CN112869784A - Novel injection puncture needle and tumor light biopsy technology thereof - Google Patents
Novel injection puncture needle and tumor light biopsy technology thereof Download PDFInfo
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Abstract
The invention relates to a novel injection puncture needle and a tumor light biopsy technology thereof, which comprise a miniature puncture needle, a hose, a micropipettor, an optical nano probe, a micro-control platform and a fluorescence imaging system. The novel puncture needle is formed by combining a miniature puncture needle, a hose, a micropipette and a micro-manipulation platform, after the novel puncture needle absorbs quantitative modification through the micropipette, the optical nanoprobe which can specifically identify tumor cells is directly punctured to a target tissue region by controlling the miniature puncture needle to accurately move through the micro-manipulation platform, and the quantitative optical nanoprobe in the micropipette is injected into the target region, and the target tumor is specifically connected with the optical nanoprobe. The fluorescence imaging system performs fluorescence imaging on the target area to judge whether the target area is diseased or not and judge the diseased area. The invention has the characteristics of small wound surface and high detection efficiency. The invention has small volume, light weight, convenient carrying and wide application. Is suitable for sampling and censoring in different places and remote areas.
Description
Technical Field
The invention belongs to the field of optical biological imaging, and relates to a novel injection puncture needle and a tumor light biopsy technology thereof.
Background
Puncture is a commonly used biopsy method, and has the advantages of low invasiveness, small wound and capability of directly taking out secretion for pathological examination. However, the subsequent pathological diagnosis of a biopsy based on aspiration still usually requires a long time and is difficult to perform intraoperatively.
Light biopsy refers to a technique for obtaining information about the state of a tissue in vivo or ex vivo by analyzing the interaction of light and tissue using an optical examination means, and thus light biopsy can provide an advanced biopsy means in real time, precisely, and objectively for clinical histopathology. The optical biopsy distinguishes and diagnoses different physiological states of the detected tissue or cell in real time according to the optical characteristics of different tissues of a human body, so that the traditional histopathology diagnosis method of diagnosing and sampling biopsy by depending on visual observation experience of doctors for a long time is eliminated, and early diagnosis of histopathology can be realized.
Fluorescence imaging is a technique that uses fluorescence signals for imaging. The fluorescent dye is transited to an excited state under the irradiation of exciting light, and the excited radiation emits a fluorescent signal. Fluorescent dyes can be classified as up-converting and down-converting dyes according to the relative magnitude of the energy of the photons that excite and fluoresce. The upconversion particles refer to fluorescent dyes that absorb short wavelength light to emit long wavelength fluorescence, and the downconversion particles refer to fluorescent dyes that absorb long wavelength light to emit short wavelength fluorescence. Compared with down-conversion particles, the up-conversion particles can penetrate deeper biological tissues, have no biological background fluorescence interference and have the characteristic of good imaging quality. The novel optical nanoprobes currently used in the biomedical field for fluorescence imaging have up-converting nanoparticles and down-converting materials with aggregation-induced emission properties. In the traditional in-vivo fluorescence imaging process, the optical nanoprobe generally enters the body through intravenous injection, and probe particles are mainly gathered at tumor tissues under the synergistic effect of a passive targeting mode dominated by an EPR effect and an active targeting mode dominated by specific targeting modification and are endocytosed by cancer cells, so that a longer blood circulation time is also needed for detecting a fluorescence signal at the tumor site.
Therefore, the invention provides a novel injection puncture needle and a tumor light biopsy technology thereof, the micro puncture needle is positioned to a target tissue area for injecting an optical nano probe, and nano particles with tumor cell targeted modification such as specific antibodies can be combined with or absorbed by tumor cells, so that the fluorescence imaging can be carried out on the tumor cells.
Disclosure of Invention
The invention aims to provide a novel method.
The invention provides a novel injection puncture needle and a tumor light biopsy technology thereof, which realize more targeted tumor part imaging.
The technical scheme adopted by the invention is disclosed.
The invention discloses a novel injection puncture needle and a tumor light biopsy technology thereof, which comprises a miniature puncture needle, a hose, a micropipette, an optical nano probe and a fluorescence imaging system, wherein the novel puncture needle is formed by combining the miniature puncture needle, the hose and the micropipette, after the novel puncture needle absorbs a quantitative optical nano probe with a targeting function, the novel puncture needle directly punctures to a target area through the miniature puncture needle, the optical nano probe is injected into the target area, and the target tumor is specifically connected with the optical nano probe. The fluorescence imaging system performs fluorescence imaging on the target area to judge whether the target area is diseased or not and judge the diseased area.
In a further embodiment, the micro-needle has an inner diameter of 80um and an outer diameter of 260 um.
In further specific implementation, the micropipette and the miniature puncture needle are connected together through a hose, so that the quantitative nano probe injected by the micropipette is realized.
In a further specific implementation, the micro puncture needle and the hose are connected in an inserting manner, the hose and the suction head of the micropipette are connected in an inserting manner, and the suction head of the micropipette and the micropipette are fixedly connected through threads.
In a further embodiment, the micropipette is provided with a knob and an indicator screen for the volume of liquid to be aspirated, and the knob can be rotated to set the number on the indicator screen to achieve the volume of liquid to be aspirated.
In further specific implementation, the position of the micro puncture needle can be accurately controlled by the micro control platform, the puncture needle can move up, down, left, right, front and back, and the micro control platform and the micro puncture needle are connected through elastic deformation of the clamping piece.
In still further embodiments, the micropipette may be replaced with other micropipette devices having smaller and finer pipette volumes.
In a further embodiment, the optical nanoprobe used can be a TPE-red molecule with aggregation-induced emission characteristics; and when the target depth is deep, selecting the up-conversion nano particles as the optical nano probe.
In a further embodiment, arginine-glycine-aspartic acid (Arg-Gly-Asp, RGD) is modified on an optical nanoprobe for recognition of α v β 3 integrin on the surface of tumor cells.
In a further embodiment, the puncture needle has a very small inner and outer diameter and high sterility, and can be used for routine micro-biopsy sampling, micro-biopsy in important organs of a human body such as the brain, the spinal cord and other parts, and routine sampling biopsy of tumors, infections or other space occupying lesions.
The technical effect produced by the invention.
Compared with the traditional medical biopsy needle, the novel injection puncture needle is thinner, the generated wound surface is smaller, and the high-efficiency and accurate judgment on whether a target area is diseased or not and the diseased range is realized by combining the tumor light biopsy technology of optical nano imaging.
The micro biopsy system can be effectively combined with single cell sequencing, single cell proteomics and other advanced detection technologies to be applied to diagnosis of various diseases besides optical biopsy. Furthermore, microscopical biopsy systems can be used for local microscopical administration.
Drawings
FIG. 1 is a schematic view of the structure of the novel injection puncture needle of the present invention
FIG. 2 is a schematic view of the tumor light biopsy technique of the novel injection puncture needle of the present invention
Description of reference numerals:
suction head of 1-miniature puncture needle 2-capillary hose 3-micropipettor
4-micropipettor 5-button 6-novel injection puncture needle of micropipettor
7-tumor tissue 8-tumor cell 9-optical nano probe
10-fluorescence imaging system.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
Example 1
The invention provides a novel injection puncture needle, which comprises a miniature puncture needle 1, a capillary hose 2 and a micropipettor 4.
The novel injection puncture needle consists of a miniature puncture needle 1, a capillary hose 2 and a micropipettor 4. The micro puncture needle 1 is used for puncturing tissue of a target area, and the inner diameter and the outer diameter of the micro puncture needle 1 are smaller than those of a biopsy needle used in medicine, for example, the inner diameter is designed to be 80um, the outer diameter is designed to be 260 um, the sizes of the inner diameter and the outer diameter are not limited to the above, and the micro puncture needle 1 with smaller values of the inner diameter and the outer diameter can be designed. The capillary hose 2 is used for connecting the miniature puncture needle 1 and the micropipettor 4. The two ends of the capillary hose 2 are respectively inserted with the micro puncture needle 1 and the suction head 3 of the micropipette, and the elastic force of the capillary hose 2 and the friction force between the micro puncture needle 1 and the suction head 3 of the micropipette are firmly combined. The micropipette 5 and the tip 3 of the micropipette are fixed to the micropipette 4 by the screw of the tip. The top of the micropipette 4 is provided with a button 5 for rotary adjustment and extrusion, the rotary button adjusts the number on the indicating plate of the micropipette to reach the amount of the medicine or the optical nano probe 9 to be absorbed, and the extrusion button realizes the absorption and the injection of the medicine or the optical nano probe 9. The micropipettor 4 can adopt other micropipette devices with smaller and more precise liquid transfer amount to realize the microinjection of novel injection puncture aiming at the medicine or the optical nanoprobe 9. The micro puncture needle 1 can be tightly clamped on a control rod of a micro control platform, and the micro control platform controls three-dimensional translation of the puncture needle up, down, left, right, front and back, tilting movement without being limited to three-dimensional movement and the like. The micromanipulation platform can be electric or manual. The micro-manipulation platform controls the micro-puncture needle to be above the tumor tissue 7 to be extracted, the micro-puncture needle of the micro-manipulation platform controls the depth of the micro-puncture needle which is penetrated into the tumor tissue accurately from top to bottom, the micro-puncture needle absorbs tissue fluid of the tumor tissue 7 through siphon, and then the micro-puncture needle carrying the tissue fluid of the tumor tissue 7 is controlled by the micro-manipulation platform to exit the tumor tissue 7.
Example 2
The invention provides a novel tumor light biopsy technology of an injection puncture needle, which comprises a novel injection puncture needle 6, an optical nano probe 9 and a fluorescence imaging system 10.
The novel injection puncture needle 6 absorbs the solution containing milligram-level probe particles, the micro puncture needle 1 of the novel injection puncture needle 6 penetrates through epidermal tissues to reach tumor tissues 7, and the solution containing the optical nano probe 9 is injected. The optical nano-probe 9 and the surface of the tumor cell 8 generate specific recognition, so that the optical nano-probe 9 and the tumor cell 8 are combined. The optical nanoprobe 9 fluoresces under excitation of excitation light in the fluorescence imaging system 10, and the fluorescing tissue is presented in the fluorescence imaging system.
The following list three optical nanoprobe types in three application scenarios, the present invention includes but is not limited to:
when the tumor tissue is in a shallow position in the body, the optical nanoprobe 9 adopts TPE-red molecules with aggregation-induced luminescence characteristics as fluorescent probes, and the polyethylene glycol PEG is modified by a nano coprecipitation method, so that the biocompatibility and biochemical stability of the nanoparticles are greatly improved. The optical nanoprobe 9 is modified with arginine-glycine-aspartic acid (Arg-Gly-Asp, RGD) for recognizing α v β 3 integrin on the surface of the tumor cell 8. Integrin is a transmembrane protein that links the intracellular and extracellular environments and is overexpressed in many types of tumor cells. Especially, α v β 3 integrin plays an important role in the neovascularization of many types of tumor tissues, the metastasis of tumor cells, and the like, and thus becomes a commonly used target site in tumor therapy. Arginine-glycine-aspartic acid (Arg-Gly-Asp, RGD) -containing polypeptide molecules can bind to α v β 3 integrin, and are a broad spectrum of cancer cell targeting moieties. Covalent connection between sulfydryl in (RGDfc) and maleimide in DPSE-PEG-Mal can be realized through knocking reaction between sulfydryl in (RGDfc) and maleimide in DPSE-PEG-Mal, and TPE-red-PEG-RGD nanoprobe solution with cancer cell targeting function can be prepared on the basis of the TPE-red-PEG-Mal nanoparticles.
The TPE-red particles are used as the optical nano-probe 9, have the effect of photodynamic therapy, realize imaging-guided tumor photodynamic therapy, and can be used for evaluating the curative effect in the process of tumor therapy in real time.
When the tumor tissue 7 is located at a deep position in the body, an up-conversion material for exciting near-infrared emission by near infrared is adopted as the optical nanoprobe 9. The up-conversion material has significant advantages in depth imaging because biological tissues absorb and scatter up-conversion excitation light less, the excitation light in the near infrared band can reach deeper tissues, autofluorescence signals of the biological tissues can not be excited, and background noise can be greatly reduced. By targeted modification, the upconverting probe is also injected into the tumor tissue 7 using a novel injection needle 6 and imaged in a fluorescence imaging system 10.
When the tumor tissue 7 is located at a deeper position in the body, an optical fiber in the form of an endoscope may be used to direct the excitation light near the tissue and collect the fluorescence signal to the fluorescence imaging system 10.
The novel injection puncture needle and the tumor light biopsy technology thereof provided by the invention have the characteristics of small wound surface and high efficiency; meanwhile, the efficient and accurate judgment on whether a target area is diseased or not and the range of the diseased is realized by combining the tumor light biopsy technology of optical nano imaging; in addition, the invention can also be applied to the field of drug administration acupuncture and moxibustion and used as a drug administration acupuncture needle; in addition, the present invention may also be used in the field of biopsies as a tissue fluid extraction.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (10)
1. A novel injection puncture needle and a tumor light biopsy technology thereof are characterized by comprising a miniature puncture needle, a hose, a micropipettor, an optical nano probe, a micro-control platform and a fluorescence imaging system,
the novel puncture needle is formed by combining a micro puncture needle, a hose, a micropipette and a micro control platform, after the novel puncture needle absorbs a quantitative optical nano probe with a targeting function through the micropipette, the micro puncture needle is controlled by the micro control platform to move accurately and directly puncture a target area, the optical nano probe is injected into the target area, and a target tumor is specifically connected with the optical nano probe; the fluorescence imaging system performs fluorescence imaging on the target area to judge whether the target area is diseased or not and judge the diseased area.
2. A novel needle and its technique of light biopsy for tumor according to claim 1, wherein: the inner diameter of the micro puncture needle is 80um, and the outer diameter is 260 um.
3. A novel needle and its technique of light biopsy for tumor according to claim 1, wherein: the micropipettor is connected with the miniature puncture needle through a capillary hose, so that the quantitative nano probe can be injected by the micropipettor.
4. A novel needle and its technique of light biopsy for tumor according to claim 1, wherein: the micro puncture needle is connected with the hose in an inserting mode, the hose is connected with the suction head of the micropipettor in an inserting mode, and the suction head of the micropipettor is fixedly connected with the micropipettor through threads.
5. A novel needle and its technique of light biopsy for tumor according to claim 1, wherein: the micropipettor is provided with a knob and an indicating screen for absorbing liquid capacity, and the number on the indicating screen can be set to achieve the required liquid absorbing capacity by rotating the knob.
6. A novel needle and its technique of light biopsy for tumor according to claim 1, wherein: the micro-control platform can accurately control the position of the micro puncture needle, the puncture needle can move up, down, left, right, front and back, and the micro-control platform is connected with the micro puncture needle through elastic deformation of the clamping piece.
7. A novel needle and its technique of light biopsy for tumor according to claim 1, wherein: the micropipette can be replaced by other micropipette devices with smaller and more precise liquid transferring amount.
8. A novel needle and its technique of light biopsy for tumor according to claim 1, wherein: the optical nano-probe used can be a material TPE-red molecule with aggregation-induced luminescence property; and when the target depth is deep, selecting the up-conversion nano particles as the optical nano probe.
9. A novel needle and its technique of light biopsy for tumor according to claim 1, wherein: arginine-glycine-aspartic acid (Arg-Gly-Asp, RGD) is modified on the optical nanoprobe for identifying the alpha v beta 3 integrin on the surface of the tumor cell.
10. A novel injection needle in accordance with claim 1, wherein: the puncture needle has extremely small inner and outer diameter and high sterility degree, and can be used for routine micro-biopsy sampling, micro-biopsy in important organs of human bodies such as brains, spinal cords and other parts, and routine sampling biopsy of tumors, infections or other space occupying lesions.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201911207703.0A CN112869784A (en) | 2019-11-29 | 2019-11-29 | Novel injection puncture needle and tumor light biopsy technology thereof |
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| CN201911207703.0A CN112869784A (en) | 2019-11-29 | 2019-11-29 | Novel injection puncture needle and tumor light biopsy technology thereof |
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| CN201911207703.0A Pending CN112869784A (en) | 2019-11-29 | 2019-11-29 | Novel injection puncture needle and tumor light biopsy technology thereof |
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Application publication date: 20210601 |