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

An overview of microneedle applications, materials, and fabrication methods

Microneedle-based microdevices promise to expand the scope for delivery of vaccines and therapeutic agents through the skin and withdrawing biofluids for point-of-care diagnostics - so-called theranostics. Unskilled and painless applications of microneedle patches for blood collection or drug delivery are two of the advantages of microneedle arrays over hypodermic needles. Developing the necessary microneedle fabrication processes has the potential to dramatically impact the health care delivery system by changing the landscape of fluid sampling and subcutaneous drug delivery. Microneedle designs which range from sub-micron to millimetre feature sizes are fabricated using the tools of the microelectronics industry from metals, silicon, and polymers. Various types of subtractive and additive manufacturing processes have been used to manufacture microneedles, but the development of microneedle-based systems using conventional subtractive methods has been constrained by the limitations and high cost of microfabrication technology. Additive manufacturing processes such as 3D printing and two-photon polymerization fabrication are promising transformative technologies developed in recent years. The present article provides an overview of microneedle systems applications, designs, material selection, and manufacturing methods

Design and Fabrication of Microneedles for Drug Delivery

Ph.DDOCTOR OF PHILOSOPH

Towards rapid 3D direct manufacture of biomechanical microstructures

The field of stereolithography has developed rapidly over the last 20 years, and commercially available systems currently have sufficient resolution for use in microengineering applications. However, they have not as yet been fully exploited in this field. This thesis investigates the possible microengineering applications of microstereolithography systems, specifically in the areas of active microfluidic devices and microneedles. The fields of micropumps and microvalves, stereolithography and microneedles are reviewed, and a variety of test builds were fabricated using the EnvisionTEC Perfactory Mini Multi-Lens stereolithography system in order to define its capabilities. A number of microneedle geometries were considered. This number was narrowed down using finite element modelling, before another simulation was used to optimise these structures. 9 × 9 arrays of 400 μm tall, 300 μm base diameter microneedles were subjected to mechanical testing. Per needle failure forces of 0.263 and 0.243 N were recorded for the selected geometries, stepped cone and inverted trumpet. The 90 μm needle tips were subjected to between 30 and 32 MPa of pressure at their failure point - more than 10 times the required pressure to puncture average human skin. A range of monolithic micropumps were produced with integrated 4 mm diameter single-layer 70 μm-thick membranes used as the basis for a reciprocating displacement operating principle. The membranes were tested using an oscillating pneumatic actuation, and were found reliable (>1,000,000 cycles) up to 2.0 PSIG. Pneumatic single-membrane nozzle/diffuser rectified devices produced flow rates of up to 1,000 μl/min with backpressures of up to 375 Pa. Another device rectified using active membrane valves was found to self-prime, and produced backpressures of up to 4.9 kPa. These devices and structures show great promise for inclusion in complex, fully integrated and active microfluidic systems fabricated using microstereolithography alone, with implications for both cost of manufacture and lead time

Development of on-farm diagnostic devices

The global population, currently 7.7 billion, is expected to grow to 9.7 billion by 2050. This is expected to lead to a 70% increase in demand for animal-based protein. Irish beef and dairy products account for over 50% of our agricultural output and DAFM’s Food Wise 2025 strategy aims to position Ireland as a world leader in sustainable agri-food production. However, the high percentage of livestock that are lost due to infectious diseases (20%), poses a challenge to achieving this sustainability, in addition to more sustainable use of antimicrobials, smarter livestock diagnostics and treatments are therefore required. The goal of this thesis was to develop a low-cost disposable biosensor that would permit point-of-care (POC) detection of diseases in bovines, through cost-effective, scalable microfabrication techniques. Such devices could enable real-time determination of the health status of animals on farm and contribute to more informed therapeutic interventions. Electrochemistry presents a viable option for POC devices in this regard and allows easy integration with portable electronics. Electrochemical Impedance Spectroscopy (EIS) is a surface sensitive technique that measures the resistive and capacitive behaviour of an electrochemical system. It lends itself to serological immunosensor development as it allows label-free detection. For the purposes of this research, silicon devices were fabricated with six microband working electrodes, gold counter, and platinum pseudo-reference electrodes. The microband working electrodes were modified with a biocompatible co-polymer. This co-polymer supported the cross-linking of a bioreceptor (e.g., anti-bovine IgG) to electrode surface, which selectively bound to the target biomolecule (bovine IgG) in serum. This EIS device could distinguish between seronegative and seropositive samples in 15 minutes making it suitable for POC applications. Additionally, the presence of six working electrodes allowed for testing of multiple samples at a time. Often, however, only a single test is required. As such, silicon presents an expensive option for disposable sensors. Hence, polymer replication methods were also investigated in this thesis. This process allowed a single silicon wafer to be repeatedly used to produce polymer structures. A microneedle format was chosen to eliminate the need for taking samples on-farm and provide a pain-free method of in vivo measurements in interstitial fluid in interstitial fluid. The fabrication method used a double-sided micro-moulding process to move towards mass manufacturing. COMSOL simulations were performed to explore the active layer on the microneedle tip surface, ensuring no diffusional overlap between electrodes and providing the most effective tip design. The microneedle structures also presented the opportunity for novel fabrication of nanoring arrays, by removing part of the protruding structure and exposing underlying nanorings. These have the potential to be highly sensitive electrochemical devices due to enhanced mass transport and high current densities, while maintaining the scalable cost-effective fabrication process of the microneedles. Devices produced steady-state CVs in a known redox molecule, with currents in the nA range

Towards rapid 3D direct manufacture of biomechanical microstructures

The field of stereolithography has developed rapidly over the last 20 years, and commercially available systems currently have sufficient resolution for use in microengineering applications. However, they have not as yet been fully exploited in this field. This thesis investigates the possible microengineering applications of microstereolithography systems, specifically in the areas of active microfluidic devices and microneedles. The fields of micropumps and microvalves, stereolithography and microneedles are reviewed, and a variety of test builds were fabricated using the EnvisionTEC Perfactory Mini Multi-Lens stereolithography system in order to define its capabilities. A number of microneedle geometries were considered. This number was narrowed down using finite element modelling, before another simulation was used to optimise these structures. 9 × 9 arrays of 400 μm tall, 300 μm base diameter microneedles were subjected to mechanical testing. Per needle failure forces of 0.263 and 0.243 N were recorded for the selected geometries, stepped cone and inverted trumpet. The 90 μm needle tips were subjected to between 30 and 32 MPa of pressure at their failure point - more than 10 times the required pressure to puncture average human skin. A range of monolithic micropumps were produced with integrated 4 mm diameter single-layer 70 μm-thick membranes used as the basis for a reciprocating displacement operating principle. The membranes were tested using an oscillating pneumatic actuation, and were found reliable (>1,000,000 cycles) up to 2.0 PSIG. Pneumatic single-membrane nozzle/diffuser rectified devices produced flow rates of up to 1,000 μl/min with backpressures of up to 375 Pa. Another device rectified using active membrane valves was found to self-prime, and produced backpressures of up to 4.9 kPa. These devices and structures show great promise for inclusion in complex, fully integrated and active microfluidic systems fabricated using microstereolithography alone, with implications for both cost of manufacture and lead time.EThOS - Electronic Theses Online ServiceEngineering and Physical Sciences Research Council (EPSRC)GBUnited Kingdo

Micromachined three-dimensional electrode arrays for in-vitro and in-vivo electrogenic cellular networks

This dissertation presents an investigation of micromachined three-dimensional microelectrode arrays (3-D MEAs) targeted toward in-vitro and in-vivo biomedical applications. Current 3-D MEAs are predominantly silicon-based, fabricated in a planar fashion, and are assembled to achieve a true 3-D form: a technique that cannot be extended to micro-manufacturing. The integrated 3-D MEAs developed in this work are polymer-based and thus offer potential for large-scale, high volume manufacturing. Two different techniques are developed for microfabrication of these MEAs - laser micromachining of a conformally deposited polymer on a non-planar surface to create 3-D molds for metal electrodeposition; and metal transfer micromolding, where functional metal layers are transferred from one polymer to another during the process of micromolding thus eliminating the need for complex and non-repeatable 3-D lithography processes. In-vitro and in-vivo 3-D MEAs are microfabricated using these techniques and are packaged utilizing Printed Circuit Boards (PCB) or other low-cost manufacturing techniques. To demonstrate in-vitro applications, growth of 3-D co-cultures of neurons/astrocytes and tissue-slice electrophysiology with brain tissue of rat pups were implemented. To demonstrate in-vivo application, measurements of nerve conduction were implemented. Microelectrode impedance models, noise models and various process models were evaluated. The results confirmed biocompatibility of the polymers involved, acceptable impedance range and noise of the microelectrodes, and potential to improve upon an archaic clinical diagnostic application utilizing these 3-D MEAs.Ph.D.Committee Chair: Mark G. Allen; Committee Member: Elliot L. Chaikof; Committee Member: Ionnis (John) Papapolymerou; Committee Member: Maysam Ghovanloo; Committee Member: Oliver Bran

Micro/Nano Structures and Systems

Micro/Nano Structures and Systems: Analysis, Design, Manufacturing, and Reliability is a comprehensive guide that explores the various aspects of micro- and nanostructures and systems. From analysis and design to manufacturing and reliability, this reprint provides a thorough understanding of the latest methods and techniques used in the field. With an emphasis on modern computational and analytical methods and their integration with experimental techniques, this reprint is an invaluable resource for researchers and engineers working in the field of micro- and nanosystems, including micromachines, additive manufacturing at the microscale, micro/nano-electromechanical systems, and more. Written by leading experts in the field, this reprint offers a complete understanding of the physical and mechanical behavior of micro- and nanostructures, making it an essential reference for professionals in this field