Implantable multi-LED devices for optogenetic studies

Abstract: This thesis reports on the development of implantable devices for optical stimulation of neural and cardiac tissue. The work describes novel approaches to realize probes with integrated light-emitting diodes (LEDs), their interface to the external instrumentation, a compact LED driving circuit, as well as their successful application in several in vivo and ex vivo optogenetic experiments. The implantable part of these devices is a slender probe shank comprising a linear array of up to 10 LEDs on its distal end. A broader part at the other end known as the probe base hosts the electrical connections for the device driving circuitry. The devices presented in this work are categorized into two types, primarily on the basis of the applied LED technology. The first approach introduces a compact silicon (Si) probe with one or two probe shanks with up to 20 micro-LEDs (μLEDs) emitting at a peak wavelength of 455nm of light. The μLEDs have a circular emitting surface of diameter 100 μm, whereas the probe shank has a cross-section 150 μm×65 μm. The second type is based on an approach combining commercially available miniature LED chips that are flipchip bonded to flexible polyimide (PI) substrates with a Si stiffening structure. The Si part imparts rigidity and planarizes the probe surface, thereby resulting in LED-chip probes with a probe shank cross-section of 285 μm×70 μm. Apertures implemented in the Si stiffener with diameters in the range of 25 μm to 175 μm enable localized neural stimulation. Two further LED-chip probe variants with up to 12 LEDs offer individually controllable bi-directional illumination. So-called optrodes feature up to 16 recording sites for electrical recording in addition to the optical functionality. They are realized in the form of planar and three-dimensional devices.
All devices are interconnected to external instrumentation using 10-μm-thin and up to 1.5-mm-wide flexible PI ribbon cables with a line resistance of about 1.1mm–1 of cable length. The time-averaged optical radiant flux for the μLED and LED-chip probes with apertures of diameter 100 μm is about 43 μW and 24 μW, respectively, when operated with 5mA at a duty cycle of 10%. In order to determine the device endurance in an electrolyte, a harsher electrical functionality stress test has been employed than reported so far. The applied multilayer polymer encapsulation of the devices endures for at least 24 h by accumulating an LED on time of approximately 9500 s in contrast to about 210 s for a typical one-day-long acute in vivo experiment where LEDs are operated with a much lower electrical power. In view of the thermal influence of LEDs on the surrounding material, integrated temperature sensors enable to obtain the temperature increase during operation of LEDs. The devices were operated with parameters typically used in animal experiments for a single 500-ms-long pulse and a pulse train consisting of 10-ms-long pulses repeated at 6 Hz, 10 Hz, 15 Hz and 50 Hz. The maximum device temperature increase of about 1.5K is measured by operating the LEDs with a single pulse. Moreover, a three-stage lumped-element thermal model has allowed to elucidate the temperature evolution in the device and its surrounding when operated by a pulse train.
Compact LED controllers weighing less than one gram with dimensions below 23mm×10mm have been designed that can individually address up to 20 LEDs on single and dual shank probes. The devices developed in this work have been used in several experiments in both neural and cardiac tissue of mice. The μLED probes have been validated in the cortex of mice to demonstrate layer-specific optical stimulation of neurons. Similarly, the LED-chip probes have been validated in the thalamus and cortex of anaesthetized mice. The LED-chip probes have also been used in proof-of-principle studies in perfused mouse hearts to demonstrate the so-called optical pacing. Further experimental trials using the LED-chip probe variants with bi-directional illumination in the cardiac septum have confirmed selective optical stimulation of the two ventricles, thereby opening new avenues in cardiac optogenetics

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Universität Freiburg, Dissertation, 2021

Klassifikation und Themen

• Schlagwort: Optogenetik ; Implantat ; MEMS ; Herzschrittmacher ; Mikrosystemtechnik

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2021
• Urheber: Ayub, Suleman
• Beteiligte Personen und Organisationen: Paul, Oliver ; Albert-Ludwigs-Universität Freiburg. Fakultät für Angewandte Wissenschaften

Weitere Informationen

• DOI: 10.6094/UNIFR/219031
• URN: urn:nbn:de:bsz:25-freidok-2190313
• Rechteinformation: Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 14.08.2025, 11:03 MESZ