Development of biodegradable microfluidic networks for tissue engineering

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2002.Includes bibliographical references.Biodegradable tissue engineering scaffolds currently suffer from poorly controlled geometries, lack of reproducibility, and severe mass transport limitations. Microfabrication is an ideal tool for attacking problems in tissue engineering due to its control of diverse size scales, from microns to centimeters, all with micron resolution and submicron precision. By enabling precision geometries and flexible designs, microfabrication has the potential to offer creative solutions to some of the major problems facing the field of tissue engineering; those of achieving rapid vascularization and recapitulating normal complex tissue microarchitecture. In this thesis, silicon micromachining, soft lithography, and traditional polymer processing are combined to develop a fully biodegradable microfabrication platform using poly(DL-lactic-co-glycolic) acid (PLGA 85:15). First, micron scale structures fabricated on silicon substrates are transferred into the surface of biodegradable films using polymer melt replica molding. Next, microchannel networks are sealed and made three-dimensional by stacking and irreversibly bonding the biodegradable films using a newly developed thermal fusion bonding process. The process is modeled and optimized to guide bonding of a wide range of microchannels while avoiding parasitic microstructure deformation. An extruded inlet/outlet scheme is implemented and combined with micromolding and fusion bonding to build fully patent, leak-free biodegradable microfluidic networks with predictable fluidic resistances. Finally, this thesis concludes with the first demonstration of long-term continuous-flow cell culture in prototype microfluidic networks, demonstrating the feasibility of using the newly developed biodegradable microdevices as cell-seeded tissue engineering scaffolds. In comparison to conventional scaffold fabrication techniques, these processes offer two orders of magnitude improvement in fabrication time and spatial resolution while offering flexible designs and unmatched reproducibility. Through these features, they have enabled construction of the first fully biodegradable microfluidic networks.by Kevin R. King.S.M

Effects of cochlear implantation on binaural hearing in adults with unilateral hearing loss

A FDA clinical trial was carried out to evaluate the potential benefit of cochlear implant (CI) use for adults with unilateral moderate-to-profound sensorineural hearing loss. Subjects were 20 adults with moderate-to-profound unilateral sensorineural hearing loss and normal or near-normal hearing on the other side. A MED-EL standard electrode was implanted in the impaired ear. Outcome measures included: (a) sound localization on the horizontal plane (11 positions, −90° to 90°), (b) word recognition in quiet with the CI alone, and (c) masked sentence recognition with the target at 0° and the masker at −90°, 0°, or 90°. This battery was completed preoperatively and at 1, 3, 6, 9, and 12 months after CI activation. Normative data were also collected for 20 age-matched control subjects with normal or near-normal hearing bilaterally. The CI improved localization accuracy and reduced side bias. Word recognition with the CI alone was similar to performance of traditional CI recipients. The CI improved masked sentence recognition when the masker was presented from the front or from the side of normal or near-normal hearing. The binaural benefits observed with the CI increased between the 1- and 3-month intervals but appeared stable thereafter. In contrast to previous reports on localization and speech perception in patients with unilateral sensorineural hearing loss, CI benefits were consistently observed across individual subjects, and performance was at asymptote by the 3-month test interval. Cochlear implant settings, consistent CI use, and short duration of deafness could play a role in this result

Asymptotic safety of quantum gravity beyond Ricci scalars

We investigate the asymptotic safety conjecture for quantum gravity including curvature invariants beyond Ricci scalars. Our strategy is put to work for families of gravitational actions which depend on functions of the Ricci scalar, the Ricci tensor, and products thereof. Combining functional renormalization with high order polynomial approximations and full numerical integration we derive the renormalization group flow for all couplings and analyse their fixed points, scaling exponents, and the fixed point effective action as a function of the background Ricci curvature. The theory is characterized by three relevant couplings. Higher-dimensional couplings show near-Gaussian scaling with increasing canonical mass dimension. We find that Ricci tensor invariants stabilize the UV fixed point and lead to a rapid convergence of polynomial approximations. We apply our results to models for cosmology and establish that the gravitational fixed point admits inflationary solutions. We also compare findings with those from fðRÞ-type theories in the same approximation and pin-point the key new effects due to Ricci tensor interactions. Implications for the asymptotic safety conjecture of gravity are indicated

Decoding Neural Activity to Assess Individual Latent State in Ecologically Valid Contexts

There exist very few ways to isolate cognitive processes, historically defined via highly controlled laboratory studies, in more ecologically valid contexts. Specifically, it remains unclear as to what extent patterns of neural activity observed under such constraints actually manifest outside the laboratory in a manner that can be used to make an accurate inference about the latent state, associated cognitive process, or proximal behavior of the individual. Improving our understanding of when and how specific patterns of neural activity manifest in ecologically valid scenarios would provide validation for laboratory-based approaches that study similar neural phenomena in isolation and meaningful insight into the latent states that occur during complex tasks. We argue that domain generalization methods from the brain-computer interface community have the potential to address this challenge. We previously used such an approach to decode phasic neural responses associated with visual target discrimination. Here, we extend that work to more tonic phenomena such as internal latent states. We use data from two highly controlled laboratory paradigms to train two separate domain-generalized models. We apply the trained models to an ecologically valid paradigm in which participants performed multiple, concurrent driving-related tasks. Using the pretrained models, we derive estimates of the underlying latent state and associated patterns of neural activity. Importantly, as the patterns of neural activity change along the axis defined by the original training data, we find changes in behavior and task performance consistent with the observations from the original, laboratory paradigms. We argue that these results lend ecological validity to those experimental designs and provide a methodology for understanding the relationship between observed neural activity and behavior during complex tasks

Assessing Intra-Event Phosphorus Dynamics in Drainage Water Using Phosphate Stable Oxygen Isotopes

Quantifying fluxes and pathways of dissolved reactive phosphorus (DRP) in tile-drained landscapes has been hampered by a lack of measurements that are sensitive to P fate and transport processes. One potential tool to help understand these dynamics is the oxygen isotope signature of phosphate (δ18OPO4); however, its potential benefits and limitations are not well understood for intra-event dynamics at the field scale. The objectives of this study were to quantify intra-event variability of δ18OPO4 signatures in tile drainage water and assess the efficacy of δ18OPO4 to elucidate mechanisms and flow pathways controlling DRP transport to tile drains. We collected water samples during a summer storm event from a subsurface (tile)-drained field located in west-central Ohio and analyzed for δ18OPO4 of DRP. Supplementary water quality measurements, hydrologic modeling, and soil temperature data were used to help understand intra-event δ18OPO4 dynamics. Results of the soil extraction analysis from our study site highlight that the soil water-extractable P (WEP) pool was not in equilibrium with long-term, temperature-dependent water isotope values. This result suggests that P-rich soils may, at least partially, retain their original source signature, which has significant implications for identifying hotspots of P delivery in watershed-scale applications. Results of the storm event analysis highlight that equilibration of leached DRP in soil water creates a gradient between isotopic compositions of pre-event shallow subsurface sources, pre-event deep subsurface sources, and the WEP tied up in surface soils. The current study represents the first intra-event analysis of δ18OPO4 and highlights the potential for phosphate oxygen isotopes as a novel tool to improve understanding of P fate and transport in artificially drained agroecosystems