UC Berkeley Researchers Bring Fluorescent Imaging To Mobile Phones For Low-cost Screening In The Field

Researchers at the University of California, Berkeley, are
proving that a camera phone can capture far more than photos of people or
pets
at play. They have now developed a cell phone microscope, or CellScope,
that not only takes color images of malaria parasites, but of tuberculosis
bacteria labeled with fluorescent markers.


The prototype CellScope, described in the July 22 issue of the
peer-reviewed, online journal PLoS ONE, moves a major step forward in
taking clinical
microscopy out of specialized laboratories into field settings for disease
screening and diagnoses.


"The same regions of the world that lack access to adequate health
facilities are, paradoxically, well-served by mobile phone networks," said
Dan
Fletcher, UC Berkeley associate professor of bioengineering and head of
the research team developing the CellScope. "We can take advantage of
these
mobile networks to bring low-cost, easy-to-use lab equipment out to more
remote settings."


The engineers attached compact microscope lenses to a holder fitted to a
cell phone. Using samples of infected blood and sputum, the researchers
were
able to use the camera phone to capture bright field images of Plasmodium
falciparum, the parasite that causes malaria in humans, and sickle-shaped
red blood cells. They were also able to take fluorescent images of
Mycobacterium tuberculosis, the bacterial culprit that causes TB in
humans.


Moreover, the researchers showed that the TB bacteria could be
automatically counted using image analysis software.
"The images can either be analyzed on site or wirelessly transmitted to
clinical centers for remote diagnosis," said David Breslauer, co-lead
author
of the study and a graduate student in the UC San Francisco/UC Berkeley
Bioengineering Graduate Group. "The system could be used to help provide
early
warning of outbreaks by shortening the time needed to screen, diagnose and
treat infectious diseases."


The engineers had previously shown that a portable microscope mounted on a
mobile phone could be used for bright field microscopy, which uses simple
white light - such as from a bulb or sunlight - to illuminate samples. The
latest development adds to the repertoire fluorescent microscopy, in
which a special dye emits a specific fluorescent wavelength to tag a
target - such as a parasite, bacteria or cell - in the sample.
"Fluorescence microscopy requires more equipment - such as filters and
special lighting - than a standard light microscope, which makes them more
expensive," said Fletcher. "In this paper we've shown that the whole
fluorescence system can be constructed on a cell phone using the existing
camera
and relatively inexpensive components."















The researchers used filters to block out background light and to restrict
the light source, a simple light-emitting diode (LED), to the 460
nanometer wavelength necessary to excite the green fluorescent dye in the
TB-infected blood. Using an off-the-shelf phone with a 3.2 megapixel
camera,
they were able to achieve a spatial resolution of 1.2 micrometers. In
comparison, a human red blood cell is about 7 micrometers in diameter.
"LEDs are dramatically more powerful now than they were just a few years
ago, and they are only getting better and cheaper," said Fletcher. "We had
to disabuse ourselves of the notion that we needed to spend many thousands
on a mercury arc lamp and high-sensitivity camera to get a meaningful
image. We found that a high-powered LED - which retails for just a few
dollars - coupled with a typical camera phone could produce a clinical
quality image sufficient for our goal of detecting in a field setting some
of the most common diseases in the developing world."


The researchers pointed out that while fluorescent microscopes include
additional parts, less training is needed to interpret fluorescent images.
Instead of sorting out pathogens from normal cells in the images from
standard light microscopes, health workers simply need to look for
something the
right size and shape to light up on the screen.


"Viewing fluorescent images is a bit like looking at stars at night," said
Breslauer. "The bright green fluorescent light stands out clearly from the
dark background. It's this contrast in fluorescent imaging that allowed us
to use standard computer algorithms to analyze the sample containing TB
bacteria."


Breslauer added that these software programs can be easily installed onto
a typical cell phone, turning the mobile phone into a self-contained field
lab and a "good platform for epidemiological monitoring."


While the CellScope is particularly valuable in resource-poor countries,
Fletcher noted that it may have a place in this country's health care
system, famously plagued with cost overruns.


"A CellScope device with fluorescence could potentially be used by
patients undergoing chemotherapy who need to get regular blood counts,"
said
Fletcher. "The patient could transmit from home the image or analyzed data
to a health care professional, reducing the number of clinic visits
necessary."


The CellScope developers have even been approached by experts in
agriculture interested in using it to help diagnose diseases in crops.
Instead of
sending in a leaf sample to a lab for diagnosis, farmers could upload an
image of the diseased leaf for analysis.
The researchers are currently developing more robust prototypes of the
CellScope in preparation for further field testing.
Other researchers on the team include Robi Maamari, a UC Berkeley research
associate in bioengineering and co-lead author of the study; Neil Switz, a
graduate student in UC Berkeley's Biophysics Graduate Group; and Wilbur
Lam, a UC Berkeley post-doctoral fellow in bioengineering and a UCSF
pediatric
hematologist.



Funding Statement:

Funding for the CellScope project comes from the Center
for Information Technology Research in the Interest of Society (CITRIS)
and
the Blum Center for Developing Economies, both at UC Berkeley, and from
Microsoft Research, Intel and the Vodafone Americas Foundation.




Competing Interests:

The authors are co-inventors on a patent application
filed by the University of California, Berkeley on the technology
described
in this manuscript.



Citation:

"Mobile Phone Based Clinical Microscopy for Global Health Applications."
Breslauer DN, Maamari RN, Switz NA, Lam WA, Fletcher DA (2009)

PLoS ONE 4(7):e6320. doi:10.1371/journal.pone.0006320

Source
PLoS ONE

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