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Electronic Control of Cell Cultures Using Conjugated Polymer Surfaces
Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, The Institute of Technology.
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In the field of bioelectronics various electronic materials and devices are used in combination with biological systems in order to create novel applications within cell biology and medicine. A famous example of a successful bioelectronics application is the pacemaker. Metals are the most common electrical conductors, whereas polymers are generally considered being insulators. However, in the late 1970s it was shown that a special class of polymers with conjugated double bonds, could in fact, after some chemical modifications, conduct electricity. This was the start of the research field known as conducting polymers, and then later on organic electronics, a research area that has grown rapidly during the last decades. Conjugated polymers are also suitable to interact and interface with cells and tissues, as they are generally soft, flexible and biocompatible. In addition, their chemical properties can be tailor-made through synthesis to fit biological requirements and functions. During the last years applications using organic bioelectronics have become numerous.

This thesis describes applications based on different conjugated polymers aiming to stimulate and control cell cultures. When culturing cells it is of interest to be able to control events such as adhesion, spreading, proliferation, differentiation and detachment. First, the impact of different polymer compositions and redox states on the adhesion of bacteria and subsequent biofilm formation was investigated. Similar polymer electrodes were also used to steer differentiation of neural stem cells, through changes in the surface exposure of a relevant biomolecule. Controlled delivery of molecules was achieved by coating nanoporous membranes with polymers that swell and contract when changing the redox state. Finally, electronic control over cell detachment using a water-soluble polymer was achieved. When applying a positive potential to this polymer, it swells, cracks and finally detaches, taking the cells that was cultured on top along with it. Together, the work and results presented in this thesis demonstrate a versatile conjugated polymer technology to achieve electronic control of the different growth stages of cell cultures as well as cellular functions.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2014. , 64 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1594
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:liu:diva-106254DOI: 10.3384/diss.diva-106254ISBN: 978-91-7519-340-3 (print)OAI: oai:DiVA.org:liu-106254DiVA: diva2:715047
Public defence
2014-05-23, K2, Kåkenhus, Campus Valla, Linköpings universitet, Linköping, 10:15 (English)
Opponent
Supervisors
Available from: 2014-04-30 Created: 2014-04-30 Last updated: 2017-02-03Bibliographically approved
List of papers
1. Salmonella Biofilm Modulation with Electrically Conducting Polymers
Open this publication in new window or tab >>Salmonella Biofilm Modulation with Electrically Conducting Polymers
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2014 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Biofilms are ubiquitous in many human activities, constituting a threat or an advantage depending on the context of application. It is therefore of great interest to obtain new materials to study and control how biofilms are formed. Here, heparin and DBS (dodecylbenzenesulfonate) are incorporated as counter-ions to the PEDOT (poly(3,4-ethylenedioxythiophene)) backbone, forming conducting polymer thin-films. Polymer synthesis is based on electrodeposition, allowing for the adjustment, during fabrication, of properties like charge and hydrophobicity, important in bacterial adhesion. The electrochemical redox state of the polymer is of fundamental importance in Salmonella enterica Serovar Typhimurium biofilm modulation. Oxidized composites show increased levels of biofilm growth compared to reduced and pristine polymer films. As a result, biofilm formation is modulated by the application of a low electric voltage. Moreover, biofilm morphology and topology are affected by both the electrochemical redox state and the incorporated counter-ion, making these materials a useful tool in biofilm engineering.

National Category
Polymer Chemistry Cell Biology
Identifiers
urn:nbn:se:liu:diva-106250 (URN)
Available from: 2014-04-30 Created: 2014-04-30 Last updated: 2017-02-03Bibliographically approved
2. Electrochemical Control of Growth Factor Presentation To Steer Neural Stem Cell Differentiation
Open this publication in new window or tab >>Electrochemical Control of Growth Factor Presentation To Steer Neural Stem Cell Differentiation
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2011 (English)In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 50, no 52, 12529-12533 p.Article in journal (Refereed) Published
Abstract [en]

Graphical Abstract

Let it grow: The conjugated polymer poly(3,4-ethylenedioxythiophene) (PEDOT) was synthesized with heparin as the counterion to form a cell culture substrate. The surface of PEDOT:heparin in the neutral state associated biologically active growth factors (see picture). Electrochemical in situ oxidation of PEDOT during live cell culture decreased the bioavailability of the growth factor and created an exact onset of neural stem cell differentiation.

Place, publisher, year, edition, pages
Weinheim: Wiley-VCH Verlagsgesellschaft, 2011
National Category
Polymer Chemistry Cell Biology
Identifiers
urn:nbn:se:liu:diva-72171 (URN)10.1002/anie.201103728 (DOI)000298332700018 ()22057546 (PubMedID)
Note
funding agencies|Swedish Research Council (VR)||Swedish Foundation for Strategic Research (SSF; the OBOE center)||Karolinska Institute||VR||Onnesjo foundation||Linkoping University||Available from: 2011-11-21 Created: 2011-11-21 Last updated: 2017-12-08
3. Electroresponsive Nanoporous Membranes by Coating Anodized Alumina with Poly(3,4-ethylenedioxythiophone) and Polypyrrole
Open this publication in new window or tab >>Electroresponsive Nanoporous Membranes by Coating Anodized Alumina with Poly(3,4-ethylenedioxythiophone) and Polypyrrole
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2014 (English)In: Macromolecular materials and engineering (Print), ISSN 1438-7492, E-ISSN 1439-2054, Vol. 299, no 2, 190-197 p.Article in journal (Refereed) Published
Abstract [en]

Electrically-active nanoporous membranes are prepared by coating the surface of anodized alumina with electroactive polymers using vapor phase polymerization with four combinations of conjugated polymers and doping ions: poly(3,4-ethylenedioxythiophone) and polypyrrole, FeCl3 and FeTs3. The permeability of the polymer-coated membranes is measured as a function of the applied electric potential. A reversible three-fold increase is found in molecular flux of a neutral dye for membranes in oxidized state compared to that in the reduced state. After analyzing various factors that may affect the molecular transport through these membranes, it is concluded that the observed behavior results mostly from swelling/deswelling of the polymers and from the confinement of the polymers inside the nanopores.

Place, publisher, year, edition, pages
Wiley-VCH Verlagsgesellschaft, 2014
Keyword
electroresponsive; membrane; nanopore; vapor phase polymerization
National Category
Materials Engineering
Identifiers
urn:nbn:se:liu:diva-103014 (URN)10.1002/mame.201200456 (DOI)000336481500006 ()
Available from: 2014-01-09 Created: 2014-01-09 Last updated: 2017-12-06
4. Electronic control of cell detachment using a self-doped conducting polymer
Open this publication in new window or tab >>Electronic control of cell detachment using a self-doped conducting polymer
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2011 (English)In: Advanced Materials, ISSN 0935-9648, E-ISSN 1521-4095, Vol. 23, no 38, 4403-4408 p.Article in journal (Refereed) Published
Abstract [en]

An electronic detachment technology based on thin films of a poly(3,4-ethylene-dioxythiophene) derivative is evaluated for controlled release of human epithelial cells. When applying a potential of 1 V, the redox-responsive polymer films detach and disintegrate and at the same time release cells cultured on top in the absence of any enzymatic treatment with excellent preservation of membrane proteins and cell viability.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2011
Keyword
bioelectronics;cell detachment;conducting polymers;electrochemistry;polymerization
National Category
Polymer Chemistry Cell Biology
Identifiers
urn:nbn:se:liu:diva-72170 (URN)10.1002/adma.201101724 (DOI)000297007000009 ()21960476 (PubMedID)
Available from: 2011-11-21 Created: 2011-11-21 Last updated: 2017-12-08
5. Electronic control over detachment of a self-doped water-soluble conjugated polyelectrolyte
Open this publication in new window or tab >>Electronic control over detachment of a self-doped water-soluble conjugated polyelectrolyte
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2014 (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 30, no 21, 6257-6266 p.Article in journal (Refereed) Published
Abstract [en]

Water-soluble conducting polymers are of interest to enable more versatile processing in aqueous media as well as to facilitate interactions with biomolecules. Here, we report a substituted poly(3,4-ethylenedioxythiophene) derivative (PEDOT-S:H) that is fully water-soluble and selfdoped. When electrochemically oxidizing a PEDOT-S:H thin film, the film detaches from the under-laying electrode. The oxidation of PEDOT-S:H starts with an initial phase of swelling followed by cracking before it finally disrupts and detaches from the electrode. We investigated the detachment mechanism and found that parameters such as the size, charge and concentration of ions in the electrolyte, the temperature and also the pH influence the characteristics of detachment. When oxidizing PEDOT-S:H, the positively charged polymer backbone is balanced by anions from the electrolyte solution and also by the sulphonate groups on the side chains (more self-doping). From our experiments, we conclude that detachment of the PEDOT-S:H film upon oxidation occurs in part due to swelling caused by an inflow of solvated anions and associated water, and in part due to rearrangements and strain within the film, caused by more self-doping. We believe that PEDOT-S:H detachment can be of interest in a number of different applications, including addressed and active control of the release of materials such as biomolecules and cell cultures.

Place, publisher, year, edition, pages
American Chemical Society, 2014
National Category
Polymer Chemistry Cell Biology
Identifiers
urn:nbn:se:liu:diva-106251 (URN)10.1021/la500693d (DOI)000336952800031 ()
Available from: 2014-04-30 Created: 2014-04-30 Last updated: 2017-12-05Bibliographically approved
6. Selective Detachment of Human Primary Keratinocytes and Fibroblasts Using an Addressable Conjugated Polymer Matrix
Open this publication in new window or tab >>Selective Detachment of Human Primary Keratinocytes and Fibroblasts Using an Addressable Conjugated Polymer Matrix
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2014 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Conjugated polymers have been used in several applications for electronic control of cell cultures over the last years. We have shown detachment of human endothelial cells using a thin film of a self-doped water-soluble conjugated polymer. Upon electrochemical oxidation, the film swells, cracks and finally detaches taking cells cultured on top along with it. The polymer can be patterned using standard photolithography. The detachment only occurs above a threshold potential of +0.7 V and this fact has been used to create a simple actively addressed matrix, based on a resistor network placed in an encapsulated back plane. The matrix has individually detachable pixels. In this paper we have evaluated detachment of human primary keratinocytes and fibroblasts using PEDOT-S:H. In addition, we have studied effects of serum proteins, added as nutrients to the cell culture medium, on the detachment properties. It was found that at prolonged incubation times protein adhesion effectively stopped the detachment. Using shorter incubation times before detachment, both keratinocytes and fibroblasts can be detached using a regular planar device as well as the matrix device for selective detachment. Spatial control of detachment could be of use when selecting cells for clonal expansion and in order to obtain a homogeneous starting population of cells aimed for tissue engineering purposes.

National Category
Polymer Chemistry Cell Biology
Identifiers
urn:nbn:se:liu:diva-106252 (URN)
Available from: 2014-04-30 Created: 2014-04-30 Last updated: 2017-02-03Bibliographically approved

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