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Development and validation of a system for the generation, characterization and subsequent air- liquid interface studies of aerosol particles

Svensson, Christian LU (2016)
Abstract
Exposure to nano-sized and nanostructured aerosol particles with tailored properties are likely to increase in society. Occupational exposure to various kinds of nanostructured aerosol particles such as soot and metal aggregates already exists. To understand the adverse human health effects of these particles, there is a need for systems that can Generate a stable output of aerosol particles, Characterize their exposure and dose, and determine their toxicological and biological effects in an Air-liquid interface setting (GCA).

The research presented in this thesis developed and validated a GCA that combines a high output of aerosol particles, online characterization, collection capabilities for a scanning electron microscope... (More)
Exposure to nano-sized and nanostructured aerosol particles with tailored properties are likely to increase in society. Occupational exposure to various kinds of nanostructured aerosol particles such as soot and metal aggregates already exists. To understand the adverse human health effects of these particles, there is a need for systems that can Generate a stable output of aerosol particles, Characterize their exposure and dose, and determine their toxicological and biological effects in an Air-liquid interface setting (GCA).

The research presented in this thesis developed and validated a GCA that combines a high output of aerosol particles, online characterization, collection capabilities for a scanning electron microscope (SEM) and transmisson electron microscopy (TEM), as well as wet samples for protein interaction studies and particle toxicological effects.

The GCA is composed of an air-liquid interface cellular exposure chamber – the Nano Aerosol Chamber for In Vitro Toxicity (NACIVT) – and an electrostatic precipitator. It also includes a high output aerosol particle generator with built-in capabilities for sintering and online mass mobility characterization, a scanning mobility particle sizer, and a tapered element oscillating microbalance (TEOM) for continuous characteristics and exposure measurements.

The output characteristics of two spark discharge generators and a high temperature evaporation furnace were determined, including mass mobility relation. The results show that all three of these generators produced a stable output of nanostructured metal aerosol particles in the 30-300 nm size range; when sintered, these were near spherical in shape. In terms of dose, number, mass and surface area, the output was comparable to that of previous studies for all generators.

The GCA with respect to toxicological studies was validated using primary human small airway epithelial cells (SAEC) and carcinoma cell line (A549). Aerosol particles of copper (Cu), palladium (Pd) and silver (Ag) were generated and administerd in the NACIVT during 1 hour exposures. For SAEC exposed to Cu, Pd or Ag, a significant (p<0.05) effect on both viability and cytokine expression was oberserved. Also a significant (p<0.05) dose response for SAEC exposed to Cu, Pd and Ag could be determined. For the A549, Cu and Pd exposure induced a significant reduction in cellular viability.

The protein interactions of the near-spherical sintered and aggregted Au nanoparticles, that were generated using high temperature evaporation furnace, were investigated in serum and human lung fluid solutions. When administered to the air-liquid interface, the spherical Au particles formed a stable film with a pinkish hue; when agitated, <100 nm aggregates of particles and proteins were formed. This film formation is suggested as a protective property of the air-liquid interface itself. (Less)
Abstract (Swedish)
Popular Abstract in Swedish

Tänk dig ett system som kan bestämma hur olika typer av luftpartiklar skadar oss när dom hamnar i våra lungor. Ett system som dessutom kan skapa luftpartiklar för dessa studier vid behov och med väl uppmätta egenskaper. Denna avhandling handlar om just ett sådant system och experiment som är viktiga för att förstå om och hur det fungerar. Systemet kallas i denna avhandling GCA, från orden Generation, Characterization och Air-liquid interface.

Det har visat sig att människan kan ta stor skada av att inandas för många partiklar av så att säga fel slag. Man kan tänka sig olika typer av luftburna metallpartiklar, som bildas när man bearbetar metall, eller sotpartiklar från förbränning. Det... (More)
Popular Abstract in Swedish

Tänk dig ett system som kan bestämma hur olika typer av luftpartiklar skadar oss när dom hamnar i våra lungor. Ett system som dessutom kan skapa luftpartiklar för dessa studier vid behov och med väl uppmätta egenskaper. Denna avhandling handlar om just ett sådant system och experiment som är viktiga för att förstå om och hur det fungerar. Systemet kallas i denna avhandling GCA, från orden Generation, Characterization och Air-liquid interface.

Det har visat sig att människan kan ta stor skada av att inandas för många partiklar av så att säga fel slag. Man kan tänka sig olika typer av luftburna metallpartiklar, som bildas när man bearbetar metall, eller sotpartiklar från förbränning. Det uppfinns också hela tiden nya industriella processer och produkter, tänk bara på nanotekniken. Man kan säga att man vill föregå olyckan, vi vill inte bara vänta och se vilka partiklar som är farliga och inte.

GCA som avhandlingen handlar om, tillhör en forkskningstradition som fokuserar på att studera celler odlade utanför kroppen, så kallat in vitro forskning. Dessa cellkulturer av lungceller exponeras sedan för partiklar direkt från luften, precis som det sker i lungan. Denna typen av experiment kommer vara väldigt viktiga framgent då EU skärpt sina regler anngående djurförsök. Det är inte heller så populärt alltid att exponera människor direkt för något man misstänker är farligt.

GCA består av flera delar, förutom kammaren där cellerna blir exponerade för partiklar har det förmågan att bestämma partiklarnas storlek, massa, ytarea och antalskoncentration. Allt detta görs för att få en så klar bild som möjligt om vilken egenskap som partiklarna har som egentligen är farlig.

Resultat från GCA visar att det ger utslag när celler blir exponerade för koppar, silver eller palladium partiklar som från luftburet tillstånd landar på cellerna. Resultaten visar att man i vissa fall kan se att effekten på cellerna blir större med en ökad exponering. Avhandlingen beskriver också resultat från ett experiment som kan komma att vara väldigt viktigt för denna typ av framtida forskning. Experimentet visar att när vissa partiklar landar på en vätskeyta stannar dom där. Detta kan betyda att gränsskiktet mellan luft och vätska har vissa beskyddande egenskaper för underliggande celler. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Prof Schmid, Otmar, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH)
organization
publishing date
type
Thesis
publication status
published
subject
keywords
nanoparticles, aggregates, aerosol, protein interactions, toxicology, dose, air liquid interface
defense location
Lecture hall Stora Hörsalen, IKDC, Sölvegatan 26, Lund University, Faculty of Engineering, LTH.
defense date
2016-02-12 10:15:00
language
English
LU publication?
yes
id
9934b507-5625-4ac2-bb87-571673d4a1dd (old id 8520402)
date added to LUP
2016-04-04 09:06:12
date last changed
2018-11-21 23:43:57
@phdthesis{9934b507-5625-4ac2-bb87-571673d4a1dd,
  abstract     = {{Exposure to nano-sized and nanostructured aerosol particles with tailored properties are likely to increase in society. Occupational exposure to various kinds of nanostructured aerosol particles such as soot and metal aggregates already exists. To understand the adverse human health effects of these particles, there is a need for systems that can Generate a stable output of aerosol particles, Characterize their exposure and dose, and determine their toxicological and biological effects in an Air-liquid interface setting (GCA). <br/><br>
The research presented in this thesis developed and validated a GCA that combines a high output of aerosol particles, online characterization, collection capabilities for a scanning electron microscope (SEM) and transmisson electron microscopy (TEM), as well as wet samples for protein interaction studies and particle toxicological effects. <br/><br>
The GCA is composed of an air-liquid interface cellular exposure chamber – the Nano Aerosol Chamber for In Vitro Toxicity (NACIVT) – and an electrostatic precipitator. It also includes a high output aerosol particle generator with built-in capabilities for sintering and online mass mobility characterization, a scanning mobility particle sizer, and a tapered element oscillating microbalance (TEOM) for continuous characteristics and exposure measurements. <br/><br>
The output characteristics of two spark discharge generators and a high temperature evaporation furnace were determined, including mass mobility relation. The results show that all three of these generators produced a stable output of nanostructured metal aerosol particles in the 30-300 nm size range; when sintered, these were near spherical in shape. In terms of dose, number, mass and surface area, the output was comparable to that of previous studies for all generators. <br/><br>
The GCA with respect to toxicological studies was validated using primary human small airway epithelial cells (SAEC) and carcinoma cell line (A549). Aerosol particles of copper (Cu), palladium (Pd) and silver (Ag) were generated and administerd in the NACIVT during 1 hour exposures. For SAEC exposed to Cu, Pd or Ag, a significant (p&lt;0.05) effect on both viability and cytokine expression was oberserved. Also a significant (p&lt;0.05) dose response for SAEC exposed to Cu, Pd and Ag could be determined. For the A549, Cu and Pd exposure induced a significant reduction in cellular viability. <br/><br>
The protein interactions of the near-spherical sintered and aggregted Au nanoparticles, that were generated using high temperature evaporation furnace, were investigated in serum and human lung fluid solutions. When administered to the air-liquid interface, the spherical Au particles formed a stable film with a pinkish hue; when agitated, &lt;100 nm aggregates of particles and proteins were formed. This film formation is suggested as a protective property of the air-liquid interface itself.}},
  author       = {{Svensson, Christian}},
  keywords     = {{nanoparticles; aggregates; aerosol; protein interactions; toxicology; dose; air liquid interface}},
  language     = {{eng}},
  school       = {{Lund University}},
  title        = {{Development and validation of a system for the generation, characterization and subsequent air- liquid interface studies of aerosol particles}},
  url          = {{https://lup.lub.lu.se/search/files/5232349/8520417.pdf}},
  year         = {{2016}},
}