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

5.26 Left Ventricular Hypertrophy Prevalence by Different Left Ventricular Mass Indexes

n/

Smart energy management and conversion

This chapter introduced power management circuits and energy storage unit designs for sub‐1 mW low power energy harvesting technologies, including indoor light energy harvesting, thermoelectric energy harvesting and vibration energy harvesting. The solutions address several of the problems associated with energy harvesting, power management and storage issues including low voltage operation, self‐start, efficiency (conversion efficiency as well as impact of power consumption of the power management circuit itself), energy density and leakage current levels. Additionally, efforts to miniaturize and integrate magnetic parts as well as integrate discrete circuits onto silicon are outlined to offer improvements in cost, size and efficiency. Finally initial results from efforts to improve energy density of storage devices using nanomaterials are introduced

An Electronic Approach for Stochastic Sensing

In recent years, we have assisted to an ever-increasing capability of electronic systems to detect extremely small signals in noisy environments. Following this trend, the capability to electronically detect single molecular binding events could bring to a new, high performance class of biosensors. One of the best transducers coding single molecule event into an electric signal is already existing in nature and widely used by cells for interacting with the external environment: the ligand-gated ion channel. The biological cell is filled with all types of ion channels that control the trafficking of ions and molecules in and out of the cell and among the subcellular structures. However, the signaling derived by ion channels upon molecular binding is intrinsically stochastic, due to the thermal agitation of the physical system at molecular scale. Properties of their gating are strongly influenced by binding between receptive sites located on the channel surface and specific target molecules. In this paper we propose to use signals deriving from ligand-gated ion channels for realizing quantitative sensors, able to detect specific chemical species in fluid mixtures. Following this goal, we have implemented an electronic system, able to record ionic currents derived by single gated ion channels having hundreds of femto-amperes of resolution. Additionally, we propose a statistical approach for processing the electrical information, in order to estimate the concentration value of the target molecules. The proposed algorithm was tested using a Monte Carlo simulator and a simple channel model taken from literature

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

Proposal of a non-invasive approach for biomechanical follow-up of heart failure patients.

Heart failure (HF) is the most important cause of death in the world. The prognosis is very poor and strictly dependent on the therapy that should be continuously optimized in function of the mechanical behaviour of the ventricle. To follow the evolution of the disease, we are testing an approach based on the biomechanical coupling between failed heart and aorta, which considers end systolic ventricular volume referred to pressure, stroke volume referred to aortic pulse and a new non invasive index of left ventricular contractility validated by Zhong et al. To test the sensitivity of our approach to monitor the HF condition and evolution, a follow up program of 10 HF patients submitted to cardiac resynchronization therapy is on course and will be concluded in the next three months

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