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Updated: Aug 26, 2025

A Microfluidic Chip for the Versatile Chemical Analysis of Single Cells
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A Scalable CMOS Molecular Electronics Chip for Single-Molecule Biosensing.

Drew A Hall, Nagaraj Ananthapadmanabhan, Chulmin Choi

    IEEE Transactions on Biomedical Circuits and Systems
    |October 3, 2022
    PubMed
    Summary
    This summary is machine-generated.

    This study introduces the first CMOS molecular electronics chip, functioning as a biosensor. It enables real-time, single-molecule detection of biological interactions, offering a new platform for various applications.

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    Area of Science:

    • Molecular electronics
    • Biosensing technology
    • Nanotechnology

    Background:

    • Classical biosensors measure ensemble averages, limiting real-time kinetic analysis.
    • Single-molecule detection requires highly sensitive and rapid readout systems.
    • Integrating molecular sensing with semiconductor technology is a key challenge.

    Purpose of the Study:

    • To report the development of the first CMOS molecular electronics chip.
    • To demonstrate its capability as a high-resolution biosensor for single-molecule interactions.
    • To establish a platform for on-chip molecular biosensing.

    Main Methods:

    • Utilized a single alpha-helical peptide (∼100 GΩ, 25 nm) as a molecular wire in a current monitoring circuit.
    • Engineered the peptide with a conjugation site for probe molecule attachment (DNA, proteins, enzymes, antibodies).
    • Implemented 16,384 sensors in a 0.18 μm CMOS technology, with a 20 μm pitch and 1 kHz frame rate readout.

    Main Results:

    • Achieved millisecond temporal resolution for monitoring current through the molecular wire.
    • Detected picoampere current pulses corresponding to transient probe-target molecular interactions.
    • Provided direct, real-time observation of single-molecule interaction kinetics.

    Conclusions:

    • The developed CMOS molecular electronics chip enables on-chip molecular biosensing.
    • This technology offers direct, real-time observation of single-molecule kinetics, surpassing ensemble-averaging methods.
    • The platform has broad potential in biological research, diagnostics, sequencing, proteomics, drug discovery, and environmental monitoring.