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Polymer Nanoliter Well Arrays for Liquid Storage and Rapid On-demand Electrochemical Release
KTH, School of Electrical Engineering (EES), Micro and Nanosystems.ORCID iD: 0000-0001-9651-4900
KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
KTH, School of Electrical Engineering (EES), Micro and Nanosystems. KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.ORCID iD: 0000-0001-8248-6670
2018 (English)In: Sensors and actuators. B, Chemical, ISSN 0925-4005, E-ISSN 1873-3077, Vol. 267, p. 111-118Article in journal (Refereed) Published
Abstract [en]

Polymer microfluidic systems are of increasing importance in several applications in biomedicine and biosensing. The integrated encapsulation, storage, and controlled release of small amounts of liquid in such systems remains an unresolved technical challenge. Here, we report two methods for the room-temperature and adhesive-free sealing of 1–330 nanoliter volumes of liquid in off-stoichiometry thiol-ene polymer well arrays by spontaneous bonding to 200 nm thin gold films. Sealed well arrays were stored for more than one month in a liquid environment with <10% liquid loss, and for more than one week in air with minimal loss. We demonstrated that controlling the electrical potential and polarity over encapsulated wells allowed for selecting one of two well opening mechanisms: slow anodic electrochemical etching, or rapid electrolytic gas pressure-induced bursting of the gold film. The results may find potential applications in diagnostic testing, in vivo drug delivery, or in spatio-temporal release of chemical compounds in biological assays.

Place, publisher, year, edition, pages
Elsevier, 2018. Vol. 267, p. 111-118
Keywords [en]
nanoliter liquid encapsulation, nanoliter liquid storage, electrochemical liquid release, off-stoichiometry thiol-ene (OSTE) polymer, nanoliter well arrays
National Category
Polymer Technologies Medical Biotechnology Biomedical Laboratory Science/Technology Electrical Engineering, Electronic Engineering, Information Engineering
Research subject
Electrical Engineering
Identifiers
URN: urn:nbn:se:kth:diva-215017DOI: 10.1016/j.snb.2018.04.013ISI: 000432775600014Scopus ID: 2-s2.0-85045401734OAI: oai:DiVA.org:kth-215017DiVA, id: diva2:1145649
Note

QC 20180515

Available from: 2017-09-29 Created: 2017-09-29 Last updated: 2019-11-04Bibliographically approved
In thesis
1. Thiol-ene and Thiol-ene-epoxy Based Polymers for Biomedical Microdevices
Open this publication in new window or tab >>Thiol-ene and Thiol-ene-epoxy Based Polymers for Biomedical Microdevices
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Within healthcare there is a market pull for biomedical devices that can rapidly perform laboratory processes, such as diagnostic testing, in a hand-held format. For this reason, biomedical devices must become smaller, more sophisticated, and easier to use for a reasonable cost. However, despite the accelerating academic research on biomedical microdevices, and especially plastic-based microfluidic chips, there is still a gap between the inventions in academia and their benefit to society. To bridge this gap there is a need for new materials which both exhibit similar properties as industrial thermoplastics, and that enable rapid prototyping in academia.

In this thesis, thiol-ene and thiol-ene-epoxy thermosets are evaluated both in terms of their suitability for rapid prototyping of biomedical microdevices and their potential for industrial manufacturing of “lab-on-chips”.

The first part of the thesis focuses on material development of thiol-ene and thiol-ene-epoxy thermosets. Chemical and mechanical properties are studied, as well as in vitro biocompatibility with cells.

The second part of the thesis focuses on microfabrication methods for both thermosets. This includes reaction injection molding, photostructuring, and surface modification. It is demonstrated how thiol-ene and thiol-ene-epoxy both provide advantageous thermo-mechanical properties and versatile surface modifications via “thiol-click chemistry”.

In the end of the thesis, two applications for both polymer platforms are demonstrated. Firstly, thiol-ene is used for constructing nanoliter well arrays for liquid storage and on-demand electrochemical release. Secondly, thiol-ene-epoxy is used to enhance the biocompatibility of neural probes by tuning their flexibility.

It is concluded that both thiol-ene and thiol-ene-epoxy thermosets exhibit several properties that are highly suitable for rapid prototyping as well as for scalable manufacturing of biomedical microdevices.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2017. p. 93
Series
TRITA-EE, ISSN 1653-5146 ; 2017:129
Keywords
biomedical microdevices, lab-on-a-chip, off-stoichiometry thiol-ene, OSTE, thiol-ene-epoxy, hybrid polymer networks, reaction injection molding, photostructuring, surface modification, bonding, liquid encapsulation, biocompatibility
National Category
Electrical Engineering, Electronic Engineering, Information Engineering Medical Engineering Medical Biotechnology Materials Engineering
Research subject
Electrical Engineering
Identifiers
urn:nbn:se:kth:diva-215110 (URN)978-91-7729-530-3 (ISBN)
Public defence
2017-11-13, F3, Lindstedtsvägen 26, Stockholm, 10:15 (English)
Opponent
Supervisors
Funder
EU, European Research CouncilEU, FP7, Seventh Framework Programme
Note

QC 20171003

Available from: 2017-10-03 Created: 2017-10-02 Last updated: 2017-10-03Bibliographically approved
2. Digital Electrical DNA Sensing
Open this publication in new window or tab >>Digital Electrical DNA Sensing
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Molecule detection is a workhorse in life sciences and medicine, for example in cancer diagnosis and virus and bacterial detection. DNA analysis can provide vital information about the state of a host organism and its medical and health condition. A central challenge in DNA sensing lays in obtaining the following key detection characteristics in a single device: low limit of detection, small sample volume, high specificity, quantification, rapid time-to-result at a low cost.

Here we investigate whether direct electrical DNA sensing in a miniaturized detector can enable such performance. The detector consists of a gold-coated thin porous membrane, functionalized with oligonucleotides receptors, that is sandwiched between two off-stoichiometric thiol-ene-epoxy layers. The device works as follows. First, target DNA in the sample is specifically recognized by padlock probe hybridization and ligation. Second, the target-receptor circular molecules are amplified by rolling circle amplification (RCA), generating long ssDNA concatemers (RCP). Third, the RCPs are stretched through the membrane pores. Fourth, DNA metallization was used to form the gold nanowires bridging both sides of membrane pores after gold enhancement, which results in a conductive path that is measured with a simple resistance measurement. The thesis describes the engineering technology that enables low LoD detection of ssDNA using a digital measurement and details the development and optimization of the detector fabrication and operation, including structural design, materials, and microfluidic operation. We demonstrated a detector with sub-aM LoD, high specificity and simple operation in a miniaturized and uncomplicated format.

 Furthermore, the thesis studies the long-term liquid storage in nL scale well arrays fabricated in off-stoichiometric thiol-ene (OSTE). We demonstrated liquid storage with < 10 % loss of stored PBS buffer for 33 days and the on-demand electrically controlled liquid release.

The thesis presents the potential of a combination DNA detector with the method of liquid storage. Combining the on-chip liquid storage and DNA detection methods could provide a powerful alternative to conventional bio-detectors used in molecular diagnostics, and improved performance in multiplexed point-of-care sensing of (ultra-low abundant) biomolecules.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2019. p. 81
Series
TRITA-EECS-AVL ; 2019:38
Keywords
DNA detection, thiol-ene-epoxy, rolling circle amplification, digital measurement, DNA stretching, microwell-array, gold nanowires, electrical measurement, specificity, limit of detection, liquid storage, disease diagnosis, lab-on-a-chip, point-of-care.
National Category
Engineering and Technology Medical and Health Sciences
Identifiers
urn:nbn:se:kth:diva-250783 (URN)978-91-7873-162-6 (ISBN)
Public defence
2019-06-11, Q2, Malvinas väg 10, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

QC 20190508

Available from: 2019-05-08 Created: 2019-05-06 Last updated: 2019-05-14Bibliographically approved

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van der Wijngaart, Wouter

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