An exploration of nucleic acid liquid biopsy using a glucose meter

Abstract

The development of non-invasive techniques for the diagnosis of cancer, characterization of mutation and monitoring treatment response could greatly reduce the morbidity and mortality caused by cancer. Nevertheless, the extremely low amount of cell free nucleic acids makes liquid biopsy a very challenging task. Herein, taking advantage of the pocket size, reliable quantitative results and simple operation of the pocket-sized personal glucose meter (PGM), we report an approach of circulating microRNA-21 (miR-21) detection with high precision and low cost. Via target-induced release of invertase from the DNA–invertase conjugate, which could convert sucrose into glucose, the detection of miR-21 in serum was linked to PGM readings. Combining the DNAzyme feedback amplification (DFA) program and highly efficient enzymatic turnover, an ultralow detection limit of 7 × 10⁻¹⁶ M for miR-21 was achieved using a PGM as the reporter. The high sensitivity and selectivity of the proposed method meets the requirement of quantifying cell free nucleic acids in serum. In addition, this approach fills the shortage of quantitative RT-PCR and next-generation sequencing in quantifying miRNAs with a short length and greatly reduces the cost of detection. We believe that widely used personal diagnosis devices could hold an important place in the booming area of liquid biopsy.