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FAST Cytometer for Rare Cell
Detection
The Fiber Array Scanning Technology
(FAST) cytometer, developed as part of the Scripps-PARC
Institute for Advanced Biomedical Sciences,
uses lasers, opto-mechanical engineering, and imaging
to detect rare cells almost 1000 times faster than
digital microscopy, the current gold standard for
sensitivity.
The term rare cells refers
to uniquely identifiable cells that occur in a sample
in extremely low concentrations – on the order
of one in millions – and are associated with a
number of conditions including cancer.
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Scientists prepare a
sample for scanning on the FAST Cytometer
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A blood test for screening and
monitoring cancer has been a long-term goal of biomedical
science. Occult tumor cells (OTCs) have been found
in peripheral blood, but their concentration is
very low – one in millions. Detection of tumor cells
in peripheral blood using immunocytochemistry and
optical scanning is a promising method for screening
and monitoring cancer. However, digital microscopy,
the current gold standard for sensitivity, is far
too slow for practical application in diagnostics
and the low specificity requires substantial subsequent
examination by a trained pathologist. To scan 50
million blood cells would take 32 hours, and thousands
of objects would need to be reexamined by an expert.
PARC Approach
PARC's FAST cytometer is a pre-scan technology that can very rapidly find
a small number of candidate objects, which are
then examined with digital microscopy to determine
if they are genuine tumor cells. The entire process
is 1000-times faster than digital microscopy alone
and has a similar sensitivity and specificity.
Testing begins with conventional
staining of OTCs with fluorescent probes. The probes
are attached to the OTC through an antibody reaction
specific to the OTC. The peripheral blood sample
is then rapidly scanned for the presence of these
probes using a directed laser.
The key innovation in this work is the asymmetrically shaped fiber-optic bundle
that collects the fluorescence. The collection end
of the bundle is wide and thin. A laser is rapidly
scanned across a sample that is positioned directly
underneath this large (50mm) aperture. The collected
fluorescence is transmitted to a collimating lens
system through a small circular aperture at the
other end of the bundle.
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Sample image generated from FAST Cytometer;
the system has detected
288 potential rare cells among over 50 million scanned
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The collimation is appropriate
for conventional optical filtering with subsequent
detection in a photomultiplier. The optical filter
system detects two emission wavelengths simultaneously
to reduce noise from the staining process. A stage
slowly moves the sample across the scanning field.
The fluorescent object location can be computed
from the position of the stage and laser beam at
the time of detection.
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