Patent Publication Number: US-9835550-B2

Title: Breath analyzer

Description:
TECHNICAL FIELD 
     This invention relates to a breath analyzer. 
     BACKGROUND ART 
     Health conditions can be found through analysis of the composition or the concentration of gases contained in the breath. 
     For example, the acetone produced in the conversion of the accumulated free fatty acids in the body into blood glucose discharges out of the body with the breath. If the body fat combustion rate could be estimated from the concentration or the discharge amount of acetone, it would be possible to use the information for health management such as dieting. 
     The detection accuracy of a semiconductor gas sensor is not sufficient for the measurement of the concentration or the discharge amount of trace amounts of acetone in the breath, and a gas chromatography mass spectrometer is too large for this purpose. 
     PRIOR ART DOCUMENT 
     Patent Document 
     
         
         [Patent Document 1] JP 2001-349888 A (Kokai) 
       
    
     SUMMARY OF INVENTION 
     Problem to be Solved by Invention 
     An object of the invention is to provide a breath analyzer that is small and has high detection accuracy, and is capable of calculating a fat oxidation rate. 
     Means for Solving Problem 
     A breath analyzer of an embodiment includes a light source, a gas cell, a detection unit and a data processing unit. The light source emits infrared light of a wavelength band including an absorption line for acetone. A breath containing sample gas is introduced to the gas cell. And the infrared light is incident on the gas cell. The detection unit receives transmitted light emerging from the gas cell, and outputs a sample signal value corresponding to an acetone discharge amount. The data processing unit, on the basis of the sample signal value, determines an approximation formula of dependence of fat oxidation rate on acetone discharge amount in advance, and calculates a fat oxidation rate for individual sample signal values using the approximation formula. When the acetone discharge amount (microliter/min) is x, the fat oxidation rate (milligram/min) y is approximated by a following formula: y=Ax+B (where A and B are constants). 
    
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
         FIG. 1  is a diagram representing a configuration of the breath analyzer according to the embodiment. 
         FIG. 2  is a graph showing the dependence of fat oxidation rate on the total acetone discharge amount. 
         FIG. 3  shows the dependence of fat oxidation rate at rest. However, the graph may be of during activity. 
         FIG. 4  is a diagram representing a configuration of a measurement system that calculates the acetone concentration or the acetone discharge amount offline. 
         FIG. 5A  is a schematic perspective view of a cutaway portion of a QCL.  FIG. 5B  is a schematic cross sectional view taken at line A-A. 
         FIG. 6  is a band diagram describing the operation of the QCL. 
     
    
    
     EMBODIMENTS OF INVENTION 
     An embodiment of the invention is described below with reference to the accompanying drawings. 
       FIG. 1  is a diagram representing a configuration of the breath analyzer according to the embodiment. 
     A breath analyzer  10  includes a light source  20 , a gas cell  30 , a detection unit  40 , and a data processing unit  50 . 
     The light source  20  emits infrared light G 1  of a wavelength band that includes at least one absorption line for acetone. The light source  20  may be configured from light-emitting devices such as a QCL (Quantum Cascade Laser), and a semiconductor laser. 
     The gas cell  30  has an inlet  12  and an outlet  14 . A sample gas SG such as breath, or a reference gas (for example, the atmosphere) RG is introduced into the gas cell  30 . Infrared light G 1  is incident on the gas cell  30 . Displacement of the gas inside the gas cell  30  can be accelerated by providing a vacuum pump  90  at the outlet  14  of the gas cell  30 . 
     The detection unit  40  receives transmitted light G 2  emerging from the gas cell  30 , and outputs a sample signal value SS corresponding to the acetone discharge amount or the acetone concentration. 
     The data processing unit  50  determines an approximation formula of dependence of fat oxidation rate on acetone discharge amount in advance, and calculates a fat oxidation rate corresponding to the sample signal value SS of each measured acetone discharge amount. Alternatively, the data processing unit  50  determines an approximation formula of dependence of fat oxidation rate on acetone concentration, and calculates a fat oxidation rate corresponding to the sample signal value SS of each measured acetone concentration. When an approximation formula obtained by using a measurement system ( FIG. 4 ; described later) is input to the data processing unit  50  in advance, it is possible to accelerate the online calculation of the fat oxidation rate for individual sample signal values SS. 
     The acetone concentration calculation method is described below. 
     Absorbance A is represented by the Lambert-Beer law (Formula (1)). Absorption coefficient α is determined by the intensity of the absorption line, the pressure, and the temperature. 
                   A   =       -     ln   ⁡     (     I     I   0       )         =         -   ln     ⁢           ⁢   T     =     α   ⁢           ⁢   L                 (   1   )               
where
 
     A: Absorbance 
     I 0 : Intensity of incident light 
     I: Intensity of transmitted light 
     T=I/I 0 : Transmittance 
     α: Absorption coefficient 
     L: Light path length 
     When a reference gas RG such as the atmosphere is introduced into the gas cell  30 , the intensity I of the light that has passed through the reference gas RG can be regarded as the same as the incident light intensity I 0 . On the other hand, by displacing inside of the gas cell  30  with a sample gas SG, transmittance T or absorbance A can be calculated from formula (1) by measuring the intensity I of the transmitted light through the sample gas SG. 
     The absorbance is represented by the following formula.
 
Absorbance=1 −I/I   0 =1− T  
 
     The absorption coefficient α can be represented by formula (2). Here, the absorption coefficient α is dependent on the intensity, the pressure, and the temperature.
 
α=∈ c   (2)
 
where
 
     c: Molar concentration 
     α: Molar absorption coefficient 
     Following formulae (1) and (2), the molar concentration c of acetone can be given by formula (3). 
     
       
         
           
             
               
                 
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     The gas flow control system is described below. The flow rates of the breath sample gas SG and the reference gas RG are measured with a flowmeter  60 , and the total discharge amount can be found by integrating the flow rate through the flowmeter  60 . The sample gas SG and the reference gas RG that have passed through the flowmeter  60  are branched. The flow rate of the gas flow directed toward the gas cell  30  is controlled at a constant rate with a flow rate restriction mechanism  70 . The flow rate control mechanism  70  may be, for example, a mass flow controller, or a needle valve. The gas that has passed through the flow rate restriction mechanism  70  is introduced into the gas cell  30  through the inlet  12 . The other gas flow discharges out of the system through a needle valve  80 . The system components, including the flowmeter  60 , the flow rate restriction mechanism  70 , and the vacuum pump  90  may be automated under the control of a controller (not illustrated). 
     The absorption spectrum of acetone has a plurality of absorption lines. In the embodiment, the infrared wavelength is, for example, 8.125 μm (corresponding to a wavenumber of 1,230.8 cm −1 ). The influence of absorption by water can be reduced with this wavelength. Preferably, the wavelength of the infrared light G 1  from the light source  20  is accurately tuned to at least one absorption line. For example, when using a QCL, current modulation may be performed to provide a wavelength range that includes a predetermined absorption line. This enables accurately measuring transmittance T at the absorption line wavelength, and determining the absorption coefficient α, and the molar concentration of acetone. 
       FIG. 2  is a graph showing the dependence of fat oxidation rate on the total acetone discharge amount. 
     The vertical axis represents fat oxidation rate (mg/min) Y, and the horizontal axis represents the total acetone discharge amount (μl/min) X.  FIG. 2  shows the dependence of fat oxidation rate at rest. However, the graph may be of during activity. The fat oxidation (combustion) rate can be measured using an automatic metabolism measurement device. For example, the fat oxidation rate may be determined by measuring parameters such as an oxygen intake amount, and a carbon dioxide discharge amount. 
     The acetone discharge amount x is determined as the product of breath discharge amount and acetone concentration. The breath discharge amount may be measured with the flowmeter  60 . 
     From a distribution of measurement points, the fat oxidation rate y and the acetone discharge amount x have a correlation. The correlation is given as a linear function using the method of least squares, as represented by the following formula (4).
 
 y=Ax+B   (4)
 
where A and B are constants.
 
     Referring to  FIG. 2 , the linear function may be, for example, y=6.52x+33.3. In this case, the determination coefficient R 2  was 0.68 as measured by subtracting the residual sum of squares and the sum of squares of the differences from the sample average from 1. The dependence of fat oxidation rate on acetone concentration during activity also may be approximated by a linear function or the like. Considering parameters such as sex differences and age, the coefficient A and the coefficient B may be determined within appropriate ranges, specifically, 6 or more and 7 or less for coefficient A, and 0 or more and 50 or less for coefficient B. 
       FIG. 3  is a graph showing the dependence of fat oxidation rate on the breath acetone concentration. 
     The vertical axis represents fat oxidation rate (mg/min) y, and the horizontal axis represents the breath acetone concentration (ppm) x. 
       FIG. 3  shows the dependence of fat oxidation rate at rest. However, the graph may be of during activity. 
     From a distribution of measurement points, the fat oxidation rate y and the breath acetone concentration x have a correlation. The correlation is given as a linear function using the method of least squares, as approximated by the following formula (5).
 
 y=Cx+D   (5)
 
where C and D are constants.
 
     The linear function may be, for example, y=51x+32.3. In this case, the determination coefficient R 2  was 0.65. Considering parameters such as sex differences and age, the coefficient C and the coefficient D may be determined within appropriate ranges, specifically, 40 or more and 60 or less for coefficient C, and 0 or more and 50 or less for coefficient D. 
     The fat oxidation rate can be estimated by measuring the acetone concentration (ppm) and the acetone discharge amount in the breath sample gas SG of interest with the breath analyzer  10  shown in  FIG. 1 . For example, it is possible to promote health by making dieting plans based on the fat oxidation rate and the body weight, taking into account circumstances such as diet, and exercise. 
     The absorption efficiency can be improved by introducing the infrared light G 1  from the light source  20  into the gas cell  30  after condensing the infrared light G 1  with an optical system  100 . It is also preferable to increase the light path length L by providing, for example, a reflecting mirror  32  inside the gas cell  30  because it can increase the absorbance A of acetone, which has a small absorption coefficient α. 
     As shown in  FIGS. 2 and 3 , calculations of fat oxidation rate from individual sample signal values SS such as an acetone concentration and an acetone discharge amount become easier when the relation between fat oxidation rate and acetone concentration or acetone discharge amount is expressed beforehand as an approximation formula. 
     As a comparative example, a semiconductor gas sensor for acetone detection is available that includes, for example, a porous film containing at least one oxide, for example, tin oxide or indium oxide, one or more oxides of, for example, tungsten and molybdenum, and an element such as platinum. However, such a semiconductor gas sensor is insufficient in terms of selectivity and sensitivity. On the other hand, a gas chromatography analyzer requires highly skilled knowledge, in addition to being large and expensive. Such devices are accordingly difficult to use in homes. The device of the embodiment, on the other hand, has high sensitivity and high accuracy, and is small enough for use by ordinary users. 
       FIG. 4  is a diagram representing a configuration of a measurement system that calculates the acetone concentration or the acetone discharge amount offline. 
     The measurement system includes the breath analyzer  10  of the embodiment, an on-off valve  206 , a switch valve  208 , and a Douglas bag  210 , among other components. 
     The fat oxidation rate (or the body fat combustion rate) can be calculated by measuring, for example, an oxygen intake amount, and a carbon dioxide discharge amount with the metabolism measurement device. 
     The breathing rate of human is, for example, 10 to 50 liters/min. For offline measurement, for example, the breath is collected in a sampling bag  210  for a total of 30 minutes (10 min×3 times), using the on-off valve  206 , and the switch valve  208 . The sample gas SG that has accumulated in the sampling bag  210  is then sent to the breath analyzer  10  by switching the switch valve  208 . The reference gas RG, for example, the atmospheric gas, is sent to the breath analyzer  10  after being cleaned with a chemical substance removing filter  212 . 
       FIG. 5A  is a schematic perspective view of a cutaway portion of a QCL.  FIG. 5B  is a schematic cross sectional view taken at line A-A. 
     A QCL  5  includes at least a substrate  110 , a stacked body  120  provided on the substrate  110 , and a dielectric layer  140 . Referring to  FIG. 5A , the QCL also includes a first electrode  150 , a second electrode  152 , and an insulating film  142 . 
     The stacked body  120  has a first cladding layer  122 , a first guide layer  123 , an active layer  124 , a second guide layer  125 , and a second cladding layer q 28 . The refractive indices of the first cladding layer  122  and the second cladding layer  128  are smaller than the refractive index of any of the first guide layer  123 , the active layer  124 , and the second guide layer  125  so that an infrared laser beam  160  can be properly trapped in the stacked direction of the active layer  124 . 
     The stacked body  120  has a stripe shape, and can be called ridge waveguide RG. Assuming that the two end faces of the ridge waveguide RG are mirror surfaces, the light of stimulated emission is emitted as an infrared laser beam  162  through the light-emitting surface. In this case, the optical axis  162  is defined as the line that connects the centers of the cross sections of the optical resonator with the mirror surface serving as a resonating surface. In other words, the optical axis  162  lies in the direction of extension of the ridge waveguide RG. 
     When the width WA in a direction parallel to a first surface  124   a  and a second surface  124   b  of the active layer  124  is too wide in a cross section perpendicular to the optical axis  162 , a higher-order mode occurs in the horizontal traverse direction, and it becomes difficult to achieve high output. It becomes easier to control the horizontal traverse direction mode when the width WA of the active layer  124  is, for example, 5 to 20 μm. 
     By making the refractive index of the dielectric layer  140  smaller than the refractive index of any of the constituent layers of the active layer  124 , the ridge waveguide RG can be configured along the optical axis  162  with the dielectric layer  140  provided on the both sides of side surfaces  120   a  and  120   b  of the stacked body  120 . 
       FIG. 6  is a band diagram describing the operation of the QCL. 
     The active layer  124  has a cascade structure in which a first region  125  and a second region  126  are alternately stacked. Through an intersubband optical transition in a quantum well layer  172 , the first region  125  can emit an infrared laser beam  60  that includes an absorption line of acetone. The second region  126  can relax the energy of electrons  170  injected from the first region  125 . 
     Reducing the well width WT to, for example, several nanometers or less in the quantum well layer  172  causes the energy level to become discrete, and creates a subband  172   a  (high level Lu) and a subband  172   b  (low level Ll), for example. The injected electrons  170  from an injection barrier layer  173  become effectively trapped in the quantum well layer  72 . When a carrier transition occurs from the high level Lu to the low level Ll, emission of light (hν) corresponding to the energy difference (Lu-Ll) occurs (optical transition). The quantum well layer  172  has a plurality of wells with overlapping wave functions, and may include common levels Lu and Ll. 
     An intersubband transition occurs in either the conduction band or the valence band. Specifically, a hole and electron recombination by p-n junction is not necessary, and emission occurs solely by the optical transition of either carrier. In the example represented in the figure, an intersubband transition occurs as the stacked body  120  injects the electrons  170  to the quantum well layer  172  via the injection barrier layer  173  under the applied voltage across the first electrode  150  and the second electrode  152 . 
     The second region  126  has a plurality of subbands (or minibands as they are also called). Preferably, the subbands have small energy differences, and are a near continuous energy band. Because the electron energy is relaxed, an infrared laser beam including an absorption line for acetone does not occur in the second region  126 . The low-level Ll electrons of the first region  125  are injected into the second region  126  through the extraction barrier layer  74 , relaxed, and injected into the first region  125  on the next stage of the cascade connection (electrons  70 ) to cause the next optical transition. Specifically, the emission of an infrared laser beam by the optical transition is tuned within a spectrum range that includes an absorption line for acetone, for example, by varying the current. 
     In the QCL of the embodiment, the substrate  110  may be InP, the quantum well layer  172  may be InGaAs, and the barrier layer may be AlInAs, for example. In this case, the crystallinity of the active layer as a whole can improve when the quantum well layer and the barrier layer are strain compensated. The substrate  110  may be GaAs, the quantum well layer may be GaAs, and the barrier layer may be InGaAs, for example. The active layer  24  may have a width WA of 14 μm, and the ridge waveguide RG may have a length L of 3 mm, for example. 
     The embodiment provides a breath analyzer that is small and has high detection accuracy, and is capable of calculating a fat oxidation rate. The breath analyzer is useful for promoting health, and for dieting, for example. 
     While certain embodiments have been described, these embodiments have been presented by way of example only, and are not intended to limit the scope of the inventions. Indeed, the novel embodiments described herein may be embodied in a variety of other forms; furthermore, various omissions, substitutions and changes in the form of the embodiments described herein may be made without departing from the spirit of the inventions. The accompanying claims and their equivalents are intended to cover such forms or modifications as would fall within the scope and spirit of the invention.