NOx delivery systems for biological media

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2012.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (p. 345-363).Elevated levels of nitric oxide (NO) in vivo are associated with a variety of cellular modifications thought to be mutagenic or carcinogenic. These processes are likely mediated by reactive nitrogen species (RNS) such as nitrogen dioxide (NO2) and peroxynitrite formed from the respective reactions of NO with oxygen and superoxide anion. Controlled delivery of these RNS at levels expected to occur in vivo is desirable in studying these processes and their role in the etiology of various diseases. Two delivery systems were developed that provide novel capabilities for steady, quantitative exposure of biological targets to RNS over periods from hours to days. Quantitative models are presented that accurately describe the behavior of both systems. The first system achieves NO concentrations of 0.6-3.0 [mu]M in a stirred, liquid-filled vessel by diffusion from a gas stream through a porous poly(tetrafluoroethylene) membrane. Oxygen, consumed by reaction with NO or by other processes, is supplied by diffusion from a separate gas stream through a loop of poly(dimethylsiloxane) tubing. The adventitious chemistry observed in a prior device for NO delivery [Wang C. Ann Biomed Eng (2003) 31:65-79] is eliminated in the present design, as evidenced by the close match to model predictions of the accumulation rate of nitrite, the stable end product of NO oxidation. The second system delivers NO2 by direct contacting of a stirred liquid with an NO2- containing gas mixture. Accumulation rates of products in the presence and absence of the NO2-reactive substrate 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) matched model predictions within 15% for all conditions studied. The predicted steady NO2 concentration in the liquid is on the order of 400 pM, similar to what is expected to be present in extracellular fluids in the presence of 1 [mu]M NO. This system appears to be the first reported with the capability for sustained, quantitative NO2 delivery to suspended cell cultures. Results from initial efforts to test a novel mixing model for bolus delivery of peroxynitrite to agitated solutions imply that the proposed model might accurately describe mixing in bolus delivery experiments with agitation by vortex mixing, but further work is required to validate the model.by Brian Thomas Skinn.Ph.D

(ECS 233rd) Multiphysics Modeling of Surface Finishing Performance in Pulsed-Waveform Electrochemical Machining

Electrochemical machining (ECM) is a manufacturing technology that allows metal to be precisely removed by electrochemical oxidation and dissolution into an electrolyte solution. ECM is suited for machining parts fabricated from “difficult to cut” materials and/or parts with complicated and intricate geometries. In ECM, the workpiece is the anode and the tool is the cathode in an electrochemical cell; by relative movement of the shaped tool into the workpiece, the mirror image of the tool is “copied” or machined into the workpiece. One notable difficulty with ECM is an inability to predict a priori the tool and process parameters required in order to satisfy the final specifications of the fabricated part [[1]]. Accordingly, there is potential value in development of a physical phenomenon-based design platform to predict optimal ECM tool shape. Such a capability is anticipated to dramatically shorten the process/tooling development cycle. A further goal of ECM is to simultaneously achieve a target surface finish on the machined part. It is thus of interest to develop the capability also to predict the distribution of local surface finish resulting from ECM processing. Modeling of the changes in local surface finish intrinsically operates on a different length scale from that of bulk material removal (μm, versus mm or cm), and thus is most easily treated separately. The physicochemical phenomena involved in the evolution of surface finish during ECM processing are strongly coupled, and include the electric field itself (primary current distribution), surface polarization and electrochemical kinetics (secondary current distribution), and fluid flow and mass transfer (tertiary current distribution). Of particular interest is modeling of pulsed-waveform ECM, for which significant practical advantages have been demonstrated [[2],[3],[4]]. While an extensive body of literature exists analyzing pulsed electrodeposition [[5],[6],[7]], comparatively little work has been published to date on pulsed ECM [[8],[9]]. This talk will discuss recent modeling work seeking to develop a solid foundation for a predictive understanding of the surface finishing aspects of ECM processes. The work described herein encompasses time-dependent modeling of one-dimensional concentration profiles under the application of pulsed current ECM waveforms, providing a foundation for future development of quantitative descriptions of the transient and steady-periodic behavior on structured substrates. Prior work (see, e.g., Ref. 3) has demonstrated the value in differential pulsed-ECM processing of surfaces with features of size comparable to or larger than the hydrodynamic boundary layer thickness (“macroprofiles”) versus surfaces with features much smaller than the boundary layer thickness (“microprofiles”). Methods are discussed for accurate estimation of a quantity termed the “transition time,” which is the value for the pulse on-time for which the metal concentration at the surface rises exactly to saturation at the end of the forward pulse. Extending the pulse duration beyond this value thus introduces mass transfer limitations to the electrochemistry occurring at the surface. References [1]. Rajurkar, K.P. et al. Annals of the CIRP 82(2), 1999. [2]. Taylor, E.J. et al. “Breaking the Chemical Paradigm in Electrochemical Engineering: Case Studies and Lessons Learned from Plating to Polishing,” in Advances in Electrochemical Science & Engineering: The Path from Discovery to Product, x, y Eds. In press. [3]. Taylor, E.J. and M. Inman. “Electrochemical Surface Finishing.” ECS Interface, Fall 2014: 57-61. [4]. Taylor, E.J. et al. U.S. Patent 9,006,147, 14 Apr 2015. [5]. Puippe, J.C. and F. Leaman, eds. “Theory and Practice of Pulse Plating.” Orlando, FL: AESF, 1986. [6]. Hansel, W.E.G. and S. Roy. “Pulse Plating.” Bad Saulgau, Germany: Leuze Verlag KG, 2012. [7]. Ibl, N. “Some Theoretical Aspects of Pulse Electrolysis.” Surface Technology 10: 81 (1980). [8]. Sautebin, R. et al. J Electrochem Soc 127(5): 1096, 1980. [9]. Sautebin, R. and D. Landolt. J Electrochem Soc 129(5): 946, 1982