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MEMS Interfaces for Bioanalysis Systems
KTH, School of Electrical Engineering (EES), Microsystem Technology.ORCID iD: 0000-0002-3996-9279
2008 (English)Doctoral thesis, comprehensive summary (Other scientific)
Abstract [en]

This thesis deals with various aspects of using open microfluidic interfaces. Three specific areas of application are studied.

The first is air-to-liquid interfacing in biosensors with possibilities for component inte­gration. A micromachined interface for airborne sample-to-liquid and droplet-to-liquid adsorption is discussed. It enables a robust sheet liquid flow serving as adsorption site. The inter­face properties are presented. Along with the interface, a novel method and system for rapid detection of dust and vapour-based narcotics and explosives traces is introduced. The QCM sensor detection principle with antibody immunoassay is described. Having shown the working principles of molecular adsorption to liquid surface and molecular detection with QCM technology, an integrated device is introduced. Diffusion as an effective transport mechanism in this microfluidic device is discussed. By holding the two components (inter­face and QCM) together with a double-sided adhesive, anisotropically vertically conductive tape, we achieve three functions, namely fixation, electrical connection and liquid sealing. Finally, enhanced electrostatic trapping of small particles to the liquid interface is demon­strated.

The second area concerns open microfluidics for the integration of capillary electropho­resis and mass spectroscopy. A technique for hyphenation between CE and MALDI-MS is presented. Two closed fused-silica capillaries were connected via a silicon chip comprising an open microcanal. The influence of the capillary-to-microcanal connection is discussed, as well as a simple technique to control evaporation from the open microcanal.

The third area concerns microfluidics enabling studies of single cells in asymmetric en­vironments. Using extracellular matrix or synthetic gel-embedding cells in an assay chamber, cells thrive and proliferate. This makes it possible to carry out medium to long term cultiva­tion of cells in a more physiological, controlled 3D environment than in traditional 2D cul­tures. The gels are discussed in terms of handling as well as their properties. A gel and micro­fluidic device for three dimensional cell culture with microgradient environments is pre­sented. Finally, a method for studying cilia-forming cells in asymmetric microfluidic environments is presented. Bending the primary cilium with a fluid flow will give rise to a response, but sensitivity to flow direction has only been sparsely studied. Design considerations are presented and discussed.

Abstract [sv]

Den här avhandlingen diskuterar olika aspekter av den öppna gränsytan hos styckevis öppna mikrofluidiksystem. Tre specifika användningsområden har studerats.

Det första är gränsytan mellan luft och vätska i en biosensor och de användningsområ­den som finns här. Ett mikrofabricerat interface för adsorption av luftburna substanser samt dropp-absorption diskuteras. Här används en rörlig vätskeyta som adsorbtionsyta och dess egenskaper presenteras. En ny metod för sprängämnes- och narkotikadetektering med interfa­cet introduceras. QCM-tekniken i kombination med antikroppskemi beskrivs. En integrerad lösning med dessa tekniker introduceras där diffusion utgör en effektiv transportmekanism. Med en dubbelsidig ledande tejp hålls komponenterna ihop, tätas och förses med ström. Slut­ligen presenteras elektrostatisk infångning av partiklar där den ena elektroden utgörs av väts­keytan.

Det andra området berör ett öppet mikrofluidiksystem för integrering av kapillärelek­trofores och masspektrometri. Teknik för att koppla ihop CE och MALDI-MS presente­ras. Två glaskapillärer har kopplats ihop med ett kiselchip med en öppen mikrokanal. Kopp­lingen mellan kapillären och chippet diskuteras liksom en enkel teknik för att kontrol­lera avdunstningen från den öppna mikrokanalen.

Det tredje området diskuterar hur mikrofluidik möjliggör studier av cellulära reaktioner i asymmetriska miljöer. Med inbäddning av celler i extracellulär matris eller syntetisk gel fås fysiologiskt relevant lokal miljö för celltillväxt och celldelning. Detta möjliggör studier av cellutveckling och cellreaktioner under lång tid i faktisk 3D-miljö till skillnad från den nuva­rande etablerade 2D-miljön. Gelerna diskuteras ur en hanteringssynpunkt liksom utifrån sina egenskaper. Ett system för cellodling i 3D med gradi­entmiljö presenteras och diskuteras. Slutligen presenteras ett system för studier av ciliefor­mande cellers respons där asymmetriska flöden ger upphov till böjning av cilier. Olika de­signaspekter diskuteras.

Place, publisher, year, edition, pages
Stockholm: KTH , 2008. , xii, 56 p.
Series
Trita-EE, ISSN 1653-5146 ; 2008:002
Keyword [en]
microfluidic interfacing, microfluidics, µTAS, sample transfer, biosensor, electronic nose, surface tension, quartz crystal microbalance, QCM, narcotics detection
National Category
Control Engineering
Identifiers
URN: urn:nbn:se:kth:diva-4609ISBN: 978-91-7178-846-7 (print)OAI: oai:DiVA.org:kth-4609DiVA: diva2:13071
Public defence
2008-02-08, Sal M3, KTH, Brinellvägen 64, Stockholm, 10:00
Opponent
Supervisors
Note
QC 20100927Available from: 2008-01-18 Created: 2008-01-18 Last updated: 2010-09-27Bibliographically approved
List of papers
1. A micromachined interface for airborne sample-to-liquid transfer and its application in a biosensor system
Open this publication in new window or tab >>A micromachined interface for airborne sample-to-liquid transfer and its application in a biosensor system
2006 (English)In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 6, no 12, 1504-1509 p.Article in journal (Refereed) Published
Abstract [en]

A novel micromachined interface for airborne sample-to-liquid adsorption and droplet-to-liquid transfer was designed and fabricated. It enables a robust sheet liquid flow serving as an adsorption site. The interface was characterised for flow and pressure properties and tested successfully for the transfer/adsorption of different samples. A qualitative theoretical model of the device characteristics is presented. We also used the interface to introduce a novel method and system for fast detection of dust- and vapour-based narcotics and explosives traces. The microfluidic vapour-to-liquid adsorption interface was coupled to a set of downstream QCM sensors. The system was tested successfully, with 50 ng cocaine samples rendering 15 Hz frequency shifts and with 100 ng heroine samples rendering 50 Hz frequency shifts. Gravitation invariance of the open liquid interface was demonstrated successfully, with the interface mounted upside down as well as vertically. The detection time was reduced to half of the time needed in previous systems. Machine size, weight and cost were reduced.

Place, publisher, year, edition, pages
RSC Publishing, 2006
National Category
Control Engineering
Identifiers
urn:nbn:se:kth:diva-14188 (URN)10.1039/b612526n (DOI)000243212600011 ()2-s2.0-33846206078 (Scopus ID)
Note

QC 20100723

Available from: 2010-07-23 Created: 2010-07-23 Last updated: 2015-06-18Bibliographically approved
2. An integrated QCM-based narcotics sensing microsystem
Open this publication in new window or tab >>An integrated QCM-based narcotics sensing microsystem
Show others...
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
3. 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: 21st IEEE International Conference on Micro Electro Mechanical Systems (IEEE MEMS 2008), IEEE conference proceedings, 2008, 595-598 p.Conference paper, Published paper (Refereed)
Abstract [en]

We introduce a novel approach for greatly improved transport and trapping of airborne sample to a microfluidic analysis system by integrating an electrohydrodynamic (EHD) air pump with a microfluidic air-liquid interface. In our system, a negative corona discharge partially ionizes the air around a sharp electrode tip while the electrostatic field accelerates airborne particles towards an electrically grounded liquid surface, where they absorb. The air-liquid interface is fixated at the microscale pores of a perforated silicon diaphragm, each pore functioning as a static Laplace valve. Our system was experimentally tested using airborne smoke particles of ammonium chloride and aqueous salt solution as the liquid. We measured that EHD enhanced transport of the particles from the air into the liquid is enhanced over 130 times compared to passive trapping.

Place, publisher, year, edition, pages
IEEE conference proceedings, 2008
Series
Proceedings: IEEE micro electro mechanical systems, ISSN 1084-6999
Keyword
Ammonium compounds; Composite micromechanics; Electric corona; Electrohydrodynamics; Fluid dynamics; Fluid mechanics; Hydrodynamics; Liquids; Mechanical engineering; Mechanics; Mechatronics; MEMS; Microelectromechanical devices; Nanofluidics; Nonmetals; Reactive ion etching; Silicon
National Category
Control Engineering
Identifiers
urn:nbn:se:kth:diva-14190 (URN)10.1109/MEMSYS.2008.4443726 (DOI)000253356900149 ()2-s2.0-50149095599 (Scopus ID)978-1-4244-1792-6 (ISBN)
Conference
21st IEEE International Conference on Micro Electro Mechanical Systems (IEEE MEMS 2008), Tucson, AZ,13-17 Jan, 2008
Projects
RPARappid
Note

QC 20100723

Available from: 2010-07-23 Created: 2010-07-23 Last updated: 2015-06-03Bibliographically approved
4. Off-line integration of CE and MALDI-MS using a closed-open-closed microchannel system
Open this publication in new window or tab >>Off-line integration of CE and MALDI-MS using a closed-open-closed microchannel system
Show others...
2007 (English)In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 28, no 14, 2458-2465 p.Article in journal (Refereed) Published
Abstract [en]

In this work, a new technique for off-line hyphenation between CE and MALDI-MS is presented. Two closed fused-silica capillaries were connected via a silicon chip comprising an open microcanal. The EOF in the system was evaluated using mesityloxide or leucine-enkephalin as a sample and with a running buffer that rendered the analyte neutrally charged. Comparison was made between the EOF in a closed system (first capillary solely included in the electrical circuit) and in a closed-open system (first capillary and microcanal included in the electrical circuit). It was concluded that the experimental values of the EOF agreed with the theory. The influence of the capillary outer diameter on the peak dispersion was investigated using a closed-open-closed system (first capillary, microcanal and second capillary included in the electrical circuit). It was clearly seen that a capillary with 375 mu m od induced considerably higher peak dispersion than a 150 mu m od capillary, due to a larger liquid dead volume in the connection between the first capillary outlet and the microcanal. Mass spectrometric analysis has also been performed following CE separation runs in a closed-open-closed system with cytochrome c and lysozyme as model proteins. It was demonstrated that a signal distribution profile of the separated analytes could be recorded over a 30 mm long microcanal.

Keyword
CE; MALDI-MS; off-line interface; silicon microcanal
National Category
Engineering and Technology
Identifiers
urn:nbn:se:kth:diva-7875 (URN)10.1002/elps.200600735 (DOI)000248390900017 ()2-s2.0-34547442877 (Scopus ID)
Note
QC 20100723Available from: 2008-01-09 Created: 2008-01-09 Last updated: 2011-11-21Bibliographically approved
5. A concept for miniaturized 3-D cell culture using an extracellular matrix gel
Open this publication in new window or tab >>A concept for miniaturized 3-D cell culture using an extracellular matrix gel
Show others...
2005 (English)In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 26, no 24, 4751-4758 p.Article in journal (Refereed) Published
Abstract [en]

This paper presents a novel method to embed, anchor, and cultivate cells in a controlled 3-D flow-through microenvironment. This is realized using an etched silicon pillar flow chamber filled with extracellular matrix (ECM) gel mixed with cells. At 4 degrees C, while in liquid form, ECM gel is mixed with cells and injected into the chamber. Raising the temperature to 37 degrees C results in a gel, with cells embedded. The silicon pillars both stabilize and increase the surface to volume ratio of the gel. During polymerization the gel shrinks, thus creating channels, which enables perfusion through the chip. The pillars increase the mechanical stability of the gel permitting high surface flow rates without surface modifications. Within the structure cells were still viable and proliferating after 6 days of cultivation. Our method thus makes it possible to perform medium- to long-term cultivation of cells in a controlled 3-D environment. This concept opens possibilities to perform studies of cells in a more physiological environment compared to traditional 2-D cultures on flat substrates.

Keyword
embedded cells; extracellular matrix; microfluidics; three-dimensional cell culture
National Category
Engineering and Technology
Identifiers
urn:nbn:se:kth:diva-11814 (URN)10.1002/elps.200500478 (DOI)000234466300020 ()2-s2.0-29644447617 (Scopus ID)
Note
QC 20100723Available from: 2009-12-28 Created: 2009-12-28 Last updated: 2010-11-19Bibliographically approved
6. A microfluidic device for parallel 3-D cell cultures in asymmetric environments
Open this publication in new window or tab >>A microfluidic device for parallel 3-D cell cultures in asymmetric environments
Show others...
2007 (English)In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 28, no 24, 4705-4712 p.Article in journal (Refereed) Published
Abstract [en]

We demonstrate a concept for how a miniaturized 3-D cell culture in biological extracellular matrix (ECM) or synthetic gels bridges the gap between organ-tissue culture and traditional 2-D cultures. A microfluidic device for 3-D cell culture including microgradient environments has been designed, fabricated, and successfully evaluated. In the presented system stable diffusion gradients can be generated by application of two parallel fluid flows with different composition against opposite sides of a gel plug with embedded cello. Culture for up to two weeks was performed showing cells still viable and proliferating. The cell tracer dye calcein was used to verify gradient formation as the fluorescence intensity in exposed cells was proportional to the position in the chamber. Cellular response to an applied stimulus was demonstrated by use of an adenosine triphosphate gradient where the onset of a stimulated intracellular calcium release also depended on cell position.

Keyword
3-D cell culture; extracellular matrix; gradient; hydrogel; microfluidics
National Category
Industrial Biotechnology
Identifiers
urn:nbn:se:kth:diva-11816 (URN)10.1002/elps.200700342 (DOI)000252465600022 ()18070345 (PubMedID)2-s2.0-37548999753 (Scopus ID)
Note
QC 20100723Available from: 2009-12-28 Created: 2009-12-28 Last updated: 2010-11-19Bibliographically approved
7. Microfluidic devices for studies of primary cilium mediated cellular response to dynamic flow conditions
Open this publication in new window or tab >>Microfluidic devices for studies of primary cilium mediated cellular response to dynamic flow conditions
Show others...
2008 (English)In: Biomedical microdevices (Print), ISSN 1387-2176, E-ISSN 1572-8781, Vol. 10, no 4, 555-560 p.Article in journal (Refereed) Published
Abstract [en]

We present the first microfabricated microfluidic devices designed specifically for studies of primary cilium mediated cellular response to dynamic flow. The primary cilium functions as a mechano-sensor in renal tubular epithelium, sensing the extracellular fluid flow. Malfunction of cilia has been implicated in e.g. polycystic kidney disease and other pathological conditions. Bending of the primary cilium by fluid flow has been shown to give rise to an intracellular calcium signal, however little is known about the sensitivity to flow duration, magnitude and direction. This paper presents a novel method for studying cilia forming cells in asymmetric microfluidic environments. The microfluidic devices presented here were designed for a dynamic control of the local fluid flow on a cellular level, and thus, enables studies of cellular responses to an amplitude, frequency and direction controlled cilium movement.

Keyword
cilia; primary cilium; microfluidic; flow sensitivity
National Category
Engineering and Technology
Identifiers
urn:nbn:se:kth:diva-11359 (URN)10.1007/s10544-008-9165-8 (DOI)000257546800010 ()18236160 (PubMedID)2-s2.0-47749089423 (Scopus ID)
Note
QC 20100723Available from: 2009-10-30 Created: 2009-10-30 Last updated: 2010-11-19Bibliographically approved

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