# US 2014/0152801 A1 · Detecting and Using Light Representative of a Sample

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- Number: US 2014/0152801 A1
- Document ID: US20140152801A1
- Status: Published application
- Kind: A1
- Application number: 14/173,500
- Filed: 2014-02-05
- Published: 2014-06-05
- Earliest claimed: 2009-10-28
- Assignees: Alentic Microscience Inc.
- Applicants: Alentic Microscience Inc.
- Inventors: Alan Marc Fine; Hershel Macaulay; Laurent Kreplak
- Web page: https://patentgrep.com/patent/US20140152801A1

## CPC

- H04N 7/18: Closed-circuit television [CCTV] systems, i.e. systems in which the video signal is not broadcast
- G02B 21/0008: {Microscopes having a simple construction, e.g. portable microscopes}
- B01L 3/502761: {specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads or physically stretching molecules}
- B01L 2200/027: for microfluidic devices
- H04N: PICTORIAL COMMUNICATION, e.g. TELEVISION
- G02B: OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE

## Abstract

An imaging device includes light sensitive locations that are separately sensitive to light received at a surface with respect to a portion of a sample associated with the surface, the light sensitive locations having a resolution of 5 microns or smaller. There is a device to associate the portion of the sample with the surface. The imaging device and a distance of the portion of the sample to the light sensitive locations are such that usable useful image of the portion of the sample can be acquired directly by operation of the imaging device. An imaging device includes light sensitive sources that are separately able to deliver light with respect to a portion of a sample associated with the surface. The light source locations having a resolution of 5 microns or smaller. There is a device to associate the portion of the sample with the surface. The imaging device and a distance of the portion of the sample to the light source locations are such that a useful image of the portion of the sample can be acquired directly by operation of the imaging device. An imaging device can include both the light source locations and the light source locations and the light sensitive locations.

## Claims

### Claim 1

An apparatus comprising
a surface with which a portion of a sample can be associated,
an imaging device that comprises light sensitive locations that are separately sensitive to light received at the surface with respect to the portion of the sample associated with the surface, the light sensitive locations having a resolution of 2 microns or smaller,
a device to associate the portion of the sample with the surface, and
the resolution of the imaging device and a distance of the portion of the sample to the light sensitive locations being such that a useful image of the portion of the sample can be acquired directly by operation of the imaging device.

### Claim 2

An apparatus comprising
a surface with which a portion of a sample can be associated,
an imaging device that comprises light source locations that are separately able to deliver light with respect to the portion of the sample, the light source locations having a resolution of 2 microns or smaller, and with a light detector to receive light from the light source locations and the sample,
the imaging device and a distance of the portion of the sample to the light source locations being such that a useful image of the portion of the sample can be acquired directly by operation of the imaging device.

### Claim 3 (depends on 1)

The apparatus of claim 1 comprising an absorbance spectroscopy element to process wavelength-dependent information from the imaging device.

### Claim 4 (depends on 3)

The apparatus of claim 3 in which the sample is homogeneous and a single image from the imaging device is sufficient for absorbance spectroscopy processing.

### Claim 5 (depends on 3)

The apparatus of claim 3 in which the sample is heterogeneous and flows past the imaging device, multiple images are captured by the imaging device, and the absorbance spectroscopy element processes the images together.

### Claim 6 (depends on 1)

The apparatus of claim 1 comprising a light amplifier.

### Claim 7 (depends on 1)

The apparatus of claim 1 in which the device to associate the portion of the sample with the surface comprises a chamber that encompasses at least a portion of the surface with which the portion of the sample is associated and is to contain the portion of the sample.

### Claim 8 (depends on 1)

The apparatus of claim 1 in which the device comprises elements for causing units of interest in the portion of the sample to tend to be located closer to the surface than other elements of the portion of the sample.

### Claim 9 (depends on 1)

The apparatus of claim 1 in which the device to associate the portion of the sample with the surface comprises a lid.

### Claim 10 (depends on 9)

The apparatus of claim 9 in which the lid is transparent to light.

### Claim 11 (depends on 9)

The apparatus of claim 9 in which the lid comprises a bottom surface arranged to touch the sample.

### Claim 12 (depends on 9)

The apparatus of claim 9 in which the lid is disposable and comprises spots of binding units that are to be aligned with the light sensitive locations of the imaging device.

### Claim 13 (depends on 9)

The apparatus of claim 9 in which the lid is suspended from an aperture in a balloon, the perimeter of which is attached at or near the imaging device.

### Claim 14 (depends on 9)

The apparatus of claim 9 comprising spots of binding units that are deposited directly onto the pixels and aligned with the light sensitive locations of the imaging device.

### Claim 15 (depends on 11)

The apparatus of claim 11 in which the bottom surface of the lid and the surface with which the portion of the sample is associated are not parallel.

### Claim 16 (depends on 11)

The apparatus of claim 11 in which the bottom surface of the lid is convex relative to the surface associated with the portion of the sample.

### Claim 17 (depends on 11)

The apparatus of claim 11 comprising a mechanism to lower the lid smoothly and maintain its bottom parallel to the surface.

### Claim 18 (depends on 11)

The apparatus of claim 11 comprising a mechanism to measure the volume of the sample space in the chamber.

### Claim 19 (depends on 18)

The apparatus of claim 18 in which the mechanism comprises at least one of absorbance using a known concentration of dye, counting of microbeads added in known concentration, and trigonometry with markers/spots on the bottom surface of the chamber lid illuminated from different positions.

### Claim 20 (depends on 1)

The apparatus of claim 1 comprising a device to associate the portion of the sample with the surface and arranged to define a sample space in which the sample space comprises a precisely known volume at the surface.

### Claim 21 (depends on 20)

The apparatus of claim 20 in which the portion of the sample contains sample units and the sample space extends from the surface by a distance that corresponds to a size of the sample units.

### Claim 22 (depends on 1)

The apparatus of claim 1 comprising a device to associate the portion of the sample with the surface and arranged to define a sample space, in which the device to associate the portion of the sample with the surface comprises a flow inlet and a flow outlet.

### Claim 23 (depends on 1)

The apparatus of claim 1 comprising an illuminator.

### Claim 24 (depends on 23)

The apparatus of claim 23 in which the illuminator is to deliver collimated light toward the surface.

### Claim 25 (depends on 24)

The apparatus of claim 24 in which the illuminator comprises a multi-point illuminator with light collimated toward the surface by anamorphic reflectors or an anamorphic prism.

### Claim 26 (depends on 1)

The apparatus of claim 1 comprising a treatment of or on the surface.

### Claim 27 (depends on 26)

The apparatus of claim 26 in which the treatment comprises an abrasion resistance material.

### Claim 28 (depends on 1)

The apparatus of claim 1 comprising a tool on which the imaging device is mounted.

### Claim 29 (depends on 28)

The apparatus of claim 28 in which the tool is elongated to fit within an enclosed space.

### Claim 30 (depends on 28)

The apparatus of claim 28 in which the tool comprises an illuminator.

### Claim 31 (depends on 1)

The apparatus of claim 1 comprising a layer on the surface to receive light at an edge of the layer and propagate it to a vicinity of the light sensitive locations.

### Claim 32 (depends on 1)

The apparatus of claim 1 comprising a pipette to contain the sample in a chamber at the surface.

### Claim 33 (depends on 31)

The apparatus of claim 31 in which the layer conducts surface plasmon illumination to the portion of the sample.

### Claim 34 (depends on 31)

The apparatus of claim 31 in which the layer comprises a totally internally reflective layer on the surface to provide illumination as an evanescent wave to the portion of the sample.

### Claim 35 (depends on 1)

The apparatus of claim 1 comprising an acoustic resonator to cause units of interest in the portion of the sample to move within the sample relative to the surface.

### Claim 36

An apparatus comprising
a device configured to enable a sample of a person or animal who is the subject of health care to be placed at a surface of a device, the surface being associated with a dense array of light sensitive locations or light emitting locations or both, and
electronics to cause information about the sample to be captured at a resolution of 2 microns or smaller by the device using light and to be provided for use in health care of the person or animal.

### Claim 37 (depends on 36)

The apparatus of claim 36 comprising a processor to process the information captured about the sample to generate results associated with units contained in the sample, and in which the processor measures units contained in the sample, and the measurement is of at least one of volume, size, shape, length, luminescence, fluorescence, scattering, birefringence, or other optical property.

### Claim 38

An apparatus comprising
a device configured to enable a surface of the device to be placed on or in the vicinity of tissue or material of a person or animal who is a subject of health care at a location, the surface being associated with a dense array of light sensitive locations or light emitting locations or both, and
electronics to cause information about the sample to be captured at a resolution of 2 microns or smaller by the device using light at the location and to be provided for use in the health care.

### Claim 39 (depends on 38)

The apparatus of claim 38 comprising
a communication facility for transmission of the information to a remote location for analysis of the information.

### Claim 40 (depends on 38)

The apparatus of claim 38 in which the device is configured to enable a surface of the device to be placed into contact with tissue or cells at a surgical site of the person or animal during a surgical procedure.

### Claim 41 (depends on 38)

A method of using the apparatus of claim 38 comprising causing information about the sample to be captured dynamically by the device using light at the location.

### Claim 42 (depends on 1)

The method of claim 1 in which the sample comprises biological cells and the method comprises using light to excite fluorescence and monitoring at least one of: dynamic changes in tissue metabolism, ion levels, membrane electrical potential, redox state, cellular energetics.

### Claim 43 (depends on 38)

The apparatus of claim 38 comprising a mechanism that enables illumination to be provided from alongside the surface of the device or from points interspersed across the surface, at least partly through tissue of the person.

### Claim 44

A method comprising
placing a sample of a person or animal who is the subject of health care at a surface of a device, the surface being associated with a dense array of light sensitive locations or light emitting locations or both,
deriving information at a resolution of 2 microns or smaller about the sample from the device using light, and
detecting a cell type using antibodies or other specific binding molecules directed against surface antigens of cells of a cell type in the sample.

### Claim 45

A method comprising
placing a sample of a person or animal who is the subject of health care at a surface of a device,
deriving information about the sample at a resolution of 2 microns or smaller from the device using light, and
generating a blood count analysis from the derived information.

### Claim 46

A method comprising
placing a sample of a person or animal who is the subject of health care at a surface of a device, the surface being associated with a dense array of light sensitive locations or light emitting locations or both,
deriving image information about the sample at a resolution of 5 microns or smaller from the device, and
diagnosing a parasitic disease using the derived image information.

### Claim 47

A method comprising
placing a sample of a person or animal at a surface of a device, the surface being associated with a dense array of light sensitive locations or light emitting locations or both,
deriving information about the sample at a resolution of 2 microns or smaller from the device, and
using the derived information to perform an assay of a cell function.

### Claim 48

A method comprising
placing a sample of a person or animal who is the subject of health care at a surface of a device, the surface being associated with a dense array of light sensitive locations or light emitting locations or both,
deriving information about the sample at a resolution of 5 microns or smaller from the device, and
performing cytogenetics using the derived information.

### Claim 49

A method comprising
placing a sample of a person or animal who is the subject of health care at a surface of a device, the surface being associated with a dense array of light sensitive locations or light emitting locations or both,
deriving information about the sample from the device,
and performing massively parallel biochemical analysis of the sample.

### Claim 50

A method comprising
placing a non-blood fluid, cellular, particulate, or other biochemical sample at a surface of a device, the surface being associated with a dense array of light sensitive locations or light emitting locations or both,
deriving information about the sample at a resolution of 2 microns or smaller from the device, and
analyzing the sample based on the derived information.

### Claim 51

An apparatus comprising
a disposable imager comprising
a device configured to enable a sample to be placed at a surface of the device, the surface being associated with a dense array of light sensitive locations or light emitting locations or both,
electronics to cause information about the sample to be captured at a resolution of 2 microns or smaller by the device using light,
a mechanism to contain the sample at the surface of the device, and
a coupler to connect and disconnect the disposable imager with a processing unit to process the captured information, the coupler enabling the disposable imager to be removed from the processing unit and replaced by another disposable imager.

### Claim 52 (depends on 51)

A method of using the apparatus of claim 51 comprising
applying the sample to the surface of the device, the surface being associated with a dense array of light sensitive locations or light emitting locations or both,
capturing the information about the sample, and
sending the captured information to the processing unit for processing.

### Claim 53

A method comprising
associating a sample with a surface of an imaging device, the surface being associated with a dense array of light sensitive locations or light emitting locations or both,
deriving information about the sample from the imaging device with high spatial resolution using light, and
inspecting the sample using a scanning probe microscope,
the inspecting by the scanning probe microscope being aided by the information derived from the imaging device.

### Claim 54 (depends on 53)

The method of claim 53 in which positioning of the scanning probe relative to the sample is aided by the information derived from the imaging device.
