Cambridge, MA
February 6,
1998
.The National Cancer Institute of the
National Institutes of Health recently awarded
One Cell Systems, Inc. a $750,000 Phase II Small
Business Innovation Research grant (SBIR) to
develop a high throughput method for isolating
pure populations of intact chromosomes using
micro-encapsulation, in situ
hybridization, and fluorescence activated cell
sorting.
Use of flow cytometry, which is
rapid, high throughput, and permits evaluation of
small sub-populations is expected to dramatically
expand the analytical options available for both
genomic and molecular cytogenetic research.
"Because of limited resolution
using relatively non-specific DNA dyes,
chromosomes which have the same size or the same
base pair composition cannot now be isolated
using flow cytometry", said Dr. Jan
Trnovsky, Principal Investigator for this
research. "In addition, since individual
chromosomes do not withstand hybridization
conditions in solution, use of flow cytometry for
chromosomal analysis is not practical" Dr.
Trnovsky continued.
Currently, since in situ
hybridization must be performed using a solid
support, such as a glass microscope slide,
analysis is limited to chromosomal aberrations
present in high frequency. The ability to rapidly
screen chromosomal samples for DNA aberrations
present in low frequency is critical to improving
an understanding of these phenomena.
Development of the gel microdrop
chromosome sorting system which combines the
specificity of in situ hybridization with
the automated analysis and recovery of flow
sorting would dramatically improve human, animal,
and plant genomic mapping and sequencing
applications.
An additional benefit of the
proposed method is that encapsulation stabilizes
chromosomes making long term storage at 4° C
possible. This integrated system for identifying,
recovering, and ultimately storing chromosomes
and chromosome fragments will improve molecular
techniques for gene transfer for both human and
plant product development.
Discovery of new genes and their
functions are the focus of intensive efforts by
pharmaceutical companies and genome researchers.
The ability to rapidly screen pure populations of
chromosomes would represent an important
improvement over existing methods with
implications for eventual automation of molecular
cytogenetic testing.
The proposed automated system is
expected to allow rapid diagnosis of chromosomal
abnormalities in a wide variety of diseases. In
addition, prognostic screening of high risk
individuals to monitor minimal residual disease
would benefit from sensitive, high throughput
cytogenetic methods.
One Cell Systems, Inc. is developing
a family of assays based on micro-encapsulation
and flow cytometry for rapid, quantitative
analysis and recovery of cells, bacteria, nuclei
and chromosomes.
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