Abstract:
Systems and methods for detection of human fat metabolism byproducts and analysis of the detection for optimizing dietary results. The present invention includes a compact opto-electronic based sensor to significantly increase (factor of 20 or more) the accuracy and minimal detection limits for a standard ketone test strip.

Description:
PRIORITY CLAIM 
       [0001]    This application claims priority to U.S. Provisional Patent Application No. 61/347,310, filed May 21, 2010, which is incorporated herein by reference. This application is a Continuation-in-Part of U.S. patent application Ser. No. 12/139,259 filed Jun. 13, 2008, which is incorporated herein by reference. 
     
    
     BACKGROUND OF THE INVENTION 
       [0002]    The connection between generation of ketones, specifically acetoacetate and b-hydroxybutyrate, in the blood and urine and the utilization of body fat is well established. It is also well known that certain reagents such as nitroprusside will change color in the presence of ketones, which proves to be a useful color indicator. 
         [0003]    In U.S. Pat. No. 5,260,291, Fritz suggests the use of standard nitroprusside test strips along with standard nitrogen test strips as a dietary aid—specifically to determine the amount of fat metabolism in a weight loss program. However, Gupta in U.S. Pat. No. 6,762,035 indicates that these strips primarily measure acetoacetate and not b-hydroxybutyrate. The data presented by Gupta suggests that the measurement of acetoacetate alone is not sufficient and that a test strip must be modified to also measure b-hydroxybutyrate to be of use. 
         [0004]    Allen, et al. in U.S. Pat. No. 7,364,551 suggests use of a portable electro-chemical device for measuring ketones in the breath. However, breath analysis is highly complex and is easily fooled by byproducts of oral bacteria and dietary intake. 
         [0005]    The difficulty of both Fritz&#39;s and Gupta&#39;s approach is that they rely on “by eye” comparison of strip color changes to a color chart. Such comparisons are extremely subjective. Issues occur with the user being all or partially color blind and baseline color of the urine sample. Moreover the color is changing dynamically (manufacture suggests reading at 20 seconds after urine application). These issues led to highly inaccurate results and severe limits on minimal detection limits. 
       SUMMARY OF THE INVENTION 
       [0006]    This invention provides systems and methods for detection of human fat metabolism byproducts and analysis of the detection for optimizing dietary results. 
         [0007]    The current invention includes a compact opto-electronic based sensor to significantly increase (factor of 20 or more) the accuracy and minimal detection limits for a standard ketone test strip. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0008]    Preferred and alternative examples of the present invention are described in detail below with reference to the following drawings: 
           [0009]      FIG. 1  is a block diagram of an exemplary system formed in accordance with an embodiment of the present invention; 
           [0010]      FIG. 2  shows an exemplary data set produced by the system shown in  FIG. 1 ; 
           [0011]      FIGS. 3   a, b  show an exemplary sensing cartridge formed in accordance with an embodiment of the present invention; and 
           [0012]      FIGS. 4   a, b  show an exemplary metabolism sensing device formed in accordance with an embodiment of the present invention. 
       
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
       [0013]    Parent U.S. patent application Ser. No. 12/139,259 (&#39;259) describes a chemical sensor that uses multiple colored light sources (e.g. LEDs) to observe changes in agent-reagent colorimetric chemical reactions taking place in an absorbing layer placed within an integrating sphere. 
         [0014]      FIG. 1  is a block diagram of an embodiment of the present invention which includes a metabolism sensing device  30 . The metabolism sensing device  30  includes a color sensor  10  combined with a sensing cartridge  12  in such a way as to produce the color sensor described in &#39;259. Specifically, the color sensor  10  is physically interfaced to the sensing cartridge  12  so that the sensing cartridge  12  forms part of an absorbing layer within an integrating sphere as described in &#39;259. As will be described in more detail later, the sensing cartridge  12  is designed to include means to apply a small urine sample that becomes the chemical agent to be tested. 
         [0015]    The metabolism sensing device  30  includes a microprocessor  14  that performs data acquisition and control of the color sensor  10 . In one embodiment, the microprocessor  14  is responsible for collecting data at specified time intervals (e.g. once per second). The microprocessor (or microcontroller)  14  includes an algorithm that processes temporal variations in the data obtained from the color sensor  10  and places a data-time stamp on that data. The microprocessor  14  stores the compendium of data, analysis results, and date-time on a non-volatile memory  16  for later use. 
         [0016]    In one embodiment, the metabolism sensing device  30  also includes a display  18  (or comparable output device) to show test results for current measurement, past measurements, trend lines and other pertinent data. The metabolism sensing device  30  also includes a user input device (e.g. a keypad or a touch screen as part of the display device) to be used for setting time, date, initiating measurements, or recalling data. 
         [0017]    The metabolism sensing device  30  also includes a digital interface device  22  (e.g. a USB port) for connecting a personal computing device  24  (e.g. a personal computer (PC), a smart phone, a tablet computer device, etc.) The personal computing device  24  includes software that allows a user to track results versus time, set and compare goals, develop trends, etc. in a typical graphical user interface (GUI) environment. 
         [0018]      FIG. 2  shows data retrieved from an exemplary metabolism sensing device  30  in which the reagent is a nitroprusside ketone sensing strip and the agent is a urine sample with a moderate level of acetoacetate (a particular ketone) present (˜15 mg/dl). Four color channels (red  80  at 630 nanometer, yellow  82  at 587 nanometers, green  84  at 570 nanometer, blue  86  at 470 nanometer) were simultaneously measured at 1 second intervals. The data shown are fractional changes in reflection for each color channel. The shift in color in ketone strips is described by the strip manufacturer as moving towards a pinkish purple as a composite (apparent) color to the eye. The data in  FIG. 2  shows that all the ‘pure’ colors are changing to give this impression. Several different time scales are clearly present in the data. The strip manufacturer&#39;s instructions are to read the color after 20 seconds. Clearly missing this time point by even a few seconds causes a significant error in the measurement. 
         [0019]    Accurate reading of the apparent color changes is challenging without the use of the colorimetric chemical sensor followed by analysis of the chemical dynamics seen in the time sequences. Time sequence analysis can be performed by measurement of decay rates on the several color channels for known concentrations. These key signatures can then be used to fit unknown samples. Sensitivity of better than 0.25 mg/dl has been demonstrated for acetoacetate, roughly a factor of 20 better than ‘by eye’ comparisons to color charts. 
         [0020]    Independent measurements on non-dieting, reduced calorie dieting and low carbohydrate (Atkins) dieting with the sensor indicated a ketone range of less than 3 mg/dl ketone concentrations (undistinguishable from zero for ‘by eye’ measurements), from 3 to 15 mg/dl for reduced calorie dieters with the high range being achieve for those performing heavy exercise and greater than 15 mg for low carbohydrate dieters. The normal dieting range is in the region of trace to very low for ‘by eye’ measurements according to the strip manufacturer&#39;s instructions. 
         [0021]    Further details of the sensing cartridge  12  are shown in  FIGS. 3   a  and  b .  FIG. 3   a  is a top view and  FIG. 3   b  is a cut away side view showing the internal components of the sensing cartridge  12 . The sensing cartridge  12  includes a cartridge housing  100 , a liquid transport body  102 , an absorbing layer  104 , and a transparent window  106 . The sensing cartridge  12  is designed to be inexpensive, so as to disposable after use. The cartridge housing  100  would be nominally produced via plastic molding processes and laid out for accurate optical alignment when placed into the device  30 . The liquid transport body  102  is designed to rapidly absorb an applied urine sample and transport the urine sample rapidly to the absorbing layer  104 . Structured plastic materials such as those found in standard pregnancy test cartridges are an example of a suitable liquid transport body  102 . The absorbing layer  104  contains the reagent (e.g. nitroprusside) within a matrix that will absorb urine from the liquid transport body  102  with which it is placed in direct contact. Ordinary filter paper is an exemplary base for such the absorbing layer  104 . The transparent window  106  allows optical access for measuring the color changes that will occur in the absorbing layer  104  when ketone in the urine reacts with the reagent (e.g. nitroprusside) in the absorbing layer  104 . 
         [0022]      FIGS. 4   a  and  b  show an example of the sensing cartridge  12  as it is placed into the metabolism sensing device  30 .  FIG. 4   a  is a top view and  FIG. 4   b  is a cut away side view showing the internal components. The device  30  includes a device housing  200  which includes a printed circuit board (PCB)  202  along with alignment guides  204  and an alignment stop  206 . The alignment guides  204  and the alignment stop  206  are placed such that insertion of the sensing cartridge  12  forces alignment of the transparent window  106  with an optically integrating housing  216  that is attached to the PCB  202 . 
         [0023]    The PCB  202  allows mounting of integrated circuits corresponding to the microcontroller  14  and the memory  16 . Of note is that some microcontrollers contain sufficient internal non-volatile memory formed as a separate integrated circuit. The display  18 , such as an alpha-numeric display or a dot-matrix display, is also connected to the PCB  202 . The digital interface  22  as in the form of a USB connector is mounted onto the PCB  202 . Other incidental components such as capacitors, resistors, clock crystals, and power connections are added to the PCB  202  as needed for correct operation of the individual integrated circuits or display. The user interface  20  is in the form of push buttons. 
         [0024]    A set of light sources (two shown)  210  and  212  and an optical detector  214  are placed inside the optically integrating housing  216  with all these components attached to the PCB  202 . The optically integrating housing  216  is open on the end opposite the PCB  202  such that it can be placed into direct contact with the transparent window  106  of the sensing cartridge  12 . This arrangement is a particular form of the optical sensor described in U.S. patent application Ser. No. 12/139,259 whereby the optically integrating housing  216 , that portion of the PCB  202  contained within the housing  200  and the absorbing layer  104  produce an ‘integrating sphere’. The light sources  210  and  212  are turned on sequentially. The illumination from the light sources  210  and  212  is scattered throughout the volume contained within the ‘integrating sphere’ whereby some portion of the scattered light is absorbed in the absorbing layer  104 , and that of the scattered light portion not absorbed is scattered back into the detector  214 . The microcontroller  16  controls the illumination process and digitally records the response from the detector  214 . 
         [0025]    In operation, the device  30  is activated through activation of one of the push buttons  20  after introduction of the sensing cartridge  12 . The user would then wet the liquid transport body  102  with a urine sample. The urine will then transport up the liquid transport body  102  until it flows into and wets the absorbing layer  104 . The wetting of the absorbing layer  104  can be readily detected by sudden change in the reflectance properties of the layer. At this point data is collected by the device  30  on a regular sampling period (e.g. 1 second). The resulting data sampled at the sampling periods will look similar to that shown in  FIG. 2 . This data can then be analyzed as compared to calibration standards to produce an estimate of the amount of ketone present in the urine sample. Results of the test can then be shown on the display  18 . The display  18  could also be used to indicate process progress. The raw data, the ketone estimate, a date-time stamp and any other useful data (e.g. a user ID) can then be stored as a data set in the memory  14 . Once completed, the sensing cartridge can be disposed. 
         [0026]    The data set stored in the memory  14  can be transferred via the digital interface  22  to the personal computing device  24  for further analysis, plotting versus time or other useful data displays. The user could also use the user input  20  to retrieve data sets stored in the memory  16  and show historical results on the display  18 . 
         [0027]    Although the current invention is directed towards detection of ketones in urine, the application can be applied to other low level metabolic byproducts for which suitable reagents can be produced is also possible as well as the application to other body fluids such as blood and saliva. 
         [0028]    While the preferred embodiment of the invention has been illustrated and described, as noted above, many changes can be made without departing from the spirit and scope of the invention. Accordingly, the scope of the invention is not limited by the disclosure of the preferred embodiment. Instead, the invention should be determined entirely by reference to the claims that follow.