Michael Schwaerzle

GaN-based micro-LED arrays on flexible substrates for optical cochlear implants

Currently available cochlear implants are based on electrical stimulation of the spiral ganglion neurons. Optical stimulation with arrays of micro-sized light-emitting diodes (µLEDs) promises to increase the number of distinguishable frequencies. Here, the development of a flexible GaN-based micro-LED array as an optical cochlear implant is reported for application in a mouse model. The fabrication of 15 µm thin and highly flexible devices is enabled by a laser-based layer transfer process of the GaN-LEDs from sapphire to a polyimide-on-silicon carrier wafer. The fabricated 50 × 50 µm2 LEDs are contacted via conducting paths on both p- and n-sides of the LEDs. Up to three separate channels could be addressed. The probes, composed of a linear array of the said µLEDs bonded to the flexible polyimide substrate, are peeled off the carrier wafer and attached to flexible printed circuit boards. Probes with four µLEDs and a width of 230 µm are successfully implanted in the mouse cochlea both in vitro and in vivo. The LEDs emit 60 µW at 1 mA after peel-off, corresponding to a radiant emittance of 6 mW mm−2.

Ultracompact optrode with integrated laser diode chips and SU-8 waveguides for optogenetic applications

This paper reports on the design, fabrication and characterization of an innovative silicon-based neural probe with optical functionality. This so-called optrode is intended as an ultracompact tool for optogenetic applications in neuroscientific research. Beside platinum microe-lectrodes for electrical recording applications, bare laser diode (LD) chips combined with waveguides (WGs) implemented in the negative photoresist SU-8 are integrated on the probe. The assembly of the bare LD chips applies flip-chip and wire bonding and benefits of a lateral alignment accuracy better ±5 μm required for the efficient coupling of light into the 15-μm-wide and 13-μm-high WGs. Undesired tissue illumination due to stray light is effectively blocked using a micromachined cover chip adhesively bonded to the probe base. Probe shafts with a length of up to 8 mm and a thickness of 50 μm carrying four electrodes and two WGs each have been realized. The maximum optical output power per WG was measured to be 29.7 mW/mm2 for LDs with a center wavelength of 650 nm.

CMOS-Based High-Density Silicon Microprobe Arrays for Electronic Depth Control in Intracortical Neural Recording–Characterization and Application

This paper reports on the characterization and intracortical recording performance of high-density complementary-metal-oxide-semiconductor (CMOS)-based silicon microprobe arrays. They comprise multiplexing units integrated on the probe shafts being part of the signal transmission path. Their electrical characterization reveals a negligible contribution on the electrode impedances of 139 ±11 kΩ and 1.2 ±0.1 MΩ and on the crosstalks of 0.12% and 0.98% for iridium oxide ( IrOx) and platinum (Pt) electrodes, respectively. The power consumption of the single-shaft probe was found to be 57.5 μW during electrode selection. The noise voltage of the switches was determined to be 5.6 nV/√Hz; it does not measurably affect the probe performance. The recording selectivity of the electrode array is demonstrated by electrical potential measurements in saline solution while injecting a stimulating current using an external probe. In-vivo recordings in anesthetized rats using all 188 electrodes with a pitch of 40.7 μm are presented and analyzed in terms of single neural activity and signal-to-noise ratio. The concept of electronic depth control is proven by performing mechanical translation of the probe shaft while electronically switching to adjacent electrodes to compensate the mechanical shift.

Miniaturized 3×3 optical fiber array for optogenetics with integrated 460 nm light sources and flexible electrical interconnection

We report on the design, fabrication, assembly, as well as optical and thermal characterization of a novel MEMS-based optical probe array for optogenetic research. The system allows the optical stimulation of neural brain tissue at 3×3 independently controllable spots. It comprises nine high-efficiency light emitting diodes (LED) integrated in a micromachined silicon (Si) housing that ensures the mechanical stability and precise alignment of 5-mm-long optical glass fibers with a diameter of 125 μm. The fibers transmit the light emitted by the LEDs (center wavelength 456 nm) into the brain tissue. A highly flexible polyimide (PI) ribbon cable provides the electrical interconnection of the LEDs to a control unit. The compact housing (volume less than 2.2 mm3) is beneficial for chronic system implantations in rodents. Furthermore, the electrical-only interconnection of this array represents a distinct advantage over conventional systems using external light sources interfaced by optical fibers. The optical characterization of the array reveals an optical output power of up to 1.28 mW/mm2 at a drive current and duty cycle of 30 mA and 10%, respectively. The corresponding temperature increase of the silicon housing is 2.2 K only.

High-density probe with integrated thin-film micro light emitting diodes (μLEDs) for optogenetic applications

We report on the design, fabrication, assembly and characterization of an innovative neural probe with optical functionality for optogenetic applications in neuroscientific research. In contrast to existing systems, thin-film micro light-emitting diodes (μLEDs) are directly integrated in probes based on silicon (Si) substrates using a wafer-level bonding process. It allows to considerably shrink the overall probe dimensions despite an increased density of the integrated light sources. Our new system approach demonstrates the integration of multiple μLEDs with a size of 112×112 μm2 at a minimal pitch of 150 μm that can be controlled individually. The all-electrical interconnection of this optical tool constitutes a distinct advantage over existing optical probes for in vivo experiments with freely behaving animals, as comparably stiff optical fibers interfacing external light sources are avoided. The optical power density of these μLEDs was measured to be up to 3.5 mW/mm2 in air, at a peak wavelength of 450 nm which fulfills the requirements for optogenetic applications.

Miniaturized tool for optogenetics based on an LED and an optical fiber interfaced by a silicon housing.

This paper reports on the design, simulation, fabrication and characterization of a tool for optogenetic experiments based on a light emitting diode (LED). A minimized silicon (Si) interface houses the LED and aligns it to an optical fiber. With a Si housing size of 550×500×380 μm3 and an electrical interconnection of the LED by a highly flexible polyimide (PI) ribbon cable is the system very variable. PI cables and Si housings are fabricated using established microsystem technologies. A 270×220×50 μm3 bare LED chip is flip-chip-bonded onto the PI cable. The Si housing is adhesively attached to the PI cable, thereby hosting the LED in a recess. An opposite recess guides the optical fiber with a diameter of 125 μm. An aperture in-between restricts the emitted LED light to the fiber core. The optical fiber is adhesively fixed into the Si housing recess. An optical output intensity at the fiber end facet of 1.71 mW/mm2 was achieved at a duty cycle of 10 % and a driving current of 30 mA.

Led-based optical cochlear implant on highly flexible triple layer polyimide substrates

This paper reports on the design, fabrication, assembly, as well as the optical, mechanical and thermal characterization of a novel MEMS-based optical cochlear implant (OCI). Building on advances in optogenetics, it will enable the optical stimulation of neural activity in the auditory pathway at 10 independently controlled spots. The optical stimulation of the spiral ganglion neurons (SGNs) promises a pronounced increase in the number of discernible acoustic frequency channels in comparison with commercial cochlear implants based on the electrical stimulation. Ten high-efficiency light-emitting diodes are integrated as a linear array onto an only 12-μm-thick highly flexible polyimide substrate with three metal and three polyimide layers. The high mechanical flexibility of this novel OCI enables its insertion into a 300 μm wide channel with an outer bending radius of 1 mm. The 2 cm long and only 240 μm wide OCI is electrically passivated with a thin layer of Cy-top™.

High-resolution neural depth probe with integrated 460 NM light emitting diode for optogenetic applications

We report on the design, assembly, and optical as well as thermal characterization of a polymer-based optrode with an integrated light source for applications in optogenetics. The novel probe allows to optically stimulate neural brain tissue in deeper brain regions and to simultaneously record brain activity using integrated macroelectrodes and microelectrodes. The optrode is based on a cylindrical polyimide (PI) probe carrying the electrodes and their respective wiring. A bare light emitting diode (LED) chip is integrated within this cylinder and electrically interconnected through a separate PI-based ribbon cable.

Hybrid intracerebral probe with integrated bare LED chips for optogenetic studies

This article reports on the development, i.e., the design, fabrication, and validation of an implantable optical neural probes designed for in vivo experiments relying on optogenetics. The probes comprise an array of ten bare light-emitting diode (LED) chips emitting at a wavelength of 460 nm and integrated along a flexible polyimide-based substrate stiffened using a micromachined ladder-like silicon structure. The resulting mechanical stiffness of the slender, 250-μm-wide, 65-μm-thick, and 5- and 8-mm-long probe shank facilitates its implantation into neural tissue. The LEDs are encapsulated by a fluropolymer coating protecting the implant against the physiological conditions in the brain. The electrical interface to the external control unit is provided by 10-μm-thick, highly flexible polyimide cables making the probes suitable for both acute and chronic in vivo experiments. Optical and electrical properties of the probes are reported, as well as their in vivo validation in acute optogenetic studies in transgenic mice. The depth-dependent optical stimulation of both excitatory and inhibitory neurons is demonstrated by altering the brain activity in the cortex and the thalamus. Local network responses elicited by 20-ms-long light pulses of different optical power (20 μW and 1 mW), as well as local modulation of single unit neuronal activity to 1-s-long light pulses with low optical intensity (17 μW) are presented. The ability to modulate neural activity makes these devices suitable for a broad variety of optogenetic experiments.

Hybrid polymer waveguide characterization for microoptical tools with integrated laser diode chips for optogenetic applications at 430 nm and 650 nm

Appropriate micro-optical tools are required to exploit the key advantages of optogenetics in neuroscience, i.e. optical stimulation and inhibition of neural tissue at high spatial as well as temporal resolutions, providing cell specificity and the opportunity to simultaneously record electrophysiological signals. Besides the need for minimally invasive probes mandatory for a reduced tissue damage, highly flexible or wireless interfaces are demanded for experiments with freely behaving animals. Both these technical system requirements are achieved by integrating miniaturized waveguides for light transmission combined with bare laser diode (LD) chips integrated directly into neural probes. This paper describes a system concept using integrated, side emitting LD chips directly coupled to miniaturized waveguides implemented on silicon (Si) substrates. It details the fabrication, assembly, and optical as well as electrical characterization of waveguides (WG) made from the hybrid polymer Ormorcere. The WGs were photolithographically patterned to have a cross-section of 20x15 μm2. Bare LD chips are flip-chip bonded to electroplated gold (Au) pads with ±5 μm accuracy relative to the WG facets. Transmitted radiant fluxes for blue (430 nm, (Al,In)GaN) and red (650 nm, AlGaInP) LDs are measured to be 150 μW (ID = 35 mA, 5% duty cycle) and 4.35 μW (ID = 225 mA, 0.5% duty cycle), respectively. This corresponds to an efficiency of the coupled and transmitted light of 44% for the red LDs. Long term measurements for 24 h using these systems with red LDs showed a decrease of the radiant flux of about 4% caused by LD aging at stable WG transmission properties. WGs immersed into Ringer’s solution showed no significant change of their optical transmission properties after four weeks of exposure to the ionic solution.