A research team led by Prof. Wu Haichen from the Institute of Chemistry, Chinese Academy of Sciences (CAS), and Prof. Liu Lei from Xihua University developed a nanopore-based enzyme-linked immunosorbent assay (NELISA) for cancer biomarker detection (Figure 1).

Early diagnosis of cancer is crucial for improving patient prognosis and significantly reducing mortality rates. Compared with radiological and invasive diagnostic methods, the detection of cancer biomarkers in body fluids—being less harmful to the body—is more suitable for early-stage diagnosis. Serum cancer biomarker detection has been used as a supportive tool in clinical diagnosis and treatment since the mid-20th century. Among various methods, enzyme-linked immunosorbent assay (ELISA) is the most widely used and currently regarded as the gold standard for body fluid biomarker detection.

However, traditional ELISA relies on colorimetric signal output, which limits its sensitivity and multiplexing capability, making it insufficient for ultra-early cancer detection. Although recent technological advancements have somewhat improved the performance of conventional ELISA, it still falls short of meeting the stringent demands of early-stage disease diagnosis.

The researchers used a peptide probe, FGXD₈⊂CB[7], which contains various enzyme-responsive groups, as an enzymatic substrate in place of conventional chromogenic substrates. After immune complex formation, an enzymatic reaction was carried out. The reaction products were then analyzed via translocation experiments using wild-type α-hemolysin nanopores. By statistically analyzing the frequency of current signals generated by FGXD₈⊂CB[7], the researchers achieved quantitative detection of biomarker concentrations in the samples.

This study integrates the strengths of ELISA and nanopore sensing technologies to create a highly sensitive, low detection limit (3–4 orders of magnitude lower than conventional methods), and multiplexed assay with strong anti-interference capability. It is expected to provide a powerful new tool for early cancer screening based on body fluid biomarker detection.

This study was published in Nature Nanotechnology

Figure 1. The design of peptide probes and procedure for NELISA

Contact:

Prof. Haichen Wu

Institute of Chemistry, Chinese Academy of Sciences

Email: haichenwu@iccas.ac.cn