KR20240041450A - optical diffraction tomographic apparatus based on multiple objective lens - Google Patents

Abstract

The present invention discloses an optical diffraction tomography apparatus. His device includes a light source that generates laser light, a steering optical system that irradiates the laser light to the sample, an imaging optical system that acquires a two-dimensional image of the sample using the laser light, and a three-dimensional tomogram from the two-dimensional image. It includes a tomography image processing unit that acquires an image.

Description

Optical diffraction tomographic apparatus based on multiple objective lens}

The present invention relates to an optical diffraction tomography device, and more specifically, to an optical diffraction tomography device that uses a MEMS mirror-based scan beam and rotates multi-magnification objective lenses to obtain three-dimensional tomography images at various magnifications. It's about the device.

Optical diffraction tomography is a quantitative phase imaging technique that can quantitatively measure phase information of optically transparent samples. The theoretical measurement principle was proposed in the late 1960s and has been experimentally verified since the 1970s. , full-scale applied research in the field of biomedical science has been conducted extensively since the 2000s. X-ray tomography is implemented with a laser. Lasers at various angles of incidence are irradiated onto a specimen, the diffracted light is measured in a holographic manner, and 3D refractive index information is restored from the measured 2D hologram. This is a method that projects the two-dimensional Fourier spectrum of the optical field measured by incident light at various angles into three-dimensional space and performs the inverse Fourier transform to obtain the three-dimensional refractive index distribution of the specimen. Because this technology can quickly measure three-dimensional refractive index distribution without preprocessing, it can be used for physiopathological research or pathological diagnosis to measure biochemical and structural changes in biological samples. However, currently commercialized optical diffraction tomography devices are specialized for imaging and analyzing high-resolution pathophysiology samples, so their range of use is limited.

Therefore, in order to use it in various fields such as identifying material properties as well as high-resolution pathology samples, it is necessary to develop a device that can change the image resolution to suit the measurement environment.

The technical problem to be solved by the present invention is to replace the incident beam steering optical system using an existing spatial light modulator with a laser incident beam steering optical system using a MEMS mirror in an optical diffraction tomographic imaging device, and to use a variety of rotating multi-magnification objective lenses. The purpose is to provide an integrated multi-magnification lens-based optical diffraction tomography technology to obtain 3D tomographic images for various magnifications.

The present invention discloses an optical diffraction tomography apparatus. His device includes a light source that produces laser light; a steering optical system that irradiates the laser light to the sample; an imaging optical system that acquires a two-dimensional image of the sample using the laser light; and a tomography image processing unit that acquires a 3D tomography image from the 2D image. Here, the steering optical system includes a focusing lens that provides the laser light to the sample; And it may include a MEMS mirror provided between the focusing lens and the light source.

According to one example, the steering optical system may further include a first tube lens provided between the focusing lens and the MEMS mirror.

According to one example, it may further include a first mirror between the focusing lens and the tube lens.

According to one example, the imaging optical system includes a plurality of objective lenses opposing the focusing lens of the steering optical system; and a camera on the plurality of objective lenses.

According to one example, the imaging optical system may further include a second tube lens between the plurality of objective lenses and the camera.

According to one example, it may further include a light transmission module provided between the light source and the steering optical system.

According to one example, the light transmission module includes: optical fibers provided between the second tube lens and the light source and between the MEMS mirror and the light source; and an optical coupler connecting the optical fibers to the light source.

According to one example, the light transmission module may further include terminals provided between one of the optical fibers and the second tube lens and between the other one of the optical fibers and the MEMS mirror.

According to one example, it may further include a beam splitter disposed adjacent to one of the terminals and provided between the camera and the second tube lens.

According to one example, the system control unit may further include a system control unit that organically controls the steering optical system and the imaging optical system to obtain a 3D tomographic image of the sample.

As described above, the optical diffraction tomography apparatus according to an embodiment of the present invention can acquire a three-dimensional tomographic image using a steering optical system that provides 360° laser light and an imaging optical system including a plurality of objective lenses. .

1 is a block diagram showing an example of an optical diffraction tomography apparatus according to the concept of the present invention.
FIG. 2 is a diagram showing an example of the steering optical system of FIG. 1.
FIG. 3 is a diagram showing the tomography principle of the tomography image processing unit of FIG. 1.
FIG. 4 is an image showing an example of a 3D tomography image acquired by the tomography image processing unit of FIG. 1.

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the attached drawings. The advantages and features of the present invention and methods for achieving them will become clear by referring to the embodiments described in detail below along with the accompanying drawings. However, the present invention is not limited to the embodiments described herein and may be embodied in different forms. Rather, the embodiments introduced herein are provided to ensure that the disclosed content is thorough and complete and to sufficiently convey the spirit of the present invention to those skilled in the art, and the present invention is defined only by the scope of the claims. The same reference numerals refer to the same elements throughout the specification.

The terms used in this specification are for describing embodiments and are not intended to limit the invention. As used herein, singular forms also include plural forms, unless specifically stated otherwise in the context. As used in the specification, "comprises" and "comprising" means that a referenced component, step, operation and/or element excludes the presence or addition of one or more other components, steps, operations and/or elements. I never do that. Additionally, in the specification laser, code, and two-photon may be understood as optical, bio, and medical terms. Since it is according to a preferred embodiment, reference signs presented according to the order of description are not necessarily limited to that order.

Figure 1 shows an example of an optical diffraction tomography apparatus 100 according to the concept of the present invention.

Referring to FIG. 1, the optical diffraction tomography apparatus 100 of the present invention includes a light source 10, a light transmission module 20, a steering optical system 30, an imaging optical system 40, a tomographic image processing unit 60, and It may include a system control unit 70.

The light source 10 may generate laser light 12. The light source 10 may provide laser light 12 to the light transmission module 20. Laser light 12 may include visible light with a wavelength of about 400 nm to about 700 nm. Alternatively, laser light 12 may include infrared light with a wavelength of about 700 nm to about 3000 nm, although the invention is not limited thereto.

The light transmission module 20 may be provided between the light source 10 and the steering optical system 30. Additionally, the light transmission module 20 may be provided between the light source 10 and the imaging optical system 40. The light transmission module 20 may provide laser light 12 to the steering optical system 30 and the imaging optical system 40. For example, light transmission module 20 may include an optical fiber module. According to one example, the light transmission module 20 may include optical fibers 22, an optical coupler 24, and terminals 26.

Optical fibers 22 may be provided between the optical coupler 24 and the terminals 26. The optical fibers 22 can easily change the path of the laser light 12. Optical fibers 22 may include single-mode optical fiber. Alternatively, the optical fibers 22 may include multimode optical fibers, and the present invention is not limited thereto.

An optical coupler 24 may be provided adjacent to the light source 10. Optical fibers 22 may branch from the optical coupler 24 and connect to terminals 26.

Terminals 26 may be provided adjacent to the steering optics 30 and imaging optics 40 . Terminals 26 may provide laser light 12 to steering optics 30 and imaging optics 40 .

The steering optical system 30 may be provided between the light transmission module 20 and the imaging optical system 40. The steering optical system 30 may provide laser light 12 to the sample 14. The steering optical system 30 can irradiate the laser light 12 to the sample 14 in an omnidirectional direction of about 360°. The steering optical system 30 may include a 4f optical system.

Figure 2 shows an example of the steering optical system 30 of Figure 1.

Referring to FIGS. 1 and 2 , the steering optical system 30 may include a MEMS mirror 32, a first tube lens 34, and a condensing lens (condense lens) 36.

A MEMS mirror 32 may be provided between one of the terminals 26 and the first tube lens 34. The MEMS mirror 32 can rotate the laser light 12 in an omnidirectional direction of about 360° with the sample 14 at its center.

The first tube lens 34 may be provided between the MEMS mirror 32 and the focusing lens 36. The first tube lens 34 may include a convex lens.

The first mirror 38 may be provided between the first tube lens 34 and the focusing lens 36. The first mirror 38 may be provided between the first tube lens 34 and the focusing lens 36. The first mirror 38 can change the path of the laser light 12.

A focusing lens 36 may be provided between the first mirror 38 and the imaging optical system 40. A focusing lens 36 may be provided between the first mirror 38 and the sample 14. The focusing lens 36 can focus the laser light 12 on the sample 14.

The first tube lens 34 and the focusing lens 36 can function as a 4f optical system. The first tube lens 34 and the focusing lens 36 can change the angle and beam size of the laser light 12 incident from the MEMS mirror 32 according to their focal length ratio. Laser light 12 may be scanned onto the sample 14. The scanning area of the laser light 12 may be from about 40 μm ² to about 120 μm ² , and the angle of incidence of the laser light 12 may be from about 3° to about 60°.

Sample 14 may be provided on stage 50 . The stage 50 may rotate the sample 14. The sample 14 may include human cells. The laser light 12 may be provided to the lower part of the sample 14 and pass through and/or penetrate the sample 14. The phase of the laser light 12 may be changed through the sample 14.

The imaging optical system 40 may be provided between the focusing lens 36 and the tomographic image processing unit 60. The imaging optical system 40 can acquire a two-dimensional image of the sample 14 using the laser light 12. According to one example, the imaging optical system 40 may include a plurality of objective lenses 42, a second tube lens 44, and a camera 46.

A plurality of objective lenses 42 may be provided on the sample 14. The plurality of objective lenses 42 can magnify the sample 14 at magnifications of approximately 20 times, approximately 40 times, and approximately 60 times. When an objective lens 42 with a magnification of about 20 is provided on the sample 14, the scanning area of the laser light 12 must be 120 μm ² or more, and when the incident angle of the laser light 12 is 60°, the MEMS mirror ( 32) has a reflection area of about 2.4 mm ² , and the laser light 12 may have an angle of incidence of about 3°.

The second tube lens 44 may be provided between the plurality of objective lenses 42 and the camera 46. The second tube lens 44 may include a convex lens.

A beam splitter 48 may be provided between the second tube lens 44 and the camera 46. The beam splitter 48 can implement a Mach-Zehnder interferometer using interference of the laser light 12. First, the beam splitter 48 may receive the laser light 12 from the light delivery module 20 and provide it to the camera 46. Next, the beam splitter 48 may receive the laser light 12 projected by the sample 14 and the plurality of objective lenses 42 and provide the laser light 12 to the camera 46. Laser light 12 may interfere at beam splitter 48. Laser light 12 may have destructive or constructive interference.

A camera 46 may be provided on the second tube lens 44. The camera 46 may receive the laser light 12 and obtain a two-dimensional image of the sample 14. Camera 46 may include a CMOS or CCD image sensor.

The tomography image processing unit 60 may be connected to the camera 46. The tomography image processing unit 60 can acquire a 3D tomography image using a 2D image. The spectrum of the 2D image can be obtained as a 3D tomographic image by inverse Fourier transform.

The system control unit 70 may be connected to the MEMS mirror 32 of the steering optical system 30. Although not shown, the system control unit 70 may be connected to the plurality of objective lenses 42 and the camera 46 of the imaging optical system 40. The system control unit 70 can organically control the steering optical system 30 and the imaging optical system 40 to obtain a three-dimensional tomographic image (64 in FIG. 4) of the sample 14.

FIG. 3 is a diagram showing the tomography principle of the tomography image processing unit 60 of FIG. 1. Here, the x and y axes are the fault plane where the sample 14 is located, and the k _x and k _y axes are two-dimensional Fourier space coordinates.

'로 가간섭성 평면파(16)를 갖는 레이저 광(12)를 조사하고, 이미징 광학계(40)는 회절파(18)를 획득하고, 단층 영상 처리부(60)는 퓨리에 공간 내의 반원 곡선(도 4의 62)을 획득하고, 상기 반원 곡선(62)을 이용하여 3차원 영상 자료를 획득할 수 있다. 회절파(18)는 시료(14)의 360° 전방위로 측정될 수 있다. 회절파(18)의 퓨리에 스펙트럼은 퓨리에 공간 내에 채워질 수 있다. 단층 영상 처리부(60)는 2차원 퓨리에 스펙트럼을 역 퓨리에 스펙트럼으로 변환하여 시료(14)의 3차원 단층 영상(도 4의 64)을 획득할 수 있다. Referring to FIGS. 1 and 3 , the tomographic image of the sample 14 may be converted into a three-dimensional image according to the Fourier diffraction principle. The steering optical system 30 operates at a specific angle in real space.

' laser light 12 having a coherent plane wave 16 is irradiated, the imaging optical system 40 acquires the diffraction wave 18, and the tomography image processing unit 60 obtains a semicircular curve in the Fourier space (FIG. 4 62) of can be obtained, and three-dimensional image data can be obtained using the semicircular curve 62. Diffracted waves 18 can be measured in 360° omnidirectionality of the sample 14. The Fourier spectrum of the diffracted wave 18 can be filled into Fourier space. The tomography image processing unit 60 may obtain a 3D tomography image (64 in FIG. 4) of the sample 14 by converting the 2D Fourier spectrum into an inverse Fourier spectrum.

FIG. 4 shows an example of a 3D tomography image 64 acquired by the tomography image processor 60 of FIG. 1 .

Referring to Figures 1 and 4, the tomographic image processor 60 fills the diffracted wave 18 with semicircular curves 62 in Fourier space, converts the semicircular curves 62 into an inverse Fourier spectrum, and produces a sample ( 14), a 3D tomographic image 64 can be obtained.

Above, examples of embodiments of the present invention have been described with reference to the attached drawings, but those skilled in the art will understand that the present invention can be implemented in other specific forms without changing its technical idea or essential features. You will understand that it can be done. Therefore, the embodiments and application examples described above should be understood as illustrative in all respects and not restrictive.

Claims (10)

A light source that generates laser light;
a steering optical system that irradiates the laser light to the sample;
an imaging optical system that acquires a two-dimensional image of the sample using the laser light; and
A tomography image processing unit that acquires a 3-dimensional tomography image from the 2-dimensional image,
The steering optics:
a focusing lens that provides the laser light to the sample; and
An optical diffraction tomography device comprising a MEMS mirror provided between the focusing lens and the light source.
According to claim 1,
The steering optical system further includes a first tube lens provided between the focusing lens and the MEMS mirror.
According to claim 1,
An optical diffraction tomography apparatus further comprising a first mirror between the focusing lens and the tube lens.
According to claim 1,
The imaging optics include:
a plurality of objective lenses opposing the focusing lens of the steering optical system; and
An optical diffraction tomography apparatus comprising a camera on the plurality of objective lenses.
According to claim 4,
The imaging optical system further includes a second tube lens between the plurality of objective lenses and the camera.
According to claim 5,
An optical diffraction tomography apparatus further comprising a light transmission module provided between the light source and the steering optical system.
According to claim 6,
The light transmission module:
optical fibers provided between the second tube lens and the light source and between the MEMS mirror and the light source; and
An optical diffraction tomography apparatus comprising an optical coupler connecting the optical fibers to the light source.
According to claim 7,
The light transmission module further includes terminals provided between one of the optical fibers and the second tube lens and between the other one of the optical fibers and the MEMS mirror.
According to claim 8,
An optical diffraction tomography apparatus disposed adjacent to one of the terminals and further comprising a beam splitter provided between the camera and the second tube lens.
According to claim 1,
An optical diffraction tomography apparatus further comprising a system control unit that organically controls the steering optical system and the imaging optical system to obtain a three-dimensional tomographic image of the sample.