Thomas Liu

Efficient Norovirus and Reovirus Replication in the Mouse Intestine Requires Microfold (M) Cells

ABSTRACT Microfold (M) cells are specialized intestinal epithelial cells that internalize particulate antigens and aid in the establishment of immune responses to enteric pathogens. M cells have also been suggested as a portal for pathogen entry into the host. While virus particles have been observed in M cells, it is not known whether viruses use M cells to initiate a productive infection. Noroviruses (NoVs) are single-stranded RNA viruses that infect host organisms via the fecal-oral route. Murine NoV (MNV) infects intestinal macrophages and dendritic cells and provides a tractable experimental system for understanding how an enteric virus overcomes the intestinal epithelial barrier to infect underlying target cells. We found that replication of two divergent MNV strains was reduced in mice depleted of M cells. Reoviruses are double-stranded RNA viruses that infect hosts via respiratory or enteric routes. In contrast to MNV, reovirus infects enterocytes in the intestine. Despite differences in cell tropism, reovirus infection was also reduced in M cell-depleted mice. These data demonstrate that M cells are required for the pathogenesis of two unrelated enteric viruses that replicate in different cell types within the intestine. IMPORTANCE To successfully infect their hosts, pathogens that infect via the gastrointestinal tract must overcome the multilayered system of host defenses. Microfold (M) cells are specialized intestinal epithelial cells that internalize particulate antigens and aid in the establishment of immune responses to enteric pathogens. Virus particles have been observed within M cells. However, it is not known whether viruses use M cells to initiate a productive infection. To address this question, we use MNV and reovirus, two enteric viruses that replicate in different cell types in the intestine, intestinal epithelial cells for reovirus and intestinal mononuclear phagocytes for MNV. Interestingly, MNV- and reovirus-infected mice depleted of M cells showed reduced viral loads in the intestine. Thus, our work demonstrates the importance of M cells in the pathogenesis of enteric viruses irrespective of the target cell type in which the virus replicates.

Nanoparticle Electric Propulsion for Space Exploration

A new electrostatic thruster technology is under development at the University of Michigan using nanoparticles as propellant with micro‐ and nano‐electromechanical systems. Termed the nanoparticle field extraction thruster (nanoFET), this highly integrated propulsion concept is a high efficiency, variable specific impulse engine type that can be readily scalable for a large range of future space science and exploration missions.

Extending hollow cathode life for electric propulsion in long-term missions

This paper will present our understanding of the hollow cathode barium depletion mechanism and the design required to achieve the required life.

Nanoparticle Electric Propulsion: Experimental Results

This paper presents experimental results concerning the nanoparticle Field Extraction Thruster (nanoFET) concept under development at the University of Michigan. The nanoFET concept offers an electric propulsion approach that can have a highly adjustable charge-to-mass ratio and electrostatic acceleration that potentially could span a specific impulse range from ~100 s to ~10,000 s and thrust power ranging from microwatts to many tens of kilowatts at high efficiency. Here, we report on experiments addressing particle charging, particle transport through an insulating liquid, particle extraction from a liquid, and Taylor cone formation. In addition, it has been shown that particles can be extracted from liquid using electric fields without the formation of Taylor cones or colloidal droplets. These experimental results have validated our initial theoretical models building confidence in the fundamental feasibility of the nanoFET concept.

Theoretical aspects of nanoparticle electric propulsion

The nanoparticle field extraction thruster (nanoFET), using charged nanoparticles to generate propulsive thrust, is currently under development at the University of Michigan. This paper discusses the theoretical aspects of nanoFET operation, including particle charging, transport, and extraction from the liquid reservoir. Considerations regarding the liquid, such as Taylor cone formation and colloid generation as well as space charge limits associated with a viscous medium, are also discussed. The paper concludes with a discussion of the relationship between particle scaling and thruster performance.

MEMS Gate Structures for Electric Propulsion Applications

Abstract : A MEMS gate prototype is under development to extract and accelerate charged particles for use with field emission cathodes and the nanoparticle field extraction thruster at the University of Michigan. Preliminary simulations suggest the desirability of a unity aspect ratio in the emission channel design to achieve electric field uniformity. Low emission threshold cubic boron nitride films have been grown, and gated testing with these films along with carbon nanotubes is in progress.

Electric propulsion of a different class: The challenges of testing for megawatt missions

Currently, there is great interest in the development of high-power electric propulsion (EP) devices that can be employed in missions requiring >100 kW levels of propulsive power. Of the candidates for such thrusters, the Nested-channel Hall thruster (NHT) has been shown to be particularly scalable to this mission requirement. To this end, the University of Michigan’s Plasmadynamics and Electric Propulsion Laboratory (PEPL), in conjunction with both the Air Force Research Laboratory (AFRL) and NASA, has developed a 100-kW-class NHT called the X3. While bringing the X3 to test-ready status, a number of developmental and facility-related challenges were encountered and overcome. This paper presents these challenges and the lessons learned associated with the X3’s design, fabrication, and testing as a case study to inform other high-power EP development efforts.

Developmental Progress of the Nanoparticle Field Extraction Thruster

The Nanoparticle Field Extraction Thruster (NanoFET) is an electrostatic accelerator technology currently under development at the University of Michigan to accelerate micro-/ nano-particles. The concept exists in two configurations: the liquid configuration stores and transports particulate propellant using microfluidics while the dry configuration eliminates the liquid feed system in favor of particle transport via piezoelectric actuators. Microgravity flight tests of the liquid-NanoFET concept indicate good agreement with theory regarding the threshold electric field for liquid surface instabilities. This threshold electric field was observed to increase in low Bond number systems as the channel diameter decreased and appeared to be governed by the largest characteristic channel orifice dimension. Particle liftoff and extraction from both liquidand air-filled reservoirs were also demonstrated in the microgravity environment. On the ground, preliminary experiments showed that particle liftoff electric fields could be reduced with the application of inertial accelerations from piezoelectrics to the charging electrode. Both the recent microgravity and ground test results for the NanoFET concept are presented.

Nanoparticle Field Extraction Thruster (nanoFET): Introduction to, Analysis of, and Experimental Results from the "No-liquid" Configuration

This paper introduces a nanoparticle field extraction thruster (nanoFET) concept that does not depend on the liquid delivery of micro and nano-particles for extraction and acceleration. The no-liquid approach potentially provides important advantages such as allowing the use of smaller particles for propellant, which may offer a greater specific impulse. The most likely developmental obstacles are the adhesion of the particles to the source electrode and the cohesion between the particles. Adhesion and cohesion models are presented along with proposed methods of overcoming each. A method of using the applied charging electric field to overcome the adhesion force is investigated, which predicts that it may be possible to remove particles with diameters down to hundreds or even tens of nanometers from a planar electrode with only the application of a high strength electric field. To investigate this particle removal model, eight test cases, involving 4 particle sizes and 2 electrode materials, are presented. A method of transporting the dry particle propellant through an ultra-fine sieve prior to the charging and accelerating stages is investigated as a method of overcoming the cohesion between the particles. A simple proof-of-concept experiment is presented which indicates that this method is capable of breaking the cohesion force under appropriate conditions, which helps to guide future research.

Reduced Gravity Testing of the Nanoparticle Field Extraction Thruster

he C-9 NanoBLUE team is a group of students within the University of Michigan’s Student Space Systems Fabrication Laboratory (S3FL) seeking hands-on undergraduate research experience. The focus of the project is the reduced gravity (microgravity) test and validation of the concept for the Nanoparticle Field Extraction Thruster (NanoFET), an electric propulsion system being developed at the University of Michigan. These microgravity tests were done as part of the NASA Reduced Gravity Student Flight Opportunities Program at NASA Johnson Space Center. Over the course of the 2007-2008 time period, the team followed S3FL’s educational methods and built upon the design and results of the previous year’s C-9 NanoBLUE team to provide useful flight data. The Student Space Systems Fabrication Laboratory is a student-run laboratory where members learn from and teach each other along with faculty and industry support. The overall goal of this organization is to provide undergraduate students the opportunity to gain hands-on research and engineering experience through real-world projects related to space systems. This goal is accomplished via the design-build-test-fly philosophy employed by each team. Each project consists of team members who take part in the application, team leads who direct tasks and coordinate the overall project, and Executive Committee members who oversee progress and assess results produced by the team. Each of these positions consists only of students within the organization. Newer members start off as team members on a project where they can work their way up to lead and mentorship positions once they demonstrate the requisite technical and leadership skills. From a lead position, a member can eventually move up to the Executive Committee where he/she can assist various teams and direct activities throughout the lab. With this structure, students who participate are able to gain valuable experience in different aspects of the aerospace industry. 1