We have developed a Si opt-neural probe with multiple waveguides and metal cover for highly accurate optical stimulation. This neural probe had 16 recording sites, three optical waveguides, and metal cover for suppressing light leakage. We evaluated electrochemical properties of the recording sites, and confirmed that the neural probe had suitable characteristics for neural recording. We also demonstrated the optical stimulation to the neurons expressing ChR2 using our probe. As a result, we succeeded multisite optical stimulation, and observed that no light leakage from the optical waveguides because of the metal cover. From in vivo experiments, we successfully recorded optically modulated local field potential using the fabricated Si neural probe with optical waveguides. Moreover, we applied current source density analysis to the recorded LFPs. As a result, we confirmed that light induced membrane current sink in locally stimulated area. Our Si opto-neural probe with multiple optical waveguides and metal-cover is one of the most versatile tools for optogenetics.

d- and l-Tryptophan (Trp) and d- and l-kynurenine (KYN) were derivatized with a chiral reagent, (S)-4-(3-isothiocyanatopyrrolidin-1-yl)-7-(N,N-dimethylaminosulfonyl)-2,1,3-benzoxadiazole (DBD-PyNCS), and were separated enantiomerically by high-performance liquid chromatography (HPLC) equipped with a triazole-bonded column (Cosmosil HILIC) using tandem mass spectrometric (MS/MS) detection. Effects of column temperature, salt (HCO NH ) concentration, and pH of the mobile phase in the enantiomeric separation, followed by MS detection of (S)-DBD-PyNCS-d,l-Trp and -d,l-KYN, were investigated. The mobile phase consisting of CH CN/10 mM ammonium formate in H O (pH 5.0) (90/10) with a column temperature of 50-60 °C gave satisfactory resolution (Rs) and mass-spectrometric detection. The enantiomeric separation of d,l-Trp and d,l-KYN produced Rs values of 2.22 and 2.13, and separation factors (α) of 1.08 and 1.08, for the Trp and KYN enantiomers, respectively. The proposed LC-MS/MS method provided excellent detection sensitivity of both enantiomers of Trp and KYN (5.1-19 nM).

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A Si neural probe is one of the most important tools for neuroscience because it can record neuronal activities in a brain densely. However, it would damage the brain during insertion. Therefore, it is necessary for the Si neural probe to reduce invasiveness to the brain. In this study, we proposed the lower invasive Si neural probe having both triangular shank and sharpened tip fabricated using Si anisotropic etching technique. From in vivo mouse brain insertion experiments, it was clearly indicated that the proposed Si neural probe had insertion force of 15 % compared to a Si probe with normal tip. The lower invasive Si neural prove becomes a versatile tool of neurophysiology and neuroscience.

For safe electrical stimulation with body-implanted devices, the degradation of stimulus electrodes must be considered because it causes the unexpected electrolysis of water and the destruction of tissues. To monitor the charge injection property (CIP) of stimulus electrodes while these devices are implanted, we have proposed a charge injection monitoring system (CIMS). CIMS can safely read out voltages produced by a biphasic current pulse to a stimulus electrode and CIP is calculated from waveforms of the acquired voltages. In this paper, we describe a wide-range and low-power analog front-end (AFE) for CIMS that has variable gain-frequency characteristics and low-power analog-to-digital (A/D) conversion to adjust to the degradation of stimulus electrodes. The designed AFE was fabricated with 0.18 µm CMOS technology and achieved a valuable gain of 20-60 dB, an upper cutoff frequency of 0.2-10 kHz, and low-power interleaving A/D conversion. In addition, we successfully measured the CIP of stimulus electrodes for body-implanted devices using CIMS.