Abstract

High-throughput screening (HTS) using ion channel recording is a powerful drug discovery technique in pharmacology. Ion channel recording with planar bilayer lipid membranes (BLM) is scalable and has very high sensitivity. A HTS system based on BLM ion channel recording faces three main challenges: (i) design of scalable microfluidic devices; (ii) design of compact ultra-low-noise transimpedance amplifiers able to detect currents in the pA range with bandwidth >10 kHz; (iii) design of compact, robust and scalable systems that integrate these two elements. This paper presents a low-noise transimpedance amplifier with integrated A/D conversion realized in CMOS 0.35 μm technology. The CMOS amplifier acquires currents in the range ±200 pA and ±20 nA, with 100 kHz bandwidth while dissipating 41 mW. An integrated digital offset compensation loop balances any voltage offsets from Ag/AgCl electrodes. The measured open-input input-referred noise current is as low as 4 fA/√Hz at ±200 pA range. The current amplifier is embedded in an integrated platform, together with a microfluidic device, for current recording from ion channels. Gramicidin-A, α-haemolysin and KcsA potassium channels have been used to prove both the platform and the current-to-digital converter.

Highlights

  • Ion channels are nanoscale pores that sit in the cell membrane, allowing communication of the cell with the external environment through ionic currents

  • This paper presents a low-noise transimpedance amplifier realized in CMOS 0.35 μm technology with a measured input-referred noise as low as 4 fA/ Hz (133 fArms at 1 kHz), a gain of 2.25 GΩ and

  • This paper presented a CMOS transimpedance amplifier based on the integrator-differentiator scheme forpresented

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Summary

A Low-Noise Transimpedance Amplifier for BLM-Based Ion Channel Recording

Marco Crescentini 1,2, *,† , Marco Bennati 3,† , Shimul Chandra Saha 4,† , Josip Ivica 4,† , Maurits de Planque 4,† , Hywel Morgan 4,† and Marco Tartagni 1,2,†.

Introduction
Ion Channel Recording Platform
Microfluidic
Sensing Frontend Rationale
C1 C3 4
Schematic
Subtractor
Noise Analysis
10. Effect themodel resetwith period
Implementation
NoiseThe
Offset Compensation Loop and Subtractor
Ion Channel Recording
Gramicidin-A
State-of-the-Art Comparison
Conclusions

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