From Cleanroom to Desktop: Emerging Micro-Nanofabrication Technology for Biomedical Applications

This review is motivated by the growing demand for low-cost, easy-to-use, compact-size yet powerful micro-nanofabrication technology to address emerging challenges of fundamental biology and translational medicine in regular laboratory settings. Recent advancements in the field benefit considerably from rapidly expanding material selections, ranging from inorganics to organics and from nanoparticles to self-assembled molecules. Meanwhile a great number of novel methodologies, employing off-the-shelf consumer electronics, intriguing interfacial phenomena, bottom-up self-assembly principles, etc., have been implemented to transit micro-nanofabrication from a cleanroom environment to a desktop setup. Furthermore, the latest application of micro-nanofabrication to emerging biomedical research will be presented in detail, which includes point-of-care diagnostics, on-chip cell culture as well as bio-manipulation. While significant progresses have been made in the rapidly growing field, both apparent and unrevealed roadblocks will need to be addressed in the future. We conclude this review by offering our perspectives on the current technical challenges and future research opportunities

A Cost Effective Direct Writing Laser System for Rapid Prototyping of Microfluidic Devices

This study is conducted to highlight the improvement in technology of manufacturing microstructures using maskless lithography technique. Direct laser writing technique was implemented, and a major section of this study is carried out on an experimental slant. Variables that were not covered experimentally were studied using lithography simulation software, GenISys – LAB. The aim of this study is to fabricate and analyze cost effective maskless lithography apparatus to ensure rapid prototyping and optimize the system to be used for at least two negative photoresist materials. A parametric study was carried out determining the best operating conditions from both perspectives of direct laser writing and material process parameters. All parameters were studied experimentally, but the impact of depth of focus was illustrated using lithography simulation. Using direct laser writing system, complex designs were manufactured. The developed system had a maximum writing speed of 0.834 mm/s. The minimum line width produced using optimized operating conditions was 3.94 μm. Experimentally, increasing laser intensity increased the line width and by increasing post bake timings, it was observed that less laser intensity was required. Simulation results showed that depth of focus plays a crucial role in manufacturing good quality 3D resist profile. We developed a cost effective direct laser writing system as a part of studying maskless lithography process for rapid manufacturing. The total cost associated to develop this system was AED 4800 ($ 1307). This system was optimized to be used with two negative photoresist materials. A significant contribution of our work is through cost effectiveness and performance to produce complex designs using a maskless lithographic process. This study will provide an opportunity for researchers to use their innovative designs with faster and cheaper methods of prototyping micro devices

Complete fabrication station of scalable microfluidic devices for sensing applications

Microfluidics has become a field of intense research in the last decades due to the interesting capabilities this type of devices have. In the sensing area, they are meant to outperform classical laboratory techniques in terms of speed, volume of sample required, resolution, handling and efficiency. However, the technology has not achieved the predicted impact on the actual sensing world. Among the issues that slow down its development, the limited scalability of the fabrication techniques used results in a poor translation from research to the market

Defining cellular microenvironments using multiphoton lithography

textTo understand the chemistry of life processes in detail is largely a challenge of resolving them in their native, cellular environment. Cell culture, first developed a century ago, has proven to be an essential tool for reductionist studies of cellular biochemistry and development. However, for the technology of cell culture to move forward and address increasingly complex problems, in vitro environments must be refined to better reflect the cellular environment in vivo. This dissertation work has focused on the development of methods to define cellular microenvironments using the high resolution, 3D capabilities of multiphoton lithography. Here, site-specific photochemistry using multiphoton excitation is applied to the photocrosslinking of proteins, providing the means to organize bioactive species into well-defined 3D microenvironments. Further, conditions have been identified that enable microfabrication to be performed in the presence of cells -- allowing cell outgrowth and motility to be directed in real time. In addition to the intrinsic chemical functionality of microfabricated protein structures, 3D protein matrices are shown to respond mechanically to changes in the chemical environment, enabling new avenues for micro-scale actuation to be explored. Complex 2D and 3D protein photocrosslinking is further facilitated by integrating transparency and automated reflectance photomasks into the fabrication system. These advances could be transformative in efforts to fabricate precise cellular scaffolding that replicates the morphological (and potentially biochemical) features of in vivo tissue microenvironments. Finally, these methods are applied to the study of microorganism behavior with single-cell resolution. Microarchitectures are designed that allow the position and motion of motile bacterial to generate directional microfluidic flow -- providing a foundation to develop micro-scale devices powered by cells.Chemistry and BiochemistryBiochemistr

Microlens Array Fabrication Technique and its Application in Surface Nanopatterning

Ph.DDOCTOR OF PHILOSOPH

Microfabricated Poly (ethylene glycol) Based Hydrogels for Microvascular Tissue Engineering Applications

Shortages in donor organs and the lack of therapeutic treatment options to address tissue loss and end-organ failure has led to intense research into tissue engineering based therapeutics. Cellular, tissue, and organ level therapeutics hold the potential to shift clinical paradigms and drastically improve healthcare outcomes. However, to date the only successful tissue engineering therapeutics have been limited to thin and avascular tissues such as skin, cartilage and the bladder. This is primarily due to the absence of a perfusable vasculature to transport nutrients and waste during in vitro tissue development and inadequate host-implant vascular integration upon implantation. In this thesis we set out to develop hydrogel microfabrication technologies to (1) improve in vitro mass transport, (2) integrate self-assembling microvascular networks with microfabricated channels and (3) incorporate and support functional parenchymal cellular elements within in vitro constructs. Application of microfabrication technologies to PEG hydrogels requires that fabrication schemes are cell compatible, robust for handling and imaging and most importantly allow for precise micron level control of both fluid perfusion and hydrogel structure fabrication. Herein we report multiple cell compatible 1 microfabrication schemes that employ multilayer replica molding and photolithographic hydrogel fabrication techniques. Systems designed with these techniques resulted in improved in vitro mass transport, integration of selfassembled microvascular networks with fabricated structures and the ability to pattern multilayer heterogeneous hydrogel structures that contain and support multiple cellular elements. The progress reported herein has broad applicability towards the development of biomaterials with highly biomimetic structural-functional characteristics. More specifically these hydrogel microfabrication technologies hold the promise to improve the therapeutic potential of tissue engineered constructs and provide more biologically applicable pre-clinical tissue models.

Grating Aligned Ferroelectric Liquid Crystal Devices

This thesis is concerned with the vertical grating alignment of ferroelectric liquid crystals (FLCs). FLCs exhibit fast electro-optic response times compared to traditional nematic devices, and so are of particular interest for use in micro-displays and liquid crystal on silicon (LCoS) spatial light modulators. Unfortunately such materials are highly susceptible to shock induced ow. This work introduces the VGA-FLC device geometry: a vertical grating aligned ferroelectric liquid crystal display. The vertical alignment gives preferential alignment to the smectic layers, and the amplitude and pitch of the grating ensure stable alignment of the c-director of the FLC. The combined effect is shown to result in a shock-stable FLC geometry. The device is addressed with in-plane electric fields, and is shown to obtain fast optical response times. The theory and physics of the device is explored, and further experiments are suggested that can be performed for device optimisation

Process planning for thick-film mask projection micro stereolithography

Mask Projection micro Stereolithography (MPuSLA) is an additive manufacturing process used to build physical components out of a photopolymer resin. Existing MPuSLA technology cut the CAD model of part into slices by horizontal planes and the slices are stored as bitmaps. A layer corresponding to the shape of each bitmap gets cured. This layer is coated with a fresh layer of resin by lowering the Z-stage inside a vat holding the resin and the next layer is cured on top of it. In our Thick-film MPuSLA(TfMPuSLA) system, incident radiation, patterned by a dynamic mask, passes through a fixed transparent substrate to cure photopolymer resin. The existing MPuSLA fabrication models can work only for controlling the lateral dimension, without any control over the thickness of the cured part. The proposed process plan controls both the lateral dimensions and the thickness of profile of the cured part. In this thesis, a novel process planning for TfMPuSLA method is developed, to fabricate films on fixed flat substrate. The process of curing a part using this system is analytically modeled as the column cure model. It is different from the conventional process - layer cure model. Column means that a CAD model of part is discretized into vertical columns instead of being sliced into horizontal layers, and all columns get cured simultaneously till the desired heights. The process planning system is modularized into geometrical, chemical, optical, mathematical and physical modules and validated by curing test parts on our system. The thesis formulates a feasible process planning method, providing a strong basis for continued investigation of MPuSLA technology in microfabrication, such as micro lens fabrication.M.S.Committee Chair: Rosen, David W.; Committee Member: Das, Suman; Committee Member: Grover, Martha A