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.