Mobile Microscopes: How the Diagnostic Power of
Your Cell Phone Can Save Lives
Monica Jain
email: monica.2.jain@gmail.com
phone: (650) 430-0019
campus: 2637 Severance St.
Los Angeles, CA 90089
home: 505 Chateau Dr.
Hillsborough, CA 94010
What if a text message could save a life? Dr. Ayogdan Ozcan and his team of
researchers have developed a cost-efficient, revolutionary device that can perform basic
diagnostics tests such as complete blood cell count and diagnosis of malaria or TB – all
on the back of a $30 camera phone. The device uses a lens-free imaging technique
known as LUCAS, which creates a holographic image of each sample cell based on
their imaged “shadows”. The shadows are imaged by diffracting a light beam through
the cells and upon a CCD chip, which collects the data for advanced image processing.
These holograms can then be compared to a holographic cell database using a simple
pattern-matching algorithm that both counts the cells and diagnoses any potential
diseases. The diagnostic results are sent back via text message to the original patient
or doctor in a matter of minutes. This device is changing the way the microscopy and
mobile health technology are being approached and may one day turn the cell phone
into an essential local and global medical device.
bio: Monica Jain is a junior studying biomedical engineering at the Viterbi School of
Engineering at University of Southern California. She loves to cook, socialize, and go
on adventures and hopes to one day own her own restaurant.
illumin tags: biomedical engineering; communication; computer science; electrical
engineering; health & medicine; physics
keywords: Cellophone; Ayodan Ozcan; LUCAS; mobile microscope; CCD; digital
holographic microscopy; optics
Mobile Microscopes: How the Diagnostic Power of
Your Cell Phone Can Save Lives
By Monica Jain
Introduction
Imagine if you could perform a complete blood cell count and diagnose deadly bacterial
diseases – on the back of your cell phone. Well, imagine no more.
An inexpensive, lightweight device is now being developed that will allow doctors and
health workers to do just that: perform basic medical diagnostics on the back of a $30 cell
phone. This camera phone attachment is a small digital microscope that, costing under $10
to produce, can perform many medical tests that normally require expensive lab
equipment and trained personnel, such as complete blood cell count, identification of
disease cells, water contamination tests, and diagnosis of infectious diseases including
malaria, cholera, and tuberculosis (TB).
It is a lightweight, cost-effective, and lens-free microscope that uses computer algorithms
instead of expensive and bulky lenses to extract loads of biological information from
simple, camera phone images.
The Global Cell Phone Network
Twenty years ago, a cell phone could do little else besides make a phone call. Today,
however, few phones are without Internet connection and accelerometers, global
positioning systems (GPS) and video cameras. The cell phone has become the Swiss Army
knife of modern technology. It comes as no surprise, then, that the cell phone is now being
retooled into a medical device as well.
What is surprising, however, is the ubiquity of cell
phones. Currently, close to 5 billion people around
the world own a cell phone [1], a majority of whom
live in resource-poor countries such as Uganda and
India (see Figure 1). Almost 90% of the world’s
population is covered by a mobile signal, and by 2015,
it is estimated that 90% of the world’s population will
carry a network-subscribed cell phone [2] (see
Figure 1). As professor Ramesh Raskar of the
Massachusetts Institute of Technology Media Labs
notes, “People who make a dollar a day have a cell
phone, which is just mind-blowing if you think about
it [3].” These facts alone make it one of the most
Figure 1: Graph depicting mobile-phone
subscription growth per billion in both
developed and developing countries
accessible resources for innovation and healthcare intervention.
Dr. Aydogan Ozcan and his team of researchers at the electrical engineering lab in the
University of California, Los Angeles (UCLA) have figured out a way to tap into this
substantial resource and provide healthcare to the masses - with a revolutionary, lens-free
cell phone attachment that can bring effective diagnostics to parts of the world in which
expensive clinical equipment and laboratories are simply out of reach.
The Inner Workings of A Revolutionary Mobile Device
LEDs, CCDs, and Diffraction Signatures
The device is composed of two key hardware components: a light-emitting diode (LED)
that illuminates the sample and a charged-coupled device (CCD) chip, identical to that
found in a consumer digital camera. Slides containing a blood or water sample are loaded
into the phone in between the LED and the light-sensing chip, “just like you insert a
memory stick [4],” says Ozcan. Each slide is then illuminated by the LED from above; as the
light passes through the given cell type, it diffracts or bends in a characteristic way. “What
we record is not an image but a diffraction signature,” says Ozcan [5]. Each cell type has a
unique diffraction signature based upon its size, shape, and refractive index [5].
The CCD chip then collects the diffraction
signatures through capacitance, the ability
of electrical devices such as the chip to
store energy—in this case, the diffracted
light waves. Capacitance in the CCD chip
operates via the gathering of electric
charge, or electrons. The chip is made up
of an array of light-sensitive pixels, or CCD
gates, which are composed of
perpendicular strips of transparent
electrode material—silicon dioxide in
Figure 2—and n-type silicon channels (nFigure 2: Illustration of one CCD gate being struck by
Channels) embedded within a p-type
photons
silicon substrate [6]. N-type silicon is a
semiconductor capable of providing extra
electrons, which the p-type silicon, normally electron-deficient, can accept and store.
Points at which the n-channels cross the electrode material are known as CCD gates and
correspond to one pixel.
When a photon of light strikes a particular gate, it dislodges electrons from the n-channels,
which causes the formation of potential barriers and wells within the p-type substrate. The
excited electrons remained trapped in these wells, and each gate begins to accumulate an
electric charge in proportion to the intensity of light at that gate. Once the image exposure
is complete, the CCDs operate as a shift register and transfer collected charges to the end of
the column for conversion and digitized imaging [7] (see Figure 3 for an analogy).
Figure 3: Bucket Brigade analogy depicting
how CCD operates as a shift register
LUCAS and Digital Holography
The CCD chip is part of the underlying technology behind the
device known as LUCAS: Lens-free Ultra-wide field of view Cell
monitoring Array platform based on Shadow Imaging. Instead
of directly imaging and magnifying cells with a lens, as a
conventional microscope does, LUCAS uses the interferometric,
or electromagnetic wave-based, technique to image cell
shadows in a process known as digital holographic microscopy
[8]. Unlike the dark shadows of the macro-world, such as our
own, the shadows - or diffraction signatures - of micro-objects,
like that of a cell or bacterium, contain an extremely rich source
of quantified information that accurately describes the object’s
spatial features [9] (see Figure 4). These micro-scale shadows
are not flat, but rather, rippled in texture, the details of which
constitute a holographic image of the cell [10]. This hologram
acts as the cell’s fingerprint and can be used to detect the cell
type and potential deformations such as sickle-cell anemia and
malarial disease.
Figure 4: An image of cell
shadows. The blue circles
represent yeast cells, the red red blood cells, and the green
circles represent beads.
Text Messages and Algorithm Matching
The holographic images are often blurry and pixilated [5]; despite their low quality,
however, the images contain all the information necessary for simple software to identify
and count the cells. With image processing software, the hologram can also be used to
reconstruct a microscopic image of the cell. A USB port carries the data between the device
and the cell phone, where it can then be sent wirelessly to a computer station for advanced
image processing.
Powerful software is able to undo any cell image overlap and, through digital computation,
retrieve an exact image of the cells. “We compensate for everything in the digital regime,”
says Ozcan [11]. A pattern-matching algorithm based on cell morphology then compares
the images with a cell library. Dr. Ozcan created this library of holographic cell and
bacterial images, or diffraction signatures, including all possible cells and bacteria to be
analyzed. Based on this image comparison, the cells in the sample are counted and
identified, both for type and potential deficiencies or differences that indicate infection.
Once the algorithm has analyzed the sample, a diagnosis is automatically text-messaged
back to the original cell phone user.
All of this happens within minutes. Currently, software that can perform the patternmatching algorithm directly on the cell phone is being developed, which would eliminate
the need to send it to a computer station and make the process even faster. In addition,
researchers are working to improve the quality of images on both the hardware and
software fronts; as Ozcan says, they hope to soon have “a decent enough resolution to show
subcellular features [11].”
Differential Interference Contrast
Ozcan and his team have also constructed a version of the microscope that uses differential
interference contrast, a technique used in conventional microscopes to enhance image
contrast. Before the LED light beam illuminates the sample, a prism is used to split the light
into two beams, each with a different polarization, or orientation in space. After the two
beams pass through the sample, a second prism is used to recombine the two beams,
producing a single image with enhanced edge contrast [11]. In effect, two images of every
cell, each of a different perspective, are generated, processed, and recombined to produce a
single holographic image with increased contrast. This technique allows the microscope to
successfully image certain strains of bacteria that are otherwise transparent to the
microscope without the use of a stain.
In contrast to the $1000 it normally costs to add prisms and differential interference
contrast abilities to a conventional microscope, this method costs only $3 extra to be
included in this revolutionary device [11].
Uses and Specs
The device can be used to perform basic diagnostics such as red, white, or complete blood
count, diagnosis of infectious diseases such as malaria, TB, or cholera, CD4 T lymphocyte
counts for HIV/AIDS patients, diagnosis of anemia or sickle-cell disease, and water
contamination tests, among others.
It weighs just 46 grams and measures
about six centimeters high and four
centimeters on each side (see Figure 5).
Despite being small and lens-less, the
microscope is able to go submicron in
terms of accuracy and specificity and can
gain a resolution of about two
micrometers, equal to a conventional 40X
microscope. The software is fast, accurate,
and has high throughput: it can image over
100,000 cells in a 20-centimeter squared
field of view in just one second [5] - with at
least a 90% accuracy rate. As Ozcan notes,
“What most excites me about this
technology is the speed that it enables… it
can look at literally millions of cells per
second, all with the holographic resolution
that we want [12].”
Figure 5: An image of the device. The numbers correspond
to the following: 1) CCD chip 2) LED light 3) Mobile phone
The Future Potential of Mobile Microscopes
In a world in which the average flow cytometer costs around $70,000, plus $5-10 for each
test, and an advanced microscope can cost upwards of $200,000, expensive lab equipment
and diagnostics are simply not an option for resource-poor countries, especially those in
which a majority of the people are making under a dollar a day. Unfortunately, it is often
these same countries that are most plagued by infectious diseases and water
contamination: an estimated 4 million people per year die of contagious infections such as
HIV/AIDS, malaria, and TB, and 6 million die from poor drinking water-related problems
[12]. These countries need a cost-efficient and effective means of performing the many
basic medical tests that their citizens require.
In the last few years, Dr. Ayogdan Ozcan and his UCLA research team have come to the
rescue with a device that, capitalizing upon the ever-expanding, global tech-infrastructure
of the mobile phones, can perform basic diagnostic tests on the back of a simple camera
phone. Essentially, Ozcan figured out a way to hack into a $30 cell phone, slide in a blood
sample, shine an LED light, capture a holographic image, and send out a text message that,
when processed and compared to a cell library, can be used to form an almost
instantaneous diagnosis of the disease. Talk about a tech-whiz bang!
Though made with the intention of solving global health issues, the device may soon also be
found in the homes of Americans. Its ability to count white blood cells and infectious cells,
for example, may be instrumental in helping doctors monitor patient response to
chemotherapy – all in the comfort of the patient’s own home.
Whether or not patients adopt mobile diagnostics at home, this simple and cost-effective
device is quickly revolutionizing the field of microscopy, diagnostics, and digital imaging.
Who knows what the future holds. It may just be that soon, bulky, expensive microscopes
will become obsolete, and the cell phone, in ranks with the stethoscope and thermometer,
will become one of the greatest medical devices of our time.
Works Cited
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http://www.popularmechanics.com/science/health/breakthroughs/cellphone-enabledhealthcare
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a Chip, vol. 10, no. 14, pp. 1741-1880, July, 2010.
[3] J. Fildes. (2010, Sept 21). Smart vision for mobile phones in the developing world
[Online]. Available: http://www.bbc.co.uk/news/technology-11374632
[4] VIDEO: http://www.youtube.com/watch?v=3KoUR2KuwjQ
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http://www.technologyreview.com/biomedicine/21439/page1/
[6] R. Repas, “Charge-coupled devices,” Machine Design, vol. 79, iss. 21, pp. 69, Nov. 2007.
[7] C. J. Wordelman and E. K. Banghart, “Charge-Coupled Devices,” in Optoelectronic
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sec. 12.2.1, pp. 344-345.
[8] T. Colomb and J. Kühn, “Digital Holographic Microscopy,” in Optical Measures of Surface
Topography, R. Leach, Ed. Berlin: Springer Berlin Heidelberg, 2011, ch. 10, pp. 209.
[9] (2009). CelloPhone [Online]. Available: http://project.vodafone-us.com/pastcompetitions/2009-competition/2009-winners/cellophone/
[10] J. E. Kasper and S. A. Feller, “Phase holograms and some other types,” in The Complete
Book of Holograms: How They Work and How to Make Them, New York: Dover Pub., 2001,
chp. 7, pp. 91.
[11] K. Bourzac. (2010, May 12). $3 Microscope Plugs into Cell Phones [Online]. Available:
http://www.technologyreview.com/biomedicine/25286/page1/
[12] VIDEO: http://www.youtube.com/watch?v=7FQUHhdGUII
Figure 1: http://www.economist.com/node/14483896
Figure 2/3: http://www.microscopyu.com/articles/digitalimaging/ccdintro.html
Figure 4: [5]
Figure 5: http://www.technologyreview.com/tr35/profile.aspx?trid=808