TY - JOUR
T1 - Noninvasive Detection of Bladder Cancer Markers Based on Gold Nanomushrooms and Sandwich Immunoassays
AU - Yang, Zi Yi
AU - Chang, Wen Huei
AU - Chiu, Yi Chun
AU - Lin, Chun Hung
N1 - Funding Information:
This study was supported by the Ministry of Science and Technology (MOST) of Taiwan under grant nos. MOST 105-2221-E-006-139- and MOST 106-2221-E-006-169-MY2. The authors gratefully acknowledge the use of EM025200, ESCA000200, EM000900, and ICP000400 belonging to the Core Facility Center of National Cheng Kung University, the shaped e-beam direct write system belonging to the Taiwan Semiconductor Research Institute, and DLS/zeta potenti al instrument in Prof. Chih-Chia Huang’s Lab, Department of Photonics, National Cheng Kung University.
Publisher Copyright:
© 2023 American Chemical Society.
PY - 2023/4/14
Y1 - 2023/4/14
N2 - Bladder cancer is one of the most common malignancies in the urinary system. Cystoscopy is the traditional standard diagnostic method for bladder cancer with subsequent biopsy or surgery. However, this method is uncomfortable for most patients because it requires anesthesia and possibly causes infections. Because of the high recurrence rate of bladder cancer, a rapid, low-cost, high-sensitivity, and noninvasive sensing method is needed. This study employed gold nanomushroom (AuNM) chips for bladder cancer biomarker detection, combining the benefits of sandwich immunoassay and localized surface plasmon resonance (LSPR) sensing. With a metal nanotransfer printing technique, which is cheap and straightforward, the AuNMs were patterned on flexible polycarbonate (PC) sheets. The gold caps stood above PC stems and provided ample spatial areas for capturing the biomarkers to be sensed. Three biomarkers served as the antigens and analytes, including human complement factor H (CFH), hyaluronic acid (HA), and nuclear matrix protein 22 (NMP22). Different antibodies, against the same biomarker, were covalently conjugated to AuNMs or gold nanoparticles, respectively. When the antibody-antigen-antibody sandwich structure formed, the plasmonic coupling between the AuNM surface and the gold nanoparticles significantly enhanced LSPR signals. The LSPR red shifts correlated quantitatively with the concentrations of the biomarkers. The limits of detection were 6.5, 8.3, and 7.0 pg/mL for CFH, HA, and NMP22, respectively. The chip’s specificity was tested and confirmed, excluding the nonspecific binding and false-positive possibility. The sensing performance of this sandwich immunoassay-based AuNM chip was better than that of the commercialized enzyme-linked immunosorbent assay. It provided a rapid, label-free, and easy operating platform for diagnosing and monitoring bladder cancer.
AB - Bladder cancer is one of the most common malignancies in the urinary system. Cystoscopy is the traditional standard diagnostic method for bladder cancer with subsequent biopsy or surgery. However, this method is uncomfortable for most patients because it requires anesthesia and possibly causes infections. Because of the high recurrence rate of bladder cancer, a rapid, low-cost, high-sensitivity, and noninvasive sensing method is needed. This study employed gold nanomushroom (AuNM) chips for bladder cancer biomarker detection, combining the benefits of sandwich immunoassay and localized surface plasmon resonance (LSPR) sensing. With a metal nanotransfer printing technique, which is cheap and straightforward, the AuNMs were patterned on flexible polycarbonate (PC) sheets. The gold caps stood above PC stems and provided ample spatial areas for capturing the biomarkers to be sensed. Three biomarkers served as the antigens and analytes, including human complement factor H (CFH), hyaluronic acid (HA), and nuclear matrix protein 22 (NMP22). Different antibodies, against the same biomarker, were covalently conjugated to AuNMs or gold nanoparticles, respectively. When the antibody-antigen-antibody sandwich structure formed, the plasmonic coupling between the AuNM surface and the gold nanoparticles significantly enhanced LSPR signals. The LSPR red shifts correlated quantitatively with the concentrations of the biomarkers. The limits of detection were 6.5, 8.3, and 7.0 pg/mL for CFH, HA, and NMP22, respectively. The chip’s specificity was tested and confirmed, excluding the nonspecific binding and false-positive possibility. The sensing performance of this sandwich immunoassay-based AuNM chip was better than that of the commercialized enzyme-linked immunosorbent assay. It provided a rapid, label-free, and easy operating platform for diagnosing and monitoring bladder cancer.
UR - http://www.scopus.com/inward/record.url?scp=85151262872&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85151262872&partnerID=8YFLogxK
U2 - 10.1021/acsanm.2c05600
DO - 10.1021/acsanm.2c05600
M3 - Article
AN - SCOPUS:85151262872
SN - 2574-0970
VL - 6
SP - 5557
EP - 5567
JO - ACS Applied Nano Materials
JF - ACS Applied Nano Materials
IS - 7
ER -