Scientists have developed a small, inexpensive camera to monitor biological activity that cannot 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.

Bio-FlatScope, the latest iteration of lensless microscopy being developed at Rice University (Houston, TX, USA), captures cellular-level, 3D details in living tissue and was tested in living creatures. The research team has also developed 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, according to the researchers. The team’s proof-of-concept study also imaged plants, hydra and even, to a limited degree, a human.

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. 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.

In order to test the Bio-FlatScope, the researchers first started by capturing cellular structures in a lily of the valley , then calcium activity in tiny, jellyfishlike hydra. Then 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. The team has identified vascular imaging as a potential clinical application of the Bio-FlatScope and believes that it could also be a good tool for seeing signs of sepsis or tumors in the oral mucosa. Long term, the team sees potential for a camera that could curve around its subject, like brain tissue.

“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,” said 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. 

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