Fabrication of Substrate-Integrated Waveguide Using Micromachining of Photoetchable Glass Substrate for 5G Millimeter-Wave Applications.

A millimeter-wave substrate-integrated waveguide (SIW) was firstly demonstrated using the micromachining of photoetchable glass (PEG) for 5G applications. A PEG substrate was used as a dielectric material of the SIW, and its photoetchable properties were used to fabricate through glass via (TGV) holes. Instead of the conventional metallic through glass via (TGV) array structures that are typically used for the SIW, two continuous empty TGV holes with metallized sidewalls connecting the top metal layer to the bottom ground plane were used as waveguide walls. The proposed TGV walls were fabricated by using optical exposure, heat development and anisotropic HF (hydrofluoric acid) etching of the PEG substrate, followed by a metal sputtering technique. The SIW was fed by microstrip lines connected to the waveguide through tapered microstrip-to-waveguide transitions. The top metal layer, including these feedlines and transitions, was fabricated by selective metal sputtering through a silicon shadow mask, which was prefabricated by a silicon deep-reactive ion-etching (DRIE) technique. The developed PEG-based process provides a relatively simple, wafer-level manufacturing method to fabricate the SIW in a low-cost glass dielectric substrate, without the formation of individual of TGV holes, complex time-consuming TGV filling processes and repeated photolithographic steps. The fabricated SIW had a dimension of 6 × 10 × 0.42 mm3 and showed an average insertion loss of 2.53 ± 0.55 dB in the Ka-band frequency range from 26.5 GHz to 40 GHz, with a return loss better than 13.86 dB. The proposed process could be used not only for SIW-based devices, but also for various millimeter-wave applications where a glass substrate with TGV structures is required.

Optrode Array for Simultaneous Optogenetic Modulation and Electrical Neural Recording.

During the last decade, optogenetics has become an essential tool for the investigation of neural signaling due to its unique capability of selective neural modulation or monitoring. As specific types of neuronal cells can be genetically modified to express opsin proteins, optogenetics enables optical stimulation or inhibition of the selected neurons. There have been several technological advances in the optical system for optogenetics. Recently, it was proposed to combine the optical waveguide for light delivery with electrophysiological recording to simultaneously monitor the neural responses to optogenetic stimulation or inhibition. In this study, an implantable optrode array (2x2 optical fibers) was developed with embedded multichannel electrodes. A light-emitting diode (LED) was employed as a light source, and a microfabricated microlens array was integrated to provide sufficient light power at the tip of the optical fibers. The optrode array system comprises the disposable part and the reusable part. The disposable part has optical fibers and electrodes, while the reusable part has the LED and electronic circuitry for light control and neural signal processing. The novel design of the implantable optrode array system is introduced in the accompanying video in addition to the procedure of the optrode implantation surgery, optogenetic light stimulation, and the electrophysiological neural recording. The results of in vivo experiments successfully showed time-locked neural spikes evoked by the light stimuli from hippocampal excitatory neurons of mice.

Design and Fabrication of Millimeter-Wave Frequency-Tunable Metamaterial Absorber Using MEMS Cantilever Actuators.

In this paper, a MEMS (Micro Electro Mechanical Systems)-based frequency-tunable metamaterial absorber for millimeter-wave application was demonstrated. To achieve the resonant-frequency tunability of the absorber, the unit cell of the proposed metamaterial was designed to be a symmetric split-ring resonator with a stress-induced MEMS cantilever array having initial out-of-plane deflections, and the cantilevers were electrostatically actuated to generate a capacitance change. The dimensional parameters of the absorber were determined via impedance matching using a full electromagnetic simulation. The designed absorber was fabricated on a glass wafer with surface micromachining processes using a photoresist sacrificial layer and the oxygen-plasma-ashing process to release the cantilevers. The performance of the fabricated absorber was experimentally validated using a waveguide measurement setup. The absorption frequency shifted down according to the applied DC (direct current) bias voltage from 28 GHz in the initial off state to 25.5 GHz in the pull-down state with the applied voltage of 15 V. The measured reflection coefficients at those frequencies were -5.68 dB and -33.60 dB, corresponding to the peak absorptivity rates of 72.9 and 99.9%, respectively.

Silicon optrode array with monolithically integrated SU-8 waveguide and single LED light source.

Objective. This paper presents a conventional light emitting diode (LED) and polymer waveguide coupled silicon optrode array.Approach. Unique lens design at the waveguide inlet enables a high light coupling efficiency with a single LED light source, and provides small power consumption compatible with a wireless optogenetic neuromodulation system. To increase the light intensity at the waveguide tip, a lensed waveguide is fabricated with epoxy-based photoresist SU-8, which has a plano-convex lens shape at the waveguide inlet to focus the light in the horizontal direction. In addition, a cylindrical lens is assembled in front of the waveguide inlet to focus the source light in the vertical direction.Main results. The glass cylindrical lens and SU-8 plano-convex lens increased the light coupling efficiency by 6.7 dB and 6.6 dB, respectively. The fabricated 1 × 4 array of optrodes is assembled with a single LED with 465 nm wavelength, which produces a light intensity of approximately 2.7 mW mm-2at the SU-8 waveguide outlet when 50 mA input current is applied to the LED. Each optrode has four recording electrodes at the SU-8 waveguide outlet. The average impedance of the iridium oxide (IrOx) electroplated recording electrodes is 43.6 kΩ.Significance.In-vivoexperiment at the hippocampus region CA1 and CA2 demonstrated the capability of optical stimulation and neural signal recording through the LED and SU-8 waveguide coupled silicon optrode array.

Multi-wavelength light emitting diode-based disposable optrode array for in vivo optogenetic modulation.

We present a light emitting diode (LED)-based optical waveguide array that can optogenetically modulate genetically targeted neurons in the brain. The reusable part of the system consists of control electronics and conventional multi-wavelength LED. The disposable part comprises optical fibers assembled with microlens array fabricated on a silicon die. Both parts can be easily assembled and separated by snap fit structure. Measured light intensity is 3.35 mW/mm2 at 469 nm and 0.29 mW/mm2 at 590 nm when the applied current is 80 mA. In all the tested conditions, the light-induced temperature rise is under 0.5°C and over 90% of the relative light intensity is maintained at 2 mm-distance from the fiber tips. We further tested the efficiency of the optical array in vivo at 469 nm. When the optical array delivers light stimulation on to the visual cortex of a mouse expressing channelrhodopsin-2, the neural activity is significantly increased. The light-driven neural activity is successfully transformed into a percept of the mouse, showing significant learning of the task detecting the cortical stimulation. Our results demonstrate that the proposed optical array interfaces well with the neural circuits in vivo and the system is applicable to guide animal behaviors.

Novel microbial photobioelectrochemical cell using an invasive ultramicroelectrode array and a microfluidic chamber.

OBJECTIVE: To fabricate a novel microbial photobioelectrochemical cell using silicon microfabrication techniques. RESULTS: High-density photosynthetic cells were immobilized in a microfluidic chamber, and ultra-microelectrodes in a microtip array were inserted into the cytosolic space of the cells to directly harvest photosynthetic electrons. In this way, the microbial photobioelectrochemical cell operated without the aid of electron mediators. Both short circuit current and open circuit voltage of the microbial photobioelectrochemical cell responded to light stimuli, and recorded as high as 250 pA and 45 mV, respectively. CONCLUSION: A microbial photobioelectrochemical cell was fabricated with potential use in next-generation photosynthesis-based solar cells and sensors.

Direct identification of on-bead peptides using surface-enhanced Raman spectroscopic barcoding system for high-throughput bioanalysis.

Recently, preparation and screening of compound libraries remain one of the most challenging tasks in drug discovery, biomarker detection, and biomolecular profiling processes. So far, several distinct encoding/decoding methods such as chemical encoding, graphical encoding, and optical encoding have been reported to identify those libraries. In this paper, a simple and efficient surface-enhanced Raman spectroscopic (SERS) barcoding method using highly sensitive SERS nanoparticles (SERS ID) is presented. The 44 kinds of SERS IDs were able to generate simple codes and could possibly generate more than one million kinds of codes by incorporating combinations of different SERS IDs. The barcoding method exhibited high stability and reliability under bioassay conditions. The SERS ID encoding based screening platform can identify the peptide ligand on the bead and also quantify its binding affinity for specific protein. We believe that our SERS barcoding technology is a promising method in the screening of one-bead-one-compound (OBOC) libraries for drug discovery.

Nanoslit membrane-integrated fluidic chip for protein detection based on size-dependent particle trapping.

This paper describes the fabrication of a nanoslit membrane-integrated fluidic chip (Nanoslit-Chip) used for trapping and concentrating micro-/nano-particles of desired size and its application in detecting biological molecules based on target-induced particle aggregation. To trap particles of a specific size, a large scale uniform sized nanoslit fluid channel array is fabricated on a silicon dioxide membrane. A small number of fluorescence labeled particles in a large volume of solution are concentrated into a monolayer of particles in a small nanoslit membrane, which enables us to effectively quantify them via fluorescence intensity. In addition, the particles of desired size (1.8 µm) are readily separated from the mixture of particles with a different size (450 nm) in Nanoslit-Chip size, and then quantified via fluorescence measurements. Finally, the Nanoslit-Chip is successfully applied to the sensitive detection of proteins by target-induced particle aggregation, trapping, and quantification. This shows its potential as a biological and clinical device for quantitative and sensitive detection of biological molecules.

Bead affinity chromatography in a temperature-controllable microsystem for biomarker detection.

This paper describes a temperature-controllable bead affinity chromatography (BAC) in a microsystem for biomarker detection, and preparing samples for matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) analysis. Cancer marker proteins were captured in the microsystem by BAC with RNA aptamer-immobilized microbeads. The captured proteins were then denatured and released from the microbeads by controlling temperature. The microsystem consists of a microreactor for trapping microbeads and a temperature control unit for thermal treatment of the trapped beads. We used polymethylsilxoane or single crystalline silicon in fabricating two different types of reaction chamber to compare the differences in performance originated from the materials. Carcinoembryonic antigen was concentrated and purified from human serum using the microsystem and detected by MALDI-TOF MS to demonstrate the usefulness of the microsystem. The microsystem simplifies a sample preparation process required for protein analysis and cancer biomarker detection, which will accelerate the process of cancer research.

A wafer-level vacuum package using glass-reflowed silicon through-wafer interconnection for nano/micro devices.

We propose a vacuum wafer-level packaging (WLP) process using glass-reflowed silicon via for nano/micro devices (NMDs). A through-wafer interconnection (TWIn) substrate with silicon vias and reflowed glass is introduced to accomplish a vertical feed-through of device. NMDs are fabricated in the single crystal silicon (SCS) layer which is formed on the TWIn substrate by Au eutectic bonding including Cr adhesion layer. The WLPof the devices is achieved with the capping glass wafer anodically bonded to the SCS layer. In order to demonstrate the successful hermetic packaging, we fabricated the micro-Pirani gauge in the SCS layer, and packaged it in the wafer-level. The vacuum level inside the packaging was measured to be 3.1 Torr with +/- 0.12 Torr uncertainty, and the packaging leakage was not detected during 24 hour after the packaging.

Surface-enhanced Raman scattering-active nanostructures and strategies for bioassays.

Surface-enhanced Raman scattering (SERS) techniques offer a number of advantages in molecular detection and analysis, particularly in terms of the multiplex detection of biomolecules. So far, many new SERS-based substrates and analytical techniques have been reported. For easy understanding, various SERS techniques are classified into the following four categories: adsorption-mediated direct detection; antibody- or ligand-mediated direct detection; binding catalyzed indirect detection; and tag-based indirect detection. Among these, recent successes of SERS tagging/encoding (nano/micro) materials and detection methods are highlighted, including our recent works. Some novel SERS-based strategies for the detection of several biological molecules are also introduced.

Automated maskless photolithography system for peptide microarray synthesis on a chip.

Maskless photolithographic peptide synthesis was performed on a glass chip using an automated peptide array synthesizer system. The peptide array synthesizer was built in a closed box, which contained optical and fluidic systems. The conditions for peptide synthesis were fully controlled by a computer program. For the peptide synthesis on a glass chip, 20 NVOC-protected amino acids were synthesized. The coupling efficiencies of two model peptide sequences were examined on ACA/APTS and PEG/CHI/GPTS chips. PEG/CHI/GPTS chip gave higher average stepwise yields of GIYWHHY (94%) and YIYGSFK (98%) than those of ACA/APTS chip. To quantify peptide-protein binding affinity, HPQ- or HPM-containing pentapeptides were synthesized on a PEG/CHI/GPTS chip and the binding event of Cy3 labeled-streptavidin was quantified. The peptide sequence of IQHPQ showed highest binding affinity with Cy3 labeled-streptavidin. The results demonstrated that the photolithographic peptide array synthesis method efficiently quantified the binding activities of protein-peptide interactions and it can be used for additional biological assay applications.

Multifunctional silver-embedded magnetic nanoparticles as SERS nanoprobes and their applications.

In this study, surface-enhanced Raman spectroscopy (SERS)-encoded magnetic nanoparticles (NPs) are prepared and utilized as a multifunctional tagging material for cancer-cell targeting and separation. First, silver-embedded magnetic NPs are prepared, composed of an 18-nm magnetic core and a 16-nm-thick silica shell with silver NPs formed on the surface. After simple aromatic compounds are adsorbed on the silver-embedded magnetic NPs, they are coated with silica to provide them with chemical and physical stability. The resulting silica-encapsulated magnetic NPs (M-SERS dots) produce strong SERS signals and have magnetic properties. In a model application as a tagging material, the M-SERS dots are successfully utilized for targeting breast-cancer cells (SKBR3) and floating leukemia cells (SP2/O). The targeted cancer cells can be easily separated from the untargeted cells using an external magnetic field. The separated targeted cancer cells exhibit a Raman signal originating from the M-SERS dots. This system proves to be an efficient tool for separating targeted cells. Additionally, the magnetic-field-induced hot spots, which can provide a 1000-times-stronger SERS intensity due to aggregation of the NPs, are studied.

The effect of physical characteristics and field position on the shoulder and elbow injuries of 490 baseball players: confirmation of diagnosis by magnetic resonance imaging.

OBJECTIVE: To evaluate the distribution of shoulder and elbow injuries confirmed by magnetic resonance imaging in throwing athletes. STUDY DESIGN: Descriptive epidemiological study. SETTING: Tertiary institution. PARTICIPANTS: Five hundred fifty-four baseball players referred to our institute for shoulder and elbow rehabilitation. INTERVENTIONS: All injured players except those with fractures underwent magnetic resonance imagings, which were read by a radiologist, and players were diagnosed by orthopedic surgeons based on the clinical and imaging findings. MAIN OUTCOME MEASURES: Analysis of baseball-related injuries was performed according to the physical characteristics of each athlete and his positions on the team. RESULTS: Junior high school players sustained a higher proportion of osteochondritis dissecans compared with high school and collegiate players. High school and collegiate players were more likely to have ulnar collateral ligament (UCL) injuries or superior labrum anterior-posterior (SLAP) lesions than junior high school players. Pitchers and outfielders were more likely to have UCL injuries than the infielders. In the junior high school group, the players with UCL injuries were taller and heavier than the players in the control group. In the high school group with UCL injuries or SLAP lesions, the players were both taller and heavier than the players in the control group. CONCLUSIONS: These data support the conclusion that there is a significant difference in the distribution of injuries according to the player's age and position. For the age-matched comparison, taller and heavier players are more likely to be affected by UCL injury or SLAP lesion.

Magnetic surface-enhanced Raman spectroscopic (M-SERS) dots for the identification of bronchioalveolar stem cells in normal and lung cancer mice.

Bronchioalveolar stem cells (BASCs) play an important role in the development of cancer. To study the characterization of BASCs, their isolation and purification are important. However, the cells are very rare in tissues and the available methods of isolating them are limited. The current study was performed to isolate BASCs in the murine lung using magnetic nanoparticle-based surface-enhanced Raman spectroscopic dots (M-SERS Dots). We used K-ras(LA1) mice, a laboratory animal model of non-small cell lung cancer of human, and C57BL/6 mice having the same age as a control. We compared the BASCs between 2 species by FACS analysis with 4 markers of BASCs, CCSP, SP-C, CD34, and Sca-1. We found that BASCs were more abundant in the K-ras(LA1) mice than in the C57BL/6 mice. Also, the M-SERS Dot-mediated positive selection of the CD34(pos) cells enabled the BASCs to be enriched to an approximately 4- to 5-fold higher level than that in the case without pre-separation. In summary, our study demonstrates the potential of using M-SERS Dots as a sorting system with very effective isolation of BASCs and multiplex targeting probe, showing that they may play an effective role in the study of BASCs in the future.

Protein separation and identification using magnetic beads encoded with surface-enhanced Raman spectroscopy.

This article presents a prototype of a surface-enhanced Raman spectroscopy (SERS)-encoded magnetic bead of 8mum diameter. The core part of the bead is composed of a magnetic nanoparticle (NP)-embedded sulfonated polystyrene bead. The outer part of the bead is embedded with Ag NPs on which labeling molecules generating specific SERS bands are adsorbed. A silica shell is fabricated for further bioconjugation and protection of SERS signaling. Benzenethiol, 4-mercaptotoluene, 2-naphthalenethiol, and 4-aminothiophenol are used as labeling molecules. The magnetic SERS beads are used as substrates for protein sensing and screening with easy handling. As a model application, streptavidin-bound magnetic SERS beads are used to illustrate selective separation in a flow cytometry system, and the screened beads are spectrally recognized by Raman spectroscopy. The proposed magnetic SERS beads are likely to be used as a versatile solid support for protein sensing and screening in multiple assay technology.

MEMS micromirror characterization in space environments.

This paper describes MEMS micromirror characterization in space environments associated with our space applications in earth observation from the International Space Station and earth's orbit satellite. The performance of the micromirror was tested for shock and vibration, stiction, outgassing from depressurization and heating, and electrostatic charging effects. We demonstrated that there is no degradation of the micromirror performance after the space environment tests. A test bed instrument equipped with the micromirrors was delivered and tested in the ISS. The results demonstrate that the proposed micromirrors are suitable for optical space systems.

An integrated microfluidic chip for the analysis of biochemical reactions by MALDI mass spectrometry.

Using an integrated microfluidic chip combined with mass spectrometry is an attractive method for parallel and multiple analyses because of its inherent simplicity, low sample consumption, and high sensitivity. To realize an effective microfluidic chip for the rapid analysis of biochemical reactions by matrix assisted laser desorption/ionization (MALDI)-mass spectrometry (MS), the basic operations on microfluids, namely loading, metering, cutting, transporting, mixing, and injecting, must be integrated. This study describes an integrated microfluidic chip with MALDI-MS that performs the on-chip analysis of biochemical reactions, such as enzymatic reactions. For on-chip multiple reactions, we present sequential fluidic manipulations with nanoliter-sized droplets, based on the precise control of wettability and the capillary pressure of a microchannel. The microfluidic chip we have developed successfully performed biochemical reactions and can dispense a droplet of a few hundred nanoliters on the MALDI target plate according to the designed multiple reaction procedure. Finally, the MS spectrum showed accurate and clear characteristic peaks for reaction products. Our investigations into reaction efficiency showed that the microfluidic chip could reduce the reaction time to one third, and the volume to one hundredth, of off-chip methods using conventional labware such as the micropipette and Eppendorf tube.

Multiplex targeting, tracking, and imaging of apoptosis by fluorescent surface enhanced Raman spectroscopic dots.

We have developed multifunctional fluorescent surface enhanced Raman spectroscopic tagging material (F-SERS dots) composed of silver nanoparticle-embedded silica spheres with fluorescent organic dye and specific Raman labels for multiplex targeting, tracking, and imaging of cellular/molecular events in the living organism. In this study, F-SERS dots fabricated with specific target antibodies (BAX and BAD) were employed for the detection of apoptosis. The F-SERS dots did not show any particular toxicity in several cell lines. The F-SERS dots could monitor the apoptosis effectively and simultaneously through fluorescent images as well as Raman signals in both cells and tissues with high selectivity. Our results clearly demonstrate that F-SERS dots can be easily applicable to multiplex analysis of diverse cellular/molecular events important for maintaining cellular homeostasis.