# US 12,001,001 B2 · Light synchronization for an imaging system

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- Number: US 12,001,001 B2
- Document ID: US12001001B2
- Status: Granted
- Kind: B2
- Application number: 18/303,507
- Filed: 2023-04-19
- Published: 2023-09-21
- Granted: 2024-06-04
- Earliest claimed: 2021-08-18
- Assignees: Araceli Biosciences Inc.
- Applicants: Araceli Biosciences Inc.
- Inventors: Marguerite Vantangoli Policelli; Marshall Anderson; David Tasker; Tyler Wilson
- Web page: https://patentgrep.com/patent/US12001001B2

## CPC

- G02B 21/244: {using image analysis techniques}
- G02B 21/362: {Mechanical details, e.g. mountings for the camera or image sensor, housings (G02B21/364 takes precedence)}
- G02B 21/06: Means for illuminating specimens
- G02B 21/082: {for incident illumination only}
- G02B 21/16: adapted for ultraviolet illumination {; Fluorescence microscopes (G02B21/0076 takes precedence)}
- G02B 21/245: {using auxiliary sources, detectors}
- 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}
- G02B: OPTICAL ELEMENTS, SYSTEMS OR APPARATUS

## Abstract

Methods and systems are provided for synchronizing image capture at a multi-detector imaging system. In one example, a method includes coordinating cycling of each microscope assembly of the multi-detector imaging system through a selection of illumination channels, each microscope assembly configured to obtain an image of a portion of one of more than one microplate wells simultaneously, to generate complete images of the more than one microplate wells concurrently.

## Claims

### Claim 1

A method for a multi-detector imaging system, comprising:
receiving an input from a user at a graphical user interface, the input including imaging protocols and a microplate type;
determining parameters of a microplate based on the microplate type;
auto-focusing an objective of each of a plurality of microscope assemblies of the multi-detector imaging system at the microplate; and
coordinating image acquisition amongst the plurality of microscope assemblies according to the imaging protocols input by the user to acquire complete images of wells of the microplate.

### Claim 2 (depends on 1)

The method of claim 1, wherein the imaging protocols includes one or more of an exposure time of each detector of the multi-detector imaging system, a set of target light frequencies for illuminating the microplate, a number of the plurality of microscope assemblies to be activated, and a type of image capture for each of the plurality of microscope assemblies.

### Claim 3 (depends on 1)

The method of claim 1, wherein the microplate is positioned above objectives of the plurality of microscope assemblies, and wherein the microplate is coupled to a sample holder by a pivotable arm with a whippletree assembly.

### Claim 4 (depends on 1)

The method of claim 1, wherein determining the parameters of the microplate includes referring to a look-up table providing physical parameters of the microplate based on the microplate, and where the look-up table includes a distance that the microplate is translated to focus the objective of each of the plurality of microscope assemblies on wells of the microplate.

### Claim 5 (depends on 1)

The method of claim 1, wherein auto-focusing the objective of each of the plurality of microscope assemblies includes optimizing a first speed at which a position of a first objective is adjusted relative to a target position and selecting speeds of adjustment of remaining objectives based on the first speed.

### Claim 6 (depends on 1)

The method of claim 1, wherein coordinating image acquisition includes capturing image data at a first well of a quadrant of the microplate simultaneously at each of the plurality of microscope assemblies.

### Claim 7 (depends on 1)

The method of claim 1, wherein coordinating image acquisition includes coordinating cycling through selected illumination channels at each of plurality of microscope assemblies.

### Claim 8

A multi-detector imaging system comprising:
two or more microscope assemblies having objectives arranged at tops of plates oriented with heights of the plates parallel with a central axis of the multi-detector imaging system, tube lenses coupled to the plates and positioned below the objectives, laser auto-focuses coupled to a central region of the plates and oriented parallel with the central axis, and light sources located between the tube lenses and the laser auto-focuses;
a microplate positioned over the objectives; and
a controller with computer readable instructions stored on non-transitory memory that, when executed, cause the controller to:
collect images of the microplate at a same light frequency output from the light sources of the two or more microscope assemblies; and
compile complete images of wells of the microplate from the collected images and display the complete images at a graphical user interface.

### Claim 9 (depends on 8)

The multi-detector imaging system of claim 8, wherein the plates are arranged in an x-shaped configuration.

### Claim 10 (depends on 8)

The multi-detector imaging system of claim 8, wherein the objectives are arranged around the central axis with a first distance between the objectives along a first horizontal axis being larger than a second distance between the objectives along a second horizontal axis, the first and the second horizontal axes perpendicular to the central axis and perpendicular to one another.

### Claim 11 (depends on 8)

The multi-detector imaging system of claim 8, wherein all of the two or more microscope assemblies are operated concurrently.

### Claim 12 (depends on 8)

The multi-detector imaging system of claim 8, wherein each well of the microplate is divided into a grid and the images are captured for each section of the grid, and wherein the complete images of the wells are compiled from the images of each section of the grid.

### Claim 13 (depends on 8)

The multi-detector imaging system of claim 8, wherein the objectives are auto-focused via laser auto-focus sensors at each well of the microplate before collecting the images.

### Claim 14 (depends on 8)

The multi-detector imaging system of claim 8, wherein the two or more microscope assemblies are configured to collect a same type of images.

### Claim 15 (depends on 8)

The multi-detector imaging system of claim 8, wherein the two or more microscope assemblies are configured to collect different types of images.

### Claim 16

A method for synchronous image capture at a multi-detector imaging system, comprising:
acquiring images concurrently at quadrants of a microplate from microscope assemblies of the multi-detector imaging system by simultaneously illuminating the quadrants of the microplate with a first frequency of light,
wherein the microscope assemblies are supported on plates oriented with heights of the plates parallel with a central axis of the multi-detector imaging system and in an x-shaped configuration, and
wherein objectives are positioned at tops of the plates, tube lenses are located below the objectives, and laser auto-focus sensors are coupled to central regions of the plates and oriented parallel with the heights of the plates.

### Claim 17 (depends on 16)

The method of claim 16, wherein the laser auto-focus sensors are used to auto-focus the objectives prior to acquiring the images and wherein the objectives are auto-focused using a light shape that is less than half of a circle and less than half of an area of an entry aperture of the objectives.

### Claim 18 (depends on 17)

The method of claim 17, wherein the objectives are auto-focused by separating a first set of reflections of a laser beam from a second set of reflections of the laser beam, the first set of reflections reflected at a first interface between a base of a well of the microplate and air and the second set of reflections reflected at a second interface between the base of the well and a sample.

### Claim 19 (depends on 17)

The method of claim 17, wherein the laser auto-focus sensors transmit a laser beam in a direction perpendicular to an optical path of the objectives and tube lenses.

### Claim 20 (depends on 16)

The method of claim 16, wherein the tube lenses are decoupled from the objectives to enable variable pairing of a focal length of the tube lenses with a magnification of the objectives.