# US 12,111,248 B2 · Image analysis and measurement of biological samples

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- Number: US 12,111,248 B2
- Document ID: US12111248B2
- Status: Granted
- Kind: B2
- Application number: 16/382,489
- Filed: 2019-04-12
- Published: 2019-11-07
- Granted: 2024-10-08
- Earliest claimed: 2013-02-18
- Assignees: Labrador Diagnostics LLC
- Applicants: Labrador Diagnostics LLC
- Inventors: Karan Mohan; Chinmay Pangarkar; James R. Wasson
- Web page: https://patentgrep.com/patent/US12111248B2

## CPC

- 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)}
- B01L 3/502715: {characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces}
- B01L 3/5085: {for multiple samples, e.g. microtitration plates}
- B01L 9/523: {for multisample carriers, e.g. used for microtitration plates}
- G01N 1/30: Staining; Impregnating {; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis}
- G01N 15/1012: {Calibrating particle analysers; References therefor}
- G01N 15/1433: using image recognition
- G01N 21/05: Flow-through cuvettes (G01N21/09 takes precedence; handling fluid samples G01N1/10)
- G01N 21/17: Systems in which incident light is modified in accordance with the properties of the material investigated (where the material investigated is optically excited causing a change in wavelength of the incident light G01N21/63)
- G01N 21/27: using photo-electric detection (G01N21/31 takes precedence){; circuits for computing concentration (logarithmic circuits G06G7/24; photometric circuits in general G01J)}
- G01N 21/6428: {Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" (in vivo A61B5/00; immunoassay G01N33/53)}
- G01N 21/645: {Specially adapted constructive features of fluorimeters}
- G01N 21/6458: {Fluorescence microscopy (fluorescence microscopes per se G02B21/0076 and G02B21/16)}
- G01N 21/6486: {Measuring fluorescence of biological material, e.g. DNA, RNA, cells (G01N21/6428 takes precedence)}
- G01N 33/487: of liquid biological material
- G01N 33/49: Blood {(chemical methods for determining blood cell populations G01N33/5094; chemical analysis of blood groups or blood types G01N33/80)}
- G01N 33/5005: {involving human or animal cells (immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025)}
- G01N 33/56966: {Animal cells}
- G01N 33/56972: {White blood cells}
- G02B 7/09: adapted for automatic focusing or varying magnification
- G02B 21/00: Microscopes
- G02B 21/0076: {arrangements using fluorescence or luminescence}
- G02B 21/088: {for both incident illumination and transillumination}
- G02B 21/125: {affording both dark- and bright-field illumination}
- G02B 21/16: adapted for ultraviolet illumination {; Fluorescence microscopes (G02B21/0076 takes precedence)}
- G02B 21/244: {using image analysis techniques}
- G02B 21/34: Microscope slides, e.g. mounting specimens on microscope slides
- G02B 21/365: {Control or image processing arrangements for digital or video microscopes (G02B21/361, G02B21/362 take precedence)}
- G02B 21/367: {providing an output produced by processing a plurality of individual source images, e.g. image tiling, montage, composite images, depth sectioning, image comparison}
- B01L 2300/0654: Lenses; Optical fibres
- B01L 2300/168: Specific optical properties, e.g. reflective coatings
- G01N 15/01: specially adapted for biological cells, e.g. blood cells (investigating sedimentation of particle suspensions in blood G01N15/05)
- G01N 2015/1014: {Constitution of reference particles}
- G01N 2015/1486: {Counting the particles}
- G01N 2021/1738: {Optionally different kinds of measurements; Method being valid for different kinds of measurement}
- G01N 2021/6439: {with indicators, stains, dyes, tags, labels, marks}
- G01N 2201/061: Sources
- G01N 2201/068: Optics, miscellaneous
- G01N 2201/12: Circuits of general importance; Signal processing
- G01N 2333/70589: CD45
- G01N 2333/70596: Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705
- 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)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- G02B: OPTICAL ELEMENTS, SYSTEMS OR APPARATUS

## Abstract

Methods, devices, apparatus, and systems are provided for image analysis. Methods of image analysis may include observation, measurement, and analysis of images of biological and other samples; devices, apparatus, and systems provided herein are useful for observation, measurement, and analysis of images of such samples. The methods, devices, apparatus, and systems disclosed herein provide advantages over other methods, devices, apparatus, and systems.

## Claims

### Claim 1

A system for analyzing a sample, the system comprising:
a dark field illumination source;
another illumination source;
a detector;
an objective lens with an aperture;
a sample holder comprising a cover, a base having a first side and a second side, a first elongate sample chamber, and a second elongate sample chamber wherein the illumination source and the detector are both located on the same side of the sample holder and wherein said another illumination source is located on another size of the sample holder, wherein the dark field illumination source is positioned so that light from the dark field illumination source to the sample holder is directed only at an oblique angle with respect to the base,
wherein the first elongate sample chamber has a first sample inlet and a first vent;
wherein the second elongate sample chamber has a second sample inlet and a second vent.

### Claim 2 (depends on 1)

The system of claim 1, wherein the cover has an exterior surface coated with an optically absorbent material.

### Claim 3 (depends on 1)

The system of claim 1, wherein the cover has an exterior surface coated with an optically absorbent ink.

### Claim 4 (depends on 1)

The system of claim 1, wherein said sample holder is movable relative to said another illumination source to a plurality of locations, wherein an optically transmissive surface of the sample holder may be illuminated by the another illumination source at each of said locations.

### Claim 5 (depends on 1)

The system of claim 1, wherein said dark field illumination source comprises a ringlight.

### Claim 6 (depends on 5)

The system of claim 5, wherein said ringlight is selected from the group consisting of a light emitting diode (LED)-based ringlight and a laser-based ringlight.

### Claim 7 (depends on 1)

The system of claim 1, further comprising a compression device configured to retain the sample holder in a desired location for illumination by the another illumination source.

### Claim 8 (depends on 1)

The system of claim 1, wherein the sample holder comprises a fluid circuit sized and configured to hold and fully confine the sample within said fluid circuit, effective that the sample remains separate from said detector.

### Claim 9 (depends on 1)

The system of claim 1, wherein said sample holder and said another illumination source comprise at least part of an optical analysis unit, said system further comprising a clinical analysis unit configured to perform clinical analysis on said sample.

### Claim 10 (depends on 9)

The system of claim 9, wherein each of said optical analysis unit and said clinical analysis unit are sized and configured to receive an aliquot of a single sample, effective that both an optical analysis and a clinical analysis may be performed on portions of a sample at the same time.

### Claim 11 (depends on 9)

The system of claim 9, wherein said clinical analysis unit is sized and configured to perform at least one clinical analysis selected from the group consisting of general chemical analysis, nucleic acid analysis, and enzyme-linked binding analysis.

### Claim 12 (depends on 1)

The system of claim 1 further comprising an automated stage for receiving the sample holder, wherein the automated stage is configured to create relative motion between the sample holder and the detector in a pattern to visualize individual portions of the sample holder, and
wherein both the dark field illumination source and the detector are located below a plane where the automated stage receives the sample holder.