JP2013213736A - Analyzer for trace constituent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an analyzer for a trace constituent, the analyzer analysing a trace constituent contained in a sample by an infrared absorptiometry in a high sensitive manner.SOLUTION: An analyzer 10 for a trace constituent includes: a light source 11 outputting a monochromatic light beam 23; a prism 30 including an incidence surface 31 for the light beam 23, a reflection surface 33 reflecting the incident light beam 23, and an output surface 32 outputting a light beam 24 which reflects on the reflection surface 33; resonators 21 which are arranged on optical axes of the light beams 23, 24 and hold the prism 30 in-between to multiply reflect the light beams 23, 24; a detector 16 detecting a light beam 25 which is multiply reflected and passes through one of the resonators 21; and an analysis part 17 for analysing a trace constituent of a sample 35 on the basis of a detection signal 26 of the detector 16 in a state where the sample 35 is made contact with the reflection surface 33 of the prism 30.

Description

  The present invention relates to a trace component analyzer that analyzes trace components contained in a sample.

Biological factors that increase with the progression of disease (cancer, diabetes, gastric ulcer, etc.) are used as tumor markers by blood tests. However, since many tumor markers are also present in the blood of a healthy person, there are only a limited number of cases where a disease can be diagnosed only by examining the tumor markers (PSA: prostate cancer can be diagnosed).
In addition, blood collection performed during a blood test gives pain and psychological pressure to the patient, and cannot be completely free from the risk of infection.

  For this reason, non-invasive monitoring of the concentration level of tumor markers in blood is expected. As an example of this non-invasive monitoring method, there is a method of detecting a tumor marker during exhalation of a patient. In particular, there are reports that the relative concentrations of volatile organic compounds (alkanes, aromatic compounds, benzene dielectrics, etc.) in breath differ between lung cancer / breast cancer patients and healthy people.

  Such tumor markers detected from the patient's breath may be endogenous compounds themselves or derived from endogenous compounds. A technique for detecting such a tumor marker from a patient's breath and monitoring the concentration of an endogenous compound in the blood has been proposed (for example, Patent Document 1).

Special table 2009-519467

  However, at present, even if mass spectrometry is used, not all endogenous compounds can be detected with sufficient sensitivity. For this reason, a technique for diagnosing a disease by detecting a tumor marker from breath has not been put into practical use.

  The present invention has been made in view of such circumstances, and an object of the present invention is to provide a trace component analyzer that analyzes a trace component contained in a sample with high sensitivity by infrared absorption spectrometry.

  In the trace component analyzer, a light source that outputs light, a prism having an incident surface of the light, a reflecting surface that reflects the incident light, and an output surface that outputs the light reflected by the reflecting surface; A resonator disposed on the optical axis that multi-reflects the light beam with the prism interposed therebetween, a detector that detects the multi-reflected light beam that has passed through the resonator, and a sample in contact with the reflective surface of the prism And an analysis unit that analyzes a trace component of the sample based on a detection signal of the detector in a state where the detection is performed.

  According to the present invention, there is provided a trace component analyzer that analyzes a trace component contained in a sample with high sensitivity by infrared absorptiometry.

The block diagram which shows 1st Embodiment of the trace component analyzer which concerns on this invention. The block diagram which shows 2nd Embodiment of the trace component analyzer which concerns on this invention. The block diagram which shows 3rd Embodiment of the trace component analyzer which concerns on this invention. The block diagram which shows 4th Embodiment of the trace component analyzer which concerns on this invention. The block diagram which shows 5th Embodiment of the trace component analyzer which concerns on this invention.

(First embodiment)
Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings.
As shown in FIG. 1, the trace component analyzer 10 according to the first embodiment includes a light source 11 that outputs a monochromatic light beam 23, an incident surface 31 of the light beam 23, and a reflective surface 33 that reflects the incident light beam 23. , And a prism 30 having an output surface 32 for outputting the light beam 24 reflected by the reflecting surface 33, and a resonance which is arranged on the optical axis of the light beams 23 and 24 and multiplexly reflects the light beams 23 and 24 with the prism 30 interposed therebetween. A sample 21 based on the detection signal 26 of the detector 16 in a state in which the sample 35 is in contact with the reflecting surface 33 of the prism 30, the detector 16 that detects the light beam 25 that has passed through the resonator 21 with multiple reflection. And an analysis unit 17 for analyzing 35 trace components.

  The sample 35 is a part of a human body (for example, a finger), and a trace component (biological factor component) serving as a marker for disease diagnosis is detected noninvasively. Specifically, a finger is pressed against the reflecting surface 33 of the prism 30 to monitor blood sugar level (glucose) and the like. In addition, the sample 35 is not specifically limited, If it aims at a component analysis through a solid surface, it will become object suitably.

The light source 11 outputs a monochromatic light beam 23 having a wavelength corresponding to a peak characteristic of the biological factor component in the absorption spectrum of the biological factor component.
The light beam 23 output from the light source 11 passes through one mirror 27 of the resonator 21 and then enters the incident surface 31 of the prism 30 perpendicularly. The light beam 23 incident on the prism 30 irradiates an evanescent wave toward the sample 35 when totally reflected by the reflection surface 33. Since the evanescent wave irradiated to the sample 35 interacts with the biological factor component to be examined, the intensity of the reflected light beam 24 decreases corresponding to the concentration of the biological factor component.

Here, as a condition for the incident light beam 23 to be totally reflected without passing through the reflecting surface 33, the incident angle of the incident light beam 23 with respect to the reflecting surface 33 is required to be equal to or larger than the critical angle. Alternatively, the difference in refractive index from the sample 35) is required to be large.
For this reason, it is desirable for the prism 30 to have a refractive index of 2 or more. Specifically, a high refractive index glass K-PSFn 214 or the like is preferably used.

The resonator 21 is arranged so that a pair of mirrors 27 and 28 that reflect a part of the incident light beam and transmit the remaining light beam are orthogonal to the optical axis of the incident light beam 23 and the optical axis of the reflected light beam 24, respectively. . When the optical path length L between the mirrors 27 and 28 is the wavelength λ of the light beams 23 and 24, the relationship of the following equation (1) is satisfied in order to satisfy the resonance condition.
mλ = 2L (m: natural number) (1)

By satisfying the relationship of this resonance condition, the light beams 23 and 24 are output by multiple reflection inside the resonator 21 and then passing through the light beam 25. Then, on the reflecting surface 33 of the prism 30, the interaction between the biological factor component in the sample 35 and the evanescent wave is repeated, and the intensity of the passing light beam 25 further decreases.
Thereby, the biological factor component (tumor marker) of interest can be monitored with high sensitivity.

The collimating lens 14 and the condenser lens 15 are installed between the light source 11 and the mirror 27 of the resonator 21. Thereby, by optimizing the collimating diameter of the collimating lens 14 and the focal length of the condensing lens 15 and performing mode matching of the resonator 21, it is possible to increase the sensitivity of the analysis of the biological factor component.
When the detector 16 receives the light beam 25 that has passed through the resonator 21, the detector 16 outputs a detection signal 26 that indicates the intensity of the light beam 25.

The analysis unit 17 stores a detection signal obtained as a result of analyzing a reference sample (not shown) that does not include a biological factor component to be examined under the same conditions as the sample 35.
Then, from the rate of change (ΔI / I) between the detection signal 26 acquired with the sample 35 in contact with the reflecting surface 33 of the prism 30 and the detection signal of the reference sample (ΔI / I), the quantitative result of the trace component of the sample 35 (biological factor) The concentration of the component (tumor marker) is derived.
Note that the accuracy of the quantitative result is further improved by executing correction in consideration of the difference in refractive index, absorbance, and evanescent light penetration length in the reference sample (not shown) in contact with the prism 30 and the sample 35. .

(Second Embodiment)
As shown in FIG. 2, in the trace component analyzer 10 according to the second embodiment, the light source 12 outputs a plurality of monochromatic lights (illustrated are two kinds of the first monochromatic light 23 a and the second monochromatic light 23 b), and is resonant. A plurality of devices 21 are arranged (two of the first resonator 21a and the second resonator 21b are shown), and the corresponding monochromatic light is selected in each of the two types (first monochromatic light 23a and second monochromatic light 23b). Multiple reflection.
2 that are the same as or correspond to those in FIG. 1 are denoted by the same reference numerals, and redundant description is omitted.

The light source 12 outputs the first monochromatic light 23a and the second monochromatic light 23b independently of each other.
The optical path length of the first resonator 21a is set so as to satisfy the resonance condition (the above formula (1)) with respect to the wavelength λ of the first monochromatic light 23a. Then, the first resonator 21a passes the second monochromatic light 23b, selectively multi-reflects only the first monochromatic light 23a, and outputs the passing light beam 25.
The optical path length of the second resonator 21b is set so as to satisfy the resonance condition (formula (1)) with respect to the wavelength λ of the second monochromatic light 23b. The second resonator 21b passes the first monochromatic light 23a, selectively multi-reflects only the second monochromatic light 23b, and outputs the passing light beam 25.

  The detector 16 individually enters the light beam 25 that has passed through the first resonator 21a and the light beam 25 that has passed through the second resonator 21b, and outputs a detection signal 26 indicating the intensity of each light beam 25.

  The light beams 23 of the plurality of monochromatic lights 23a and 23b each have a wavelength corresponding to a peak characteristic of the biological factor component in the absorption spectrum of the biological factor component. For this reason, in the trace component analyzer 10 according to the second embodiment, since the biofactor component (tumor marker) is detected based on a plurality of absorption spectra, the quantitative accuracy of the trace component of the sample 35 is improved. Alternatively, monitoring of a plurality of biological factor components (tumor markers) can be performed with a single device.

As a specific example, the first monochromatic light 23a is matched with the absorption spectrum of the volatile organic compound, and the second monochromatic light 23b is matched with the absorption spectrum of glucose.
In this case, the mirrors 27a and 28a of the first resonator 21a multiple-reflect the light beam 23 having a wavelength corresponding to the absorption spectrum (about 3000 cm ⁻¹ ) of the volatile organic compound, but having a wavelength corresponding to the absorption spectrum of glucose. The light beam 23 is transmitted. The mirrors 27b and 28b of the second resonator 21b multiple-reflect the light beam 23 having a wavelength corresponding to the absorption spectrum of glucose, but transmit the light beam 23 having a wavelength corresponding to the absorption spectrum of the volatile organic compound.
Thereby, the trace component analyzer 10 which can analyze the volatile organic compound which is the biological factor component in the breath of the lung cancer / breast cancer patient and the glucose which is the biological factor component of diabetes by one unit is provided.

(Third embodiment)
As shown in FIG. 3, the trace component analyzing apparatus 10 according to the third embodiment moves one of the pair of mirrors (mirror 28) constituting the resonator 21 to change the optical path length L where multiple reflection occurs. An optical path length variable unit 22 to be varied is further provided.
3 that are the same as or correspond to those in FIG. 1 are denoted by the same reference numerals, and redundant description is omitted.

The optical path length variable unit 22 is configured by a feeding mechanism using a stepping motor, a piezoelectric element, or the like, and is driven so that the relationship between the wavelength λ of the light beams 23 and 24 and the optical path length L satisfies the resonance condition (formula (1)). Specifically, based on the detection signal 26 of the detector 16, the position of the mirror 28 is adjusted while observing the intensity of the received passing light beam 25.
By providing the function of finely adjusting the optical path length L in this way, a high enhancement rate is realized inside the resonator 21 and a highly sensitive microanalysis can be performed.

(Fourth embodiment)
As shown in FIG. 4, in the trace component analysis apparatus 10 according to the fourth embodiment, the light beam output from the light source 13 is continuous light 23 c, and the detection signal 26 of the detector 16 is Fourier transformed and passes through the resonator 21. And a spectroscopic unit 18 for guiding the wavelength spectrum of the light beam 25.
4 that are the same as or correspond to those in FIG. 3 are denoted by the same reference numerals, and redundant description is omitted.

Here, as the continuous light 23c, light in the infrared band in which the sample 35 absorbs a large amount of energy is used.
When the continuous light 23c is incident on the resonator 21 from the light source 13, the intensity of the monochromatic light having the wavelength λ that satisfies the resonance condition (Equation (1)) exhibits a maximum value due to resonance. Here, when attention is paid to one monochromatic light constituting the continuous light 23c, the intensity thereof changes sinusoidally in accordance with the continuous change of the optical path length L by the optical path length variable unit 22. Corresponding to the change in the optical path length L, the intensity of each monochromatic light constituting the continuous light 23c changes sinusoidally at different periods corresponding to each wavelength. For this reason, the detector 16 receives the passing light beam 25 in which the monochromatic lights whose intensity changes sinusoidally are superimposed.

The spectroscopic unit 18 derives the wavelength spectrum of the passing light beam 25 by performing Fourier transform on the detection signal 26 of the detector 16 and calculating the intensity of each of the monochromatic light constituting the continuous light 23c.
In addition, although the method of performing a data calculation (Fourier transform) after detecting the light intensity of the passing light 25 by the detector 16 is shown as the spectroscopic method of the passing light 25, the passing light 25 is detected by hardware using a diffraction grating or the like. There is also a method of spectroscopy.
Thus, by using the continuous light 23c for the light source 13, light absorption characteristics in a wide band can be obtained, so that qualitative analysis of the sample 35 is also possible.

(Fifth embodiment)
As shown in FIG. 5, in the trace component analyzer 10 according to the fifth embodiment, the reflecting surface 33 of the prism 30 is provided with a sample chamber 34 that accommodates and pressurizes a sample (not shown).
5 that are the same as or correspond to those in FIG. 1 are denoted by the same reference numerals, and redundant description is omitted.

The sample chamber 34 includes a sealing port 36 that encloses a gaseous sample (not shown) and a pressurizing unit 37 that pressurizes the stored sample.
The fifth embodiment aims to monitor the concentration of volatile organic compounds (alkanes, aromatic compounds, benzene dielectrics, etc.) in the breath of lung cancer / breast cancer patients.
After confining the exhaled breath as a sample in the sample chamber 34, the density of the biological factor component in the chamber can be increased by pressurization, and high sensitivity analysis is possible even under a dilute concentration condition.

  According to the trace component analyzer of at least one embodiment described above, since trace components contained in a sample can be analyzed with high sensitivity by infrared absorption spectrometry, for example, a non-invasive biological factor component (tumor) Marker) can be monitored with high accuracy.

  Although several embodiments of the present invention have been described, these embodiments are presented by way of example and are not intended to limit the scope of the invention. These embodiments can be implemented in various other forms, and various omissions, replacements, changes, and combinations can be made without departing from the scope of the invention. These embodiments and their modifications are included in the scope and gist of the invention, and are also included in the invention described in the claims and the equivalents thereof.

  DESCRIPTION OF SYMBOLS 10 ... Trace component analyzer, 11 ... Light source of monochromatic light, 12 ... Light source of several monochromatic light, 13 ... Light source of continuous light, 14 ... Collimating lens, 15 ... Condensing lens, 16 ... Detector, 17 ... Analysis part , 18 ... spectral part, 21 ... resonator, 21a ... first resonator, 21b ... second resonator, 22 ... optical path length variable part, 23 ... incident ray (ray), 23a ... first monochromatic light, 23b ... first 2 monochromatic light, 23c ... continuous light, 24 ... reflected ray (ray), 25 ... passing ray (ray), 26 ... detection signal, 27 (27a, 27b) ... mirror, 28 (28a, 28b) ... mirror, 30 ... Prism, 31 ... incident surface, 32 ... output surface, 33 ... reflecting surface, 34 ... sample chamber, 35 ... sample, 36 ... filling port, 37 ... pressurizing section, L ... optical path length.

Claims (6)

A light source that outputs light rays;
A prism having an incident surface of the light beam, a reflective surface that reflects the incident light beam, and an output surface that outputs the light beam reflected by the reflective surface;
A resonator that is arranged on the optical axis of the light beam and multi-reflects the light beam across the prism;
A detector that detects the light beam that has passed through the resonator with the multiple reflection;
An analysis unit that analyzes a trace component of the sample based on a detection signal of the detector in a state in which the sample is in contact with the reflecting surface of the prism. In the trace component analyzer of Claim 1,
The light component output from the light source is monochromatic light. In the trace amount analyzer according to claim 2,
The light source outputs a plurality of monochromatic lights,
A plurality of the resonators are arranged, and the single component light corresponding to each of the resonators is selectively multiple-reflected, and the trace component analyzing apparatus is characterized in that In the trace component analyzer of any one of Claims 1-3,
The trace component analyzing apparatus, further comprising: an optical path length varying unit that moves one of the pair of mirrors constituting the resonator to vary the optical path length in which the multiple reflection occurs. In the trace amount analyzer according to claim 4,
The light beam output from the light source is continuous light,
A trace component analyzing apparatus, further comprising a spectroscopic unit that performs a Fourier transform on a detection signal of the detector and derives a wavelength spectrum of a light beam that has passed through the resonator. In the trace component analyzer of any one of Claims 1-5,
The trace component analyzing apparatus according to claim 1, wherein a sample chamber for storing and pressurizing the sample is provided on the reflecting surface of the prism.

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