U.S. patent application number 17/083647 was filed with the patent office on 2021-02-11 for sample carrier for optical measurements.
This patent application is currently assigned to S.D. SIGHT DIAGNOSTICS LTD. The applicant listed for this patent is S.D. SIGHT DIAGNOSTICS LTD. Invention is credited to Yochay Shlomo Eshel, Sarah Levy Schreier, Sharon Pecker, Joseph Joel Pollak, Trevor Ruggiero, Amir Zait.
Application Number | 20210041417 17/083647 |
Document ID | / |
Family ID | 1000005181329 |
Filed Date | 2021-02-11 |
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United States Patent
Application |
20210041417 |
Kind Code |
A1 |
Pollak; Joseph Joel ; et
al. |
February 11, 2021 |
SAMPLE CARRIER FOR OPTICAL MEASUREMENTS
Abstract
Apparatus and methods are described for determining a property
of a biological sample. A sample carrier includes a glass substrate
configured to define a first surface of a sample chamber that is
configured to receive the sample, and a plastic substrate
configured to define a second surface of the sample chamber. The
height of the sample chamber at each location within the sample
chamber is defined by a gap between the first surface and the
second surface. An adhesive adheres the glass substrate to the
plastic substrate. The plastic substrate is shaped such that the
sample chamber defines a first region and a second region, with the
sample chamber defining a predefined variation in height between
the first region and the second region. Other applications are also
described.
Inventors: |
Pollak; Joseph Joel; (Neve
Daniel, IL) ; Levy Schreier; Sarah; (Jaffa, IL)
; Eshel; Yochay Shlomo; (Sde Warburg, IL) ; Zait;
Amir; (Binyamina, IL) ; Pecker; Sharon;
(Rehovot, IL) ; Ruggiero; Trevor; (Somerville,
MA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
S.D. SIGHT DIAGNOSTICS LTD |
Tel Aviv |
|
IL |
|
|
Assignee: |
S.D. SIGHT DIAGNOSTICS LTD
Tel Aviv
IL
|
Family ID: |
1000005181329 |
Appl. No.: |
17/083647 |
Filed: |
October 29, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
16098893 |
Nov 5, 2018 |
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PCT/IL2017/050523 |
May 11, 2017 |
|
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17083647 |
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62334521 |
May 11, 2016 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
G01N 21/59 20130101;
G01N 21/64 20130101; G01N 2201/0662 20130101; G01N 33/50 20130101;
G01N 21/0303 20130101; G01N 21/31 20130101 |
International
Class: |
G01N 33/50 20060101
G01N033/50; G01N 21/31 20060101 G01N021/31; G01N 21/59 20060101
G01N021/59; G01N 21/64 20060101 G01N021/64; G01N 21/03 20060101
G01N021/03 |
Claims
1. Apparatus for determining a property of a biological sample, the
apparatus comprising: a sample carrier that comprises: a glass
substrate configured to define a first surface of a sample chamber
that is configured to receive the sample; a plastic substrate
configured to define a second surface of the sample chamber, a
height of the sample chamber at each location within the sample
chamber being defined by a gap between the first surface and the
second surface; and an adhesive that adheres the glass substrate to
the plastic substrate, the plastic substrate being shaped such that
the sample chamber defines a first region and a second region, with
the sample chamber defining a predefined variation in height
between the first region and the second region.
2. The apparatus according to claim 1, wherein the plastic
substrate is shaped such that the height of the chamber varies
between the first and second regions in a predefined stepped
manner.
3. The apparatus according to claim 1, wherein the plastic
substrate is shaped such that the height of the chamber varies
between the first and second regions in a predefined gradual
manner.
4. The apparatus according to claim 1, wherein the adhesive
comprises a pressure-sensitive adhesive.
5. The apparatus according to claim 1, wherein the plastic
substrate is shaped such that the sample chamber defines at least
first, second, and third regions, the height of the sample chamber
varying between each of the first, second, and third regions in a
predefined manner.
6. The apparatus according to claim 1, further comprising a
computer processor configured to: receive data relating to a first
optical measurement that is performed upon a portion of the sample
that is disposed within the first region, receive data relating to
a second optical measurement that is performed upon a portion of
the sample that is disposed within the second region, and determine
the property of the sample by using a relationship between the
first optical measurement, the second optical measurement, and the
predefined variation in height between the first region and the
second region.
7. The apparatus according to claim 6, further comprising a
microscope, wherein the computer processor is configured to receive
the data relating to at least one of the first and second optical
measurements by receiving imaging data from the microscope.
8. The apparatus according to claim 6, wherein the computer
processor is configured to receive the data relating to at least
one of the first and second optical measurements by receiving data
relating to a parameter selected from the group consisting of:
optical absorption, transmittance, fluorescence, and
luminescence.
9. The apparatus according to claim 6, wherein the computer
processor is configured to determine the property of the sample by
determining a property selected from the group consisting of: a
density of a component of the sample, a concentration of a
component of the sample, and a count of a component of the
sample.
10. The apparatus according to claim 6, wherein the computer
processor is configured to determine an absolute height of the
sample chamber within at least one of the first and second regions,
using the relationship between the first optical measurement, the
second optical measurement, and the predefined variation in height
between the first region and the second region.
11. The apparatus according to claim 6, wherein the computer
processor is configured to determine the property of the sample,
by: subtracting a parameter derived from the first optical
measurement from a parameter derived from the second optical
measurement; and determining the property of the sample, based upon
a relationship between a result of the subtracting and the
predefined variation in height between the first region and the
second region.
12. The apparatus according to claim 6, wherein the computer
processor is configured to determine the property of the sample,
by: dividing a parameter derived from the second optical
measurement by a parameter derived from the first optical
measurement; and determining the property of the sample, based upon
a relationship between a result of the dividing and the predefined
variation in height between the first region and the second
region
13. The apparatus according to claim 6, wherein the biological
sample includes a blood sample, and wherein the computer processor
is configured to determine the property of the biological sample by
determining a property of the blood sample.
14. The apparatus according to claim 13, wherein the computer
processor is configured to determine the property of the sample by
determining a property selected from the group consisting of: a
concentration of a given component within the blood sample, a count
of a given component within the blood sample, and a density of a
given component within the blood sample.
15. The apparatus according to claim 6, wherein the plastic
substrate is shaped such that the sample chamber defines at least
first, second, and third regions, the height of the sample chamber
varying between each of the first, second, and third regions in a
predefined manner.
16. The apparatus according to claim 15, wherein the computer
processor is configured to: receive data relating to a third
optical measurement that is performed upon a portion of the sample
that is disposed within the third region; and to determine the
property of the sample, by performing statistical analysis with
respect to the first, second, and third optical measurements, and
the predefined variation in height between the first, second, and
third regions.
17. The apparatus according to claim 15, wherein the computer
processor is configured to: determine a signal level of the
biological sample, and based upon the determined signal level,
select two out of the first, second, and third regions upon which
to perform, respectively, the first and second optical
measurements.
18. A method for determining a property of a biological sample, the
method comprising: placing the sample into the a sample chamber of
a sample carrier, that includes: a glass substrate configured to
define a first surface of a sample chamber that is configured to
receive the sample, a plastic substrate configured to define a
second surface of the sample chamber, a height of the sample
chamber at each location within the sample chamber being defined by
a gap between the first surface and a second surface, and an
adhesive that adheres the glass substrate to the plastic substrate,
the plastic substrate being shaped such that the sample chamber
defines a first region and a second region, with the sample chamber
defining a predefined variation in height between the first region
and the second region; performing a first optical measurement upon
a portion of the sample that is disposed within the first region;
performing a second optical measurement upon a portion of the
sample that is disposed within the second region; and determining
the property of the sample by using a relationship between the
first optical measurement, the second optical measurement, and the
predefined variation in height between the first region and the
second region.
19. A method comprising: manufacturing a sample carrier that
defines a sample chamber for housing a biological sample, by
placing an adhesive between a glass substrate and a plastic
substrate; and coupling the glass substrate to the plastic
substrate by applying pressure to the adhesive, such that the glass
substrate defines a first surface of the sample chamber and the
plastic substrate defines a second surface of the sample chamber, a
height of the sample chamber at each location within the sample
chamber being defined by a gap between the first surface and a
second surface, the plastic substrate being shaped such that the
sample chamber defines a first region and a second region, with the
sample chamber defining a predefined variation in height between
the first region and the second region.
20. The method according to claim 19, wherein the adhesive includes
a pressure-sensitive adhesive and, wherein coupling the glass
substrate to the plastic substrate by applying pressure to the
adhesive comprises applying pressure to the pressure-sensitive
adhesive.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a continuation of U.S. Ser. No.
16/098,893 to Pollak (published as US 2019/0302099), which is a US
national phase application of PCT Application No. PCT/IL2017/050523
to Pollak (published as WO 17/195205), filed May 11, 2017, which
claims priority from U.S. Provisional Patent Application No.
62/334,521 to Pollak, filed May 11, 2016, entitled "Sample carrier
for optical measurements."
[0002] The present application is related to PCT Application No.
PCT/IL2017/050526 to Zait (published as WO 17/195208), filed May
11, 2017, entitled "Performing optical measurements on a sample,"
which claims priority from U.S. Provisional Patent Application No.
62/334,517 to Zait, filed May 11, 2016, entitled "Method and
Apparatus for Estimating Dilution and Concentration."
[0003] Each of the above-referenced applications is incorporated
herein by reference.
FIELD OF EMBODIMENTS OF THE INVENTION
[0004] Some applications of the presently disclosed subject matter
relate generally to detecting components in a bodily sample, and in
particular, to detecting components of a blood sample by performing
optical measurements.
BACKGROUND
[0005] In some optics-based methods (e.g., diagnostic, and/or
analytic methods), a property of a biological sample, such as a
blood sample, is determined by performing an optical measurement.
For example, the density of a component (e.g., a count of the
component per unit volume) may be determined by counting the
component within a microscopic image. Similarly, the concentration
and/or density of a component may be measured by performing optical
absorption, transmittance, fluorescence, and/or luminescence
measurements upon the sample. Typically, the sample is placed into
a sample carrier and the measurements are performed with respect to
a portion of the sample that is contained within a chamber of the
sample carrier. The measurements that are performed upon the
portion of the sample that is contained within the chamber of the
sample carrier are analyzed in order to determine a property of the
sample.
SUMMARY OF EMBODIMENTS
[0006] In accordance with some applications of the present
invention, a sample carrier includes one or more sample chambers
configured to house a biological sample (such as, a blood sample).
The one or more sample chambers typically define at least first and
second regions thereof, and the height of the one or more sample
chambers varies between the first and second regions in a
predefined manner. For example, the height of the one or more
sample chambers may vary between the first and second regions in a
predefined stepped manner, or in a predefined gradual manner.
[0007] Typically, in order to perform optical analysis upon the
sample, it is desirable to know the optical path length, the
volume, and/or the thickness of the portion of the sample upon
which the optical measurements were performed. Further typically,
optical measurements are performed upon a portion of the sample
disposed in a sample carrier that is defined by two or more
opposing surfaces (e.g., a top surface and a bottom surface). In
order to provide a desired level of precision for determining the
parameter of the sample from the optical measurement, it is
desirable for the two or more opposing surfaces to be separated by
a distance that is correspondingly tightly set or tightly
controlled. However, in some manufacture or assembly processes, the
distance between the opposing surfaces may vary substantially.
[0008] As described hereinabove, in accordance with some
applications of the present invention, one or more sample chambers
of a sample carrier define at least first and second regions
thereof, and the height of the one or more sample chambers varies
between the first and second regions in a predefined manner.
Typically, the sample carrier includes a first substrate the
defines a first surface of the one or more sample chambers (e.g.
the lower surface of the one or more sample chambers), and a second
substrate that defines one or more surfaces of the one or more
sample chambers that oppose the first surface (e.g. upper surfaces
of the one or more sample chambers). The second substrate is shaped
to define the one or more surfaces that oppose the first surface,
such that one or more surfaces that oppose the first surface define
the manner in which the height of the one or more sample chambers
varies between the first and second regions (e.g., by defining two
or more stepped surfaces that are parallel to the first surface,
and oppose the first surface). Typically, manufacturing tolerances
within a single substrate, and especially between nearby surfaces,
are tighter than manufacturing tolerances on positioning between
different substrates or even between opposing surfaces lying within
the same substrate. Therefore, it is typically the case that by
having a single substrate define the manner in which the height of
the one or more sample chambers varies between the first and second
regions, the height difference between the first and second regions
is relatively precise.
[0009] Typically, a first optical measurement is performed upon a
portion of the sample that is disposed within the first region of
the one or more sample chambers, and a second optical measurement
is performed upon a portion of the sample that is disposed within
the second region. A property of the sample is determined by using
a relationship between the first optical measurement, the second
optical measurement, and the predefined variation in height between
the first region and the second region.
[0010] For some applications, a sample carrier is provided that
includes one or more sample chambers configured to house the
sample. The one or more sample chambers define at least first and
second regions thereof, and the height of the one or more sample
chambers varies between the first and second regions. A biological
sample is categorized and is placed into the one or more sample
chambers of the sample carrier. Based upon the categorization of
the biological sample, one of the regions of the sample carrier is
selected upon which to perform optical measurements for measuring a
given measurand. For example, if a sample, and/or a monolayer
formed by the sample, has a relatively low density of red blood
cells, then measurements may be performed upon a region of the
sample carrier having a relatively great height, for example, such
that there is a sufficient density of cells, and/or such that there
is a sufficient density of cells within the monolayer, to provide
statistically reliable data. Such measurements may include, for
example, red blood cell density measurements, measurements of other
cellular attributes, (such as counts of abnormal red blood cells,
red blood cells that include intracellular bodies (e.g., pathogens,
Howell-Jolly bodies), etc.), and/or hemoglobin concentration.
Conversely, if a sample, and/or a monolayer formed by the sample,
has a relatively high density of red blood cells, then such
measurements may be performed upon a region of the sample carrier
having a relatively low height, for example, such that there is a
sufficient sparsity of cells, and/or such that there is a
sufficient sparsity of cells within the monolayer formed by the
sample, that the cells can be identified within microscopic images.
For some applications, such methods are performed even without the
difference in heights between the regions being precisely
known.
[0011] There is therefore provided, in accordance with some
applications of the present invention, apparatus for determining a
property of a biological sample, the apparatus including:
[0012] a sample carrier that includes one or more sample chambers
configured to house the sample, the one or more sample chambers
defining at least first and second regions thereof, a height of the
one or more sample chambers varying between the first and second
regions in a predefined manner; and
[0013] a computer processor configured to: [0014] receive data
relating to a first optical measurement that is performed upon a
portion of the sample that is disposed within the first region,
[0015] receive data relating to a second optical measurement that
is performed upon a portion of the sample that is disposed within
the second region, and [0016] determine the property of the sample
by using a relationship between the first optical measurement, the
second optical measurement, and the predefined variation in height
between the first region and the second region.
[0017] In some applications, the height of the one or more sample
chambers varies between the first and second regions in a
predefined stepped manner.
[0018] In some applications, the height of the one or more sample
chambers varies between the first and second regions in a
predefined gradual manner.
[0019] In some applications, the computer processor is configured
to receive the data relating to at least one of the first and
second optical measurements by receiving imaging data from a
microscope.
[0020] In some applications, the computer processor is configured
to receive the data relating to at least one of the first and
second optical measurements by receiving data relating to a
parameter selected from the group consisting of: optical
absorption, transmittance, fluorescence, and luminescence.
[0021] In some applications, the computer processor is configured
to determine the property of the sample by determining a density of
a component of the sample. In some applications, the computer
processor is configured to determine the property of the sample by
determining a concentration of a component of the sample. In some
applications, the computer processor is configured to determine the
property of the sample by determining a count of a component of the
sample.
[0022] In some applications, the computer processor is configured
to determine an absolute height of the one or more sample chambers
within at least one of the first and second regions, using the
relationship between the first optical measurement, the second
optical measurement, and the predefined variation in height between
the first region and the second region.
[0023] In some applications, the computer processor is configured
to determine the property of the sample, by:
[0024] subtracting a parameter derived from the first optical
measurement from a parameter derived from the second optical
measurement; and
[0025] determining the property of the sample, based upon a
relationship between a result of the subtracting and the predefined
variation in height between the first region and the second
region.
[0026] In some applications, the computer processor is configured
to determine the property of the sample, by:
[0027] dividing a parameter derived from the second optical
measurement by a parameter derived from the first optical
measurement; and
[0028] determining the property of the sample, based upon a
relationship between a result of the dividing and the predefined
variation in height between the first region and the second
region
[0029] In some applications, the biological sample includes a blood
sample, and the computer processor is configured to determine the
property of the biological sample by determining a property of the
blood sample. In some applications, the computer processor is
configured to determine the property of the sample by determining a
concentration of a given component within the blood sample. In some
applications, the computer processor is configured to determine the
property of the sample by determining a count of a given component
within the blood sample. In some applications, the computer
processor is configured to determine the property of the sample by
determining a density of a given component within the blood
sample.
[0030] In some applications, the one or more sample chambers define
at least first, second, and third regions thereof, the height of
the one or more sample chambers varying between each of the first,
second, and third regions in a predefined manner.
[0031] In some applications, the computer processor is configured
to:
[0032] receive data relating to a third optical measurement that is
performed upon a portion of the sample that is disposed within the
third region; and
[0033] to determine the property of the sample, by performing
statistical analysis with respect to the first, second, and third
optical measurements, and the predefined variation in height
between the first, second, and third regions.
[0034] In some applications, the computer processor is configured
to:
[0035] determine a signal level of the biological sample, and
[0036] based upon the determined signal level, select two out of
the first, second, and third regions upon which to perform,
respectively, the first and second optical measurements.
[0037] In some applications, the sample carrier includes:
[0038] a first substrate that defines a first surface; and
[0039] a second substrate that defines one or more surfaces that
oppose the first surface, and
[0040] the second substrate is shaped to define the one or more
surfaces that oppose the first surface, such that one or more
surfaces that oppose the first surface define the manner in which
the height of the one or more sample chambers varies between the
first and second regions.
[0041] In some applications, the second substrate defines second
and third surfaces, the second and third surfaces (a) opposing the
first surface, (b) being parallel to the first surface, and (c)
being stepped with respect to each other. In some applications, the
second substrate that defines at least a second surface, the second
surface (a) opposing the first surface, and (b) being non-parallel
with respect to the first surface.
[0042] There is further provided, in accordance with some
applications of the present invention, a method for determining a
property of a biological sample, the method including:
[0043] providing a sample carrier, the sample carrier including one
or more sample chambers configured to house the sample, the one or
more sample chambers defining at least first and second regions
thereof, a height of the one or more sample chambers varying
between the first and second regions in a predefined manner;
[0044] placing the sample into the one or more sample chambers;
[0045] performing a first optical measurement upon a portion of the
sample that is disposed within the first region;
[0046] performing a second optical measurement upon a portion of
the sample that is disposed within the second region; and
[0047] determining the property of the sample by using a
relationship between the first optical measurement, the second
optical measurement, and the predefined variation in height between
the first region and the second region.
[0048] There is further provided, in accordance with some
applications of the present invention, a computer software product,
for use with a biological sample that is placed within a sample
carrier that includes one or more sample chambers configured to
house the sample, the one or more sample chambers defining at least
first and second regions thereof, a height of the one or more
sample chambers varying between the first and second regions, in a
predefined manner, the computer software product including a
non-transitory computer-readable medium in which program
instructions are stored, which instructions, when read by a
computer cause the computer to perform the steps of:
[0049] receiving data relating to a first optical measurement that
is performed upon a portion of the sample that is disposed within
the first region;
[0050] receiving data relating to a second optical measurement that
is performed upon a portion of the sample that is disposed within
the second region; and
[0051] determining the property of the sample by using a
relationship between the first optical measurement, the second
optical measurement, and the predefined variation in height between
the first region and the second region.
[0052] There is further provided, in accordance with some
applications of the present invention, a method performing optical
measurements on a biological sample, the method including:
[0053] providing a sample carrier that includes one or more sample
chambers configured to house the sample, the one or more sample
chambers defining at least first and second regions thereof, a
height of the one or more sample chambers varying between the first
and second regions;
[0054] categorizing the biological sample;
[0055] placing the sample into the one or more sample chambers;
and
[0056] based upon the categorization of the biological sample,
selecting one of the first and second regions upon which to perform
optical measurements for measuring a given measurand.
[0057] In some applications, categorizing the sample includes
receiving an indication of the categorization of the sample. In
some applications, categorizing the sample includes categorizing
the sample based upon a density of one or more components within
the sample. In some applications, categorizing the sample includes
categorizing the sample based upon a surface density of one or more
components within a monolayer formed by the sample. In some
applications, categorizing the sample includes categorizing the
sample based upon a concentration of one or more components within
the sample. In some applications, categorizing the sample includes
categorizing the sample based upon a count of one or more
components within the sample. In some applications, categorizing
the sample includes measuring a parameter of the sample selected
from the group consisting of: optical absorption, transmittance,
fluorescence, and luminescence, by performing a preliminary optical
measurement upon the sample. In some applications, categorizing the
sample includes performing microscopic imaging upon the sample.
[0058] In some applications, selecting one of the first and second
regions upon which to perform optical measurements for measuring
the given measurand includes selecting one of the first and second
regions upon which to perform counting of a given component within
the sample, by performing microscopic imaging upon the region. In
some applications, selecting one of the first and second regions
upon which to perform optical measurements for measuring the given
measurand includes selecting one of the first and second regions
upon which to measure a concentration of a given component within
the sample, by measuring a parameter selected from the group
consisting of: optical absorption, transmittance, fluorescence, and
luminescence.
[0059] In some applications:
[0060] the one or more sample chambers define at least first,
second, and third regions thereof, a height of the one or more
sample chambers varying between each of the first, second, and
third regions in a predefined manner; and
[0061] based upon the identified property of the biological sample,
selecting two out of the first, second, and third regions upon
which to perform, respective, first and second optical measurements
for measuring the given measurand.
[0062] In some applications, the method further includes:
[0063] performing the, respective, first and second optical
measurements upon the selected two regions; and
[0064] measuring the given measurand by using a relationship
between the first optical measurement, the second optical
measurement, and the predefined variation in height between the
selected two regions.
[0065] In some applications, the biological sample includes a blood
sample, and selecting one of the first and second regions upon
which to perform optical measurements for measuring the given
measurand includes selecting one of the first and second regions
upon which to perform optical measurements for measuring a given
measurand of the blood sample.
[0066] In some applications, selecting one of the first and second
regions upon which to perform optical measurements for measuring
the given measurand includes selecting one of the first and second
regions upon which to measure a concentration of a given component
within the blood sample, by measuring a parameter selected from the
group consisting of: optical absorption, optical transmittance,
fluorescence, and luminescence. In some applications, selecting one
of the first and second regions upon which to perform optical
measurements for measuring the given measurand includes selecting
one of the first and second regions upon which to perform counting
of a given component within the blood sample, by performing
microscopic imaging upon the region.
[0067] There is further provided, in accordance with some
applications of the present invention, apparatus for determining a
property of a biological sample, the apparatus including:
[0068] a sample carrier that includes one or more sample chambers
configured to house the sample, the one or more sample chambers
defining at least first and second regions thereof, a height of the
one or more sample chambers varying between the first and second
regions; and
[0069] a computer processor configured to: [0070] categorize the
biological sample, and [0071] based upon the categorization of the
biological sample, select one of the first and second regions upon
which to perform optical measurements for measuring a given
measurand of the biological sample.
[0072] There is further provided, in accordance with some
applications of the present invention, a computer software product,
for use with a biological sample that is placed within a sample
carrier that includes one or more sample chambers configured to
house the sample, the one or more sample chambers defining at least
first and second regions thereof, a height of the one or more
sample chambers varying between the first and second regions, the
computer software product including a non-transitory
computer-readable medium in which program instructions are stored,
which instructions, when read by a computer cause the computer to
perform the steps of:
[0073] categorizing the biological sample; and
[0074] based upon the categorization of the biological sample,
selecting one of the first and second regions upon which to perform
optical measurements for measuring a given measurand of the
biological sample.
[0075] There is further provided, in accordance with some
applications of the present invention, apparatus for performing
optical measurements on a biological sample, the apparatus
including:
[0076] a sample carrier that includes one or more sample chambers
configured to house the sample,
[0077] the one or more sample chambers defining at least first,
second, and third regions thereof, a height of the one or more
sample chambers varying between each of the first, second, and
third regions in a predefined manner.
[0078] There is further provided, in accordance with some
applications of the present invention, a method for performing
optical measurements on a biological sample, the method
including:
[0079] providing a sample carrier, the sample carrier including one
or more sample chambers configured to house the sample, the one or
more sample chambers defining at least first and second regions
thereof, a height of the one or more sample chambers varying
between the first and second regions;
[0080] placing the sample into the one or more sample chambers;
[0081] measuring a first measurand, by performing a first optical
measurement upon a portion of the sample that is disposed within
the first region; and
[0082] measuring a second measurand, by performing a second optical
measurement upon a portion of the sample that is disposed within
the second region.
[0083] In some applications, the biological sample includes a blood
sample, measuring the first measurand includes measuring a first
measurand of the blood sample performing the first optical
measurement upon a portion of the blood sample that is disposed
within the first region, and measuring the second measurand
includes measuring a second measurand of the blood sample by
performing a second optical measurement upon a portion of the
sample that is disposed within the second region.
[0084] In some applications, measuring the first measurand of the
blood sample includes determining a count of a first component
within the blood sample by performing microscopic imaging upon the
portion of the sample that is disposed within the first region, and
measuring the second measurand of the blood sample includes
determining a count of a second component within the blood sample
by performing microscopic imaging upon the portion of the sample
that is disposed within the second region.
[0085] In some applications, measuring the first measurand of the
blood sample includes measuring a concentration of a first
component within the blood sample, by performing, upon the portion
of the sample that is disposed within the first region, an optical
measurement of a parameter selected from the group consisting of:
optical absorption, transmittance, fluorescence, and luminescence.
In some applications, measuring the second measurand of the blood
sample includes measuring a concentration of a second component
within the blood sample, by performing, upon the portion of the
sample that is disposed within the second region, an optical
measurement of a parameter selected from the group consisting of:
optical absorption, transmittance, fluorescence, and luminescence.
In some applications, measuring the second measurand of the blood
sample includes determining a count of a second component within
the blood sample by performing microscopic imaging upon the portion
of the sample that is disposed within the second region.
[0086] There is further provided, in accordance with some
applications of the present invention, apparatus for determining a
property of a biological sample, the apparatus including:
[0087] a sample carrier that includes one or more sample chambers
configured to house the sample, the one or more sample chambers
defining at least first and second regions thereof, a height of the
one or more sample chambers varying between the first and second
regions; and
[0088] a computer processor configured to: [0089] measure a first
measurand, by receiving a first optical measurement performed upon
a portion of the sample that is disposed within the first region;
and [0090] measure a second measurand, by receiving a second
optical measurement performed upon a portion of the sample that is
disposed within the second region.
[0091] There is further provided, in accordance with some
applications of the present invention, a computer software product,
for use with a biological sample that is placed within a sample
carrier that includes one or more sample chambers configured to
house the sample, the one or more sample chambers defining at least
first and second regions thereof, a height of the one or more
sample chambers varying between the first and second regions, the
computer software product including a non-transitory
computer-readable medium in which program instructions are stored,
which instructions, when read by a computer cause the computer to
perform the steps of:
[0092] measuring a first measurand, by receiving a first optical
measurement performed upon a portion of the sample that is disposed
within the first region; and
[0093] measuring a second measurand, by receiving a second optical
measurement performed upon a portion of the sample that is disposed
within the second region.
[0094] There is further provided, in accordance with some
applications of the present invention, a method performing optical
measurements on a biological sample, the method including:
[0095] providing a sample carrier that includes one or more sample
chambers configured to house the sample, the one or more sample
chambers defining at least first and second regions thereof, a
height of the one or more sample chambers varying between the first
and second regions;
[0096] categorizing a measurand of the biological sample that is to
be measured;
[0097] placing the sample into the one or more sample chambers;
and
[0098] based upon the categorization of the measurand, selecting
one of the first and second regions upon which to perform optical
measurements for measuring the identified measurand.
[0099] In some applications, the biological sample includes a blood
sample, categorizing the measurand of the biological sample that is
to be measured includes categorizing a measurand of the blood
sample that is to be measured.
[0100] In some applications, selecting one of the first and second
regions upon which to perform optical measurements for measuring
the identified measurand includes selecting one of the first and
second regions upon which to measure a concentration of a given
component within the blood sample, by measuring a parameter
selected from the group consisting of: optical absorption,
transmittance, fluorescence, and luminescence. In some
applications, selecting one of the first and second regions upon
which to perform optical measurements for measuring the identified
measurand includes selecting one of the first and second regions
upon which to perform microscopic imaging.
[0101] There is further provided, in accordance with some
applications of the present invention, apparatus for determining a
property of a biological sample, the apparatus including:
[0102] a sample carrier that includes one or more sample chambers
configured to house the sample, the one or more sample chambers
defining at least first and second regions thereof, a height of the
one or more sample chambers varying between the first and second
regions; and
[0103] a computer processor configured to: [0104] categorize a
measurand of the biological sample that is to be measured, and
[0105] based upon the categorization of the measurand, select one
of the first and second regions upon which to perform optical
measurements for measuring the identified measurand.
[0106] There is further provided, in accordance with some
applications of the present invention, a computer software product,
for use with a biological sample that is placed within a sample
carrier that includes one or more sample chambers configured to
house the sample, the one or more sample chambers defining at least
first and second regions thereof, a height of the one or more
sample chambers varying between the first and second regions, the
computer software product including a non-transitory
computer-readable medium in which program instructions are stored,
which instructions, when read by a computer cause the computer to
perform the steps of:
[0107] categorizing a measurand of the biological sample that is to
be measured; and
[0108] based upon the categorization of the measurand, selecting
one of the first and second regions upon which to perform optical
measurements for measuring the identified measurand.
[0109] The present invention will be more fully understood from the
following detailed description of embodiments thereof, taken
together with the drawings, in which:
BRIEF DESCRIPTION OF THE DRAWINGS
[0110] FIG. 1 is a block diagram showing components of a biological
sample analysis system, in accordance some applications of the
present invention;
[0111] FIG. 2 is a schematic cross-sectional illustration of a
sample carrier that defines a variation in height that is stepped,
in accordance with some applications of the present invention;
[0112] FIG. 3 is a schematic cross-sectional illustration of a
sample carrier that defines a variation in height that is gradual,
in accordance with some applications of the present invention;
[0113] FIG. 4 is a schematic cross-sectional illustration of a
sample carrier that includes one or more sample chambers that
define first, second, and third regions, the height of the one or
more sample chambers varying between each of the first, second, and
third regions in a predefined manner, in accordance with some
applications of the present invention;
[0114] FIG. 5 is a flowchart showing steps of algorithm that is
performed in accordance with some applications of the present
invention; and
[0115] FIG. 6 is a flowchart showing steps of algorithm that is
performed in accordance with some applications of the present
invention.
DETAILED DESCRIPTION OF EMBODIMENTS
[0116] Reference is now made to FIG. 1, which is block diagram
showing components of a biological sample analysis system 20, in
accordance some applications of the present invention. Typically, a
biological sample (e.g., a blood sample) is placed into a sample
carrier 22. While the sample is disposed in the sample carrier,
optical measurements are performed upon the sample using one or
more optical measurement devices 24. For example, the optical
measurement devices may include a microscope (e.g., a digital
microscope), a spectrophotometer, a photometer, a spectrometer, a
camera, a spectral camera, a hyperspectral camera, a fluorometer, a
spectrofluorometer, and/or a photodetector (such as a photodiode, a
photoresistor, and/or a phototransistor). For some applications,
the optical measurement devices include dedicated light sources
(such as light emitting diodes, incandescent light sources, etc.)
and/or optical elements for manipulating light collection and/or
light emission (such as lenses, diffusers, filters, etc.). For some
applications, a microscope system is used that is generally similar
to the microscope system described in US 2014/0347459 to
Greenfield, which is incorporated herein by reference.
[0117] A computer processor 28 typically receives and processes
optical measurements that are performed by the optical measurement
device. Further typically, the computer processor controls the
acquisition of optical measurements that are performed by the one
or more optical measurement devices. The computer processor
communicates with a memory 30. A user (e.g., a laboratory
technician) sends instructions to the computer processor via a user
interface 32. For some applications, the user interface includes a
keyboard, a mouse, a joystick, a touchscreen device (such as a
smartphone or a tablet computer), a touchpad, a trackball, a
voice-command interface, and/or other types of user interfaces that
are known in the art. Typically, the computer processor generates
an output via an output device 34. Further typically, the output
device includes a display, such as a monitor, and the output
includes an output that is displayed on the display. For some
applications, the processor generates an output on a different type
of visual, text, graphics, tactile, audio, and/or video output
device, e.g., speakers, headphones, a smartphone, or a tablet
computer. For some applications, user interface 32 acts as both an
input interface and an output interface, i.e., it acts as an
input/output interface. For some applications, the processor
generates an output on a computer-readable medium (e.g., a
non-transitory computer-readable medium), such as a disk, or a
portable USB drive, and/or generates an output on a printer.
[0118] Reference is now made to FIG. 2, which is a schematic
cross-sectional illustration of sample carrier 22, in accordance
with some applications of the present invention. The sample carrier
defines one or more sample chambers 40, into which the sample is
placed. The one or more sample chambers typically define at least a
first region 42 (which is shallower) and a second region 44 (which
is deeper), the height of the one or more sample chambers varying
between the first and second regions in a predefined manner. For
example, as shown in FIG. 2, the height of the one or more sample
chambers varies between the first and second regions in a
predefined stepped manner.
[0119] Typically, in order to perform optical analysis upon the
sample, it is desirable to know the optical path length, the
volume, and/or the thickness of the portion of the sample upon
which the optical measurements were performed, as precisely as
possible. Further typically, the optical measurements are performed
upon a portion of the sample disposed in a sample carrier that is
defined by two or more opposing surfaces. In order to provide the
desired level of precision, it is desirable for the two or more
opposing surfaces to be separated by a distance that is
correspondingly tightly set or tightly controlled. However, in some
manufacture or assembly processes, the distance between the
opposing surfaces may vary substantially. For example, in some
instances, two or more of the opposing surfaces lie in separate
substrates that are bonded relative to each other during
manufacture or assembly (e.g. using thermal bonding,
solvent-assisted bonding, ultrasonic welding, laser welding, heat
staking, adhesive, mechanical clamping and/or additional
substrates).
[0120] For example, as shown in FIG. 2, the height of first region
42 of the sample chamber is defined by a lower surface 46 that is
defined by a first substrate 48 (e.g., a glass or a plastic
substrate) and by upper surface 50 that is defined by a second
substrate 52 (e.g., a plastic substrate, such as an
injection-molded plastic substrate). The first and second
substrates are bonded to each other by an adhesive layer 53, e.g.,
a pressure-sensitive adhesive. Examples of the adhesive layer
include an additional physical layer (such as a pressure-sensitive
adhesive layer), a sandwich of pressure-sensitive adhesive and a
carrier layer (such as a polyethylene terephthalate layer), a
bonding layer (such as a solvent-assisted bonding layer), or a
layer resulting from a process performed upon the top and bottom
substrates (such as ultrasonic welding) without necessarily
introducing additional materials or pieces. Although the adhesive
layer has a nominal thickness, it is typically the case that, for
example, due to variation in the manufactured thickness of the
pressure-sensitive adhesive or in the pressure applied during its
application, the actual thickness of the layer is different from
the nominal thickness. For example, the two substrates may be
bonded using a pressure-sensitive adhesive layer with a nominal
thickness that is configured to separate the opposing surfaces by a
separation of 100 micrometers. In such a case, variation in the
manufactured thickness of the pressure-sensitive adhesive layer or
in the pressure applied during its application may result in a
final thickness that may lie, for example, as far as 20 micrometers
greater or less than the nominal thickness.
[0121] Typically, an optical measurement is performed on the
sample. For example, the density of a component may be determined
by performing a count of the component within a microscopic image.
Similarly, the concentration and/or density of a component may be
measured by performing optical absorption, transmittance,
fluorescence, and/or luminescence measurements upon the sample.
Without being bound by theory, an uncertainty of 20 percent in the
distance separating the two opposing surfaces (as described in the
above example), may, in turn, correspond to 20 percent uncertainty
in parameters of the sample that are derived from the optical
measurements that are performed upon the sample (such as, the
derived concentration and/or density of a component within the
sample).
[0122] For example, for some applications, the concentration of a
component is determined by measuring optical absorption. The
absorption measurements are analyzed based upon the Beer-Lambert
Law, in accordance with which the resulting optical intensity I
after passing through a distance h in a sample containing
concentration .rho. of a substance with absorptivity coefficient
.alpha. is I=I.sub.0.times.e.sup.-.alpha..rho.h, where I.sub.0 is
incident the light intensity before passing through the sample.
Thus, for some applications, when passing light through a sample
within a sample chamber having a height h (which is defined by the
distance between the opposing surfaces), I and I.sub.0 are measured
and the concentration of a given component is deduced using the
known height and the known absorptivity coefficient of the
component. For example, such a technique may be used to measure the
hemoglobin concentration of a blood sample (e.g., using absorption
techniques that are known in the art, such as, by first staining
hemoglobin using a suitable dye that provides an optical absorption
signature, or by performing the measurements upon unstained
hemoglobin). For some applications, additional measurements are
performed at different wavelengths to further improve the accuracy
in determining the concentration. For such techniques, uncertainty
in the height h of the sample chamber results in a corresponding
uncertainty in the derived concentration.
[0123] For some applications, the density (e.g. count per unit
volume) of a component is measured. For example, such measurements
may be performed in order to count the number of red blood cells,
white blood cells, platelets, reticulocytes, Howell-Jolly bodies,
bacteria, and/or parasites of a given type per unit volume, such as
when performing a complete blood count or a diagnostic test.
Typically, for such applications, images (e.g., microscopic images)
of the sample are acquired, and the count per unit volume is
determined based upon the count of the component within the images
and the corresponding volume within which the count was measured.
As the volume is equal to height times area, any uncertainty in the
height of the sample chamber results in uncertainty in the volume,
and a corresponding uncertainty in the count per unit volume.
[0124] For some applications, one or more of the following
measurements are performed upon a sample within a sample chamber:
bacteria or virus concentration, contaminant concentration (e.g. in
drinking water), turbidity measurement (e.g. in water, urine), and
enzymatic assays (including enzyme-linked immunosorbent assays).
For such measurements, uncertainty in the height of the sample
chamber results in uncertainty in the measurement
[0125] In accordance with some applications of the present
invention, the above-described problems associated with uncertainty
relating to the height of a sample chamber are at least partially
overcome. Referring again to FIG. 2, sample chamber defines first
region 42 and a second region 44. The height of first region 42 of
the sample chamber is defined by lower surface 46 that is defined
by first substrate 48 and by upper surface 50 that is defined by
second substrate 52. The height of second region 44 of the sample
chamber is defined by lower surface 46 and by second upper surface
54 that is defined by second substrate 52. As shown second upper
surface 54 is stepped with respect to first upper surface 50, and
both surfaces 50 and 54 are parallel to lower surface 46. The first
and second substrates are bonded to each other by adhesive layer
53, e.g., a pressure-sensitive adhesive, such that absolute height
h of the first region 42 (which is shallower) is uncertain, e.g.,
for the reasons described hereinabove. The step between first upper
surface 50 and second upper surface 54, provides a predefined
height difference .DELTA.h between the first, shallower region and
the second, deeper region, such that even though height h of the
first region is not known to a sufficient degree of accuracy, the
height difference .DELTA.h is known to a sufficient degree of
accuracy to determine a parameter of the sample, using the
techniques described herein.
[0126] As shown in FIG. 2, second substrate 52 is shaped to define
surfaces 50 and 54, such that surfaces 50 and 54 define the manner
in which the height of the one or more sample chambers varies
between the first and second regions. Typically, relative
manufacturing tolerances within a single substrate, and especially
between nearby surfaces, are tighter than manufacturing tolerances
on positioning between different substrates or even between
opposing surfaces lying within the same substrate. Therefore, it is
typically the case that by having a single substrate define the
manner in which the height of the one or more sample chambers
varies between the first and second regions, the height difference
between the first and second regions is relatively precise. For
example, second substrate 52 may be manufactured with relatively
tight tolerances, for example, using injection molding, embossing
or machining.
[0127] An illustrative example of how the height difference
.DELTA.h may be used to determine a parameter of the sample is as
follows. In order to determine the density of white blood cells
within a blood sample, the number of white blood cells within a
microscopic image within a given area A within region 42 may be
counted, and the number of white blood cells within the same area
within region 44 may also be counted. The difference between these
two numbers is equal to the number of white blood cells in a volume
equal to area A multiplied by height difference .DELTA.h.
Therefore, the number of white blood cells within this volume is
divided by the known volume, to provide the density of white blood
cells per unit volume in the solution that is disposed in the
carrier. Typically, this value is used to extrapolate an amount or
concentration of white blood cells in a stock sample, from which
the solution in the sample carrier was produced.
[0128] For some applications, additional steps are performed to
reduce the error in estimating the white blood cell density. For
example, a choice of height differences may be provided, such that
a suitable height difference is chosen, and/or such that
measurements obtained across multiple height differences are
integrated using a statistical method (e.g. averaging, regression,
curve-fitting or other techniques known in the art). For some
applications, the above-described technique is performed but with
different areas being measured in regions 42 and 44, and with the
volume being calculated by correcting for the area difference
between the areas that were measured in regions 42 and 44.
[0129] For some applications, the above-described technique is used
to determine the density (e.g., the count per unit volume) of other
components within a blood sample, including but limited to red
blood cells, platelets, anomalous white blood cells, circulating
tumor cells, reticulocytes, Howell Jolly bodies, pathogens (such
as, Plasmodium or Babesia), etc.
[0130] It is noted that although height h of first, shallower
region 42 is shown in FIG. 2 as being defined solely be the
thickness of adhesive layer 53, the height h may be defined by a
combination of the adhesion layer and protrusions or extrusions
from first substrate 48 and/or second substrate 52. For some
applications, the thickness of the adhesive layer varies not only
between sample carriers, but even in the same carrier or even along
a single sample chamber. Such variation may affect absolute height
h of the first region or the height difference between the first
and second regions. If this variation is known in advance, it is
typically factored into calculations that are performed upon the
optical measurements. Typically, the variation in the thickness of
the adhesive layer is less than 10 percent along the regions upon
which the optical measurements are performed.
[0131] It is further noted that, although in FIG. 2 regions 42 and
44 are shown as being regions within a single sample chamber
without any separation between the two regions, for some
applications, regions 42 and 44 are regions within respective
sample chambers that are at least partially separated from each
other. In accordance with some applications, the chambers are
positioned adjacent to one another, in a linear array, or in any
regular lattice shape. For some applications, the chambers are
separated from one another by an adhesive layer or a spacer. For
some applications, the chambers are positioned adjacent to one
another and are filled with the sample using capillary forces.
Typically, for such applications, the sample is inserted into the
sample carrier via an entry hole, and the sample chamber defines an
air exit hole via which air exits the sample carrier, in order to
facilitate filling of the sample carrier with the sample. For some
such applications, the sample chambers are arranged such that the
chamber that has the greatest height is closest to the entry hole,
and the sample chamber that has the lowest height is closest to the
to the air exit hole, with any additional chambers being arranged
in corresponding height order.
[0132] For some applications, an optical measurement is performed
by providing optical windows on the sample carrier. For example,
absorption measurements may be performed by illuminating a sample
through a region of one of the substrates (e.g., top substrate 52)
that defines an optical window 60 and measuring light coming out
through a region of the other substrate (e.g. bottom substrate 48)
that defines an optical window 62. For some applications, a
reflective surface is used to allow the light to enter and exit
through the same optical window (e.g., window 60). This may be
used, for example, in the case of an absorption or density
measurement, with the analysis having to account, for example, for
light having gone through the sample twice. For some applications
fluorescence is measured using one or more optical windows. For
example, epifluorescence measurements may be performed through a
single optical window, since the emitted light may be detected
through the same optical window as used for excitation light. For
some applications, luminescence is measured using one or more
optical windows.
[0133] Although FIG. 2 shows only upper substrate 52 defining the
stepped surfaces, for some applications, both the upper and lower
substrates define surfaces that are stepped with respect to one
another (or they both define a surface that is sloped or curved, as
described hereinbelow). For some applications, only the lower
substrate defines surfaces that are stepped with respect to one
another (or defines a surface that is sloped or curved, as
described hereinbelow). For some applications, measurements are
performed in a lateral direction, with respect to the sample
carrier, and a substrate that defines the lateral surfaces of the
one or more sample chambers defines surfaces that are stepped with
respect to one another (or defines a surface that is sloped or
curved, as described hereinbelow).
[0134] Reference is now made to FIG. 3, which is a schematic
illustration of sample carrier 22, in accordance with some
applications of the present invention. Sample carrier 22 as shown
in FIG. 3 is generally similar to sample carrier 22 as described
hereinabove, expect that second substrate 52 is shaped such that
the height of the one or more sample chambers varies in a gradual
manner. As shown, for some applications, a single sloped surface 64
defined by second substrate 52 defines the manner in which the
height of the one or more sample chambers varies. For such
applications, the height difference between first and second
regions upon which optical measurements are performed is determined
based upon the predefined slope of the surface and the relative
spacing of the first and second regions upon which the measurements
are performed. For some applications, differently shaped surfaces
defined by second substrate 52 define the manner in which the
height of the one or more sample chambers varies between the first
and second regions. For example, a curved surface may be used,
which may allow measurements with a larger height difference to be
taken in one region versus another region.
[0135] Reference is now made to FIG. 4, which is a schematic
cross-sectional illustration of sample carrier 22, the sample
carrier including one or more sample chambers that define first
region 42, second region 44, and a third region 66, the height of
the one or more sample chambers varying between each of the first,
second, and third regions in a predefined manner, in accordance
with some applications of the present invention. Sample carrier is
generally as described hereinabove, except for the differences
described below. As shown, the height of the second region is
greater than the height of the first region by a height difference
.DELTA.h1, and the height of the third region is greater than the
height of the second region by a height difference .DELTA.h2 (such
that the height of the third region is greater than the height of
the first region by a height difference (.DELTA.h1+.DELTA.h2)) The
height differences between the regions are defined by three
surfaces 50, 54, and 66 defined by second substrate 52, each of the
three surfaces opposing surface 46, defined by first substrate 48.
It is noted that the scope of the present invention includes using
a sample carrier that defines more than three regions (e.g., 4-10
regions) having predefined height differences between them, and
which are defined by a single substrate, mutatis mutandis.
[0136] Reference is now made to FIG. 5, which is a flowchart
showing steps of algorithm that is performed by computer processor
28, in accordance with some applications of the present invention.
The flowchart is described with reference to the sample carrier
shown in FIG. 2, but the algorithm could be applied to other
embodiments of the sample carrier as described herein, mutatis
mutandis. For some applications, in order to determine the
concentration of a given component within a biological sample that
is disposed within sample carrier 22, light is transmitted through
regions 42 and 44. The light intensity detected after transmission
through these regions is detected by optical measurement device 24,
and these light intensity measurements are received by computer
processor in step 70. In step 72, for each of these measurements,
the detected light intensity is divided by the incident light
intensity. In step 74, the natural logarithm of the outputs of step
72 is calculated. In step 76, the outputs of step 74 are divided by
the absorptivity coefficient of the component being measured, which
provides .rho..times.h for region 42 and
.rho..times.(h+.DELTA..sub.h) for region 44. In step 78, the output
of step 76 for region 42 is subtracted from the output of step 76
for region 44, which provides .rho..DELTA..sub.h. In step 80, the
output of step 78 is divided by the known height difference, to
provide the concentration .rho..
[0137] For some applications, three or more regions having a known
height variation between them are used (e.g., using a sample
chamber as shown in FIG. 4), and the algorithm shown in FIG. 5 is
repeated with respect to respective pairs of regions with known
height differences between them, such that the concentration of the
component is determined using different combinations of measured
light intensities. Typically, measurements obtained across multiple
height differences are integrated using a statistical method (e.g.
averaging, regression, curve-fitting or other techniques known in
the art), in order to provide a final determination of the
concentration of the component. For some applications,
discrepancies between the different measurements are used as an
indication that there are errors in the measurement or that the
sample preparation was not performed correctly (e.g., due to
unsuccessful filling of the sample carrier, resulting in remaining
bubbles, or untreated blood, etc.). For some applications, in
response thereto, a sample is rejected from being used, and/or the
computer processor determines that the results obtained for the
sample should be treated with a decreased level of confidence
relative to other samples or portions thereof, and a corresponding
indication is generated upon the output device.
[0138] For some applications, the intensity of light that is
reflected from the sample is measured, rather than measuring light
that is transmitted from the sample. For such applications, the
algorithm described with reference to FIG. 5 is modified
accordingly.
[0139] For some applications, similar techniques are applied to
optical measurements that relate to fluorescence or luminescence
optical signatures. For example, the detected luminescence of a
sample may be proportional to the volume assayed by an optical
detector, which in turn may be proportional to sample height. The
techniques described herein allow a practitioner to perform the
measurement in two or more separate regions of the device that have
predefined height differences therebetween. For some applications,
the height differences are known to a greater degree of accuracy
than the overall height of the sample chamber, as described
hereinabove. For some applications, the height differences are
used, for example, to mathematically infer sample luminescence per
unit volume, which in turn may be used to assess the concentration,
count or density of a component of the sample.
[0140] For some application, the techniques described with
reference to FIG. 5 are used in order to determine the
concentration of hemoglobin and/or other components within a blood
sample.
[0141] As described hereinabove, for some applications
concentration is determined by comparing the light intensity before
passing through the sample to the measured light intensity after
light has been transmitted through, or reflected by, the sample. As
the measured light intensity may be up to a few orders of magnitude
smaller than the transmitted light intensity, this may require the
ability to provide accurate light intensity measurements over a
large dynamic range of measured intensities. Alternatively, one may
provide the incident light and measure the transmitted or reflected
light at a range of different emitter or detector settings, in
which case this may require precise knowledge of how the emitter or
detector behavior changes with changing the settings (e.g. how
emitted light intensity varies with input current).
[0142] For some applications of the present invention, the
concentration of a given component within the sample is determined
without requiring knowledge of the intensity of the transmitted
light intensity, by comparing measured light intensities
corresponding to respective regions within the sample carrier, and
without changing the intensity of the incident light between
measurements. For example, with reference to the sample carrier as
shown in FIG. 2, if the measured intensity of light transmitted
through region 42 is defined as I.sub.h and the measured intensity
of light transmitted through region 42 is defined as
I.sub.h+.DELTA..sub.1, the concentration of a given component .rho.
is given by:
.rho. = 1 .alpha. .DELTA. 1 log I h I h + .DELTA. 1 .
##EQU00001##
[0143] For some such applications, the actual system setting used
is chosen such as to provide desirable operating conditions.
[0144] For some applications, sample carrier 22 defines three or
more regions with predefined height differences between them, for
example, as shown in FIG. 4. For some applications, the regions
upon which to perform the measurements are selected, based upon the
concentration of one or more components within the sample that is
being analyzed, such as to provide a dynamic range of
concentrations of the sample that can be measured. For example, for
lower concentrations of the sample, absorption through a larger
optical length may be measured, while for higher concentrations of
the sample, absorption through a smaller optical length may be
measured. In order to provide a range of optical lengths via which
measurements can be performed, the sample carrier may be shaped to
define several regions having different height differences between
them (e.g., a second region being greater in height than a first
region by 30 micrometers, a third region being greater in height
than the second region by 60 micrometers, a fourth region being
greater in height than the third region by 120 micrometers, etc.).
Alternatively, the sample carrier may be shaped to define several
repetitions of the same or a similar height difference (e.g., a
second region being greater in height than a first region by 30
micrometers, a third region being greater in height than the second
region by 30 micrometers, a fourth region being greater in height
than the third region by 30 micrometers, etc.). In the latter case,
for low concentration of the sample, one would choose which
combination of regions to use, such as to provide a suitable height
difference, based upon the concentration of one or more components
within the sample. For some applications, the regions upon which
measurements are performed are chosen to provide repeated
measurements at the same height difference, or to provide a
plurality of measurements at different height differences. For some
applications, measurements obtained across multiple height
differences are integrated using a statistical method (e.g.
averaging, regression, curve-fitting or other techniques known in
the art), in order to provide a final determination of the
concentration of a component.
[0145] In general, the scope of the present invention includes (a)
providing a sample carrier, such as sample carrier 22 as described
herein, (b) categorizing a biological sample, (c) placing the
sample into the one or more sample chambers of the sample carrier,
and (d) based upon the categorization of the biological sample,
selecting one of the regions of the sample carrier upon which to
perform optical measurements for measuring a given measurand. For
example, if a sample, and/or a monolayer formed by the sample, has
a relatively low density of red blood cells, then measurements may
be performed upon a region of the sample carrier having a
relatively great height, such that there is a sufficient density of
cells, and/or such that there is a sufficient density of cells
within the monolayer formed by the sample, to provide statistically
reliable data. Such measurements may include, for example red blood
cell density measurements, measurements of other cellular
attributes, (such as counts of abnormal red blood cells, red blood
cells that include intracellular bodies (e.g., pathogens,
Howell-Jolly bodies), etc.), and/or hemoglobin concentration.
Conversely, if a sample, and/or a monolayer formed by the sample,
has a relatively high density of red blood cells, then such
measurements may be performed upon a region of the sample carrier
having a relatively low height, for example, such that there is a
sufficient sparsity of cells, and/or such that there is a
sufficient sparsity of cells within the monolayer of cells formed
by the sample, that the cells can be identified within microscopic
images. For some applications, such methods are performed even
without the variation in height between the regions of the one or
more sample chambers being precisely known.
[0146] For some applications, the sample is categorized based on
receiving an indication of the categorization of the sample (e.g.,
the sample may be labelled to indicate its categorization and this
categorization may be inputted into the computer processor).
Alternatively or additionally, the categorization includes
performing microscopic imaging upon the sample, and/or measuring a
parameter of the sample, such as optical absorption, transmittance,
fluorescence, and/or luminescence measurements, by performing a
preliminary optical measurement upon the sample. For some
applications, the sample is categorized based on the concentration
of one or more components within the sample, and/or based on the
density (e.g., a count per unit volume) of one or more components
within the sample. For some applications, a monolayer is formed
within the sample carrier (for example, using techniques as
described in U.S. Pat. No. 9,329,129 to Pollak, which is
incorporated herein by reference), and the sample is categorized
based upon a surface density of one or more components of the
sample within the monolayer.
[0147] For some applications, based upon the measurand that is
being measured, the region within the sample carrier upon which to
perform optical measurements is selected. For example, a region of
the sample chamber having a relatively great height may be used to
perform a white blood cell count (e.g., to reduce statistical
errors which may result from a low count in a shallower region),
white blood cell differentiation, and/or to detect more rare forms
of white blood cells. Conversely, in order to determine mean
corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), red
blood cell distribution width (RDW), red blood cell morphologic
features, and/or red blood cell abnormalities, optical measurements
(e.g., microscopic images) may be obtained from a region of the
sample chamber having a relatively low height, since in such
regions the cells are relatively sparsely distributed across the
area of the region, and/or form a monolayer in which the cells are
relatively sparsely distributed. Similarly, in order to count
platelets, classify platelets, and/or extract any other attributes
(such as volume) of platelets, optical measurements (e.g.,
microscopic images) may be obtained from a region of the sample
chamber having a relatively low height, since within such regions
there are fewer red blood cells which overlap (fully or partially)
with the platelets in microscopic images, and/or in a
monolayer.
[0148] In accordance with the above-described examples, it is
preferable to use a region of the sample carrier having a lower
height for performing optical measurements for measuring some
measurands within a sample (such as a blood sample), whereas it is
preferable to use a region of the sample carrier having a greater
height for performing optical measurements for measuring other
measurands within such a sample. Therefore, for some applications,
a first measurand within a sample is measured, by performing a
first optical measurement upon a portion of the sample that is
disposed within a first region of the sample carrier, and a second
measurand of the same sample is measured, by performing a second
optical measurement upon a portion of the sample that is disposed
within a second region of the sample carrier. For some
applications, the first and second measurands are normalized with
respect to each other, for example, using techniques as described
in a PCT application being filed on even date herewith, entitled
"Performing optical measurements on a sample," which is
incorporated herein by reference.
[0149] For some applications, a sample carrier as described herein
is used to determine hemoglobin concentration within an undiluted
blood sample using green light (500 nm-600 nm). For some such
applications, the nominal height of the lowest region of the sample
carrier is between greater than 1 micrometer, and/or less than 300
micrometers (e.g., 1-300 micrometers). Typically, the predefined
height differences between regions of the sample carrier are
greater than 5 micrometers and/or less than 500 micrometers (e.g.,
5-500 micrometers). For some applications, the area of each of the
regions is less than 100 square millimeters, e.g., less than 25
square millimeters, although the exact dimensions typically depend
on the substrate that is used and the fabrication method.
[0150] For some applications, a sample carrier as described herein
is configured such that first and second regions of the sample
chambers (which are as described hereinabove) are imaged using a
microscope (e.g., by providing optical windows, as described
hereinabove). For some such applications, the nominal height of the
lowest region of the sample carrier is between greater than 40
micrometers, and/or less than 450 micrometers (e.g., 4-450
micrometers). For some applications, the area of each of the
regions that is configured to be imaged by the microscope is less
than 400 square millimeters.
[0151] Reference is now made to FIG. 6, which is a flowchart
showing steps of an algorithm that is performed, in accordance with
some applications of the present invention. The flowchart is
described with reference to the sample carrier shown in FIG. 2, but
the algorithm could be applied to other embodiments of the sample
carrier as described herein, mutatis mutandis. For some
applications, the algorithm shown in FIG. 6 is used to determine
the actual height h of region 42 of sample carrier 22. In a first
step 90, an optical measurement is received from the first,
shallower region 42, and a property of the sample within the region
is determined, the property corresponding to height h. For example,
white blood cell count within region 42 may be measured. In a
second step 92, an optical measurement is obtained from the second,
deeper region 44, and a property of the sample within region 44 is
determined, the property corresponding to height h+.DELTA.h. For
example, white blood cell count within region 44 may be measured.
In a third step 94, the property within the height difference
.DELTA.h is determined. For example, the white blood cell count
within the height difference may be determined by subtracting the
white blood cell count from shallower region 42 from the white
blood cell count from deeper region 44 (assuming that the areas
measured in both of the regions were equal). In a fourth step 96, a
property of the sample is determined based upon the known height
difference and the property within the height difference. For
example, the white blood cell count per unit volume may be
determined based upon the white blood cell count within the height
difference and the known height difference. In a fifth step 98,
height h is calculated based upon the determined property of the
sample and the property that was obtained in step 90 within region
42. For example, based on the white blood cell count within region
42, and the determined white blood cell count per unit volume
within the sample, the volume of region 42 is derived, based upon
which height h is derived.
[0152] For some applications, the sample as described herein is a
sample that includes blood or components thereof (e.g., a diluted
or non-diluted whole blood sample, a sample including predominantly
red blood cells, or a diluted sample including predominantly red
blood cells), and parameters are determined relating to components
in the blood such as platelets, white blood cells, anomalous white
blood cells, circulating tumor cells, red blood cells,
reticulocytes, Howell-Jolly bodies, etc.
[0153] In general, it is noted that although some applications of
the present invention have been described with respect to a blood
sample, the scope of the present invention includes applying the
apparatus and methods described herein to a variety of samples. For
some applications, the sample is a biological sample, such as,
blood, saliva, semen, sweat, sputum, vaginal fluid, stool, breast
milk, bronchioalveolar lavage, gastric lavage, tears and/or nasal
discharge. The biological sample may be from any living creature,
and is typically from warm blooded animals. For some applications,
the biological sample is a sample from a mammal, e.g., from a human
body. For some applications, the sample is taken from any domestic
animal, zoo animals and farm animals, including but not limited to
dogs, cats, horses, cows and sheep. Alternatively or additionally,
the biological sample is taken from animals that act as disease
vectors including deer or rats.
[0154] For some applications, similar techniques to those described
hereinabove are applied to a non-bodily sample. For some
applications, the sample is an environmental sample, such as, a
water (e.g. groundwater) sample, surface swab, soil sample, air
sample, or any combination thereof. In some embodiments, the sample
is a food sample, such as, a meat sample, dairy sample, water
sample, wash-liquid sample, beverage sample, and any combination
thereof.
[0155] Applications of the invention described herein can take the
form of a computer program product accessible from a
computer-usable or computer-readable medium (e.g., a non-transitory
computer-readable medium) providing program code for use by or in
connection with a computer or any instruction execution system,
such as computer processor 28. For the purposes of this
description, a computer-usable or computer readable medium can be
any apparatus that can comprise, store, communicate, propagate, or
transport the program for use by or in connection with the
instruction execution system, apparatus, or device. The medium can
be an electronic, magnetic, optical, electromagnetic, infrared, or
semiconductor system (or apparatus or device) or a propagation
medium. Typically, the computer-usable or computer readable medium
is a non-transitory computer-usable or computer readable
medium.
[0156] Examples of a computer-readable medium include a
semiconductor or solid state memory, magnetic tape, a removable
computer diskette, a random-access memory (RAM), a read-only memory
(ROM), a rigid magnetic disk and an optical disk. Current examples
of optical disks include compact disk-read only memory (CD-ROM),
compact disk-read/write (CD-R/W) and DVD.
[0157] A data processing system suitable for storing and/or
executing program code will include at least one processor (e.g.,
computer processor 28) coupled directly or indirectly to memory
elements (e.g., memory 30) through a system bus. The memory
elements can include local memory employed during actual execution
of the program code, bulk storage, and cache memories which provide
temporary storage of at least some program code in order to reduce
the number of times code must be retrieved from bulk storage during
execution. The system can read the inventive instructions on the
program storage devices and follow these instructions to execute
the methodology of the embodiments of the invention.
[0158] Network adapters may be coupled to the processor to enable
the processor to become coupled to other processors or remote
printers or storage devices through intervening private or public
networks. Modems, cable modem and Ethernet cards are just a few of
the currently available types of network adapters.
[0159] Computer program code for carrying out operations of the
present invention may be written in any combination of one or more
programming languages, including an object-oriented programming
language such as Java, Smalltalk, C++ or the like and conventional
procedural programming languages, such as the C programming
language or similar programming languages.
[0160] It will be understood that blocks of the flowcharts shown in
FIGS. 5 and 6 and combinations of blocks in the flowcharts, can be
implemented by computer program instructions. These computer
program instructions may be provided to a processor of a
general-purpose computer, special purpose computer, or other
programmable data processing apparatus to produce a machine, such
that the instructions, which execute via the processor of the
computer (e.g., computer processor 28) or other programmable data
processing apparatus, create means for implementing the
functions/acts specified in the flowcharts and/or algorithms
described in the present application. These computer program
instructions may also be stored in a computer-readable medium
(e.g., a non-transitory computer-readable medium) that can direct a
computer or other programmable data processing apparatus to
function in a particular manner, such that the instructions stored
in the computer-readable medium produce an article of manufacture
including instruction means which implement the function/act
specified in the flowchart blocks and algorithms. The computer
program instructions may also be loaded onto a computer or other
programmable data processing apparatus to cause a series of
operational steps to be performed on the computer or other
programmable apparatus to produce a computer implemented process
such that the instructions which execute on the computer or other
programmable apparatus provide processes for implementing the
functions/acts specified in the flowcharts and/or algorithms
described in the present application.
[0161] Computer processor 28 is typically a hardware device
programmed with computer program instructions to produce a special
purpose computer. For example, when programmed to perform the
algorithms described with reference to FIGS. 5 and 6, computer
processor 28 typically acts as a special purpose sample-analysis
computer processor. Typically, the operations described herein that
are performed by computer processor 28 transform the physical state
of memory 30, which is a real physical article, to have a different
magnetic polarity, electrical charge, or the like depending on the
technology of the memory that is used.
[0162] The apparatus and methods described herein may be used in
conjunction with apparatus and methods described in any one of the
following patent applications, all of which are incorporated herein
by reference: [0163] US 2012/0169863 to Bachelet; [0164] US
2014/0347459 to Greenfield; [0165] US 2015/0037806 to Pollak;
[0166] US 20150316477 to Pollak; [0167] US 20160208306 to Pollak;
[0168] US 20160246046 to Yorav Raphael; [0169] US 20160279633 to
Bachelet; [0170] WO 16/030897 to Yorav Raphael; [0171] WO 17/046799
to Eshel; [0172] WO 17/168411 to Eshel.
[0173] There is provided, in accordance with some applications of
the present invention, the following inventive concepts:
Inventive concept 1. A method for performing optical measurements
on a biological sample, the method comprising:
[0174] providing a sample carrier that comprises one or more sample
chambers configured to house the sample, the one or more sample
chambers defining at least first and second regions thereof, a
height of the one or more sample chambers varying between the first
and second regions;
[0175] categorizing the biological sample;
[0176] placing the sample into the one or more sample chambers;
and
[0177] based upon the categorization of the biological sample,
selecting one of the first and second regions upon which to perform
optical measurements for measuring a given measurand.
Inventive concept 2. The method according to inventive concept 1,
wherein categorizing the sample comprises receiving an indication
of the categorization of the sample. Inventive concept 3. The
method according to inventive concept 1, wherein categorizing the
sample comprises categorizing the sample based upon a density of
one or more components within the sample. Inventive concept 4. The
method according to inventive concept 1, wherein categorizing the
sample comprises categorizing the sample based upon a surface
density of one or more components within a monolayer formed by the
sample. Inventive concept 5. The method according to inventive
concept 1, wherein categorizing the sample comprises categorizing
the sample based upon a concentration of one or more components
within the sample. Inventive concept 6. The method according to
inventive concept 1, wherein categorizing the sample comprises
categorizing the sample based upon a count of one or more
components within the sample. Inventive concept 7. The method
according to inventive concept 1, wherein categorizing the sample
comprises measuring a parameter of the sample selected from the
group consisting of: optical absorption, transmittance,
fluorescence, and luminescence, by performing a preliminary optical
measurement upon the sample. Inventive concept 8. The method
according to inventive concept 1, wherein categorizing the sample
comprises performing microscopic imaging upon the sample. Inventive
concept 9. The method according to inventive concept 1, wherein
selecting one of the first and second regions upon which to perform
optical measurements for measuring the given measurand comprises
selecting one of the first and second regions upon which to perform
counting of a given component within the sample, by performing
microscopic imaging upon the region. Inventive concept 10. The
method according to inventive concept 1, wherein selecting one of
the first and second regions upon which to perform optical
measurements for measuring the given measurand comprises selecting
one of the first and second regions upon which to measure a
concentration of a given component within the sample, by measuring
a parameter selected from the group consisting of: optical
absorption, transmittance, fluorescence, and luminescence.
Inventive concept 11. The method according to any one of inventive
concepts 1-10, wherein:
[0178] the one or more sample chambers define at least first,
second, and third regions thereof, a height of the one or more
sample chambers varying between each of the first, second, and
third regions in a predefined manner; and
[0179] based upon the identified property of the biological sample,
selecting two out of the first, second, and third regions upon
which to perform, respective, first and second optical measurements
for measuring the given measurand.
Inventive concept 12. The method according to inventive concept 11,
further comprising:
[0180] performing the, respective, first and second optical
measurements upon the selected two regions; and
[0181] measuring the given measurand by using a relationship
between the first optical measurement, the second optical
measurement, and the predefined variation in height between the
selected two regions.
Inventive concept 13. The method according to any one of inventive
concepts 1-10, wherein the biological sample includes a blood
sample, and wherein selecting one of the first and second regions
upon which to perform optical measurements for measuring the given
measurand comprises selecting one of the first and second regions
upon which to perform optical measurements for measuring a given
measurand of the blood sample. Inventive concept 14. The method
according to inventive concept 13, wherein selecting one of the
first and second regions upon which to perform optical measurements
for measuring the given measurand comprises selecting one of the
first and second regions upon which to measure a concentration of a
given component within the blood sample, by measuring a parameter
selected from the group consisting of: optical absorption, optical
transmittance, fluorescence, and luminescence. Inventive concept
15. The method according to inventive concept 13, wherein selecting
one of the first and second regions upon which to perform optical
measurements for measuring the given measurand comprises selecting
one of the first and second regions upon which to perform counting
of a given component within the blood sample, by performing
microscopic imaging upon the region. Inventive concept 16.
Apparatus for determining a property of a biological sample, the
apparatus comprising:
[0182] a sample carrier that comprises one or more sample chambers
configured to house the sample, the one or more sample chambers
defining at least first and second regions thereof, a height of the
one or more sample chambers varying between the first and second
regions; and
[0183] a computer processor configured to: [0184] categorize the
biological sample, and [0185] based upon the categorization of the
biological sample, select one of the first and second regions upon
which to perform optical measurements for measuring a given
measurand of the biological sample. Inventive concept 17. A
computer software product, for use with a biological sample that is
placed within a sample carrier that comprises one or more sample
chambers configured to house the sample, the one or more sample
chambers defining at least first and second regions thereof, a
height of the one or more sample chambers varying between the first
and second regions, the computer software product comprising a
non-transitory computer-readable medium in which program
instructions are stored, which instructions, when read by a
computer cause the computer to perform the steps of:
[0186] categorizing the biological sample; and
[0187] based upon the categorization of the biological sample,
selecting one of the first and second regions upon which to perform
optical measurements for measuring a given measurand of the
biological sample.
Inventive concept 18. Apparatus for performing optical measurements
on a biological sample, the apparatus comprising:
[0188] a sample carrier that comprises one or more sample chambers
configured to house the sample,
[0189] the one or more sample chambers defining at least first,
second, and third regions thereof, a height of the one or more
sample chambers varying between each of the first, second, and
third regions in a predefined manner.
Inventive concept 19. A method for performing optical measurements
on a biological sample, the method comprising:
[0190] providing a sample carrier, the sample carrier including one
or more sample chambers configured to house the sample, the one or
more sample chambers defining at least first and second regions
thereof, a height of the one or more sample chambers varying
between the first and second regions;
[0191] placing the sample into the one or more sample chambers;
[0192] measuring a first measurand, by performing a first optical
measurement upon a portion of the sample that is disposed within
the first region; and
[0193] measuring a second measurand, by performing a second optical
measurement upon a portion of the sample that is disposed within
the second region.
Inventive concept 20. The method according to inventive concept 19,
wherein the biological sample includes a blood sample, wherein
measuring the first measurand comprises measuring a first measurand
of the blood sample performing the first optical measurement upon a
portion of the blood sample that is disposed within the first
region, and wherein measuring the second measurand comprises
measuring a second measurand of the blood sample by performing a
second optical measurement upon a portion of the sample that is
disposed within the second region. Inventive concept 21. The method
according to inventive concept 20, wherein measuring the first
measurand of the blood sample comprises determining a count of a
first component within the blood sample by performing microscopic
imaging upon the portion of the sample that is disposed within the
first region, and wherein measuring the second measurand of the
blood sample comprises determining a count of a second component
within the blood sample by performing microscopic imaging upon the
portion of the sample that is disposed within the second region.
Inventive concept 22. The method according to inventive concept 20,
wherein measuring the first measurand of the blood sample comprises
measuring a concentration of a first component within the blood
sample, by performing, upon the portion of the sample that is
disposed within the first region, an optical measurement of a
parameter selected from the group consisting of: optical
absorption, transmittance, fluorescence, and luminescence.
Inventive concept 23. The method according to inventive concept 22,
wherein measuring the second measurand of the blood sample
comprises measuring a concentration of a second component within
the blood sample, by performing, upon the portion of the sample
that is disposed within the second region, an optical measurement
of a parameter selected from the group consisting of: optical
absorption, transmittance, fluorescence, and luminescence.
Inventive concept 24. The method according to inventive concept 22,
wherein measuring the second measurand of the blood sample
comprises determining a count of a second component within the
blood sample by performing microscopic imaging upon the portion of
the sample that is disposed within the second region. Inventive
concept 25. Apparatus for determining a property of a biological
sample, the apparatus comprising:
[0194] a sample carrier that comprises one or more sample chambers
configured to house the sample, the one or more sample chambers
defining at least first and second regions thereof, a height of the
one or more sample chambers varying between the first and second
regions; and
[0195] a computer processor configured to: [0196] measure a first
measurand, by receiving a first optical measurement performed upon
a portion of the sample that is disposed within the first region;
and [0197] measure a second measurand, by receiving a second
optical measurement performed upon a portion of the sample that is
disposed within the second region. Inventive concept 26. A computer
software product, for use with a biological sample that is placed
within a sample carrier that comprises one or more sample chambers
configured to house the sample, the one or more sample chambers
defining at least first and second regions thereof, a height of the
one or more sample chambers varying between the first and second
regions, the computer software product comprising a non-transitory
computer-readable medium in which program instructions are stored,
which instructions, when read by a computer cause the computer to
perform the steps of:
[0198] measuring a first measurand, by receiving a first optical
measurement performed upon a portion of the sample that is disposed
within the first region; and
[0199] measuring a second measurand, by receiving a second optical
measurement performed upon a portion of the sample that is disposed
within the second region.
Inventive concept 27. A method for performing optical measurements
on a biological sample, the method comprising:
[0200] providing a sample carrier that comprises one or more sample
chambers configured to house the sample, the one or more sample
chambers defining at least first and second regions thereof, a
height of the one or more sample chambers varying between the first
and second regions;
[0201] categorizing a measurand of the biological sample that is to
be measured;
[0202] placing the sample into the one or more sample chambers;
and
[0203] based upon the categorization of the measurand, selecting
one of the first and second regions upon which to perform optical
measurements for measuring the identified measurand.
Inventive concept 28. The method according to inventive concept 27,
wherein the biological sample includes a blood sample, wherein
categorizing the measurand of the biological sample that is to be
measured comprises categorizing a measurand of the blood sample
that is to be measured. Inventive concept 29. The method according
to inventive concept 28, wherein selecting one of the first and
second regions upon which to perform optical measurements for
measuring the identified measurand comprises selecting one of the
first and second regions upon which to measure a concentration of a
given component within the blood sample, by measuring a parameter
selected from the group consisting of: optical absorption,
transmittance, fluorescence, and luminescence. Inventive concept
30. The method according to inventive concept 28, wherein selecting
one of the first and second regions upon which to perform optical
measurements for measuring the identified measurand comprises
selecting one of the first and second regions upon which to perform
microscopic imaging. Inventive concept 31. Apparatus for
determining a property of a biological sample, the apparatus
comprising:
[0204] a sample carrier that comprises one or more sample chambers
configured to house the sample, the one or more sample chambers
defining at least first and second regions thereof, a height of the
one or more sample chambers varying between the first and second
regions; and
[0205] a computer processor configured to: [0206] categorize a
measurand of the biological sample that is to be measured, and
[0207] based upon the categorization of the measurand, select one
of the first and second regions upon which to perform optical
measurements for measuring the identified measurand. Inventive
concept 32. A computer software product, for use with a biological
sample that is placed within a sample carrier that comprises one or
more sample chambers configured to house the sample, the one or
more sample chambers defining at least first and second regions
thereof, a height of the one or more sample chambers varying
between the first and second regions, the computer software product
comprising a non-transitory computer-readable medium in which
program instructions are stored, which instructions, when read by a
computer cause the computer to perform the steps of:
[0208] categorizing a measurand of the biological sample that is to
be measured; and
[0209] based upon the categorization of the measurand, selecting
one of the first and second regions upon which to perform optical
measurements for measuring the identified measurand.
[0210] It will be appreciated by persons skilled in the art that
the present invention is not limited to what has been particularly
shown and described hereinabove. Rather, the scope of the present
invention includes both combinations and subcombinations of the
various features described hereinabove, as well as variations and
modifications thereof that are not in the prior art, which would
occur to persons skilled in the art upon reading the foregoing
description.
* * * * *