A CMOS Molecular Electronics Chip for Single-Molecule Biosensing

Molecular electronics is the concept of integrating single molecules into circuits as functional elements. For nearly 50 years, this has been envisioned as a way to extend Moore's Law to physical scaling limits [1]. However, beyond scaling advantages, using single molecules in circuits as sensor elements enables a broad range of biomolecular sensing applications that integrated circuits cannot otherwise perform. Unlike classical biosensors that rely on indirect reporter methods to detect molecular probe-target interactions (e.g., as in Fig. 12.6.1 with optical, enzymatic, or magnetic reporters), in the molecular electronics approach, current directly passes through a probe molecule, whose interactions with a target molecule are detected through modulation of the probe molecule's conductance [2]. This approach enables label-free, ultra-sensitive, real-time, all-electronic single-molecule sensors to be deployed on low-cost, highly scalable CMOS sensor array chips. The resulting platform extends these “on-chip” advantages to a wide variety of biosensing applications, such as in diagnostics, drug discovery, DNA sequencing, and proteomics [3]–[5].