TY - JOUR
T1 - A Scalable CMOS Molecular Electronics Chip for Single-Molecule Biosensing
AU - Hall, Drew A.
AU - Ananthapadmanabhan, Nagaraj
AU - Choi, Chulmin
AU - Zheng, Le
AU - Pan, Paul P.
AU - Von Jutrzenka, Christoph
AU - Nguyen, Thuan
AU - Rizo, Jose
AU - Weinstein, Macklan
AU - Lobaton, Raymond
AU - Sinha, Prem
AU - Sauerbrey, Trevor
AU - Sigala, Cruz
AU - Bailey, Kathryne
AU - Mudondo, Paul J.
AU - Chaudhuri, Ashesh Ray
AU - Severi, Simone
AU - Fuller, Carl W.
AU - Tour, James M.
AU - Jin, Sungho
AU - Mola, Paul W.
AU - Merriman, Barry
N1 - Publisher Copyright:
© 2007-2012 IEEE.
PY - 2022/12/1
Y1 - 2022/12/1
N2 - 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.
AB - 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.
KW - Single-molecule biosensor
KW - biosensor
KW - high-impedance sensor
KW - molecular electronics
KW - transimpedance amplifier
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U2 - 10.1109/TBCAS.2022.3211420
DO - 10.1109/TBCAS.2022.3211420
M3 - Article
C2 - 36191107
AN - SCOPUS:85139864252
SN - 1932-4545
VL - 16
SP - 1030
EP - 1043
JO - IEEE Transactions on Biomedical Circuits and Systems
JF - IEEE Transactions on Biomedical Circuits and Systems
IS - 6
ER -