CN212340999U - Optical coherence tomography system based on gold nanocages - Google Patents

Optical coherence tomography system based on gold nanocages Download PDF

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CN212340999U
CN212340999U CN202020367945.8U CN202020367945U CN212340999U CN 212340999 U CN212340999 U CN 212340999U CN 202020367945 U CN202020367945 U CN 202020367945U CN 212340999 U CN212340999 U CN 212340999U
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laser
optical fiber
fiber coupler
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钟俊平
岑颖珊
曾亚光
韩定安
谭海曙
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Foshan University
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Abstract

The utility model discloses an optical coherence tomography system based on gold nanometer cage, include: the system comprises a sample for injecting a permeable gold nanocage solution, a light path system, a reference arm light path system, a sample arm light path system, a spectrometer system and a linear array CCD camera optical signal acquisition system; the utility model discloses a sample, light path system, reference arm light path system, sample arm light path system, spectrum appearance system and the linear array CCD camera collection light signal system of infiltration gold nanometer cage solution are injected, have realized the tomography, have successfully restrained the signal in infiltration region, have improved the contrast of gathering the image effectively, easy operation, safety, easy to realize to OCT imaging contrast has been improved effectively; the utility model discloses can be used to the coherent tomography of optics.

Description

Optical coherence tomography system based on gold nanocages
Technical Field
The utility model relates to an optical imaging technical field especially relates to an optical coherence tomography system based on gold nanometer cage.
Background
Optical Coherence Tomography (OCT) is a new three-dimensional tomographic imaging technology developed gradually in the 90 s of the 20 th century, mainly based on the low coherence interference principle to obtain the tomographic capability in the depth direction, and to reconstruct a two-dimensional or three-dimensional image of the internal structure of a transparent sample by scanning, and has been currently applied in the fields of biomedicine and the like. The signal contrast of a high-resolution three-dimensional tomographic image of the inside of a biological tissue obtained by OCT is derived from the spatial variation of the optical reflection (scattering) characteristics of the inside of a sample. Under the condition, the OCT imaging is insufficient, for example, for diagnosing tumor, because the tumor tissue and the surrounding normal tissue have quite similar components, the normal tissue and the abnormal tissue are difficult to distinguish in the OCT imaging image.
At present, methods for improving the contrast ratio of OCT imaging in the market mainly include two major categories, namely, the contrast ratio of imaging is improved by algorithm processing, and the contrast ratio of an acquired original signal is improved by a physical method. Conventional methods, although simple, do not take into account local information and global histogram equalization may also produce some noise over-emphasis. Although the improved method improves the contrast ratio higher than the traditional method, the contrast ratio is still not high. And the algorithm method can only be used for improving two areas with larger information difference acquired through OCT, and is difficult to accurately extract two signal areas and realize contrast improvement when the edge difference of the signal areas of the target area and the non-target area of the original information is not large, even the image is distorted. The images obtained by the physical methods cannot completely improve the signal value of the target area or inhibit the signal value of the non-target area, and the processing process of some physical methods is time-consuming and tedious.
SUMMERY OF THE UTILITY MODEL
The utility model aims at providing an optics coherent chromatography imaging system based on gold nanometer cage to solve one or more technical problem that exist among the prior art, provide a profitable selection or create the condition at least.
The technical scheme adopted for solving the technical problems is as follows: an optical coherence tomography system based on gold nanocages, comprising: the system comprises a sample for injecting a permeable gold nanometer cage solution, a light path system, a reference arm light path system, a sample arm light path system, a spectrometer system and a linear array CCD camera optical signal acquisition system.
The light source system comprises a low-coherence broadband light source and an optical fiber coupler; the low-coherence broadband light source is used for generating a near-infrared laser beam; the optical fiber coupler is used for splitting the near-infrared laser beam generated by the low-coherence broadband light source into two beams of laser.
The reference arm optical path system comprises a convex lens, a single-sided reflector and a stepping motor; a beam of laser split by the optical fiber coupler vertically irradiates the convex lens and the single-sided reflector in sequence and is reflected by the single-sided reflector to form a beam of reversible laser; the stepping motor is respectively connected with the convex lens and the single-sided reflector.
The sample arm optical path system comprises a two-dimensional scanning galvanometer, a focusing lens with 1% reflection, a sample and a sample loading platform; the sample is placed on the sample loading platform; and the other laser beam split by the optical fiber coupler is sequentially emitted into the two-dimensional scanning galvanometer, the focusing lens with 1% reflection and the sample, and is reflected by the sample to form another reversible laser beam.
The optical fiber coupler is also used for forming two beams of reversible laser into interference light.
The spectrometer system comprises a diffraction grating and a double cemented lens.
The linear array CCD camera optical signal acquisition system comprises a linear array CCD camera; and the interference light of the optical fiber coupler is sequentially emitted into the diffraction grating, the double-cemented lens and the linear array CCD camera.
The utility model has the advantages that: the utility model discloses a sample, light path system, reference arm light path system, sample arm light path system, spectrum appearance system and linear array CCD camera collection light signal system of injection infiltration gold nanometer cage solution has realized tomography, has successfully restrained the signal of infiltration region, has improved the contrast of gathering the image effectively, easy operation, safety, easy realization to OCT imaging contrast has been improved effectively.
Additional aspects and advantages of the invention will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the invention.
Drawings
The above and/or additional aspects and advantages of the present invention will become apparent and readily appreciated from the following description of the embodiments, taken in conjunction with the accompanying drawings of which:
fig. 1 is a structural diagram of an optical coherence tomography system based on a gold nanocage provided by the present invention;
fig. 2 is a signal data diagram of a cross section of a sample target region of an optical coherence tomography system based on a gold nanocage provided by the present invention;
FIG. 3 is a signal diagram of the same interference depth of a sample of an optical coherence tomography system based on a gold nanocage provided by the present invention;
fig. 4 is a full depth information map of two different positions of a sample of an optical coherence tomography system based on a gold nanocage.
Detailed Description
Reference will now be made in detail to embodiments of the present invention, examples of which are illustrated in the accompanying drawings, wherein like reference numerals refer to the same or similar elements or elements having the same or similar function throughout. The embodiments described below with reference to the drawings are exemplary only for the purpose of explaining the present invention, and should not be construed as limiting the present invention.
In the description of the present invention, it should be understood that the orientation or positional relationship indicated with respect to the orientation description, such as up, down, front, rear, left, right, etc., is based on the orientation or positional relationship shown in the drawings, and is only for convenience of description and simplification of description, and does not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and thus, should not be construed as limiting the present invention.
In the description of the present invention, a plurality of means are one or more, a plurality of means are two or more, and the terms greater than, less than, exceeding, etc. are understood as not including the number, and the terms greater than, less than, within, etc. are understood as including the number. If the first and second are described for the purpose of distinguishing technical features, they are not to be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated or implicitly indicating the precedence of the technical features indicated.
In the description of the present invention, unless there is an explicit limitation, the words such as setting, installation, connection, etc. should be understood in a broad sense, and those skilled in the art can reasonably determine the specific meanings of the above words in combination with the specific contents of the technical solution.
Referring to fig. 1, an optical coherence tomography system based on gold nanocages includes: the system comprises a sample 8 for injecting a permeable gold nanometer cage solution, a light path system, a reference arm light path system, a sample arm light path system, a spectrometer system and a linear array CCD camera optical signal acquisition system.
The optical path system comprises a low coherence broadband light source 1 and an optical fiber coupler 2, the reference arm optical path system comprises a convex lens 3, a single-sided reflector 4 and a stepping motor 5, the sample arm optical path system comprises a two-dimensional scanning galvanometer 6, a focusing lens 7 with 1% reflection and a sample loading platform 9, and the spectrometer system comprises a diffraction grating 10 and a double-cemented lens 11; the linear array CCD camera light signal acquisition system comprises a linear array CCD camera 12.
The gold nanometer cage is a hollow porous gold nanometer material. The surface of the particles is easily modified by biomolecules and has low toxicity. The hollow structure of the gold nano cage-shaped particle can be used for filling medicines for treating diseases, and the outer layer is modified by corresponding aptamer or antibody and the like, so that the aim of controlling the medicines to treat the diseases can be achieved. As the absorption cross section of the gold nano cage in the near infrared region is about 5 orders of magnitude higher than that of the traditional dye molecule. Therefore, the nano material has the capability of effectively improving the contrast of the OCT image and assisting diagnosis and treatment at the same time.
30 mu L of 25 mu g/ml gold nanocage solution is injected (smeared) to a target area to be scanned of a sample 8, the gold nanocage solution freely permeates for one hour, then the area to be scanned of the sample 8 is placed in a laser scanning range, the gold nanocage material has strong optical extinction property, the absorption and scattering capacity to light in a near infrared area is strong, the surface is easily modified by biomolecules, the gold nanocage can be used as a contrast agent for optical tomography, a large amount of laser energy is absorbed by the gold nanocage, the reflection light intensity of the smeared area is weakened or even disappears, signals are inhibited, the reflection intensity of a target object in an image collected by an OCT system is reduced, and the contrast of the image is improved.
The low coherence broadband light source 1 is used to generate a near infrared laser beam.
OCT obtains the chromatographic capacity in the depth direction based on the principle of low coherence interference, realizes the scanning reconstruction of a two-dimensional or three-dimensional image of the internal structure of biological tissue or transparent material by changing the light propagation direction, and the strength of the signal brightness of the OCT derives from the optical reflection (scattering) characteristic of the internal structure of the biological tissue or the transparent material. In order to present deeper biological tissue structures, OCT systems typically use highly penetrating near-infrared light as the light source.
The optical fiber coupler 2 is used for dividing the near-infrared laser beam generated by the low-coherence broadband light source 1 into two laser beams, and forming interference light by reversible laser of the two laser beams, wherein the splitting ratio is 50: 50. Light splitting prevents laser backflow from damaging the light source.
The optical fiber coupler 2 is also called a splitter, a connector, an adapter, and an optical fiber flange, is an element for realizing optical signal splitting/combining or for extending an optical fiber link, and belongs to the field of optical passive elements. And the optical device realizes the distribution or combination of optical signal power among different optical fibers. The optical fiber is formed by utilizing the mutual exchange of guided wave energy in the adjacent optical fiber core areas of different optical fiber surfaces.
The convex lens 3 is used for vertically receiving a laser beam split by the optical fiber coupler 2 and focusing the laser beam on the single-sided reflector 4, and the B film convex lens 3 is adopted to match with the dispersion parameters of the sample arm.
And the single-sided reflector 4 can reflect the projected light back and is used for reflecting the laser to form reversible laser.
The stepping motor 5 is respectively connected with the convex lens 3 and the single-side reflector 4, and the stepping motor 5 moves to drive the convex lens 3 and the single-side reflector 4 to move, so that the change of the optical path of the laser beam is realized.
The two-dimensional scanning galvanometer 6 is used for receiving another laser beam split by the fiber coupler 2 and changing the direction of the laser beam.
The focusing lens 7 with 1% reflection, namely the focusing lens with 1% reflectivity, is used for receiving the laser after changing the direction and focusing;
the sample loading platform 9 is used for loading the sample 8, and the sample 8 placed on the sample loading platform 9 receives the focused laser and reflects the focused laser to form a reversible laser.
The diffraction grating 10 is for receiving the interference light passing through the fiber coupler 2 and splitting the interference light. The diffraction grating 10 is one type of grating 10. It subjects the amplitude or phase (or both) of the incident light to periodic spatial modulation by a regular structure.
The double cemented lens 11 is used for collimating the split laser light into parallel light.
The line CCD camera 12 is used to receive the laser light focused into parallel light by the double cemented lens 11.
Fig. 2 to 4 show signal data diagrams of the target region of the sample 8, and fig. 2 shows a signal data diagram of a cross section of the target region of the sample 8, because of the characteristic of high infrared spectrum absorption of the gold nanocage, reflected light is extremely low in the region of the sample 8 coated with the gold nanocage solution, and laser cannot enter the tissue of the sample 8. Therefore, the information of the area where the gold nano-cage material solution permeates in the collected image is lower than that of the area where the gold nano-cage material solution does not permeate, the signal of the permeation area is well inhibited, and the contrast of the collected image is greatly improved.
Fig. 3 is a signal diagram of the same interference depth, and it can be seen from the diagram that a fault occurs in a signal at the junction of a penetration region and a non-penetration region, that is, the signal contrast of the penetration region and the non-penetration region is large.
Fig. 4 is a map of the total depth information for two different locations. Where the dotted line is the signal of the non-permeable area and the solid line is the signal of the permeable area. It can be seen that the signal in the non-permeable region decays slowly with depth, and the signal in the permeable region has a higher value only at the surface of sample 8, and immediately thereafter decays in a discontinuous manner and is lower than the signal in the non-permeable region at the same distance from the surface. The contrast ratio of the gold nanocage material solution to OCT imaging is greatly improved.
The optical coherence tomography method based on the gold nanocages is further included, and comprises the following steps:
s100, injecting a permeable gold nanocage solution into a to-be-scanned area of the sample 8, and placing the sample in a system laser scanning range;
specifically, 30 μ L of a 25 μ g/ml gold nanocage solution was injected into a target region to be scanned of the sample 8, left for one hour, and then the region to be scanned of the sample 8 was placed within the laser scanning range.
S200, checking the working state of the OCT system, starting the system to scan and display the sample 8 in real time, and finely adjusting the position of the sample 8 according to the scanning result displayed in real time to enable the OCT system to accurately irradiate the scanning laser on the area to be scanned;
s300, the main process of the OCT system for realizing the tomography of the sample 8 is as follows:
s301, in an optical path system, a low-coherence broadband light source 1 generates a near-infrared laser beam, and the near-infrared laser beam is split into two laser beams through an optical fiber coupler 2 with a splitting ratio of 50: 50;
s302, on a reference arm light path, enabling the optical fiber coupler 2 to vertically inject a beam of split laser into the center of the convex lens 3 and focus the laser on the reflector 4 to form a reversible reference beam which returns to the optical fiber coupler 2 according to an original light path; the stepping motor 5 drives the convex lens 3 and the reflecting mirror 4 to move, and the optical path of the reference beam is changed;
the stepping motor 5 drives the convex lens 3 and the reflector 4 to move, changes the optical path of the reference beam and provides an optical path reference value for the detection optical path system.
S303, on the light path of the sample arm, the optical fiber coupler 2 emits the other beam of split laser into the two-dimensional scanning galvanometer 6, the two-dimensional scanning galvanometer 6 changes the movement direction of the laser to enable the laser to emit into the focusing lens 7 with 1% reflection, the focusing lens 7 with 1% reflection focuses the laser to enable the laser to scan a sample 8 placed on a sample loading table 9, and the laser is reflected by the sample 8 to form another reversible laser which returns to the optical fiber coupler 2 according to the original light path;
the laser is reflected by the sample 8 to form another reversible laser which returns according to the original optical path to provide the optical path sample value for the detection optical path system.
S304, in a spectrometer system, the optical fiber coupler 2 realizes interference of two reflected reversible lasers to generate interference light which enters the grating 10; the grating 10 splits the interference light, and the double cemented lens 11 collimates the split laser into parallel light;
two reflected reversible lasers meet and interfere in the optical fiber coupler 2, interference light enters the grating 10 from the other path to be subjected to multi-slit diffraction, the interference light is split, first-order diffraction fringes after splitting are taken, the split laser is collimated into parallel light by the double-cemented lens 11, and all energy can be guaranteed to be absorbed by the collecting element.
S305, in the optical signal collecting system of the line CCD camera, the light sensing element of the line CCD camera 12 receives the laser light focused into parallel light by the double cemented lens 11.
The parameters of two beams of reversible laser reflected by the reference arm light path and the sample arm light path after the two beams of reversible laser interfere on the optical fiber coupler 2 meet the following conditions:
Figure DEST_PATH_GDA0002806691160000091
Figure DEST_PATH_GDA0002806691160000092
wherein I is the laser intensity after the interference; r1 and r2 are reflection coefficients of the reference arm light path and the sample arm light path respectively; a is the amplitude of laser amplitude; k is the wave vector; Δ z is the optical path difference; n is the total number of the optical path differences from one to different, namely the total number of the CCD of the camera; y is the number of different wavelengths of the interference light; x is 1 to y; i is an imaginary unit;
and S400, calculating and storing the scanning result.
Specifically, a document is created, trigger signal data of the linear array CCD camera 12 is collected, the trigger signal data of the linear array CCD camera 12 is added to the document, meanwhile, the trigger signal data of the linear array CCD camera 12 is processed, background light is subtracted, data without the background light is added into a queue, and the data with the background light is processed again; the data added into the queue is discharged out of the queue and stored into a document; and when the document acquires data with enough frame number, ending the acquisition, calculating the acquired data to obtain contrast, storing the data, and closing the scanning system.
The utility model discloses a sample 8, optical path system, reference arm optical path system, sample arm optical path system, spectrum appearance system and linear array CCD camera collection light signal system of injection infiltration gold nanometer cage solution has realized tomography, has successfully restrained the signal of infiltration region, has improved the contrast of gathering the image effectively, easy operation, safety, realizes easily to OCT formation of image contrast has been improved effectively.
The embodiments of the present invention have been described in detail with reference to the accompanying drawings, but the present invention is not limited to the above embodiments, and various changes can be made without departing from the spirit of the present invention within the knowledge of those skilled in the art.

Claims (1)

1. An optical coherence tomography system based on gold nanocages is characterized in that: the method comprises the following steps:
injecting a sample penetrating the gold nanocage solution;
the light source system comprises a low-coherence broadband light source and an optical fiber coupler; the low-coherence broadband light source is used for generating a near-infrared laser beam; the optical fiber coupler is used for splitting the near-infrared laser beam generated by the low-coherence broadband light source into two beams of laser;
the reference arm optical path system comprises a convex lens, a single-sided reflector and a stepping motor; a beam of laser split by the optical fiber coupler vertically irradiates the convex lens and the single-sided reflector in sequence and is reflected by the single-sided reflector to form a beam of reversible laser; the stepping motor is respectively connected with the convex lens and the single-sided reflector;
the sample arm optical path system comprises a two-dimensional scanning galvanometer, a focusing lens with 1% reflection, a sample and a sample loading platform; the sample is placed on the sample loading platform; another laser beam split by the optical fiber coupler is sequentially emitted into the two-dimensional scanning galvanometer, the focusing lens with 1% reflection and the sample, and is reflected by the sample to form another reversible laser beam;
the optical fiber coupler is also used for forming interference light by the two beams of reversible laser;
the spectrometer system comprises a diffraction grating and a double cemented lens;
the linear array CCD camera optical signal acquisition system comprises a linear array CCD camera; and the interference light of the optical fiber coupler is sequentially emitted into the diffraction grating, the double-cemented lens and the linear array CCD camera.
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