ARRAY LEVEL FOURIER PTYCHOGRAPHIC IMAGING

• US 20190317311A1
• Filed: 01/08/2019
• Published: 10/17/2019
• Est. Priority Date: 01/26/2015
• Status: Active Grant

• Current Assignee: California Institute of Technology
• Original Assignee: California Institute of Technology
• Inventors: Kim, Jinho, Yang, Changhuei
• Granted Patent: US 10,732,396 B2
• Time in Patent Office: Days
• CPC Class Codes: G01N 2021/6478 Special lenses
• CPC Class Codes: G01N 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 21/6456 Spatial resolved fluorescence measurements; Imaging
• CPC Class Codes: G01N 21/6458 Fluorescence microscopy fluorescence microscopes per se G02B21/0076 and G02B21/16
• CPC Class Codes: G01N 2201/0446 Multicell plate, sequential
• CPC Class Codes: G02B 13/0095 Relay lenses or rod lenses in instruments for viewing the inside of hollow bodies G02B23/2446
• CPC Class Codes: G02B 21/0076 arrangements using fluorescence or luminescence
• CPC Class Codes: G02B 21/16 adapted for ultraviolet illumination ; Fluorescence microscopes G02B21/0076 takes precedence
• CPC Class Codes: G02B 21/365 Control or image processing arrangements for digital or video microscopes G02B21/361, G02B21/362 take precedence
• CPC Class Codes: 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
• CPC Class Codes: H04N 23/45 for generating image signals from two or more image sensors being of different type or operating in different modes, e.g. with a CMOS sensor for moving images in combination with a charge-coupled device [CCD] for still images
• CPC Class Codes: H04N 23/56 provided with illuminating means
• CPC Class Codes: H04N 23/957 Light-field or plenoptic cameras or camera modules

Abstract

In one aspect an imaging system includes: an illumination system including an array of light sources; an optical system including one or more lens arrays, each of the lens arrays including an array of lenses, each of the lenses in each of the one or more lens arrays in alignment with a corresponding set of light sources of the array of light sources; an imaging system including an array of image sensors, each of the image sensors in alignment with a corresponding lens or set of lenses of the one or more lens arrays, each of the image sensors configured to acquire image data based on the light received from the corresponding lens or set of lenses; a plate receiver system capable of receiving a multi-well plate including an array of wells, the plate receiver system configured to align each of the wells with a corresponding one of the image sensors; and a controller configured to control the illumination of the light sources and the acquisition of image data by the image sensors, the controller further configured to perform: an image acquisition process including a plurality of scans, each scan associated with a unique pattern of illumination, each of the image sensors configured to generate an image for a respective one of the wells during each scan; and an image reconstruction process during which the controller performs a fourier ptychographic operation to generate a reconstructed image for each of the wells based on the image data captured for the respective well during each of the scans.

Claims

1-13. -13. (canceled)

14. A system for array-level Fourier ptychographic imaging, the system comprising:

a plurality of optical arrangements, each optical arrangement having one or more lenses configured to receive light from a corresponding sample well of an array of sample wells in a multi-well plate received into the system during operation;

a plurality of image sensors configured to receive light from the plurality of optical arrangements and acquire image data based on the light received;

an illumination system configured to illuminate the array of sample wells in parallel such that each sample well is illuminated sequentially with light at different angles of incidence; and

a processor configured to perform a Fourier ptychographic operation to generate a reconstructed image for each of the sample wells based on the image data acquired for the respective sample well from light provided at the different angles of incidence by the illumination system.

15. The system of claim 14, wherein each optical arrangement comprises a first lens and a second lens.

16. The system of claim 15, wherein each optical arrangement further comprises a third lens.

17. The system of claim 14, wherein the illumination system further comprises at least one or more excitation light sources, each excitation light source configured to illuminate one of the sample wells, wherein each excitation light source is configured to provide excitation light with power higher than the illumination from the array of light elements.

19. The system of claim 14, wherein each optical arrangement further comprises a filter configured to filter excitation light, the filter located between the multi-well plate and the array of image sensors.

20. The system of claim 14, wherein the plurality of optical arrangements comprises at least one lens array.

21. The system of claim 14, wherein the multi-well plate has one of 6 wells, 12 wells, 96 wells, 384 wells, 1536 wells, 3456 wells, or 9600 wells.

22. The system of claim 14, wherein the illumination system includes an array of light elements configured to illuminate the array of sample wells in parallel.

23. The system of claim 22, wherein the array of light elements is a light emitted diode (LED) matrix.

24. The system of claim 22, wherein the array of light elements is configured to sequentially activate light elements to generate a sequence of different illumination patterns.

25. The system of claim 22, wherein the array of light elements is configured such that each activated light element illuminates a plurality of sample wells at each exposure time.

26. The system of claim 22, wherein the array of light elements is configured such that each activated light element illuminates a single sample well at each exposure time.

27. The system of claim 14, wherein the Fourier ptychographic operation includes aberration correction for correcting for any aberrations in the system.

18. The system of claim 18, wherein the processor is further configured to generate a fluorescence image for each of the sample wells illuminated by excitation light from the one or more excitation light sources.

28. A system for imaging an array of sample wells, the system comprising:

at least one lens array, each lens configured to receive light from a corresponding sample well of the array of sample wells;

a plurality of image sensors configured to receive light from the at least one array of lenses and acquire image data based on the received light;

an array of light elements configured to illuminate the array of sample wells in parallel with illumination such that each sample well is provided sequentially with illumination at different angles of incidence;

at least one excitation light source configured to illuminate at least one sample well of the array of sample wells, wherein the at least one excitation light source provides illumination at a different time than the array of light elements; and

a processor configured to;

perform a Fourier ptychographic operation to generate a reconstructed image for each sample well based on the image data acquired for the respective sample well from the sequential illumination with light at different angles of incidence, and

generate, for each of the at least one sample well, a fluorescence image based on the image data acquired for the respective sample well from the excitation light.

29. The system of claim 28, further comprising an optical filter configured to filter excitation light, the optical filter located between the array of sample wells and the plurality of image sensors.

30. The system of claim 29, wherein the at least one excitation light source is side-mounted.

31. The system of claim 28, wherein the at least one excitation light source provides excitation light with power higher than power of the illumination from the array of light elements.

32. The system of claim 28, wherein the array of sample wells is part of a multi-well plate.

33. The system of claim 32, wherein the multi-well plate has one of 6 wells, 12 wells, 96 wells, 384 wells, 1536 wells, 3456 wells, or 9600 wells.

34. The system of claim 28, wherein the array of light elements is a light emitted diode (LED) matrix.

35. The system of claim 28, wherein the array of light elements is configured to sequentially activate different light elements of the array of light elements to generate a sequence of different illumination patterns.