Rapid lung cancer detection system based on femtosecond laser and Raman spectrum analysis

Abstract

The invention discloses a rapid lung cancer detection system based on femtosecond laser and Raman spectrum analysis, which relates to the technical field of spectrum diagnosis equipment and comprises a substrate manufacturing module, a sample loading module and a detection module, the substrate manufacturing module comprises a femtosecond laser, a half-wave plate, a Glan-Taylor prism, a filter, a shutter, a light source, a monitor, a lens, a beam splitter, a dichroic mirror, a microscope objective and a metal substrate, and the substrate manufacturing module is used for manufacturing a nano microstructure for the metal substrate under the femtosecond laser. According to the metal substrate disclosed by the invention, a super-hydrophobic micro-nano structure is constructed on the metal surface in one step by femtosecond laser, the metal substrate has the capabilities of SERS enhancement and instant enrichment of body fluid molecules, and detection integration is realized; the method is non-invasive in the whole process, high in sensitivity, high in specificity, low in cost and capable of entering a bedside or an operation in a portable mode, and a novel in-situ, non-invasive and low-cost second-level judgment tool is provided for early screening, curative effect monitoring and incisal margin evaluation of high-risk groups.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of spectral diagnosis equipment, in particular to a lung cancer rapid detection system based on femtosecond laser and Raman spectrum analysis. BACKGROUND

[0002] Small cell lung cancer (SCLC) progresses fast and is easy to metastasize, and a bedside detection technology that can realize "second-level" discrimination before biopsy is urgently needed in clinical practice; existing serum markers, imaging and electron microscopy biopsy have bottlenecks such as low sensitivity, long cycle and high false negative rate, and conventional SERS substrates are difficult to be directly used for trace exhaled air or pleural effusion samples due to droplet spreading and poor signal repeatability. Femtosecond laser can construct super-hydrophobic micro-nano structures on the metal surface in one step, which can instantly capture and enrich target molecules, significantly improve the Raman enhancement factor, and realize the collection of SERS fingerprints at the level of body fluid and single cell; combined with a portable Raman probe, specific waveform discrimination of SCLC can be quickly completed, with high sensitivity and strong specificity, providing an in-situ, non-invasive and low-cost new path for early screening of high-risk groups and rapid evaluation of intraoperative margins.

[0003] Femtosecond laser is a kind of ultrashort pulse laser with extremely high spatial resolution and extremely small heat affected zone, which is widely used in micro-nano processing. The microstructure manufactured on the metal surface can be used to enhance the Raman signal (i.e. surface enhanced Raman scattering, SERS) and improve the detection sensitivity. Raman spectrum is a non-invasive and label-free spectral analysis technology that can reflect the molecular structure information of the tissue. There is a significant difference in Raman spectral characteristics between cancerous lung tissue and normal lung tissue, which has the potential for rapid, non-invasive and molecular-level diagnosis. SUMMARY

[0004] To achieve the above object, the present application provides the following technical scheme: a lung cancer rapid detection system based on femtosecond laser and Raman spectrum analysis, comprising a substrate manufacturing module, a sample loading module and a detection module. The substrate manufacturing module comprises a femtosecond laser, a half-wave plate, a Gartler prism, a filter, a shutter, a light source, a monitor, a lens, a beam splitter, a dichroic mirror, a microscope objective and a metal substrate. The substrate manufacturing module is used to make nano microstructure on the metal substrate under the femtosecond laser. The sample loading module comprises a conveying table, a motor and a sample dropper. The detection module comprises a microscope, a light mirror assembly, a laser and a grating light source module. The light mirror assembly is used to superimpose the light paths of the laser and the grating light source module and then irradiate the metal substrate through the microscope.

[0005] As preferred, the optical mirror assembly comprises optical mirror one, optical mirror two, optical mirror three, optical mirror four and optical mirror five, the optical mirror four irradiates the light path of the grating light source module to the optical mirror five, the optical mirror three irradiates the light path of the laser to the optical mirror five, the light paths of the grating light source module and the laser are superimposed at the optical mirror five and then irradiate the metal substrate through the microscope.

[0006] As preferred, the grating light source module comprises a refrigeration unit and a light source emitter.

[0007] The present application has the following advantages: The present application can complete the tissue sample detection at one time, and is non-invasive throughout; the metal substrate is one-step formed without photoresist, and is environmentally friendly and efficient; the prepared super-hydrophobic surface can inhibit protein adsorption and reduce background fluorescence; the metal substrate with nano microstructure is used once, which can avoid cross contamination; Raman detection can realize early rapid screening of malignant tumors. The metal substrate is constructed with a femtosecond laser to form a super-hydrophobic micro-nano structure on the metal surface, which has the ability of SERS enhancement and instant enrichment of body fluid molecules, and realizes detection integration; the sensitivity is high, the specificity is strong, and the cost is low, which can be portable into the bedside or intraoperative, and provides an in-situ, non-invasive and low-cost second-level discrimination tool for early screening, efficacy monitoring and incisal edge evaluation of high-risk groups. BRIEF DESCRIPTION OF DRAWINGS

[0008] Figure 1 It is a schematic diagram of the overall structure of the present application; Figure 2 It is a schematic diagram of the structure of the femtosecond laser, monitor and microscope objective lens in the present application; Figure 3 It is a schematic diagram of the structure of the sample loading module in the present application; Figure 4 It is a schematic diagram of the structure of the detection module in the present application.

[0009] In the figure: 1, femtosecond laser; 2, half-wave plate; 3, G-Lens; 4, filter; 5, shutter; 6, light source; 7, monitor; 8, lens; 9, beam splitter; 10, dichroic mirror; 11, microscope objective lens; 12, metal substrate; 13, transfer table; 14, motor; 15, sample dropper; 16, microscope; 17, optical mirror one; 18, optical mirror two; 19, optical mirror three; 20, optical mirror four; 21, laser; 22, optical mirror five; 23, grating light source module. DETAILED DESCRIPTION

[0010] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor are within the scope of protection of the present application.

[0011] The application will be further described in detail below according to the drawings and embodiments.

[0012] As shown in the drawings, Figures 1 to 4 A lung cancer rapid detection system based on femtosecond laser and Raman spectrum analysis comprises a substrate manufacturing module, a sample loading module and a detection module, and the substrate manufacturing module, the sample loading module and the detection module are electrically connected with an external controller. As shown in the drawings, Figure 2 and Figure 3 The substrate manufacturing module is used for manufacturing nano microstructure on a metal substrate 12 under femtosecond laser, and comprises a femtosecond laser 1, a half-wave plate 2, a Gouy prism 3, a filter 4, a shutter 5, a light source 6, a monitor 7, a lens 8, a beam splitter 9, a dichroic mirror 10, a microscope objective 11 and the metal substrate 12. As shown in the drawings, Figure 3 The sample loading module comprises a conveying table 13, a motor 14 and a sample dropper 15, and the conveying table 13 is used for conveying the metal substrate 12. As shown in the drawings, Figure 4 The detection module is used for performing Raman detection on a tissue sample carried by the metal substrate 12 to analyze whether the tissue sample is diseased, and the detection module comprises a microscope 16, an optical lens assembly, a laser 21 and a grating light source module 23. The optical lens assembly is used for superimposing the light paths of the laser 21 and the grating light source module 23 and then irradiating the metal substrate 12 through the microscope 16. The grating light source module 23 comprises a refrigeration unit and a light source emitter.

[0013] The optical lens assembly comprises an optical lens one 17, an optical lens two 18, an optical lens three 19, an optical lens four 20 and an optical lens five 22. The optical lens four 20 irradiates the light path of the grating light source module 23 to the optical lens five 22, and the optical lens three 19 irradiates the light path of the laser 21 to the optical lens five 22. The light paths of the grating light source module 23 and the laser 21 are superimposed at the optical lens five 22 and then irradiate the metal substrate 12 through the microscope 16.

[0014] The working principle of all the above embodiments is as follows: The laser emitted by the femtosecond laser 1 passes through the half-wave plate 2, the Gouy prism 3, the filter 4 and the shutter 5 in sequence and then enters the dichroic mirror 10 through the rapid opening and closing of the shutter 5. At the same time, the monitoring light emitted by the monitor 7 passes through the lens 8 and then, together with the visible light emitted by the light source 6, enters the dichroic mirror 10 through the beam splitter 9. The combined light formed by the laser, the monitoring light and the visible light entering the dichroic mirror 10 enters the microscope objective 11 to manufacture microstructure on the metal substrate 12. After the surface nano microstructure manufacturing of the metal substrate 12 is completed, the motor 14 drives the conveying table 13 to rotate, and the metal substrate 12 on which the surface nano microstructure manufacturing is completed is conveyed to below the sample dropper 15 to complete the sample dropping operation, and then the metal substrate 12 is continuously conveyed to the detection module. After the metal substrate 12 moves to the position corresponding to the microscope 16, the transfer table 13 stops rotating, the light path of the grating light source module 23 and the laser 21 is superimposed through the optical lens assembly, and then irradiates the tissue sample carried by the metal substrate 12 through the microscope 16 to perform Raman detection and analyze whether the tissue sample is pathological.

[0015] In summary, the present application can complete the detection of the tissue sample at one time, and is non-invasive throughout; the metal substrate 12 is one-step formed, and does not need photoresist, is environmentally friendly and efficient; the prepared super-hydrophobic surface can inhibit protein adsorption and reduce background fluorescence; the metal substrate 12 with nano microstructure is used once, and cross contamination can be avoided; Raman detection can realize early rapid screening of malignant tumors.

[0016] The metal substrate 12 constructs the super-hydrophobic micro-nano structure on the metal surface by femtosecond laser, has the ability of SERS enhancement and instant enrichment of body fluid molecules, realizes integrated detection, has high sensitivity, strong specificity and low cost, can be portable into bedside or intraoperative, provides in-situ, non-invasive and low-cost second-level discrimination new tools for early screening, efficacy monitoring and incisal edge evaluation of high-risk groups.

[0017] Although the embodiments of the present application have been shown and described, it can be understood by those skilled in the art that various changes, modifications, replacements and variations can be made to the embodiments without departing from the principles and spirits of the present application, and the scope of the present application is defined by the appended claims and their equivalents.

Claims

1. A lung cancer rapid detection system based on femtosecond laser and Raman spectroscopy analysis, characterized in that, The substrate manufacturing module, the sample loading module and the detection module are included; The substrate manufacturing module includes a femtosecond laser (1), a half-wave plate (2), a Gouger-Lens (3), a filter (4), a shutter (5), a light source (6), a monitor (7), a lens (8), a beam splitter (9), a dichroic mirror (10), a microscope objective (11) and a metal substrate (12), and is used for manufacturing nano microstructure on the metal substrate (12) under the femtosecond laser; The sample loading module includes a conveying table (13), a motor (14) and a sample dropper (15); The detection module includes a microscope (16), an optical lens assembly, a laser (21) and a grating light source module (23), and the optical lens assembly is used for superimposing the light paths of the laser (21) and the grating light source module (23) and then irradiating the metal substrate (12) through the microscope (16). 2.The lung cancer rapid detection system based on femtosecond laser and Raman spectrum analysis according to claim 1, characterized in that, The optical lens assembly includes an optical lens one (17), an optical lens two (18), an optical lens three (19), an optical lens four (20) and an optical lens five (22), the optical lens four (20) irradiates the light path of the grating light source module (23) to the optical lens five (22), the optical lens three (19) irradiates the light path of the laser (21) to the optical lens five (22), and the light paths of the grating light source module (23) and the laser (21) are superimposed at the optical lens five (22) and then irradiate the metal substrate (12) through the microscope (16). 3.The lung cancer rapid detection system based on femtosecond laser and Raman spectrum analysis according to claim 2, characterized in that, The grating light source module (23) includes a refrigeration unit and a light source emitter.

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