A. James Clark School of Engineering
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The collections in this community comprise faculty research works, as well as graduate theses and dissertations.
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Item Additive Manufacturing of Microfluidic Technologies via In Situ Direct Laser Writing(2021) Alsharhan, Abdullah; Sochol, Ryan; Mechanical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Innovations in microfluidic technologies hold great promise for a wide range of chemical, biomedical, and soft robotic applications. Unfortunately, key drawbacks associated with soft lithography-based microfabrication processes hinder such progress. To address these challenges, we advance a novel submicron-scale additive manufacturing (AM) strategy, termed “in situ direct laser writing (isDLW)”. IsDLW is an approach that benefits from the architectural versatility and length scales inherent to two-photon polymerization (2PP), while simultaneously supporting the micro-to-macro interfaces required for its effective utilization in microfluidic applications. In this dissertation, we explore isDLW strategies that enable passive and active 3D microfluidic technologies capable of enhancing “on-chip” autonomy and sophistication. Initially, we use poly(dimethylsiloxane) (PDMS)-based isDLW to fabricate microfluidic diodes that enable unidirectional rectification of fluid flow. We introduce a novel cyclic olefin polymer (COP)-based isDLW strategy to address several limitations related to structural adhesion and compatibility of PDMS microchannels. We use this COP-based approach to print microfluidic transistors comprising flexible and free-floating components that enable both “normally open” (NO) and “normally closed” (NC) functionalities—i.e., source-to-drain fluid flow (QSD) through the transistor is either permitted (NC) or obstructed (NO) when a gate input (PG) is applied. As an exemplar, we employ COP-based isDLW to print an integrated microfluidic circuit (IMC) comprised of soft microgrippers downstream of NC microfluidic transistors with distinct PG thresholds. All of these microfluidic circuit elements are printed within microchannels ≤ 40 μm in height, representing the smallest such components (to our knowledge). Theoretical and experimental results illustrate on the operational efficacy of these components as well as characterize their performance at different input conditions, while IMC experimental results demonstrate sequential actuation of the microrobotic components to realize target gripper operations with a single PG input. Furthermore, to investigate the utility of this strategy for static microfluidic technologies, we fabricate: (i) interwoven bioinspired microvessels (inner diameters < 10 μm) capable of effective isolation of distinct microfluidic flow streams, and (ii) deterministic lateral displacement (DLD) microstructures that enable continuous sorting of submicron particles (860 nm). In combination, these results suggest that the developed AM strategies offer a promising pathway for advancing state-of-the-art microfluidic technologies for various biological and soft robotic applications.Item TOWARD PHANTOM DEVELOPMENT FOR MEDICAL IMAGING USING DIRECT LASER WRITING(2020) Lamont, Andrew Carl; Sochol, Ryan D.; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)An important tool for the performance analysis and standardization of medical imaging technologies is the phantom, which offers specifically defined properties that mimic the structural and optical characteristics of a tissue of interest. The development of phantoms for high-resolution (i.e., micro-scale) three-dimensional (3D) imaging modalities can be challenging, however, as few manufacturing techniques can capture the architectural complexity of biological tissues at such scales. Direct Laser Writing (DLW) is an evolving additive manufacturing technique with nano-scale precision that can fabricate micro and nanostructures with unparalleled geometric complexity. This dissertation outlines the unique microfluidic-based DLW strategies that have been developed for novel micro-scale phantom production. First, I will outline the development and characterization of an in situ DLW strategy used to adhere printed components to the surfaces of a microchannel. I will then explain how we have leveraged this strategy for a proof-of-concept retinal cone outer segment phantom that is laden with light-scattering Titanium (IV) Dioxide nanoparticles. This phantom has valuable implications for the performance analysis of the emerging ophthalmological modality, adaptive optics-optical coherence tomography (AO-OCT). Next, I will describe the development and characterization of a microfluidic-based multi-material DLW strategy to fabricate single components from multiple materials with minimal registration error between the materials. Ultimately, we intend to use this method to develop multi-material platforms and phantoms, including high-aspect-ratio multi-material retinal cone phantoms for AO-OCT. Finally, to demonstrate the applicability of this method for applications beyond AO-OCT, I present a preliminary phantom production strategy for the light microscopy-based modality, whole slide imaging (WSI). Specifically, we assess the DLW and light microscopy performance of dyed photoresists and offer a preliminary multi-material demonstration, which are pivotal first steps toward the creation of a first-generation multi-material WSI phantom. This work provides valuable insights and strategies that leverage microfluidic-based DLW techniques to fabricate novel micro-scale phantoms. It is anticipated that these strategies will have a lasting impact, not only on the production of phantoms for medical imaging modalities, but also for the fabrication of advanced microfluidic and multi-material microstructures for fields such as meta-materials, micro-optics, lab-on-a-chip, and organ-on-a-chip.Item ACTIVE AND PASSIVE MICROFLUIDICS FOR SAMPLE DISCRETIZATION, MANIPULATION AND MULTIPLEXING(2020) Padmanabhan, Supriya; DeVoe, Don L; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The use of microfluidic technology to compartmentalize an initial sample into discrete and isolated volumes is an important step for many biological and chemical applications, that allows molecules, cells, particles, reagents, and analytes to be spatially constrained, providing unique benefits for their characterization, sorting, and manipulation with low reagent consumption. Discretization can also increase the overall throughput and enable multiplexing. In this dissertation, two platforms are described to enable microfluidic sample discretization and manipulation. First, (2D) microwell arrays fabricated in thermoplastic cyclic olefin copolymer (COP) are explored as a new approach toward the development of high throughput, low-cost components in disposable diagnostics by utilizing a passive discretization technique. Performance of various 2D array designs is characterized numerically and experimentally to assess the impact of thermoplastic surface energy, fluid flow rate, and device geometry on sample filling and discretization. The design principles are used to successfully scale up the platform without affecting device performance. Loop-mediated isothermal amplification (LAMP) on chip is used to demonstrate the platform’s potential for discretized nucleic acid testing. Next, pin spotting in nanoliter-scale 2D arrays is demonstrated as technique for high resolution reagent integration to enable multiplexed testing in diagnostics. The potential for nucleic-acid diagnostics is evaluated by performing rolling circle amplification (RCA) on chip with integrated reagents. Finally, an innovative platform enabling complex discretization and manipulation of aqueous droplets is presented. The system uses simple membrane displacement trap elements as an active technique to perform multiple functions including droplet discretization, release, metering, capture, and merging. Multi-layer polydimethylsiloxane (PDMS) devices with membrane displacement trap (MDT) arrays are used to discretize sample into nanoliter scale droplet volumes, and reliably manipulate individual droplets within the arrays. Performance is characterized for varying capillary number flows, membrane actuation pressures, trap and membrane geometries, and trapped droplet volumes, with operational domains established for each platform function. The novel approach to sample digitization and droplet manipulation is demonstrated through discretization of a dilute bacteria sample, metering of individual traps to generate droplets containing single bacteria, and merging of the resulting droplets to pair the selected bacteria within a single droplet.Item THE APPLICATION OF MICRODEVICES FOR INVESTIGATING BIOLOGICAL SYSTEMS(2018) Shang, Wu; Bentley, William E; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The gastrointestinal (GI) tract is a complex ecosystem with cells from different kingdoms organized within dynamically-changing structures and engaged in complex communication through a network of molecular signaling pathways. One challenge for researchers is that the GI tract is largely inaccessible to experimental investigation. Even animal models have limited capabilities for revealing the rich spatiotemporal variation in the intestine and fail to predict human responses due to genetic variation. Exciting recent advances in in vitro organ model (i.e., organ-on- chips (OOC)) based on microfluidics are offering new hope that these experimental systems may be capable of recapitulating the complexities in structure and context inherent to the intestine. A current limitation to OOC systems is that while they can recapitulate structure and context, they do not yet offer capabilities to observe or engage in the molecular based signaling integral to the functioning of this complex biological system. This dissertation focuses on developing microfluidic tools that provide access to interrogating signaling events amongst populations in the GI tract (e.g., microbes and enterocytes). First, a membrane-based gradient generator is built to establish linear and stable chemical gradients for investigating gradient-mediated behaviors of bacteria. Specifically, this platform enables the study of bacterial chemotaxis and potentially facilitates the development of genetically rewired lesion-targeted probiotics. Second, “electrobiofabrication” is coupled with microelectronics, for the first time, to create molecular-to-electronic (i.e., “molectronic”) sensors to observe and report the dynamic exchange of biochemical information in OOC systems. Last, to address the issue of poor compatibility between OOCs and sensors, we assemble OOCs with molectronic sensors in a modular format. The concept of modularity greatly reduces the system complexity and enables sensors to be built immediately before applications, avoiding functional decay of active biorecognition components after long-term device storage and use. We envision this work will “open” OOC systems for molecular measurement and interrogation, which, in turn, will expand the in vitro toolbox that researchers can use to design, build and test for the investigation of GI disease and drug discovery.Item MICROFLUIDIC ASSAY PERFORMANCE ENHANCEMENT USING POROUS VOLUMETRIC DETECTION ELEMENTS FOR IMPEDEMETRIC AND OPTICAL SENSING(2016) Wiederoder, Michael; DeVoe, Don L; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Microfluidic technologies have great potential to help create automated, cost-effective, portable devices for rapid point of care (POC) diagnostics in diverse patient settings. Unfortunately commercialization is currently constrained by the materials, reagents, and instrumentation required and detection element performance. While most microfluidic studies utilize planar detection elements, this dissertation demonstrates the utility of porous volumetric detection elements to improve detection sensitivity and reduce assay times. Impedemetric immunoassays were performed utilizing silver enhanced gold nanoparticle immunoconjugates (AuIgGs) and porous polymer monolith or silica bead bed detection elements within a thermoplastic microchannel. For a direct assay with 10 µm spaced electrodes the detection limit was 0.13 fM AuIgG with a 3 log dynamic range. The same assay was performed with electrode spacing of 15, 40, and 100 µm with no significant difference between configurations. For a sandwich assay the detection limit was10 ng/mL with a 4 log dynamic range. While most impedemetric assays rely on expensive high resolution electrodes to enhance planar senor performance, this study demonstrates the employment of porous volumetric detection elements to achieve similar performance using lower resolution electrodes and shorter incubation times. Optical immunoassays were performed using porous volumetric capture elements perfused with refractive index matching solutions to limit light scattering and enhance signal. First, fluorescence signal enhancement was demonstrated with a porous polymer monolith within a silica capillary. Next, transmission enhancement of a direct assay was demonstrated by infusing aqueous sucrose solutions through silica bead beds with captured silver enhanced AuIgGs yielding a detection limit of 0.1 ng/mL and a 5 log dynamic range. Finally, ex situ functionalized porous silica monolith segments were integrated into thermoplastic channels for a reflectance based sandwich assay yielding a detection limit of 1 ng/mL and a 5 log dynamic range. The simple techniques for optical signal enhancement and ex situ element integration enable development of sensitive, multiplexed microfluidic sensors. Collectively the demonstrated experiments validate the use of porous volumetric detection elements to enhance impedemetric and optical microfluidic assays. The techniques rely on commercial reagents, materials compatible with manufacturing, and measurement instrumentation adaptable to POC diagnostics.Item Thermoplastic microfluidic technologies for portable and disposable bioanalytical and diagnostic platforms(2015) Rahmanian, Omid David; DeVoe, Don L; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Portable and cost-effective medical diagnostic technologies that require minimal external infrastructure for their operation are highly desirable for on-field military operations, defense against acts of bioterrorism, and infectious disease screening in resource-limited environments. Miniaturized Total Analysis Systems (µTAS) have the potential to fulfill this un-met need via low-cost, portable, and disposable point-of-care (POC) diagnostic devices. Inherent advantages of µTAS systems can be utilized to transform diagnostic technologies that currently require significant investment in centralized laboratories and highly trained personnel into automated, integrated, and miniaturized platforms. This dissertation addresses the development of microfabrication techniques and resulting component technologies that are realized in low-cost thermoplastic substrates. A thermoplastic microfabrication technique termed orogenic microfabrication, based on a non-reversible solvent-assisted swelling mechanism, is developed to provide unique capabilities for microscale and nanoscale patterning in rigid thermoplastics with minimal infrastructure. Orogenic microfabrication is compatible with multiple masking techniques including photolithography, chemical surface modification, contact and noncontact spotting, and inkjet deposition techniques, with each masking method offering unique influence on resulting orogenic structures that can be applied to microfluidic and µTAS systems. Direct ink masking is further explored as a low-cost rapid prototyping tool for fabrication of simple microfluidic devices where channel formation and bonding are combined into a single step, resulting in fully enclosed microfluidic channels within 30 minutes. Chemical surface passivation by UV-ozone treatment is utilized in combination with orogenic swelling and thermocompression bonding to develop single-use burst valves with tunable burst pressures. In addition to assisting in on-chip fluid manipulation, the normally closed burst valves enable on-chip reagent packaging and hermetic sealing of bioactive material in lyophilized format, and can be used for delivery of stored reagents for a range of disposable point-of-care assays. On-chip integrated micropumps are also developed, using simple fabrication process compatible with conventional thermoplastic fabrication techniques such as direct micromilling or injection molding. Direct displacement of liquid reagents using screw-assisted pumping can be operated either automatically or manually, with on-demand delivery of liquid reagents in a wide range of flow rates typically used in microfluidic applications. Collectively, the technologies developed in this dissertation may be applied to the future development of simple, disposable, and portable diagnostic devices that have the potential to be operated without off-chip instrumentation. On-chip storage of buffers and reagents in either dry or liquid format, and on-demand delivery of liquid reagents is packaged in a miniaturized, portable, and automated platform that can be operated in resource-constrained settings by practitioners with minimal expertise.Item Bio-Inspired Polymer Microparticles for Targeted Recognition and Response(2014) Arya, Chandamany; Raghavan, Srinivasa R.; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Microbeads and microcapsules are container structures that are frequently used in biomedical applications. In this dissertation, we have sought to impart new functionalities to these particles, inspired by phenomena observed with biological cells. We have engineered polymer microparticles that recognize and respond to specific species from the surroundings (e.g. cells, polymer chains, metal ions). Three classes of new microparticles are reported, which are each reminiscent of a different type of biological cell in terms of recognition capabilities and response. In the first part of this dissertation, we create functionalized microbeads from the biopolymer, chitosan, and use these to selectively recognize and capture Circulating Tumor Cells (CTCs) from blood. The microbeads are functionalized with a protein (streptavidin) and packed into an array within a microfluidic device. Blood samples with biotin-labeled CTCs are flowed over the packed bed of chitosan beads. Similar to how macrophages adhere to foreign bacteria (i.e. antibody-antigen interactions), the streptavidin-labeled chitosan beads can selectively recognize and adhere to the biotin-labeled CTCs. We show that such a packed bed of chitosan beads could serve as an inexpensive platform for customized capture of different rare cells (cancer cells, stem cells etc) from blood. In the next study, we develop a class of microbeads that undergo clustering (aggregation) in the presence of specific polymers. The inspiration for this comes from the cells (e.g., platelets) and polymers involved during the formation of blood clots. Our system consists of chitosan microbeads coated with cyclodextrins (sugar molecules with a hydrophobic binding pocket), which are then exposed to a polymer that is decorated with hydrophobic units. The particles bind to the polymer chains via hydrophobic interactions and in turn, the particles are induced to form clusters. Subsequently, the polymer precipitates and forms a matrix around the particle clusters, leading to a structure that is reminiscent of a blood clot (platelets enveloped by a mesh of fibrin chains). Lastly, we develop a class of microparticles that have the ability to selectively destroy other microparticles. The inspiration here is from the body's immune system, where cells like the killer T cells selectively destroy cancer and virus infected cells without harming healthy cells. Towards this end, we synthesize two types of microparticles: chitosan capsules that contain the enzyme glucose oxidase (GOx), and beads of a different biopolymer, alginate that are crosslinked with copper (Cu2+) ions. The chitosan capsules enzymatically convert glucose from the surroundings into gluconate ions. When these capsules approach the alginate/copper beads, the gluconate ions chelate the copper ions, leading to the disintegration of the alginate beads. Other beads that do not contain Cu2+ are not affected in this process.Item Droplet Dynamics in Microfluidic Junctions(2012) Boruah, Navadeep; Dimitrakopoulos, Panagiotis; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The dynamics of droplets in confined microfluidic geometries is a problem of fundamental interest as such flow conditions occur in multiphase flows in porous media, biological systems, microfluidics and material science applications. In this thesis, we investigate computationally the dynamics of naturally buoyant droplets, with constant surface tension, in cross-junctions and T-junctions constructed from square microfluidic channels. A three-dimensional fully-implicit interfacial spectral boundary element method is employed to compute the interfacial dynamics of the droplets in the junctions and investigate the problem physics for a wide range of flow rates, viscosity ratios and droplet sizes. Our investigation reveals that as the flow rate or the droplet size increases, the droplets show a rich deformation behavior as they move inside the microfluidic devices. In the cross-junction, after obtaining a bullet-like shape before the flow intersection, the droplet become very slender inside the junction (to accommodate the intersecting flows), then it obtains an inverse-bullet shape as it exits the junction which reverts to a more pointed bullet-like shape far downstream. In the T-junction, the droplet obtains a skewed-bullet shape and a highly deformed slipper shape after entering the flows intersection. The viscosity ratio also has strong effects on the droplet deformation especially for high-viscosity droplets which do not have the time to accommodate the much slower deformation rate during their channel motion. Our results are in agreement with experimental findings, and provide physical insight on the confined droplet deformation.Item Motion of elastic capsules in microfluidic channels(2010) Kuriakose, Shugi; Dimitrakopoulos, Panagiotis; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Capsule flow dynamics in microchannels plays a significant role in complex biological phenomena, such as the microcirculation, and in engineering applications, such as in microfluidic devices for drug delivery and cell sorting. In this thesis, we investigate the motion of elastic capsules in wall-bounded flows by extending the Membrane Spectral Boundary Element method developed by Dodson and Dimitrakopoulos for free-suspended flows. First, a validation study of the method is performed for the axisymmetric capsule motion in a cylindrical channel. For a capsule moving along the centerline of a cylindrical channel, our computational model successfully reproduced the parachute shape observed in earlier experimental and computational studies. Next, we investigate the flow dynamics of a strain-hardening Skalak capsule moving along the centerline in a square and a rectangular channel. We examine how the capillary number and capsule size influence the deformation and physical properties of the capsule. For large capsules in a square channel, our investigation reveals that the steady-state capsule shape is non-axisymmetric. The capsule assumes a shape similar to the channel's cross-section i.e. a square shape with rounded edges. Buckling of the capsule's upstream end resulting in a negative edge curvature is observed at higher capillary numbers and for large capsule sizes. For the largest capsules studied, we also observe the development of dimples at the capsule's lateral surface. A comparative study of capsule motion and deformation in cylindrical and square channels shows that the capsule deformation in a cylindrical channel is similar to that in a square channel at a larger capillary number. In a rectangular channel, we observe a three-dimensional (i.e. non-axisymmetric) deformation of the capsule at high capillary numbers resulting in dimpling of the capsule's upstream end at steady state. We also consider the transient motion of a capsule in a converging square microchannel and investigate the influence of viscosity ratio, capillary number and capsule size on the evolution of capsule properties. As the capsule moves through the converging region a fluctuation in the geometric and physical properties of the capsule is observed.Item Using Feedback Control of Microflows to Independently Steer Multiple Particles(IEEE, 2006-08) Shapiro, Benjamin; Armani, Michael D.; Chaudhary, Satej; Probst, RolandIn this paper, we show how to combine microfluidics and feedback control to independently steer multiple particles with micrometer accuracy in two spatial dimensions. The particles are steered by creating a fluid flow that carries all the particles from where they are to where they should be at each time step. Our control loop comprises sensing, computation, and actuation to steer particles along user-input trajectories. Particle locations are identified in real-time by an optical system and transferred to a control algorithm that then determines the electrode voltages necessary to create a flow field to carry all the particles to their next desired locations. The process repeats at the next time instant. Our method achieves inexpensive steering of particles by using conventional electroosmotic actuation in microfluidic channels. This type of particle steering does not require optical traps and can noninvasively steer neutral or charged particles and objects that cannot be captured by laser tweezers. (Laser tweezers cannot steer reflective particles, or particles where the index of refraction is lower than (or for more sophisticated optical vortex holographic tweezers does not differ substantially from) that of the surrounding medium.)We show proof-of-concept PDMS devices, having four and eightelectrodes, with control algorithms that can steer one and three particles, respectively. In particular, we demonstrate experimentally that it is possible to use electroosmotic flow to accurately steer and trap multiple particles at once.