Blood analysis is crucial for early cancer screening and improving patient survival rates. However, developing an effective strategy for early cancer detection using high-throughput blood analysis is still challenging. Herein, a novel automatic super-hydrophobic platform is developed together with a deep learning (DL)-based label-free serum and surface-enhanced Raman scattering (SERS), along with an automatic high-throughput Raman spectrometer to build an effective point-of-care diagnosis system. A total of 695 high-quality serum SERS spectra are obtained from 203 healthy volunteers, 77 leukemia M5, 94 hepatitis B virus, and 321 breast cancer patients. Serum SERS signals from the normal (n = 183) and patient (n = 443) groups are used to assess the DL model, which classify them with a maximum accuracy of 100%. Furthermore, when SERS is combined with DL, it exhibits excellent diagnostic accuracy (98.6%) for the external held-out test set, indicating that this method can be used to develop a high throughput, rapid, and label-free tool for screening diseases.

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The present study evaluated the capability of saliva analysis combining membrane protein purification with surface-enhanced Raman spectroscopy (SERS) for noninvasive detection of nasopharyngeal carcinoma (NPC). A rapid and convenient protein purification method based on cellulose acetate membrane was developed. A total of 659 high-quality SERS spectra were acquired from purified proteins extracted from the saliva samples of 170 patients with pathologically confirmed NPC and 71 healthy volunteers. Spectral analysis of those saliva protein SERS spectra revealed specific changes in some biochemical compositions, which were possibly associated with NPC transformation. Furthermore, principal component analysis combined with linear discriminant analysis (PCA-LDA) was utilized to analyze and classify the saliva protein SERS spectra from NPC and healthy subjects. Diagnostic sensitivity of 70.7%, specificity of 70.3%, and diagnostic accuracy of 70.5% could be achieved by PCA-LDA for NPC identification. These results show that this assay based on saliva protein SERS analysis holds promising potential for developing a rapid, noninvasive, and convenient clinical tool for NPC screening.

Modified nucleoside in urine samples is one of the most common biomarkers for cancer screening. Therefore, we developed a novel detection method for modified nucleoside detection in human urine. In this work, the modified nucleoside from real cancer patient's urine samples was first separated and purified using the affinity chromatography (AC) technology relying on its specific adsorption capacity. Then, surface-enhanced Raman spectroscopy (SERS) technology with the capability of single molecular detection was used to sensitively characterize the biomolecular features of modified nucleoside. A total of 141 high-quality SERS spectra of urinary modified nucleoside can be obtained from 50 gastric cancer patients and 43 breast cancer patients, as well as 48 healthy volunteers. Using principal component analysis combined with linear discriminant analysis (PCA-LDA), the diagnostic sensitivities for identifying gastric cancer vs normal, breast cancer vs normal, gastric cancer vs breast cancer were 84.0%, 76.7% and 82.0%, respectively, and the corresponding diagnostic specificities for each combination were 95.8%, 87.5% and 90.7%, respectively. These results show that this novel method based on urinary modified nucleoside detection combining AC and SERS technologies holds promising potential for developing a specific, non-invasive and label-free tool for cancer screening. K E Y W O R D S affinity chromatography, cancer screening, modified nucleoside, surfaceenhanced Raman spectroscopy