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Microfluidics in Surface Modified PDMS: Towards Miniaturized Diagnostic Tools
Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Technology, Department of Engineering Sciences.
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

There is a strong trend in fabricating miniaturized total analytical systems, µTAS, for various biochemical and cell biology applications. These miniaturized systems could e.g. gain better separation performances, be faster, consume less expensive reagents and be used for studies that are difficult to access in the macro world. Disposable µTAS eliminate the risk of carry-over and can be fabricated to a low cost.

This work focused on the development of µTAS modules with the intentional use for miniaturized diagnostics. Modules for blood separation, desalting, enrichment, separation and ESI-MS detection were successfully fabricated. Surface coatings were additionally developed and evaluated for applications in µTAS with complex biological samples. The first heparin coating could be easily immobilized in a one-step-process, whereas the second heparin coating was aimed to form a hydrophilic surface that was able to draw blood or plasma samples into a microfluidic system by capillary forces.

The last mentioned heparin surface was further utilized when developing a chip-based sensor for performing CD4-count in human blood, an important marker to determine the stage of an HIV-infection.

All devices in this work were fabricated in PDMS, an elastomeric polymer with the advantage of rapid and less expensive prototyping of the microfabricated master. It was shown that PDMS could be considered as the material of choice for future commercial µTAS. The devices were intentionally produced using a low grade of fabrication complexity. It was however demonstrated that even with low complexity, it is possible to integrate several functional chip modules into a single microfluidic device.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2006. , p. 52
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 241
Keywords [en]
Materials science, µTAS, micro total analysis system, PDMS, poly(dimethylsiloxane), microfluidics, heparin, blood filtration, on-chip, ESI-MS, desalting, QCM-D, biocompatible, CD4, capillary flow, lab-on-chip, microfabrication, enrichment, point-of-care, hydrophilic, oxidation
Keywords [sv]
Materialvetenskap
Identifiers
URN: urn:nbn:se:uu:diva-7270ISBN: 91-554-6716-4 (print)OAI: oai:DiVA.org:uu-7270DiVA, id: diva2:169223
Public defence
2006-12-08, Polhemsalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 09:30
Opponent
Supervisors
Available from: 2006-11-17 Created: 2006-11-17Bibliographically approved
List of papers
1. A hybrid poly(dimethylsiloxane) microsystem for on-chip whole blood filtration optimized for steroid screening
Open this publication in new window or tab >>A hybrid poly(dimethylsiloxane) microsystem for on-chip whole blood filtration optimized for steroid screening
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2006 (English)In: Biomedical Microdevices, ISSN 1387-2176, Vol. 8, no 1, p. 73-79Article in journal (Refereed) Published
National Category
Engineering and Technology
Identifiers
urn:nbn:se:uu:diva-95123 (URN)
Available from: 2006-11-17 Created: 2006-11-17 Last updated: 2016-06-22
2. Functionality and stability of heparin immobilized onto poly(dimethylsiloxane)
Open this publication in new window or tab >>Functionality and stability of heparin immobilized onto poly(dimethylsiloxane)
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2005 (English)In: Colloids and Surfaces B: Biointerfaces, ISSN 0927-7765, E-ISSN 1873-4367, Vol. 45, no 2, p. 76-81Article in journal (Refereed) Published
Abstract [en]

Poly(dimethylsiloxane) (PDMS) has become an attractive material when working in the field of microfluidics, mainly because of the rapid prototyping process it involves. The increased surface volume ratio in microchannels makes the interaction between sample and material surface highly important, evident when handling complex biological samples such as plasma or blood. This study demonstrates a new grade of non-covalent heparin surface that adds efficient anticoagulant property to the PDMS material. The surface modification is a simple and fast one-step process performed at neutral pH, optimal when working with closed microsystems. The heparin formed a uniform and functional coating on hydrophobic PDMS with comparatively high level of antithrombin-binding capacity. In addition, long-term studies revelaed that the immobilized heparin was more or less stable in the microchannels over a time of three weeks. Recalcified plasma in contact with native PDMS showed complete coagulation after 1 h, while no fibrin formation was detected in plasma incubated on heparin-coated PDMS within the same time. In conclusion, we see the heparin coating developed and evaluated in this study as a tool that greatly facilitates the use of PDMS in microfluidics dealing with plasma or blood samples.

National Category
Physical Sciences
Identifiers
urn:nbn:se:uu:diva-95124 (URN)10.1016/j.colsurfb.2005.07.004 (DOI)
Available from: 2006-11-17 Created: 2006-11-17 Last updated: 2018-05-31Bibliographically approved
3. Bioactive heparin immobilized onto microfluidic channels in poly(dimethylsiloxane) results in hydrophilic surface properties
Open this publication in new window or tab >>Bioactive heparin immobilized onto microfluidic channels in poly(dimethylsiloxane) results in hydrophilic surface properties
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2005 (English)In: Colloids and Surfaces B: Biointerfaces, ISSN 0927-7765, E-ISSN 1873-4367, Vol. 46, no 4, p. 240-247Article in journal (Refereed) Published
National Category
Engineering and Technology
Identifiers
urn:nbn:se:uu:diva-95125 (URN)10.1016/j.colsurfb.2005.10.009 (DOI)
Available from: 2006-11-17 Created: 2006-11-17 Last updated: 2017-12-14Bibliographically approved
4. Bioactivated PDMS microchannel evaluated as sensor for human CD4+ cells: The concept of a point-of-care method for HIV monitoring
Open this publication in new window or tab >>Bioactivated PDMS microchannel evaluated as sensor for human CD4+ cells: The concept of a point-of-care method for HIV monitoring
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2007 (English)In: Sensors and actuators. B, Chemical, ISSN 0925-4005, E-ISSN 1873-3077, Vol. 123, no 2, p. 847-855Article in journal (Refereed) Published
Abstract [en]

Up to today, the number of CD4(+) lymphocytes remains the most important biological marker to determine the clinical stage of an HIV-infection. Analysis by flow cytometry, the standard method used today, is unsuitable in many developing countries, because of high costs involved and practical inconveniences. We here present the concept of an inexpensive PDMS-based point-of-care device for CD4(-)count. A simple fluorescence microscope for stained leucocytes counting is the only detection equipment needed. The biosensor surface consists of an initial heparin-based coating that adds hydrophilicity and thromboresistance to the PDMS material. The specific capturing chemistry is based on an avidin/biotin-antibody surface architecture. Pure capillary forces draw whole blood, as well as rinsing buffer, into the biosensor channel, minimizing the need of external equipment. Detection of the captured cells was performed by fluorescence imaging of HOECHST (stains cell nuclei) and CD3-FITC signals. It was shown that the non-specific adsorption of CD4(-) leucocytes was minimal to none. and the detection could therefore be done by only counting the easy identifiable HOECHST+ cells. Characterization of the biosensor coating process was additionally performed with the quartz crystal microbalance-dissipation technique.

Keywords
PDMS, poly(dimethylsiloxane), HIV, CD4-count, point-of-care
National Category
Chemical Sciences Engineering and Technology Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-95126 (URN)10.1016/j.snb.2006.10.034 (DOI)000247060100029 ()
Available from: 2006-11-17 Created: 2006-11-17 Last updated: 2018-06-04Bibliographically approved
5. Microfluidic PDMS-based sensor for CD4 cell count
Open this publication in new window or tab >>Microfluidic PDMS-based sensor for CD4 cell count
Manuscript (Other academic)
Identifiers
urn:nbn:se:uu:diva-95127 (URN)
Available from: 2006-11-17 Created: 2006-11-17 Last updated: 2010-01-13Bibliographically approved
6. A simplified method for capillary embedment into microfluidic devices exemplified by sol-gel based preconcentration
Open this publication in new window or tab >>A simplified method for capillary embedment into microfluidic devices exemplified by sol-gel based preconcentration
2007 (English)In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 28, no 24, p. 4758-4764Article in journal (Refereed) Published
Abstract [en]

We here describe an alternative method of embedding ftinctionalized capillaries into microdevices fabricated in PDMS. The capillaries have square-shaped outer dimensions and fit into elastic PDMS channel networks of similar dimensions. By modifying the capillary off-chip, the technique makes it possible to integrate a new chip function without risking contamination of already existing chemically patterned areas because of new reagent solutions. Leak-free insertion of these capillaries has earlier been reported, where a thin layer of uncured PDMS bonded the capillary to the microchannel and the lid structure. In this new approach, oxygen plasma is used to bond the square capillary to the PDMS, eliminating the risk of dogging the microsystem with uncured prepolymer. The new embedding technique was exemplified and evaluated by inserting a square capillary piece containing monolithic sol-gel for sample preconcentration application. The assembled microdevice was run with mass spectrometric detection, showing that peptides were preconcentrated without leakage from either the sol-gel itself or around the inserted capillary. Repeated preconcentration runs showed migration times better than 3% for all peptides. We believe that the presented microchip assembling technique greatly simplifies the insertion of functionalized capillary pieces, e.g., an initial preconcentrator to a PDMS device containing other downstream modules.

Keywords
microfluidics, PDMS, preconcentration, sol-gel
National Category
Chemical Sciences Engineering and Technology
Identifiers
urn:nbn:se:uu:diva-95128 (URN)10.1002/elps.200700221 (DOI)000252465600028 ()18008304 (PubMedID)
Available from: 2006-11-17 Created: 2006-11-17 Last updated: 2018-06-04Bibliographically approved
7. Sample pretreatment on a microchip with an integrated electrospray emitter
Open this publication in new window or tab >>Sample pretreatment on a microchip with an integrated electrospray emitter
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2006 (English)In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 27, no 11, p. 2075-2082Article in journal (Refereed) Published
Keywords
Electrospray emitter, Microchip, PDMS, Sample pretreatment
National Category
Chemical Sciences Engineering and Technology
Identifiers
urn:nbn:se:uu:diva-95129 (URN)10.1002/elps.200500763 (DOI)
Available from: 2006-11-17 Created: 2006-11-17 Last updated: 2017-12-14Bibliographically approved
8. Electrokinetic-driven microfluidic system in poly(dimethylsiloxane) for mass spectrometry detection integrating sample injection, capillary electrophoresis, and electrospray emitter on-chip
Open this publication in new window or tab >>Electrokinetic-driven microfluidic system in poly(dimethylsiloxane) for mass spectrometry detection integrating sample injection, capillary electrophoresis, and electrospray emitter on-chip
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2005 (English)In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 26, no 24, p. 4674-4683Article in journal (Refereed) Published
National Category
Chemical Sciences
Identifiers
urn:nbn:se:uu:diva-95130 (URN)10.1002/elps.200500338 (DOI)
Available from: 2006-11-17 Created: 2006-11-17 Last updated: 2025-04-07Bibliographically approved
9. Instant oxidation of closed microchannels
Open this publication in new window or tab >>Instant oxidation of closed microchannels
2007 (English)In: Journal of Micromechanics and Microengineering, ISSN 0960-1317, E-ISSN 1361-6439, Vol. 17, no 4, p. N16-N21Article in journal (Refereed) Published
Abstract [en]

A new method for instant oxidation of closed, bonded microchannels is presented and evaluated. By placing the tip-formed electrode of a corona plasma equipment in the reservoir of a PDMS microstructure, the plasma spark can spread into the microchannel and oxidize the inner PDMS channel walls. By applying this process, the non-specific adsorption of hydrophobic affinity analytes is markedly decreased, here evaluated with the fluorescent dye Rhodamine B and standard protein BSA. The results show that the surface adsorption in plasma-treated channels is reduced significantly, e.g. the amount of BSA adsorbed at 35 mm distance from the reservoir is only 35% of the amount of BSA adsorbed in non-treated channels. The surface shows very low adsorption during the first 200 min after oxidation, and has recovered (90%) its hydrophobicity first after 24 h. This method of instant surface oxidation has in our group been widely used to simplify microfluidic studies of microstructure prototypes, since the need of other more complicated surface modifications to lower analyte adsorption is eliminated.

Keywords
Hydrophobicity, Proteins, Hydrophobic compound, Adsorption, Plasma, Dimethylsiloxane polymer, Oxidation, Surface treatments, Fluidics, Microfluidics
National Category
Engineering and Technology
Identifiers
urn:nbn:se:uu:diva-95131 (URN)10.1088/0960-1317/17/4/N02 (DOI)000245434200030 ()
Available from: 2006-11-17 Created: 2006-11-17 Last updated: 2017-12-14Bibliographically approved

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