Luke P. Lee, assistant professor of bioengineering at UC Berkeley,
and his doctoral student Sunghoon Kwon have captured an image of a
plant cell with a microlens smaller than the period at the end of this
"It's shrinking a million dollar machine down to a size that can
balance on the tip of a ballpoint pen," said Lee, who presented the
results at a recent International Conference on Micro Electro Mechanical
Systems. "The microlens and scanner we've made is a crucial part of
a microscope that is 500 to 1,000 times smaller than anything in its
In testing the accuracy of the microlens and scanner, Kwon placed
a cell sample taken from a flowering lily, Convallaria majalis, onto
the platform of a conventional confocal microscope. Without moving
the sample, they captured a cross-sectional image of the cell wall,
first with the traditional microscope, then with the microlens scanner.
They found that the two images matched, showing for the first time
that his microscopic lens could perform as well as a conventional one.
"Honestly, we were shocked," said Lee, who also is co-director of
the Berkeley Sensor & Actuator Center. "What we've finally shown is
a proof of concept. We have tested only 2-D images now, but it's just
a matter of time and manpower before we get the first 3-D image."
The microlens and scanner are part of a device Lee is developing
called the micro confocal imaging array, or micro-CIA. The micro-CIA
belongs to a group of devices known as Bio-Polymer-Opto-Electro-Mechanical-Systems,
or BioPOEMS. Invented by Lee, BioPOEMS marry the world of optics to
that of microelectromechanical systems, or MEMS, for use in biological
The size and sensitivity of the micro-CIA would allow technicians
to quickly test even trace amounts of anthrax or smallpox in the field.
It could become a crucial part of a "lab-on-a-chip," where researchers
can study genes and proteins in ways unimagined decades ago. Lee is
particularly excited by the potential for advancements in medicine
possible with a miniaturized microscope.
"You could put this device on the tip of an endoscope that could
be guided inside a cancer patient," said Lee. "Doctors could then see
how tumor cells behave in vivo. It would also be feasible to deliver
drugs directly to the tumor cell, and then view how the cell responds
to the drugs."
High-end confocal microscopes, which house several lasers, take up
to a meter of desk space, can cost more than $1 million and typically
require highly-trained operators to run them, said Lee. The high cost
of owning and running confocal microscopes limits the amount of research
that can be done with them, he said.
"My goal is to not only shrink the size of these microscopes, but
to make them as easy and as cheap to use as a digital camera," said
Lee. It is with a hint of populist sentiment that Lee began devising
a teeny version of the confocal microscope, the micro-CIA. He envisions
a future where confocal microscopy is as common as a Bunsen burner
in academic and industry research labs.
Unlike scanning electron microscopes, which construct 3-D topological
images of dead cells, confocal microscopes can capture images of nanoscale
activity inside living cells. Confocal microscopes also allow researchers
to focus on specific components inside the cell, such as DNA strands,
Cell parts marked with a fluorescent dye are "excited" by the laser
and emit light back at specific wavelengths. Mitochondria, for instance,
emit a fluorescent red color while nucleic acids emit a fluorescent
blue, depending upon the molecular labeling of each component in the
cell. To form 3-D images, 2-D slices are stacked together in a way
similar to how an MRI image is formed.
Equipped with a microlens about 300 microns in diameter, the microscopic
scanner Lee tested is a square of about 1 millimeter on each side and
can move a distance of 50 to 100 microns. Lee is also testing a nanolens
as small as 500 nanometers in diameter, or 200 times thinner than a
strand of human hair, and smaller than the average red blood cell.
Lee's design of the micro-CIA will include three scanners stacked
vertically above the staging platform where samples are studied. The
scanners will measure each of the three axes - X, Y and Z - in three-dimensional
To make the scanner and lens, Lee employed technology similar to
that used to manufacture microchips. The lens is made of a tiny drop
of polymer shaped by surface tension and hardened by exposure to ultraviolet
light. To focus the lens, Lee and Kwon adjusted the distance between
the lens and sample. While it is also possible to focus by changing
the shape of the lens, Lee said doing so would likely increase the
cost and complexity of production, something he wants to avoid.
Comb-drives on each side of the microlens act as microactuators,
tiny engines powered by electrostatic forces that move the microlens
back and forth 4,500 times per second. Sensors then pick up fluorescent
signals and feed the data back to a computer where the image is displayed
in real time.
Lee's work is part of UC Berkeley's Health Sciences Initiative, which
brings together scientists from disparate fields in the pursuit of
major advances in health and medicine.
The research is part of a three-year project funded by the Defense
Advanced Research Projects Agency.