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Chemical delivery array with millisecond neurotransmitter release
Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.ORCID iD: 0000-0002-9845-446X
Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.ORCID iD: 0000-0001-5154-0291
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2016 (English)In: Science Advances, E-ISSN 2375-2548, Vol. 2, no 11, article id e1601340Article in journal (Refereed) Published
Abstract [en]

Technologies that restore or augment dysfunctional neural signaling represent a promising route to deeper understanding and new therapies for neurological disorders. Because of the chemical specificity and subsecond signaling of the nervous system, these technologies should be able to release specific neurotransmitters at specific locations with millisecond resolution. We have previously demonstrated an organic electronic lateral electrophoresis technology capable of precise delivery of charged compounds, such as neurotransmitters. However, this technology, the organic electronic ion pump, has been limited to a single delivery point, or several simultaneously addressed outlets, with switch-on speeds of seconds. We report on a vertical neurotransmitter delivery device, configured as an array with individually controlled delivery points and a temporal resolution of 50 ms. This is achieved by supplementing lateral electrophoresis with a control electrode and an ion diode at each delivery point to allow addressing and limit leakage. By delivering local pulses of neurotransmitters with spatiotemporal dynamics approaching synaptic function, the high-speed delivery array promises unprecedented access to neural signaling and a path toward biochemically regulated neural prostheses.

Place, publisher, year, edition, pages
Washington: American Association for the Advancement of Science (A A A S) , 2016. Vol. 2, no 11, article id e1601340
National Category
Atom and Molecular Physics and Optics Computer Engineering Other Engineering and Technologies not elsewhere specified Biomedical Laboratory Science/Technology Signal Processing
Identifiers
URN: urn:nbn:se:liu:diva-133161DOI: 10.1126/sciadv.1601340ISI: 000391267800033PubMedID: 27847873OAI: oai:DiVA.org:liu-133161DiVA, id: diva2:1055206
Available from: 2016-12-12 Created: 2016-12-12 Last updated: 2020-12-07Bibliographically approved
In thesis
1. Organic electronics for precise delivery of neurotransmitters
Open this publication in new window or tab >>Organic electronics for precise delivery of neurotransmitters
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Organic electronic materials, that is, carbon-based compounds that conduct electricity, have emerged as candidates for improving the interface between conventional electronics and biological systems. The softness of these materials matches the elasticity of biological tissue better than conventional electronic conductors, allowing better contact to tissue, and the mixed ionic-electronic conductivity can improve the signal transduction between electronic devices and electrically excitable cells. This improved communication between electronics and tissue can significantly enhance, for example, electrical stimulation for therapy and electrical recording for diagnostics.

The ionic conductivity of organic electronic materials makes it possible to achieve ion-specific ionic currents, where the current consists of migration of specific ions. These ions can be charged signalling substances, such as neurotransmitters, that can selectively activate or inhibit cells that contain receptors for these substances. This thesis describes the development of chemical delivery devices, where delivery is based on such ion-specific currents through ionically and electronically conducting polymers. Delivery is controlled by electrical signals, and allows release of controlled amounts of neurotransmitters, or other charged compounds, to micrometer-sized regions.

The aims of the thesis have been to improve spatial control and temporal resolution of chemical delivery, with the ultimate goal of selective interaction with individual cells, and to enable future therapies for disorders of the nervous system. Within the thesis, we show that delivery can alleviate pain through local delivery to specific regions of the spinal cord in an animal model of neuropathic pain, and that epilepsy-related signalling can be suppressed in vitro. We also integrate the delivery device with electrodes for sensing, to allow simultaneous electrical recording and delivery at the same position. Finally, we improve the delay from electrical signal to chemical delivery, approaching the time domain of synaptic signaling, and construct devices with several individually controlled release sites.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. p. 108
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1817
National Category
Textile, Rubber and Polymeric Materials Condensed Matter Physics Biomedical Laboratory Science/Technology Materials Chemistry Neurosciences
Identifiers
urn:nbn:se:liu:diva-133164 (URN)10.3384/diss.diva-133164 (DOI)978-91-7685-616-1 (ISBN)
Public defence
2017-01-11, Kåkenhus sal K3 (Önnesjösalen), Linköpings Universitet, Norrköping, 10:00 (English)
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Supervisors
Available from: 2016-12-12 Created: 2016-12-12 Last updated: 2019-10-29Bibliographically approved
2. Organic Bioelectronics for Neurotransmitter Release at the Speed of Life
Open this publication in new window or tab >>Organic Bioelectronics for Neurotransmitter Release at the Speed of Life
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The signaling dynamics in neuronal networks includes processes ranging from lifelong neuromodulation to direct synaptic neurotransmission. In chemical synapses, the time delay it takes to pass a signal from one neuron to the next lasts for less than a millisecond. At the post-synaptic neuron, further signaling is either up- or down-regulated, dependent on the specific neurotransmitter and receptor. While this up- and down-regulation of signals usually runs perfectly well and enables complex performance, even a minor dysfunction of this signaling system can cause major complications, in the shape of neurological disorders. The field of organic bioelectronics has the ability to interface neurons with high spatiotemporal recording and stimulation techniques. Local chemical stimulation, i.e. local release of neurotransmitters, enables the possibility of artificially altering the chemical environment in dysfunctional signaling pathways to regain or restore neural function. To successfully interface the biological nervous system with electronics, a range of demands must be met. Organic bioelectronic techniques and materials are capable of reaching the demands on the biological as well as the electronic side of the interface. These demands span from high performance biocompatible materials, to miniaturized and specific device architectures, and high dose control on demand within milliseconds.

The content of this thesis is a continuation of the development of organic bioelectronic devices for neurotransmitter delivery. Organic materials are utilized to electrically control the dose of charged neurotransmitters by translating electric charge into controlled artificial release. The first part of the thesis, Papers 1 and 2, includes further development of the resistor-type release device called the organic electronic ion pump. This part includes material evaluation, microfluidic incorporation, and device design considerations. The aim for the second part of this thesis, Papers 3 and 4, is to enhance temporal performance, i.e. reduce the delay between electrical signal and neurotransmitter delivery to corresponding delay in biological neural signaling, while retaining tight dosage control. Diffusion of neurotransmitters between nerve cells is a slow process, but since it is restricted to short distances, the total time delay is short. In our organic bioelectronic devices, several orders of magnitude in speed can be gained by switching from lateral to vertical delivery geometries. This is realized by two different types of vertical diodes combined with a lateral preload and waste configuration. The vertical diode assembly was further expanded with a control electrode that enables individual addressing in each of several combined release sites. These integrated circuits allow for release of neurotransmitters with high on/off release ratios, approaching delivery times on par with biological neurotransmission.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2020. p. 77
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 2104
National Category
Electrical Engineering, Electronic Engineering, Information Engineering Polymer Technologies Medical Engineering
Identifiers
urn:nbn:se:liu:diva-171789 (URN)10.3384/diss.diva-171789 (DOI)9789179297558 (ISBN)
Public defence
2021-01-13, Online and K1 (kåkenhus) Please contact Jennie Jordenlöv, jennie.jordenlov@liu.se to get the Zoom link, Campus Norrköping, Norrköping, 14:00 (English)
Opponent
Supervisors
Available from: 2020-12-07 Created: 2020-12-07 Last updated: 2021-01-18Bibliographically approved

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