Compensation Technique for Current-to-Voltage Converters for LSI Patch Clamp System Using High Resistive Feedback

Hiroki YOTSUDA  Retdian NICODIMUS  Masahiro KUBO  Taro KOSAKA  Nobuhiko NAKANO  

IEICE TRANSACTIONS on Fundamentals of Electronics, Communications and Computer Sciences   Vol.E99-A   No.2   pp.531-539
Publication Date: 2016/02/01
Online ISSN: 1745-1337
DOI: 10.1587/transfun.E99.A.531
Type of Manuscript: Special Section PAPER (Special Section on Analog Circuit Techniques and Related Topics)
patch clamp measurement,  current-to-voltage converter,  low-noise amplifier,  high resistive feedback,  stabilization,  

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Patch clamp measurement technique is one of the most important techniques in the field of electrophysiology. The elucidation of the channels, nerve cells, and brain activities as well as contribution of the treatment of neurological disorders is expected from the measurement of ion current. A current-to-voltage converter, which is the front end circuit of the patch clamp measurement system is fabricated using 0.18µm CMOS technology. The current-to-voltage converter requires a resistance as high as 50MΩ as a feedback resistor in order to ensure a high signal-to-noise ratio for very small signals. However, the circuit becomes unstable due to the large parasitic capacitance between the poly layer and the substrate of the on-chip feedback resistor and the instability causes the peaking at lower frequency. The instability of a current-to-voltage converter with a high-resistance as a feedback resistor is analyzed theoretically. A compensation circuit to stabilize the amplifier by driving the N-well under poly resistor to suppress the effect of parasitic capacitance using buffer circuits is proposed. The performance of the proposed circuit is confirmed by both simulation and measurement of fabricated chip. The peaking in frequency characteristic is suppressed properly by the proposed method. Furthermore, the bandwidth of the amplifier is expanded up to 11.3kHz, which is desirable for a patch clamp measurement. In addition, the input referred rms noise with the range of 10Hz ∼ 10kHz is 2.09 Arms and is sufficiently reach the requirement for measure of both whole-cell and a part of single-channel recordings.