Research

Rice team designs lens-free fluorescent microscope

FlatScope may be the world's tiniest, lightest microscope for biological applications and beyond


0305_FLATSCOPE-1-WEB
By Mike Williams | March 7, 2018

Lenses are no longer necessary for some microscopes, according to Rice University engineers developing FlatScope, a thin fluorescent microscope whose abilities promise to surpass those of old-school devices.

A paper in Science Advances by Rice engineers Ashok Veeraraghavan, Jacob Robinson, Richard Baraniuk and their labs describes 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.

FlatScope eliminates the tradeoff that hinders traditional microscopes in which arrays of lenses can either gather less light from a large field of view or gather more light from a smaller field.

The Rice team began developing the device as part of a federal initiative by the Defense Advanced Research Projects Agency as an implantable, high-resolution neural interface. But the device’s potential is much greater. The researchers claim FlatScope, an advance on the labs’ earlier FlatCam, could be used as an implantable endoscope, a large-area imager or a flexible microscope.

“We think of this as amping up FlatCam so it can solve even bigger problems,” Baraniuk said.

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.

The Rice team takes a different approach. It uses the same charge-coupled device (CCD) chips found in all electronic cameras to capture incoming light, but the comparisons stop there. 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.

This 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 program interprets to produce images.

The algorithm can focus on any part of the three-dimensional data the scope captures and produce images of objects smaller than a micron anywhere in the field.

That resolution is what makes the device a microscope, Robinson said. “A camera in your mobile phone or DSLR typically gets on the order of 100-micron resolution,” he said. “When you take a macro photo, the resolution is about 20 to 50 microns.

“I think of a microscope as something that allows you to image things on the micron scale,” he said. “That means 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, Robinson said. “It wasn’t as trivial as simply applying the FlatCam algorithm to the same techniques we used to image things that are far away,” he said.

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, that computational problem requires a matrix of a million times a million elements,” Robinson said. “It’s an incredibly big matrix. But because we break it down through this pattern of rows and columns, our matrix is 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. From early versions of FlatCam that required an hour or more to process an image, FlatScope captures 30 frames of 3-D data per second.

Veeraraghavan said the burgeoning internet of things may provide many applications for flat cameras and microscopes. That in turn would drive down costs. “One of the big advantages of this technology compared with traditional cameras is that because we don’t need lenses, we don’t need postfabrication assembly,” he said. “We can imagine this rolling off a fabrication line.”

But their primary targets are medical uses, from implantable scopes for the clinic to palm-sized microscopes for the battlefield. “To be able to carry a microscope in your pocket is a neat technology,” Veeraraghavan said.

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.

Rice graduate students Jesse Adams and Vivek Boominathan are lead authors of the paper. Co-authors are graduate students Daniel Vercosa and Fan Ye. Baraniuk is the Victor E. Cameron Professor of Electrical and Computer Engineering. Robinson is an assistant professor, and Veeraraghavan is an associate professor of electrical and computer engineering.

The National Science Foundation and the Defense Advanced Research Projects Agency funded the research.




Social Posts

profile_image

Texas Children's

@TexasChildrens

@TCHheartcenter outpatient clinic in Legacy Tower is open! The outpatient clinic is located on the 21st and 22nd floors of Legacy Tower and has been specially configured to offer families a more personal approach to care. Learn more: https://t.co/NsJBJuUOHz https://t.co/p9C3y8pil6

33 mins ago
profile_image

UTMB Health

@utmbhealth

RT @SWilliams_MD: Forging collaborations (Dr. Adibi, Dr. Jana @SWilliams_MD) @MDAndersonNews @UTMBUrology @utmbhealth at Victory Lakes camp…

34 mins ago
profile_image

MD Anderson Cancer Center

@MDAndersonNews

Congrats to our @McNeill_Dr for receiving the #cancerFIERCE award for launching Project CHURCH, an effort to reach African American communities and engage them in #cancerprevention and research. #BidenCancerSummit #endcancer https://t.co/BjT4NnSCNt

35 mins ago
profile_image

MD Anderson Cancer Center

@MDAndersonNews

“There’s always a way to make it work,” says survivor Hilary McQuiston-Fall of adjusting to life after overcoming chondrosarcoma with a hemipelvectomy: https://t.co/aPY2LflzIM @drjustinbird @AdelmanMDPhD #endcancer https://t.co/vIog5d2not

56 mins ago
profile_image

UTMB Health

@utmbhealth

RT @UTMB_Pathology: Outstanding noon lecture from @utmbhealth’s Breast Radiologist, Dr. Quan Nguyen on breast imaging. It’s great to learn…

57 mins ago
profile_image

Texas Children's

@TexasChildrens

This week’s Radio Lollipop broadcast was extra special as @HoustonTexans players, @BIG_DADDY_K74 and @GregMancz and Texans Analyst John Harris joined in on the fun at @TexasChildrens! Learn more --> https://t.co/V9NxttLCyR (Ft: @texanscare) https://t.co/iDpW8onVlq

59 mins ago
profile_image

CHI St. Luke's Health

@CHI_StLukes

Spending the weekend in @BayAreaHouston? Discover our favorite restaurants that inspire health and happiness in Southeast Houston! https://t.co/UoyLCYktfW #WeHeartBayArea https://t.co/3wxB11a7xq

1 hour ago
profile_image

BCMHouston

@bcmhouston

RT @plupo1: Excited to be a part of this new Gabriella Miller Kids First Project with Karen Rabin, ⁦@Junjyang⁩, Stephanie Sherman and other…

1 hour ago
profile_image

Texas Children's

@TexasChildrens

RT @TCHFetalCenter: Texas Children's Fetal Center here! Delivering our first #tweet! Check out our website for more information on #TexasCh…

1 hour ago
profile_image

UTHealth

@UTHealth

RT @ConnieAssiff: Happening Now: Dr. Carmel B. Dyer @UTHealth sharing how Vascular #Dementia is affecting her Mother after a stroke Family…

1 hour ago
profile_image

Veterans Affairs

@DeptVetAffairs

Veterans find healing, recovery in the surf during National Veterans Summer Sports Clinic https://t.co/LjxsgKvu51 via #VAntagePoint

1 hour ago
profile_image

University of Houston

@UHouston

Congratulations to @UHClearLake and President Blake, Go Hawks! #UHCLHawks https://t.co/P0GNRZ5X1o

1 hour ago
profile_image

BCMHouston

@bcmhouston

RT @BCMCancer: Follow our series #BreastCancerBreakthroughs on Facebook, and read Marion Gordey’s story on grace under fire while fighting…

2 hours ago
profile_image

BCMHouston

@bcmhouston

Fall arrives Saturday, but it still feels like summer here in Houston. Here are some of our students from the 1990 Aesculapian Yearbook trying to keep cool by taking a dip in the Alkek Fountain. https://t.co/GGFWYtJCjg #TBT https://t.co/nDhzXUekWt

2 hours ago
profile_image

TexasHeartInstitute

@Texas_Heart

RT @StrokeAHA_ASA: Mediterranean diet may lower #stroke risk in women https://t.co/Bk0PgaVQha

2 hours ago