A multimodal microimplant for combined light/liquid delivery and multi-site electrical recording

As optogenetic neuronal control strategies develop and get widely adopted in neurobiology labs, the demand for devices allowing combined light delivery and electrophysiological recording is growing. These devices, commonly called opto-electrodes or optrodes, already exist under a wide variety of forms, from the simple home made single optical fiber + single electrode to more complex microfabricated multi-fiber/multi-electrode systems. In the past years, Zhang et al. integrated an optical fibre in a Utah Array, and NeuroNexus assembled an optical fiber on their standard silicon shaft. Other groups implemented waveguides directly into the optrode fabrication process: Cho et al. integrated a microstructured SU-8 waveguide on the shaft of a Michigan Probe and the group of Ed Boyden integrated 12 silicon oxynitride waveguides on silicon shafts (paper1, paper2). Royer et al. in the Buszaki lab managed to establish silicon based shaft arrays with integrated optical fibers.

In a recent paper published in “Lab on a Chip”, the Stieglitz and Lüthi labs introduced a novel optrode which also comprises a microfluidic channel for liquid delivery at the tip of the probe. This channel can be used for example to inject a solution containing a virus right under the waveguide tip and around the electrical recording sites. The detailed specifications of this “multimodal” implant can be found below. The different components of the implant were tested separately. Their characterization of the microfluidic channel proved the ability to deliver fluid through the channel without delamination of the channel from the polyimide substrate. The hybrid channel assembly was stable at pressures up to 1.4 bar, resulting in flow rates of about 240 µl/min. They then connected an optical fiber to the implant and measured the transmission loss through the SU-8 waveguide. At 473 nm, the output power of the waveguide was 1 to 2 mW while the output power of the optical fibre was 35 mW. Finally the authors recorded single unit activity using this implant in a mouse expressing ChR2 in the neocortex (ChR2 was delivered using a AAV, which was not injected through the implant but with a conventional pressure ejection system and a glass pipette). Units recorded throughout the cortical region expressing ChR2 showed light-evoked modulation of their firing as expected.

Schematic of the multimodal implant concept.

Schematic of the multimodal implant concept. From Rubehn et al. 2013..

Caption

Left: photograph of a fully assembled shaft with electrical, optical, and fluidic capabilities and their respective connectors (from left to right: electrical, optical, fluidic). Middle: light micrograph from the backside showing the transparent channel walls and the polyimide foil with eight integrated electrode sites and interconnect lines. Right: Scanning electron micrograph of another device showing the frontside with a concave waveguide output face, nine electrode sites, one square shaped channel opening in the polyimide foil, and a lateral channel opening in the SU-8 channel wall. From Rubehn et al. 2013..

Specs: the implant has a polyimide-based shaft including 9 platinum electrode sites with a diameter of 30 µm and a centre-to-centre distance of 50 µm. The shaft comprises a 300 nm thick platinum thin-film sandwiched between two 5 µm thick polyimide (PI) layers. Within the PI foil, the electrode sites are connected via conductor paths on a flexible cable to solder pads designed to contact SMD Omnetics connectors. An SU-8 waveguide is placed on top of the PI shaft separated from the PI by a 200 nm thick tungsten–titanium layer (tungsten–titanium has a good adhesion to SU-8). This metal cladding is needed to prevent the light from coupling into the PI substrate which has a higher refractive index than the SU-8. The waveguide is glued into a custom made optical adapter with epoxy (the waveguide is covered with a 200 nm gold layer to prevent the light from leaving the waveguide towards the epoxy glue – gold was chosen as it can easily be removed with a drop of potassium iodide–iodine solution). The gold and tungsten–titanium cladding layers have no electrical contact to the platinum leads and electrode sites as the platinum structures are insulated by the second layer of polyimide. Thus, the electrode sites are not short cut by the cladding. The waveguide ends in front of the electrode sites thus, neurons which are stimulated by the light exiting the waveguide will be closest to the electrode sites for recording. The channel is implemented by attaching a U-profile with an outer cross-section of 190 mm by 65 mm, an inner cross-section of 50 mm by 45 mm and a length of 7 mm to the rear side of the PI shaft. The U-profile was made of SU-8 and was processed on a separate wafer. The channel outlet at the tip of the shaft is a hole in the PI between two electrode sites. Thus, the fluid can be applied to the same tissue volume which is also electrically and optically interfaced.

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