Ultrasensitive Detection of Cancer Cells Combining Enzymatic Signal Amplification with an Aerolysin Nanopore

Anal Chem. 2018 Jan 2;90(1):1029-1034. doi: 10.1021/acs.analchem.7b04584. Epub 2017 Dec 19.

Abstract

Sensitive detection of cancer cells at extremely low concentrations would greatly facilitate the screening and early diagnosis of cancer. Herein, we present a novel nanopore-based strategy for ultrasensitive detection of Ramos cells (human Burkitt's lymphoma cells), by combining the enzymatic signal amplification with an aerolysin nanopore sensor. In this assay, an aptamer for Ramos cells was prehybridized with a short complementary DNA. The presence of target cells causes the target-aptamer complex to unwind to free the complementary DNA, which would subsequently trigger the enzymatic cycling amplification. This process eventually generated a large number of output DNA, which could quantitatively produce characteristic current events when translocated through aerolysin. The proposed method exhibits excellent sensitivity, and as few as 5 Ramos cells could be detected. With good selectivity, the approach can allow for the determination of cancer cells in human serum, offering a powerful tool for biomedical research and clinical diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aptamers, Nucleotide / genetics
  • Bacillus Phages / enzymology
  • Bacterial Toxins / chemistry*
  • Biological Assay / methods*
  • Brevibacillus / enzymology
  • Burkitt Lymphoma / diagnosis*
  • Cell Line, Tumor
  • DNA / chemistry
  • DNA / genetics
  • DNA-Directed DNA Polymerase / chemistry
  • Endodeoxyribonucleases / chemistry
  • Humans
  • Nanopores*
  • Nucleic Acid Amplification Techniques / methods*
  • Nucleic Acid Hybridization
  • Pore Forming Cytotoxic Proteins / chemistry*

Substances

  • Aptamers, Nucleotide
  • Bacterial Toxins
  • Pore Forming Cytotoxic Proteins
  • aerolysin
  • DNA
  • DNA-Directed DNA Polymerase
  • Endodeoxyribonucleases