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CN-121995058-A - Detection method and system for early diagnosis biomarker of gestational liver injury

CN121995058ACN 121995058 ACN121995058 ACN 121995058ACN-121995058-A

Abstract

The invention belongs to the technical field of biomarker detection, and discloses a biomarker detection method for early diagnosis of liver injury in gestation, which solves the problems of dependence on large laboratory equipment, long time consumption and insufficient single index accuracy in the conventional diagnosis of liver injury in gestation, can realize rapid early screening of basic medical institutions, reduces the risks of serious complications such as liver failure in gestation and the like, and has the advantages that each module is connected through a plug-in interface, the assembly time is less than or equal to 2 minutes, the weight of the whole device is only 150g, the size is equivalent to a mobile phone, and the method is suitable for primary screening scenes of basic clinics, community hospitals and houses, so that the whole process of sampling-detection-result-out is completed within 30 minutes.

Inventors

  • ZHENG JIAYONG

Assignees

  • 温州市人民医院

Dates

Publication Date
20260508
Application Date
20251219

Claims (10)

  1. 1. A method for detecting early diagnosis biomarkers of gestational liver injury, comprising: The method comprises the steps of obtaining a pregnant fingertip blood sample, carrying out plasma separation, respectively introducing the separated sample into three aptamer-modified nanogold probe systems, enabling specific micro ribonucleic acid, hepatic cell membrane injury factors and inflammation-associated proteins of liver injury in the sample to be combined with corresponding aptamers, generating fluorescence signal enhancement after the aptamers are combined with the markers, calculating the concentration of the corresponding markers according to the intensities of the three types of fluorescence signals, and grading the risk of liver injury in the gestation period according to an established correlation model of the fluorescence intensity and the liver injury degree.
  2. 2. The method of claim 1, wherein the marker screening is based on gestational population cohort data and wherein the screening for gestational liver injury specific microribonucleic acid, hepatocyte membrane damage factor, and inflammation-associated protein comprises a two-dimensional combination of markers.
  3. 3. The method of claim 1, wherein the aptamer-modified nanogold probe is in a fluorescence quenching state when the tag is unbound, and wherein the tag binds such that the fluorophore is separated from the quenching distance, producing a detectable fluorescence enhancement signal.
  4. 4. The method of claim 1, wherein plasma separation is accomplished by a laminar flow separation structure of microfluidic channels, which inertly deflects blood cells out of the separation zone, thereby obtaining a supernatant for detection.
  5. 5. The method of claim 1, wherein the risk classification is based on the marker concentration corresponding to the low risk, medium risk and high risk intervals, respectively, and the classification output is achieved by a mapping relationship between fluorescence intensity and concentration.
  6. 6. A biomarker detection system for performing the early diagnosis of gestational liver injury method of claim 1, comprising: The device comprises a sample processing module, a detection reaction module, a signal acquisition module, a data processing module and a display module, wherein the sample processing module is used for collecting fingertip blood and separating blood plasma, the detection reaction module comprises three detection channels which are physically separated, an aptamer modified nano gold probe and a fluorescent group corresponding to a marker are pre-coated in each channel, the signal acquisition module is used for carrying out optical excitation and intensity acquisition on fluorescent signals generated in each detection channel, the data processing module is used for calculating the marker concentration according to the acquired fluorescent intensity and carrying out liver injury risk classification, and the display module is used for outputting detection results.
  7. 7. The system of claim 6, wherein the sample processing module comprises a microfluidic chip unit, and wherein the automatic separation and quantitative transport of plasma is achieved by defining a channel cross section and a flow velocity profile within the chip.
  8. 8. The system of claim 6, wherein three detection channels are used for detecting liver injury specific microribonucleic acid, liver cell membrane injury factor and inflammation-associated protein during gestation, respectively, and the three channels are isolated from each other to avoid cross reaction interference.
  9. 9. The system of claim 6, wherein the signal acquisition module comprises a light source excitation unit for illuminating each detection channel and a photo-electric sensing unit for acquiring fluorescent intensity at regular time intervals and outputting signal values.
  10. 10. The system of claim 6, wherein the data processing module stores a nonlinear conversion model between fluorescence intensity and marker concentration and generates a risk classification result based on the model in combination with a marker threshold interval.

Description

Detection method and system for early diagnosis biomarker of gestational liver injury Technical Field The invention belongs to the technical field of biomarker detection, and particularly relates to a method and a system for detecting early diagnosis biomarkers of liver injury in gestation period. Background Prior art one WO2017210147A1 (LIVER DISEASE-related biomarkers and methods of use thereof) The disclosure discloses a group of biomarker combinations related to liver diseases (including liver fibrosis, cirrhosis, fatty liver, etc.), and is used for diagnosing, monitoring liver disease states, distinguishing liver disease types or stages. The technical problems are that (1) the literature is mainly focused on early diagnosis of general population of liver diseases, is not adapted to a special physiological state of 'gestation period', is not used for describing that a sample is a pregnant woman population or a special environment of gestation period, (2) the detection marker combination of the literature covers liver injury related indexes, but does not definitely comprise a double-dimensional (liver injury-inflammation) combination of 'micro ribonucleic acid + liver cell membrane injury factors + inflammation related proteins', and does not embody an innovative detection mechanism of nano gold probe + fluorescence quenching, (3) in terms of sample acquisition and detection flow, the industrial friendly schemes of portability, small blood volume sampling, microfluidic automatic separation and the like are not highlighted in the disclosure, so that the technology is limited in application in a basic level or pregnancy period rapid screening scene. Prior art II US20100196942A1 (Biomarkers of liver injury) The application discloses a series of new, sensitive and specific liver injury markers, including enzymes related to liver ischemia, urea/nitric oxide circulation related enzymes, microstructure disruption related products and the like, which are used for diagnosis and monitoring of liver injury. The technical problem is that (1) the application scenario of the literature is mainly a disease model for liver ischemia and hepatocyte injury guidance, but not a specific crowd with gestational liver injury although aiming at liver injury detection. The pregnancy liver injury is usually not considered along with pregnancy related physiological changes (such as hormone level, hemodynamics and blood plasma component change), more detection methods still depend on traditional biochemical detection or enzyme activity detection, a novel signal amplification mechanism of a nanogold-aptamer-fluorescence quenching technology is not involved, and (3) in sample adaptation (such as fingertip blood, small-volume blood plasma separation and microfluidic chip) and risk grading output, the method is not deeply described, and only marker-liver injury related detection is not used, so that the method lacks systematic design of industrialization easy operation and rapid output risk grade. From the above analysis, it can be seen that, although the two prior arts are related to the field of "liver injury detection", the following common technical gap exists: the scene suitability is insufficient, and the crowd with the unique physiological background is not specially oriented to gestation. The innovation of the detection system is incomplete, and a scheme for combining a three-marker combination of micro ribonucleic acid, membrane injury factor and inflammatory protein and a nano gold aptamer fluorescence mechanism is lacking. The industrialization application capability is weak, and the process optimization in the aspects of sample collection, separation, portable detection, risk classification output and the like is lacking. Therefore, the scheme is innovative in layout at the notch, and is designed for early screening of liver injury in gestation period, fingertip sampling with small blood volume, microfluidic separation, nano gold-fluorescence quenching system, multi-marker combination and risk grading output, so that the method has stronger novelty and creativity. Disclosure of Invention Aiming at the problems existing in the prior art, the invention provides a method for detecting early diagnosis biomarkers of liver injury in gestation period. The invention is realized in such a way that the detection method of the early diagnosis biomarker for the liver injury in gestation period comprises the following steps: step 1, screening and combining markers; step2, innovating a detection method; Step 3, sample adaptation optimization; And 4, judging results and grading risks. Further, the marker screening and combining: through clinical queue research, 3 high specificity markers, namely, liver injury specific microRNA (such as miR-122) in gestation period, liver cell membrane injury factors (such as glutathione S transferase) and inflammation associated proteins (such as IL-6) are screened out, so that a liver injury-inflammation