A Scalable CMOS Molecular Electronics Chip for Single-Molecule Biosensing

This work reports the first CMOS molecular electronics chip. It is configured as a biosensor, where the primary sensing element is a single molecule molecular wire consisting of a similar to 100 G Omega, 25 nm long alpha-helical peptide integrated into a current monitoring circuit. The engineered peptide contains a central conjugation site for attachment of various probe molecules, such as DNA, proteins, enzymes, or antibodies, which program the biosensor to detect interactions with a specific target molecule. The current through the molecular wire under a dc applied voltage is monitored with millisecond temporal resolution. The detected signals are millisecond-scale, picoampere current pulses generated by each transient probe-target molecular interaction. Implemented in a 0.18 mu m CMOS technology, 16k sensors are arrayed with a 20 mu m pitch and read out at a 1 kHz frame rate. The resulting biosensor chip provides direct, real-time observation of the single-molecule interaction kinetics, unlike classical biosensors that measure ensemble averages of such events. This molecular electronics chip provides a platform for putting molecular biosensing on-chip to bring the power of semiconductor chips to diverse applications in biological research, diagnostics, sequencing, proteomics, drug discovery, and environmental monitoring.

Automated summary

This work presents the first CMOS molecular electronics chip that allows direct, real-time observation of molecular interaction kinetics. It provides a new platform for applications in biological research, diagnostics, drug discovery, and more.