System for identifying correlations among concentration values of breath biomarkers and formulating relevant transformation equations

Abstract

Present invention relates to a system which is capable of, using concentration value of a molecule (e.g. O2) present in the breathing air, analyzing and identifying the concentration value of other different molecules (CO, H2O, CO2, N2O) present in the same breathing air, characterized as comprising a processor which compute concentration values of CO, N2O, H2O and CO2 based on a mathematical algorithm. In the present invention, measurement of these molecules are only for illustrative purposes. The method employed also applies to other molecules and their combinations.

Description

[0001] SYSTEM FOR IDENTIFYING CORRELATIONS AMONG CONCENTRATION VALUES OF BREATH BIOMARKERS AND FORMULATING RELEVANT TRANSFORMATION EQUATIONS

[0002] Technological Field:

[0003] The present invention relates to a method which is capable of identifying correlations among concentration values of breath biomarkers and formulating the equations for transformations among them. In this way, concentration value of one single molecule can be used to analyze other different molecules simultaneously. Thus, breath analysis can be performed in a more effective, faster, easier and more cost-effective way.

[0004] State of Art:

[0005] Breath analysis is a popular study topic in clinical and scientific studies because of its advantages such as being non-invasive and easily reproducible. Different methods are employed in the breath analysis in order to analyze multiple molecules simultaneously. Multiple laser sources (or sensor systems) or adjustable dual-mode laser systems can be used for simultaneous measurement of multiple molecules. If isolated absorption lines of analyzed molecules fall within the adjustment range of fine wavelength of laser used, then it is possible to detect and quantify multiple molecules simultaneously. However, using multiple laser sources (or sensor systems) or dual-mode laser substantially increases the size and price of sensors. With these methods, a maximum of three to four molecules can be analyzed.

[0006] The literature survey we conducted resulted in a patent application no. EP1850112A1. This invention describes a device which can measure concentrations of multiple gases with high precision and simultaneously using gas correlation method. This method uses reference and probe gas cells specifically designed for each analysis gas based on the principle that different gases absorb infrared light at different rates. Device comprises a light source emitting a broad band of infrared light, collimator, gas correlation filter, multi-reflective gas sample cell, and infrared detector. This structure allows high- precision measurement of low-concentration gases in applications such as environmental pollution monitoring and atmospheric analysis.

[0007] The literature survey we conducted resulted in a patent application no. CN117110223 A. Invention relates to technical area of flue gas pollution source monitoring. Invention provides a NO2 detector. NO2 detector comprises a sample gas inlet, an air inlet, an O3 generator, an O3 generator valve, a stop valve, Noxscrubber, Noxscrubber valve, NOXand O3 scrubber, a reaction cavity, an activated carbon adsorber, a moisture stabilizer, a NO2 detection chamber, a LED light source, and a pump.

[0008] Although aforementioned inventions provide a solution for identification of the concentrations of different gaseous elements, they do not relate to analysis of different molecules using concentration value of one single molecule. Therefore, they do not relate to present invention in any aspects.

[0009] As a result, there is a need for a new technology that can overcome the disadvantages mentioned above.

[0010] Description of Invention:

[0011] Present invention provides a system which uses concentration value of a molecule contained in breathing air in order to simultaneously analyze other different molecules present in the same breathing air. One embodiment of the invention established correlation between concentration values of oxygen molecule (O2), and carbon dioxide (CO2), nitrous oxide (N2O), carbon monoxide (CO) and water vapor (H2O) molecules, and formulated equations for transformations among them. Such correlation is established for the first time in the world in the relevant technological field. Other embodiments of the invention is possible using other molecules. Therefore, our invention provides a new, more comprehensive method which enable a more effective, faster, easier and less-costly breath analysis for non-invasive diagnosis and monitoring of diseases in the healthcare industry, in particular.

[0012] Our invention does not require expensive and large sensors unlike the currently available systems. It can be realized with commercially available cost-effective and compact sensors, eliminating the need for multiple laser sources and adjustable dualmode lasers. This not only reduces costs, but also makes the system portable and compact.

[0013] Method used in the invention is generally applicable. Our embodiment of the invention used oxygen molecule (O2), carbon dioxide (CO2), nitrous oxide (N2O), carbon monoxide (CO) and water vapor (H2O), and established a high degree of correlation between (O2) and other molecules. Analyses resulted in significantly higher R2values between concentration values of O2 and CO2, N2O, CO, and H2O: 0.97, 0.98, 0.995, and 0.97, respectively. This demonstrates that the measurements are reliable and the results obtained are capable of competing with currently available technologies in terms of accuracy.

[0014] Our invention also consumes lower energy than other systems requiring multiple laser source or dual-mode laser. This allows the system run for longer periods and, therefore, provides energy savings.

[0015] Our invention has the capability of fast analysis unlike the currently available methods. Analysis duration is shortened significantly as concentration value of only one single molecule (for instance, O2 molecule) is measured to calculate concentration values of other molecules. In addition, its portable structure makes it easy to use in different locations.

[0016] It will be possible to use our invention in various healthcare applications such as diagnosis of diseases based on breath analysis, and non-invasive monitoring of the treatment processes. Furthermore, it will also be possible to adapt our invention for use in fields such as indoor security, environmental analyses and industrial applications. Description of Drawings:

[0017] Invention will be described through references to appended drawings, and therefore specifications of the invention will be understood more clearly and appreciated, however, this is not intended to limit invention to these certain embodiments. On the contrary, it is intended to cover all alternatives, modifications, embodiments, and equivalences that can be included in the field of the invention defined by the appended claims. It should be understood that the details provided and / or shown is provided and / or shown in order to describe the preferred embodiments of the present invention, and facilitate the most useful and easier-to-understand definition both for embodiments of the methods and rules and conceptual particulars of the invention. In these drawings;

[0018] Figure 1 A schematic representation showing working mechanism of invention.

[0019] Figure 2 Graphical representation showing correlation between O2 and CO2 molecules.

[0020] Figure 3 Graphical representation showing correlation between O2 and NO2 molecules.

[0021] Figure 4 Graphical representation showing correlation between O2 and CO molecules.

[0022] Figure 5 Graphical representation showing correlation between O2 and H2O molecules.

[0023] While the figures that will help this innovation to be understood are enumerated as it is defined in annexed picture, they are presented below with their names.

[0024] Legend:

[0025] 1. QEP AS sensor

[0026] 2. MuPAS sensor

[0027] 3. Electro-chemical sensor

[0028] 4. Processor Gg. Breathing air inlet

[0029] G¥. Breathing air outlet

[0030] Detailed Description of Invention:

[0031] Present invention relates to design of a new system which, using one single molecule, enable simultaneous analysis of other different molecules. The embodiment of the invention we studied established correlations between concentration values of O2 molecule and CO2, N2O, CO, and H2O. However, other embodiments of the invention is possible with different molecules.

[0032] Concentration values of CO and H2O were obtained by means of QEPAS (photoacoustic absorption spectroscopy) sensor (1). Concentration values of CO2 and N2O were obtained by means of MuPAS (multi-pass absorption spectroscopy) sensor (2). Concentration value of O2 was measured by means of chemical sensor (3).

[0033] As a light source in QEPAS sensor (1), distributed feedback quantum cascade laser was used to detect the absorptions of CO and H2O. Laser driver / thermoelectric cooler controller was used to control the temperature and injection flow of the laser. Laser beam was collimated by means of a 3 mm focal length aspherical lens and then sent to QEPAS cell to analyze molecules. In this method, wavelength modulation spectroscopy technique was used to improve signal-noise ratio (SNR) by shifting measured signals to higher frequencies to reduce 1 / f noise. Injection flow of laser is modulated by a high- frequency (in kHz range) sinusoidal function superimposed on a slower ramp function. Present invention applied a sinusoidal vibration at 12455 Hz and a ramp signal at 10 mHz to the flow injected to the laser in order to modulate and scan the laser beam. Output voltage of QEPAS cell was demodulated by means of a DSP dual-phase lock-in amplifier.

[0034] Experimental setup of MuPAS sensor (2) is based on a multi-pass absorption spectroscopy. A laser at 4474 nm wavelength (DFB QCL) was used as an excitation source to target the CO2 and N2O absorption lines. Laser chip was operated by a diode / TEC controller. Laser beam was collimated by a 3 mm focal length aspherical lens and then sent to a compact multi-pass absorption cell with an optical path of 3.2 meters in order to analyze the biomarkers present in the breathing air. The laser beam leaving the cell were measured by a detector. Electrical signals generated by detector were sent to processor (4).

[0035] A 3-electrode electrochemical sensor (3) was used to analyze the oxygen molecules.

[0036] Then, the concentration value of oxygen molecules so obtained was used to compute the concentration values of CO, N2O, H2O and CO2 based on a mathematical algorithm executed by the processor (4), i.e. x = A * (1 + (y / x))'z, {Figure 2-5}, where; x = concentration value of any of CO, N2O, H2O, or CO2 , y = concentration value of O2,

[0037] A = concentration factor, z = exponential factor.

[0038] Correspondence analyses demonstrated a significantly high degree of correlation.

[0039] In the formula, concentration factor can be any value in the range of 10 - 30, and exponential factor can be any negative value in the range of 0.9 - 1.1.

[0040] Figure 2 shows the correlation between concentrations of breath molecules studied. When CO2 concentration values are plotted against O2 / CO2 ratio (O2 normalized to CO2), a very significant correlation between concentration values is obtained. Correspondence analysis resulted in an R-squared value of 0.97.

[0041] Similar to Figure 2, graphical representations in Figures 3 to 5 show the correlations between O2 and N2O, between O2 and CO, and between O2 and H2O. For these latter figures, correspondence analyses resulted in R2values of 0.98, 0.995, and 0.97, respectively.

[0042] Values provided herein and therein are only for illustrative purposes. The method used also applies to all similar studies.

Claims

CLAIMS1- Invention is a system which comprises a QEPAS sensor (1) to detect absorptions of CO and H2O, a MuPAS sensor (2) to detect absorptions of CO2 and N2O, an electrochemical sensor (3) to detect O2 absorptions in order to identify, using concentration value of a molecule (e.g. O2) present in the breathing air, the concentration values of other different molecules (e.g. CO, N2O, H2O, and CO2), characterized as comprising- a processor (4) which uses concentration value of a molecule to compute the concentration values of other different molecules based on a mathematical algorithm.2- A system according to Claim 1, comprising a processor (4) which executes a mathematical algorithmic function, i.e. x = A * (1 + (y / x))‘z, where; x = concentration value of any of CO, N2O, H2O, or CO2 , y = concentration value of O2,A = concentration factor, z = exponential factor.

Images