IEEE Transactions on Biomedical Circuits and Systems · 2012 · 56 citations · 28 references
EngineeringBioengineeringBiomedical EngineeringBiosensorsNanotechnologySensorsBiological SensorsBiosensor DesignDna BiosensorsMolecular SensorsNanosensorsNucleic Acid BiosensorsAmplificationDna SensorsDna-based BiosensingMicrofluidic Diagnostic DevicesNanopore SensingNanopore-based DetectionPatch-clamp AnalysisSaturation
The paper proposes a fully integrated high‑sensitivity patch‑clamp system for single‑molecule DNA analysis using a nanopore sensor. The system comprises an amplification block with a headstage, voltage‑gain differential amplifier, and track‑and‑hold circuit, and a compensation block that prevents headstage saturation from parasitic capacitances, employing an instrumentation‑amplifier topology and a compensation switch to reduce offset and capacitance effects while keeping hardware simple. Fabricated in a 0.35 µm CMOS process, the device was demonstrated with an α‑hemolysin nanopore, successfully detecting individual single‑stranded DNA molecules traversing the 1.5 nm pore.
In this paper, a fully integrated high-sensitivity patch-clamp system is proposed for single-molecule deoxyribonucleic acid (DNA) analysis using a nanopore sensor. This system is composed of two main blocks for amplification and compensation. The amplification block is composed of three stages: 1) a headstage, 2) a voltage-gain difference amplifier, and 3) a track-and-hold circuit, that amplify a minute ionic current variation sensed by the nanopore while the compensation block avoids the headstage saturation caused by the input parasitic capacitances during sensing. By employing design techniques novel for this application, such as an instrumentation--amplifier topology and a compensation switch, we minimize the deleterious effects of the input-offset voltage and the input parasitic capacitances while attaining hardware simplicity. This system is fabricated in a 0.35 μm 4M2P CMOS process and is demonstrated using an α-hemolysin protein nanopore for detection of individual molecules of single-stranded DNA that pass through the 1.5 nm-diameter pore. In future work, the refined system will functionalize single and multiple solid-state nanopores formed in integrated microfluidic devices for advanced DNA analysis, in scientific and diagnostic applications.
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