Rice engineers have developed a wide-field microscope thinner than a credit card, small enough to sit on a fingertip and capable of micrometer resolution over a volume of several cubic millimeters.

Traditional fluorescent microscopes are essential tools in biology. They pick up fluorescent signals from particles inserted into cells and tissues that are illuminated with specific wavelengths of light. The technique allows scientists to probe and track biological agents with nanometer-scale resolution. But like all traditional microscopes, telescopes and cameras, their resolution depends on the size of their lenses, which can be large and heavy and limit their use in biological applications.

A new approach developed by the Rice engineers uses the chips found in typical electronic cameras to capture incoming light in order to develop a flat microscope they called FlatScope. Like the FlatCam project that inspired it, FlatScope’s field of view equals the size of the CCD sensor, which can be as large or as small as required. It’s flat because it replaces the array of lenses in a traditional microscope with a custom amplitude mask. The mask, which resembles a bar code, sits directly in front of the CCD. Light that comes through the mask and hits the sensor becomes data that a computer algorithm interprets to produce images. The algorithm can focus on any part of the three-dimensional data the scope captures and it can produce images of objects smaller than a micron anywhere in the field.

FlatScope, developed at Rice University, captures three-dimensional data that passes through a mask and then to a fingernail-sized camera chip. It sends that data to a computer that processes it back into an image. The camera may be used as an implantable endoscope, a large-area imager, or a flexible microscope. (Photo courtesy of Jeff Fitlow)

The resolution is what makes the device a microscope. Mobile phone cameras typically have on the order of 100-micron resolution. When you take a macro photo, the resolution is about 20 to 50 microns. A microscope typically allows you to image things on the micron scale — things that are smaller than the diameter of a human hair, like cells, parts of cells, or the fine structure of fibers.

Achieving that resolution required modifications to the FlatCam mask to further cut the amount of light that reaches the sensor, as well as a rewrite of their software. The mask is akin to the aperture in a lensed camera that focuses light onto the sensor, but it’s only a few hundred micrometers from the sensor and allows only a fraction of the available light to get through, limiting the amount of data to simplify processing. In the case of a megapixel camera, the computational problem requires a matrix of a million times a million elements. The engineers have reduced this problem by breaking it down through a pattern of rows and columns, requiring a matrix of just 1 million elements. That cuts the data for each snapshot from six terabytes to a more practical 21 megabytes, which translates to short processing times. In contrast to early versions of FlatCam that required an hour or more to process an image, FlatScope captures 30 frames of 3-D data per second.

The goal is to adapt this new device for medical uses, from implantable scopes for the clinic to palm-sized microscopes for the battlefield. The researchers noted that while their current work is focused on fluorescent applications, FlatScope could also be used for bright-field, dark-field, and reflected-light microscopy. They suggested an array of FlatScopes on a flexible background could be used to match the contours of a target.

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Photonics & Imaging Technology Magazine

This article first appeared in the July, 2018 issue of Photonics & Imaging Technology Magazine.

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