CN110274708B - Tumor cell nanoscale quantum three-dimensional thermal imaging system - Google Patents
Tumor cell nanoscale quantum three-dimensional thermal imaging system Download PDFInfo
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Abstract
A tumor cell nanoscale quantum three-dimensional thermal imaging system comprises a nanometer positioning platform connected with the output of a controller, a tumor cell sample is placed on the nanometer positioning platform, an excitation light source and a microscope objective are arranged above the sample, the output of the microscope objective is connected with a spectroscope through an optical filter, and light is divided into reflected light and transmitted light by the spectroscope; the reflected light is connected with the input of the spectrometer through the tube mirror, the output of the spectrometer is connected with the first input of the workstation, and the tube mirror and the spectrometer form a quantum temperature measuring light path; the transmission light is connected with the input of the EMCCD detector through the first convex lens, the phase modulation sheet and the second convex lens, the output of the EMCCD detector is connected with the second input of the workstation, the first convex lens, the phase modulation sheet, the second convex lens and the EMCCD detector form a three-dimensional positioning light path, and the output of the workstation is connected with the input of the display; the invention realizes the rapid and lossless real-time detection of the temperature field in the tumor cells, and obtains the three-dimensional temperature field of the tumor cells.
Description
Technical Field
The invention relates to the technical field of biological thermal imaging, in particular to a tumor cell nanoscale quantum three-dimensional thermal imaging system.
Background
The pathological change mechanism research of tumor cells is a hotspot in the biomedical field, and the micro-nano scale heat generation and transmission under the unconventional conditions are directly related to the tumor cell metabolism and pathological changes. Due to the thermal sensitivity of tumor cells, temperature itself is a key factor in pathological research and comprehensive treatment of tumor cells, such as hyperthermia to reduce the metabolism of tumor cells, enhance the killing effect of radiation and improve the chemotherapeutic effect of drugs. Research on the development of therapeutic modalities for tumor cells is also going to be advanced towards the thermal analysis of biomolecules, such as the thermal tolerance of tumor cells associated with Heat Shock Proteins (HSP), and the immune response initiated by the thermal therapy of tumor cells, and the nano-scale thermal imaging means is urgently needed. Therefore, the nano-scale three-dimensional thermal imaging system for tumor cells can become an important hardware basis for tumor cell research to be deeper at a microscopic level and a more precise level.
The quantum dot as a nano fluorescent probe has unique photo-thermal characteristics, and a good mathematical mapping relation can be established between the fluorescent optical parameters and the temperature, so that the quantum dot becomes a nano temperature probe. The quantum dot has the advantages that the quantum dot has good biocompatibility, and various biological molecules such as polypeptide, protein, DNA and the like can be combined with the quantum dot, so that the quantum dot probe can be better marked on the surface of a cell and even on an organelle. Meanwhile, the small size and high fluorescence intensity of the quantum dots also make the quantum dots an excellent probe for optical three-dimensional positioning. The current cell thermal imaging means is mostly limited to the average temperature of a plane, loses axial temperature information and is not beneficial to the temperature field analysis of the biological micro-nano structure of tumor cells.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention aims to provide a tumor cell nanoscale quantum three-dimensional thermal imaging system which can realize the rapid, efficient and lossless real-time detection of the temperature field in the tumor cell and can obtain the three-dimensional temperature field of the tumor cell.
In order to achieve the purpose, the invention adopts the technical scheme that:
a tumor cell nanoscale quantum three-dimensional thermal imaging system comprises a nanometer positioning platform 2, wherein the control input of the nanometer positioning platform 2 is connected with the output of a controller 1, a tumor cell sample 3 is placed on the nanometer positioning platform 2, an excitation light source 4 and a microscope objective 5 are arranged above the tumor cell sample 3, the output of the microscope objective 5 is connected with the input of a spectroscope 7 through an optical filter 6, light is divided into two paths by the spectroscope 7, one path is reflected light, and the other path is transmitted light; the reflected light of the spectroscope 7 is connected with the input of a spectrometer 9 through a tube mirror 8, the output of the spectrometer 9 is connected with the first input of a workstation 14, and the tube mirror 8 and the spectrometer 9 form a quantum temperature measuring light path;
the transmission light of the spectroscope 7 is connected with the input of an EMCCD detector 13 through a first convex lens 10, a phase modulation sheet 11, a second convex lens 12, the output of the EMCCD detector 13 is connected with the second input of a workstation 14, the first convex lens 10, the phase modulation sheet 11, the second convex lens 12 and the EMCCD detector 13 form a three-dimensional positioning light path, and the phase modulation sheet 11 is used for modulating the light path through a specific double-spiral point spread function so as to realize the mapping between the optical signal and the axial displacement of a target quantum point;
an output of the workstation 14 is connected to an input of a display 15.
The excitation light source 4 is an ultraviolet light source, or a mercury lamp, or a laser light source.
The nanometer positioning platform 2 is a piezoelectric XYZ three-dimensional nanometer positioning platform or a piezoelectric Z-direction one-dimensional nanometer positioning platform.
The controller 1, the nanometer positioning platform 2, the excitation light source 4, the microscope objective 5, the optical filter 6, the spectroscope 7, the tube lens 8, the spectrometer 9, the first convex lens 10, the phase modulation sheet 11, the second convex lens 12, the EMCCD detector 13, the workstation 14 and the display 15 are placed on the vibration isolation platform 16.
The tumor cell sample 3 is labeled by quantum dots with biomolecular ligands in advance.
The invention has the beneficial effects that:
according to the tumor cell nanoscale quantum three-dimensional thermal imaging system, quantum dots are used as target probes, the tumor cells marked by the quantum dots are used as thermal imaging objects, the special photo-thermal characteristics of the quantum dots are utilized, the high-nanoscale three-dimensional thermal imaging requirements of the tumor cells are met, the temperature field in the tumor cells can be rapidly, efficiently and nondestructively detected in real time, and effective technical support is provided for revealing the metabolic process and pathological change mechanism of the tumor cells.
Drawings
Fig. 1 is a schematic structural view of the present invention.
Detailed Description
The invention is described in detail below with reference to the figures and examples.
As shown in fig. 1, a tumor cell nanoscale quantum three-dimensional thermal imaging system comprises a nanometer positioning platform 2, wherein the control input of the nanometer positioning platform 2 is connected with the output of a controller 1, the controller 1 realizes the control of the motion process of the nanometer positioning platform 2 by programming an input instruction in advance, a tumor cell sample 3 is placed on the nanometer positioning platform 2, the nanometer positioning platform 2 is used for carrying out axial nanoscale movement on the tumor cell sample 3, further layered thermal imaging on the tumor cell sample 3 is realized, an excitation light source 4 and a microscope objective lens 5 are arranged above the tumor cell sample 3, the output of the microscope objective lens 5 is connected with the input of a spectroscope 7 through an optical filter 6, light is divided into two paths by the spectroscope 7, one path is reflected light, and the other path is transmitted light; the reflected light of the spectroscope 7 is connected with the input of a spectrometer 9 through a tube mirror 8, the output of the spectrometer 9 is connected with the first input of a workstation 14, and the tube mirror 8 and the spectrometer 9 form a quantum temperature measuring light path;
the transmission light of the spectroscope 7 is connected with the input of an EMCCD detector 13 through a first convex lens 10, a phase modulation sheet 11, a second convex lens 12, the output of the EMCCD detector 13 is connected with the second input of a workstation 14, the first convex lens 10, the phase modulation sheet 11, the second convex lens 12 and the EMCCD detector 13 form a three-dimensional positioning light path, the phase modulation sheet 11 is used for modulating the light path through a specific double-spiral point spread function so as to realize the mapping between the optical signal and the axial displacement of the target quantum point, and the convex lens is mainly used for collecting light rays;
the output of the workstation 14 is connected with the input of the display 15, and the workstation 14 realizes the conversion of the optical signal data with the temperature and the three-dimensional coordinate values, and processes and analyzes the data so as to obtain the three-dimensional temperature field of the tumor cells.
The excitation light source 4 is an ultraviolet light source, or a mercury lamp, or a laser light source.
The nanometer positioning platform 2 is a piezoelectric XYZ three-dimensional nanometer positioning platform or a piezoelectric Z-direction one-dimensional nanometer positioning platform.
The controller 1, the nanometer positioning platform 2, the excitation light source 4, the microscope objective 5, the optical filter 6, the spectroscope 7, the tube lens 8, the spectrometer 9, the first convex lens 10, the phase modulation sheet 11, the second convex lens 12, the EMCCD detector 13, the workstation 14 and the display 15 are placed on the vibration isolation platform 16 to prevent the influence caused by the vibration of the surrounding environment.
The tumor cell sample 3 is labeled by quantum dots with biomolecular ligands in advance, because the quantum dots have better biocompatibility.
The working principle of the invention is as follows:
the invention is provided based on the cell marking function of quantum dots and the principle of quantum photo-thermal characteristics, because for tumor cells, the internal nanoscale thermal characteristics and temperature field distribution information of the tumor cells can provide theoretical basis for the pathological change mechanism of the tumor cells, and the invention is helpful for disclosing the cytopathic process and researching the treatment method of temperature control. The quantum dots are used as probes, have excellent fluorescence performance and unique photo-thermal characteristics, and meanwhile, the quantum dots can have good biocompatibility through modification of biomolecules, so that intracellular labeling can be realized conveniently.
Firstly, tumor cells marked by quantum dots are taken as experimental samples, the tumor cells need to be marked by the quantum dots with biomolecular ligands before imaging, and necessary sample preparation processes are carried out.
The tumor cell sample 3 is placed at a proper position in the center of the nanometer positioning platform 2 to ensure that excitation light can irradiate the sample, then the excitation light source 4 is opened to excite quantum dots in the tumor cell sample 3, and the nanometer positioning platform 2 is adjusted to enable the target and the microscope objective 5 to finish focusing so as to obtain a clear imaging picture. The method comprises the following steps that quantum dots in a tumor cell sample 3 emit fluorescence under the irradiation of exciting light, the fluorescence is emitted after the exciting light and stray light are removed through a microscope objective 5 in an amplification imaging mode, a light ray is divided into two paths through a spectroscope 7, a reflection light path enters a quantum temperature measuring light path, the fluorescence light rays are collected through a tube lens 8 and enter a spectrometer 9 by utilizing the special photo-thermal performance of the quantum dots, an optical signal is converted into a spectral curve through the spectrometer 9, the temperature value of the quantum dots can be further obtained through the known mathematical mapping relation between the temperature of the quantum dots and spectral parameters, and the temperature value is used as the local temperature of the positions where the quantum dots are located in; the transmission light path enters a three-dimensional positioning light path, the high fluorescence intensity and the nanometer size of the quantum dots are utilized, the fluorescence light is converted into point light from parallel light through a first convex lens, then the point light is modulated by a phase modulation sheet 11 to become double-spiral light beams, the rotation angle of the double light spots obtained through imaging and the axial displacement of a target form a mathematical mapping relation, the modulated light is converged through a second convex lens 12 and then enters an EMCCD detector 13 to generate a double-light-spot map, the plane coordinate value of the quantum dots can be obtained through measuring the central position of the double light spots, and then the three-dimensional coordinate value of the quantum dots can be finally formed.
Because the information in the cell thickness direction which can be acquired in each imaging is limited, once the measuring plane is too far away from the focal plane, the imaging plane becomes fuzzy, so that the controller 1 is input with a program instruction to control the movement of the nanometer positioning platform 2 and further control the displacement of the cell sample on the nanometer positioning platform, thereby acquiring the three-dimensional temperature information of a plurality of planes of cells. The data of the spectrometer 9 and the EMCCD detector 13 are transmitted to the workstation 14 through a data interface and a data line, and the display 15 is matched with the workstation 14 to complete the processing and analysis of the data, and finally obtain the three-dimensional temperature field of the tumor cells.
Claims (4)
1. A tumor cell nanoscale quantum three-dimensional thermal imaging system comprises a nanometer positioning platform (2), and is characterized in that: the control input of the nanometer positioning platform (2) is connected with the output of the controller (1), a tumor cell sample (3) is placed on the nanometer positioning platform (2), an excitation light source (4) and a microscope objective (5) are arranged above the tumor cell sample (3), the output of the microscope objective (5) is connected with the input of the spectroscope (7) through an optical filter (6), light is divided into two paths by the spectroscope (7), one path is reflected light, and the other path is transmitted light; the reflected light of the spectroscope (7) is connected with the input of the spectrometer (9) through the tube mirror (8), the output of the spectrometer (9) is connected with the first input of the workstation (14), and the tube mirror (8) and the spectrometer (9) form a quantum temperature measuring light path;
the transmission light of the spectroscope (7) is connected with the input of an EMCCD detector (13) through a first convex lens (10), a phase modulation sheet (11) and a second convex lens (12), the output of the EMCCD detector (13) is connected with the second input of a workstation (14), the first convex lens (10), the phase modulation sheet (11), the second convex lens (12) and the EMCCD detector (13) form a three-dimensional positioning light path, and the phase modulation sheet (11) is used for modulating the light path through a specific double-spiral point spread function so as to realize mapping between an optical signal and the axial displacement of a target quantum point;
the output of the workstation (14) is connected with the input of the display (15);
the tumor cell sample (3) is labeled by quantum dots with biomolecular ligands in advance.
2. The tumor cell nanoscale quantum three-dimensional thermal imaging system according to claim 1, wherein: the excitation light source (4) is an ultraviolet light source, or a mercury lamp, or a laser light source.
3. The tumor cell nanoscale quantum three-dimensional thermal imaging system according to claim 1, wherein: the nanometer positioning platform (2) is a piezoelectric XYZ three-dimensional nanometer positioning platform or a piezoelectric Z-direction one-dimensional nanometer positioning platform.
4. The tumor cell nanoscale quantum three-dimensional thermal imaging system according to claim 1, wherein: the device comprises a controller (1), a nanometer positioning platform (2), an excitation light source (4), a microscope objective (5), an optical filter (6), a spectroscope (7), a tube lens (8), a spectrometer (9), a first convex lens (10), a phase modulation sheet (11), a second convex lens (12), an EMCCD detector (13), a workstation (14) and a display (15), which are arranged on a vibration isolation platform (16).
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