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Design and Operation of Hybrid Microfluidic Iontronic Probes for Regulated Drug Delivery
Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering.
INSERM, INS, Inst Neurosci Syst, Aix Marseille University, Marseille, France.
INSERM, INS, Inst Neurosci Syst, Aix Marseille University, Marseille, France.
Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering.ORCID iD: 0000-0002-9845-446X
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2021 (English)In: Advanced Materials Technologies, E-ISSN 2365-709X, Vol. 6, no 2, article id 2001006Article in journal (Refereed) Published
Abstract [en]

Highly controlled drug delivery devices play an increasingly important role in the development of new neuroengineering tools. Stringent - and sometimes contradicting - demands are placed on such devices, ranging from robustness in freestanding devices, to overall device miniaturization, while maintaining precise spatiotemporal control of delivery with high chemical specificity and high on/off ratio. Here, design principles of a hybrid microfluidic iontronic probe that uses flow for long-range pressure-driven transport in combination with an iontronic tip that provides electronically fine-tuned pressure-free delivery are explored. Employing a computational model, the effects of decoupling the drug reservoir by exchanging a large passive reservoir with a smaller microfluidic system are reported. The transition at the microfluidic-iontronic interface is found to require an expanded ion exchange membrane inlet in combination with a constant fluidic flow, to allow a broad range of device operation, including low source concentrations and high delivery currents. Complementary to these findings, the free-standing hybrid probe monitored in real time by an external sensor is demonstrated. From these computational and experimental results, key design principles for iontronic devices are outlined that seek to use the efficient transport enabled by microfluidics, and further, key observations of hybrid microfluidic iontronic probes are explained.

Place, publisher, year, edition, pages
Hoboken, New Jersey: John Wiley & Sons, 2021. Vol. 6, no 2, article id 2001006
Keywords [en]
bioelectronics, drug delivery, iontronics, microfluidics, organic electronics
National Category
Medical Materials
Identifiers
URN: urn:nbn:se:liu:diva-172686DOI: 10.1002/admt.202001006ISI: 000607538700001OAI: oai:DiVA.org:liu-172686DiVA, id: diva2:1519237
Conference
2021/01/18
Funder
Swedish Foundation for Strategic Research Knut and Alice Wallenberg FoundationVinnovaSwedish Research CouncilEU, European Research Council, 2018
Note

Additional Funding agencies: FLAG‐ERA. Grant Number: JTC2017; EPIGRAPH. Grant Number: ANR‐17‐GRF2‐0001; Swedish Government Strategic Research Area in Materials Science on Advanced Functional Materials at Linköping University. Grant Number: 2009‐00971; A*MIDEX ION. Grant Number: 2IONXXID/REID/ID17HRU208

Available from: 2021-01-18 Created: 2021-01-18 Last updated: 2025-02-09Bibliographically approved
In thesis
1. 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)
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Available from: 2020-12-07 Created: 2020-12-07 Last updated: 2021-01-18Bibliographically approved

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Arbring Sjöström, TheresiaTybrandt, KlasPoxson, DavidSimon, Daniel TBerggren, Magnus

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