Detection of cancer biomarkers using the STMBJ single-molecule conductance approach. (a) Liquid biopsy samples contain circulating nucleic acids that can be detected with a complementary DNA probe capable of binding to STM electrodes. (b) STMBJ detection of the hybridized biomarker, resulting in a step in the conductance–distance signal. (c) Example of collected conductance–distance curves. Control phosphate buffer solution (black), green: example raw data curves collected from the G12C sample. (d) Histogram built from curves with steps (black: Phosphate buffer blank, green: G12C RNA sample), 118 from a total 5399 curves acquired in the experiment. Credit: Scientific Reports, doi: https://doi.org/10.1038/s41598-023-39450-6

Electrical detection of KRAS mutations. (a) Sequences for G12C 18nt mismatch and perfect match. (b) Example conductance versus distance curves (Black: blank, Blue: mismatch, Green: perfect match). (c) Histograms for G12C mismatch (379 from a total 5203 curves acquired) and perfect match (212 from a total 13,958 curves acquired) overlapped with phosphate buffer blank (Blue: G12C 18nt mismatch, Green: G12C 18nt perfect match, Black: phosphate buffer blank). (d) Sequences for G12V 18nt mismatch (healthy) and perfect match (cancerous). (e) Raw conductance versus distance curves (Black: blank, Purple: mismatch, Light blue Blue: perfect match). (f) Histograms for G12V mismatch (75 from a total 5024 curves acquired) and perfect match (116 from a total 10,159 curves acquired) overlapped with phosphate buffer blank (Purple: G12V 18nt mismatch, Light blue: G12V 18nt perfect match, Gray: phosphate buffer blank). Credit: Scientific Reports, doi: https://doi.org/10.1038/s41598-023-39450-6

High specificity of the STMBJ approach for cancer detection: In situ hybridization for perfect match G12C. (a) Histogram for blank phosphate buffer (3 from a total 1150 curves acquired). (b) Histogram for G12C DNA probe (3 from a total 661 curves acquired). (c) Conductance histogram including both G12C and wild-type DNA:RNA hybrids (111 from a total 5631 curves acquired). Credit: Scientific Reports, doi: https://doi.org/10.1038/s41598-023-39450-6

High sensitivity of the STMBJ approach for cancer detection. (a) Conductance histograms for G12C titration experiments (concentration varies from 300 μM to 0. The control experiment in phosphate buffer solution (black) shows no peaks in the histogram. (b) Limit of Detection (LoD), Example of SNR calculation for a 6 pM concentration sample. (c) Average SNR for each concentration (with a linear fit) to get the concentration for a SNR=3, Blue vertical line: theoretical concentration where a single molecule is present in the sample volume: around 0.1 aM). Credit: Scientific Reports, doi: https://doi.org/10.1038/s41598-023-39450-6