# US 11,307,196 B2 · Sample carrier for optical measurements

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- Number: US 11,307,196 B2
- Document ID: US11307196B2
- Status: Granted
- Kind: B2
- Application number: 16/098,893
- Filed: 2017-05-11
- Published: 2019-10-03
- Granted: 2022-04-19
- Earliest claimed: 2016-05-11
- Assignees: S.D. Sight Diagnostics Ltd.
- Applicants: S.D. Sight Diagnostics Ltd.
- Inventors: Joseph Joel Pollak; Sarah Levy Schreier; Yochay Shlomo Eshel; Amir Zait; Sharon Pecker; Trevor Ruggiero
- Web page: https://patentgrep.com/patent/US11307196B2

## CPC

- G01N 33/50: Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing (measuring or testing processes involving enzymes or microorganisms, compositions or test papers therefor; processes for forming such compositions, condition responsive control in microbiological or enzymological processes C12Q)
- G01N 21/0303: {Optical path conditioning in cuvettes, e.g. windows; adapted optical elements or systems; path modifying or adjustment (G01N21/031 - G01N21/15 take precedence)}
- G01N 21/31: Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry {(G01N21/72 takes precedence)}
- G01N 21/59: Transmissivity (G01N21/25 takes precedence)
- G01N 21/64: Fluorescence; Phosphorescence
- G01N 2201/0662: Comparing measurements on two or more paths in one sample
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Apparatus and methods are described for determining a property of a biological sample. A sample carrier (22) includes one or more sample chambers (40) that define at least a first region (42) and a second region (44), the height of the one or more sample chambers varying between the first and second regions in a predefined manner. A computer processor (28) receives data relating to a first optical measurement that is performed upon a portion of the sample that is disposed within the first region, receives data relating to a second optical measurement that is performed upon a portion of the sample that is disposed within the second region, and determines 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 regions. Other applications are also described.

## Claims

### Claim 1

Apparatus for determining a property of a biological sample, the apparatus comprising:
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, 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, the sample carrier comprising:
a first substrate that defines a first surface;
a second substrate that defines one or more surfaces that oppose the first surface, the second substrate being 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, second, and third regions; and
an adhesive layer that adheres the first substrate to the second substrate; and
a computer processor configured to:
determine a concentration of one or more components within the biological sample,
based upon the determined concentration of the one or more components within the biological sample, select two out of the first, second, and third regions upon which to perform, respectively, first and second optical measurements, such that in response to the one or more components having a relatively lower concentration, regions having a relatively larger height difference are selected, and in response to the one or more components having a relatively higher concentration, regions having a relatively smaller height difference are selected,
receive data relating to the first optical measurement that is performed upon a portion of the sample that is disposed within a first one of the selected regions,
receive data relating to the second optical measurement that is performed upon a portion of the sample that is disposed within a second one of the selected regions, 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 selected region and the second selected region.

### Claim 2 (depends on 1)

The apparatus according to claim 1, wherein the height of the one or more sample chambers varies between the first, second, and third regions in a predefined stepped manner.

### Claim 3 (depends on 1)

The apparatus according to claim 1, wherein the height of the one or more sample chambers varies between the first, second, and third regions in a predefined gradual manner.

### Claim 4 (depends on 1)

The apparatus according to claim 1, 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 a microscope.

### Claim 5 (depends on 1)

The apparatus according to claim 1, 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.

### Claim 6 (depends on 1)

The apparatus according to claim 1, wherein the computer processor is configured to determine the property of the sample by determining at least one 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.

### Claim 7 (depends on 1)

The apparatus according to claim 1, wherein the computer processor is configured to determine an absolute height of the one or more sample chambers within at least one of the first, second, and third regions, using the relationship between the first optical measurement, the second optical measurement, and the predefined variation in height between the first selected region and the second selected region.

### Claim 8 (depends on 1)

The apparatus according to claim 1, 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 selected region and the second selected region.

### Claim 9 (depends on 1)

The apparatus according to claim 1, 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 selected region and the second selected region.

### Claim 10 (depends on 1)

The apparatus according to claim 1, 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.

### Claim 11 (depends on 1)

The apparatus according to claim 1, wherein the second substrate defines second, third, and fourth surfaces, the second, third, and fourth surfaces (a) opposing the first surface, (b) being parallel to the first surface, and (c) being stepped with respect to each other.

### Claim 12 (depends on 1)

The apparatus according to claim 1, wherein the second substrate 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.

### Claim 13

A method for determining a property of a biological sample, the method comprising:
placing the sample into one or more sample chambers of a sample carrier, 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 the first, second, and third regions in a predefined manner, the sample carrier including:
a first substrate that defines a first surface,
a second substrate that defines one or more surfaces that oppose the first surface, the second substrate being 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, second, and third regions, and
an adhesive layer that adheres the first substrate to the second substrate;
determining a concentration of one or more components within the biological sample;
based upon the determined concentration of the one or more components within the biological sample, selecting two out of the first, second, and third regions upon which to perform, respectively, first and second optical measurements, such that in response to the one or more components having a relatively lower concentration, regions having a relatively larger height difference are selected, and in response to the one or more components having a relatively higher concentration, regions having a relatively smaller height difference are selected;
performing the first optical measurement upon a portion of the sample that is disposed within the first selected region;
performing the second optical measurement upon a portion of the sample that is disposed within the second selected 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 selected region and the second selected region.

### Claim 14 (depends on 13)

The method according to claim 13, wherein placing the sample into the one or more sample chambers of the sample carrier comprises placing the sample into the one or more sample chambers of the sample carrier, the height of the one or more sample chambers varying between the first, second, and third regions in a predefined stepped manner.

### Claim 15 (depends on 13)

The method according to claim 13, wherein placing the sample into the one or more sample chambers of the sample carrier comprises placing the sample into the one or more sample chambers of the sample carrier, the height of the one or more sample chambers varying between the first, second, and third regions in a predefined gradual manner.

### Claim 16 (depends on 13)

The method according to claim 13, wherein performing at least one of the first and second optical measurements comprises performing an optical measurement upon the sample using a microscope.

### Claim 17 (depends on 13)

The method according to claim 13, wherein performing at least one of the first and second optical measurements comprises determining a parameter selected from the group consisting of: optical absorption, transmittance, fluorescence, and luminescence by performing imaging upon the sample.

### Claim 18 (depends on 13)

The method according to claim 13, wherein determining the property of the sample comprises determining at least one 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.

### Claim 19 (depends on 13)

The method according to claim 13, further comprising determining an absolute height of the one or more sample chambers within at least one of the first, second, and third regions, using the relationship between the first optical measurement, the second optical measurement, and the predefined variation in height between the first selected region and the second selected region.

### Claim 20 (depends on 13)

The method according to claim 13, wherein determining the property of the sample comprises:
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 selected region and the second selected region.

### Claim 21 (depends on 13)

The method according to claim 13, wherein determining the property of the sample comprises:
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 selected region and the second selected region.

### Claim 22 (depends on 13)

The method according to claim 13, wherein the biological sample includes a blood sample, and wherein determining the property of the biological sample comprises determining a property of the blood sample.

### Claim 23 (depends on 13)

The method according to claim 13, wherein placing the sample into the one or more sample chambers of the sample carrier comprises placing the sample into the one or more sample chambers of the sample carrier, the second substrate of the sample carrier defining second, third, and fourth surfaces, the second, third, and fourth surfaces (a) opposing the first surface, (b) being parallel to the first surface, and (c) being stepped with respect to each other.

### Claim 24 (depends on 13)

The method according to claim 13, wherein placing the sample into the one or more sample chambers of the sample carrier comprises placing the sample into the one or more sample chambers of the sample carrier, the second substrate of the sample carrier defining at least a second surface, the second surface (a) opposing the first surface, and (b) being non-parallel with respect to the first surface.

### Claim 25

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, second, and third regions thereof, a height of the one or more sample chambers varying between the first, second, and third regions, in a predefined manner, the sample carrier including a first substrate that defines a first surface, and a second substrate that defines one or more surfaces that oppose the first surface, the second substrate being 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, second, and third regions, and an adhesive layer that adheres the first substrate to the second substrate; 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:
determining a concentration of one or more components within the biological sample;
based upon the determined concentration of the one or more components within the biological sample, selecting two out of the first, second, and third regions upon which to perform, respectively, first and second optical measurements, such that in response to the one or more components having a relatively lower concentration, regions having a relatively larger height difference are selected, and in response to the one or more components having a relatively higher concentration, regions having a relatively smaller height difference are selected;
receiving data relating to the first optical measurement that is performed upon a portion of the sample that is disposed within the first selected region;
receiving data relating to the second optical measurement that is performed upon a portion of the sample that is disposed within the second selected 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 selected region and the second selected region.

### Claim 26 (depends on 1)

The apparatus according to claim 1, wherein the adhesive layer comprises a pressure-sensitive adhesive layer.

### Claim 27 (depends on 13)

The method according to claim 13, wherein the adhesive layer comprises a pressure-sensitive adhesive layer.
