FEATURE NEUROPHOTONICS
‘Many of the building blocks have existed for a decade or more’
Historical breakthroughs such as g
from the existing infrared photonics circuit paradigm, which is widely used in telecoms applications, to visible photonics circuits. ‘More specifically,’ he said, ‘blue light, to match the excitation optical spectrum of fluorescent biomarkers. We nucleated this effort at Caltech in our Kalvi Nanoscience Institute (KNI) cleanroom and with our partners at Leti-CEA in France, and at AMF in Singapore. Of course the “reverse” efforts – developing optogenetic reporters that function in the infrared – also open up the possibility of using infrared photonics circuits as well. It is worth noting that the development of near-infrared optogenetic reporters is something that has been gaining momentum recently.’
Making a breakthrough Some of these recent breakthroughs in molecular reporters can enable multimodal and multi-physical sensing. Likewise, optogenetic actuators enable optical control of neural activity, and the genetically encoded delivery of molecular reporters and actuators that provide specificity of cell type. In terms of the challenges, in particular when it comes to the hardware, Moreaux feels that a key technological challenge is the integration of light delivery and photon sensors on the same chip with implantable form factors (shanks). ‘In other words,’ he said, ‘an integrated technology that allows for both the delivery of patterned, pulsed light and photon detection, such as integration of CMOS and photonics circuitry (silicone nitrate).’ The ability of the technology to be
mass-produced will be essential if the technology is to be widely-adopted. So
18 Electro Optics March 2021
another challenge, said Moreaux, is that this integration capability must not only be achieved at a small, proof-of-concept scale, but also at the foundry scale. In addition, as integrated neurophotonics uses light to transduce the electrical signals of neuronal activity, development on the optical reporter side is also essential if the technology is to be used to map brain circuits and other applications. ‘While there have certainly been a lot of
advancements in the area of optogenetic reporters in the past decade,’ said Moreaux, ‘there are certain challenges to consider in order to optimise their use in the context of integrated neurophotonics. For example, finer control of the spatial density of reporter expression: too dense, you lose the ability to separate between neurons, not dense enough, you lose out on taking full advantage of the technology.’ Beyond the technological challenges, of
course, the monetary investment needed to develop this type of technology is also a huge hurdle. ‘Buy-in for this type of investment,’ said Moreaux ‘is more likely to gain traction in areas where there is a greater chance for larger tangible return on investment, such as in the clinical arena.’ Despite some of these challenges,
Moreaux believes that the methodology is potentially scalable. ‘Multiple modules can be tiled to densely cover extended regions deep in the brain,’ he said. ‘We anticipate that this will ultimately permit interrogation – simultaneous recording and patterned stimulation of millions of neurons, at arbitrary positions and depths in the brain – to unveil dynamics of neural networks with single-cell resolution and specificity of cell type.’
low-loss wafer-scale mass-production processes for visible-wavelength integrated nanophotonics have been achieved by working with foundry partners, said Moreaux. This, in turn, has allowed the demonstration of coherent optical beam formation in brain tissue; the realisation of beam-steerable phased arrays of micro- emitters and selective-plane illumination with micro-emitter probe arrays; and the creation of implantable, angle-selective single-photon microdetector arrays. ‘These constitute the fundamental
building blocks for complete implantable visible-wavelength functional imaging systems with microscale dimensions,’ said Moreaux. ‘Further, we have validated the foundational physics for the integrated photonics paradigm by developing and implementing computational methods to evaluate the fluorescent photon yield in scattering media. With these tools, we have validated our computational approach for optical source separation and localisation and, thereby, have been able to identify practical, realisable architectures, that can enable dense volumetric activity reconstruction at depth.’ The systems are based on mass-
production processes that are already routinely carried out in existing electronic- and photonic-chip foundries. Industry partnerships like these, believes Moreaux, will be essential in making this work a commercial reality. ‘Partnerships with mixed photonics and CMOS fabrication technology foundry partners will be important to co-integrate the different functional bricks of the technology on implantable shanks,’ he explained. ‘Likewise, industry partners with post- processing and optoelectronic packaging expertise. We have already been collaborating with CEA-Leti and AMF, as well as IBM and TSMC for the CMOS chip fabrication.’ All of these developments and
partnerships together, believe the research team, validate the potential of integrated neurophotonics. This means, said Moreaux, that ‘they offer near-term prospects for wide deployment to the neuroscience research community.’ EO
@electrooptics |
www.electrooptics.com
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