WO2003055381A1 - Identification d'echantillon, analyse de la composition chimique et evaluation de l'etat physique de l'echantillon au moyen des spectres obtenus a differentes temperatures de l'echantillon - Google Patents

Identification d'echantillon, analyse de la composition chimique et evaluation de l'etat physique de l'echantillon au moyen des spectres obtenus a differentes temperatures de l'echantillon Download PDF

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Publication number
WO2003055381A1
WO2003055381A1 PCT/CA2003/000006 CA0300006W WO03055381A1 WO 2003055381 A1 WO2003055381 A1 WO 2003055381A1 CA 0300006 W CA0300006 W CA 0300006W WO 03055381 A1 WO03055381 A1 WO 03055381A1
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WIPO (PCT)
Prior art keywords
sample
temperature
spectrum
radiation
spectral
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PCT/CA2003/000006
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English (en)
Inventor
Romuald Pawluczyk
Karl Sampara
Sheu-Ju Hu
Mang Li
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Cme Telemetrix Inc.
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Priority to AU2003203067A priority Critical patent/AU2003203067A1/en
Priority to CA002471583A priority patent/CA2471583A1/fr
Publication of WO2003055381A1 publication Critical patent/WO2003055381A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14546—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring analytes not otherwise provided for, e.g. ions, cytochromes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry

Definitions

  • the present invention relates to a method of identifying components of a sample at different temperatures. More specifically, this invention provides a method of sample identification, chemical composition analysis, and testing the physical state of a sample by analyzing spectra obtained from a sample subjected to different temperatures.
  • Material objects produce or absorb electromagnetic radiation in certain parts of the spectrum of electromagnetic radiation.
  • Spectral distribution of the produced radiation by an object, or effect of the object on the spectrum of the radiation following interaction with the object depends on the chemical composition of the object, its physical state (for example, but not limited to gas, liquid, solid), and existing physical conditions acting on the object (for example but not limited to, pressure, temperature).
  • spectral characteristics of the radiation produced by an object, or changes in the spectrum of radiation interacting with the object can be used for identifying chemical elements and compounds in the object, or for identifying physical conditions acting on the object.
  • spectral specificity of the radiation produced by an object may be used for identification or the analysis of the chemical composition of an object, the specificity of spectral changes under different conditions, temperature in particular, is not recognized and, as a result, is not used in practice.
  • emission, absorbance and Raman spectroscopy are used to extract information from a sample using spectral measurements of electromagnetic radiation of the sample.
  • Each of these methods under certain condition can be used for identification of chemical elements and compounds of a sample, or for the determination of a relative or absolute, concentration of the elements and compounds in the sample.
  • a chemical element generates or absorbs electromagnetic radiation in a characteristic set of narrow spectral bands distributed in a specific fasliion within the electromagnetic radiation spectrum, including its visible part, when the element is in a form of free atoms and heated to sufficiently high temperature.
  • the pattern of these bands can be used for identifying chemical elements present in the sample.
  • information on relative intensity of radiation or absorption levels at these bands can be used for measuring the relative concentration of one or more elements in the sample under investigation.
  • the absolute concentration of the element in the sample may be determined.
  • Substances containing molecular compounds also produce specific images of emission and absorption bands due to transition between different vibration modes of molecules. Since the amount of energy needed to change a vibration mode of molecule is much lower than that needed to change electron energy level within the atom, emission and absorption bands of molecules are usually placed in middle and far infrared bands of the spectrum. Detection of such bands is difficult and emission spectra of molecules are seldom recorded. However, various indirect detection methods for measurement of absorption spectra may be used, for example Raman spectroscopy, which allows detection of transitions between different vibration modes ofmolecules.
  • Spectrum radiation affected by a light-absorbing sample may be determined by two factors: the spectral characteristics of radiation used for measurement, and the absorbing properties of the tested sample. To ensure that measurement results are independent of the spectral characteristics of the used radiation, the result needs to be suitably corrected, Such a correction is possible when spectral characteristics of used radiation are known. Since properties of all radiation sources can change with time, sometimes quite rapidly, the spectral characteristics of used radiation needs to be measured at a time that is close to the time of sample measurement. Furthermore, it is preferred that this measurement is made using the same measurement equipment as that used for the measurement of radiation affected by the sample.
  • the impact of samples on the radiation can be identified as a ratio of spectral distribution of radiation affected by the sample to that of radiation incident on the sample.
  • the negative decimal logarithm of this ratio is called the spectral optical density of the sample and it can be used for identification of one or more chemical compounds.
  • the spectral optical density may also be used, with further processing, to determine the relative or absolute concentration of one or more compounds in a sample. This can be determined with acceptable precision if the sample average absorbance is relatively small and if the differences in the absorbance in bands where radiation is absorbed, and non-absorbed, are large enough to provide a sufficient signal to noise ratio. For highly absorbing samples, this condition usually cannot be satisfied, and calculation of spectral optical density cannot be performed with required precision.
  • the present invention relates to a method of identifying components of a sample at different temperatures. More specifically, this invention provides a method of sample identification, chemical composition analysis, and testing the physical state of a sample by analyzing spectra obtained from a sample subjected to different temperatures.
  • the present invention provides a method for identifying a chemical compound, analyzing a chemical composition or investigating a physical change of a sample, the method comprising obtaining spectra of electromagnetic radiation of the sample at two or more than two different temperatures.
  • the present invention also provides a method (A) for identifying a chemical compound, analyzing a chemical composition or investigating a physical change of a sample comprising: i) collecting one or more than one spectrum of radiation of the sample at a first temperature and averaging the result to obtain a first spectrum, and obtaining one or more than one spectrum of radiation of the sample at one or more than one second temperature, and averaging the result at each temperature, to obtain one or more than one second spectrum; iii) calculating a difference in absorbance between the first and the one or more than one second spectrum; and iv) using the difference in the absorbance, identifying a chemical compound, analyzing a chemical composition or investigating a physical changes of the sample.
  • the invention also pertains to the method as just defined (Method A), wherein in the step of calculating (step iii)), a negative decimal logarithm of a ratio of radiation intensity registered for the sample at the one or more than one second temperature to a radiation intensity obtained at the first temperature, is determined.
  • This invention embraces method (Method A) as defined above wherein in the step of calculating (step iii)) comprises a) determining a mean value of registered spectra for each wavelength measured for the fist spectrum and the one or more than one second spectrum; a) calculating the standard deviation for each wavelength; and b) obtaining a ratio of the mean value to the standard deviation.
  • the present invention also provides the method as defoined above (Method A), wherein in the step of collecting (step i)), the temperature of the sample continuously changes between the first temperature, and the one or more than one second temperature.
  • the temperature of the sample can be changed in discrete manner between the first temperature and the one or more than one second temperature.
  • the first temperature and the one or more than one second temperature of the sample can be adjusted outside of, or inside of, a sample compartment. 10.
  • the first temperature and the one or more than one second temperature of the sample may result from radiation that is used for spectral analysis.
  • the first temperature can be lower than the one or more than one second temperature, or the first temperature can be higher than the one or more than one second temperature.
  • the present invention also pertains to the method as defined above (Method A), wherein, in the step of calculating (step iii)), a running average, a standard deviation, and a relative thermal spectral change are calculated for sets of measurements, where each set of measurements is collected at the one or more than one second temperature, and a thermal dynamic of change in the sample is determed.
  • a spectral analyzer is used to obtained the first spectrum and the one or more spectrum, the spectral analyzer selected from the group consisting of a grating scanning spectrometer, a prism scanning spectrometer, a grating and prism spectrometers with detector arrays, a Fourier transform spectrometer, a filter switching spectrometer, a tuneable filter spectrometer, a Fabry- Perot scanning spectrometer, an acousto-optical tuneable filter and an instrument allowing for spectrum analysis.
  • a spectral analyzer selected from the group consisting of a grating scanning spectrometer, a prism scanning spectrometer, a grating and prism spectrometers with detector arrays, a Fourier transform spectrometer, a filter switching spectrometer, a tuneable filter spectrometer, a Fabry- Perot scanning spectrometer, an acousto-optical tuneable filter and an instrument allowing for spectrum
  • the method consists in multiple repetition of the following steps:
  • the methods defined above can be performed in many different ways, provided that a set of spectra of the electromagnetic radiation obtained following interaction with the sample obtained at two or more than two different temperatures is collected.
  • a set of spectra of the electromagnetic radiation obtained following interaction with the sample obtained at two or more than two different temperatures is collected.
  • the spectral absorbance of the sample depends on temperature, therefore spectra obtained at different temperature have different spectral content.
  • This invention overcomes existing limitations in the art of spectral measurement methodology and provides a method for conducting spectral measurements and data processing resulting in a specific response.
  • the methods described herein do not require measurements of spectral intensity distribution of radiation used for illumination of the sample during absorption measurements.
  • the present invention overcomes existing limitations of in the recognition of phase transition of a chemical compound, and provides a spectral measurement methodology based on analysis of thermal dynamics of abso ⁇ tion spectra of a compound using the dependence of the thermal dynamic of the abso ⁇ tion spectra on temperature range in which the absorbance spectra are collected.
  • Figure 1 shows a block diagram of a typical spectroscopic system.
  • Figure 2 shows a flow chart of standard measurement process leading to the production of an abso ⁇ tion spectrum of a sample, and that can be used for chemical sample identification and analysis.
  • Figure 3 shows spectra of different samples obtained using a spectrometer and prior art methods.
  • Figure 3A shows the spectrum of water.
  • Figure 3B shows the spectrum of 50% methanol solution in water.
  • Figure 3C sho ⁇ vs spectrum of methanol.
  • Figure 4 shows a flow chart of measurement processes leading to the production of an abso ⁇ tion difference created by changes in sample temperature.
  • Figure 5 shows changes of absorbance of a sample obtained while gradually warming up a sample from refrigerator (about 4°C) to room temperature (about 20°C).
  • Figure 5A shows the spectrum of water.
  • Figure 5B shows the spectrum of 50% methanol solution in water.
  • Figure 5C shows spectrum of methanol.
  • Figure 6 shows a scatter plot of measured (predicted) concentrations against reference data for a mixture of intralipid in water in the presence of two interfering analytes calculated from a difference of abso ⁇ tion measured at two different temperatures.
  • Three independent sets of data with correlation coefficient between all three components below 0.2 were used for model development, model verification and method validation.
  • Figure 7 shows a scatter plot of measured concentrations against reference data for protein concentration in animal sera calculated from a difference of abso ⁇ tion measured at two different temperatures.
  • Figure 8 shows a scatter plot of measured concentrations against reference data for cholesterol concentration in animal sera calculated from a difference of abso ⁇ tion measured at two different temperatures.
  • Figure 9 shows a scatter plot of measured concentrations against reference data for bilirubin concentration in animal sera calculated from a difference of abso ⁇ tion measured at two different temperatures.
  • Figure 10 shows a scatter plot of measured concentrations against reference data for sodium ions concentration in animal sera calculated from a difference of abso ⁇ tion measured at two different temperatures.
  • Figure 11 shows a flow chart of a measurement process leading to the production of a spectral response representing an average thermal change and the thermal dynamic of a spectral signal.
  • the obtained value reaches a maximum in spectral bands where absorbance demonstrates the highest stability (i.e. the smallest variability).
  • Figure 12 shows examples of the spectral stability of absorbance spectra of samples measured as described herein. The spectra were calculated as a ratio of the averaged spectral intensity of radiation affected (in this particular case transmitted) by the sample for a defined period of time, during which temperature of the sample was gradually increasing, to the standard deviation of the variability of the spectral intensity of the radiation during the same time period.
  • Figure 12A shows the thermal spectral stability of water.
  • Figure 12B shows the thermal spectral stability of 50% methanol solution in water.
  • Figure 12C shows the thermal spectral stability of methanol.
  • Figure 13 shows spectral stability of a water sample over about two minute time period as measured using the method described herein, with about a half minute time between the end of one measurement and beginning next measurement.
  • Figure 13A shows the relative thermal spectral stability for water at the beginning of the experiment.
  • Figure 13B shows the relative thermal spectral stability for water at about 2 rnin.
  • Figure 13C shows the relative thermal spectral stability for water at about 4 min.
  • Figure 13D shows the relative thermal spectral stability for water at about 6 min.
  • Figure 13E shows the relative thermal spectral stability for water at about 8 min.
  • the present invention relates to a method of sample identification and chemical composition analysis of a sample at different temperatures. More specifically, this invention provides a method of sample identification, chemical composition analysis, and testing the physical state of a sample by analyzing spectra obtained from a sample subjected to different temperatures. This invention also pertains to the field of spectral measurements of an object containing a complex molecular composition. More specifically, this invention relates, but is not limited, to methods of identifying chemical compounds, analyzing chemical compositions, and observing physical changes in a sample absorbing electromagnetic radiation. In particular, the present invention provides methods for identifying a chemical compound, analyzing the chemical composition of a sample, and testing the physical state of a sample using spectra obtained at different temperatures of the sample.
  • a stable source of electromagnetic radiation for example but not limited to a lamp
  • a radiation beam forming component for example, but not limited to, mirrors or lenses, for efficient collection of radiation from the source (101) and for forming a radiation beam that can be used for sample illumination.
  • Filters may be used for removal of unwanted radiation as required;
  • sample compartment (104) equipped with a sample holder (1041) to hold the sample (1042) in a desired position.
  • the sample compartment, or sample holder may be equipped with temperature measuring and controlling elements (1043), for temperature monitoring and to keep a constant sample temperature during measurement, or to change the temperature in a controlled fashion by heating or cooling;
  • - radiation collecting optics for example consisting of lenses or mirrors to collect radiation affected by the sample, to form a radiation beam of a required shape, and to direct the beam for further analysis;
  • a spectrum analyzer (106) that decomposes the delivered radiation beam received from the collecting optics (105) into particular spectral components and directs them to a radiation detector (107).
  • a spectrum analyzer is a grating spectrometer that angularly disperses radiation of different wavelengths in different directions, so that particular spectral components are registered with separate detectors, for example, in a form of a detector array.
  • Non- limiting examples of a spectral analyzer include grating scanning spectrometer, a prism scanning spectrometer, a grating and prism spectrometers with detector arrays, a Fourier transform spectrometer, a filter switching spectrometer, a tuneable filter spectrometer, a Fabry-Perot scanning spectrometer, an acousto-optical tuneable filter, and any instrument that allows for spectrum analysis of a sample.
  • the signal from the radiation detector (107) can be preprocessed or processed with a suitable electronic circuit (108), converted into a digital form by means of A/D converter (109), and directed to computer (110), which can process, store, display or send obtained information to an external user (111) for further utilization.
  • the same computer (110) can be also used to perform numerous other functions, for example verification of calibration and performance of the analyzer, and control the function of the analyzer for example, but not limited to, opening and closing shutter (103), verification of sample (1042) presence in the sample compartment (104), or measurement and control of sample temperature (1043) and the like.
  • Instrument preparation for measurement typically involves verifying, in a trial run, the functionality of the instrument and measurement parameters, for example amplification or integration time, slit width, scanning speed, measurement time, sample temperature or other criteria as required.
  • an attenuator that replaces the sample, may be present for this step (2-2).
  • one or more than one measurement of instrument internal noise RD may be obtained and stored (2-3) using the same setting of all system parameters (as for step 2-2), with exception that the shutter is in the closed position to block radiation from the source to detector.
  • the sample is introduced into the optical path (step 2-4), and the settings of the instrument are modified to accommodate instrument performance as required by attenuated by the sample radiation level, and one or more than one light SL and dark SD measurements are performed (steps 2-5 and 2-6).
  • the data is stored for further processing and analysis.
  • step 2-5 Usually light measurements (2-5) are conducted either at room temperature or after the sample reaches a temperature set by a sample temperature controlling system. Variation in sample temperature during measurement is undesirable and is typically considered as a factor that affects the precision of measurement.
  • steps 2-2, 2-3, 2-5 and 2-6; RL, RD, SL and SD, respectively are collected results of the same kind of measurements (if more than one measurement was obtained) are averaged (step 2-7; 2-7a - reference light, 2-7b - reference dark, 2- 7c - sample light and 2-7d - sample dark) and dark signals are subtracted from the light signal (step 2-S; 2-Sa - for reference measurement and step 2-8b - for sample).
  • both measurements, the reference measurement and sample measurement (2-Sa and 2- ⁇ b) are normalized for amplification, or integration times (if different amplifications or integration times were applied during these measurements), and the absorbance is calculated (step 2-10) as a decimal logarithm of ratio of spectral intensity of radiation affected, and not affected, by the sample. Obtained spectra can be used either for identification, or concentration, of a chemical compound (step2-ll) with results presented, as in step 2-12, or the results used for measurement of the concentration of the compound of interest in the sample (steps 2-21 to 2-27).
  • the absorbance data can be used for sample identification or, after suitable calibration, for analysis of sample composition (steps 2-11 and 2-12). In many cases, especially for light scattering samples such a simple procedure may not be sufficient, and more advanced measurement methods are required.
  • These methods include: collecting data from larger set of samples (2-21) and development of one or more statistical models (steps 2-22 to2-24) that represent the relation between measured spectral values and the concentrations of analytes of interest in the sample; applying one of many available mathematical methods for example, but not limited to, Partial Least Square fitting (PLS), or Principal Components Analysis (PCA) or Neural Network and using the developed method; the model validation, using statistically justified set of independent measurements (2-24) and predicting in step 2-26 the concentration of the analytes for which the mathematical models have already been built, using data obtained in step 2-25. Results can be presented (2-27).
  • PLS Partial Least Square fitting
  • PCA Principal Components Analysis
  • Neural Network Neural Network
  • the order of spectral data collection steps 2-2 to 2-6 may be varied, and that the required data can be collected in any other order.
  • a sample measurement can be taken before reference and dark measurements.
  • the number of measurements obtained, the order of data averaging, or the normalization of the data can be performed in any order without departure from the spirit of the method.
  • a method for chemical composition analysis and a method for the analysis of physical state of a sample using spectra obtained from a sample at different temperatures are provided.
  • step 4-1 the instrument is prepared for measurements. This step may include spectrum measurement of a radiation beam in the absence of the sample (as in step 2-2), but this measurement is not required for use in further steps. Also step 2-3 and 2-6 (reference and sample dark measurement, respectively) are not required for use in this method. Step 4-1 may be further modified to set the instrument parameters to values that are optimal for light sample collection. After the instrument is ready, the sample at the preset temperature is introduced into spectrometer (4-2), where the temperature control system either maintains the initial temperature, or it brings the sample temperature to a desired level.
  • one or more than one spectrum (SL1) of radiation affected by the sample is collected (4-3), after ⁇ vhich the sample temperature is modified (4-4) using the temperature control system of the spectrometer (1043, Figure 1) or an external temperature controller (not shown in Figure 1), and another one or more than one spectrum (SL2) of radiation affected by the sample at the new temperature is collected (4-6).
  • the spectra in each group are averaged and difference in absorbance of the sample being at these two temperatures is calculated as a negative decimal logarithm or ratio of the measured spectral radiation intensity (4-10). Results obtained in this manner can be used in a similar fashion (steps 4-11 and 4-12 or 4-21 to 4-27) as the sample absorbance measured in the process represented in Figure 2.
  • the sample is placed in the measurement compartment of the spectrometer (4-2).
  • the sample may be cooled to refrigerator temperature, for example from about 0°C to about 8°C, and be introduced into system in step 4-2 for continuous spectrum and temperature collection (step 4-3) until the sample reaches a desired temperature (4-4), for example about 18°C to about 25°C (room or any other temperature).
  • the results obtained using this method represent differences in the averaged absorbance, over selected groups of absorbance of the sample, that arise from the difference of averaged temperature when the corresponding groups of spectra were collected.
  • An advantage of the approach described herein consists of eliminating a reference measurement, which in some cases, especially in spectroscopic systems that are specific for measuring light scattering samples, is problematic.
  • the measurements obtained using the present method may be conducted using cooled samples, for example which is not to be considered limiting in any manner, to refrigerator temperature, and then placing the sample in the compartment of a spectrometer held at room temperature to permit warming of the sample over time.
  • Ten groups of spectral measurements comprising radiation transmitted by a sample housed within a radiation scattering container can be collected for each sample, and the absorbance difference calculated for selected measurement groups, for example the second and ninth groups. The difference between these two groups may then be used for further analysis.
  • the absorbance difference between the any group of measurements may be used for analysis of the chemical composition of a sample.
  • the difference in absorbance can be used for analysis of chemical composition of sample in similar fashion as the real absorbance of a sample measured as outlined in Figure 2.
  • Figure 6 shows a scatter plot of intralipid concentrations in water in presence of two non-correlated interferents as predicted by a model, against the concentration of intralipid used for sample preparation. This result indicates a very good predictability of intralipid concentration (all measurements line up along the line with slope 1 (45° line), and an acceptable measurement precision, as almost all measurements are contained within +/- 20% error range.
  • Figure 7 shows a scatter plot for protein concentration in animal sera
  • Figure 8, 9 and 10 present results for cholesterol, bilirubin and sodium ions. While not all analytes can be measured with the same precision, since not all analytes in natural concentrations provide a signal that is sufficient for spectroscopic measurement, the results demonstrate a very good level of predictability - in all cases results line up along line with slope 1.
  • Different information may be derived when the spectral distribution of radiation intensity obtained during a continuous change in the temperature of the sample is averaged and divided by the standard deviation of these variations at each spectral measurement point. If the instrument noise is measured in similar way in the absence of the sample is low, this ratio, called dynamic range of instrument, shows a high value. For non-absorbing samples this ratio would be preserved. For the samples uniformly absorbing radiation across the whole spectrum, the ratio can be scaled down if the same instrument settings are used for spectral intensity distribution, or for determining the radiation affected by the sample, as those used for unaffected radiation. However, as described herein, it was noted that in the presence of the sample, whose temperature varied during measurement, the response is different from that as expected. Furthermore, in portions of spectra where sample absorbance is small, and where no changes in dynamic range were expected, a large variability in dynamic range was observed.
  • temperature-affected dynamic range is sample specific and strongly depends on a mean value and the temperature variability range during time when the to be averaged spectra of affected by the sample radiation, are collected. This method can provide information on the position of isosbestic points in a sample spectrum.
  • thermal isosbestic points These points were observed as intersections of two or more water abso ⁇ tion spectra taken at different temperatures.
  • tests were performed using different chemical compounds of organic and non-organic origin. It has been observed that each sample produces a different, specific pattern that is dependent on mean temperature, and the temperature variability range as shown in Figures 12 A-C, and Figures 13 A-E.
  • the method proposed in the present invention allows for a quantitative characterization of the thermal behavior of absorbing properties of a sample.
  • the proposed ratio shows high values in portions of the spectra where absorbance of the sample is not affected by the sample and the absorbance is stable, and low values where the impact of temperature is large, and where stability of the sample absorbance is low. Therefore, these measurements represent the thermal dynamic of the signal across the spectrum that results from changes in the temperatures of the sample. The thermal dynamic of the signal should reach a maximum at thermal isosbestic points of the sample.
  • Step 11-1 can be used to set the instrument parameters to values that are optimal for collection of radiation affected by the sample.
  • the spectra of radiation affected by the sample are collected as the sample temperature is changed in a controlled manner.
  • this step can be performed in many ways depending on requirements, and on available equipment.
  • the sample is cooled to refrigerator temperature, from about 0°C to about 8°C, and it is introduced into the sample holder (step 11-2) and the continuous spectrum is collected (11-3) until the sample reaches a desired temperature, for example but not limited to room temperature.
  • the process of changing the temperature may take different amounts of time, depending of thermal properties of sample holder, or if a sample temperature controller used. In the latter case, the dynamic of the process can be adjusted to increase the detail of thennal dynamic to be resolved. Generally speaking, the slower the process, the more details can be revealed. However, it is required that the measuring instrument is stable enough during the time period for the collection and averaging of each group of spectra. Due to the high sensitivity to the temperature and temperature variations, it is preferred that such spectra have to be collected under controlled thermal conditions.
  • One of skill in the art appreciates that numerous ways of changing the temperature can be realized during or between time periods when consecutive groups of spectra are collected.
  • the obtained spectra (11-5) are divided in subgroups containing, for example, but not limited to, groups comprising an equal number of measurements, or groups corresponding to the same temperature increase during the time when the selected group of measurement were collected. All measurements belonging to a single group are averaged (11-7) to obtain a mean value for each wavelength. Simultaneously, the standard deviation of variability within the group at each wavelength is calculated (11-8), and for each wavelength, the ratio of the mean to the standard deviation, is calculated (1 1-20).
  • stepwise change can be applied (steps 11-2 to 11 - 10 in the right column in chart of Figure 11) and the ratio of the mean to the standard deviation can be calculated
  • This data can be presented in a form of a set of graphs (one for each group of measurements), that represent the thermal dynamic of the changes (spectral dependence of these changes will be referred here as the thermodynamic signal) in a spectrum of radiation affected by the sample at a certain mean temperature, and whose temperature changed during measurement within the range determined by measurement system.
  • Comparison of the results obtained for different groups, and registered at different temperatures of samples shows the variability of the the ⁇ nodynarnic signal as function of sample composition, mean temperature and temperature range, over which the spectra were averaged. Because of high sample specificity, the result can be used for identification of chemical compounds (11-21) or used for analysis of spectral thermodynamic (1- 31). The result of the analysis may be presented (11-22 and 11-32) or transferred for further use.
  • the average spectral thermal dynamic of the signal affected by the sample radiation strongly depends on temperature and the temperature variability range used for averaging. These results may therefore be used to identify temperature points where properties of the substances change dramatically for some reason. Without wishing to be bound by theory, the observed changes at temperature points may occur, for example, as a result of a mesomo ⁇ hic phase transition, or other physical change in the sample, for example a transition from monomer to dimmer and the reverse, or thermal related transitions between different internal structures of solids and liquids.
  • the temperature dependent data can be collected in many different ways for example, but not limited to, by measurement of light affected by the sample at two or more than two distinctive different temperatures, for example one at a low temperature, and the other, or remaining measurements, at any elevated temperature, for example but not limited to from about 0°K to a temperature accessible with present day technology without damage to sample or used measuring apparatus. Selection of a temperature range to be used will depend upon the sample and the physical state of the sample being analyzed. In this regard, spectra may be obtained spanning any desired temperature range. Measurements can be also taken in reversed order with a first measurement obtained at a higher temperature, and a second and all other consecutive measurements obtained at lower temperatures. Also the transition from one temperature to another, or for averaging measurements from low to high or from high to low, can be performed either continuously or in discrete steps with constant or variable temperature change from one temperature setting to another.
  • the method of the present invention may be used on any sample for which a chemical composition analysis or analysis of physical state may be desired.
  • the sample may comprise a body part of a subject, for example, but not limited to a finger, toe, earlobe, arm or back, samples of various natural or synthetic products, self contained or in a container, samples or portions of various products and materials.
  • the sample may comprise a solid, semi-solid, fluid, vapor or gas obtained from any source, for example, but not limited to blood, urine, mucus, sweat, lymph, excrement, secretions and the like, dairy products, any fonn of food or drinks, a chemical product for example but not limited to plastics, products of semiconductor industry, products of petrochemical industry, wood and paper industry products, neutral and hazardous products in loose or contained form, clear and contaminated water, clear or contaminated air, gases or vapors and so on.
  • Samples that are not part of living creature are considered in vitro samples, while parts of life forms such as humans, animal, plants, bacteria and all other living creatures, which have to be tested without damage to functionality, are considered in vivo samples.
  • the sample may be an in vivo human or animal sample, for example, but not limited to, a finger of a subject placed in an apparatus capable of changing temperature and analyzing the chemical composition of a sample by taking the spectrum of radiation affected by the sample.
  • an apparatus capable of changing temperature and analyzing the chemical composition of a sample by taking the spectrum of radiation affected by the sample.
  • the sample may be provided in vitro, for example, but not wishing to be limiting in any manner by placing blood or other body fluid taken from a subject into a cuvette or other holder for analysis. Further, if the sample is an in vitro sample, then it may be subjected to processing prior to chemical composition analysis. Any processing step known in the art may be employed.
  • processing steps may include, but are not limited to purification, centrifugation. separating contaminating or other chemical constituents prior to analysis, diluting, concentrating, reacting components in the sample with endogenous or exogenously added reagents or any combination thereof.
  • the method of the present invention may be employed to analyze any chemical component within a sample.
  • chemical components may include, but are not limited to one or more proteins, sugars, lipids, and the like or any other component of organic or inorganic origin. Any physiological or nonphysiological chemical component in a biological or nonbiological sample may be analyzed by the method of the present invention.
  • the spectra which are used in the method of the present invention to analyze a chemical component in a sample or their physical state are obtained by exposing the sample to a suitable source of electromagnetic radiation, for example, but not limited to that is the infra-red, near infra-red, visible, and ultraviolet wavelength ranges.
  • a suitable source of electromagnetic radiation for example, but not limited to that is the infra-red, near infra-red, visible, and ultraviolet wavelength ranges.
  • the source employs infrared or near infrared wavelengths.
  • the spectra of one or more than one compound of interest changes with a change in temperature. Furthermore, in samples comprising two or more compounds, the spectra of the sample changes with changes in temperature, in a manner that is distinct from the changes in the spectra of each compound separately. Therefore, these changes may be used to identify and characterize compounds of interest within a sample.
  • the method comprises generating a first spectrum of a sample at a first temperature, and obtaining one or more second spectra of the sample, at one or more second temperatures. Therefore, at least two or more spectra may be obtained from a sample. In the simplest method, only two spectra are obtained. Preferably, the first and second spectra are generated over a plurality of identical one or more wavelengths. Also contemplated by the method of the present invention, multiple spectra may be generated, and optionally averaged at the first temperature, second temperature, or both. Further, the present invention contemplates generating spectra at more than two temperatures and using the information to determine the presence and concentration of a chemical component of interest within a sample and evaluating a thermal dynamic of the sample, thereby obtaining information on its physical state.
  • the first temperature and second temperature of the first and second spectra respectively, are different. Any temperature may be used in the present invention.
  • the first temperature may be different from the second temperature, for example but not limited to, by about 0.1°C to about 500°C, or from about 1°C to about 100°C.
  • both the first and second temperatures are within the range of about 0°C to about 50°C, for example but not limited to about 20°C to about 40°C.
  • temperatures outside this range are also contemplated and can be used for different samples, especially of non-organic origin.
  • the temperatures are selected so that no damage occurs to the sample, for example, but not limited to denaturation of proteins, precipitation of chemical constituents, or destruction of the chemical component of interest in the sample, or causing discomfort to an individual or living creature.
  • the temperature of the sample may be adjusted by any means known in the art.
  • the temperature of sample held within a cuvette or other holder may be adjusted by heating or cooling a chamber which holds the sample.
  • an in vivo sample such as a finger or the like may be heated or cooled by the receptor device used to hold the sample, or by the beam source, for example, but not limited to an infrared beam including that employed for testing of sample in an infra-red portion of the spectrum.
  • the beam may be the same or different from the electromagnetic radiation source used for the analysis of the sample, furthermore, microwave radiation can be used for sample heating.
  • the first spectrum obtained for the sample at a first temperature is compared to the second spectrum at a second temperature and the presence and amount of a chemical component of interest within the sample is determined.
  • the comparison may involve computing the difference between the spectra or a point in the spectra.
  • a calibration algorithm may be employed in the comparison, for example, but not limited to adjust for interfering or other components in a sample.
  • a certain number of spectra are registered at least at two different temperatures, the results averaged and standard deviation of mean value calculated.
  • a ratio of the mean value to the standard deviation can be calculated (relative thermal spectral change ratio), and used for chemical analysis, or for investigation of structural changes in a sample that is related to temperature change.
  • the ratio can be further processed in any known way, for example but not limited to smoothed normalized or normalized to a dynamic range of the instrument, as required.
  • spectra in samples comprising two or more compounds changes with temperature in a manner that is distinct from the changes in the spectra of each compound separately, and indicative of the compounds in the sample
  • differences or the relative spectral thermal change between spectra obtained from the same sample at different or varying temperatures may be used to identify and characterize compounds of interest within an sample, or to observe structural changes of the sample.
  • Such a method eliminates need for reference measurements of spectral content of radiation used for analysis and enables measurement, or increases the accuracy of the measurement, of a compound of interest. Further the method of the present invention does not require the use of a reference measurement, since by obtaining repeated spectra from the same sample, interfering factors are co ⁇ ected for.

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Abstract

L'invention concerne un procédé d'identification d'échantillon, d'analyse de la composition chimique et de l'évaluation de l'état physique de l'échantillon au moyen de spectres obtenus suite à l'interaction d'un rayonnement électromagnétique avec l'échantillon porté à différentes températures.
PCT/CA2003/000006 2002-01-04 2003-01-06 Identification d'echantillon, analyse de la composition chimique et evaluation de l'etat physique de l'echantillon au moyen des spectres obtenus a differentes temperatures de l'echantillon WO2003055381A1 (fr)

Priority Applications (2)

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AU2003203067A AU2003203067A1 (en) 2002-01-04 2003-01-06 Sample identification, chemical composition analysis and testing of physical state of the sample using spectra obtained at different sample temperatures
CA002471583A CA2471583A1 (fr) 2002-01-04 2003-01-06 Identification d'echantillon, analyse de la composition chimique et evaluation de l'etat physique de l'echantillon au moyen des spectres obtenus a differentes temperatures de l'echantillon

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US34434502P 2002-01-04 2002-01-04
US60/344,345 2002-01-04

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102005027237B3 (de) * 2005-06-13 2007-01-25 Siemens Ag Sensorvorrichtung zum Erfassen eines Gasanteils in der Luft und Messvorrichtung mit einer Sensorvorrichtung
CN102829870A (zh) * 2012-09-05 2012-12-19 天津奇谱光电技术有限公司 一种光学频谱分析设备
CN102841071A (zh) * 2011-06-23 2012-12-26 中国石油化工股份有限公司 由二维相关红外异步光谱识别原油种类的方法

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WO1991011136A1 (fr) * 1990-02-02 1991-08-08 Boston Advanced Technologies, Inc. Systemes d'analyse de matieres basee sur la detection de rapports de reflectance
US5068536A (en) * 1989-01-19 1991-11-26 Futrex, Inc. Method for providing custom calibration for near infrared instruments for measurement of blood glucose
EP0536304A1 (fr) * 1990-06-27 1993-04-14 Futrex Inc Mesure non invasive de glycemie.
US5886347A (en) * 1994-07-13 1999-03-23 Horiba, Ltd. Analytical method for multi-component aqueous solutions and apparatus for the same

Patent Citations (4)

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Publication number Priority date Publication date Assignee Title
US5068536A (en) * 1989-01-19 1991-11-26 Futrex, Inc. Method for providing custom calibration for near infrared instruments for measurement of blood glucose
WO1991011136A1 (fr) * 1990-02-02 1991-08-08 Boston Advanced Technologies, Inc. Systemes d'analyse de matieres basee sur la detection de rapports de reflectance
EP0536304A1 (fr) * 1990-06-27 1993-04-14 Futrex Inc Mesure non invasive de glycemie.
US5886347A (en) * 1994-07-13 1999-03-23 Horiba, Ltd. Analytical method for multi-component aqueous solutions and apparatus for the same

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102005027237B3 (de) * 2005-06-13 2007-01-25 Siemens Ag Sensorvorrichtung zum Erfassen eines Gasanteils in der Luft und Messvorrichtung mit einer Sensorvorrichtung
CN102841071A (zh) * 2011-06-23 2012-12-26 中国石油化工股份有限公司 由二维相关红外异步光谱识别原油种类的方法
CN102829870A (zh) * 2012-09-05 2012-12-19 天津奇谱光电技术有限公司 一种光学频谱分析设备

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