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Integrating Biosensors for Air Monitoring and Breath-Based Diagnostics
KTH, School of Electrical Engineering (EES), Micro and Nanosystems.ORCID iD: 0000-0001-6443-878X
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The air we breathe is the concern of all of us but nevertheless we only know very little about airborne particles, and especially which biological microorganisms they contain. Today, we live in densely populated societies with a growing number of people, making us particularly vulnerable to air transmission of pathogens. With the recent appearance of highly pathogenic types of avian influenza in southeast Asia and the seasonal outbreaks of gastroenteritis caused by the extremely contagious norovirus, the need for portable, sensitive and rapid instruments for on-site detection and monitoring of airborne pathogens is apparent.

Unfortunately, the integration incompatibility between state-of-the-art air sampling techniques and laboratory based analysis methods makes instruments for in-the-field rapid detection of airborne particles an unresolved challenge.

This thesis aims at addressing this challenge by the development of novel manufacturing, integration and sampling techniques to enable the use of label-free biosensors for rapid and sensitive analysis of airborne particles at the point-of-care or in the field.

The first part of the thesis introduces a novel reaction injection molding technique for the fabrication of high quality microfluidic cartridges. In addition, electrically controlled liquid aspiration and dispensing is presented, based on the use of a thermally actuated polymer composite integrated with microfluidic cartridges.

The second part of the thesis demonstrates three different approaches of biosensor integration with microfluidic cartridges, with a focus on simplifying the design and integration to enable disposable use of the cartridges.

The third part to the thesis presents a novel air sampling technique based on electrophoretic transport of airborne particles directly to microfluidic cartridges. This technique is enabled by the development of a novel microstructured component for integrated air-liquid interfacing. In addition, a method for liquid sample mixing with magnetic microbeads prior to downstream biosensing is demonstrated.In the fourth part of the thesis, three different applications for airborne particle biosensing are introduced and preliminary experimental results are presented.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2015. , xix, 85 p.
Series
TRITA-EE, ISSN 1653-5146 ; 2015:020
National Category
Medical Laboratory and Measurements Technologies
Identifiers
URN: urn:nbn:se:kth:diva-165454ISBN: 978-91-7595-560-5 (print)OAI: oai:DiVA.org:kth-165454DiVA: diva2:808742
Public defence
2015-05-22, Q2, Osquldas väg 10, KTH, Stockholm, 10:00 (English)
Opponent
Supervisors
Projects
RPARappidNorosensor
Funder
EU, FP7, Seventh Framework ProgrammeVINNOVASwedish Research CouncilSwedish Foundation for Strategic Research
Note

QC 20150429

Available from: 2015-04-29 Created: 2015-04-28 Last updated: 2015-04-29Bibliographically approved
List of papers
1. Reaction injection molding and direct covalent bonding of OSTE+ polymer microfluidic devices
Open this publication in new window or tab >>Reaction injection molding and direct covalent bonding of OSTE+ polymer microfluidic devices
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2015 (English)In: Journal of Micromechanics and Microengineering, ISSN 0960-1317, E-ISSN 1361-6439, Vol. 25, no 7Article in journal (Refereed) Published
Abstract [en]

In this article, we present OSTE+RIM, a novel reaction injection molding (RIM) process that combines the merits of off-stoichiometric thiol–ene epoxy (OSTE+) thermosetting polymers with the fabrication of high quality microstructured parts. The process relies on the dual polymerization reactions of OSTE+ polymers, where the first curing step is used in OSTE+RIM for molding intermediately polymerized parts with well-defined shapes and reactive surface chemistries. In the facile back-end processing, the replicated parts are directly and covalently bonded and become fully polymerized using the second curing step, generating complete microfluidic devices. To achieve unprecedented rapid processing, high replication fidelity and low residual stress, OSTE+RIM uniquely incorporates temperature stabilization and shrinkage compensation of the OSTE+ polymerization during molding. Two different OSTE+ formulations were characterized and used for the OSTE+RIM fabrication of optically transparent, warp-free and natively hydrophilic microscopy glass slide format microfluidic demonstrator devices, featuring a storage modulus of 2.3 GPa and tolerating pressures of at least 4 bars. 

Place, publisher, year, edition, pages
Institute of Physics (IOP), 2015
Keyword
off-stoichiometric thiol–ene, epoxy, OSTE+, reaction injection molding, device fabrication, polymers, microfluidics
National Category
Nano Technology
Identifiers
urn:nbn:se:kth:diva-165616 (URN)10.1088/0960-1317/25/7/075002 (DOI)
Note

QC 201500618

Available from: 2015-04-29 Created: 2015-04-29 Last updated: 2017-12-04Bibliographically approved
2. Liquid Aspiration and Dispensing Based on an Expanding PDMS Composite
Open this publication in new window or tab >>Liquid Aspiration and Dispensing Based on an Expanding PDMS Composite
2008 (English)In: Journal of microelectromechanical systems, ISSN 1057-7157, E-ISSN 1941-0158, Vol. 17, no 5, 1254-1262 p.Article in journal (Refereed) Published
Abstract [en]

In this paper, we present the development of active liquid aspiration and dispensing units designed for vertical, as well as lateral, liquid aspiration. The devices are based on a single-use thermally expanding polydimethylsiloxane (PDMS) composite, which allows altering its surface topography by means of individually addressable integrated heaters. Devices are designed in order to create an enclosed cavity in the system, due to locally expanding the initially unstructured composite. This enables negative volume displacement and leads to the event of liquid aspiration. To enable this device functionality, two different techniques of selectively creating permanent PDMS bonds have been developed. One approach utilizes the plasma-assisted PDMS bonding technique, together with a patterned antistiction layer to form reversibly, as well as irreversibly, bonded regions. Another approach utilizes microcontact printing of PDMS curing agent, which serves as a patterned intermediate layer for adhesive bonding. Fabricated prototype devices successfully demonstrated the aspiration and release of liquid volumes ranging from 28 to 815 nL. The devices are entirely fabricated from low-cost materials, using wafer-level processes only and do not require external means for liquid actuation.

Place, publisher, year, edition, pages
IEEE Press, 2008
Keyword
Fabrication, fluidics, micropumps, wafer-scale integration, total analysis systems, on-a-chip, flow-control, micropump, pumps, fabrication, devices, valves
National Category
Other Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
urn:nbn:se:kth:diva-17922 (URN)10.1109/jmems.2008.921728 (DOI)000260464800021 ()2-s2.0-53649109088 (Scopus ID)
Note

QC 20100817

Available from: 2010-08-05 Created: 2010-08-05 Last updated: 2015-06-18Bibliographically approved
3. An integrated QCM-based narcotics sensing microsystem
Open this publication in new window or tab >>An integrated QCM-based narcotics sensing microsystem
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2008 (English)In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 8, no 10, 1648-1657 p.Article in journal (Refereed) Published
Abstract [en]

We present the design, fabrication and successful testing of a 14 x 14 x 4 mm(3) integrated electronic narcotics sensing system which consists of only four parts. The microsystem absorbs airborne narcotics molecules and performs a liquid assay using an integrated quartz crystal microbalance (QCM). A vertically conductive double-sided adhesive foil (VCAF) was used and studied as a novel material for LOC and MEMS applications and provides easy assembly, electrical contacting and liquid containment. The system was tested for measuring cocaine and ecstasy, with successful detection of amounts as small as 100 ng and 200 ng, respectively These levels are of interest in security activities in customs, prisons and by the police.

Place, publisher, year, edition, pages
RSC Publishing, 2008
Keyword
electronic nose, quartz crystal microbalance, microsystem, narcotics detection, air-liquid interfacing, diaphragm, microfluidics, micro electro mechanical systems, molecular transport
National Category
Control Engineering
Identifiers
urn:nbn:se:kth:diva-14189 (URN)10.1039/b800487k (DOI)000260466300007 ()2-s2.0-52749089053 (Scopus ID)
Note

QC 20100723. Tidigare titel: An integrated narcotics sensing microsystem

Available from: 2010-07-23 Created: 2010-07-23 Last updated: 2015-06-18Bibliographically approved
4. ONE STEP INTEGRATION OF GOLD COATED SENSORS WITH OSTE POLYMER CARTRIDGES BY LOW TEMPERATURE DRY BONDING
Open this publication in new window or tab >>ONE STEP INTEGRATION OF GOLD COATED SENSORS WITH OSTE POLYMER CARTRIDGES BY LOW TEMPERATURE DRY BONDING
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2011 (English)In: 16th IEEE International Conference on Solid-State Sensors, Actuators and Microsystems (IEEE TRANSDUCERS 2011), IEEE conference proceedings, 2011, 2778-2781 p.Conference paper, Published paper (Refereed)
Abstract [en]

We propose and demonstrate a novel one step method to integrate gold coated sensors with cartridges by dry covalent bonding. The cartridges are replica molded in an UV-curable off-stoichiometry thiol-ene (OSTE) polymer, featuring an excess of thiol functional groups that covalently bond to the surface of gold coated sensors upon contact. The method is demonstrated by the integration of a gold coated quartz crystal to a microfludic OSTE cartridge. The resulting bond interface is shown to be completely homogenous and void free and the package is tested successfully to a differential pressure of up to 2 bars. The performance of the biosensor chip is evaluated by measuring the unspecific binding of 0.5% albumin, resulting in a total frequency drop 205 Hz. This approach delivers a simple but rapid high quality integration aiming for the production of robust, low cost and disposable biosensor chips

Place, publisher, year, edition, pages
IEEE conference proceedings, 2011
Keyword
Biosensor, OSTE
National Category
Other Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
urn:nbn:se:kth:diva-49224 (URN)10.1109/TRANSDUCERS.2011.5969534 (DOI)2-s2.0-80052133989 (Scopus ID)978-1-4577-0157-3 (ISBN)
Conference
16th IEEE International Conference on Solid-State Sensors, Actuators and Microsystems (IEEE TRANSDUCERS 2011), Beijing, China, 5-9 Jun, 2011
Projects
RPARappid
Note

QC 20111129

Available from: 2011-11-25 Created: 2011-11-25 Last updated: 2015-06-03Bibliographically approved
5. Integration of microfluidics with grating coupled silicon photonic sensors by one-step combined photopatterning and molding of OSTE
Open this publication in new window or tab >>Integration of microfluidics with grating coupled silicon photonic sensors by one-step combined photopatterning and molding of OSTE
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2013 (English)In: Optics Express, ISSN 1094-4087, E-ISSN 1094-4087, Vol. 21, no 18, 21293-21298 p.Article in journal (Refereed) Published
Abstract [en]

We present a novel integration method for packaging silicon photonic sensors with polymer microfluidics, designed to be suitable for wafer-level production methods. The method addresses the previously unmet manufacturing challenges of matching the microfluidic footprint area to that of the photonics, and of robust bonding of microfluidic layers to biofunctionalized surfaces. We demonstrate the fabrication, in a single step, of a microfluidic layer in the recently introduced OSTE polymer, and the subsequent unassisted dry bonding of the microfluidic layer to a grating coupled silicon photonic ring resonator sensor chip. The microfluidic layer features photopatterned through holes (vias) for optical fiber probing and fluid connections, as well as molded microchannels and tube connectors, and is manufactured and subsequently bonded to a silicon sensor chip in less than 10 minutes. Combining this new microfluidic packaging method with photonic waveguide surface gratings for light coupling allows matching the size scale of microfluidics to that of current silicon photonic biosensors. To demonstrate the new method, we performed successful refractive index measurements of liquid ethanol and methanol samples, using the fabricated device. The minimum required sample volume for refractive index measurement is below one nanoliter.

Place, publisher, year, edition, pages
Optical Society of America, 2013
Keyword
biosensor, microfluidics, oste
National Category
Other Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
urn:nbn:se:kth:diva-127716 (URN)10.1364/oe.21.021293 (DOI)000324867100092 ()2-s2.0-84884552942 (Scopus ID)
Projects
CellRing
Funder
Swedish Research Council, B0460801EU, European Research Council, 267528
Note

This paper was published in Optics Express and is made available as an electronic reprint with the permission of OSA.  The paper can be found at the following URL on the OSA website:http://dx.doi.org/10.1364/oe.21.021293. Systematic or multiple reproduction or distribution to multiple locations via electronic or other means is prohibited and is subject to penalties under law.

Qc 20130913

Available from: 2013-09-04 Created: 2013-09-04 Last updated: 2017-12-06Bibliographically approved
6. Electrohydrodynamic Enhanced Transport and Trapping of Airborne Particles to a Microfluidic Air-Liquid Interface
Open this publication in new window or tab >>Electrohydrodynamic Enhanced Transport and Trapping of Airborne Particles to a Microfluidic Air-Liquid Interface
2008 (English)In: Micro System Workshop 2008, 2008Conference paper, Published paper (Other academic)
National Category
Other Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
urn:nbn:se:kth:diva-49200 (URN)
Conference
Micro System Workshop, MSW08. Göteborg, Sweden. 6-7 Maj
Projects
RPARappid
Note

QC 20111130

Available from: 2011-11-25 Created: 2011-11-25 Last updated: 2016-06-13Bibliographically approved
7. 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, 344-352 p.Article 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
Keyword
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: 2017-12-05Bibliographically approved

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