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Claims  |
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We claim:
1. A cell analyze apparatus comprising:
a flow cell through which a cell float fluid flows;
a light source for irradiating a light beam onto cells flowing through said
flow cell;
cell light information detecting means for detecting, for each said cell
irradiated by the light beam, cell light information with respect to a
plurality of parameters;
cell population subdividing means for detecting minimal points in
histograms of cell light information obtained by said cell light
information detecting means with respect to one or more parameters to
subdivide a population of the cells in the cell float fluid into functions
based on the minimal points;
cell light information collecting means for collecting, based on one or
more of the fractions produced by said cell population subdividing means,
cell light information of an objective cell population from the cell light
information attained by said cell light information detecting means;
cell light information processing means for processing the cell light
information of the objective cell population collected by said cell light
information collecting means;
output means for outputting results of the processing conducted by said
cell light information processing means; and
parameter converting means for converting said one or more parameters
depending on a predetermined conversion expression,
said cell population subdividing means detecting minimal points from
histograms of the cell light information with respect to new parameters
attained through a conversion achieved by said parameter converting means.
2. A cell analyze apparatus according to claim 1 wherein:
said cell light information collecting means includes a cell light
information separating means,
said cell light information separating means separating, from the cell
light information detected by said cell light information detecting means,
cell light information of a cell population belonging to one or more
fractions with respect to a parameter,
said cell light information collecting means collecting, from the separated
cell light information, cell light information of a cell population
belonging to a predetermined fraction with respect to other parameters.
3. A cell analyze apparatus according to claim 1 further including:
maximum frequency point extracting means for processing the cell light
information of the objective cell population collected by said cell light
information collecting means to extract a maximum frequency point on a
cytogram of parameters associated with the fraction of the cell
population;
direct line generating means for radially drawing direct lines from the
maximum frequency point extracted by said maximum frequency point
extracting means on the cytogram;
boundary point extracting means for extracting boundary points based on
histograms on the respective direct lines produced by said direct line
generating means; and
second cell light information collecting means for linking the boundary
points extracted by said boundary point extracting means to form a final
fraction to collect cell light information of an objective cell population
based on the final fraction.
4. A cell analyze apparatus according to claim 1 further including:
histogram generating means for processing the cell light information
collected by said cell light information collecting means to attain, for
each predetermined frequency of a parameter, a histogram of another
parameter;
boundary point extracting means for extracting boundary points based in
each histogram generated by said histogram generating means; and
second cell light information collecting means for linking the boundary
points extracted by said boundary point extracting means to form a final
fraction to collect cell light information of an objective cell population
based on the final fraction.
5. A cell analyze apparatus according to claim 1 further including:
histogram generating means for generating a histogram of cell light
information with respect to at least a parameter of the cell light
information detected by said cell light information detecting means;
minimal point detecting means for detecting a minimal point of the
histogram created by said histogram generating means; and
unnecessary information removal means for setting a noise threshold based
on the minimal point detected by said minimal point detecting means to
remove, by use of the noise threshold, unnecessary information included in
the cell light information detected by said cell light information
detecting means.
6. A cell analyze apparatus according to claim 1 further including:
sample supply means for sequentially sipping a plurality of samples to
supply the sipped samples to said flow cell; and
measurement condition setting means for setting to said cell light
information processing means an optimal measurement condition depending on
the sample to be supplied by said sample supply means.
7. A cell analyze apparatus comprising:
a flow cell through which a cell float fluid flows;
a light source for irradiating a light beam onto cells flowing through said
flow cell;
cell light information detecting means for detecting, for each said cell
irradiated by the light beam, cell light information with respect to a
plurality of parameters;
cell population subdividing means for detecting minimal points in
histograms of cell light information obtained by said cell light
information detecting means with respect to one or more parameters to
subdivide a population of the cells in the cell float fluid into fractions
based on the minimal points;
cell light information collecting means for collecting, based on one or
more of the fractions produced by said cell population subdividing means,
cell light information of an objective cell population from the cell light
information attained by said cell light information detecting means;
cell light information processing means for processing the cell light
information of the objective cell population collected by said cell light
information collecting means; and
output means for outputting results of the processing conducted by said
cell light information processing means,
said cell light information collecting means having cell light information
separating means,
said cell light information separating means separating, from the cell
light information detected by said cell light information detecting means,
cell light information of a cell population belonging to one or more
fractions with respect to a parameter,
said cell light information collecting means collecting, from the separated
cell light information, cell light information of a cell population
belonging to a predetermined fraction with respect to other parameters.
8. A cell analyze apparatus comprising:
a flow cell through which a cell float fluid flows;
a light source for irradiating a light beam onto cells flowing through said
flow cell;
cell light information detecting means for detecting, for each said cell
irradiated by the light beam, cell light information with respect to a
plurality of parameters;
cell population subdividing means for subdividing, based on one or more
parameters obtained by said cell light information detecting means, a
population of the cells in the cell float fluid into fractions;
first cell light information collecting means for collecting, based on one
or more of the fractions produced by said cell population subdividing
means, cell light information of an objective cell population from the
cell light information attained by said cell light information detecting
means;
cell light information processing means for processing the cell light
information detected by said cell light information detecting means and
the cell light information of the objective cell population collected by
said first cell light information collecting means;
output means for outputting results of the processing conducted by said
cell light information processing means;
Maximum frequency point extracting means for processing the cell light
information of the objective cell population collected by said first cell
light information collecting means to extract a maximum frequency point on
a cytogram of parameters associated with the fraction of the cell
population;
direct line generating means for radially drawing direct lines from the
maximum frequency point extracted by said maximum frequency point
extracting means on the cytogram;
boundary point extract means for extracting boundary points based on
histograms of the respective direct lines produced by said direct line
generating means; and
second cell light information collecting means for linking the boundary
points extracted by said boundary point extracting means to form a final
fraction to collect cell light information of an objective cell population
based on the final fraction.
9. A cell analyze apparatus according to claim 8, wherein said boundary
point extracting means extracts as boundary points where the histogram
intersects a threshold value or the minimal points of the histograms.
10. A cell analyze apparatus comprising:
a flow cell through which a cell float fluid flows;
a light source for irradiating a light beam onto cells flowing through said
flow cell;
cell light information detecting means for detecting, for each said cell
irradiated by the light beam, cell light information with respect to a
plurality of parameters;
cell population subdividing means for subdividing, based on one or more
parameters obtained by said cell light information detecting means, a
population of the cells in the cell float fluid;
first cell light information collecting means for collecting, based on one
or more fractions of the fractions produced by said cell population
subdividing means, cell light information of an objective cell population
from the cell light information detected by said cell light information
detecting means;
cell light information processing means for processing the cell light
information detected by said cell light information detecting means and
the cell light information of the objective cell population collected by
said first cell light information collecting means;
output means for outputting results of the processing conducted by said
cell light information processing means;
histogram generating means for processing the cell light information
collected by said first cell light information collecting means to attain,
for each predetermined frequency of a parameter, a histogram of other
parameters;
boundary point extracting means for extracting boundary points based on
each histogram generated by said histogram generating means; and
second cell light information collecting means for linking the boundary
points extracted by said boundary point extracting means to form a final
fraction to collect cell light information of an objective cell population
based on the final fraction.
11. A cell analyze apparatus according to claim 10, wherein said boundary
point extracting means extracts as boundary points where the histogram
intersects a threshold value or the minimal points of the histograms.
12. A cell analyze apparatus comprising:
a flow cell through which a cell float fluid flows;
a light source for irradiating a light beam onto cells flowing through said
flow cell;
cell light information detecting means for detecting, for each said cell
irradiated by the light beam, cell light information with respect to a
plurality of parameters;
cell light information discriminating means for discriminating cell light
information of an objective cell population from the cell light
information detected by said cell light information detecting means;
cell light information processing means for processing the cell light
information detected by said cell light information detecting means and
the cell light information discriminated by said cell light information
discriminating means;
output means for outputting results of the processing conducted by said
cell light information processing means;
histogram generating means for generating a histogram of cell light
information with respect to at least a parameter of the cell light
information detected by said cell light information detecting means;
minimal point detecting means for detecting a minimal point of the
histogram created by said histogram generating means; and
unnecessary information removal means for setting a noise threshold based
on the minimal point detected by said minimal point detecting means to
remove, by use of the noise threshold, unnecessary information included in
the cell light information detected by said cell light information
detecting means.
13. A cell analyze apparatus comprising:
a flow cell through which a cell float fluid flows;
a light source for irradiating a light beam onto cells flowing through said
flow cell;
cell light information detecting means for detecting, for each said cell
irradiated by the light beam, cell light information with respect to a
plurality of parameters;
cell light information discriminating means for discriminating cell light
information of an objective cell population from the cell light
information detected by said cell light information detecting means;
cell light information processing means for processing the cell light
information detected by said cell light information detecting means and
the cell light information discriminated by said cell light information
discriminating means;
output means for outputting results of the processing conducted by said
cell light information processing means;
sample supply means for sequentially sipping a plurality of samples to
supply the sipped samples to said flow cell; and
measurement condition setting means for setting to said cell light
information processing means an optimal measurement condition depending on
the sample to be supplied by said sample supply means. |
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Claims |
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Description |
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BACKGROUND OF THE INVENTION
1. Field of the invention
The present invention relates to an apparatus for analyzing cells by means
of flow cytometry.
2. Description of the Prior Art
In flow cytometry, a sample including cells (or particles like cells)
conjugated, for example, by use of fluorescent dye or antibodies is passed
together with sheath fluid into a crystal flow cell. The sample is wrapped
in a pressurized sheath flow so that a thin, stable stream of the sample
(laminar flow) flows through the center of the flow cell (hydro-dynamic
focusing). The cells line up within stream and the flow past a focused
laser beam (the sensing zone) at a constant speed. At this point, scatter
lights and fluorescence from the cells are measured simultaneously by some
independent sensors. The computer analyses the strength of these signals
and uses it to classify the cells.
As cell analyzer by flow cytometry, there has been known an apparatus
including a flow cell for producing a thin stream, a light source (for
example, a laser device) to apply a light beam onto cells flowing through
the flow cell, a sensor or detector for detecting light information of
cell on which the light beam is irradiated so as to convert the
information into electric signals, and a computer achieving operations
such as an analysis process of the light information of the cells thus
represented in the form of electric signals.
In this cell analyze apparatus of the prior art, a sample in which cells
conjugated a fluorescent dye or antibodies are floating is supplied into
the flow cell together with sheath fluid. A sheath flow is then formed in
the flow cell such that owing to the hydro-dynamic focusing effect, the
cells are arranged in a line along a center axis of the flow cell.
When a light beam is applied onto the cells, there are developed scatter
lights and fluorescence such that the intensity of the lights and
fluorescence are detected as parameters constituting the cell light
information by means of light detectors such as a photoelectric
multiplier.
Incidentally, there exists a case in which cell analysis is desired to be
effected on one cell population selected from a plurality of cell
populations included in the sample. For example, in a case of an analysis
to be conducted on lymphocyte subsets or phagocytosis of human blood
cells, whole blood is employed as a sample. That is, in this situation,
incubated with a monoclonal antibody conjugated with a fluorescent dye [in
a case of two-color analysis, for example, an OKT4 monoclonal antibody
conjugated with fluorescenin isothiocyanate (FITC; green fluorescence) and
an OKT8 monoclonal antibody conjugated with phycoerythrin (PE; red
fluorescence)] After it is caused to react upon whole blood so as to be
thereafter subjected to hemolysate a sample is thereby prepared.
The laser beam is irradiated onto each cell flowing through the flow cell
so as to detect by means of detectors which measure four parameters,
namely, an intensity of forward light scattering I.sub.0 (of scatter light
in a direction along the optical axis of the radiated beam), an intensity
of 90.degree. or right angle light scattering (of scatter light in a
direction orthogonal to the optical axis of the radiated laser beam), an
intensity of green fluorescence I.sub.g, and an intensity of red
fluorescence I.sub.r, thereby obtaining light information of the cell (to
be called cell light data in some cases). The sample includes, in addition
to lymphocytes, other substances such as monocytes and granulocytes and
hence it is necessary to discriminate the data related to lymphocytes from
other cells.
For this purpose, there has been known a method called a window method in
which the cell light information associated with a desired cell population
is discriminated and is gathered. (For details, refer to the Japanese
Patent Unexamined Publication (Kokai) No. 62-134559, for example. )
According to the window method, in a space including a coordinate system
constituted with one or more parameters selected from the light
information items of the cells, the operator establishes an analysis
region or area called a window such that light information of the cells
belonging to the area is collected as the light information of the
objective cell population.
For example, in lymphocyte subset analysis, there are adopted two
parameters including the intensity of forward light scattering I.sub.0 to
represent cell size and the intensity of right angle light scattering
I.sub.90 to indicate complexity of cell internal matter so as to draw a
cytogram in which the abscissa and the ordinate designate the values of
I.sub.90 and I.sub.0, respectively. In this diagram, the values of
I.sub.90 and I.sub.0 are normalized depending on the maximum values
measured so as to set a maximum value of the scale to 256 (eight bits).
The values are represented in the unit of channels (ch); moreover, b, c,
and d respectively designate distributions of lymphocytes, monocytes, and
granulocytes, respectively. In the graph, a stands for a distribution of
debris, which includes substances such as membrane components of red blood
cell and is usually removed at the noise threshold.
For analysis of lymphocytes, a reference sample (a sample of a person of a
normal health) is employed so as to set a window e as indicated by
double-dot-and-dash lines in FIG. 1. Data related to lymphocytes
associated with the window e is selected (extracted) from the data
gathered through the measurement. The data thus selected for lymphocytes
is subjected to computations of the intensity I.sub.g and I.sub.r of the
green and red fluorescence, respectively so as to attain the positive
ratios of the reaction with a monoclonal antibody conjugated with a
fluorescent dye such that the results are displayed on the CRT or are
printed out on a sheet of paper by means of the printer.
However, according to the window method above, it is necessary in some
cases for the operator to change the window depending on a sample so as to
collect the light information of the objective cell population. For
example, in lymphocyte subset analysis, since the location, size, and
contour or shape of the distribution b of lymphocytes shown in FIG. 1 vary
depending on the sample, the operator is required to change the window e
in a corresponding fashion. Such a change of window prevents an automatic
measurement of a great number of samples from being conducted with high
efficiency.
In order to cope with such a difficulty, the present applicant has already
filed an application of an automatic cell analyze apparatus in which the
measurement is automatically carried out without necessitating the
operator to establish the window (Japanese Patent Application No.
62-22884: Kokai No. 63-191043). In accordance with the cell analyzer
above, one or more parameters selected from the cell light information
items are employed to generate histograms such that minimal points
(associated with the smallest frequency value in the distribution) are
detected from the histograms so as to subdivide the cell populations to
establish an analysis area including one or more subdivided regions or
partitions, thereby collecting light information of cells belonging to the
analysis area as the light information of the objective cell population.
In this description, the minimal point does not indicate a minimal point
defined in a sense of mathematics, namely, indicates a portion of a valley
appearing between adjacent peaks in the frequency distribution.
For example, in the case of the lymphocyte subset analysis, as can be seen
from FIGS. 2a and 2b, there are produced histograms associated with the
intensity of right angle light scattering I.sub.90 forward light
scattering I.sub.0 in which the ordinate designates the number n of cells.
There are detected minimal points p.sub.1, p.sub.2, and p.sub.3 of the
histogram of I and minimal points p.sub.4 and p.sub.5 of the histogram of
I.sub.0. These minimal points p.sub.1 to p.sub.5 are represented in a
cytogram related to I.sub.90 and I.sub.0 so as to obtain partitions or
fractions indicated with broken lines in FIG. 1. Since the distribution of
lymphocytes is included in the fraction B, there are retrieved, from the
light information items of all the measured cells, light information items
of cells belonging to the fraction B, namely, of cells for which I.sub.90
is at least p.sub.1 and at most p.sub.2 and for which I.sub.0 is at least
p.sub.4 and at most p.sub.5, thereby collecting the light information of
lymphocytes.
However, depending on samples, particularly, in a case of blood of a
patient, there cannot be extracted any expected minimal points from the
histograms produced with respect to one or more parameters above and hence
the light information of the objective cell population cannot be attained
in some cases. For example, in the lymphocyte subset analysis, there
exists sometimes such case that the above minimal points p.sub.a or
p.sub.1 cannot be detected in a histogram of the intensity of right angle
light scattering I.sub.90 depending on conditions, histograms of such case
being shown in FIGS. 8a and 8b which will be described later.
On the other hand, even if such minimal points are detected and there is
determined a fraction containing the objective cell population, it is
required to retrieve data items of all the measured cells by use of the
two parameters so as to gather the light information of the objective cell
population, which leads to a problem that a considerably long period of
time is necessary for the data collect processing.
On the other hand, in the cell analyze apparatus of the prior art above,
cell light information collect means gathers the light information of the
objective cell population. However, as shown in FIG. 1, the fraction is a
region having a rectangular shape in the cytogram; in consequence, the
fraction is not completely matched with the shape or contour of the
distribution of the objective cell population and hence light information
of unnecessary cells are included in the attained light information of the
objective cell population, namely, there arises a problem that the
analysis precision is lowered.
As a method to determine an analysis area more suitably matched with the
contour of the distribution of the objective cell population, there has
been known the contour trace method, which however requires a long period
of computation time and hence is not suitable with respect to the
efficiency of the cell analysis.
Generally, the sample includes, in addition to the cells, other substances
such as dust and dirt in a small amount; furthermore, the sheath fluid
also includes a slight amount of dust. When such dust passes through the
flow cell, unnecessary information, namely, a noise appears in the cell
light information. For example, in a case of lymphocyte subset analysis,
as shown in FIG. 3a, substances such as membrane components of
erythrocytes remained in the sample as a result of hemolysis may appear as
a ghost (debris) a as described above, or the dust in the sample or sheath
fluid may be detected as a noise ni.
To overcome this difficulty, in the cell analyze apparatus of the prior
art, there is disposed a noise threshold circuit in a signal processing
circuit to process signals supplied from the light detectors or
photosensors such that the noise threshold levels Nh and Ns are
established as shown in FIGS. 3a and 3b so as to remove the ghost a of red
blood cell and the noise ni due to the dust, thereby guaranteeing the
reliability of the cell analysis. In order to set the noise threshold
values, the operator inputs threshold levels to the computer, which in
turn transfers the received levels to the noise threshold cirucit. Namely,
the computer operates only as an interface between the operator and the
noise threshold circuit; in other words, in the conventional cell
analyzer, it can be considered that the noise is removed by means of the
hardware system.
In this situation, however, in a case where a great amount of samples are
to be processed in a sequential fashion, for example, when an automatic
sampler or an auto-sampler automatically supplying samples is used, due to
the ghost of red blood cell and the dust in the sheath fluid, there is
frequently required an operation to rearrange the noise threshold levels
again, which leads to a problem that the efficiency of the inspection is
reduced. In addition, if the change of the setting of the noise threshold
levels is mistakenly ignored or if the setting change is inappropriately
achieved, there arises a problem that the reliability is lowered in the
cell analysis.
Recently, in the cell analyze apparatus above, in order to measure a large
amount of samples efficiently, there has been considered an introduction
of a so-called auto-sampler, which automatically supplies samples to the
measurement system. Furthermore, with a provision of the auto-sampler, a
direct contact can be avoided between the samples and the operator, which
is favorable with respect to the prevention of bio-hazard.
However, there exist many factors exerting influences onto the positive
ratio and hence the measurement conditions vary among the sample
processing methods. For example, since the reaction between the various
monoclonar antibodies and cells characterizes the results measurement,
even when the identical detector is employed, the measurement cannot be
conducted by use of the same detection gain. Moreover, due to the
difference among the types of linkages between the monoclonal antibodies
and fluorescent materials, there is required a correction to be effected
when an intensity of the fluorescence is detected.
In consequence, for each sample, it is necessary to select and to set an
appropriate measurement condition; however, the selection and setting
operation requires knowledge gathered through a long experiece, and hence,
conventionally, the operator achieves the select and set operation while
monitoring the data. This job however necessitates an experienced skill
and a considerable volume of labor; in consequence, the reliability of
measured results cannot be increased and a great amount of samples cannot
be efficiently subjected to the measurements. As a result, even if the
auto-sampler is adopted so as to automatically conduct only the operation
to supply the samples, the operation to select and to set the measurement
condition is kept unchanged like in the case of the conventional system,
and hence it is impossible to increase the efficiency of the measurements
and to improve the the reliability of measured results.
SUMMARY OF THE INVENTION
It is therefore an object of the present invention to provide a cell
analyzer in which even when a minimal point cannot be extracted from a
histogram, the light information can be collected for the objective cell
population and the information collection speed can be increased, thereby
removing the problems above.
Another object of the present invention is to provide a cell analyze
apparatus in which a fraction matching with a distribution of the
objective cell population can be determined in a short period of
processing time.
Still another object of the present invention is to provide a cell
analyzing device in which appropriate noise threshold levels can be
automatically established for each sample.
Another object of the present invention is to provide a cell analyze
apparatus in which an optimal measurement condition can be automatically
set for each sample so as to increase the reliability of measured results
and to measure a great number of sample with highly efficiency.
The present invention is applicable to a cell analyze apparatus comprising
a flow cell in which a cell float fluid including floating cells (also
including particles like cells) flows, a light source for irradiating a
light beam onto cells flowing through the flow cell, cell light
information detect means operative for each cell onto which the light beam
is irradiated for detecting cell light information with respect to a
plurality of parameters, cell population subdivide means subdividing a
cell population in the cell float fluid based on one or more parameters
attained by the cell light information means, cell light information
collect means for collecting cell light information of an objective cell
population from cell light information detected by the cell light
information detect means based on one or more fractions selected from the
fractions obtained by the cell population subdivide means, cell light
information process means for processing cell light information of the
objective cell population collected by the cell light information collect
means, and output means for outputting results of the processing effected
by the cell light information process means.
According to the present invention, there is provided an apparatus
including parameter convert means for converting one or more parameters by
use of a predetermined conversion expression wherein the cell population
subdivide means detects minimal points from histograms associated with
cell light information with respect to the new parameters attained through
the conversion conducted by the parameter convert means so as to subdivide
into fractions the cell population based on the minimal points.
Referring now to an example of an analysis of lymphocyte subset,
description will be given of the operation of the cell analyze apparatus
with reference to the graph of FIG. 9. In this diagram, there is
schematically shown a cytogram with the abscissa and the ordinate
respectively representing the intensity I.sub.90 of right angle scattered
light and the intensity I.sub.0 of forward scattered light. In a case
where a minimal point cannot be detected in a histogram associated with
I.sub.90 or I.sub.0, there may exist a possibility that in histograms
associated with I.sub.90 ' and I.sub.0 ' obtained by rotating the axes of
I.sub.90 and I.sub.0, for example, by an angle .theta., a minimal point
can be detected so as to determine a fraction or a region B' including the
distribution of lymphocytes.
Naturally, the conversion of I.sub.90 ' and I.sub.0 ', namely, the
conversion of parameters are not limited to the simple rotation. An
expression to be used for the conversion is optimized so that a minimal
point can be easily detected in a histogram associated with the converted
parameters.
Since the cell analyze apparatus according to the present invention
includes the parameter convert means for converting one or more parameters
by use of a predetermined conversion expression and is characterized in
that the cell population subdivide means detects a minimal point from a
histogram of the cell light information related to the new parameters
converted by the parameter convert means, even if any minimal point cannot
be detected from the histograms, it is possible to detect minimal points
from histograms associated with the new parameters thus attained through
the conversion, thereby advantageously collect the cell light information
of the objective cell population.
In addition, the cell analyzer according to the present invention includes
cell light information separate means charaterized in that the cell light
information separate means separates cell light information of a cell
population belonging to said one or more fractions with respect to a
parameter from the cell light information detected by the cell light
information detect means and that the cell light information collect means
processes the separated cell light information so as to collect cell light
information of a cell population belonging to one or more fractions with
respect to other parameters.
In consequence, since the processing is not effected by retrieving the cell
light information of all cells for each of the parameters, which is the
case of the conventional system; the processing can be achieve at a higher
speed.
Furthermore, according to the present invention, there is provided an
apparatus comprising maximum frequency point extract means for processing
cell light information of an object cell population collected by the cell
light information collect means so as to extract a maximum frequency point
on a cytogram of parameters associated with fractions of the cell
population, direct line produce means for radially drawing on the cytogram
direct lines from the maximum frequency point extracted by the maximum
frequency point extract means, boundary point extract means for extracting
boundary points based on histograms associated with the respective direct
lines produced by the direct line produce means, and second cell light
information collect means for linking the boundary points extracted by the
boundary point extract means so as to form an area as a final fraction,
thereby collecting cell light information of the objective cell population
based on the final fraction.
Referring now to FIGS. 14 and 15a to 15c associated with the embodiment,
description will be given of the cell analyze device according to the
present invention. For the partition B attained by the cell population
subdivide means, the cell light information collect means gathers cell
light information of an objective cell population, and then a maximum
frequency point q is extracted from the cytogram (FIG. 14) so as to
radially draw direct lines l.sub.1 to l.sub.12 from the point q.
Histograms on these lines l.sub.1 to l.sub.12 are attained as shown in
FIGS. 15a, 15b, and 15c. Assuming here points where the histograms
intersect a predetermined threshold value or minimal points x of the
histograms to be boundary points r, the boundary points r.sub.1 to
r.sub.12 on the respective direct lines l.sub.1 to l.sub.12 are linked to
each other so as to obtain a fraction B" more suitably matched with with
the distribution of the objective cell population. If the light
information of the objective cell population is gathered depending on the
fraction thus determined, the light information related to unnecessary
cells or the like is not included in the resultant light information,
which hence possibly improves the accuracy of the cell analysis.
In consequence, according to the present invention, a fraction more
suitably adaptive to the objective cell population can be established in a
reduced period of time, which leads to an advantage that the cell analysis
is conducted with a higher precision.
Moreover, the apparatus in accordance with the present invention includes
histogram generate means for processing the cell light information
collected by the cell light information collect means to produce, for each
predetermined frequency of a parameter, a histogram associated with
another parameter, boundary point extract means for extracting boundary
points by use of the histogram produced by the histogram generate means,
and second cell light information collect means for linking the boundary
points extracted by the boundary point extract means so as to form an area
as a final fraction, thereby collecting cell light information of the
objective cell population based on the final fraction.
Referring now to FIGS. 17, 18a, and 18b associated with the embodiment,
description will be given of the cell analyzer according to the present
invention. For the partition B established by the cell population
subdivide means, the cell light information collect means effects a
collection of the light information associated with an objective cell
population, so that the histogram generate means processes the collected
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