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|Advancing BRAIN research with implantable MEMS optoelectrodes|
|Keywords: Implantable medical devices, MEMS, Micro opto-electronic packaging|
|The mammalian brain is often compared to an electrical circuit, and its dynamics and function are governed by communication across different types of neural cells called neurons. To treat many neurological disorders like Alzheimer�s and Parkinson�s, which are characterized by inhibition or amplification of neural activity in a particular region or lack of communication between different regions of the brain, there is a need to troubleshoot neural networks at cellular or local circuit level with the help of innovative neural technologies. In this work, we introduce a novel implantable MEMS-based optoelectrode that can optically manipulate a wide range of neuron types in an animal brain while simultaneously recording its neural electrical activity. The optoelectrode consists of scalable optical waveguide mixers monolithically integrated on a Michigan neural probe ; and is capable of generating multiple stimulation patterns of multi-color light at precise spatial locations in the brain. The electrical neural signals from light-modulated neurons are picked up via low-noise recording channels placed strategically around the waveguide emission ports. We report design, micro-fabrication, integrated opto-electronic packaging and validation of the optoelectrode. Other than being compact, modular and minimally invasive, our technology integrates efficient optical, thermal and electrical design - all in one fully packaged microsystem. It also addresses the limitations of all available optoelectrodes, which often rely on mechanically invasive and bulky devices [2,] and/or can control only one neuron type via mono-color light at a single site ; and hence have limited function and control. We present, for the first time, the integration of coupling lensing mechanism for a neural optoelectrode package . The compact optoelectrode design consists of 7 μm-thick and 30 μm-wide dielectric optical waveguide mixers, which are monolithically integrated on a 22μm- thick silicon neural probe. The waveguide mixers are coupled to injection laser diodes (ILDs) via eight gradient-index (GRIN) lenses assembled on the probe backend, eliminating the need of external fiber optic connections. While such optoelectrodes with integrated light sources (fiber-less) offer attractive optoelectrode solutions, they are challenging to implement for implantable devices for several reasons. First, on-probe light sources generate heat and risk thermal damage to the surrounding tissue during operation. Second, the close proximity of electrical traces on a compact scale makes them susceptible to electromagnetic interference (EMI) coupling, generating stimulation-locked artifacts. EMI-induced artifacts may obscure or distort neural activity near the stimulation site for tens or hundreds of milliseconds. Third, packaging multiple sources of different wavelengths (for independent control of different neuron types) in a single micro-assembly poses design challenges of its own. In our design, GRIN lenses along with epi-down eutectic flip-chipped ILDs on a silicon heat sink enable many micro-packaging advantages. It provides efficient optical coupling with large alignment tolerance to provide wide optical power range (10 to 3000 mW/mm2 irradiance) at stimulation ports. It keeps thermal dissipation and electromagnetic interference generated by light sources sufficiently far from the sensitive neural signals, allowing thermal and electrical noise management on a multilayer printed circuit board. These results were validated via simulation models and bench tests. Our bio-heat transfer model in indicates only 1 oC increase local brain tissue temperature when 8 ILDs are pulsed simultaneously (200 ms pulse width, 10% duty cycle) for 10 s continuously , which is more than adequate for neural circuit-analysis. The lumped-circuit model used to better understand EMI coupling mechanisms during diode-based activation, successfully limited stimulation-induced artifacts to amplitudes under 100 μV upto waveguide optical output power of 450 μW . Finally, we demonstrate device validation and verification to study densely populated brain regions in both anesthetized and awake behaving animals. The fully packaged devices were used to manipulate variety of neural circuits in vivo expressing different combinations of light-sensitive proteins called opsins, such as, Channelrhodopsin-2, Archaerhodopsin and ChrimsonR [4,5]. We report successful activation and silencing of neurons and high quality neural recording with stimulation artifacts less than 100 μV, demonstrating potential use of this technology in the functional dissection of neural circuits. There are several possibilities to expand the presented optoelectrode design for future implantable technologies. This will be discussed further in this talk.|
|Komal Kampasi, Postdoctoral researcher
Lawrence Livermore National Laboratory
San Francisco, CA