Anal. Chem.: fluorescence sensor array based on nano metal organic framework for pathological screening of colon cancer

Colon cancer is one of the most common cancers in the world, and the fourth most common cause of cancer-related death Although blood tests using multiple cancer biomarkers such as CEA or CA199 have been used for clinical diagnosis of this cancer, because these biomarkers also exist in some other diseases, there is not enough sensitivity and specificity to make a clear diagnosis Histopathological examination is still the gold standard for the diagnosis of colon cancer It can provide more information for the study of cancer performance, including the occurrence, differentiation, invasion and metastasis of cancer, so as to guide the best treatment and monitor the prognosis information However, tissue biopsy is the process of analyzing complex samples, which involves the extraction of cells or tissues and the analysis of pathological sections to determine the presence and extent of cancer In addition, the process of paraffin embedding and tissue sectioning needs special operation of trained experimenters, and it is very time-consuming In most cases, these medical results depend on the individual judgment of the pathologist, and subjectivity can easily lead to inaccurate diagnosis results Therefore, it is urgent to develop reasonable methods for simple, rapid and accurate histopathological examination of colon cancer Recently, Professor Li Genxi of Nanjing University and Professor Liu Ping of the First Affiliated Hospital of Nanjing Medical University worked together to propose a sensor array based on three kinds of nano metal organic frameworks (nmofs), which can effectively identify normal and colon cancer pathological tissues This method uses the whole cell proteomic characteristics of colon tissue and the interaction between three structurally stable nmofs to carry out simple, rapid and accurate histopathological screening of colon cancer Relevant achievements were published on the international authoritative journal of Analytical Chemistry (DOI: 10.1021 / ACS Anlchem 9b02381) with the title of "sensorarray fabricated with nanoscale metal organic frameworks for the histopathological examination of colon cancer" Figure 1 sensor array based on three kinds of nano metal organic framework (source: anal Chem.) firstly, the author prepared three kinds of nano MOFs: Cu MOFs, Fe MOFs, Zr MOFs, and characterized them by powder X-ray diffraction (PXRD) and transmission electron microscopy (TEM) Among them, Cu nmofs is a spherical nanostructure with an average diameter of 200 nm (Fig 2b); Fe MOFs is a typical octahedral nanostructure with a particle size of 220-270 nm (Fig 2D); Zr MOFs is a rod-shaped nanoparticle with an average length of about 460 nm and a width of about 110 nm (Fig 2F) Fig 2 PXRD and TEM characterization of three kinds of nmofs: Cu MOFs (A and b), f e MOFs (C and D), Zr MOFs (E and F) (source: anal Chem.) then, the author constructed the sensor array The DNA labeled with 5-carboxytetramethylrhodamine was incubated with different nmofs, and then fluorescence titration was performed When nmofs was added, the fluorescence signal decreased significantly at 570 nm Based on the selective noncovalent interaction between these components and DNA adsorbed nmofs, a sensor array was designed and constructed Then, the three kinds of nmofs were selected as scaffolds to adsorb two kinds of fluorescence labeled ssDNA and nano quenching agents for signal transduction SsDNA is adsorbed on nmofs by π - π stacking to form six recognition elements (np1-np6) to construct sensor array, which is quenched in varying degrees by remote energy transfer Then the author added the analyte, because there are many hydrophobic and hydrophilic sites on the surface of the protein, they will interact with the organic parts or accessible coordination sites on the surface of nmofs through intermolecular force, ssDNA will release DNA from the surface of nmofs through binding competition, resulting in the change of fluorescence intensity In this paper, LDA was used to identify the fingerprints for histopathological screening of colon cancer, which improved the efficiency of pathological screening of colon cancer Finally, the colon cells cultured in vitro were introduced into the sensor array to further verify the feasibility of the method and screen the actual samples Under the same conditions, the authors incubated the probe with different cell types to obtain fluorescence response data (Figure 3a) Two typical factors (69.21% and 30.79%) were obtained by using the original data of fluorescence signal change collected by LDA analysis, and the fluorescence change fingerprint relative to the sensor system was obtained (Fig 3b) The three fluorescence fingerprint regions are located in different quadrants, and there is no overlap between the 95% confidence ellipse regions Therefore, proteins, amphiphilic phospholipids and carbohydrates can distinguish cancer colon cells from normal cells At the same concentration of protein (150 ng), the sample was added to the test solution containing nmofs / DNA probe After incubation for 30 min, the fluorescence intensity was measured to obtain the average fluorescence intensity diagram (Fig 3C) Using the original data of fluorescence signal changes collected by LDA analysis, the cancer tissue samples were divided into the right area of the standard score map, while the other two samples were divided into the left area and there was no overlap between them (Figure 3D), which proved the potential difference of protein expression The application of the sensor array in colon cancer screening has clinical specificity and accuracy Figure 3 response of cell lines and tissue samples based on array (source: anal Chem.) Summary: Professor Li Genxi's team of Nanjing University and Professor Liu Ping of the First Affiliated Hospital of Nanjing Medical University worked together to propose a DNA element based nmofs component to construct a fluorescence sensor array for fluorescence analysis of colorectal cancer tissue Using sensor array, researchers can quickly identify various analytes in standard samples and complex clinical samples by LDA, and this method has high sensitivity and accuracy, greatly improving the diagnosis efficiency This method realizes the preliminary clinical diagnosis of unknown colorectal cancer, which provides a supplementary strategy for the traditional histopathological diagnosis.