Title :
A Patch-Clamp ASIC for Nanopore-Based DNA Analysis
Author :
Kim, Jung-Ho ; Maitra, R. ; Pedrotti, K.D. ; Dunbar, W.B.
Author_Institution :
Dept. of Comput. Eng., Univ. of California, Santa Cruz, Santa Cruz, CA, USA
Abstract :
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.
Keywords :
CMOS integrated circuits; DNA; bioelectric potentials; biomedical electronics; biosensors; capacitive sensors; instrumentation amplifiers; molecular biophysics; nanomedicine; nanoporous materials; nanosensors; proteins; sample and hold circuits; α-hemolysin protein nanopore; 4M2P CMOS process; amplification block; compensation block; compensation switch; diagnostic applications; fully integrated high-sensitivity patch-clamp system; hardware simplicity; headstage saturation; input parasitic capacitances; input-offset voltage; instrumentation-amplifier topology; integrated microfluidic devices; minute ionic current variation amplification; multiple solid-state nanopores; nanopore sensor; nanopore-based DNA analysis; patch-clamp ASIC; refined system; scientific applications; single solid-state nanopores; single-molecule deoxyribonucleic acid analysis; single-stranded DNA; size 0.35 mum; size 1.5 nm; track-and-hold circuit; voltage-gain difference amplifier; Bandwidth; Capacitance; DNA; Gain; Nanobioscience; Noise; Transient analysis; $alpha$-hemolysin nanopore; biomedical application-specified integrated circuit (ASIC); dead-time compensation; deoxyribonucleic acid (DNA) analysis; gene sequencer; lab-on-a-chip; on-chip biosensor; patch-clamp technique; single-molecule science; solid-state nanopore; transimpedance amplifier; Algorithms; Amplifiers, Electronic; Biosensing Techniques; DNA; DNA, Single-Stranded; Equipment Design; Hemolysin Proteins; Hydrogen-Ion Concentration; Ions; Microfluidic Analytical Techniques; Nanopores; Nanotechnology; Patch-Clamp Techniques; Proteins; Signal Processing, Computer-Assisted; Temperature;
Journal_Title :
Biomedical Circuits and Systems, IEEE Transactions on
DOI :
10.1109/TBCAS.2012.2200893
