News Article
Caltech Bio-engineers Develop Microscope On A Chip
The chip offers a multitude of applications in life sciences and
technology.
Researchers at the California Institute
of Technology have turned science fiction into reality with their
development of a super compact high resolution microscope, small
enough to fit on a finger tip. This "microscopic microscope"
operates without lenses but has the magnifying power of a top quality
optical microscope, can be used in the field to analyse blood samples
for malaria or check water supplies for giardia and other pathogens,
and can be mass produced for around $10.
"The whole thing is truly compact,
it could be put in a cell phone, and it can use just sunlight for
illumination, which makes it very appealing for third world
applications," says Changhuei Yang, assistant professor of
electrical engineering and bioengineering at Caltech, who developed
the device, dubbed an optofluidic microscope, along with his
colleagues at Caltech.
The new instrument combines traditional
computer chip technology with microfluidics, the channelling of fluid
flow at incredibly small scales. An entire optofluidic microscope
chip is about the size of a US quarter, although the part of the
device that images objects is only the size of Washington's nose on
that quarter.
"Our research is motivated by the
fact that microscopes have been around since the 16th century, and
yet their basic design has undergone very little change and has
proven prohibitively expensive to miniaturise. Our new design
operates on a different principle and allows us to do away with
lenses and bulky optical elements," says Yang.
The fabrication of the microscopic chip
is disarmingly simple. A layer of metal is coated onto a grid of
charge coupled device (CCD) sensor (the same sensors that are used in
digital cameras). Then, a line of tiny holes, less than one millionth
of a meter in diameter, is punched into the metal, spaced five
micrometers apart. Each hole corresponds to one pixel on the sensor
array. A microfluidic channel, through which the liquid containing
the sample to be analysed will flow, is added on top of the metal and
sensor array. The entire chip is illuminated from above; sunlight is
sufficient.
When the sample is added, it flows,
either by the simple force of gravity or drawn by an electric charge,
horizontally across the line of holes in the metal. As cells or small
organisms cross over the holes, one hole after another, the objects
block the passage of light from above onto the sensor below. This
produces a series of images, consisting of light and shadow, akin to
the output of a pinhole camera.
Because the holes are slightly skewed,
so that they create a diagonal line with respect to the direction of
flow, the images overlap slightly. All of the images are then pieced
together to create a surprisingly precise two dimensional picture of
the object.
Yang is now in discussion with biotech
companies to mass produce the chip. The platform into which the chip
is integrated can vary depending upon the needs of the user. For
example, health workers in rural areas could carry cheap, compact
models to test individuals for malaria, and disposable versions could
be carried into the battlefield. "We could build hundreds or
thousands of optofluidic microscopes onto a single chip, which would
allow many organisms to be imaged and analysed at once," says
Xiquan Cui, the lead graduate student on the project.
In the future, the microscope chips
could be incorporated into devices that are implanted into the human
body. "An implantable microscope analysis system can
autonomously screen for and isolate rogue cancer cells in blood
circulation, thus, providing important diagnostic information and
helping arrest the spread of cancer," says Yang.
The paper, "Lens less high
resolution on chip optofluidic microscopes for Caenorhabditis elegans
and cell imaging," was published July 28 in the early online
edition of the Proceedings of the National Academy of Sciences.
Yang's co-authors are graduate students Xiquan Cui and Lap Man Lee;
post doctoral research associates Xin Heng and Weiwei Zhong; Paul W.
Sternberg, the Thomas Hunt Morgan Professor of Biology and an
Investigator with the Howard Hughes Medical Institute; and Demetri
Psaltis, the Thomas G. Myers Professor of Electrical Engineering at
Caltech.
The work was funded by DARPA's Centre
for Optofluidic Integration at Caltech, the Wallace Coulter
Foundation, the National Science Foundation, and the National
Institutes of Health.
of Technology have turned science fiction into reality with their
development of a super compact high resolution microscope, small
enough to fit on a finger tip. This "microscopic microscope"
operates without lenses but has the magnifying power of a top quality
optical microscope, can be used in the field to analyse blood samples
for malaria or check water supplies for giardia and other pathogens,
and can be mass produced for around $10.
"The whole thing is truly compact,
it could be put in a cell phone, and it can use just sunlight for
illumination, which makes it very appealing for third world
applications," says Changhuei Yang, assistant professor of
electrical engineering and bioengineering at Caltech, who developed
the device, dubbed an optofluidic microscope, along with his
colleagues at Caltech.
The new instrument combines traditional
computer chip technology with microfluidics, the channelling of fluid
flow at incredibly small scales. An entire optofluidic microscope
chip is about the size of a US quarter, although the part of the
device that images objects is only the size of Washington's nose on
that quarter.
"Our research is motivated by the
fact that microscopes have been around since the 16th century, and
yet their basic design has undergone very little change and has
proven prohibitively expensive to miniaturise. Our new design
operates on a different principle and allows us to do away with
lenses and bulky optical elements," says Yang.
The fabrication of the microscopic chip
is disarmingly simple. A layer of metal is coated onto a grid of
charge coupled device (CCD) sensor (the same sensors that are used in
digital cameras). Then, a line of tiny holes, less than one millionth
of a meter in diameter, is punched into the metal, spaced five
micrometers apart. Each hole corresponds to one pixel on the sensor
array. A microfluidic channel, through which the liquid containing
the sample to be analysed will flow, is added on top of the metal and
sensor array. The entire chip is illuminated from above; sunlight is
sufficient.
When the sample is added, it flows,
either by the simple force of gravity or drawn by an electric charge,
horizontally across the line of holes in the metal. As cells or small
organisms cross over the holes, one hole after another, the objects
block the passage of light from above onto the sensor below. This
produces a series of images, consisting of light and shadow, akin to
the output of a pinhole camera.
Because the holes are slightly skewed,
so that they create a diagonal line with respect to the direction of
flow, the images overlap slightly. All of the images are then pieced
together to create a surprisingly precise two dimensional picture of
the object.
Yang is now in discussion with biotech
companies to mass produce the chip. The platform into which the chip
is integrated can vary depending upon the needs of the user. For
example, health workers in rural areas could carry cheap, compact
models to test individuals for malaria, and disposable versions could
be carried into the battlefield. "We could build hundreds or
thousands of optofluidic microscopes onto a single chip, which would
allow many organisms to be imaged and analysed at once," says
Xiquan Cui, the lead graduate student on the project.
In the future, the microscope chips
could be incorporated into devices that are implanted into the human
body. "An implantable microscope analysis system can
autonomously screen for and isolate rogue cancer cells in blood
circulation, thus, providing important diagnostic information and
helping arrest the spread of cancer," says Yang.
The paper, "Lens less high
resolution on chip optofluidic microscopes for Caenorhabditis elegans
and cell imaging," was published July 28 in the early online
edition of the Proceedings of the National Academy of Sciences.
Yang's co-authors are graduate students Xiquan Cui and Lap Man Lee;
post doctoral research associates Xin Heng and Weiwei Zhong; Paul W.
Sternberg, the Thomas Hunt Morgan Professor of Biology and an
Investigator with the Howard Hughes Medical Institute; and Demetri
Psaltis, the Thomas G. Myers Professor of Electrical Engineering at
Caltech.
The work was funded by DARPA's Centre
for Optofluidic Integration at Caltech, the Wallace Coulter
Foundation, the National Science Foundation, and the National
Institutes of Health.
