Amyloid beta oligomers induce neuronal elasticity changes in age-dependent manner: a force spectroscopy study on living hippocampal neurons

Small soluble species of amyloid-beta (Aβ) formed during early peptide aggregation stages are responsible for several neurotoxic mechanisms relevant to the pathology of Alzheimer's disease (AD), although their interaction with the neuronal membrane is not completely understood. This study quantifies the changes in the neuronal membrane elasticity induced by treatment with the two most common Aβ isoforms found in AD brains: Aβ40 and Aβ42. Using quantitative atomic force microscopy (AFM), we measured for the first time the static elastic modulus of living primary hippocampal neurons treated with pre-aggregated Aβ40 and Aβ42 soluble species. Our AFM results demonstrate changes in the elasticity of young, mature and aged neurons treated for a short time with the two Aβ species pre-aggregated for 2 hours. Neurons aging under stress conditions, showing aging hallmarks, are the most susceptible to amyloid binding and show the largest decrease in membrane stiffness upon Aβ treatment. Membrane stiffness defines the way in which cells respond to mechanical forces in their environment and has been shown to be important for processes such as gene expression, ion-channel gating and neurotransmitter vesicle transport. Thus, one can expect that changes in neuronal membrane elasticity might directly induce functional changes related to neurodegeneration

Organic film thickness influence on the bias stress instability in Sexithiophene Field Effect Transistors

In this paper, the dynamics of bias stress phenomenon in Sexithiophene (T6) Field Effect Transistors (FETs) has been investigated. T6 FETs have been fabricated by vacuum depositing films with thickness from 10 nm to 130 nm on Si/SiO2 substrates. After the T6 film structural analysis by X-Ray diffraction and the FET electrical investigation focused on carrier mobility evaluation, bias stress instability parameters have been estimated and discussed in the context of existing models. By increasing the film thickness, a clear correlation between the stress parameters and the structural properties of the organic layer has been highlighted. Conversely, the mobility values result almost thickness independent

Label-Free Detection of Escherichia coli Based on Thermal Transport through Surface Imprinted Polymers

This work focuses on the development of a label-free biomimetic sensor for the specific and selective detection of bacteria. The platform relies on the rebinding of bacteria to synthetic cell receptors, made by surface imprinting of polyurethane-coated aluminum chips. The heat-transfer resistance (Rth) of these so-called surface imprinted polymers (SIPs) was analyzed in time using the heat-transfer method (HTM). Rebinding of target bacteria to the synthetic receptor led to a measurable increase in thermal resistance at the solid–liquid interface. Escherichia coli and Staphylococcus aureus were used as model organisms for several proof-of-principle experiments, demonstrating the potential of the proposed platform for point-of-care bacterial testing. The results of these experiments indicate that the sensor is able to selectively detect bacterial rebinding to the SIP surface, distinguishing between dead and living E. coli cells on one hand and between Gram-positive and Gram-negative bacteria on the other hand (E. coli and S. aureus). In addition, the sensor was capable of quantifying the number of bacteria in a given sample, enabling detection at relatively low concentrations (104 CFU mL–1 range). As a first proof-of-application, the sensor was exposed to a mixed bacterial solution containing only a small amount (1%) of the target bacteria. The sample was able to detect this trace amount by using a simple gradual enrichment strategy

Closed-loop optical stimulation and recording system with gpu-based real-time spike sorting

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Direct detection of molecular biorecognition by dipole sensing mechanism

This work investigates the feasibility of transducing molecular-recognition events into a measurable potentiometric signal. It is shown for the first time that biorecognition of acetylcholine (ACh) can be translated to conformational changes in the enzyme, acetylcholine-esterase (AChE), which in turn induces a measurable change in surface potential. Our results show that a highly sensitive detector for ACh can be obtained by the dilute assembly of AChE on a floating gate derived field effect transistor (FG-FET). A wide concentration range response is observed for ACh (10-2-10-9M) and for the inhibitor carbamylcholine CCh (10-6-10-11M). These enhanced sensitivities are modeled theoretically and explained by the combined response of the device to local pH changes and molecular dipole variations due to the enzyme-substrate recognition event. © 2009 American Chemical Society

Closed-loop optical neural stimulation based on a 32-channel low-noise recording system with online spike sorting

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An SU-8 liquid cell for surface acoustic wave biosensors

One significant challenge facing biosensor development is packaging. For surface acoustic wave based biosensors, packaging influences the general sensing performance. The acoustic wave is generated and received thanks to interdigital transducers and the separation between the transducers defines the sensing area. Liquids used in biosensing experiments lead to an attenuation of the acoustic signal while in contact with the transducers. We have developed a liquid cell based on photodefinable epoxy SU-8 that prevents the presence of liquid on the transducers, has a small disturbance effect on the propagation of the acoustic wave, does not interfere with the biochemical sensing event, and leads to an integrated sensor system with reproducible properties. The liquid cell is achieved in two steps. In a first step, the SU-8 is precisely patterned around the transducers to define 120 mu m thick walls. In a second step and after the dicing of the sensors, a glass capping is placed manually and glued on top of the SU-8 walls. This design approach is an improvement compared to the more classical solution consisting of a pre-molded cell that must be pressed against the device in order to avoid leaks, with negative consequences on the reproducibility of the experimental results. We demonstrate the effectiveness of our approach by protein adsorption monitoring. The packaging materials do not interfere with the biomolecules and have a high chemical resistance. For future developments, wafer level bonding of the quartz capping onto the SU-8 walls is envisioned.Anglai

Towards the formation of neuro-transistor artificial chemical synapse

Highly sensitive biosensor for detection of acetylcholine (ACh) and competitive acetylcholinesterase (AChE) inhibitor, eserine, is investigated. Peculiar microelectronic configuration of an ion-sensitive field-effect transistor (ISFET) in addition to a right choice of the pH-transducing nanolayers allows recording a response of the enzyme-modified ISFET (EnFET) to a wide range of ACh concentrations. We demonstrate a remarkable improvement of at least three orders of magnitude in dose response to ACh. Described bioelectronic system reveals clear response, when the catalytic activity of the immobilized AChE is inhibited in a reversible manner by eserine, competitive inhibitor of AChE. ©2007 IEEE