CBET-EPSRC: Hybrid organic-CMOS devices for optogenetic simulation and lens-free fluorescence imaging of the brain

Brain functions such as perception, motor control, learning, and memory arise from the coordinated activation of neuronal assemblies distributed across multiple brain areas. While major progress has been made in understanding the response properties of individual cells, circuit interactions remain poorly understood. One of the fundamental obstacles to understanding these interactions has been the difficulty of observing the activity of large distributed populations of neurons in freely behaving animals. By combining highly engineered genetically encoded light-sensitive ion channels (typically Channelrhodopsins, ChRs) with fluorescent voltage or calcium sensors, it has become possible to achieve precise, non-invasive and high-speed control and monitoring of neuronal networks with optical techniques, both in cell culture and in live and awake animals. Conventional microscopy approaches have been employed for building these optical interfaces, resulting in very complex implementation which makes freely behaving animal studies difficult. In addition, conventional microscopy techniques, even those that use two photon techniques or light-sheet imaging, are limited by scattering and absorption in the brain tissue, allowing only superficial coverage for brains as small as that of the mouse.
In this proposal, we will develop an approach for light delivery that surmounts these limitations. It enables complete coverage of all neurons within a target volume, permits functional imaging with cellular resolution in highly scattering brain tissue, and has long-term prospects for human applications. Our approach is based on distributing a dense 3-D lattice of emitter and detector pixels within the brain itself. These pixel arrays are embedded onto neural probes, realized as implantable, ultra-narrow shanks. These probes are readily producible though existing CMOS (complementary metal-oxide-semiconductor) foundries augmented by organic LED (OLED) technology. This hybrid device platform for optogenetic stimulation and recording combines angle-sensitive CMOS single-photon avalanche diodes (A-SPADs) for detection and angle-emitting OLEDs for light generation. Due to their amorphous morphology, the organic materials used in OLEDs can be deposited directly onto silicon chips, without lattice matching constraints, thus facilitating true monolithic integration of light sources on CMOS technology.

In this proposal, the PIs will train graduate and undergraduate students in a truly cross-disciplinary international research environment combining circuit design, biophotonics, and nanotechnology with applications in neuroscience. The work will influence curriculum development in bioelectronics and biophotonics and there is a robust outreach effort involving both PIs. The new science possible with this platform will further our understanding of the functioning of the brain with an impact in hundreds of neuroscience labs. Dissemination will begin with introduction of prototypes into selected labs. Wider dissemination may happen through a start-up venture, similar to dissemination approaches used by the PIs in other activities.