Enzyme-Powered Pumps : From Fundamentals to Applications
- Author:
- Ortiz-Rivera, Isamar
- Published:
- [University Park, Pennsylvania] : Pennsylvania State University, 2017.
- Physical Description:
- 1 electronic document
- Additional Creators:
- Sen, Ayusman, 1951-
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- etda.libraries.psu.edu , Connect to this object online.
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- Restrictions on Access:
- Open Access.
- Summary:
- Non-mechanical nano and microfluidic devices that function without the aid of an external power source, and can be tailored to meet specific needs, represent the next generation of smart devices. Recently, we have shown that surface-bound enzymes can act as pumps driving large-scale fluid flows in the presence of any substance that triggers the enzymatic reaction (e.g. substrate, co-factor, or biomarker). The fluid velocities attained in such systems depend directly on the enzymatic reaction rate and the concentration of the substance that initiates enzymatic catalysis. The use of biochemical reactions to power a micropump offers the advantages of specificity, sensitivity, and selectively, eliminating at the same time the need of an external power source, while providing biocompatibility. More importantly, these self-powered pumps overcome a significant obstacle in nano- and micro-fluidics: the need to use external pressure-driven pumps to push fluids through devices. Certainly, the development of enzyme-powered devices opens up new venues in biochemical engineering, particularly in the biomedical field. However, in order to take this concept to the next level, and design more precise, complex and efficient devices, a complete understanding of the fundamental principles for actuation and the factors that exert an effect in the output of the micropump, as well as an experimental assessment of some of their potential applications, is necessary. The work highlighted in this dissertation covers all the studies performed with enzyme-powered pumps, from the development of the micropump design, to the efforts invested in understanding the enzyme pump concept as a whole. The data collected to date, aims to expand our knowledge about enzyme-powered micropumps from the inside out: not only by exploring the different applications of these devices at the macroscale, but also by investigating in depth the mechanism of pump activation behind these systems. Specifically, we have focused on: (1) The general features that characterize the pumping behavior observed in enzyme-powered pumps, as well as the optimization of the device, (2) the possible mechanisms behind fluid motion, including the role of enzyme coverage and/or activity on the transduction of chemical energy into mechanical fluid flow in these devices, covering also the effect of the thermodynamics of the enzymatic reaction in the pumping behavior, and (3) the applicability of enzyme pumps as fluid flow-based inhibitor assays and as drug delivery devices. Our findings in each of these areas, gets us closer to our ultimate goal, where we aim to identify the optimal conditions needed for enzyme micropump operation, and construct a general model that could accurately predict enzyme micropump behavior for any enzyme-substrate combination.The information aforementioned has been divided in four chapters. Chapter 1 gives a quick glance into the development of enzyme-powered micropumps: from the systems and observed behaviors inspiring this work, to the first systems that were developed. The stability, duration, and extent of fluid pumping of enzyme pumps in general, are also discussed, along with the optimization of the enzyme-pump design. This chapter aims to provide a general idea of the motivation behind the concept of enzyme-powered pumps, what are enzyme-powered pumps, and which are the key features that characterize these systems. Chapter 2 is an extensive analysis of the mechanisms of actuation proposed for enzyme-powered micropumps. This chapter not only covers the first attempts to understand how enzyme pumps work, but also explores further the behavior of urease-powered pumps, which fluid flow patterns cannot be completely predicted only by considering thermal or solutal gradients. The findings of these studies could allow us to rationally control fluid flow for the directed delivery of payloads at designated locations. In Chapters 3 and 4, our focus was to highlight the potential application of enzyme-powered pumps for sensing and delivery. Chapter 3 explores the use of enzyme pumps as fluid flow-based inhibitor assays. At fixed concentrations of an enzyme and its substrate, the presence of an inhibitor can be detected by monitoring the decrease in fluid flow speed. Using this principle, sensors for toxic substances, like mercury, cyanide and azide, were designed using urease and catalase-powered pumps, respectively, with limits of detection well below the concentrations permitted by the Environmental Protection Agency (EPA). Chapter 4 demonstrates that, apart from their applicability as sensors, enzyme pumps can also be used for stimuli-responsive release, if the architecture applied for the design of the enzyme pump consists of a porous scaffold (e.g. hydrogel), that serves both as the platform for enzyme immobilization and as the host for guest molecules to be released. These proof-of-concept devices were developed with the idea of using the flows generated by enzymatic catalysis to power cargo release, only in the presence of the correct stimuli (e.g. release of insulin in the presence of glucose; release of antidotes in the presence of a toxic agent). In the cases studied, cargo release was directly proportional to the concentration of enzyme substrate in solution, highlighting the sensitivity of the device and its potential for drug delivery purposes.
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- Dissertation Note:
- Ph.D. Pennsylvania State University 2017.
- Reproduction Note:
- Microfilm (positive). 1 reel ; 35 mm. (University Microfilms 106-29106)
- Technical Details:
- The full text of the dissertation is available as an Adobe Acrobat .pdf file ; Adobe Acrobat Reader required to view the file.
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