JPH10274623A - Non-invasive biological optical measurement device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a small non-invasive living body capable of detecting information transmitted and diffused in a sample, obtaining information inside the sample, and rapidly scanning a position to obtain information in a depth direction. To provide an optical measurement device. SOLUTION: Light emitted from a low coherence light source 2 is divided by a demultiplexing element 4 into irradiation light applied to a sample 8 and reference light reflected by a mirror 5 having a step. The light (signal light) backscattered by the sample is multiplexed with the reference light by the demultiplexing element 4 and detected by the photodetector 11. Mirror 5
Is rotated by a motor 6. The mirror 5 has twelve sector shapes having a step, and the optical path length of the reference light changes when the reference light is reflected by the thin portion of the mirror 6 and when the reference light is reflected by the thick portion, and the signal light is emitted. The set position can be scanned in the depth direction.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a non-invasive living body optical measuring apparatus, and more particularly to a non-invasive living body optical measuring apparatus adapted to obtain information inside a sample by heterodyne detecting light that has diffused and transmitted through an opaque and thick sample such as a living body. The present invention relates to an invasive biological light measurement device.

[0002]

2. Description of the Related Art A device for obtaining information inside a sample by irradiating a non-uniform sample with light from a superluminescent diode and heterodyne detecting light scattered by the sample and transmitted / diffused in a medium, Optics Letters, 19 (1994) 590-592 (Optics Letters 19 (1994) p.
pp. 590-592), and the 57th Annual Meeting of the Japan Society of Applied Physics, Proceedings, Volume 0 (1996), page 1213. In these techniques, the coherence length is several tens.
The light of the super luminescent diode of μm is split into two by a demultiplexer, and one is irradiated to the sample, and the other is PZT
And then used as reference light for heterodyne detection. By combining the signal light and the reference light reflected from the sample with the multiplexer and performing heterodyne detection, the light path length of the light scattered by the sample until detection is equal to the light path length of the reference light. Only those components are detected. Only a signal of light scattered or reflected at a position at a specific depth from the sample surface is obtained. In the above-described conventional technology, the optical path length of the signal light is scanned by scanning the sample with the xyz stage, and the depth of extracting the signal in the sample is changed.

[0003]

In the above prior art, there is a problem in that scanning in the depth direction takes time because scanning of the optical path length is performed by a horizontally moving stage. Therefore, it has been difficult to apply the method to a sample that requires high-speed measurement due to body motion artifacts such as a living body. Further, since the reciprocating motion is performed in the horizontal direction, it is difficult to reduce the size of the entire apparatus.

An object of the present invention is to provide an apparatus for irradiating a sample with a light source having a short coherence length and performing heterodyne detection of light scattered by the sample to obtain information on a specific depth inside the sample. It is an object of the present invention to provide a configuration which can be operated at a high speed by the above-mentioned device.

[0005]

According to the present invention, in order to achieve the above object, a light source and light emitted from the light source are split, one of the split lights is used as irradiation light, and the other is used as reference light,
By irradiating the sample with the irradiation light, the signal light and the reference light are transmitted and diffused through the sample and multiplexed from the sample, and the multiplexed light is multiplexed by the multiplexing / demultiplexing means. It is characterized by having a light detecting means for heterodyne detecting the combined light, and a means for changing at least one optical path length of the irradiation light, the reference light, and the signal light. Irradiation light, reference light, and the reference light may be reflected by a reflecting member having at least two mirror surfaces that are parallel and not coplanar to change at least one optical path length of the signal light, Alternatively, at least one of the irradiation light and the signal light may be transmitted through a transmission member having a refractive index distribution or a transmission member having a different thickness depending on the position. The light source is a superluminescent diode, a light emitting diode, or a laser diode that emits light having a coherence length of 30 mm or less.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION

(First Embodiment) FIG. 1 shows a configuration diagram of a first embodiment of the present invention. The apparatus of this embodiment includes a light source driving circuit 1, a low coherence light source 2, a lens 3, a splitter 4, a mirror 5 having a step, a motor 6, a motor controller 7, a sample 8, a PZ
T9, xz stage 10, photodetector 11, amplifier 12,
It comprises a lock-in amplifier 13 and a computer 14. In this embodiment, the low coherence light source 2 has a wavelength of 7
A super luminescent diode having a coherence length of 80 nm and a coherence length of 50 μm is used. The low coherence light source 2 is driven by the light source driving circuit 1 at a constant output.
The light emitted from the low coherence light source 2 is converted into a parallel light beam by a lens 3 and then split into two by a demultiplexer 4. One of the lights is irradiation light applied to the sample 8. The other light is reflected by the mirror 5 having a step, and is used as reference light.
The mirror 5 is rotated by the motor 6. A motor control device 7 for driving the motor 6 is controlled by a computer 14. The irradiation light backscattered by the sample 8 is
By using the demultiplexing element 4 as a multiplexer as signal light, the signal light is multiplexed with the reference light reflected by the mirror 5 having a step, and heterodyne detected by the photodetector 11. The sample 8 is attached to the PZT 9, and the PZT 9 is driven by the internal oscillator of the lock-in amplifier 13 to vibrate in the optical axis direction, and the phase of the signal light is modulated at a constant frequency. The output of the photodetector 11 is converted into a voltage signal by the amplifier 12 and then input to the lock-in amplifier 13. The measurement result of the lock-in amplifier 13 is taken in by the computer 14 in synchronization with the rotation of the motor 6. Scanning in the surface direction of the sample 8 is performed by the xz stage 10.

FIG. 2 is a partially enlarged view of FIG. The motor 6 rotates the mirror 5. The mirror 5 has a disk shape, a circle is equally divided into 12 sectors, and a step of 20 μm is provided between each sector. When the reference light is reflected by the thinnest portion of the mirror 5 and when it is reflected by the thickest portion, the optical path length of the reference light is 2 ×
20 × 12 μm = 480 μm. Therefore, the position in the sample for detecting the scattered light (signal light) can be scanned in the depth direction (480 μm / n). n
Is the refractive index of the sample. The positions of the sample 8 and the mirror 5 are set such that, when the reference light is reflected by the thickest portion of the mirror 5, the optical path length of the reference light and the optical path length of the component reflected in the vicinity of the sample surface of the signal light are equal. Is set.

FIG. 3 is a diagram showing the results of measurement using this example using pork as a sample. This is the optical path length dependence of the scattered light detection signal when a predetermined point on the sample 8 is irradiated with light. This result shows the distribution of the refractive index, scattering coefficient, and absorption coefficient in the sample in the depth direction. A strong signal was obtained at a depth of about 200 μm. This result reflects the presence of a streak at a depth of about 150 μm obtained by observing a sample cut after the measurement according to the present embodiment. ing. In this embodiment, the rotation of the mirror is set to 6000 per minute, and scanning in the depth direction can be performed in 10 ms per point. By scanning the sample in the surface direction with the xz stage 10, a three-dimensional tomographic image can be obtained in a short time. By processing an image obtained with a light source having a plurality of wavelengths, the distribution of chemical substances inside a biological sample or the like can be obtained.

(Second Embodiment) FIG. 4 shows a configuration diagram of a second embodiment of the present invention. In this embodiment, basically, the same configuration as that of the first embodiment is used. The main change is that, instead of reflecting the reference light with a stepped mirror, the irradiation light for irradiating the sample 8 and the signal light scattered and reflected from the sample are changed by the optical path length when transmitting the light. That is, the light is transmitted through the rotating transparent plate 16 which is different in some parts. In this embodiment, the mirror 15 that reflects the reference light is vibrated by the PZT 9 to modulate the phase of the reference light.

FIG. 5 is a partially enlarged view of FIG. The transparent rotating plate 16 has a disk shape, and each of the fan-shaped portions divided into 12 equal parts is made of a material having a different refractive index. Disk 16
Has a thickness of 2 mm, and each sector has a refractive index of 1.50
There is a difference of 0.01 in the range of 1.61. Sample 8
Irradiation light and signal light from the sample 8 irradiate the disk 1
6, the optical path length of the signal light changes by 2.times.0.01.times.2 mm = 40 .mu.m depending on the fan shape to be transmitted. In this embodiment, since the reference light is phase-modulated, it can be attached to a living biological sample to perform in vivo measurement. Another effect of the present embodiment is that the accuracy required for the transparent rotating plate 16 is relatively low because the transmission of a flat plate having a refractive index distribution is used instead of the reflection by the mirror with a step, and the processing is difficult. It is easy. Further, in this embodiment, the transparent rotating plate 16 made of a flat disk having a refractive index distribution is used. However, the same effect can be obtained by substituting a transparent plate having the same shape as the stepped mirror 5. Can be

In the above embodiment, a superluminescent diode is used as a low coherence light source. However, a light emitting diode or a surface light emitting diode may be used if light intensity is not so required, or a semiconductor laser may be operated at a threshold current or less. Any light source having a coherence length shorter than the required spatial resolution, such as a transmitted one, a semiconductor laser having an anti-reflection coating on its end face, or a semiconductor laser whose end face has been melted, can be used.

[0012]

According to the present invention, it is possible to scan a position for obtaining information in the depth direction at a high speed with a small device. As a result, the refractive index, absorption coefficient, and scattering coefficient at a predetermined position inside the sample can be obtained at high speed, or the distribution of those values can be imaged in a short time and subjected to image processing, etc. The distribution of substances can be known.

[Brief description of the drawings]

FIG. 1 is a configuration diagram of a first embodiment of the present invention.

FIG. 2 is a partially enlarged view of FIG.

FIG. 3 is a diagram showing a measurement result according to the first embodiment of the present invention.

FIG. 4 is a configuration diagram of a second embodiment of the present invention.

FIG. 5 is a partially enlarged view of FIG. 4;

[Explanation of symbols]

DESCRIPTION OF SYMBOLS 1 ... Light source drive circuit, 2 ... Low coherence light source, 3 ... Lens, 4 ... Demultiplexing element, 5 ... Mirror having a step, 6 ... Motor, 7 ... Motor control device, 8 ... Sample, 9 ... PZT, 1
0 ... xz stage, 11 ... photodetector, 12 ... amplifier, 1
3: Lock-in amplifier, 14: Computer, 15: Mirror, 16: Rotating transparent plate.

Claims (6)

[Claims] 1. A light source, wherein light emitted from the light source is split, one of the split lights is used as irradiation light, and the other is used as reference light,
The irradiating light is transmitted through the sample by irradiating the sample, the signal light emitted from the sample is diffused and multiplexed, and the reference light is multiplexed by the demultiplexing and multiplexing means. Light detection means for heterodyne detection of the multiplexed combined light, and in a non-invasive biological light measurement device having, at least two mirror surfaces that are parallel and not on the same plane,
A reflecting member that reflects the reference light and changes the optical path length of the reference light, and a rotating member that rotates the reflecting member,
A non-invasive living body optical measurement device comprising: 2. A light source, wherein light emitted from the light source is split, one of the split lights is used as irradiation light, and the other is used as reference light,
The irradiating light is transmitted through the sample by irradiating the sample, the signal light emitted from the sample is diffused and multiplexed, and the reference light is multiplexed by the demultiplexing and multiplexing means. Light detection means for heterodyne detection of the multiplexed multiplexed light, and, in a non-invasive biological light measurement device having, by transmitting at least one of the irradiation light and the signal light,
A non-invasive living body light measuring device, comprising: a transmitting member that changes an optical path length of at least one of the irradiation light and the signal light; and a rotating member that rotates the transmitting member. 3. The non-invasive living body optical measurement device according to claim 2, wherein the transmission member has a refractive index distribution. 4. The non-invasive living body light measurement device according to claim 2, wherein the thickness of the transmission member varies depending on the position. 5. The light source according to claim 1, wherein the light source is a superluminescent diode, a light emitting diode, or a laser diode that emits light having a coherence length of 30 mm or less. Non-invasive biological light measurement device. 6. A light source, wherein light emitted from the light source is split, one of the split lights is used as irradiation light, and the other is used as reference light,
The irradiating light is transmitted through the sample by irradiating the sample, the signal light emitted from the sample is diffused and multiplexed, and the reference light is multiplexed by the demultiplexing and multiplexing means. A non-invasive living body optical measurement device having heterodyne detection of the multiplexed multiplexed light, wherein the irradiation light, the reference light, and the signal light have means for periodically changing at least one optical path length. A non-invasive living body optical measurement device, characterized in that: