An Automatic Offset Correction Platform for High-Throughput Ion-Channel Electrophysiology

High-throughput ion channel screening for drug discovery is at the base of the recent shift of resources in the pharmaceutical industry towards addressing drug safety issues earlier in the discovery process. Very few examples of parallel ion-channel recording platforms are currently present in literature, due to the complexity of the setup. However, single-junction Ag/AgCl electrodes suffer of intrinsic voltage offsets, due to the electrode-buffer interface variability. This is very critical, since ion- channel recording requires high accuracy (pA resolution) within the full-scale (nA range), limiting the operability of the measurement, especially on a multi-channel approach. This paper presents an automatic offset correction system fully implemented on a lipid bilayer membrane platform. The platform allows offset-free recording of ion-channel signals acquired and displayed by means of a graphical user interface

An Automatic System for Bilayer Lipid Membrane Formation and Monitoring

Ion channels are natural nanometric pores formed by proteins across cell membranes. They are responsible of part of cell signaling and a large part of pharmaceutical compounds are interacting with them. Therefore, single ion channel screening is being proposed as a fundamental technique for investigating the function of cell membrane proteins with pharmaceutical compounds. The technique consisting in embedding ion channels in artificial bilayer lipid membranes (BLM) is gaining attention over patch clamp approach due to its characteristics of performing parallel tests over selected classes of channels. However, no valid procedures for automatic formation and real time monitoring of BLM arrays have been presented so far. More specifically, since BLM is based on a manual and time-consuming technique, there is a strong need of automatic systems for forming BLMs in a fully parallel fashion for testing compounds in high throughput screening (HTS) fashion. In this paper, an automatic liquid dispensing system for BLM formation is presented using commercial 3+1 axes movement stepper machine together with a multi-sensor technique for monitoring BLM formation in real time. As proof of this concept, the automatic dispensing system is interfaced with an 8 channel electronic interface where low noise amplifiers are able to automatically sense BLM formations by means of current sensing

A Disposable Microfluidic Array Platform for Automatic Ion Channel Recording

High-throughput ion channel screening for drug discovery is the gold standard for investigating the function of chan- nel proteins and it is at the base of the recent shift of resources in the pharmaceutical industry towards addressing drug safety issues earlier in the discovery process. This paper presents a versatile, low-cost and disposable microfluidic device realized using a micromilling process fa- brication of polyoxymethilene homopolymer (DelrinTM) substrates. The devices are suitable to host lipid bilayer mem- brane arrays for ion channel recording activities using a fully automated approach and are embedded in a parallel readout hybrid electronic system

A Nanosensor Interface based on Delta-Sigma Arrays

An emerging area of biosensors is based on the use of structures provided by recent advances of Nanotechnology such as nanowires, nanotubes and nanopores. Among them, the integration of natural nanopores such as ion channels with electronics is a promising approach to develop rapid, sensitive and reliable biosensors able to detect low concentration of target molecules or DNA sequencing. This paper presents a compact and low-cost system able to readout, process and record current in the pA range, provided by biological or synthetic nanopores. The approach is based on the idea that by processing the outputs of a large amount of single- molecule nanosensors would result in a significant increase of resolution and signal-to-noise ratio. The approach consists of an electronic interface able to detect current-based array of nanosensors, where the management of very large amount of data is critical for the readout process. As working example, we acquired the single molecule signals derived from non-covalent bindings between single α-hemolysin pores, embedded into an artificial lipid bilayer, and β-cyclodextrin molecules. The system embeds the electronic readout with the microfluidic where is placed the nanosensor array. The electronic interface is a 0.5mm2 current amplifier based on an array of ΣΔ converters. Then the high rate data streams are processed and downsampled by a DSP that communicates with a PC via a USB interface for data processing and storage

Sub-pA Delta-Sigma Current Amplifier for Single Molecule Nanosensors

A current-readout front-end for nanosensors based on a ΔΣ converter approach features an input-equivalent noise of 5fA/√Hz in a 1kHz bandwidth.The front-end detects ion-channel activity caused by single-molecule interactions. The device occupies 0.5mm2 in 0.35μm 2P4M CMOS and consumes less than 23mW