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Currently, liquid biopsy method is mainly used for tumor detection based on genomic molecular alterations in vitro. Liquid biopsy is superior to traditional tissue biopsy techniques and its diagnosis time of disease and repeated diagnosis of liquid biopsy are new breakthroughs in clinical application. Liquid biopsy method can be used to detect most human disease based on genetic biomarkers from body fluids, among which, special biomarkers in blood and cerebrospinal fluid (CSF) samples are the main research objects, and have made good achievements in preliminary clinical applications. The application of optical spectroscopy in the field of liquid biopsy has aroused great interest among researchers and demonstrated the potential of its clinical application for oncology. The aim of this study is to reveal the optical spectroscopic characteristics of the main biochemical components of CSF of brain tumor using visible resonance Raman (VRR) spectroscopy ex vivo. Tumor-associated proteins, glucose, lactate and other metabolites released to CSF can be used as markers for liquid biopsy. We studied the VRR spectra of CSF samples from 7 types of brain tumor patients. The characteristic VRR modes that were found and may be used as a combination of multiple analyte biomarkers include amyloid-β and tau protein, excess neurotransmitters such as glutamic acid derived from the exchange with interstitial fluid (ISF), DNA, glucose, lactate, etc. for optical liquid biopsy analyses. Another interesting finding was that CSF of different types of tumors showed different images similar to the crystallization of water under the optical microscope. Considering our previous study, the current study on CSF provides another proof that the VRR system can provide a complete scan region of 200 - 4000cm-1 as a clinical tool for non-invasive diagnosis of brain disease.
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