Ultrasensitive Detection of Serum MicroRNA Using Branched DNA-Based SERS Platform Combining Simultaneous Detection of α-Fetoprotein for Early Diagnosis of Liver Cancer

Abstract

We provided an ultrasensitive sensing strategy for microRNA detection by first employing branched DNA. With the aid of microcontact printing, we realized the multiplex sensing of different kinds of liver cancer biomarkers: microRNA and protein simultaneously. Delicately designed branched DNA included multiple complementary sticky ends as probe to microRNA capture and the double-stranded rigid branched core to increase the active sticky-ends distance and expose more DNA probes for sensitivity. The branched DNA enables 2 orders of magnitude increase in sensitivity for microRNA detection over single-stranded DNA. The limit of detection reaches as low as 10 attomolar (S/N = 3) for miR-223 and 10–12 M for α-fetoprotein. In addition, this system shows high selectivity and appropriate reproducibility (the relative standard deviation is less than 20%) in physiological media. Serum samples are tested and the results of α-fetoprotein are in good agreement with the current gold-standard method, electrochemiluminescence immunoassay analyzer. The results suggest the reliability of this approach in physiological media and show high potential in the sensing of low abundant microRNA in serum, especially for early diagnosis of primary liver cancers.

Surface-Enhanced Raman Spectroscopy in Cancer Diagnosis, Prognosis and Monitoring

“…In a similar fashion as for other cancer biomarkers, various strategies for SERS analysis has been applied for detection of multiple proteins exploiting SEPs as labelling agents and, mainly, antibody/aptamers as surface elements for selective target capturing [52]. In addition to these approaches, a novel hybrid SERS sensing scheme is progressively emerging as an efficient strategy for ultrasensitive quantification of proteins in complex biological matrices by profiting from the large target molecular size [58,69,70,71,72]. Here, the surface recognition elements are derivatized with a SERS-active moiety that firmly binds the plasmonic surface and acts as an efficient signal transducer by yielding an intense vibrational signature.…”

Rapid, quantitative and ultra-sensitive detection of cancer biomarker by a SERRS-based lateral flow immunoassay using bovine serum albumin coated Au nanorods

“…It should be noted that AFP antigens (or other cancer biomarkers) are secreted by human cells, and exhibit a baseline concentration in human blood, which will be obviously elevated in case of HCC or other liver cancer-related disease. [47][48][49] Owing to the low amount of AFP (<20 ng mL À1 ) that naturally exists in normal human blood or serum, human biological samples were excluded from this study. In the proposed SERRS-strip, a pair of mouse anti-human AFP antibodies was used as the specic antibody for human AFP detection, and wouldn't immune bind to any components in bovine serum.…”

Recent advances in surface‑enhanced Raman spectroscopy based liquid biopsy for colorectal cancer (Review)

“…SERS analysis can also be applied for the detection of proteins, as for other biomarkers in cancer (44). Compared to the classic SERS approach, a new SERS hybrid detection method was developed for protein quantification, taking into account the high dimensions of these molecules (63,64). Using this method, some elements from the surface of the molecules can be recognized by an active part of SERS that binds firmly the plasmonic surface and acts as an efficient transducer of signal by producing an intense vibrational signature.…”