Efficient Illumination for a Light-Addressable Potentiometric Sensor.

A light-addressable potentiometric sensor (LAPS) is a chemical sensor that is based on the field effect in an electrolyte-insulator-semiconductor structure. It requires modulated illumination for generating an AC photocurrent signal that responds to the activity of target ions on the sensor surface. Although high-power illumination generates a large signal, which is advantageous in terms of the signal-to-noise ratio, excess light power can also be harmful to the sample and the measurement. In this study, we tested different waveforms of modulated illuminations to find an efficient illumination for a LAPS that can enlarge the signal as much as possible for the same input light power. The results showed that a square wave with a low duty ratio was more efficient than a sine wave by a factor of about two.

Simultaneous In Situ Imaging of pH and Surface Roughening during the Progress of Crevice Corrosion of Stainless Steel.

Stainless steel plays an important role in industry due to its anti-corrosion characteristic. It is known, however, that local corrosion can damage stainless steel under certain conditions. In this study, we developed a novel measurement system to observe crevice corrosion, which is a local corrosion that occurs inside a narrow gap. In addition to pH imaging inside the crevice, another imaging technique using an infrared light was combined to simultaneously visualize surface roughening of the test piece. According to experimental results, the lowering of local pH propagated inside the crevice, and after that, the surface roughening started and expanded due to propagation of corrosion. The real-time measurement of the pH distribution and the surface roughness can be a powerful tool to investigate the crevice corrosion.

Estimation of Potential Distribution during Crevice Corrosion through Analysis of I-V Curves Obtained by LAPS.

Crevice corrosion is a type of local corrosion which occurs when a metal surface is confined in a narrow gap on the order of 10 µm filled with a solution. Because of the inaccessible geometry, experimental methods to analyze the inner space of the crevice have been limited. In this study, a light-addressable potentiometric sensor (LAPS) was employed to estimate the potential distribution inside the crevice owing to the IR drop by the anodic current flowing out of the structure. Before crevice corrosion, the I-V curve of the LAPS showed a potential shift, depending on the distance from the perimeter. The shift reflected the potential distribution due to the IR drop by the anodic current flowing out of the crevice. After crevice corrosion, the corrosion current increased exponentially, and a local pH change was detected where the corrosion was initiated. A simple model of the IR drop was used to calculate the crevice gap, which was 12 µm-a value close to the previously reported values. Thus, the simultaneous measurement of the I-V curves obtained using a LAPS during potentiostatic electrolysis could be applied as a new method for estimating the potential distribution in the crevice.

Modeling of the Return Current in a Light-Addressable Potentiometric Sensor.

A light-addressable potentiometric sensor (LAPS) is a chemical sensor with a field-effect structure based on semiconductor. Its response to the analyte concentration is read out in the form of a photocurrent generated by illuminating the semiconductor with a modulated light beam. As stated in its name, a LAPS is capable of spatially resolved measurement using a scanning light beam. Recently, it has been pointed out that a part of the signal current is lost by the return current due to capacitive coupling between the solution and the semiconductor, which may seriously affect the sensor performance such as the signal-to-noise ratio, the spatial resolution, and the sensitivity. In this study, a circuit model for the return current is proposed to study its dependence on various parameters such as the diameter of contact area, the modulation frequency, the specific conductivity of the solution, and the series resistance of the circuit. It is suggested that minimization of the series resistance of the circuit is of utmost importance in order to avoid the influence of the return current. The results of calculation based on this model are compared with experimental results, and its applicability and limitation are discussed.

Thermally Drawn CNT-Based Hybrid Nanocomposite Fiber for Electrochemical Sensing.

Nowadays, bioelectronic devices are evolving from rigid to flexible materials and substrates, among which thermally-drawn-fiber-based bioelectronics represent promising technologies thanks to their inherent flexibility and seamless integration of multi-functionalities. However, electrochemical sensing within fibers remains a poorly explored area, as it imposes new demands for material properties-both the electrochemical sensitivity and the thermomechanical compatibility with the fiber drawing process. Here, we designed and fabricated microelectrode fibers made of carbon nanotube (CNT)-based hybrid nanocomposites and further evaluated their detailed electrochemical sensing performances. Carbon-black-impregnated polyethylene (CB-CPE) was chosen as the base material, into which CNT was loaded homogeneously in a concentration range of 3.8 to 10 wt%. First, electrical impedance characterization of CNT nanocomposites showed a remarkable decrease of the resistance with the increase in CNT loading ratio, suggesting that CNTs notably increased the effective electrical current pathways inside the composites. In addition, the proof-of-principle performance of fiber-based microelectrodes was characterized for the detection of ferrocenemethanol (FcMeOH) and dopamine (DA), exhibiting an ultra-high sensitivity. Additionally, we further examined the long-term stability of such composite-based electrode in exposure to the aqueous environment, mimicking the in vivo or in vitro settings. Later, we functionalized the surface of the microelectrode fiber with ion-sensitive membranes (ISM) for the selective sensing of Na+ ions. The miniature fiber-based electrochemical sensor developed here holds great potential for standalone point-of-care sensing applications. In the future, taking full advantage of the thermal drawing process, the electrical, optical, chemical, and electrochemical modalities can be all integrated together within a thin strand of fiber. This single fiber can be useful for fundamental multi-mechanistic studies for biological applications and the weaved fibers can be further applied for daily health monitoring as functional textiles.

Positive patterning of ferritin and fibronectin molecules on silicon by the atomic force microscopic anodic oxidation technique.

Oxide dots fabricated on silicon (111) by the Atomic Force Microscopy (AFM) anodic oxidation technique was used for the patterning of two different proteins namely, ferritin and fibronectin. Si surfaces were oxidized by the SC1 process and then modified with octadecyltrichlorosilane (OTS) for passivation. Oxide dots were fabricated by applying a bias voltage between the AFM probe and the silicon surface. Furthermore, surface functionalization of oxide dots was achieved through gamma-aminopropyltriethoxysilane (gamma-APTES) and glutaraldehye modification to establish a covalent bond between aldehydes and amino groups of protein molecules. Topographies after each modification steps were monitored by AFM. We were able to achieve positive patterning of ferritin molecules up to an average density of 6 x 10(9)/cm2 on gamma-APTES-covered dots, while 9 x 10(8)/cm2 of ferritin molecules remained on the OTS surface. In contrast to this observation, fibronectin molecules were patterned successfully only on oxide dots, and we did not observe any fibronectin molecules on the OTS surface.

Miniature multiplexed label-free pH probe in vivo.

Correlating in-brain pH fluctuations with the pathophysiology has been impeded by the lack of in vivo techniques to precisely determine local pH changes. Here, we developed an all-in-one pH probe for spatially-resolved and label-free pH sensing in vivo, based on a field-effect pH sensor, i.e., a light-addressable potentiometric sensor (LAPS), coupled to a flexible multimodal fiber. A readout photocurrent from the LAPS, elicited from a modulated light source, registers the localized surface potential change, proportional to the pH change. Upon simultaneous illuminations at multi-spot by a plurality of light sources with different modulation frequencies, pH changes at multiple designated spots are obtained via demultiplexing this photocurrent. To enable its in vivo applications, we combined the LAPS with a multimodal fiber fabricated by the convergence thermal drawing. Such fiber seamlessly integrates a multicore optical waveguide in the center for the light delivery, surrounded by electrodes for leading out photocurrent and serving as a pseudo-reference electrode, respectively. Such hybrid all-in-one pH probes can measure pH changes at 14 pixels simultaneously with a spatial resolution of 250 µm and a temporal resolution of 30 Hz. The pH sensitivity was characterized as 57.5 ± 2.2 mV/pH homogeneously across all measurable pixels. Such probes have been implanted into the hippocampal formation of rats and their capabilities to capture pH changes at multiple pixels were evaluated at both physiological and pathological conditions. Technologies developed here represents a new class of in vivo chemical sensing technologies enabling the spatially-resolved investigation of intrinsic chemical signals in deep brain structures with high spatial and temporal resolutions.

Polymer-fiber-coupled field-effect sensors for label-free deep brain recordings.

Electrical recording permits direct readout of neural activity but offers limited ability to correlate it to the network topography. On the other hand, optical imaging reveals the architecture of neural circuits, but relies on bulky optics and fluorescent reporters whose signals are attenuated by the brain tissue. Here we introduce implantable devices to record brain activities based on the field effect, which can be further extended with capability of label-free electrophysiological mapping. Such devices reply on light-addressable potentiometric sensors (LAPS) coupled to polymer fibers with integrated electrodes and optical waveguide bundles. The LAPS utilizes the field effect to convert electrophysiological activity into regional carrier redistribution, and the neural activity is read out in a spatially resolved manner as a photocurrent induced by a modulated light beam. Spatially resolved photocurrent recordings were achieved by illuminating different pixels within the fiber bundles. These devices were applied to record local field potentials in the mouse hippocampus. In conjunction with the raster-scanning via the single modulated beam, this technology may enable fast label-free imaging of neural activity in deep brain regions.

Light-Addressable Potentiometric Sensors for Quantitative Spatial Imaging of Chemical Species.

A light-addressable potentiometric sensor (LAPS) is a semiconductor-based chemical sensor, in which a measurement site on the sensing surface is defined by illumination. This light addressability can be applied to visualize the spatial distribution of pH or the concentration of a specific chemical species, with potential applications in the fields of chemistry, materials science, biology, and medicine. In this review, the features of this chemical imaging sensor technology are compared with those of other technologies. Instrumentation, principles of operation, and various measurement modes of chemical imaging sensor systems are described. The review discusses and summarizes state-of-the-art technologies, especially with regard to the spatial resolution and measurement speed; for example, a high spatial resolution in a submicron range and a readout speed in the range of several tens of thousands of pixels per second have been achieved with the LAPS. The possibility of combining this technology with microfluidic devices and other potential future developments are discussed.

Polymer Composite with Carbon Nanofibers Aligned during Thermal Drawing as a Microelectrode for Chronic Neural Interfaces.

Microelectrodes provide a direct pathway to investigate brain activities electrically from the external world, which has advanced our fundamental understanding of brain functions and has been utilized for rehabilitative applications as brain-machine interfaces. However, minimizing the tissue response and prolonging the functional durations of these devices remain challenging. Therefore, the development of next-generation microelectrodes as neural interfaces is actively progressing from traditional inorganic materials toward biocompatible and functional organic materials with a miniature footprint, good flexibility, and reasonable robustness. In this study, we developed a miniaturized all polymer-based neural probe with carbon nanofiber (CNF) composites as recording electrodes via the scalable thermal drawing process. We demonstrated that in situ CNF unidirectional alignment can be achieved during the thermal drawing, which contributes to a drastic improvement of electrical conductivity by 2 orders of magnitude compared to a conventional polymer electrode, while still maintaining the mechanical compliance with brain tissues. The resulting neural probe has a miniature footprint, including a recording site with a reduced size comparable to a single neuron and maintained impedance that was able to capture neural activities. Its stable functionality as a chronic implant has been demonstrated with the long-term reliable electrophysiological recording with single-spike resolution and the minimal tissue response over the extended period of implantation in wild-type mice. Technology developed here can be applied to basic chronic electrophysiological studies as well as clinical implementation for neuro-rehabilitative applications.

Molecular fluorescence from H2TBP porphyrin film on Ag substrate excited by tunneling electrons.

Molecular fluorescence from H(2)TBP porphyrin (H(2)TBPP) films on Ag substrate is excited by a scanning tunneling microscope (STM) at ambient conditions. The molecular films are prepared by spin-casting method. The thickness of films can be controlled by the times of dropping H(2)TBPP solution. Molecular fluorescence of as-above prepared H(2)TBPP films with 4-14nm thickness at both polarities of applied bias voltage are well defined in good matching with its photoluminescence spectrum, which suggests the same decay channel associated with the HOMO-LUMO radiative transitions similar to H(2)TBPP/Au. The thickness dependence of light emission intensity of molecular fluorescence has been studied. The results show that for thicker film, molecular fluoresceence tends to be much stronger due to the effective decoupling of the emitter from the metal substrate.

Light-Addressable Potentiometric Sensor as a Sensing Element in Plug-Based Microfluidic Devices.

A plug-based microfluidic system based on the principle of the light-addressable potentiometric sensor (LAPS) is proposed. The LAPS is a semiconductor-based chemical sensor, which has a free addressability of the measurement point on the sensing surface. By combining a microfluidic device and LAPS, ion sensing can be performed anywhere inside the microfluidic channel. In this study, the sample solution to be measured was introduced into the channel in a form of a plug with a volume in the range of microliters. Taking advantage of the light-addressability, the position of the plug could be monitored and pneumatically controlled. With the developed system, the pH value of a plug with a volume down to 400 nL could be measured. As an example of plug-based operation, two plugs were merged in the channel, and the pH change was detected by differential measurement.

Investigation on light-addressable potentiometric sensor as a possible cell-semiconductor hybrid.

This article reports an investigation on light-addressable potentiometric sensor (LAPS) to be used as a possible biological cell-semiconductor hybrid that will enable us to make an interface between the physical and biological system. To increase the surface potential sensitivity, we used a LAPS structure with single insulator (SiO2) coated with poly-L-ornithine and laminin (PLOL) on Si. Efficient culturing of PC-12 and nerve cells of Lymnaea stagnalis on PLOL-coated Si3N4 and SiO2 was achieved. The thickness of the PLOL layer was found to be about 4 nm by the atomic force microscope (AFM) measurement. Using the advantage of this thin layer of PLOL, we compared the performance of a novel structure to the previously reported "PLOL-coated Si3N4/SiO2/Si" structure. Due to high insulating capacitance, the photocurrent response of the novel LAPS was found to be very steep. As a result, higher sensitivity was achieved. This steepness did not degrade during 10 days when the sensor surface was kept in contact with the cell culture medium and environment. The thickness of PLOL layer, its ability to improve the biological cell adhesion, enhanced sensitivity, and experiment with simulated neural action potential (AP) applied to the novel LAPS show a good promise for LAPS to be a biological cell-semiconductor hybrid.

Generation of spatial filters by ICA for detecting motor-related oscillatory EEG.

To detect the imagined limb movement from EEG for the use in BCI, the increase (ERS) and decrease (ERD) of the band power of the EEG originated from the sensorimotor cortex are commonly used. A spatial filter using neighboring channels is generally applied to the measured EEG for detecting such brain activity related to the motor imagery. However, the configuration and location of the spatial filter have been selected by the empirical method on trial-and-error basis. In this study, we recorded the EEG during motor imagery of left hand, right hand and feet from five subjects, and the ICA (independent component analysis) was applied to discover the spatial filters for extracting event-related EEG components of the motor imagery. It was suggested that the application of ICA might offer the experimenters appropriate local spatial filters, or at least, the "initial guess" for designing or selecting custom local spatial filters.

A NIRS-based brain-computer interface system during motor imagery: system development and online feedback training.

A brain-computer interface (BCI) to detect motor imagery from cerebrum hemodynamic data measured by NIRS (near-infrared spectroscopy) was constructed and the effect of the online feedback training for subjects was evaluated. Concentrations of Oxy- and deOxy-hemoglobin in the motor cortex during motor imagery of subject's right hand was measured by 52-channel NIRS system, and the mean magnitude of measured signal near C3 in the International 10-20 System was visually fed back online to the subject. On two out of three subjects, it was shown that the ratio between the averaged value and the standard deviation over trials (S/N ratio) of Oxy-hemoglobin signal elicited by the imagery of subject's right hand was increased by the 5-day online feedback training. Detailed investigation of the effect of the online feedback training on brain activities was left for further study.

A brain-computer interface (BCI) system based on auditory stream segregation.

An auditory brain-computer interface (BCI) which detected event-related potential (ERP) elicited by selective attention to one of the tone streams was proposed. Each tone in two kinds of frequency oddball tone sequences with different tone frequency range was presented alternatively to subjects, and they were perceived by subjects as two kinds of segregated streams. Event-related potentials elicited by two kinds of deviant tones were classified by linear discriminant analysis (LDA) to find which streams subjects paid selective attention. By the experiments to six subjects, it was shown that this system could realize binary selection from two kinds of segregated tone streams.

Detection of protein-protein interactions on SiO2/Si surfaces by spectroscopic ellipsometry.

We have applied spectroscopic ellipsometry to sensitive detection of specific protein-protein interactions on SiO2/Si substrates. First, the change of ellipticity of the reflected polarized light (600-1100 nm) was correlated with the thickness of the protein layer immobilized on SiO2/Si surfaces by measuring monomeric (myoglobin) and homotetrameric (hemoglobin) proteins with a similar monomer size. Protein-protein interactions were then measured with the antigen/antibody and cell-surface receptor/ligand systems; in each system either of the two proteins was bound to SiO2/Si substrates. Consequently, significant ellipticity changes were observed only for the cases where the interactions were specific. A specific antibody binding was also detectable with an antigen displayed on the surface of bacteriophage particles. These results show the usefulness of spectroscopic ellipsometry for sensitive detection of protein-protein interactions and its applicability to a detection method for the protein-based biochips to be developed in the future.