Noise Analysis and Performance Comparison of Low Current Measurement Systems for Biomedical Applications

In this paper, we report on the noise analysis of low current measurement systems for biomedical applications and their fundamental limits. We analyzed resistive feedback, capacitive feedback and current amplifier circuits for low current measurement systems. Detailed noise analysis for different biomedical applications are presented and matched with measurement data using a 0.5-μm fabrication process. Based on the theoretical analysis and the corresponding measurement results, the capacitive feedback system provides better noise performance for the measurement of low current than the others. The capacitive feedback circuit is capable of measuring 750 fA RMS at a 10 kHz sampling rate, whereas the resistive feedback provides 4 pA and the current conveyor provides 600 pA at the same bandwidth. This paper provides design guidelines to maximize the performance of low current measuring system for biomedical instrumentation and to provide the best performance available with CMOS technologies.

[1]  Eugenio Culurciello,et al.  An Integrated Patch-Clamp Amplifier in Silicon-on-Sapphire CMOS , 2006, IEEE Transactions on Circuits and Systems I: Regular Papers.

[2]  Gert Cauwenberghs,et al.  16-Channel Integrated Potentiostat for Distributed Neurochemical Sensing , 2006, IEEE Transactions on Circuits and Systems I: Regular Papers.

[3]  Kartikeya Murari,et al.  VLSI Potentiostat Array With Oversampling Gain Modulation for Wide-Range Neurotransmitter Sensing , 2007, IEEE Transactions on Biomedical Circuits and Systems.

[4]  Berin Martini,et al.  Performance comparison of low current measurement systems for biomedical applications , 2010, Proceedings of 2010 IEEE International Symposium on Circuits and Systems.

[5]  Eugenio Culurciello,et al.  Integrated patch-clamp biosensor for high-density screening of cell conductance , 2008 .

[6]  I. Willner,et al.  Probing Biomolecular Interactions at Conductive and Semiconductive Surfaces by Impedance Spectroscopy: Routes to Impedimetric Immunosensors, DNA‐Sensors, and Enzyme Biosensors , 2003 .

[7]  M. Sampietro,et al.  Very high sensitivity CMOS circuit to track fast biological current signals , 2006, 2006 IEEE Biomedical Circuits and Systems Conference.

[8]  E. Culurciello,et al.  An integrated Silicon-on-sapphire Patch-clamp amplifier , 2006, 2006 IEEE/NLM Life Science Systems and Applications Workshop.

[9]  Eugenio Culurciello.  Silicon-on-Sapphire Circuits and Systems , 2009 .

[10]  J.G. Harris,et al.  A time-based VLSI potentiostat for ion current measurements , 2006, IEEE Sensors Journal.

[11]  Mark A. Reed,et al.  Label-free immunodetection with CMOS-compatible semiconducting nanowires , 2007, Nature.

[12]  Shantanu Chakrabartty,et al.  A Multichannel Femtoampere-Sensitivity Potentiostat Array for Biosensing Applications , 2006, IEEE Transactions on Circuits and Systems I: Regular Papers.

[13]  Robin F. B. Turner,et al.  A CMOS potentiostat for amperometric chemical sensors , 1987 .

[14]  D. Branton,et al.  The potential and challenges of nanopore sequencing , 2008, Nature Biotechnology.

[15]  Erik Bruun.  Analysis of the Noise Characteristics of CMOS Current Conveyors , 1997 .

[16]  Eugenio Culurciello,et al.  An Integrated Patch-Clamp Potentiostat With Electrode Compensation , 2009, IEEE Transactions on Biomedical Circuits and Systems.

[17]  Eugenio Culurciello,et al.  Patch-clamp amplifiers on a chip , 2010, Journal of Neuroscience Methods.

[18]  Ali Hajimiri,et al.  On noise processes and limits of performance in biosensors , 2007 .

[19]  R. Bracewell.  The Fourier transform. , 1989, Scientific American.

[20]  Marco Sampietro,et al.  A Current-Sensitive Front-End Amplifier for Nano-Biosensors with a 2MHz BW , 2007, 2007 IEEE International Solid-State Circuits Conference. Digest of Technical Papers.

[21]  Robert H Blick,et al.  Whole cell patch clamp recording performed on a planar glass chip. , 2002, Biophysical journal.

[22]  Eugenio Culurciello,et al.  An integrated patch-clamp system with dual Input , 2010, Proceedings of 2010 IEEE International Symposium on Circuits and Systems.

[23]  M. Sampietro,et al.  Transimpedance Amplifier for High Sensitivity Current Measurements on Nanodevices , 2009, IEEE Journal of Solid-State Circuits.

[24]  R. Kakerow,et al.  Low-power Single-chip CMOS Potentiostat , 1995, Proceedings of the International Solid-State Sensors and Actuators Conference - TRANSDUCERS '95.

[25]  B. Sakmann,et al.  Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches , 1981, Pflügers Archiv.

[26]  R. Dutton,et al.  Comprehensive study of noise processes in electrode electrolyte interfaces , 2004 .

[27]  Marco Carminati,et al.  Ultra-low-noise CMOS current preamplifier from DC to 1 MHz , 2009 .

[28]  Rashid Bashir,et al.  Nanopores : sensing and fundamental biological interactions , 2011 .

[29]  Gregory T. A. Kovacs,et al.  An integrated CMOS potentiostat for miniaturized electroanalytical instrumentation , 1994, Proceedings of IEEE International Solid-State Circuits Conference - ISSCC '94.

[30]  G. Cauwenberghs,et al.  Wide-range, picoampere-sensitivity multichannel VLSI potentiostat for neurotransmitter sensing , 2004, The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[31]  F. Sigworth,et al.  Microchip technology in ion-channel research , 2005, IEEE Transactions on NanoBioscience.

[32]  James L. Rae,et al.  Technology of Patch- Clamp Electrodes , 2007 .

[33]  E. Culurciello,et al.  Ultralow Current Measurements With Silicon-on-Sapphire Integrator Circuits , 2009, IEEE Electron Device Letters.

[34]  Gert Cauwenberghs,et al.  VLSI potentiostat array for distributed electrochemical neural recording , 2002, 2002 IEEE International Symposium on Circuits and Systems. Proceedings (Cat. No.02CH37353).