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US 12,467,735 B2Granted
Apparatus and method for light sheet imaging with optical coherence gating
AssigneeUniversity of Kent
InventorAdrian Podoleanu
Life of this patent
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Abstract
Methods and devices are disclosed to perform depth resolved imaging using parallel lateral detection employing a photodetector block in a detection path that is substantially perpendicular to the direction of light excitation, with applications in microscopy of samples. The photodetector block either comprises a single 1D array of photodetectors or a 2D array of photodetectors. Methods and devices are disclosed to perform coherence gating in configurations of light sheet tomography, to enable simultaneous depth resolved measurements of structure and of index of refraction variation.
Claims21
Apparatus for imaging a sample, comprising:
- an optical source of coherence length Lc in air, where Lc is less than 20 microns;
- a photodetector block, wherein the photodetector block comprises an array of H photodetectors;
- wherein the optical source is arranged to drive a first optical splitter with two outputs, where the first optical splitter is arranged such that, at its 1st output, an excitation sample wave is sent towards an excitation launcher, wherein the excitation launcher is arranged to launch the excitation sample wave along an axis X towards the sample to be imaged, irradiating H scattering centres x1, x2, . . . xh, . . . xH in the sample, and where the spatial extension of the excitation sample wave along its transversal direction, w, is less than 11Lc,
- wherein from each scattering centre xh, the excitation sample wave is scattered into a component scattered sample wave along a detection path,
- where the component scattered sample wave travels a length SL(h) up to pixel h of the array of the photodetector block;
- where the fraction of the excitation sample wave intercepted by the scattering centre h, leading to the scattered sample wave, represents a component of the excitation sample wave, with h=1, 2 . . . H, where each such component travelled a length EL(h) from the first optical splitter up to scattering centre at xh,
- where the detection path is along an axis Z that makes a detection angle that is substantially perpendicular to the direction of the excitation wave, X, and where the axis Z is also along the depth direction in the sample,
- a forming image interface placed along the detection path,
- conveying the H component scattered sample waves onto the photodetector block,
- where the photodetector block is oriented substantially perpendicular to the detection path,
- where the forming image interface forms an image of each scattering centre in the sample at x1, x2, . . . xh, . . . xH onto respective photodetectors 1,2, . . . h, . . . H of the array of the photodetector block,
- and where due to travelling through the sample, due to the optical properties of the sample and due to the geometrical distance between scattering centres xh and xh+1 along axis X,
- the component excitation sample wave travelling from the scattering centre at xh−1 to the scattering centre at xh encounters an optical path length variation □EL(h) given by the product of the distance between xh−1 and xh multiplied by n, where n is the index of refraction of the sample, and
- where the first optical splitter is arranged such the 2nd output of the 1st optical splitter delivers a reference wave that is conveyed towards the photodetector block via a reference block,
- where the reference block is equipped with a device to adjust the length of the reference wave travelled RL(h) from the point of splitting in the 1st optical splitter through the reference block up to each photodetector h of the photodetector block, and where
- the optical path difference OPD(h) between the path lengths EL(h)+SL(h) and RL(h) differ from photodetector h to photodetector h+1,
- where the variation of OPD(h) from one edge of the photodetector block to the other measured within the detection plane, |OPD(H)−OPD(1)|, is greater than 50Lc,
- and where the optical source, the 1st optical splitter and the two paths lengths travelled by each component excitation sample wave plus each component scattered sample wave up to the photodetector h on one side and the path travelled by the reference wave up to photodetector h on the other side, form a two beam interferometer for each photodetector h, where such H interferometers present similar optical coherence tomography axial resolution intervals of Lc,
- where the apparatus further comprises:
- a signal processing block for processing the signals delivered by the H photodetectors of the array, wherein the signal processing block is configured to carry out a procedure to process the interference signal due to superposition of scattered sample waves and reference wave on each photodetector h,
- where the signal processing block produces a raw en-face image of scattering centres x1, x2, . . . xh, . . . xH, whose intensity for each photodetector in the image is modulated by the strength of interference of signal from respective photodetectors 1, 2, . . . h, . . . H and where the depth resolution of the en-face image along Z is due to the combined effect of the thickness of the excitation sample wave, w, and of the coherence length in the sample, obtained by dividing the coherence length in air, Lc, by the index of refraction n of the sample.
18 more elements
Method to produce coherence gating images of a sample, the method comprising:
- using an optical source of coherence length Lc, where Lc is less than 20 microns, that is split in a splitter into an excitation sample wave and a reference wave,
- where the spatial extension of the excitation sample wave along its transversal direction, w, is less than 11Lc,
- using at least a 1D array of photodetectors h=1, 2 . . . H in a camera, oriented perpendicular to a detection direction, and where the excitation sample wave is launched towards a sample with scattering centres along an excitation direction substantially parallel to the camera, to excite the sample, and where the excitation direction is substantially perpendicular to the detection direction, where the detection direction and excitation directions define a detection plane and where the scattering centres in the sample generate scattered sample waves along the detection direction intercepted by a forming image interface that conveys an image on the camera of the scattering centres in the sample and where due to the non-zero value of the angle between the detection direction and the excitation direction and due to the index of refraction of the sample, the length travelled by the excitation sample wave through the sample varies by a differential path |x′−x| from a scattering centre at x to the next at x′, where the scattering centres at x and x′ are conjugate via the forming image interface with camera photodetectors h and h+1 respectively, from a camera photodetector h to next, h+1 in its row placed in the detection plane, and where the signals produced by each camera photodetector h are subject to coherence gating, that is implemented by using the reference wave superposed on the camera, and where for each photodetector h, an optical path difference OPD(h) is defined between:
- (i) the length of the sample wave from the splitter up to photodetector h made from the length of the excitation sample wave up to the scattering centre x and the length of the scattering sample wave from the scattering centre up to photodetector h and (ii) the length of the reference wave from the splitter up to photodetector h,
- and a signal processing procedure is applied to the signal from each photodetector to:
- (i) evaluate its strength of interference versus OPD, (ii) integrate the interference signal along OPD axis to deliver an overall strength of interference signal from each photodetector and (iii) produce an interference 1D en-face image of pixels, with a pixel for each photodetector by using for each pixel signal, the overall strength of interference so evaluated for each respective photodetector and where the thickness of the en-face image is determined by a combination of two factors, the thickness of the excitation sample wave w and the coherence length in the sample, Lc/n, where n is the index of refraction of the sample.
3 more elements
Dependencies are inferred from the claim text.