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Novel Microfluidic Devices Based on a Thermally Responsive PDMS Composite
KTH, School of Electrical Engineering (EES), Microsystem Technology.
2007 (English)Doctoral thesis, comprehensive summary (Other scientific)
Abstract [en]

The field of micro total analysis systems (μTAS) aims at developments toward miniaturized and fully integrated lab-on-a-chip systems for applications, such as drug screening, drug delivery, cellular assays, protein analysis, genomic analysis and handheld point-of-care diagnostics. Such systems offer to dramatically reduce liquid sample and reagent quantities, increase sensitivity as well as speed of analysis and facilitate portable systems via the integration of components such as pumps, valves, mixers, separation units, reactors and detectors.

Precise microfluidic control for such systems has long been considered one of the most difficult technical barriers due to integration of on-chip fluidic handling components and complicated off-chip liquid control as well as fluidic interconnections. Actuation principles and materials with the advantages of low cost, easy fabrication, easy integration, high reliability, and compact size are required to promote the development of such systems.

Within this thesis, liquid displacement in microfluidic applications, by means of expandable microspheres, is presented as an innovative approach addressing some of the previously mentioned issues. Furthermore, these expandable microspheres are embedded into a PDMS matrix, which composes a novel thermally responsive silicone elastomer composite actuator for liquid handling. Due to the merits of PDMS and expandable microspheres, the composite actuator's main characteristic to expand irreversibly upon generated heat makes it possible to locally alter its surface topography. The composite actuator concept, along with a novel adhesive PDMS bonding technique, is used to design and fabricate liquid handling components such as pumps and valves, which operate at work-ranges from nanoliters to microliters. The integration of several such microfluidic components promotes the development of disposable lab-on-a-chip platforms for precise sample volume control addressing, e.g. active dosing, transportation, merging and mixing of nanoliter liquid volumes. Moreover, microfluidic pumps based on the composite actuator have been incorporated with sharp and hollow microneedles to realize a microneedle-based transdermal patch which exhibits on-board liquid storage and active dispensing functionality. Such a system represents a first step toward painless, minimally invasive and transdermal administration of macromolecular drugs such as insulin or vaccines.

The presented on-chip liquid handling concept does not require external actuators for pumping and valving, uses low-cost materials and wafer-level processes only, is highly integrable and potentially enables controlled and cost-effective transdermal microfluidic applications, as well as large-scale integrated fluidic networks for point-of care diagnostics, disposable biochips or lab-on-a-chip applications.

This thesis discusses several design concepts for a large variety of microfluidic components, which are promoted by the use of the novel composite actuator. Results on the successful fabrication and evaluation of prototype devices are reported herein along with comprehensive process parameters on a novel full-wafer adhesive bonding technique for the fabrication of PDMS based microfluidic devices.

Place, publisher, year, edition, pages
Stockholm: KTH , 2007. , xii, 68 p.
Series
Trita-EE, ISSN 1653-5146 ; 2007:31
Keyword [en]
MEMS, microsystem technology, micro total analysis system, lab-on-a-chip, microfluidics, composite actuator, expandable microspheres, PDMS, poly dimethylsiloxane, disposable, wafer bonding, adhesive bonding, PDMS bonding, adhesive PDMS bonding, selective PDMS bonding, microcontact printing
National Category
Other Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
URN: urn:nbn:se:kth:diva-4470ISBN: 978-91-7178-732-3 (print)OAI: oai:DiVA.org:kth-4470DiVA: diva2:12419
Public defence
2007-09-07, F3, Lindstedtsvägen 26, KTH, 10:00
Opponent
Supervisors
Note
QC 20100817Available from: 2007-08-21 Created: 2007-08-21 Last updated: 2010-08-17Bibliographically approved
List of papers
1. A Thermally Responsive PDMS Composite and its Microfluidic Applications
Open this publication in new window or tab >>A Thermally Responsive PDMS Composite and its Microfluidic Applications
2007 (English)In: Journal of microelectromechanical systems, ISSN 1057-7157, E-ISSN 1941-0158, Vol. 16, no 1, 50-57 p.Article in journal (Refereed) Published
Abstract [en]

This paper describes a novel composite actuator for controlled liquid actuation in microsystems which is based on a thermally responsive elastomer. The composite actuator consists of expandable microspheres incorporated in a polydimethylsiloxane (PDMS) matrix and entails the merits of both PDMS and expandable microspheres. The main characteristic of the composite actuator is to expand upon heat. The expansion is irreversible and the relative volume increase is measured up to 270% of its original volume after heating to 80 degrees C. The composite was used to fabricate single-use microfluidic pumps and valves. We show the displacement of liquids in the range of nanoliters even against counter pressures up to 100 kPa. Moreover, liquid flow in microchannels was entirely blocked by means of the integrated valves. The valves can withstand pressures up to 140 kPa. The devices are fabricated using low-cost materials only, and the composite actuator allows using wafer-level processing. The fluidic components based on the novel composite are highly integrable and do not require external actuators.

Keyword
Fluidics; Microactuators; Micropumps; Channel flow; Microactuators; Microchannels; Microfluidics; Microspheres; Thermal expansion; Valves (mechanical); Integrated valves; Micropumps; Polydimethylsiloxane
National Category
Other Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
urn:nbn:se:kth:diva-7397 (URN)10.1109/JMEMS.2006.886025 (DOI)000244434300008 ()2-s2.0-33947208945 (Scopus ID)
Note
QC 20100817Available from: 2007-08-21 Created: 2007-08-21 Last updated: 2017-12-14Bibliographically approved
2. A Disposable Lab-on-a-chip Platform with Embedded Fluid Actuators for Active Nanoliter Liquid Handling
Open this publication in new window or tab >>A Disposable Lab-on-a-chip Platform with Embedded Fluid Actuators for Active Nanoliter Liquid Handling
Show others...
2007 (English)In: Biomedical microdevices (Print), ISSN 1387-2176, E-ISSN 1572-8781, Vol. 9, no 1, 61-67 p.Article in journal (Refereed) Published
Abstract [en]

In this work we present the development of a disposable liquid handling lab-on-a-chip (LOC) platform with embedded actuators for applications in analytical chemistry. The proposed platform for nanoliter liquid handling is based on a thermally responsive silicone elastomer composite, consisting of PDMS and expandable microspheres. In our LOC platform, we integrate active dosing, transportation and merging of nanoliter liquid volumes. The disposable platform successfully demonstrates precise sample volume control with smart microfluidic manipulation and on-chip active microfluidic components. It is entirely fabricated from low-cost materials using wafer-level processing. Moreover, an enzymatic reaction and real-time detection was successfully conducted to exemplify its applicability as an LOC.

Keyword
Biochip; Lab-on-a-chip; Microfluidics; Micropump; PDMS composite; Chemical analysis; Elastomers; Enzyme kinetics; Microactuators; Fluidic devices; dimeticone; microsphere; silastic; accuracy; article; biochip; composite material; controlled study; cost; disposable equipment; enzyme mechanism; equipment design; laboratory test; microfluidic analysis; microfluidics; priority journal; Chemistry, Analytical; Disposable Equipment; Equipment Design; Equipment Failure Analysis; Microchemistry; Microfluidic Analytical Techniques; Nanotechnology; Solutions; Specimen Handling
National Category
Other Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
urn:nbn:se:kth:diva-7398 (URN)10.1007/s10544-006-9015-5 (DOI)000243256000008 ()17106636 (PubMedID)2-s2.0-33845986752 (Scopus ID)
Note
QC 20100817Available from: 2007-08-21 Created: 2007-08-21 Last updated: 2017-12-14Bibliographically approved
3. Wafer-Level Process for Single-Use Buckling Film Microliter-Range Pumps
Open this publication in new window or tab >>Wafer-Level Process for Single-Use Buckling Film Microliter-Range Pumps
Show others...
2007 (English)In: Journal of microelectromechanical systems, ISSN 1057-7157, E-ISSN 1941-0158, Vol. 16, no 4, 795-801 p.Article in journal (Refereed) Published
Abstract [en]

In this paper, we present the development of disposable single-use microfluidic pumps entirely based on a straightforward wafer-level fabrication scheme, which allows for precise integrated active dosing in the microliter range. To accomplish stroke-lengths needed for microliter-range applications, we utilize a new method of bending of a unimorph-composite-actuator film. The unimorph composite actuator consists of a temperature-sensitive silicone elastomer composite, i.e., polydimethylsiloxane, with incorporated expandable microspheres. The fabricated micropumps successfully demonstrated precise liquid-volume control, both at low and high flow rates, and show a standard deviation of 6.7% for consecutive pump experiments. Moreover, the method of fluorescent thermometry was used to measure the thermal load on liquid volumes dispensed with the micropumps. The liquid temperature reaches a maximum of 50 degrees C during the operation. The presented fully integrated single-use micropumps are electrically controllable, do not require external means for liquid actuation, are made of low-cost materials only, and might potentially be used in drug-delivery applications.

Keyword
Fabrication; Fluidics; Micropumps; Wafer-scale integration; Actuators; Bending (deformation); Buckling; Composite films; Microspheres; Pumps; Temperature; WSI circuits; Composite actuators; Microliter-range pumps; Wafer-level fabrication scheme; Microfluidics
National Category
Other Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
urn:nbn:se:kth:diva-7399 (URN)10.1109/JMEMS.2007.901642 (DOI)000248578700003 ()2-s2.0-34547684912 (Scopus ID)
Note

QC 20100817

Available from: 2007-08-21 Created: 2007-08-21 Last updated: 2017-12-14Bibliographically approved
4. 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: 2017-12-12Bibliographically approved
5. The fabrication of microfluidic structures by means of full-wafer adhesive bonding using a poly(dimethylsiloxane) catalyst
Open this publication in new window or tab >>The fabrication of microfluidic structures by means of full-wafer adhesive bonding using a poly(dimethylsiloxane) catalyst
2007 (English)In: Journal of Micromechanics and Microengineering, ISSN 0960-1317, E-ISSN 1361-6439, Vol. 17, no 8, 1710-1714 p.Article in journal (Refereed) Published
Abstract [en]

In this work, we present the use of a PDMS ( poly( dimethylsiloxane)) curing-agent as the intermediate layer for adhesive full-wafer bonding suitable for fabrication of microfluidic structures. The curing-agent of the two-component silicone rubber (Sylgard 184) is spin coated on a substrate, brought into contact with another PDMS layer and heat cured to create an irreversible seal which is as strong as or even stronger than plasma-assisted PDMS bonding. The maximum bond strength is measured to 800 kPa when bonding together PDMS and silicon. The applicability of the new PDMS adhesive bonding method is verified by means of fabricating microfluidic structures. Using this method allows for wafer-level bonding of PDMS to various materials such as PDMS, glass or silicon and more importantly to selectively bond different layers by using a patterned adhesive bonding technique. Moreover, precise alignment of the structural layers is facilitated since curing is initiated upon heat which is an advantage when fabricating multilayer microfluidic devices.

Keyword
Catalysts; Microfabrication; Microstructure; Silicon wafers; Spin coating; Full-wafer adhesive bonding; Microfluidic structures; Microfluidics
National Category
Other Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
urn:nbn:se:kth:diva-7402 (URN)10.1088/0960-1317/17/8/038 (DOI)000248776800037 ()2-s2.0-34547655760 (Scopus ID)
Note
QC 20100817Available from: 2007-08-21 Created: 2007-08-21 Last updated: 2017-12-14Bibliographically approved
6. A Compact, Low-cost Microliter-range Liquid Dispenser based on Expandable Microspheres
Open this publication in new window or tab >>A Compact, Low-cost Microliter-range Liquid Dispenser based on Expandable Microspheres
Show others...
2006 (English)In: Journal of Micromechanics and Microengineering, ISSN 0960-1317, E-ISSN 1361-6439, Vol. 16, no 12, 2740-2746 p.Article in journal (Refereed) Published
Abstract [en]

This work presents a new low-cost liquid dispenser for the dispensing of microliters to milliliter volumes. The dispensing mechanism is based on a thermal actuator where highly expandable microspheres expand into a liquid reservoir consequently displacing any stored liquid. All device components are made out of low-cost materials and the fabrication process has the potential for high volume batch manufacturing. The device utilizes the property of the expandable microspheres to form a heat insulating layer between the heat source and the delivered liquid. Moreover, it does not require any feed back or complicated flow metering. The device was successfully tested showing a mean dispensed volume of 101 mu 1 with a standard deviation of 3.2% and with a maximum temperature of 59 degrees C in the liquid during actuation. It was shown that the dispenser is strong enough to deliver against counter pressures as high as 75 kPa. The device can also function as a low flow rate dispenser as demonstrated in a microfluidic dye laser application. The flow rate can be controlled between 1 mu 1 h(-1) and 2400 mu 1 h(-1) by adjusting the actuation power.

Keyword
FLOW-CONTROL; VALVE; Actuators; Dye lasers; Fluidics; Pressure effects; Reservoirs (water); Thermal insulating materials; Expandable microspheres; Heat insulating layers; Milliliter volumes; Volume batch manufacturing; Dispensers
National Category
Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
urn:nbn:se:kth:diva-7458 (URN)10.1088/0960-1317/16/12/030 (DOI)000242475200030 ()2-s2.0-33846117051 (Scopus ID)
Note

QC 20100623

Available from: 2007-09-10 Created: 2007-09-10 Last updated: 2017-12-14Bibliographically approved
7. Painless Drug Delivery through Microneedle-based Transdermal Patches featuring Active Infusion
Open this publication in new window or tab >>Painless Drug Delivery through Microneedle-based Transdermal Patches featuring Active Infusion
Show others...
2008 (English)In: IEEE Transactions on Biomedical Engineering, ISSN 0018-9294, E-ISSN 1558-2531, Vol. 55, no 3, 1063-1071 p.Article in journal (Refereed) Published
Abstract [en]

This paper presents the first microneedle-based transdermal patch with integrated active dispensing functionality. The electrically controlled system consists of a low-cost dosing and actuation unit capable of controlled release of liquid in the microliter range at low flow-rates and minimally invasive, side-opened, microneedles. The system was successfully tested in vivo by insulin administration to diabetic rats. Active infusion of insulin at 2 mu l/h was compared to passive, diffusion-driven, delivery. Continuous active infusion caused significantly higher insulin concentrations in blood plasma. After a 3-h delivery period, the insulin concentration was five times larger compared to passive delivery. Consistent with insulin concentrations, actively administered insulin resulted in a significant decrease of blood glucose levels. Additionally, insertion and liquid injection was verified on human skin. This study shows the feasibility of a patch-like system with on-board liquid storage and dispensing capability. The proposed device represents a first step towards painless and convenient administration of macromolecular drugs such as insulin or vaccines.

Keyword
drug delivery; insulin; intradermal; microneedles; transdermal; HOLLOW MICRONEEDLES; MEMS MATERIALS; IN-VIVO; DEVICES; BIOCOMPATIBILITY; IMMUNIZATION; PENETRATION; TECHNOLOGY; TRANSPORT; FUTURE
National Category
Medical Laboratory and Measurements Technologies
Identifiers
urn:nbn:se:kth:diva-7461 (URN)10.1109/TBME.2007.906492 (DOI)000253733800023 ()18334398 (PubMedID)2-s2.0-39749199632 (Scopus ID)
Note
QC 20100624Available from: 2007-09-10 Created: 2007-09-10 Last updated: 2017-12-14Bibliographically approved

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