Potential of biodegradable microneedles as a transdermal delivery vehicle for lidocaine

There has been an increasing interest in applying biotechnology in formulating and characterising new and innovative drug delivery methods, e.g., drug-loaded biodegradable microneedles within the area of transdermal delivery technology. Recently, microneedles have been proposed for use in pain management, e.g., post-operative pain management through delivery of a local anaesthetic, namely, lidocaine. Lidocaine is a fairly common, marketed prescription-based, local anaesthetic pharmaceutical, applied for relieving localised pain and lidocaineloaded microneedles have been explored. The purpose of this review is to evaluate the properties of biodegradable polymers that may allow the preparation of microneedle systems, methods of preparing them and pharmacokinetic conditions in considering the potential use of lidocaine for delivery through the skin

Challenges in flexible microsystem manufacturing : fabrication, robotic assembly, control, and packaging.

Microsystems have been investigated with renewed interest for the last three decades because of the emerging development of microelectromechanical system (MEMS) technology and the advancement of nanotechnology. The applications of microrobots and distributed sensors have the potential to revolutionize micro and nano manufacturing and have other important health applications for drug delivery and minimal invasive surgery. A class of microrobots studied in this thesis, such as the Solid Articulated Four Axis Microrobot (sAFAM) are driven by MEMS actuators, transmissions, and end-effectors realized by 3-Dimensional MEMS assembly. Another class of microrobots studied here, like those competing in the annual IEEE Mobile Microrobot Challenge event (MMC) are untethered and driven by external fields, such as magnetic fields generated by a focused permanent magnet. A third class of microsystems studied in this thesis includes distributed MEMS pressure sensors for robotic skin applications that are manufactured in the cleanroom and packaged in our lab. In this thesis, we discuss typical challenges associated with the fabrication, robotic assembly and packaging of these microsystems. For sAFAM we discuss challenges arising from pick and place manipulation under microscopic closed-loop control, as well as bonding and attachment of silicon MEMS microparts. For MMC, we discuss challenges arising from cooperative manipulation of microparts that advance the capabilities of magnetic micro-agents. Custom microrobotic hardware configured and demonstrated during this research (such as the NeXus microassembly station) include micro-positioners, microscopes, and controllers driven via LabVIEW. Finally, we also discuss challenges arising in distributed sensor manufacturing. We describe sensor fabrication steps using clean-room techniques on Kapton flexible substrates, and present results of lamination, interconnection and testing of such sensors are presented

Robustness and repeatability of interdigitated electrodes on a substrate tested in an aqueous environment

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2011.Cataloged from PDF version of thesis.Includes bibliographical references (p. 75-77).Interdigitated electrodes are currently being used as sensing components in microfluidic lab-on-a-chip devices. The Daktari Diagnostics system uses these electrodes to measure the change in impedance of a fluid in an assay chamber. In order to improve quality assurance, a new testing method was developed and validated to characterize the sources of potential defects in the electrodes. In the new test, the electrodes are used to measure the impedance when placed in solutions of different known conductivities. The data was used to estimate the linear relationship between the inverse of the measured impedance to the solution conductivities. The repeatability tests found an average slope of 1.438x10-5 cm/characteristic length with a standard deviation of 8.52x10 -8 cm/characteristic length. It was found that the number of defective fingers or bending the electrodes significantly changes the electrode performance with a 95% confidence interval.by Jacklyn Holmes.M.Eng

Design of a micro-interdigitated electrode for impedance measurement performance in a biochemical assay

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2011.Cataloged from PDF version of thesis.Includes bibliographical references (p. 75-77).The performance of interdigitated electrodes for impedance measurements is dependent upon the geometric design of the electrode pattern and can be significantly impacted by manufactured variability or defects. For processes which rely on precise electrode performance, such as the biochemical assay in the Daktari CD4 diagnostic system, it is necessary to minimize variation through robust design and quality control. Interdigitated electrode design was investigated to identify design strategies which maximize electrode sensitivity and minimize performance variability in produced parts, while potentially reducing the complexity of quality testing. Several configurations were developed to address these goals by increasing the sensing region for a specified electrode area and creating designs which can be more easily manufactured with low variability. Design modifications included alterations to interdigitated finger orientation, finger geometry, and gap width. Test findings indicate that optimal designs contain narrow gap widths with electrode fingers parallel to the longest dimension of the electrode. These benefits may be further enhanced by replacing straight finger edges with geometrical features, such as scalloped edges. The design changes identified can be used to improve interdigitated electrode performance for an array of applications and reduce performance variability caused by variation in the manufacturing process.by Linda Donoghue.M.Eng

MODELING THE PHYSICS OF FAILURE FOR ELECTRONIC PACKAGING COMPONENTS SUBJECTED TO THERMAL AND MECHANICAL LOADING

This dissertation presents three separate studies that examined electronic components using numerical modeling approaches. The use of modeling techniques provided a deeper understanding of the physical phenomena that contribute to the formation of cracks inside ceramic capacitors, damage inside plated through holes, and to dynamic fracture of MEMS structures. The modeling yielded numerical substantiations for previously proposed theoretical explanations. Multi-Layer Ceramic Capacitors (MLCCs) mounted with stiffer lead-free solder have shown greater tolerance than tin-lead solder for single cycle board bending loads with low strain rates. In contrast, flexible terminations have greater tolerance than stiffer standard terminations under the same conditions. It has been proposed that residual stresses in the capacitor account for this disparity. These stresses have been attributed to the higher solidification temperature of lead free solders coupled with the CTE mismatch between the board and the capacitor ceramic. This research indicated that the higher solidification temperatures affected the residual stresses. Inaccuracies in predicting barrel failures of plated through holes are suspected to arise from neglecting the effects of the reflow process on the copper material. This research used thermo mechanical analysis (TMA) results to model the damage in the copper above the glass transition temperature (Tg) during reflow. Damage estimates from the hysteresis plots were used to improve failure predictions. Modeling was performed to examine the theory that brittle fracture in MEMS structures is not affected by strain rates. Numerical modeling was conducted to predict the probability of dynamic failure caused by shock loads. The models used a quasi-static global gravitational load to predict the probability of brittle fracture. The research presented in this dissertation explored drivers for failure mechanisms in flex cracking of capacitors, barrel failures in plated through holes, and dynamic fracture of MEMS. The studies used numerical modeling to provide new insights into underlying physical phenomena. In each case, theoretical explanations were examined where difficult geometries and complex material properties made it difficult or impossible to obtain direct measurements

Integrated sensors for process monitoring and health monitoring in microsystems

This thesis presents the development of integrated sensors for health monitoring in Microsystems, which is an emerging method for early diagnostics of status or “health” of electronic systems and devices under operation based on embedded tests. Thin film meander temperature sensors have been designed with a minimum footprint of 240 m × 250 m. A microsensor array has been used successfully for accurate temperature monitoring of laser assisted polymer bonding for MEMS packaging. Using a frame-shaped beam, the temperature at centre of bottom substrate was obtained to be ~50 ºC lower than that obtained using a top-hat beam. This is highly beneficial for packaging of temperature sensitive MEMS devices. Polymer based surface acoustic wave humidity sensors were designed and successfully fabricated on 128° cut lithium niobate substrates. Based on reflection signals, a sensitivity of 0.26 dB/RH% was achieved between 8.6 %RH and 90.6 %RH. Fabricated piezoresistive pressure sensors have also been hybrid integrated and electrically contacted using a wire bonding method. Integrated sensors based on both LiNbO3 and ZnO/Si substrates are proposed. Integrated sensors were successfully fabricated on a LiNbO3 substrate with a footprint of 13 mm × 12 mm, having multi monitoring functions for simultaneous temperature, measurement of humidity and pressure in the health monitoring applications

Microneedle assisted percutaneous delivery of lidocaine carboxymethylcellulose with gelatine co-polymer hydrogel

Local anaesthetic drugs are usually administered as symptom relieving drug formulations for the treatment of pain in superficial skin extremities. The anaesthesia is delivered into skin tissues at the site of pain because of nociceptive receptors. Concerns that exist regarding local anaesthetic drug formulations are low drug encapsulation efficiency, polydispersity of colloidal formulations, chemical interactions of released local anaesthetic drug with skin proteins and bulk viscoelastic properties. Complimenting drug formulation characteristics are the desirable rates of controlled release of drug molecules from chosen formulations pertaining to favourable in vitro skin permeation kinetics are imperative pharmaceutics based research areas because skin percutaneous delivery has distinct barrier property restrictions for passive diffusion (PD) of active molecules. Lidocaine is currently the active anaesthetic molecule of choice in local anaesthesia by clinicians because of minimum toxicity and good potency. It is a low molecular weight drug comprising of electron donating and electron withdrawing functional groups with the capacity to interact by hydrogen bonding and electrostatic interactions with several drug formulation vehicles. In this work, a naturally occurring bi-polymeric formulation was achieved with lidocaine NaCMC:gelatine hydrogel. Lidocaine NaCMC:gelatine ratio of 1:2.3 was the most favourable formulation because of faster skin permeation kinetics. Lidocaine NaCMC:gelatine 1:2.7 provided the highest drug encapsulation efficiency. This resulted in high, sustained permeation rates after adaptation of the microneedle (MN) poke and patch technique, past the stratum corneum layer of skin for quick target delivery in attaining a maximum permeation flux of near 6.0 µg/cm2/h in the hypodermis layer. Mass balance of in vitro studies using an indirect approach to quantify lidocaine permeation showed significant lidocaine permeation in skin. Subsequent vertical and horizontal (depth averaged) in vitro studies using similar MN techniques resulted in crossing minimum therapeutic level across a 10 mm radius from the epicentre of the skin sample at major reduced lag times of minutes for vertical permeation and within 0.5 hours for horizontal permeation. Furthermore, the spreadability of lidocaine NaCMC:gelatine hydrogel shows favourability in the control of droplet spreading on MN treated skin

Wireless Applications of Radio Frequency Micro-Electro-Mechanical Systems

With mass proliferation of wireless communication technologies, there is a continuous demand on fast data transmission rate and efficient use of frequency spectrum. As a result, reconfigurable systems are of significant importance and research is being conducted in numerous universities. The purpose of this research is to develop novel RF MEMS based reconfigurable wireless systems. By utilizing the RF MEMS switches as a basic building block, this thesis focus on developing a unique design technique for the design and development of RF MEMS delay line phase shifter, frequency reconfigurable antennas and pattern reconfigurable antennas. This thesis work is divided into four parts: 1. Investigation and development of nano-electro-mechanical systems (NEMS) based 3-bit phase shifter. Analyzing the slow wave structure to further reduce the size of delay line phase shifter. 2. Development of frequency reconfigurable antennas to compete with broadband and multi-band antennas. Two novel MEMS-loaded frequency reconfigurable antennas were designed with spectrum switchable between WPAN band (57 to 66 GHz) and the whole E-band (71 to 86 GHz). 3. Investigation of microstrip-to-coplanar striplines (CPS) transition balun used for antennas to explain the inherent phase delay of this type of structure. Based on the discovery, a pattern reconfigurable quasi-Yagi antenna was designed. The antenna exhibits excellent RF performance, compact size and switchable end-fire radiation pattern with the goal to replacing existing phased array antennas. It has the full functionality of a multi-antenna phased array plus phase shifting network while its size is same as a fixed single Yagi antenna. 4. Development of full seven masks all metal fabrication process of the RF MEMS integrated reconfigurable antennas. The fabrication processes are optimized based on Australian National Fabrication Facility (ANFF) New South Wales node’s equipment

RF-MEMS Switch Module in a 0.25 µm SiGe:C BiCMOS Process

Drahtlose Kommunikationstechnologien im Frequenzbereich bis 6 GHz wurden in der Vergangenheit in Bezug auf Leistungsfaehigkeit und Frequenzbereich kontinuierlich verbessert. Aufgrund der Skalierung nach dem Mooreschen Gesetz koennen heutzutage mm-Wellen Schaltkreise in CMOS-Technologien hergestellt werden. Durch die Einfuehrung von SiGe zur Realisierung einer leistungsfaehigen BiCMOS-Technologie wurde ebenfalls eine Verbesserung der Frequenzeigenschaften und Ausgangsleistungen erreicht, wodurch aktive CMOS- oder BiCMOS-Bauelemente vergleichbare Leistungsparameter zu III-V Technologien bei geringeren Kosten bereitstellen koennen. Bedingt durch das niederohmige Silizium-Substrat der BiCMOS-Technologie weisen vor allem passive Komponenten hoehere Verluste auf und weder III-V- noch BiCMOS-Technologien bieten hochlineare Schaltkomponenten mit geringen Verlusten und geringen Leistungsaufnahmen im mm-Wellen Bereich. RF-MEMS Schalter sind bekannt fuer ihre ausgezeichneten HF-Eigenschaften. Die Leistungsaufnahme von elektrostatisch angetriebenen RF-MEMS Schaltern ist vernachlaessigbar und es koennen im Vergleich zu halbleiter-basierten Schaltern hoehere Leistungen verarbeitet werden. Nichtsdestotrotz wurden RF-MEMS Schalter hauptsaechlich als eigenstaendige Komponenten entwickelt. Zur Systemintegration wird meist ein System-in-Package (SiP) Ansatz angewandt, der fuer niedrige Frequenzen geeignet ist, aber bei mm-Wellenanwendungen durch parasitaere Verluste an seine Grenzen stoesst. In dieser Arbeit wird ein in eine BiCMOS-Technologie integrierter RF-MEMS Schalter fuer mm-Wellen Anwendungen gezeigt. Das Design, die Integration und die experimentellen Ergebnisse sowie verschiedene Packaging-Konzepte werden beschrieben Zur Bereitstellung der hohen Auslenkungs-Spannungen wurde eine Ladungspumpe auf dem Chip integriert. Zum Schluss werden verschiedene, rekonfigurierbare mm-Wellen Schaltkreise zur Demonstration der Leistungsfaehigkeit des Schalters gezeigt.Wireless communication technologies have continuously advanced for both performance and frequency aspects, mainly for the frequencies up to 6 GHz. The results of Moore’s law now also give the opportunity to design mm-wave circuits using advanced CMOS technologies. The introduction of SiGe into CMOS, providing high performance BiCMOS, has also enhanced both the frequency and the power performance figures. The current situation is that the active devices of both CMOS and BiCMOS technologies can provide performance figures competitive with III-V technologies while having still the advantage of low cost. However, similar competition cannot be pronounced for the passive components considering the low-resistive substrates of BiCMOS technologies. Moreover, both III-V and BiCMOS technologies have the lack of low-loss and low-power consumption, as well as highly linear switching and tuning components at mm-wave frequencies. RF-MEMS switch technologies have been well-known with excellent RF- performance figures. The power consumption of electrostatic RF-MEMS switches is negligible and they can handle higher power levels compared to their semiconductor counterparts. However, RF-MEMS switches have been mostly demonstrated as standalone processes and have started to be used as commercial off-the-shelf (COTS) devices recently. The full system integration is typically done by a System-in-Package (SiP) approach. Although SiP is suitable for lower frequencies, the packaging parasitics limit the use of this approach for the mm-wave frequencies. In this thesis, a fully BiCMOS embedded RF-MEMS switch for mm-wave applications is proposed. The design, the implementation and the experimental results of the switch are provided. The developed RF-MEMS switch is packaged using different packaging approaches. To actuate the RF-MEMS switch, an on-chip high voltage generation circuit is designed and characterized. The robustness and the reliability performance of the switch are also presented. Finally, the developed RF-MEMS switch is successfully demonstrated in re-configurable mm-wave circuits

Damage assessment in reinforced concrete using contactless ultrasound

The poor state of the deteriorating national infrastructure makes essential the need for implementation of non-destructive evaluation (NDE) and structural health monitoring (SHM) for existing concrete structures. Conventional contact-type ultrasonic testing (UT) methods offer efficient and useful approaches to characterize internal defects in concrete structures in a nondestructive fashion. However, the large testing areas normally associated with concrete structures make conventional ultrasonic methods extremely labor- and time-intensive. Contactless, or air-coupled, UT systems offer a solution to this limitation. In this thesis, high-performance contactless UT systems are studied, developed, implemented and verified in order to characterize several different type of damage (delamination, distributed microcracking, and rail seat deterioration) in concrete structures. The work comprises new hardware system design and testing approach development. The hardware, comprising the modified sensors and the automation/robotic scanning system, are designed and assembled by the author. The performance of the system is optimized with respect to generated pulse frequency content and energy, signal to noise ratio, and rapid data collection and scanning. Dynamic finite element method (FEM or FE) simulations of mechanical wave-based NDE methods are developed and described in order to support the system construction, theory verification, and experimental work. The FE models simulate generation and detection of air-coupled transient waves in air and wave interactions at the interface between concrete and air from internal defects and random scatterers. Next, three NDE applications with different types of damage are reported. New experimental and analytical approaches are introduced and deployed for each case, where the fully contactless UT system is used for each. The first study deploys multichannel analysis of surface waves (MASW) measurements interpreted through Lamb wave mode analysis; 3-D images are generated that make use of the Lamb wave mode jump condition in order to identify the presence of underlying delamination defects. The next application incorporates ultrasonic backscatter measurements to characterize distributed microcracking damage in concrete. Two different backscatter measurement schemes – time domain energy subtraction analysis (ESA) and spectral variance analysis (SVA) – are developed and applied through numerical simulation and experiment. The experiments are deployed using concrete samples containing well controlled artificial damage and imparted cracking damage. Both coherent and incoherent wave analyses are performed to study scatter characteristics. The backscatter energy measurements are sensitive to the presence of distributed microcracks as compared with conventional UT approaches. Also backscatter approaches provide statistically significant distinctions between damage levels in concrete. The collected backscatter data are also applied to image and identify localized regions of damage. In the third application, surface waves are used to interrogate interfacial damage related to rail seat deterioration (RSD) in concrete rail ties. Results from the UT tests on concrete tie samples are reported, where experimental results provide clear distinction among different RSD levels. Close proximity and large-offset scan configurations, which is appropriate for application to rail structures in situ, are proposed. Finally, future efforts toward additional implementation to actual bridge, nuclear power plant, and rail-field tests are proposed based on the work reported here