Lensless camera captures cellular-level, 3D details in living tissue
Date:
March 7, 2022
Source:
Rice University
Summary:
The lensless Bio-FlatScope is a small, inexpensive camera to
monitor biological activity that can't be captured by conventional
instruments.
The device could eventually be used to look for signs of cancer
or sepsis or become a valuable endoscopy tool.
FULL STORY ==========================================================================
Want to monitor the brain of a running tiger?
========================================================================== First, catch the tiger.
Then attach Bio-FlatScope, the latest iteration of lensless microscopy
being developed at Rice University.
That particular use is fanciful but not far-fetched, according to Jacob Robinson, an electrical and computer engineer at Rice's George R. Brown
School of Engineering who led the recent effort to test Bio-FlatScope
in living creatures.
The research team's FlatCam, a lensless device that channels light through
a mask and directly onto a camera sensor, aimed primarily outward at
the world at large. The raw images looked like static, but a custom
algorithm used the data they contained to reconstruct what the camera saw.
The new device looks inward to image micron-scale targets like cells
and blood vessels inside the body, even through the skin. Bio-FlatScope captures images that no lensed camera can see -- showing, for example,
dynamic changes in the fluorescent-tagged neurons in running mice.
==========================================================================
One advantage over other microscopes is that light captured by
Bio-FlatScope can be refocused after the fact to reveal 3D details. And
without lenses, the scope's field of view is the size of the sensor
(at close range to the target) or wider, without distortion.
A small, low-cost Bio-FlatScope could eventually look for signs of
cancer or sepsis or become a valuable tool for endoscopy, said Robinson,
who teamed with colleagues at Rice's Neuroengineering Initiative on
the project.
The team's proof-of-concept study also imaged plants, hydra and even,
to a limited degree, a human. Their results appear in Nature Biomedical Engineering.
The mechanism combines a sophisticated phase mask to generate patterns of
light that fall directly onto the chip, according to the researchers. The
mask in the original FlatCam looks something like a bar code and limits
the amount of light that passes through to the camera sensor. But it
doesn't work well for biological samples.
The Bio-FlatScope phase mask looks more like the random map of a natural landscape, with no straight lines. "We had to start from scratch and
think about how to make it function in a realistic biological setting," Robinson said.
========================================================================== "Being random allows the mask to be pretty diverse in gathering light
from all directions," said postdoctoral researcher Vivek Boominathan,
one of four lead authors on the study. "And then we take the random
input, which is called Perlin noise, and do some processing to get these high-contrast contours." At the sensor, light that comes through the
mask appears as a point spread function, a pair of blurry blobs that
seems useless but is actually key to acquiring details about objects
below the diffraction limit that are too small for many microscopes to
see. The blobs' size, shape and distance from each other indicate how
far the subject is from the focal plane. Software reinterprets the data
into an image that can be refocused at will.
A tiger was a little beyond their budget, so the researchers started
small, first capturing cellular structures in a lily of the valley,
then calcium activity in tiny, jellyfishlike hydra. They moved on to
monitoring a running rodent, attaching the Bio-FlatScope to a rodent's
skull and setting it down on a wheel. The data showed fluorescent-tagged neurons in a region of the animal's brain, connecting activity in the
motor cortex with motion and resolving blood vessels as small as 10
microns in diameter.
In collaboration with Rebecca Richards-Kortum and research scientist
Jennifer Carns from Rice Bioengineering, the team identified vascular
imaging as a potential clinical application of the Bio-FlatScope. Graduate student and co- lead author Jimin Wu offered her lower lip to see if
light passing through to the camera could deliver structural details of
the blood vessels within.
"It was kind of an engineering challenge because it's difficult to
position the Bio-FlatScope at the correct position and keep it there,"
Wu said. "But it showed us it could be a good tool for seeing signs of
sepsis, because pre- sepsis changes the density of the vasculature. Cancer
also alters the morphology of the microvasculature." "We can imagine
it would be hard to stick a microscope in that position, but maybe a
little clip you put on your lip would be able to look for things like
sepsis or tumors in the oral mucosa," Robinson said.
Long term, the team sees potential for a camera that could curve around
its subject, like brain tissue, "so it could match the morphology of
what you're looking at," Robinson said. "Or maybe you could fold it up,
stick it in place and have it unfold and deploy.
"You could also do really interesting things by bending it for a fisheye effect, or you could curve it inward and have very high light-collection efficiency," he said.
Co-lead authors of the study include Rice alumnus Jesse Adams and Applied Physics graduate student Dong Yan. Co-authors are Rice graduate students
Sibo Gao and Soonyoung Kim; postdoctoral alumnus Alex Rodriguez; Caleb
Kemere, an associate professor of electrical and computer engineering
and of bioengineering; and Ashok Veeraraghavan, a professor of electrical
and computer engineering.
Richards-Kortum is the Malcolm Gillis University Professor, a professor
of bioengineering and electrical and computer engineering and director
of the Rice360 Institute for Global Health Technology. Robinson is
an associate professor of electrical and computer engineering and of bioengineering, and he, Kemere and Veeraraghavan are core members of
the Rice Neuroengineering Initiative.
The Defense Advanced Research Projects Agency (N66001-17-C-4012), the
National Institutes of Health (RF1NS110501) and the National Science
Foundation (1730574) supported the research.
========================================================================== Story Source: Materials provided by Rice_University. Original written
by Mike Williams. Note: Content may be edited for style and length.
========================================================================== Journal Reference:
1. Adams, J.K., Yan, D., Wu, J. et al. In vivo lensless microscopy
via a
phase mask generating diffraction patterns with high-contrast
contours.
Nat Biomed Eng, 2022 DOI: 10.1038/s41551-022-00851-z ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/03/220307112957.htm
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