| Purpose: The appearance of nipple discharge is significant in breast patients for clinical diagnosis.It can be the earliest clinical symptom of breast duct cancer.In order to develop methods targeted for patients with nipple discharge to assess the benign and malignant breast diseases and improve the specificity of detection and reduce unnecessary mastectomy for patients.We designed a novel targeted detection probe based on surface-enhanced Raman spectroscopy technology for clinical patients.In vitro detection of carcinoembryonic antigen(CEA)in nipple discharge can minimize the invasiveness of the detection method.This technology can improve the accuracy of novel non-invasive diagnostic techniques to assist doctors in distinguishing between benign and malignant nipple discharge and predict early breast cancer.Method: Herein,a simple surface-enhanced Raman spectroscopy technique was used to detect nipple discharge.The Raman nanoprobe was synthesized combined with biological immunology and chemical method,and the surface-functionalized nanomicrosphere assembly of targeted specific antibodies was used to identify the targeted CEA.Utilizing the plasma Raman enhancement effect of colloidal silver nanospheres(Ag NPs),the targeting antibody(Ab1)that can specifically recognize CEA is connected,and the Raman signaling molecule 4-aminobiphenyl(4-ABP)was connected.The signal peak was enhanced,and silver nano-Raman probes(Ag NPs-Ab1/4ABP)were made.Magnetic nanospheres(MNs)are used to connect the targeting antibody(Ab2)that specifically recognizes CEA to make magnetic nano-capture probes(MNs-Ab2).Due to the specific recognition interaction between the protein and the targeting antibody,a "sandwich" was formed,which can specifically identify CEA in nipple discharge.The accurate and sensitive combination takes place in the solution environment.Results: We detected the content of CEA in nipple discharge in 13 patients by ELISA kit.In these results,we found that the level of CEA in nipple discharge is significantly positively correlated with the degree of breast lesions.The targeted Raman probe we designed detected the CEA content in the nipple discharge of 10 patients successfully.And the Raman probe had a good linear recognition at a concentration of0 ng/m L to 20 ng/m L.This method fills the gap in the detection technology for patients with nipple discharge.In addition,the content of CEA in nipple discharge detected by our Raman probe method was compared with the enzyme-linked immunosorbent assay(ELISA)method,and our designed detection can replace it.Conclusion: For the first time,we applied surface-enhanced Raman spectroscopy to detect the content of carcinoembryonic antigen in nipple discharge.This technical method has the advantages of high specificity,low dosage,less human error introduced,strong sensitivity,high acceptability,visualization of detection results,and ease of large-scale detection.Clinically,it can be used to evaluate the benign and malignant of nipple discharge,and it is of great significance for the detection of early potential breast cancer with small lesions.At the same time,it also provides reference ideas for the early detection of other secretory diseases. |