JP2007079278A - Material state measuring device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To accurately measure a substance state at a plurality of depths with a high frequency.
SOLUTION: A disc-shaped scanning disk 32 in which ten adjustment glasses 34a to 34j having different thicknesses are arranged in an annular shape is arranged between a microchannel 12 and an objective lens 22, and the scanning disk 32 is rotated. When the adjustment glasses 34 a to 34 j are aligned with the objective lens 22 in a state where the motor 38 is provided and the scanning disk 32 is rotated at a high speed, images are taken by the camera 28 in synchronization. Since the thicknesses of the adjustment glasses 34a to 34j are different, it is possible to photograph the state of the substance in the microchannel 12 by changing the focal position with a high frequency in the thickness direction of the microchannel 12. As a result, the state of the substance in the thickness direction of the microchannel 12 can be accurately measured with a high frequency.
[Selection] Figure 1

Description

  The present invention relates to a substance state measuring apparatus, and more particularly to a substance state measuring apparatus that measures a state of a substance having a predetermined thickness or less.

Conventionally, as this kind of substance state measuring apparatus, a three-dimensional confocal laser microscope system including an actuator that moves an objective lens in the optical axis direction has been proposed (for example, see Patent Document 1). In this system, the scanning waveform for driving the actuator that scans the focal length of the objective lens is a triangular or stepped waveform, thereby suppressing vibration during scanning.
JP-A-2005-37690

  However, since the three-dimensional confocal laser microscope system described above involves movement of the objective lens in the optical axis direction, if the scanning speed (scanning frequency) is increased, vibration occurs even if the scanning waveform is adjusted, and the scanning frequency is increased. Can not do it.

  One object of the substance state measurement apparatus of the present invention is to measure substance states at a plurality of depths at a high frequency. Another object of the substance state measuring apparatus of the present invention is to accurately measure the state of an extremely thin substance.

  The substance state measuring apparatus of the present invention employs the following means in order to achieve at least a part of the above object.

The substance state measuring apparatus of the present invention is
A substance state measuring device for measuring the state of a substance having a predetermined thickness or less,
An objective lens disposed at a predetermined distance from the substance;
An imaging optical system for forming an image from the objective lens;
A focal length adjusting means for adjusting the focal length so that the focal length becomes a plurality of depths within the predetermined thickness with a period of a predetermined frequency or more without moving the objective lens in the optical axis direction;
It is a summary to provide.

  In the substance state measuring apparatus of the present invention, the focal length is adjusted so that the focal length becomes a plurality of depths within a predetermined thickness with a period of a predetermined frequency or more without moving the objective lens in the optical axis direction. By providing the distance adjusting means, the state of the substance at a plurality of depths can be measured with a period of a predetermined frequency or more.

  Here, as the “substance state”, any one of a substance flow velocity, substance concentration, substance temperature, substance shape, substance relative position, and substance distance can be measured. As the “predetermined thickness”, for example, 1 mm, 500 μm, 100 μm, 50 μm, 10 μm, etc. can be used. In this case, the state of an extremely thin substance can be measured with high accuracy. Further, as the “predetermined frequency”, a frequency of 10 Hz or more, for example, 10 Hz, 20 Hz, 30 Hz, 50 Hz, 100 Hz, 1000 Hz, or the like can be used. By increasing the frequency in this way, it is possible to accurately measure the state of the substance that changes with time.

  In such a substance state measuring device of the present invention, the focal length adjusting means includes a plurality of adjusting members formed as a plurality of thicknesses of a light-transmitting material having a refractive index different from that of air at a cycle of the predetermined frequency or more. It may be a means for adjusting the focal length by being arranged on the optical axis of the objective lens. In this case, the focal length adjusting means includes an adjustment disk in which the plurality of adjustment members are arranged in an annular shape on a disk-shaped disk, and a rotation for rotating the adjustment disk at a period equal to or higher than the predetermined frequency. It can also be a means having a means. In this way, the frequency can be set to the rotation frequency, and the frequency can be increased. Further, in this case, the focal length adjusting means may be a means having a pair of lenses above and below the adjusting disk on the optical axis of the objective lens. If it carries out like this, a focal distance can be adjusted by making parallel light into non-parallel light in the part of parallel light.

  In the substance state measuring apparatus of the present invention, the focal length adjusting means may be disposed between the objective lens and the substance. Further, the focal length adjusting means may be arranged between the objective lens and the imaging optical system.

  Furthermore, the substance state measuring apparatus of the present invention may be provided with a confocal scanner for reducing the depth of focus on the optical axis of the objective lens. In this way, the state of an extremely thin substance can be measured with higher accuracy.

  Next, the best mode for carrying out the present invention will be described using examples.

  FIG. 1 is a configuration diagram showing an outline of a configuration of a three-dimensional microscope system 20 which is a substance state measuring apparatus as an embodiment of the present invention. As shown in the figure, the three-dimensional microscope system 20 of the embodiment is a device that three-dimensionally measures the flow velocity of the substance flowing in the microchannel 12 having a layer thickness of 1 mm or less mounted on the mounting table 10. The objective lens 22 and the imaging optical system 24 included in a normal microscope system, a high-performance camera 28 for photographing, and the objective lens 22 disposed between the objective lens 22 and the microchannel 12 are configured. A focal length adjustment mechanism 30 that adjusts the focal length without movement in the optical axis direction, and a computer 40 that controls photographing by the camera 28 and adjustment of the focal length by the focal length adjustment mechanism 30 are provided. Here, since the objective lens 22, the imaging optical system 24, the camera 28, and the computer 40 included in a normal microscope system are well known, detailed description thereof will be omitted.

  As shown in FIG. 2, the focal length adjustment mechanism 30 includes a disk-shaped scanning disk 32 in which ten adjustment glasses 34a to 34j formed of glass having a refractive index different from that of air are arranged in an annular shape, And a motor 38 for rotating the scanning disk 32. The ten adjustment glasses 34a to 34j are formed as disk-shaped flat glass whose thickness increases in order so as to increase from 1 mm to 0.1 mm. The motor 38 is composed of, for example, a stepping motor, and rotates the scanning disk 32 at a desired number of rotations, for example, about 100 rpm to 20,000 rpm.

  FIG. 3 is an explanatory diagram illustrating an example of the relationship between the adjustment glasses 34 a and 34 f having different thicknesses and the focal position in the three-dimensional microscope system 20. As shown in the drawing, since the thickness Da of the adjustment glass 34a is thinner than the thickness Df of the adjustment glass 34f, the focal position when the thin adjustment glass 34a is used is shallower than when the thick adjustment glass 34f is used. When this is considered with respect to ten adjustment glasses 34a to 34j having different thicknesses, it can be understood that ten substances at different focal positions can be measured by the three-dimensional microscope system 20 of the embodiment.

  Now, the scanning disk 32 in which the adjustment glasses 34a to 34j adjusted so that the focal position is changed every 44 μm in the thickness direction of the micro flow path 12 having a thickness of 0.3 mm is rotated at 6,000 rpm. Consider a case in which the camera 28 is controlled so as to capture images in synchronization with the timing when the adjustment glasses 34 a to 34 j are aligned with the objective lens 22. In this case, the substance in the microchannel 12 can be photographed at a depth of 44 μm at a frequency of 100 Hz in the thickness direction of the microchannel 12. By performing such imaging by scanning in the horizontal direction in FIG. 1 or in the front and back direction of the paper, the substance in the microchannel 12 can be imaged as a three-dimensional image. The measurement results of the three-dimensional flow velocity of the substance in the microchannel 12 are shown in FIGS. In the figure, “x” indicates the position of the microchannel 12 in the front and back direction of the paper surface in FIG. 1, “y” indicates the position of the microchannel 12 in the left-right direction in FIG. 1, and “z” indicates the microflow path. The position of the path 12 in the vertical direction (thickness direction) in FIG. 1 is shown, and “U” means the flow velocity.

  Here, as a measurement target, for example, if the microparticles with an index color are mixed and flowed in the microchannel 12 and the presence of the microparticle is measured, the tertiary of the substance in the microchannel 12 is measured. The original flow rate can be measured, and the three-dimensional temperature of the substance in the microchannel 12 can be measured by mixing and measuring fine particles that develop color in response to the temperature. Similarly, the three-dimensional concentration of the substance in the microchannel 12 can be measured. As described above, the measurement target can increase the flow rate, temperature, concentration, etc. of the substance, and can visualize any substance, such as a cell, three-dimensionally as long as the substance is in the microchannel 12. Can do.

  According to the three-dimensional microscope system 20 of the embodiment described above, the disk-shaped scanning disk 32 in which the adjustment glasses 34 a to 34 j having different thicknesses are arranged in an annular shape is rotated, and the adjustment glasses 34 a to 34 j are the objective lens 22. By photographing with the camera 28 in synchronism with the position matched with, the state of the substance in the thickness direction of the microchannel 12 can be accurately measured with a high frequency. In addition, since the objective lens 22 is not moved in the direction of the optical axis only by rotating the scanning disk 32, even if the scanning frequency (the number of rotations of the scanning disk 32) is increased, the measurement accuracy does not decrease due to vibration.

  FIG. 6 is a block diagram showing an outline of the configuration of a three-dimensional microscope system 20B which is a substance state measuring apparatus as a second embodiment of the present invention. As shown in the figure, the three-dimensional microscope system 20B of the second embodiment includes a focal length adjusting mechanism 30B disposed between the objective lens 22 and the imaging optical system 24, an imaging optical system 24, and a camera. The configuration is the same as that of the three-dimensional microscope system 20 of the first embodiment except that a confocal scanner 26 for reducing the focal length is provided between the three-dimensional microscope system 20 and the first embodiment. Since the confocal scanner 26 is a well-known scanner, detailed description thereof is omitted.

  The focal length adjustment mechanism 30B has the same configuration as the focal length adjustment mechanism 30 of the first embodiment, that is, a disc-shaped scanning disk 32 in which ten adjustment glasses 34a to 34j are arranged in an annular shape, and this scanning. In addition to a motor 38 for rotating the disk 32, a concave lens 36 a is disposed between the scanning disk 32 and the imaging optical system 24 to convert parallel light into non-parallel light, and the scanning disk 32 and the objective lens 22. And a convex lens 36 b for collecting non-parallel light to the objective lens 22.

  FIG. 7 is an explanatory diagram showing an example of the relationship between the adjustment glasses 34a and 34f having different thicknesses and the focal position in the three-dimensional microscope system 20B. As shown in the figure, the concave lens 36a causes the parallel light to be made non-parallel light and enter the adjusting glasses 34a and 34f having different thicknesses. As in the first embodiment, the thickness Da of the adjustment glass 34a is thinner than the thickness Df of the adjustment glass 34f. Therefore, the thick adjustment glass 34f is used as the focal point when the thin adjustment glass 34a is used for non-parallel light. It becomes shallower than usual. If this is considered with respect to ten adjustment glasses 34a to 34j having different thicknesses, it can be understood that ten substances at different focal positions can be measured by the three-dimensional microscope system 20B of the second embodiment.

  Even in the three-dimensional microscope system 20B of the second embodiment described above, the disk-shaped scanning disk 32 in which the adjustment glasses 34a to 34j having different thicknesses are arranged in an annular shape is rotated, and the adjustment glasses 34a to 34j become the objective lens 22. By photographing with the camera 28 in synchronization with the matching position, the state of the substance in the thickness direction of the microchannel 12 can be accurately measured with a high frequency. In addition, since the focal length adjustment mechanism 30B is disposed between the imaging optical system 24 and the objective lens 22, the objective lens 22 having a large numerical aperture (NA) can be used. As a result, the resolution can be improved and the depth of focus can be reduced. Further, since the confocal scanner 26 is used, the depth of focus can be further reduced. As a result, the state of the substance in the thinner microchannel 12 can be measured with high resolution.

  In the three-dimensional microscope system 20B of the second embodiment, a concave lens 36a that is arranged between the scanning disk 32 and the imaging optical system 24 to make parallel light non-parallel light, the scanning disk 32, the objective lens 22, and the like. A pair of lenses with a convex lens 36b for collecting non-parallel light to the objective lens 22 is provided between the lens and the lens. However, in addition to the pair of lenses, one or more lenses are further provided. It does not matter.

  In the three-dimensional microscope system 20B of the second embodiment, the confocal scanner 26 is provided. However, the confocal scanner 26 may not be provided. On the other hand, in the three-dimensional microscope system 20 of the first embodiment, the confocal scanner 26 is not provided, but the confocal scanner 26 may be provided.

  In the three-dimensional microscope system 20 of the first embodiment and the three-dimensional microscope system 20B of the second embodiment, the ten adjustment glasses 34a to 34j are arranged in an annular shape on the scanning disk 32, but are arranged in an annular shape. The number of adjusting glasses to be used is not limited to ten, and may be any number.

  In the three-dimensional microscope system 20 of the first embodiment and the three-dimensional microscope system 20B of the second embodiment, the adjustment glasses 34a to 34j are formed of glass, but any material having a refractive index different from that of air can be adjusted. Glass 34a-34j may be formed.

  In the three-dimensional microscope system 20 of the first embodiment and the three-dimensional microscope system 20B of the second embodiment, the thickness of the microchannel 12 is 0.3 mm, but the thickness of the microchannel 12 is limited to 0.3 mm. It does not matter, and various thicknesses such as 1 mm, 500 μm, 100 μm, 50 μm, and 10 μm may be used.

  In the three-dimensional microscope system 20 of the first embodiment and the three-dimensional microscope system 20B of the second embodiment, the scanning disk 32 is rotated at a rotational speed of about 100 rpm to 20,000 rpm. Any number can be used. For example, the scanning disk 32 may be rotated so that the frequency is 10 Hz, 20 Hz, 30 Hz, 50 Hz, 100 Hz, 1000 Hz, or the like.

  In the three-dimensional microscope system 20 of the first embodiment and the three-dimensional microscope system 20B of the second embodiment, the microchannel 12 is rotated by rotating the scanning disk 32 in which ten adjustment glasses 34a to 34j are arranged in an annular shape. The state of the substance in the thickness direction is measured at a high frequency, but any material can be used as long as the focal length can be changed without moving the objective lens 22 in the optical axis direction. Absent.

  In the three-dimensional microscope system 20 of the first embodiment and the three-dimensional microscope system 20B of the second embodiment, the flow rate of the substance flowing in the microchannel 12 having a layer thickness of 1 mm or less is measured in three dimensions. In addition to the flow rate of the substance, the concentration of the substance and the temperature of the substance in the microchannel 12 having a layer thickness of 1 mm or less may be measured in three dimensions. Moreover, instead of the substance flowing in such a microchannel, the state of various substances such as the shape of the substance placed on the slide glass, the relative position of the substance, and the distance between the substances may be measured in three dimensions. .

  The best mode for carrying out the present invention has been described with reference to the embodiments. However, the present invention is not limited to these embodiments, and various modifications can be made without departing from the gist of the present invention. Of course, it can be implemented in the form.

  The present invention is applicable to manufacturing industries such as a microscope system and a substance state measuring device.

It is a block diagram which shows the outline of a structure of the three-dimensional microscope system 20 which is a substance state measuring apparatus as one Example of this invention. 3 is a configuration diagram illustrating an example of a configuration of a scanning disk 32. FIG. It is explanatory drawing which shows an example of the relationship between the adjustment glass 34a and 34f from which thickness differs, and the focus position in the three-dimensional microscope system 20. It is explanatory drawing which shows an example of the measurement result of the three-dimensional flow velocity of the substance in the microchannel 12. It is explanatory drawing which shows an example of the measurement result of the three-dimensional flow velocity of the substance in the microchannel 12. It is a block diagram which shows the outline of a structure of the three-dimensional microscope system 20B which is a substance state measuring apparatus as 2nd Example of this invention. It is explanatory drawing which shows an example of the relationship between the adjustment glass 34a and 34f from which thickness differs, and the focus position in the three-dimensional microscope system 20B.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 Mounting stand, 12 Micro flow path, 20, 20B Three-dimensional microscope system, 22 Objective lens, 24 Imaging optical system, 26 Confocal scanner, 28 Camera, 30, 30b Focal length adjustment mechanism, 32 Scanning disk, 34a-34j Adjustment glass, 36a concave lens, 36b convex lens, 38 motor, 40 computer.

Claims (10)

A substance state measuring device for measuring the state of a substance having a predetermined thickness or less,
An objective lens disposed at a predetermined distance from the substance;
An imaging optical system for forming an image from the objective lens;
A focal length adjusting means for adjusting the focal length so that the focal length becomes a plurality of depths within the predetermined thickness with a period of a predetermined frequency or more without moving the objective lens in the optical axis direction;
A substance state measuring device.   The focal length adjusting means arranges a plurality of adjusting members formed as a plurality of thicknesses of a light-transmitting material having a refractive index different from that of air on the optical axis of the objective lens at a period equal to or higher than the predetermined frequency. 2. The substance state measuring apparatus according to claim 1, wherein said substance state measuring device is means for adjusting said focal length.   The focal length adjustment means includes an adjustment disk in which the plurality of adjustment members are arranged in an annular shape on a disk-shaped disk, and a rotation means that rotates the adjustment disk at a cycle that is equal to or higher than the predetermined frequency. The substance state measuring apparatus according to claim 2, wherein the substance state measuring apparatus comprises:   4. The substance state measuring device according to claim 3, wherein the focal length adjusting means is a means having a pair of lenses above and below the adjusting disk on the optical axis of the objective lens.   The substance state measuring apparatus according to claim 1, wherein the focal length adjusting unit is disposed between the objective lens and the substance.   5. The substance state measuring apparatus according to claim 1, wherein the focal length adjusting means is disposed between the objective lens and the imaging optical system.   The substance state measurement according to any one of claims 1 to 6, wherein any one of a substance flow rate, substance concentration, substance temperature, substance shape, substance relative position, and substance distance is measured as the substance state. apparatus.   The substance state measuring apparatus according to claim 1, wherein the predetermined thickness is 1 mm or less.   The substance state measuring apparatus according to claim 1, wherein the predetermined frequency is a frequency of 10 Hz or more. The substance state measurement apparatus according to claim 1, further comprising a confocal scanner that reduces a depth of focus on an optical axis of the objective lens.

Images