CN111351831A - Detection and marking device and detection method based on mass spectrometry in histology - Google Patents

Abstract

The invention discloses a detection and marking device based on mass spectrometry in histology, which comprises: the device comprises a handheld sampling system, a marking system, a sample introduction system, an ionization system, a mass analyzer, a detector, a central control system and a display; the detection method is characterized in that mass spectrometry is introduced into the detection of tissues in operation and the marking of boundaries before lesion excision, and mass spectrometry information data of exposed tissues are obtained through deep learning to judge the range, the boundaries and the properties of lesion tissues in an operation area. With the increase of the detection time and the detection number, the detection method continuously expands the hyperspectral database of the specific pathological change tissue, updates and optimizes the trained model in real time according to the mass spectrum data of the new specific pathological change tissue and the corresponding normal tissue, automatically optimizes the classification method, further improves the specificity and sensitivity of tissue type and property detection, and realizes rapid pathological detection and diagnosis in the operation area tissue operation.

Description

Intraoperative detection and labeling equipment and detection method of tissue based on mass spectrometry

technical field

The invention is based on mass spectrometry analysis of tissue intraoperative detection and labeling equipment and its detection method, which are used for rapid intraoperative detection and labeling of surgical area tissue in the surgical operation, so as to determine the type, nature and lesion boundary of the surgical area tissue, and guide the surgeon. Perform surgery.

Background technique

Surgery is the oldest and most important means of treating tumors, and it has become the first choice for most (75%-80%) patients with solid tumors to obtain a cure. Surgical treatment of tumors has also become one of the important contents of surgical work. However, during the operation, the surgeon usually performs tumor resection under the naked eye or under the microscope, so he often encounters the following problems: 1. Whether the diseased tissue in the operation area is tumor tissue; 2. The tumor tissue in the operation area 3. Whether there is tumor dissemination and metastasis in the adjacent lymph nodes and/or organs; 4. Whether there is tumor infiltration in the surgical margin during tumor resection; 5. Whether the surgical resection of the tumor is sufficient; Some unexpected findings and the determination of the nature of suspicious micro-organisms (such as parathyroid glands, fallopian tubes or vas deferens, etc.). These issues are very critical, and directly affect the surgeon's judgment on the patient's disease status, which in turn affects the selection and modification of the surgical plan, and is related to the patient's disease recovery status. However, these questions cannot be discovered or answered before the operation, and only emerge one by one during the operation. Therefore, during the operation, quickly answering the above questions has become the key to the success or failure of surgical treatment of tumors and other diseases.

For this reason, people have invented intraoperative histopathological diagnosis, the most commonly used at present is the rapid biopsy of intraoperative biopsy, referred to as intraoperative freezing. Intraoperative freezing is the fastest method for pathological diagnosis in surgery today. It is the emergency work of the pathology department and one of the most challenging tasks in the pathology department. It is to quickly slice the pathological tissue excised in the operation in a cryostat, and after special staining, the pathologist can make a pathological diagnosis. It perfectly solves the above problems.

At present, although intraoperative freezing is the fastest method for pathological diagnosis during surgery, it still has important defects. Apart from the limited accuracy of slice quality due to limitations of material sampling, specimen ice crystals, preparation, and short diagnosis time, the most important drawback of intraoperative freezing is that it takes a long time, which increases the risk of anesthesia and surgery. It usually takes as long as 40 minutes to 1 hour from the surgeon taking tissue samples for inspection, to the pathologist making diagnosis and information feedback. During this time, the patient continues to maintain anesthesia, the surgical incision is kept open, and the surgery The only option is to wait. Therefore, the anesthesia time and operation time of patients are increased, the risk of anesthesia and operation is increased, the operation efficiency is reduced, and the waste of medical resources is also caused. Therefore, there is an urgent need to develop a method or device for rapid intraoperative pathological diagnosis to solve this problem.

Mass spectrometry (MS) is an analytical technique that detects the mass-to-charge ratio of charged particles, that is, the moving ions (charged atoms, molecules or molecular fragments, such as molecular ions, isotopic ions, Fragment ions, rearranged ions, multiply charged ions, metastable ions, negative ions and ions generated by ion-molecular interactions) are separated according to their mass-to-charge ratios and detected. By analyzing these ions, information such as molecular weight, chemical structure, dissociation law, and certain interrelationships between certain ions formed by the decomposition of single molecules can be inferred. Therefore, mass spectrometry can be used to detect small molecular compounds, biological macromolecules, and elemental compositions. As a complex system analysis technology, mass spectrometry has become an indispensable analytical tool for modern life sciences and medical research, especially the research on genomics, proteomics and metabolomics of tissues and cells. Mass spectrometry technology has developed rapidly in recent years, and modern mass spectrometry instruments have better sensitivity and higher mass accuracy and resolution, and have begun to be miniaturized.

During the development of the disease, there will be differences in gene expression, protein synthesis, material metabolism, etc. between the diseased area tissue and the surrounding normal tissue, which provides an opportunity for the application of mass spectrometry analysis. Using mass spectrometry technology to sample and detect local tissues, and compare and analyze with the standard atlas, can realize the judgment and identification of tissue components. Therefore, in order to solve the current problems of rapid pathological diagnosis in surgical operations, we designed a new type of medical equipment and method that can be used in surgery and can realize rapid histopathological determination based on mass spectrometry analysis.

SUMMARY OF THE INVENTION

(1) Technical problems solved

In view of the deficiencies of the prior art, the present invention provides an intraoperative detection and labeling device based on mass spectrometry analysis, which utilizes mass spectrometry technology to realize the detection of tissue in the surgical area according to the tissue information exposed in the operation, and can quickly distinguish the tissue without removing the tissue. Different tissue types can quickly display the boundary of the diseased tissue in the operation area, can quickly and automatically mark the diseased tissue in the operation area, realize the rapid pathological diagnosis of the operation area tissue during the operation, confirm and mark the edge of the diseased tissue in real time, and guide the operator to complete the resection. Diseased tissue and avoid the disadvantages of traditional intraoperative pathological examination.

(2) Technical solutions

In order to achieve the above purpose, the present invention provides the following technical solutions: an intraoperative detection and labeling device based on mass spectrometry analysis, including: a hand-held sampling system, a labeling system, a sampling system, an ionization system, a mass analyzer, a detector, a central control system, display;

The hand-held sampling system is a pen-shaped design, the hand-held sampling system is electrically connected with the sampling system, and the hand-held sampling system is held by the operator to directly touch the exposed tissue in the surgical area to conduct material components in a single-point area. Collection of samples; the sampling system is electrically connected to the ionization system to ensure the entry of samples without affecting the vacuum state of the vacuum system; the ionization system is in the vacuum system, and the ionization system is The system is electrically connected with the mass analyzer, the ionization system ionizes the sent analysis sample to obtain ions with sample information, and finally the ions are accelerated and sent to the mass analyzer; the mass analyzer is in the vacuum system, The mass analyzer is electrically connected to the detector, and the mass analyzer separates and arranges ions with different mass-to-charge ratios into spectra; the detector is in a vacuum system, and the detector is electrically connected to the real-time transmission system, Its function is to detect ions of various mass-to-charge ratios, and transmit the detection information to the real-time transmission system; the real-time transmission system is electrically connected to the central control system; the central control system is electrically connected to the display; the The central control system is also electrically connected to the marking system; after the central control system receives the mass spectrometry information data and judges the tissue type and property of the detected point, the central control system controls the marking system to mark the detection point according to the judgment result , and presented on the display screen of the display in the form of an image; the marking principle is that normal tissue is not marked, and diseased tissue is marked (such as methylene blue, etc.); the display displays the mass spectrometry information of the detected sample in real time; the marking system and the The sampling system is integrated; the vacuum system provides a vacuum working environment for the ionization system, mass analyzer and detector.

A detection method based on mass spectrometry analysis of tissue intraoperative detection and labeling equipment, characterized in that: the detection method is to introduce mass spectrometry analysis into intraoperative tissue detection and marking of the boundary before lesion resection, and obtain mass spectral information data of exposed tissue through deep learning , to judge the scope, boundary and nature of the diseased tissue in the operation area, and the detection method includes the following steps:

Step 1: Analyze and process the mass spectrometry data of a specific diseased tissue (such as a certain tumor) to obtain characteristic mass spectral data of a specific diseased tissue (such as a certain tumor); use the same method to obtain the characteristics of the same diseased tissue of different individuals nature spectrum data, and train the model;

Step 2: Analyze and process the mass spectrometry data of the normal tissue corresponding to the specific diseased tissue (such as the normal tissue around a certain tumor) to obtain the characteristic mass spectrum of the normal tissue corresponding to the specific diseased tissue (such as the normal tissue surrounding a certain tumor) data; use the same method to obtain characteristic mass spectrometry data of normal tissue corresponding to the same diseased tissue of different individuals, and train the model;

Step 3: Establish a characteristic mass spectrometry data classification method for a specific diseased tissue;

Step 4: Acquire the mass spectrometry data of the exposed tissue in the surgical area in real time, and use the acquired mass spectrometry data as the basis for judging the tissue type, lesion tissue range, boundary and nature in the entire surgical area;

Step 5: The newly collected mass spectrometry data of the diseased tissue and its corresponding normal tissue need to be determined after the postoperative pathological diagnosis is confirmed; if the pathological diagnosis confirms that the diseased tissue is the specific diseased tissue, the normal tissue is a specific one The normal tissue corresponding to the diseased tissue, the newly collected mass spectrometry data of the diseased tissue and its corresponding normal tissue will be included in the training model for the characteristic mass spectrometry data of the specific diseased tissue and the training model for the characteristic mass spectrometry data of the normal tissue, respectively. The classification model data is expanded and perfected; if the pathological diagnosis result is not the diseased tissue, the data will be included in the database of the corresponding disease.

(3) Beneficial effects

The present invention provides a detection method based on mass spectrometry analysis of intraoperative detection and labeling equipment. Has the following beneficial effects:

The present invention uses the mass spectrometry data of the exposed tissue in the operation area collected in real time as the basis for judging the type and nature of the tissue in the operation area. The type and nature of the tissue in the operation area are determined through the training model of confirmed data and the data retraining model of later confirmed cases, so as to define the location, boundary and nature of the diseased tissue in the operation area to guide the surgeon to perform the operation. The method for rapid intraoperative detection of tissue based on mass spectrometry analysis provided by the present invention has the function of online real-time self-learning, and has an intelligent database of specific diseased tissue, that is, the database can be connected with pathological diagnosis data or manually input pathological diagnosis, according to postoperative histopathology The diagnosis results are stored in newly acquired mass spectrometry data. With the increase of detection time and detection quantity, the detection method will continuously expand the hyperspectral database of the specific diseased tissue, and update and optimize the trained model in real time according to the new mass spectral data of the specific diseased tissue and the corresponding normal tissue. Automatically optimize the classification method, further improve the specificity and sensitivity of tissue type and property detection, and realize rapid intraoperative pathological detection and diagnosis of tissue in the surgical area.

Description of drawings

FIG. 1 is a structural system diagram of a mass spectrometry-based tissue detection and labeling device of the present invention;

FIG. 2 is a flow chart of the detection method of the present invention based on mass spectrometry analysis of the detection and labeling equipment in tissue surgery.

Detailed ways

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, but not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

As shown in Figures 1-2, the present invention provides a technical solution: an intraoperative detection and labeling device based on mass spectrometry analysis, including: a hand-held sampling system, a labeling system, a sampling system, an ionization system, a mass analyzer, a detection device, central control system, display;

The hand-held sampling system is a pen-shaped design, the hand-held sampling system is electrically connected with the sampling system, and the hand-held sampling system is held by the operator to directly touch the exposed tissue in the surgical area to conduct material components in a single-point area. Collection of samples; the sampling system is electrically connected to the ionization system to ensure the entry of samples without affecting the vacuum state of the vacuum system; the ionization system is in the vacuum system, and the ionization system is The system is electrically connected with the mass analyzer, the ionization system ionizes the sent analysis sample to obtain ions with sample information, and finally the ions are accelerated and sent to the mass analyzer; the mass analyzer is in the vacuum system, The mass analyzer is electrically connected to the detector, and the mass analyzer separates and arranges ions with different mass-to-charge ratios into spectra; the detector is in a vacuum system, and the detector is electrically connected to the real-time transmission system, Its function is to detect ions of various mass-to-charge ratios, and transmit the detection information to the real-time transmission system; the real-time transmission system is electrically connected to the central control system; the central control system is electrically connected to the display; the The central control system is also electrically connected to the marking system; after the central control system receives the mass spectrometry information data and judges the tissue type and property of the detected point, the central control system controls the marking system to mark the detection point according to the judgment result , and presented on the display screen of the display in the form of an image; the marking principle is that normal tissue is not marked, and diseased tissue is marked (such as methylene blue, etc.); the display displays the mass spectrometry information of the detected sample in real time; the marking system and the The sampling system is integrated; the vacuum system provides a vacuum working environment for the ionization system, mass analyzer and detector.

A detection method based on mass spectrometry analysis of tissue intraoperative detection and labeling equipment, characterized in that: the detection method is to introduce mass spectrometry analysis into intraoperative tissue detection and marking of the boundary before lesion resection, and obtain mass spectral information data of exposed tissue through deep learning , to judge the scope, boundary and nature of the diseased tissue in the operation area, and the detection method includes the following steps:

Step 1: Analyze and process the mass spectrometry data of a specific diseased tissue (such as a certain tumor) to obtain characteristic mass spectral data of a specific diseased tissue (such as a certain tumor); use the same method to obtain the characteristics of the same diseased tissue of different individuals nature spectrum data, and train the model;

Step 2: Analyze and process the mass spectrometry data of the normal tissue corresponding to the specific diseased tissue (such as the normal tissue around a certain tumor) to obtain the characteristic mass spectrum of the normal tissue corresponding to the specific diseased tissue (such as the normal tissue surrounding a certain tumor) data; use the same method to obtain characteristic mass spectrometry data of normal tissue corresponding to the same diseased tissue of different individuals, and train the model;

Step 3: Establish a characteristic mass spectrometry data classification method for a specific diseased tissue;

Step 4: Acquire the mass spectrometry data of the exposed tissue in the surgical area in real time, and use the acquired mass spectrometry data as the basis for judging the tissue type, lesion tissue range, boundary and nature in the entire surgical area;

Step 5: The newly collected mass spectrometry data of the diseased tissue and its corresponding normal tissue need to be determined after the postoperative pathological diagnosis is confirmed; if the pathological diagnosis confirms that the diseased tissue is the specific diseased tissue, the normal tissue is a specific one The normal tissue corresponding to the diseased tissue, the newly collected mass spectrometry data of the diseased tissue and its corresponding normal tissue will be included in the training model for the characteristic mass spectrometry data of the specific diseased tissue and the training model for the characteristic mass spectrometry data of the normal tissue, respectively. The classification model data is expanded and perfected; if the pathological diagnosis result is not the diseased tissue, the data will be included in the database of the corresponding disease.

It should be noted that, in this document, relational terms such as first and second are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any relationship between these entities or operations. any such actual relationship or sequence exists. Moreover, the terms "comprising", "comprising" or any other variation thereof are intended to encompass a non-exclusive inclusion such that a process, method, article or device that includes a list of elements includes not only those elements, but also includes not explicitly listed or other elements inherent to such a process, method, article or apparatus. Without further limitation, an element qualified by the phrase "comprising a..." does not preclude the presence of additional identical elements in a process, method, article or apparatus that includes the element.

Although embodiments of the present invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, and substitutions can be made in these embodiments without departing from the principle and spirit of the invention and modifications, the scope of the present invention is defined by the appended claims and their equivalents.

Claims (3)

1. Intraoperative detection and labeling equipment for tissue analysis based on mass spectrometry, including: handheld sampling system, labeling system, sampling system, ionization system, mass analyzer, detector, central control system, display; The hand-held sampling system is a pen-shaped design, the hand-held sampling system is electrically connected with the sampling system, and the hand-held sampling system is held by the operator to directly touch the exposed tissue in the surgical area to conduct material components in a single-point area. Collection of samples; the sampling system is electrically connected to the ionization system to ensure the entry of samples without affecting the vacuum state of the vacuum system; the ionization system is in the vacuum system, and the ionization system is The system is electrically connected with the mass analyzer, the ionization system ionizes the sent analysis sample to obtain ions with sample information, and finally the ions are accelerated and sent to the mass analyzer; the mass analyzer is in the vacuum system, The mass analyzer is electrically connected to the detector, and the mass analyzer separates and arranges ions with different mass-to-charge ratios into spectra; the detector is in a vacuum system, and the detector is electrically connected to the real-time transmission system, Its function is to detect ions of various mass-to-charge ratios, and transmit the detection information to the real-time transmission system; the real-time transmission system is electrically connected to the central control system; the central control system is electrically connected to the display; the The central control system is also electrically connected to the marking system; after the central control system receives the mass spectrometry information data and judges the tissue type and property of the detected point, the central control system controls the marking system to mark the detection point according to the judgment result , and presented on the display screen of the display in the form of an image; the display displays the mass spectrum information of the detected sample in real time; the marking system is integrated with the sampling system; the vacuum system is the ionization system, mass analyzer , The detector provides a vacuum working environment. 2 . The intraoperative detection and labeling device based on mass spectrometry analysis of claim 1 , wherein the central control system is used to receive various mass spectrometry information data. 3 . 3. The detection method based on mass spectrometry analysis of tissue intraoperative detection and labeling equipment according to claim 1-2, wherein the detection method is to introduce mass spectrometry analysis into intraoperative tissue detection and marking of the boundary before lesion resection , obtain the mass spectrometry information data of the exposed tissue through deep learning to judge the scope, boundary and nature of the diseased tissue in the operation area, and the detection method includes the following steps: Step 1: analyze and process the mass spectrometry data of the specific lesion tissue to obtain the characteristic mass spectrometry data of the specific lesion tissue; use the same method to obtain the characteristic mass spectrometry data of the same lesion tissue of different individuals, and train the model; Step 2: analyze and process the mass spectrometry data of the normal tissue corresponding to the specific diseased tissue to obtain characteristic mass spectrometry data of the normal tissue corresponding to the specific diseased tissue; use the same method to obtain the characteristics of the normal tissue corresponding to the same diseased tissue of different individuals nature spectrum data, and train the model; Step 3: Establish a characteristic mass spectrometry data classification method for a specific diseased tissue; Step 4: Acquire the mass spectrometry data of the exposed tissue in the surgical area in real time, and use the acquired mass spectrometry data as the basis for judging the tissue type, lesion tissue range, boundary and nature in the entire surgical area; Step 5: The newly collected mass spectrometry data of the diseased tissue and its corresponding normal tissue need to be determined after the postoperative pathological diagnosis is confirmed; if the pathological diagnosis confirms that the diseased tissue is the specific diseased tissue, the normal tissue is a specific one The normal tissue corresponding to the diseased tissue, the newly collected mass spectrometry data of the diseased tissue and its corresponding normal tissue will be included in the training model for the characteristic mass spectrometry data of the specific diseased tissue and the training model for the characteristic mass spectrometry data of the normal tissue, respectively. The classification model data is expanded and perfected; if the pathological diagnosis result is not the diseased tissue, the data will be included in the database of the corresponding disease.

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