Design, modeling, fabrication, and testing of a multistage micro gas compressor with piezoelectric unimorph diaphragm and passive microvalves for microcooling applications

This dissertation investigates the development of a multistage micro gas compressor utilizing multiple pump stages cascaded in series to increase the pressure rise with passive microvalves and piezoelectric unimorph diaphragms. This research was conducted through modeling, simulation, design, and fabrication of the microcompressor and its components. A single-stage and a two-stage microcompressor were developed to demonstrate and compare the performance and effectiveness of using a cascaded multistage design. Steady fluid flow through static microvalves structure was studied to gain insight on its gas flow dynamics and characteristics. Transient analysis combined with the structure\u27s interaction was investigated with an analytical model and FEM model. The static analysis and transient analysis enabled lumped model parameter extraction for modeling and simulations. The transient FEM solution of the microvalve fluid-structure interaction (FSI) allows for extraction of the damping ratio for the lumped model. The microvalves were fabricated with MEMS microfabrication methods and integrated into a machined microcompressor housing. Study from the simulation of the microvalve fluid-structure dynamics in Simulink showed the frequency of the microvalves, at which frequency the mierovalve is more prone to leakage. Simulation indicated that the reverse leakage from the sealing of the microvalve can have a significant impact on the pressure rise performance of the compressor. A model of the single- and the two-stage microcompressor were developed with Simulink to observe the dynamics and performance of the multistage microcompressor. The simulation shows the dead volume between the two chambers to decrease in the overall pressure rise of the multistage microcompressor. Operating scenarios with different frequency and in phase and out of phase actuation between stages were simulated to understand the dynamics and performance of the multistage design. The fabricated single- and two-stage microcompressor produced a maximum pressure rise of 10 kPa and 18 kPa, respectively, and a maximum flow rate of 32 sccm for both. To obtain these maximum pressure rises, the microcompressors were operated at high frequency at the resonance of the piezoelectric diaphragm. This dissertation investigated the feasibility and operation of a multistage gas microcompressor with passive microvalves, allowing the exploration of its miniaturization

Implantable Microsystem Technologies For Nanoliter-Resolution Inner Ear Drug Delivery

Advances in protective and restorative biotherapies have created new opportunities to use site-directed, programmable drug delivery systems to treat auditory and vestibular disorders. Successful therapy development that leverages the transgenic, knock-in, and knock-out variants of mouse models of human disease requires advanced microsystems specifically designed to function with nanoliter precision and with system volumes suitable for implantation. The present work demonstrates a novel biocompatible, implantable, and scalable microsystem consisted of a thermal phase-change peristaltic micropump with wireless control and a refillable reservoir. The micropump is fabricated around a catheter microtubing (250 μm OD, 125 μm ID) that provided a biocompatible leak-free flow path while avoiding complicated microfluidic interconnects. Direct-write micro-scale printing technology was used to build the mechanical components of the pump around the microtubing directly on the back of a printed circuit board assembly. In vitro characterization results indicated nanoliter resolution control over the desired flow rates of 10–100 nL/min by changing the actuation frequency, with negligible deviations in presence of up to 10× greater than physiological backpressures and ±3°C ambient temperature variation. A biocompatibility study was performed to evaluate material suitability for chronic subcutaneous implantation and clinical translational development. A stand-alone, refillable, in-plane, scalable, and fully implantable microreservoir platform was designed and fabricated to be integrated with the micropump. The microreservoir consists two main components: a cavity for storing the drug and a septum for refilling. The cavity membrane is fabricated with thin Parylene-C layers, using a polyethylene glycol (PEG) sacrificial layer. The septum thickness is minimized by pre-compression down to 1 mm. The results of in vitro characterization indicated negligible restoring force for the optimized cavity membrane and thousands of punctures through the septum without leakage. The micropump and microreservoir were integrated into microsystems which were implanted in mice. The microtubing was implanted into the round window membrane niche for infusion of a known ototoxic compound (sodium salicylate) at 50 nL/min for 20 min. Real-time shifts in distortion product otoacoustic emission thresholds and amplitudes were measured during the infusion. The results match with syringe pump gold standard. For the first time a miniature and yet scalable microsystem for inner ear drug delivery was developed, enabling drug discovery opportunities and translation to human

Micro Electromechanical Systems (MEMS) Based Microfluidic Devices for Biomedical Applications

Micro Electromechanical Systems (MEMS) based microfluidic devices have gained popularity in biomedicine field over the last few years. In this paper, a comprehensive overview of microfluidic devices such as micropumps and microneedles has been presented for biomedical applications. The aim of this paper is to present the major features and issues related to micropumps and microneedles, e.g., working principles, actuation methods, fabrication techniques, construction, performance parameters, failure analysis, testing, safety issues, applications, commercialization issues and future prospects. Based on the actuation mechanisms, the micropumps are classified into two main types, i.e., mechanical and non-mechanical micropumps. Microneedles can be categorized according to their structure, fabrication process, material, overall shape, tip shape, size, array density and application. The presented literature review on micropumps and microneedles will provide comprehensive information for researchers working on design and development of microfluidic devices for biomedical applications

Microdosing for drug delivery application—A review

There is an increasing amount of research on microfluidic actuators with the aim to improve drug dosing applications. Micropumps are promising as they reduce the size and energy consumption of dosing concepts and enable new therapies. Even though there are evident advantages, there are only few examples of industrial microdosing units and micropump technology has not yet found widespread application. To answer the evoked question of what limits the application of microdosing technology for drug delivery, this work provides a comprehensive insight into the subject of drug dosing. We highlight and analyse specific microfluidic challenges and requirements in medical dosing: safety relevant aspects, such as prevention of freeflow and backflow; dosing-specific requirements, such as dosing precision and stability; and system-specific aspects, such as size, weight, and power restrictions or economic aspects. Based on these requirements, we evaluate the suitability of different mechanical micropumps and actuation mechanisms for drug administration. In addition to research work, we present industrial microdosing systems that are commercially available or close to market release. We then summarize outstanding technical solutions that ensure sufficient fluidic performance, guarantee a safe use, and fulfil the specific requirements of medical microdosing

Development of novel micropneumatic grippers for biomanipulation

Microbjects with dimensions from 1 μm to 1 mm have been developed recently for different aspects and purposes. Consequently, the development of handling and manipulation tools to fulfil this need is urgently required. Micromanipulation techniques could be generally categorized according to their actuation method such as electrostatic, thermal, shape memory alloy, piezoelectric, magnetic, and fluidic actuation. Each of which has its advantage and disadvantage. The fluidic actuation has been overlooked in MEMS despite its satisfactory output in the micro-scale. This thesis presents different families of pneumatically driven, low cost, compatible with biological environment, scalable, and controllable microgrippers. The first family demonstrated a polymeric microgripper that was laser cut and actuated pneumatically. It was tested to manipulate microparticles down to 200 microns. To overcome the assembly challenges that arise in this family, the second family was proposed. The second family was a micro-cantilever based microgripper, where the device was assembled layer by layer to form a 3D structure. The microcantilevers were fabricated using photo-etching technique, and demonstrated the applicability to manipulate micro-particles down to 200 microns using automated pick-and-place procedure. In addition, this family was used as a tactile-detector as well. Due to the angular gripping scheme followed by the above mentioned families, gripping smaller objects becomes a challenging task. A third family following a parallel gripping scheme was proposed allowing the gripping of smaller objects to be visible. It comprises a compliant structure microgripper actuated pneumatically and fabricated using picosecond laser technology, and demonstrated the capability of gripping microobject as small as 100 μm microbeads. An FEA modelling was employed to validate the experimental and analytical results, and excellent matching was achieved

Hydrodynamic focusing micropump module with PDMS/nickel-particle composite diaphragms for microfluidic systems

In this research, a rapid prototype of multi-fluidic speed-modulating (MFSM) micropump which enables modulation of hydrodynamic focusing in micro-fluidic flow has been designed, fabricated, and characterized. The size of the entire module is 33 mm x 25 mm x 8 mm and comprises of three MFSM micropumps to achieve hydrodynamic focusing. These pumps are simultaneously operated by the same actuation source. Each micropump consists of Tesla-type valves in the bottom layer and PDMS/Ni-particle composite (PNPC) diaphragm in the middle layer. The deflection of the diaphragm is obtained by the external pneumatic force, and the permanent magnet controls the displacement resulting from interaction between the magnetic field and the PNPC diaphragm. Analyses of the magnetic modulation force, the flow rate of the MFSM micropump, and the hydrodynamic focused channel modulation are presented. The individual micropump can pump DI water at flow rate of 107 ìl/min, and the combination of the three micropumps is able to make the flow rate of 321 ìl/min within a hydrodynamic focusing channel. This research successfully examines the possibility of modulation of a neighboring channel flow rate through interaction with a magnetic force field to achieve hydrodynamic focusing of flow in the central channel. With appropriate magnetic interaction with diaphragm, the central channel flow width can also be varied. This technique can be utilized for possible application in drug delivery system (DDS), lab-on-a-chip (LOC) or micro total analysis system (ìTAS), and in a point of care testing (POCT) system

Design of a Monosized Droplet Generator

This dissertation focuses on the development and validation of an instrument that allows the formation of drops. This document starts by showing the design developed for this purpose. After the development of the design, the pieces were built using 3D printing. When the process was complete, the device was assembled and validated. For the validation of this instrument, it was necessary to create a test station which is shown in chapter 3. After the entire assembly process, the validation tests were carried out. In the validation phase, water was applied to be ejected by the apparatus. Six different flow rates were implemented in order to determine the effect of the flow rate on the formation and behavior of the drops. The results of these tests were obtained through visualization methods. After all the images were collected in the testing phase, they were analyzed for the extraction of diameters. After the tests of undisturbed droplet formation were completed, the disturbed generation of droplets was proceeded to test. In this testing phase, three flows were chosen from the previous phase and imposed. The flow rates chosen for the disturbed phase of the generation of droplets were: 2.5, 4 and 5 ml/min. The proceedings for these tests was the flow and signal implementation. After the flow was implemented, the electromagnetic wave was built to be implemented in the piezoelectric cell. The electromagnetic signal consists of a square wave of constant amplitude (20 Vpp), where the frequency is periodically increased. The study with several frequencies aims to investigate the influence of frequency on the forma- tion of drops for the case of this instrument. This study allows testing whether the apparatus is capable of creating consecutive drops with high repeatability in terms of diameter and spacing between drops. Like the undisturbed cases, the disturbed droplet formation was also tested through visualization and image analysis.Esta dissertação foca-se no desenvolvimento e validação de um instrumento que permite a for- mação de gotas. Este documento começa por mostrar o design desenvolvido para este propósito. Após o desenvolvimento do design, as peças foram construídas recorrendo à impressão 3D. Após a impressão das peças, procedeu-se à montagem e validação do dispositivo. Para a validação deste instrumento, foi necessário criar uma estação de testes que é mostrada no capítulo 3. Após todo o processo de montagem, realizaram-se os testes de validação. Na fase de validação, usou-se água para a validação do aparelho. Seis caudais diferentes foram implementados, de forma a determinar o efeito do caudal na formação e comportamento das gotas. Os resultados destes testes foram obtidos através de métodos de visualização. Após todas as imagens serem recolhidas na fase de testes, estas foram analisadas para a extracção de diâmetros. Depois deste processo ter sido concluido, procedeu-se a testar a geração de gotas perturbada. Nesta fase de testes, três caudais foram escolhidos de entre os im,postos na primeira fase de validação e impostos. Os caudais escolhidos para a fase perturbada da geração de gotas foram: 2.5, 4 e 5 ml/min. O procedimento para estes testes foi a implementação do caudal e do sinal. Após a implementação do caudal, a onda electromagnética foi construída para implementar na célula piezoeléctrica. O sinal electromagnético consiste numa onda quadrada de amplitude constante (20 Vpp), onde a frequência é periodicamente aumentada. O estudo com várias frequências visa a investigação da influência da frequência na formação de gotas para o caso deste instrumento. Este estudo permite testar se o aparato é capaz de criar gotas consecutivas com alta repetibilidade no que toca a diâmetros e espaçamento entre gotas. À semelhança dos casos não perturbados, a formação perturbada de gotas também foi testada através de visualização e análise de imagem

Recent advances in micro-electro-mechanical devices for controlled drug release applications

In recent years, controlled release of drugs has posed numerous challenges with the aim of optimizing parameters such as the release of the suitable quantity of drugs in the right site at the right time with the least invasiveness and the greatest possible automation. Some of the factors that challenge conventional drug release include long-term treatments, narrow therapeutic windows, complex dosing schedules, combined therapies, individual dosing regimens, and labile active substance administration. In this sense, the emergence of micro-devices that combine mechanical and electrical components, so called micro-electro-mechanical systems (MEMS) can offer solutions to these drawbacks. These devices can be fabricated using biocompatible materials, with great uniformity and reproducibility, similar to integrated circuits. They can be aseptically manufactured and hermetically sealed, while having mobile components that enable physical or analytical functions together with electrical components. In this review we present recent advances in the generation of MEMS drug delivery devices, in which various micro and nanometric structures such as contacts, connections, channels, reservoirs, pumps, valves, needles, and/or membranes can be included in their design and manufacture. Implantable single and multiple reservoir-based and transdermal-based MEMS devices are discussed in terms of fundamental mechanisms, fabrication, performance, and drug release applications.Fil: Villarruel Mendoza, Luis A.. Comisión Nacional de Energía Atómica. Gerencia de Área de Investigación y Aplicaciones no Nucleares. Gerencia de Desarrollo Tecnológico y Proyectos Especiales. Departamento de Micro y Nanotecnología; ArgentinaFil: Scilletta, Natalia Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Área de Investigación y Aplicaciones no Nucleares. Gerencia de Desarrollo Tecnológico y Proyectos Especiales. Departamento de Micro y Nanotecnología; ArgentinaFil: Bellino, Martin Gonzalo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Constituyentes | Comision Nacional de Energia Atomica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Constituyentes.; ArgentinaFil: Desimone, Martín Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Catalano, Paolo Nicolás. Comisión Nacional de Energía Atómica. Gerencia de Área de Investigación y Aplicaciones no Nucleares. Gerencia de Desarrollo Tecnológico y Proyectos Especiales. Departamento de Micro y Nanotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Design of a Detachable Acoustically-Actuated Platform for Separation of Whole Blood and Nanoparticles

Blood-based diagnostic tests have become a widespread paradigm for clinical disease diagnosis. Such tests are designed to detect small molecules in blood, which are indicative of a particular disease. Current blood-based diagnostic tests utilize specialized equipment, manual steps, and trained technicians. These factors limit the access of patients to testing. Lab-on-a-chip techniques, which enable handling of samples on the micron scale, have the potential to replace and simplify the current processes. In addition, sensitive optical assays that utilize functionalized nanoparticles have been developed for applications at the point-of-care. These assays require a consistent nanoparticle concentration. In this work, an acoustic platform to replace the first step in blood-based diagnostic assays, blood separation, is developed and tested for use with nanoparticle-based assays. The presented system uses a surface acoustic wave transducer integrated with a detachable microfluidic channel to achieve blood separation. The concept of a single-injection system, in which nanoparticles are mixed with an unprocessed sample, is tested. A standing wave generated by the transducer creates areas of high and low pressure across the microfluidic channel that cause displacement of blood components, based on size, from the sample stream to adjacent buffer fluid streams. The ability of this system to separate undiluted whole blood and nanoparticles is assessed. Fabrication of the standing surface acoustic wave transducer and microfluidic channel are described in detail. A detachable system is proposed to allow reuse of the transducer. Results from blood separation experiments using different transducer and channel designs are presented. To improve the transducer performance in experiments longer than several minutes, a temperature-regulation system was built. The first whole blood separation experiment using a detachable microchannel and standing surface acoustic waves is reported. Finally, the effect of the acoustic mechanism on functionalized nanoparticles is tested. The results indicate that a detachable acousto-fluidic system using surface acoustic waves may be used for effective whole blood separation when using temperature regulation. For maintenance of nanoparticle concentration and use of a single-injection system, the acoustic properties of the buffer must be tuned