Li, Cheng YiCheng YiLiSANDY HUEY-JEN HSUChang, Cheng ChungCheng ChungChangWang, Gou JenGou JenWang2021-11-152021-11-152021-10-011530437Xhttps://scholars.lib.ntu.edu.tw/handle/123456789/586673Biliary atresia is the most common cause of childhood liver disease and is the main cause of liver replacement. The use of an effective early screening technique can efficiently improve the therapeutic effect on children with biliary atresia, especially those in the remote rural areas. This study introduces a novel method for detecting direct bilirubin by Raman spectroscopy using composite surface-enhanced Raman spectroscopy (SERS) chips. These chips were created by spreading silver nanowires on the nanostructure surface of an anodic aluminum oxide substrate. Experimental results demonstrated that the detection limit of direct bilirubin concentration vastly improved far below the disease criteria of bilirubin in adults and infants. Meanwhile, using only $10~\mu \text{L}$ of direct bilirubin, a wide detection range from 10-7 to 10-4 M was obtained, covering the clinic reference range with R2 of 0.98336 at the peak value of 1.616 cm-1. Furthermore, the results revealed that the proposed composite SERS substrates possessed good statistical relative standard deviation and reproducibility (N = 3) of 4.6% and 2.2%, respectively. Thus, the composite SERS chip combined with the Raman spectroscopy approach can be integrated with portable Raman spectrometer for the effective clinical detection of direct bilirubin.composite SERS substrate | Direct bilirubin detection | surface-enhanced Raman spectroscopy[SDGs]SDG3journal article10.1109/JSEN.2021.31020842-s2.0-85112628332https://api.elsevier.com/content/abstract/scopus_id/85112628332