Patent Document

CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    The application is a Continuation of U.S. application Ser. No. 12/471,935, filed May 26, 2009, now allowed, which claims benefit to U.S. Provisional Application No. 61/055,480, filed May 23, 2008, which are incorporated herein by reference in their entirety. 
     
    
     BACKGROUND OF THE INVENTION 
       [0002]    1. Field of the Invention 
         [0003]    The present invention relates to a health monitoring device and, more particularly, to a glucose monitoring device. 
         [0004]    2. Description of the Related Art 
         [0005]    For many people, the need to measure and monitor blood glucose levels is very important. Conventionally, a sample of blood needs to be drawn and placed in a measuring device in order to accurately measure in vivo blood glucose concentrations. 
         [0006]    There is a need to develop a non-invasive technique to accurately measure in vivo blood glucose concentrations. 
         [0007]    The device and method of the present invention addresses this need. 
       BRIEF SUMMARY OF THE INVENTION 
       [0008]    The invention relates to the development of technical means for chemical analysis of acetone in the air, namely portable devices for quantitative analysis micro amounts of acetone in exhaled air, primarily the indirect noninvasive blood glucose or insulin monitoring in human blood. 
         [0009]    There are invasive devices for determining the content of glucose in the blood of diabetics, athletes, and pregnant women. These devices have substantial disadvantages that limit their use. Primarily, these devices require damage to blood vessels, when drawing blood samples; moreover (except chromatographic analysis) they do not give necessary precision. 
         [0010]    It is known that a larger quantity of acetone vapors contained in exhaled air of diabetics, pregnant women, people engaged in heavy physical labor, and athletes at high physical loads. 
         [0011]    It is also known that the concentration of acetone in exhaled air correlates with the content of glucose in the blood. In other words t the acetone is a reliable biological marker that allows control of glucose in the blood. 
         [0012]    As established by biochemical studies t glucose in the blood is one of the main suppliers of energy to the body. If the blood has not enough insulin t which transports glucose molecules to the cells of the body (diabetes), or if glucose is expired (because high physical activity), the body begins the process of oxidation of fats. It fills a deficit of energy. But the oxidation of fats results in acetone as a by-product. This is the reason for increasing of the acetone content in the exhaled air. 
         [0013]    Thus, the increasing of acetone in the exhaled air of diabetics shows a deficit of insulin in the blood. In the case of people engaged in heavy physical labor, acetone is demonstration of glucose deficit in the blood. 
         [0014]    For people with diabetes, increasing of the acetone content in the exhaled air may be a signal for insulin injections. For people of heavy physical labor, increased acetone content in the exhaled air may be a signal to take additional products that contain sugar or glucose. 
         [0015]    From numerous scientific publications it is well known that the concentration of acetone in exhaled air is correlated with the content of glucose in the blood. In other words, the acetone is a reliable biological marker for monitoring the content of glucose in the blood. 
         [0016]    There are devices for noninvasive determining of the glucose content in the blood of people with diabetes. These devices also have disadvantages, which do not allow them to be used widely. The main drawback of is the lack of precision and selectivity in relation to acetone. 
         [0017]    The lack of precision—is the main drawback of the mentioned devices as well as incorrect and inaccurate information about the content of glucose in the blood can lead to serious consequences for the patient. 
         [0018]    For example, one known device is a method that uses cavity ringtown spectroscopy. Through a small cameral fitted with mirrors, air filled air with vapor of acetone, the beam of infrared laser is given. The beam is reflected by mirrors. This mirror method does not provide an opportunity to build a simple and reliable portable device. 
         [0019]    A few noninvasive devices for determining glucose in the blood by determining the concentration of acetone in exhaled air are described in the literature. They are based on direct determining of acetone&#39;s concentration by optical methods. These devices are not optimal because they have low accuracy, are complicated, and cumbersome. 
         [0020]    The present invention has created a handheld portable device, which will determine the concentration of acetone in exhaled air with a minimum content of acetone 3-5 mg/liter with an accuracy that will satisfy doctors and patients. 
         [0021]    In one embodiment, the present invention is a device for measuring the concentration of acetone in exhaled air in order to determine the content of glucose in the blood, comprising: 
         [0022]    (a) an inlet for expirated air; 
         [0023]    (b) a dosator for receiving air from said inlet; 
         [0024]    (c) an actuator for receiving air from said dosator with substantially the same volume for each measurement, said actuator interrupts air from said inlet when said dosator reaches a specified volume; 
         [0025]    (d) a chemical cell containing a solution; 
         [0026]    (e) a light emitter constructed and arranged for emitting light to pass through and spectrally analyze said solution; 
         [0027]    (f) an optical sensor; and 
         [0028]    (g) a microprocessor; 
         [0000]    wherein said microprocessor produces an output correlating measurements of said optical sensor with blood glucose concentration. 
         [0029]    The device has an actuator that controls a valve that fills said dosator with a predetermined volume of gas. The actuator controls either or both of a valve that fills said dosator with a predetermined volume of gas and a valve that releases gas from a filled dosator into a chemical cell. 
         [0030]    The device of claim  1  wherein said chemical cell contains a solution to selectively react with acetone from expired air. The solution contains a solute selected from Sodium Iodate, Sodium Nitroprusside, Metadiamine, Phenylhydrazone, Furfural, o-Nitrobenzaldehyde, or combinations thereof. 
         [0031]    The device further comprises an output of a numerical value, wherein said numerical value is produced by said microprocessor and correlates the difference in optical absorbance of an unreacted chemical cell solution with a chemical cell solution reacted with acetone from exhaled air to produce an output congruous with blood glucose concentration. The output is displayed on a screen, transmitted wirelessly to a receiving device, or combinations thereof. 
         [0032]    The present invention further includes a method for determining acetone concentration in exhaled air and correlating said acetone concentration with blood glucose levels, said method comprising: 
         [0033]    (a) providing a device according to the invention; 
         [0034]    (b) initiating a blank reading spectral of said chemical sensor solution; 
         [0035]    (c) instructing a user to inhale and hold their breath for about 3-5 seconds; 
         [0036]    (d) having said user exhale into an inlet of said device; 
         [0037]    (e) taking a spectral reading of said chemical cell solution after reaction with acetone in expired air; 
         [0038]    said device measures the change in absorbance from said blank reading with said spectral reading after reaction of said chemical cell solution with acetone from expired air and said device produces an output whereby said difference in absorbance is correlated with blood glucose concentration of said user. 
         [0039]    Additional aspects of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The aspects of the invention will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed. 
     
    
     
       BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS 
         [0040]    The accompanying drawings, which are incorporated in and constitute part of this specification, illustrate embodiments of the invention and together with the description, serve to explain the principles of the invention. The embodiments illustrated herein are presently preferred; it being understood, however, that the invention is not limited to the precise arrangements and instrumentalities shown, wherein: 
           [0041]      FIG. 1  is a top perspective view of the device; 
           [0042]      FIG. 2  is a bottom perspective view of the device; 
           [0043]      FIG. 3  is a block scheme of the measurement system; 
           [0044]      FIG. 4  is a block scheme of the measurement system; 
           [0045]      FIG. 5  is a cross section of the chemical cell; 
           [0046]      FIG. 6  is a graph of precent optical absorbance vs. Na-nitroprusside concentration in mcg/ml; 
           [0047]      FIG. 7  is an absorbance spectrum; 
           [0048]      FIG. 8  is a scatterplot with linear representation of best fit line correlating blood glucose concentration with acetone concentration in exhaled air; 
           [0049]      FIG. 9  is a graph correlating the change in optical absorbance vs. acetone concentration in mcg/liter in exhaled air; 
           [0050]      FIG. 10  is a scatterplot with linear representation of best fit line correlating blood glucose concentration with acetone concentration in exhaled air; and, 
           [0051]      FIG. 11  is a graph of absorbance spectra of several light emitting diode (LED) sources. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0052]    Device  10  has an inlet  12  that directs exhaled air from a person into first tube  26  and ultimately into dosator  11 . Dosator  11  holds exhaled air until dosator  11  if filled. An actuator  21  closes a valve when dosator  11  is filled such that the volume delivered to the measurement parts of the system is substantially constant. The actuator  21  is either mechanical or electrical and is calibrated to close a valve based on a predetermined volume of exhaled air in dosator  11 . When dosator  11  is filled, and valve is closed, actuator  21  directs exhaled air from within dosator  11  through second air tube  27  and into chemical cell inlet  28 . Chemical cell  23  is housed in cell cavity  14  formed in device housing  13 . Chemical cell  23  has a sensor solution for selectively reacting with components of exhaled air. Chemical cell  23  is positioned such that it is between light emitter  25  and optical sensor  17 . A beam of light  32  from light emitter  25  passes through chemical cell  23  and is detected by optical sensor  17 . Optical sensor  17  is operatively connected with a microprocessor  22  and an electrical amplifier  20 . Microprocessor  22  received light absorbance measurements from optical sensor  17  and using programmed correlation information, assigns a numerical value to acetone concentration. (A converter  19  converts the optical signal into an electrical signal.) The acetone concentration is processed using a mathematical algorithm to produce a correlation with conventional blood glucose concentration. Screen  15  displays a numerical value of blood glucose concentration based on the concentration of acetone in exhaled air. 
         [0053]    Chemical cell  23  is a truncated cone and has solution  35  filled therein to level such that air is present above solution  35  in the interior of chemical cell  23 . 
         [0054]    Chemical cell  23  is a truncated cone. This configuration is advantageous as the shape reduces the scattering and focus beam of light from the light emitter  25 . This reduction in scattering allows the maximum amount of light from the light emitter  25  to reach optical sensor  17 . Other form shapes lacks this advantage. 
         [0055]    Chemical cell outlet  30  has valve  31  that regulates the rate at which air exits chemical cell  23 . Air that exits chemical cell outlet  30  and valve  31  is vented to the atmosphere. In a preferred embodiment, device  10  has a second air tube  27  that is a capillary with a diameter of 30-50 microns. In solution  35 , which is a water-alcohol solution of sodium-nitroprusside and sodium hydroxide, a foam is not formed, and air bubbles with diameter of 50-70 microns pass through the solution  35 . The solution  35  itself remains in the chemical cell  23 . 
         [0056]    The device of the presentation invention is constructed and arranged to carry out an inventive method through a novel system. The device, system, and method of the invention comprise:
       Chemical cell  23  that can form a complex chemical compound with acetone (this compound is determined by a spectral method in the near UV spectral region),   Sampling exhaled air using a constant-volument container,   Receiving an analytical result, using a novel cell design.       
 
         [0060]    Chemical cell  23  is a mini-cell, this is filled with solution  35  of an organic compound, easily quickly and selectively reacting with acetone. The product of interaction acetone with organic compounds is forming a color complex, defined by spectral method. 
         [0061]    The analytical result is achieved by the registration of a molecular spectrum, followed by intensification of an electrical signal. 
         [0062]    The scheme of the device is represented in the  FIGS. 3-5 . The device works as follows: 
         [0063]    Exhaled air enters into the inlet  12  of device  10 . Dosator  11  is a bellow or balloon type structure that is filled to a fixed volume. Once dosator  11  is filled, an actuator  21  closes a valve to restrict any additional air from entering dosator  11  and a valve is opened by the system automatically sends air through second air tube  27  to interact with a solution  35  in chemical cell  23 . 
         [0064]    The solution  35  is a chemical solution of an organic compound, easily, quickly and selectively reacting with acetone. The solution  35  is placed in a chemical cell  23  that is preferably a mini-cell. 
         [0065]    In chemical cell  23  a foam will not be formed. The air leaves the chemical cell  23  through cell outlet  30 , not taking the chemical reagents from the solution  35  because of a very low surface tension of the solution  35 . In addition, the design of the chemical cell  23  and the input and output air&#39;s system will protect against the loss of reagents from the chemical cell  23 . 
         [0066]    The system is constructed and arranged such that the presence of air entering chemical cell  23  through chemical cell inlet  28  activates the system. Once the air has passed through the solution  35  of the chemical cell  23 , the measurement system turns on. 
         [0067]    Acetone, which is one component of exhaled air, quickly and quantitatively reacts with the solution  35 , resulting in a new chemical complex compound, suitable for the precise definition by spectral methods. 
         [0068]    A beam of light  32  from light emitter  25  passes through a filter-monochromator  18  (i.e. a monochromatic screen), after that through the solution of the reacted solution  35 , and said beam falls upon an optical sensor  17  that is a photometer photosensitive element. Optical sensor  17  produces an electric signal that is intensified in an electrical amplifier  20 , and the signal is processed by microprocessor  22  to ultimately be displayed on screen  15 . A battery  16 , which can be covered by a housing cover  6 , provides power. 
         [0069]    The light emitter  25  is selected based on correlation with the maximum emission needed in the field. In the examples described herein, light emitter  25  is an LED-7 which has a maximum emission correlating with sodium nitroprusside absorbance. If other chemical sensors are used, other sources of emission are selected. Selection of a light emitter  25  is based on those light sources with a maximum emission that coincides or is close to the field of absorption of the particular chemical cell  23 . 
         [0070]    In the examples herein, the light source (LED-7) used as light emitter  25  in the present invention has a constant spectral characteristic as shown in  FIG. 10 . While passing the beam of light through the solution  35  of the chemical cell  23 , the partial absorption of the emission occurs in the field of 380-420 nm. After the interaction of solution  35  with acetone, beam from the light emitter  25  passes again through the solution  35 . As the acetone takes out the portion of the chemical cell  23  (proportional to the concentration of acetone) from this spectral region (380-420 nm), the second absorption in the 380-420 nm is lower than in the first case. The difference between the two absorptions gives the change in the concentration of chemical sensor and proportionally—the concentration of acetone in 1 liter of breath. 
         [0071]    Monochromatic screen is an optical filter  24  that is a transparent color film, which transmits a narrow interval of optical emission within approximately 350-450 nm. A monochromatic screen (filter) will be used to remove unwanted optical “noise” and increase the sensitivity of the device. 
         [0072]    In order to obtain reproducible results of air sampling, a patient needs to inhale air into the lungs, keep the air in the lungs for 3-5 seconds | and then exhale out the air into inlet  12  where expirated air enters device  10 . 
         [0073]    Device  10  measures the concentration of acetone in air introduced into the device in a range from about 3-5 mg/liter. The present invention has discovered the range of acetone concentration of about 3-5 mg/liter is sufficient for accurate correlation with glucose concentrations in the blood. 
         [0074]    There are several organic compounds that will achieve the desired result. The present invention contemplates selection of at least one organic compound to carry out the objective of the present invention. The reaction product obtained from the interaction of acetone with at least one organic compound forms a color complex, defined by spectral method. 
         [0075]    The device, system, and method of the present invention utilize particular chemical reagents capable of rapid interaction with traces of acetone in exhaled air. The suitable reagents include, but are not limited to: 
       Sodium Iodate, 
     Sodium Nitroprusside, 
     Metadiamine, 
     Phenyl-hydrazone, 
     Furfural, and 
       [0076]    o-Nitrobenzaldehyde. 
         [0077]    The stoichiometric calculation of concentrations of sodium nitroprusside and sodium hydroxide was made. As a base, the actual concentrations of acetone (5 to 80 mcg/liter of breath) were used. The resulting concentrations of both reagents are necessary and sufficient to capture any amount of acetone in the specified limits. 
         [0078]    For other chemical sensors similar stoichiometric calculations can be made. 
         [0079]    In a preferred embodiment, the device, system, and method of the present invention utilizes the following reaction scheme: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0080]    The device  10  has microprocessor  22  incorporated and operatively associated with all the components of device  10 . 
         [0081]    Microprocessor  22  provides the following functions and other functions as needed: 
       Pneumatic System Control 
       [0000]    
       
         
           
             Fixing the amount of breath in dosator  11 , 
             Change the actuator  21  for the air flow, 
             Control the speed of air passing through the solution  35  of the chemical cell  23 . 
           
         
       
     
       Optical—Chemical System Control 
       [0000]    
       
         
           
             Turning on a light emitter  25 , 
             Recording of the optical sensor  17 , such as, for instance, an optical diode. 
           
         
       
     
       Reform of Electrical Signal to Device Index 
       [0000]    
       
         
           
             Recalculation and correlation of the electrical signal from an optical sensor  17  to the concentration of acetone, 
             Recalculation and correlation of the concentration of acetone detected to the concentration of glucose in blood, 
             Sending the result to the screen  15  of the device  10 , 
             Sending results by e-mail. 
           
         
       
     
         [0091]    The microprocessor is contemplated to have appropriate transmission mechanism to wirelessly transmit by email, text message or other wireless transmission, the results of a particular test to an email or server. 
         [0092]    Control of Device Systems
       Turning on the device,   Control sequencing of device work,   Turning off the device.       
 
       Example 1 
       [0096]    Sodium hydroxide and sodium nitroprusside are dissolved in a mixture of water and ethanol (a ratio of 50:50) to create a solution  35 . The use of water-ethanol mixture as a solvent prevents a neutralization of sodium hydroxide by carbon dioxide (carbon dioxide is a part of the exalted air). 
         [0097]    The solution  35  in the amount of 0.5 ml is poured into the chemical cell  23 . The chemical cell  23  is a hollow truncated cone, made of transparent plastic. The entrance for the air, the chemical cell inlet  28 , is in the wide part of the cone of chemical cell  23 , and in the narrow part there is a chemical cell outlet  30  for air that is regulated by an valve  31  that ultimately vents air from the chemical cell  23  to the atmosphere. Chemical cell  23  is oriented vertically in the optical measurement system of device  10 . The wide part of the chemical cell  23  is facing down, to the source of light, a light emitter  25 . The narrow part of the chemical cell  23  is facing up—to an optical sensor  17 . 
         [0098]    A light emitter  25  is a light source in the optical system. As a light source, the LED-7 element is selected. Its optical performance is presented in  FIG. 11 . For other chemical cell sensors  23  other emitters can be selected, mainly from the group LED. 
         [0099]    Before testing begins, a measurement is recorded of the optical absorption of the solution  35  (the first measuring) as a blank. The absorbance spectrum of the chemical cell  23 , including sodium nitroprusside and sodium hydroxide in the water—ethanol mixture is presented in  FIG. 7 : 
         [0100]    The spectrum has a maximum absorption at 393 nm. An absolute value of the maximum depends on the concentration of sodium nitroprusside in the solution  35 . The dependence of maximum absorption (an optical density) on the concentration of sodium nitroprusside is presented is presented below in  FIG. 6 . 
         [0101]    To determine acetone in the exhaled air the following concentrations of the solution  35  are selected: 
         [0000]    
       
         
               
               
               
             
           
               
                   
                   
               
             
             
               
                   
                 Sodium-nitroprusside 
                 450-600 micrograms/ml, 
               
               
                   
                 Sodium hydroxide 
                 630-850 micrograms/ml. 
               
               
                   
                   
               
             
          
         
       
     
         [0102]    The device  10  is now ready to measure acetone in exhaled air. Dosator  11  is filled with 1 liter of the exhaled air that enters device  10  through inlet  12  and is delivered to dosator  11  through first air tube  26 . Dosator  11  is controlled by actuator  21  that controls one or more air regulator valves. Once dosator  11  is filled, actuator  21  restricts additional air from exiting dosator  11 . Actuator  21  allows air to exit dosator  11  through second air tube  27  that is directed into chemical cell inlet  28  and ultimately into solution  35  in chemical cell  23  and exits through chemical cell outlet  30  and is released to the atmosphere. Exalted acetone enters into a chemical reaction with the solution  35  and forms a new chemical substance as demonstrated by reaction scheme  1 . 
         [0103]    Device  10  has operative electronics and microprocessor components such that when dosator  11  is empty, light emitter  25  turns on. The optical absorption of sodium nitroprusside, which remained after the formation of the new chemical substance (the second measuring) is measured and recorded. 
         [0104]    After reaction with acetone in exhaled air, the absorption peak of sodium nitroprusside is reduced. The optical components of device  10  measure the absorbance of solution  35  after reaction with acetone in exhaled air. 
         [0105]    The difference between the first measurement i.e. before reaction with acetone in exhaled air, and second measurement i.e. after reaction with exhaled air is processed in a microprocessor  22  that has computer readable information for corresponding the concentration of acetone in the exhaled air based on the change in absorbance of solution  35 . Laboratory results are presented in  FIG. 9 . 
         [0106]    The present device, system, and method correlate the concentration of the exalted acetone proportional to the concentration of glucose in the blood. 
         [0107]    Experimental Correlation 
         [0108]    Measurement of the exalted acetone (two voluntaries) showed the presence of acetone in amounts of 27 and 42 mg/l. For determination of glucose, the published data on the correlation between the content of exalted acetone and the content of glucose in the blood are used. 
         [0109]      FIGS. 8 and 10  present data on the correlation. In accordance with these data the content of glucose in the blood of patients is found equal to 70 and 105 mg/dl. Measurement of glucose with a standard device has confirmed the reliability of the results. A comparison was made with a standard device Accu-Check Go® (Roche Diagnostics, Indianapolis, Ind.). The difference between the device of the invention and the Accu Check® was 19% for one patient and 4% for the second patient. 
         [0110]    The analytical result is achieved by the registration of molecular spectrum, followed by intensification of an electrical signal. 
         [0111]    While the invention has been described in its preferred form or embodiment with some degree of particularity, it is understood that this description has been given only by way of example and that numerous changes in the details of construction, fabrication, and use, including the combination and arrangement of parts, may be made without departing from the spirit and scope of the invention. 
         [0112]    Having thus described the invention of the present application in detail and by reference to embodiments thereof, it will be apparent that modifications and variations are possible without departing from the scope of the invention defined in the appended claims as follows:

Technology Category: 3