivalent time intervals to equivalent positional intervals. The analog electronics and ADC must support the high SNR and linearity inherent to the signal. To maintain the SNR and linearity of the signal, the data acquisition subsystem 300 can support an SNR and distortion of at least 100 dBc. The data acquisition subsystem 300 can produce a digitized representation of the signal. In some embodiments, a 24-bit delta-sigma ADC can be operated at 96 or 192 kHz. In systems with only one channel of the signal to be digitized (instead of the two or more common in delta-sigma ADCs), the signal can be passed through both inputs of the ADC and averaged after digitization. This operation can help reduce any uncorrelated noise introduced by the ADC. If system performance requirements allow, an alternative analog-to-digital converter can be used in which sample acquisition is synchronized with solid-state light source modulation rather than captured at equivalent time intervals. The digitized signal can be passed to the computer subsystem 400 for further processing, as will be discussed below.

[0086] The constant-time sampling data acquisition subsystem 300 has several distinctly different advantages compared to other methods of digitizing signals. These advantages include a wider dynamic range, lower noise, reduced spectral artifacts, detector noise-limiting operation, and simpler and less expensive analog electronics. In addition, the constant-time sampling technique allows for digital compensation for frequency response distortions introduced into the analog electronics before the ADC. This includes nonlinear phase errors in amplification and filtering circuits, as well as the less-than-ideal frequency response of the photodetector. The uniformly sampled digital signal allows for the application of one or more digital filters whose cumulative frequency response is the reciprocal of the transfer function of the analog electronics (see, for example, U.S. Patent No. 7,446,878, incorporated herein by reference).

[0087] (Computer subsystem 400) The computer subsystem 400 performs several functions, including converting digitized data acquired from the data acquisition subsystem 300 into intensity relative to the wavelength spectrum, performing spectral anomaly checks on the spectrum, spectral preprocessing in preparation for determining the target attribute, determining the target attribute, checking the system status, display and processing requirements associated with the user interface, and data transfer and storage. In some embodiments, the computer subsystem is contained in a dedicated personal computer or laptop computer connected to other subsystems of the present invention. In other embodiments, the computer subsystem is a dedicated embedded computer.

[0088] After digitizing the data from the detector and converting it into intensity relative to the wavelength spectrum, the computer system can check the spectrum for outliers or bad scans. Outlier samples or bad scans violate the assumed relationship between the measured signal and the desired properties. Examples of outlier conditions include conditions in which the calibrated instrument is operated outside of specific operating ranges such as ambient temperature, ambient humidity, vibration tolerance, component tolerances, and power levels. In addition, outliers may occur if the composition or concentration of the sample differs from the composition or concentration range of the sample used to construct the calibration model. Calibration models are discussed later in this disclosure. Outliers or bad scans can be removed, and the remaining good spectra can be averaged together to produce an average single-beam spectrum for measurement. The intensity spectrum can be converted to absorbance by taking the base-10 logarithm (-log10) of the spectrum. The absorbance spectrum can be scaled to renormalize the noise.

[0089] In conjunction with the calibration model obtained from the calibration subsystem 500, a scaled absorbance spectrum can be used to determine the desired attribute. After determining the desired attribute, the computer subsystem 400 can report the result 830, for example, to the subject, to the operator or administrator, to a recording system, or to a remote monitor. The computer subsystem 400 can also report the level of confidence in the goodness of the result. If the confidence level is low, the computer subsystem 400 can withhold the result and ask the subject to re-examine it. If necessary, additional information can be provided instructing the user to take corrective action. See, for example, U.S. Patent Application No. 20040204868, incorporated herein by reference. The result can be reported visually on a display, audibly, and / or by printed means. In addition, the result can be stored to form a historical record of the attribute. In other embodiments, the result can be stored and transmitted to remote monitoring or storage equipment via the internet, telephone lines, or mobile phone services.

[0090] The computer subsystem 400 includes a central processing unit (CPU), memory, storage device, display, and preferably a communication link. An embodiment of the CPU is an Intel Pentium® microprocessor. The memory may be static random access memory (RAM) and / or dynamic random access memory. The storage device can be achieved using non-volatile RAM or a disk drive. Liquid crystal, LED, or other displays may be preferred. The communication link may, in embodiments, be a high-speed serial link, an Ethernet® link, or a wireless communication link. The computer subsystem may, for example, derive attribute measurements from received and processed interferograms, perform calibration maintenance, perform calibration movement, perform instrument diagnostics, store a history of measured alcohol concentrations and other relevant information, and, in some embodiments, communicate with a remote host to send and receive data and new software updates.

[0091] The computer system 400 may also include a communication link that enables the transfer of target alcohol measurement records and corresponding spectra to an external database. In addition, the communication link can be used to download new software to the computer and update multivariate calibration models. The computer system can be considered an information appliance. Examples of information appliances include personal digital assistants, web-enabled mobile phones, and handheld computers.

[0092] (Calibration subsystem 500) To obtain alcohol measurements, a calibration model is used in conjunction with spectral information. In some embodiments, the calibration model is formed by collecting blood reference measurements and simultaneous spectral data for multiple subjects under a wide variety of environmental conditions. In these embodiments, spectral data can be collected from each subject over a range of blood alcohol concentrations. In other embodiments, a hybrid calibration model may measure the alcohol concentration of the subject spectrum. In this case, the term hybrid model indicates that a partial least squares (PLS) calibration model was created using a combination of in vitro and in vivo spectral data. The in vitro portion of the data was a 0.1 mm path length transmission spectrum of 500 mg / dL water alcohol, measured using a non-invasive measurement system configured for transmission measurements. The transmission spectrum was proportional to the 0.1 mm path length transmission spectrum of water, converted to absorbance, and normalized to unit path length and concentration.

[0093] Light propagation through tissue is a composite function of diffuse reflection optical tissue sampler design, physiological variables, and wavenumber. Consequently, the path length of light through tissue exhibits wavenumber dependence, which is not encountered in non-dispersive transmission measurements. To address this wavenumber dependence, the interaction of the optical tissue sampler with the scattering properties of human tissue was modeled via Monte Carlo simulation using a commercially available ray tracing software package (TracePro). Using the resulting model of light-tissue interaction, estimates of the effective path length of light through the dermal and subcutaneous tissue layers were generated as a function of wavenumber. Effective path length (1 eff ) is defined as follows:

[0094]

number

[0095] In vivo data included non-invasive tissue spectra collected from individuals who did not consume alcohol. A hybrid model was formed by adding pure alcohol spectrum weighted by various alcohol "concentrations" (ranging from 0 to 160 mg / dL) to the non-invasive tissue spectral data. The PLS calibration model was constructed by regressing synthetic alcohol concentrations onto the hybrid spectral data. Figure 19 shows a schematic diagram of the hybrid calibration formation process. The hybrid calibration in this study used approximately 1500 non-invasive tissue spectra collected from 133 subjects over a three-month period.

[0096] The use of a hybrid calibration model can offer significant advantages over a calibration model constructed from spectra collected from subjects who consumed alcohol. The hybrid modeling process allows for the generation of calibration spectra containing higher concentrations of alcohol (up to 160 mg / dL in this study) than would be considered safe for consumption in human subject studies (120 mg / dL is the safe upper limit). This can result in a stronger calibration with a wider range of analyte concentrations, allowing for more accurate prediction of higher alcohol concentrations. This may be important because alcohol concentrations observed in the field can be more than twice the maximum safe dose in a clinical research environment. The hybrid calibration process also prevents correlation between alcohol and spectrally interfering substances in tissues. For example, random addition of alcohol signals to the calibration spectrum prevents alcohol concentration from correlating with water concentration. Therefore, the hybrid approach prevents the possibility of measurements erroneously tracking changes in tissue water content instead of alcohol concentration.

[0097] Once formed, it is desirable that the calibration remains stable and produces accurate attribute predictions over the long term. This process, called calibration maintenance, can consist of several methods that can be used individually or in combination. The first method is to create the calibration in a manner that makes it inherently robust. Several different types of instrument and environmental variations can affect the predictive capability of the calibration model. It is possible and desirable to reduce the magnitude of the impact of these variations by incorporating instrument and environmental variations into the calibration model.

[0098] However, it is difficult to cover the entire possible range of instrument conditions during the calibration period. System permutations may cause the instrument to operate outside the space of the calibration model. Measurements taken while the instrument is in an improperly modeled state may exhibit predictive errors. In the case of in vivo optical measurements of medically significant attributes, these types of errors can lead to erroneous measurements that reduce the usefulness of the system. Therefore, it is often advantageous to use additional calibration maintenance techniques throughout the instrument's lifecycle to continuously verify and correct the instrument's condition.

[0099] Examples of problematic equipment and environmental variations include, but are not limited to, changes in the levels of environmental interfering substances such as water vapor or CO2 gas, changes in the matching of the equipment's optical components, fluctuations in the output power of the equipment's lighting system, and changes in the spatial and angular distribution of light emitted by the equipment's lighting system.

[0100] Calibration and maintenance techniques are discussed in U.S. Patent No. 6,983,176, “Optically Similar Reference Samples and Related Methods for Multivariate Calibration Models Used in Optical Spectroscopy,” U.S. Patent No. 7,092,832, “Adaptive Compensation for Measurement Distortions in Spectroscopy,” U.S. Patent No. 7,098,037, “Accommodating Subject and Instrument Variations in Spectroscopic Determinations,” and U.S. Patent No. 7,202,091, “Optically Similar Reference Samples,” which are incorporated herein by reference. Some of the disclosed methods utilize environmentally inert, non-tissue samples, such as integrating spheres, which may or may not contain the desired attributes, for monitoring the instrument over time. Samples can be incorporated into the optical path of the instrument or interface using a sampling subsystem, similar to tissue measurements. Samples may use transmittance or reflectance and may contain stable spectral features or none of their own spectral features may contribute. As long as the spectrum is stable or predictable over time, the material can be a solid, liquid, or gel. Any unexplained change in the spectrum collected from the sample over time indicates that the instrument is being perturbed or drifted by environmental influences. The spectral changes can then be used to correct subsequent tissue measurements in humans to ensure accurate attribute measurements.

[0101] Another means of achieving successful calibration maintenance is to update the calibration using measurements collected on the instrument over time. Typically, knowledge of a reference value for the analyte property of interest is required to perform such an update. However, in some applications, the reference value is known, though not always, to be a specific value. In this case, this knowledge can be used to update the calibration even if the specific value of the analyte property is not known for each measurement. For example, in alcohol screening in residential care facilities, the majority of measurements are performed by the individual on individuals who, in accordance with alcohol consumption restrictions, thus have a zero alcohol concentration. In this case, alcohol concentration measurements or related spectra obtained from devices disclosed according to various embodiments of the present invention can be used in conjunction with an estimated zero as a reference value. Thus, the calibration can be updated to include new information as it is collected in the field. This approach can also be used to perform calibration shifts, as measurements with an estimated zero can be used at the time of system manufacture or installation to remove any system-specific bias in the measurement of the analyte property of interest. Calibration maintenance updates or calibration shift implementations can be achieved, though not limited to, by various means such as orthogonal signal correction (OSV), orthogonal modeling techniques, neural networks, inverse regression methods (PLS, PCR, MLR), direct regression methods (CLS), classification schemes, simple central or shifting windows, principal component analysis, or combinations thereof.

[0102] Once a calibration is established, it is often desirable to transfer that calibration to all existing and future units. This process is commonly referred to as calibration transfer. Although not required, calibration transfer eliminates the need for calibration to be determined in each system manufactured. This represents a significant saving of time and cost, which can affect the difference between the success or failure of a product. Calibration transfer arises from the fact that optical and electronic components differ from unit to unit, and collectively, this can result in significant differences in the spectra obtained from multiple instruments. For example, two solid-state light sources may have different color temperatures, thereby resulting in different light distributions for the two light sources. The responsiveness of two detectors can also differ significantly, resulting in additional spectral differences.

[0103] Similar to calibration maintenance, several methods can be used to effectively achieve calibration shift. The first method is to construct the calibration using multiple instruments. The presence of multiple instruments allows spectral variations associated with instrument differences to be determined during the calibration formation process and orthogonalized to the attribute signal. This approach reduces the net attribute signal but can be an effective means of achieving calibration shift.

[0104] An additional calibration transfer method involves explicitly determining the difference in the spectral characteristics of the system with respect to what is used to construct the calibration. In this case, the spectral difference can then be used to correct the spectral measurement before predicting attributes on the system, or it can be used to directly correct the predicted attribute values. Spectroscopic characteristics specific to an instrument can be determined from the relative difference between the spectrum of a stable sample collected from the system of interest and what is used to construct the calibration. The samples described in the Calibration Maintenance section are also applicable to calibration transfers. See, for example, U.S. Patent No. 6,441,388, “Method and Apparatus for Spectroscopic Calibration Transfer,” which is incorporated herein by reference.

[0105] (Alcohol measurement method) Depending on the intended use, the measured properties of the analyte can be considered in two aspects. The first aspect is "walk-up" or "general-purpose," representing properties of the analyte where previous measurements of the sample (e.g., the subject) are not used when determining the properties of the analyte from the current measurement of interest. When measuring in vivo alcohol, drunk driving falls into this category, as in most cases the individual being tested will not have been measured previously with an alcohol measuring device. Therefore, the individual's prior knowledge is not available for the current determination of the properties of the analyte.

[0106] The second aspect, referred to as “registered” or “adjusted,” describes a situation where previous measurements from a sample or object are available when determining the analyte properties of the current measurement. An example of an environment to which this aspect can be applied is an automotive interlock, where a limited number of people are permitted to drive or operate a vehicle or machine. Additional information regarding embodiments of registered or adjustable applications can be found in U.S. Patents 6,157,041 and 6,528,809, entitled “Method and Apparatus for Tailoring Spectroscopic Calibration Models,” which are incorporated herein by reference, respectively. In registered applications, the combination of biometric measurements and analyte property measurements may be particularly advantageous because the same spectroscopic measurement can assess whether a predictive operator is authorized to use the instrument or vehicle via biometrics, while the analyte property can assess a health level (e.g., not having consumed alcohol).

[0107] (Methods for determining biometric validation or identification from spectral signals) Biometric identification refers to the process of using one or more physical or behavioral characteristics to identify an individual or other biological entity. There are two common biometric modes: identification and verification. Biometric identification attempts to answer the question, "Do I know you?" A biometric measurement device collects a set of biometric data from a target individual. From this information alone, it assesses whether the individual has been previously registered in a biometric system. Systems that perform biometric identification tasks, such as the FBI's Automated Fingerprint Identification System (AFIS), are generally very expensive (millions of dollars or more) and require minutes to detect a match between an unknown sample and a massive database containing hundreds of thousands or millions of entries. In biometric verification, the relevant question is, "Are you the person you claim to be?" This mode is used when an individual claims identity using a code, magnetic card, or other means, and the device uses the biometric data to verify the individual's identity by comparing the target biometric data with the intended identity and corresponding registration data. Apparatus and methods for monitoring the presence or concentration of alcohol or abuse substances in a controlled environment may use either of these biometric modes.

[0108] There also exists at least one variation between these two modes, which is also suitable for use in various embodiments of the present invention. This variation arises when a small number of individuals are included in a registration database and the biometric application only requires a determination of whether the target individual is among the registered set. In this case, the precise identity of the individual is not required, and therefore the task differs somewhat from (and is often easier than) the identification tasks described above. This variation may be useful in applications where the biometric system is used in a manner where the individual being examined must be part of an approved group and be sober, but the specific identity of the individual is not required. The term “identity characteristics” includes all of the modes, variations, and combinations or variations thereof described above.

[0109] There are three main data elements associated with biometric measurements: calibration, registration, and target spectral data. Calibration data is used to establish spectral features important for biometric determination. This set of data consists of a series of spectroscopic tissue measurements collected from one or more individuals of known identity. Preferably, these data are collected over a period of time and under the conditions of the set, so that multiple spectra are collected for each individual, while covering nearly the entire range of physiological conditions that the individual is expected to experience. In addition, one or more instruments used for spectral collection should also generally cover the entire range of instrument and environmental effects that it or a sister instrument is likely to encounter during actual use. These calibration data are then analyzed in such a way that they establish spectral wavelengths or “factors” (i.e., linear combinations of wavelengths or spectral shapes) that are sensitive to interpersonal spectral differences, while minimizing sensitivity to intrapersonal, instrument (both intra-instrumental and inter-instrumental), and environmental effects. These wavelengths or factors are then used to perform the biometric determination task.

[0110] The second primary set of spectral data used for biometric determination is registered spectral data. The purpose of registered spectra for a given object or individual is to generate a "representation" of the object's unique spectral characteristics. Registered spectra are collected from individuals who need to be approved or otherwise recognized by the biometric system. Each registered spectrum can be collected over a period of several seconds or minutes. Two or more registered measurements may be collected from an individual to ensure similarity between measurements and to exclude one or more measurements if artifacts are detected. If one or more measurements are discarded, additional registered spectra can be collected. Registered measurements for a given object can be averaged together, combined in different ways, or stored separately. In any case, the data is stored in a registration database. In some cases, each set of registered data is associated with an identifier (e.g., password or key code) of the individual against whom the spectrum was measured. For identification tasks, the identifier can be used for record-keeping purposes to track who accessed the biometric system and when. For verification tasks, the identifier is used to extract a suitable set of registered data against which verification is performed.

[0111] The third and final primary set of data used in a biometric system is spectral data, collected when an individual attempts to use the biometric system for identification or verification. This data is called the target spectrum. It is compared to measurements stored in a registration database (or a subset of the database in the case of identity verification) using classification wavelengths or factors obtained from a calibration set. For biometric identification, the system compares the target spectrum to all registered spectra and reports a match if one or more of the registered individual's data are sufficiently similar to the target spectrum. If more than one registered individual matches the target, the system may report all matching individuals or report the best match as the identified individual. For biometric verification, the target spectrum is accompanied by a claimed identity, collected using a magnetic card, typed username or identifier, transponder, signal from another biometric system, or other means. The claimed identity is then used to read the corresponding set of spectral data from the registration database, against which a biometric similarity determination is performed and the identity is verified or rejected. If the similarity is insufficient, the biometric determination may be canceled, and a new target measurement may be attempted.

[0112] In one verification method, principal component analysis is applied to calibration data to generate spectral factors. These factors are then applied to the spectral difference obtained between the target spectrum and the registered spectrum to generate Mahalanobis distance and spectral residual scale values ​​as similarity metrics. Identity is verified only if the aforementioned distance and scale are below predetermined thresholds described for each. Similarly, in an example of a biometric identification method, Mahalanobis distance and spectral residual scale are calculated for the target spectrum for each of the database spectra. The identity of the individual providing the test spectrum is established as one or more individuals associated with the database measurements that produced the minimum Mahalanobis distance and spectral residual scale below predetermined thresholds described for each.

[0113] In this method example, an identification or verification task is implemented when an individual attempts to perform an action that is authorized for a limited number of people (e.g., performing a spectroscopic measurement, entering a controlled facility, passing through an immigration checkpoint). The individual's spectral data is used to identify or verify their identity. In this method, the individual first registers with the system by collecting one or more representative tissue spectra. If more than one spectrum is collected during registration, these spectra are checked for consistency and can only be recorded if they are sufficiently similar, limiting the possibility of sample artifacts that could corrupt the registration data. For the implementation of verification, identifiers such as PIN codes, magnetic card numbers, usernames, badges, voice patterns, other biometrics, or any other identifiers can also be collected and associated with one or more verified registration spectra.

[0114] During subsequent use, biometric identification can be performed by collecting a spectrum from the individual seeking approval. This spectrum can then be compared to a spectrum in a registered approval database, and if the match to the approved database input is better than a predetermined threshold, identification can be performed. The verification task may require the individual to present an identifier in addition to the collected spectrum, even if the spectrum is similar. The identifier can then be used to select a specific registered database spectrum, and approval can be granted if the current spectrum is sufficiently similar to the selected registered spectrum. If the biometric task is associated with an approved behavior for only one individual, the verification and identification tasks are identical and both simplify to the certainty that only one approved individual is attempting the behavior without requiring a separate identifier.

[0115] Biometric measurements, regardless of mode, can be performed in a variety of ways, including linear discriminant analysis, quadratic discriminant analysis, K-nearest neighbors, neural networks, and other multivariate analysis or classification techniques. Some of these methods rely on establishing a fundamental spectral shape (factors, weight vectors, eigenvectors, latent variables, etc.) in an intrapersonal calibration database, and then using standard outlier methodologies (spectral F ratio, Mahalanobis distance, Euclidean distance, etc.) to determine the consistency of input measurements with a registration database. The fundamental spectral shape can be generated by several means as disclosed herein.

[0116] Firstly, the fundamental spectral shape can be generated based on a simple spectral decomposition (eigenvalue analysis, Fourier analysis, etc.) of calibration data. A second method for generating the fundamental spectral shape relates to the creation of a general model, such as that described in U.S. Patent No. 6,157,041, entitled "Methods and Apparatus for Tailoring Spectroscopic Calibration Models," which is incorporated by reference. In this application, the fundamental spectral shape is generated through a calibration procedure performed on intrapersonal spectral features. The fundamental spectral shape can be generated by creating a calibration based on simulated constructive variation. Simulated constructive variation can model variations introduced by actual physiological, environmental, or instrumental variations, or it can simply be an artificial spectral variation. It is recognized that other means for determining the fundamental shape will be applicable to the identification and verification methods of the disclosed embodiments of the present invention. These methods can be used either in conjunction with or instead of the techniques described above.

[0117] (Calibration check sample) In addition to disposable parts to ensure the safety of the object, disposable calibration check samples can be used to verify that the instrument is in proper operating conditions. In many commercial applications of alcohol measurement, the instrument's condition must be verified to ensure that subsequent measurements will provide accurate alcohol concentration or attribute estimates. The instrument's condition is often checked immediately before the object measurement. In some embodiments, the calibration check sample may contain alcohol. In other embodiments, the check sample may be an environmentally stable, spectrally inert sample such as an integrating sphere. The check sample may be a gas or liquid injected or flowed through a spectral sampling chamber. The check sample may also be a solid, such as a gel, which may contain alcohol. The check sample may be constructed to work in conjunction with a sampling subsystem or incorporated into another region of the system's optical path. These embodiments are intended to be illustrative and are not limited to the various possible calibration check samples.

[0118] (Direction of change (DOC) and rate of change (ROC)) A method for measuring the direction and magnitude of changes in the concentration of tissue components such as alcohol using spectroscopy is considered to be within the scope of the present invention. The non-invasive measurements obtained from the present invention are essentially half-time-resolved. This allows attributes such as alcohol concentration to be determined as a function of time. The time-resolved alcohol concentration can then be used to determine the rate and direction of change of alcohol concentration. In addition, the direction of change information can be used to partially compensate for any differences between blood and non-invasive alcohol concentrations caused by physiological dynamics. See, for example, U.S. Patent No. 7,016,713, “Determination of Direction and Rate of Change of an Analyte,” and U.S. Patent Application No. 20060167349, “Apparatus for Noninvasive Determination of Rate of Change of an Analyte,” which are incorporated herein by reference, respectively. Various techniques for enhancing rate and direction signals have been revealed. Some of these techniques include heating elements, rubrifractants, and refractive index matching media. The present invention is not limited to any particular form of enhancement or equilibrium. These enhancements are not required in this invention but are included for illustrative purposes only.

[0119] (Safety of the subject) Another aspect of non-invasive alcohol measurement is the safety of the object being measured. While it is desirable, but not required, to protect each object and prevent fluid or pathogen transfer between objects to prevent contamination or movement of pathogens during measurement, this is not always necessary. For example, in some embodiments, isopropyl wipes can be used to clean the sampling site and / or sampling subsystem surface of each object before measurement. In other embodiments, a disposable thin film of a material such as ACLAR can be placed between the sampling subsystem and the object before each measurement to prevent physical contact between the object and the instrument. In other embodiments, both cleaning and film can be used simultaneously. As described in the sampling subsystem portion of this disclosure, the film can also be attached to a positioning device and then applied to the sampling site of the object. In this embodiment, the positioning device can work in conjunction with the sampling subsystem to prevent the object from moving during measurement, while the film provides protection.

[0120] (Local interfering substance) In object measurements, the presence of local interfering substances on the sampling site is a significant concern. Many local interfering substances have spectral characteristics in the near-infrared region and therefore contribute significant measurement errors when present. One embodiment of the present invention addresses the possibility of local interfering substances in three ways that can be used individually or in combination. First, disposable cleaning agents, similar to those described in the section on object safety, can be used. The use of cleaning agents may be at the discretion of the system operator or may be a mandatory step in the measurement process. Multiple cleaning agents can also be used, each targeting different types of local interfering substances individually. For example, one cleaning agent can be used to remove greases and oils, while another can be used to remove consumer goods such as cologne or perfume. The purpose of the cleaning agents is to remove local interfering substances before attribute measurement to prevent them from affecting the accuracy of the system.

[0121] A second method to mitigate the presence of local interfering substances is to determine whether one or more interfering substances are present on the sampling site. The multivariate calibration models used in the calibration subsystem provide unique outlier measurements that provide crucial information about the presence of unmodeled (local or otherwise) interfering substances. As a result, they provide insights into the reliability of attribute measurements. Figure 20 shows examples of outlier measurements from non-invasive measurements collected during a clinical study. All large measurements (clearly separated from the majority of points) correspond to measurements where oil was intentionally applied to the target sampling site. These measurements do not specifically identify the cause of the outliers but indicate that the associated attribute measurement is questionable. Exaggerated outlier measurements (e.g., values ​​exceeding a fixed threshold) can be used to trigger fixed responses such as repeated measurements, application of alternative calibration models, or sampling site washing procedures. This is represented in Figure 20 as a “spectrum check OK” decision point.

[0122] The final local interference mitigation method involves fitting a calibration model to include the spectral characteristics of the local interference substance. The fitted calibration model can either be created on demand or selected from an existing library of calibration models. Each calibration in the library will target the mitigation of different interference substances or types of interference substances, such as oil. In some embodiments, an appropriate calibration model can be selected based on a portion of the collected spectrum not described by the original calibration model. This portion of the spectrum is called the calibration model residue. Since each local interference substance or type of interference substance has a unique near-infrared spectrum, the calibration model residue can be used to identify local interference substances.

[0123] Next, the model residue or the pure spectrum of the interfering substance (obtained from a stored library) can be incorporated into the spectrum used to form the calibration. Then, the multivariate calibration can be reshaped with the new spectrum so that the portion of the attribute signal perpendicular to the interfering substance can be determined. The new calibration model is then used to measure the target attribute and then to reduce the effect of the local interfering substance on the accuracy of the attribute measurement. The resulting model will reduce the effect of the interfering substance on the alcohol measurement at the expense of measurement accuracy when the interfering substance is not present. This process is called calibration immunization. The immunization process is similar to the hybrid calibration formation process shown in Figure 19, but includes an additional step of mathematical addition of spectral variations of the interfering substance. Note that due to the effect of the immunization process on measurement accuracy, it may be desirable to specifically immunize them rather than trying to identify possible interfering substances for each measurement and create a calibration that is immune to all possible interfering substances. Further details can be found in U.S. Patent No. 20070142720, “Apparatus and methods for mitigating the effects of foreign interferents on analyte measurements in spectroscopy,” which is incorporated herein by reference.

[0124] (Advantages of semiconductor light source alternatives) Most light sources used in NIR and IR spectroscopy are blackbody radiators. The light emitted by a blackbody radiator is governed by Planck's law, which states that the intensity of the emitted light is a function of the blackbody's wavelength and temperature. Figure 21 shows the 4000–8000 cm⁻¹ range used by alcohol measuring devices. -1 The area (2.5~1.25μm) is shaded, from 100 to 33000 cm². -1The normalized NIR spectra of 1300–3000K blackbody radiators over the (100–0.3μm) range are shown. 1300K is a reasonable temperature for ceramic-based blackbody light sources, and 3000K is a reasonable temperature for quartz tungsten halogen (QTH) lamps, which are often used for spectroscopic applications. Figure 21 shows that a significant amount of light is emitted at wavelengths outside the target range for measuring alcohol, and that the optical efficiencies of both blackbody light sources are not ideal, with the ceramic light source having an optical efficiency of 58% and the QTH being only 18%.

[0125] In addition to optical efficiency, blackbody light sources can have poor electrical efficiency. While practical blackbody light sources require a significant amount of power, not all of it is converted into synchrotron radiation. Power and light intensity measurements of hundreds of ceramic blackbody light sources show an average light intensity of 1.1W for a power of 24W (4.4% electrical efficiency). When combined with an optical efficiency of 58%, the overall efficiency of a ceramic blackbody is approximately 2.5%. In other words, with 24W of power, approximately 0.6W of light intensity is obtained for the target 4000-8000cm². -1 It is emitted within the region. Since not all of the light emitted by the light source is collected by the rest of the optical system, further losses are incurred.

[0126] As indicated by low electrical efficiency, most of the applied power is converted into heat, resulting in losses exceeding the required power, which is higher than desired. The heat generated by the blackbody light source can affect the thermal state and stability of the spectroscopic measurement device. Consequently, in some cases, the device must reach thermal equilibrium before being powered on and measurements can be taken. The equilibrium time associated with a blackbody light source can range from several minutes to several hours, which can be unfavorable in some cases.

[0127] Blackbody light sources exhibit an aging effect as the material resistance changes. From an optical perspective, there are two significant implications associated with light source degradation. First, as the resistance increases, the amount of emitted light intensity decreases. In one experiment, the measured intensity over time observed for a demonstrative ceramic blackbody light source showed a 50% reduction in power over 3500 hours. The intensity degradation over time tends to be essentially exponential and can necessitate the replacement of light sources at regular intervals, which can be disadvantageous in some development environments. Second, the temperature of the light source changes, modifying the distribution of light as a function of wavelength. Depending on the significance of the color temperature change, the stability of the spectroscopic device over time can be affected. Solid-state light sources do not fail critically like incandescent bulbs and have a typical lifespan of 50,000 to 100,000 hours. As a result, solid-state light sources offer the potential for a ten-fold improvement in light source lifespan and a corresponding reduction in the need for daily maintenance compared to blackbody light sources.

[0128] Semiconductor light sources such as diode lasers can have a small emission area driven by the size of the semiconductor die itself and compared to their blackbody counterparts. Photon emission cannot occur outside the area of the die once it is generated within the semiconductor structure. Any non-uniformity within that area, however small it may be for the size of the output of the lighting system (which can be several millimeters or more depending on the application), can be advantageous. Thus, the spatial output will be very stable as long as the die (or multiple dies if multiple semiconductors are employed) does not physically move. The purpose of the subsequent spatial homogenizer is then to evenly distribute the light emitted by the die over the entire area of the lighting system output. 2 or more depending on the application). Thus, a small size (a typical emission area is 0.3 mm x 0.3 mm square or 0.09 mm 2 ) can be advantageous.

[0129] Another advantage of semiconductor light sources such as diode lasers, VCSELs, and LEDs is their ability to incorporate more than one dye into the same physical package. For example, additional solid-state light sources of the same type can be included to increase the light intensity at corresponding wavelengths. Such an approach allows for an unprecedented level of control over both specific wavelengths and relative intensity emitted by the illumination system. This can be used to highlight wavelengths important to a given analyte, such as alcohol, while reducing output at less important wavelengths. Up to several hundred solid-state light sources can be incorporated into the same package, whether all are of the same type or a mixture, while maintaining an integrated optical range that matches applications in non-invasive analyte measurements such as alcohol.

[0130] Another advantage of semiconductor light sources is their ability to select which light source is on at a given time, and to synchronize their outputs via voltage or current and temperature. As a result, a single illumination system can be optimized for measuring multiple analytes. For example, when measuring alcohol in tissue, a given set of solid light sources can be activated. Similarly, different sets can be activated when measuring different analytes such as cholesterol or glucose.

[0131] (Methods for spatial and angular homogenization) At the input to the tissue sampling subsystem 200, optical homogenizers such as optical diffusers, optical pipes, and other scramblers can be incorporated into some embodiments of the illumination / modulation subsystem 100 to provide reproducible and preferably uniform radiance. Uniform radiance can ensure good photometric accuracy and uniform illumination of the tissue. Uniform radiance can also reduce errors associated with manufacturing differences between solid light sources. Uniform radiance can be utilized to achieve accurate and precise measurements. See, for example, U.S. Patent No. 6,684,099, incorporated herein by reference.

[0132] A frosted glass plate is an example of an optical diffuser. The polished surface of the plate effectively scrambles the radiation angles diverging from a solid light source and its transmission optics. An optical pipe can be used to homogenize the radiation intensity so that it is spatially uniform at the output of the optical pipe. In addition, an optical pipe with a double bend will scramble the radiation angles. For the creation of uniform spatial intensity and angular distribution, the cross-section of the optical pipe should not be circular. Square, hexagonal, and octagonal cross-sections are effective scrambling geometric shapes. The output of the optical pipe can be directly coupled to the input of a tissue sampler or used in conjunction with additional transmission optics before the light is transmitted to the tissue sampler. See, for example, U.S. Patent Application No. 09 / 832,586, “Illumination Device and Method for Spectroscopic Analysis,” incorporated herein by reference.

[0133] In exemplary embodiments, the radiant homogenizer is an optical pipe. Optical pipes are generally fabricated from metals, amorphous glass, crystals, polymers, or other similar materials, or combinations thereof. Physically, an optical pipe has a proximal end, a distal end, and a length between them. For this application, the length of the optical pipe is measured by drawing a straight line from the proximal end to the distal end of the optical pipe. Thus, identical segments of the optical pipe 91 may have varying lengths depending on the shape formed by the segment. The length of the segment can easily vary with the intended application of the optical pipe.

[0134] In exemplary embodiments, the segments form an S-shaped optical pipe. The S-shaped bend of the optical pipe provides angular homogenization of light as it passes through the optical pipe. However, it is recognized that angular homogenization can be achieved in other ways. Multiple bends or non-S-shaped bends can be used. Furthermore, a straight optical pipe can be used if the inner surface of the optical pipe includes a diffuse reflective coating that covers at least a portion of its length. The coating provides angular homogenization as light travels through the pipe. Alternatively, the inner surface of the optical pipe can be modified to include recesses or "microstructures" such as micro-optical diffusers or lenses that achieve angular homogenization. Finally, a polished diffuser can be used to provide some angular homogenization.

[0135] The cross-section of the optical pipe may also form various shapes. In particular, the cross-section of the optical pipe is preferably polygonal in shape to provide spatial homogenization. Polygonal cross-sections include all polygonal forms having three to many sides. Certain polygonal cross-sections have been shown to improve the spatial homogenization of channel radiation. For example, an optical pipe having a hexagonal cross-section along its entire length provided improved spatial homogenization compared to an optical pipe with a cylindrical cross-section of the same length.

[0136] In addition, the cross-section along the entire length of the optical pipe may vary. For example, the shape and diameter of any cross-section at one point along the length of the optical pipe may vary with a second cross-section obtained at a second point along the same segment of the pipe. In some embodiments, the optical pipe is a hollow structure between two ends. In these embodiments, at least one lumen or conduit may extend along the length of the optical pipe. The lumen of a hollow optical pipe generally possesses reflective properties. These reflective properties contribute to channeling radiation along the length of the optical pipe, so that radiation may be emitted at the distal end of the pipe. The inner diameter of the lumen may further possess one of the following: a smooth, diffuse, or textured surface. The surface properties of the reflective lumen or conduit help to spatially and angularly homogenize the radiation as it travels along the length of the optical pipe.

[0137] In additional embodiments, the optical pipe is a solid structure. The solid core can be covered with a cover plate, a coating, or a coating process. Again, a solid optical pipe generally provides internal reflection. This internal reflection allows radiation entering the proximal end of the solid optical pipe to be guided through the length of the pipe. The guided radiation may then be emitted outward from the distal end of the pipe without significant loss of radiation intensity.

[0138] A faceted elliptic reflector is an embodiment of the present invention that produces only a portion of the desired characteristics in the output radiation. In the case of a faceted reflector, spatial homogenization is achieved, but angular homogenization is not. In other cases, such as passing the output of a standard system through frosted glass, angular homogenization is achieved, but spatial homogenization is not. In these embodiments, where only angular or spatial homogenization (but not both) is produced, some improvement in the performance of the spectroscopic system can be expected. However, the degree of improvement is not expected to be as great as in systems where spatial and angular homogenization of radiation is achieved simultaneously.

[0139] Another method for creating both angular and spatial homogenization is to use an integrating sphere in the illumination system. While it is common to use an integrating sphere to detect light from a light-scattering sample, it has not been used as part of an illumination system when attempting to non-invasively measure the analyte. In practice, radiation emitted from an emitter can be coupled into the integrating sphere along with subsequent irradiation of the tissue through an exit port. The emitter can also be located inside the integrating sphere. While the integrating sphere would result in exceptional angular and spatial homogenization, the efficiency of this system is significantly lower than other embodiments previously identified.

[0140] Furthermore, it is recognized that other modifications can be made to the disclosed system to achieve the desired homogenization of light. For example, a solid light source can be placed inside the optical pipe in a sealed array, which would eliminate the need for a reflector. In addition, the optical pipe can be replaced with an integrator, with the light source placed inside the integrator. Moreover, the system can be used in non-infrared applications to achieve similar results in different wavelength ranges, depending on the type of analysis being performed.

[0141] (Description of an example embodiment) In an embodiment of the present invention ( schematically depicted in Figure 22), the non-invasive alcohol measurement system consists of 13 diode lasers used to measure 22 distinctly different wavelengths. Table 1 lists each diode laser and the relevant target peak wavelengths that will be examined during the measurement.

[0142] [Table 1] In this embodiment, each diode laser is stabilized at a constant temperature. The peak wavelength of each diode laser is controlled based on the circuit shown in Figure 5 (each diode laser has its own circuit), which also allows the diode lasers to be turned on and off. The specific state (on / off) of each diode laser at a given time during measurement is determined by a predetermined Hadamard or similar coding matrix. In embodiments incorporating solid-state light sources, the Hadamard matrix is ​​a pattern of on / off states relative to time for each diode laser, stored in software and implemented electronically rather than by a physical mask or chopper that would mechanically modulate the solid-state light source. This allows the on / off states stored in software to be communicated to the electronic control circuit of each diode laser during measurement.

[0143] Since some of the diode lasers in Table 1 are involved in two wavelength locations, it may be difficult to achieve an Hadamard scheme that incorporates all wavelengths. In this case, a combination of scanning and Hadamard coding can enable all target wavelengths to be measured. In this embodiment, all diode lasers (for those with more than one target wavelength) are tuned to their first target wavelength, and the Hadamard coding scheme is used to achieve the associated multiplexing benefit. The diode lasers can then be tuned to their second target wavelength, and a second Hadamard coding scheme can be used. Diode lasers with only one target wavelength can be measured in one or both groups, or they can be split between groups.

[0144] Furthermore, the groups can be interleaved in time. For example, for a 2-second measurement, the first group can be measured in the first second and the second group in the second second. Alternatively, the measurements can occur alternately at 0.5-second intervals over 2 seconds. The measurement times do not need to be symmetrical across the groups. For example, it may be desirable to optimize the signal-to-noise ratio by weighting the measurement times toward one group or the other. Those skilled in the art will recognize that balancing the measurement times, the number of groups, the scan-to-Hadamard ratio, and many permutations of interleaving are possible and considered in embodiments of the present invention.

[0145] In the embodiment, the outputs of each diode laser are combined and homogenized using an optical pipe with a hexagonal cross-section. In some embodiments, the optical pipe may include one or more bends to provide angular homogenization in addition to spatial homogenization. In any case, at the output of the optical pipe, the emission of all diode lasers is preferably spatially and angularly homogenized so that all wavelengths have substantially equivalent spatial and angular content when introduced to the input of the sampling subsystem 200.

[0146] Homogenized light is introduced into the input of the optical probe. In this embodiment, the input consists of 225 0.37 NA silica-silica optical fibers (referred to as illumination fibers) arranged in a geometric shape that matches the cross-section of the optical homogenizer. The light is then transmitted to the sample interface. The light exits the optical probe and enters the sample, and a portion of the light interacts with the sample and is collected by 64 collection fibers. In this exemplary embodiment, the collection fibers are 0.37 NA silica-silica fibers.

[0147] The optical probe output arranges the collection fibers in a geometric shape that matches the introduction into the homogenizer. In an example embodiment, the homogenizer is a hexagonal optical pipe. The homogenizer ensures that the contents of each collection fiber contribute substantially equally to the measured optical signal. This can be important for samples such as human tissue, which may be inherently heterogeneous. The output of the homogenizer is then focused onto a photodetector. In an exemplary embodiment, the photodetector is an extended InGaAs diode whose output current varies with the amount of incident light.

[0148] Next, the processing subsystem filters and processes the current and converts it into a digital signal using a 2-channel delta-sigma ADC. In this embodiment, the processed analog detector signal is split and introduced into both ADC channels. Since the embodiment involves a VCSEL with two measurement groups (e.g., two target wavelengths), an Hadamard transform is applied to the spectral signals acquired from each group, and subsequent transforms are combined to form an intensity spectrum. The intensity spectrum is then transformed logarithmically to base 10 before subsequent alcohol concentration determination.

[0149] The examples of embodiments are suitable for applications combining alcohol with either the “registered” or “walk-up / general-purpose” aspect, as well as other analyte properties such as abuse substances. Furthermore, any of the discussed aspects or combinations can be considered independently or in combination with the measurement of biometric properties.

[0150] 3,245 alcohol measurements were obtained from 89 individuals on five non-invasive alcohol systems, measuring spectra incorporating 22 wavelengths into the “walk-up” pattern. The measurements spanned a wide range of demographics and environments. Figure 23 shows the near-infrared spectroscopic measurements obtained from the study. Figure 24 compares the non-invasive alcohol concentrations obtained from the spectroscopic measurements shown in Figure 23 with the simultaneous capillary blood alcohol concentration (BAC).

[0151] Another embodiment is shown in Figure 39, which uses 39 diode lasers and 39 wavelengths measured. Table 2 shows the diode lasers and their target wavelengths.

[0152] [Table 2] The remaining system parameters, including the sampling subsystem, optical homogenizer, detector, and processing, are identical to those of the previously described embodiments. Figure 25 shows 8,999 spectroscopic measurements obtained from 134 individuals on six non-invasive measurement devices. Figure 26 shows the resulting non-invasive alcohol measurements for venous blood alcohol.

[0153] In some embodiments, calibration shifts can be performed using a small number of measurements for a sample, along with known properties of the analyte. For non-invasive alcohol measurement, each instrument may have a small number of measurements taken for individuals in which alcohol is absent. Any non-zero alcohol result on an instrument becomes a measurement error that can be used to correct subsequent measurements on that instrument. The number of measurements used to estimate the correction can vary and generally depend on the required correction accuracy. Generally, this process is analogous to instrument-specific calibrations corresponding to alcohol devices such as individually calibrated breath testers.

[0154] A similar approach can be applied to calibration and maintenance. In many applications of alcohol testing, the majority of measurements are performed on individuals who are unlikely to have alcohol present. For example, in workplace safety where employees are routinely tested for alcohol, employees are far more likely to be alcohol-free than intoxicated (e.g., most people enter the workplace alcohol-free). In this case, the true alcohol concentration can be assumed to be zero and the median, or other means can be used to exclude low-frequency true alcohol events in order to estimate instrument correction. This can be implemented as a running median filter, moving window, or a more sophisticated multivariate algorithm to determine an appropriate correction for a given time.

[0155] Those skilled in the art will recognize that the present invention can be expressed in various forms other than the specific embodiments described and considered herein. Accordingly, deviations in form and detail can be made without departing from the scope and spirit of the invention.

[0156] (Ongoing system calibration) To maintain maximum accuracy and precision over operating conditions and time, it is desirable to have information about the state of the alcohol measuring device (e.g., the optical and electrical components contributing to the measurement) immediately before tissue measurement. This is called a "calibration measurement." While current and temperature-related controls are employed on certain sensing components of the system, there are a significant number of mechanical and optical error contributing factors that can change with time and temperature. In addition, even with fixed controls, there may be errors associated with the operation of electrical components, as well as factors related to surface treatment, and potential light contamination of the probe must also be considered. Therefore, it is desirable to measure the complete optical and electrical state of the device against a known standard sample immediately before measuring the tissue sample of interest. The measurement of the standard sample then allows subsequent (or preceding) tissue measurements to be corrected for the current state of the alcohol measuring device.

[0157] To obtain calibration measurements, light from the light source / modulation subsystem (100) is delivered to a standard sample by the sampling subsystem (200), where it interacts with the standard sample. A portion of the light is collected by the sampling subsystem (200) and coupled to a photodetector in the data acquisition subsystem (300). One way to achieve this is to use an optical fiber that is distinctly different from that of the sampling surface (e.g., skin tissue, the surface being measured). In this case, the light delivered to the standard sample will travel a different path than the light examining the skin. This difference in optical paths may be acceptable in some embodiments. Furthermore, in other embodiments, the optical fiber itself can function as the standard sample (e.g., the optical fiber collects light from the light source / modulation subsystem (100) and delivers it directly to a photodetector in the data acquisition subsystem (300)). In some embodiments of these approaches, a gating mechanism can be applied to select which optical path (the path to the skin sampling surface or the path to the calibration sample) is being measured by the photodetector at a given time. While these approaches are acceptable in some embodiments, they are not optimal in the sense that a different path than that of the actual probe is being measured.

[0158] Therefore, in order to maintain substantially the same optical path and calibration standard for the light used to examine skin tissue, a method is required to place a movable calibration standard with known characteristics at the tissue interface of the sampling subsystem (200). The calibration sample can be measured immediately before the tissue measurement and then removed for the actual measurement. The calibration sample can be manually inserted into the path, but an automated method for insertion and removal is preferred in some embodiments.

[0159] One such method for automated calibration sample insertion is to integrate it into the probe head cover or into a button that the user interacts with. The main elements of such a method would be as follows: 1) A movable door very close to the tissue interface, to which a reflective standard surface is added on the back. 2) A method for moving the door out of the way so that the tissue measurement surface is directly presented to the probe. 3) Method for returning the reflective surface to its stationary position. It should be noted that a person skilled in the art can design any number of electromechanical or mechanical mechanisms to achieve this objective.

[0160] In the first embodiment, the movable door is covered on its back with a suitable reflective material and slide, allowing the sensing head to rotate to the finger surface. A spring provides the restoring force necessary to return to the stationary / calibration position.

[0161] In the second embodiment, a sliding button acts as a guide for a semi-flexible tape fixed to the bottom end. The back of the flexible tape is covered with a suitable reflective surface. The movement of the sliding button allows the tape to slide below the window opening on the surface of the button, allowing the sensor to make contact with a finger. A spring provides the restoring force necessary to return to the stationary / calibration position. Note that alternative embodiments can be designed such that the sensing head is stationary, while the door / button and / or calibration sample are the only moving parts.

[0162] Furthermore, without altering the basic concept, the embodiment can be enhanced with styling features and finger guides to help facilitate placement, and it should be noted that the mechanism and additional styling features will function equally well whether the dorsal side of the finger, the palmar side of the finger, or other skin surface is presented.

[0163] Referring to Figure 28, the system depicted in Figure 1 can be incorporated into the starting system of any transport vehicle (including all forms of land, water, and air transport). For example, the system can be incorporated as an electromechanical component of an ignition system, including a starter button, turning a key, or other typically used forms in which the driver activates the power to prepare the transport vehicle for movement.

[0164] Such a system can be used to measure the presence or concentration of an analyte or biometric identifier in an individual attempting to start a transport vehicle, when the measured information is used to modify the vehicle's subsequent electromechanical response. For example, biometric identification may be used to identify a specific driver (from a possible group of drivers) and to modify the position or orientation of driver and / or control settings, such as infotainment settings or vehicle actuator settings. In another embodiment, as illustrated in Figure 27, the system can be used to measure the concentration of an analyte to enable or disable the ability to start a transport vehicle and / or initiate an alternative operation. For example, measuring alcohol in a motor vehicle driver above a legal threshold may limit their ability to start a transport vehicle, or it may trigger a telematics system to provide an automated call to an alternative form of transportation, including a designated driver and / or taxi.

[0165] In another embodiment, the system can be integrated into a transport vehicle control system that is in continuous or near-continuous contact with an operator, such as a steering wheel, handlebars, or control stick. As such, the system can perform analyte and / or biometric measurements that are used to influence subsequent transport vehicle operations or trigger alternative operations, either continuously or periodically, or triggered by other control logic.

[0166] In another embodiment, the system can be integrated into a transport vehicle or facility access system (e.g., entrance door, trunk, etc.) and thus perform analyte and / or biometric measurements used to influence access to the entrance and / or subsequent level control upon entry.

[0167] In another embodiment, the system can be integrated into other transport vehicle subsystems, and direct contact between the operator's skin and the sampling subsystem 200 is maintained temporarily, periodically, or continuously. Slightly modified embodiments are also possible in which semi-passive contact is maintained, and in which contact is made through an action initiated by the operator. In such cases, continuous or periodic analyte and / or biometric measurements can be performed that affect subsequent transport vehicle operations or trigger alternative operations.

[0168] In the system described in Figure 28, the human-machine interaction between the operator and the sampling subsystem 200 must be coupled with the sampling subsystem to trigger a measurement, and can be configured to inform the intended operator of the presence of the system and the intended body part and / or location. For example, the use of audible and / or verbal and / or lighting and / or tactile feedback can be used to educate the operator and provide positive / negative feedback about the proper measurement process and / or the results of the measurement.

[0169] An embodiment of the present invention ( schematically depicted in Figures 29a-b) differs from the system depicted in Figure 22 by directly coupling discrete solid-state light sources of various wavelengths into a homogenizer made of a material that minimizes losses across all supported wavelengths, thereby reducing the need for a coupling mechanism between the solid-state light source, homogenizer, and sensing subsystem. In this embodiment, the material, size, shape, and coating of the homogenizer can be controlled to optimize light transmission and minimize losses while directly providing the sensor subsystem 200 emitter.

[0170] Figure 7 depicts a system in which multiple distinctly different emitters are used, and in an alternative embodiment depicted in Figure 30, a single emitter can be created using several lattice zones with distinctly different current paths that produce distinctly different wavelengths when driven in combination with current. By changing which combination of lattices is driven over time, distinctly different wavelengths can be achieved in the time-domain signal. In this way, a number of wavelengths can be sampled over time in a predetermined pattern. Knowledge of the sampling sequence in the detector and processor can be used to obtain the spectroscopic measurements described in subsequent embodiments.

[0171] In another embodiment, the system further includes one or more air, temperature, and relative humidity sensors, the measurements derived from these sensors being available to subsystem 400 to correct and / or improve the analyte and / or biometric measurements to compensate for anthropogenic variations due to these environmental influences and / or variations in individual subsystems due to the extended system (for example, if the measurement subsystem 200 is spatially or thermally distinct from subsystem 100, or if the system emitter and detector are temperature-compensated to a fixed value (independent of ambient conditions), but the optical fibers, homogenizer, and coupler require temperature compensation based on ambient conditions).

[0172] When performing several analytes measurements where the probability of the analyte's presence in a population of potential operators is low, it may be advantageous to perform a simpler, earlier measurement to first determine whether any given analyte is present, and then, only if detected, perform a subsequent measurement of the analyte's concentration. This is illustrated in Figure 31. For example, in the case of alcohol as the analyte, the majority of predicted car operators will not have alcohol in their system when attempting to start their vehicle. To reduce the average measurement time, presence measurements can be used.

[0173] In many safety applications, at least two heterogeneous technology sensors must detect signals to make a decision to activate an action. This greatly reduces the tendency for false positives due to undetected single-sensor failures or errors. In similar situations, the system described in Figure 32 can be combined to include one or more independent sensors indicating the presence or concentration of the analyte and / or confirming a biometric measurement.

[0174] The system in Figure 22 depicts a system utilizing a discrete-wavelength solid-state light source, while the alternative embodiment depicted in Figure 33 depicts a system utilizing a single broad-spectrum blackbody source coupled to a discrete-wavelength filter that allows only the intended wavelengths to pass through. The subsequent processing steps remain the same as those previously shown, but undesirable system noise can be avoided in the detection and discrimination processes.

[0175] In the previously described embodiments of the system utilizing diode lasers, the modulation characteristics of these devices can vary deterministically based on the driver and compensation circuit, as well as the ambient temperature and the electromechanical properties of the device itself (e.g., laser grating structure, material, size, shape, and heating / cooling components). As illustrated in Figure 34, the modulation time may be shortened by waiting until the solid light source intensity settles to a desired level (T2). To improve the modulation rate available for multiplexed light of various wavelengths, the a priori modulation characteristics can be compensated in the detector logic, thus shortening the settling time (T1).

[0176] It should be understood that both the general and detailed descriptions above are illustrative and descriptive only, and do not limit the invention.

[0177] For the purposes of this disclosure, the term “joined” means joining two components (electrically or mechanically) directly or indirectly to one another. Such joinings may be inherently static or inherently movable. Such joinings may be achieved using two components (electrically or mechanically) and any additional intermediate members that are integrally formed with each other as a single body, or using two components or two components and any additional members that are attached to each other. Such joinings may be inherently permanent, or alternatively, inherently removable or detachable.

[0178] The diffuser structures and arrangements shown in preferred and other exemplary embodiments are illustrative only. While only a few embodiments of the airbag assembly are described in detail in this disclosure, a person skilled in the art reviewing this disclosure will readily understand that many modifications are possible (e.g., variations in the size, dimensions, structure, shape, and proportions of various elements, parameter values, mounting arrangement, material use, orientation, etc.) without significantly departing from the novel teachings and merits of the subject matter described herein. Accordingly, all such modifications achievable by a person skilled in the art from this disclosure within the scope and spirit of the invention are included as further embodiments of the invention. Any order or sequence of process or method steps may be changed or rearranged according to alternative embodiments. Other substitutions, modifications, changes, and omissions may be made to the designs, operating conditions, and arrangements of preferred and other exemplary embodiments without departing from the spirit of the application.

Claims

1. A system for non-invasively measuring an object to be analyzed by a motor vehicle driver and controlling the vehicle based on the measured value of the object to be analyzed, wherein the system is A laser bar, wherein the laser bar is A first plurality of solid-state light sources, each of the first plurality of solid-state light sources being a first plurality of solid-state light sources that emits light of a first wavelength, A second plurality of solid light sources, each of the second plurality of solid light sources emits light of a second different wavelength, and A laser bar equipped with, A first optical transmission fiber for receiving and combining the light emitted by the first plurality of solid-state light sources to provide a first combined ray, A second optical transmission fiber for receiving and combining the light emitted by the second plurality of solid-state light sources to provide a second combined ray, An optical cable for receiving the first combined ray and the second combined ray, and an internal reflective optical homogenizer configured to combine the first combined ray and the second combined ray to provide a third combined ray, A sampling subsystem comprising a movable door, a standard sample coupled to the back of the movable door, and a sampling surface, wherein the tissue of the automobile driver is placed on the sampling surface, and the sampling subsystem is configured to introduce the third combined ray emitted by the optical cable (i) into the tissue of the automobile driver when the movable door is in a first position, and (ii) into the standard sample when the movable door is in a second position, One or more photodetectors configured to detect portions of the third combined ray that are not absorbed by the tissue of the automobile driver and the standard sample, A controller configured to provide a signal to a device configured to control the automobile, based on the light detected by one or more photodetectors, calculates the measured value of the analyte in the tissue of the automobile driver and the measured value of the analyte in the standard sample, determines whether (i) the measured value of the analyte in the tissue of the automobile driver exceeds a predetermined value, and (ii) the measured value of the analyte in the sample matches a predetermined measured value of the analyte in the standard sample, and provides a signal to the device configured to control the automobile. A system that includes these features.

2. The system according to claim 1, wherein the laser bar further comprises a single means for controlling the temperature of each of the first plurality of solid light sources and each of the second plurality of solid light sources.

3. The system according to claim 1, further comprising a biometric device configured to identify or verify the identity of the motor vehicle driver, wherein the biometric device collects a set of biometric data from the motor vehicle driver, compares the set of biometric data with a set of registration data corresponding to authorized motor vehicle drivers stored in the biometric device, and, if applicable, identifies which of the authorized motor vehicle drivers provided the set of biometric data.

4. The system according to claim 3, wherein a predictive driver provides an intended identity to the vehicle, the biometric device collects a set of biometric data from the predictive driver, and the biometric device verifies whether the actual identity of the predictive driver is the intended identity of the predictive driver by comparing the set of biometric data of the predictive driver with the set of registration data corresponding to the intended identity of the predictive driver.

5. The system according to claim 1, wherein the intensity of each of the first plurality of solid-state light sources and the second plurality of solid-state light sources is modulated independently.

6. The system according to claim 1, wherein the light emitted by at least one of the first plurality of solid light sources and the second plurality of solid light sources, and the light detected by the one or more photodetectors, have wavelengths between 1,000 nm and 2,500 nm.

7. The system according to claim 1, further comprising a microcontroller configured to turn on and off the first plurality of solid-state light sources and the second plurality of solid-state light sources according to a set of states defined by a predetermined modulation scheme.

8. The system according to claim 1, wherein each of the first plurality of solid light sources and the second plurality of solid light sources is configured to be tuned to a plurality of peak wavelength locations such that the system can measure locations at more wavelengths than the total number of solid light sources provided in the system.

9. The system according to claim 1, wherein the optical homogenizer is configured to provide uniform radiance of the third combined ray introduced into the tissue of the automobile driver by the sampling subsystem.

10. The system according to claim 1, wherein the measured value of the analyte includes the presence, concentration, rate of change of the concentration, direction of change of the concentration, or a combination thereof of the analyte.

11. The system according to claim 1, wherein the first plurality of solid-state light sources and the second plurality of solid-state light sources are arranged in a planar array.

12. The system according to claim 1, wherein the first plurality of solid light sources and the second plurality of solid light sources are divided into one or more groups, and each solid light source within the one or more groups is placed on the common carrier for each group with a predetermined spacing between other solid light sources placed on the same common carrier.

13. The system according to claim 1, wherein the first plurality of solid-state light sources and the second plurality of solid-state light sources are located within a single semiconductor to form the laser bar.

14. A method for non-invasively measuring an object to be analyzed by a motor vehicle driver and controlling the vehicle based on the measured value of the object to be analyzed, wherein the method is: To provide a system for non-invasively measuring an object to be analyzed by a motor vehicle driver and controlling the vehicle based on the measured value of the object to be analyzed, wherein the system is A laser bar, wherein the laser bar is A first plurality of solid-state light sources, each of the first plurality of solid-state light sources being a first plurality of solid-state light sources that emits light of a first wavelength, A second plurality of solid light sources, each of the second plurality of solid light sources emits light of a second different wavelength, and A laser bar equipped with, A first optical transmission fiber for receiving and combining the light emitted by the first plurality of solid-state light sources to provide a first combined ray, A second optical transmission fiber for receiving and combining the light emitted by the second plurality of solid-state light sources to provide a second combined ray, An optical cable for receiving the first combined ray and the second combined ray, and an internal reflective optical homogenizer configured to combine the first combined ray and the second combined ray to provide a third combined ray, A sampling subsystem comprising a movable door, a standard sample coupled to the back of the movable door, and a sampling surface, wherein the tissue of the automobile driver is placed on the sampling surface, and the sampling subsystem is configured to introduce the third combined ray emitted by the optical cable (i) into the tissue of the automobile driver when the movable door is in a first position, and (ii) into the standard sample when the movable door is in a second position, One or more photodetectors configured to detect portions of the third combined ray that are not absorbed by the tissue of the automobile driver and the standard sample, A controller configured to provide a signal to a device configured to control the automobile, based on the light detected by one or more photodetectors, calculates the measured value of the analyte in the tissue of the automobile driver and the measured value of the analyte in the standard sample, determines whether (i) the measured value of the analyte in the tissue of the automobile driver exceeds a predetermined value, and (ii) the measured value of the analyte in the standard sample matches a predetermined measured value of the analyte in the standard sample, and provides a signal to a device configured to control the automobile. To be equipped with, The light ray is introduced into the tissue of the automobile driver by (i) moving the movable door to the first position, or (ii) moving the movable door to the standard sample by the second position. The one or more photodetectors detect the portion of the light that is not absorbed by the vehicle driver's tissue or the standard sample, The controller calculates the measured value of the substance to be analyzed in the automobile driver's tissue or the standard sample based on the light detected by the one or more photodetectors, The controller determines whether (i) the measured value of the analyte in the tissue of the automobile driver exceeds a predetermined value, or (ii) the measured value of the analyte in the standard sample matches a predetermined measured value of the analyte in the standard sample. Controlling the automobile based on the measured values ​​of the analyte in the tissue of the automobile driver or in the standard sample. Methods that include...

15. The method according to claim 14, wherein the laser bar further comprises a single means for controlling the temperature of each of the first plurality of solid light sources and each of the second plurality of solid light sources.

16. The method according to claim 14, further comprising turning on and off at least one of the first plurality of solid light sources and the second plurality of solid light sources by a microcontroller in accordance with a set of states defined by a predetermined modulation scheme.

17. The method according to claim 14, wherein the measured value of the analyte includes the presence, concentration, rate of change of the concentration, direction of change of the concentration, or a combination thereof of the analyte.

18. The system according to claim 1, wherein the first plurality of solid light sources and the second plurality of solid light sources are arranged in close proximity to each other to enable a single temperature control for adjusting the temperatures of the first plurality of solid light sources and the second plurality of solid light sources.

19. The system according to claim 1, wherein the internally reflective optical homogenizer has a hexagonal cross-section.

20. The method according to claim 14, wherein the first plurality of solid light sources and the second plurality of solid light sources are arranged in close proximity to each other so as to enable a single temperature control for adjusting the temperatures of the first plurality of solid light sources and the second plurality of solid light sources.

21. The method according to claim 14, wherein the internal reflection type optical homogenizer has a hexagonal cross-section.

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