SEAD DORIC, DORIC LENSES INC.
Optics and microscopy have always played important
roles in neuroscience. The innovations brought by optogenetics
and fiber photometry, in the context of freely
moving animals and behavioral research, have only reinforced
those roles. Conventional microscopy has been complemented
by imaging of individual neuronal activity within a selected
group of tagged neurons by a miniature fluorescent microscope,
or miniscope, mounted directly on the heads of freely moving,
tethered lab animals.
Miniscopes and fiber photometry, combined with optogenetics,
provide the basis for modern behavioral neuroscience studies.
There is now even a word — “neurophotonics” — coined to
refer to the use of photonic devices and light in neuroscience.
The future of behavioral neuroscience lies in the convergence
or fusion of optogenetics, genetically encoded indicators, fiber
photometry, various forms of microscopy, and good old electrophysiology.
As I sit at the helm of Doric Lenses Inc., my job is to anticipate
the future need for neurophotonic hardware and accordingly
redirect the company’s research and development efforts.
I do this by analyzing sales reports and by sifting through a pile
of requests coming from some of the most famous and not-sofamous
neuroscience institutions around the world.
From what I have seen, behavioral research is still dominated
by freely moving, tethered animals. These experiments in which
they appear need light and electrical signal sources, rotary
joints, electrical and optical cords, liquid tubing, detectors, and
skull-mounted one-site or multisite brain interfaces in the form
of simple fiber optic cannulas or hybrid implants.
Optogenetics equipment has matured and gained general
acceptance. The new light-sensitive opsins require precise light
sources that take into account the size of emitters, the ease of
signal modulation, and the activation spectrum. The market of
brain interfaces — which is a trendy name for all sorts of fiber
optic and hybrid cannulas, electrical implants, and head stages as
ports of entry to the brain — requires never-ending diversification
in types and geometries.
Fiber photometry equipment that was initially very modular,
with detectors and light sources connected to fluorescent cubes
with optical fibers, is slowly being replaced by more compact
cubes in which detectors and LED light sources are attached
directly to the cubes. The elimination of unnecessary optical
fibers improves the signal-to-noise ratio and makes the setup
more user-friendly. Consequently, neuroscientists can spend less
time fiddling with the equipment and more time doing experiments.
Multisite fiber photometry and CMOS and sCMOS detectors
are becoming increasingly popular. Many electrophysiology
companies are embracing fiber photometry as a complementary
sensor to their existing equipment.
Miniscopes are gaining more acceptance as their design
improves and researchers learn to master cannula implantation.
The varifocal objective is becoming a norm rather than an option.
Adding two-fluorophore imaging to head-mounted fluorescence
microscopy, or combining fluorescence microscopy with optogenetics
or electrophysiology, is becoming more common.
The larger picture of neuroscience
Although neuroscientists are using various brain interfaces to
study the brain’s functions and malfunctions on the lab animal
level, the ultimate goal is understanding the inner workings of
the human brain. They hope to begin repairing its ills and creating
a direct communication channel between the human brain
and the computer, machine, or parts of the body that have lost
their natural connections to the brain. It is not a question of if it
will happen on a larger scale, but when it will happen. As I write
this column, the news is out about Elon Musk’s Neuralink brainmachine
interface development. So far, this interface, which has
generated a lot of hype, does not involve humans or optics, but
that will change sooner rather than later.
Unlike almost universal government support for university
neuroscience research, there is a very little direct government
support for neurophotonic hardware development (at least in
Canada where I am based). This industry, consisting of relatively
small niche companies, lives off proceeds from sales of
equipment to the less-regulated lab-animal-level neuroscience
research market. To get through development, FDA approvals,
clinical trials, and distribution channels, neurophotonic hardware
for human use will require government programs (such
as those of the National Institutes of Health), venture capital
involvement of the Elon Musk type, or acquisitions of niche
players by larger health care companies.
In the meantime, the existing neurophotonics industry is preparing
itself for that “human phase” by sharpening its tools with
whatever profits it can generate through sales to the lab animal
research market. This is vast uncharted territory with a huge
disruptive potential. Neurophotonics is entering a phase of rapid
and rewarding growth — and the photonics component of that
movement should not be underestimated.
Meet the author
Sead Doric, Ph.D., physicist by profession, is
founder and CEO of Doric Lenses Inc. As a
researcher, he has published several scientific
papers on gradient index optics and holds a
number of optics-related patents. As an entrepreneur
and engineer, he leads or participates in
development of many Doric Lenses products.
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