Multi-drug resistant efflux transporters found in Blood-Brain Barrier (BBB) acts as a functional barrier, by pumping out most of the drugs into the blood. Previous studies showed focused ultrasound (FUS) induced microbubble oscillation can disrupt the BBB by loosening the tight junctions in the brain endothelial cells; however, no study was performed to investigate its impact on the functional barrier of the BBB. In this study, the BBB in rat brains were disrupted using the MRI guided FUS and microbubbles. The immunofluorescence study evaluated the expression of the P-glycoprotein (P-gp), the most dominant multi-drug resistant protein found in the BBB. Intensity of the P-gp expression at the BBB disruption (BBBD) regions was significantly reduced (63.2 ± 18.4%) compared to the control area. The magnitude of the BBBD and the level of the P-gp down-regulation were significantly correlated. Both the immunofluorescence and histologic analysis at the BBBD regions revealed no apparent damage in the brain endothelial cells. The results demonstrate that the FUS and microbubbles can induce a localized down-regulation of P-gp expression in rat brain. The study suggests a clinically translation of this method to treat neural diseases through targeted delivery of the wide ranges of brain disorder related drugs.

We describe an in situ fluorescence optical detection system to demonstrate real-time and non-invasive detection of reaction products in a microfluidic device while under perfusion within a standard incubator. The detection system is designed to be compact and robust for operation inside a mammalian cell culture incubator for quantitative detection of fluorescent signal from microfluidic devices. When compared to a standard plate reader, both systems showed similar biphasic response curves with two linear regions. Such a detection system allows real-time measurements in microfluidic devices with cells without perturbing the culture environment. In a proof-of-concept experiment, the cytochrome P450 1A1/1A2 activity of a hepatoma cell line (HepG2/C3A) was monitored by measuring the enzymatic conversion of ethoxyresorufin to resorufin. The hepatoma cell line was embedded in Matrigel(TM) construct and cultured in a microfluidic device with medium perfusion. The response of the cells, in terms of P450 1A1/1A2 activity, was significantly different in a plate well system and the microfluidic device. Uninduced cells showed almost no activity in the plate assay, while uninduced cells in Matrigel(TM) with perfusion in a microfluidic device showed high activity. Cells in the plate assay showed a significant response to induction with 3-Methylcholanthrene while cells in the microfluidic device did not respond to the inducer. These results demonstrate that the system is a potentially useful method to measure cell response in a microfluidic system.

A Brain-Machine interface (BMI) allows for direct communication between the brain and machines. Neural probes for recording neural signals are among the essential components of a BMI system. In this report, we review research regarding implantable neural probes and their applications to BMIs. We first discuss conventional neural probes such as the tetrode, Utah array, Michigan probe, and electroencephalography (ECoG), following which we cover advancements in next-generation neural probes. These next-generation probes are associated with improvements in electrical properties, mechanical durability, biocompatibility, and offer a high degree of freedom in practical settings. Specifically, we focus on three key topics: (1) novel implantable neural probes that decrease the level of invasiveness without sacrificing performance, (2) multi-modal neural probes that measure both electrical and optical signals, (3) and neural probes developed using advanced materials. Because safety and precision are critical for practical applications of BMI systems, future studies should aim to enhance these properties when developing next-generation neural probes.

From active developments and applications of various devices to acquire outside and inside information and to operate based on feedback from that information, the sensor market is growing rapidly. In accordance to this trend, the surface plasmon resonance (SPR) sensor, an optical sensor, has been actively developed for high-sensitivity real-time detection. In this study, the fundamentals of SPR sensors and recent approaches for enhancing sensing performance are reported. In the section on the fundamentals of SPR sensors, a brief description of surface plasmon phenomena, SPR, SPR-based sensing applications, and several configuration types of SPR sensors are introduced. In addition, advanced nanotechnology- and nanofabrication-based techniques for improving the sensing performance of SPR sensors are proposed: (1) localized SPR (LSPR) using nanostructures or nanoparticles; (2) long-range SPR (LRSPR); and (3) double-metal-layer SPR sensors for additional performance improvements. Consequently, a high-sensitivity, high-biocompatibility SPR sensor method is suggested. Moreover, we briefly describe issues (miniaturization and communication technology integration) for future SPR sensors.

Metallic nanostructures have recently been demonstrated to improve the performance of optical sensing and imaging techniques due to their remarkable localization capability of electromagnetic fields. Particularly, the zero-dimensional nanostructure, commonly called a nanoparticle, is a promising component for optical measurement systems due to its attractive features, e.g., ease of fabrication, capability of surface modification and relatively high biocompatibility. This review summarizes the work to date on metallic nanoparticles for optical sensing and imaging applications, starting with the theoretical backgrounds of plasmonic effects in nanoparticles and moving through the applications in Raman spectroscopy and fluorescence biosensors. Various efforts for enhancing the sensitivity, selectivity and biocompatibility are summarized, and the future outlooks for this field are discussed. Convergent studies in optical sensing and imaging have been emerging field for the development of medical applications, including clinical diagnosis and therapeutic applications.