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Zinc Oxide Nanostructure Based Electrochemical Sensors and Drug Delivery to Intracellular Environments
Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, The Institute of Technology.
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The nanoscale science and nanostructure engineering have well established in the fabrication of novel electrochemical biosensors with faster response and higher sensitivity than of planar sensor configurations. Moreover nanostructures are suggested and used as efficient carrier of photosensitizers for cancerous cell treatment. The semi-conductor zinc oxide (ZnO) nanostructures have attracted much interest because of its unique piezoelectric, polar semiconducting, large surface area, catalytic properties, and being biosafe and biocompatible combined with the easiness of growth. This implies that ZnO nanostructures have a wide range of applications in optoelectronics, sensors, transducers, energy conversion and medical sciences. The aim of this study is to highlight recent developments in materials and techniques for electrochemical biosensing, photodynamic therapy, design, operation, and fabrication. The sensors in this study were used to detect and monitor real changes of metal ions and glucose across human fat cells and frog cells using changes in the electrochemical potential at the interface to the intracellular microenvironments. This thesis relates specifically to “zinc oxide nanostructure based electrochemical sensors and drug delivery to intracellular environments” for biological, biochemical and chemical applications.

The first part of the thesis presents extra and intracellular studies on metal ions such as Ca2+, Mg2+, and Na+…..etc selectively sensed by using ZnO nanorods grown on the tip of a borosilicate glass capillary (0.7 μm in diameter) with the aim to produce proto-type electrochemical extra/intracellular biosensors. The single human adipocyte and frog oocyte cells were used to selectively measure the intracellular free metal ions concentration. To make the sensors selective for metal ions with sufficient selectivity and stability, plastic membrane coatings containing specific ionophores were applied. These functionalized ZnO nanorods sensors showed high sensitivity and good stability with linear electrochemical potential versus a wide metal ion concentration range of interest. The measured intracellular values were consistent with values reported in the literature. Furthermore we have successfully determined that the intracellular potassium (K+) concentration decrease is not obligatory for apoptosis. The aim of this study is to show the possibility of using K+ selective microelectrode to detect and monitor intracellular changes of K+ concentration during injection of various test solution and chemically induced apoptosis in Xenopus laevis oocytes parallel with electrophysiological measurements to verify the accuracy.

The second part, presents the calcium ion (Ca2+) detection using functionalized ZnO nanorods attached as an extended gate metal oxide semiconductor field effect transistor (MOSFET). The electrochemical response was coupled directly to the gate of a commercial MOSFET to study the I-V characterization. Here we verified that ZnO nanorods grown on any thin wire can be combined with conventional electronic component to produce a sensitive and selective biosensor.

In the third part, we have performed the experiment to determine glucose concentration intracellularly and in airway surface liquid (ASL) with functionalized ZnO nanorod-coated microelectrodes. In this study, the GOD enzyme was immobilised electrostatically, drawing on the fact that there is a large difference in the isoelectric points of ZnO and glucose oxidase. Insulin has been found to affect the glucose uptake in human adipocytes and frog Xenopus laevis. The large size of these cells makes it possible to microinject specific reagents that interrupt or activate signal transmission to glucose. The measured glucose concentration in human adipocytes or frog oocytes and ASL using our ZnO nanorod sensor was consistent with values of glucose concentration reported in the literature by using other indirect techniques.

The fourth and final part covers the application of ZnO nanorods to cancer cells for photodynamic therapy. The ZnO nanorods were conjugated with protoporphyrin for local mediated photochemistry and efficient treatment of a single cancer cell. The ZnO nanorods were used as an efficient photosensitizer carrier system and at the same time providing intrinsic white light to achieve necrosis of the cancer cell. Breast cancer cells were used to study the catalytic effect of ZnO for treatment. The grown ZnO nanorods were conjugated with protoporphyrin dimethyl ester (PPDME), which absorbs the light emitted by the ZnO nanorods and cause the cytotoxicity which appears to involve the generation of reactive singlet oxygen inside the cell.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press , 2011. , 64 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1376
Keyword [en]
ZnO nanorods, Intracellular electrochemical sensor, Functionalization, Metal ions, Glucose, Human Adipocytes, Frog Oocytes, Airway surface liquid
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:liu:diva-68856ISBN: 978-91-7393-142-7 (print)OAI: oai:DiVA.org:liu-68856DiVA: diva2:421436
Public defence
2011-09-02, K3, Kåkenhus, Campus Norrköping, Linköpings universitet, Norrköping, 10:15 (English)
Opponent
Supervisors
Available from: 2011-06-08 Created: 2011-06-08 Last updated: 2014-01-15Bibliographically approved
List of papers
1. Studies on Calcium Ion Selectivity of ZnO Nanowire Sensors Using Ionophore Membrane Coatings
Open this publication in new window or tab >>Studies on Calcium Ion Selectivity of ZnO Nanowire Sensors Using Ionophore Membrane Coatings
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2008 (English)In: Research Letters in Nanotechnology, ISSN 1687-6849, Vol. 2008, no Article ID 701813Article in journal (Refereed) Published
Abstract [en]

Zinc oxide nanorods with 100nm diameter and 900nm length were grown on the surface of a silver wire (0.25mm in diameter)

with the aim to produce electrochemical nanosensors. It is shown that the ZnO nanorods exhibit a Ca2+-dependent electrochemical

potentiometric behavior in an aqueous solution. The potential difference was found to be linear over a large logarithmic

concentration range (1 μM to 0.1 M) using Ag/AgCl as a reference electrode and the response time was less than one minute.

In order to adapt the sensors for calcium ion measurements in biological fluids with sufficient selectivity and stability, plastic

membrane coatings containing ionophores were applied. These functionalized ZnO nanorods sensors showed a high sensitivity

(26.55 mV/decade) and good stability.

Place, publisher, year, edition, pages
Hindawi Publishing Corporation, 2008
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-19514 (URN)10.1155/2008/701813 (DOI)
Available from: 2009-06-25 Created: 2009-06-25 Last updated: 2014-01-15Bibliographically approved
2. Functionalized zinc oxide nanorod with ionophore-membrane coatingas an intracellular Ca2+ selective sensor
Open this publication in new window or tab >>Functionalized zinc oxide nanorod with ionophore-membrane coatingas an intracellular Ca2+ selective sensor
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2009 (English)In: Applied Physics Letters, ISSN 0003-6951, E-ISSN 1077-3118, Vol. 95, no 2, 23703- p.Article in journal (Refereed) Published
Abstract [en]

The tip of a borosilicate glass capillary with functionalized hexagonal ZnO nanorods was used to make a sensitive electrochemical intracellular Ca2+ sensor. To adjust the sensor for Ca2+ measurements with sufficient selectivity and stability, polyvinyl chloride (PVC) membrane containing Ca2+ ionophores were coated on the surface. The membrane covered ZnO nanorods exhibited a Ca2+-dependent electrochemical potential difference versus an Ag/AgCl reference electrode. The potential difference was linear over a large concentration range (100 nM to 10 mM). The measurements of Ca2+ concentrations using our ZnO nanorods sensor in human fat cells or in frog egg cells were consistent with values of Ca2+ concentrations reported in the literature. This nanoelectrode device paves the way to measurements of intracellular biochemical species in specific locations within single living cells.

Place, publisher, year, edition, pages
EBSCO/American Institute of Physics, 2009
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-19516 (URN)10.1063/1.3176441 (DOI)
Note
On the day of the defence date the status of this article was Submitted.Available from: 2009-06-25 Created: 2009-06-25 Last updated: 2014-01-15Bibliographically approved
3. Selective calcium ion detection with functionalized ZnO nanorods-extendedgate MOSFET
Open this publication in new window or tab >>Selective calcium ion detection with functionalized ZnO nanorods-extendedgate MOSFET
2009 (English)In: Biosensors & bioelectronics, ISSN 0956-5663, E-ISSN 1873-4235, Vol. 24, no 11, 3379-3382 p.Article in journal (Refereed) Published
Abstract [en]

Zinc oxide nanorod-extended gate field effect transistor (MOSFET) is demonstrated for the detection of calcium (Ca2+) ions. ZnO nanorods were grown on the surface of a silver wire to produce an electrochemical nanosensor for selectively detecting Ca2+. The electrochemical response from the interaction between the ZnO nanorods and Ca2+ in an aqueous solution is coupled directly to the gate of a field effect transistor (MOSFET). The induced voltage change on the gate results in a measureable current response. In order to adapt the sensors for Ca2+ ions measurements in biological fluids with sufficient selectivity and stability, a plastic membrane coating containing ionophores was applied on the nanorods. The sensor exhibited a linear response within the range of interest from 1 μM to 1 mM. This work demonstrates a simple technique for sensitive detection of Ca2+ ions by efficient transfer of the chemical response directly to a standard electronic component producing a low impedance signal.

Place, publisher, year, edition, pages
ELSEVIER, 2009
Keyword
Calcium ions, electrochemical sensor, ZnO nanorods, MOSFET
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-19515 (URN)10.1016/j.bios.2009.04.011 (DOI)
Available from: 2009-06-25 Created: 2009-06-25 Last updated: 2014-01-15Bibliographically approved
4. Intracellular potassium (K+) concentration decrease is not obligatory for apoptosis
Open this publication in new window or tab >>Intracellular potassium (K+) concentration decrease is not obligatory for apoptosis
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2011 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 286, no 46, 39823-39828 p.Article in journal (Refereed) Published
Abstract [en]

K+ efflux is observed as an early event in the apoptotic process in various cell types. Loss of intracellular K+ and subsequent reduction in ionic strength is suggested to release the inhibition of proapoptotic caspases. In this work, a new K+-specific microelectrode was used to study possible alterations in intracellular K+ in Xenopus laevis oocytes during chemically induced apoptosis. The accuracy of the microelectrode to detect changes in intracellular K+ was verified with parallel electrophysiological measurements within the same cells. In concordance with previous studies on other cell types, apoptotic stimuli reduced the intracellular K+ concentration in Xenopus oocytes and increased caspase-3 activity. The reduction in intracellular K+ was prevented by dense expression of voltage-gated K (Kv) channels. Despite this, the caspase-3 activity was increased similarly in Kv channel expressing oocytes as in oocytes not expressing Kv channels. Thus, in Xenopus oocytes caspase-3 activity is not dependent on the intracellular concentration of K+.

Place, publisher, year, edition, pages
American Society for Biochemistry and Molecular Biology, 2011
Keyword
Caspase-3 activation, Electrophysiology, Intracellular K+ concentrations, K+-selective microelectrode, Xenopus laevis oocytes
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-68853 (URN)10.1074/jbc.M111.262725 (DOI)000296925700016 ()
Note
Funding agencies|Swedish Research Council||Swedish Heart-Lung Foundation||Swedish Brain Foundation||County Council of Ostergotland, King Gustaf V and Queen Victorias Freemasons Foundation||Swedish Society for Medical Research||Available from: 2011-06-08 Created: 2011-06-08 Last updated: 2017-12-11Bibliographically approved
5. Functionalised ZnO-nanorod-based selective electrochemical sensor for intracellular glucose
Open this publication in new window or tab >>Functionalised ZnO-nanorod-based selective electrochemical sensor for intracellular glucose
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2010 (English)In: Biosensors & bioelectronics, ISSN 0956-5663, E-ISSN 1873-4235, Vol. 25, no 10, 2205-2211 p.Article in journal (Refereed) Published
Abstract [en]

In this article, we report a functionalised ZnO-nanorod-based selective electrochemical sensor for intracellular glucose. To adjust the sensor for intracellular glucose measurements, we grew hexagonal ZnO nanorods on the tip of a silver-covered borosilicate glass capillary (0.7 mu m diameter) and coated them with the enzyme glucose oxidase. The enzyme-coated ZnO nanorods exhibited a glucose-dependent electrochemical potential difference versus an Ag/AgCl reference microelectrode. The potential difference was linear over the concentration range of interest (0.5-1000 mu M). The measured glucose concentration in human adipocytes or frog oocytes using our ZnO-nanorod sensor was consistent with values of glucose concentration reported in the literature; furthermore, the sensor was able to show that insulin increased the intracellular glucose concentration. This nanoelectrode device demonstrates a simple technique to measure intracellular glucose concentration.

Place, publisher, year, edition, pages
Elsevier Science B.V., Amsterdam., 2010
Keyword
ZnO nanorods; Functionalisation; Intracellular glucose; Electrochemical sensor
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-58381 (URN)10.1016/j.bios.2010.02.025 (DOI)000278702600004 ()
Note
Original Publication: Muhammad Asif, Syed Usman Ali, Omer Nour, Magnus Willander, Cecilia Brännmark, Peter Strålfors, Ulrika Englund, Fredrik Elinder and Bengt Danielsson, Functionalised ZnO-nanorod-based selective electrochemical sensor for intracellular glucose, 2010, Biosensors & bioelectronics, (25), 10, 2205-2211. http://dx.doi.org/10.1016/j.bios.2010.02.025 Copyright: Elsevier Science B.V., Amsterdam. http://www.elsevier.com/ Available from: 2010-08-13 Created: 2010-08-11 Last updated: 2017-12-12
6. In situ quantification of glucose concentration in airway surface liquid with functionalized ZnO nanorod-coated microelectrodes
Open this publication in new window or tab >>In situ quantification of glucose concentration in airway surface liquid with functionalized ZnO nanorod-coated microelectrodes
(English)Manuscript (preprint) (Other academic)
Abstract [en]

The surface of the airways that conduct gases into and out of the lungs has components that are crucial in protecting the host from inhaled and aspirated pathogens. The thin (4-7µm height) layer of airway surface liquid (ASL) that lines the airways has physicochemical properties that are important for normal function of these antimicrobial components. Among these properties, low glucose concentration is required for normal antimicrobial activity. Current methods for assessing the ASL have important flaws (temporal resolution, dilution factors, collection volume), which have been a recurring obstacle for understanding diseases in which ASL composition is abnormal. To circumvent these problems, microelectrodes coated with ZnO nanorods and immobilized glucose oxidase was used to determine glucose concentration in ASL of well-differentiated cultures of human airway epithelia. The sensor responded to glucose linearly over a concentration range of 0.128 to 8mM and the effects of electroactive interferents were minimal. The measured concentration of glucose in ASL was consistent with values previously reported. This method confirms the presence of a transepithelial glucose concentration gradient in human airway epithelia and is an important step towards characterizing the physicochemical properties of ASL and understanding diseases caused by changes in ASL composition.

Keyword
Zinc Oxide, Mucosa, Lung, Electrode, Glucose
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-68854 (URN)
Available from: 2011-06-08 Created: 2011-06-08 Last updated: 2014-01-15Bibliographically approved
7. Intracellular ZnO Nanorods Conjugated with Protoporphyrin for Local Mediated Photochemistry and Efficient Treatment of Single Cancer Cell
Open this publication in new window or tab >>Intracellular ZnO Nanorods Conjugated with Protoporphyrin for Local Mediated Photochemistry and Efficient Treatment of Single Cancer Cell
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2010 (English)In: NANOSCALE RESEARCH LETTERS, ISSN 1931-7573, Vol. 5, no 10, 1669-1674 p.Article in journal (Refereed) Published
Abstract [en]

ZnO nanorods (NRs) with high surface area to volume ratio and biocompatibility is used as an efficient photosensitizer carrier system and at the same time providing intrinsic white light needed to achieve cancer cell necrosis. In this letter, ZnO nanorods used for the treatment of breast cancer cell (T47D) are presented. To adjust the sample for intracellular experiments, we have grown the ZnO nanorods on the tip of borosilicate glass capillaries (0.5 mu m diameter) by aqueous chemical growth technique. The grown ZnO nanorods were conjugated using protoporphyrin dimethyl ester (PPDME), which absorbs the light emitted by the ZnO nanorods. Mechanism of cytotoxicity appears to involve the generation of singlet oxygen inside the cell. The novel findings of cell-localized toxicity indicate a potential application of PPDME-conjugated ZnO NRs in the necrosis of breast cancer cell within few minutes.

Place, publisher, year, edition, pages
Springer Science Business Media, 2010
Keyword
ZnO nanorods, Cancer cell necrosis, Photodynamic therapy, Protoporphyrin dimethyl ester
National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-61180 (URN)10.1007/s11671-010-9693-z (DOI)000283124800022 ()21076704 (PubMedID)
Available from: 2010-11-05 Created: 2010-11-05 Last updated: 2014-09-25
8. Growth and Structure of ZnO Nanorods on a Sub-Micrometer Glass Pipette and Their Application as Intracellular Potentiometric Selective Ion Sensors
Open this publication in new window or tab >>Growth and Structure of ZnO Nanorods on a Sub-Micrometer Glass Pipette and Their Application as Intracellular Potentiometric Selective Ion Sensors
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2010 (English)In: Materials, ISSN 1996-1944, Vol. 3, 4657-4667 p.Article in journal (Refereed) Published
Abstract [en]

This paper presents the growth and structure of ZnO nanorods on a sub-micrometer glass pipette and their application as an intracellular selective ion sensor. Highly oriented, vertical and aligned ZnO nanorods were grown on the tip of a borosilicate glass capillary (0.7 μm in diameter) by the low temperature aqueous chemical growth (ACG) technique. The relatively large surface-to-volume ratio of ZnO nanorods makes them attractive for electrochemical sensing. Transmission electron microscopy studies show that ZnO nanorods are single crystals and grow along the crystal’s c-axis. The ZnO nanorods were functionalized with a polymeric membrane for selective intracellular measurements of Na

 

+. The membrane-coated ZnO nanorods exhibited a Na+-dependent electrochemical potential difference versus

an Ag/AgCl reference micro-electrode within a wide concentration range from 0.5 mM to 100 mM. The fabrication of functionalized ZnO nanorods paves the way to sense a wide range of biochemical species at the intracellular level.

National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-64303 (URN)10.3390/ma3094657 (DOI)
Available from: 2011-01-21 Created: 2011-01-18 Last updated: 2016-08-31Bibliographically approved

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