Probe-screened carbon nanotube field-effect transistor biosensor to enhance breast cancer-related gene assay

• A Y 2 O 3 / HfO 2 bilayer dielectric process improves the environmental stability of the CNT-FET DNA sensor. • The detection performance of three nucleic acid probes, DNA, PMO, and PNA, was systematically investigated for the first time to define the optimal BRCA1 sensor configuration. • The PNA-modified CNT-FET features excellent aM level sensitivity, notably superior to the DNA and PMO-modified sensors. • Breast cancer patients and healthy individuals are successfully distinguished by the developed sensor. BRCA1 gene testing is a trump card for liquid biopsy and early diagnosis in breast cancer, which has been limited, however, by the fact that the current mainstream methods such as gene sequencing are expensive, time-consuming and complex. In this study, a semiconductor carbon nanotube (CNT)-based field-effect transistor (FET) DNA sensor, with a floating gate (FG) structure and Y 2 O 3 / HfO 2 high κ bilayer gate dielectric, was constructed. A key advance here is that the detection performance of three nucleic acid probes, DNA, phosphorodiamidate morpholino oligos (PMO) and peptide nucleic acid (PNA), was systematically investigated for the first time to define the optimal BRCA1 sensor configuration. The PNA-functionalized FG CNT-FET sensor stood out with an excellent sensitivity (LOD: 1.38 aM) and good specificity. What is more, the developed sensor also exhibited good anti-interference capability in serum BRCA1 testing, owing to the passivation of the bilayer dielectric. Importantly, the breast cancer patients and healthy individuals were successfully distinguished by our method, which is fully consistent with the gene sequencing results. This work represents a desirable analytical platform for the simple, sensitive, and accurate liquid biopsy of breast cancer. And we envision that the developed method will provide ideas for the construction of future DNA sensors and the selection of their recognition elements.