JP2003508745A - Analyte determination method using arrays of near infrared, adjacent visible spectrum and longer near infrared wavelengths - Google Patents

Abstract

Abstract: A method is described that uses spectral data collected simultaneously in a continuous array of discrete wavelengths of the visible spectrum adjacent to the infrared and near-infrared portions of the light spectrum. Spectral data is collected using multiple detectors with different sensitivity ranges. Certain detectors may be sensitive to the visible and, in some cases, the near infrared portion of the radiation. Spectral data from the infrared spectrum is collected by an infrared detector, and in some embodiments, is insensitive to visible light.

Description

Detailed Description of the Invention

FIELD OF THE INVENTION The present invention relates to many complex component structures that change over time (eg, blood constituents in blood, or biological tissues or body parts), or in particular living organisms such as humans and animals. Apparatus and methods for detecting and monitoring the concentration levels of one or more components in blood and biological tissue components of a subject.

BACKGROUND OF THE INVENTION The application of spectroscopy for chemical analysis is known. However, it has been used primarily for automated analysis because over the years there has not been a sufficiently sensitive detector for the infrared to locate information about the vibrational states of molecules, especially those that are the roots of life. Advances in IR detector technology have dramatically changed many existing detectors, instruments and methods for such applications. This has also paved the way for new applications, but has imposed new requirements on the technology. One of the most important applications is the non-intrusive analysis of the chemical composition of living subjects.

Light in the spectral range 500 nm to 770 nm belongs to the visible portion of the spectrum, but it does not cover the entire visible range and is directly adjacent to the infrared portion of the spectrum, and is therefore referred to herein as Adjacent Visible (AV). Is generally justified. The infrared portion (IR) of the electromagnetic spectrum is divided into near infrared (NIR), which extends beyond the visible to 2700 nm, and mid-infrared radiation (MIR), which extends beyond the NIR range and further into the far-red range (FIR). Is widely accepted. There are some photodetectors (mainly silicon) whose sensitivity covers the visible part of the spectrum and the beginning part of the NIR. As a result, the visible range portion adjacent to the NIR and the visible adjacent NIR portion will be referred to herein as AV / NIR, while the rest of the NIR range is referred to as the "long wavelength NIR region" or "LWNIR". I will decide.

Non-Intensive Technology The previously mentioned devices for non-intrusively monitoring the concentration of blood components in patients are known.
Sensors are typically used to externally measure either the concentration of a component in the gas emitted by the body or the concentration of a component contained in body fluids such as tears, salvia, urine. Alternatively, blood components are identified by measuring the attenuation of some radiation that has passed through parts of the patient's body, such as the ear lobes, fingers. In many cases, the radiation is measured in individual, narrow band spectral sources of 1, 2 or a limited number obtained from narrow band sources (US Pat. No. 4,655,225; US Pat. No. 4). , 883,953
No .; U.S. Pat. No. 4,882,492). Some of these devices make measurements in a limited number of relatively narrow spectral bands that are continuously selected from spectrally broad light by a set of interchangeable narrow band spectral filters. Analysis of the absolute and relative changes in light intensity in these bands under certain conditions provides important information about body composition. The filter exchanges and filter exchange times required for their stability in order to obtain accurate measurements make the measurement process very long and very frequent, with a significant time delay for measurements in different bands. Since the psychology of a living person changes variously depending on the physical state, various wavelengths are measured under the change of the physical state of the body, which makes it impossible to measure the components of the body. Another source of error in systems with a limited number of discrete spectral bands is the wavelength shift of the selected band between measurements and instruments. There are several medical and other applications where component measurements are not possible due to these two sources of error. In such cases, it is important to perform measurements on all spectra almost at the same time and store information about all spectra as much as possible. This applies other techniques that measure a large number (eg 128 or 256) of wavelengths in a specified range and a limited number of wavelengths, all of which are used to measure the entire spectrum of light that interacts with the sample. Will be realized. Other techniques for measuring the entire spectrum typically use wavelengths in the AV / NIR range (US Pat. No. 5,3,5).
61,758 and U.S. Pat. No. 4,975,581). Here, an array of photoconductive detectors made by the application of well-established silicon technology could be used for a long time for the simultaneous registration of spectra at multiple discrete points. There are several advantages to measuring the full spectrum. One of them is that the spectra provide disturbing substances (eg other analytes) and effects (eg light scattering) along with information about the desired analyte. A second advantage is the ability to record complete information about the spectrum, even if it shifts due to changes in sample temperature. Finally, a third advantage is that even if the wavelength calibration of the instrument is lost, it is easily extracted once all information is stored in the spectrum and new wavelength calibration data is available. That is. However, there is insufficient information available in the above range, the available information is insufficient for accurate measurement of body components, or the previously mentioned spectral range (usually at long wavelengths).
Outside additional information may be required. Because of the sharper analyte spectrum present in the 1100 to 1700 nm region, it may be sufficient to perform the measurement at a limited number of wavelengths only in the 1100 to 1700 nm region. However, although often they provide information about the analyte of interest, there is not enough independent information about other analytes whose absorption spectrum interferes with that of the desired analyte. The additional information obtained in the previously mentioned spectral range 580 nm to 1100 nm serves to eliminate ambiguities penetrated by disturbing analytes. If the samples show temporal variability, it is clear that simultaneous measurement of the entire spectral range under consideration is preferred in order to eliminate possible errors caused by sample variations.

Moreover, as discussed above for shorter spectral ranges, in some cases spectral measurements at a limited number of points within the 1100 to 1700 nm spectral region may not be sufficient for recognition of the desired analyte. There is a nature. In addition, usually the measurements are both: fluctuations in the spectral position of the selected point and width,
And very sensitive to the shape of the spectral bands measured at those points. Therefore, the method in which the measurement of different parts of the spectrum is performed from different parts of the sample at different times or within a limited number of points is not sufficient for accurate analytes of the components of the sample. Potential and more advanced instruments are needed. A method is provided by the present invention that eliminates these limitations and provides a suitable instrument for such measurements. Overall, the non-intrusive devices and techniques described above have not been sufficiently accurate to be used in place of infringing techniques in measuring patient blood constituent concentrations. Some of them have been designed to measure only one component and require physical changes to the instrument to adapt them to the measurement of various components. For some devices, it takes an unreasonably long time to obtain a result, or for others it is not provided in a form that is easy to use, or they cannot measure the concentrations of multiple components simultaneously.
For example, using a device that calculates a dosage for insulin management and using a device that gives inaccurate readings, it is clear that the patient will have disastrous results.

It has been recognized that simultaneous spectrum collection is only possible with the application of multiple photoconductive detectors. Technically, this is brought about by the spatial distribution of the radiation composed of different wavelengths by a dispersive device (eg a diffraction grating) and its intensity recorded by an array of photoconductive detectors. In such a case, the signals recorded by each detector array are read almost simultaneously. This technology has been recognized,
And many spectrometers with photoconductive detectors are available on the market. Unfortunately, the array devices that can be used have various limitations, and thus the capabilities of such spectrometers.

The most important limitation of each array is its sensitivity range, which depends on the materials used to make the array. The sensitivity range determines in what spectral range the incorporated instrument can operate a particular array application.
Designed with the application of photoconductive detector arrays, grating spectrometers have additional inherent limitations, which impose even tighter constraints on instrument performance. One such constraint is the presence of additional diffraction orders in the light diffracted by the grating. Its secondary presence imposes the condition that the spectral range of an array-based instrument cannot be wider than one octave unless the spectral filter is placed in front of the array. The production of such a filter is not easy, and therefore the instrument is constructed to cover one octave or less, and a cutoff filter that removes radiation with shorter wavelengths usually removes that degree of impulse. Used for. As a result, the spectral range of existing array-based instruments is such that the longest measurement wavelength of the analysis light is always less than twice the shortest wavelength analyzed by the spectrometer.

Finally, due to the limited number of elements in the array and the length of the array, it is very often impossible to achieve high resolution even in its limited spectral range. As a result, the performance of array-based instruments is a compromise between these factors, and therefore it is very often that the spectrometer cannot provide the information needed for a particular application. . Furthermore, the measurement problem remains unsolved when these applications require simultaneous recording of a broad spectrum (eg, non-invasive in-vivo diagnostics).

SUMMARY OF THE INVENTION For some applications of relatively simple instruments, measurement of infrared radiation at one or a few wavelengths is sufficient, for example glucose in blood in the human body. For more demanding applications such as concentration, significantly more advanced instruments are needed. In particular, it has been found to be important for such applications to collect data in a wide spectral range covering at least the near infrared and the portion of the spectrum adjacent to its visible portion. For living subjects, it is important that the information be collected simultaneously over the entire spectral range of interest, or else the physical changes of the microorganisms during the measurement can significantly influence the measurement error. Has been discovered. Finally, due to the dependence of the molecular vibrational spectrum on temperature, it has been found important to have as complete information as possible about the spectrum. Therefore, there is a growing need to build spectroscopic devices with the ability to simultaneously collect information in as wide a spectrum as possible. This effort includes techniques for collecting the spectrum of light in the application of a rotating grating or any similar scanning instrument with a Fourier transform spectrometer.

Accordingly, the present invention uses a more accurate non-invasive device and for a short time by simultaneous measurement of optical signals in several different spectral ranges using individual array-based spectrometers. Measuring the concentration level of a particular component of the sample during,
Alternatively, a method of measuring the concentration level of one or a number of different components is provided.

The present invention provides that the measurement accuracy of the analyte to be measured by a spectrum instrument for measuring total spectral absorption / reflectance in the AV / NIR region is such that one or multiple arrays of wavelengths in the infrared region It is improved by adding measurement values.

In its broader aspect, the invention comprises the steps of placing a sample in a non-invasive device capable of emitting radiation, directing the radiation onto the sample, and measuring the radiation collected from the sample. Calculating a concentration level based on the emitted radiation, wherein the radiation emitted onto and collected from the biological tissue begins at 500 nm and extends to the AV / NIR range and 110
A method is provided which is at a wavelength in the possible LIR range of 0 nm to 1700 nm.

According to one embodiment, a method for measuring blood constituent concentration levels in living subjects such as humans and animals, which is broad in a polychromatic light source or other single or required range. A method is provided, characterized in that other radiation sources emitting light in the spectrum are used. A number of spectral analysis devices, including sensitive photoconductive detector arrays, which are possible in different spectral ranges, are under consideration, preferably in the range 500 to 1100 nm and 900 to 1700 nm.
It provides sensitivity and resolution over the nm and further parts of the spectral range. This method comprises the steps of: -delivering light of a continuous wavelength (whether from one source or from multiple sources) towards a sample or a portion of interest; -light being emitted towards a sample or portion thereof and interaction. Collecting the continuous light after it has finished, and-at least two parts for separately delivering the collected light to a corresponding number of spectral analyzers, namely at least one for AV / NIR and WNI.
Splitting into at least another one for R, and-forming each part of the light into a light beam suitable for simultaneous analysis of the corresponding spectral content of each part, preferably by a dispersive element, preferably a diffraction grating. Spatially dispersing a contiguous portion of the light intended for analysis on an individual spectral analyzer into a dispersion spectrum of the component wavelengths at each selected portion; and a suitable photoconductive detector. Forming the dispersed light in each portion by the array into a light beam suitable for detection, and wherein the array of photoconductive detectors makes a measurement of the dispersed light in the selected portion or the entire AV / NIR spectral range, And at least one or multiple arrays are added for measuring at least selected partial or full LWNIR spectral range And it features.

Preferably, these measurements are made simultaneously, sequentially or in any combination thereof. The measurement results are transferred to a microprocessor, and the concentration level of the sample, in particular of said at least one component of said blood or biological tissue, is calculated and a result for each concentration level is produced.

According to another embodiment of the present invention, there is provided a non-invasive device for measuring concentration levels of components occurring in samples of subjects such as humans and animals, especially blood and biological tissues. In particular, the adjacent visible spectrum and the broad spectrum light in the near infrared range brought about by the radiation or the light source are enhanced by one or the required number of stabilizing power supplies. The device (or devices) is shaped so that a portion of the sample or object is placed in contact with the receptor. The receptor has a means for removing ambient light and is aligned with the light source (s) to allow the sample or body part (
Alternatively, when biological tissue) is placed in contact with the receptor, the light source (plurality of light sources) is activated, and light having continuous wavelengths is sent toward the portion. The device is AV / NIR and LWNIR after the light is directed towards the sample or part of it
Means are provided for collecting light in the spectral region. Means for dispersing light collected over the broad spectrum into a dispersion spectrum of component wavelengths and AV / NI
Means are also provided for simultaneously or sequentially measuring optical signals of many different wavelengths in the R and LWNIR regions. Means are provided for converting the results of these measurements over the dispersion spectrum into concentrations of at least one component using the formula for at least one component. Means are also provided for determining the concentration level of at least one component of the blood or biological tissue and then producing a result for each determined concentration level.

According to one embodiment of the invention, illuminating the sample with successive wavelengths from adjacent visible and near infrared (AV / NIR) regions, and after the radiation has been directed towards the part. Collecting the radiation and dispersing the continuous collected radiation into a dispersive spectrum of component wavelengths to the detector, the detector measuring at least one of the transmitted or reflected radiation from the collected radiation. Doing and transferring the measurements to the processor, irradiating the sample with successive wavelengths in the longer wavelength near infrared (LWNIR) region, and after the radiation has been directed towards the sample or part thereof A step of detecting radiation in one or multiple bands by a detector, wherein the detector detects the radiation transmitted or reflected. At least one measurement, and transferring the measurement to a processor, wherein the processor calculates the concentration of the constituent in the sample based on the measurement and one or a number of calibration algorithms, preferably one Alternatively, a method for determining a constituent concentration of a sample is provided, characterized in that a number of individual energy sources are used to provide the radiation.

According to another embodiment of the method of the present invention, the detector of the AV / NIR is one or a number of spectrum instruments having an array of silicon detectors and the LWN
The IR detector is one or more spectroscopic instruments with an individual array of infrared sensitive detectors for each band of radiation.

According to yet another embodiment of the method of the present invention, the detector of the AV / NIR is one or multiple spectrum instruments having an array of silicon detectors, the LWN
The IR detector is one or many spectral instruments with an individual array of infrared sensitive detectors, and the measurement of the radiation in each band is suitable for an array of infrared sensitive detectors. A detector made of a material, preferably infrared sensitive,
It is a GaAs detector.

According to another embodiment, a spectrometer having an array of silicon detectors records all light in the visible, visible / infrared and adjacent regions of the visible and infrared ranges within the spectral sensitivity range of the detector. And preferably an infrared sensitive detector records light in the individual infrared ranges within their spectral sensitivity range.

According to another embodiment of the method, all detectors record light in their considerable sensitivity range almost simultaneously.

According to another aspect of the invention, illuminating the sample with a component of wavelengths from the AV / NIR region, collecting radiation after the radiation has been directed towards the portion, and collecting successively. Dispersing the collected radiation into a dispersion spectrum of the component wavelengths to the detector, the detector making at least one measurement of the transmitted or reflected radiation from the collected radiation, and the measured value to the processor. Transferring, illuminating the sample with wavelengths in one or multiple bands in the LWNIR region, and detecting radiation in one or multiple bands with a detector after the radiation is directed toward the sample. The detector makes at least one measurement of the transmitted or reflected radiation and the measured value is processed. A processor for calculating the concentration of the constituent in the sample based on the measured value and one or more calibration algorithms, preferably for use by one or more individual energy sources to provide radiation. A method of determining a component concentration of a sample is provided.

According to another embodiment of the method of the present invention, the detector of the AV / NIR is one or a number of spectrum instruments having an array of silicon detectors and the LWN
The IR detector is one or more spectroscopic instruments with an individual array of infrared sensitive detectors for each band of radiation.

According to yet another embodiment of the method of the present invention, the detector of the AV / NIR is one or multiple spectral instruments having an array of silicon detectors, the LWN
The IR detector is one or many spectral instruments with an individual array of infrared sensitive detectors, and the measurement of the radiation in each band is suitable for an array of infrared sensitive detectors. A detector made of a material, preferably infrared sensitive,
It is a GaAs detector.

According to another embodiment, a spectrometer with a silicon detector array is visible, visible /
The infrared and detectors record all light in the visible, the range adjacent to the infrared range within the spectral sensitivity range, and preferably the infrared sensitive detectors are individual reds within those spectral sensitivity ranges. Record light in the outer range.

According to another embodiment of the method, all detectors record light in their considerable sensitivity range almost simultaneously.

According to yet another aspect of the invention, the steps of irradiating the sample with a component of wavelength from the AV / NIR region and collecting radiation after the radiation has been directed towards that portion are contiguous. Dispersing the collected radiation into a dispersive spectrum of component wavelengths to a detector, the detector making at least one measurement of the transmitted or reflected radiation from the collected radiation, and a processor for processing the measurements. To the sample, irradiating the sample with components of consecutive wavelengths from the LWNIR region, collecting radiation after the radiation has been directed to that portion, and wavelengths of one or multiple bands in the LWNIR region. The sample onto the sample and split the continuous collected radiation into a distributed spectrum in the emission band to the detector. The detector making at least one measurement of the transmitted or reflected radiation, and the step of transferring the measurement to a processor, based on the measurement and one or more calibration algorithms, A method is provided for determining the constituent concentration of a sample, characterized in that a processor calculates the constituent concentration in the sample and preferably one or more individual energy sources are used to provide the radiation.

According to another embodiment of the method of the present invention, the detector of the AV / NIR is one or a number of spectrum instruments having an array of silicon detectors and the LWN
The IR detector is one or more spectroscopic instruments with an individual array of infrared sensitive detectors for each band of radiation.

According to yet another embodiment of the method of the present invention, the detector of the AV / NIR is one or a number of spectral instruments having an array of silicon detectors, the LWN
The IR detector is one or many spectral instruments with an individual array of infrared sensitive detectors, and the measurement of the radiation in each band is suitable for an array of infrared sensitive detectors. A detector made of a material, preferably infrared sensitive,
It is a GaAs detector.

According to another embodiment, a spectrometer with a silicon detector array is visible, visible /
The infrared and detectors record all light in the visible, the range adjacent to the infrared range within the spectral sensitivity range, and preferably the infrared sensitive detectors are individual reds within those spectral sensitivity ranges. Record light in the outer range.

According to another embodiment of the method, all detectors record light in their considerable sensitivity range almost simultaneously.

According to a preferred embodiment of any of the above methods, the sample is the finger of the subject.

Other features and advantages of the invention will be apparent from the following detailed description. However, while displaying the preferred embodiments of the present invention, the detailed description and specific examples are given for the purpose of description only, and therefore various changes and modifications within the spirit and scope of the present invention will be apparent to those skilled in the art from this detailed description. It should be understood that it will be.

DETAILED DESCRIPTION OF THE INVENTION As used herein, “concentratio”
"n)" or "concentration level" means the total or partial amount of the components of the solution, whether in vitro or in vivo.

As used herein, “constituent”
"Means a substance found in biological tissue, or an analyte, and includes, for example, glucose, bilirubin, proteins, such as carbohydrates such as albumin or hemoglobin.

As used herein, “in a solution
on) ”means in a liquid environment, such as a pore fluid or other body fluid.

As used herein, “issue” means any tissue of an object, including, for example, blood, extracellular spaces, and body parts such as fingers or ear lobes. May mean the entire composition of

As used herein, “subject” means any organ of the animal kingdom, including preferably humans.

As noted above, light in the spectral range 500 nm to 770 nm is referred to herein as adjacent visible (AV). As used herein, the infrared portion (IR) of the electromagnetic spectrum is the near infrared (NIR), which extends beyond the visible to about 2700 nm, the NIR range, and the far infrared range (FIR). Is split into mid-infrared radiation that further spreads over. Further, the visible portion adjacent to the NIR and the portion of the NIR adjacent to the visible are referred to as AV / NIR, and the remaining portion of the NIR range is referred to as the "long wavelength NIR region" or "LWNIR".

According to a preferred embodiment, it is assumed that in each case the measurement of the light intensity in any given spectral band with a given center wavelength is carried out at a signal-to-noise ratio high enough to obtain the desired result. ing.

As discussed above, the present invention adds a significant improvement in the ability to measure analytes of various samples (especially in biological tissue) using a non-intrusive spectrum instrument—ie, LWNIR. Or one or multiple arrays of wavelength measurements in the IR region need only be applied to full spectrum absorption measurements in the 500 to 1100 nm region to achieve significant improvements in analyte measurement accuracy. is doing. In particular, the measurement accuracy of the object to be analyzed realized by the method described above is the total spectral absorption measurement at 1100 to 1300 nm (“first region”) and the total spectral absorption measurement at 1590 to 1700 nm (“second region”). Or either of them is added to the total spectral absorption measurement at 500 to 1100 nm, preferably in the AV / NIR region, more preferably the addition of the first region to the second region. As a result, a significant improvement in the measurement accuracy of the analyte is brought about. It will be readily justified that the method involves the addition of measurements of total spectral absorption from other regions or the entire range of LWNIR or IR.

Among other reasons, AV / NIR because the silicon detector is sensitive in that range
Ranges have been used. Silicon detectors, and in particular silicon-based detector arrays, provide better noise and dynamic range performance, are readily available and are relatively inexpensive. However, the 900 to 1700 nm and even IR wavelength range yields sharper spectra for many of the analytes of interest, as shown in FIG. Indium gallium arsenide (InGaAs) detectors may be used to measure spectra in this region, and other detector arrays cover the IR range further. Unfortunately, these detectors result in poorer noise and dynamic range performance compared to silicon, with the result that a lower signal-to-noise ratio subtracts the benefit of a sharper spectrum.

To obtain the advantages of spectral measurements in IR, one or multiple arrays of spectra are added to the measurements in the AV / NIR region. The results are each significantly better than those obtained by spectral measurements in either range. A suitable conduit, such as a fiber optic bundle, delivers light to a sample or biological tissue, such as a finger. The light emanating from the fingers is focused and delivered by a separate conduit, such as a separate fiber optic bundle, to an individual set of detectors. As mentioned previously, silicon diode arrays are used to detect light in the AV / NIR region, InGaAs photodiode arrays detect light in the LWNIR region, and other detector arrays further detect light in the IR range. Can be used for As used herein, "light", "illumination (i
“Lumination”, “radiation” all refer to the light energy provided by a source capable of delivering sufficient radiation of a desired wavelength.

Any device capable of delivering radiation within the scope of this invention can be used and are within the scope of this invention.

As previously mentioned, the light source can emit light over a very wide bandwidth, including light adjacent to the infrared, visible and near infrared spectra. According to a preferred embodiment, the light from the light source (or source) is delivered by any optical means to a sample contained in a suitable receptor. In particular, the light first passes through a collimator (a collection by a lens that focuses the light into a narrow, collimated beam directed towards a receptor). In another embodiment, when examining light scattered by a sample,
Light in the form of a broad divergent light beam is delivered by fiber optic means directly to the sample or to the receptor containing the sump. A suitable receptor is shaped to contain the measurement sample. For example, such a sample may be part of an object, for example the human finger or arm, to be measured. A suitable receptor may be a sample holder in the form of any transparent container, or in some applications in the form of a calibrated cuvette with parallel walls. Alternatively, the part of the human or animal to which the light is to be delivered may be arranged in the vicinity of the receptor rather than in the receptor. In addition, the integrated cavity acts as a sample receptor with light coupled to the cavity either directly or by some optical means including optical fibers. After interaction of the light with the sample, the light is collected by some optical means. The light from the sample may be light that has either passed through the sample (eg, a part of the body or biological tissue), or has reflected it, or a combination thereof. The light collected is preferably the light that has passed through the sample.

The collected light is split into the required number of light beams and each of them is directed towards an individual spectral analyzer, preferably an array-based spectrophotometer. Prior to entering the spectrometer, each beam of light is shaped into an appropriately narrowed fiber or optical source that is optically narrowed by a set of optical elements and slits. The light from the narrowed light source may either be collected or sent directly to the diffractive means.

The radiation from the sample interacts with dispersive means such as a grating, which disperses the radiation into its component wavelengths so that light from the LWNIR and IR regions is an array of detectors, preferably InGaAs detectors. In the AV / NIR region, the light strikes the detector, preferably along the length of the linear silicon array of detectors. As will be readily appreciated by those skilled in the art, these arrays consist of individual detectors,
In addition, it has good sensitivity in the wavelength range corresponding to the AV and IR regions. Although not necessary, it is preferred that all detectors be electronically scanned simultaneously to measure the signals registered by each individual unit. The results from the detector are sent to a microprocessor for analysis of the measured values from the detector, PLS or PCR
Finally, a concentration result for each component is generated by applying one of many known chemical measurement methods such as a shape sample. The results are displayed on a display device or printed on a printer. The keyboard allows the user to control the device, for example to identify the particular component to be measured. Timing and control may be controlled by activating the device with a microprocessor.
For example, control may be performed so as to determine the number of times and timing of measurement. The light source or source is a quartz-halogen or tungsten-halogen bulb assisted by another light source such as a laser or a light emitting diode (LED) (or other light source capable of emitting radiation in the required areas of AV and IR). You may Any such source is powered by a regulated power source, such as a DC power source or by a battery. Each linear array detector preferably has a sufficient number of spectral ranges required to provide adequate spectral resolution.

The standard measurement procedure is to take a reference measurement of the incident light (which is the light generated by the device if part of the object is not in contact with the receptor) and take the measurement while the sample is present at the receptor. including. Next, the negative logarithm of the ratio of the sample measurement to the reference measurement is calculated and compared to the reference measurement.

Although it is not a limitation of the method of the present invention, the second derivative of the measurement is taken to reduce the variability of the results caused by the change in path length for light.

The noise level in the device may be reduced by a multi-element scanning technique so that a large number of measurements are taken by the detector and then the results are averaged. It is preferable to scan the linear array detector and IR detector multiple times during a few iterations and then average the results.

Glucose concentration measurement is an embodiment of this invention, while various components found in human and animal blood, such as amino acids, nitrogen, blood oxygenation, to name a few. Concentrations of carbon dioxide, cortisol, creatine, creatinine, glucose, ketones, lipids, fats, ureas, amino acids, fatty acids, glycosylated hemoglobin, cholesterol, alcohols, lactates, Ca ++, K +, Cl-MHCO ₃ − and HPO ₄ −. This device and method can be used to measure levels. In fact, as will be apparent to those skilled in the art, the method and apparatus can be modified to measure several components at the same time, which in the end will change its properties over time, resulting in AV and IR regions. It is also modified to measure the chemical composition of any other material or sample demonstrating specific spectral characteristics in

[0051]   The following description does not limit the exemplary embodiments of the invention.

(Best Mode for Carrying Out the Invention) In FIG. 2, a light source 21 having a certain number (n1) emits light having a wide spectrum covering the entire required spectrum range. The light source includes a power source, a light source, means for collecting light from these sources, and means for concentrating the light on the intended optics and mixing the light from these sources to direct it to the sample. The light from the light source is collected by the light collecting means, preferably by a number of fiber bundles 22, optionally through a light mixing device 23 (eg a glass rod) and optionally a light forming device 24 (eg a light collimator, or a focus). It is delivered through a matching lens) to a sample receptor 25 (sample holder, finger holder, integral cavity or other device for holding the sample) containing the sample 26 (eg human fingers). After interaction with the sample, the light is collected by a light collecting device 27 (eg, another light bundle,
Or any light collecting optics, lens) and optionally split into a number of parts covering all possible spectral bands. The splitting is done by convenient splitting of the fiber which multiplies the stroke of the optical fiber, or by using a broadband or dichroic beam splitter or offset.

Each “portion” of light is directed towards an individual spectral analyzer 28, preferably an array-based spectrometer. The number (n2) of the spectrometer (generally different from the number of the light source) is chosen to cover the entire spectral range under consideration for the test sample with the required resolution.

A light beam forming optical device for the light emission means together with the spectrum analyzer, a specific one for a predetermined spectrum analyzer, a spectrum specific dispersion element or an optical filtering element, a light beam formation device for dispersed light, and a photodetector Optionally included.

The signals from each array are read by one or many specialized electronics boards (29), typically various specific arrays or detectors, to provide the appropriate electrical signals in addition to collecting the signals. By doing so, control of the array is executed. An electrical cable 210 connects the board to a computer 211 that "supervises" the operation of the board, captures information from the board, stores it, and uses many available chemical measurement methods (sample PLS or PCR). For processing the information gathered from the array into information about the chemical composition of the test sample using one of the following) and presenting it to the user in the required format (graph or any other signal). provide. A light source of the kind n1 was chosen to illuminate all spectral bands of interest in both the AV and IR ranges and was generally chosen to ensure detection in these spectral bands with the required resolution. It is important to justify that it may differ from the number n2 of the spectrum analyzer (eg spectrometer).

While this invention has been described with reference to what is presently considered to be the preferred examples, it should be understood that this invention is not limited to the disclosed examples. On the contrary, the invention is intended to cover various modifications and equivalents included within the spirit and scope of the appended claims.

All publications, patents and patent applications referenced herein are specifically and individually indicated to be incorporated by reference in their entirety for each publication, patent, and patent application. The books are incorporated to the same extent as their overall reference.

[Brief description of drawings]

1 shows absorption spectra from 500-1380 nm for human serum albumin with globulin, glucose, urea, creatine, cholesterol and water displacement compensation,

FIG. 2 is a diagram illustrating the general concept of simultaneous collection of spectra over a broad spectral range by an array-based instrument, each of which covers an individual spectral range, and in connection with these figures, FIG. The invention will be described below.

─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Cecina, Thomas             United States 02052 Massachusetts             Medfield Oriole Law, Tutu             Do 23 (72) Inventor Caddell, Theodore, E.             Canada N 0 B 1 N 0 Onta             Rio Conestogo Elgin Sutori             East East 13 F-term (reference) 2G059 AA01 BB12 BB13 CC16 CC18                       EE01 EE02 EE10 EE12 GG01                       GG02 GG03 GG10 HH01 HH02                       JJ05 JJ11 JJ17 JJ22 KK01                       KK04 MM03 MM14                 4C038 KK10 KL05 KL07 KM01 KX02

Claims (25)

[Claims] 1. A method of determining a constituent concentration of a sample, comprising: irradiating the sample with broad spectrum radiation from adjacent visible and near infrared (AV / NIR) regions, the radiation being directed toward the sample. And then collecting the radiation, and dispersing the collected radiation into a dispersion spectrum of the component wavelengths to the AV / NIR detector, where the AV / NIR detector transmits or reflects from the collected radiation. Measuring at least one of the emitted radiation, transferring the measurement to a processor, exposing the sample to a broad spectrum of radiation in the longer wavelength near infrared (LWNIR) region, and emitting the radiation to the sample. LWN emission of one or multiple bands after being directed towards
Detecting with an IR detector, the LWNIR detector making at least one measurement of the transmitted or reflected radiation; and transferring the measured value to a processor, the measured value and one or A method wherein the processor calculates the concentration of the component in the sample based on a number of calibration algorithms. 2. A method according to claim 1, characterized in that one or more individual energy sources are used for producing the radiation. 3. The AV / NIR detector is one or multiple spectral instruments having an array of silicon detectors, and the LWNIR detector is an infrared sensitive detector for radiation in each band. 3. A method as claimed in any one of claims 1 or 2, characterized in that it is one or a multiplicity of spectroscopic instruments having an individual array of. 4. The AV / NIR detector is one or more spectral instruments having an array of silicon detectors and the LWNIR detector is one or more having an array of infrared sensitive detectors. Spectral instrument according to claim 1, wherein the radiation of each band is measured from a suitable member of an array of detectors sensitive to infrared radiation. The method described in. 5. The method according to claim 1, wherein the infrared sensitive detector is an InGaAs detector. 6. A spectrometer having an array of silicon detectors records all light in the visible, visible / infrared and adjacent regions of the visible and infrared ranges within the spectral sensitivity range of the detector. The method according to any one of claims 1 to 5. 7. A spectrometer having infrared sensitive detectors records light in the individual infrared ranges within their spectral sensitivity range. The method described in any one of. 8. A method as claimed in any one of claims 1 to 7, characterized in that all detectors record light in their considerable sensitivity range almost simultaneously. 9. A method of determining a constituent concentration of a sample, comprising: irradiating the sample with broad spectrum radiation from the AV / NIR region; collecting radiation after the radiation is directed toward the sample. Dispersing the collected radiation into a dispersive spectrum of component wavelengths to an AV / NIR detector, the AV / NIR detector measuring at least one of the transmitted or reflected radiation from the collected radiation. The steps of performing and transferring the measured values to the processor; exposing the sample to radiation in one or multiple bands in the LWNIR region; and emitting the radiation in one or multiple bands after the radiation is delivered to the sample. The step of detecting by the LWNIR detector, wherein the LWNIR detector is transmitted or reflected. Performing at least one measurement of the radiation and transferring the measurement to a processor, the processor calculating a concentration of the component in the sample based on the measurement and one or more calibration algorithms. How to characterize. 10. A method according to claim 9, characterized in that one or more individual energy sources are used to bring about the emission of the required spectral content. 11. The AV / NIR detector is one or more spectral instruments having an array of silicon detectors, and the LWNIR detector is an infrared sensitive detector for radiation in each band. 11. A method according to any of claims 9 or 10, characterized in that it is one or a multiplicity of spectroscopic instruments having an individual array of. 12. The AV / NIR detector is one or multiple spectral instruments having an array of silicon detectors and the LWNIR detector is one or more having an individual array of infrared sensitive detectors. Aspects of multiple spectral instruments, and wherein the measurement of the radiation in each band is made by a suitable member of an array of infrared sensitive detectors. The method described in crab. 13. The method according to claim 9, wherein the detector sensitive to infrared rays is an InGaAs detector. 14. A spectrometer having a silicon detector array records all light in the visible, visible / infrared and regions adjacent to the visible and infrared ranges within the spectral sensitivity range of the detector. The method according to any one of claims 9 to 13. 15. An infrared sensitive detector records light in the individual infrared ranges within their spectral sensitivity range. The method described. 16. A method according to any one of claims 9 to 15, characterized in that all detectors record light in their considerable sensitivity range almost simultaneously. 17. A method of determining a constituent concentration of a sample, comprising: irradiating the sample with broad spectrum radiation from the AV / NIR region; collecting radiation after the radiation is directed toward the sample. Dispersing the collected radiation into a dispersive spectrum of component wavelengths to an AV / NIR detector, the AV / NIR detector performing at least one measurement of transmitted and reflected radiation from the collected radiation. Performing and transferring the measurements to the processor; exposing the sample to broad spectrum emission from the LWNIR region;
Collecting the radiation after it has been directed toward the sample, and dispersing the collected radiation into the dispersion spectrum of the emission band to the detector of the LWNIR, where the detector of the LWNIR is transmitted and reflected. Comprising making at least one measurement of the radiation and transferring the measurement to a processor, the processor calculating a concentration of the component in the sample based on the measurement and one or more calibration algorithms. How to characterize. 18. Method according to claim 17, characterized in that one or more individual energy sources are used to bring about the emission of the required spectral content. 19. The AV / NIR detector is one or more spectral instruments having an array of silicon detectors, and the LWNIR detector is an infrared sensitive detector for radiation in each band. 19. A method according to any of claims 17 or 18, characterized in that it is one or a multiplicity of spectroscopic instruments having an individual array of. 20. The AV / NIR detector is one or more spectral instruments having an array of silicon detectors and the LWNIR detector is one or more spectral detectors having an array of infrared sensitive detectors. 19. A spectral instrument, and the measurement of the radiation in each band is carried out by a suitable member of an array of infrared sensitive detectors. The method described. 21. The method according to claim 17, wherein the infrared-sensitive detector is an InGaAs detector. 22. A spectrometer having an array of silicon detectors records all light in the visible, visible / infrared and ranges adjacent to the visible and infrared ranges within the spectral sensitivity range of the detector. A method according to any of claims 17 to 21. 23. A spectrometer having infrared sensitive detectors records light in the individual infrared ranges within their spectral sensitivity range.
The method according to any one of items 7 to 22. 24. A method according to any one of claims 17 to 23, characterized in that all detectors record light in their considerable sensitivity range almost simultaneously. 25. The method according to any one of claims 1 to 24, wherein the sample is a target finger.