WO2010127500A1 - Device and method for using genetic information to detect urogenital tumors - Google Patents

Abstract

A device and method for using genetic information to detect tumors of the urogenital system comprises a reaction module preset with at least a urogenital tumor DNA database sequence information, a signal reaction detection module and a processing module preset with status information. The reaction module, the signal reaction detection module and the processing module are linked in proper order. The reaction module is used for reactions with DNA samples to be tested. The signal reaction detection module detects status information of reactions, and sends the information to the processing module. The processing module performs analysis on the basis of the received status information and the preset status information. The device and method perform high-flux automatic detection of malignant tumors of the urogenital system and provide for early evaluation and detection of genetic risk in tumor patients.

Description

 Apparatus and method for detecting genitourinary tumor using genetic information

 [1] The present invention relates to an apparatus and method for detecting a tumor of the genitourinary system.

 Background technique

 [2] Cancer is a general term for a class of similar diseases that invade human tissues and organs by the rapid growth of abnormal cells, often referred to as malignant tumors. The World Health Organization (WHO) warns that cancer is threatening everyone, young or old, rich or poor, men, women or children. Cancer poses a huge burden on patients, families and society. Cancer is the leading cause of death worldwide, including in developing countries.

[3] Parkin et al reported that in 2002, the global incidence of new malignant tumors was about 10.1 million / year, the death toll was 6.2 million / year, and the number of cancer cases was 22.4 million. New malignant tumors are on the rise every year. The incidence and death of malignant tumors in the world has increased by about 22% in the past 10 years.

 It is estimated that by 2020, there will be nearly 20 million new cases of new cancer cases, and the death toll can reach 12 million / year. According to the ranking of China's cancer incidence rate and top ten malignant tumors in 2006 provided by the Cancer Prevention Office of the Ministry of Health, China's annual new cancer cases are 2.2 million, and the number of cancer deaths is 1.6 million. In the past 20 years, one out of every 4 to 5 deaths in China has died of cancer, ranking first among deaths.

 [4] Male genitourinary malignancies mainly include prostate cancer, bladder cancer, renal cell carcinoma and testicular cell tumors. Prostate cancer is the most important type of male genitourinary tumor, and it is a disease unique to humans. The incidence of other mammals is extremely rare. Prostate cancer is the most common cancer in men, the second most common cause of death in men, second only to lung cancer; it occurs in older men over 50 years of age. The 5-year survival rate of the early prostate is 78%-95%, and the late stage is 27%-64%. Therefore, early detection and early treatment are very important.

[5] The incidence of bladder cancer ranks 7th in the world in cancer, and its incidence accounts for 2.3% of the total number of cancers, more male than female (male: female = 3.5:1). Among the risk factors known and potentially causing bladder cancer, smoking and occupational exposure to aromatic amines are the most important. Most hospitals, now, because CT is feasible and more economical than MRI, have been used as the primary test for assessing tumor staging. Treatment mainly includes surgery and non-surgical treatment. In recent years, the clinical guidelines for bladder cancer abroad have been based on the morphology, size, and size of SBC treatment, endovascular perfusion, and follow-up. Sub-classifications such as number, pathological grade, and clinical stage were used for clinical selection. The application of other therapeutic methods such as gene therapy, targeted therapy, and tumor vaccine in the treatment of SBC is still in the exploratory stage and needs further study.

 [6] Renal cell carcinoma is a group of malignant tumors that occur from the renal tubular epithelium, accounting for more than 90% of adult kidney malignancies.

, 12 males with common tumors and 17 females. Men in industrially developed regions (including Japan) have a similar morbidity rate to non-Hodgkin's lymphoma, ranking sixth, and in underdeveloped regions, the incidence rate is 16, similar to nasopharyngeal carcinoma. Women are separated between 12 and 17 in developed and developing countries. The incidence is low in Africa and Asia. The current diagnostic method can detect very small kidney masses and the treatment methods have changed. With the extensive use of local nephrectomy and laparoscopy, preoperative impact testing is more important, including conventional power CT and chest X-ray. The comprehensive treatment includes surgery, chemotherapy, radiotherapy, biological immunotherapy and some physical therapy. With the advancement of surgical techniques, the operation of preserving renal tissue for early or accidental discovery of renal cell tumor has achieved satisfactory results. The effect is very impressive. Specific treatment should be personalized according to the basic conditions of the lesion

[7] Testicular tumors account for 1% to 2% of all male tumors, of which more than 80% are malignant. Testicular tumors are the most complex tumors in the urinary system, with the most histological features and the most closely related tumors. The disease occurs mostly in young adults. In male 15-35 ages, the incidence of testicular tumors is second only to leukemia, malignant lymphoma and brain tumors. There are regional and ethnic differences in their incidence rates in the world. In China, the morbidity and mortality rate are about 1/100,000. The incidence of this disease is lower than that of other tumors, but the proportion of malignant is higher, more than 95% is malignant, and it occurs mostly in the most active sexual stage. The treatments include surgery, chemotherapy and radiation therapy. Testicular cancer can be completely cured, SEER data reported that the 5-year survival rate of testicular cancer patients was 95.7%, if it is confined to the testis, the 5-year survival rate can reach 99.5%, 5-year survival of local lymph node metastasis Rate up to 96.3%

 The 5-year survival rate of distant lymph node metastasis is 70.1%.

 [8] The occurrence of malignant tumors is closely related to the DNA sequence changes of certain genes in the genome.

Prostate cancer cases caused by mutants of the LAC2 gene account for 2% to 5% of total prostate cancer cases. In addition, DNA sequence changes of PSA, KLK5, PCA3, ADAM15, STK1 and other genes have also been shown to be associated with the development of prostate cancer, but at this stage there is no high-throughput automated detection device and method for genitourinary malignancies. . Disclosure of invention

technical problem

 The technical problem to be solved by the present invention is to overcome the deficiencies of the prior art and to provide a detection apparatus and method capable of performing high-throughput automatic detection of a tumor of a urinary colonization system.

Technical solution

 The technical solution adopted by the present invention to solve the technical problem thereof is: a device for detecting urogenital tumors by using genetic information, comprising a reaction module, a signal reaction detection module and a pre-preparation of at least a sequence information of a genitourinary tumor DNA library; a processor module with status information, a reaction module, a signal reaction detection module, and a processor module connection, the reaction module is configured to react with the DNA sample to be tested, and the signal reaction detection module detects the status information of the reaction, and feeds back the status information to the The processor module analyzes the status information and the preset status information according to the feedback.

 The reaction module includes a DNA probe containing sequence information of a genitourinary tumor DNA library and a DNA probe containing control sequence information. The reaction module includes micropores (e.g., nanotubes and microtubules) having coordinates, and the microwells correspond one-to-one with the DNA probes. The reaction module further includes a reaction system including a DNA detection reaction solution and a wash solution. The signal reaction detection module is further connected with a sensor module. The reaction module is a DNA microarray chip comprising a DNA probe containing sequence information of the genitourinary tumor DN A library and a DNA probe containing control sequence information.

 The signal response detection module includes an image sensor for acquiring an image of the reaction module. The processor module is further connected with a display module and an interface module.

A device for detecting urogenital tumors by using genetic information, comprising a reaction module preset with urogenital tumor DNA library sequence information and control sequence information, a signal reaction detection module and a processor module preset with state information, a reaction module The signal reaction detection module and the processor module are sequentially connected, the reaction module is configured to react with the DNA sample to be tested, the signal reaction detection module detects the status information of the reaction, and feeds the status information to the processor module, and the processor module is The feedback status information and preset status information are analyzed. The reaction module has a plurality of coordinate points, each of which is provided with a DNA probe containing information on the genitourinary tumor DNA library sequence or a DNA probe containing control sequence information. The reaction module has a plurality of micropores, each micropore corresponding to one coordinate, and each micropore has a DNA containing urogenital tumor DNA library sequence information or DNA containing control sequence information. [14] A method for detecting a genitourinary tumor using genetic information, comprising the steps of: a) distributing a sample of DNA to be tested on a surface of a DNA microarray chip, and reacting with DNA in a preset DNA probe or microwell; b) Obtain DNA samples and DNA to be tested

 Status information of the probe reaction; c) analysis based on the acquired status information and preset status information. In the step c), the judgment result is obtained by comparing the acquired state information with the preset state information, and the state information is selected from the group consisting of: color, brightness, current on and off, level.

 Beneficial effect

 [15] The beneficial effects of the present invention are: through the reaction module and the DNA to be tested

 The sample reaction, the signal reaction detection module detects the reaction state, the processor module compares the state information and obtains the analysis result, thereby realizing high-throughput automated detection of urogenital tumors, capable of

 Comprehensive analysis of susceptibility to DNA sequence changes in all malignancies in the subject's genome, including prostate cancer, bladder cancer, renal cell carcinoma, and testicular cell tumors.

 Early assessment and prediction of genetic risk in patients with cancer to be measured.

 DRAWINGS

 BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a block diagram showing a configuration of an apparatus for detecting a genitourinary tumor using genetic information in the present embodiment. Fig. 2 is a view showing the configuration of a DNA microarray chip according to the present embodiment.

 Embodiments of the invention

 [17] As shown in FIG. 1 and FIG. 2, the apparatus for detecting urogenital tumors by using genetic information includes a reaction module, a sensor module, a signal reaction detecting module, a processor module, a display module, and an interface module. The reaction module and the sensor module are all connected to the signal reaction detection module; the signal reaction detection module is connected to the processor module; the display module and the interface module are all connected to the processor module. The reaction module is preset with urogenital tumor DNA library sequence information and control sequence information. The sample to be tested is evenly distributed on the surface of the reaction module, and the signal reaction detection module detects the reaction state of the reaction module and the sample to be tested and the feedback information of the sensor module, and is sent to the processor module after preprocessing. The processor module processes and analyzes the calculated result values and sends them to the display module for display or to the interface module for output.

[18] The sample to be tested is taken from the blood or other tissues of the object to be tested (such as hair follicles, etc.), and after special treatment, a DNA sample with better detection characteristics is obtained, and the special treatment is coupled with a fluorescent dye as in the prior art. [19] The reaction module includes a reaction system, at least one DNA probe containing urogenital tumor DNA library sequence information, and at least one DNA probe containing control sequence information, and each urogenital tumor DNA library sequence information corresponds to a control Sequence information, the genitourinary tumor DNA library sequence information such as characteristic DNA sequences of various pathogens of urogenital malignant tumors, such malignant tumors such as prostate cancer, bladder cancer, renal cell carcinoma and testicular cell tumor, the characteristic DNA DNA sequences such as ELAC2, PSA, KLK5, PC A3, ADAM15, STK1 and the like. Each DNA probe corresponds to one coordinate and the DNA probe can be coupled to fluorescein, biotin or other label. The reaction system includes a DNA detection reaction solution and a washing solution.

 [20] The signal response detection module includes an image sensor with a microscope head (eg CCD, CMOS)

 Sensor), after pre-processing (such as photoelectric conversion, AD analog-to-digital conversion), input to the processor module, and the state value of the reaction system state, such as temperature, special ion, humidity, etc., which is fed back by the sensor module Transfer to the processor module after processing.

 [21] The sensor module monitors the temperature, specific ions, humidity, etc. of the reaction system of the reaction module.

 [22] The processor module can be an embedded or PC hardware and software system architecture, which can analyze and process the information transmitted by the signal reaction detection module and the sensor module. The processor module can be built-in image recognition and processing software module, and complete the coordinate confirmation, brightness recognition, color recognition, or check the current on and off, the level of the image of the reaction module to achieve qualitative analysis, and if there is brightness, the coordinates are indicated. The DNA of the spot reacts with the sample to be tested. The DNA sequence consists of four bases, A, T, C, and G, which are paired with 1\C and G. The DNA hybridization reaction is described below as an example. As shown in Figure 2, the DNA sequence of the A-coordinate DNA probe is shown. The DNA sequence of the AATTCG, M coordinate DNA probe is TGCGA. If the A coordinate has brightness, it means there is a complementary sequence (TTAAGC); if the M point has no brightness, it means there is no complementary DNA sequence that reacts with it. (ACGCT). The DNA probe containing the control sequence information of the reaction module is a DNA probe of a normal gene.

 [23] Display module for display, such as CRT, LCD LED

 And other types of displays. The interface module is used to realize the signal connection between the entire detecting device and the outside world, such as various serial communication and network interfaces.

 [24] Detection of genitourinary malignancies using a DNA library:

[25] Reference OMIM (Human Mendelian Inheritance Online, Online Mendelian Inheritance in Man), select N genitourinary tumor DNA library sequence information, and customize the reaction module with DNA library sequence information and control sequence information.

 [26] Taking the tissue containing DNA genetic information such as blood or hair follicles to be tested, after pre-processing, making it a DNA sample with good detection characteristics, the DNA sample is fully matched with the coordinates of the reaction module. The DNA probe is hybridized, and after washing to remove the unreacted DNA sample, the reaction signal is sent to the processor module via the signal reaction detection module. The processor module converts the response signal into an interpretable signal for qualitative analysis of the reaction between the DNA library sequence information in the reaction module and the sample to be tested, thereby interpreting the health level of the genitourinary system of the subject to be tested.

 [27] In the present embodiment, the DNA library sequence information is characteristic DNA information of various pathogens of urogenital malignant tumors, and the reaction module includes DNA probes of a plurality of normal genes as an analysis control, and the sample to be tested and the DNA probe are detected. The reaction of the needle is used for qualitative analysis of the sample to be tested. The reaction module is a DNA microarray chip having a plurality of DN A probes. After the reaction module reacts with the DNA sample to be tested, the state information (such as color, brightness, gray level, current, level) of the reaction module changes, such as the color of the image before the reaction module reacts, the brightness, and the color of the image after the reaction. The brightness is different, the current on/off state or the level is different; the image of the reaction module and the state information of the reaction module are obtained by the signal reaction detection module and fed back to the processor module, and the processor module compares the state information with the preset state information. ,

 The health of the genitourinary system can be analyzed. In the same way, since each DNA sequence of the reaction module has its own coordinates, it is possible to visually determine which gene of the patient is mutated by changing the state information of the coordinate (for example, the DNA probe changes from no brightness to brightness). The reaction module may include only a DNA probe containing information on the sequence of the urinary tract system tumor DNA library, or a DNA probe containing information on the sequence of the genitourinary tumor DNA library and a DNA probe containing control sequence information.

 [28] A method for detecting urogenital tumors using genetic information, comprising the following steps:

 [29] a) uniformly distributing the sample to be tested (which can be coupled with the fluorescent dye) on the surface of the reaction module, and reacting with the DNA in the preset DNA probe or microwell;

 [30] b) The signal reaction detection module preprocesses the detected reaction module and the reaction state information of the sample to be tested, and the information (temperature, special ion, humidity, etc.) fed back by the sensor module to the processor module, the processor The result value calculated by the module is displayed by the display module or output via the interface module.

[31] The above is a further detailed description of the present invention in connection with a specific preferred embodiment, and cannot be recognized. The specific implementation of the invention is limited only to these descriptions. It will be apparent to those skilled in the art that the present invention may be made without departing from the spirit and scope of the invention.

Claims

Claim  [1] A device for detecting urogenital tumors by using genetic information, comprising: a reaction module including at least a sequence information of a genitourinary tumor DNA library, a signal reaction detecting module, and a processor pre-set with state information; The module, the reaction module, the signal reaction detection module and the processor module are connected, the reaction module is configured to react with the DNA sample to be tested, the signal reaction detection module detects the status information of the reaction, and feeds the status information to the processor module, the processor The module analyzes based on the feedback status information and preset status information.  [2] The apparatus for detecting urogenital tumors using genetic information according to claim 1, wherein: the reaction module comprises a DNA probe containing sequence information of a genitourinary tumor DNA library and DNA containing control sequence information. Probe.  [3] The apparatus for detecting urogenital tumors using genetic information according to claim 2, wherein: the reaction module comprises micropores having coordinates, and the micropores are in one-to-one correspondence with the DNA probes.  [4] The apparatus for detecting a tumor of a genitourinary system using genetic information according to claim 1, wherein the reaction module further comprises a reaction system comprising a DNA detecting reaction solution and a washing liquid.  [5] The apparatus for detecting urogenital tumors using genetic information according to claim 5, wherein: the signal reaction detecting module is further connected with a sensor module for feeding back state information of the reaction system.  [6] The apparatus for detecting urogenital tumors using genetic information according to claim 1, wherein: the reaction module is a DNA microarray chip, and the DNA microarray chip comprises a sequence information of a genitourinary tumor DNA library. DNA probe and DNA probe containing control sequence information [7] The apparatus for detecting a genitourinary system tumor using genetic information according to any one of claims 1 to 6, wherein the signal reaction detecting module comprises an image sensor for acquiring an image of the reaction module.  [8] The apparatus for detecting urogenital tumors using genetic information according to claim 7, wherein: the processor module is further connected with a display module and an interface module. [9] A device for detecting urogenital tumors using genetic information, characterized by: including presets a reaction module having a urogenital tumor DNA library sequence information and a control sequence information, a signal reaction detection module, and a processor module preset with state information, the reaction module, the signal reaction detection module, and the processor module are sequentially connected, and the reaction module is used In response to the DNA sample to be tested, the signal reaction detection module detects the status information of the reaction, and feeds the status information to the processor module, and the processor module performs analysis according to the feedback status information and the preset status information. [10] The apparatus for detecting a tumor of a genitourinary system using genetic information according to claim 9, wherein: the reaction module further comprises a reaction system including a DNA detection reaction solution and a washing solution, and the signal reaction The detection module is also connected with a sensor module for feeding back reaction system status information.  [11] The apparatus for detecting urogenital tumors using genetic information according to claim 9 or 10, wherein: the reaction module has a plurality of coordinate points, and each coordinate point is provided with a DNA library containing a genitourinary tumor A DNA probe of sequence information or a DNA probe containing control sequence information.  [12] The apparatus for detecting a tumor of a genitourinary system using genetic information according to claim 9 or 10, wherein: the reaction module has a plurality of micropores, each micropore corresponding to one coordinate, and each micropore DNA containing information on the sequence of the genitourinary tumor DNA library or DNA containing the control sequence information is built in.  [13] The apparatus for detecting a tumor of a genitourinary system using genetic information according to claim 9 or 10, wherein: the signal reaction detecting module includes an image sensor for acquiring an image of a reaction module, and the image sensor acquires a response After the image state information, the processor module analyzes the image state information after the reaction and the preset image state information.  [14] A method for detecting a urogenital tumor using genetic information, comprising: step a) distributing a DNA sample to be tested on a surface of a DNA microarray chip, and a preset DNA probe or a micropore DNA reaction;  b) obtaining state information of the reaction of the DNA sample to be tested with the DNA probe or the DNA in the micropore; c) performing analysis according to the acquired state information and preset state information. [15] The method for detecting a genitourinary system tumor using genetic information according to claim 14, wherein: in the step c), comparing the acquired state information with preset state information As a result of the judgment, the status information is selected from the following: color, brightness, current on and off, high and low levels. The method for detecting a tumor of a genitourinary system using genetic information according to claim 14 or 15, wherein: in the step a), the DNA sequence of the preset DNA probe or the DNA sequence of the DNA in the microwell is selected from the group consisting of : DN of ELAC2, PSAs KLK5, PCA3, ADAM 15s STK1 gene A sequence.