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An electrostatic sampling device for point-of-care detection of bioaerosols
KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.ORCID iD: 0000-0001-6915-257X
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Bioaerosols are not only a significant factor of air quality but contribute greatly to the spread of infectious diseases, specifically through expired pathogen-laden aerosols. Clear examples of airborne transmission include: the recent influenza pandemic of 2009, the ongoing tuberculosis epidemic, and yearly norovirus out- breaks, which affect millions of people worldwide and pose serious threats to public healthcare systems. Given these acute concerns and the critical lack of knowledge of the field, it is important to develop methods for sampling and detecting these air- borne pathogens. Specifically, detection at the point-of-care can play an important role in improving the outcome of patient care by providing rapid and convenient diagnostics.

Electrostatic precipitation has emerged as a promising sampling tool for bio- aerosols, which together with a rapid analysis technique, can provide a powerful and integrated approach to pathogen detection or disease diagnosis at the point- of-care. Moreover, such a sampling-detection scheme could be a potentialy non- invasive breath sampling tool for diagnosis of respiratory infectious diseases.

This thesis presents a sampling device based on electrostatic precipitation, for capture of bioaerosols, and designed for use at point-of-care settings. A multi-point- to-plane electrode configuration allows charging of aerosol particles and direct air- to-liquid capture within a miniaturized volume with potentential for concatenation with on-site detection methods. Performance of the device was evaluated, using non-biological aerosols, for geometric (inter-electrode distance), electrical (inter- electrode potential and corona current), and aerosol parameters (particle size and gas velocity). Moreover, four different collector designs were investigated for im- proved collection efficiency and other features suitable for point-of-care settings (e.g. easy sample extraction and minimized volume).

The device was then validated, using bioaerosols, both in vitro and in vivo. In vitro validation was performed by capturing aerosolized influenza virus and analyz- ing the device collection efficiency. Lastly, prototype devices, designed for point- of-care, were validated in vivo with patients at the clinical setting. A pilot study was performed to capture exhaled pathogens from infected patients, with success- ful capture of exhaled bacteria.

Abstract [sv]

Bioaerosoler är inte enbart en signifikant faktor för luftkvalitet utan bidrar även mycket till spridningen av infektionssjukdomar, särskilt genom utandning av pato- genbelastade aerosoler. Tydliga exempel på luftburen överföring inkluderar: den se- naste influensapandemin under 2009, den pågående tuberkulosepidemin, och det årliga norovirusutbrott som påverkar miljontals människor världen över och utgör alvarliga hot mot folkhälsovårdssystemen. Med tanke på dessa akuta problem och den kritiska bristen på kunskap inom området är det viktigt att utveckla metoder för provtagning och detektering av dessa luftburna patogener. Specifikt kan detek- tion vid vårdpunkten spela en viktig roll för att förbättra resultatet as patientvården genom att tillhandahålla snabb och lämplig diagnostik.

Elektrostatisk utfällning har framkommit som ett lovande provtakningsverktyg för bioareosoler och kan, tillsammans med en snabb analys teknik, ge ett kraftfullt och integrerat tillvägagångsätt för detektering av patogener eller diagnos av sjuk- domar direkt vid vårdpunkten. Dessutom skulle ett sådant provtagning-detektions system kunna vara ett potentiellt icke-invasivt andprovtagningsverktyg för att dia- gnostisera infektionssjukdomar i andningsorganen.

Denna avhandling presenterar en elektrostatisk utfällningsenhet (ESP) för prov- tagning av bioaerosoler. Enheten är konstruerade för användning direkt på vård- platsen, har funktionen att fånga luft i vätska samt potential för sammanlänkning med platsens diagnosmetoder. En konfiguration med flera punkter-till-plan elektro- der möjliggör för laddning och avlägsnande av aerosolpartiklar för infångning i en vätskevolym på några hundra mikroliter. Infångning direkt i vätska ger inte enbart ett stabilt uppsamlings-, lagrings-, och transportmedium för patogener; det är även idealt för de flesta biologiska analyser, och den minimerade uppsamlingsvolymen resulterar i minimerade utspädningsfaktorer.

Utvecklingen av enheten beskrivs i den första delen, där icke-biologiska för- söksaerosoler används för att studera effekten av geometriska-, elektriska-, och ae- rosolparametrar på prestandan. Därutöver undersöks och optimeras utformningen av vätskekollektorn för elektrostatiskinfångning och hantering.

Validering av enheten, både in vitro och in vivo, beskrivs i den andra delen av av- handlingen och inkluderar användning biologiska aerosoler. Specifikt används ae- rosoliserad influensa för att genomföra en in vitro validering av ESP enheten, vars prestanda utvärderas för odlade och kliniska stammar. Slutligen utförs en validering in vivo vid vårdpunkten genom att använda ESP-enheten för att fånga patogener från utandningsluft.

Place, publisher, year, edition, pages
KTH Royal Institute of Technology, 2018. , p. 45
Series
TRITA-EECS-AVL ; 2018:32
Keywords [en]
electrostatic sampling; bioaerosols; point-of-care; breath sampling; electrostatic precipitation; microfluidic collection; corona discharge; air sampling; non-invasive diagnostics; exhaled breath analysis; on-site detection; aerosol sampling
National Category
Electrical Engineering, Electronic Engineering, Information Engineering Diagnostic Biotechnology
Research subject
Electrical Engineering
Identifiers
URN: urn:nbn:se:kth:diva-226955ISBN: 978-91-7729-748-2 (print)OAI: oai:DiVA.org:kth-226955DiVA, id: diva2:1202682
Public defence
2018-05-29, D3, Lindstedsvägen 5, Stockholm, 13:30 (English)
Opponent
Supervisors
Note

QC 20180502

Available from: 2018-05-02 Created: 2018-04-29 Last updated: 2018-05-02Bibliographically approved
List of papers
1. Aerosol sampling using an electrostatic precipitator integrated with a microfluidic interface
Open this publication in new window or tab >>Aerosol sampling using an electrostatic precipitator integrated with a microfluidic interface
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2015 (English)In: Sensors and actuators. B, Chemical, ISSN 0925-4005, E-ISSN 1873-3077, Vol. 212, p. 344-352Article in journal (Refereed) Published
Abstract [en]

In this work, the development of a point-of-care (PoC) system to capture aerosol from litres of air directly onto a microfluidic lab-on-chip for subsequent analysis is addressed. The system involves an electrostatic precipitator that uses corona charging and electrophoretic transport to capture aerosol droplets onto a microfluidic air-to-liquid interface for downstream analysis. A theoretical study of the governing geometric and operational parameters for optimal electrostatic precipitation is presented. The fabrication of an electrostatic precipitator prototype and its experimental validation using a laboratory-generated aerosolized dye is described. Collection efficiencies were comparable to those of a state-of-the-art Biosampler impinger, with the significant advantage of providing samples that are at least 10 times more concentrated. Finally, we discuss the potential of such a system for breath-based diagnostics.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
breath analysis, poc, point-of-care, lab-on-chip, loc, microfluidics, aerosol, sampling, medical device, diagnostics, electrostatic precipitation, corona discharge
National Category
Other Electrical Engineering, Electronic Engineering, Information Engineering Other Medical Biotechnology
Research subject
Electrical Engineering
Identifiers
urn:nbn:se:kth:diva-144986 (URN)10.1016/j.snb.2015.02.008 (DOI)000351017700043 ()2-s2.0-84923763722 (Scopus ID)
Projects
Rappid
Note

QC 20150223

Available from: 2014-05-05 Created: 2014-05-05 Last updated: 2018-04-29Bibliographically approved
2. The Influence of Air Flow Velocity and Particle Size on the Collection Efficiency of Electrostatic Aerosol Samplers
Open this publication in new window or tab >>The Influence of Air Flow Velocity and Particle Size on the Collection Efficiency of Electrostatic Aerosol Samplers
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(English)Manuscript (preprint) (Other academic)
Keywords
ESP, aerosol
National Category
Fluid Mechanics and Acoustics
Research subject
Engineering Mechanics
Identifiers
urn:nbn:se:kth:diva-196855 (URN)
Funder
Swedish Research CouncilEU, FP7, Seventh Framework Programme, 604244
Note

QC 20161124

The research presented here has received funding from he KTH Linné FLOW Center, the Swedish Research Council (VR) and the European Unions Seventh Framework Programme (FP7) under Grant Agreement No. 604244 (Norosensor). 

Available from: 2016-11-24 Created: 2016-11-24 Last updated: 2018-04-29Bibliographically approved
3. Efficient electrostatic sampling of aerosols into liquid
Open this publication in new window or tab >>Efficient electrostatic sampling of aerosols into liquid
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Despite an increasing demand for the identification and quantification of airborne pathogens, there is an unmet need for point-of-care instruments that provide both capture and analysis of bioaerosols. The integration of electrostatic precipitation of aerosol particles directly into liquid with lab-on-a-chip-based biomolecular analysis has been previously suggested as a promising solution for this purpose.

This work investigates liquid collector designs for such instruments. We hypothesize that the geometry of the collector; and the position of its air-liquid interface with respect to the electrostatic field and aerosol flow, can be optimized for a maximum sample concentration.

We designed four liquid collectors with a small form factor, adapted for concatenating point-to-plane electrostatic precipitators with integrated downstream analysis. The collectors were evaluated for their absolute mass collection and their sample concentration, by sampling radioactive aerosol and color dye aerosol. 

Collectors with their air-liquid surface parallel to the charged aerosol flow performed significantly better than those shaped as a cup with an air-liquid surface perpendicular to the flow. Whereas the electrostatic precipitators with the best performing collector designs captured only 32% of the aerosol mass compared to a commercial impinger, their resulting sample concentration was 4 times higher.    

Keywords
Electrostatic precipitation; Bioaerosol; Point-of-care; Microfluidic collection; Corona discharge; Air sampling
National Category
Other Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
urn:nbn:se:kth:diva-226952 (URN)
Note

QC 20180502

Available from: 2018-04-29 Created: 2018-04-29 Last updated: 2018-05-02Bibliographically approved
4. Sampling and detection of airborne influenza virus towards point-of-care applications
Open this publication in new window or tab >>Sampling and detection of airborne influenza virus towards point-of-care applications
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, PlosONEArticle in journal (Refereed) Published
Abstract [en]

Airborne transmission of the influenza virus contributes significantly to the spread of this infectious pathogen, particularly over large distances when carried by aerosol droplets with long survival times. Efficient sampling of virus-loaded aerosol in combination with a low limit of detection of the collected virus could enable rapid and early detection of airborne influenza virus at the point-of-care setting. Here, we demonstrate a successful sampling and detection of airborne influenza virus using a system specifically developed for such applications. Our system consists of a custom-made electrostatic precipitation (ESP)-based bioaerosol sampler that is coupled with downstream quantitative polymerase chain reaction (qPCR) analysis. Aerosolized viruses are sampled directly into a miniaturized collector with liquid volume of 150 μL, which constitutes a simple and direct interface with subsequent biological assays. This approach reduces sample dilution by at least one order of magnitude when compared to other liquid-based aerosol bio-samplers. Performance of our ESP-based sampler was evaluated using influenza virus-loaded sub-micron aerosols generated from both cultured and clinical samples. Despite the miniaturized collection volume, we demonstrate a collection efficiency of at least 10% and sensitive detection of a minimum of 3721 RNA copies. Furthermore, we show that an improved extraction protocol can allow viral recovery of down to 303 RNA copies and a maximum sampler collection efficiency of 47%. A device with such a performance would reduce sampling times dramatically, from a few hours with current sampling methods down to a couple of minutes with our ESP-based bioaerosol sampler.

Place, publisher, year, edition, pages
Plos One, 2017
National Category
Diagnostic Biotechnology Medical Laboratory and Measurements Technologies
Identifiers
urn:nbn:se:kth:diva-199971 (URN)10.1371/journal.pone.0174314.s007 (DOI)000399174400024 ()2-s2.0-85016328510 (Scopus ID)
Note

QC 20170125

Available from: 2017-01-20 Created: 2017-01-20 Last updated: 2018-04-29Bibliographically approved
5. Sampling pathogens from breath using electrostatic and filter methods for diagnosis of lower respiratory tract infections– pilot study
Open this publication in new window or tab >>Sampling pathogens from breath using electrostatic and filter methods for diagnosis of lower respiratory tract infections– pilot study
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2018 (English)Report (Refereed)
Abstract [en]

A pilot study at a primary care center in Belgium sampled exhaled breath from patients presenting with flu-like symptoms. Electrostatic sampling methods revealed S. aureus, while filter sampling revealed virus. Additionally, for the first time, an electrostatic device was verified for exhaled breath at a clinical point-of-care setting.

National Category
Medical Biotechnology
Identifiers
urn:nbn:se:kth:diva-226954 (URN)
Note

QC 20180502

Available from: 2018-04-29 Created: 2018-04-29 Last updated: 2018-05-02Bibliographically approved

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