Referral odyssey plot to visualize causes of surgical delay in mesial temporal lobe epilepsy with hippocampal sclerosis.

The "odyssey plot" was used to visualize referral delays in epilepsy surgery. Participants were 36 patients (19 males; 13-67 years, median 27 years) with mesial temporal lobe epilepsy with hippocampal sclerosis (HS) who underwent resection surgery. The "referral odyssey plot" included five clinical episodes: seizure onset (T1), first visits to a non-epileptologist (T2) and to an epileptologist (T3), first admission to our epilepsy monitoring unit (EMU) (T4), and resection surgery (T5). For each patient, we identified the first seizure type: the physician who first diagnosed focal aware seizure (FAS), focal impaired awareness seizure (FIAS), focal to bilateral tonic-clonic seizure (FBTCS), and radiologically suspected HS. Within the overall delay (T1-T5, median 18 years; interquartile range [IQR] 14), non-epileptologist's delay (T2-T3, 11.5 years; IQR 12.25) was far (p < 0.0001) longer than patient's (T1-T2, 0 year; IQR 2.25), epileptologist's (T3-T4, 1 year; IQR 4), or after-EMU delay (T4-T5, 1 year; IQR 1). FAS onset cases had significantly longer T1-T2 (N = 5, median 7 years; IQR 6) than FIAS (N = 22, 0 year; IQR 1, p < 0.005) or FBTCS onset cases (N = 9, 0 year; IQR 0, p < 0.001). FAS was correctly diagnosed first by non-epileptologists in 17.9%, by out-patient epileptologists in 35.7%, and at the EMU in 46.4%. FIAS was correctly diagnosed first by non-epileptologists in 94.4% and by out-patient epileptologists in 5.6%. Non-epileptologists diagnosed FBTCS in all cases. HS was diagnosed by non-epileptologists in 13.9%, by out-patient epileptologists in 47.2%, and at the EMU in 38.9%. Early referral to epileptologists is most critical for early surgery. Early utilization of the EMU is highly recommended because FAS is often overlooked by outpatient epileptologists. The odyssey plot will be useful to improve the healthcare system for other types of epilepsy.

Sarcomatoid carcinoma of the pancreas with rare long-term survival: a case report.

BACKGROUND: Sarcomatoid carcinoma of the pancreas (SCP) tends to have similar or even worse prognosis than that of conventional pancreatic ductal adenocarcinoma. The clinical and pathological features of SCP remain poorly characterized owing to its rarity. CASE PRESENTATION: A 58-year-old man was admitted to our hospital with the chief complaints of upper abdominal pain and weight loss. Abdominal contrast computed tomography revealed a 5-cm low-density mass in the pancreatic body. Magnetic resonance cholangiopancreatography revealed an obstruction of the main pancreatic duct and a dilation of the distal main pancreatic duct. Based on the clinicoradiological findings, pancreatic body cancer was suspected, and the distal pancreatectomy was performed. A pathological examination revealed that the tumor was composed of an area of invasive ductal adenocarcinoma and an area of sarcomatous spindle-shaped cells; the latter component predominated. The spindle cells were immunohistochemically positive for both cytokeratin and vimentin, and thus, a pathological diagnosis of SCP was made. In addition, immunohistochemical analysis suggested the sarcomatous component might be derived from the adenocarcinoma component via the process of epithelial-mesenchymal transition. After the operation, the patient received 6 months of chemotherapy with gemcitabine. At 10 years after the operation, the patient is alive with no recurrence. CONCLUSIONS: The current case study presented a SCP patient with long-term survival after the operation. It was worth noting that the sarcomatous component of the tumor pathologically showed lower MIB-1 labeling index compared with those in previously reported SCP cases, which might account for the long-term survival of the patient.

A comprehensive understanding of lowly-hydrolyzed polyvinyl alcohol-based ternary solid dispersions with the use of a combined mixture-process design.

We recently reported lowly hydrolyzed polyvinyl alcohol (L-PVA, 70-74% hydrolyzed, about 580 polymerized, JR-05) as a promising matrix for hot-melt extrusion (HME) due to its unique micelle formation ability compared to the most commonly used PVA (87-89% hydrolyzed, about 580 polymerized). In the present study, we focused on the effect of composition [indomethacin (IND), L-PVA, sorbitol] and process parameters (temperature and screw speed) on each response, i.e. processing torque, and physicochemical properties such as residual crystallinity, residual ratio, and area under the dissolution curve (AUDC) in supersaturated solution using a HME by applying the design of experiment (DoE) approach. To overcome the poor processability of L-PVA, given its semicrystalline nature, we applied sorbitol as a plasticizer and systematically and simultaneously evaluated its influence on the outputs based on the mixture design combined with process factors. Few studies have focused on comprehensive evaluation of the composition and HME process conditions because obtaining a design space requires numerous experiments. We found that incorporating sorbitol into the L-PVA greatly improved the processing torque. However, sorbitol negatively influenced the degree of residual crystallinity and the AUDC of IND. Lastly, we established a laboratory-scale design space that could achieve high supersaturation and ensure adequate miscibility between each component, using an acceptable processing torque for HME, by applying the minimum amount of sorbitol. These fundamental results suggest that sorbitol maximizes the potency of L-PVA as a carrier in HME.

[Neoadjuvant Proton Beam Chemoradiotherapy for Locally Advanced Gall Bladder Cancer-A Case Report].

A 67-year-old man visited our hospital due to progressing appetite loss and fever. He presented with a fist-sized palpable mass in his right hypochondrium. Abdominal CT showed a 10 cm diameter tumor that originated from the gall bladder infiltrating the abdominal wall, liver, duodenum, and colon. Blood tests revealed leukocytosis, elevated C-reactive protein level, and severe malnutrition. FDG-PET showed markedly high uptake in the tumor and diffuse uptake in the spine. Owing to the inability of oral intake, he underwent laparoscopic gastrojejunostomy and intraoperative tumor biopsy, which demonstrated pathologically G-CSF-producing carcinoma in the gall bladder. For the rapidly progressive tumor, he underwent proton beam chemoradiotherapy as preoperative treatment. The tumor markedly shrunk with dramatic improvement of his inflammatory and nutritional status. Consequently, R0 resection could be performed by combination surgeries of right hemi-colectomy, pancreatoduodenectomy, and partial liver resection. He received adjuvant chemotherapy and was alive without recurrence 12 months after tumor resection. To our knowledge, this is the first report of the use of neoadjuvant proton beam chemoradiotherapy in biliary cancer.

[A Case of Pathological Complete Response Following Neoadjuvant Chemotherapy with Gemcitabine plus Nab-Paclitaxel in Borderline Resectable Pancreatic Cancer].

We report a resected case with a pathological complete response(pCR)after neoadjuvant chemotherapy for borderline resectable pancreatic cancer(BRPC). A 67-year-old woman who had been treated for type 2 diabetes mellitus in our hospital presented with an exacerbation of diabetes. An abdominal CT scan confirmed a hypovascular mass in the pancreas body consistent with BRPC. After 3 courses of chemotherapy with gemcitabine plus nab-paclitaxel(GnP), her elevated DUPAN-2 level normalized. A follow up CT scan revealed that the tumor had decreased in size, and no distant metastasis was detected. Distal pancreatectomy with en-bloc celiac axis resection was performed. Histopathological examination of the resected specimens showed no evidence of residual cancer cells(pCR). The patient remains disease-free 8 months after surgery. Neoadjuvant GnP chemotherapy may be useful for BRPC.

Nanoscale-Tipped High-Aspect-Ratio Vertical Microneedle Electrodes for Intracellular Recordings.

Intracellular recording nanoscale electrode devices provide the advantages of a high spatial resolution and high sensitivity. However, the length of nanowire/nanotube-based nanoelectrodes is currently limited to <10 µm long due to fabrication issues for high-aspect-ratio nanoelectrodes. The concept reported here can address the technological limitations by fabricating >100 µm long nanoscale-tipped electrodes, which show intracellular recording capability.

Co-Design Method and Wafer-Level Packaging Technique of Thin-Film Flexible Antenna and Silicon CMOS Rectifier Chips for Wireless-Powered Neural Interface Systems.

In this paper, a co-design method and a wafer-level packaging technique of a flexible antenna and a CMOS rectifier chip for use in a small-sized implantable system on the brain surface are proposed. The proposed co-design method optimizes the system architecture, and can help avoid the use of external matching components, resulting in the realization of a small-size system. In addition, the technique employed to assemble a silicon large-scale integration (LSI) chip on the very thin parylene film (5 µm) enables the integration of the rectifier circuits and the flexible antenna (rectenna). In the demonstration of wireless power transmission (WPT), the fabricated flexible rectenna achieved a maximum efficiency of 0.497% with a distance of 3 cm between antennas. In addition, WPT with radio waves allows a misalignment of 185% against antenna size, implying that the misalignment has a less effect on the WPT characteristics compared with electromagnetic induction.

A novel approach to a fine particle coating using porous spherical silica as core particles.

Abstract The applicability of porous spherical silica (PSS) was evaluated as core particles for pharmaceutical products by comparing it with commercial core particles such as mannitol (NP-108), sucrose and microcrystalline cellulose spheres. We investigated the physical properties of core particles, such as particle size distribution, flow properties, crushing strength, plastic limit, drying rate, hygroscopic property and aggregation degree. It was found that PSS was a core particle of small particle size, low friability, high water adsorption capacity, rapid drying rate and lower occurrence of particle aggregation, although wettability is a factor to be carefully considered. The aggregation and taste-masking ability using PSS and NP-108 as core particles were evaluated at a fluidized-bed coating process. The functional coating under the excess spray rate shows different aggregation trends and dissolution profiles between PSS and NP-108; thereby, exhibiting the formation of uniform coating under the excess spray rate in the case of PSS. This expands the range of the acceptable spray feed rates to coat fine particles, and indicates the possibility of decreasing the coating time. The results obtained in this study suggested that the core particle, which has a property like that of PSS, was useful in overcoming such disadvantages as large particle size, which feels gritty in oral cavity; particle aggregation; and the long coating time of the particle coating process. These results will enable the practical fine particle coating method by increasing the range of optimum coating conditions and decreasing the coating time in fluidized bed technology.

Somatosensory evoked spikes in normal adults detected by magnetoencephalography.

OBJECTIVE: Somatosensory evoked spikes (SESs) have been reported only in children aged under 14 years and are considered as an age-dependent phenomenon. However, we detected SESs in adult patients with epilepsy using magnetoencephalography (MEG). The present study investigated whether MEG can detect SESs in normal adults. METHODS: Spontaneous MEG was recorded during measurement of somatosensory evoked fields (SEFs) for bilateral electrical median nerve stimuli in 30 healthy adults. RESULTS: Bilateral SESs were observed in 10 adults but none in the other 20 subjects. SESs consisted of one or two peaks, and the first peak latency corresponded to that of the second peak (M2) of SEFs. The first SES peak was identical to the M2 in isofield map pattern, as well as location and orientation of the equivalent current dipole (ECD). M2 ECD strength in the 10 subjects with SESs was larger (p <0.0001) than in 20 without SESs. CONCLUSIONS: All-or-nothing detection of bilateral SESs by MEG in normal adults must depend on the signal-to-noise issue of symmetrical SEFs and background brain activity. SIGNIFICANCE: Our results further confirm the higher sensitivity of MEG compared to scalp EEG for the detection of focal cortical sources tangential to the scalp such as SESs.

Super-selective injection of propofol into the intracranial arteries enables Patient's self-evaluation of expected neurological deficit.

INTRODUCTION: It is hard to realize the extent of the expected postoperative neurological deficit for patients themselves. The provision of appropriate information can contribute not only to examining surgical indications but also to filling the gap between patient and expert expectations. We hypothesized that propofol infusion into the intracranial arteries (ssWada) could induce focal neurological symptoms with preserved wakefulness, enabling the patients to evaluate the postsurgical risk subjectively. METHODS: Presurgical evaluation using ssWada was performed in 28 patients with drug-resistant epilepsy. Based on anatomical knowledge, propofol was super-selectively infused into the intracranial arteries including the M1, M2, and M3 segments of the middle cerebral artery (MCA), A2 segment of the anterior cerebral artery, and P2 segment of the posterior cerebral artery to evaluate the neurological and cognitive symptoms. We retrospectively analyzed a total of 107 infusion trials, including their target vessels, and elicited symptoms of motor weakness, sensory disturbance, language, unilateral hemispatial neglect (UHN), and hemianopsia. We evaluated preserved wakefulness which enabled subjective evaluations of the symptoms and comparison of the subjective experience to the objective findings, besides adverse effects during the procedure. RESULTS: Preserved wakefulness was found in 97.2% of all trials. Changes in neurological symptoms were positively evaluated for motor weakness in 51.4%, sensory disturbance in 5.6%, language in 48.6%, UHN in 22.4%, and hemianopsia in 32.7%. Six trials elicited seizures. Multivariate analysis showed significant correlations between symptom and infusion site of language and left side, language and MCA branches, motor weakness and A2 or M2 superior division, and hemianopsia and P2. Transient adverse effect was observed in 8 cases with 12 infusion trials (11.2 %). CONCLUSION: The ssWada could elicit focal neurological symptoms with preserved wakefulness. The methodology enables specific evaluation of risk for cortical resection and subjective evaluation of the expected outcome by the patients.

[Analysis of the eligibility of elderly colorectal cancer patients for adjuvant chemotherapy combined with polysaccharide K].

We enrolled 62 elderly patients( ≥70 years of age) with colorectal cancer who had undergone surgery and postoperative adjuvant chemotherapy at our department and analyzed the overall surviva(l OS) and disease-free surviva(l DFS) to identify the patients who responded to treatment. Postoperative adjuvant chemotherapy was performed with oral anticancer agents, including doxifluridine( 5'-DFUR), uracil/tegafur( UFT), and UFT/Leucovorin( LV); all patients also received polysaccharide K( PSK), an immunomodulator, in combination with chemotherapy. The 3-year OS and DFS rates for all patients were 83.4% and 78.6%, respectively, with no significant differences in these rates based on the chemotherapeutic agents used. The patients were assigned to low and high groups on the basis of the median cut-off values of each clinical laboratory parameter and the data obtained were subjected to univariate analysis. The results of the univariate analysis suggested that carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125) levels were significant prognostic factors. Further multivariate analysis using Cox regression analysis identified the preoperative CEA level alone as an independent factor. When stratification analysis was performed using a preoperative CEA level of 4.0 ng/mL as the cut-off value, the results indicated that the outcome of patients with a high preoperative CEA level may be 8-fold worse than that of patients with a low preoperative CEA level. For these patients, the use of chemotherapeutic drugs that elicit a more potent antitumor effect should be considered.

Language MEG predicts postoperative verbal memory change in left mesial temporal lobe epilepsy.

OBJECTIVE: To clarify whether preoperative language magnetoencephalography (MEG) predicts postoperative verbal memory (VM) changes in left mesial temporal lobe epilepsy (LMTLE). METHODS: We reviewed 18 right-handed patients with LMTLE who underwent anterior temporal lobectomy or selective amygdala hippocampectomy, 12 with (HS+) and 6 without hippocampal sclerosis (HS-). Patients underwent neuropsychological assessment before and after surgery. MEG was measured with an auditory verbal learning task in patients preoperatively and in 15 right-handed controls. Dynamic statistical parametric mapping (dSPM) was used for source imaging of task-related activity. Language laterality index (LI) was calculated by z-score of dSPM in language-related regions. LI in the region of HS+ and HS- was compared to controls. The correlation between LI and postoperative VM change was assessed in HS+ and HS-. RESULTS: Preoperative LI in supramarginal gyrus showed greater right-shifted lateralization in both HS+ and HS- than in controls. Right-shifted LI in supramarginal gyrus was correlated with postoperative VM increase in HS+ (p = 0.019), but not in HS-. CONCLUSIONS: Right-shifted language lateralization in dSPM of MEG signals may predict favorable VM outcome in HS+ of LMTLE. SIGNIFICANCE: Findings warrant further investigation of the relation between regional language laterality index and postoperative verbal memory changes.

Nanoscale tipped microwire arrays enhance electrical trap and depth injection of nanoparticles.

Nanoscale devices have the potential to measure biological tissues as well as individual cells/neurons. However, three-dimensional (3D) multi-site probing remains problematic because only planar-type device designs are applicable to sample surfaces. Herein we report 3D nanoscale electrode tipped microwire arrays with high aspect ratios. A nanoscale tipped wire is formed by isotropic silicon etching to the tip of a vapor-liquid-solid grown silicon microwire. After coating the wire with a metal (e.g., Pt and Au), only the nanotip section can be exposed from the surrounding outer shell (e.g., SiO(2) and parylene) by photoresist spray coating and subsequent cycled photoresist etchings. As a promising device application, we demonstrate the trapping of polystyrene nanoparticles in a solution using a fabricated Au-nanotip wire array. The sharpened nanotip has a 150 nm curvature radius and a 4.2 µm(2) electrode area. The nanotip wires exhibit a locally enhanced trapping performance with a low trapping voltage of 20 mV. Moreover, these trapped nanoparticles can be injected into a soft material (gelatin), demonstrating a multi-site wide-area batch depth injection and an assembly of nanoparticles. Such nanotip wire arrays should be applicable to trap numerous particles, including DNA/molecules attached to Au particles, and may realize injection into biological tissues and individual cells/neurons.

A miniature integrated multimodal sensor for measuring pH, EC and temperature for precision agriculture.

Making several simultaneous measurements with different kinds of sensors at the same location in a solution is difficult because of crosstalk between the sensors. In addition, because the conditions at different locations in plant beds differ, in situ measurements in agriculture need to be done in small localized areas. We have fabricated a multimodal sensor on a small Si chip in which a pH sensor was integrated with electrical conductivity (EC) and temperature sensors. An ISFET with a Si(3)N(4) membrane was used for the pH sensor. For the EC sensor, the electrical conductivity between platinum electrodes was measured, and the temperature sensor was a p-n junction diode. These are some of the most important measurements required for controlling the conditions in plant beds. The multimodal sensor can be inserted into a plant bed for in situ monitoring. To confirm the absence of crosstalk between the sensors, we made simultaneous measurements of pH, EC, and temperature of a pH buffer solution in a plant bed. When the solution was diluted with hot or cold water, the real time measurements showed changes to the EC and temperature, but no change in pH. We also demonstrated that our sensor was capable of simultaneous in situ measurements in rock wool without being affected by crosstalk.

Nanoscale-tipped wire array injections transfer DNA directly into brain cells ex vivo and in vivo.

Genetic modification to restore cell functions in the brain can be performed through the delivery of biomolecules in a minimally invasive manner into live neuronal cells within brain tissues. However, conventional nanoscale needles are too short (lengths of ~10 µm) to target neuronal cells in ~1-mm-thick brain tissues because the neuronal cells are located deep within the tissue. Here, we report the use of nanoscale-tipped wire (NTW) arrays with diameters < 100 nm and wire lengths of ~200 µm to address biomolecule delivery issues. The NTW arrays were manufactured by growth of silicon microwire arrays and nanotip formation. This technique uses pinpoint, multiple-cell DNA injections in deep areas of brain tissues, enabling target cells to be marked by fluorescent protein (FP) expression vectors. This technique has potential for use for electrophysiological recordings and biological transfection into neuronal cells. Herein, simply pressing an NTW array delivers and expresses plasmid DNA in multiple-cultured cells and multiple-neuronal cells within a brain slice with reduced cell damage. Additionally, DNA transfection is demonstrated using brain cells ex vivo and in vivo. Moreover, knockdown of a critical clock gene after injecting a short hairpin RNA (shRNA) and a genome-editing vector demonstrates the potential to genetically alter the function of living brain cells, for example, pacemaker cells of the mammalian circadian rhythms. Overall, our NTW array injection technique enables genetic and functional modification of living cells in deep brain tissue areas, both ex vivo and in vivo.

Determination of language areas in patients with epilepsy using the super-selective Wada test.

The Wada test is the gold standard for determining language-dominant hemisphere. However, the precise determination of language areas in each patient requires more invasive methods, such as electrocortical stimulation. Some studies have reported the use of anesthetic injection into selective cerebral arteries to predict postoperative function. To assess the function of the anterior and posterior language areas separately, we developed an advanced test named the "super-selective Wada test" (ssWada). The ssWada procedure is as follows: an endovascular neurosurgeon identifies the arterial branches of the middle cerebral artery (MCA) perfusing the anterior language area of the inferior frontal gyrus and the posterior language area of the posterior part of the superior temporal gyrus using angiography. Behavioral neurologists assess language symptoms before and after propofol administration using a microcatheter tip in the selected arterial branch. From 30 serial patients with epilepsy who underwent ssWada test at Tohoku University Hospital, we retrospectively reviewed patients in whom multiple areas in the bilateral MCA region was examined. Eight cases were identified in this study. All eight cases had been considered for resection of the area overlapping the classical language area. Three of the eight cases were left-dominant, and the within-hemisphere distribution was also considered typical. One case was determined to be left-dominant but atypical in the intra-hemispheric functional distribution. Two cases were right-dominant, and the intra-hemispheric functional distribution was considered a mirror image of the typical pattern. The remaining two cases were considered atypical, not only in terms of bilateral language function, but also in terms of anterior-posterior functional distribution. This case series demonstrates the potential utility of ssWada in revealing separate function of the anterior and posterior language areas. The ssWada allows simulation of local surgical brain resection and detailed investigation of language function, which potentially contributes to planning the resection area. Although indications for ssWada are quite limited, it could play a complementary role to noninvasive testing because it provides information related to resection using a different approach.

Magnetoencephalography to confirm epileptiform discharges mimicking small sharp spikes in temporal lobe epilepsy.

OBJECTIVE: To determine whether magnetoencephalography (MEG) can identify epileptiform discharges mimicking small sharp spikes (SSSs) on scalp electroencephalography (EEG) in patients with temporal lobe epilepsy (TLE). METHODS: We retrospectively reviewed simultaneous scalp EEG and MEG recordings of 83 consecutive patients with TLE and 49 with extra-TLE (ETLE). RESULTS: SSSs in scalp EEG were detected in 15 (18.1%) of 83 TLE patients compared to only two (4.1%) of 49 ETLE patients (p = 0.029). Five of the 15 TLE patients had MEG spikes with concurrent SSSs in EEG, but neither of the 2 ETLE patients. Three of these 5 TLE patients had additional interictal epileptiform discharges (IEDs) in EEG and MEG. Equivalent current dipoles (ECDs) of MEG spikes with concurrent SSSs and IEDs showed no difference in temporal lobe localization and horizontal orientation, whereas ECD moments were smaller in MEG spikes with concurrent SSSs than those with IEDs. CONCLUSIONS: SSSs were more common in TLE than in ETLE. At least some morphologically diagnosed SSSs are true but low-amplitude epileptiform discharges in TLE which can be identified with simultaneous MEG. SIGNIFICANCE: Simultaneous MEG is useful to identify epileptiform discharges mimicking SSSs in patients with TLE.

Possible spontaneous regression of hepatocellular carcinoma with unique histopathological features confirmed by surgical resection: a case report.

BACKGROUND: Spontaneous regression of hepatocellular carcinoma (HCC) is a rare event, and its clinicopathological features and underlying mechanism are not fully understood. CASE PRESENTATION: An 84-year-old female with hepatitis C virus infection and diabetes mellitus was referred to our hospital for further examination. Abdominal ultrasonography showed a 3.4-cm solid tumor with a heterogeneous irregular center and no fibrous capsule in liver segment 8 (S8). An enhanced computed tomography (CT) scan revealed a tumor in S8 with heterogeneous enhancement in the arterial phase and washed out insufficiently in the portal and equilibrium phase. The enhanced pattern on magnetic resonance imaging was similar to that of CT. Although the imaging findings were not typical for HCC, liver resection (S8) was performed with HCC as the most probable diagnosis. Histopathological examination of the resected specimen showed that the tumor was well to moderately differentiated HCC with unique features. Approximately half of the tumor was composed of well-differentiated HCC that was focally accompanied by dense lymphocyte infiltration. The other half of the tumor was fibrotic tissue that resembled an inflammatory pseudotumor. Several foci of moderately differentiated HCC were scattered within the tumor with a nodule-in-nodule appearance, and the foci totally showed coagulative necrosis. On immunostaining, lymphocytes in the tumor stroma were positive for CD8 and programmed death 1. The expression of programmed death-ligand 1 was observed in carcinoma cells and macrophages specifically within the lymphocyte-rich area of HCC. CONCLUSIONS: We consider this case representative of spontaneous regression of HCC, and the immune response against HCC might contribute to tumor regression, leading to complex histopathological appearances. This case may provide insight into the mechanism of spontaneous regression of HCC.

Microtube-based electrode arrays for low invasive extracellular recording with a high signal-to-noise ratio.

We report on the development of a microtube electrode array as a neural interface device. To combine the desired properties for the neural interface device, such as low invasiveness with a small needle and a good signal-to-noise ratio in neural recordings, we applied the structure of a glass pipette electrode to each microtube electrode. The device was fabricated as sub-5-microm-diameter out-of-plane silicon dioxide microtube arrays using silicon microneedle templates, which are grown by the selective vapor-liquid-solid method. The microtubes had inner diameters of 1.9-6.4 microm and a length of 25 microm. Impedances ranged from 220 kOmega to 1.55 MOmega, which are less than those for conventional microneedles. In addition, the microtube electrodes had less signal attenuation than conventional microneedle electrodes. We confirmed that the effects of parasitic capacitances between neighboring microtubes and channels were sufficiently small using a test signal. Finally, neural responses evoked from a rat peripheral nerve were recorded in vivo using a microtube electrode to confirm that this type of electrode can be used for both electrophysiological measurements and as a neural interface device.

Nanoscale sharpening tips of vapor-liquid-solid grown silicon microwire arrays.

We developed out-of-plane, high aspect ratio, nanoscale tip silicon microwire arrays for application to penetrating, multisite, nanoscale biological sensors. Silicon microwire arrays selectively grown by gold-catalyzed vapor-liquid-solid growth of silicon can be formed to create sharpened nanotips with a tip diameter of less than 100 nm by utilizing batch-processed silicon chemical etching for only 1-3 min. The tip angles achieved ranged from 11 degrees to 38 degrees. The nanotip silicon microwires can perform gelatin penetration without wire breakdown, indicating their potential penetrating capability for measurements inside biological tissues.