Biochip-based device for cell analysis May
30, 2012 This is an assembled flow
cytometry chip with size comparable to a US quarter. Credit: Tony Jun Huang, Penn State (Phys.org) -- Inexpensive, portable devices
that can rapidly screen cells for leukemia or HIV may soon be possible thanks
to a chip that can produce three-dimensional focusing of a stream of cells,
according to researchers. "HIV is diagnosed based on counting CD4
cells," said Tony Jun Huang, associate professor of engineering science
and mechanics, Penn
State . "Ninety
percent of the diagnoses are done using flow cytometry." Huang
and his colleagues designed a mass-producible device that can focus particles
or cells in a single stream and performs three different optical assessments
for each cell. They believe the device represents a major step toward low-cost
flow cytometry chips for clinical diagnosis in hospitals, clinics and in the
field. "The full potential of flow cytometry as
a clinical diagnostic tool has yet to be realized and is still in a process of
continuous and rapid development," the team said in a recent issue of
Biomicrofluidics. "Its current high cost, bulky size, mechanical
complexity and need for highly trained personnel have limited the utility of
this technique." Flow cytometry typically looks at cells in
three ways using optical sensors. Flow cytometers use a tightly focused laser
light to illuminate focused cells and to produce three optical signals from
each cell. These signals are fluorescence from antibodies bound to cells, which
reveals the biochemical characteristics of cells; forward scattering, which
provides the cell size and its refractive index; and side scattering, which
provides cellular granularity. Processing these signals allows diagnosticians to
identify individual cells in a mixed cell population, identify fluorescent
markers and count cells and other analysis to diagnose and track the
progression of HIV, cancer and other diseases. "Current
machines are very expensive costing $100,000," said Huang. "Using our
innovations, we can develop a small one that could cost about $1,000." One
reason the current machines are so large and expensive is the method used to
channel cells into single file and the necessary alignment of lasers and
multiple sensors with the single-file cell stream. Currently, cells are guided
into single file using a delicate three-dimensional flow cell that is difficult
to manufacture. More problematic is that these current machines need multiple
lenses and mirrors for optical alignment. "Our
approach needs only a simple one-layer, two-dimensional flow cell and no
optical alignment is required," said Huang. Huang
and his team used a proprietary technology named microfluidic drifting to
create a focused stream of particles. Using a curved microchannel, the
researchers took advantage of the same forces that try to move passengers in a
car to the outside of a curve when driving. The microfluidic chip's
channelbegins as a main channel that contains the flow of carrier liquid and a
second channel that comes in perpendicularly that carries the particles or
cells. Immediately after these two channels join, the channel curves 90
degrees, which moves all the cells into a horizontal line. After the curve,
liquid comes into the channel on both sides, forcing the horizontal line of
cells into single file. The cells then pass through a microlaser beam. An
advantage of this microfluidic flow cytometry chip is that it can be
mass-produced by molding and standard lithographic processes. The fibers for
the optical-fiber delivered laser beams and optical signals already exist. "The
optical fibers are automatically aligned once inserted into the chip, therefore
requiring no bulky lenses and mirrors for optical alignment," said Huang.
"Our machine is small enough it can be operated by battery, which makes it
usable in Africa and other remote
locations." The researchers tested the device using
commercially available, cell-sized fluorescent beads. They are now testing the
device with actual cells.
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