A Scalable CMOS Molecular Electronics Chip for Single-Molecule Biosensing

Drew A. Hall, Nagaraj Ananthapadmanabhan, Chulmin Choi, Le Zheng, Paul P. Pan, Christoph Von Jutrzenka, Thuan Nguyen, Jose Rizo, Macklan Weinstein, Raymond Lobaton, Prem Sinha, Trevor Sauerbrey, Cruz Sigala, Kathryne Bailey, Paul J. Mudondo, Ashesh Ray Chaudhuri, Simone Severi, Carl W. Fuller, James M. Tour, Sungho JinPaul W. Mola, Barry Merriman

Research output: Contribution to journalArticlepeer-review


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 ∼100 GΩ, 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 μm CMOS technology, 16k sensors are arrayed with a 20 μm 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.

Original languageEnglish (US)
Pages (from-to)1030-1043
Number of pages14
JournalIEEE Transactions on Biomedical Circuits and Systems
Issue number6
StatePublished - Dec 1 2022
Externally publishedYes


  • Single-molecule biosensor
  • biosensor
  • high-impedance sensor
  • molecular electronics
  • transimpedance amplifier

ASJC Scopus subject areas

  • Electrical and Electronic Engineering
  • Biomedical Engineering


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