Microfabricated Sampling Probes for Monitoring Brain Chemistry at High Spatial and Temporal Resolution

Monitoring neurochemical dynamics has played a crucial role in elucidating brain function and related disorders. An essential approach for monitoring neurochemicals is to couple sampling probes to analytical measurements; however, this approach is inherently limited by poor spatial and temporal resolution. In this work, we have developed miniaturized sampling probes and analytical technology to overcome these limitations. Conventional sampling probes were handmade and have several disadvantages, including large sizes (over 220 µm in diameter) and limited design flexibility. To address these disadvantages, we have used microfabrication to manufacture sampling probes. By bulk micromachining of Si, microchannels and small sampling regions can be fabricated within a probe, with an overall dimension of ~100 µm. For development of a dialysis probe, nanoporous anodic aluminum oxide was adapted for monolithically embedding a membrane. Coupling the probe to liquid chromatography-mass spectrometry, multiple neurochemicals were measured at basal conditions, including dopamine and acetylcholine. Comparing to conventional dialysis probes, the microfabricated dialysis probe provided at least 6-fold improvement in spatial resolution and potentially had lower tissue disruption. Furthermore, we have continued the development of a microfabricated push-pull probe. We enhanced functionality of the probe by integrating an additional channel into the probe for chemical delivery. Further, we demonstrated that the probe can feasibly be coupled to droplet microfluidic devices for improved temporal resolution. Nanospray ionization mass spectrometry was used for multiplexed measurements of neurochemicals in nanoliter droplet samples. Utility of the integrated system was demonstrated by monitoring in vivo dynamics during potassium stimulation of 4 neurochemicals, including glutamate and GABA. The probe provided unprecedented spatial resolution and temporal resolution as high as ~5 s. Additionally, we highlighted versatility of the method by coupling the probe to another high-throughput assay, i.e., droplet-based microchip capillary electrophoresis for rapid separation (less than 3 s) and measurement of multiple amino acid neurochemicals. This collection of work illustrates that development of the microfabricated sampling probes and their compatible microfluidic systems are highly beneficial for studying brain chemistry. The integrated miniaturized analytical technology can potentially be useful for solving other problems of biological significance.PHDChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/144094/1/nonngern_1.pd

Development of fiber-based siglemode-multimode fiber with micro convex lens displacement sensor

Various sensitive industrial applications require micro-displacement detection in order to realize a precise movement control. This micrometer displacement can be detected using a fiber-based displacement sensor that offers micro displacement detection and is immuned against electromagnetic radiation. This kind of sensor, however, has limitations on its sensing range and sensitivity. In order to comprehend the limitations, a new configuration of fiber-based displacement sensor with improved sensing range and sensitivity is designed and presented in this thesis. The developed displacement sensor works according to the Fabry-Perot Interferometry (FPI) principle. In general, the proposed displacement sensor consists of two parts; an optical semireflecting fiber mirror attached with micro-convex lens as a sensor head and a highly reflective coated gold mirror. These two components are arranged in parallel to form a Fabry-Perot cavity. In this work, the new sensor configuration is realized by fusion splicing a segment of 9/125 µm single mode fiber (SMF) to one end of 10 mm long section of 62.5/125 multimode fiber (MMF). The other end of the MMF is ultraviolet (UV) cured with a liquid composition of Norland Optical Adhesive 61 (NOA) that forms a micro-convex lens at the sensor head. Physical characterization of the fabricated SMF-MMF with NOA micro-convex lens (SMFMMF- Lens) sensor shows that this sensor has a reflectivity of 6.8% with 210 µm focal length, f(h). These outcomes attribute to an increase of reflected optical power and also an improvement on the sensing range. In order to sense the displacement, 200 nm thickness of sputtered gold mirror is attached to the movable object for characterization process. The SMF-MMF-Lens sensor performances are analyzed in terms of intensity and fringe response analysis. For this purpose, a broad light source ranging from 1530 nm to 1565 nm wavelength is injected into the sensor and the reflected light is captured using an optical spectrum analyzer (OSA). The intensity response showed that this SMF-MMF-Lens sensor managed to sense displacement within 10 µm to 520 µm sensing range with sensitivity of 566.4 µW/µm. Employing OSA with 1 nm resolution results in the SMF-MMF-Lens sensor having resolution of about 1.77 pm/W. Within the tested range, 10 µm to 310 µm displacement range exhibits a good linear response which corresponds to 3/2 of the lens focal length. For the fringe response analysis, it is identified that the SMF-MMF-Lens sensor was able to detect displacement of 10 µm to 520 µm sensing range with the sensitivity of 0.0284 fringes/ µm. The entire sensing range for fringe analysis is linear. For comparison purposes, conventional sensors with SMF and SMF-MMF configurations are fabricated for sensor performance analysis. The sensitivity of SMF-MMF-Lens sensor improved at about 77.72% and 9.7% in comparison to the conventional SMF-MMF sensor for its intensity and fringes response analysis, respectively

Endoscopic Optical Coherence Tomography imaging of the airway

A narrowing, either of the nasal airway or the large airways, causes impaired airflow and results in respiratory insufficiency. Imaging the airways is important for the diagnostic evaluation of airway disorders. Existing approaches, such as bronchoscopy/ endoscopy or Computed Tomography (CT), are either qualitative or are impractical to use for routine assessments. Endoscopic Optical coherence Tomography (OCT) can be used to obtain quantitative images of the dynamic airway in real-time and to reconstruct airway volumes.In order to image the large airways, an OCT system with a long imaging range and high sensitivity is necessary. The data acquisition scheme for an endoscopic OCT system with a wavelength swept laser source was developed and refined to enable imaging in the large airways. A pressure acquisition system was also integrated to allow synchronous, invasive, pressure measurements to be made in conjunction with OCT scans. Experiments were performed in mechanically ventilated pigs to demonstrate the airway imaging capabilities of the OCT system. The results obtained from OCT were validated against CT scans acquired during the same exam. The combined pressure and OCT-derived cross sectional area plots, measured in vivo over a respiratory cycle, exhibited hysteresis loops, indicating the viscoelastic nature of the airway deformation. Endoscopic OCT imaging was also performed in the nasal cavities of cadaver heads to assess the outcomes of functional rhinoplasty procedures. OCT-derived volumes of the nasal airway were compared against CT volumes and found to depict the nasal vault faithfully.A fiber-optic probe with a low numerical aperture lens at its tip is better suited for imaging large luminal organs, as the distance between the probe and the tissue surface is unknown and variable. A novel, multi-segment, all-fiber lens, that can produce nearly collimated beams with working distances larger than 14 mm, was designed, fabricated, and tested. Finally, the non-unform rotation distortion produced by a super-elastic Nitinol tube drive-shaft was compared against the performance of a torque coil drive-shaft. It is hoped that the results presented will help advance the adoption of endoscopic OCT in routine clinical practice for the assessment of airway disorders.Doctor of Philosoph

California Extremely Large Telescope: Conceptual Design for a Thirty-Meter Telescope

Following great success in the creation of the Keck Observatory, scientists at the California Institute of Technology and the University of California have begun to explore the scientific and technical prospects for a much larger telescope. The Keck telescopes will remain the largest telescopes in the world for a number of years, with many decades of forefront research ahead after that. Though these telescopes have produced dramatic discoveries, it is already clear that even larger telescopes must be built if we are to address some of the most profound questions about our universe. The time required to build a larger telescope is approximately ten years, and the California community is presently well-positioned to begin its design and construction. The same scientists who conceived, led the design, and guided the construction of the Keck Observatory have been intensely engaged in a study of the prospects for an extremely large telescope. Building on our experience with the Keck Observatory, we have concluded that the large telescope is feasible and is within the bounds set by present-day technology. Our reference telescope has a diameter of 30 meters, the largest size we believe can be built with acceptable risk. The project is currently designated the California Extremely Large Telescope (CELT)

Photolithographic and replication techniques for nanofabrication and photonics

In the pursuit of economical and rapid fabrication solutions on the micro and nano scale, polymer replication has proven itself to be a formidable technique, which despite zealous development by the research community, remains full of promise. This thesis explores the potential of elastomers in what is a distinctly multidisciplinary field. The focus is on developing innovative fabrication solutions for planar photonic devices and for nanoscale devices in general. Innovations are derived from treatments of master structures, imprintable substrates and device applications. Major contributions made by this work include fully replicated planar integrated optical devices, nanoscale applications for photolithographic standing wave corrugations (SWC), and a biologically templated, optical fiber based, surface-enhanced Raman scattering (SERS) sensor. The planar devices take the form of dielectric rib waveguides which for the first time, have been integrated with long-period gratings by replication. The heretofore unemployed SWC is used to demonstrate two innovations. The first is a novel demonstration of elastomeric sidewall photolithographic mask, which exploits the capacity of elastomers to cast undercut structures. The second demonstrates that the corrugations themselves in the absence of elastomers, can be employed as shadow masks in a directional flux to produce vertical stacks of straight lines and circles of nanowires and nanoribbons. The thesis then closes by conceptually combining the preceding demonstrations of waveguides and nanostructures. An optical fiber endface is em ployed for the first time as a substrate for patterning by replication, wherein the pattern is a nanostructure derived from a biological template. This replicated nanostructure is used to impart a SERS capability to the optical fiber, demonstrating an ultra-sensitive, integrated photonic device realized at great economy of both time and money, with very real potential for mass fabrication

NASA Tech Briefs, May 1997

Topics covered include: Advanced Composites, Plastics and Metals; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery/Automation; Manufacturing/Fabrication; Mathematics and Information Sciences; Life Sciences; Books and Reports

Electrostatic MEMS Actuators using Gray-scale Technology

The majority of fabrication techniques used in micro-electro-mechanical systems (MEMS) are planar technologies, which severely limits the structures available during device design. In contrast, the emerging gray-scale technology is an attractive option for batch fabricating 3-D structures in silicon using a single lithography and etching step. While gray-scale technology is extremely versatile, limited research has been done regarding the integration of this technology with other MEMS processes and devices. This work begins with the development of a fundamental empirical model for predicting and designing complex 3-D photoresist structures using a pixilated gray-scale technique. A characterization of the subsequent transfer of such 3-D structures into silicon using deep reactive ion etching (DRIE) is also provided. Two advanced gray-scale techniques are then introduced: First, a double exposure technique was developed to exponentially increase the number of available gray-levels; improving the vertical resolution in photoresist. Second, a design method dubbed compensated aspect ratio dependent etching (CARDE) was created to anticipate feature dependent etch rates observed during gray-scale pattern transfer using deep reactive ion etching (DRIE). The developed gray-scale techniques were used to integrate variable-height components into the actuation mechanism of electrostatic MEMS devices for the first time. In static comb-drives, devices with 3-D comb-fingers were able to demonstrate >34% improvement in displacement resolution by tailoring their force-engagement characteristics. Lower driving voltages were achieved by reducing suspension heights to decrease spring constants (from 7.7N/m to 2.3N/m) without effecting comb-drive force. Variable-height comb-fingers also enabled the development of compact, voltage-controlled electrostatic springs for tuning MEMS resonators. Devices in the low-kHz range demonstrated resonant frequency tuning >17.1% and electrostatic spring constants up to 1.19 N/m (@70V). This experience of integrating 3-D structures within electrostatic actuators culminated in the development of a novel 2-axis optical fiber alignment system using 3-D actuators. Coupled in-plane motion of electrostatic actuators with integrated 3-D wedges was used to deflect an optical fiber both horizontally and vertically. Devices demonstrated switching speeds <1ms, actuation ranges >35μm (in both directions), and alignment resolution <1.25μm. Auto-alignment to fixed indium-phosphide waveguides with <1.6μm resolution in <10 seconds was achieved by optimizing search algorithms

Integrated Guided-Wave Structures and Techniques for Millimeter-Wave and Terahertz Electronics and Photonics

RÉSUMÉ Pour faire face à la demande croissante en bande passante, les prochaines générations des systèmes sans fil et filaires devront exploiter la large gamme spectrale 100 GHz-1 Térahertz (THz) et au-delà. Cependant, les éléments constitutifs intégrés qui définiront les architectures et les normes des systèmes à très haute fréquence ne sont pas claires et généralement pas du tout disponible. Cette thèse contribue à ce nouveau défi en explorant de nouveaux concepts et techniques de transmission d’onde pour le développement des circuits intégrés et les systèmes électroniques et photoniques en ondes millimétriques (MMW) et THz. Les lignes de transmission sont les éléments constitutifs de tous les circuits électroniques et photoniques intégrés. En dépit d'une expansion substantielle des applications électroniques et photoniques vers les THz, la structure de base des lignes de transmission standard, mis au point dans les années 1950, n'a pas évolué. L'un des problèmes fondamentaux dans le développement de systèmes électroniques et photoniques intégré THz est les limites intrinsèques de ces lignes de transmission classiques. Les dispositifs à ondes progressives électro-optiques et optoélectroniques ont été conçus sur la base de ces lignes de transmission, et sont donc limités en débit en raison de la limitation des performances au spectre RF. Plusieurs tentatives ont été faites pour améliorer ces lignes de transmission. Cependant, la configuration structurelle inhérente du métal est toujours l'obstacle dominant qui impose un mode de fonctionnement particulier qui est sujette à l'atténuation et la dispersion à une fréquence plus élevée. Pour faire face aux problèmes mentionnés et pour répondre à ces défis technologiques contraignants, trois orientations sont traités dans cette thèse: électro-optique, micro-ondes et optique. Pour la première orientation, la ligne SIW est utilisée en tant que structure à onde progressive alternative d'un Modulateur EO sur polymère. Dans ce cas, la fréquence porteuse est déterminée par la fréquence de fonctionnement de la ligne SIW. Dans ce travail, la conception est faite pour un modulateur EO atteignant plus de 22% de la bande passante optique avec la fréquence centrale de 160 GHz.----------ABSTRACT In order to keep up with rising global demand for bandwidth, future generations of both wireless and wireline technology will need to exploit the spectral range over 100 GHz - 1 terahertz (THz) and beyond. However, the integrated building blocks that will well define such an ultra-high frequency system technology architecture and protocol are unclear and mostly unavailable. This dissertation set the stage in responding to this emerging challenge by exploring new guided wave structures, concepts and techniques for the development of millimeter-wave (mmW) and THz electronic and photonic integrated circuits and systems. Radiofrequency integrated circuits are the backbone of all modern computing and communication electronic and photonic networks and systems. Likewise, transmission lines are the most fundamental building blocks of all the electronic and photonics integrated circuits. In spite of a substantial expansion of electronic and photonic applications towards THz, the basic structure of traditional transmission lines, developed in the 1950s, has not been modified or evolved. One of the fundamental bottlenecks in the development of THz integrated electronic and photonic systems has been the inherent limitations of those conventional transmission lines. The traveling-wave electro-optic and opto-electronic devices have been made based on those transmission lines, and are therefore limited in speed because of the RF spectrum performance limitations. Several attempts have been made to improve those transmission lines. However, the inherent structural configuration is still the dominant obstacle that dictates a particular operating mode that is prone to attenuation and dispersion at higher frequencies. To tackle those mentioned problems and to respond to those constraining technological challenges, three research orientations are considered in this PhD thesis: electro-optic, microwave, and optics. For the first orientation, SIW (substrate integrated waveguide) is used as an alternative traveling-wave structure of a polymer EO modulator. In this case, the carrier frequency is determined by the SIW frequency of operation. The design in this work is completed for an EO modulator with the center frequency of 160 GHz achieving more than 22% optical bandwidth