JP2003508744A - Analyte quantification method using NIR, adjacent visible spectrum and discrete NIR wavelength - Google Patents

Abstract

(57) Abstract: Illustrated is to irradiate a body part of a patient with a broad spectrum continuum of radiation in the adjacent infrared and near infrared ranges of the electromagnetic spectrum, and to direct radiation to the part. Collecting the band of radiation after the radiation and dispersing the continuum of collected radiation into a dispersed spectrum of component wavelengths onto a detector (120), wherein the detector separates the collected radiation from the collected radiation. Taking at least one measurement of the transmitted or reflected radiation of the radiation and transmitting the measurement to the processor (300) and then one or more discrete wavelengths of radiation from a longer near infrared range. Measuring the concentration of a blood component within a living patient's body part (80), comprising measuring the absorption or reflectance of the same species with respect to and using the measurement to calculate the concentration of the component It is because of the way.

Description

Detailed Description of the Invention

FIELD OF THE INVENTION The present invention, in addition to discrete, longer wavelengths in the near infrared region of the optical spectrum,
A non-invasive apparatus and method for monitoring concentration levels of blood components of a living patient, such as a human or animal, using the full spectrum of the near infrared portion of the light spectrum and the adjacent visible spectrum.

BACKGROUND OF THE INVENTION Invasive Techniques Invasive techniques for measuring blood components are commonly used. These techniques are painful, potentially dangerous to operate, and expensive. A typical procedure is
Obtaining a blood sample from a vein, which sample is then tested in a medical laboratory using a number of chemical procedures to measure each component separately. Alternatively, the home glucose test is spotted on enzyme-based, semi-permeable membrane test strips, based on visual color comparison with a standard color chart, or more accurate and unambiguous spectral emission techniques (eg, , Reflexibility) is used to allow finger sticks to react with insulin administration for a certain length of time. There is a risk of infection and patients may develop a rash when these invasive techniques are used.

Non-invasive Techniques Past devices for non-invasively monitoring the concentration of blood components in a patient are known. Sensors are commonly used to externally measure either the concentration of components in the gas emitted by the body, the concentration contained in sweating, or the concentration contained in body fluids such as tears, saliva or urine specimens. An example of this method is the Glucowatch developed by Cygnus. It draws interstitial fluid from some part of the body onto the patch and measures glucose in that fluid. This method is ideal in that the patch causes inflammation and each patch that lasts for 12 hours needs to be calibrated using a reference method that utilizes an invasive finger stick to obtain a blood sample. is not. Instead, the blood component passes through a part of the patient's body, such as the earlobe, or
Alternatively, it is measured using radiation reflected from body parts such as the fingers or forearms. However, some of the past radiation devices have had radiation sources that emit light at only one wavelength or at two wavelengths (eg, US Pat. No. 4,655,2).
25, U.S. Pat. No. 4,883,953, and U.S. Pat. No. 4,882,492). Other older devices have multiple light sources, but only a limited number of wavelengths to be measured (US Pat. Nos. 4,915,827, 5,028, US Pat.
787, No. 5,077,476, No. 5,237,178, No. 5,319,
200 and 5,438,201). Some of these older devices have obtained a large number of discrete lamps whose light is optically coupled to the test specimen through a number of optical filters, each with its own designated transmission wavelength. Had a wavelength source. In addition, some older devices are controlled to take a series of measurements at successively higher or lower wavelengths. This can be extremely time consuming.

Other techniques include a large number within a certain range (eg 128 or 256).
, And a technique for measuring a limited number of wavelengths. Techniques for measuring the complete spectrum are typically
Wavelengths ranging from 580 nm to 1100 nm are used (eg US Pat. No. 5,36).
1,758 and U.S. Pat. No. 4,975,581). The advantage of full spectrum measurements is that they provide not only information about the interfering substances (eg other analytes) and effects (eg light scattering), but also about the desired analyte.

Some of the methods of measuring a limited number of wavelengths utilize the 1100 nm to 1700 nm region due to the sharper analyte spectra present in this range.
There are other methods for measuring wavelengths in the 600 nm to 1100 nm region. These methods provide information related to the analyte of interest, but are unable to provide sufficiently independent information about other analytes whose absorption interferes with the desired analyte.

[0006] Some older devices that take measurements at the earlobe have measured changes in the thickness of the patient's earlobe compared to the earlobe of other patients, or of the transmission path length for pulsations of blood through the patient. Do not take change into account. Alternatively, they either do not take into account temperature variations in the earlobe from patient to patient, or the results vary with prolonged treatment.

Overall, past non-invasive devices and techniques have not been sufficiently accurate to be used in place of invasive techniques in measuring blood component concentration levels by patients. Alternatively, they are designed to measure only one component and must be physically modified to measure another. Or the device is
It takes an excessively long time to produce results. Alternatively, the device does not produce results in a convenient format. Alternatively, they cannot measure the results of two or more components at the same time. Obviously, if the device gives inaccurate readings, disastrous results will occur, for example, for the patient using the device to calculate a dosage for insulin administration.

SUMMARY OF THE INVENTION The present invention provides a method for measuring the concentration level of a particular component, or alternatively, the concentration level of a plurality of different components in a non-invasive device, comprising: The method produces accurate, reliable, and short-term results.

We have found that measurements on a continuum of wavelengths between 500 nm and 1100 nm interfere with the concentration of the desired analyte, and, very importantly, many other analytes. Found to provide additional information about. The inventor
By adding a limited number of discrete wavelength measurements in the 00 nm to 1700 nm region to the complete spectral absorption measurements of the continuum at wavelengths of 500 nm to 1100 nm, it was revealed that the accuracy of the analyte measurement is enhanced. Using this combination, it is possible to obtain a significant improvement in analyte measurement accuracy. As used herein, the 500 nm to 1100 nm region is the "AV and NIR region".
The region from 1100 nm to 1700 nm is called the "longer wavelength NIR region" or "LWNIR".

According to a preferred embodiment, in each case the discrete wavelength measurement is at a signal-to-noise ratio high enough to achieve the desired result.

Accordingly, in its broadest aspect, the present invention provides for placing tissue in a non-invasive device capable of emitting radiation, directing a radiator onto the tissue, and measuring the radiation collected from the tissue. That the radiation directed onto the tissue and collected from the tissue has a wavelength in the range of 500 nm to 1100 nm, and 1100 nm to 170 nm.
Calculating the concentration level based on the measured radiation, which is that of a discrete wavelength continuum in the range of 0 nm, and provides a method for monitoring the concentration level of a component in tissue.

According to one aspect, the present invention provides a living or living animal, such as a human or an animal, in which for the AV and NIR regions a polychromatic light source or other radiation source emitting a wide spectrum of light in the range of 500 nm to 1100 nm is used. A method for determining the concentration level of a blood component in a patient is provided. For this range, the method includes directing light in a continuum of wavelengths onto a portion of the patient's body simultaneously, collecting the continuum of light after the light is directed onto the portion, and collecting. Focusing the collected light onto a diffraction grating, dispersing a continuum of light into a dispersed spectrum of the component wavelengths of the collected light onto a linear array detector, and linear array detection. Transmitting at least one measurement of reflected light transmitted from light collected in the near visible spectrum and near infrared range from the 500 nm to 1100 nm region, the measurement being transferred to a microprocessor. To be done. LW
For the NIR region, the method includes directing one or more narrowband sources of light onto a body part, and (depending on the particular configuration chosen) one or more narrowbands.
Collecting on one or more detectors, these measurements also being transferred to the microprocessor. The microprocessor then uses these measurements and calibration algorithms to calculate concentration levels of the at least one component of the blood and tissue.

In another aspect of the invention, irradiating the tissue with a broad spectrum of radiation in the AV and NIR regions, irradiating the tissue with radiation in the longer wavelength NIR region, and in the AV and NIR region Measuring at least one of the transmitted or reflected radiation from the tissue at a wavelength and a continuum of one or more discrete wavelengths within the longer wavelength NIR region, and determining the concentration of the component based on the measurement. And polishing, thereby determining the concentration of the component in the tissue, the method for determining the concentration of the component in the tissue of the patient.

Preferably, the continuum of wavelengths from the AV and NIR regions is 500 nm and 1100.
between nm.

According to another embodiment, the discrete wavelength in the longer wavelength NIR region is 1100n.
between m and 1700 nm.

Yet according to another embodiment, the one or more discrete wavelengths are 1100 nm and 1
It is between 300 nm.

According to another embodiment, the one or more discrete wavelengths are 1590 nm and 1700 nm.
between nm.

According to another embodiment, at least one of which is 1100 nm and 1300 n.
At least two discrete wavelengths that are between m and at least one of which is between 1590 nm and 1700 nm are measured.

According to yet another embodiment, the discrete wavelength measurements are 1150 nm, 1195 n
m, 1215 nm, 1230 nm, 1240 nm and 1250 nm.

According to another embodiment, the discrete wavelength measurements are at 1595 nm, 1610 nm and 1620 nm.

According to another embodiment, the discrete wavelength measurements are 1150 nm, 1195 nm, 12
At 15 nm, 1230 nm, 1240 nm, and 1250 nm, and 1
At 595 nm, 1610 nm and 1620 nm.

Yet according to another embodiment, the radiation at each discrete wavelength is provided by a separate energy source.

According to another embodiment, the wavelength at each of the discrete wavelengths is provided sequentially.

According to another embodiment, radiation at all discrete wavelengths is provided simultaneously.

According to another embodiment, the single energy source is 1100 nm to 1300 nm.
Provides continuous energy over the radiation range of.

Another embodiment provides a single energy source that provides continuous energy over the radiation range of 1140 nm to 1260 nm.

According to another embodiment, the single energy source provides radiation in the range of 500 nm to 1300 nm.

According to another embodiment, the step of irradiating the tissue in the AV and NIR region as well as in the longer wavelength NIR region is performed simultaneously, said AV and NIR
Measurements in each of the regions as well as the longer wavelength NIR region are made simultaneously.

According to yet another aspect of the invention, irradiating a portion of a patient's body with a broad spectrum of radiation in the AV and NIR regions, and radiation from the AV and NIR regions after the radiation is directed onto the body. To disperse the collected radiation into a dispersed spectrum of component wavelengths onto a detector, the detector at least one of the transmitted and reflected radiation from the collected radiation.
Taking one measurement, transferring the measurement to a processor, irradiating a part of the patient's body with radiation in the longer wavelength NIR region, and after the radiation has been directed onto the part. , Detecting one or more discrete wavelengths in the longer wavelength NIR region, the detector taking at least one measurement of the reflected radiation and transferring the measurement to a processor Calculating a concentration of said component of said blood based on the measured value and one or more calibration algorithms, and measuring the concentration of the blood component in a body part of a living patient. A method for doing so is provided.

According to one embodiment, the detector is a linear array detector and the measurement is for absorbed radiation.

According to another embodiment, the continuum of wavelengths from the AV and NIR regions is 500 nm.
And 1100 nm.

According to another embodiment, the discrete wavelength in the longer wavelength NIR region is 110
It is between 0 nm and 1700 nm.

According to another embodiment, the one or more discrete wavelengths are 1100 nm and 130.
It is between 0 nm.

According to another embodiment, the one or more discrete wavelengths are 1590 nm and 170.
It is between 0 nm.

According to another embodiment, at least one of which is 1100 nm and 130.
0 nm, at least one of which is 1590 nm and 1700 nm
At least one discrete wavelength, which is between

According to another embodiment, the discrete wavelength measurements are 1150 nm, 1195 nm, 1
At 215 nm, 1230 nm, 1240 nm and 1250 nm.

According to another embodiment, the discrete wavelength measurements are at 1595 nm, 1610 nm and 1620 nm.

According to another embodiment, the discrete wavelength measurements are 1150 nm, 1195 nm, 1
At 215 nm, 1230 nm, 1240 nm, and 1250 nm, 1595
nm, 1610 nm and 1620 nm.

According to yet another aspect of the present invention, irradiating a body part of a patient with a first continuum of a broad spectral band of radiation in the AV and NIR regions, and after the radiation has been directed to the part, the radiation Collecting a first band of the, and dispersing a continuum of collected radiation into a dispersed spectrum of component wavelengths onto a detector, the detector transmitting and reflecting from the collected radiation. Taking at least one measurement of the radiation, transferring the measurement to the processor, and irradiating the body part of the patient with a second continuum of the radiation band within the NIR region of the longer radio wave. Collecting a second band of radiation after the radiation has been directed onto the body and dispersing the continuum of collected radiation into a dispersed spectrum of the component wavelengths onto the detector This Detecting one or more discrete wavelengths within a longer wavelength NIR region, a detector taking at least one measurement of radiation transmitted and reflected from the collected radiation; A processor, based on the value and the one or more calibration algorithms, calculating and thereby determining a concentration of the component of the blood, the concentration of the blood component in a living body part of the patient comprising: A method of measuring is provided.

According to one embodiment, the detector is a linear array detector and the measurement is for absorbed radiation.

According to another embodiment, the continuum of wavelengths from the AV and NIR regions is 500 n
It is between m and 1100 nm.

According to another embodiment, the discrete wavelength in the longer wavelength NIR region is 110
It is between 0 nm and 1700 nm.

According to another embodiment, the one or more discrete wavelengths are 1100 nm and 13
It is between 00 nm.

According to another embodiment, the one or more discrete wavelengths are 1590 nm and 17
It is between 00 nm.

According to another embodiment, at least one of which is 1100 nm and 1300 n.
At least two discrete wavelengths are measured, which are between m and at least one of which is between 1590 nm and 1700 nm.

According to another embodiment, the discrete wavelength measurements are 1150 nm, 1195 nm, 12
At 15 nm, 1230 nm, 1240 nm and 1250 nm.

According to another embodiment, the discrete wavelength measurements are 1595 nm, 1610 nm and 1
At 620 nm.

According to another embodiment, the discrete wavelength measurements are 1150 nm, 1195 nm, 12
At 15 nm, 1230 nm, 1240 nm, and 1250 nm, and 1
At 595 nm, 1610 nm, and 1620 nm.

[0049]   According to another embodiment, the patient is a human and the body part is a finger.

[0050]   According to another embodiment, the component is glucose and the tissue is blood.

[0051]   According to another embodiment, a second source of radiation is provided at discrete wavelengths.

[0052]     (Detailed Description of the Invention)

As used herein, “concentration” or “concentration level” means the amount or quantity of a component in a solution, whether the solution is in vitro or in vivo.

As used herein, “component” means a substance, an analyte found in tissue, including, for example, glucose, carbohydrates such as bilirubin, proteins such as albumin, or hemoglobin.

As used herein, “in solution” means within a liquid environment, such as interstitial body fluids, or other body fluids.

As used herein, “tissue” means any tissue of a patient's body, including, for example, blood, extracellular spaces, etc., and the entire composition of a body part such as a finger or earlobe. May mean.

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

As mentioned above, the inventor has found that in order to improve the ability to measure an analyte in the tissue of a patient using a non-invasive device that uses spectral data, a longer wavelength A limited number of discrete wavelength measurements in the NIR range from 500 nm to 110
It is only necessary to add to the complete spectral absorption measurements on a continuum of wavelengths in the 0 nm region to obtain a significant improvement in the accuracy of analyte measurements. For certain analyte measurements, the accuracies achieved using the methods described above range from 1100 nm to 1300 nm (“
The first region ") and a limited number of discrete wavelength measurements in the 1590 nm to 1700 nm (" second region ") region are added to the complete spectral absorption measurements in the region of 500 nm to 1100 nm to achieve analyte measurement accuracy. It will be improved by getting a significant improvement. Preferably, the wavelengths in the first region are 1150 nm, 1195 nm, 121
5 nm, 1230 nm, 1240 nm and 1250 nm. Significant improvements can be made by adding only those wavelengths to the first region. Also,
The addition of wavelengths, preferably 1595, 1610, and 1620, in the second region can further improve accuracy. However, high light loss due to water absorption at wavelengths in the second region makes measurements at these wavelengths more difficult. The method of the present invention provides for body part measurements taken in the AV and NIR areas and added to the measurements taken in the first area or in either the first and second areas. It will be readily appreciated that the method includes the addition of measurements in all three areas, and the measurements may be taken simultaneously or sequentially.

The range of 580 nm to 1100 nm has been used, inter alia, because silicon detectors are sensitive within that range. Silicon detectors, especially silicon-based detector arrays, provide excellent noise and dynamic range performance, are readily available, and are relatively inexpensive. However, from 900 nm to 170
The 0 nm wavelength range provides a sharper spectrum for many of the analytes of interest, as can be seen with reference to FIG. Indium gallium arsenide (InGaAs) detector arrays are typically used to measure spectra in this region. They provide noise and dynamic range performance that is inferior to silicon. In this way, the lower signal-to-noise ratio offsets some of the sharper spectral advantages. Other detector arrays may also be used in these first and second areas.

In one embodiment, narrow band light is used to illuminate the tissue to achieve a high signal-to-noise ratio for measurements at wavelengths in the first region or the second region. Narrowband illumination allows much higher brightness in certain bands, for example 10 nm, than can be exploited in broadband sources, as safety considerations limit the amount of light energy that can be delivered to the finger. That is, more optical power for each wavelength can be delivered to the detector, thus facilitating achieving a high signal-to-noise ratio. As one of ordinary skill in the art will readily appreciate, one method is to continuously illuminate the finger at a rate high enough to reduce enough error from short-term absorption changes in the finger due to heartbeat pulses and other effects. right. This method is depicted in FIG.

Referring to FIG. 3, the illumination source (10) for the device of the invention has sufficient power,
It can be any source of narrowband light with wavelength stability and consistency, and amplitude safety. Examples of such devices are diode lasers, LEDs, narrower, tightly controlled bands, and each LE to provide photoluminescent materials.
LED with filter associated with D.

Light is delivered by a suitable conductor, such as a fiber (20) to the finger (30). The light emanating from the finger is collected and fiber or other suitable conductor (40)
Is delivered to a single detector (50). In the case of light of this wavelength, InGaA
The s photodiode is the preferred detector. "Light", as used here,
"Illumination", "radiation" all refer to the light energy provided by one or more sources capable of delivering sufficient light at each of the desired wavelengths.

In another embodiment, the fingers are simultaneously illuminated with the narrowband source. This is shown in Figure 4.
Shown in. Light from a plurality of narrow band light sources (60) is delivered to a finger (80) by a suitable lead (70). The collected light is collected by a conductor (90) into a spectrometer (1
00), separated into its individual wavelengths using a diffraction grating (110), and then delivered to individual detectors or detector arrays (120). This method, to some extent, reduces the optical power per wavelength band that can be applied, but eliminates the error present in the first method due to finger absorption changes that could be achieved at each wavelength differently.

In a third embodiment, a light source that delivers continuous energy within a selected discrete wavelength range, such as 1100 nm to 1300 nm, is used to illuminate the finger. The collected light will be separated into its individual wavelengths using a diffraction grating and then delivered to individual detectors or detector arrays. This method may further reduce the optical power per applicable wavelength band, but it offers the advantage that the measurement accuracy of the system does not depend on the wavelength stability of the light source. The light source in this embodiment is described as being specific to the discrete wavelength range. It is also possible to use the same light source used for supplying energy in the wavelength range of 500 nm to 1100 nm for this purpose. An additional alternative is to increase the light intensity in the discrete wavelength range from 500 nm to 11 by a second source that provides energy in the discrete wavelength range and in addition only in the discrete wavelength range.
Using the same light source used to deliver energy in the 00 nm wavelength range.

Regarding measurements in the AV and NIR regions, the light source can emit light over a very wide bandwidth, including light in the AV and NIR, eg polychromatic sources may be used. Light sources that are special in this area are preferred. According to one embodiment, the light from the light source first passes through a collimator, which is a collection of lenses that concentrates the light into a narrow, collimated beam that is directed to the receptor. The receptor is shaped therein to receive that part of the patient being measured, for example the human finger or ear. Alternatively, the receptor could be shaped such that the part of the human or animal on which the light has to be directed is placed closer to the receptor than to the receptor. In any event, the body part contacts the receptor and light is directed onto the body part and dispersed by the body part. The dispersed light is collected by a lens and directed through a break into the diffractive means. Alternatively, the means for collecting light after it has been directed onto the receptor is an optical fiber that transmits said light to a diffractive means. The collected light may be light that has passed through a part of the body or reflected away from the part of the body, or a combination thereof. Preferably, the collected light is the light that has passed through the part of the patient.

The light from the diffraction grating disperses the light into its component wavelengths so that the light in the AV and NIR regions falls along the length of the linear array detector. As will be appreciated, the array consists of individual detectors whose extent corresponds to the AV and NIR regions. The array detectors are electronically scanned by the microprocessor to measure the intensity of the light at each individual device, or reflected from the tissue within the recipient. The detector is connected to a microprocessor to produce an output spectrum, the microprocessor analyzes the measurements from the linear array detector and detects the individual InGaA
The s-detector ultimately produces a result for each concentration level sought. The results can be shown on a display and / or printed on a printer. The keyboard allows the user to, for example, specify a particular component to be measured,
Allows you to control the device. Timing and control controls the device and may be activated by a microprocessor to determine, for example, the number and timing of measurements.

The polychromatic light source may be a quartz halogen or tungsten-halogen bulb and is powered by a stabilized power source, such as a DC power source, or by a battery. Preferably, the linear array detector has at least 10 elements, more preferably 250 to 300 units for measurements in the AV and NIR regions. The additional advantage of a linear array detector is that it reduces the effect of pulses on the optical signal waveform for beating because each diode is exposed to pulsating light at exactly the same time interval. Is.

After the measurements are taken for transmission and / or reflectance, the reciprocal of these measurements is logged. That is, log 1 / T and log 1 / R, and in this case T
And R represent transmittance and reflectance, respectively. The reference set of measurements is the light that is taken from the incident light and that is generated within the device when no part of the patient is in contact with the receptor. Absorbance is then calculated when a portion of the patient, such as a finger, contacts the receptor as a ratio of measurements compared to a reference set of measurements.

Although not to be construed as a limitation on the method of the present invention, a second derivative of the measurement is optionally taken to reduce any variability in the results that would be caused by changes in the path length of the light. Good.

The noise level in the instrument is determined by the linear array detector after taking a number of measurements,
It may be reduced by a multiple scan technique that averages the results. Preferably, the linear array detector and the discrete longer wavelength detector are scanned many times for multiple iterations before averaging the results.

[0071]   Known methods for calculations such as PLS and PCR may be used.

Although measuring glucose concentration is a preferred embodiment of the present invention, the apparatus and method may include, for example, amino acids, nitrogen, blood oxygenation reactions, carbon dioxide, cortisol, creatine, to name but a few. In human and animal blood, such as creatinine, glucose, ketones, lipids, urine, fatty acids, glycosylated hemoglobin, cholesterol, alcohols, lactates, CA ⁺⁺ , K ⁺ , CL ⁻ m HCO ₃ ⁻ and HPO ₄ ^−. It can be used to determine the concentration levels of the various other components found. In fact, as will be apparent to those skilled in the art,
The method and apparatus can be modified to measure multiple components simultaneously.

A number of non-limiting examples are illustrative of the present invention. Examples Example 1 Simulator Simulators have been developed to assist in the analysis of analyte measurement alternatives.
It simulated all the components of the system according to the invention, namely the light source, the light transmission means, the optics, the filter and the detector. It simulated not only a number of interfering substances, but also the loss of light through the body part based on the measured spectrum of the analyte of interest. The simulator randomly created combinations of body components and then created spectra for each combination. An example of a combination created is, for example, first aggregate glucose 5 mM, total Hb 14 g / dL and O ₂ Sat 95%. Sample No. 2 was glucose 7 mM, total Hb 13.
5 g / dL and O ₂ Sat 98%. It then calculated the absorption values based on these spectra as well as instrument and detector characteristics such as noise, drift, and factors that achieve the spectrum. The absorption measurements were then processed by the same algorithms routinely used in the instrument to calculate analyte predictions such as those described above.

Using this simulator, the two wavelength ranges from 580 nm to 1100 n
It has been determined to provide a surprisingly significant improvement in glucose measurement accuracy when added to m measurements. These areas are 1100 nm to 1300 nm
And 1590 nm to 1700 nm. We have found that the detection of numerous specific wavelength combinations provides a great deal of improvement. According to a preferred embodiment, the specific wavelengths are as follows. 1150nm, 1195n in the first region
m, 1215 nm, 1230 nm, 1240 nm, and 1250 nm, and 1595 nm, 1610 nm, and 1620 nm in the second region.

Noise and other errors were added to the absorption measurements by the simulator, as the improvement in glucose accuracy depends on the accuracy with which these measurements can be made. A chart was constructed relating the improvement ratio (glucose error only from 580 nm to 1100 nm measurements / glucose error from combined measurements) to the error in the absorption measurements. This relationship is shown in the attached FIG. The improvement ratio in this chart is only for the six wavelengths in the first region as defined above from 580 nm to 1
Calculated based on adding to 100 nm measurements.

Example 2 Feasibility Model As shown in FIG. 5, the light source (140) has a collimator (Oriel # 60).
076) (150) and shutters (Oriel # 71446) (160), followed by a brightness control (Oriel 68850) (130), 1
00 Watt Tungsten Halogen Lamp Assembly (Oriel QTH # 600
A feasibility model consisting of 67) was constructed. The individual wavelengths in the 1150 nm to 1250 nm region as defined in the preferred embodiment described above are produced by passing light through an interference filter with a bandwidth of about 10 nm (Orion). Continuous lighting is a device control device (MacPherson # 747) (180)
Rotated Filter Wheel (MacPherson # 941) (170)
This is accomplished by mounting these filters on top of. As will be appreciated by those in the art, other means can be used to achieve delivery of discrete wavelengths within this range.

To further block stray light, the light beam passed through another bandpass filter (190) with a transmission range of 1140 nm to 1260 nm (Orion). Light is delivered via a bifurcated fiber (210) to a finger receptor such as that described in US Pat. No. 5,429,128. Light that passes through the finger (230) is bifurcated (240).
Cooled InGaAs photodiode (Hamamatsu # G5832-
13) Delivered up to (260). The current from the photodiode is the current preamplifier and amplifier (Stanford Research # SR570 and SR560) (270
And 280). The resulting voltage is converted to a digital signal and the data acquisition board (National Instruments AT-A1-16XE10
) (290) to the computer (300).

The second leg of the illumination and collection bifurcated fibers (220 and 250) was used to connect a silicon-based spectrometer measuring absorption in the range 580 nm to 1100 nm.

To date, noise and drift in the feasibility model will give rise to a range of absorption errors of about 200 μOD and the level predicted by our simulator will give an improvement ratio of 1.12. Despite these errors, two diabetic volunteers were measured for a total of 3 days. Each day, 16 spectra were collected over a period of about 8 hours while each volunteer was following their normal diet and course of insulin injections. Using each set of spectral measurements, blood was drawn from a finger stick via a capillary and measured on a reference instrument (YSI). The data is 580n
Processed for calibration using only measurements in the range m to 1100 nm and using those referenced above for the first region. The results were as follows. Wavelength region SEC % improvement ratio 580nm to 1100nm 1.86 580nm to 1100nm slightly 1150 to 1250 1.23 34% 1.17

Although this remedy is important, a much better improvement, and thus a lower glucose error, can be achieved using a measurement configuration that results in a lower absorption measurement error, as shown in FIG. .

Although the present invention has been described with respect to what is presently considered to be the preferred examples, it should be understood that the 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 as if each individual publication, patent or patent application was incorporated by reference in its entirety. Are incorporated by reference to the same extent as and to the same extent as a whole.

[Brief description of drawings]

The present invention will now be described with respect to the drawings.

FIG. 1 shows the absorption spectrum from 500 nm to 1380 nm of human serum albumin with globulin, glucose, urine, creatine, cholesterol, and water displacement compensation.

FIG. 2 is a graph showing improved glucose prediction with respect to absorbance error of measurements at discrete longer NIR wavelengths.

FIG. 3 illustrates one embodiment of the present invention, a plurality of narrow band sources that are sequentially energized,
FIG. 6 shows a single detector.

FIG. 4 illustrates another aspect of the invention that provides multiple narrowband light sources and multiple detectors that are simultaneously energized.

FIG. 5 comprises a feasibility model of the system for determining the concentration of components,
FIG. 6 shows an additional embodiment of the invention.

─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Paulakuji, Romande             Canada N2L 5p1onta             Rio Waterloo Rose Lawn Pre             Base 362 (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 BB13 CC02 CC13 CC15                       CC18 EE01 EE02 EE12 FF06                       GG01 GG03 GG10 JJ02 JJ05                       JJ17 KK01 KK04 MM14 PP04                 4C038 KK10 KL05 KL07 KX02

Claims (39)

[Claims] 1. Irradiating tissue with broad spectrum radiation in the AV and NIR regions; irradiating tissue with radiation in the longer wavelength NIR region; wavelengths in the AV and NIR region; and longer. Measuring at least one of the transmitted or reflected radiation from the tissue in one or more continuums of discrete wavelengths in the wavelength NIR region, and based on the measured values, calculating the concentration of the component, Determining the concentration of the component in the tissue, the method comprising: determining the concentration of the component in the tissue of the patient. 2. A continuum of wavelengths from the AV and NIR regions is 500 nm and 11
The method according to claim 1, which is between 00 nm. 3. Discrete wavelengths within the longer wavelength NIR region are 1100 nm and 1
The method according to claim 1 or 2, which is between 700 nm. 4. The one or more discrete wavelengths are 1100 nm and 1300 nm.
The method of claim 13, wherein the method is between. 5. The one or more discrete wavelengths are 1590 nm and 1700 nm.
The method of claim 3, wherein the method is between. 6. The method of claim 3, wherein at least two discrete wavelengths are measured, at least one of which is between 1100 nm and 1300 nm and at least one of which is between 1590 nm and 1700 nm. . 7. A discrete wavelength measurement value is 1150 nm, 1195 nm, 1215n.
m, 1230 nm, 1240 nm and 1250 nm. 7. A method according to any one of claims 3, 4 and 6. 8. The discrete wavelength measurement values are 1595 nm, 1610 nm and 1620.
7. The method of any one of claims 3, 5 and 6 in nm. 9. The discrete wavelength measurement values are 1150 nm, 1195 nm, 1215n.
m, 1230 nm, 1240 nm and 1250 nm, and 1595n
7. The method according to claim 3, which is at m, 1610 nm and 1620 nm. 10. The method according to claim 1, wherein the radiation at each discrete wavelength is provided by a separate energy source. 11. The method according to claim 1, wherein the radiation at each of the discrete wavelengths is provided in succession. 12. A method according to claim 1, wherein radiation at all discrete wavelengths is provided simultaneously. 13. The method according to claim 1, wherein the single energy source provides continuous energy in the radiation range of 1100 nm to 1300 nm. 14. The method of claim 13, wherein the single energy source provides continuous energy in the radiation range of 1140 nm to 1260 nm. 15. The method according to claim 1, wherein the single energy source provides radiation in the range of 500 nm to 1300 nm. 16. The step of simultaneously irradiating the tissue in the AV and NIR regions and in the longer wavelength NIR region is performed simultaneously, and the measurement in each of the AV and NIR region and the longer wavelength NIR region is performed simultaneously. The method according to any one of claims 1 to 15. 17. Irradiating a portion of the patient's body with a broad spectrum of radiation in the AV and NIR regions; collecting radiation from the AV and NIR regions after the radiation has been directed onto the body; At least one of the transmitted and reflected radiation from the collected radiation that disperses the collected radiation into a dispersed spectrum of component wavelengths onto the detector.
Taking one measurement, transferring the measurement to a processor, irradiating a part of the patient's body with radiation in the longer wavelength NIR region, and after the radiation has been directed onto the part, Detecting one or more discrete wavelengths in the longer wavelength NIR region, the detector taking at least one measurement of the transmitted and reflected radiation, and transferring the measurement to a processor; Calculating a concentration of said component of said blood based on the value and one or more calibration algorithms, and measuring the concentration of the blood component in a body part of a living patient, comprising: the method of. 18. The method of claim 17, wherein the detector is a linear array detector and the measurement is for absorbed radiation. 19. A continuum of wavelengths from the AV and NIR regions is 500 nm and 1
The method according to claim 17 or 18, which is between 100 nm. 20. The discrete wavelength in the longer wavelength NIR region is 1100 nm.
19. The method according to claim 17 or 18, which is between 1 and 1700 nm. 21. The one or more discrete wavelengths are 1100 nm and 1300 nm.
21. The method of claim 20, wherein the method is between. 22. The one or more discrete wavelengths are 1590 nm and 1700 n.
21. The method of claim 20, wherein the method is between m. 23. The method of claim 20, wherein at least two discrete wavelengths are measured, at least one of which is between 1100 nm and 1300 nm and at least one of which is between 1590 nm and 1700 nm. . 24. The discrete wavelength measurement values are 1150 nm, 1195 nm, 1215.
nm, 1230 nm, 1240 nm and 1250 nm.
25. The method according to any one of 23 and 23. 25. The discrete wavelength measurement values are 1595 nm, 1610 nm and 162.
24. The method according to any one of claims 19, 20 and 23, which is at 0 nm. 26. Discrete wavelength measurement values are 1150 nm, 1195 nm, 1215.
nm, 1230 nm, 1240 nm and 1250 nm, and 1595
24. The method according to any one of claims 20 or 23 at nm, 1610 nm and 1620 nm. 27. Irradiating a part of the patient's body with a first continuum of a broad spectral band of radiation in the AV and NIR regions, the first band of radiation being directed after the radiation is directed onto the part. Collecting and dispersing a continuum of collected radiation into a dispersed spectrum of component wavelengths onto the detector, the detector detecting at least one of the transmitted and reflected radiation from the collected radiation. Taking one measurement, transferring the measurement to a processor, irradiating a part of the patient's body with a second continuum of the radiation band within the longer NIR region, and directing the radiation onto the part. And then collecting a second band of radiation and dispersing the continuum of collected radiation into a dispersed spectrum of component wavelengths onto the detector, one within the longer wavelength NIR region. Also Detecting a plurality of discrete wavelengths, the detector taking at least one measurement of transmitted and reflected radiation from the collected radiation, transferring the measurement to a processor, and measuring And based on the one or more calibration algorithms, a processor calculates and thereby determines the concentrations of the constituents of the blood, and determining the concentration of the blood constituents in the body part of the living patient. Method for measuring. 28. The method of claim 27, wherein the detector is a linear array detector and the measurement is for absorbed radiation. 29. A continuum of wavelengths from the AV and NIR regions is 500 nm and 1
29. The method according to claim 27 or 28, which is between 100 nm. 30. The discrete wavelength in the longer wavelength NIR region is 1100 nm.
29. The method of claim 27 or 28, which is between 1 and 1700 nm. 31. The one or more discrete wavelengths are 1100 nm and 1300.
31. The method of claim 30, which is between nm. 32. The one or more discrete wavelengths are 1590 nm and 1700 n.
31. The method of claim 30, wherein the method is between m. 33. The method of claim 30, wherein at least two discrete wavelengths are measured, at least one of which is between 1100 nm and 1300 nm and at least one of which is between 1590 nm and 1700 nm. . 34. The discrete wavelength measurement values are 1150 nm, 1195 nm, 1215.
nm, 1230 nm, 1240 nm and 1250 nm.
And 33. The method according to any one of 35. The discrete wavelength measurement values are 1595 nm, 1610 nm and 162.
34. The method according to any one of claims 30, 31, and 33 at 0 nm. 36. Discrete wavelength measurement values are 1150 nm, 1195 nm, 1215.
nm, 1230 nm, 1240 nm, and 1250 nm, and 159
34. The method according to any one of claims 30 or 33, which is at 5 nm, 1610 nm and 1620 nm. 37. The patient is a human and the body part is a finger.
The method according to any one of 1. 38. The method of any one of claims 1-37, wherein the component is glucose and the tissue is blood. 39. The method of any one of claims 1-38, wherein a second source of radiation is provided for discrete wavelengths.