Shape complementarity processes for ultrashort-burst sensitive M13-PEG-WS2-powered MCF-7 cancer cell sensors

Biomarkers have the potential to be utilized in disease diagnosis, prediction and monitoring. The cancer cell type is a leading candidate for next-generation biomarkers. Although traditional digital biomolecular sensor (DBS) technology has shown to be effective in assessing cell-based interactions, low cell-population detection of cancer cell types is extremely challenging. Here, we controlled the electrical signature of a two-dimensional (2D) nanomaterial, tungsten disulfide (WS2), by utilizing a combination of the Phage-integrated Polymer and the Nanosheet (PPN), viz., the integration of the M13-conjugated polyethylene glycol (PEG) and the WS2, through shape-complementarity phenomena, and developed a sensor system, i.e., the Phage-based DBS (P-DBS), for the specific, rapid, sensitive detection of clinically-relevant MCF-7 cells. The P-DBS attains a detection limit of 12 cells per mu L, as well as a contrast of 1.25 between the MCF-10A sample signal and the MCF-7 sample signal. A reading length of 200 mu s was further achieved, along with a relative cell viability of similar to 100% for both MCF-7 and MCF-10A cells and with the PNN. Atomistic simulations reveal the structural origin of the shape complementarity-facilitated decrease in the output impedance of the P-DBS. The combination of previously unreported exotic sensing materials and digital sensor design represents an approach to unlocking the ultra-sensitive detection of cancer cell types and provides a promising avenue for early cancer diagnosis, staging and monitoring.

Automated summary

Biomarkers have the potential to be utilized in disease diagnosis, prediction and monitoring. This study developed a Phage-based Digital Biomolecular Sensor (P-DBS) for specific, rapid and sensitive detection of clinically-relevant MCF-7 cells. By utilizing a combination of Phage-integrated Polymer and Nanosheet (PPN) technology to control the electrical signature of tungsten disulfide (WS2), the P-DBS achieved efficient detection of low cell-population cancer cell types.